ORCID Profile
0000-0002-4634-6221
Current Organisations
Universidade Estadual Paulista Júlio de Mesquita Filho
,
University of Queensland
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Psychology | Other Behavioural And Cognitive Sciences | Sensory Processes, Perception And Performance | Other Psychology and Cognitive Sciences | Population Trends And Policies | Social Policy And Planning | Cultural Studies | Mental Health | Multicultural, Intercultural and Cross-cultural Studies | Health, Clinical And Counselling Psychology | Developmental Psychology And Ageing | Social And Community Psychology | Personality, Abilities And Assessment | Road And Rail Transportation | Developmental Psychology and Ageing | Transport Engineering | Social Policy | Transportation and Freight Services | Social and Community Psychology
ANZSRC Socio-Economic Objective (SEO)
The aged | Health related to ageing | Road safety | Families | Gender | Injury control | Ageing and Older People | Expanding Knowledge in Psychology and Cognitive Sciences | Communication Across Languages and Culture | Health policy economic outcomes | Automotive equipment | Other road transport | Productivity | Mental health | Other social development and community services |
Related Links
Publications
Structural evidence for a fatty acid-independent myotoxic mechanism for a phospholipase A2-like toxin
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.BBAPAP.2017.12.008
Abstract: The myotoxic mechanism for PLA
The Structure of HLA-B8 Complexed to an Immunodominant Viral Determinant: Peptide-Induced Conformational Changes and a Mode of MHC Class I Dimerization
Publisher: The American Association of Immunologists
Date: 11-2002
DOI: 10.4049/JIMMUNOL.169.9.5153
Abstract: EBV is a ubiquitous human pathogen that chronically infects up to 90% of the population. Persistent viral infection is characterized by latency and periods of viral replication that are kept in check by a strong antiviral CTL response. Despite the size of the EBV genome, CTL immunity focuses on only a few viral determinants but expands a large primary and memory response toward these epitopes. In unrelated HLA-B8+ in iduals, the response to the immunodominant latent Ag FLRGRAYGL from Epstein Barr nuclear Ag 3A is largely comprised of CTL clones with identical conserved αβ TCR structures. To better understand the structural correlates of Ag immunodominance and TCR selection bias, we have solved the crystal structure of the HLA-B8-FLRGRAYGL peptide complex to a resolution of 1.9 Å. The structure confirms the importance of P3-Arg, P5-Arg, and P9-Leu as dominant anchor residues involved in peptide binding to HLA-B8. A bulged conformation of the bound peptide provides a structural basis for the critical role of the P7-Tyr residue in T cell recognition. The peptide also induces backbone and side-chain conformational changes in HLA-B8 that are transmitted along the peptide-binding groove in a domino effect. The HLA-B8-FLRGRAYGL complex crystallizes as a dimer in the asymmetric unit and is oriented such that both peptide ligands are projected in the same plane suggesting a higher order arrangement of MHC-peptide complexes that could be involved in formation of the class I Ag-loading complex or in T cell activation.
A Systematic Review of Psychotherapy Approaches for Anxiety in Parkinson’s Disease
Publisher: Informa UK Limited
Date: 30-05-2022
DOI: 10.1080/07317115.2022.2074814
Abstract: Anxiety is common in Parkinson's disease (PD), negatively impacting daily functioning and quality of life in PD patients and their families. This systematic review evaluates the effectiveness of different psychotherapeutic approaches for reducing anxiety in PD and provides recommendations for clinical practise. Following PRISMA guidelines, 36 studies were included and risk of bias was evaluated. We identified cognitive behavioral therapy (CBT), mindfulness-based therapies, acceptance and commitment therapy, and psychodrama psychotherapies. There is good evidence-base for anxiety reduction using CBT approaches, but with mixed results for mindfulness-based therapies. Other therapeutic approaches were under researched. Most randomized control trials examined anxiety as a secondary measure. There was a paucity of interventions for anxiety subtypes. Secondarily, studies revealed the consistent exclusion of PD patients with cognitive concerns, an importance of care partner involvement, and a growing interest in remote delivery of psychotherapy interventions. Person-centered anxiety interventions tailored for PD patients, including those with cognitive concerns, and trials exploring modalities other than CBT, warrant future investigations. Practitioners should consider PD-specific anxiety symptoms and cognitive concerns when treating anxiety. Key distinctions between therapeutic modalities, therapy settings and delivery methods should guide treatment planning.
Beyond hemostasis: a snake venom serine protease with potassium channel blocking and potential antitumor activities
Publisher: Springer Science and Business Media LLC
Date: 11-03-2020
DOI: 10.1038/S41598-020-61258-X
Abstract: Snake venom serine proteases (SVSPs) are complex and multifunctional enzymes, acting primarily on hemostasis. In this work, we report the hitherto unknown inhibitory effect of a SVSP, named collinein-1, isolated from the venom of Crotalus durissus collilineatus , on a cancer-relevant voltage-gated potassium channel (hEAG1). Among 12 voltage-gated ion channels tested, collinein-1 selectively inhibited hEAG1 currents, with a mechanism independent of its enzymatic activity. Corroboratively, we demonstrated that collinein-1 reduced the viability of human breast cancer cell line MCF7 (high expression of hEAG1), but does not affect the liver carcinoma and the non-tumorigenic epithelial breast cell lines (HepG2 and MCF10A, respectively), which present low expression of hEAG1. In order to obtain both functional and structural validation of this unexpected discovery, where an unusually large ligand acts as an inhibitor of an ion channel, a recombinant and catalytically inactive mutant of collinein-1 (His43Arg) was produced and found to preserve its capability to inhibit hEAG1. A molecular docking model was proposed in which Arg79 of the SVSP 99-loop interacts directly with the potassium selectivity filter of the hEAG1 channel.
Multisensory Installations in Residential Aged-Care Facilities: Increasing Novelty and Encouraging Social Engagement Through Modest Environmental Changes
Publisher: SLACK, Inc.
Date: 09-2014
DOI: 10.3928/00989134-20140731-01
Abstract: class="ftSection" span class="ftInlineSubsectionTitle" How to Obtain Contact Hours by Reading this Article /span class="ftSection" span class="ftInlineSubsectionTitle" Instructions /span strong .3 /strong contact hours will be awarded by Villanova University College of Nursing upon successful completion of this activity. A contact hour is a unit of measurement that denotes 60 minutes of an organized learning activity. This is a learner-based activity. Villanova University College of Nursing does not require submission of your answers to the quiz. A contact hour certificate will be awarded once you register, pay the registration fee, and complete the evaluation form online at ext-link xmlns:xlink="999/xlink" ext-link-type="uri" xlink:href="ev_students.asp?action=browse& main=Nursing+Journals& misc=564" ev_students.asp?action=browse& main=Nursing+Journals& misc=564 /ext-link . To obtain contact hours you must: list list-type="order" li st-item label . /label /list-item /list Read the article, & Multisensory Installations in Residential Aged-Care Facilities: Increasing Novelty and Encouraging Social Engagement Through Modest Environmental Changes& found on pages 20& ndash , carefully noting any tables and other illustrative materials that are included to enhance your knowledge and understanding of the content. Be sure to keep track of the amount of time (number of minutes) you spend reading the article and completing the quiz. list-item label . /label Read and answer each question on the quiz. After completing all of the questions, compare your answers to those provided within this issue. If you have incorrect answers, return to the article for further study. /list-item list-item label . /label Go to the Villanova website listed above to register for contact hour credit. You will be asked to provide your name contact information and a VISA, MasterCard, or Discover card number for payment of the $20.00 fee. Once you complete the online evaluation, a certificate will be automatically generated. /list-item This activity is valid for continuing education credit until August 31, 2016. / class="ftSection" span class="ftInlineSubsectionTitle" Contact Hours /span This activity is co-provided by Villanova University College of Nursing and SLACK Incorporated. Villanova University College of Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center& rsquo s Commission on Accreditation. / class="ftSection" span class="ftInlineSubsectionTitle" Activity Objectives /span list list-type="order" list-item label . /label Explore the benefits of indoor garden installations in aged-care facilities. /list-item list-item label . /label Describe the study results of indoor garden installations on social engagement. /list-item /list / class="ftSection" span class="ftInlineSubsectionTitle" Disclosure Statement /span Neither the planners nor the authors have any conflicts of interest to disclose. / / class="ftSection" span class="ftInlineSubsectionTitle" The current study examined the effect of an indoor simulated garden installation that included visual, auditory, and olfactory stimuli on resident well-being, compared to the effect elicited by a reminiscence installation and a control no-installation condition. A quasi-experimental ABA design was used (i.e., two intervention conditions plus a wait-list control condition). A survey instrument was administered to nursing home residents ( em N /em = 33) at three time points (pre-, during, and post intervention) over an 8-week period, which measured mood, behavior, health, and social interaction. Additionally, staff reports ( em N /em = 24) were collected. Both the nature-based and non-nature-based installations led to enhanced well-being and significantly more social benefits for residents because of their novel and aesthetic appeal, compared with the control condition. Residents in the nature-based installation condition reported more satisfaction with their living environment during the intervention phase than those in the comparison conditions. The results show that an indoor garden simulation is a relatively inexpensive way to transform a disused indoor area of an aged-care facility for the benefit of residents and staff. [ em Journal of Gerontological Nursing, 40 /em (9), 20& ndash .] /span / class="ftAuthorNotes" Dr. Scott is Postdoctoral Researcher, Dr. Masser is Associate Professor, and Dr. Pachana is Professor, School of Psychology, The University of Queensland, St. Lucia, Queensland, Australia. Dr. Pachana is also Co-Director, UQ Ageing Mind Initiative, The University of Queensland, St. Lucia, Queensland, Australia. The authors have disclosed no potential conflicts of interest, financial or otherwise. The authors thank the staff and residents who participated in this study. Address correspondence to Theresa L. Scott, PhD, Postdoctoral Researcher, School of Psychology, The University of Queensland, St. Lucia, Queensland 4072, Australia e-mail: theresa.scott@uq.edu.au. / class="ftHistory-received" Received: March 02, 2014 / class="ftHistory-accepted" Accepted: July 01, 2014 br / br / style="text-transform: uppercase padding: 3px 10px border: 1px solid #dddddd width: 273px font-size: 11px " Do you want to Participate in the a href="~/link.aspx?_id=9F2D189677774BA9A16A01338B2FF284& _z=z" span style="text-decoration: none " CNE activity /span /a ? /
Phospholipase A2 Inhibitors from Snake Blood (sbPLIs)
Publisher: Springer Netherlands
Date: 2016
Delirium in Australian Hospitals: A Prospective Study
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/284780
Abstract: Objectives . Australian data regarding delirium in older hospitalized patients are limited. Hence, this study aimed to determine the prevalence and incidence of delirium among older patients admitted to Australian hospitals and assess associated outcomes. Method . A prospective observational study ( n = 493 ) of patients aged ≥70 years admitted to four Australian hospitals was undertaken. Trained research nurses completed comprehensive geriatric assessments using standardized instruments including the Confusion Assessment Method to assess for delirium. Nurses also visited the wards daily to assess for incident delirium and other adverse outcomes. Diagnoses of dementia and delirium were established through case reviews by independent physicians. Results . Overall, 9.7% of patients had delirium at admission and a further 7.6% developed delirium during the hospital stay. Dementia was the most important predictor of delirium at ( OR = 3.18 , 95% CI: 1.65–6.14) and during the admission ( OR = 4.82 95% CI: 2.19–10.62). Delirium at and during the admission predicted increased in-hospital mortality ( OR = 5.19 , 95% CI: 1.27–21.24 OR = 31.07 , 95% CI: 9.30–103.78). Conclusion. These Australian data confirm that delirium is a common and serious condition among older hospital patients. Hospital clinicians should maintain a high index of suspicion for delirium in older patients.
Mindfulness for motor and nonmotor dysfunctions in Parkinson's disease
Publisher: Hindawi Limited
Date: 2016
DOI: 10.1155/2016/7109052
Abstract: Background . Motor and nonmotor symptoms negatively influence Parkinson’s disease (PD) patients’ quality of life. Mindfulness interventions have been a recent focus in PD. The present study explores effectiveness of a manualized group mindfulness intervention tailored for PD in improving both motor and neuropsychiatric deficits in PD. Methods . Fourteen PD patients completed an 8-week mindfulness intervention that included 6 sessions. The Five Facet Mindfulness Questionnaire (FFMQ), Geriatric Anxiety Inventory, Hamilton Depression Rating Scale, PD Cognitive Rating Scale, Unified PD Rating Scale, PD Quality of Life Questionnaire, and Outcome Questionnaire (OQ-45) were administered before and after the intervention. Participants also completed the FFMQ-15 at each session. Gains at postassessment and at 6-month follow-up were compared to baseline using paired t -tests and Wilcoxon nonparametric tests. Results . A significant increase in FFMQ-Observe subscale, a reduction in anxiety, depression, and OQ-45 symptom distress, an increase in PDCRS-Subcortical scores, and an improvement in postural instability, gait, and rigidity motor symptoms were observed at postassessment. Gains for the PDCRS were sustained at follow-up. Conclusion . The mindfulness intervention tailored for PD is associated with reduced anxiety and depression and improved cognitive and motor functioning. A randomised controlled trial using a large s le of PD patients is warranted.
Preliminary X-ray crystallographic studies of a tetrameric phospholipase A2formed by two isoforms of crotoxin B fromCrotalus durissus terrificusvenom
Publisher: International Union of Crystallography (IUCr)
Date: 30-11-2007
A Review of Tobacco, Alcohol, Adiposity, and Activity as Predictors of Cognitive Change
Publisher: Informa UK Limited
Date: 03-2012
COVID-19 and psychogeriatrics: the view from Australia
Publisher: Cambridge University Press (CUP)
Date: 12-05-2020
Depression rating scales in Parkinson's disease: A critical review updating recent literature
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.JAD.2015.05.059
Abstract: Depression is a prominent non-motor symptom in Parkinson's disease (PD). Assessing depression in PD remains a challenge due to the overlap of somatic symptoms between depression and PD. Other neuropsychiatric manifestations associated with PD, such as cognitive decline, also complicate assessment of depression. Therefore it is critical to investigate the validity of depression rating scales for use in PD. This will allow evaluation of observer- and self-report instruments to be administered in neurologically ill geriatric populations such as PD, and identification of appropriate scales to use in cognitively challenged PD patients. The present review includes all studies examining the validity of depression rating scales in PD. It discusses the usefulness of 13 depression rating scales in PD. The clinician-rated and widely used HAMD-17 and the self-report GDS scales are recommended for screening and measuring severity of depression in PD. The GDS-15 may be a preferred choice due to its brevity and ease of use design for older adults. Other valid and reliable instruments to use in PD include self-rated scales, such as the HADS-D, HDI, and the BDI, and the observer-report, MADRS. The CSDD displayed satisfactory validity and reliability for identification of PD patients with and without dementia. The PHQ-2, PHQ-10, SDS, CES-D, UPDRS-Depression item, IDS-SR, and IDS-C each showed some evidence of validity or reliability, however further research on the psychometric properties of these scales when used in a PD population are required.
Crystallization and preliminary X-ray diffraction analysis of importin-α complexed with NLS peptidomimetics
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.BBAPAP.2005.03.014
Abstract: Importin-alpha is the nuclear import receptor that recognizes cargo proteins with nuclear localization sequences (NLSs). The study of NLS peptidomimetics can provide a better understanding of the requirements for the molecular recognition of cargo proteins by importin-alpha, and potentially engender a large number of applications in medicine. Importin-alpha was crystallized with a set of six NLS peptidomimetics, and X-ray diffraction data were collected in the range 2.1-2.5 A resolution. Preliminary electron density calculations show that the ligands are present in the crystals.
Crystal structure of a phospholipase A2 from Bothrops asper venom: Insights into a new putative “myotoxic cluster”
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.BIOCHI.2016.12.015
Abstract: Snake venoms from the Viperidae and Elapidae families often have several phospholipases A
Structure of BthA-I complexed withp-bromophenacyl bromide: possible correlations with lack of pharmacological activity
Publisher: International Union of Crystallography (IUCr)
Date: 19-11-2005
Biochemical and structural characterization of the RT domain of Leishmania sp. telomerase reverse transcriptase
Publisher: Elsevier BV
Date: 11-2023
Search for efficient inhibitors of myotoxic activity induced by ophidian phospholipase A2-like proteins using functional, structural and bioinformatics approaches
Publisher: Springer Science and Business Media LLC
Date: 24-01-2019
DOI: 10.1038/S41598-018-36839-6
Abstract: Ophidian accidents are considered an important neglected tropical disease by the World Health Organization. Particularly in Latin America, Bothrops snakes are responsible for the majority of the snakebite envenomings that are not efficiently treated by conventional serum therapy. Thus, the search for simple and efficient inhibitors to complement this therapy is a promising research area, and a combination of functional and structural assays have been used to test candidate ligands against specific ophidian venom compounds. Herein, we tested a commercial drug (acetylsalicylic acid, ASA) and a plant compound with antiophidian properties (rosmarinic acid, RA) using myographic, crystallographic and bioinformatics experiments with a phospholipase A 2 -like toxin, MjTX-II. MjTX-II/RA and MjTX-II/ASA crystal structures were solved at high resolution and revealed the presence of ligands bound to different regions of the toxin. However, in vitro myographic assays showed that only RA is able to prevent the myotoxic effects of MjTX-II. In agreement with functional results, molecular dynamics simulations showed that the RA molecule remains tightly bound to the toxin throughout the calculations, whereas ASA molecules tend to dissociate. This approach aids the design of effective inhibitors of PLA 2 -like toxins and, eventually, may complement serum therapy.
Influence of Quaternary Conformation on the Biological Activities of the Asp49-phospholipases A2s from Snake Venoms
Publisher: Bentham Science Publishers Ltd.
Date: 08-2009
DOI: 10.2174/092986609788923301
Abstract: One of the main components of snake venoms are the Asp49-phospholipases A(2), also known as svPLA(2)s. The study of these toxins is a matter of great scientific interest due to their wide variety of biological effects. In this work we present strong evidences found in literature and other aspects which strengthen the importance of quaternary assembly for understanding the activities and molecular evolution of svPLA(2)s.
Structural and Calorimetric Studies Demonstrate that Xeroderma Pigmentosum Type G (XPG) Can Be Imported to the Nucleus by a Classical Nuclear Import Pathway via a Monopartite NLS Sequence
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.JMB.2016.01.019
Abstract: Xeroderma pigmentosum type G (XPG) proteins are involved in DNA lesion recognition and promotion of nucleotide excision repair. Specific mutations in these proteins may lead to Cockayne syndrome, in which the patients may display severe developmental retardation and neurological abnormalities. No structural information is available for their spacer region or the C-terminal domain, which are important, respectively, for specific nucleotide excision repair activity and substrate specificity, as well as nuclear translocation. Immunofluorescence studies suggested two specific regions of the XPG C-terminus as potential bipartite nuclear localization sequences, which would be responsible for its translocation to the nucleus by the classical nuclear import pathway mediated by the importin-α (Impα). Thus, in order to test these hypotheses and gain insight into the structural basis for the nuclear import process for the XPG protein, we solved the crystal structures of complexes formed by the Impα and peptides corresponding to both putative nuclear localization signal (NLS) sequences (XPG1 and XPG2) and performed isothermal titration calorimetry assays to determine their binding affinities. Structural experiments confirm the binding of both NLS peptides to Impα but, unexpectedly, they bind to the receptor as monopartite NLSs. The isothermal titration calorimetry assays demonstrated that XPG1 and XPG2 peptides bind to two separate binding sites, but with high affinity to the major NLS-binding site of the Impα, resembling classical monopartite SV40 TAg NLS. The results lead to insights about what distinguishes monopartite and bipartite NLSs, as well as the differential roles of XPG1 and XPG2 NLSs in the nuclear localization of XPG.
Crystallization and preliminary X-ray diffraction analysis of myotoxin I, a Lys49-phospholipase A2fromBothrops moojeni
Publisher: International Union of Crystallography (IUCr)
Date: 13-09-2005
SEQUENCE SLIDER: integration of structural and genetic data to characterize isoforms from natural sources
Publisher: Oxford University Press (OUP)
Date: 02-2022
DOI: 10.1093/NAR/GKAC029
Abstract: Proteins isolated from natural sources can be composed of a mixture of isoforms with similar physicochemical properties that coexist in the final steps of purification. Yet, even where unverified, the assumed sequence is enforced throughout the structural studies. Herein, we propose a novel perspective to address the usually neglected sequence heterogeneity of natural products by integrating biophysical, genetic and structural data in our program SEQUENCE SLIDER. The aim is to assess the evidence supporting chemical composition in structure determination. Locally, we interrogate the experimental map to establish which side chains are supported by the structural data, and the genetic information relating sequence conservation is integrated into this statistic. Hence, we build a constrained peptide database, containing most probable sequences to interpret mass spectrometry data (MS). In parallel, we perform MS de novo sequencing with genomic-based algorithms to detect point mutations. We calibrated SLIDER with Gallus gallus lysozyme, whose sequence is unequivocally established and numerous natural isoforms are reported. We used SLIDER to characterize a metalloproteinase and a phospholipase A2-like protein from the venom of Bothrops moojeni and a crotoxin from Crotalus durissus collilineatus. This integrated approach offers a more realistic structural descriptor to characterize macromolecules isolated from natural sources.
An Evaluation of 3-Rhamnosylquercetin, a Glycosylated Form of Quercetin, against the Myotoxic and Edematogenic Effects of sPLA2fromCrotalus durissus terrificus
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/341270
Abstract: This paper shows the results of quercitrin effects on the structure and biological activity of secretory phospholipase (sPLA 2 ) from Crotalus durissus terrificus , which is the main toxin involved in the pharmacological effects of this snake venom. According to our mass spectrometry and circular dichroism results, quercetin was able to promote a chemical modification of some amino acid residues and modify the secondary structure of C. d. terrificus sPLA 2 . Moreover, molecular docking studies showed that quercitrin can establish chemical interactions with some of the crucial amino acid residues involved in the enzymatic activity of the sPLA 2 , indicating that this flavonoid could also physically impair substrate molecule access to the catalytic site of the toxin. Additionally, in vitro and in vivo assays showed that the quercitrin strongly diminished the catalytic activity of the protein, altered its Vmax and Km values, and presented a more potent inhibition of essential pharmacological activities in the C. d. terrificus sPLA 2 , such as its myotoxicity and edematogenic effect, in comparison to quercetin. Thus, we concluded that the rhamnose group found in quercitrin is most likely essential to the antivenom activities of this flavonoid against C. d. terrificus sPLA 2 .
