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Biology subjects

Fulop, T.

Publications and source records attributed to Fulop, T..

4 recordsLinked to original sources

Discovering Secondary Protein Structures via Local Euler Curvature

Protein structure analysis and classification, which is fundamental for predicting protein function, still poses formidable challenges in the fields of molecular biology, mathematics, physics and computer science. In the present work we exploit recent advances in computational topology to define a new intrinsic unsupervised topological fingerprint for proteins. These fingerprints, computed via Local Euler Curvature (LECs), identify secondary protein structures, such as Helices and Sheets, by capturing their distinctive topological signatures. Using an extensive protein residue database, the proposed computational framework not only distinguishes between structural classes via unsupervised clustering but also achieves remarkable accuracy in classifying proteins structures through supervised machine learning classifier. We also show that the internal structure of LEC space embeds the information about the secondary structure of proteins. Beyond its immediate implications for the advancement of critical application areas such as drug design and biotechnology, our approach opens a fascinating avenue towards characterizing the multiscale structures of diverse biopolymers based solely on their geometric and topological attributes.

biochemistry↗

Tracking the progression of Alzheimer's disease with peripheral blood monocytes

BackgroundAlzheimers disease (AD) is the most common form of dementia with the symptoms gradually worsening over the years. However, the driving pathological processes occur well before the appearance of symptoms. AD patients display signs of systemic inflammation, suggesting that it could precede the well-established AD hallmarks. We recently showed that the innate immune response in the form of monocyte activation is detectable at the pre-clinical stage. ObjectivesOur goal here is to characterize changes of gene expression in peripheral blood monocytes from patients at different stages of AD progression and validate potential biomarkers for a better prognosis and diagnosis of AD clinical spectrum. ResultsWe performed a whole transcriptome analysis on monocytes purified from healthy subjects, Mild Cognitive Impairment (MCI) and AD patients, and established the list of genes differentially expressed in monocytes during the disease evolution. We observed that, in the top 500 genes differentially expressed, a majority of these genes were upregulated (65%) during AD progression. These genes are mainly involved in chemokine/cytokine-mediated signaling pathways. We further confirmed several biomarkers by quantitative PCR and immunoblotting and showed that they are often deregulated at pre-clinical stages of the disease (MCI stage), supporting the hyperactivation of monocytes in MCI patients. PerspectivesOur findings provide evidence that the pre-clinical stage of AD can be detected in monocytes using a specific set of biomarkers, highlighting the importance to study the early innate immune response in AD. Our results open the possibility to use these biomarkers with different diagnostic methodologies to better predict and efficiently treat AD.

neuroscience↗

Interaction mechanism between the HSV-1 glycoprotein B and the antimicrobial peptide Amyloid-β

Unravelling the mystery of Alzheimers Disease (AD) requires urgent resolution given the worldwide increase of the aging population. There is a growing concern that the current leading AD hypothesis, the amyloid cascade hypothesis, does not stand up to validation with respect to emerging new data. Indeed, several paradoxes are being discussed in the literature, for instance, both the deposition of the Amyloid-Beta peptide (A{beta}) and the intracellular neurofibrillary tangles (NFTs) could occur within the brain without any cognitive pathology. Thus, these paradoxes suggest that something more fundamental is at play in the onset of the disease and other key and related pathomechanisms have to be investigated. The present study follows our previous investigations on the infectious hypothesis, which posits that some pathogens are linked to late onset AD. Our studies also build upon the shattering finding that A{beta} is a powerful antimicrobial agent capable of inhibiting pathogens as observed in in vitro experiments. Herein, we ask what are the molecular mechanisms in play when A{beta} neutralizes infectious pathogens? To answer this question, we probed at nanoscale lengths with FRET (Forster Resonance Energy Transfer), the interaction between A{beta} peptides and glycoprotein B (responsible of virus-cell binding) within the HSV-1 virion. We concluded that there is indeed a close interaction, likely nonspecific or semi-specific, between the two types of molecules, which participate in virus neutralization.

neuroscience↗

A Multi-Phenotype System to Discover Therapies for Age-Related Dysregulation of the Immune Response to Viral Infections

Age-related immune dysregulation contributes to increased susceptibility to infection and disease in older adults. We combined high-throughput laboratory automation with machine learning to build a multi-phenotype aging profile that models the dysfunctional immune response to viral infection in older adults. From a single well, our multi-phenotype aging profile can capture changes in cell composition, physical cell-to-cell interaction, organelle structure, cytokines, and other hidden complexities contributing to age-related dysfunction. This system allows for rapid identification of new potential compounds to rejuvenate older adults immune response. We used our technology to screen thousands of compounds for their ability to make old immune cells respond to viral infection like young immune cells. We observed beneficial effects of multiple compounds, of which two of the most promising were disulfiram and triptonide. Our findings indicate that disulfiram could be considered as a treatment for severe coronavirus disease 2019 and other inflammatory infections.

immunology↗