80 research outputs found

    Postmortem Brain Imaging in Alzheimer\u27s Disease and Related Dementias: The South Texas Alzheimer\u27s Disease Research Center Repository

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    Background: Neuroimaging bears the promise of providing new biomarkers that could refine the diagnosis of dementia. Still, obtaining the pathology data required to validate the relationship between neuroimaging markers and neurological changes is challenging. Existing data repositories are focused on a single pathology, are too small, or do not precisely match neuroimaging and pathology findings. Objective: The new data repository introduced in this work, the South Texas Alzheimer’s Disease research center repository, was designed to address these limitations. Our repository covers a broad diversity of dementias, spans a wide age range, and was specifically designed to draw exact correspondences between neuroimaging and pathology data. Methods: Using four different MRI sequences, we are reaching a sample size that allows for validating multimodal neuroimaging biomarkers and studying comorbid conditions. Our imaging protocol was designed to capture markers of cerebrovascular disease and related lesions. Quantification of these lesions is currently underway with MRI-guided histopathological examination. Results: A total of 139 postmortem brains (70 females) with mean age of 77.9 years were collected, with 71 brains fully analyzed. Of these, only 3% showed evidence of AD-only pathology and 76% had high prevalence of multiple pathologies contributing to clinical diagnosis. Conclusion: This repository has a significant (and increasing) sample size consisting of a wide range of neurodegenerative disorders and employs advanced imaging protocols and MRI-guided histopathological analysis to help disentangle the effects of comorbid disorders to refine diagnosis, prognosis and better understand neurodegenerative disorders

    INVESTIGATION ON THE PRODUCTION OF L-GLUTAMINASE FROM PSEUDOMONAS STUTZERI STRAIN UNDER SOLID STATE FERMENTATION USING VARIOUS AGRO RESIDUES

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    Solid state fermentation was carried out for the production of L-glutaminase by Pseudomonas stutzeri PIMS6 using different agro residues including green gram husk, Bengal gram husk, cattle feed, wheat bran and groundnut oil cake as solid substrates. L-glutaminase has received significant attention in recent years owing to its potential applications in medicine as an anticancer agent, as an efficient anti-retroviral agent and as a biosensor. In food industries it is used as a flavor and aroma enhancing agent. The maximum yield (55.24 U/gds) of L-glutaminase by Pseudomomonas stutzeri PIMS6 was obtained using cattle feed at 75% initial moisture content, initial pH 8.0, supplemented with glucose (1.0%), ammonium sulphate (1.0%),  inoculated with 5% of inoculum and incubated at 37°C for 96 h. Both physico-chemical and nutritional parameters played a significant role in the production of the enzyme L-glutaminase.Keywords: L-glutaminase, Pseudomonas stutzeri PIMS6, Cattle feed, Solid state fermentation

    Dynamic Profiling of β-Coronavirus 3CL M<sup>pro</sup>Protease Ligand-Binding Sites

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    Data availability statement: The trajectories of Mpro simulations and models of the metastable states can be downloaded from 10.5281/zenodo.4782284.β-coronavirus (CoVs) alone has been responsible for three major global outbreaks in the 21st century. The current crisis has led to an urgent requirement to develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components are required as a backup against the emergence of lethal viral variants. One such target is the main protease (Mpro) that plays an indispensable role in viral replication. The availability of over 270 Mpro X-ray structures in complex with inhibitors provides unique insights into ligand–protein interactions. Herein, we provide a comprehensive comparison of all nonredundant ligand-binding sites available for SARS-CoV2, SARS-CoV, and MERS-CoV Mpro. Extensive adaptive sampling has been used to investigate structural conservation of ligand-binding sites using Markov state models (MSMs) and compare conformational dynamics employing convolutional variational auto-encoder-based deep learning. Our results indicate that not all ligand-binding sites are dynamically conserved despite high sequence and structural conservation across β-CoV homologs. This highlights the complexity in targeting all three Mpro enzymes with a single pan inhibitor.There was no funding for this wor

    Inhibition of Macrophage Migration Inhibitory Factor Ameliorates Ocular Pseudomonas aeruginosa-Induced Keratitis