Identification of continuous interaction sites in PLA2-based protein complexes by peptide arrays
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.BIOCHI.2009.08.006
Abstract: Crotoxin (CA.CB) is a beta-neurotoxin from Crotalus durissus terrificus snake venom that is responsible for main envenomation effects upon biting by this snake. It is a heterodimer of an acidic protein (CA) devoid of any biological activity per se and a basic, enzymatically active, PLA(2) counterpart (CB). Both lethal and enzymatic activities of crotoxin have been shown to be inhibited by CNF, a protein from the blood of C. d. terrificus snakes. CNF replaces CA in the CA.CB complex, forming a stable, non-toxic complex CNF.CB. The molecular sites involved in the tight interfacial protein-protein interactions in these PLA(2)-based complexes have not been clearly determined. To help address this question, we used the peptide arrays approach to map possible interfacial interaction sites in CA.CB and CNF.CB. Amino acid stretches putatively involved in these interactions were firstly identified in the primary structure of CB. Further analysis of the interfacial availability of these stretches in the presumed biologically active structure of CB, suggested two interaction main sites, located at the amino-terminus and beta-wing regions. Peptide segments at the carboxyl-terminus of CB were also suggested to play a secondary role in the binding of both CA and CNF.
Anxiety Symptoms in Australian Memory Clinic Attendees with Cognitive Impairment: Differences Between Self-, Carer-, and Clinician-Report Measures
Publisher: Informa UK Limited
Date: 06-07-2023
Replication Protein A Presents Canonical Functions and Is Also Involved in the Differentiation Capacity of Trypanosoma cruzi
Publisher: Public Library of Science (PLoS)
Date: 16-12-2016
Towards toxin PEGylation: The example of rCollinein-1, a snake venom thrombin-like enzyme, as a PEGylated biopharmaceutical prototype
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.IJBIOMAC.2021.09.004
Abstract: PEGylation was firstly described around 50 years ago and has been used for more than 30 years as a strategy to improve the drugability of biopharmaceuticals. However, it remains poorly employed in toxinology, even though it may be a promising strategy to empower these compounds in therapeutics. This work reports the PEGylation of rCollinein-1, a recombinant snake venom serine protease (SVSP), able to degrade fibrinogen and inhibit the hEAG1 potassium channel. We compared the functional, structural, and immunogenic properties of the non-PEGylated (rCollinein-1) and PEGylated (PEG-rCollinein-1) forms. PEG-rCollinein-1 shares similar kinetic parameters with rCollinein-1, maintaining its capability of degrading fibrinogen, but with reduced activity on hEAG1 channel. CD analysis revealed the maintenance of protein conformation after PEGylation, and thermal shift assays demonstrated similar thermostability. Both forms of the enzyme showed to be non-toxic to peripheral blood mononuclear cells (PBMC). In silico epitope prediction indicated three putative immunogenic peptides. However, immune response on mice showed PEG-rCollinein-1 was devoid of immunogenicity. PEGylation directed rCollinein-1 activity towards hemostasis control, broadening its possibilities to be employed as a defibrinogenant agent.
Shaping attitudes: The association between prior contact with residential aged care and resistance to enter residential aged care
Publisher: Wiley
Date: 05-09-2019
DOI: 10.1111/OPN.12268
Abstract: The ageing population is increasing, and negative attitudes towards older people are all too common and largely overlooked. However, little research has examined how ageist, prejudice, and discrimination, that often occur in healthcare settings, impact the community's perceptions of entering Residential Aged Care (RAC) in the future. In particular, studies have not investigated how contact with RAC influences in iduals' attitudes towards RAC facilities, residents and staff. This study is the first to examine in iduals' resistance towards living in RAC using the contact hypothesis, a theory of prejudice reduction. To explore how positive or negative contact with RAC residents and staff impacts in iduals' behavioural intentions towards entering RAC in the future. To examine whether perceptions of trust, independence and RAC staff mediate the relationship between contact and behavioural intentions towards entering RAC in the future. A cross-sectional survey design. Data were collected via online surveys using contact (positive or negative), trust, independence, perceptions of RAC staff and resistance levels (mild refusal or extreme refusal) measures. Participants (n = 373) from Australia and USA were recruited using social media, word of mouth and Amazons Mechanical Turk. In iduals who experienced negative contact with RAC residents and staff were more likely to report intense resistance to RAC, "I would rather die than enter RAC". Whereas, positive contact with RAC residents and staff was associated with reductions in the adverse appraisal of RAC staff a diminished perception that in iduals lost their independence, and an increased trust in RAC residents, facilities and staff. Participants from USA reported greater levels of resistance towards RAC in comparison with participants from Australia. This study demonstrates how interactions with RAC residents, facilities and staff are critical in shaping attitudes towards RAC. It is recommended that the public are exposed to opportunities where they can experience positive contact with RAC. RAC facilities can promote interaction between the public and RAC residents through encouraging participation in community partnership programs/intergenerational programs.
The Intriguing Phospholipases A2 Homologues: Relevant Structural Features on Myotoxicity and Catalytic Inactivity
Publisher: Bentham Science Publishers Ltd.
Date: 08-2009
DOI: 10.2174/092986609788923310
Abstract: Phospholipases A(2) homologues are found in the venom of Crotalinae snakes, being their main action related to myonecrosis induction. Although many studies on these toxins had already been performed, their mechanism of action remains unclear. Here, important aspects about these toxins are reviewed, including their correct biological assembly and how essential is the natural substitution D49K for their catalytic inactivity.
Adoption Can Be a Risky Business: Risk Factors Predictive of Dogs Adopted from RSPCA Queensland Being Returned
Publisher: MDPI AG
Date: 26-09-2022
DOI: 10.3390/ANI12192568
Abstract: Not all dog adoptions are successful. This two-year retrospective study used survival (i.e., time-to-event) analyses to investigate readmissions for dogs adopted from RSPCA Queensland shelters between 1 January 2019 and 31 December 2020. A better understanding of temporal patterns and risk factors associated with readmission may help RSPCA Queensland shelters better target and tailor resources to improve retention by adopters. The failure function (the cumulative percentage of adoptions that were readmitted by day of the adoption period) increased rapidly during the first 14 days of the adoption period. Approximately two-thirds of all returns occurred in this period. This readmission rate may have been influenced by the RSPCA Queensland adoption-fee refund policy. The cumulative percentage of adoptions that were readmitted plateaued at just under 15%. Dog size, age, coat colour, breed, and spending time in foster before adoption were factors associated with the risk of readmission. Failure functions for a low and a high-risk adoption ex le demonstrated the large degree of difference in hazard of readmission between covariate patterns, with estimated percentages of adoptions being returned by 90 days for those ex les being 2% and 17%, respectively. Spending time in foster care before adoption appears to be protective against readmission, presumably because it supports a successful transition to the new home environment. Behaviour support and training provided for dogs during foster care may contribute to improve their outcomes. These findings highlight the profile of the higher-risk dogs potentially providing shelters with an opportunity to examine where and how resources could be allocated to maximize outcomes for the overall cohort. Population attributable 90-day failure estimates were calculated for each of bodyweight and age at adoption, coat colour, spending time in foster care before adoption, and breed. This calculation shows the expected reduction in the cumulative percentage of dogs readmitted by day 90 if the hazards of readmission for higher risk categories were reduced to those of a lower risk category. Expected reductions for in idual factors ranged from 1.8% to 3.6% with one additional estimate of 6.8%. Risk of readmission could be reduced through increased development of foster capacity and capability, targeted interventions, improved adopter-dog matching processes, and more effective targeting of support for higher risk dogs, such as older or larger dogs. Population impact analyses provide a macro view that could assist shelters in strategically assessing the return on investment for various strategies aiming to improve adoption outcomes and potentially reduce readmissions.
Identification, description and structural analysis of beta phospholipase A2 inhibitors (sbβPLIs) from Latin American pit vipers indicate a binding site region for basic snake venom phospholipases A2
Publisher: Elsevier BV
Date: 04-2019
Letters In Response
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-1997
Structural Basis for the Inhibition of a Phospholipase A2-Like Toxin by Caffeic and Aristolochic Acids
Publisher: Public Library of Science (PLoS)
Date: 20-07-2015
Cognitive Behavior Therapy for Anxiety in Parkinson’s Disease: Outcomes for Patients and Caregivers
Publisher: Informa UK Limited
Date: 04-10-2017
DOI: 10.1080/07317115.2016.1240131
Abstract: Anxiety negatively impacts the quality of life of Parkinson's disease (PD) patients and caregivers. Despite high prevalence, there is a paucity of trials investigating effective treatments for anxiety in PD. This uncontrolled study investigated the use of a manualized and tailored Cognitive Behavior Therapy (CBT) for anxiety in PD. Participants completed 6 weekly CBT sessions. Pre-, post- and follow-up (3 and 6 months) assessments were made. Change in outcomes were analysed using t-tests and Reliability Change Index. Of 17 PD patients who agreed to CBT, 12 completed the intervention. This study showed a significant reduction in Hamilton Anxiety Rating Scale scores in PD immediately post CBT (t(11) = 3.59, p < .01), maintained at 3-month (t(8) = 2.83, p = .02) and 6-month (t(7) = 2.07, p = .04) follow-up. A reduction in caregiver burden (t(11) = 2.68, p = .03) was observed post intervention. Improvements in motor disability (t(11) = 2.41, p = .04) and cognitive scores (t(11) = -2.92, p = .01) were also observed post intervention and at follow-up. Tailored CBT can be used to treat anxiety in PD. This study provides preliminary evidence suggesting that tailored CBT reduces anxiety in PD with persisting benefits, and lowers caregiver burden.
Crystal structure of a myotoxic Asp49-phospholipase A2 with low catalytic activity: Insights into Ca2+-independent catalytic mechanism
Publisher: Elsevier BV
Date: 04-2008
DOI: 10.1016/J.BBAPAP.2008.01.007
Abstract: A myotoxic Asp49-phospholipase A2 (Asp49-PLA2) with low catalytic activity (BthTX-II from Bothrops jararacussu venom) was crystallized and the molecular-replacement solution has been obtained with a dimer in the asymmetric unit. The quaternary structure of BthTX-II resembles the myotoxic Asp49-PLA2 PrTX-III (piratoxin III from B. pirajai venom) and all non-catalytic and myotoxic dimeric Lys49-PLA2S. Despite of this, BthTX-II is different from the highly catalytic and non-myotoxic BthA-I (acidic PLA2 from B. jararacussu) and other Asp49-PLA2S. BthTX-II structure showed a severe distortion of calcium-binding loop leading to displacement of the C-terminal region. Tyr28 side chain, present in this region, is in an opposite position in relation to the same residue in the catalytic activity Asp49-PLA2S, making a hydrogen bond with the atom O delta 2 of the catalytically active Asp49, which should coordinate the calcium. This high distortion may also be confirmed by the inability of BthTX-II to bind Na+ ions at the Ca2+-binding loop, despite of the crystallization to have occurred in the presence of this ion. In contrast, other Asp49-PLA2S which are able to bind Ca2+ ions are also able to bind Na+ ions at this loop. The comparison with other catalytic, non-catalytic and inhibited PLA2S indicates that the BthTX-II is not able to bind calcium ions consequently, we suggest that its low catalytic function is based on an alternative way compared with other PLA2S.
Clinical issues in the treatment of anxiety and depression in older adults with Parkinson's disease
Publisher: Wiley
Date: 09-10-2013
DOI: 10.1002/MDS.25689
Abstract: A significant proportion of persons affected by Parkinson's disease (PD) are over age 65 years. Mental health issues are often less a focus of treatment in this population than physical manifestations of the illness. Anxiety or depression alone, as well as comorbid depression and anxiety, are underrecognized in patients with PD and are associated with deleterious effects on physical and interpersonal functioning, negatively impacting quality of life and well-being. We offer a brief overview of salient clinical points with respect to assessment and treatment approaches to enhance efficacy of the treatment of mental health symptoms in older adults with PD. Cognitive behavior therapy involves the patient learning to overcome behavioral avoidance associated with anxiety and challenge unhelpful negative cognitions. It is suggested that cognitive behavior therapy is an effective approach to treatment of anxiety and depression in PD and should be offered as a treatment to patients.
Structural and Functional Studies of a Bothropic Myotoxin Complexed to Rosmarinic Acid: New Insights into Lys49-PLA2 Inhibition
Publisher: Public Library of Science (PLoS)
Date: 21-12-2011
Structural insights for fatty acid binding in a Lys49-phospholipase A2: crystal structure of myotoxin II from Bothrops moojeni complexed with stearic acid
Publisher: Elsevier BV
Date: 02-2005
DOI: 10.1016/J.BIOCHI.2004.11.005
Abstract: The crystal structure of dimeric Lys49-phospholipase A2 myotoxin-II from Bothrops moojeni (MjTX-II) co-crystallized with stearic acid (C(18)H(36)O(2)) has been determined at a resolution of 1.8 A. The electron density maps permitted the unambiguous inclusion of six stearic acid molecules in the refinement. Two stearic acid molecules could be located in the substrate-binding cleft of each monomer in positions, which favor the interaction of their carboxyl groups with active site residues. The way of binding of stearic acids to this Lys49-PLA(2)s is analogous to phospholipids and transition state analogues to catalytically active PLA(2)s. Two additional stearic acid molecules were located at the dimer interface region, defining a hitherto unidentified acyl-binding site on the protein surface. The strictly conserved Lys122 for Lys49-PLA(2)s may play a fundamental role for stabilization of legend-protein complex. The comparison of MjTX-II/satiric acid complex with other Lys-PLA(2)s structures whose putative fatty acids were located at their active site is also analysed. Molecular details of the stearic acid rotein interactions provide insights to binding in group I/II PLA(2)s, and to the possible interactions of Lys49-PLA(2)s with target membranes.
Structural and functional characterization of suramin-bound MjTX-I from Bothrops moojeni suggests a particular myotoxic mechanism
Publisher: Springer Science and Business Media LLC
Date: 09-07-2018
DOI: 10.1038/S41598-018-28584-7
Abstract: Local myonecrosis is the main event resulting from snakebite envenomation by the Bothrops genus and, frequently, it is not efficiently neutralized by antivenom administration. Proteases, phospholipases A 2 (PLA 2 ) and PLA 2 -like toxins are found in venom related to muscle damage. Functional sites responsible for PLA 2 -like toxins activity have been proposed recently they consist of a membrane docking-site and a membrane rupture-site. Herein, a combination of functional, biophysical and crystallographic techniques was used to characterize the interaction between suramin and MjTX-I (a PLA 2 -like toxin from Bothrops moojeni venom). Functional in vitro neuromuscular assays were performed to study the biological effects of the protein-ligand interaction, demonstrating that suramin neutralizes the myotoxic effect of MjTX-I. Calorimetric assays showed two different binding events: (i) inhibitor-protein interactions and (ii) toxin oligomerization processes. These hypotheses were also corroborated with dynamic light and small angle X-ray scattering assays. The crystal structure of the MjTX-I/suramin showed a totally different interaction mode compared to other PLA 2 -like/suramin complexes. Thus, we suggested a novel myotoxic mechanism for MjTX-I that may be inhibited by suramin. These results can further contribute to the search for inhibitors that will efficiently counteract local myonecrosis in order to be used as an adjuvant of conventional serum therapy.
Initiating Structural Studies Of Lys49-Pla2 Homologues Complexed With An Anionic Detergent, A Fatty Acid And A Natural Lipid
Publisher: Bentham Science Publishers Ltd.
Date: 10-2003
Abstract: Lys49-Phospholipase A2 (Lys49-PLA(2) - EC 3.1.1.4) homologues damage membranes by a Ca2+-independent mechanism which does not involve catalytic activity. Both MjTX-II from Bothrops moojeni and BthTX-I from Bothrops jararacussu are dimeric in solution and in the crystalline states, and a model for the Ca2+-independent membrane damaging mechanism has been suggested in which flexibility at the dimer interface region permits quaternary structural transitions between "open" and "closed" membrane bound dimer conformations which results in the perturbation of membrane phospholipids and disruption of the bilayer structure. With the aim of gaining insights into the structural determinants involved in protein/lipid association, we report here the crystallization and preliminary X-ray analysis of the (i) MjTX-II/SDS complex at a resolution of 2.78A, (ii) MjTX-II/STE complex at a resolution of 1.8 A and (iii) BthTX-I/DMPC complex at 2.72A. These complexes were crystallized by the hanging drop vapour-diffusion technique in (i) HEPES buffer (pH 7.5) 1.8M ammonium sulfate with 2% (w/v) polyethyleneglycol 400, in (ii) 0.6-0.8 M sodium citrate as the precipitant (pH 6.0-6.5) and in (iii) sodium citrate buffer (pH 5.8) and PEG 4000 and 20% isopropanol, respectively. Single crystals of these complexes have been obtained and X-ray diffraction data have been collected at room temperature using a R-AXIS IV imaging plate system and graphite monochromated Cu Kalpha X-ray radiation generated by a Rigaku RU300 rotating anode generator for (i) and (iii) and using using a Synchrotron Radiation Source (Laboratório Nacional de Luz Sincrotron, LNLS, C inas, Brazil) for (ii).
The impact of overshooting deep convection on local transport and mixing in the tropical upper troposphere/lower stratosphere (UTLS)
Publisher: Copernicus GmbH
Date: 12-06-2015
Abstract: Abstract. In this study we examine the simulated downward transport and mixing of stratospheric air into the upper tropical troposphere as observed on a research flight during the SCOUT-O3 c aign in connection with a deep convective system. We use the Advanced Research Weather and Research Forecasting (WRF-ARW) model with a horizontal resolution of 333 m to examine this downward transport. The simulation reproduces the deep convective system, its timing and overshooting altitudes reasonably well compared to radar and aircraft observations. Passive tracers initialised at pre-storm times indicate the downward transport of air from the stratosphere to the upper troposphere as well as upward transport from the boundary layer into the cloud anvils and overshooting tops. For ex le, a passive ozone tracer (i.e. a tracer not undergoing chemical processing) shows an enhancement in the upper troposphere of up to about 30 ppbv locally in the cloud, while the in situ measurements show an increase of 50 ppbv. However, the passive carbon monoxide tracer exhibits an increase, while the observations show a decrease of about 10 ppbv, indicative of an erroneous model representation of the transport processes in the tropical tropopause layer. Furthermore, it could point to insufficient entrainment and detrainment in the model. The simulation shows a general moistening of air in the lower stratosphere, but it also exhibits local dehydration features. Here we use the model to explain the processes causing the transport and also expose areas of inconsistencies between the model and observations.
Health Across Generations: Findings From the Australian Longitudinal Study on Women’s Health
Publisher: SAGE Publications
Date: 22-11-2017
Abstract: Interpretation of changes in health and health care utilization patterns across the life span depends on an understanding of the effects of age, period, and cohort. The purpose of this article is to illustrate differences among three generations of women in demographic factors, health risk factors, and health status indicators from 1996 to 2008. The article examines data from the Australian Longitudinal Study on Women’s Health, a broad-ranging project funded by the Australian Government Department of Health and Ageing (DoHA) and involving three age groups of women (born in the periods 1973—1978, 1946—1951, and 1921—1926) who were first surveyed in 1996 and will be surveyed every 3 years until at least 2015. Patterns in selected demographic factors (marital status and level of educational qualification), health risk factors (smoking, alcohol consumption, physical activity, and body mass index [BMI]), and health status indicators (asthma, hypertension, diabetes and depression physical functioning and mental health scores from the SF-36) were examined to illustrate ex les of biological age, generational differences, or period effects that affect all age groups and generations simultaneously. The results can be used to inform the development of responsive and effective models for both prevention and management of chronic disease, including health and aged-care systems that will meet the needs of different generations of women across their life span.
Prospective observational study of dementia and delirium in the acute hospital setting
Publisher: Wiley
Date: 27-02-2013
DOI: 10.1111/J.1445-5994.2012.02962.X
Abstract: Dementia and delirium appear to be common among older patients admitted to acute hospitals, although there are few Australian data regarding these important conditions. The aim of this study was to determine the prevalence and incidence of dementia and delirium among older patients admitted to acute hospitals in Queensland and to profile these patients. Prospective observational cohort study (n = 493) of patients aged 70 years and older admitted to general medical, general surgical and orthopaedic wards of four acute hospitals in Queensland between 2008 and 2010. Trained research nurses completed comprehensive geriatric assessments and obtained detailed information about each patient's physical, cognitive and psychosocial functioning using the interRAI Acute Care and other standardised instruments. Nurses also visited patients daily to identify incident delirium. Two physicians independently reviewed patients' medical records and assessments to establish the diagnosis of dementia and/or delirium. Overall, 29.4% of patients (n = 145) were considered to have cognitive impairment, including 102 (20.7% of the total) who were considered to have dementia. This rate increased to 47.4% in the oldest patients (aged ≥ 90 years). The overall prevalence of delirium at admission was 9.7% (23.5% in patients with dementia), and the rate of incident delirium was 7.6% (14.7% in patients with dementia). The prevalence of dementia and delirium among older patients admitted to acute hospitals is high and is likely to increase with population aging. It is suggested that hospital design, staffing and processes should be attuned better to meet these patients' needs.
