ORCID Profile
0000-0002-8290-813X
Current Organisations
National Supercomputing Centre Singapore
,
Macquarie University
,
Griffith University
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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.
Artificial Intelligence and Image Processing not elsewhere classified | Bioinformatics Software | Molecular Evolution | Theoretical And Computational Chemistry Not Elsewhere Classified | Biochemistry and Cell Biology | Gene Expression | Theoretical and Computational Chemistry | Artificial Intelligence and Image Processing | Biotechnology Not Elsewhere Classified | Veterinary Sciences | Condensed Matter Physics—Electronic And Magnetic Properties; | Optics And Opto-Electronic Physics | Cell Development, Proliferation and Death | Systems Biology | Parasitology
Flora, Fauna and Biodiversity of environments not elsewhere classified | Computer Software and Services not elsewhere classified | Information Processing Services (incl. Data Entry and Capture) | Expanding Knowledge in the Biological Sciences | Biological sciences | Earth sciences | Chemical sciences | Physical sciences |
Publisher: CSIRO Publishing
Date: 2018
DOI: 10.1071/CH18416
Abstract: Sir Derek Barton’s seminal work on steroid conformational analysis opened up a new era of enquiry into how the preferred conformation of any molecule could have profound effects on its physical–chemical properties and activities. Conformation-based effects on molecular activity and reactivity continue to manifest, with one key area of investigation currently focussed on conformational entropy in driving protein–ligand interactions. Carrying on from Barton’s initial insight on natural product conformational properties, new questions now address how conformational flexibility within a bioactive natural product structural framework (reasonable chaos), can be directed to confer dynamically new protein–ligand interactions beyond the basic lock–key model (imaginative order). Here we summarise our work on exploring conformational ersity from fluorinated natural product fragments, and how this approach of conformation-coupled ersity-oriented synthesis can be used to iteratively derive ligands with enhanced specificity against highly homologous protein domains. Our results demonstrate that the conformation entropic states of highly conserved protein domains differ significantly, and this conformational ersity, beyond primary sequence analysis, can be duly captured and exploited by natural-product derived ligands with complementary conformational dynamics for enhancing recognition specificity in drug lead discovery.
Publisher: Wiley
Date: 05-1985
Publisher: Oxford University Press (OUP)
Date: 19-12-2007
DOI: 10.1093/BIB/BBL038
Abstract: T-cell recognition of peptide/major histocompatibility complex (MHC) is a prerequisite for cellular immunity. Recently, there has been an influx of bioinformatics tools to facilitate the identification of T-cell epitopes to specific MHC alleles. This article examines existing computational strategies for the study of peptide/MHC interactions. The most important bioinformatics tools and methods with relevance to the study of peptide/MHC interactions have been reviewed. We have also provided guidelines for predicting antigenic peptides based on the availability of existing experimental data.
Publisher: American Chemical Society (ACS)
Date: 21-09-2017
DOI: 10.1021/ACS.JPROTEOME.7B00354
Abstract: The evidence that any protein exists in the Human Proteome Project (HPP protein evidence 1 or PE1) has revolved primarily (although not exclusively) around mass spectrometry (MS) (93% of PE1 proteins have MS evidence in the latest neXtProt release), with robust and stringent, well-curated metrics that have served the community well. This has led to a significant number of proteins still considered "missing" (i.e., PE2-4). Many PE2-4 proteins have MS evidence of unacceptable quality (small or not enough unitypic peptides and unacceptably high protein eptide FDRs), transcriptomic, or antibody evidence. Here we use a Chromosome 7 PE2 ex le called Prestin to demonstrate that clear and robust criteria/metrics need to be developed for proteins that may not or cannot produce clear-cut MS evidence while possessing significant non-MS evidence, including disease-association data. Many of the PE2-4 proteins are inaccessible, spatiotemporally expressed in a limited way, or expressed at such a very low copy number as to be unable to be detected by current MS methodologies. We propose that the HPP community consider and lead a communal initiative to accelerate the discovery and characterization of these types of "missing" proteins.
Publisher: Springer Science and Business Media LLC
Date: 2010
Publisher: Elsevier BV
Date: 08-2009
Publisher: Wiley
Date: 20-09-2021
DOI: 10.1002/FSN3.2595
Abstract: Fermented foods are an essential source of nutrition for the communities living in developing areas of the world. Additionally, traditional fermented products are a rich source of various bioactive components. Experimental research regarding the functional exploration of these products is a way forward for better human health. Among fermented foods, Koumiss is rich in vitamins especially vitamin C and minerals, i.e., phosphorus and calcium. In addition, it is also rich in vitamins A, E, B2, B12, and pantothenic acid. High concentrations of lactose in milk favor bacterial fermentation, as the original cultures decompose it into lactic acid. Koumiss contains essential fatty acids such as linoleic and linolenic acid. Koumiss offers many health benefits including boosting the immune system and maintains blood pressure, good effect on the kidneys, endocrine glands, gut system, liver, and nervous and vascular system. The rich microflora from the fermented product has a pivotal role in maintaining gut health and treating various digestive diseases. The core focus of the current review paper is to highlight the nutritional and therapeutic potential, i.e., anticarcinogenic, hypocholesterolemia effect, antioxidative properties, antibacterial properties, antibacterial spectrum, intestinal enlargement, and β‐galactosidase activity, of Koumiss as a traditional fermented product. Moreover, history and production technology of the Koumiss are also the main part of this review paper.
Publisher: Springer Science and Business Media LLC
Date: 12-2009
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.SBI.2019.03.022
Abstract: GPCRs constitute the largest druggable family having targets for 475 Food and Drug Administration (FDA) approved drugs. As GPCRs are of great interest to pharmaceutical industry, enormous efforts are being expended to find relevant and potent GPCR ligands as lead compounds. There are tens of millions of compounds present in different chemical databases. In order to scan this immense chemical space, computational methods, especially machine learning (ML) methods, are essential components of GPCR drug discovery pipelines. ML approaches have applications in both ligand-based and structure-based virtual screening. We present here a cheminformatics overview of ML applications to different stages of GPCR drug discovery. Focusing on olfactory receptors, which are the largest family of GPCRs, a case study for predicting agonists for an ectopic olfactory receptor, OR1G1, compares four classical ML methods.
Publisher: MDPI AG
Date: 04-02-2021
Abstract: Stone fruits, including peach (Prunus persica L.), nectarine (Prunus nucipersica L.), plum (Prunus domestica L.) and apricot (Prunus armeniaca L.) are common commercial fruits in the market. However, a huge amount of stone fruits waste is produced throughout the food supply chain during picking, handling, processing, packaging, storage, transportation, retailing and final consumption. These stone fruits waste contain high phenolic content which are the main contributors to the antioxidant potential and associated health benefits. The antioxidant results showed that plum waste contained higher concentrations of total phenolic content (TPC) (0.94 ± 0.07 mg gallic acid equivalents (GAE)/g) and total flavonoid content (TFC) (0.34 ± 0.01 mg quercetin equivalents (QE)/g), while apricot waste contained a higher concentration of total tannin content (TTC) (0.19 ± 0.03 mg catechin equivalents (CE)/g) and DPPH activity (1.47 ± 0.12 mg ascorbic acid equivalents (AAE)/g). However, nectarine waste had higher antioxidant capacity in ferric reducing-antioxidant power (FRAP) (0.98 ± 0.02 mg AAE/g) and total antioxidant capacity (TAC) (0.91 ± 0.09 mg AAE/g) assays, while peach waste showed higher antioxidant capacity in 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assay (0.43 ± 0.09 mg AAE/g) as compared to other stone fruits waste. Qualitative and quantitative phenolic analysis of Australian grown stone fruits waste were conducted by liquid chromatography coupled with electrospray-ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) and HPLC-photodiode array detection (PDA). The LC-ESI-QTOF-MS/MS result indicates that 59 phenolic compounds were tentatively characterized in peach (33 compounds), nectarine (28), plum (38) and apricot (23). The HPLC-PDA indicated that p-hydroxybenzoic acid (18.64 ± 1.30 mg/g) was detected to be the most dominant phenolic acid and quercetin (19.68 ± 1.38 mg/g) was the most significant flavonoid in stone fruits waste. Hence, it could be concluded that stone fruit waste contains various phenolic compounds and have antioxidant potential. The results could support the applications of these stone fruit wastes in other food, feed, nutraceutical and pharmaceutical industries.
Publisher: Springer Science and Business Media LLC
Date: 12-2012
DOI: 10.1186/1471-2164-13-S7-S8
Abstract: Helminths are important socio-economic organisms, responsible for causing major parasitic infections in humans, other animals and plants. These infections impose a significant public health and economic burden globally. Exceptionally, some helminth organisms like Caenorhabditis elegans are free-living in nature and serve as model organisms for studying parasitic infections. Excretory/secretory proteins play an important role in parasitic helminth infections which make these proteins attractive targets for therapeutic use. In the case of helminths, large volume of expressed sequence tags (ESTs) has been generated to understand parasitism at molecular level and for predicting excretory/secretory proteins for developing novel strategies to tackle parasitic infections. However, mostly predicted ES proteins are not available for further analysis and there is no repository available for such predicted ES proteins. Furthermore, predictions have, in the main, focussed on classical secretory pathways while it is well established that helminth parasites also utilise non-classical secretory pathways. We developed a free Helminth Secretome Database (HSD), which serves as a repository for ES proteins predicted using classical and non-classical secretory pathways, from EST data for 78 helminth species (64 nematodes, 7 trematodes and 7 cestodes) ranging from parasitic to free-living organisms. Approximately 0.9 million ESTs compiled from the largest EST database, dbEST were cleaned, assembled and analysed by different computational tools in our bioinformatics pipeline and predicted ES proteins were submitted to HSD. We report the large-scale prediction and analysis of classically and non-classically secreted ES proteins from erse helminth organisms. All the Unigenes (contigs and singletons) and excretory/secretory protein datasets generated from this analysis are freely available. A BLAST server is available at sd , for checking the sequence similarity of new protein sequences against predicted helminth ES proteins.
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: American Chemical Society (ACS)
Date: 20-09-2021
Publisher: Nepal Journals Online (JOL)
Date: 30-09-2021
Abstract: The severe and life-threatening nature of the COVID-19 infection, the ARDS (acute respiratory distress syndrome) as well as the cytokine storm induced by the infection, commands lifesaving high doses of steroid therapy. As in all pharmacological therapies adverse effects are present. One such adverse effect which is being reported is corticosteroid induced avascular necrosis of the femoral head/ osteonecrosis of the femoral head. It must be noted that AVN principally affects the femoral head and most commonly the anterolateral aspect thereof as it is the crux of weight bearing. Corticosteroids induce fat mobilization and this thus innately enhances the likelihood of fat emboli developing from the liver to occlude minor blood vessels in the femur, this thereby compromises the microvascular environment. Superadded to this the steroid therapy disrupts calcium metabolism and homeostasis which induces hypertrophy in the intramedullary fat cells, Gaucher cells and inflammatory cells whilst increasing the activity of osteoclasts, thus increasing bone resorption and decreasing calcium uptake and deposition ultimately leading to an insufficiency in the trabecular and cortical bone. This insufficiency thus equates to an increased intraosseous pressure which impedes intramedullary circulation and results in avascular necrosis. It is evident that avascular necrosis is directly caused by high dose steroid therapy, however the case reports have very clearly indicated that the rapid onset of AVN post recovery from the COVID-19 infection cannot be solely attributed to steroid therapy and that another benefactor induced by the COVID-19 infection is at play. It is thus vital for treating physicians to take cognisance of this adverse effect post recovery and therefore should ensure that prophylactic bisphosphonate therapy is initiated timeously and congruently.
Publisher: Elsevier BV
Date: 2021
Publisher: American Association for Cancer Research (AACR)
Date: 15-09-2023
Publisher: Springer Science and Business Media LLC
Date: 2009
Publisher: Wiley
Date: 06-1983
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.BIOTECHADV.2008.10.002
Abstract: Hookworms of humans are blood-feeding parasitic nematodes of major socio-economic significance in a wide range of countries. They cause a neglected tropical disease (NTD) called "hookworm disease" (=necatoriasis and/or ancylostomiasis). Necator americanus is the most widely distributed hookworm of humans and is a leading cause of iron deficiency anaemia, which can cause physical and mental retardation and deaths in children as well as adverse maternal-foetal outcomes. Currently, there is a significant focus on the development of new approaches for the prevention and control of hookworms in humans. Technological advances are underpinning the discovery of drug and vaccine targets through insights into the molecular biology and genomics of these parasites and their relationship with the human host. In spite of the widespread socio-economic impacts of human necatoriasis, molecular datasets for N. americanus are scant, limiting progress in molecular research. The present article explores all currently available EST datasets for adult and larval stages of N. americanus using a semi-automated bioinformatic pipeline. In the current repertoire of molecules now available, some have been or are being considered as candidate vaccines against N. americanus. Among others, the most abundant sets of molecules relate to the pathogenesis-related protein (PRP) superfamily, comprising various members, such as the Ancylostoma-secreted or activation-associated proteins (ASPs) and the kunitz-type proteins, both of which are inferred to play key roles in the interplay between N. americanus and the human host. Understanding the molecular biology of these and other novel molecules discovered could have important implications for finding new ways of disrupting the pathways that they are involved in, and should facilitate the identification of new drug and vaccine targets. Also, the bioinformatic prediction of the essentiality of genes and gene products as well as molecular network connectivity of nematode-specific genes, together with sequencing by 454 technology, are likely to assist in the genomic discovery efforts in the very near future, to also underpin fundamental, molecular research of hookworms.
Publisher: Elsevier
Date: 2019
Publisher: MDPI AG
Date: 28-04-2021
DOI: 10.3390/PR9050781
Abstract: Kiwifruit hold significant nutritional value and are a good source of antioxidants due to their erse range of bioactive compounds. Kiwifruit waste is generated throughout the food supply chain, particularly during transportation and storage. Kiwifruit rejected from the retail market due to unfavorable appearance still possess potential economic value as kiwifruit are abundant in phenolic compounds. The present work studied the phenolic profile and antioxidant potential of rejected kiwifruit, including SunGold (Actinidia chinensis), Hayward (Actinidia deliciosa), and round organic Hayward (Actinidia deliciosa). Regarding phenolics estimation, SunGold possessed the highest TPC (0.72 ± 0.01 mg GAE/g), while Hayward exhibited the highest TFC (0.05 ± 0.09 mg QE/g). In antioxidant assays, SunGold showed the highest antioxidant activities in DPPH (0.31 ± 0.35 mg AAE/g), FRAP (0.48 ± 0.04 mg AAE/g), ABTS (0.69 ± 0.07 mg AAE/g), •OH-RSA (0.07 ± 0.03 mg AAE/g) assays, and FICA (0.19 ± 0.07 mg EDTA/g), whereas Hayward showed the highest RPA (0.09 ± 0.02 mg AAE/g) and TAC (0.57 ± 0.04 mg AAE/g). Separation and characterization of phenolics were conducted using LC-ESI-QTOF-MS/MS. A total of 97 phenolics were tentatively characterized from rejected SunGold (71 phenolics), Hayward (55 phenolics), and round organic Hayward (9 phenolics). Hydroxycinnamic acids and flavonols were the most common phenolics characterized in the three s les. The quantitative analysis was conducted by HPLC-PDA and found that chlorogenic acid (23.98 ± 0.95 mg/g), catechin (23.24 ± 1.16 mg/g), and quercetin (24.59 ± 1.23 mg/g) were the most abundant phenolics present in the rejected kiwifruit s les. The notable presence of phenolic compounds and their corresponding antioxidant capacities indicate the potential value of rescuing rejected kiwifruit for further utilization and commercial exploitation.
Publisher: Springer Science and Business Media LLC
Date: 19-01-2014
DOI: 10.1038/NG.2875
Publisher: Springer Science and Business Media LLC
Date: 02-2019
Publisher: American Chemical Society (ACS)
Date: 11-01-2013
DOI: 10.1021/PR301082P
Abstract: The chromosome-centric human proteome project aims to systematically map all human proteins, chromosome by chromosome, in a gene-centric manner through dedicated efforts from national and international teams. This mapping will lead to a knowledge-based resource defining the full set of proteins encoded in each chromosome and laying the foundation for the development of a standardized approach to analyze the massive proteomic data sets currently being generated. The neXtProt database lists 946 proteins as the human proteome of chromosome 7. However, 170 (18%) proteins of human chromosome 7 have no evidence at the proteomic, antibody, or structural levels and are considered "missing" in this study as they lack experimental support. We have developed a protocol for the functional annotation of these "missing" proteins by integrating several bioinformatics analysis and annotation tools, sequential BLAST homology searches, protein domain/motif and gene ontology (GO) mapping, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Using the BLAST search strategy, homologues for reviewed non-human mammalian proteins with protein evidence were identified for 90 "missing" proteins while another 38 had reviewed non-human mammalian homologues. Putative functional annotations were assigned to 27 of the remaining 43 novel proteins. Proteotypic peptides have been computationally generated to facilitate rapid identification of these proteins. Four of the "missing" chromosome 7 proteins have been substantiated by the ENCODE proteogenomic peptide data.
Publisher: MDPI AG
Date: 12-08-2021
DOI: 10.3390/IJMS22168686
Abstract: Oral cancer is a major global health problem with high incidence and low survival rates. The oral cavity contains biofilms as dental plaques that harbour both Gram-negative and Gram-positive bacterial antigens, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), respectively. LPS and LTA are known to stimulate cancer cell growth, and the bioactive phytochemical capsaicin has been reported to reverse this effect. Here, we tested the efficacy of oral cancer chemotherapy treatment with capsaicin in the presence of LPS, LTA or the combination of both antigens. LPS and LTA were administered to Cal 27 oral cancer cells prior to and/or concurrently with capsaicin, and the treatment efficacy was evaluated by measuring cell proliferation and apoptotic cell death. We found that while capsaicin inhibits oral cancer cell proliferation and metabolism (MT Glo assay) and increases cell death (Trypan blue exclusion assay and Caspase 3/7 expression), its anti-cancer effect was significantly reduced on cells that are either primed or exposed to the bacterial antigens. Capsaicin treatment significantly increased oral cancer cells’ suppressor of cytokine signalling 3 gene expression. This increase was reversed in the presence of bacterial antigens during treatment. Our data establish a rationale for clinical consideration of bacterial antigens that may interfere with the treatment efficacy of oral cancer.
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.BIOTECHADV.2007.01.008
Abstract: There are substantial gaps in the knowledge of the molecular processes of development and reproduction in parasitic nematodes, despite the fact that understanding such processes could lead to novel ways of treating and controlling parasitic diseases, through blocking or disrupting key biological pathways. Biotechnological advances through large-scale sequencing projects, approaches for the analysis of differential gene and protein expression and functional genomics (e.g., double-stranded RNA interference) now provide opportunities to investigate the molecular basis of developmental processes in some parasitic nematodes. The porcine nodule worm, Oesophagostomum dentatum (order Strongylida), may provide a platform for testing the function of genes from this and related nematodes, given that this species can be grown and maintained in culture in vitro for periods longer than other nematodes of the same order. In this article, we review relevant biological, biochemical and molecular biological and genomic information about O. dentatum and propose that the O. dentatum - pig system provides an attractive model for exploring molecular developmental and reproductive processes in strongylid nematodes, leading toward new intervention methods and biotechnological outcomes.
