ORCID Profile
0000-0001-8727-4984
Current Organisation
Macquarie University
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Plant Cell and Molecular Biology | Proteomics and Intermolecular Interactions (excl. Medical Proteomics) | Plant Biology | Plant Physiology |
Plant Production and Plant Primary Products not elsewhere classified | Expanding Knowledge in the Biological Sciences
Publisher: Wiley
Date: 18-01-2012
Abstract: We describe the PloGO R package, a simple open-source tool for plotting gene ontology (GO) annotation and abundance information, which was developed to aid with the bioinformatics analysis of multi-condition label-free proteomics experiments using quantitation based on spectral counting. PloGO can incorporate abundance (raw spectral counts) or normalized spectral abundance factors (NSAF) data in addition to the GO annotation, as well as handle multiple files and allow for a targeted collection of GO categories of interest. Our main aims were to help identify interesting subsets of proteins for further analysis such as those arising from a protein data set partition based on the presence and absence or multiple pair-wise comparisons, as well as provide GO summaries that can be easily used in subsequent analyses. Though developed with label-free proteomics experiments in mind it is not specific to that approach and can be used for any multi-condition experiment for which GO information has been generated.
Publisher: Frontiers Media SA
Date: 21-02-2022
Abstract: Root system architecture (RSA) is an important agronomic trait with vital roles in plant productivity under water stress conditions. A deep and branched root system may help plants to avoid water stress by enabling them to acquire more water and nutrient resources. Nevertheless, our knowledge of the genetics and molecular control mechanisms of RSA is still relatively limited. In this study, we analyzed the transcriptome response of root tips to water stress in two well-known genotypes of rice: IR64, a high-yielding lowland genotype, which represents a drought-susceptible and shallow-rooting genotype and Azucena, a traditional, upland, drought-tolerant and deep-rooting genotype. We collected s les from three zones (Z) of root tip: two consecutive 5 mm sections (Z1 and Z2) and the following next 10 mm section (Z3), which mainly includes meristematic and maturation regions. Our results showed that Z1 of Azucena was enriched for genes involved in cell cycle and ision and root growth and development whereas in IR64 root, responses to oxidative stress were strongly enriched. While the expansion of the lateral root system was used as a strategy by both genotypes when facing water shortage, it was more pronounced in Azucena. Our results also suggested that by enhancing meristematic cell wall thickening for insulation purposes as a means of confronting stress, the sensitive IR64 genotype may have reduced its capacity for root elongation to extract water from deeper layers of the soil. Furthermore, several members of gene families such as NAC , AP2/ERF , AUX/IAA , EXPANSIN , WRKY , and MYB emerged as main players in RSA and drought adaptation. We also found that HSP and HSF gene families participated in oxidative stress inhibition in IR64 root tip. Meta-quantitative trait loci (QTL) analysis revealed that 288 differentially expressed genes were colocalized with RSA QTLs previously reported under drought and normal conditions. This finding warrants further research into their possible roles in drought adaptation. Overall, our analyses presented several major molecular differences between Azucena and IR64, which may partly explain their differential root growth responses to water stress. It appears that Azucena avoided water stress through enhancing growth and root exploration to access water, whereas IR64 might mainly rely on cell insulation to maintain water and antioxidant system to withstand stress. We identified a large number of novel RSA and drought associated candidate genes, which should encourage further exploration of their potential to enhance drought adaptation in rice.
Publisher: Elsevier BV
Date: 03-2018
Publisher: Springer Science and Business Media LLC
Date: 24-07-2020
Publisher: MDPI AG
Date: 14-01-2020
DOI: 10.3390/MICROORGANISMS8010115
Abstract: The E. gracilis Zm-strain lacking chloroplasts, characterized in this study, was compared with the earlier assessed wild type Z-strain to explore the role of chloroplasts in heavy metal accumulation and tolerance. Comparison of the minimum inhibitory concentration (MIC) values indicated that both strains tolerated similar concentrations of mercury (Hg) and lead (Pb), but cadmium (Cd) tolerance of the Z-strain was twice that of the Zm-strain. The ability of the Zm-strain to accumulate Hg was higher compared to the Z-strain, indicating the existence of a Hg transportation and accumulation mechanism not depending on the presence of chloroplasts. Transmission electron microscopy (TEM) showed maximum accumulation of Hg in the cytosol of the Zm-strain and highest accumulation of Cd in the chloroplasts of the Z-strain indicating a difference in the ability of the two strains to deposit heavy metals in the cell. The highly abundant heavy metal transporter MTP2 in the Z-strain may have a role in Cd transportation to the chloroplasts. A multidrug resistance-associated protein highly increased in abundance in the Zm-strain could be a potential Hg transporter to either cytosol or mitochondria. Overall, the chloroplasts appear to have major role in the tolerance and accumulation of Cd in E. gracilis.
Publisher: Elsevier BV
Date: 11-2017
Publisher: Elsevier BV
Date: 11-2019
Publisher: Elsevier BV
Date: 04-2023
Publisher: Bentham Science Publishers Ltd.
Date: 13-12-2016
Publisher: American Chemical Society (ACS)
Date: 13-01-2015
DOI: 10.1021/PR501091E
Abstract: iTRAQ labeling of peptides is widely used for quantitative comparison of biological s les using mass spectrometry. However, iTRAQ determined protein ratios have varying credibility depending on the number and quality of the peptide ratios used to generate them, and accounting for this becomes problematic particularly in the multirun scenario needed for larger scale biological studies. One approach to this problem relies on the use of sophisticated statistical global models using peptide ratios rather than working directly with the protein ratios, but these yield complex models whose solution relies on computational approaches such as stage-wise regression, which are nontrivial to run and verify. Here we evaluate an alternative pragmatic approach to finding differentially expressed proteins based on combining protein ratio p-values across experiments in a fashion similar to running a meta-analysis across different iTRAQ runs. Our approach uses the well-established Stouffer's Z-transform for combining p-values, alongside a ratio trend consistency measure, which we introduce. We evaluate this method with data from two iTRAQ experiments using plant and animal models. We show that in the specific context of iTRAQ data analysis this method has advantages of simplicity, high tolerance of run variability, low false discovery rate, and emphasis on proteins identified with high confidence.
Publisher: Springer Science and Business Media LLC
Date: 11-01-2022
DOI: 10.1007/S12035-021-02709-Y
Abstract: Retinoid X receptors (RXRs) present a subgroup of the nuclear receptor superfamily with particularly high evolutionary conservation of ligand binding domain. The receptor exists in α, β, and γ isotypes that form homo-/heterodimeric complexes with other permissive and non-permissive receptors. While research has identified the biochemical roles of several nuclear receptor family members, the roles of RXRs in various neurological disorders remain relatively under-investigated. RXR acts as ligand-regulated transcription factor, modulating the expression of genes that plays a critical role in mediating several developmental, metabolic, and biochemical processes. Cumulative evidence indicates that abnormal RXR signalling affects neuronal stress and neuroinflammatory networks in several neuropathological conditions. Protective effects of targeting RXRs through pharmacological ligands have been established in various cell and animal models of neuronal injury including Alzheimer disease, Parkinson disease, glaucoma, multiple sclerosis, and stroke. This review summarises the existing knowledge about the roles of RXR, its interacting partners, and ligands in CNS disorders. Future research will determine the importance of structural and functional heterogeneity amongst various RXR isotypes as well as elucidate functional links between RXR homo- or heterodimers and specific physiological conditions to increase drug targeting efficiency in pathological conditions.
Publisher: American Chemical Society (ACS)
Date: 20-12-2012
DOI: 10.1021/PR300864K
Abstract: The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level. This project attempts simultaneously to establish a sound basis for the development of diagnostic, prognostic, therapeutic, and preventive medical applications. In Iran, current efforts focus on mapping the proteome of the human Y chromosome. The male-specific region of the Y chromosome (MSY) is unique in many aspects and comprises 95% of the chromosome's length. The MSY continually retains its haploid state and is full of repeated sequences. It is responsible for important biological roles such as sex determination and male fertility. Here, we present the most recent update of MSY protein-encoding genes and their association with various traits and diseases including sex determination and reversal, spermatogenesis and male infertility, cancers such as prostate cancers, sex-specific effects on the brain and behavior, and graft-versus-host disease. We also present information available from RNA sequencing, protein-protein interaction, post-translational modification of MSY protein-coding genes and their implications in biological systems. An overview of Human Y chromosome Proteome Project is presented and a systematic approach is suggested to ensure that at least one of each predicted protein-coding gene's major representative proteins will be characterized in the context of its major anatomical sites of expression, its abundance, and its functional relevance in a biological and/or medical context. There are many technical and biological issues that will need to be overcome in order to accomplish the full scale mapping.
Publisher: Springer US
Date: 25-08-2021
DOI: 10.1007/978-1-0716-1967-4_17
Abstract: In this protocol we describe our workflow for analyzing complex, multi-condition quantitative proteomic experiments, with the aim to extract biological insights. The tool we use is an R package, PloGO2, contributed to Bioconductor, which we can optionally precede by running correlation network analysis with WGCNA. We describe the data required and the steps we take, including detailed code ex les and outputs explanation. The package was designed to generate gene ontology or pathway summaries for many data subsets at the same time, visualize protein abundance summaries for each biological category examined, help determine enriched protein subsets by comparing them all to a reference set, and suggest key highly correlated hub proteins, if the optional network analysis is employed.
Publisher: Springer Science and Business Media LLC
Date: 09-07-2020
DOI: 10.1186/S12967-020-02448-Z
Abstract: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million in iduals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore the mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to the genetic pool of local populations. For this study, we analysed 2301 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CL pro ) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements. Our results demonstrate that bat-CoV shares 96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. Using state of the art in silico approaches, this study further investigates the interaction of repurposed drugs with the SARS-CoV-2 3CL pro enzyme, which regulates viral replication machinery. Overall, this study provides insights into the evolving mutations, with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat the nCovid-19 pandemic.
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.EXPNEUROL.2019.01.015
Abstract: Retinoid X receptors (RXRs) play an important role in transcription, are involved in numerous cellular networks from cell proliferation to lipid metabolism and are essential for normal eye development. RXRs form homo or heterodimers with other nuclear receptors, bind to DNA response elements and regulate several biological processes including neurogenesis. Mounting evidence suggests that RXR activation by selective RXR modulators (sRXRms) may be neuroprotective in the central nervous system. However, their potential neuroprotective role in the retina and specifically in glaucoma remains unexplored. This study investigated changes in RXR expression in the human and mouse retina under glaucomatous stress conditions and investigated the effect of RXR modulation on the RGCs using pharmacological approaches. RXR protein levels in retina were downregulated in both human glaucoma and experimental RGC injury models while RXR agonist, bexarotene treatment resulted in upregulation of RXR expression particularly in the inner retinal layers. Retinal electrophysiological recordings and histological analysis indicated that inner retinal function and retinal laminar structure were preserved upon treatment with bexarotene. These protective effects were associated with downregulation of ER stress marker response upon bexarotene treatment under glaucoma conditions. Overall, retinal RXR modulation by bexarotene significantly protected RGCs in vivo in both acute and chronic glaucoma models.
Publisher: Wiley
Date: 11-05-2023
DOI: 10.1002/ALZ.13086
Abstract: Vascular amyloid beta (Aβ) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients. We tested the hypothesis that the retinal vascular tight junctions (TJs) were compromised and linked to disease status. TJ components and Aβ expression in capillaries and larger blood vessels were determined in post mortem retinas from 34 MCI or AD patients and 27 cognitively normal controls and correlated with neuropathology. Severe decreases in retinal vascular zonula occludens‐1 (ZO‐1) and claudin‐5 correlating with abundant arteriolar Aβ 40 deposition were identified in MCI and AD patients. Retinal claudin‐5 deficiency was closely associated with cerebral amyloid angiopathy, whereas ZO‐1 defects correlated with cerebral pathology and cognitive deficits. We uncovered deficiencies in blood–retinal barrier markers for potential retinal imaging targets of AD screening and monitoring. Intense retinal arteriolar Aβ 40 deposition suggests a common pathogenic mechanism of failed Aβ clearance via intramural periarterial drainage.