Crystal structure of a phospholipase A2 homolog complexed with p-bromophenacyl bromide reveals important structural changes associated with the inhibition of myotoxic activity
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.BBAPAP.2009.07.005
Abstract: For the first time, the structure of a catalytic inactive phospholipase A(2) homolog (Lys49-PLA(2)s) complexed with p-bromophenacyl bromide (BPB) has been solved by X-ray crystallography. Lys49-PLA(2)s are among the main components of Viperidae snake venoms, causing myonecrosis and other actions despite their catalytic inactivity. BPB, a classic inhibitor of catalytic-active PLA(2)s, has been used since the 1970s because it binds specifically the His48 residue of the catalytic site. Curiously, when Lys49-PLA(2) is chemically modified by BPB, it causes a partial inhibition of the myotoxic function which is associated with the C-terminus and not with the catalytic site. The structure of PrTX-I complexed to BPB revealed unambiguously that the inhibitor binds covalently to His48, causing a distortion of the Ca(2)(+)-binding loop region and C-terminus rearrangement in one of its monomers. The comparison between the apo and BPB-complexed PrTX-I structures showed an increased symmetry between the two monomers with the formation of an interchain hydrogen bond between Tyr119 residues. PrTX-I undergoes tertiary and quaternary structural changes when complexed to BPB which could be related to reduction of myotoxicity and other toxic activities. We also proposed a novel myotoxic inhibition hypothesis integrating "myotoxic" and "active" sites for bothropic Lys49-PLA(2)s.
In vivo uptake of a haem analogue Zn protoporphyrin IX by the human malaria parasite P. falciparum‐infected red blood cells
Publisher: Wiley
Date: 08-2010
DOI: 10.1042/CBI20090427
Who Is Pulling the Leash? Effects of Human Gender and Dog Sex on Human–Dog Dyads When Walking On-Leash
Publisher: MDPI AG
Date: 16-10-2020
DOI: 10.3390/ANI10101894
Abstract: Previous studies have indicated that human gender and canine sex influences human–dog interactions. However, the majority of studies have considered the interaction when dogs were off-leash and the behavioural interactions when dogs are walked on a leash have not been addressed. This study investigated human–dog interactions when shelter volunteers take shelter dogs for an on-leash walk. Video records were made of 370 walks, involving 74 volunteers and 111 shelter dogs, and a leash tension meter was used to determine the pull strength of dogs and walkers. Human gender and canine sex had dyadic effects during the walk. Male dogs tended to pull more frequently and created increased leash tensions. Dogs displayed more stress related behaviours when interacting with men than women, with the signs being spending less time holding the tail in the high position, and more frequent gazing and lip-licking behaviours. Finally, there was a greater pre-disposition in women to use verbal commands, and language typically used with babies, while men were more inclined to have physical contact with dogs. This study’s results may be used to match shelter dogs with appropriate men and women volunteers for walking exercise of the dog, and to improve potential dog socialisation efforts by shelters.
The synthetic varespladib molecule is a multi-functional inhibitor for PLA2 and PLA2-like ophidic toxins
Publisher: Elsevier BV
Date: 07-2021
Structural basis of phospholipase A2-like myotoxin inhibition by chicoric acid, a novel potent inhibitor of ophidian toxins
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.BBAGEN.2018.08.002
Abstract: Specific compounds found in vegetal species have been demonstrated to be efficient inhibitors of snake toxins, such as phospholipase A Myographic and histological techniques were used to evaluate the inhibitory effect of chicoric acid (CA) against BthTX-I myotoxin. Isothermal titration calorimetry assays were used to measure the affinity between the inhibitor and the toxin. X-ray crystallography was used to reveal details of this interaction. CA prevented the blockade of indirectly evoked muscle contraction and inhibited muscle damage induced by BthTX-I. The inhibitor binds to the toxin with the highest affinity measured for a natural compound in calorimetric assays. The crystal structure and molecular dynamics simulations demonstrated that CA binds at the entrance of the hydrophobic channel of the toxin and binds to one of the clusters that participates in membrane disruption. CA prevents the myotoxic activity of the toxin, preventing its activation by simultaneous binding with two critical regions. CA is a potential myotoxic inhibitor to other PLA
Biophysical studies suggest a new structural arrangement of crotoxin and provide insights into its toxic mechanism
Publisher: Springer Science and Business Media LLC
Date: 03-03-2017
DOI: 10.1038/SREP43885
Abstract: Crotoxin (CTX) is the main neurotoxin found in Crotalus durissus rattlesnake venoms being composed by a nontoxic and non-enzymatic component (CA) and a toxic phospholipase A 2 (CB). Previous crystallographic structures of CTX and CB provided relevant insights: (i) CTX structure showed a 1:1 molecular ratio between CA and CB, presenting three tryptophan residues in the CA/CB interface and one exposed to solvent (ii) CB structure displayed a tetrameric conformation. This study aims to provide further information on the CTX mechanism of action by several biophysical methods. Our data show that isolated CB can in fact form tetramers in solution however, these tetramers can be dissociated by CA titration. Furthermore, CTX exhibits a strong reduction in fluorescence intensity and lifetime compared with isolated CA and CB, suggesting that all tryptophan residues in CTX may be hidden by the CA/CB interface. By companying spectroscopy fluorescence and SAXS data, we obtained a new structural model for the CTX heterodimer in which all tryptophans are located in the interface, and the N-terminal region of CB is largely exposed to the solvent. Based on this model, we propose a toxic mechanism of action for CTX, involving the interaction of N-terminal region of CB with the target before CA dissociation.
Interactions of the male contraceptive target EPPIN with semenogelin-1 and small organic ligands
Publisher: Springer Science and Business Media LLC
Date: 09-2023
Comparative Biochemical Studies of Myotoxic Phospholipase A2 From Bothrops Venom
Publisher: Bentham Science Publishers Ltd.
Date: 06-2001
PLA2-like proteins myotoxic mechanism: a dynamic model description
Publisher: Springer Science and Business Media LLC
Date: 14-11-2017
DOI: 10.1038/S41598-017-15614-Z
Abstract: Phospholipase A 2 -like (PLA 2 -like) proteins contribute to the development of muscle necrosis in Viperidae snake bites and are not efficiently neutralized by current antivenom treatments. The toxic mechanisms of PLA 2 -like proteins are devoid of catalytic activity and not yet fully understood, although structural and functional experiments suggest a dimeric assembly and that the C-terminal residues are essential to myotoxicity. Herein, we characterized the functional mechanism of bothropic PLA 2 -like structures related to global and local measurements using the available models in the Protein Data Bank and normal mode molecular dynamics (NM-MD). Those measurements include: (i) new geometric descriptions between their monomers, based on Euler angles (ii) characterizations of canonical and non-canonical conformations of the C-terminal residues (iii) accessibility of the hydrophobic channel (iv) inspection of ligands and (v) distance of clustered residues to toxin interface of interaction. Thus, we described the allosteric activation of PLA 2 -like proteins and hypothesized that the natural movement between monomers, calculated from NM-MD, is related to their membrane disruption mechanism, which is important for future studies of the inhibition process. These methods and strategies can be applied to other proteins to help understand their mechanisms of action.
Crystallization and preliminary X-ray diffraction analysis of a Lys49-phospholipase A2complexed with caffeic acid, a molecule with inhibitory properties against snake venoms
Publisher: International Union of Crystallography (IUCr)
Date: 22-01-2011
Structural and Functional Characterization of Neuwiedase, a Nonhemorrhagic Fibrin(ogen)olytic Metalloprotease from Bothrops neuwiedi Snake Venom
Publisher: Elsevier BV
Date: 09-2000
Abstract: A fibrino(geno)lytic nonhemorrhagic metalloprotease (neuwiedase) was purified from Bothrops neuwiedi snake venom by a single chromatographic step procedure on a CM-Sepharose column. Neuwiedase represented 4.5% (w/w) of the crude desiccated venom, with an approximate Mr of 20,000 and pI 5.9. As regards the amino acid composition, neuwiedase showed similarities with other metalloproteases, with high proportions of Asx, Glx, Leu, and Ser. Atomic absorption spectroscopy showed that one mole of Zn2+ and one mole of Ca2+ were present per mole of protein. The cDNA encoding neuwiedase was isolated by RT-PCR from venom gland RNA, using oligonucleotides based on the partially determined amino-acid sequences of this metalloprotease. The full sequence contained approximately 594 bp, which codified the 198 amino acid residues with an estimated molecular weight of 22,375. Comparison of the nucleotide and amino acid sequences of neuwiedase with those of other snake venom metalloproteases showed a high level of sequential similarity. Neuwiedase has two highly conserved characteristics sequences H142E143XXH146XXG149XXH152 and C164I165M166. The three-dimensional structure of neuwiedase was modeled based on the crystal structure of Crotalus adamanteus Adamalysin II. This model revealed that the zinc binding site region showed a high structural similarity with other metalloproteases. The proteolyitc specificity, using the Bbeta-chain of oxidized insulin as substrate, was shown to be directed to the Ala14-Leu15 and Tyr16-Leu17 peptide bonds which were preferentially hydrolyzed. Neuwiedase is a Aalpha,Bbeta fibrinogenase. Its activity upon the Aalpha chain of fibrinogen was detected within 15 min of incubation. The optimal temperature and pH for the degradation of both Aalpha and Bbeta chains were 37 degrees C and 7.4-8.0, respectively. This activity was inhibited by EDTA and 1,10-phenantroline. Neuwiedase also showed proteolytic activity upon fibrin and some components of the extracellular matrix. However, it did not show TAME esterase activity and was not able to inhibit platelet aggregation.
The Importance of Social Groups for Retirement Adjustment: Evidence, Application, and Policy Implications of the Social Identity Model of Identity Change
Publisher: Wiley
Date: 07-10-2019
DOI: 10.1111/SIPR.12049
Structural and Phylogenetic Studies with MjTX-I Reveal a Multi-Oligomeric Toxin – a Novel Feature in Lys49-PLA2s Protein Class
Publisher: Public Library of Science (PLoS)
Date: 03-04-2013
Providing information on mental well-being during audiological consultations: exploring barriers and facilitators using the COM-B model
Publisher: Informa UK Limited
Date: 17-02-2023
Structure of Importin-α from a Filamentous Fungus in Complex with a Classical Nuclear Localization Signal
Publisher: Public Library of Science (PLoS)
Date: 19-06-2015
Role of flanking sequences and phosphorylation in the recognition of the simian-virus-40 large T-antigen nuclear localization sequences by importin-
Publisher: Portland Press Ltd.
Date: 15-10-2003
DOI: 10.1042/BJ20030510
Abstract: The nuclear import of simian-virus-40 large T-antigen (tumour antigen) is enhanced via phosphorylation by the protein kinase CK2 at Ser112 in the vicinity of the NLS (nuclear localization sequence). To determine the structural basis of the effect of the sequences flanking the basic cluster KKKRK, and the effect of phosphorylation on the recognition of the NLS by the nuclear import factor importin-α (Impα), we co-crystallized non-autoinhibited Impα with peptides corresponding to the phosphorylated and non-phosphorylated forms of the NLS, and determined the crystal structures of the complexes. The structures show that the amino acids N-terminally flanking the basic cluster make specific contacts with the receptor that are distinct from the interactions between bipartite NLSs and Impα. We confirm the important role of flanking sequences using binding assays. Unexpectedly, the regions of the peptides containing the phosphorylation site do not make specific contacts with the receptor. Binding assays confirm that phosphorylation does not increase the affinity of the T-antigen NLS to Impα. We conclude that the sequences flanking the basic clusters in NLSs play a crucial role in nuclear import by modulating the recognition of the NLS by Impα, whereas phosphorylation of the T-antigen enhances nuclear import by a mechanism that does not involve a direct interaction of the phosphorylated residue with Impα.
The Availability of Psychological Services for Aged Care Residents in Australia: A Survey of Facility Staff
Publisher: Informa UK Limited
Date: 12-2017
DOI: 10.1111/AP.12244
Structural and functional evidence for membrane docking and disruption sites on phospholipase A2-like proteins revealed by complexation with the inhibitor suramin
Publisher: International Union of Crystallography (IUCr)
Date: 26-09-2015
DOI: 10.1107/S1399004715014443
Abstract: Local myonecrosis resulting from snakebite envenomation is not efficiently neutralized by regular antivenom administration. This limitation is considered to be a significant health problem by the World Health Organization. Phospholipase A 2 -like (PLA 2 -like) proteins are among the most important proteins related to the muscle damage resulting from several snake venoms. However, despite their conserved tertiary structure compared with PLA 2 s, their biological mechanism remains incompletely understood. Different oligomeric conformations and binding sites have been identified or proposed, leading to contradictory data in the literature. In the last few years, a comprehensive hypothesis has been proposed based on fatty-acid binding, allosteric changes and the presence of two different interaction sites. In the present study, a combination of techniques were used to fully understand the structural–functional characteristics of the interaction between suramin and MjTX-II (a PLA 2 -like toxin). In vitro neuromuscular studies were performed to characterize the biological effects of the protein–ligand interaction and demonstrated that suramin neutralizes the myotoxic activity of MjTX-II. The high-resolution structure of the complex identified the toxin–ligand interaction sites. Calorimetric assays showed two different binding events between the protein and the inhibitor. It is demonstrated for the first time that the inhibitor binds to the surface of the toxin, obstructing the sites involved in membrane docking and disruption according to the proposed myotoxic mechanism. Furthermore, higher-order oligomeric formation by interaction with interfacial suramins was observed, which may also aid the inhibitory process. These results further substantiate the current myotoxic mechanism and shed light on the search for efficient inhibitors of the local myonecrosis phenomenon.
Molecular Components of the Neurospora crassa pH Signaling Pathway and Their Regulation by pH and the PAC-3 Transcription Factor
Publisher: Public Library of Science (PLoS)
Date: 24-08-2016
P3‐151: Change in adiposity measures and cognition in Australian aging women
Publisher: Wiley
Date: 07-2010
A C-type lectin induces NLRP3 inflammasome activation via TLR4 interaction in human peripheral blood mononuclear cells
Publisher: Springer Science and Business Media LLC
Date: 22-06-2023
Crystallization and preliminary X-ray diffraction analysis of a myotoxic Lys49-PLA2fromBothrops jararacussuvenom complexed withp-bromophenacyl bromide
Publisher: International Union of Crystallography (IUCr)
Date: 31-05-2006
Structural Biology and Regulation of Protein Import into the Nucleus
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.JMB.2015.10.023
Abstract: Proteins are translated in the cytoplasm, but many need to access the nucleus to perform their functions. Understanding how these nuclear proteins are transported through the nuclear envelope and how the import processes are regulated is therefore an important aspect of understanding cell function. Structural biology has played a key role in understanding the molecular events during the transport processes and their regulation, including the recognition of nuclear targeting signals by the corresponding receptors. Here, we review the structural basis of the principal nuclear import pathways and the molecular basis of their regulation. The pathways involve transport factors that are members of the β-karyopherin family, which can bind cargo directly (e.g., importin-β, transportin-1, transportin-3, importin-13) or through adaptor proteins (e.g., importin-α, snurportin-1, symportin-1), as well as unrelated transport factors such as Hikeshi, involved in the transport of heat-shock proteins, and NTF2, involved in the transport of RanGDP. Solenoid proteins feature prominently in these pathways. Nuclear transport factors recognize nuclear targeting signals on the cargo proteins, including the classical nuclear localization signals, recognized by the adaptor importin-α, and the PY nuclear localization signals, recognized by transportin-1. Post-translational modifications, particularly phosphorylation, constitute key regulatory mechanisms operating in these pathways.
Neutralization of a bothropic PLA2-like protein by caftaric acid, a novel potent inhibitor of ophidian myotoxicity
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.BIOCHI.2020.01.010
Abstract: Envenoming by snakebite is an important global health issue that has received little attention, leading the World Health Organization to naming it as neglected tropical disease. Several snakebites present serious local symptoms manifested on victims that may not be efficiently neutralized by serum therapy. Phospholipase A
Exploring the health and wellbeing benefits of gardening for older adults
Publisher: Cambridge University Press (CUP)
Date: 27-08-2014
DOI: 10.1017/S0144686X14000865
Abstract: Research shows that contact with nature plays a vital role in our psychological wellbeing. Domestic gardening is common among older adults who spend more leisure hours gardening than any other age group. Despite this, few studies have systematically explored the significance of domestic gardens in relation to older adults' health and wellbeing. This study examined the perceived therapeutic benefits of gardening, and the effect of ageing in relation to older gardeners' continued participation in gardening, using quantitative and qualitative data from a survey of Australian older adult gardeners (N=331). The quantitative data, which included frequencies, were analysed using the PASW Statistics 18.0 package. The qualitative data, which included participants' responses to open questions, were analysed by deriving themes via Leximancer, an innovative text analytics software that uses word association information to elicit concepts, extracting the most important and grouping these according to themes. In relation to the reasons for gardening, several themes were identified including valuing the aesthetics of gardens, connecting with nature, achievement, and physical and mental activity. The benefits of gardening, and the variety of ways that respondents had adapted or modified their gardening activities in order to continue, are also reported. Gardening was more than a casual leisure pursuit for these participants, who saw it as critical to their physical and psychological wellbeing.
Comparison between apo and complexed structures of bothropstoxin-I reveals the role of Lys122 and Ca2+-binding loop region for the catalytically inactive Lys49-PLA2s
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.JSB.2010.03.019
Abstract: Phospholipases A(2) (Asp49-PLA(2)s) are enzymes responsible for cellular membrane disruption through Ca(2+)-dependent hydrolysis of phospholipids. A class of these proteins (Lys49-PLA(2)s) does not show catalytic activity but can exert a pronounced local myotoxic effect that is not neutralized by serum therapy. In this work, we present five structures of Lys49-PLA(2)s from snakes of the Bothrops genus in apo form, complexed with PEG molecules and chemically modified by p-bromofenacil bromide (BPB), a classic inhibitor of PLA(2). We present herein an extensive structural analysis including: (i) the function of hydrophobic long-chain molecules as Lys49-PLA(2)s inhibitors, (ii) the role of Lys122, previously indicated as being responsible for Lys49-PLA(2)s catalytic inactivity and, (iii) a structural comparison of the Ca(2+)-binding loop region between Lys49 and Asp49-PLA(2)s. The Lys122 analysis of 30 different monomers for apo and complexed Lys49-PLA(2)s structures shows that this residue is very flexible and may bind to different carboxyl groups giving stability to the crystal structures. The structural comparisons of the Ca(2+)-binding loop region between Lys49 and Asp49-PLA(2)s reveal the importance of the Tyr28 residue conservation in Asp49-PLA(2)s to the integrity of this loop. The Tyr28 residue stabilizes this region by an interaction with Gly35 residue. In Lys49-PLA(2)s and low-catalytic Asp49-PLA(2)s this interaction does not occur, preventing the binding of Ca(2+).
RPA-1 from Leishmania amazonensis (LaRPA-1) structurally differs from other eukaryote RPA-1 and interacts with telomeric DNA via its N-terminal OB-fold domain
Publisher: Wiley
Date: 15-11-2014
DOI: 10.1016/J.FEBSLET.2014.11.005
Abstract: Replication protein A-1 (RPA-1) is a single-stranded DNA-binding protein involved in DNA metabolism. We previously demonstrated the interaction between LaRPA-1 and telomeric DNA. Here, we expressed and purified truncated mutants of LaRPA-1 and used circular dichroism measurements and molecular dynamics simulations to demonstrate that the tertiary structure of LaRPA-1 differs from human and yeast RPA-1. LaRPA-1 interacts with telomeric ssDNA via its N-terminal OB-fold domain, whereas RPA from higher eukaryotes show different binding modes to ssDNA. Our results show that LaRPA-1 is evolutionary distinct from other RPA-1 proteins and can potentially be used for targeting trypanosomatid telomeres.
Structural and functional studies of a snake venom phospholipase A2-like protein complexed to an inhibitor from Tabernaemontana catharinensis
Publisher: Elsevier BV
Date: 03-2023
DOI: 10.1016/J.BIOCHI.2022.10.011
Abstract: Snake envenomation is an ongoing global health problem and tropical neglected disease that afflicts millions of people each year. The only specific treatment, antivenom, has several limitations that affects its proper distribution to the victims and its efficacy against local effects, such as myonecrosis. The main responsible for this consequence are the phospholipases A
Functional and structural studies of a Phospholipase A2-like protein complexed to zinc ions: Insights on its myotoxicity and inhibition mechanism
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.BBAGEN.2016.08.003
Abstract: One of the main challenges in snakebite envenomation treatment is the development of stable, versatile and efficient anti-venom therapies. Local myotoxicity in accidents involving snakes from the Bothrops genus is still a consequence of serum therapy inefficient neutralization that may lead to permanent sequelae in their victims. One of the classes of toxins that participate in muscle necrosis is the PLA Myographic and electrophysiological techniques were used to evaluate the inhibitory effect of zinc ions, isothermal titration calorimetry assays were used to measure the affinity between zinc ions and the toxin and X-ray crystallography was used to reveal details of this interaction. We demonstrated that zinc ions can effectively inhibit the toxin by the interaction with two different sites, which are related to two different mechanism of inhibition: preventing membrane disruption and impairing the toxin state transition. Furthermore, structural study presented here included an additional step in the current myotoxic mechanism improving the comprehension of the allosteric transition that PLA Our findings show that zinc ions are inhibitors of PLA Zinc is a new candidate that can assist in anti-venom treatments and can promote the design of new and even more accurate structure-based inhibitors for PLA
Crystallization and preliminary X-ray crystallographic analysis of importin-α fromNeurospora crassa
Publisher: International Union of Crystallography (IUCr)
Date: 25-03-2202
DOI: 10.1107/S2053230X14005068
Abstract: Importin-α recognizes cargo proteins that contain classical nuclear localization sequences (NLS) and, in complex with importin-β, is able to translocate nuclear proteins through the nuclear pore complex. The filamentous fungus Neurospora crassa is a well studied organism that has been widely used as a model organism for fundamental aspects of eukaryotic biology, and is important for understanding the specific mechanisms of protein transport to the cell nucleus. In this work, the crystallization and preliminary X-ray diffraction analysis of importin-α from N. crassa (IMPα-Nc) complexed with a classical NLS peptide (SV40 NLS) are reported. IMPα-Nc–SV40 NLS crystals diffracted X-rays to 2.0 Å resolution and the structure was solved by molecular-replacement techniques, leading to a monomeric structure. The observation of the electron-density map indicated the presence of SV40 NLSs interacting at both the minor and major NLS-binding sites of the protein.