Publisher: Bentham Science Publishers Ltd.
Date: 10-11-2020
DOI: 10.2174/1573407216666200127130014
Abstract: Nowadays, bioactive moieties of plants are gaining attention amongst the masses to mitigate lifestyle related dysfunctions owing to their safe nature and functional properties. Considering phytochemistry and cost-effectiveness of cabbage, the current project was designed to probe the antioxidant capacity of locally grown green and red cabbage. The total polyphenols and free radical scavenging ability of red and green cabbage were determined using spectrophotometer while HPLC analysis was carried out to further fractionate phenolic acids and flavonoid constituents. Apart from this, antioxidant vitamins including vitamin C tocopherol and β-carotene were also detected using HPLC system. The red cabbage showed higher amount of total polyphenols and flavonoids (224.37±6.96 & 219.15±10.30 mg/100g F.W.) than green cabbage (58.41±3.01 & 34.04±1.06 mg/100g F.W.) along with the existence of anthocyanins (69.86±4.12 mg/100g F.W.) in red cabbage. Comparative HPLC analysis regarding antioxidant moieties showed significant proportion of kempferol (171.10±5.99 mg/100g F.W.) followed by vitamin C (139.07±2.23 mg/100g F.W.) in red cabbage however, vitamin C (121.46±3.28 mg/100g F.W.) was found as the major antioxidant in green cabbage. The red cabbage depicted higher free radical quenching and reducing ability in contrast to green cabbage using DPPH (1, 1-diphenyl-2-picrylhydrazyl), ABTS [2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid)], FRAP (ferric reducing antioxidant power) and PFRAP (potassium ferricyanide reducing antioxidant power) and H2O2 scavenging ability assays. In the nutshell, red cabbage showed better free radical scavenging ability as compared to green cabbage based on variation and quantification of antioxidant indices.
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.JSB.2014.01.001
Abstract: Integrin αvβ6 is an epithelially-restricted heterodimeric transmembrane glycoprotein, known to interact with the urokinase plasminogen activating receptor (uPAR), playing a critical role in cancer progression. While the X-ray crystallographic structures of segments of other integrin heterodimers are known, there is no structural information for the complete αvβ6 integrin to assess its direct interaction with uPAR. We have performed structural analysis of αvβ6·uPAR interactions using model data with docking simulations to pinpoint their interface, in accord with earlier reports of the β-propeller region of integrin α-chain interacting with uPAR. Interaction of αvβ6·uPAR was demonstrated by our previous study using immunoprecipitation coupled with proteomic analysis by mass spectrometry. Recently this interaction was validated with proximity ligation assays and peptide arrays. The data suggested that two potential peptide regions from domain II and one peptide region from domain III of uPAR, interact with αvβ6 integrin. Only the peptide region from domain III is consistent with the three-dimensional interaction site proposed in this study. The molecular basis of integrin αvβ6·uPAR binding using structural data is discussed for its implications as a potential therapeutic target in cancer management.
Publisher: Elsevier BV
Date: 11-2015
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.THERIOGENOLOGY.2019.05.036
Abstract: Reproduction efficiency of male animals is one of the key factors influencing the sustainability of livestock. Mass spectrometry (MS) based proteomics has become an important tool for studying seminal plasma proteomes. In this review, we summarize bioinformatics analysis strategies for current proteomics approaches, for identifying novel biomarkers of reproductive robustness.
Publisher: Oxford University Press (OUP)
Date: 26-05-2007
DOI: 10.1093/BIB/BBL015
Abstract: Expressed sequence tag (EST) sequencing projects are underway for numerous organisms, generating millions of short, single-pass nucleotide sequence reads, accumulating in EST databases. Extensive computational strategies have been developed to organize and analyse both small- and large-scale EST data for gene discovery, transcript and single nucleotide polymorphism analysis as well as functional annotation of putative gene products. We provide an overview of the significance of ESTs in the genomic era, their properties and the applications of ESTs. Methods adopted for each step of EST analysis by various research groups have been compared. Challenges that lie ahead in organizing and analysing the ever increasing EST data have also been identified. The most appropriate software tools for EST pre-processing, clustering and assembly, database matching and functional annotation have been compiled (available online from biolinfo.org/EST). We propose a road map for EST analysis to accelerate the effective analyses of EST data sets. An investigation of EST analysis platforms reveals that they all terminate prior to downstream functional annotation including gene ontologies, motif attern analysis and pathway mapping.
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Springer Science and Business Media LLC
Date: 12-2017
Publisher: Oxford University Press (OUP)
Date: 2004
DOI: 10.1093/NAR/GKH051
Publisher: Springer Science and Business Media LLC
Date: 18-12-2018
DOI: 10.1038/S41598-018-36203-8
Abstract: The biological process known as post-translational modification (PTM) contributes to ersifying the proteome hence affecting many aspects of normal cell biology and pathogenesis. There have been many recently reported PTMs, but lysine phosphoglycerylation has emerged as the most recent subject of interest. Despite a large number of proteins being sequenced, the experimental method for detection of phosphoglycerylated residues remains an expensive, time-consuming and inefficient endeavor in the post-genomic era. Instead, the computational methods are being proposed for accurately predicting phosphoglycerylated lysines. Though a number of predictors are available, performance in detecting phosphoglycerylated lysine residues is still limited. In this paper, we propose a new predictor called PhoglyStruct that utilizes structural information of amino acids alongside a multilayer perceptron classifier for predicting phosphoglycerylated and non-phosphoglycerylated lysine residues. For the experiment, we located phosphoglycerylated and non-phosphoglycerylated lysines in our employed benchmark. We then derived and integrated properties such as accessible surface area, backbone torsion angles, and local structure conformations. PhoglyStruct showed significant improvement in the ability to detect phosphoglycerylated residues from non-phosphoglycerylated ones when compared to previous predictors. The sensitivity, specificity, accuracy, Mathews correlation coefficient and AUC were 0.8542, 0.7597, 0.7834, 0.5468 and 0.8077, respectively. The data and Matlab/Octave software packages are available at belavit/PhoglyStruct .
Publisher: Springer Science and Business Media LLC
Date: 12-2019
DOI: 10.1186/S12860-019-0241-0
Abstract: Toll-like receptor 9 is a key innate immune receptor involved in detecting infectious diseases and cancer. TLR9 activates the innate immune system following the recognition of single-stranded DNA oligonucleotides (ODN) containing unmethylated cytosine-guanine (CpG) motifs. Due to the considerable number of rotatable bonds in ODNs, high-throughput in silico screening for potential TLR9 activity via traditional structure-based virtual screening approaches of CpG ODNs is challenging. In the current study, we present a machine learning based method for predicting novel mouse TLR9 (mTLR9) agonists based on features including count and position of motifs, the distance between the motifs and graphically derived features such as the radius of gyration and moment of Inertia. We employed an in-house experimentally validated dataset of 396 single-stranded synthetic ODNs, to compare the results of five machine learning algorithms. Since the dataset was highly imbalanced, we used an ensemble learning approach based on repeated random down-s ling. Using in-house experimental TLR9 activity data we found that random forest algorithm outperformed other algorithms for our dataset for TLR9 activity prediction. Therefore, we developed a cross-validated ensemble classifier of 20 random forest models. The average Matthews correlation coefficient and balanced accuracy of our ensemble classifier in test s les was 0.61 and 80.0%, respectively, with the maximum balanced accuracy and Matthews correlation coefficient of 87.0% and 0.75, respectively. We confirmed common sequence motifs including ‘CC’, ‘GG’,‘AG’, ‘CCCG’ and ‘CGGC’ were overrepresented in mTLR9 agonists. Predictions on 6000 randomly generated ODNs were ranked and the top 100 ODNs were synthesized and experimentally tested for activity in a mTLR9 reporter cell assay, with 91 of the 100 selected ODNs showing high activity, confirming the accuracy of the model in predicting mTLR9 activity. We combined repeated random down-s ling with random forest to overcome the class imbalance problem and achieved promising results. Overall, we showed that the random forest algorithm outperformed other machine learning algorithms including support vector machines, shrinkage discriminant analysis, gradient boosting machine and neural networks. Due to its predictive performance and simplicity, the random forest technique is a useful method for prediction of mTLR9 ODN agonists.
Publisher: Springer Science and Business Media LLC
Date: 2018
Publisher: Hindawi Limited
Date: 03-07-2021
DOI: 10.1111/JFPP.15690
Publisher: American Chemical Society (ACS)
Date: 12-01-2016
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Publisher: Woodhead Publishing Limited
Date: 2013
Publisher: Wiley
Date: 06-2020
DOI: 10.1002/CPBI.101
Publisher: Springer Science and Business Media LLC
Date: 12-2012
DOI: 10.1186/1471-2164-13-S7-S1
Abstract: The theme of the 2012 International Conference on Bioinformatics (InCoB) in Bangkok, Thailand was "From Biological Data to Knowledge to Technological Breakthroughs." Besides providing a forum for life scientists and bioinformatics researchers in the Asia-Pacific region to meet and interact, the conference also hosted thematic sessions on the Pan-Asian Pacific Genome Initiative and immunoinformatics. Over the seven years of conference papers published in BMC Bioinformatics and four years in BMC Genomics, we note that there is increasing interest in the applications of -omics technologies to the understanding of diseases, as a forerunner to personalized genomic medicine.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.BJA.2018.03.020
Abstract: The Standardising Endpoints for Perioperative Medicine group was established to derive an appropriate set of endpoints for use in clinical trials related to anaesthesia and perioperative medicine. Anaesthetic or analgesic technique during cancer surgery with curative intent may influence the risk of recurrence or metastasis. However, given the current equipoise in the existing literature, prospective, randomised, controlled trials are necessary to test this hypothesis. As such, a cancer subgroup was formed to derive endpoints related to research in onco-anaesthesia based on a current evidence base, international consensus and expert guidance. We undertook a systematic review to identify measures of oncological outcome used in the oncological, surgical, and wider literature. A multiround Delphi consensus process that included up to 89 clinician-researchers was then used to refine a recommended list of endpoints. We identified 90 studies in a literature search, which were the basis for a preliminary list of nine outcome measures and their definitions. A further two were added during the Delphi process. Response rates for Delphi rounds one, two, and three were 88% (n=9), 82% (n=73), and 100% (n=10), respectively. A final list of 10 defined endpoints was refined and developed, of which six secured approval by ≥70% of the group: cancer health related quality of life, days alive and out of hospital at 90 days, time to tumour progression, disease-free survival, cancer-specific survival, and overall survival (and 5-yr overall survival). Standardised endpoints in clinical outcomes studies will support benchmarking and pooling (meta-analysis) of trials. It is therefore recommended that one or more of these consensus-derived endpoints should be considered for inclusion in clinical trials evaluating a causal effect of anaesthesia-analgesia technique on oncological outcomes.
Publisher: Elsevier BV
Date: 04-2019
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.JPROT.2021.104384
Abstract: The collection of blood plasma is minimally invasive, and the fluid is a rich source of proteins for biomarker studies in both humans and animals. Plasma protein analysis by mass spectrometry (MS) can be challenging, though modern data acquisition strategies, such as sequential window acquisition of all theoretical fragment ion spectra (SWATH), enable reproducible quantitation of hundreds of proteins in non-depleted plasma from humans and laboratory model animals. Although there is strong potential to enhance veterinary and translational research, SWATH-based plasma proteomics in non-laboratory animals is virtually non-existent. One limitation to date is the lack of comprehensively annotated genomes to aid protein identification. The current study established plasma peptide spectral repositories for sheep and cattle that enabled quantification of over 200 proteins in non-depleted plasma using SWATH approach. Moreover, bioinformatics pipeline was developed to leverage inter-species homologies to enhance the depth of baseline libraries and plasma protein quantification in bovids. Finally, the practical utility of using bovid libraries for SWATH data extraction in taxonomically related non-domestic ungulate species (giraffe) has been demonstrated. SIGNIFICANCE: Ability to quickly generate comprehensive spectral libraries is limiting the applicability of data-independent acquisition, such as SWATH, to study proteomes of non-laboratory animals. We describe an approach to obtain relatively shallow foundational plasma repositories from domestic ruminants and employ homology searches to increase the depth of data, which we subsequently extend to unsequenced ungulates using SWATH method. When applied to cross-species proteomics, the number of proteins quantified by our approach far exceeds what is traditionally used in plasma protein tests.
Publisher: Springer Science and Business Media LLC
Date: 2009
Publisher: Public Library of Science (PLoS)
Date: 22-02-2011
Publisher: Springer Science and Business Media LLC
Date: 2009
Publisher: AIP Publishing
Date: 11-1991
DOI: 10.1063/1.461539
Abstract: The radial behavior of the average local ionization energy Ī(r) has been investigated for the atoms He–Kr, using ab initio Hartree–Fock atomic wave functions. Ī(r) is found to decrease in a stepwise manner with the inflection points serving effectively to define boundaries between electronic shells. There is a good inverse correlation between polarizability and the ionization energy in the outermost region of the atom, suggesting that Ī(r) may be a meaningful measure of local polarizabilities in atoms and molecules.
Publisher: Springer Science and Business Media LLC
Date: 2004
Publisher: Wiley
Date: 23-12-2010
Publisher: Springer Science and Business Media LLC
Date: 02-2007
DOI: 10.1186/1471-2105-9-S1-S10
Abstract: The analysis of expressed sequence tags (EST) offers a rapid and cost effective approach to elucidate the transcriptome of an organism, but requires several computational methods for assembly and annotation. Researchers frequently analyse each step manually, which is laborious and time consuming. We have recently developed ESTExplorer, a semi-automated computational workflow system, in order to achieve the rapid analysis of EST datasets. In this study, we evaluated EST data analysis for the parasitic nematode Trichostrongylus vitrinus (order Strongylida) using ESTExplorer, compared with database matching alone. We functionally annotated 1776 ESTs obtained via suppressive-subtractive hybridisation from T. vitrinus , an important parasitic trichostrongylid of small ruminants. Cluster and comparative genomic analyses of the transcripts using ESTExplorer indicated that 290 (41%) sequences had homologues in Caenorhabditis elegans , 329 (42%) in parasitic nematodes, 202 (28%) in organisms other than nematodes, and 218 (31%) had no significant match to any sequence in the current databases. Of the C. elegans homologues, 90 were associated with 'non-wildtype' double-stranded RNA interference (RNAi) phenotypes, including embryonic lethality, maternal sterility, sterile progeny, larval arrest and slow growth. We could functionally classify 267 (38%) sequences using the Gene Ontologies (GO) and establish pathway associations for 230 (33%) sequences using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Further examination of this EST dataset revealed a number of signalling molecules, proteases, protease inhibitors, enzymes, ion channels and immune-related genes. In addition, we identified 40 putative secreted proteins that could represent potential candidates for developing novel anthelmintics or vaccines. We further compared the automated EST sequence annotations, using ESTExplorer, with database search results for in idual T. vitrinus ESTs. ESTExplorer reliably and rapidly annotated 301 ESTs, with pathway and GO information, eliminating 60 low quality hits from database searches. We evaluated the efficacy of ESTExplorer in analysing EST data, and demonstrate that computational tools can be used to accelerate the process of gene discovery in EST sequencing projects. The present study has elucidated sets of relatively conserved and potentially novel genes for biological investigation, and the annotated EST set provides further insight into the molecular biology of T. vitrinus , towards the identification of novel drug targets.
Publisher: Elsevier BV
Date: 09-2011
Publisher: Wiley
Date: 09-2004
DOI: 10.1110/PS.04631204
Publisher: Hindawi Limited
Date: 28-04-2020
DOI: 10.1111/JFPP.14497
Publisher: Springer Science and Business Media LLC
Date: 02-2008
DOI: 10.1186/1471-2105-9-S1-S15
Abstract: Type I signal peptidases (SPases) are essential membrane-bound serine proteases responsible for the cleavage of signal peptides from proteins that are translocated across biological membranes. The crystal structure of SPase in complex with signal peptide has not been solved and their substrate-binding site and binding specificities remain poorly understood. We report here a structure-based model for Escherichia coli DsbA 13–25 in complex with its endogenous type I SPase. The bound structure of DsbA 13–25 in complex with its endogenous type I SPase reported here reveals the existence of an extended conformation of the precursor protein with a pronounced backbone twist between positions P3 and P1'. Residues 13–25 of DsbA occupy, and thereby define 13 subsites, S7 to S6', within the SPase substrate-binding site. The newly defined subsites, S1' to S6' play critical roles in the substrate specificities of E. coli SPase. Our results are in accord with available experimental data. Collectively, the results of this study provide interesting new insights into the binding conformation of signal peptides and the substrate-binding site of E. coli SPase. This is the first report on the modeling of a precursor protein into the entire SPase binding site. Together with the conserved precursor protein binding conformation, the existing and newly identified substrate binding sites readily explain SPase cleavage fidelity, consistent with existing biochemical results and solution structures of inhibitors in complex with E. coli SPase. Our data suggests that both signal and mature moiety sequences play important roles and should be considered in the development of predictive tools.
Publisher: Frontiers Media SA
Date: 15-09-2020
Publisher: Wiley
Date: 23-12-2010
Publisher: Elsevier
Date: 2018
Publisher: Elsevier
Date: 2013
Publisher: American Chemical Society (ACS)
Date: 07-1997
DOI: 10.1021/JP971051U
Publisher: Springer Science and Business Media LLC
Date: 08-2020
DOI: 10.1186/S12906-020-03033-Z
Abstract: Several flavonoids have been recognized as nutraceuticals, and myricetin is a good ex le. Myricetin is commonly found in plants and their antimicrobial and antioxidant activities is well demonstrated. One of its beneficial biological effects is the neuroprotective activity, showing preclinical activities on Alzheimer, Parkinson, and Huntington diseases, and even in amyotrophic lateral sclerosis. Also, myricetin has revealed other biological activities, among them as antidiabetic, anticancer, immunomodulatory, cardiovascular, analgesic and antihypertensive. However, few clinical trials have been performed using myricetin as nutraceutical. Thus, this review provides new insights on myricetin preclinical pharmacological activities, and role in selected clinical trials.
Publisher: Elsevier BV
Date: 2000
DOI: 10.1016/S0161-5890(00)00024-9
Abstract: Complement factor H (fH) is a member of a family of proteins involved in the regulation of complement activation (RCA). These proteins share a common structural motif, the Short Consensus Repeat (SCR), which is structurally conserved among related genes and between phylogenetically ergent species. fH is composed of 20 such SCRs and a variety of biological functions have been localised to specific SCR domains. The majority of in idual SCRs identified are encoded by single exons, and processes such as gene conversion, duplication and exon shuffling have been implicated in the evolution and genomic radiation of SCR-encoding genes. We have analysed two GenBank sequence entries relating to two overlapping PAC clones sequenced at the Sanger Centre which contain the entire human fH gene and two adjacent fH-related (fHR) genes, fHR-1 and fHR-3. Here, we report the detailed analysis of the assembled 221 kb of contiguous, ungapped genomic sequence from human chromosome 1q32, in part employing the RUMMAGE-DP automated annotation tool. Genomic duplications involving fH and fHR exons were identified and Alu/L1 repeat dating established that the duplications occurred after the separation of rodent and primate lineages. The analysis indicates that retrotransposition as well as single and multiple exon duplication events are likely to have been involved in SCR radiation and RCA gene evolution, facilitated by conservation of splice-phasing and the single-exon, single-SCR nature of the encoded domains.
