Biology subjects

Andrade, B.

Publications and source records attributed to Andrade, B..

6 recordsLinked to original sources

bioRxiv2025

Two distinct cytokine response clusters identified in healthcare workers with apparent resistance to infection with Mycobacterium tuberculosis despite sustained occupational exposure

IntroductionEvidence exists that some individuals resist ("Resisters") Mycobacterium tuberculosis (Mtb) infection despite sustained exposure, but the protective mechanisms involved are not fully understood. We investigated immune responses induced by ex vivo stimulation of peripheral blood mononuclear cells (PBMC) with live Mtb in Resisters compared to those with latent TB infection (LTBI). MethodsHIV-uninfected healthcare workers working in high TB exposure healthcare facilities for over 5 years were screened for Mtb sensitization using the interferon-gamma release assay (IGRA) and the tuberculin skin test (TST). We identified Resisters (TST<10mm and IGRA<0.35 IU/mL, n=129) and those with LTBI (TST[≥]10mm and IGRA[≥]0.35 IU/mL n=145). We selected a subset of extreme resisters (TST=0mm and IGRA<0.2 IU/mL; n=26) and extreme LTBI (TST[≥]15mm and IGRA[≥]1 IU/mL; n=24) for these analyses. Blood was collected and PBMC isolated and cultured with live H37Rv Mtb for 18 hours. Supernatants were collected and used for measuring 65 secreted analytes by Luminex. We also evaluated cell-associated cytokine expression by CD4 T cells and monocytes in these participants using flow cytometry. ResultsUsing the feature selection in R, we identified a set of 4 cytokines: IL-17A, MCP-1, IL-8, and MDC, which collectively classified extreme Resisters from extreme LTBI with an area-under-the-curve (AUC) of 0.67 (0.54-0.85). Focusing only on the extreme Resisters, and using hierarchical clustering, participants in this group segregated into two main clusters (Resister_c1 and Resister_c2). Further analyses identified 37 cytokines that were significantly higher and 15 cytokines that were lower in Resister_c2 compared with Resister_c1. A set of 5 cytokines (TRAIL, MIP-1{beta}, Fractalkine, GRO- and IL-1) collectively classified these two clusters with an AUC of 1 (1-1). CD4 T cell and monocyte responses to Mtb did not significantly differ between the two clusters. ConclusionsMtb-specific immune responses segregate extreme Resisters into two distinct clusters in individuals with apparent resistance to Mtb infection and may allow discrimination of individuals with true resistance from those with infection but have alternative immune responses not detected by IGRA and TST.

immunology↗

bioRxiv2024

Contextual Neural Dynamics During Time Perception in Primate Ventral Premotor Cortex

Understanding how time perception adapts to cognitive demands remains a significant challenge. In some contexts, the brain encodes time categorically (as "long" or "short"), while in others, it encodes precise time intervals on a continuous scale. Although the ventral premotor cortex (VPC) is known for its role in complex temporal processes, such as speech, its specific involvement in time estimation remains underexplored. In this study, we investigated how the VPC processes temporal information during a time interval comparison task (TICT) and a time interval categorization task (TCT) in primates. We found a notable heterogeneity in neuronal responses associated with time perception across both tasks. While most neurons responded during time interval presentation, a smaller subset retained this information during the working memory periods. Population-level analysis revealed distinct dynamics between tasks: in TICT, population activity exhibited a linear and parametric relationship with interval duration, whereas in TCT, neuronal activity diverged into two distinct dynamics corresponding to the interval categories. During delay periods, these categorical or parametric representations remained consistent within each task context. This contextual shift underscores the VPCs adaptive role in interval estimation and highlights how temporal representations are modulated by cognitive demands. Significance StatementThe neural representation of time has long intrigued neuroscientists, particularly how it adapts to cognitive demands. Depending on the task, the brain encodes time either categorically ("long" or "short") or as precise intervals. While the ventral premotor cortex (VPC) is known for its role in temporal processes, its role in time estimation remains underexplored. Here, we examined how the VPC processes temporal information in primates during a time interval comparison task (TICT) and a categorization task (TCT). The VPC exhibited heterogeneous neuronal responses with distinct dynamics: a linear, parametric relationship in TICT and bifurcated dynamics in TCT. These representations remained consistent during delay periods, underscoring the VPCs adaptive role in time interval estimation.