Crystallization and preliminary X-ray crystallographic studies of a Lys49-phospholipase A2homologue fromBothrops pirajaivenom complexed with rosmarinic acid
Publisher: International Union of Crystallography (IUCr)
Date: 27-05-2010
Structural basis of nuclear import of flap endonuclease 1 (FEN1)
Publisher: International Union of Crystallography (IUCr)
Date: 15-06-2012
Biochemical, pharmacological and structural characterization of BmooMP-I, a new P–I metalloproteinase from Bothrops moojeni venom
Publisher: Elsevier BV
Date: 12-2020
The clinical spectrum of anxiety in Parkinson's disease
Publisher: Wiley
Date: 07-2014
DOI: 10.1002/MDS.25937
Abstract: Anxiety is common in Parkinson's disease (PD), and contributes to increased disability and poorer quality of life. In spite of its significant impact, the symptomatology, chronology, and neurobiology of anxiety in PD are all poorly understood, and this hinders accurate diagnosis and development of effective treatment strategies. This review investigates and updates literature related to the clinical spectrum of anxiety in PD. The reported prevalence of anxiety in PD varies considerably, with emerging interest in the frequency of the DSM-IV residual category of "Anxiety disorder, not otherwise specified" (Anxiety disorder NOS), which is observed in up to 25% of PD patients. By design, there are no standardized diagnostic criteria for Anxiety disorder NOS, because this is the category applied to in iduals who do not meet diagnostic criteria for any other current anxiety disorder. Anxiety rating scales incompletely capture anxiety symptoms that relate specifically to PD symptoms and the complications arising from PD therapy. Consequently, these scales have been deemed inappropriate for use in PD, and there remains a need for the development of a new PD-specific anxiety scale. Research establishing accurate symptom profiles of anxiety in PD is sparse, although characterizing such symptomatology would likely improve clinical diagnosis and facilitate targeted treatment strategies. Research into the neurobiological and psychological underpinnings of anxiety in PD remains inconclusive. Anxiety can precede the onset of PD motor symptoms or can develop after a diagnosis of PD. Further investigations focused on the chronology of anxiety and its relationship to PD diagnosis are required.
Relationship between changes in body weight and cognitive function in middle-aged and older women
Publisher: Wiley
Date: 11-10-2012
DOI: 10.1002/GPS.2797
Abstract: Although several longitudinal studies indicate that weight loss precedes dementia in men and women, the relationship between weight changes and cognitive performance is unclear. This study investigated the relationship between changes in adiposity and cognitive function in community-dwelling women. Data were derived from the Longitudinal Assessment of Women Study, a population-based study of 511 urban women initially aged 40-79 years. We analyzed data from 334 women who had complete information on demographics, cardiovascular risk factors, medical status, weight, height, and waist-to-hip ratio and cognitive scores at baseline and after a mean of 7.45 years of follow-up. Cognition was assessed at baseline and follow-up using the Mini Mental State Examination the Auditory Delayed Index, Visual Delayed Index, and Working Memory Index from the Wechsler Memory Scale, Third Edition and the Processing Speed Index from the Wechsler Adult Intelligence Scale, Third Edition. Associations were adjusted for age, education, baseline cognitive performance, cardiovascular risk factors, menopausal status, and apolipoprotein E-4 status. In multivariate analysis, both weight gain and loss were associated with poor Visual Delayed Index performance at follow-up compared with stable weight (β = -4.02 ± 1.57, p = 0.011 β = -6.50 ± 2.39, p = 0.007, respectively). No significant associations were found between body mass index, waist circumference, or waist-to-hip ratio and any cognitive domains at follow-up. Changes in cognitive performance were not associated with changes in adiposity measures. Weight loss and weight gain were associated with poor cognitive performance in middle-aged and older women compared with women with stable weight.
Phylogenetic and structural studies of a novel equine papillomavirus identified from aural plaques
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.VETMIC.2012.08.025
Abstract: Papillomaviruses (PVs) infect a wide range of animal species and show great genetic ersity. To date, excluding equine sarcoids, only three species of PVs were identified associated with lesions in horses: Equus caballus papillomavirus 1 (EcPV1-cutaneous), EcPV2 (genital) and EcPV3 (aural plaques). In this study, we identified a novel equine PV from aural plaques, which we designated EcPV4. Cutaneous s les from horses with lesions that were microscopically diagnosed as aural plaques were subjected to DNA extraction, lification and sequencing. Rolling circle lification and inverse PCR with specific primers confirmed the presence of an approximately 8 kb circular genome. The full-length EcPV4 L1 major capsid protein sequence has 1488 nucleotides (495 amino acids). EcPV4 had a sequence identity of only 53.3%, 60.2% and 51.7% when compared with the published sequences for EcPV1, EcPV2 and EcPV3, respectively. A Bayesian phylogenetic analysis indicated that EcPV4 clusters with EcPV2, but not with EcPV1 and EcPV3. Using the current PV classification system that is based on the nucleotide sequence of L1, we could not define the genus of the newly identified virus. Therefore, a structural analysis of the L1 protein was carried out to aid in this classification because EcPV4 cause lesion similar to the lesion caused by EcPV3. A comparison of the superficial loops demonstrated a distinct amino acid conservation pattern between EcPV4/EcPV2 and EcPV4/EcPV3. These results demonstrate the presence of a new equine PV species and that structural studies could be useful in the classification of PVs.
Crystal structures of BnSP-7 and BnSP-6, two Lys49-phospholipases A2: quaternary structure and inhibition mechanism insights
Publisher: Elsevier BV
Date: 11-2003
DOI: 10.1016/J.BBRC.2003.10.047
Abstract: Phospholipases A(2) are components of Bothrops venoms responsible for disruption of cell membrane integrity via hydrolysis of its phospholipids. A class of PLA(2)-like proteins has been described which despite PLA(2) activity on artificial substrate, due to a D49K mutation, is still highly myonecrotic. This work reports the X-ray structure determination of two Lys49-PLA(2)s from Bothrops neuwiedi pauloensis (BnSP-7 and BnSP-6) and, for the first time, the comparison of eight dimeric Lys49-PLA(2)s. This comparison reveals that there are not just two ("open" and "closed") but at least six different conformations. The binding of fatty acid observed in three recent Lys49-PLA(2) structures seems to be independent of their quaternary conformation. Cys29 polarization by Lys122 is not significant for BnSP-7 and BnSP-6 or other structures not bound by fatty acids. These structures may be in an "active" state when nothing is bound to them and the Lys122/Cys29 interactions are weak or absent.
Anxiety rating scales in Parkinson's disease: a critical review updating recent literature
Publisher: Cambridge University Press (CUP)
Date: 23-06-2015
DOI: 10.1017/S1041610215000885
Abstract: Assessing anxiety in Parkinson's disease (PD) has been a recent focus, and a number of studies have extensively investigated the validity of anxiety rating scales in PD. The present review aims to provide an overview of anxiety scales widely used and/or validated in PD, and to highlight recommendations for future research required in this area. A literature search was performed using terms such as Parkinson* disease, psychiatric, depress*, anxiety, assessment, scales, and valid* in PsycInfo, PubMed, and Web of Science databases. Validation studies and reviews focussed on assessment of anxiety in PD were included. The literature search identified nine anxiety rating scales. The new Parkinson's Anxiety Scale (PAS) showed good psychometric properties. Having a simple design appropriate for older adults and items focussed on cognitive anxiety, the Geriatric Anxiety Inventory (GAI) also appeared promising for use in PD. The Beck Anxiety Inventory (BAI), Hospital Anxiety and Depression Scale, and Hamilton Anxiety Rating Scale (HAM-A) did not demonstrate satisfactory psychometric characteristics when used in PD, while other scales had limited or no evidence of validity or reliability to infer judgments. PAS and GAI are can be recommended for use in PD without dementia. Usefulness of these scales to assess anxiety in dementia should be examined in the future. Moreover, the complex symptomatology of anxiety relating to “off” PD medication states were not addressed in these scales. Further research is required to develop an anxiety scale tailored for PD.
Editorial
Publisher: Bentham Science Publishers Ltd.
Date: 08-2009
Walking behaviour and patterns of perceived access to neighbourhood destinations in older adults from a low-density (Brisbane, Australia) and an ultra-dense city (Hong Kong, China)
Publisher: Elsevier BV
Date: 2019
Companion Animals and Health in Older Populations: A Systematic Review
Publisher: Informa UK Limited
Date: 17-08-2019
DOI: 10.1080/07317115.2019.1650863
Abstract: . The aim of this systematic literature review (SLR) was to investigate the effect of companion animals (whether simply as pets or used in more formal intervention approaches) on the physical and mental health of older adults (aged 60+). . The reviewers identified key search terms and conducted a systematic search of the PsycINFO and PubMed databases. The 70 articles reviewed were evaluated through tabular and thematic analysis. . In 52 of the studies examined, companion animals positively contributed to the mental and/or physical health of older adults. With respect to mental health, involvement with a companion animal improved participant quality of life and effectively attenuated symptoms of depression, anxiety, cognitive impairment, and the behavioral and psychiatric symptoms of dementia (BPSD). In relation to physical health, marked increases in physical activity and improvements in blood pressure and heart rate variability were the only consistent physical health improvements observed from companion animal interactions. . Animal companionship can benefit the mental and physical health of older adults, although more and better controlled research on this topic is required. . Use of companion animals has the potential to be an effective treatment or adjunct therapy to improve the health status and quality of life of older in iduals.
Triacontyl p-coumarate: An inhibitor of snake venom metalloproteinases
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.PHYTOCHEM.2012.10.007
Abstract: Snake venom metalloproteinases (SVMPs) participate in a number of important biological, physiological and pathophysiological processes and are primarily responsible for the local tissue damage characteristic of viperid snake envenomations. The use of medicinal plant extracts as antidotes against animal venoms is an old practice, especially against snake envenomations. Such plants are sources of many pharmacologically active compounds and have been shown to antagonize the effects of some venoms and toxins. The present study explores the activity of triacontyl p-coumarate (PCT), an active compound isolated from root bark of Bombacopsis glabra vegetal extract (Bg), against harmful effects of Bothropoides pauloensis snake venom and isolated toxins (SVMPs or phospholipase A(2)). Before inhibition assays, Bg or PCT was incubated with venom or toxins at ratios of 1:1 and 1:5 (w/w venom or isolated toxins/PCT) for 30 min at 37°C. Treatment conditions were also assayed to simulate snakebite with PCT inoculated at either the same venom or toxin site. PCT neutralized fibrinogenolytic activity and plasmatic fibrinogen depletion induced by B. pauloensis venom or isolated toxin. PCT also efficiently inhibited the hemorrhagic (3MDH - minimum hemorrhagic dose injected i.d into mice) and myotoxic activities induced by Jararhagin, a metalloproteinase from B. jararaca at 1:5 ratio (toxin: inhibitor, w/w) when it was previously incubated with PCT and injected into mice or when PCT was administered after toxin injection. Docking simulations using data on a metalloproteinase (Neuwiedase) structure suggest that the binding between the protein and the inhibitor occurs mainly in the active site region causing blockade of the enzymatic reaction by displacement of catalytic water. Steric hindrance may also play a role in the mechanism since the PCT hydrophobic tail was found to interact with the loop associated with substrate anchorage. Thus, PCT may provide a alternative to complement ophidian envenomation treatments.
DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.BIOCHI.2017.11.013
Abstract: MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The in idual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed.
Quantitative Decomposition of Dynamics of Mathematical Cell Models: Method and Application to Ventricular Myocyte Models
Publisher: Public Library of Science (PLoS)
Date: 19-06-2015
Structural Basis of Importin-α-Mediated Nuclear Transport for Ku70 and Ku80
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.JMB.2011.07.038
Abstract: Ku70 and Ku80 form a heterodimeric complex involved in multiple nuclear processes. This complex plays a key role in DNA repair due to its ability to bind DNA double-strand breaks and facilitate repair by the nonhomologous end-joining pathway. Ku70 and Ku80 have been proposed to contain bipartite and monopartite nuclear localization sequences (NLSs), respectively, that allow them to be translocated to the nucleus independently of each other via the classical importin-α (Impα)/importin-β-mediated nuclear import pathway. To determine the structural basis of the recognition of Ku70 and Ku80 proteins by Impα, we solved the crystal structures of the complexes of Impα with the peptides corresponding to the Ku70 and Ku80 NLSs. Our structural studies confirm the binding of the Ku80 NLS as a classical monopartite NLS but reveal an unexpected binding mode for Ku70 NLS with only one basic cluster bound to the receptor. Both Ku70 and Ku80 therefore contain monopartite NLSs, and sequences outside the basic cluster make favorable interactions with Impα, suggesting that this may be a general feature in monopartite NLSs. We show that the Ku70 NLS has a higher affinity for Impα than the Ku80 NLS, consistent with more extensive interactions in its N-terminal region. The prospect of nuclear import of Ku70 and Ku80 independently of each other provides a powerful regulatory mechanism for the function of the Ku70/Ku80 heterodimer and independent functions of the two proteins.
Structural basis of recognition of monopartite and bipartite nuclear localization sequences by mammalian importin-α11Edited by K. Nagai
Publisher: Elsevier BV
Date: 04-2000
Cultivating the Acceptance of Assistance Dogs in Aged Care through Deliberative Democracy
Publisher: MDPI AG
Date: 20-08-2023
DOI: 10.3390/ANI13162680
Abstract: Assistance dogs provide significant benefits to older adult owners. However, despite protective legislation, aged care facilities continue to not allow owners to retain their dogs on relocation. The purpose of the current study was to explore whether older adults should be allowed to retain their dog on relocation to an aged care facility, and what factors should impact this decision. Further, if allowed to retain their dog, what would be the best practice to allow for this? A deliberative democracy methodology was used, with a range of key stakeholders recruited. Focus groups were held, with follow-up questionnaires to establish deliberation for all questions. Results indicated that with sufficient objective measurement, fair decisions can be made to ensure the welfare and well-being of the owner and dog. Key policy and procedure changes would also be necessary to ensure ongoing support, such as training, care plans, and emergency directives. By ensuring sufficient policies and procedures are in place, training and support could lead to an ideal outcome where facilities could be at the forefront of a better future for aged care.
Neuromuscular paralysis by the basic phospholipase A 2 subunit of crotoxin from Crotalus durissus terrificus snake venom needs its acid chaperone to concurrently inhibit acetylcholine release and prod
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.TAAP.2017.08.021
Abstract: Crotoxin (CTX), a heterodimeric phospholipase A Experiments were conducted using mice phrenic-diaphragm preparations. Real-time fluorescence video microscopy and liquid scintillation spectrometry techniques were used to detect transmitter exocytosis and nerve-evoked [ Both CTX (5μg/mL) and its basic PLA Data show that CTX exerts a presynaptic inhibitory action on ACh release that is highly dependent on its intrinsic PLA
Validity and reliability of the Geriatric Anxiety Inventory in Parkinson's disease*
Publisher: Wiley
Date: 29-12-2012
DOI: 10.1111/J.1741-6612.2010.00487.X
Abstract: To examine the psychometric properties of a novel anxiety rating scale, the Geriatric Anxiety Inventory (GAI) in Parkinson's disease (PD). The predictive validity of the GAI was tested against the presence of any DSM-IV anxiety disorders in 58 PD patients using receiver operating curve analysis. The concurrent validity of this scale was also studied against the state half of the Spielberger State Trait Anxiety Inventory (STAI). The internal consistency and test-retest reliability of the GAI were also examined. The GAI displayed good concurrent validity against the STAI and the DSM-IV. It also showed good internal consistency and test-retest reliability. This study suggested that the GAI is an appropriate scale to use in non-demented PD patients.
Structural and functional properties of Bp-LAAO, a new l-amino acid oxidase isolated from Bothrops pauloensis snake venom
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.BIOCHI.2008.12.004
Abstract: An L-amino acid oxidase (Bp-LAAO) from Bothrops pauloensis snake venom was highly purified using sequential chromatography steps on CM-Sepharose, Phenyl-Sepharose CL-4B, Benzamidine Sepharose and C18 reverse-phase HPLC. Purified Bp-LAAO showed to be a homodimeric acidic glycoprotein with molecular weight around 65kDa under reducing conditions in SDS-PAGE. The best substrates for Bp-LAAO were L-Met, L-Leu, L-Phe and L-Ile and the enzyme showed a strong reduction of its catalytic activity upon L-Met and L-Phe substrates at extreme temperatures. Bp-LAAO showed leishmanicidal, antitumoral and bactericidal activities dose dependently. Bp-LAAO induced platelet aggregation in platelet-rich plasma and this activity was inhibited by catalase. Bp-LAAO-cDNA of 1548bp codified a mature protein with 516 amino acid residues corresponding to a theoretical isoelectric point and molecular weight of 6.3 and 58kDa, respectively. Additionally, structural and phylogenetic studies identified residues under positive selection and their probable location in Bp-LAAO and other snake venom LAAOs (svLAAOs). Structural and functional investigations of these enzymes can contribute to the advancement of toxinology and to the elaboration of novel therapeutic agents.
Still in first gear: Exploration of barriers for implementing driving cessation support
Publisher: Wiley
Date: 26-05-2023
DOI: 10.1111/AJAG.13218
Abstract: Driving cessation is a major life transition lack of support in this process may lead to deleterious outcomes in terms of physical, mental and social well‐being. Despite approaches to driving cessation being developed, their integration into ongoing geriatric clinical practice has been slow. Health‐care providers were surveyed about their impressions of the barriers and facilitators to implementing a driving cessation intervention as part of regular clinical services. Methods of funding the intervention were queried. Surveys were sent via professional listserves and a snowballing strategy employed. Twenty‐nine completed surveys were analysed by content analysis. Participants identified that an understanding of driving cessation and optimal driving cessation supports was required. They identified four key approaches to support the implementation of driving cessation support: the need to consider complexity and emotional support needs in clinical contexts knowing and showing the outcomes by clearly communicating the benefits and values to different stakeholders managing systemic barriers included workforce issues, funding models and efforts required for initiating and sustaining an intervention and not doing it alone , but instead developing processes supports to collaboratively provide access to programs. The current study reveals a recognition of unmet needs of older persons and families regarding driving cessation as well as signalling service delivery, costing and workforce needs which act as barriers.
Brief on the Role of Psychologists in Residential and Home Care Services for Older Adults
Publisher: Informa UK Limited
Date: 12-2017
DOI: 10.1111/AP.12209
Management of Sleep Disturbances in Parkinson’s Disease Patients, Carers and the Patient and Carer Dyadic Relationship: A Scoping Review
Publisher: Informa UK Limited
Date: 13-11-2020
DOI: 10.1080/07317115.2018.1539424
Abstract: Sleep disturbances are a debilitating non-motor symptom in Parkinson's disease (PD) and negatively impact patients, their carers and the patient-carer dyadic relationship. This review outlines the phenomenology, as well as factors associated with and treatment of sleep disturbances, in PD patients and their informal carers. The following terms were used in four databases: Parkinson*, sleep* disturbance*, carer*, dyad*, intervention* and treatment*. Across the articles reviewed, the frequency of reported sleep disturbances in PD ranged between 60% and 98%. Common sleep problems in PD included insomnia, excessive day time sleepiness, REM sleep behavior disorder (RBD), sleep apnoea, periodic limb movements and sleep attacks. Within dyads, significant correlations were found with depression, anxiety and carer burden relating to night time care in particular. Despite the negative impact of sleep disturbance in PD, the evidence-base for treatment remains limited. While addressing in idual factors associated with sleep disturbances, it is also important to emphasize the needs arising from the patient-carer dyadic relationship. While a number of non-pharmacological interventions were suggested in the literature, further well-controlled trials are still required. Multiple approaches are required to reduce sleep disturbances and associated burden in PD.
Different motivations for volunteering are associated with different outcomes for Australian animal welfare volunteers: a mixed-methods analysis
Publisher: Informa UK Limited
Date: 23-01-2023
Structural basis for phospholipase A2-like toxin inhibition by the synthetic compound Varespladib (LY315920)
Publisher: Springer Science and Business Media LLC
Date: 20-11-2019
DOI: 10.1038/S41598-019-53755-5
Abstract: The World Health Organization recently listed snakebite envenoming as a Neglected Tropical Disease, proposing strategies to significantly reduce the global burden of this complex pathology by 2030. In this context, effective adjuvant treatments to complement conventional antivenom therapy based on inhibitory molecules for specific venom toxins have gained renewed interest. Varespladib (LY315920) is a synthetic molecule clinically tested to block inflammatory cascades of several diseases associated with elevated levels of secreted phospholipase A 2 (sPLA 2 ). Most recently, Varespladib was tested against several whole snake venoms and isolated PLA 2 toxins, demonstrating potent inhibitory activity. Herein, we describe the first structural and functional study of the complex between Varespladib and a PLA 2 -like snake venom toxin (MjTX-II). In vitro and in vivo experiments showed this compound’s capacity to inhibit the cytotoxic and myotoxic effects of MjTX-II from the medically important South American snake, Bothrops moojeni . Crystallographic and bioinformatics analyses revealed interactions of Varespladib with two specific regions of the toxin, suggesting inhibition occurs by physical blockage of its allosteric activation, preventing the alignment of its functional sites and, consequently, impairing its ability to disrupt membranes. Furthermore, based on the analysis of several crystallographic structures, a distinction between toxin activators and inhibitors is proposed.
Culturally Appropriate Assessment of Depression and Anxiety in Older Torres Strait Islanders: Limitations and Recommendations
Publisher: Informa UK Limited
Date: 13-06-2022
DOI: 10.1080/07317115.2022.2086090
Abstract: The aim of the study was to assess the prevalence of anxiety and depression in older Aboriginal and Torres Strait Islander adults. A modified version of the PHQ-9 (KICA-dep) and the Geriatric Anxiety Inventory (GAI) were administered as part of a wider dementia prevalence study conducted in the Torres Strait. Results were compared to diagnoses obtained on Geriatric review to evaluate their applicability in the region. A total of 236 participants completed the KICA-dep and 184 completed the GAI short form. Of these, 10.6% were identified with depression and 15.8% with anxiety. Some participants found questions about suicide ideation and self-harm offensive and others had difficulty understanding concepts on the GAI. The KICA-dep performed poorly in comparison to diagnosis on geriatric clinical review, so results are unlikely to reflect the true prevalence of depression in the region. Further research is required to explore the underlying dimensions of depression and anxiety and terminology used to express mood symptoms in the Torres Strait. • Current mental health screening tools are not applicable for the Torres Strait• More work is required to determine how symptoms of depression and anxiety are expressed within Torres Strait communities.