Publisher: Elsevier BV
Date: 08-1999
Publisher: Springer Science and Business Media LLC
Date: 12-2006
DOI: 10.1186/1471-2105-7-S5-S14
Abstract: Caspases belong to a class of cysteine proteases which function as critical effectors in apoptosis and inflammation by cleaving substrates immediately after unique sites. Prediction of such cleavage sites will complement structural and functional studies on substrates cleavage as well as discovery of new substrates. Recently, different computational methods have been developed to predict the cleavage sites of caspase substrates with varying degrees of success. As the support vector machines (SVM) algorithm has been shown to be useful in several biological classification problems, we have implemented an SVM-based method to investigate its applicability to this domain. A set of unique caspase substrates cleavage sites were obtained from literature and used for evaluating the SVM method. Datasets containing (i) the tetrapeptide cleavage sites, (ii) the tetrapeptide cleavage sites, augmented by two adjacent residues, P 1 ' and P 2 ' amino acids and (iii) the tetrapeptide cleavage sites with ten additional upstream and downstream flanking sequences (where available) were tested. The SVM method achieved an accuracy ranging from 81.25% to 97.92% on independent test sets. The SVM method successfully predicted the cleavage of a novel caspase substrate and its mutants. This study presents an SVM approach for predicting caspase substrate cleavage sites based on the cleavage sites and the downstream and upstream flanking sequences. The method shows an improvement over existing methods and may be useful for predicting hitherto undiscovered cleavage sites.
Publisher: Springer New York
Date: 2010
Publisher: Royal Society of Chemistry (RSC)
Date: 1994
DOI: 10.1039/FT9949002047
Publisher: Elsevier
Date: 2006
Publisher: Wiley
Date: 2003
Publisher: Springer Science and Business Media LLC
Date: 2010
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.BIOPHA.2021.112191
Abstract: Tobacco is grown in large quantities worldwide as a widely distributed commercial crop. From the harvest of the field to the process into the final product, a series of procedures generate enormous amount of waste materials that are rarely recycled. In recent years, numerous potential bioactive compounds have been isolated from tobacco, and the molecular regulatory mechanisms related to the performance of some functionalities have been identified. This review describes the source of tobacco waste and expounds a large amount of biomass during the tobacco processing, and the necessity of exploring the reuse of tobacco waste. In addition, the review summarizes the bioactive compounds from tobacco that have been discovered so far, and links them to various functions from tobacco extracts, including anti-inflammatory, antitumor, antibacterial, and antioxidant, thus proving the potential value from tobacco waste reuse. In this regard, nornicotine in tobacco is the culprit of many health issues, while the polyphenols and polysaccharides often contribute to the health benefits of tobacco extract. In addition, it is hard to ignore that realization of these functions of tobacco extracts require the involvement of intestinal flora metabolism, which should be considered in the development of new product dosage forms.
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.MCP.2009.03.003
Abstract: Expressed sequence tag (EST) data representing transcripts with a high level of differential hybridization in suppressive-subtractive hybridization (SSH)-based microarray analysis between adult female and male Ascaris suum were subjected to detailed bioinformatic analysis. A total of 361 ESTs clustered into 209 sequences, of which 52 and 157 represented transcripts that were enriched in female and male A. suum, respectively. Thirty (57.7%) of the 'female' subset of 52 sequences had orthologues/homologues in other parasitic nematodes and/or Caenorhabditis elegans, 13 (25%) exclusively in other parasitic nematodes and nine (17.3%) had no match in any other organism for which sequence data are currently available the C. elegans orthologues encoded molecules involved in reproduction as well as embryonic and gamete development, such as vitellogenins and chitin-binding proteins. Of the 'male' subset of 157 sequences, 73 (46.5%) had orthologues/homologues in other parasitic nematodes and/or C. elegans, 57 (37.5%) in other parasitic nematodes only, and 22 (14.5%) had no significant similarity match in any other organism the C. elegans orthologues encoded predominantly major sperm proteins (MSPs), kinases and phosphatases, actins, myosins and an Ancylostoma secreted protein-like molecule. The findings of the present study should support further genomic investigations of A. suum.
Publisher: CSIRO Publishing
Date: 25-06-2021
DOI: 10.1071/AN20667
Abstract: Plants are integral components of pig and poultry feed, and aside from their raw nutritive value, some phytochemicals contain bioactive compounds. The aim of the present paper is to review recent advances in the use of some phytochemicals in pig and poultry feed, focusing on the ex les of isoquinoline alkaloids, polyphenol rich sugarcane extracts and superoxide dismutase-rich melon pulp extracts. As gut health is critical for efficient production, the review will focus on recent results modulating oxidative stress within the gastrointestinal tract and the potential mechanisms of action.
Publisher: Springer Science and Business Media LLC
Date: 30-11-2011
Publisher: Springer Science and Business Media LLC
Date: 30-11-2011
Publisher: Oxford University Press (OUP)
Date: 27-03-2008
DOI: 10.1093/BIB/BBN025
Publisher: MDPI AG
Date: 26-10-2021
Abstract: Olfactory receptors (ORs) constitute the largest superfamily of G protein-coupled receptors (GPCRs). ORs are involved in sensing odorants as well as in other ectopic roles in non-nasal tissues. Matching of an enormous number of the olfactory stimulation repertoire to its counterpart OR through machine learning (ML) will enable understanding of olfactory system, receptor characterization, and exploitation of their therapeutic potential. In the current study, we have selected two broadly tuned ectopic human OR proteins, OR1A1 and OR2W1, for expanding their known chemical space by using molecular descriptors. We present a scheme for selecting the optimal features required to train an ML-based model, based on which we selected the random forest (RF) as the best performer. High activity agonist prediction involved screening five databases comprising ~23 M compounds, using the trained RF classifier. To evaluate the effectiveness of the machine learning based virtual screening and check receptor binding site compatibility, we used docking of the top target ligands to carefully develop receptor model structures. Finally, experimental validation of selected compounds with significant docking scores through in vitro assays revealed two high activity novel agonists for OR1A1 and one for OR2W1.
Publisher: Elsevier
Date: 2019
Publisher: Elsevier BV
Date: 2020
Publisher: Informa UK Limited
Date: 2021
Publisher: Wiley
Date: 23-12-2010
Publisher: Elsevier BV
Date: 03-1986
Publisher: Cold Spring Harbor Laboratory
Date: 20-04-2023
DOI: 10.1101/2023.04.18.537422
Abstract: The assembly of reference-quality, chromosome-resolution genomes for both model and novel eukaryotic organisms is an increasingly achievable task for single research teams. However, the overwhelming abundance of sequencing technologies, assembly algorithms, and post-assembly processing tools currently available means that there is no clear consensus on a best-practice computational protocol for eukaryotic de novo genome assembly. Here, we provide a comprehensive benchmark of 28 state-of-the-art assembly and polishing packages, in various combinations, when assembling two eukaryotic genomes using both next-generation (Illumina HiSeq) and third-generation (Oxford Nanopore and PacBio CLR) sequencing data, at both controlled and open levels of sequencing coverage. Recommendations are made for the most effective tools for each sequencing technology and the best performing combinations of methods, evaluated against common assessment metrics such as contiguity, computational performance, gene completeness, and reference reconstruction, across both organisms and across sequencing coverage depth.
Publisher: Wiley
Date: 23-01-2006
DOI: 10.1002/PSC.744
Abstract: Scorpion toxins are important physiological probes for characterizing ion channels. Molecular databases have limited functional annotation of scorpion toxins. Their function can be inferred by searching for conserved motifs in sequence signature databases that are derived statistically but are not necessarily biologically relevant. Mutation studies provide biological information on residues and positions important for structure-function relationship but are not normally used for extraction of binding motifs. 3D structure analyses also aid in the extraction of peptide motifs in which non-contiguous residues are clustered spatially. Here we present new, functionally relevant peptide motifs for ion channels, derived from the analyses of scorpion toxin native and mutant peptides.
Publisher: Springer Science and Business Media LLC
Date: 07-10-2022
DOI: 10.1186/S12935-022-02721-9
Abstract: Plants-based natural compounds are well-identified and recognized chemoprotective agents that can be used for primary and secondary cancer prevention, as they have proven efficacy and fewer side effects. In today's scenario, when cancer cases rapidly increase in developed and developing countries, the anti-cancerous plant-based compounds become highly imperative. Among others, the Asteraceae (Compositae) family's plants are rich in sesquiterpenoid lactones, a subclass of terpenoids with wide structural ersity, and offer unique anti-cancerous effects. These plants are utilized in folk medicine against numerous diseases worldwide. However, these plants are now a part of the modern medical system, with their sesquiterpenoid lactones researched extensively to find more effective and efficient cancer drug regimens. Given the evolving importance of sesquiterpenoid lactones for cancer research, this review comprehensively covers different domains in a spectrum of sesquiterpenoid lactones viz (i) Guaianolides (ii) Pseudoguaianolide (iii) Eudesmanolide (iv) Mel odinin A and (v) Germacrene, from important plants such as Cynara scolymus (globe artichoke), Arnica montana (wolf weeds), Spilanthes acmella , Taraxacum officinale, Mel odium, Solidago spp. The review, therefore, envisages being a helpful resource for the growth of plant-based anti-cancerous drug development.
Publisher: Cold Spring Harbor Laboratory
Date: 20-04-2023
DOI: 10.1101/2023.04.18.537425
Abstract: 1 The assembly of reference-quality, chromosome-level genomes for both model and novel eukaryotic organisms is an increasingly achievable task for single research teams. However, the broad variety of sequencing technologies, assembly algorithms, and post-assembly processing tools currently available means that there is no clear consensus on a best-practice computational protocol for eukaryotic de novo genome assembly. An ever-increasing field of algorithms and packages with unique parameters, setup requirements, and environments makes it difficult for groups to pick up and test new tools, despite potential benefits. Here, we present a comprehensive Snakemake-based pipeline for eukaryotic genome assembly, Pyro , to further assist future de novo assembly and benchmarking projects. Pyro combines 20 assembly and eight polishing packages, comprising 30 different assembly approaches and up to 48 different polishing approaches in combination. These are available across Illumina short-read, Nanopore and PacBio CLR long-read technologies in one container, complete with data preparation, quality metric calculation and result reporting. We demonstrate Pyro effectiveness by running Pyro on publicly available Illumina, Nanopore and PacBio CLR read sets for Arabidopsis thaliana , producing 12 candidate assembly options with minimal initial input or configuration, each with extremely high contiguity and completeness. Pyro is highly customizable to expert needs, while also providing an accessible suggested set of tools for more casual users based on simple inputs. Pyro is available as a Singularity container suitable for execution on any Unix-compatible OS, and is freely available on GitHub ( enomeassembler yro ). This pipeline provides a one-stop solution for a variety of de novo eukaryotic genome assembly needs, and will also assist in the assessment of new tools as a convenient benchmark-generating platform.
Publisher: Oxford University Press (OUP)
Date: 23-07-2018
DOI: 10.1093/BIOINFORMATICS/BTY660
Abstract: Large-scale peptide mass spectrometry (MS)/MS reference libraries are essential for the comprehensive analysis of data-independent acquisition (DIA) MS datasets, providing a comprehensive set of spectra for identification and quantification of proteins. We have developed a novel web-based R-package (iSwathX) for combining reference libraries that is compatible with different DIA analysis software. This open-source web GUI automates the process of normalization and combination of spectral libraries and provides a user-friendly method for performing library format conversions, analysis and visualizations, with no need for programing familiarity. iSwathX is freely accessible at biolinfo.shinyapps.io/iSwathX with the R-package and Shiny source code available from GitHub (noor/iSwathX). Supplementary data are available at Bioinformatics online.
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.FUNBIO.2014.01.009
Abstract: Oomycetes form a unique group of microorganisms that share hyphal morphology with fungi. Most of pathogenic oomycetes infect plants, while some species are capable of infecting animals. Pythium insidiosum is the only oomycete that can infect both humans and animals, and causes a life-threatening infectious disease, called 'pythiosis'. Controlling an infection caused by P. insidiosum is problematic because effective antimicrobial drugs are not available. Information on the biology and pathogenesis of P. insidiosum is limited. We generated a P. insidiosum transcriptome of 26 735 unigenes, using the 454 sequencing platform. As adaptations to increased temperature inside human hosts are required for a successful pathogen, we generated P. insidiosum transcriptomes at 28 °C and 37 °C and identified 625 up-regulated and 449 down-regulated genes at 37 °C. Comparing the proteomes of oomycetes, fungi, and parasites provided clues on the evolutionary history of P. insidiosum. Potential virulence factors of P. insidiosum, including putative effectors, were identified. Pythium insidiosum harbored an extensive repertoire of ∼ 300 elicitin domain-containing proteins. The transcriptome, presented herein, provides an invaluable resource for exploring P. insidiosum's biology, pathogenesis, and evolution.
Publisher: Elsevier BV
Date: 12-1982
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.JTBI.2017.08.014
Abstract: Protein-protein interaction plays a crucial role in the cellular biological processes. Interface prediction can improve our understanding of the molecular mechanisms of the related processes and functions. In this work, we propose a classification method to recognize the interface residue based on the features of a weighted residue interaction network. The random forest algorithm is used for the prediction and 16 network parameters and the B-factor are acting as the element of the input feature vector. Compared with other similar work, the method is feasible and effective. The relative importance of these features also be analyzed to identify the key feature for the prediction. Some biological meaning of the important feature is explained. The results of this work can be used for the related work about the structure-function relationship analysis via a residue interaction network model.
Publisher: Springer Science and Business Media LLC
Date: 2007
Publisher: Wiley
Date: 16-12-2013
Publisher: Elsevier BV
Date: 03-2001
DOI: 10.1016/S1567-5769(00)00040-0
Abstract: Foreign particles and damaged host cells can activate the complement system leading to their destruction by the host defense system. Factor H (fH) plays a vital role in restricting complement activation on host cells through interactions with polyanions such as heparin, while allowing activation to proceed on foreign surfaces. Complement activation by damaged host cells is also down regulated by fH, which is localized to injured areas through interactions with C-reactive protein (CRP). A number of pathogens have developed mechanisms by which they can also bind fH and thus exploit its protective properties. One such organism is Group A Streptococcus (GAS) which mediates fH binding via its surface expressed M-protein. fH consists of 20 conserved short consensus repeat (SCR) units and mutagenesis studies indicate that the seventh repeat is responsible for interactions with heparin, CRP and M-protein. We recently performed molecular modelling of fH SCR 7 and identified a cluster of positively charged residues on one face of the domain. By alanine replacement mutagenesis, we demonstrated that these residues are involved in heparin, CRP and M protein binding, which indicates that there is a common site within fH SCR 7 responsible for multiple ligand recognition.
Publisher: American Chemical Society (ACS)
Date: 05-1988
DOI: 10.1021/JA00219A014
Publisher: Elsevier BV
Date: 04-2019
Publisher: Springer Science and Business Media LLC
Date: 12-2016
Publisher: Public Library of Science (PLoS)
Date: 09-01-2008
Publisher: MDPI AG
Date: 29-01-2022
DOI: 10.3390/IJMS23031562
Abstract: Oral cancer is the most common form of head and neck squamous cell carcinoma (HNSCC) and most frequently presents as oral squamous cell carcinoma (OSCC), which is associated with an alarmingly high mortality rate. Internationally, a plethora of research to further our understanding of the molecular pathways related to oral cancer is performed. This research is of value for early diagnosis, prognosis, and the investigation of new drugs that can ameliorate the harmful effects of oral cancer and provide optimal patient outcomes with minimal long-term complications. Two pathways on which the progression of OSCC depends on are those of proliferation and apoptosis, which overlap at many junctions. Herein, we aim to review these pathways and factors related to OSCC progression. Publicly available search engines, PubMed and Google Scholar, were used with the following keywords to identify relevant literature: oral cancer, proliferation, proliferation factors, genes, mutations, and tumor suppressor. We anticipate that the use of information provided through this review will further progress translational cancer research work in the field of oral cancer.
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Publisher: Royal Society of Chemistry (RSC)
Date: 1983
DOI: 10.1039/F29837901699
Publisher: Oxford University Press (OUP)
Date: 04-01-2011
Publisher: Elsevier BV
Date: 08-2021
Publisher: Oxford University Press (OUP)
Date: 08-05-2027
DOI: 10.1093/NAR/GKM378
Publisher: Springer Science and Business Media LLC
Date: 2011
Publisher: Elsevier BV
Date: 12-2004
Publisher: Informa UK Limited
Date: 11-07-2022
Publisher: Public Library of Science (PLoS)
Date: 02-04-2012
Publisher: Open Access Text Pvt, Ltd.
Date: 2016
DOI: 10.15761/CPB.1000115
Publisher: Oxford University Press (OUP)
Date: 28-06-2007
DOI: 10.1093/BIOINFORMATICS/BTM334
Abstract: Summary: Caspases belong to a unique class of cysteine proteases which function as critical effectors of apoptosis, inflammation and other important cellular processes. Caspases cleave substrates at specific tetrapeptide sites after a highly conserved aspartic acid residue. Prediction of such cleavage sites will complement structural and functional studies on substrates cleavage as well as discovery of new substrates. We have recently developed a support vector machines (SVM) method to address this issue. Our algorithm achieved an accuracy ranging from 81.25 to 97.92%, making it one of the best methods currently available. CASVM is the web server implementation of our SVM algorithms, written in Perl and hosted on a Linux platform. The server can be used for predicting non-canonical caspase substrate cleavage sites. We have also included a relational database containing experimentally verified caspase substrates retrievable using accession IDs, keywords or sequence similarity. Availability: asvm/index.html Contact: shoba.ranganathan@mq.edu.au Supplementary information: asvm/help/index.html
Publisher: Springer New York
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 2009
DOI: 10.1186/GM113
Publisher: MDPI AG
Date: 05-01-2023
DOI: 10.3390/IJMS24021050
Abstract: Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, with an estimated 5-year survival rate of only 40–50%, largely due to late detection and diagnosis. Emerging evidence suggests that the human microbiome may be implicated in OSCC, with oral microbiome studies putatively identifying relevant bacterial species. As the impact of other microbial organisms, such as fungi and viruses, has largely been neglected, a bioinformatic approach utilizing the Trans-Proteomic Pipeline (TPP) and the R statistical programming language was implemented here to investigate not only bacteria, but also viruses and fungi in the context of a publicly available, OSCC, mass spectrometry (MS) dataset. Overall viral, bacterial, and fungal composition was inferred in control and OSCC patient tissue from protein data, with a range of proteins observed to be differentially enriched between healthy and OSCC conditions, of which the fungal protein profile presented as the best potential discriminator of OSCC within the analysed dataset. While the current project sheds new light on the fungal and viral spheres of the oral microbiome in cancer in silico, further research will be required to validate these findings in an experimental setting.