Publisher: American Chemical Society (ACS)
Date: 11-06-2015
DOI: 10.1021/ACS.JPROTEOME.5B00211
Abstract: In the rapidly growing economies of Asia and Oceania, food security has become a primary concern. With the rising population, growing more food at affordable prices is becoming even more important. In addition, the predicted climate change will lead to drastic changes in global surface temperature and changes in rainfall patterns that in turn will pose a serious threat to plant vegetation worldwide. As a result, understanding how plants will survive in a changing climate will be increasingly important. Such challenges require integrated approaches to increase agricultural production and cope with environmental threats. Proteomics can play a role in unraveling the underlying mechanisms for food production to address the growing demand for food. In this review, the current status of food crop proteomics is discussed, especially in regard to the Asia and Oceania regions. Furthermore, the future perspective in relation to proteomic techniques for the important food crops is highlighted.
Publisher: MDPI AG
Date: 14-03-2022
Abstract: Alzheimer’s disease (AD) is one of the most complicated progressive neurodegenerative brain disorders, affecting millions of people around the world. Ageing remains one of the strongest risk factors associated with the disease and the increasing trend of the ageing population globally has significantly increased the pressure on healthcare systems worldwide. The pathogenesis of AD is being extensively investigated, yet several unknown key components remain. Therefore, we aimed to extract new knowledge from existing data. Ten gene expression datasets from different brain regions including the hippoc us, cerebellum, entorhinal, frontal and temporal cortices of 820 AD cases and 626 healthy controls were analyzed using the robust rank aggregation (RRA) method. Our results returned 1713 robust differentially expressed genes (DEGs) between five brain regions of AD cases and healthy controls. Subsequent analysis revealed pathways that were altered in each brain region, of which the GABAergic synapse pathway and the retrograde endocannabinoid signaling pathway were shared between all AD affected brain regions except the cerebellum, which is relatively less sensitive to the effects of AD. Furthermore, we obtained common robust DEGs between these two pathways and predicted three miRNAs as potential candidates targeting these genes hsa-mir-17-5p, hsa-mir-106a-5p and hsa-mir-373-3p. Three transcription factors (TFs) were also identified as the potential upstream regulators of the robust DEGs ELK-1, GATA1 and GATA2. Our results provide the foundation for further research investigating the role of these pathways in AD pathogenesis, and potential application of these miRNAs and TFs as therapeutic and diagnostic targets.
Publisher: Elsevier BV
Date: 2019
Publisher: Medknow
Date: 2020
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: American Chemical Society (ACS)
Date: 10-08-2015
DOI: 10.1021/ACS.JPROTEOME.5B00333
Abstract: One of the major objectives of the Human Y Chromosome Proteome Project is to characterize sets of proteins encoded from the human Y chromosome. Lysine (K)-specific demethylase 5D (KDM5D) is located on the AZFb region of the Y chromosome and encodes a JmjC-domain-containing protein. KDM5D, the least well-documented member of the KDM5 family, is capable of demethylating di- and trimethyl H3K4. In this study, we detected two novel splice variants of KDM5D with lengths of 2650bp and 2400bp that correspond to the 100 and 80 kDa proteins in the human prostate cancer cell line, DU-145. The knockdown of two variants using the short interfering RNA (siRNA) approach increased the growth rate of prostate cancer cells and reduced cell apoptosis. To explore the proteome pattern of the cells after KDM5D downregulation, we applied a shotgun label-free quantitative proteomics approach. Of 820 proteins present in all four replicates of two treatments, the abundance of 209 proteins changed significantly in response to KDM5D suppression. Of these, there were 102 proteins observed to be less abundant and 107 more abundant in KDM5D knockdown cells compared with control cells. The results revealed that KDM5D knockdown altered the abundance of proteins involved in RNA processing, protein synthesis, apoptosis, the cell cycle, and growth and proliferation. In conjunction, these results provided new insights into the function of KDM5D and its splice variants. The proteomics data are available at PRIDE with ProteomeXchange identifier PXD000416.
Publisher: Elsevier BV
Date: 05-2021
DOI: 10.1016/J.PRETEYERES.2020.100899
Abstract: Alzheimer's Disease (AD) is a devastating neurodegenerative disorder of the brain, clinically characterised by cognitive deficits that gradually worsen over time. There is, at present, no established cure, or disease-modifying treatments for AD. As life expectancy increases globally, the number of in iduals suffering from the disease is projected to increase substantially. Cumulative evidence indicates that AD neuropathological process is initiated several years, if not decades, before clinical signs are evident in patients, and diagnosis made. While several imaging, cognitive, CSF and blood-based biomarkers have been proposed for the early detection of AD their sensitivity and specificity in the symptomatic stages is highly variable and it is difficult to justify their use in even earlier, pre-clinical stages of the disease. Research has identified potentially measurable functional, structural, metabolic and vascular changes in the retina during early stages of AD. Retina offers a distinctively accessible insight into brain pathology and current and developing ophthalmic technologies have provided us with the possibility of detecting and characterising subtle, disease-related changes. Recent human and animal model studies have further provided mechanistic insights into the biochemical pathways that are altered in the retina in disease, including amyloid and tau deposition. This information coupled with advances in molecular imaging has allowed attempts to monitor biochemical changes and protein aggregation pathology in the retina in AD. This review summarises the existing knowledge that informs our understanding of the impact of AD on the retina and highlights some of the gaps that need to be addressed. Future research will integrate molecular imaging innovation with functional and structural changes to enhance our knowledge of the AD pathophysiological mechanisms and establish the utility of monitoring retinal changes as a potential biomarker for AD.
Publisher: American Chemical Society (ACS)
Date: 07-01-2013
DOI: 10.1021/PR300865T
Abstract: Infection of Mexican lime trees (Citrus aurantifolia L.) with the specialized bacterium "CandidatusPhytoplasma aurantifolia" causes witches' broom disease. Witches' broom disease has the potential to cause significant economic losses throughout western Asia and North Africa. We used label-free quantitative shotgun proteomics to study changes in the proteome of Mexican lime trees in response to infection by "Ca. Phytoplasma aurantifolia". Of 990 proteins present in five replicates of healthy and infected plants, the abundances of 448 proteins changed significantly in response to phytoplasma infection. Of these, 274 proteins were less abundant in infected plants than in healthy plants, and 174 proteins were more abundant in infected plants than in healthy plants. These 448 proteins were involved in stress response, metabolism, growth and development, signal transduction, photosynthesis, cell cycle, and cell wall organization. Our results suggest that proteomic changes in response to infection by phytoplasmas might support phytoplasma nutrition by promoting alterations in the host's sugar metabolism, cell wall biosynthesis, and expression of defense-related proteins. Regulation of defense-related pathways suggests that defense compounds are induced in interactions with susceptible as well as resistant hosts, with the main differences between the two interactions being the speed and intensity of the response.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Bentham Science Publishers Ltd.
Date: 28-11-2020
DOI: 10.2174/1389201021666200515135548
Abstract: Heart dysfunctions are the major complications of trastuzumab in patients with Human Epidermal growth factor Receptor-2 (HER2)-positive breast cancers. In this study, the cytotoxicity of trastuzumab on H9c2 cardiomyoblasts was demonstrated, and the proteome changes of cells were investigated by a tandem mass tagging quantitative approach. The Differentially Abundant Proteins (DAPs) were identified and functionally enriched. We determined that carvedilol, a non-selective beta-blocker, could effectively inhibit trastuzumab toxicity when administrated in a proper dose and at the same time. The proteomics analysis of carvedilol co-treated cardiomyoblasts showed complete or partial reversion in expressional levels of trastuzumab-induced DAPs. Downregulation of proteins involved in the translation biological process is one of the most important changes induced by trastuzumab and reversed by carvedilol. These findings provide novel insights to develop new strategies for the cardiotoxicity of trastuzumab.
Publisher: Wiley
Date: 14-10-2020
DOI: 10.1111/ACEL.13246
Abstract: Despite growing evidence for the characteristic signs of Alzheimer's disease (AD) in the neurosensory retina, our understanding of retina–brain relationships, especially at advanced disease stages and in response to therapy, is lacking. In transgenic models of AD (APP SWE /PS1 ∆E9 ADtg mice), glatiramer acetate (GA) immunomodulation alleviates disease progression in pre‐ and early‐symptomatic disease stages. Here, we explored the link between retinal and cerebral AD‐related biomarkers, including response to GA immunization, in cohorts of old, late‐stage ADtg mice. This aged model is considered more clinically relevant to the age‐dependent disease. Levels of synaptotoxic amyloid β‐protein (Aβ) 1–42 , angiopathic Aβ 1–40 , non‐amyloidogenic Aβ 1–38 , and Aβ 42 /Aβ 40 ratios tightly correlated between paired retinas derived from oculus sinister (OS) and oculus dexter (OD) eyes, and between left and right posterior brain hemispheres. We identified lateralization of Aβ burden, with one‐side dominance within paired retinal and brain tissues. Importantly, OS and OD retinal Aβ levels correlated with their cerebral counterparts, with stronger contralateral correlations and following GA immunization. Moreover, immunomodulation in old ADtg mice brought about reductions in cerebral vascular and parenchymal Aβ deposits, especially of large, dense‐core plaques, and alleviation of microgliosis and astrocytosis. Immunization further enhanced cerebral recruitment of peripheral myeloid cells and synaptic preservation. Mass spectrometry analysis identified new parallels in retino‐cerebral AD‐related pathology and response to GA immunization, including restoration of homeostatic glutamine synthetase expression. Overall, our results illustrate the viability of immunomodulation‐guided CNS repair in old AD model mice, while shedding light onto similar retino‐cerebral responses to intervention, providing incentives to explore retinal AD biomarkers.
Publisher: American Chemical Society (ACS)
Date: 17-10-2014
DOI: 10.1021/PR500719F
Abstract: Repeat administration of psychostimulants, such as meth hetamine, produces a progressive increase in locomotor activity (behavioral sensitization) in rodents that is believed to represent the underlying neurochemical changes driving psychoses. Alterations to the prefrontal cortex (PFC) are suggested to mediate the etiology and maintenance of these behavioral changes. As such, the aim of the current study was to investigate changes to protein expression in the PFC in male rats sensitized to meth hetamine using quantitative label-free shotgun proteomics. A meth hetamine challenge resulted in a significant sensitized locomotor response in meth hetamine pretreated animals compared to saline controls. Proteomic analysis revealed 96 proteins that were differentially expressed in the PFC of meth hetamine treated rats, with 20% of these being previously implicated in the neurobiology of schizophrenia in the PFC. We identified multiple biological functions in the PFC that appear to be commonly altered across meth hetamine-induced sensitization and schizophrenia, and these include synaptic regulation, protein phosphatase signaling, mitochondrial function, and alterations to the inhibitory GABAergic network. These changes could inform how alterations to the PFC could underlie the cognitive and behavioral dysfunction commonly seen across psychoses and places such biological changes as potential mediators in the maintenance of psychosis vulnerability.
Publisher: Aging and Disease
Date: 2020
Publisher: Elsevier BV
Date: 08-2020
Publisher: Elsevier BV
Date: 10-2013
Publisher: Wiley
Date: 17-01-2011
Abstract: In this review we examine techniques, software, and statistical analyses used in label-free quantitative proteomics studies for area under the curve and spectral counting approaches. Recent advances in the field are discussed in an order that reflects a logical workflow design. Ex les of studies that follow this design are presented to highlight the requirement for statistical assessment and further experiments to validate results from label-free quantitation. Limitations of label-free approaches are considered, label-free approaches are compared with labelling techniques, and forward-looking applications for label-free quantitative data are presented. We conclude that label-free quantitative proteomics is a reliable, versatile, and cost-effective alternative to labelled quantitation.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.PLAPHY.2019.11.017
Abstract: Young wheat seedlings are desiccation tolerant and have the capacity to withstand long dehydration period. In this study, we characterized the proteome and metabolome of wheat seedlings during desiccation and after recovery. Functional classification of differentially identified proteins revealed dynamic changes in the number and abundance of proteins observed during stress and recovery. Desiccation resulted in a decline in the abundance of proteins associated with photosynthesis and carbohydrate reserves, along with an increase in the presence of proteins associated with stress and defense response, such as peroxiredoxins and antioxidant enzymes. Following recovery, the abundance of stress-responsive proteins returned either partially or completely to their baseline level, confirming their importance to the seedling's desiccation response. Furthermore, proteins involved in carbohydrate metabolism, as well as fructose-bisphosphate aldolase and fructokinase-2 and phosphorylated metabolites as the substrate or the end-product, showed the inverse pattern during desiccation and after re-watering. This may reflect the fact that plants maintained energy supply during stress to protect seedlings from further damage, and for use in subsequent recovery after rewatering period. This study provides novel insights into the molecular mechanisms underlying the desiccation tolerance of wheat seedlings, and paves the way for more detailed molecular analysis of this remarkable phenomenon.