Alkylation of Histidine Residues ofBothrops jararacussuVenom Proteins and Isolated Phospholipases
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/981923
Abstract: Crude venom of Bothrops jararacussu and isolated phospholipases A 2 (PLA 2 ) of this toxin (BthTX-I and BthTX-II) were chemically modified (alkylation) by p -bromophenacyl bromide (BPB) in order to study antibody production capacity in function of the structure-function relationship of these substances (crude venom and PLA 2 native and alkylated). BthTX-II showed enzymatic activity, while BthTX-I did not. Alkylation reduced BthTX-II activity by 50% while this process abolished the catalytic and myotoxic activities of BthTX-I, while reducing its edema-inducing activity by about 50%. Antibody production against the native and alkylated forms of BthTX-I and -II and the cross-reactivity of antibodies to native and alkylated toxins did not show any apparent differences and these observations were reinforced by surface plasmon resonance (SPR) data. Histopathological analysis of mouse gastrocnemius muscle sections after injection of PBS, BthTX-I, BthTX-II, or both myotoxins previously incubated with neutralizing antibody showed inhibition of the toxin-induced myotoxicity. These results reveal that the chemical modification of the phospholipases A 2 (PLA 2 ) diminished their toxicity but did not alter their antigenicity. This observation indicates that the modified PLA 2 may provide a biotechnological tool to attenuate the toxicity of the crude venom, by improving the production of antibodies and decreasing the local toxic effects of this poisonous substance in animals used to produce antivenom.
Are the national guidelines for health behaviour appropriate for older Australians? Evidence from the Men, Women and Ageing project
Publisher: Wiley
Date: 29-12-2010
DOI: 10.1111/J.1741-6612.2010.00498.X
Abstract: To review findings from the Men, Women and Ageing (MWA) longitudinal studies and consider their implications for national health guidelines. Guidelines for good health for older adults in the areas of body mass index (BMI), physical activity, alcohol consumption and smoking behaviours are compared with MWA findings. Findings from MWA suggest that current BMI guidelines may be too narrow because BMI in the overweight range appears to be protective for both older men and women. Across all levels of BMI, even low levels of physical activity decrease mortality risk compared with being sedentary. Our findings suggest that consideration should be given to having different alcohol guidelines for older men and women and should include recommendations for alcohol-free days. The benefit of quitting smoking at any age is apparent for both women and men. Current national guidelines in the areas discussed in this paper should be reviewed for older people.
RuCl2(CO)2(N-methylimidazole)2Isomers: Synthesis, Characterization and Reactivity
Publisher: Sociedade Brasileira de Quimica (SBQ)
Date: 1996
Molecular characterization and phylogenetic analysis of BjussuMP-I: A RGD-P-III class hemorrhagic metalloprotease from Bothrops jararacussu snake venom
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1016/J.JMGM.2006.09.010
Abstract: Snake venom metalloproteases (SVMPs) embody zinc-dependent multidomain enzymes responsible for a relevant pathophysiology in envenomation, including local and systemic hemorrhage. The molecular features responsible for hemorrhagic potency of SVMPs have been associated with their multidomains structures which can target these proteins them to several receptors of different tissues and cellular types. BjussuMP-I, a SVMP isolated from the Bothrops jararacussu venom, has been characterized as a P-III hemorrhagic metalloprotease. The complete cDNA sequence of BjussuMP-I with 1641bp encodes open reading frames of 547 amino acid residues, which conserve the common domains of P-III high molecular weight hemorrhagic metalloproteases: (i) pre-pro-peptide, (ii) metalloprotease, (iii) disintegrin-like and (iv) rich cysteine domain. BjussuMP-I induced lyses in fibrin clots and inhibited collagen- and ADP-induced platelet aggregation. We are reporting, for the first time, the primary structure of an RGD-P-III class snake venom metalloprotease. A phylogenetic analysis of the BjussuMP-I metalloprotease/catalytic domain was performed to get new insights into the molecular evolution of the metalloproteases. A theoretical molecular model of this domain was built through folding recognition (threading) techniques and refined by molecular dynamics simulation. Then, the final BjussuMP-I catalytic domain model was compared to other SVMPs and Reprolysin family proteins in order to identify eventual structural differences, which could help to understand the biochemical activities of these enzymes. The presence of large hydrophobic areas and some conserved surface charge-positive residues were identified as important features of the SVMPs and other metalloproteases.
Synthesis, characterization and molecular structures of the pyridinium trans-bis(pyridine)tetrachlororuthenate(III) and pyridinium trans-(carbonyl)(pyridine)tetrachlororuthenate(III)
Publisher: FapUNIFESP (SciELO)
Date: 1997
SEQUENCE SLIDER: expanding polyalanine fragments for phasing with multiple side-chain hypotheses
Publisher: International Union of Crystallography (IUCr)
Date: 25-02-2020
DOI: 10.1107/S2059798320000339
Abstract: Fragment-based molecular-replacement methods can solve a macromolecular structure quasi- ab initio . ARCIMBOLDO , using a common secondary-structure or tertiary-structure template or a library of folds, locates these with Phaser and reveals the rest of the structure by density modification and autotracing in SHELXE . The latter stage is challenging when dealing with diffraction data at lower resolution, low solvent content, high β-sheet composition or situations in which the initial fragments represent a low fraction of the total scattering or where their accuracy is low. SEQUENCE SLIDER aims to overcome these complications by extending the initial polyalanine fragment with side chains in a multisolution framework. Its use is illustrated on test cases and previously unknown structures. The selection and order of fragments to be extended follows the decrease in log-likelihood gain (LLG) calculated with Phaser upon the omission of each single fragment. When the starting substructure is derived from a remote homolog, sequence assignment to fragments is restricted by the original alignment. Otherwise, the secondary-structure prediction is matched to that found in fragments and traces. Sequence hypotheses are trialled in a brute-force approach through side-chain building and refinement. Scoring the refined models through their LLG in Phaser may allow discrimination of the correct sequence or filter the best partial structures for further density modification and autotracing. The default limits for the number of models to pursue are hardware dependent. In its most economic implementation, suitable for a single laptop, the main-chain trace is extended as polyserine rather than trialling models with different sequence assignments, which requires a grid or multicore machine. SEQUENCE SLIDER has been instrumental in solving two novel structures: that of MltC from 2.7 Å resolution data and that of a pneumococcal lipoprotein with 638 residues and 35% solvent content.
Structural bases for a complete myotoxic mechanism: Crystal structures of two non-catalytic phospholipases A2-like from Bothrops brazili venom
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.BBAPAP.2013.10.009
Abstract: Bothrops brazili is a snake found in the forests of the Amazonian region whose commercial therapeutic anti-bothropic serum has low efficacy for local myotoxic effects, resulting in an important public health problem in this area. Catalytically inactive phospholipases A2-like (Lys49-PLA2s) are among the main components from Bothrops genus venoms and are capable of causing drastic myonecrosis. Several studies have shown that the C-terminal region of these toxins, which includes a variable combination of positively charged and hydrophobic residues, is responsible for their activity. In this work we describe the crystal structures of two Lys49-PLA2s (BbTX-II and MTX-II) from B. brazili venom and a comprehensive structural comparison with several Lys49-PLA2s. Based on these results, two independent sites of interaction were identified between protein and membrane which leads to the proposition of a new myotoxic mechanism for bothropic Lys49-PLA2s composed of five different steps. This proposition is able to fully explain the action of these toxins and may be useful to develop efficient inhibitors to complement the conventional antivenom administration.
Structure and catalytic mechanism of glucosamine 6-phosphate deaminase from Escherichia coli at 2.1 å resolution
Publisher: Elsevier BV
Date: 12-1995
DOI: 10.1016/S0969-2126(01)00270-2
Abstract: Glucosamine 6-phosphate deaminase from Escherichia coli is an allosteric hexameric enzyme which catalyzes the reversible conversion of D-glucosamine 6-phosphate into D-fructose 6-phosphate and ammonium ion and is activated by N-acetyl-D-glucosamine 6-phosphate. Mechanistically, it belongs to the group of aldoseketose isomerases, but its reaction also accomplishes a simultaneous amination/deamination. The determination of the structure of this protein provides fundamental knowledge for understanding its mode of action and the nature of allosteric conformational changes that regulate its function. The crystal structure of glucosamine 6-phosphate deaminase with bound phosphate ions is presented at 2.1 A resolution together with the refined structures of the enzyme in complexes with its allosteric activator and with a competitive inhibitor. The protein fold can be described as a modified NAD-binding domain. From the similarities between the three presented structures, it is concluded that these represent the enzymatically active R state conformer. A mechanism for the deaminase reaction is proposed. It comprises steps to open the pyranose ring of the substrate and a sequence of general base-catalyzed reactions to bring about isomerization and deamination, with Asp72 playing a key role as a proton exchanger.
Anti-Metalloprotease P-I Single-Domain Antibodies: Tools for Next-Generation Snakebite Antivenoms
Publisher: Hindawi Limited
Date: 19-07-2022
DOI: 10.1155/2022/2748962
Abstract: In order to address the global antivenom crisis, novel antivenoms need to present high therapeutic efficacy, broad neutralization ability against systemic and local damage, sufficient safety, and cost-effectiveness. Due to biological characteristics of camelid single-domain antibodies (VHH) such as high affinity, their ability to penetrate dense tissues, and facility for genetic manipulation, their application in antivenoms has expanded considerably. VHHs that are active against the metalloprotease BjussuMP-II from the snake Bothrops jararacussu were selected. After isolation of BjussuMP-II, a camelid was immunized with the purified toxin in order to construct the recombinant phage library. Following a round of biopanning, 52% of the selected clones were able to recognize BjussuMP-II in an ELISA assay. After sequencing, seven sequence profiles were identified. One selected clone (VHH61) showed cross-reactivity to B. brazili venom, but did not recognize the Crotalus and Lachesis genera, indicating specificity for the Bothrops genus. Through in vitro tests, the capacity to neutralize the toxicity triggered by BjussuMP-II was observed. Circular dichroism spectroscopy indicated a robust secondary structure for VHH61, and the calculated melting temperature ( T M ) for the clone was 56.4°C. In silico analysis, through molecular docking of anti-BjussuMP-II VHHs with metalloprotease, revealed their potential interaction with amino acids present in regions critical for the toxin’s conformation and stability. The findings suggest that anti-BjussuMP-II VHHs may be beneficial in the development of next-generation antivenoms.
Caring for a loved one with Parkinson’s disease: the role of coping styles and relationship quality
Publisher: Cambridge University Press (CUP)
Date: 07-02-2022
DOI: 10.1017/S1041610221002866
Abstract: Informal carers play an essential role in the care of in iduals with Parkinson’s disease (PD). This role, however, is often fraught with difficulties, including emotional, physical, and financial. Coping styles and relationship quality have been hypothesized to influence the impact of stressors. The aim of this study is to examine the relationship between carers’ coping style, relationship quality, and carer burden. Cross-sectional. Thirty-nine PD patient carer dyads were included in the study. Participants completed self-rated questionnaires including the Dyadic Adjustment Scale, Zarit Burden Interview, and Brief Coping Orientation to Problems Experienced Inventory. Correlational analyses found significant and positive correlation between carer burden and all three coping styles (problem-focused, emotion-focused, and dysfunctional). There was also a moderate association between carers’ perceived relationship quality and satisfaction and carer burden. Regression analyses found that carer’s gender, severity of PD, relationship quality, emotion-focused, and dysfunctional coping styles did not predict carer burden. Conversely, problem-focused coping style predicted carer burden. The results highlight that there is no perfect way to react and care for a loved one and serves as important information for practitioners who design and implement interventions.
Biochemical, functional, structural and phylogenetic studies on Intercro, a new isoform phospholipase A2 from Crotalus durissus terrificus snake venom
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.BIOCHI.2013.08.028
Abstract: Crotoxin is a neurotoxin from Crotalus durissus terrificus venom that shows immunomodulatory, anti-inflammatory, antimicrobial, antitumor and analgesic activities. Structurally, this toxin is a heterodimeric complex composed by a toxic basic PLA2 (Crotoxin B or CB) non-covalently linked to an atoxic non-enzymatic and acidic component (Crotapotin, Crotoxin A or CA). Several CA and CB isoforms have been isolated and characterized, showing that the crotoxin venom fraction is, in fact, a mixture of different molecules derived from the combination of distinct subunit isoforms. Intercro (IC) is a protein from the same snake venom which presents high similarity in primary structure to CB, indicating that it could be an another isoform of this toxin. In this work, we compare IC to the crotoxin complex (CA/CB) and/or CB in order to understand its functional aspects. The experiments with IC revealed that it is a new toxin with different biological activities from CB, keeping its catalytic activity but presenting low myotoxicity and absence of neurotoxic activity. The results also indicated that IC is structurally similar to CB isoforms, but probably it is not able to form a neurotoxic active complex with crotoxin A as observed for CB. Moreover, structural and phylogenetic data suggest that IC is a new toxin with possible toxic effects not related to the typical CB neurotoxin.
Crystallization and preliminary X-ray diffraction analysis of crotoxin B fromCrotalus durissus collilineatusvenom
Publisher: International Union of Crystallography (IUCr)
Date: 23-09-2009
Memory and communication support in dementia: Research-based strategies for caregivers
Publisher: Cambridge University Press (CUP)
Date: 20-09-2011
DOI: 10.1017/S1041610210001845
Abstract: Background: Difficulties with memory and communication are prominent and distressing features of dementia which impact on the person with dementia and contribute to caregiver stress and burden. There is a need to provide caregivers with strategies to support and maximize memory and communication abilities in people with dementia. In this project, a team of clinicians, researchers and educators in neuropsychology, psychogeriatrics, nursing and speech pathology translated research-based knowledge from these fields into a program of practical strategies for everyday use by family and professional caregivers. Methods: From the available research evidence, the project team identified compensatory or facilitative strategies to assist with common areas of difficulty, and structured these under the mnemonics RECAPS (for memory) and MESSAGE (for communication). This information was adapted for presentation in a DVD-based education program in accordance with known characteristics of effective caregiver education. Results: The resultant DVD comprises (1) information on the nature and importance of memory and communication in everyday life (2) explanations of common patterns of difficulty and preserved ability in memory and communication across the stages of dementia (3) acted vignettes demonstrating the strategies, based on authentic s les of speech in dementia and (4) scenarios to prompt the viewer to consider the benefits of using the strategies. Conclusion: Using a knowledge-translation framework, information and strategies can be provided to family and professional caregivers to help them optimize residual memory and communication in people with dementia. Future development of the materials, incorporating consumer feedback, will focus on methods for enabling wider dissemination.
Update of recent literature on remotely delivered psychotherapy interventions for anxiety and depression
Publisher: Mary Ann Liebert Inc
Date: 08-2019
Bothrops moojeni myotoxin-II, a Lys49-phospholipase A2 homologue: An example of function versatility of snake venom proteins
Publisher: Elsevier BV
Date: 03-2006
DOI: 10.1016/J.CBPC.2005.11.020
Abstract: MjTX-II, a myotoxic phospholipase A(2) (PLA(2)) homologue from Bothrops moojeni venom, was functionally and structurally characterized. The MjTX-II characterization included: (i) functional characterization (antitumoral, antimicrobial and antiparasitic effects) (ii) effects of structural modifications by 4-bromophenacyl bromide (BPB), cyanogen bromide (CNBr), acetic anhydride and 2-nitrobenzenesulphonyl fluoride (NBSF) (iii) enzymatic characterization: inhibition by low molecular weight heparin and EDTA and (iv) molecular characterization: cDNA sequence and molecular structure prediction. The results demonstrated that MjTX-II displayed antimicrobial activity by growth inhibition against Escherichia coli and Candida albicans, antitumoral activity against Erlich ascitic tumor (EAT), human breast adenocarcinoma (SK-BR-3) and human T leukemia cells (JURKAT) and antiparasitic effects against Schistosoma mansoni and Leishmania spp., which makes MjTX-II a promising molecular model for future therapeutic applications, as well as other multifunctional homologous Lys49-PLA(2)s or even derived peptides. This work provides useful insights into the structural determinants of the action of Lys49-PLA(2) homologues and, together with additional strategies, supports the concept of the presence of others "bioactive sites" distinct from the catalytic site in snake venom myotoxic PLA(2)s.
BthTX-II from Bothrops jararacussu venom has variants with different oligomeric assemblies: An example of snake venom phospholipases A2 versatility
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.IJBIOMAC.2021.09.083
Abstract: Phospholipases A
Recurrent readmissions in medical patients: A prospective study
Publisher: Wiley
Date: 12-10-2010
DOI: 10.1002/JHM.811
Abstract: Hospital readmissions are common and costly. A recent previous hospitalization preceding the index admission is a marker of increased risk of future readmission. To identify factors associated with an increased risk of recurrent readmission in medical patients with 2 or more hospitalizations in the past 6 months. Prospective cohort study. Australian teaching hospital acute medical wards, February 2006-February 2007. 142 inpatients aged ≥ 50 years with a previous hospitalization ≤ 6 months preceding the index admission. Patients from residential care, with terminal illness, or with serious cognitive or language difficulties were excluded. Demographics, previous hospitalizations, diagnosis, comorbidities and nutritional status were recorded in hospital. Participants were assessed at home within 2 weeks of hospital discharge using validated questionnaires for cognition, literacy, activities of daily living (ADL)/instrumental activities of daily living (IADL) function, depression, anxiety, alcohol use, medication adherence, social support, and financial status. Unplanned readmission to the study hospital within 6 months. A total of 55 participants (38.7%) had a further unplanned hospital admission within 6 months. In multivariate analysis, chronic disease (adjusted odds ratio [OR] 3.4 95% confidence interval [CI], 1.3-9.3, P = 0.002), depressive symptoms (adjusted OR, 3.0 95% CI, 1.3-6.8, P = 0.01), and underweight (adjusted OR, 12.7 95% CI, 2.3-70.7, P = 0.004) were significant predictors of readmission after adjusting for age, length of stay and functional status. In this high-risk patient group, multiple chronic conditions are common and predict increased risk of readmission. Post-hospital interventions should consider targeting nutritional and mood status in this population.
Factors related to sleep disturbances for individuals with Parkinson’s disease: a regional perspective
Publisher: Cambridge University Press (CUP)
Date: 23-09-2019
DOI: 10.1017/S1041610219001212
Abstract: Sleep disturbances negatively impact the quality of life of patients with Parkinson’s disease (PD). While persons living in regional areas are at higher risk of PD, PD is poorly managed in regional communities. This study examined factors associated with sleep problems in PD in a regional context. A mixed-methods cross-sectional design was used. Patients with PD were recruited from the Queensland Parkinson’s Project database. Those who agreed to participate were sent a questionnaire assessing aspects of sleep, depression, anxiety, quality of life, and PD severity. Qualitative information was also gathered. Correlations between variables were examined thematic analyses were performed for qualitative data. All participants (n = 49) reported sleep disturbances, with 73% (n = 36) reporting sleep disturbance to be problematic. Global sleep dysfunction positively correlated with daytime napping (r = .34, p = .01), watching the clock when unable to sleep (r = .38, p = .01), staying in bed when unable to sleep (r = .43, p = .01), and going to bed hungry (r = .31, p = .03) and negatively correlated with daytime exercise (r = -.32, p = .02). Positive correlations were observed between global sleep dysfunction and depression (r = .55, p = .01), anxiety (r = .31, p = .04), and dysfunctional sleep beliefs (r = .39, p = .01). There is a clear need for identifying factors related to sleep disturbances in PD for effective management.
Secreted Phospholipases A2 from Animal Venoms in Pain and Analgesia
Publisher: MDPI AG
Date: 19-12-2017
Preliminary X-ray crystallographic studies of BthTX-II, a myotoxic Asp49-phospholipase A2with low catalytic activity fromBothrops jararacussuvenom
Publisher: International Union of Crystallography (IUCr)
Date: 24-07-2006
Positive ageing and gardening: development and testing of a gardening survey measuring benefits of leisure gardening
Publisher: International Society for Horticultural Science (ISHS)
Date: 07-2016
Nuclear transport of the Neurospora crassa NIT-2 transcription factor is mediated by importin-α
Publisher: Portland Press Ltd.
Date: 06-12-2017
DOI: 10.1042/BCJ20170654
Abstract: The Neurospora crassa NIT-2 transcription factor belongs to the GATA transcription factor family and plays a fundamental role in the regulation of nitrogen metabolism. Because NIT-2 acts by accessing DNA inside the nucleus, understanding the nuclear import process of NIT-2 is necessary to characterize its function. Thus, in the present study, NIT-2 nuclear transport was investigated using a combination of biochemical, cellular, and biophysical methods. A complemented strain that produced an sfGFP–NIT-2 fusion protein was constructed, and nuclear localization assessments were made under conditions that favored protein translocation to the nucleus. Nuclear translocation was also investigated using HeLa cells, which showed that the putative NIT-2 nuclear localization sequence (NLS 915TISSKRQRRHSKS927) was recognized by importin-α and that subsequent transport occurred via the classical import pathway. The interaction between the N. crassa importin-α (NcImpα) and the NIT-2 NLS was quantified with calorimetric assays, leading to the observation that the peptide bound to two sites with different affinities, which is typical of a monopartite NLS sequence. The crystal structure of the NcImpα/NIT-2 NLS complex was solved and revealed that the NIT-2 peptide binds to NcImpα with the major NLS-binding site playing a primary role. This result contrasts other recent studies that suggested a major role for the minor NLS-binding site in importin-α from the α2 family, indicating that both sites can be used for different cargo proteins according to specific metabolic requirements.