Publisher: Springer Science and Business Media LLC
Date: 2009
Publisher: Wiley
Date: 04-2003
Abstract: The complement inhibitor factor H (fH) interacts via its seventh short consensus repeat (SCR) domain with multiple ligands including heparin, streptococcal M protein and C-reactive protein (CRP). The aim of this study was to localize the residues in SCR 7 required for these interactions. We initially built a homology model of fH SCR 6-7 using the averaged NMR structures of fH SCR 15-16 and vaccinia control protein SCR 3-4 as templates. Electrostatic potentials of the model's surface demonstrated a co-localization of three clusters of positively charged residues on SCR 7, labeled site A (R369 and K370), site B (R386 and K387) and site C (K392). These residues, localized to the linker region preceding SCR 7 and to the end of a "hypervariable loop" in SCR 7, were systematically replaced with uncharged alanine residues in an fH construct containing SCR 1-7. The resulting proteins were expressed in the methylotrophic yeast, Pichia pastoris. By ELISA analysis we demonstrated: first, that substituting site A inhibited heparin and CRP binding secondly, that substituting site B inhibited binding to heparin, CRP and M protein and thirdly, that substituting site C clearly inhibited only heparin binding.
Publisher: Wiley
Date: 07-2022
DOI: 10.1002/CPZ1.506
Abstract: With evidence emerging that the microbiome has a role in the onset of many human diseases, including cancer, analyzing these microbial communities and their proteins (i.e., the metaproteome) has become a powerful research tool. The Trans‐Proteomic Pipeline (TPP) is a free, comprehensive software suite that facilitates the analysis of mass spectrometry (MS) data. By utilizing available microbial proteomes, TPP can identify microbial proteins and species, with an acceptable peptide false‐discovery rate (FDR). An application to a publicly available oral cancer dataset is presented as an ex le to identify the viral metaproteome on the oral cancer invasive tumor front. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1 : Collection of data and resources Basic Protocol 2 : Analysis of MS data using TPP Basic Protocol 3 : Analysis of TPP output using R in RStudio
Publisher: Springer New York
Date: 2013
Publisher: Elsevier BV
Date: 09-1991
Publisher: Springer New York
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 12-2012
Publisher: Springer New York
Date: 2013
Publisher: Springer New York
Date: 2013
Publisher: Elsevier BV
Date: 05-1984
Publisher: Springer New York
Date: 2009
Publisher: Elsevier BV
Date: 02-2005
DOI: 10.1016/J.GENE.2004.09.024
Abstract: We report here for the first time the molecular characterization of a hyaluronidase from an aquatic source. SFHYA1 is the hyaluronidase found in the venom gland of stonefish, Synanceja horrida. Using a cDNA segment lified with degenerate oligonucleotides based on the amino acid sequences of a conserved region in testicular-type hyaluronidases and a tryptic fragment of SFHYA1, clones encoding the precursor of this enzyme were isolated from a cDNA library prepared from stonefish venom glands. The deduced amino acid sequence of SFHYA1 shows that SFHYA1 is expressed as a precursor peptide with a 28-residue signal peptide for targeting it into endoplasmic reticulum. Mature SFHYA1 is a polypeptide composed of 449 residues containing three potential N-glycosylation sites, four putative hyaluronan-binding motifs [B(X)7B] and various residues implicated in substrate binding and catalysis. This cDNA was expressed in an active form in insect-cells but not in E. coli. Homology-based computational analyses suggested that SFHYA1 closely resembles the PH-20 family of hyaluronidases.
Publisher: Wiley
Date: 12-1980
Publisher: MDPI AG
Date: 09-2020
DOI: 10.3390/FOODS9091206
Abstract: Fruit peels have a erse range of phytochemicals including carotenoids, vitamins, dietary fibres, and phenolic compounds, some with remarkable antioxidant properties. Nevertheless, the comprehensive screening and characterization of the complex array of phenolic compounds in different fruit peels is limited. This study aimed to determine the polyphenol content and their antioxidant potential in twenty different fruit peel s les in an ethanolic extraction, including their comprehensive characterization and quantification using the LC-MS/MS and HPLC. The obtained results showed that the mango peel exhibited the highest phenolic content for TPC (27.51 ± 0.63 mg GAE/g) and TFC (1.75 ± 0.08 mg QE/g), while the TTC (9.01 ± 0.20 mg CE/g) was slightly higher in the avocado peel than mango peel (8.99 ± 0.13 mg CE/g). In terms of antioxidant potential, the grapefruit peel had the highest radical scavenging capacities for the DPPH (9.17 ± 0.19 mg AAE/g), ABTS (10.79 ± 0.56 mg AAE/g), ferric reducing capacity in FRAP (9.22 ± 0.25 mg AA/g), and total antioxidant capacity, TAC (8.77 ± 0.34 mg AAE/g) compared to other fruit peel s les. The application of LC-ESI-QTOF-MS/MS tentatively identified and characterized a total of 176 phenolics, including phenolic acids (49), flavonoids (86), lignans (11), stilbene (5) and other polyphenols (25) in all twenty peel s les. From HPLC-PDA quantification, the mango peel s le showed significantly higher phenolic content, particularly for phenolic acids (gallic acid, 14.5 ± 0.4 mg/g) and flavonoids (quercetin, 11.9 ± 0.4 mg/g), as compared to other fruit peel s les. These results highlight the importance of fruit peels as a potential source of polyphenols. This study provides supportive information for the utilization of different phenolic rich fruit peels as ingredients in food, feed, and nutraceutical products.
Publisher: Springer Science and Business Media LLC
Date: 30-11-2011
DOI: 10.1186/1471-2164-12-S3-S22
Abstract: Lysosomal β-D-mannosidase is a glycosyl hydrolase that breaks down the glycosidic bonds at the non-reducing end of N-linked glycoproteins. Hence, it is a crucial enzyme in polysaccharide degradation pathway. Mutations in the MANBA gene that codes for lysosomal β-mannosidase, result in improper coding and malfunctioning of protein, leading to β-mannosidosis. Studying the location of mutations on the enzyme structure is a rational approach in order to understand the functional consequences of these mutations. Accordingly, the pathology and clinical manifestations of the disease could be correlated to the genotypic modifications. The wild-type and inherited mutations of β-mannosidase were studied across four different species, human, cow, goat and mouse employing a previously demonstrated comprehensive homology modeling and mutational mapping technique, which reveals a correlation between the variation of genotype and the severity of phenotype in β-mannosidosis. X-ray crystallographic structure of β-mannosidase from Bacteroides thetaiotaomicron was used as template for 3D structural modeling of the wild-type enzymes containing all the associated ligands. These wild-type models subsequently served as templates for building mutational structures. Truncations account for approximately 70% of the mutational cases. In general, the proximity of mutations to the active site determines the severity of phenotypic expressions. Mapping mutations to the MANBA gene sequence has identified five mutational hot-spots. Although restrained by a limited dataset, our comprehensive study suggests a genotype-phenotype correlation in β-mannosidosis. A predictive approach for detecting likely β-mannosidosis is also demonstrated where we have extrapolated observed mutations from one species to homologous positions in other organisms based on the proximity of the mutations to the enzyme active site and their co-location from different organisms. Apart from aiding the detection of mutational hotspots in the gene, where novel mutations could be disease-implicated, this approach also provides a way to predict new disease mutations. Higher expression of the exoglycosidase chitobiase is said to play a vital role in determining disease phenotypes in human and mouse. A bigger dataset of inherited mutations as well as a parallel study of β-mannosidase and chitobiase activities in prospective patients would be interesting to better understand the underlying reasons for β-mannosidosis.
Publisher: Public Library of Science (PLoS)
Date: 16-04-2014
Publisher: Springer New York
Date: 2013
Publisher: Elsevier
Date: 2019
Publisher: Springer New York
Date: 2013
Publisher: Informa UK Limited
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: World Scientific Pub Co Pte Lt
Date: 10-2015
Publisher: Springer Science and Business Media LLC
Date: 12-2008
Publisher: Springer New York
Date: 2013
Publisher: Springer Netherlands
Date: 2003
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.BJA.2017.12.037
Abstract: Maximising patient comfort during and after surgery is a primary concern of anaesthetists and other perioperative clinicians, but objective measures of what constitutes patient comfort in the perioperative period remain poorly defined. The Standardised Endpoints in Perioperative Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus process that included up to 89 clinician researchers was then used to refine a recommended list of outcome measures. We identified 122 studies in a literature search, which were the basis for a preliminary list of 24 outcome measures and their definitions. The response rates for Delphi Rounds 1, 2, and 3 were 100% (n=22), 90% (n=79), and 100% (n=13), respectively. A final list of six defined endpoints was identified: pain intensity (at rest and during movement) at 24 h postoperatively, nausea and vomiting (0-6 h, 6-24 h, and overall), one of two quality-of-recovery (QoR) scales (QoR score or QoR-15), time to gastrointestinal recovery, time to mobilisation, and sleep quality. As standardised outcomes will support benchmarking and pooling (meta-analysis) of trials, one or more of these recommended endpoints should be considered for inclusion in clinical trials assessing patient comfort and pain after surgery.
Publisher: MDPI AG
Date: 29-12-2020
Abstract: Berries are grown worldwide with the most consumed berries being blackberries (Rubus spp.), blueberries (Vaccinium corymbosum), red raspberries (Rubus idaeus) and strawberries (Fragaria spp.). Berries are either consumed fresh, frozen, or processed into wines, juices, and jams. In recent times, researchers have focused their attention on berries due to their abundance in phenolic compounds. The current study aimed to evaluate the phenolic content and their antioxidant potential followed by characterization and quantification using LC-ESI-QTOF-MS/MS and HPLC-PDA. Blueberries were highest in TPC (2.93 ± 0.07 mg GAE/gf.w.) and TFC (70.31 ± 1.21 µg QE/gf.w.), whereas the blackberries had the highest content in TTC (11.32 ± 0.13 mg CE/gf.w.). Blueberries had the highest radical scavenging capacities for the DPPH (1.69 ± 0.09 mg AAE/gf.w.), FRAP (367.43 ± 3.09 µg AAE/gf.w.), TAC (1.47 ± 0.20 mg AAE/gf.w.) and ABTS was highest in strawberries (3.67 ± 0.14 mg AAE/gf.w.). LC-ESI-QTOF-MS/MS study identified a total of 65 compounds including 42 compounds in strawberries, 30 compounds in raspberries, 28 compounds in blueberries and 21 compounds in blackberries. The HPLC-PDA quantification observed phenolic acid (p-hydroxybenzoic) and flavonoid (quercetin-3-rhamnoside) higher in blueberries compared to other berries. Our study showed the presence of phenolic acids and provides information to be utilized as an ingredient in food, pharmaceutical and nutraceutical industries.
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Springer Science and Business Media LLC
Date: 10-11-2020
DOI: 10.1038/S41598-020-76317-6
Abstract: Protein structure prediction is a grand challenge. Prediction of protein structures via the representations using backbone dihedral angles has recently achieved significant progress along with the on-going surge of deep neural network (DNN) research in general. However, we observe that in the protein backbone angle prediction research, there is an overall trend to employ more and more complex neural networks and then to throw more and more features to the neural networks. While more features might add more predictive power to the neural network, we argue that redundant features could rather clutter the scenario and more complex neural networks then just could counterbalance the noise. From artificial intelligence and machine learning perspectives, problem representations and solution approaches do mutually interact and thus affect performance. We also argue that comparatively simpler predictors can more easily be reconstructed than the more complex ones. With these arguments in mind, we present a deep learning method named Simpler Angle Predictor (SAP) to train simpler DNN models that enhance protein backbone angle prediction. We then empirically show that SAP significantly outperforms existing state-of-the-art methods on well-known benchmark datasets: for some types of angles, the differences are above 3 in mean absolute error (MAE). The SAP program along with its data is available from the website ahnewton/sap .
Publisher: MDPI AG
Date: 04-05-2021
Abstract: Spices have long been used to improve food flavor, due to their appealing fragrance and sensory attributes. Nowadays, spices-based bioactives, particularly phenolic compounds, have gained attention due to their wide range of significant effects in biological systems. The present study was conducted to characterize the 12 widely used spices (allspice, black cardamom, black cumin, black pepper, cardamom, cinnamon, clove, cumin, fennel, nutmeg, star-anise, and turmeric) for their phenolics with the liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS2), polyphenols estimation, and their antioxidant potential. Total phenolics, total flavonoids, and total tannin content and their antioxidant activities were estimated in all spices. Clove and allspice had the highest value of total polyphenol content (215.14 and 40.49 mg gallic acid equivalent (GAE) per g of s le), while clove and turmeric had the highest total flavonoids (5.59 mg quercetin equivalent (QE) per g of s le) and total tannin contents (23.58 mg catechin equivalent (CE) per g of s le), respectively. On the other hand, black cumin and black pepper had the highest phosphomolybdate activity (15.61 and 15.43 mg ascorbic acid equivalent (AAE) per g of s le), while clove was almost identified with highest free radical scavenging capacity. A positive correlation was observed among phenolic compounds and antioxidant activities. In this quest, a total of 79 phenolic compounds were tentatively characterized by using LC-ESI-QTOF-MS2 including 26 phenolic acids, 33 flavonoids, 16 other polyphenols, and 4 lignans. The high-performance liquid chromatography coupled with photodiode array detector (HPLC-PDA) quantification of phenolic compounds exhibited higher phenolic acids. These results provided us some valuable information that spices have powerful antioxidant potential that can be further used in human food and animal feed as a supplement for different health promoting applications.
Publisher: Wiley
Date: 05-1990
Publisher: Nepal Journals Online (JOL)
Date: 31-12-2021
Abstract: The SARS-CoV-2 virus which causes the disease termed COVID-19 ripped through the globe in the latter part of 2019 and has left a state of fear, death and destruction in its wake. The Omicron variant was officially announced by the South African authorities on the 24th of November 2021, with the first confirmed s le of the infection being collected on the 9th of November 2021. The initial cases were flagged as a possible new variant due to the stark differences in the presentation and clinical features of the patients. At the time of Omicron’s discovery, the predominant variant circulating within South Africa was the Delta variant B.1.617.2 which typically presented with more severe and stark symptoms. Omicron spread rapidly within the Southern African content and abroad, principally South Africa, Botswana, Hongkong and Israel were among the first countries to record cases of the new variant. The first European case of the Omicron variant was confirmed on the 26th of November 2021 in Belgium. Towards the end of November 2021 cases of the new variant had been confirmed and recorded in France, the United Kingdom, Germany, Portugal and Scotland. Additional cases of the Omicron variant have been confirmed in Canada and Australia. At this current point in the development of the Omicron upsurge in cases the international community should aim for further vaccinations among their fellow countrymen, but more so vaccine equality should be ensured. Such equality should be ensured in the developing nations as the virus does not respect any boundaries or territories and thus a higher level of vaccination worldwide will confer greater protection to the global community as a whole.
Publisher: Elsevier BV
Date: 08-2019
Publisher: Springer New York
Date: 2014
DOI: 10.1007/978-1-4939-1115-8_27
Abstract: Structure-based clustering technique is useful for identifying superfamilies of major histocompatibility complex (MHC) proteins with similar binding specificities. The resolved MHC superfamilies play an important role in vaccine development, from discovering new targets for broad-based vaccines and therapeutics to optimizing the affinity and selectivity of hits. Here, we describe a protocol and provide a summary for grouping MHC proteins according to their structural interaction characteristics.
Publisher: Springer Science and Business Media LLC
Date: 13-10-2005
Abstract: The signal peptide plays an important role in protein targeting and protein translocation in both prokaryotic and eukaryotic cells. This transient, short peptide sequence functions like a postal address on an envelope by targeting proteins for secretion or for transfer to specific organelles for further processing. Understanding how signal peptides function is crucial in predicting where proteins are translocated. To support this understanding, we present SPdb signal peptide database proline.bic.nus.edu.sg/spdb , a repository of experimentally determined and computationally predicted signal peptides. SPdb integrates information from two sources (a) Swiss-Prot protein sequence database which is now part of UniProt and (b) EMBL nucleotide sequence database. The database update is semi-automated with human checking and verification of the data to ensure the correctness of the data stored. The latest release SPdb release 3.2 contains 18,146 entries of which 2,584 entries are experimentally verified signal sequences the remaining 15,562 entries are either signal sequences that fail to meet our filtering criteria or entries that contain unverified signal sequences. SPdb is a manually curated database constructed to support the understanding and analysis of signal peptides. SPdb tracks the major updates of the two underlying primary databases thereby ensuring that its information remains up-to-date.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.JPROT.2013.06.017
Abstract: Echinostomes are cosmopolitan parasites that infect a large number of different warm-blooded hosts, both in nature and in the laboratory. They also constitute an important group of food-borne trematodes of public health importance mainly in Southeast Asia and the Far East. In addition, echinostomes are an ideal model to study several aspects of intestinal helminth biology, since they present a number of advantages. For ex le, echinostomes are large worms whose life cycle is relatively easy to maintain in the laboratory. Recently, several studies documented their great value in the study of intestinal helminth-vertebrate host relationship. Detailed knowledge of their genome, transcriptome and proteome is likely to have an important impact on the development of control strategies for intestinal helminths. We present the first transcriptome of the adult stage of Echinostoma caproni using 454 sequencing coupled to a semi-automated bioinformatic analyses. 557,236 raw sequence reads were assembled into 28,577 contiguous sequences using iAssembler. 23,296 putative proteins were characterized based on homology, gene ontology and/or biochemical pathways. Comparisons of the transcriptome of E. caproni with those of other trematodes revealed similarities in the transcription pattern of molecules inferred to have key roles in parasite-host interactions. Enzymatic proteins like kinases and peptidases were abundant. Of the 3415 predicted excretory/secretory proteins compiled (including non-classical secretory proteins), 180 different proteins were confirmed by proteomic analysis. Potential drug targets were also identified. In this study the first transcriptome of the adult stage of E. caproni is presented and compared to those of other trematodes revealing similarities in transcription for molecules inferred to have key roles in parasite-host interactions. 3415 predicted excretory/secretory proteins were compiled, being 180 different proteins confirmed by proteomic analysis. The current transcriptome data increased by nine times the number of previous protein identifications. In addition, potential drug targets for this parasite were identified. The present dataset should provide a solid foundation for future fundamental genomic, proteomic, and metabolomic explorations of E. caproni, as well as a basis for applied outcomes, such as the development of novel methods of intervention against this model organism and related parasites.
Publisher: MDPI AG
Date: 20-12-2018
DOI: 10.3390/IJMS20010016
Abstract: Post-translational modifications (PTMs) can occur soon after translation or at any stage in the lifecycle of a given protein, and they may help regulate protein folding, stability, cellular localisation, activity, or the interactions proteins have with other proteins or biomolecular species. PTMs are crucial to our functional understanding of biology, and new quantitative mass spectrometry (MS) and bioinformatics workflows are maturing both in labelled multiplexed and label-free techniques, offering increasing coverage and new opportunities to study human health and disease. Techniques such as Data Independent Acquisition (DIA) are emerging as promising approaches due to their re-mining capability. Many bioinformatics tools have been developed to support the analysis of PTMs by mass spectrometry, from prediction and identifying PTM site assignment, open searches enabling better mining of unassigned mass spectra—many of which likely harbour PTMs—through to understanding PTM associations and interactions. The remaining challenge lies in extracting functional information from clinically relevant PTM studies. This review focuses on canvassing the options and progress of PTM analysis for large quantitative studies, from choosing the platform, through to data analysis, with an emphasis on clinically relevant s les such as plasma and other body fluids, and well-established tools and options for data interpretation.