Publisher: Elsevier BV
Date: 03-2015
Publisher: Springer Science and Business Media LLC
Date: 10-04-2018
DOI: 10.1007/S12035-018-1041-9
Abstract: Retinoid X-receptors (RXRs) are members of the ligand-dependent transcription factor family of nuclear receptors that have gained recent research focus as potential targets for neurodegenerative disorders. Bexarotene is an RXR pharmacological agonist that is shown to be neuroprotective through its effects in promoting amyloid beta (Aβ) uptake by the glial cells in the brain. This study aimed to evaluate the dose-dependent effects of bexarotene on RXR expression in SH-SY5Y neuroblastoma cells and validate the drug effects in the brain in vivo. The protein expression studies were carried out using a combination of various drug treatment paradigms followed by expression analysis using Western blotting and immunofluorescence. Our study demonstrated that bexarotene promoted the expression of RXR α, β and γ isoforms at optimal concentrations in the cells and in the mice brain. Interestingly, a decreased RXR expression was identified in Alzheimer's disease mouse model and in the cells that were treated with Aβ. Bexarotene treatment not only rescued the RXR expression loss caused by Aβ treatment (p < 0.05) but also protected the cells against Aβ-induced ER stress (p < 0.05) and pro-apoptotic BAD protein activation (p < 0.05). In contrast, higher concentrations of bexarotene upregulated the ER stress proteins and led to BAD activation. Our study revealed that these downstream neurotoxic effects of high drug concentrations could be prevented by pharmacological targeting of the TrkB receptor. The ER stress and BAD activation induced by high concentrations of bexarotene were rescued by the TrkB agonist, 7,8 dihydroxyflavone (p < 0.05) while TrkB inhibitor CTX-B treatment further exacerbated these effects. Together, these findings suggest a cross-talk of TrkB signalling with downstream effects of bexarotene toxicity and indicate that therapeutic targeting of RXRs could prevent the Aβ-induced molecular neurotoxic effects.
Publisher: Wiley
Date: 03-2012
Abstract: Mechanisms of drought tolerance are complex, interacting, and polygenic. This paper describes patterns of gene expression at precise physiological stages of drought in 35-day-old seedlings of Oryza sativa cv. Nipponbare. Drought was imposed gradually for up to 15 days, causing abscisic acid levels to rise and growth to cease, and plants were then re-watered. Proteins were identified from leaf s les after moderate drought, extreme drought, and 3 and 6 days of re-watering. Label-free quantitative shotgun proteomics resulted in identification of 1548 non-redundant proteins. More proteins were down-regulated in early stages of drought but more were up-regulated as severe drought developed. After re-watering, there was notable down regulation, suggesting that stress-related proteins were being degraded. Proteins involved in signalling and transport became dominant as severe drought took hold but decreased again on re-watering. Most of the nine aquaporins identified were responsive to drought, with six decreasing rapidly in abundance as plants were re-watered. Nine G-proteins appeared in large amounts during severe drought and dramatically degraded once plants were re-watered. We speculate that water transport and drought signalling are critical elements of the overall response to drought in rice and might be the key to biotechnological approaches to drought tolerance.
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.SURVOPHTHAL.2021.06.001
Abstract: There is a strong interrelationship between eye and brain diseases. It has been shown that neurodegenerative changes can spread bidirectionally in the visual pathway along neuronal projections. For ex le, damage to retinal ganglion cells in the retina leads to degeneration of the visual cortex (anterograde degeneration) and vice versa (retrograde degeneration). The underlying mechanisms of this process, known as trans-synaptic degeneration (TSD), are unknown, but TSD contributes to the progression of numerous neurodegenerative disorders, leading to clinical and functional deterioration. The hierarchical structure of the visual system comprises of a strong topographic connectivity between the retina and the visual cortex and therefore serves as an ideal model to study the cellular effect, clinical manifestations, and deterioration extent of TSD. With this review we provide comprehensive information about the neural connectivity, synapse function, molecular changes, and pathophysiology of TSD in visual pathways. We then discuss its bidirectional nature and clinical implications in neurodegenerative diseases. A thorough understanding of TSD in the visual pathway can provide insights into progression of neurodegenerative disorders and its potential as a therapeutic target.
Publisher: Wiley
Date: 26-11-2018
DOI: 10.1111/JNC.14614
Publisher: Springer Science and Business Media LLC
Date: 03-2022
DOI: 10.1007/S00018-022-04185-6
Abstract: Neuroserpin is an axonally secreted serpin that is involved in regulating plasminogen and its enzyme activators, such as tissue plasminogen activator (tPA). The protein has been increasingly shown to play key roles in neuronal development, plasticity, maturation and synaptic refinement. The proteinase inhibitor may function both independently and through tPA-dependent mechanisms. Herein, we discuss the recent evidence regarding the role of neuroserpin in healthy and diseased conditions and highlight the participation of the serpin in various cellular signalling pathways. Several polymorphisms and mutations have also been identified in the protein that may affect the serpin conformation, leading to polymer formation and its intracellular accumulation. The current understanding of the involvement of neuroserpin in Alzheimer’s disease, cancer, glaucoma, stroke, neuropsychiatric disorders and familial encephalopathy with neuroserpin inclusion bodies (FENIB) is presented. To truly understand the detrimental consequences of neuroserpin dysfunction and the effective therapeutic targeting of this molecule in pathological conditions, a cross-disciplinary understanding of neuroserpin alterations and its cellular signaling networks is essential.
Publisher: MDPI AG
Date: 03-04-2023
DOI: 10.3390/PROTEOMES11020012
Abstract: Photoreceptor cells are highly susceptible to oxidative-stress-induced damage due to their high metabolic rate. Oxidative stress plays a key role in driving pathological events in several different ocular diseases, which lead to retinal degeneration and ultimately blindness. A growing number of studies have been performed to understand downstream events caused by ROS induced oxidative stress in photoreceptor cells however, the underlying mechanisms of ROS toxicity are not fully understood. To shed light on ROS induced downstream pathological events, we employed a tandem mass tag (TMT) labelling-based quantitative mass-spectrometric approach to determine proteome changes in 661W photoreceptor cells following oxidative stress induction via the application of different concentrations of H2O2 at different time points. Overall, 5920 proteins were identified and quantified, and 450 differentially expressed proteins (DEPs) were identified, which were altered in a dose and time dependent manner in all treatment groups compared to the control group. These proteins were involved in several biological pathways, including spliceosome and ribosome response, activated glutathione metabolism, decreased ECM-receptor interaction, oxidative phosphorylation, abnormally regulated lysosome, apoptosis, and ribosome biogenesis. Our results highlighted ECM receptor interaction, oxidative phosphorylation and spliceosome pathways as the major targets of oxidative stress that might mediate vascular dysfunction and cellular senescence.
Publisher: American Chemical Society (ACS)
Date: 11-04-2016
DOI: 10.1021/ACS.JPROTEOME.5B01043
Abstract: Caffeine is a plant-derived psychostimulant and a common additive found in a wide range of foods and pharmaceuticals. The orbitofrontal cortex (OFC) is rapidly activated by flavours, integrates gustatory and olfactory information, and plays a critical role in decision-making, with dysfunction contributing to psychopathologies and neurodegenerative conditions. This study investigated whether long-term consumption of caffeine causes changes to behavior and protein expression in the OFC. Male adult Sprague-Dawley rats (n = 8 per group) were treated for 26 days with either water or a 0.6 g/L caffeine solution. Locomotor behavior was measured on the first and last day of treatment, then again after 9 days treatment free following exposure to a mild stressor. When tested drug free, caffeine-treated animals were hyperactive compared to controls. Two hours following final behavioral testing, brains were rapidly removed and prepared for proteomic analysis of the OFC. Label free shotgun proteomics found 157 proteins differentially expressed in the caffeine-drinking rats compared to control. Major proteomic effects were seen for cell-to-cell communication, cytoskeletal regulation, and mitochondrial function. Similar changes have been observed in neurological disorders including Alzheimer's disease, Parkinson's disease, and schizophrenia.
Publisher: MDPI AG
Date: 18-11-2022
Abstract: Neuropeptide Y (NPY), a sympathetic neurotransmitter, is involved in various physiological functions, and its dysregulation is implicated in several neurodegenerative diseases. Glutamate excitotoxicity, endoplasmic reticulum (ER) stress, and oxidative stress are the common mechanisms associated with numerous neurodegenerative illnesses. The present study aimed to elucidate the protective effects of NPY against glutamate toxicity and tunicamycin-induced ER stress in the human neuroblastoma SH-SY5Y cell line. We exposed the SH-SY5Y cells to glutamate and tunicamycin for two different time points and analyzed the protective effects of NPY at different concentrations. The protective effects of NPY treatments were assessed by cell viability assay, and the signalling pathway changes were evaluated by biochemical techniques such as Western blotting and immunofluorescence assays. Our results showed that treatment of SH-SY5Y cells with NPY significantly increased the viability of the cells in both glutamate toxicity and ER stress conditions. NPY treatments significantly attenuated the glutamate-induced pro-apoptotic activation of ERK1/2 and JNK/BAD pathways. The protective effects of NPY were further evident against tunicamycin-induced ER stress. NPY treatments significantly suppressed the ER stress activation by downregulating BiP, phospho-eIF2α, and CHOP expression. In addition, NPY alleviated the Akt/FoxO3a pathway in acute oxidative conditions caused by glutamate and tunicamycin in SH-SY5Y cells. Our results demonstrated that NPY is neuroprotective against glutamate-induced cell toxicity and tunicamycin-induced ER stress through anti-apoptotic actions.
Publisher: Wiley
Date: 12-2022
DOI: 10.1002/ALZ.063251
Abstract: Blood‐brain barrier (BBB) breakdown in Alzheimer’s disease (AD) is linked to cerebral amyloid‐beta (Aβ) accumulation and cognitive decline. Previously, we identified substantial retinal pericyte loss along with vascular amyloidosis in mild cognitively impaired (MCI) and AD patients. In double transgenic APP SWE /PS1 ∆E9 (ADtg) mice, we further demonstrated substantial retinal capillary degeneration and microvascular leakage in comparison to wild type (WT) mice. Here, we sought to expand our investigation of inner blood‐retinal barrier (iBRB) integrity in relation to retinal and cerebral pathological benchmarks in MCI and AD patients compared to cognitively normal (CN) controls. Postmortem human eyes and brains were obtained from USC‐ADRC. Retinas were isolated from 35 AD patients, 15 MCI patients, and 20 age‐ and sex‐matched healthy controls. Retinal cross sections spanning along ora serrata to optic disc were prepared from four pre‐defined quadrants: superiortemporal, temporalinferior, inferiornasal, and nasalsuperior. Histological examination was performed by immunostaining for different Aβ alloforms, tight junctions (zonula occulden‐1, claudin‐1 and ‐5), and blood vessels (lectin). Retinal microvessels were isolated for evaluating capillary degeneration. Stereological quantifications were performed and then correlated with the respective neuropathological reports of these patients. Mass spectrometry analysis of proteins isolated from another AD and control patients’ cohort was conducted to validate our data. Our preliminary results showed early and significant downregulation of zonula occulden‐1 in retinal blood vessels of MCI and AD patients compared to controls. Downregulation of this key tight junction molecule was associated with increased retinal vascular Aβ accumulation. In addition, significant deficiencies of vascular‐related proteins including smoothelin, vascular endothelial zinc finger 1 (VEZF1), catenin isoform 1 were detected in retinal homogenates from AD patients versus controls by global proteome analysis. Analysis of isolated retinal blood vessels revealed capillary degeneration along with Alzheimer’s‐relevant vascular pathology in these patients. Our data suggested an early alteration of iBRB integrity that contributed to Aβ accumulation in retinal blood vessels, consistent with previous reports in BBB of AD patients. Our results provide new insights into AD‐related vascular pathomechanisms in the retina that can be further evaluated for retinal imaging.