Using indoor plants and natural elements to positively impact occupants of residential aged-care facilities
Publisher: International Society for Horticultural Science (ISHS)
Date: 07-2016
Mitochondrial sirtuin TcSir2rp3 affects TcSODA activity and oxidative stress response in Trypanosoma cruzi
Publisher: Cold Spring Harbor Laboratory
Date: 06-09-2021
DOI: 10.1101/2021.09.06.458705
Abstract: Trypanosoma cruzi , the etiological agent of Chagas disease, faces a variety of environmental scenarios during its life cycle in both invertebrate and vertebrate hosts, which include changes in the redox environment that requires a fine regulation of a complex antioxidant arsenal of enzymes. Reversible post-translational modifications, as lysine acetylation, are a fast and economical way for cells to react to environmental conditions. Acetylation neutralizes the lysine positive charge conferring novel properties to the modified proteins, from changes in enzymatic activity to subcellular localization. Recently, we found that the main antioxidant enzymes, including the mitochondrial superoxide dismutase A (TcSODA) are acetylated in T. cruzi , suggesting that protein acetylation could participate in the oxidative stress response in T. cruzi . Therefore, we investigated whether mitochondrial lysine deacetylase sirtuin 3 (TcSir2rp3) was involved in the activity control of TcSODA. We observed an increased resistance to hydrogen peroxide and menadione two oxidant compounds in parasites overexpressing TcSir2rp3. Increased resistance was also found for benznidazole and nifurtimox, the two drugs available for treatment of Chagas disease, known to induce reactive oxidative and nitrosactive species in the parasite. In parallel, TcSir2rp3 overexpressing parasites showed parasites showed a reduction in the ROS levels after treatment with benznidazole and nifurtimox, suggesting a role of TcSir2rp3 in the oxidative stress response. To better understand the way TcSir2rp3 could contributes to oxidative stress response, we analyzed the expression of a key antioxidant enzyme, TcSODA, in the TcSir2rp3 overexpressing parasites and did not detect any increase in protein levels of this enzyme. However, we found that parasites overexpressing TcSir2rp3 presented higher levels of superoxide dismutase activity, and also that TcSir2rp3 and TcSODA interacts in vivo. Knowing that TcSODA is acetylated at lysine residues K44 and K97, and that K97 is located at similar region in the protein structure as K68 in human manganese superoxide dismutase (MnSOD), responsible to regulates MnSOD activity, we generated mutated versions of TcSODA at K44 and K97 and found that replacing K97 by glutamine, which mimics an acetylated lysine, negatively affects the enzyme activity in vitro. By using molecular dynamics approaches we revealed that acetylation of K97 induces specific conformational changes in TcSODA with respect of hydrogen bonding pattern to neighbor residues, specifically D94 and E96, suggesting a key participation of this residue to modulate the affinity to O 2 - by changing the charge availability on the surface of the enzyme. Taken together, our results showed for the first time the involvement of lysine acetylation in the maintenance of homeostatic redox state in trypanosomatids, contributing to the understanding of mechanisms used by T. cruzi to progress during the infection and opening the opportunity to explore protein acetylation as potential drug target in this parasite.
Characteristics of Cognitive Behavioral Therapy for Older Adults Living in Residential Care: Protocol for a Systematic Review (Preprint)
Publisher: JMIR Publications Inc.
Date: 21-01-2018
Abstract: he prevalence rates of depressive and anxiety disorders are high in residential aged care settings. Older adults in such settings might be prone to these disorders because of losses associated with transitioning to residential care, uncertainty about the future, as well as a decline in personal autonomy, health, and cognition. Cognitive behavioral therapy (CBT) is efficacious in treating late-life depression and anxiety. However, there remains a dearth of studies examining CBT in residential settings compared with community settings. Typically, older adults living in residential settings have higher care needs than those living in the community. To date, no systematic reviews have been conducted on the content and the delivery characteristics of CBT for older adults living in residential aged care settings. he objective of this paper is to describe the systematic review protocol on the characteristics of CBT for depression and/or anxiety for older adults living in residential aged care settings. his protocol was developed in compliance with the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Studies that fulfill the inclusion criteria will be identified by systematically searching relevant electronic databases, reference lists, and citation indexes. In addition, the PRISMA flowchart will be used to record the selection process. A pilot-tested data collection form will be used to extract and record data from the included studies. Two reviewers will be involved in screening the titles and abstracts of retrieved records, screening the full text of potentially relevant reports, and extracting data. Then, the delivery and content characteristics of different CBT programs of the included studies, where available, will be summarized in a table. Furthermore, the Downs and Black checklist will be used to assess the methodological quality of the included studies. ystematic searches will commence in May 2018, and data extraction is expected to commence in July 2018. Data analyses and writing will happen in October 2018. n this section, the limitations of the systematic review will be outlined. Clinical implications for treating late-life depression and/or anxiety, and implications for residential care facilities will be discussed. ROSPERO 42017080113 www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=80113 (Archived by WebCite at 0dV4Qf54) R1-10.2196/9902
Prospective observational study of dementia in older patients admitted to acute hospitals
Publisher: Wiley
Date: 23-04-2013
DOI: 10.1111/AJAG.12021
Abstract: Few Australian studies have examined the impact of dementia on hospital outcomes. The aim of this study was to determine the relative contribution of dementia to adverse outcomes in older hospital patients. Prospective observational cohort study (n = 493) of patients aged ≥70 years admitted to four acute hospitals in Queensland. Trained research nurses completed comprehensive geriatric assessments using standardised instruments and collected data regarding adverse outcomes. The diagnosis of dementia was established by independent physician review of patients' medical records and assessments. Patients with dementia (n = 102, 20.7%) were significantly older (P = 0.01), had poorer functional ability (P < 0.01), and were more likely to have delirium at admission (P < 0.01) than patients without dementia. Dementia (odds ratio = 4.8, P < 0.001) increased the risk of developing delirium during the hospital stay. Older patients with dementia are more impaired and vulnerable than patients without dementia and are at greater risk of adverse outcomes when hospitalised.
Social prescribing: A narrative review of how community engagement can improve wellbeing in later life
Publisher: Wiley
Date: 14-06-2022
DOI: 10.1002/CASP.2631
Abstract: Social prescribing is being proposed by policy makers as a solution to primarily address lowered wellbeing and increased loneliness in older adults. Previous reviews have found a lack of supporting evidence for social prescribing. However, these reviews were using a narrow definition which may have left out some important evaluations. Therefore, this review aims to evaluate the evidence for social prescribing programs using a broader definition to encompasses a variety of referral pathways and activities. The review was conducted by searching PsycINFO, PubMed, Scopus, and ProQuest Social Sciences databases, and a final 77 articles were included. We found that there were five main themes in the outcomes reported: social connection improvement in the management of health and health status improvement in mental health and wellbeing life enrichment and link worker support. Social prescribing programs appeared to have generally positive impacts however there was a large variety in both programs reported and quality of the research, which made drawing definitive conclusions difficult. Researchers evaluating programs in future should attempt to recruit larger s le sizes and use a mixed methods approach to further examine the evidence base for social prescribing.
Barriers and facilitators to asking adults with hearing loss about their emotional and psychological well-being: a COM-B analysis
Publisher: Informa UK Limited
Date: 18-04-2023
DOI: 10.1080/14992027.2022.2056090
Abstract: To explore the barriers and facilitators faced by hearing healthcare clinicians (HHCs) with respect to asking adults with hearing loss (HL) about their emotional well-being. This qualitative study was conducted using semi-structured in idual interviews and focus groups. The interview topic guide was developed based on the COM-B model. Fifteen HHCs of a single hearing services organisation in Western Australia across 13 clinic locations participated. Barriers and facilitators that may influence HHCs' behaviour of routinely asking adults about their emotional well-being include having the knowledge and skills to ask about emotional well-being, forgetting to ask, awareness of the emotional impacts of HL, time and tools for asking, clients' reactions to being asked, supportive peers, normalisation of discussions relating to emotional well-being, presence of significant others, emotions associated with asking, being in the habit of asking, reminders, beliefs about consequences and confidence or capabilities, and scope of audiology practice. Application of the COM-B model identified barriers in capabilities (e.g. knowledge), opportunities (e.g. tools), and motivation (e.g. beliefs about benefits of asking about emotions) that need to be addressed for HHCs to ask their clients about their emotional well-being.
Comparative structural studies on Lys49-phospholipases A2 from Bothrops genus reveal their myotoxic site
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.JSB.2009.04.003
Abstract: Phospholipases A(2) (PLA(2)s) are membrane-associated enzymes that hydrolyze phospholipids at the sn-2 position, releasing lysophospholipids and free fatty acids. Phospholipase A(2) homologues (Lys49-PLA(2)s) are highly myotoxic and cause extensive tissue damage despite not showing measurable catalytic activity. They are found in different snake venoms and represent one third of bothropic venom composition. The importance of these toxins during envenomation is related to the pronounced local myotoxic effect they induce since this effect is not neutralized by serum therapy. We present herein three structures of Lys49-PLA(2)s from Bothrops genus snake venom crystallized under the same conditions, two of which were grown in the presence of alpha-tocopherol (vitamin E). Comparative structural analysis of these and other Lys49-PLA(2)s showed two different patterns of oligomeric conformation that are related to the presence or absence of ligands in the hydrophobic channel. This work also confirms the biological dimer indicated by recent studies in which both C-termini are in the dimeric interface. In this configuration, we propose that the myotoxic site of these toxins is composed by the Lys 20, Lys115 and Arg118 residues. For the first time, a residue from the short-helix (Lys20) is suggested as a member of this site and the importance of Tyr119 residue to myotoxicity of bothropic Lys49-PLA(2)s is also discussed. These results support a complete hypothesis for these PLA(2)s myotoxic activity consistent with all findings on bothropic Lys49-PLA(2)s studied up to this moment, including crystallographic, bioinformatics, biochemical and biophysical data.
Crotoxin: Novel activities for a classic β-neurotoxin
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.TOXICON.2010.01.011
Abstract: Crotoxin, the main toxin of South American rattlesnake (Crotalus durissus terrificus) venom, was the first snake venom protein to be purified and crystallized. Crotoxin is a heterodimeric beta-neurotoxin that consists of a weakly toxic basic phospholipase A(2) and a non-enzymatic, non-toxic acidic component (crotapotin). The classic biological activities normally attributed to crotoxin include neurotoxicity, myotoxicity, nephrotoxicity and cardiotoxicity. However, numerous studies in recent years have shown that crotoxin also has immunomodulatory, anti-inflammatory, anti-microbial, anti-tumor and analgesic actions. In this review, we describe the historical background to the discovery of crotoxin and its main toxic activities and then discuss recent structure-function studies and investigations that have led to the identification of novel pharmacological activities for the toxin.
Isolation and biochemical characterization of a γ-type phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.TOXICON.2014.01.012
Abstract: In the present work, we describe the isolation and partial structural and biochemical characterization of the first phospholipase A2 inhibitor (γPLI) from Crotalus durissus collilineatus (Cdc) snake serum. Initially, the Cdc serum was subjected to a Q-Sepharose ion exchange column, producing six peaks at 280 nm absorbance (Q1-Q6). Subsequently, Q4 fraction was submitted to affinity chromatography with immobilized PLA2 BnSP-7, a step that resulted in two fractions (NHS-1 and NHS-2). The latter contained the inhibitor, denominated γCdcPLI. The molecular mass of γCdcPLI, determined by Matrix-Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF), was 22,340 Da. Partial sequences obtained by Edman degradation and by mass spectrometry (MALDI-TOF/TOF), showed similarity, as expected, to other related inhibitors. Circular dichroism (CD) analysis showed the presence of approximately 22% alpha helices and 29% beta sheets in the protein secondary structure. Additionally, CD studies also indicated no significant changes in the secondary structure of γCdcPLI when it is complexed to BpPLA2-TXI. On the other hand, dynamic light scattering (DLS) assays showed a temperature-dependent oligomerization behavior for this inhibitor. Biochemical analyses showed γCdcPLI was able to inhibit the enzymatic, cytotoxic and myotoxic activities of PLA2s. Structural and functional studies performed on this inhibitor may elucidate the action mechanisms of PLA2 inhibitors. In addition, we hope this study may contribute to investigating the potential use of these inhibitors for the treatment of snakebite or inflammatory diseases in which PLA2s may be involved.
Structural and evolutionary insights into endogenous alpha-phospholipase A 2 inhibitors of Latin American pit vipers
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.TOXICON.2016.01.058
Abstract: Phospholipases A2 are major components of snake venoms (svPLA2s) and are able to induce multiple local and systemic deleterious effects upon envenomation. Several snake species are provided with svPLA2 inhibitors (sbPLIs) in their circulating blood, which confer a natural resistance against the toxic components of homologous and heterologous venoms. The sbPLIs belong to any of three structural classes named α, β and γ. In the present study, we identified, characterized and performed structural and evolutionary analyses of sbαPLIs transcripts and the encoded proteins, in the most common Latin American pit vipers belonging to Crotalus, Bothrops and Lachesis genera. Mutation data indicated that sbαPLIs from Latin American snakes might have evolved in an accelerated manner, similarly to that reported for sbαPLIs from Asian snakes, and possibly co-evoluted with svPLA2s in response to the ersity of target enzymes. The importance of sbαPLI trimerization for the effective binding and inhibition of acidic svPLA2s is discussed and conserved cationic residues located at the central pore of the inhibitor trimer are suggested to be a significant part of the binding site of sbαPLIs to acidic svPLA2s. Our data contribute to the current body of knowledge on the structural and evolutionary characteristics of sbPLIs, in general, and may assist in the future development of selective inhibitors for secretory PLA2 from several sources.
Crystallization and preliminary X-ray diffraction studies of BmooPLA2-I, a platelet-aggregation inhibitor and hypotensive phospholipase A2fromBothrops moojenivenom
Publisher: International Union of Crystallography (IUCr)
Date: 19-07-2011
Structural basis for the specificity of bipartite nuclear localisation sequence binding by importin-
Publisher: Elsevier BV
Date: 12-2009
Crystallization and preliminary X-ray diffraction studies of FHA domains of Dun1 and Rad53 protein kinases
Publisher: International Union of Crystallography (IUCr)
Date: 03-2001
DOI: 10.1107/S0907444901002116
Abstract: Forkhead-associated (FHA) domains are modular protein-protein interaction domains of approximately 130 amino acids present in numerous signalling proteins. FHA-domain-dependent protein interactions are regulated by phosphorylation of target proteins and FHA domains may be multifunctional phosphopeptide-recognition modules. FHA domains of the budding yeast cell-cycle checkpoint protein kinases Dun1p and Rad53p have been crystallized. Crystals of the Dun1-FHA domain exhibit the symmetry of the space group P6(1)22 or P6(5)22, with unit-cell parameters a = b = 127.3, c = 386.3 A diffraction data have been collected to 3.1 A resolution on a synchrotron source. Crystals of the N-terminal FHA domain (FHA1) of Rad53p diffract to 4.0 A resolution on a laboratory X-ray source and have Laue-group symmetry 4/mmm, with unit-cell parameters a = b = 61.7, c = 104.3 A.
Structural and functional studies with mytoxin II from Bothrops moojeni reveal remarkable similarities and differences compared to other catalytically inactive phospholipases A2-like
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.TOXICON.2013.06.013
Abstract: Lys49-phospholipases A₂ (Lys49-PLA₂s) are proteins found in bothropic snake venoms (Viperidae family) and belong to a class of proteins which presents a phospholipase A2 scaffold but are catalytically inactive. These proteins (also known as PLA₂s-like toxins) exert a pronounced local myotoxic effect and are not neutralized by antivenom, being their study relevant in terms of medical and scientific interest. Despite of the several studies reported in the literature for this class of proteins only a partial consensus has been achieved concerning their functional-structural relationships. In this work, we present a comprehensive structural and functional study with the MjTX-II, a dimeric Lys49-PLA₂ from Bothrops moojeni venom which includes: (i) high-resolution crystal structure (ii) dynamic light scattering and bioinformatics studies in order to confirm its biological assembly (iii) myographic and electrophysiological studies and, (iv) comparative studies with other Lys49-PLA₂s. These comparative analyses let us to get important insights into the role of Lys122 amino acid, previously indicated as responsible for Lys49-PLA₂s catalytic inactivity and added important elements to establish the correct biological assembly for this class of proteins. Furthermore, we show two unique sequential features of MjTX-II (an amino acid insertion and a mutation) in comparison to all bothropic Lys49-PLA₂s that lead to a distinct way of ligand binding at the toxin's hydrophobic channel and also, allowed the presence of an additional ligand molecule in this region. These facts suggest a possible particular mode of binding for long-chain ligands that interacts with MjTX-II hydrophobic channel, a feature that may directly affect the design of structure-based ligands for Lys49-PLA₂s.
Crystallization and Preliminary X-Ray Diffraction Studies of Two Myotoxic Lys49-Phospholipases A2 Complexed with α-Tocopherol
Publisher: Bentham Science Publishers Ltd.
Date: 11-2005
Abstract: BnSP-7 and BnSP-6, two Lys49-phospholipase A2 isolated from Bothrops neuwiedi pauloensis snake venom, were co-crystallized with alpha-tocopherol and X-ray diffraction data were collected for both complexes (2.2 and 2.6 A). A new "alternative" quaternary conformation for these two complexes compared with all other dimeric Lys49-PLA2 has been observed.
Structural basis of the myotoxic inhibition of the Bothrops pirajai PrTX-I by the synthetic varespladib
Publisher: Elsevier BV
Date: 04-2023
DOI: 10.1016/J.BIOCHI.2022.11.006
Abstract: Varespladib (LY315920) is a potent inhibitor of human group IIA phospholipase A
Structural and calorimetric studies reveal specific determinants for the binding of a high-affinity NLS to mammalian importin-alpha
Publisher: Portland Press Ltd.
Date: 16-07-2021
DOI: 10.1042/BCJ20210401
Abstract: The classical nuclear import pathway is mediated by importin (Impα and Impβ), which recognizes the cargo protein by its nuclear localization sequence (NLS). NLSs have been extensively studied resulting in different proposed consensus however, recent studies showed that exceptions may occur. This mechanism may be also dependent on specific characteristics of different Impα. Aiming to better understand the importance of specific residues from consensus and adjacent regions of NLSs, we studied different mutations of a high-affinity NLS complexed to Impα by crystallography and calorimetry. We showed that although the consensus sequence allows Lys or Arg residues at the second residue of a monopartite sequence, the presence of Arg is very important to its binding in major and minor sites of Impα. Mutations in the N or C-terminus (position P1 or P6) of the NLS drastically reduces their affinity to the receptor, which is corroborated by the loss of hydrogen bonds and hydrophobic interactions. Surprisingly, a mutation in the far N-terminus of the NLS led to an increase in the affinity for both binding sites, corroborated by the structure with an additional hydrogen bond. The binding of NLSs to the human variant Impα1 revealed that these are similar to those found in structures presented here. For human variant Impα3, the bindings are only relevant for the major site. This study increases understanding of specific issues sparsely addressed in previous studies that are important to the task of predicting NLSs, which will be relevant in the eventual design of synthetic NLSs.
Validation of the interRAI cognitive performance scale against independent clinical diagnosis and the mini-mental state examination in older hospitalized patients
Publisher: Springer Science and Business Media LLC
Date: 19-02-2013
DOI: 10.1007/S12603-012-0439-8
Abstract: To compare the diagnostic accuracy of the interRAI Acute Care (AC) Cognitive Performance Scale (CPS2) and the Mini-Mental State Examination (MMSE), against independent clinical diagnosis for detecting dementia in older hospitalized patients. The study was part of a prospective observational cohort study of patients aged ≥70 years admitted to four acute hospitals in Queensland, Australia, between 2008 and 2010. Recruitment was consecutive and patients expected to remain in hospital for ≥48 hours were eligible to participate. Data for 462 patients were available for this study. Trained research nurses completed comprehensive geriatric assessments and administered the interRAI AC and MMSE to patients. Two physicians independently reviewed patients' medical records and assessments to establish the diagnosis of dementia. Indicators of diagnostic accuracy included sensitivity, specificity, predictive values, likelihood ratios and areas under receiver (AUC) operating characteristic curves. 85 patients (18.4%) were considered to have dementia according to independent clinical diagnosis. The sensitivity of the CPS2 [0.68 (95%CI: 0.58-0.77)] was not statistically different to the MMSE [0.75 (0.64-0.83)] in predicting physician diagnosed dementia. The AUCs for the 2 instruments were also not statistically different: CPS2 AUC = 0.83 (95%CI: 0.78-0.89) and MMSE AUC = 0.87 (95%CI: 0.83-0.91), while the CPS2 demonstrated higher specificity [0.92 95%CI: 0.89-0.95)] than the MMSE [0.82 (0.77-0.85)]. Agreement between the CPS2 and clinical diagnosis was substantial (87.4% κ=0.61). The CPS2 appears to be a reliable screening tool for assessing cognitive impairment in acutely unwell older hospitalized patients. These findings add to the growing body of evidence supporting the utility of the interRAI AC, within which the CPS2 is embedded. The interRAI AC offers the advantage of being able to accurately screen for both dementia and delirium without the need to use additional assessments, thus increasing assessment efficiency.
In-solution structural studies involving a phospholipase A2-like myotoxin and a natural inhibitor: Plasticity of oligomeric assembly affects mechanisms of inhibition
Publisher: Elsevier BV
Date: 02-2021
Structural and thermodynamic studies of the tobacco calmodulin-like rgs-CaM protein
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.IJBIOMAC.2016.08.016
Abstract: The tobacco calmodulin-like protein rgs-CaM is involved in host defense against virus and is reported to possess an associated RNA silencing suppressor activity. Rgs-CaM is also believed to act as an antiviral factor by interacting and targeting viral silencing suppressors for autophagic degradation. Despite these functional data, calcium interplay in the modulation of rgs-CaM is still poorly understood. Here we show that rgs-CaM displays a prevalent alpha-helical conformation and possesses three functional Ca
Cultivating the Acceptance of Assistance Dogs in Aged Care Through Deliberative Democracy
Publisher: MDPI AG
Date: 28-06-2023
DOI: 10.20944/PREPRINTS202306.2028.V1
Abstract: Assistance dogs provide significant benefits to older adult owners. However, despite protective legislation, aged care facilities continue to not allow owners to retain their dog on relocation. The purpose of the current study was to explore whether older adults should be allowed to retain their dog on relocation to an aged care facility, and what factors should impact this decision. Further, if allowed to retain their dog, what would be the best practice to allow for this. A deliberative democracy methodology was used, with a range of key stakeholders recruited. Focus groups were held, with follow up questionnaire to establish deliberation for all questions. Results indicated that with sufficient objective measurement, fair decisions can be made to ensure the welfare and wellbeing for owner and dog. Key policy and procedure changes would also be necessary to ensure ongoing support, such as training, care plans, and emergency directives. By ensuring sufficient policies and procedures are in place, training and support could lead to an ideal outcome where facilities could be at the forefront of a better future for aged care.