Publisher: Springer Science and Business Media LLC
Date: 10-2010
Publisher: Springer New York
Date: 26-10-2012
Publisher: Springer Science and Business Media LLC
Date: 06-09-2021
Publisher: Science Repository OU
Date: 08-02-2021
DOI: 10.31487/J.DOBCR.2021.01.03
Abstract: Oral biofilms harbour gram-negative bacterial antigen lipopolysaccharide (LPS) involved in oral cancer progression and gram-positive bacterial surface-associated adhesive, lipoteichoic acid (LTA). Thus, we hypothesised that LPS and LTA together would increase the proliferation of cancer cells compared to stimulation by LPS alone. Oral cancer cell lines SCC4, SCC9, SCC25, Cal 27 and the normal oral cell line, OKF6, were studied. The bacterial antigen stimulation indices were determined using the MT Glo assay. Cell proliferation after bacterial antigen stimulation was validated by clonogenic assays. Phosphokinase array, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot were employed to study proliferative and apoptotic pathways in bacterial antigen-stimulated cells. Bacterial antigens significantly stimulated Cal 27 (p ≤ 0.001) alone. SCC4 and SCC9 showed negligible stimulation with either antigen, while SCC25 results were comparable to OKF6. The combined antigen stimulation of Cal 27 led to a decrease in phosphorylated p53 and β-catenin and higher PI3K compared to LPS only stimulated cells (p ≤ 0.001). Combined bacterial antigen stimulation results in increased proliferation of Cal 27 cells due to lowering of tumor suppressor proteins and increased tumor proliferation-related proteins.
Publisher: Springer Science and Business Media LLC
Date: 10-2010
Publisher: Wiley
Date: 26-11-2003
Publisher: Oxford University Press (OUP)
Date: 07-2003
DOI: 10.1093/NAR/GKG561
Abstract: Splicing is a biological phenomenon that removes the non-coding sequence from the transcripts to produce a mature transcript suitable for translation. To study this phenomenon, information on the intron-exon arrangement of a gene is essential, usually obtained by aligning mRNA/EST sequences to their cognate genomic sequences. MGAlign is a novel, rapid, memory efficient and practical method for aligning mRNA/EST and genome sequences. We present here a freely available web service, MGAlignIt (origin.bic.nus.edu.sg/mgalign/mgalignit), based on MGAlign. Besides the alignment itself, this web service allows users to effectively visualize the alignment in a graphical manner and to perform limited analysis on the alignment output. The server also permits the alignment to be saved in several forms, both graphical and text, suitable for further processing and analysis by other programs.
Publisher: Wiley
Date: 14-07-2015
DOI: 10.1002/PRO.2736
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7OB00129K
Abstract: Enhanced selectivity for homologous ATP sites by composite chemical and conformational perturbation by stereospecific fluorination.
Publisher: Wiley
Date: 06-08-1984
DOI: 10.1016/0014-5793(84)80795-4
Abstract: The energy profiles for single occupancy by Cs+, K+ and Na+ in the gramicidin A channel assumed to be in a head-to-head beta 6.3 3.3 helical dimeric structure, were computed: (A) allowing complete conformational freedom to the ethanolamine end, (B) constraining it to stay in its intrinsically preferred conformation. Whatever the constraint, both the entrance barrier and the central barrier appear in the order Cs+ less than K+ less than Na+. Introducing the flexibility of the tail modifies appreciably the profiles and the location of the extrema along it.
Publisher: Public Library of Science (PLoS)
Date: 24-09-2008
Publisher: Hindawi Limited
Date: 28-07-2020
DOI: 10.1111/JFPP.14748
Publisher: Oxford University Press (OUP)
Date: 18-11-2010
DOI: 10.1093/NAR/GKQ1173
Publisher: Cambridge University Press (CUP)
Date: 05-2002
DOI: 10.1017/S0031182002002329
Abstract: A cDNA was isolated from an adult male Oesophagostomum dentatum gene library by screening with a male-specific, partial expressed sequence tag (EST) probe identified previously using a differential display technique. The full-length cDNA of 642 bp included 5′ and 3′ untranslated regions of 44 and 121 nucleotides, respectively, and encoded a predicted protein with a putative 18 amino acid signal sequence and a mature polypeptide of 14.7 kDa comprising ∼15% cysteine residues. The amino acid sequence showed similarity with a number of proteins from Caenorhabditis elegans , parasitic nematodes, insects and hibia, all of which contain a trypsin inhibitor-like cysteine-rich domain. A 3-dimensional structure model constructed for the O. dentatum protein (designated OdmCRP) inferred that it is composed of 2 domains, each with 5 disulfide bonds, which are indicative of the Ascaris family of serine protease inhibitors. These findings indicate that OdmCRP, with 2 structural domains relating to functionally active sites, is a new member of this inhibitor family.
Publisher: Springer Science and Business Media LLC
Date: 12-2012
DOI: 10.1186/1471-2105-13-S17-S24
Abstract: The transcriptome of an organism can be studied with the analysis of expressed sequence tag (EST) data sets that offers a rapid and cost effective approach with several new and updated bioinformatics approaches and tools for assembly and annotation. The comprehensive analyses comprehend an organism along with the genome and proteome analysis. With the advent of large-scale sequencing projects and generation of sequence data at protein and cDNA levels, automated analysis pipeline is necessary to store, organize and annotate ESTs. TranSeqAnnotator is a workflow for large-scale analysis of transcriptomic data with the most appropriate bioinformatics tools for data management and analysis. The pipeline automatically cleans, clusters, assembles and generates consensus sequences, conceptually translates these into possible protein products and assigns putative function based on various DNA and protein similarity searches. Excretory/secretory (ES) proteins inferred from ESTs/short reads are also identified. The TranSeqAnnotator accepts FASTA format raw and quality ESTs along with protein and short read sequences and are analysed with user selected programs. After pre-processing and assembly, the dataset is annotated at the nucleotide, protein and ES protein levels. TranSeqAnnotator has been developed in a Linux cluster, to perform an exhaustive and reliable analysis and provide detailed annotation. TranSeqAnnotator outputs gene ontologies, protein functional identifications in terms of mapping to protein domains and metabolic pathways. The pipeline is applied to annotate large EST datasets to identify several novel and known genes with therapeutic experimental validations and could serve as potential targets for parasite intervention. TransSeqAnnotator is freely available for the scientific community at estexplorer.biolinfo.org/TranSeqAnnotator/ .
Publisher: Public Library of Science (PLoS)
Date: 28-02-2012
Publisher: MDPI AG
Date: 07-07-2021
DOI: 10.3390/ANI11072026
Abstract: The increased bacterial resistance to synthetic antibiotics and consumer awareness about the health and food safety concerns have triggered the ban on the use of antibiotic growth promotors (AGPs) in the poultry industry. This situation encouraged the poultry sector and industry to explore safe alternatives to AGPs and focus on developing more sustainable feed management strategies to improve the intestinal health and growth performance of poultry. Consequently, phytogenic feed additives (PFAs) have emerged as natural alternatives to AGPs and have great potential in the poultry industry. In recent years, cinnamon (one of the most widely used spices) has attracted attention from researchers as a natural product with numerous health benefits for poultry. The essential oils in cinnamon, in particular, are of interest because of their antioxidant, anti-microbial, anti-inflammatory, antifungal, and hypocholesterolaemic effects, in addition to their ability to stimulate digestive enzymes in the gut. This review mainly emphasizes the potential impact of cinnamon as a natural feed additive on overall gut health, nutrient digestibility, blood biochemical profile, gene expression, gut microbiota and immune response.
Publisher: Wiley
Date: 09-04-2012
DOI: 10.1111/J.1365-3024.2011.01304.X
Abstract: The advent and integration of high-throughput '-omics' technologies (e.g. genomics, transcriptomics, proteomics, metabolomics, glycomics and lipidomics) are revolutionizing the way biology is done, allowing the systems biology of organisms to be explored. These technologies are now providing unique opportunities for global, molecular investigations of parasites. For ex le, studies of a transcriptome (all transcripts in an organism, tissue or cell) have become instrumental in providing insights into aspects of gene expression, regulation and function in a parasite, which is a major step to understanding its biology. The purpose of this article was to review recent applications of next-generation sequencing technologies and bioinformatic tools to large-scale investigations of the transcriptomes of parasitic nematodes of socio-economic significance (particularly key species of the order Strongylida) and to indicate the prospects and implications of these explorations for developing novel methods of parasite intervention.
Publisher: IEEE
Date: 06-2010
Publisher: MDPI AG
Date: 17-08-2020
Abstract: The bioaccessibility and activity of polyphenols is dependent on their structure and entrapment in the food matrix. While dietary lipids are known to transit into the colon, the impact of different lipids on the microbiome, and their interactions with dietary polyphenols are largely unknown. Here, we investigated the effect of dietary lipids on the bioaccessibility of polyphenols from purple/black carrots and adaptation of the gut microbiome in a simulated in vitro digestion-fermentation. Coconut oil, sunflower oil, and beef tallow were selected to represent common dietary sources of medium-chain fatty acids (MCFAs), long-chain polyunsaturated fatty acids (PUFAs), and long-chain polysaturated fatty acids (SFAs), respectively. All lipids promoted the bioaccessibility of both anthocyanins and phenolic acids during intestinal digestion with coconut oil exhibiting the greatest protection of anthocyanins. Similar trends were shown in antioxidant assays (2,2-Diphenyl-1-pricrylhydrazyl (DPPH), ferric reducing ability (FRAP), and total phenolic content (TPC)) with higher phytochemical bioactivities observed with the addition of dietary lipids. Most bioactive polyphenols were decomposed during colonic fermentation. Black carrot modulated ersity and composition of a simulated gut microbiome. Dramatic shifts in gut microbiome were caused by coconut oil. Inclusion of sunflower oil improved the production of butyrate, potentially due to the presence of PUFAs. The results show that the impact of polyphenols in the digestive tract should be considered in the context of other components of the diet, particularly lipids.
Publisher: Wiley
Date: 16-12-2010
DOI: 10.1002/DDR.20404
Publisher: American Chemical Society (ACS)
Date: 05-1991
DOI: 10.1021/JO00011A060
Publisher: Frontiers Media SA
Date: 10-05-2022
Publisher: Springer Science and Business Media LLC
Date: 06-02-2013
Abstract: Cancer is a complex disease where molecular mechanism remains elusive. A systems approach is needed to integrate erse biological information for the prognosis and therapy risk assessment using mechanistic approach to understand gene interactions in pathways and networks and functional attributes to unravel the biological behaviour of tumors. We weighted the functional attributes based on various functional properties observed between cancerous and non-cancerous genes reported from literature. This weighing schema was then encoded in a Boolean logic framework to rank differentially expressed genes. We have identified 17 genes to be differentially expressed from a total of 11,173 genes, where ten genes are reported to be down-regulated via epigenetic inactivation and seven genes are up-regulated. Here, we report that the overexpressed genes IRAK1 , CHEK1 and BUB1 may play an important role in ovarian cancer. We also show that these 17 genes can be used to form an ovarian cancer signature, to distinguish normal from ovarian cancer subjects and that the set of three genes, CHEK1, AR, and LYN , can be used to classify good and poor prognostic tumors. We provided a workflow using a Boolean logic schema for the identification of differentially expressed genes by integrating erse biological information. This integrated approach resulted in the identification of genes as potential biomarkers in ovarian cancer.
Publisher: Bentham Science Publishers Ltd.
Date: 08-07-2013
DOI: 10.2174/09298665113209990056
Abstract: Molecular function in cellular processes is governed by protein-protein interactions (PPIs) within biological networks. Selective yet specific association of these protein partners contributes to erse functionality such as catalysis, regulation, assembly, immunity, and inhibition in a cell. Therefore, understanding the principles of protein-protein association has been of immense interest for several decades. We provide an overview of the experimental methods used to determine PPIs and the key databases archiving this information. Structural and functional information of existing protein complexes confers knowledge on the principles of PPI, based on which a classification scheme for PPIs is then introduced. Obtaining high-quality non-redundant datasets of protein complexes for interaction characterisation is an essential step towards deciphering their underlying binding principles. Analysis of physicochemical features and their documentation has enhanced our understanding of the molecular basis of protein-protein association. We describe the erse datasets created/collected by various groups and their key findings inferring distinguishing features. The currently available interface databases and prediction servers have also been compiled.
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: Elsevier BV
Date: 08-1985
Publisher: Springer New York
Date: 2008
Publisher: Elsevier BV
Date: 03-2006
DOI: 10.1016/J.TOXICON.2005.12.001
Abstract: Scorpion toxins are important experimental tools for characterization of vast array of ion channels and serve as scaffolds for drug design. General public database entries contain limited annotation whereby rich structure-function information from mutation studies is typically not available. SCORPION2 contains more than 800 records of native and mutant toxin sequences enriched with binding affinity and toxicity information, 624 three-dimensional structures and some 500 references. SCORPION2 has a set of search and prediction tools that allow users to extract and perform specific queries: text searches of scorpion toxin records, sequence similarity search, extraction of sequences, visualization of scorpion toxin structures, analysis of toxic activity, and functional annotation of previously uncharacterized scorpion toxins. The SCORPION2 database is available at sdmc.i2r.a-star.edu.sg/scorpion/.
Publisher: Wiley
Date: 09-2013
DOI: 10.1002/JGM.2740
Publisher: Springer Science and Business Media LLC
Date: 2009
Publisher: Oxford University Press (OUP)
Date: 07-11-2007
DOI: 10.1093/BIOINFORMATICS/BTL563
Abstract: Motivation: Classification of human leukocyte antigen (HLA) proteins into supertypes underpins the development of epitope-based vaccines with wide population coverage. Current methods for HLA supertype definition, based on common structural features of HLA proteins and/or their functional binding specificities, leave structural interaction characteristics among different HLA supertypes with antigenic peptides unexplored. Methods: We describe the use of structural interaction descriptors for the analysis of 68 peptide/HLA class I crystallographic structures. Interaction parameters computed include the number of intermolecular hydrogen bonds between each HLA protein and its corresponding bound peptide, solvent accessibility, gap volume and gap index. Results: The structural interactions patterns of peptide/HLA class I complexes investigated herein vary among in idual alleles and may be grouped in a supertype dependent manner. Using the proposed methodology, eight HLA class I supertypes were defined based on existing experimental crystallographic structures which largely overlaps (77% consensus) with the definitions by binding motifs. This mode of classification, which considers conformational information of both peptide and HLA proteins, provides an alternative to the characterization of supertypes using either peptide or HLA protein information alone. Contact: shoba@els.mq.edu
Publisher: Springer Science and Business Media LLC
Date: 05-2018
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 05-2008
DOI: 10.1167/IOVS.07-1297
Abstract: A Tyr-to-His (Y402H) sequence variant in the factor H (FH) and factor H-like protein (FHL-1) gene is strongly associated with an increased susceptibility for age-related macular degeneration (AMD). The purpose of this study was to understand how the Y402H variant in FH/FHL-1 contributes to the pathogenesis of AMD and, in particular, whether interactions mediated by FH/FHL-1, including binding to C-reactive protein (CRP), group A streptococcal M protein (GAS M6), heparin, and retinal pigment epithelial cells (RPE), are affected. FH was purified from sera of patients homozygous for FH(Y402) or (H402), and recombinant FH fragments representing FHL-1 were generated. Proteins were analyzed for binding to CRP, GAS M6, heparin, and RPE cells. Binding of the FH and FH1 to seven polymorphic variants to CRP and M protein was reduced. The variant did not influence the interaction of FH with heparin but did reduce binding of FHL-1. Binding of the FH and FHL-1 polymorphic variant to RPE cells was not affected. The FH Y402H polymorphism associated with AMD causes a reduction in binding of FH and FHL-1 to CRP and M protein. Both variants show comparable binding to RPE cells, indicating that AMD is unlikely to manifest as a result of impaired host cell-surface recognition. The decreased interaction between FH and CRP, which is essential for the anti-inflammatory function of CRP, provides a possible pathophysiological explanation for the association of the Y402H variant with AMD.
Publisher: Hindawi Limited
Date: 27-05-2021
DOI: 10.1111/JFPP.15618
Publisher: Elsevier
Date: 2018
Publisher: Public Library of Science (PLoS)
Date: 11-05-2010
Publisher: Springer Science and Business Media LLC
Date: 04-2019
Publisher: Elsevier BV
Date: 1982
Publisher: Nepal Journals Online (JOL)
Date: 31-12-2021
Abstract: Background: The novel coronavirus disease 2019 (COVID-19) outbreak, caused by the pathogenic severe acute respiratory syndrome-2 (SARS-CoV-2) virus, is exponentially spreading across the globe. Methods: The current systematic review was performed utilizing electronic databases i.e. PubMed, MEDLINE and EMBASE. We searched for the keywords "COVID-19 AND "pregnancy" between January 1st, 2020 until December 31, 2020. Results: Out of 4005 records which were identified, 36 original studies were included in this systematic review. Pooled prevalence of vertical transmission was 10%, 95% CI: 4-17%. Pooled prevalence of neonatal mortality was 7%, 95% CI: 0-21%. Conclusion: The contemporary evidence suggests that the incubation period of COVID-19 is 2-14 days, and this infection could be transmitted even from the infected asymptomatic in iduals. It is found that the clinical presentation of pregnant women with COVID-19 infection is comparable with the infected non-pregnant females, and the frequent symptoms were fever, cough, myalgia, sore throat and malaise. There are some cases with severe maternal morbidity and perinatal deaths secondary to COVID-19 infection. Under these circumstances, the pregnant women should focus on maintaining personal hygiene, proper nutrition and extreme social distancing to reduce the risk of COVID-19. Therefore, a systematic data reporting for evidence base clinical assessment, management and pregnancy outcomes is essential for prevention of COVID-19 infection among pregnant women.
Publisher: Nepal Journals Online (JOL)
Date: 31-12-2021
Abstract: The SARS-CoV-2 pandemic has firmly rooted itself within our countries, communities, homes and now everyday lives. The impact of this global pandemic is immeasurable as it is catastrophic in nature and involves both a human and financial loss. Suicide and self-harm (SH) are both a serious public health and social issue. It is however preventable via the use of timely, evidence-based and many times low-cost interventions and therapies. The current situation depicted Nepal shows a true indicator of the mental health of the nation, as a precipitating factor (i.e., the extreme stress of COVID-19 and the lockdown) has exposed the submerged “ice-berg” phenomenon of disease. It is evident that COVID-19 and the lockdown had a massively negative effect on the mental health of the population in Nepal. The increased rates of suicide and self-harm also simultaneously exposed the great pre-existing fragility of the mental health of the nation. It is therefore vital that both Nepal and other countries alike take cognizance of the fact that extra support and preventative measures need to be introduced during this difficult period and that further national programs must be employed to best aid the mental health of their fellow countrymen.