Publisher: Elsevier BV
Date: 09-2015
Publisher: Springer Science and Business Media LLC
Date: 08-09-2022
DOI: 10.1186/S40478-022-01439-Z
Abstract: Single cell RNA sequencing studies identified novel neurodegeneration-associated microglial (MGnD/DAM) subtypes activated around cerebral amyloid plaques. Micro-RNA (miR)-155 of the TREM2-APOE pathway was shown to be a key transcriptional regulator of MGnD microglial phenotype. Despite growing interest in studying manifestations of Alzheimer’s disease (AD) in the retina, a CNS organ accessible to noninvasive high-resolution imaging, to date MGnD microglia have not been studied in the AD retina. Here, we discovered the presence and increased populations of Clec7a + and Galectin-3 + MGnD microglia in retinas of transgenic APP SWE /PS1 L166P AD-model mice. Conditionally targeting MGnD microglia by miR-155 ablation via the tamoxifen-inducible Cre ERT2 system in APP SWE /PS1 L166P mice diminished retinal Clec7a + and Galectin-3 + microglial populations while increasing homeostatic P2ry12 + microglia. Retinal MGnD microglia were often adhering to microvessels their depletion protected the inner blood-retina barrier and reduced vascular amyloidosis. Microglial miR-155 depletion further limits retinal inflammation. Mass spectrometry analysis revealed enhanced retinal PI3K-Akt signaling and predicted IL-8 and Spp1 decreases in mice with microglia-specific miR-155 knockout. Overall, this study identified MGnD microglia in APP SWE /PS1 L166P mouse retina. Transcriptional regulation of these dysfunctional microglia mitigated retinal inflammation and vasculopathy. The protective effects of microglial miR-155 ablation should shed light on potential treatments for retinal inflammation and vascular damage during AD and other ocular diseases.
Publisher: Medknow
Date: 15-03-2023
Publisher: Frontiers Media SA
Date: 27-03-2018
Publisher: American Chemical Society (ACS)
Date: 22-07-2015
DOI: 10.1021/ACS.JPROTEOME.5B00512
Abstract: Although it is apparent that chromosome complement mediates sexually dimorphic expression patterns of some proteins that lead to functional differences, there has been insufficient evidence following the manipulation of the male-specific region of the Y chromosome (MSY) gene expression during neural development. In this study, we profiled the expression of 23 MSY genes and 15 of their X-linked homologues during neural cell differentiation of NTERA-2 human embryonal carcinoma cell line (NT2) cells in three different developmental stages using qRT-PCR, Western blotting, and immunofluorescence. The expression level of 12 Y-linked genes significantly increased over neural differentiation, including RBMY1, EIF1AY, DDX3Y, HSFY1, BPY2, PCDH11Y, UTY, RPS4Y1, USP9Y, SRY, PRY, and ZFY. We showed that siRNA-mediated knockdown of DDX3Y, a DEAD box RNA helicase enzyme, in neural progenitor cells impaired cell cycle progression and increased apoptosis, consequently interrupting differentiation. Label-free quantitative shotgun proteomics based on a spectral counting approach was then used to characterize the proteomic profile of the cells after DDX3Y knockdown. Among 917 reproducibly identified proteins detected, 71 proteins were differentially expressed following DDX3Y siRNA treatment compared with mock treated cells. Functional grouping indicated that these proteins were involved in cell cycle, RNA splicing, and apoptosis, among other biological functions. Our results suggest that MSY genes may play an important role in neural differentiation and demonstrate that DDX3Y could play a multifunctional role in neural cell development, probably in a sexually dimorphic manner.
Publisher: Elsevier
Date: 2017
Publisher: MDPI AG
Date: 27-09-2023
DOI: 10.3390/JCM12196219
Publisher: Informa UK Limited
Date: 29-10-2018
DOI: 10.1080/14789450.2018.1539669
Abstract: Human embryonic stem cells (hESCs) have unique biological features and attributes that make them attractive in various areas of biomedical research. With heightened applications, there is an ever increasing need for advancement of proteome analysis. Membrane proteins are one of the most important subset of hESC proteins as they can be used as surface markers. Areas covered: This review discusses commonly used surface markers of hESCs, and provides in-depth analysis of available hESC membrane proteome reports and the existence of these markers in many other cell types, especially cancer cells. Appreciating, existing ambiguity in the definition of a membrane protein, we have attempted a meta analysis of the published membrane protein reports of hESCs by using a combination of protein databases and prediction tools to find the most confident plasma membrane proteins in hESCs. Furthermore, responsiveness of plasma membrane proteins to differentiation has been discussed based on available transcriptome profiling data bank. Expert commentary: Combined transcriptome and membrane proteome analysis highlighted additional proteins that may eventually find utility as new cell surface markers.
Publisher: Springer Science and Business Media LLC
Date: 03-11-2021
DOI: 10.1007/S00441-021-03537-1
Abstract: The preconditioning of human sperm with sublethal nitrosative stress before cryopreservation can potentially improve the thawed sperm quality. However, the underlying mechanisms behind this protective strategy are not entirely understood. We compared the cryosurvival of human sperm exposed to 0.01 μM nitric oxide (NO) throughout the cryopreservation and used multiplexed quantitative proteomics approach to identify changes in the proteome profile of preconditioned sperm cells. Semen s les were obtained from 30 normospermia donors and then each s le was ided into three equal parts: fresh (F), frozen-control (C), and frozen exposed to nitric oxide (NO). The sperm undergoing mild sublethal stress showed higher values for motility and viability compared to the frozen control sperm. Moreover, out of 2912 identified proteins, 248 proteins were detected as differentially abundant proteins (DAPs) between cryopreserved groups and fresh group (F) (p < 0.05). Gene ontology (GO) analysis of differentially abundant proteins indicated that the abundance of proteins associated with glycolysis, gluconeogenesis, and fertilization processes was reduced while oxidative phosphorylation pathway was increased in abundance in cryopreserved sperm compared to the fresh sperm. Moreover, redox protein such as thioredoxin 17 was increased in abundance in the NO group compared to the control freezing group. Therefore, the pre-conditioning of sperm prior to cryopreservation may play an important role in maintaining the redox balance in mitochondria of sperm after freezing. Overall, our results indicate that arylsulfatase A (ARSA), serine protease 37 (PRSS37), and sperm surface protein (SP17) may potentially serve as protein biomarkers associated with screening the fertilization potential of the thawed sperm.
Publisher: Wiley
Date: 08-08-2022
Abstract: Fingolimod (FTY720) is an oral drug approved by the Food and Drug Administration (FDA) for management of multiple sclerosis (MS) symptoms, which has also shown beneficial effects against Alzheimer's (AD) and Parkinson's (PD) diseases pathologies. Although an extensive effort has been made to identify mechanisms underpinning its therapeutic effects, much remains unknown. Here, we investigated Fingolimod induced proteome changes in the cerebellum (CB) and frontal cortex (FC) regions of the brain which are known to be severely affected in MS, using a tandem mass tag (TMT) isobaric labeling‐based quantitative mass‐spectrometric approach to investigate the mechanism of action of Fingolimod. This study identified 6749 and 6319 proteins in CB and FC, respectively, and returned 2609 and 3086 differentially expressed proteins in mouse CB and FC, respectively, between Fingolimod treated and control groups. Subsequent bioinformatics analyses indicated a metabolic reprogramming in both brain regions of the Fingolimod treated group, where oxidative phosphorylation was upregulated while glycolysis and pentose phosphate pathway were downregulated. In addition, modulation of neuroinflammation in the Fingolimod treated group was indicated by upregulation of retrograde endocannabinoid signaling and autophagy pathways, and downregulation of neuroinflammation related pathways including neutrophil degranulation and the IL‐12 mediated signaling pathway. Our findings suggest that Fingolimod may exert its protective effects on the brain by inducing metabolic reprogramming and neuroinflammation pathway modulation.
Publisher: Oxford University Press (OUP)
Date: 06-2015
Publisher: Wiley
Date: 02-2016
Abstract: In most Westernized societies, there has been an alarming increase in the consumption of sugar-sweetened drinks. For many adults these drinks represent a substantial proportion of their total daily caloric intake. Here we investigated whether extended exposure to sugar changes behavior and protein expression in the orbitofrontal cortex (OFC). Male adult Sprague-Dawley rats (n = 8 per group) were treated for 26 days with either water or a 10% sucrose solution. Locomotor behavior was measured on the first and last day of treatment, then 1 week after treatment. Following the 1-week period free from treatment, sucrose treated rats were significantly more active than the control. Two hours following final behavioral testing, brains were rapidly removed and prepared for proteomic analysis of the OFC. Label free quantitative shotgun proteomic analyses of three rats from each group found 290 proteins were differentially expressed in the sucrose treated group when compared to the control group. Major changes in the proteome were seen in proteins related to energy metabolism, mitochondrial function and the cellular response to stress. This research does not seek to suggest that sugar will cause specific neurological disorders, however similar changes in proteins have been seen in neurological disorders such as Alzheimer's disease, Parkinson's disease and schizophrenia.
Publisher: Springer Science and Business Media LLC
Date: 23-06-2020
Publisher: American Chemical Society (ACS)
Date: 02-12-2011
DOI: 10.1021/PR2008779
Abstract: Rice (Oryza sativa L. cv. IR64) was grown in split-root systems to analyze long-distance drought signaling within root systems. This in turn underpins how root systems in heterogeneous soils adapt to drought. The approach was to compare four root tissues: (1) fully watered (2) fully droughted and split-root systems where (3) one-half was watered and (4) the other half was droughted. This was specifically aimed at identifying how droughted root tissues altered the proteome of adjacent wet roots by hormone signals and how wet roots reciprocally affected dry roots hydraulically. Quantitative label-free shotgun proteomic analysis of four different root tissues resulted in identification of 1487 nonredundant proteins, with nearly 900 proteins present in triplicate in each treatment. Drought caused surprising changes in expression, most notably in partially droughted roots where 38% of proteins were altered in level compared to adjacent watered roots. Specific functional groups changed consistently in drought. Pathogenesis-related proteins were generally up-regulated in response to drought and heat-shock proteins were totally absent in roots of fully watered plants. Proteins involved in transport and oxidation-reduction reactions were also highly dependent upon drought signals, with the former largely absent in roots receiving a drought signal while oxidation-reduction proteins were strongly present during drought. Finally, two functionally contrasting protein families were compared to validate our approach, showing that nine tubulins were strongly reduced in droughted roots while six chitinases were up-regulated, even when the signal arrived remotely from adjacent droughted roots.
Publisher: Oxford University Press (OUP)
Date: 13-03-2018
Publisher: Springer Science and Business Media LLC
Date: 21-08-2017
DOI: 10.1038/S41598-017-08688-2
Abstract: Neuroserpin is a serine protease inhibitor that regulates the activity of plasmin and its activators in the neuronal tissues. This study provides novel evidence of regulatory effect of the neuroserpin on plasmin proteolytic activity in the retina in glaucoma. Human retinal and vitreous tissues from control and glaucoma subjects as well as retinas from experimental glaucoma rats were analysed to establish changes in plasmin and neuroserpin activity. Neuroserpin undergoes oxidative inactivation in glaucoma which leads to augmentation of plasmin activity. Neuroserpin contains several methionine residues in addition to a conserved reactive site methionine and our study revealed enhanced oxidation of Met residues in the serpin under glaucoma conditions. Met oxidation was associated with loss of neuroserpin inhibitory activity and similar findings were observed in the retinas of superoxide dismutase (SOD) mutant mice that have increased oxidative stress. Treatment of purified neuroserpin with H2O2 further established that Met oxidation inversely correlated with its plasmin inhibitory activity. Dysregulation of the plasmin proteolytic system associated with increased degradation of the extracellular matrix (ECM) proteins in the retina. Collectively, these findings delineate a novel molecular basis of plasmin activation in glaucoma and potentially for other neuronal disorders with implications in disease associated ECM remodelling.