Issues Regarding the Welfare of Assistance Dogs
Publisher: MDPI AG
Date: 23-11-2022
DOI: 10.3390/ANI12233250
Abstract: While the roles and efficacy of assistance animals have received attention in the literature, there has been less research focused on animal welfare issues regarding assistance animals. This is a pertinent area, given the burgeoning of types of assistance animals, situations in which they are employed, and access issues arising from increased assistance animal engagement. Animal welfare as pertains to assistance animals is discussed in this paper with respect to overall research on animal welfare concerns in a variety of contexts, training and access issues, and legal and regulatory concerns. Relevant ex les from global contexts, as well as the specific Australian context, are offered. Conclusions include that while human quality of life is often considered and protected in laws and policies, this is much less true for assistance animals. Additional attention is required to ensure that the quality of life of both persons with disabilities and their assistance animals can be ensured. Support for a person to meet the needs of an assistance animal, as well as considerations for keeping such working dyads together in changed circumstances (e.g., following a move to an assisted living mode of accommodation), are recommended.
Dimensions of stereotypical attitudes among older adults: Analysis of two countries.
Publisher: Wiley
Date: 13-10-2016
DOI: 10.1111/GGI.12613
Abstract: Much research on attitudes towards older adults has used younger adults as participants and identified a range of negative attitudes towards older persons. Comparatively little literature has explored the attitudes of older adults themselves towards their own age cohort. The present study explicitly compared attitudes towards other older adults from s les of 195 older adults in Australia and 172 older Canadians. Attitudinal measures included the Aging Attitudes Questionnaire (assesses older adults' attitudes toward other older adults), Fraboni Scale of Ageism (assesses younger adults' attitudes toward older adults) and the Reactions to Aging Questionnaire (assesses attitudes toward one's own aging), as well as a scale measuring knowledge of aging, the Facts on Aging Quiz, adapted for Australia and Canada. Responses on the three attitudinal measures were subjected to principal components analysis. Two components emerged in both s les, one defined by the Reactions to Aging Questionnaire and Aging Attitudes Questionnaire scales and the second by the Fraboni Scale of Ageism scales. Regression analyses to ascertain prediction of scores on the Facts on Aging Quiz, adapted for Australia and Facts on Aging Quiz, adapted for Canada showed that only the Aging Attitudes Questionnaire scale for Physical Changes predicted scores on the Facts on Aging Quiz, adapted for Australia and no attitudes predicted Facts on Aging Quiz, adapted for Canada scores. It appears that older adults distinguish between their own aging and aging in others. Knowledge of aging appears to be predicted only by attitudes toward physical changes. Given increasing proportions of older adults in the population, as well as increasing access to aging information available to older cohorts, continued research on how older adults view themselves and the aging process is important, and will almost certainly continue to evolve over time. Geriatr Gerontol Int 2016 16: 1226-1230.
Mapping possible interaction sites for crotoxin in CNF, a gamma PLA2 inhibitor from Crotalus durissus terrificus rattle snake, using SPOT synthesis
Publisher: Elsevier BV
Date: 10-2023
Crystallization and preliminary X-ray diffraction analysis of three myotoxic phospholipases A2fromBothrops brazilivenom
Publisher: International Union of Crystallography (IUCr)
Date: 31-07-2012
Rosmarinic acid, a new snake venom phospholipase A2 inhibitor from Cordia verbenacea (Boraginaceae): antiserum action potentiation and molecular interaction
Publisher: Elsevier BV
Date: 09-2005
DOI: 10.1016/J.TOXICON.2005.04.023
Abstract: Many plants are used in traditional medicine as active agents against various effects induced by snakebite. The methanolic extract from Cordia verbenacea (Cv) significantly inhibited paw edema induced by Bothrops jararacussu snake venom and by its main basic phospholipase A2 homologs, namely bothropstoxins I and II (BthTXs). The active component was isolated by chromatography on Sephadex LH-20 and by RP-HPLC on a C18 column and identified as rosmarinic acid (Cv-RA). Rosmarinic acid is an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid [2-O-cafeoil-3-(3,4-di-hydroxy-phenyl)-R-lactic acid]. This is the first report of RA in the species C. verbenacea ('baleeira', 'whaler') and of its anti-inflammatory and antimyotoxic properties against snake venoms and isolated toxins. RA inhibited the edema and myotoxic activity induced by the basic PLA2s BthTX-I and BthTX-II. It was, however, less efficient to inhibit the PLA2 activity of BthTX-II and, still less, the PLA2 and edema-inducing activities of the acidic isoform BthA-I-PLA2 from the same venom, showing therefore a higher inhibitory activity upon basic PLA2s. RA also inhibited most of the myotoxic and partially the edema-inducing effects of both basic PLA2s, thus reinforcing the idea of dissociation between the catalytic and pharmacological domains. The pure compound potentiated the ability of the commercial equine polyvalent antivenom in neutralizing lethal and myotoxic effects of the crude venom and of isolated PLA2s in experimental models. CD data presented here suggest that, after binding, no significant conformation changes occur either in the Cv-RA or in the target PLA2. A possible model for the interaction of rosmarinic acid with Lys49-PLA2 BthTX-I is proposed.
Structural studies with crotoxin B from Crotalus durissus collilineatus venom suggest a heterodimeric assembly formed by two new isoforms
Publisher: Elsevier BV
Date: 09-2023
Structural and Functional Characterization of BnSP-7, a Lys49 Myotoxic Phospholipase A2 Homologue from Bothrops neuwiedi pauloensis Venom
Publisher: Elsevier BV
Date: 06-2000
The crystal and molecular structure of bis[l, 3-bis(diphenylphosphino) propane] dichlororuthenium (ii)
Publisher: Informa UK Limited
Date: 10-1993
Corona protein impacts on alternating current biosusceptometry signal and circulation times of differently coated MnFe
Publisher: Future Medicine Ltd
Date: 10-2021
Abstract: Background: We evaluated the impacts of corona protein (CP) formation on the alternating current biosusceptometry (ACB) signal intensity and in vivo circulation times of three differently coated magnetic nanoparticles (MNP): bare, citrate-coated and bovine serum albumin-coated MNPs. Methods: We employed the ACB system, gel electrophoresis and mass spectrometry analysis. Results: Higher CP formation led to a greater reduction in the in vitro ACB signal intensity and circulation time. We found fewer proteins forming the CP for the bovine serum albumin-coated MNPs, which presented the highest circulation time in vivo among the MNPs studied. Conclusion: These data showed better biocompatibility, stability and magnetic signal uniformity in biological media for bovine serum albumin-coated MNPs than for citrate-coated MNPs and bare MNPs.
Factors Related to Sleep Disturbances for Informal Carers of Individuals With PD and Dyadic Relationship: A Rural Perspective
Publisher: SAGE Publications
Date: 13-08-2021
Abstract: This study examines factors related to sleep disturbances, and the dyadic sleep relationship, in a convenience s le of 29 persons with Parkinson disease (PD) and spouse carer dyads living in regional Queensland. Carers completed questionnaires on sleep, depression, anxiety, carer burden, and well-being. Regarding carers, 66% reported sleep disturbances related to nocturnally care demands. Less than half of informal carers with a disturbed sleep had informed a health professional of this problem. Medication was the most commonly advised sleep intervention (44%). Sleep disturbances in informal carers correlated with increasing carer burden, depression scores, anxiety scores, poor quality of life, negative cognitions related to their sleep disturbance, and poor sleep hygiene. Regarding patient-carer dyads, 59% reported both the in iduals having problematic sleep disturbances. Patient sleep disturbance correlated with informal carer increase in depression and anxiety scores, and poor carer burden. Informal carer’s sleep disturbance correlated with patient anxiety scores and severity of complications from PD therapy. Evidence-based sleep interventions addressing such dyads in rural areas warrant future study.
Characteristics of Cognitive Behavioral Therapy for Older Adults Living in Residential Care: Protocol for a Systematic Review
Publisher: JMIR Publications Inc.
Date: 04-07-2018
DOI: 10.2196/RESPROT.9902
Insights on the structure of native CNF, an endogenous phospholipase A2 inhibitor from Crotalus durissus terrificus, the South American rattlesnake
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.BBAPAP.2014.05.001
Abstract: Several snake species possess endogenous phospholipase A2 inhibitors (sbPLIs) in their blood plasma, the primary role of which is protection against an eventual presence of toxic phospholipase A2 (PLA2) from their venom glands in the circulation. These inhibitors have an oligomeric structure of, at least, three subunits and have been categorized into three classes (α, β and γ) based on their structural features. SbγPLIs have been further sub ided into two subclasses according to their hetero or homomeric nature, respectively. Despite the considerable number of sbγPLIs described, their structures and mechanisms of action are still not fully understood. In the present study, we focused on the native structure of CNF, a homomeric sbγPLI from Crotalus durissus terrificus, the South American rattlesnake. Based on the results of different biochemical and biophysical experiments, we concluded that, while the native inhibitor occurs as a mixture of oligomers, tetrameric arrangement appears to be the predominant quaternary structure. The inhibitory activity of CNF is most likely associated with this oligomeric conformation. In addition, we suggest that the CNF tetramer has a spherical shape and that tyrosinyl residues could play an important role in the oligomerization. The carbohydrate moiety, which is present in most sbγPLIs, is not essential for the inhibitory activity, oligomerization or complex formation of the CNF with the target PLA2. A minor component, comprising no more than 16% of the s le, was identified in the CNF preparations. The amino-terminal sequence of that component is similar to the B subunits of the heteromeric sbγPLIs however, the role played by such molecule in the functionality of the CNF, if any, remains to be determined.
Probing the Specificity of Binding to the Major Nuclear Localization Sequence-binding Site of Importin-α Using Oriented Peptide Library Screening
Publisher: Elsevier BV
Date: 06-2010
Remote delivery of psychological interventions for Parkinson's disease
Publisher: Cambridge University Press (CUP)
Date: 11-05-2018
DOI: 10.1017/S1041610218000340
Abstract: Over two-thirds of Parkinson's disease (PD) patients experience comorbid neuropsychiatric symptoms, which adversely impact their quality of life and often require intervention. There is a preference for non-pharmacological, psychological approaches in addressing these symptoms. Given mobility limitations, travel burden, and cost, accessibility to psychological treatment can be problematic in this population. There has been a recent shift toward delivering care via telehealth in PD. Accordingly, this review aimed to examine remotely delivered psychological interventions for PD patients. Most of the telehealth studies for PD involved Cognitive Behavioral Therapy (CBT) based anxiety and depression telephone interventions with relatively short (one month) follow-up periods. Although a preliminary work indicates efficacy, future studies should demonstrate the non-inferiority of these telehealth programs compared to face-to-face delivery, and examine the long-term outcomes of remotely delivered therapy. Video-conferencing (VC) appears to be a promising modality to overcome noted limitations of telephone delivery, and has demonstrated efficacy for PD speech programs. Further research should be conducted evaluating telehealth VC modalities for delivery of psychotherapy including CBT, as well as mindfulness-based therapy and acceptance and commitment therapy for remote treatment of depression and anxiety in PD.
Phospholipase A2 Myotoxins from Bothrops Snake Venoms: Structure- Function Relationship
Publisher: Bentham Science Publishers Ltd.
Date: 11-2004
Social support and subsequent disability: it is not the size of your network that counts
Publisher: Oxford University Press (OUP)
Date: 27-03-2012
Abstract: high levels of social support and engagement may help sustain good health and functional ability. However, the definition of social support in previous research has been inconsistent and findings are mixed. The aim of this analysis was to explore the effect of two aspects of social support on subsequent disability in a group of community dwelling older women and men. data were drawn from two concurrent prospective observational cohort studies of community-based older Australian women (N = 2,013) and men (N = 680). Baseline and follow-up data were drawn from the second (1999) and fifth (2008) surveys of the women and the second (2001) and third (2008) surveys of the men. At baseline, social support was measured by the two subscales (social network and subjective support) of the Duke Social Support Index (DSSI). The outcome measure was Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs). overall, social network size was not associated with subsequent disability in either women or men. After adjusting for health status at baseline, lack of satisfaction with social support was associated with greater difficulties in ADLs and IADLs for both women and men. our results suggest that the provision of social support is insufficient to limit subsequent disability: support provided must be subjectively perceived to be relevant and adequate.
Insights into the role of oligomeric state on the biological activities of crotoxin: Crystal structure of a tetrameric phospholipase A2 formed by two isoforms of crotoxin B from Crotalus
Publisher: Wiley
Date: 14-02-2008
DOI: 10.1002/PROT.21980
Abstract: Crotoxin B (CB or Cdt PLA(2)) is a basic Asp49-PLA(2) found in the venom of Crotalus durissus terrificus and it is one of the subunits that constitute the crotoxin (Cro). This heterodimeric toxin, main component of the C. d. terrificus venom, is completed by an acidic, nontoxic, and nonenzymatic component (crotoxin A, CA or crotapotin), and it is related to important envenomation effects such as neurological disorders, myotoxicity, and renal failure. Although Cro has been crystallized since 1938, no crystal structure of this toxin or its subunits is currently available. In this work, the authors present the crystal structure of a novel tetrameric complex formed by two dimers of crotoxin B isoforms (CB1 and CB2). The results suggest that these assemblies are stable in solution and show that Ser1 and Glu92 of CB1 and CB2, respectively, play an important role in the oligomerization. The tetrameric and dimeric conformations resulting from the association of the isoforms may increase the neurotoxicity of the toxin CB by the creation of new binding sites, which could improve the affinity of the molecular complexes to the presynaptic membrane.
The knowledge and skills assessment (KASA) tool in the Australian Dementia Behaviour Management Advisory Service: Development and initial testing
Publisher: Cambridge University Press (CUP)
Date: 06-01-2016
DOI: 10.1017/S1041610215002070
Abstract: As the global population ages, it is important that the professional care workforce is well prepared to support the needs of people with dementia. In Australia, the Dementia Behaviour Management Advisory Service (DBMAS) supports people with dementia and their carers through an interdisciplinary team approach. To provide DBMAS Behaviour Consultants with a tool to guide them in their professional development, this project aimed to develop a self-assessment tool to enable self-reflection on clinical competencies required for working in the service and identification of areas where further development would be required. A multi-stage process was applied in the development of the tool, including review of the relevant literature and focus groups with DBMAS Behaviour Consultants and Team Leaders. The tool encompasses both skills and knowledge in working with people with dementia and caregivers. A pilot study including 14 DBMAS consultants was conducted to assess the utility of the measure and ensure variability of ratings across knowledge and skill areas relative to time working in DBMAS. The Knowledge and Skills Assessment (KASA) was developed and is now used in DBMAS service both with novice Behaviour Consultants and more experienced staff, and is also being used as an on-line version, accompanied with case vignettes. The KASA provides a valuable self-assessment tool for professional care staff working in dementia care, but would nevertheless still warrant further testing of its psychometric characteristics.
Molecular cloning and structural modelling of gamma-phospholipase A2 inhibitors from Bothrops atrox and Micrurus lemniscatus snakes
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.IJBIOMAC.2017.05.076
Abstract: Phospholipases A
Adapting psychotherapy for older patients with Parkinson's disease
Publisher: Cambridge University Press (CUP)
Date: 07-04-2016
DOI: 10.1017/S1041610216000569
Abstract: Emotional distress associated with Parkinson's disease (PD) increases disease burden and decreases functioning. The literature supports the benefits of psychological interventions for amelioration of emotional distress in persons with PD. The objective of this study is to apply the Contextual Adult Lifespan Theory for Adapting Psychotherapy (CALTAP) to enhancing psychological treatment for persons with PD. This paper uses case ex les to demonstrate the usefulness of the CALTAP model in helping patients and clinicians separate disease symptoms from the aging process. The ex les also illustrate how working in this way can be beneficial in reducing emotional distress in persons with PD. CALTAP contributes to helping persons with PD and persons treating them understand the effects of the disease, separate disease effects from aging processes, and think through the influences of social context, cohort effects, and cultural differences. The CALTAP model can guide adaptations to psychological interventions for emotional distress in PD and potentially improve their effects.
A novel synthetic quinolinone inhibitor presents proteolytic and hemorrhagic inhibitory activities against snake venom metalloproteases
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.BIOCHI.2015.11.031
Abstract: Metalloproteases play a fundamental role in snake venom envenomation inducing hemorrhagic, fibrigen(ogen)olytic and myotoxic effects in their victims. Several snake venoms, such as those from the Bothrops genus, present important local effects which are not efficiently neutralized by conventional serum therapy. Consequently, these accidents may result in permanent sequelae and disability, creating economic and social problems, especially in developing countries, leading the attention of the World Health Organization that considered ophidic envenomations a neglected tropical disease. Aiming to produce an efficient inhibitor against bothropic venoms, we synthesized different molecules classified as quinolinones - a group of low-toxic chemical compounds widely used as antibacterial and antimycobacterial drugs - and tested their inhibitory properties against hemorrhage caused by bothropic venoms. The results from this initial screening indicated the molecule 2-hydroxymethyl-6-methoxy-1,4-dihydro-4-quinolinone (Q8) was the most effective antihemorrhagic compound among all of the assayed synthetic quinolinones. Other in vitro and in vivo experiments showed this novel compound was able to inhibit significantly the hemorrhagic and/or proteolytic activities of bothropic crude venoms and isolated snake venom metalloproteases (SVMPs) even at lower concentrations. Docking and molecular dynamic simulations were also performed to get insights into the structural basis of Q8 inhibitory mechanism against proteolytic and hemorrhagic SVMPs. These structural studies demonstrated that Q8 may form a stable complex with SVMPs, impairing the access of substrates to the active sites of these toxins. Therefore, both experimental and structural data indicate that Q8 compound is an interesting candidate for antiophidic therapy, particularly for the treatment of the hemorrhagic and necrotic effects induced by bothropic venoms.
Gallic acid anti-myotoxic activity and mechanism of action, a snake venom phospholipase A2 toxin inhibitor, isolated from the medicinal plant Anacardium humile
Publisher: Elsevier BV
Date: 08-2021
A structure-based proposal for a comprehensive myotoxic mechanism of phospholipase A2-like proteins from viperid snake venoms
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.BBAPAP.2014.09.015
Abstract: Envenomation via snakebites is an important public health problem in many tropical and subtropical countries that, in addition to mortality, can result in permanent sequelae as a consequence of local tissue damage, which represents a major challenge to antivenom therapy. Venom phospholipases A2 (PLA2s) and PLA2-like proteins play a leading role in the complex pathogenesis of skeletal muscle necrosis, nevertheless their precise mechanism of action is only partially understood. Recently, detailed structural information has been obtained for more than twenty different members of the PLA2-like myotoxin subfamily. In this review, we integrate the available structural, biochemical and functional data on these toxins and present a comprehensive hypothesis for their myotoxic mechanism. This process involves an allosteric transition and the participation of two independent interaction sites for docking and disruption of the target membrane, respectively, leading to a five-step mechanism of action. Furthermore, recent functional and structural studies of these toxins complexed with ligands reveal erse neutralization mechanisms that can be classified into at least three different groups. Therefore, the data summarized here for the PLA2-like myotoxins could provide a useful molecular basis for the search for novel neutralizing strategies to improve the treatment of envenomation by viperid snakes.
Biophysical Characterization of Interactions Involving Importin-α during Nuclear Import
Publisher: Elsevier BV
Date: 09-2001
Designing Virtual Reality Assisted Psychotherapy for Anxiety in Older Adults Living with Parkinson’s Disease: Integrating Literature for Scoping
Publisher: Informa UK Limited
Date: 06-01-2020
Replication Protein A‐1 Has a Preference for the Telomeric G‐rich Sequence in Trypanosoma cruzi
Publisher: Wiley
Date: 04-11-2017
DOI: 10.1111/JEU.12478
Abstract: Replication protein A (RPA), the major eukaryotic single-stranded binding protein, is a heterotrimeric complex formed by RPA-1, RPA-2, and RPA-3. RPA is a fundamental player in replication, repair, recombination, and checkpoint signaling. In addition, increasing evidences have been adding functions to RPA in telomere maintenance, such as interaction with telomerase to facilitate its activity and also involvement in telomere capping in some conditions. Trypanosoma cruzi, the etiological agent of Chagas disease is a protozoa parasite that appears early in the evolution of eukaryotes. Recently, we have showed that T. cruziRPA presents canonical functions being involved with DNA replication and DNA damage response. Here, we found by FISH/IF assays that T. cruziRPA localizes at telomeres even outside replication (S) phase. In vitro analysis showed that one telomeric repeat is sufficient to bind RPA-1. Telomeric DNA induces different secondary structural modifications on RPA-1 in comparison with other types of DNA. In addition, RPA-1 presents a higher affinity for telomeric sequence compared to randomic sequence, suggesting that RPA may play specific roles in T. cruzi telomeric region.