Publisher: American Chemical Society (ACS)
Date: 23-07-2015
DOI: 10.1021/PR5013009
Abstract: This paper summarizes the recent activities of the Chromosome-Centric Human Proteome Project (C-HPP) consortium, which develops new technologies to identify yet-to-be annotated proteins (termed "missing proteins") in biological s les that lack sufficient experimental evidence at the protein level for confident protein identification. The C-HPP also aims to identify new protein forms that may be caused by genetic variability, post-translational modifications, and alternative splicing. Proteogenomic data integration forms the basis of the C-HPP's activities therefore, we have summarized some of the key approaches and their roles in the project. We present new analytical technologies that improve the chemical space and lower detection limits coupled to bioinformatics tools and some publicly available resources that can be used to improve data analysis or support the development of analytical assays. Most of this paper's content has been compiled from posters, slides, and discussions presented in the series of C-HPP workshops held during 2014. All data (posters, presentations) used are available at the C-HPP Wiki (c-hpp.webhosting.rug.nl/) and in the Supporting Information.
Publisher: Springer Science and Business Media LLC
Date: 27-08-2018
DOI: 10.1038/S41598-018-31289-6
Abstract: The arrangement of amino acids in a protein sequence encodes its native folding. However, the same arrangement in aggregation-prone regions may cause misfolding as a result of local environmental stress. Under normal physiological conditions, such regions congregate in the protein’s interior to avoid aggregation and attain the native fold. We have used solvent accessibility of aggregation patches (SAAP p ) to determine the packing of aggregation-prone residues. Our results showed that SAAP p has low values for native crystal structures, consistent with protein folding as a mechanism to minimize the solvent accessibility of aggregation-prone residues. SAAP p also shows an average correlation of 0.76 with the global distance test (GDT) score on CASP12 template-based protein models. Using SAAP p scores and five structural features, a random forest machine learning quality assessment tool, SAAP-QA, showed 2.32 average GDT loss between best model predicted and actual best based on GDT score on independent CASP test data, with the ability to discriminate native-like folds having an AUC of 0.94. Overall, the Pearson correlation coefficient (PCC) between true and predicted GDT scores on independent CASP data was 0.86 while on the external CAMEO dataset, comprising high quality protein structures, PCC and average GDT loss were 0.71 and 4.46 respectively. SAAP-QA can be used to detect the quality of models and iteratively improve them to native or near-native structures.
Publisher: Public Library of Science (PLoS)
Date: 31-10-2013
Publisher: MDPI AG
Date: 22-11-2021
Abstract: The bacterial antigen, lipopolysaccharide (LPS) and disruptions in calcium channels are independently known to influence oral cancer progression. Previously, we found that bacterial antigens, LPS and lipoteichoic acid (LTA) act as confounders during the action of capsaicin on Cal 27 oral cancer proliferation. As calcium channel drugs may affect oral cancer cell proliferation, we investigated the effect of ML218 HCl, a T-type voltage-gated calcium channel blocker, on the proliferation of Cal 27 oral cancer cells. We hypothesized that ML218 HCl could effectively reduce LPS-induced oral cancer cell proliferation. LPS and LTA antigens were added to Cal 27 oral cancer cells either prior to and/or concurrently with ML218 HCl treatment, and the efficacy of the treatment was evaluated by measuring Cal 27 proliferation, cell death and apoptosis. ML218 HCl inhibited oral cancer cell proliferation, increased apoptosis and cell death, but their efficacy was significantly reduced in the presence of bacterial antigens. ML218 HCl proved more effective than capsaicin in reducing bacterial antigen-induced Cal 27 oral cancer cell proliferation. Our results also suggest an interplay of proliferation factors during the bacterial antigens and calcium channel drug interaction in Cal 27. Bacterial antigen reduction of drug efficacy should be considered for developing newer pharmacological agents or testing the efficacy of the existing oral cancer chemotherapeutic agents. Finally, voltage gated calcium channel drugs should be considered for future oral cancer research.
Publisher: Frontiers Media SA
Date: 29-06-2021
DOI: 10.3389/FPHAR.2021.575877
Abstract: The current coronavirus disease (COVID-19) outbreak is a significant threat to human health and the worldwide economy. Coronaviruses cause a variety of diseases, such as pneumonia-like upper respiratory tract illnesses, gastroenteritis, encephalitis, multiple organ failure involving lungs and kidneys which might cause death. Since the pandemic started there have been more than 107 million COVID-19 infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ∼2.4 million deaths globally. SARS-CoV-2 is easily transmitted from person-to-person and has spread quickly across all continents. With the continued increase in morbidity and mortality caused by COVID-19, and the damage to the global economy, there is an urgent need for effective prevention and treatment strategies. The advent of safe and effective vaccines has been a significant step forward in the battle against COVID-19, however treatment of the symptoms associated with the disease still requires new anti-viral and anti-inflammatory drug therapies. To this end, scientists have been investigating available natural products that may be effective against SARS-CoV-2, with some products showing promise in fighting several viral infections. Since many natural products are dietary components or are prepared as dietary supplements people tend to consider them safer than synthetic drugs. For ex le, Traditional Chinese Medicines have been effectively utilized to treat SARS-CoV-2 infected patients with promising results. In this review, we summarize the current knowledge of COVID-19 therapies and the therapeutic potential of medicinal plant extracts and natural compounds for the treatment of several viral infections, with special emphasis on SARS-CoV-2 infection. Realistic strategies that can be employed for the effective use of bioactive compounds for anti-SARS-CoV-2 research are also provided.
Publisher: Springer Science and Business Media LLC
Date: 08-05-2020
Publisher: Elsevier
Date: 2019
Publisher: Elsevier BV
Date: 08-2007
DOI: 10.1016/J.GENE.2007.03.011
Abstract: A full-length cDNA (Tv-ant-1) encoding an adenine nucleotide translocator (ANT or ADP/ATP translocase) (Tv-ANT-1) was isolated from Trichostrongylus vitrinus (order Strongylida), an economically important parasitic nematode of small ruminants. The uninterrupted open reading frame (ORF) of 894 nucleotides encoded a predicted protein of 297 amino acids, containing characteristic motifs [RRRMMM] and PX(D,E)XX(K,R). Comparison with selected sequences from the free-living nematode Caenorhabditis elegans, cattle and human showed that Tv-ANT-1 is relatively conserved. Sequence identity was the greatest in and near the consensus sequence RRRMMM, and in the six hydrophobic regions predicted to be associated with alpha-helices and to traverse the cell membrane. Phylogenetic analyses of selected amino acid sequence data, using the neighbor-joining and maximum parsimony methods, revealed Tv-ANT-1 to be most closely related to the molecule (Ce-ANT-3) inferred from the tag-61 gene of C. elegans. Comparison of the genomic organization of the full-length Tv-ant-1 gene was similar to that of tag-61. Analysis of the region (5'-UTR) upstream of Tv-ant-1 identified some promoter components, including GATA transcription factor, CAAT and E-box elements. Transcriptional analysis by reverse transcription polymerase chain reaction (RT-PCR) showed that Tv-ant-1 was transcribed in all developmental stages of T. vitrinus, including the first- to fourth- stage larvae (L(1)-L(4)) as well as female and male adults. RNA interference, conducted by feeding C. elegans with double-stranded RNA (dsRNA) from Tv-ant-1 cDNA (using the homologous gene from C. elegans as a positive control), revealed no gene silencing. In spite of nucleotide identities of 100% in 23-30 bp stretches of sequence between the genes Tv-ant-1 and tag-61, these identities seem to be insufficient to achieve effective silencing in C. elegans using the parasite homologue/orthologue Tv-ant-1. This first insight into an ANT of T. vitrinus provides a foundation for exploring its role in developmental and/or survival processes of trichostrongylid nematodes.
Publisher: Frontiers Media SA
Date: 07-04-2021
DOI: 10.3389/FMOLB.2021.617176
Abstract: G protein-coupled receptors (GPCRs) are the largest family of membrane proteins with more than 800 members. GPCRs are involved in numerous physiological functions within the human body and are the target of more than 30% of the United States Food and Drug Administration (FDA) approved drugs. At present, over 400 experimental GPCR structures are available in the Protein Data Bank (PDB) representing 76 unique receptors. The absence of an experimental structure for the majority of GPCRs demand homology models for structure-based drug discovery workflows. The generation of good homology models requires appropriate templates. The commonly used methods for template selection are based on sequence identity. However, there exists low sequence identity among the GPCRs. Sequences with similar patterns of hydrophobic residues are often structural homologs, even with low sequence identity. Extending this, we propose a biophysical approach for template selection based principally on hydrophobicity correspondence between the target and the template. Our approach takes into consideration other relevant parameters, including resolution, similarity within the orthosteric binding pocket of GPCRs, and structure completeness, for template selection. The proposed method was implemented in the form of a free tool called Bio-GATS, to provide the user with easy selection of the appropriate template for a query GPCR sequence. Bio-GATS was successfully validated with recent published benchmarking datasets. An application to an olfactory receptor to select an appropriate template has also been provided as a case study.
Publisher: Frontiers Media SA
Date: 26-04-2021
DOI: 10.3389/FPHAR.2021.625386
Abstract: Nigella is a small genus of the family Ranunculaceae, which includes some popular species due to their culinary and medicinal properties, especially in Eastern Europe, Middle East, Western, and Central Asia. Therefore, this review covers the traditional uses and phytochemical composition of Nigella and, in particular, Nigella sativa . The pharmacological studies reported in vitro , in vivo, and in humans have also been reviewed. One of the main strength of the use of Nigella is that the seeds are rich in the omega-6 fatty acid linoleic acid and provide an extra-source of dietary phytochemicals, including the bioactive thymoquinone, and characteristics saponins, alkaloids, and flavonoids. Among Nigella species, N . sativa L. is the most studied plant from the genus. Due to the phytochemical composition and pharmacological properties, the seed and seed oil from this plant can be considered as good candidates to formulate functional ingredients on the basis of folklore and scientific knowledge. Nonetheless, the main limations are that more studies, especially, clinical trials are required to standardize the results, e.g. to establish active molecules, dosage, chemical profile, long-term effects and impact of cooking/incorporation into foods.
Publisher: Springer Science and Business Media LLC
Date: 2001
DOI: 10.1007/PL00006956
Publisher: Elsevier BV
Date: 12-2010
Publisher: World Scientific Pub Co Pte Lt
Date: 12-2007
DOI: 10.1142/S0219720007003119
Abstract: Rich information on point mutation studies is scattered across heterogeneous data sources. This paper presents an automated workflow for mining mutation annotations from full-text biomedical literature using natural language processing (NLP) techniques as well as for their subsequent reuse in protein structure annotation and visualization. This system, called mSTRAP (Mutation extraction and STRucture Annotation Pipeline), is designed for both information aggregation and subsequent brokerage of the mutation annotations. It facilitates the coordination of semantically related information from a series of text mining and sequence analysis steps into a formal OWL-DL ontology. The ontology is designed to support application-specific data management of sequence, structure, and literature annotations that are populated as instances of object and data type properties. mSTRAPviz is a subsystem that facilitates the brokerage of structure information and the associated mutations for visualization. For mutated sequences without any corresponding structure available in the Protein Data Bank (PDB), an automated pipeline for homology modeling is developed to generate the theoretical model. With mSTRAP, we demonstrate a workable system that can facilitate automation of the workflow for the retrieval, extraction, processing, and visualization of mutation annotations — tasks which are well known to be tedious, time-consuming, complex, and error-prone. The ontology and visualization tool are available at .
Publisher: MDPI AG
Date: 20-01-2021
Abstract: Pear (Pyrus communis L.) is widely spread throughout the temperate regions of the world, such as China, America and Australia. This fruit is popular among consumers due to its excellent taste and perceived health benefits. Various bioactive compounds, which contribute to these health benefits, have been detected in the pear fruits, including a range of phenolic compounds. Five Australian grown pear varieties, which include Packham’s Triumph, Josephine de Malines, Beurre Bosc, Winter Nelis and Rico were selected for this study to examine the phenolic compounds in pears. Beurre Bosc exhibited the highest total polyphenol content (TPC) (3.14 ± 0.02 mg GAE/g), total tannin content (TTC) (1.43 ± 0.04 mg CE/g) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) (5.72 ± 0.11 mg AAE/g), while the Josephine de Malines variety was high in total flavonoid content (TFC) (1.53 ± 0.09 mg QE/g), ferric reducing antioxidant power (FRAP) (4.37 ± 0.04 mg AAE/g), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (4.44 ± 0.01 mg AAE/g) and total antioxidant capacity (TAC) (5.29 ± 0.09 mg AAE/g). The liquid chromatography coupled with electrospray-ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) data indicate that a total of 73 phenolic compounds were detected in Beurre Bosc (37 compounds), Josephine de Malines (34), Rico (22), Packham’s Triumph (15) and Winter Nelis (9), respectively. From HPLC-PDA quantification, the Beurre Bosc pear variety showed significantly higher in phenolic acids (chlorogenic acid 17.58 ± 0.88 mg/g) and while flavonoids were significantly higher in Josephine de Malines (catechin 17.45 ± 1.39 mg/g), as compared to other pear varieties. The analyses suggest that the Australian grown pears might contain an ideal source of phenolic compounds which benefit human health. The information provided by the present work can serve as practical supporting data for the use of pears in the nutraceutical, pharmaceutical and food industries.
Publisher: Springer New York
Date: 2008
Publisher: MDPI AG
Date: 11-08-2020
DOI: 10.3390/ANI10081391
Abstract: The gastrointestinal tract of the chicken harbors very complex and erse microbial communities including both beneficial and harmful bacteria. However, a dynamic balance is generally maintained in such a way that beneficial bacteria predominate over harmful ones. Environmental factors can negatively affect this balance, resulting in harmful effects on the gut, declining health, and productivity. This means modulating changes in the chicken gut microbiota is an effective strategy to improve gut health and productivity. One strategy is using modified diets to favor the growth of beneficial bacteria and a key candidate are polyphenols, which have strong antioxidant potential and established health benefits. The gut microbiota-polyphenol interactions are of vital importance in their effects on the gut microbiota modulation because it affects not only the composition of gut bacteria but also improves bioavailability of polyphenols through generation of more bioactive metabolites enhancing their health effects on morphology and composition of the gut microbiota. The object of this review is to improve the understanding of polyphenol interactions with the gut microbiota and highlights their potential role in modulation of the gut microbiota of chicken.
Publisher: Springer Science and Business Media LLC
Date: 2010
DOI: 10.4056/SIGS.147362
Publisher: MDPI AG
Date: 30-01-2023
Abstract: Breakthrough research in the field of immune checkpoint inhibitors and the development of a human papilloma virus vaccine triggered a plethora of research in the field of cancer immunotherapy. Both had significant effects on the treatment of head and neck squamous cell carcinoma. The advent of preclinical models and multidisciplinary approaches including bioinformatics, genetic engineering, clinical oncology, and immunology helped in the development of tumour-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapy. Here, we discuss different immunotherapies such as adoptive T-cell transfer, immune checkpoint inhibitors, interleukins, and cancer vaccines for the treatment of head and neck cancer. This review showcases the intrinsic relation between the understanding and implementation of basic biology and clinical practice. We also address potential limitations of each immunotherapy approach and the advantages of personalized immunotherapy. Overall, the aim of this review is to encourage further research in the field of immunotherapy for head and neck cancer.
Publisher: Springer Science and Business Media LLC
Date: 2006
Publisher: Springer Science and Business Media LLC
Date: 12-2008
Publisher: Elsevier BV
Date: 04-1999
DOI: 10.1016/S1093-3263(99)00023-6
Abstract: Whey acidic proteins (WAP) from the mouse, rat, rabbit, camel, and pig comprise two "four-disulfide core" domains. From a detailed analysis of all sequences containing this domain, we propose a new PROSITE motif ([KRHGVLN]-X-¿PF¿-X-[CF]-[PQSVLI]-X(9,19)-C-¿P¿-X-[DN]-X-¿N¿ -[CE]-X(5)-C-C) to accurately identify new four-disulfide core proteins. A consensus model for the WAP proteins is proposed, based on the human mucous proteinase inhibitor crystal structure. This article presents a detailed atomic model for the two-domain porcine WAP sequence by comparative modeling. Surface electrostatic potential calculations indicate that the second domain of the pig WAP model is similar to the functional human mucous proteinase inhibitor domains, whereas the first domain may be nonfunctional.
Publisher: Elsevier
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 12-2016
Publisher: Springer Science and Business Media LLC
Date: 12-2009
DOI: 10.1186/1471-2164-10-S3-S6
Abstract: Caspases belong to a class of cysteine proteases which function as critical effectors in cellular processes such as apoptosis and inflammation by cleaving substrates immediately after unique tetrapeptide sites. With hundreds of reported substrates and many more expected to be discovered, the elucidation of the caspase degradome will be an important milestone in the study of these proteases in human health and disease. Several computational methods for predicting caspase cleavage sites have been developed recently for identifying potential substrates. However, as most of these methods are based primarily on the detection of the tetrapeptide cleavage sites - a factor necessary but not sufficient for predicting in vivo substrate cleavage - prediction outcomes will inevitably include many false positives. In this paper, we show that structural factors such as the presence of disorder and solvent exposure in the vicinity of the cleavage site are important and can be used to enhance results from cleavage site prediction. We constructed a two-step model incorporating cleavage site prediction and these factors to predict caspase substrates. Sequences are first predicted for cleavage sites using CASVM or GraBCas. Predicted cleavage sites are then scored, ranked and filtered against a cut-off based on their propensities for locating in disordered and solvent exposed regions. Using an independent dataset of caspase substrates, the model was shown to achieve greater positive predictive values compared to CASVM or GraBCas alone, and was able to reduce the false positives pool by up to 13% and 53% respectively while retaining all true positives. We applied our prediction model on the family of receptor tyrosine kinases (RTKs) and highlighted several members as potential caspase targets. The results suggest that RTKs may be generally regulated by caspase cleavage and in some cases, promote the induction of apoptotic cell death - a function distinct from their role as transducers of survival and growth signals. As a step towards the prediction of in vivo caspase substrates, we have developed an accurate method incorporating cleavage site prediction and structural factors. The multi-factor model augments existing methods and complements experimental efforts to define the caspase degradome on the systems-wide basis.
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.BIOTECHADV.2009.03.005
Abstract: Parasitic nematodes infect humans, other animals and plants, and impose a significant public health and economic burden worldwide due to the diseases that they cause. A better understanding of parasite genomes, host-parasite relationships and the molecular biology of parasites themselves will enable the rational development of diagnostic tests and/or safe anti-parasitic compounds, following the functional annotation of parasite genomic sequences. With only a few completely sequenced nematode genomes, expressed sequence tag (EST) datasets provide a low-cost alternative ("poor man's genome") to whole genome sequences and a glimpse of the transcriptome of an organism. EST data require a number of computational methods for their pre-processing, clustering, assembly and annotation to yield biologically relevant information. In this article, we review the steps involved in EST data analysis, the development of new semi-automated bioinformatic pipelines and their application to parasitic nematodes of major socio-economic significance, focused on identifying molecules involved in key biological processes or pathways that might serve as targets for new drugs or vaccines.