Publisher: Wiley
Date: 21-07-2020
DOI: 10.1002/JCB.29822
Publisher: Springer International Publishing
Date: 2016
Publisher: MDPI AG
Date: 27-09-2021
DOI: 10.3390/BIOM11101411
Abstract: Cannabis (Cannabis sativa), popularly known as marijuana, is the most commonly used psychoactive substance and is considered illicit in most countries worldwide. However, a growing body of research has provided evidence of the therapeutic properties of chemical components of cannabis known as cannabinoids against several diseases including Alzheimer’s disease (AD), multiple sclerosis (MS), Parkinson’s disease, schizophrenia and glaucoma these have prompted changes in medicinal cannabis legislation. The relaxation of legal restrictions and increased socio-cultural acceptance has led to its increase in both medicinal and recreational usage. Several biochemically active components of cannabis have a range of effects on the biological system. There is an urgent need for more research to better understand the molecular and biochemical effects of cannabis at a cellular level, to understand fully its implications as a pharmaceutical drug. Proteomics technology is an efficient tool to rigorously elucidate the mechanistic effects of cannabis on the human body in a cell and tissue-specific manner, drawing conclusions associated with its toxicity as well as therapeutic benefits, safety and efficacy profiles. This review provides a comprehensive overview of both in vitro and in vivo proteomic studies involving the cellular and molecular effects of cannabis and cannabis-derived compounds.
Publisher: Wiley
Date: 21-08-2022
Abstract: Drought is responsible for major losses in rice production. Root tips contain meristematic and elongation zones that play major roles in determination of root traits and adaptive strategies to drought. In this study we analysed two contrasting genotypes of rice: IR64, a lowland, drought‐susceptible, and shallow‐rooting genotype and Azucena, an upland, drought‐tolerant, and deep‐rooting genotype. S les were collected of root tips of plants grown under control and water deficit stress conditions. Quantitative proteomics analysis resulted in the identification of 7294 proteins from the root tips of IR64 and 6307 proteins from Azucena. Data are available via ProteomeXchange with identifier PXD033343. Using a Partial Least Square Discriminant Analysis on 4170 differentially abundant proteins, 1138 statistically significant proteins across genotypes and conditions were detected. Twenty two enriched biological processes showing contrasting patterns between two genotypes in response to stress were detected through gene ontology enrichment analysis. This included identification of novel proteins involved in root elongation with specific expression patterns in Azucena, including four Expansins and seven Class III Peroxidases. We also detected an antioxidant network and a metallo‐sulfur cluster assembly machinery in Azucena, with roles in reactive oxygen species and iron homeostasis, and positive effects on root cell cycle, growth and elongation.
Publisher: Elsevier BV
Date: 11-2015
Publisher: Ivyspring International Publisher
Date: 2021
DOI: 10.7150/THNO.55472
Publisher: Springer Science and Business Media LLC
Date: 11-02-2023
DOI: 10.1007/S00401-023-02548-2
Abstract: Alzheimer’s disease (AD) pathologies were discovered in the accessible neurosensory retina. However, their exact nature and topographical distribution, particularly in the early stages of functional impairment, and how they relate to disease progression in the brain remain largely unknown. To better understand the pathological features of AD in the retina, we conducted an extensive histopathological and biochemical investigation of postmortem retina and brain tissues from 86 human donors. Quantitative examination of superior and inferior temporal retinas from mild cognitive impairment (MCI) and AD patients compared to those with normal cognition (NC) revealed significant increases in amyloid β-protein (Aβ 42 ) forms and novel intraneuronal Aβ oligomers (AβOi), which were closely associated with exacerbated retinal macrogliosis, microgliosis, and tissue atrophy. These pathologies were unevenly distributed across retinal layers and geometrical areas, with the inner layers and peripheral subregions exhibiting most pronounced accumulations in the MCI and AD versus NC retinas. While microgliosis was increased in the retina of these patients, the proportion of microglial cells engaging in Aβ uptake was reduced. Female AD patients exhibited higher levels of retinal microgliosis than males. Notably, retinal Aβ 42 , S100 calcium-binding protein B + macrogliosis, and atrophy correlated with severity of brain Aβ pathology, tauopathy, and atrophy, and most retinal pathologies reflected Braak staging. All retinal biomarkers correlated with the cognitive scores, with retinal Aβ 42 , far-peripheral AβOi and microgliosis displaying the strongest correlations. Proteomic analysis of AD retinas revealed activation of specific inflammatory and neurodegenerative processes and inhibition of oxidative phosphorylation/mitochondrial, and photoreceptor-related pathways. This study identifies and maps retinopathy in MCI and AD patients, demonstrating the quantitative relationship with brain pathology and cognition, and may lead to reliable retinal biomarkers for noninvasive retinal screening and monitoring of AD.
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.JPROT.2013.09.017
Abstract: Piriformospora indica is a mutualistic root endophytic fungus, which transfers several benefits to hosts including enhance plant growth and increase yield under both normal and stress conditions. It has been shown that P. indica root-colonization enhances water stress tolerance based on general and non-specific plant-species mechanism. To better understand the molecular mechanism of P. indica-mediated drought stress tolerance, we designed a set of comparative experiments to study the impact of P. indica on barely plants cultivar "Golden Promise" grown under different drought levels [Filed capacity (F.C.) and 25% F.C.]. P. indica enhanced root and shoot biomass of colonized plants under both well-watered and water-deficit conditions. Proteome analysis of P. indica-colonized barley leaves under well-treated and water-deficit conditions resulted in detection of 726 reproducibly protein spots. Mass spectrometry analysis resulted in the identification of 45 differentially accumulated proteins involved in photosynthesis, reactive oxygen scavenging, metabolisms, signal transduction, and plant defense responses. Interestingly, P. indica increased the level of proteins involved in photosynthesis, antioxidative defense system and energy transport. We propose that P. indica-mediated drought stress tolerance in barely is through photosynthesis stimulation, energy releasing and enhanced antioxidative capacity in colonized plants. Plant mutualistic symbionts offer long-term abiotic stress tolerance through the host adaptation to environmental stress. There have been a few published proteomic studies of plant symbionts to drought, and this is thought to be the first proteomic analysis, demonstrating the impact of endophyte on barley plant under drought stress. For some of identified proteins like TCTP and PCNA, a connection to physiological function in plants is novel, and can be the best candidates for sources of drought tolerance in future studies.
Publisher: No publisher found
Date: 2017
Publisher: Elsevier
Date: 2017
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.NEUROSCIENCE.2017.09.028
Abstract: PTPN11 is associated with regulation of growth factor signaling pathways in neuronal cells. Using SH-SY5Y neuroblastoma cells, we showed that adeno-associated virus (AAV)-mediated PTPN11 upregulation was associated with TrkB antagonism, reduced neuritogenesis and enhanced endoplasmic reticulum (ER) stress response leading to apoptotic changes. Genetic knock-down of PTPN11 on the other hand leads to increased TrkB phosphorylation in SH-SY5Y cells. ER stress response induced by PTPN11 upregulation was alleviated pharmacologically by a TrkB agonist. Conversely the enhanced ER stress response induced by TrkB receptor antagonism was ameliorated by PTPN11 suppression, providing evidence of cross-talk of PTPN11 effects with TrkB actions. BDNF treatment of neuronal cells with PTPN11 upregulation also resulted in reduced expression of ER stress protein markers. This study provides evidence of molecular interactions between PTPN11 and the TrkB receptor in SH-SY5Y cells. The results reinforce the role played by PTPN11 in regulating neurotrophin protective signaling in neuronal cells and highlight that PTPN11 dysregulation promotes apoptotic activation. Based on these findings we suggest that blocking PTPN11 could have potential beneficial effects to limit the progression of neuronal loss in neurodegenerative disorders.
Publisher: Oxford University Press (OUP)
Date: 31-10-2020
DOI: 10.1093/GIGASCIENCE/GIAA116
Abstract: Generation of oligodendrocytes is a sophisticated multistep process, the mechanistic underpinnings of which are not fully understood and demand further investigation. To systematically profile proteome dynamics during human embryonic stem cell differentiation into oligodendrocytes, we applied in-depth quantitative proteomics at different developmental stages and monitored changes in protein abundance using a multiplexed tandem mass tag-based proteomics approach. Our proteome data provided a comprehensive protein expression profile that highlighted specific expression clusters based on the protein abundances over the course of human oligodendrocyte lineage differentiation. We identified the eminence of the planar cell polarity signalling and autophagy (particularly macroautophagy) in the progression of oligodendrocyte lineage differentiation—the cooperation of which is assisted by 106 and 77 proteins, respectively, that showed significant expression changes in this differentiation process. Furthermore, differentially expressed protein analysis of the proteome profile of oligodendrocyte lineage cells revealed 378 proteins that were specifically upregulated only in 1 differentiation stage. In addition, comparative pairwise analysis of differentiation stages demonstrated that abundances of 352 proteins differentially changed between consecutive differentiation time points. Our study provides a comprehensive systematic proteomics profile of oligodendrocyte lineage cells that can serve as a resource for identifying novel biomarkers from these cells and for indicating numerous proteins that may contribute to regulating the development of myelinating oligodendrocytes and other cells of oligodendrocyte lineage. We showed the importance of planar cell polarity signalling in oligodendrocyte lineage differentiation and revealed the autophagy-related proteins that participate in oligodendrocyte lineage differentiation.
Publisher: American Chemical Society (ACS)
Date: 08-10-2015
Publisher: Springer Science and Business Media LLC
Date: 05-08-2023
DOI: 10.1007/S12035-023-03535-0
Abstract: Glaucoma is a leading cause of permanent blindness worldwide and is characterized by neurodegeneration linked to progressive retinal ganglion cell (RGC) death, axonal damage, and neuroinflammation. Glutamate excitotoxicity mediated through N-methyl-D-aspartate (NMDA) receptors plays a crucial role in glaucomatous RGC loss. Sphingosine 1-phosphate receptors (S1PRs) are important mediators of neurodegeneration and neuroinflammation in the brain and the retina. Siponimod is an immunomodulatory drug for multiple sclerosis and is a selective modulator of S1PR subtypes 1 and 5 and has been shown to have beneficial effects on the central nervous system (CNS) in degenerative conditions. Our previous study showed that mice administered orally with siponimod protected inner retinal structure and function against acute NMDA excitotoxicity. To elucidate the molecular mechanisms behind these protective effects, we investigated the inflammatory pathways affected by siponimod treatment in NMDA excitotoxicity model. NMDA excitotoxicity resulted in the activation of glial cells coupled with upregulation of the inflammatory NF-kB pathway and increased expression of TNFα, IL1-β, and IL-6. Siponimod treatment significantly reduced glial activation and suppressed the pro-inflammatory pathways. Furthermore, NMDA-induced activation of NLRP3 inflammasome and upregulation of neurotoxic inducible nitric oxide synthase (iNOS) were significantly diminished with siponimod treatment. Our data demonstrated that siponimod induces anti-inflammatory effects via suppression of glial activation and inflammatory singling pathways that could protect the retina against acute excitotoxicity conditions. These findings provide insights into the anti-inflammatory effects of siponimod in the CNS and suggest a potential therapeutic strategy for neuroinflammatory conditions.
Publisher: Frontiers Media SA
Date: 30-07-2020
Publisher: Springer Science and Business Media LLC
Date: 24-10-2020
Publisher: Wiley
Date: 02-2010
Abstract: In this review we examine current approaches used for proteomic analysis of temperature stress in plants. Rapid advances in this field in recent years are discussed, including metabolic, chemical and isotopic labeling, and label-free quantitative techniques. These are compared and contrasted with well-established methods such as 2-DE approaches. Ex les of applications of various methods are presented, and technical difficulties and limitations of each are also considered. Results of previous studies are examined in detail, and commonly occurring temperature stress response proteins are collated. We conclude that technical advances, and improvements in genome sequence availability, will have an ever increasing impact on our understanding of molecular mechanisms of stress response in plants.