Geographic variations in the composition of myotoxins from Bothrops neuwiedi snake venoms: biochemical characterization and biological activity
Publisher: Elsevier BV
Date: 11-1998
DOI: 10.1016/S1095-6433(98)10136-8
Abstract: (1) Venom pools from Bothrops neuwiedi (Bn) and from two subspecies, namely Bothrops neuwiedi pauloensis (Bnp) and Bothrops neuwiedi urutu (Bnu), collected in the States of São Paulo (SP) and Minas Gerais (MG), Brazil, were electrophoretically examined. Basic toxins with different isoelectric points were identified in the venom collected in São Paulo (BnSP). These toxins were absent in the corresponding pools from Minas Gerais (BnMG, BnpMG and BnuMG). (2) BnSP, but not BnMG, BnpMG or BnuMG, showed two myotoxins (pI approximately equal to 8.6 and 8.8, respectively) which were isolated by ion-exchange chromatography on CM-Sepharose. (3) From BnMG, three myotoxic isoforms (pI approximately equal to 8.2 and M(r) = 13,600) were isolated by chromatography on CM-Sepharose followed by reversed-phase high-performance liquid chromatography. (4) The chemical and biological characterization of these toxins showed a high similarity with the Lys-49 myotoxins from other bothropic venoms. (5) Doses up to 5 LD50 (i.p.) of p-bromophenacyl bromide alkylated BnSP-7 caused a total loss of lethality in 18-22-g mice, thus indicating that the LD50 was increased by greater than 5-fold. At this dose myotoxicity was also not detectable, but the edematogenic activity on the rat paw apparently did not change.
How Well Do Caregivers Detect Depression and Anxiety in Patients With Parkinson Disease?
Publisher: SAGE Publications
Date: 02-08-2018
Abstract: Depression and anxiety are prevalent in Parkinson disease (PD) yet underrecognized in clinical practice. Caregiver reports are frequently utilized to aid in the assessment of neuropsychiatric symptoms but little is known about caregivers’ ability to recognize them in patients with PD. This study sought to examine the accuracy of caregiver reports. Eighty patient–caregiver dyads were involved. Accuracy of caregiver recognition was assessed by examining the level of agreement between caregiver ratings on the Neuropsychiatric Inventory and patients’ diagnosis of depression and anxiety on the Mini-International Neuropsychiatric Interview (MINI)-Plus. The agreement between caregiver report and MINI-Plus diagnosis was low for both depression (6.3%) and anxiety (17.5%). The presence of depression was overreported, while anxiety was largely underestimated by caregivers. Caregiver distress significantly predicted inaccurate caregiver identification of depression ( R 2 = .51, P .001) and anxiety ( R 2 = .08, P .05). Results indicate that caregivers may be poor at recognizing depression and anxiety in patients with PD. Utilization of caregiver report should take into account potential biases that affect caregiver judgment.
Factors associated with the increased risk of dementia found in the Torres Strait
Publisher: Wiley
Date: 05-08-2021
DOI: 10.1111/AJAG.12980
Abstract: To identify the specific risk factors for dementia in the Torres Strait. This research was conducted as part of a cross‐sectional dementia prevalence study conducted in the Torres Strait. Participants underwent a comprehensive health assessment, where data on risk factors were collected, and a Geriatrician assessment, which was used to establish dementia diagnoses. A total of 276 Torres Strait residents aged between 45 and 93 participated in the study. Cerebrovascular disease, chronic kidney disease and older age were the most significant risk factors in this population. Once adjusted for age, cerebrovascular disease, chronic kidney disease, diabetes, low education and problems with mobility and incontinence were significantly associated with dementia. Reducing dementia risk in the Torres Strait requires multifactorial interventions to address potentially modifiable risk factors with a particular focus on addressing the development of chronic midlife diseases.
Preliminary X-Ray Crystallographic Studies of a Lys49-Phospholipase A2 Homologue from Bothrops pirajai Venom Complexed with p-Bromophenacyl Bromide and α-Tocopherol Inhibitors
Publisher: Bentham Science Publishers Ltd.
Date: 07-2007
DOI: 10.2174/092986607781483796
Abstract: PrTX-I, a non-catalytic and myotoxic Lys49-PLA(2) from Bothrops pirajai venom has been crystallized alone and in complex with bromophenacyl bromide (BPB), alpha tocopherol and alpha tocopherol acetate inhibitors. These crystals have shown to diffract X-rays between 2.34 and 1.65 A resolution. All complexes crystals are isomorphous and belong to the space group P2(1) whereas native PrTX-I crystals belong to the P3(1)21.
Transcriptionally active LTR retrotransposons in Eucalyptus genus are differentially expressed and insertionally polymorphic
Publisher: Springer Science and Business Media LLC
Date: 14-08-2015
Crystal Structure of Myotoxin II, a Monomeric Lys49-Phospholipase A2 Homologue Isolated from the Venom of Cerrophidion (Bothrops) godmani
Publisher: Elsevier BV
Date: 06-1999
Correlating biological activity to thermo-structural analysis of the interaction of CTX with synthetic models of macrophage membranes
Publisher: Springer Science and Business Media LLC
Date: 09-12-2021
DOI: 10.1038/S41598-021-02552-0
Abstract: The important pharmacological actions of Crotoxin (CTX) on macrophages, the main toxin in the venom of Crotalus durissus terrificus , and its important participation in the control of different pathophysiological processes, have been demonstrated. The biological activities performed by macrophages are related to signaling mediated by receptors expressed on the membrane surface of these cells or opening and closing of ion channels, generation of membrane curvature and pore formation. In the present work, the interaction of the CTX complex with the cell membrane of macrophages is studied, both using biological cells and synthetic lipid membranes to monitor structural alterations induced by the protein. Here we show that CTX can penetrate THP-1 cells and induce pores only in anionic lipid model membranes, suggesting that a possible access pathway for CTX to the cell is via lipids with anionic polar heads. Considering that the selectivity of the lipid composition varies in different tissues and organs of the human body, the thermostructural studies presented here are extremely important to open new investigations on the biological activities of CTX in different biological systems.
A calmodulin-like protein (LCALA) is a new Leishmania amazonensis candidate for telomere end-binding protein
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.BBAGEN.2017.08.011
Abstract: Leishmania spp. telomeres are composed of 5'-TTAGGG-3' repeats associated with proteins. We have previously identified LaRbp38 and LaRPA-1 as proteins that bind the G-rich telomeric strand. At that time, we had also partially characterized a protein: DNA complex, named LaGT1, but we could not identify its protein component. Using protein-DNA interaction and competition assays, we confirmed that LaGT1 is highly specific to the G-rich telomeric single-stranded DNA. Three protein bands, with LaGT1 activity, were isolated from affinity-purified protein extracts in-gel digested, and sequenced de novo using mass spectrometry analysis. In silico analysis of the digested peptide identified them as a putative calmodulin with sequences identical to the T. cruzi calmodulin. In the Leishmania genome, the calmodulin ortholog is present in three identical copies. We cloned and sequenced one of the gene copies, named it LCalA, and obtained the recombinant protein. Multiple sequence alignment and molecular modeling showed that LCalA shares homology to most eukaryotes calmodulin. In addition, we demonstrated that LCalA is nuclear, partially co-localizes with telomeres and binds in vivo the G-rich telomeric strand. Recombinant LCalA can bind specifically and with relative affinity to the G-rich telomeric single-strand and to a 3'G-overhang, and DNA binding is calcium dependent. We have described a novel candidate component of Leishmania telomeres, LCalA, a nuclear calmodulin that binds the G-rich telomeric strand with high specificity and relative affinity, in a calcium-dependent manner. LCalA is the first reported calmodulin that binds in vivo telomeric DNA.
Identification of a putative nuclear localization signal in maspin protein shed light into its nuclear import regulation
Publisher: Cold Spring Harbor Laboratory
Date: 20-11-2018
DOI: 10.1101/474379
Abstract: Maspin (SERPINB5) is a potential tumor suppressor gene with pleiotropic biological activities, including regulation of cell proliferation, death, adhesion, migration and gene expression. Several studies suggest that subcellular localization plays an essential role on maspin tumor suppression activity. In this study we investigated the molecular mechanisms underlying maspin nucleocytoplasmic shuttling. An in vitro nuclear-import assay using digitonin-permeabilized HeLa cells demonstrated that maspin enters the nucleus by an energy-and carrier-independent mechanism. However, previous studies indicated that maspin subcellular localization is regulated in the cell. Using a nuclear localization signal (NLS) prediction software, we identified a putative NLS in the maspin amino acid sequence. To distinguish between passive and regulated nuclear translocation, maspinNLS or the full-length protein (MaspinFL) were fused to 5GFP, rendering the construct too large to enter the nucleus passively. Unexpectedly, 5GFP-maspinNLS, but not maspinFL-5GFP, entered the nucleus of HeLa cells. Dominant-negative Ran-GTPase mutants RanQ69L or RanT24N, suppressed 5GFP-maspinNLS nuclear localization. In summary, we provide evidence that maspin translocates to the nucleus passively. In addition, we identified a peptide in the maspin protein sequence, which is able to drive a 5GFP construct to the nucleus in an energy-dependent manner.
The feasibility and acceptability of high-intensity interval training for adults with mental illness: A pilot study
Publisher: Elsevier BV
Date: 10-2017
Use of the Behaviour Change Wheel to design an intervention to improve the provision of mental wellbeing support within the audiology setting
Publisher: Springer Science and Business Media LLC
Date: 02-05-2023
DOI: 10.1186/S43058-023-00427-1
Abstract: This study describes the development of an intervention to increase the frequency of audiologists’ asking about and providing information regarding mental wellbeing within adult audiology services. The Behaviour Change Wheel (BCW), an eight-step systematic process, was followed to develop the intervention. Reports describing the first four steps are published elsewhere. This report describes the final four steps and details the intervention developed. A multifaceted intervention was developed to change audiologists’ behaviours relating to providing mental wellbeing support to adults with hearing loss. Specifically, three behaviours were targeted: (1) asking clients about their mental wellbeing, (2) providing general information on the mental wellbeing impacts of hearing loss, and (3) providing personalised information on managing the mental wellbeing impacts of hearing loss. A variety of intervention functions and behaviour change techniques were incorporated into the intervention, including instruction and demonstration, information about others approval, adding objects to the environment, use of prompts/cues, and endorsement from credible sources. This study is the first to use the Behaviour Change Wheel to develop an intervention targeting mental wellbeing support behaviours in audiologists and confirms the usability and usefulness of the approach in a complex area of clinical care. The systematic development of the Ask, Inform, Manage, Encourage, Refer (AIMER) intervention will facilitate a thorough evaluation of its effectiveness in the next phase of this work.
Crystallization and preliminary X-ray diffraction analysis of a myotoxic phospholipase A2 homologue from Bothrops neuwiedi pauloensis venom
Publisher: Elsevier BV
Date: 07-1999
DOI: 10.1016/S0167-4838(99)00120-X
Abstract: Crystals of a myotoxic phospholipase A(2) from Bothrops neuwiedi pauloensis have been obtained. They diffracted at 2.5 A resolution using a synchrotron radiation source and belong to space group P3(1)21. Preliminary analysis shows that there are two molecules in the asymmetric unit.
BmajPLA 2 -II, a basic Lys49-phospholipase A 2 homologue from Bothrops marajoensis snake venom with parasiticidal potential
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.IJBIOMAC.2017.04.013
Abstract: Snake venoms contain various proteins, especially phospholipases A
SEQUENCE SLIDER: integration of structural and genetic data to characterize isoforms from natural source
Publisher: Cold Spring Harbor Laboratory
Date: 20-09-2021
DOI: 10.1101/2021.09.16.460517
Abstract: Proteins isolated from natural source can be composed of a mixture of isoforms with similar physicochemical properties that coexists in final steps of purification, toxins being prominent ex les. Sequence composition is enforced throughout structural studies even when unsubstantiated. Herein, we propose a novel perspective to address the usually neglected heterogeneity of natural products by integrating biophysical, genetic and structural data in our program SEQUENCE SLIDER. The aim is to assess the evidence supporting chemical composition in structure determination. Locally, we interrogate the experimental map to establish which side chains are supported by the structural data and the genetic information relating sequence conservation is integrated in this statistic. Hence, we build a constrained peptide database, containing most probable sequences to interpret mass spectrometry data (MS). In parallel, we perform MS de novo sequencing with genomic-based algorithms that foresee point mutations. We calibrated SLIDER with Gallus gallus lysozyme, for which sequence is unequivocally established and numerous natural isoforms are reported. We used SLIDER to characterise a metalloproteinase and a phospholipase A2-like protein from the venom of Bothrops moojeni and a crotoxin from Crotalus durissus collilineatus . This integrated approach offers a more realistic structural descriptor to characterize macromolecules isolated from natural source. The method SEQUENCE SLIDER integrates biophysical, genetic and structural data to assign sequence. It joins crystallography, mass spectrometry and phylogenetic data to characterize isoforms. Sequence heterogeneity of four proteins purified directly from snake venom was established.
Comparative study of the interactions between fungal transcription factor nuclear localization sequences with mammalian and fungal importin-alpha
Publisher: Springer Science and Business Media LLC
Date: 29-01-2020
DOI: 10.1038/S41598-020-58316-9
Abstract: Importin-α (Impα) is an adaptor protein that binds to cargo proteins (containing Nuclear Localization Sequences - NLSs), for their translocation to the nucleus. The specificities of the Impα/NLS interactions have been studied, since these features could be used as important tools to find potential NLSs in nuclear proteins or even for the development of targets to inhibit nuclear import or to design peptides for drug delivery. Few structural studies have compared different Impα variants from the same organism or Impα of different organisms. Previously, we investigated nuclear transport of transcription factors with Neurospora crassa Impα (NcImpα). Herein, NIT-2 and PAC-3 transcription factors NLSs were studied in complex with Mus musculus Impα (MmImpα). Calorimetric assays demonstrated that the PAC-3 NLS peptide interacts with both Impα proteins with approximately the same affinity. The NIT-2 NLS sequence binds with high affinity to the Impα major binding site from both organisms, but its binding to minor binding sites reveals interesting differences due to the presence of additional interactions of NIT-2-NLS with MmImpα. These findings, together with previous results with Impα from other organisms, indicate that the differential affinity of NLSs to minor binding sites may be also responsible for the selectivity of some cargo proteins recognition and transport.
Structural studies with BnSP-7 reveal an atypical oligomeric conformation compared to phospholipases A2-like toxins
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.BIOCHI.2017.07.009
Abstract: There are 2.5 million cases of snakebite per year and approximately 100,000 to 150,000 deaths. Thus, it is considered an important public health problem by the World Health Organization. Snakes from the Bothrops genus may cause severe local effects in the victims, so it is important to develop inhibitors to treat local effects in patients. In addition, approximately 30 different species of bothropic snakes have been described that may present differences in their venom composition. Small structural differences in the venom proteins may result in different ligands binding. Herein, BnSP-7, a PLA
Structure of 1,4‐bis(diphenylphosphinoyl)butane
Publisher: International Union of Crystallography (IUCr)
Date: 15-12-1991
Guidelines for the provision of psychological services for older adults
Publisher: Informa UK Limited
Date: 03-2006
Crystallization and preliminary X-ray diffraction analysis of an acidic phospholipase A2 complexed with p-bromophenacyl bromide and α-tocopherol inhibitors at 1.9- and 1.45-Å resolution
Publisher: Elsevier BV
Date: 06-2004
Characteristics and effectiveness of cognitive behavioral therapy for older adults living in residential care: a systematic review
Publisher: Informa UK Limited
Date: 09-11-2019
DOI: 10.1080/13607863.2019.1686457
Abstract: Cognitive behavioral therapy (CBT) for depression and anxiety for older adults living in residential aged care facilities (RACFs) needs to accommodate the care needs of residents and the circumstances of RACFs. This systematic review examines the delivery and content characteristics of these interventions, in relation to participant satisfaction, staff appraisal, uptake rate, attrition rate, and treatment effectiveness. Such a review could provide important information for the development of future CBT-based interventions. Studies that examined the application of CBT for depression or anxiety in RACFs were identified by systematically searching a number of relevant databases. Reference lists of all included studies were examined, and citation searches on the Web of Science were conducted. Two independent reviewers were involved in screening articles and in extracting data and assessing methodological quality of the selected studies. Across the 18 studies included in this review, the most common therapeutic strategy was pleasant activities scheduling. Studies varied on treatment duration (2-24 weeks), number of sessions (6-24), and length of sessions (10-120 min). Residents and staff members were satisfied with the CBT interventions. The average uptake rate was 72.9%. The average attrition rate was 19.9%. Statistically significant results were reported in 8 of the 12 randomized controlled trials (RCTs). In these eight RCTs, CBT was characterized by psychoeducation, behavioral activation, and problem-solving techniques further, the therapists in six of these studies had training in psychology. CBT interventions for depression and anxiety are acceptable to RACF residents and judged positively by staff members. Effective studies differed from non-effective studies on content and training characteristics, but not on other delivery features.
Disease-specific anxiety symptomatology in Parkinson's disease
Publisher: Cambridge University Press (CUP)
Date: 10-02-2016
DOI: 10.1017/S1041610215002410
Abstract: Symptoms of anxiety relating to Parkinson's disease (PD) occur commonly and include symptomatology associated with motor disability and complications arising from PD medication. However, there have been relatively few attempts to profile such disease-specific anxiety symptoms in PD. Consequently, anxiety in PD is underdiagnosed and undertreated. The present study characterizes PD-related anxiety symptoms to assist with the more accurate assessment and treatment of anxiety in PD. Ninety non-demented PD patients underwent a semi-structured diagnostic assessment targeting anxiety symptoms using relevant sections of the Mini International Neuropsychiatric Interview (MINI-plus). In addition, they were assessed for the presence of 30 PD-related anxiety symptoms derived from the literature, the clinical experience of an expert panel and the PD Anxiety-Motor Complications Questionnaire (PDAMCQ). The onset of anxiety in relation to the diagnosis of PD was determined. Frequent ( %) PD-specific anxiety symptoms included distress, worry, fear, agitation, embarrassment, and social withdrawal due to motor symptoms and PD medication complications, and were experienced more commonly in patients meeting DSM-IV criteria for an anxiety disorder. The onset of common anxiety disorders was observed equally before and after a diagnosis of PD. Patients in a residual group of Anxiety Not Otherwise Specified had an onset of anxiety after a diagnosis of PD. Careful characterization of PD-specific anxiety symptomatology provides a basis for conceptualizing anxiety and assists with the development of a new PD-specific measure to accurately assess anxiety in PD.
A Systematic Review of the Effect of Assistance Dog Ownership on Practical Support, Health, and Wellbeing: Implications for Older Adults.
Publisher: Informa UK Limited
Date: 02-08-2022
DOI: 10.1080/07317115.2022.2100728
Abstract: While assistance dog use has received considerable recent attention, few studies have focused on benefits for older adults. The current review examined effects of assistance dog acquisition across practical, mental, physical, and social wellbeing domains for older adults. Further, it compared assistance dog types and identified potential barriers to acquisition. A systematic review was completed. Criteria focused on older adults with relevant disabilities (visual/hearing impairments, and PTSD), who received support from an assistance dog (guide, hearing or other assistance dog). Identified studies (n = 2,951) were screened, 256 assessed for eligibility, and 28 included, with key information extracted and summarized. All dog types demonstrated benefits across all assessed domains. Disadvantages and acquisition barriers were identified. However, limited empirical evidence was available, and no studies focused exclusively on older adults, revealing the need for studies including this age-group. While results indicated support for assistance dog acquisition, disadvantages and barriers require further attention. Methodologically improved research should focus on assistance dog acquisition for older persons. The study indicated assistance dog acquisition could produce positive clinical impacts, including on mental health and everyday functioning. Thus, acquisition could be considered as part a multi-faceted treatment or recommended to appropriate older adults.
Associations Between Latent Classes of Perceived Neighborhood Destination Accessibility and Walking Behaviors in Older Adults of a Low-Density and a High-Density City
Publisher: Human Kinetics
Date: 08-2019
Abstract: To examine associations between perceived destination accessibility within different distances from home and self-reported overall amounts of walking for different purposes among older adults (aged ≥ 65 years) in Brisbane, Australia ( N = 793) and Hong Kong, China ( N = 484). Perceived neighborhood destination accessibility types were derived from latent class analysis using comparable measures of perceived distance to 12 destinations from epidemiological studies in the two cities. Associations of perceived destination accessibility with measures of within-neighborhood walking were also estimated in Hong Kong participants. Better perceived destination accessibility was positively associated with the likelihood of walking in Brisbane participants only. Perceived destination accessibility within a short distance from home (5-min walk) was negatively related to the amount of within-neighborhood walking for transport in Hong Kong residents who walked. Our findings suggest that providing moderate-to-high, but not extreme, levels of destination accessibility may be optimal for the promotion of walking in older community dwellers.
Structural, functional, and bioinformatics studies reveal a new snake venom homologue phospholipase A2 class
Publisher: Wiley
Date: 27-09-2010
DOI: 10.1002/PROT.22858
Abstract: Phospholipases A₂ (PLA₂s) are enzymes responsible for membrane disruption through Ca(2+) -dependent hydrolysis of phospholipids. Lys49-PLA₂s are well-characterized homologue PLA₂s that do not show catalytic activity but can exert a pronounced local myotoxic effect. These homologue PLA₂s were first believed to present residual catalytic activity but experiments with a recombinant toxin show they are incapable of catalysis. Herein, we present a new homologue Asp49-PLA₂ (BthTX-II) that is also able to exert muscle damage. This toxin was isolated in 1992 and characterized as presenting very low catalytic activity. Interestingly, this myotoxic homologue Asp49-PLA₂ conserves all the residues responsible for Ca(2+) coordination and of the catalytic network, features thought to be fundamental for PLA₂ enzymatic activity. Previous crystallographic studies of apo BthTX-II suggested this toxin could be catalytically inactive since a distortion in the calcium binding loop was observed. In this article, we show BthTX-II is not catalytic based on an in vitro cell viability assay and time-lapse experiments on C2C12 myotube cell cultures, X-ray crystallography and phylogenetic studies. Cell culture experiments show that BthTX-II is devoid of catalytic activity, as already observed for Lys49-PLA₂s. Crystallographic studies of the complex BthTX-II/Ca(2+) show that the distortion of the calcium binding loop is still present and impairs ion coordination even though Ca(2+) are found interacting with other regions of the protein. Phylogenetic studies demonstrate that BthTX-II is more phylogenetically related to Lys49-PLA₂s than to other Asp49-PLA₂s, thus allowing Crotalinae subfamily PLA₂s to be classified into two main branches: a catalytic and a myotoxic one.
Crystal structure of an acidic platelet aggregation inhibitor and hypotensive phospholipase A2 in the monomeric and dimeric states: insights into its oligomeric state
Publisher: Elsevier BV
Date: 10-2004
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