Publisher: Springer Science and Business Media LLC
Date: 12-2012
DOI: 10.1186/1471-2164-13-S7-S10
Abstract: Teladorsagia circumcincta (order Strongylida) is an economically important parasitic nematode of small ruminants (including sheep and goats) in temperate climatic regions of the world. Improved insights into the molecular biology of this parasite could underpin alternative methods required to control this and related parasites, in order to circumvent major problems associated with anthelmintic resistance. The aims of the present study were to define the transcriptome of the adult stage of T. circumcincta and to infer the main pathways linked to molecules known to be expressed in this nematode. Since sheep develop acquired immunity against T. circumcincta , there is some potential for the development of a vaccine against this parasite. Hence, we infer excretory/secretory molecules for T. circumcincta as possible immunogens and vaccine candidates. A total of 407,357 ESTs were assembled yielding 39,852 putative gene sequences. Conceptual translation predicted 24,013 proteins, which were then subjected to detailed annotation which included pathway mapping of predicted proteins (including 112 excreted/secreted [ES] and 226 transmembrane peptides), domain analysis and GO annotation was carried out using InterProScan along with BLAST2GO. Further analysis was carried out for secretory signal peptides using SignalP and non-classical sec pathway using SecretomeP tools. For ES proteins, key pathways, including Fc epsilon RI, T cell receptor, and chemokine signalling as well as leukocyte transendothelial migration were inferred to be linked to immune responses, along with other pathways related to neurodegenerative diseases and infectious diseases, which warrant detailed future studies. KAAS could identify new and updated pathways like phagosome and protein processing in endoplasmic reticulum. Domain analysis for the assembled dataset revealed families of serine, cysteine and proteinase inhibitors which might represent targets for parasite intervention. InterProScan could identify GO terms pertaining to the extracellular region. Some of the important domain families identified included the SCP-like extracellular proteins which belong to the pathogenesis-related proteins (PRPs) superfamily along with C-type lectin, saposin-like proteins. The 'extracellular region' that corresponds to allergen V5/Tpx-1 related, considered important in parasite-host interactions, was also identified. Six cysteine motif (SXC1) proteins, transthyretin proteins, C-type lectins, activation-associated secreted proteins (ASPs), which could represent potential candidates for developing novel anthelmintics or vaccines were few other important findings. Of these, SXC1, protein kinase domain-containing protein, trypsin family protein, trypsin-like protease family member (TRY-1), putative major allergen and putative lipid binding protein were identified which have not been reported in the published T. circumcincta proteomics analysis. Detailed analysis of 6,058 raw EST sequences from dbEST revealed 315 putatively secreted proteins. Amongst them, C-type single domain activation associated secreted protein ASP3 precursor, activation-associated secreted proteins (ASP-like protein), cathepsin B-like cysteine protease, cathepsin L cysteine protease, cysteine protease, TransThyretin-Related and Venom-Allergen-like proteins were the key findings. We have annotated a large dataset ESTs of T. circumcincta and undertaken detailed comparative bioinformatics analyses. The results provide a comprehensive insight into the molecular biology of this parasite and disease manifestation which provides potential focal point for future research. We identified a number of pathways responsible for immune response. This type of large-scale computational scanning could be coupled with proteomic and metabolomic studies of this parasite leading to novel therapeutic intervention and disease control strategies. We have also successfully affirmed the use of bioinformatics tools, for the study of ESTs, which could now serve as a benchmark for the development of new computational EST analysis pipelines.
Publisher: MDPI AG
Date: 25-09-2021
Abstract: Bananas are an essential source of staple food and fruit worldwide and are widely regarded as the world’s largest fruit crop, with more than 100 million tons total annual production. Banana peel, a by-product that represents about 40% of the entire banana’s weight, and pulp are rich in bioactive compounds and have a high antioxidant capacity. As the production of polyphenols in fruit and vegetables is highly dependent on environmental conditions, genetic factors, and the level of maturity, this study aims to characterize six Australian banana cultivars in various stages of ripening for their phenolic compounds using the liquid chromatography-electrospray ionization quadrupole time of flight mass spectrometry (LC-ESI-QTOF-MS/MS), polyphenols quantification with the high-performance liquid chromatography coupled with photodiode array detector (HPLC-PDA), and their antioxidant capacity. All bananas were analysed for total polyphenols content (TPC), total flavonoids content (TFC), and total tannin content (TTC) and their antioxidant activities. Ripe Ducasse peel and pulp contained the highest amounts of total polyphenols content (1.32 and 1.28 mg gallic acid equivalent (GAE) per gram of s le), total tannin contents (3.34 mg catechin equivalent (CE) per gram of s le), and free radical scavenging capacity (106.67 mg ascorbic acid equivalent (AAE) per g of s le). In contrast, ripe Plantain peel had the greatest total flavonoids (0.03 mg quercetin equivalent (QE) per g of s le). On the other hand, unripe Ladyfinger pulp possessed the highest total antioxidant activity (1.03 mg AAE/g of s le). There was a positive correlation between flavonoids and antioxidant activities. By using LC-ESI-QTOF-MS/MS, a total of 24 phenolic compounds were tentatively characterized in this research, including six phenolic acids, 13 flavonoids, and five other polyphenols. Quantification of phenolic compounds by the high-performance liquid chromatography coupled with photodiode array detector (HPLC-PDA) revealed a higher content of phenolic acids. These findings confirmed that banana peel and pulp have considerable antioxidant activity and can be employed in human food and animal feed for variant health enhancement uses.
Publisher: Springer Science and Business Media LLC
Date: 2014
Publisher: MDPI AG
Date: 09-03-2021
DOI: 10.3390/APP11052421
Abstract: Apples (Malus domestica) are one of the most widely grown and consumed fruits in the world that contain abundant phenolic compounds that possess remarkable antioxidant potential. The current study characterised phenolic compounds from five different varieties of Australian grown apples (Royal Gala, Pink Lady, Red Delicious, Fuji and Smitten) using LC-ESI-QTOF-MS/MS and quantified through HPLC-PDA. The phenolic content and antioxidant potential were determined using various assays. Red Delicious had the highest total phenolic (121.78 ± 3.45 mg/g fw) and total flavonoid content (101.23 ± 3.75 mg/g fw) among the five apple s les. In LC-ESI-QTOF-MS/MS analysis, a total of 97 different phenolic compounds were characterised in five apple s les, including Royal Gala (37), Pink Lady (54), Red Delicious (17), Fuji (67) and Smitten (46). In the HPLC quantification, phenolic acid (chlorogenic acid, 15.69 ± 0.09 mg/g fw) and flavonoid (quercetin, 18.96 ± 0.08 mg/g fw) were most abundant in Royal Gala. The obtained results highlight the importance of Australian apple varieties as a rich source of functional compounds with potential bioactivity.
Publisher: Hindawi Limited
Date: 31-10-2021
DOI: 10.1111/JFPP.16058
Publisher: MDPI AG
Date: 03-02-2022
DOI: 10.3390/APPLMICROBIOL2010010
Abstract: Mass spectrometry (MS) is one of the key technologies used in proteomics. The majority of studies carried out using proteomics have focused on identifying proteins in biological s les such as human plasma to pin down prognostic or diagnostic biomarkers associated with particular conditions or diseases. This study aims to quantify microbial (viral and bacterial) proteins in healthy human plasma. MS data of healthy human plasma were searched against the complete proteomes of all available viruses and bacteria. With this baseline established, the same strategy was applied to characterize the metaproteomic profile of different SARS-CoV-2 disease stages in the plasma of patients. Two SARS-CoV-2 proteins were detected with a high confidence and could serve as the early markers of SARS-CoV-2 infection. The complete bacterial and viral protein content in SARS-CoV-2 s les was compared for the different disease stages. The number of viral proteins was found to increase significantly with the progression of the infection, at the expense of bacterial proteins. This strategy can be extended to aid in the development of early diagnostic tests for other infectious diseases based on the presence of microbial biomarkers in human plasma s les.
Publisher: Springer Science and Business Media LLC
Date: 14-01-2020
DOI: 10.1186/S40816-020-0150-Y
Abstract: Flaxseed has emerged as a potential source of bioactive components that can be utilized in routine diet to address lifestyle disorders. In this context, three studies were carried out on the basis of induction therapies i.e. Study I (Normal diet), Study II (Hyperglycemic diet 40% sucrose) and Study III (Hypercholesterolemic diet 1.5% cholesterol) using Sprague Dawley rats. Each study was further split into three groups based on diets Control (free from flaxseed powder or extract), Functional diet (incorporation of flaxseed powder 10%) and Nutraceutical diet (inclusion of ethanolic extract of flaxseed 5%). During experimental period, hyperglycemic and hyperlipidemic parameters were evaluated alongside, alterations in hematological aspects were also assessed. Feed intake and body weight demonstrated significant response ( p 0.05 ) of diets and study intervals however, water intake was substantially influenced by study intervals. In study II (hyperglycemic rats), maximum decline in glucose level was recorded (9.02%) in rats administered with extract based diet. In the same group, maximum increase in insulin (5.90%) was noted. Regarding lipid profile, the bioevaluation trials revealed maximum reduction in serum cholesterol (13.10%) in study III (hypercholesterolemic rats) on the provision of flaxseed extract (nutraceutical diet) followed by flaxseed powder (functional diet) i.e. 7.85%. Further, maximum decrease in low density lipoprotein-cholesterol (LDL-c) was reported i.e. 14.28% on supplementation of flaxseed extract to hypercholesterolemic rats. Thus, flaxseed extract based intervention has shown higher bioefficacy to address hyperglycemia and hypercholesterolemia in comparison to flaxseed powder.
Publisher: American Chemical Society (ACS)
Date: 27-01-2018
Abstract: (-)-Balanol is an adenosine triphosphate mimic that inhibits protein kinase C (PKC) isozymes and cAMP-dependent protein kinase (PKA) with limited selectivity. While PKA is known as a tumor promoter, PKC isozymes can be tumor promoters or suppressors. In particular, PKCε is frequently involved in tumorigenesis and a potential target for anticancer drugs. We recently reported that stereospecific fluorination of balanol yielded a balanoid with enhanced selectivity for PKCε over other PKC isozymes and PKA, although the global fluorine effect behind the selectivity enhancement is not fully understood. Interestingly, in contrast to PKA, PKCε is more sensitive to this fluorine effect. Here we investigate the global fluorine effect on the different binding responses of PKCε and PKA to balanoids using molecular dynamics (MD) simulations. For the first time to the best of our knowledge, we found that a structurally equivalent residue in each kinase, Thr184 in PKA and Ala549 in PKCε, is essential for the different binding responses. Furthermore, the study revealed that the invariant Lys, Lys73 in PKA and Lys437 in PKCε, already known to have a crucial role in the catalytic activity of kinases, serves as the main anchor for balanol binding. Overall, while Thr184 in PKA attenuates the effect of fluorination, Ala549 permits remote response of PKCε to fluorine substitution, with implications for rational design of future balanol-based PKCε inhibitors.
Publisher: Oxford University Press (OUP)
Date: 03-08-2010
DOI: 10.1093/NAR/GKQ667
Publisher: Informa UK Limited
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 2010
Publisher: Elsevier BV
Date: 06-2021
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.BJA.2018.02.007
Abstract: There is a need for robust, clearly defined, patient-relevant outcome measures for use in randomised trials in perioperative medicine. Our objective was to establish standard outcome measures for postoperative pulmonary complications research. A systematic literature search was conducted using MEDLINE, Web of Science, SciELO, and the Korean Journal Database. Definitions were extracted from included manuscripts. We then conducted a three-stage Delphi consensus process to select the optimal outcome measures in terms of methodological quality and overall suitability for perioperative trials. From 2358 records, the full texts of 81 manuscripts were retrieved, of which 45 met the inclusion criteria. We identified three main categories of outcome measure specific to perioperative pulmonary outcomes: (i) composite outcome measures of multiple pulmonary outcomes (27 definitions) (ii) pneumonia (12 definitions) and (iii) respiratory failure (six definitions). These were rated by the group according to suitability for routine use. The majority of definitions were given a low score, and many were imprecise, difficult to apply consistently, or both, in large patient populations. A small number of highly rated definitions were identified as appropriate for widespread use. The group then recommended four outcome measures for future use, including one new definition. A large number of postoperative pulmonary outcome measures have been used, but most are poorly defined. Our four recommended outcome measures include a new definition of postoperative pulmonary complications, incorporating an assessment of severity. These definitions will meet the needs of most clinical effectiveness trials of treatments to improve postoperative pulmonary outcomes.
Publisher: Springer Science and Business Media LLC
Date: 12-2008
DOI: 10.1186/1471-2105-9-S12-S25
Abstract: The customary medicinal plant knowledge possessed by the Australian Aboriginal people is a significant resource. Published information on it is scattered throughout the literature, in heterogeneous data formats, and is scattered among various Aboriginal communities across Australia, due to a multiplicity of languages. This ancient knowledge is at risk due to loss of bio ersity, cultural impact and the demise of many of its custodians. We have developed the Customary Medicinal Knowledgebase (CMKb), an integrated multidisciplinary resource, to document, conserve and disseminate this knowledge. CMKb is an online relational database for collating, disseminating, visualising and analysing initially public domain data on customary medicinal plants. The database stores information related to taxonomy, phytochemistry, biogeography, biological activities of customary medicinal plant species as well as images of in idual species. The database can be accessed at mkb . Known bioactive molecules are characterized within the chemoinformatics module of CMKb, with functions available for molecular editing and visualization. CMKb has been developed as a prototype data resource for documenting, integrating, disseminating, analysing multidisciplinary customary medicinal plant data from Australia and to facilitate user-defined complex querying. Each species in CMKb is linked to online resources such as the Integrated Taxonomic Information System (ITIS), NCBI Taxonomy, Australia's SpeciesLinks-Integrated Botanical Information System (IBIS) and Google images. The bioactive compounds are linked to the PubChem database. Overall, CMKb serves as a single knowledgebase for holistic plant-derived therapeutics and can be used as an information resource for bio ersity conservation, to lead discovery and conservation of customary medicinal knowledge.
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.SBI.2019.04.007
Abstract: G protein-coupled receptors (GPCRs) are key membrane-embedded receptor proteins, with critical roles in cellular signal transduction. In the era of precision medicine, understanding the role of natural variants on GPCR function is critical, especially from a pharmacogenomics viewpoint. Studies involved in mapping variants to GPCR structures are briefly reviewed here. The endocannabinoid system involving the central nervous system (CNS), the human cannabinoid receptor 1 (CB1), is an important drug target and its variability has implications for disease susceptibility and altered drug and pain response. We have carried out a computational study to map deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) to CB1. CB1 mutations were computationally evaluated from neutral to deleterious, and the top twelve deleterious mutations, with structural information, were found to be either close to the ligand binding region or the G-protein binding site. We have mapped these to the active and inactive CB1 X-ray crystallographic structures to correlate variants with available phenotypic information. We have also carried out molecular dynamics simulations to functionally characterize four selected mutants.
Publisher: Elsevier BV
Date: 09-1983
Publisher: Elsevier
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 12-2006
DOI: 10.1186/1471-2105-7-S5-S7
Abstract: Pemphigus vulgaris (PV) is a severe autoimmune blistering skin disorder that is strongly associated with major histocompatibility complex class II alleles DRB1*0402 and DQB1*0503. The target antigen of PV, desmoglein 3 (Dsg3), is crucial for initiating T-cell response in early disease. Although a number of T-cell specificities within Dsg3 have been reported, the number is limited and the role of T-cells in the pathogenesis of PV remains poorly understood. We report here a structure-based model for the prediction of peptide binding to DRB1*0402 and DQB1*0503. The scoring functions were rigorously trained, tested and validated using experimentally verified peptide sequences. High predictivity is obtained for both DRB1*0402 ( r 2 = 0.90, s = 1.20 kJ/mol, q 2 = 0.82, s press = 1.61 kJ/mol) and DQB1*0503 ( r 2 = 0.95, s = 1.20 kJ/mol, q 2 = 0.75, s press = 2.15 kJ/mol) models, compared to experimental data. We investigated the binding patterns of Dsg3 peptides and illustrate the existence of multiple immunodominant epitopes that may be responsible for both disease initiation and propagation in PV. Further analysis reveals that DRB1*0402 and DQB1*0503 may share similar specificities by binding peptides at different binding registers, thus providing a molecular mechanism for the dual HLA association observed in PV. Collectively, the results of this study provide interesting new insights into the pathology of PV. This is the first report illustrating high-level of cross-reactivity between both PV-implicated alleles, DRB1*0402 and DQB1*0503, as well as the existence of a potentially large number of T-cell epitopes throughout the entire Dsg3 extracellular domain (ECD) and transmembrane region. Our results reveal that DR4 and DR6 PV may initiate in the ECD and transmembrane region respectively, with implications for immunotherapeutic strategies for the treatment of this autoimmune disease.
Publisher: Oxford University Press (OUP)
Date: 11-02-2020
DOI: 10.1093/BIB/BBZ163
Abstract: Statistically, accurate protein identification is a fundamental cornerstone of proteomics and underpins the understanding and application of this technology across all elements of medicine and biology. Proteomics, as a branch of biochemistry, has in recent years played a pivotal role in extending and developing the science of accurately identifying the biology and interactions of groups of proteins or proteomes. Proteomics has primarily used mass spectrometry (MS)-based techniques for identifying proteins, although other techniques including affinity-based identifications still play significant roles. Here, we outline the basics of MS to understand how data are generated and parameters used to inform computational tools used in protein identification. We then outline a comprehensive analysis of the bioinformatics and computational methodologies used in protein identification in proteomics including discussing the most current communally acceptable metrics to validate any identification.
Publisher: Springer Science and Business Media LLC
Date: 12-2006
Publisher: Elsevier BV
Date: 07-2000
Publisher: Cold Spring Harbor Laboratory
Date: 30-11-2021
DOI: 10.1101/2021.11.29.470496
Abstract: Transient receptors are related to oral cancer pain. Previously capsaicin (TRPV1 agonist) was shown to induce cell death in oral cancer cells. We hypothesised that these receptors are present in oral cancer. We examined the presence of cannabinoid receptors (CB1 and CB2) and targets (TRPV1, TRPA1, Ca V 3.1, Ca V 3.2, Ca V 3.3) via quantitative polymerase chain reaction (qPCR) in oral cancer cells SCC4, SCC9, SCC25, Cal27, and normal oral cell line OKF6. Cannabinoid receptors are absent in all the cell lines, while TRPA1 is only present in normal cells, but absent in all the oral cancer cell lines. Voltage-gated calcium channels are present in all the cell lines. TRPA1 could be the possible future prognostic indicator of oral squamous cell carcinoma. Future functionality assays could use precancerous cell lines to follow the loss of TRPA1.