Publisher: Springer Science and Business Media LLC
Date: 20-05-2010
Abstract: Transcript profiling of closely related species provides a means for identifying genes potentially important in species ersification. However, the predictive value of transcript profiling for inferring downstream-physiological processes has been unclear. In the present study we use shotgun proteomics to validate inferences from microarray studies regarding physiological differences in three Pachycladon species. We compare transcript and protein profiling and evaluate their predictive value for inferring glucosinolate chemotypes characteristic of these species. Evidence from heterologous microarrays and shotgun proteomics revealed differential expression of genes involved in glucosinolate hydrolysis (myrosinase-associated proteins) and biosynthesis (methylthioalkylmalate isomerase and dehydrogenase), the interconversion of carbon dioxide and bicarbonate (carbonic anhydrases), water use efficiency (ascorbate peroxidase, 2 cys peroxiredoxin, 20 kDa chloroplastic chaperonin, mitochondrial succinyl CoA ligase) and others (glutathione-S-transferase, serine racemase, vegetative storage proteins, genes related to translation and photosynthesis). Differences in glucosinolate hydrolysis products were directly confirmed. Overall, prediction of protein abundances from transcript profiles was stronger than prediction of transcript abundance from protein profiles. Protein profiles also proved to be more accurate predictors of glucosinolate profiles than transcript profiles. The similarity of species profiles for both transcripts and proteins reflected previously inferred phylogenetic relationships while glucosinolate chemotypes did not. We have used transcript and protein profiling to predict physiological processes that evolved differently during ersification of three Pachycladon species. This approach has also identified candidate genes potentially important in adaptation, which are now the focus of ongoing study. Our results indicate that protein profiling provides a valuable tool for validating transcript profiles in studies of adaptive ergence.
Publisher: Wiley
Date: 25-11-2018
Abstract: Western blotting as an orthogonal validation tool for quantitative proteomics data has rapidly become a de facto requirement for publication. In this viewpoint article, the pros and cons of western blotting as a validation approach are discussed, using ex les from our own published work, and how to best apply it to improve the quality of data published is outlined. Further, suggestions and guidelines for some other experimental approaches are provided, which can be used for validation of quantitative proteomics data in addition to, or in place of, western blotting.
Publisher: MDPI AG
Date: 12-11-2020
DOI: 10.3390/IJMS21228532
Abstract: Gastrointestinal (GI) cancer remains one of the common causes of morbidity and mortality. A high number of cases are diagnosed at an advanced stage, leading to a poor survival rate. This is primarily attributed to the lack of reliable diagnostic biomarkers and limited treatment options. Therefore, more sensitive, specific biomarkers and curative treatments are desirable. Functional proteomics as a research area in the proteomic field aims to elucidate the biological function of unknown proteins and unravel the cellular mechanisms at the molecular level. Phosphoproteomic and glycoproteomic studies have emerged as two efficient functional proteomics approaches used to identify diagnostic biomarkers, therapeutic targets, the molecular basis of disease and mechanisms underlying drug resistance in GI cancers. In this review, we present an overview on how functional proteomics may contribute to the understanding of GI cancers, namely colorectal, gastric, hepatocellular carcinoma and pancreatic cancers. Moreover, we have summarized recent methodological developments in phosphoproteomics and glycoproteomics for GI cancer studies.
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.JPROT.2016.03.009
Abstract: About 75% of plant yield potential has been estimated to be lost to environmental stresses, even in developed agricultures. To facilitate the biotechnological improvement of crop productivity, genes and proteins that control crop adaptation to a wide range of environments will need to be identified. Due to the challenges faced in text/data mining, there is a large gap between the data available to researchers and the hundreds of published plant stress proteomics articles. Plant stress proteome database (PlantPReS www.proteome.ir) is an open online proteomic database, which currently (as of October 2015) comprises >20,413 entries from 456 manually curated articles, and contains >10,600 unique stress responsive proteins. Since every aspect of the experiments, including protein name, accession number, plant type, tissue, stress types, organelles, and developmental stage has been digitized, experimental data can be rapidly accessed and integrated. Furthermore, PlantPReS enables researchers to perform multiple analyses on the database using the filtration mode, and the results of each query indicate a series of proteins for which a set of selected criteria is met. The query results can be displayed in either text or graphical format. The promise of text and data mining to facilitate and enhance research fundamentally has not yet been achieved, mainly because great numbers of stress-associated proteins are not deposited in databases. PlantPReS is a valuable database for the vast majority of researchers working in proteomics and plant stress areas. It has a user-friendly interface with a number of useful features, including a search engine, analysis tools, gene ontology, a function for cross-referencing useful external databases, and the expression pattern of stress associated proteins.
Publisher: Elsevier BV
Date: 02-2018
Publisher: Wiley
Date: 08-2019
Abstract: Beneficial microbes have a positive impact on the productivity and fitness of the host plant. A better understanding of the biological impacts and underlying mechanisms by which the host derives these benefits will help to address concerns around global food production and security. The recent development of omics-based technologies has broadened our understanding of the molecular aspects of beneficial plant-microbe symbiosis. Specifically, proteomics has led to the identification and characterization of several novel symbiosis-specific and symbiosis-related proteins and post-translational modifications that play a critical role in mediating symbiotic plant-microbe interactions and have helped assess the underlying molecular aspects of the symbiotic relationship. Integration of proteomic data with other "omics" data can provide valuable information to assess hypotheses regarding the underlying mechanism of symbiosis and help define the factors affecting the outcome of symbiosis. Herein, an update is provided on the current and potential applications of symbiosis-based "omic" approaches to dissect different aspects of symbiotic plant interactions. The application of proteomics, metaproteomics, and secretomics as enabling approaches for the functional analysis of plant-associated microbial communities is also discussed.
Publisher: The Royal Society
Date: 28-10-2016
Abstract: We performed proteomics analysis on four skin and one muscle tissue s les taken from three ancient Egyptian mummies of the first intermediate period, approximately 4200 years old. The mummies were first dated by radiocarbon dating of the accompany-\\break ing textiles, and morphologically examined by scanning electron microscopy of additional skin s les. Proteins were extracted, separated on SDS–PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) gels, and in-gel digested with trypsin. The resulting peptides were analysed using nanoflow high-performance liquid chromatography–mass spectrometry. We identified a total of 230 unique proteins from the five s les, which consisted of 132 unique protein identifications. We found a large number of collagens, which was confirmed by our microscopy data, and is in agreement with previous studies showing that collagens are very long-lived. As expected, we also found a large number of keratins. We identified numerous proteins that provide evidence of activation of the innate immunity system in two of the mummies, one of which also contained proteins indicating severe tissue inflammation, possibly indicative of an infection that we can speculate may have been related to the cause of death. This article is part of the themed issue ‘Quantitative mass spectrometry’.
Publisher: Wiley
Date: 09-03-2021
Publisher: American Chemical Society (ACS)
Date: 13-09-2017
DOI: 10.1021/ACS.JPROTEOME.7B00322
Abstract: Mouse embryonic stem cells (mESCs) can be maintained in a pluripotent state when cultured with 2 inhibitors (2i) of extracellular signal-regulated kinase (MEK) and glycogen synthase kinase-3 (GSK3), and Royan 2 inhibitors (R2i) of FGF4 and TGFβ. The molecular mechanisms that control ESC self-renewal and pluripotency are more important for translating stem cell technologies to clinical applications. In this study, we used the shotgun proteomics technique to compare the proteome of the ground state condition (R2i- and 2i-grown cells) to that of serum. Out of 1749 proteins identified, 171 proteins were differentially expressed (p < 0.05) in the 2i, R2i, and serum s les. Gene ontology (GO) analysis of differentially abundant proteins showed that the focal adhesion signaling pathway significantly down-regulated under ground state conditions. mESCs had highly adhesive attachment under the serum condition, whereas in the 2i and R2i culture conditions, a loss of adhesion was observed and the cells were rounded and grew in compact colonies on gelatin. Quantitative RT-PCR showed reduced expression of the integrins family in the 2i and R2i conditions. The serum culture had more prominent phosphorylation of focal adhesion kinase (FAK) compared to 2i and R2i cultures. Activity of the extracellular signal-regulated kinase (ERK)1/2 decreased in the 2i and R2i cultures compared to serum. Activation of integrins by Mn
Publisher: Elsevier BV
Date: 2019
Publisher: Wiley
Date: 14-10-2016
Abstract: Caffeine is a psychostimulant commonly consumed with high levels of sugar. The increased availability of highly caffeinated, high sugar energy drinks could put some consumers at risk of being exposed to high doses of caffeine and sugar. Notably, research that has examined the consequences of this combination is limited. Here, we explored the effect of chronic exposure to caffeine and/or sugar on behavior and protein levels in the orbitofrontal cortex (OFC) of rats. The OFC brain region has been implicated in neuropsychiatric conditions, including obesity and addiction behaviors. Adult male Sprague-Dawley rats were treated for 26 days with control, caffeine (0.6 g/L), 10% sugar, or combination of both. Locomotor behavior was measured on the first and last day of treatment, then 1 week after treatment. Two hours following final behavioral testing, brains were rapidly removed and prepared for proteomic analysis of the OFC. Label-free quantitative shotgun analysis revealed that 21, 12, and 23% of proteins identified in the OFC were differentially expressed by sugar and/or caffeine. The results demonstrate that the intake of high levels of sugar and/or low to moderate levels of caffeine has different behavioral consequences. Moreover, each treatment results in a unique proteomic profile with different implications for neural health.
Publisher: Informa UK Limited
Date: 03-04-2021
DOI: 10.1080/14789450.2021.1918550
Abstract: Mitochondrial dysfunction is involved in Alzheimer's disease (AD) pathogenesis. Mitochondria have their own genetic material however, most of their proteins (∼99%) are synthesized as precursors on cytosolic ribosomes, and then imported into the mitochondria. Therefore, exploring proteome changes in these organelles can yield valuable information and shed light on the molecular mechanisms underlying mitochondrial dysfunction in AD. Here, we review AD-associated mitochondrial changes including the effects of amyloid beta and tau protein accumulation on the mitochondrial proteome. We also discuss the relationship of ApoE genetic polymorphism with mitochondrial changes, and present a meta-analysis of various differentially expressed proteins in the mitochondria in AD.
Publisher: Impact Journals, LLC
Date: 06-11-2015
Publisher: Medknow
Date: 2023
Publisher: Elsevier BV
Date: 09-2019
Publisher: Springer Science and Business Media LLC
Date: 12-02-2016
DOI: 10.1038/SREP20765
Abstract: Giardia duodenalis is responsible for the majority of parasitic gastroenteritis in humans worldwide. Host-parasite interaction models in vitro provide insights into disease and virulence and help us to understand pathogenesis. Using HT-29 intestinal epithelial cells (IEC) as a model we have demonstrated that initial sensitisation by host secretions reduces proclivity for trophozoite attachment, while inducing virulence factors. Host soluble factors triggered up-regulation of membrane and secreted proteins, including Tenascins, Cathepsin-B precursor, cystatin and numerous Variant-specific Surface Proteins (VSPs). By comparison, host-cell attached trophozoites up-regulated intracellular pathways for ubiquitination, reactive oxygen species (ROS) detoxification and production of pyridoxal phosphate (PLP). We reason that these results demonstrate early pathogenesis in Giardia involves two independent host-parasite interactions. Motile trophozoites respond to soluble secreted signals, which deter attachment and induce expression of virulence factors. Trophozoites attached to host cells, in contrast, respond by up-regulating intracellular pathways involved in clearance of ROS, thus anticipating the host defence response.
Publisher: Springer New York
Date: 15-12-2016
DOI: 10.1007/978-1-4939-6740-7_5
Abstract: In this chapter we describe the workflow we use for labeled quantitative proteomics analysis using tandem mass tags (TMT) starting with the s le preparation and ending with the multivariate analysis of the resulting data. We detail the step-by-step process from s le processing, labeling, fractionation, and data processing using Proteome Discoverer through to data analysis and interpretation in the context of a multi-run experiment. The final analysis and data interpretation rely on an R package we call TMTPrepPro, which are deployed on a local GenePattern server, and used for generating various outputs which are also outlined herein.