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    Pseudomonas aeruginosa causes severe sight-threatening corneal infections, with the inflammatory response to the pathogen being the major factor resulting in damage to the cornea that leads to loss of visual acuity. We found that mice deficient for macrophage migration inhibitory factor (MIF), a key regulator of inflammation, had significantly reduced consequences from acute P. aeruginosa keratitis. This improvement in the outcome was manifested as improved bacterial clearance, decreased neutrophil infiltration, and decreased inflammatory responses when P. aeruginosa-infected MIF knock out (KO) mice were compared to infected wild-type mice. Recombinant MIF applied to infected corneas restored the susceptibility of MIF deficient mice to P. aeruginosa-induced disease, demonstrating that MIF is necessary and sufficient to cause significant pathology at this immune privileged site. A MIF inhibitor administered during P. aeruginosa-induced infection ameliorated the disease-associated pathology. MIF regulated epithelial cell responses to infection by enhancing synthesis of proinflammatory mediators in response to P. aeruginosa infection and by promoting bacterial invasion of corneal epithelial cells, a correlate of virulence in the keratitis model. Our results uncover a host factor that elevates inflammation and propagates bacterial cellular invasion, and further suggest that inhibition of MIF during infection may have a beneficial therapeutic effect

    Memory for Self-Performed Actions in Individuals with Asperger Syndrome

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    Memory for action is enhanced if individuals are allowed to perform the corresponding movements, compared to when they simply listen to them (enactment effect). Previous studies have shown that individuals with Autism Spectrum Disorders (ASD) have difficulties with processes involving the self, such as autobiographical memories and self performed actions. The present study aimed at assessing memory for action in Asperger Syndrome (AS). We investigated whether adults with AS would benefit from the enactment effect when recalling a list of previously performed items vs. items that were only visually and verbally experienced through three experimental tasks (Free Recall, Old/New Recognition and Source Memory). The results showed that while performance on Recognition and Source Memory tasks was preserved in individuals with AS, the enactment effect for self-performed actions was not consistently present, as revealed by the lower number of performed actions being recalled on the Free Recall test, as compared to adults with typical development. Subtle difficulties in encoding specific motor and proprioceptive signals during action execution in individuals with AS might affect retrieval of relevant personal episodic information. These disturbances might be associated to an impaired action monitoring system

    Atypical Neurophysiology Underlying Episodic and Semantic Memory in Adults with Autism Spectrum Disorder

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    Individuals with autism spectrum disorder (ASD) show atypicalities in episodic memory (Boucher et al. in Psychological Bulletin, 138 (3), 458-496, 2012). We asked participants to recall the colours of a set of studied line drawings (episodic judgement), or to recognize line drawings alone (semantic judgement). Cycowicz et al. (Journal of Experimental Child Psychology, 65, 171-237, 2001) found early (300 ms onset) posterior old-new event-related potential effects for semantic judgements in typically developing (TD) individuals, and occipitally focused negativity (800 ms onset) for episodic judgements. Our results replicated findings in TD individuals and demonstrate attenuated early old-new effects in ASD. Late posterior negativity was present in the ASD group, but was not specific to this time window. This non-specificity may contribute to the atypical episodic memory judgements characteristic of individuals with ASD

    PDBe-KB: collaboratively defining the biological context of structural data

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    The Protein Data Bank in Europe - Knowledge Base (PDBe-KB, https://pdbe-kb.org) is an open collaboration between world-leading specialist data resources contributing functional and biophysical annotations derived from or relevant to the Protein Data Bank (PDB). The goal of PDBe-KB is to place macromolecular structure data in their biological context by developing standardised data exchange formats and integrating functional annotations from the contributing partner resources into a knowledge graph that can provide valuable biological insights. Since we described PDBe-KB in 2019, there have been significant improvements in the variety of available annotation data sets and user functionality. Here, we provide an overview of the consortium, highlighting the addition of annotations such as predicted covalent binders, phosphorylation sites, effects of mutations on the protein structure and energetic local frustration. In addition, we describe a library of reusable web-based visualisation components and introduce new features such as a bulk download data service and a novel superposition service that generates clusters of superposed protein chains weekly for the whole PDB archive
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