Publisher: Elsevier BV
Date: 10-1984
Publisher: Oxford University Press (OUP)
Date: 2006
DOI: 10.1093/NAR/GKJ152
Publisher: Oxford University Press (OUP)
Date: 2003
DOI: 10.1093/BIOINFORMATICS/19.1.159
Abstract: Summary: The relationship between intron distribution in the eukaryotic gene and protein structural elements is essential for understanding the origin and evolution of genes. XdomView is a web-based viewer mapping protein structural domains and intron positions in eukaryotic homologues to its tertiary structure. The association of sequence signals to 3D structure in XdomView provides a valuable visualization environment for eukaryotic gene organization, gene evolution, protein folding and protein structure classification. Availability: Freely available from surya.bic.nus.edu.sg/xdom Contact: shoba@bic.nus.edu.sg * To whom correspondence should be addressed.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 11-2001
DOI: 10.1109/5254.972070
Publisher: Informa UK Limited
Date: 25-05-2022
Publisher: Springer Science and Business Media LLC
Date: 12-2009
Publisher: MDPI AG
Date: 21-10-2020
Abstract: Heat stress (HS) compromises productivity of pork production, in part as a result of increased oxidative stress and inflammatory responses, particularly within the gastrointestinal tract. This study aimed to investigate whether plant-derived betaine and isoquinoline alkaloids could ameliorate HS in pigs. Fifty female Large White × Landrace grower pigs, which were acclimated to control (CON), control plus betaine (BET), or control plus isoquinoline alkaloids (IQA) diets for 14 days were then exposed to heat stress or thermoneutral condition. Both BET and IQA partially ameliorated increases in respiration rate (p = 0.013) and rectal temperature (p = 0.001) associated with HS conditions. Heat stress increased salivary cortisol concentrations and reduced plasma creatinine, lactate, and thyroid hormone concentrations. Heat stress increased colon FD4 permeability, which was reduced by IQA (p = 0.030). Heat stress increased inflammation in the jejunum and ileum, as indicated by elevated interleukin-1β (p = 0.022) in the jejunum and interleukin-1β (p = 0.004) and interleukin-8 (p = 0.001) in the ileum. No differences in plasma total antioxidant capacity (TAC) were observed with HS, but betaine increased plasma TAC compared to IQA. Dietary BET increased betaine concentrations in the jejunum, ileum (p 0.001 for both), plasma, liver, kidney (p 0.010 for all), urine (p = 0.002) and tended to be higher in muscle (p = 0.084). Betaine concentration was not influenced by HS, but it tended to be higher in plasma and accumulated in the liver. These data suggest that betaine and isoquinoline alkaloids supplementation ameliorated consequences of heat stress in grower pigs and protected against HS induced increases in colonic permeability.
Publisher: Springer Science and Business Media LLC
Date: 12-2009
Publisher: MDPI AG
Date: 08-06-2021
Abstract: Chicory and lucerne are used as specialised forages in sheep or dairy production systems in some parts of the world. Recently, these plants are gaining attention as raw materials in the search for natural antioxidants for use in animal feeds, human foods and nutraceutical formulations. The antioxidant potential of these plants is credited to polyphenols, a subgroup of phytochemicals. Therefore, phenolic characterisation is an essential step before their use as ingredients in animal feeds, human food or nutraceutical preparations. In this study, we performed qualitative and quantitative analysis of polyphenols in chicory and lucerne. Profiling of polyphenols from chicory and lucerne was performed by LC-ESI/QTOF-MS with a total of 80 phenolic compounds identified in chicory and lucerne. The quantification of polyphenols was achieved by high performance liquid chromatography, coupled with a photo diode array (HPLC-PDA). Chicoric acid was the major phenolic acid found in chicory, with the highest concentration (1692.33 ± 0.04 µg/g DW) among all the polyphenols quantified in this study. 2-hydroxybenzoic acid was the major phenolic acid found in lucerne, with the highest concentration of 1440.64 ± 0.04 µg/g DW. Total phenolic, flavonoids and total tannin contents were measured, and the antioxidant potential was determined by 2,2-Diphenyl-1-picrylhydrazyl, Ferric Reducing Antioxidant Power, 2,2-Azino-bis-3-ethylbenzothiazoline-6-sulfonic Acid, Hydroxyl (OH−) Radical Scavenging Activity, Chelating Ability of Ferrous Ion (Fe2+) and Reducing Power (RPA) assays. Both chicory (8.04 ± 0.33 mg AAE/g DW) and lucerne (11.29 ± 0.25 mg AAE/g DW) showed high values for Hydroxyl (OH−) Radical Scavenging Activity. The current study allowed us to draw a profile of polyphenols from chicory and lucerne. They provided a molecular fingerprint useful for the application of these plant materials in human foods, animal feeds and pharmaceutical formulations.
Publisher: Elsevier BV
Date: 2008
DOI: 10.1016/J.IJPARA.2007.07.001
Abstract: In the present study, a bioinformatic-microarray approach was employed for the analysis of selected expressed sequence tags (ESTs) from Haemonchus contortus, a key parasitic nematode of small ruminants. Following a bioinformatic analysis of EST data using a semiautomated pipeline, 1885 representative ESTs (rESTs) were selected, to which oligonucleotides (three per EST) were designed and spotted on to a microarray. This microarray was hybridized with cyanine-dye labelled cRNA probes synthesized from RNA from female or male adults of H. contortus. Differential hybridisation was displayed for 301 of the 1885 rESTs ( approximately 16%). Of these, 165 (55%) had significantly greater signal intensities for female cRNA and 136 (45%) for male cRNA. Of these, 113 with increased signals in female or male H. contortus had homologues in Caenorhabditis elegans, predicted to function in metabolism, information storage and processing, cellular processes and signalling, and embryonic and/or larval development. Of the rESTs with no known homologues in C. elegans, 24 ( approximately 40%) had homologues in other nematodes, four had homologues in various other organisms and 30 (52%) had no homology to any sequence in current gene databases. A genetic interaction network was predicted for the C. elegans orthologues of the gender-enriched H. contortus genes, and a focused analysis of a subset revealed a tight network of molecules involved in amino acid, carbohydrate or lipid transport and metabolism, energy production and conversion, translation, ribosomal structure and biogenesis and, importantly, those associated with meiosis and/or mitosis in the germline during oogenesis or spermatogenesis. This study provides a foundation for the molecular, biochemical and functional exploration of selected molecules with differential transcription profiles in H. contortus, for further microarray analyses of transcription in different developmental stages of H. contortus, and for an extended functional analysis once the full genome sequence of this nematode is known.
Publisher: Elsevier BV
Date: 09-2005
DOI: 10.1016/J.JMGM.2005.01.003
Abstract: Scorpion toxins are common experimental tools for studies of biochemical and pharmacological properties of ion channels. The number of functionally annotated scorpion toxins is steadily growing, but the number of identified toxin sequences is increasing at much faster pace. With an estimated 100,000 different variants, bioinformatic analysis of scorpion toxins is becoming a necessary tool for their systematic functional analysis. Here, we report a bioinformatics-driven system involving scorpion toxin structural classification, functional annotation, database technology, sequence comparison, nearest neighbour analysis, and decision rules which produces highly accurate predictions of scorpion toxin functional properties.
Publisher: Springer Science and Business Media LLC
Date: 08-08-2011
Publisher: American Chemical Society (ACS)
Date: 10-12-2021
Publisher: Elsevier
Date: 2013
Publisher: Wiley
Date: 05-1997
Abstract: Fast synaptic neurotransmission is mediated by ligand-gated ion-channel (LGIC) receptors, which include receptors for acetylcholine, serotonin, GABA, glycine, and glutamate. LGICs are pentamers with extracellular ligand-binding domains and form integral membrane ion channels that are selective for cations (acetylcholine and serotonin 5HT3 receptors) or anions (GABAA and glycine receptors and the invertebrate glutamate-binding chloride channel). They form a protein superfamily with no sequence similarity to any protein of known structure. Using a 1D-3D structure mapping approach, we have modeled the extracellular ligand-binding domain based on a significant match with the SH2 and SH3 domains of the biotin repressor structure. Refinement of the model based on knowledge of the large family of SH2 and SH3 structures, sequence alignments, and use of structure templates for loop building, allows the prediction of both monomer and pentamer models. These are consistent with medium-resolution electron microscopy structures and with experimental structure/function data from ligand-binding, antibody-binding, mutagenesis, protein-labeling and subunit-linking studies, and glycosylation sites. Also, the predicted polarity of the channel pore calculated from electrostatic potential maps of pentamer models of superfamily members is consistent with known ion selectivities. Using the glycine receptor alpha 1 subunit, which forms homopentamers, the monomeric and pentameric models define the agonist and antagonist (strychnine) binding sites to a deep crevice formed by an extended loop, which includes the invariant disulfide bridge, between the SH2 and SH3 domains. A detailed binding site for strychnine is reported that is in strong agreement with known structure/function data. A site for interaction of the extracellular ligand-binding domain with the activation of the M2 transmembrane helix is also suggested.
Publisher: Elsevier BV
Date: 05-2011
Publisher: Elsevier BV
Date: 2015
DOI: 10.1038/MTM.2015.15
Publisher: Elsevier
Date: 2019
Publisher: Informa UK Limited
Date: 2005
Publisher: Springer Science and Business Media LLC
Date: 09-10-2023
Publisher: Springer Science and Business Media LLC
Date: 2011
Publisher: Springer Science and Business Media LLC
Date: 26-01-2021
DOI: 10.1186/S12935-021-01777-3
Abstract: Prostate cancer (PC) is a multifactorial disease characterized by the abrogation of androgen receptor signaling. Advancement in microbiology techniques has highlighted the significant role of microRNAs (miRNAs) in the progression of PC cells from an androgen-dependent to an androgen-independent state. At that stage, prostate tumors also fail to respond to currently practiced hormone therapies. So, studies in recent decades are focused on investigating the anti-tumor effects of natural compounds in PC. Curcumin is widely recognized and now of huge prestige for its anti-proliferative abilities in different types of cancer. However, its limited solubility, compatibility, and instability in the aqueous phase are major hurdles when administering. Nanoformulations have proven to be an excellent drug delivery system for various drugs and can be used as potential delivery platforms for curcumin in PC. In this review, a shed light is given on the miRNAs-mediated regulation of androgen receptor (AR) signaling and miRNA-curcumin interplay in PC, as well as on curcumin-based nanoformulations that can be used as possible therapeutic solutions for PC.
Publisher: MDPI AG
Date: 09-05-2021
DOI: 10.3390/SEPARATIONS8050062
Abstract: Custard apple is an edible fruit grown in tropical and subtropical regions. Due to its abundant nutrient content and perceived health benefits, it is a popular food for consumption and is utilized as a medicinal aid. Although some published research had provided the phenolic compound of custard apple, the comprehensive phenolic profiling of Australian grown custard apple is limited. Hence, this research aimed to evaluate the phenolic content and antioxidant potential by various phenolic content and antioxidant assays, followed by characterization and quantification of the phenolic profile using LC-ESI-QTOF-MS/MS and HPLC-PDA. African Pride peel had the highest value in TPC (61.69 ± 1.48 mg GAE/g), TFC (0.42 ± 0.01 mg QE/g) and TTC (43.25 ± 6.70 mg CE/g), followed by Pink’s Mammoth peel (19.37 ± 1.48 mg GAE/g for TPC, 0.27 ± 0.03 mg QE/g for TFC and 10.25 ± 1.13 mg CE/g for TTC). African Pride peel also exhibited the highest antioxidant potential for TAC (43.41 ± 1.66 mg AAE/g), FRAP (3.60 ± 0.14 mg AAE/g) and ABTS (127.67 ± 4.60 mg AAE/g), whereas Pink’s Mammoth peel had the highest DPPH (16.09 ± 0.34 mg AAE/g), RPA (5.32 ± 0.14 mg AAE/g), •OH-RSA (1.23 ± 0.25 mg AAE/g) and FICA (3.17 ± 0.18 mg EDTA/g). LC-ESI-QTOF-MS/MS experiment successfully characterized 85 phenolic compounds in total, encompassing phenolic acids (20), flavonoids (42), stilbenes (4), lignans (6) and other polyphenols (13) in all three parts (pulp, peel and seeds) of custard apple. The phenolic compounds in different portions of custard apples were quantified by HPLC-PDA, and it was shown that African Pride peel had higher concentrations of the most abundant phenolics. This is the first study to provide the comprehensive phenolic profile of Australian grown custard apples, and the results highlight that each part of custard apple can be a rich source of phenolics for the utilization of custard apple fruit and waste in the food, animal feeding and nutraceutical industries.
Publisher: Oxford University Press (OUP)
Date: 03-2006
DOI: 10.1093/BIOINFORMATICS/BTL071
Abstract: Motivation: While processing of MHC class II antigens for presentation to helper T-cells is essential for normal immune response, it is also implicated in the pathogenesis of autoimmune disorders and hypersensitivity reactions. Sequence-based computational techniques for predicting HLA-DQ binding peptides have encountered limited success, with few prediction techniques developed using three-dimensional models. Methods: We describe a structure-based prediction model for modeling peptide-DQ3.2β complexes. We have developed a rapid and accurate protocol for docking candidate peptides into the DQ3.2β receptor and a scoring function to discriminate binders from the background. The scoring function was rigorously trained, tested and validated using experimentally verified DQ3.2β binding and non-binding peptides obtained from biochemical and functional studies. Results: Our model predicts DQ3.2β binding peptides with high accuracy [area under the receiver operating characteristic (ROC) curve AROC & 0.90], compared with experimental data. We investigated the binding patterns of DQ3.2β peptides and illustrate that several registers exist within a candidate binding peptide. Further analysis reveals that peptides with multiple registers occur predominantly for high-affinity binders. Contact: shoba@els.mq.edu.au Supplementary information: Supplementary data is available at Bioinformatics online.
Publisher: Wiley
Date: 07-2011
DOI: 10.1002/JGM.1582
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.JEP.2011.11.008
Abstract: Documentation of Australian bush medicines is of utmost importance to the preservation of this disappearing and invaluable knowledge. This collaboration between the Yaegl Aboriginal community in northern New South Wales (NSW), Australia and an academic institution, demonstrates an effective means of preserving and adding value to this information. Questionnaire-guided interviews were performed with community Elders under a framework of participatory action research. Medicinal plant knowledge was collated in a handbook to aid interviews and to be used as an ongoing resource by the community. Specimens for all non-cultivar plants that were discussed were collected and deposited in herbaria with unique voucher numbers. This medicinal knowledge was checked against the literature for reports of related use and studies of biological activity. Nineteen Elders were interviewed, leading to discussions on fifty four plant preparations used for medicinal purposes. These plant preparations involved thirty two plants coming from twenty one families, reflecting the botanical ersity of the area. The plants retained in the Yaegl pharmacopoeia correspond to their accessibility and ease of preparation, reflected in their ongoing utilisation. Several plant uses did not appear elsewhere in the literature. This study is the first comprehensive documentation of the medicinal knowledge of the Yaegl Aboriginal community. It has been conducted using participatory action research methods and adds to the recorded customary knowledge of the region. The customary medicinal knowledge retained by the Yaegl Aboriginal community is related to the evolving needs of the community and accessibility of plants.
Publisher: MDPI AG
Date: 05-11-2021
Abstract: Culinary spices and herbs have been used to impart a characteristic flavour and aroma in food due to their appealing fragrance. Recently, bioactive compounds from herbs, especially phenolics, have gained much attention due to their potential health outcomes. The aim of this study was to characterize and quantify the phenolic compounds from 10 widely used Australian-grown herbs (oregano, rosemary, bay, basil, sage, fenugreek, dill, parsley, mint and thyme). For this purpose, liquid chromatography mass spectrometry (LC-MS) was used for the complete profiling of polyphenolic compounds and quantification of abundant phenolic compounds was completed with high-performance liquid chromatography—photodiode array detection (HPLC-PDA). Polyphenols from Australian-grown herbs were estimated through total phenolic content (TP), total flavonoids (TF) and total tannins (TT) along with their in-vitro antioxidant activities. Oregano and mint were estimated with the highest value of TP (140.59 ± 9.52 and 103.28 ± 8.08 mg GAE/g, milligram gallic acid equivalent/gram) while rosemary and mint had the highest TF (8.19 ± 0.74 and 7.05 ± 0.43 mg QE (quercetin equivalent)/g). In this study, eighty-four (84) phenolic compounds were screened and confirmed through LC-MS/MS by comparing their masses and fragmentation pattern with published libraries. The results of this study validate the use of these herbs as bioactives and their positive impact on human health.
Publisher: Springer Netherlands
Date: 2003
Publisher: American Society of Clinical Oncology (ASCO)
Date: 06-2022
DOI: 10.1200/JCO.2022.40.16_SUPPL.E18053
Abstract: e18053 Background: Biofilm formation is a continuous process in oral cancer patients, despite proper extirpation/elimination of a bacterial plaque via a surgical procedure or antibiotic treatment. Also, elimination of a bacterial plaque does not necessarily remove extant bacterial antigen-stimulated oral cancer cells. Therefore, combination drug treatment may be an appropriate approach to elucidate the confounding effects of bacterial antigens on anti-cancer drugs. Methods: Our drug combination strategy addressed both Gram-positive (Lipoteichoic acid [LTA]) and Gram-negative (Lipopolysaccharide [LPS]) bacterial antigens, to determine the effect of anti-cancer drugs on LPS/LTA/LPS+LTA-stimulated preclinical oral cancer models (SCC4, SCC9, SCC25, and Cal 27). The drug combination strategy was designed in six phases of treatment. In phase 1, plated cells were treated with different combinations of bacterial antigens in combination with anti-cancer drugs. In the phases 2 and 3, inhibitory drugs were introduced in the presence of bacterial antigens after 24 hours and 72 hours of bacterial antigen stimulation. In phases 4 and 5, inhibitory drugs were added after 24 hours and 72 hours of bacterial antigen stimulation. In phase 6, inhibitory drugs were applied in the absence of, and without stimulation with, bacterial antigens. Metabolic assays, reverse transcription quantitative PCR, Western blot, Proteome Profiler, apoptotic and ELISA assays were performed to validate the novel drug combination strategy. Results: Anti-cancer drug treatment on preclinical oral cancer models resulted in 43.6% ± 3.3% of precancerous models being apoptotic. To mimic pre-existing unhygenic conditions in oral cancer patients, prior stimulation of preclinical model with LPS+LTA 72 hours before drug treatment, reduced apoptosis to 32.2% ± 1.1% of cells. Apoptosis was almost annulled (2.98% ± 0.3% p 0.01) when drug treatment was carried out along with bacterial antigens. Treatment with drugs in the absence of bacterial antigens resulted in significantly more apoptotic cells than in presence of bacterial antigens (p 0.0001). Metabolic and viability assay showed similar results like apoptotic assay. Conclusions: Bacterial antigens mimic the presence of Gram-negative and Gram-positive bacteria and thus severely affect the efficacy of anti-cancer drugs. The novel drug combination strategy redesigns the pharmacological management of oral squamous cell carcinoma.
Publisher: Public Library of Science (PLoS)
Date: 2005
Start Date: 2018
End Date: 2020
Funder: Australian Research Council
View Funded ActivityStart Date: 2015
End Date: 2015
Funder: Australian Research Council
View Funded ActivityStart Date: 2009
End Date: 2009
Funder: Australian Research Council
View Funded ActivityStart Date: 2006
End Date: 2008
Funder: Australian Research Council
View Funded ActivityStart Date: 2008
End Date: 2010
Funder: Australian Research Council
View Funded ActivityStart Date: 03-2018
End Date: 03-2024
Amount: $438,211.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2015
End Date: 01-2016
Amount: $540,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 07-2006
End Date: 12-2008
Amount: $241,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 10-2009
End Date: 12-2009
Amount: $500,000.00
Funder: Australian Research Council
View Funded Activity