Publisher: Medknow
Date: 2020
Publisher: Wiley
Date: 03-11-2020
DOI: 10.1111/PCE.13908
Abstract: The development of gametes in plants is acutely susceptible to heatwaves as brief as a few days, adversely affecting pollen maturation and reproductive success. Pollen in cotton ( Gossypium hirsutum ) was differentially affected when tetrad and binucleate stages were exposed to heat, revealing new insights into the interaction between heat and pollen development. Squares were tagged and exposed to 36/25°C (day/night, moderate heat) or 40/30°C (day/night, extreme heat) for 5 days. Mature pollen grains and leaves were collected for physiological and proteomic responses. While photosynthetic competence was not compromised even at 40°C, leaf tissues became leakier. In contrast, pollen grains were markedly smaller after the tetrad stage was exposed to 40°C and boll production was reduced by 65%. Sugar levels in pollen grains were elevated after exposure to heat, eliminating carbohydrate deficits as a likely cause of poor reproductive capacity. Proteomic analysis of pure pollen s les revealed a particularly high abundance of 70‐kDa heat shock (Hsp70s) and cytoskeletal proteins. While short‐term bursts of heat had a minor impact on leaves, male gametophyte development was profoundly damaged. Cotton acclimates to maxima of 36°C at both the vegetative and reproductive stages but 5‐days exposure to 40°C significantly impairs reproductive development.
Publisher: Cold Spring Harbor Laboratory
Date: 26-10-2020
DOI: 10.1101/2020.10.26.355149
Abstract: Measuring host-bacteriophage dynamics is an important approach to understanding bacterial survival functions and responses to infection. The model Microviridae bacteriophage φX174 is endemic to the human gut and has been studied for over seventy years but the host response to infection has never been investigated in detail. To address this gap in our understanding of this important interaction within our microbiome we have measured host Escherichia coli C proteomic and transcriptomic response to φX174 infection. We used mass spectrometry and RNA-seq to identify and quantify all 11 φX174 proteins and over 1,700 E. coli proteins, enabling us to comprehensively map host pathways involved in φX174 infection. Most notably, we see significant host responses centered on membrane damage and remodeling, cellular chaperone and translocon activity, and lipoprotein processing, which we speculate is due to the peptidoglycan-disruptive effects of the φX174 lysis protein E on MraY activity. We also observe the massive upregulation of small heat-shock proteins IbpA/B, along with other heat shock pathway chaperones, and speculate on how the specific characteristics of holdase protein activity may be beneficial for viral infections. Together, this study enables us to begin to understand the proteomic and transcriptomic host responses of E. coli to Microviridae infections and contributes insights to the activities of this important model phage. A major part of the healthy human gut microbiome are the Microviridae bacteriophage, exemplified by the model φX174 phage. Although much has been learned from studying φX174 over the last half century, until this work, the E. coli host response to infection has never been investigated in detail. We reveal the proteomic and transcriptomic pathways differentially regulated during the φX174 infection cycle, and uncover the details of a coordinated cellular response to membrane damage that results in increased lipoprotein processing and membrane trafficking, likely due to the phage antibiotic-like lysis protein. We also reveal that small heat shock proteins IbpA/B are massively upregulated during infection and that these holdase chaperones are highly conserved across the domains of life, indicating that reliance on them is likely widespread across viruses.
Publisher: MDPI AG
Date: 06-01-2020
DOI: 10.3390/IJMS21010363
Abstract: Rice is a critically important food source but yields worldwide are vulnerable to periods of drought. We exposed eight genotypes of upland and lowland rice (Oryza sativa L. ssp. japonica and indica) to drought stress at the late vegetative stage, and harvested leaves for label-free shotgun proteomics. Gene ontology analysis was used to identify common drought-responsive proteins in vegetative tissues, and leaf proteins that are unique to in idual genotypes, suggesting ersity in the metabolic responses to drought. Eight proteins were found to be induced in response to drought stress in all eight genotypes. A total of 213 proteins were identified in a single genotype, 83 of which were increased in abundance in response to drought stress. In total, 10 of these 83 proteins were of a largely uncharacterized function, making them candidates for functional analysis and potential biomarkers for drought tolerance.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Wiley
Date: 18-04-2019
Abstract: Plants require a distinctive cohort of enzymes to coordinate cell ision and expansion. Proteomic analysis now enables interrogation of immature leaf bases where these processes occur. Hence, proteins in tissues s led from leaves of a drought-tolerant rice (IAC1131) are investigated to provide insights into the effect of soil drying on gene expression relative to the drought-sensitive genotype Nipponbare. Shoot growth zones are dissected to estimate the proportion of iding cells and extract protein for subsequent tandem mass tags quantitative proteomic analysis. Gene ontology annotations of differentially expressed proteins provide insights into responses of Nipponbare and IAC1131 to drought. Soil drying does not affect the percentage of mitotic cells in IAC1131. More than 800 proteins across most functional categories increase in drought (and decrease on rewatering) in IAC1131, including proteins involved in "organizing the meristem" and "new cell formation". On the other hand, the percentage of iding cells in Nipponbare is severely impaired during drought and fewer than 200 proteins respond in abundance when growing zones undergo a drying cycle. Remarkably, the proteomes of the growing zones of each genotype respond in a highly distinctive manner, reflecting their contrasting drought tolerance even at the earliest stages of leaf development.
Publisher: Springer Science and Business Media LLC
Date: 16-12-2015
DOI: 10.1038/SREP17985
Abstract: The differentiation potential of pluripotent embryonic stem cells (ESCs) can be manipulated via serum and medium conditions for direct cellular development or to maintain a naïve ground state. The self-renewal state of ESCs can thus be induced by adding inhibitors of mitogen activated protein kinase (MAPK) and glycogen synthase kinase-3 (Gsk3), known as 2 inhibitors (2i) treatment. We have used a shotgun proteomics approach to investigate differences in protein expressions between 2i- and serum-grown mESCs. The results indicated that 164 proteins were significantly upregulated and 107 proteins downregulated in 2i-grown cells compared to serum. Protein pathways in 2i-grown cells with the highest enrichment were associated with glycolysis and gluconeogenesis. Protein pathways related to organ development were downregulated in 2i-grown cells. In serum-grown ESCs, protein pathways involved in integrin and focal adhesion and signaling proteins involved in the actin cytoskeleton regulation were enriched. We observed a number of nuclear proteins which were mostly involved in self-renewal maintenance and were expressed at higher levels in 2i compared to serum - Dnmt1, Map2k1, Parp1, Xpo4, Eif3g, Smarca4/Brg1 and Smarcc1/Baf155. Collectively, the results provided an insight into the key protein pathways used by ESCs in the ground state or metastable conditions through 2i or serum culture medium, respectively.
Publisher: Aging and Disease
Date: 2023
Publisher: Elsevier BV
Date: 05-2022
Publisher: Springer Science and Business Media LLC
Date: 02-2019
DOI: 10.1007/S12035-019-1479-4
Abstract: Increased amyloid β (Aβ) aggregation is a hallmark feature of Alzheimer's disease (AD) pathology. The APP/PS1 mouse model of AD exhibits accumulation of Aβ in the retina and demonstrates reduced retinal function and other degenerative changes. The overall molecular effects of AD pathology on the retina remain undetermined. Using a proteomics approach, this study assessed the molecular effects of Aβ accumulation and progression of AD pathology on the retina. Retinal tissues from younger (2.5 months) and older 8-month APP/PS1 mice were analysed for protein expression changes. A multiplexed proteomics approach using chemical isobaric tandem mass tags was applied followed by functional and protein-protein interaction analyses using Ingenuity pathway (IPA) and STRING computational tools. We identified approximately 2000 proteins each in the younger (upregulated 50 downregulated 36) and older set of APP/PS1 (upregulated 85 downregulated 79) mice retinas. Amyloid precursor protein (APP) was consistently upregulated two to threefold in both younger and older retinas (p < 0.0001). Mass spectrometry data further revealed that older APP/PS1 mice retinas had elevated levels of proteolytic enzymes cathepsin D, presenilin 2 and nicastrin that are associated with APP processing. Increased levels of proteasomal proteins Psma5, Psmd3 and Psmb2 were also observed in the older AD retinas. In contrast to the younger animals, significant downregulation of protein synthesis and elongation associated proteins such as Eef1a1, Rpl35a, Mrpl2 and Eef1e1 (p < 0.04) was identified in the older mice retinas. This study reports for the first time that not only old but also young APP/PS1 animals demonstrate increased amyloid protein levels in their retinas. Quantitative proteomics reveals new molecular insights which may represent a cellular response to clear amyloid build-up. Further, downregulation of ribosomal proteins involved in protein biosynthesis was observed which might be considered a toxicity effect.
Publisher: Elsevier BV
Date: 2022
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.RBMO.2018.04.043
Abstract: What is the molecular basis of infertility related to uterine dysfunction in women with polycystic ovary syndrome (PCOS)? In this study, differences in protein expression between PCOS and normal endometrium were identified using a proteomic approach based on two-dimensional electrophoresis (2-DE) coupled with mass spectrometry (MS). The proteome of endometrium were analysed during the proliferative (on day 2 or 3 before ovulation, n = 6) and luteal phases (on day 3-5 after ovulation, n = 6) from healthy women and PCOS patients (12-14 days after spontaneous bleeding, n = 12). The differentially expressed proteins were categorized based on the biological process using the DAVID bioinformatics resources. Over 803 reproducible protein spots were detected on gels, and 150 protein spots showed different intensities between PCOS and normal women during the proliferative and luteal phases. MS analysis detected 70 proteins out of 150 spots. For four of the 70 proteins, 14-3-3 protein, annexin A5, SERPINA1 and cathepsin D, 2-DE results were validated and localized by Western blot and immunohistochemistry, respectively, and their gene expression profiles were confirmed by real-time quantitative PCR. The obtained results corresponded to the proteomic analysis. The differentially expressed proteins identified are known to be involved in apoptosis, oxidative stress, inflammation and the cytoskeleton. The processes related to the differentially expressed proteins play important roles in fecundity and fecundability. The present study may reveal the cause of various endometrial aberrations as a limiting factor for achieving pregnancy in PCOS women.
Publisher: Informa UK Limited
Date: 31-12-2021
Publisher: Wiley
Date: 18-09-2013
Abstract: The typical Western diet, rich in high saturated fat and refined sugar (HFS), has been shown to increase cognitive decline with aging and Alzheimer's disease, and to affect cognitive functions that are dependent on the hippoc us, including memory processes and reversal learning. To investigate neurophysiological changes underlying these impairments, we employed a proteomic approach to identify differentially expressed proteins in the rat dorsal and ventral hippoc us following maintenance on an HFS diet. Rats maintained on the HFS diet for 8 weeks were impaired on a novel object recognition task that assesses memory and on a Morris Water Maze task assessing reversal learning. Quantitative label-free shotgun proteomic analysis was conducted on biological triplicates for each group. For the dorsal hippoc us, 59 proteins were upregulated and 36 downregulated in the HFS group compared to controls. Pathway ana-lysis revealed changes to proteins involved in molecular transport and cellular and molecular signaling, and changes to signaling pathways including calcium signaling, citrate cycle, and oxidative phosphorylation. For the ventral hippoc us, 25 proteins were upregulated and 27 downregulated in HFS fed rats. Differentially expressed proteins were involved in cell-to-cell signaling and interaction, and cellular and molecular function. Changes to signaling pathways included protein ubiquitination, ubiquinone biosynthesis, oxidative phosphorylation, and mitochondrial dysfunction. This is the first shotgun proteomics study to examine protein changes in the hippoc us following long-term consumption of a HFS diet, identifying changes to a large number of proteins including those involved in synaptic plasticity and energy metabolism. All MS data have been deposited in the ProteomeXchange with identifier PXD000028.
Publisher: Oxford University Press (OUP)
Date: 28-06-2017
Publisher: Frontiers Media SA
Date: 22-02-2019
Publisher: Wiley
Date: 15-12-2023
Publisher: Wiley
Date: 22-10-2022
DOI: 10.1002/GLIA.24285
Abstract: As the understanding of immune responses in Alzheimer's disease (AD) is in its early phases, there remains an urgency to identify the cellular and molecular processes driving chronic inflammation. In AD, a subpopulation of astrocytes acquires a neurotoxic phenotype which prompts them to lose typical physiological features. While the underlying molecular mechanisms are still unknown, evidence suggests that myeloid differentiation primary response 88 (MyD88) adaptor protein may play a role in coordinating these cells' immune responses in AD. Herein, we combined studies in human postmortem s les with a conditional genetic knockout mouse model to investigate the link between MyD88 and astrocytes in AD. In silico analyses of bulk and cell‐specific transcriptomic data from human postmortem brains demonstrated an upregulation of MyD88 expression in astrocytes in AD versus non‐AD in iduals. Proteomic studies revealed an increase in glial fibrillary acidic protein in multiple brain regions of AD subjects. These studies also showed that although overall MyD88 steady‐state levels were unaffected by AD, this protein was enriched in astrocytes near amyloid plaques and neurofibrillary tangles. Functional studies in mice indicated that the deletion of astrocytic MyD88 protected animals from the acute synaptic toxicity and cognitive impairment caused by the intracerebroventricular administration of β‐amyloid (Aβ). Lastly, unbiased proteomic analysis revealed that loss of astrocytic MyD88 resulted in altered astrocyte reactivity, lower levels of immune‐related proteins, and higher expression of synaptic‐related proteins in response to Aβ. Our studies provide evidence of the pivotal role played by MyD88 in the regulation of astrocytes response to AD.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier BV
Date: 09-2018
Publisher: Springer Science and Business Media LLC
Date: 23-12-2022
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.JPROT.2014.10.018
Abstract: Comparative physiology and proteomic analyses were conducted to monitor the stress response of two wheat genotypes (SERI M 82 (SE) and SW89.5193/kAu2 (SW)) with contrasting responses to drought stress. Under stress condition, the tolerant genotype (SE) produced higher shoot and root biomasses, longer roots and accumulated higher level of ABA in leaves. Physiological measurements suggested that the SE genotype was more efficient in water absorption and could preserve more water presumably by controlling stomata closure. Proteomic analysis showed an increased abundance of proteins related to defense and oxidative stress responses such as GLPs, GST, and SOD, and those related to protein processing such as small HSPs in roots of both genotypes in response to drought stress. Interestingly, the abundance of proteins such as endo-1,3-beta-glucosidase, peroxidase, SAMS, and MDH significantly increased in roots or leaves of the SE genotype and decreased in that of the SW one. In addition, an increased abundance of APX was detected in leaves and roots of the SE genotype and a decreased abundance of 14-3-3 and ribosomal proteins were noted in the SW one in response to drought stress. Our findings led to a better understanding about the integrated physiology and proteome responses of wheat genotypes with nearly contrasting responses to drought stress. We applied a comparative physiology and proteomic analysis to decipher the differential responses of two contrasting wheat genotypes to drought stress. Based on physiological measurements the tolerant genotype (SE) showed better drought response by developing deep root system, higher root and shoot biomasses, and higher level of ABA in leaves. Proteomic analysis showed an increased abundance of proteins related to defense and oxidative stress responses such as GLPs, GST, and SOD, and those related to protein processing such as small HSPs in roots of both genotypes in response to drought stress. In addition, the abundance of proteins such as glucan endo-1,3-beta-glucosidase, peroxidases, SAMS, and MDH increased in roots or leaves of the tolerant genotype (SE) and decreased in that of the sensitive genotype (SW). Overall, proteins related to oxidative stress, protein processing and photosynthesis showed decreased abundance to a greater extent in the sensitive genotype (SW).
Publisher: Medknow
Date: 02-10-2024
Publisher: American Society for Microbiology
Date: 29-06-2021
DOI: 10.1128/MSYSTEMS.00046-21
Abstract: A major part of the healthy human gut microbiome is the Microviridae bacteriophage, exemplified by the model φX174 phage, and their E. coli hosts. Although much has been learned from studying φX174 over the last half-century, until this work, the E. coli host response to infection has never been investigated in detail.
Publisher: Elsevier BV
Date: 06-2023
Publisher: CSIRO Publishing
Date: 2015
DOI: 10.1071/FP14274
Abstract: Salinity is a limiting factor affecting crop growth. We evaluated the responses of a salt-tolerant recombinant inbred rice (Oryza sativa L.) line, FL478, and the salt-sensitive IR29. Seedlings were exposed to salt stress and the growth rate was monitored to decipher the effect of long-term stress. At Day 16, IR29 produced lower shoot biomass than FL478. Significant differences for Na+ and K+ concentrations and Na+ : K+ ratios in roots and shoots were observed between genotypes. Changes in the proteomes of control and salt-stressed plants were analysed, identifying 59 and 39 salt-responsive proteins in roots and leaves, respectively. Proteomic analysis showed greater downregulation of proteins in IR29. In IR29, proteins related to pathways involved in salt tolerance (e.g. oxidative stress response, amino acid biosynthesis, polyamine biosynthesis, the actin cytoskeleton and ion compartmentalisation) changed to combat salinity. We found significant downregulation of proteins related to photosynthetic electron transport in IR29, indicating that photosynthesis was influenced, probably increasing the risk of reactive oxygen species formation. The sensitivity of IR29 might be related to its inability to exclude salt from its transpiration stream, to compartmentalise excess ions and to maintain a healthy photosynthetic apparatus during salt stress, or might be because of the leakiness of its roots, allowing excess salt to enter apoplastically. In FL478, superoxide dismutase, ferredoxin thioredoxin reductase, fibre protein and inorganic pyrophosphatase, which may participate in salt tolerance, increased in abundance. Our analyses provide novel insights into the mechanisms behind salt tolerance and sensitivity in genotypes with close genetic backgrounds.
Publisher: Elsevier BV
Date: 2020
Publisher: Springer International Publishing
Date: 2016
Publisher: American Chemical Society (ACS)
Date: 14-05-2020
Publisher: American Chemical Society (ACS)
Date: 14-10-2013
DOI: 10.1021/PR400936D
Abstract: Legume seeds and peanuts, in particular, are an inexpensive source of plant proteins and edible oil. A comprehensive understanding of seed metabolism and the effects of water-deficit stress on the incorporation of the main storage reserves in seeds, such as proteins, fatty acids, starch, and secondary metabolites, will enhance our ability to improve seed quality and yield through molecular breeding programs. In the present study, we employed a label-free quantitative proteomics approach to study the functional proteins altered in the midmature (65-70 days postanthesis) peanut seed grown under water-deficit stress conditions. We created a pod-specific proteome database and identified 93 nonredundant, statistically significant, and differentially expressed proteins between well-watered and drought-stressed seeds. Mapping of these differential proteins revealed three candidate biological pathways (glycolysis, sucrose and starch metabolism, and fatty acid metabolism) that were significantly altered due to water-deficit stress. Differential accumulation of proteins from these pathways provides insight into the molecular mechanisms underlying the observed physiological changes, which include reductions in pod yield and biomass, reduced germination, reduced vigor, decreased seed membrane integrity, increase in storage proteins, and decreased total fatty acid content. Some of the proteins encoding rate limiting enzymes of biosynthetic pathways could be utilized by breeders to improve peanut seed production during water-deficit conditions in the field. The data have been deposited to the ProteomeXchange with identifier PXD000308.
Publisher: Elsevier BV
Date: 02-2018
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.JPROT.2016.05.014
Abstract: Rice is the major staple food for more than half of world's population. As global climate changes, we are observing more floods, droughts and severe heat waves. Two rice cultivars with contrasting genetic backgrounds and levels of tolerance to drought, Nipponbare and IAC1131, were used in this study. Four-week-old seedlings of both cultivars were grown in large soil volumes and then exposed to moderate and extreme drought for 7days, followed by 3days of re-watering. Mature leaves were harvested from plants from each treatment for protein extraction and subsequent shotgun proteomic analysis, with validation of selected proteins by western blotting. Gene Ontology (GO) annotations of differentially expressed proteins provide insights into the metabolic pathways that are involved in drought stress resistance. Our data indicate that IAC1131 appears to be better able to cope with stressful conditions by upregulating a suite of stress and defence response related proteins. Nipponbare, in contrast, lacks the range of stress responses shown by the more stress tolerant variety, and responds to drought stress by initiating a partial shutdown of chlorophyll biosynthesis in an apparent attempt to preserve resources. In this study, two rice genotypes with contrasting drought tolerance were exposed to soil water deficits, and proteomic changes were observed in mature leaf laminae. Plants were well watered and then switched to conditions of either moderate drought or extreme drought followed by three days of recovery. Proteins were identified and quantified using both label-free and Tandem Mass Tag multiplexing approaches. Several biochemical pathways were significantly altered in response to water deficit. Most notably, the up-regulation of ClpD1 protease responded strongly in the drought-tolerant landrace this protein is typically involved in heat and osmotic stress response. In contrast, porphyrin and chlorophyll biosynthesis pathways were down-regulated, indicating suppression of the photosynthetic machinery.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.JPROT.2017.02.007
Abstract: Male infertility accounts for half of the infertility problems experienced by couples. Azoospermia, having no measurable level of sperm in seminal fluid, is one of the known conditions resulting in male infertility. In order to elucidate the complex molecular mechanisms causing male azoospermia, label-free quantitative shotgun proteomics was carried out on testicular tissue specimens from patients with obstructive azoospermia and non-obstructive azoospermia, including maturation arrest (MA) and Sertoli cell only syndrome (SCOS). The abundance of 520 proteins was significantly changed across three groups of s les. We were able to identify several functional biological pathways enriched in azoospermia s les and confirm selected differentially abundant proteins, using multiple histological methods. The results revealed that cell cycle and proteolysis, and RNA splicing were the most significant biological processes impaired by the substantial suppression of proteins related to the aforementioned categories in SCOS tissues. In the MA patient testes, generation of precursor metabolites and energy as well as oxidation-reduction were the most significantly altered processes. Novel candidate proteins identified in this study include key transcription factors, many of which have not previously been shown to be associated with azoospermia. Our findings can provide substantial insights into the molecular regulation of spermatogenesis and human reproduction. The obtained data showed a drastic suppression of proteins involved in spliceosome, cell cycle and proteasome proteins, as well as energy and metabolic production in Sertoli cell only syndrome testis tissue, and to a lesser extent in maturation arrest s les. Moreover, we identified new transcription factors that are highly down-regulated in SCOS and MA patients, thus helping to understand the molecular complexity of spermatogenesis in male infertility. Our findings provide novel candidate protein targets associated with SCOS or MA azoospermia.
Publisher: Wiley
Date: 25-01-2019
Publisher: Springer Science and Business Media LLC
Date: 26-07-2022
DOI: 10.1038/S41467-022-31707-4
Abstract: There are currently no treatments for geographic atrophy, the advanced form of age-related macular degeneration. Hence, innovative studies are needed to model this condition and prevent or delay its progression. Induced pluripotent stem cells generated from patients with geographic atrophy and healthy in iduals were differentiated to retinal pigment epithelium. Integrating transcriptional profiles of 127,659 retinal pigment epithelium cells generated from 43 in iduals with geographic atrophy and 36 controls with genotype data, we identify 445 expression quantitative trait loci in cis that are asssociated with disease status and specific to retinal pigment epithelium subpopulations. Transcriptomics and proteomics approaches identify molecular pathways significantly upregulated in geographic atrophy, including in mitochondrial functions, metabolic pathways and extracellular cellular matrix reorganization. Five significant protein quantitative trait loci that regulate protein expression in the retinal pigment epithelium and in geographic atrophy are identified - two of which share variants with cis- expression quantitative trait loci, including proteins involved in mitochondrial biology and neurodegeneration. Investigation of mitochondrial metabolism confirms mitochondrial dysfunction as a core constitutive difference of the retinal pigment epithelium from patients with geographic atrophy. This study uncovers important differences in retinal pigment epithelium homeostasis associated with geographic atrophy.
Start Date: 06-2019
End Date: 12-2023
Amount: $400,000.00
Funder: Australian Research Council
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