neuroscience↗

bioRxiv2024

Molecular Genomic Insights into Melanoma Associated Proteins PRAME and BAP1

BackgroundMelanoma, a worldwide widespread skin cancer with over 325,000 yearly incidences, demands a thorough understanding of its molecular components to create effective therapeutics. This study looks at the PRAME (cutaneous melanoma-associated antigen) and BAP1 (gene controlling gene-environment interactions) proteins, which are important in melanoma development and are important for understanding the molecular landscape of melanoma. IntroductionWhile playing a crucial role in melanoma, the structural and functional characteristics of PRAME and BAP1 remain unidentified. This work tries to unravel their complexities by investigating conserved residues, sequence invariance, and other molecular characteristics that contribute to their importance in melanoma. Promising therapeutic targets for melanoma therapy are identified by analyzing these proteins at the molecular level. MethodsThe study makes extensive use of bioinformatics methods to analyze PRAME and BAP1, including sequence conservation, inherent disorder, polyglutamic acid presence, and polarity alterations. Established approaches are used to investigate residue changes and their effects on protein folding, aggregation, and interactions. ResultsPRAME and BAP1 conserved residues highlight their critical roles in protein function and interaction. Sequence invariance indicates the possibility of functional relevance and evolutionary conservation. In intrinsically disordered proteins (IDPRs), PRAME has enhanced intrinsic disorder and flexibility, whereas BAP1 has changed disorder-promoting residue sequences. Polyglutamic acid strings are found in both proteins, emphasizing their modulatory involvement in protein interactions. Protein folding and aggregation are influenced by polarity shifts, with a balanced distribution of acidic and basic residues preserving native structures. The ratios and distributions of amino acids, particularly neutral residues, have a profound influence on interactions and gene dysregulation. ConclusionPRAME and BAP1 structural and functional understanding pave the way for diagnostic and tailored treatment options in melanoma. Differences in residue alterations, polarity distributions, and amino acid ratios provide intriguing drug design options. This research contributes to a better knowledge of melanoma-associated two proteins, opening the path for novel diagnostic and therapy techniques in skin cancer and beyond.

bioinformatics↗

bioRxiv2023

SARS-CoV-2 NSP14 governs mutational instability and assists in making new SARS-CoV-2 variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the rapidly evolving RNA virus behind the COVID-19 pandemic, has spawned numerous variants since its 2019 emergence. The multifunctional NSP14 enzyme, possessing exonuclease and mRNA capping capabilities, serves as a key player. Notably, single and co-occurring mutations within NSP14 significantly influence replication fidelity and drive variant diversification. This study comprehensively examines 120 co-mutations, 68 unique mutations, and 160 conserved residues across NSP14 homologs, shedding light on their implications for phylogenetic patterns, pathogenicity, and residue interactions. Quantitative physicochemical analysis categorizes 3953 NSP14 variants into three clusters, revealing genetic diversity. This research underscores the dynamic nature of SARS-CoV-2 evolution, primarily governed by NSP14 mutations. Understanding these genetic dynamics provides valuable insights for therapeutic and vaccine development.

bioinformatics↗

bioRxiv2022

SARS-CoV-2 variants show a gradual declining pathogenicity and pro-inflammatory cytokine stimulation and an increasing antigenic and anti-inflammatory cytokine induction

Hyper-transmissibility with decreased disease severity are typical characteristics of Omicron variant. To understand this phenomenon, we used various bioinformatics approaches to analyze randomly selected genome sequences (one each) of the Gamma, Delta, and Omicron variants submitted to NCBI from 15 to 31 December 2021. We show that: (i) Pathogenicity of SARS-CoV-2 variants decreases in the order: Wuhan > Gamma > Delta > Omicron; however, the antigenic property follows the order: Omicron > Gamma > Wuhan > Delta. (ii) Omicron Spike RBD has lower pathogenicity but higher antigenicity than other variants. (iii) Decreased disease severity by Omicron variant may be due to its decreased pro-inflammatory and IL-6 stimulation and increased IFN-{gamma} and IL-4 induction efficacy. (iv) Mutations in N protein are associated with decreased IL-6 induction and human DDX21-mediated increased IL-4 production in Omicron. (v) Due to mutations, the stability of S, M, N, and E proteins decreases in the order: Omicron > Gamma > Delta > Wuhan. (vi) Stronger Spike RBD-hACE2 binding in Omicron is associated with increased transmissibility. However, the lowest stability of the Omicron Spike protein makes Spike RBD-hACE2 interaction weak for systemic infection and for causing severe disease. Finally (vii), the highest instability of Omicron E protein may also be associated with decreased viral maturation and low viral load leading to less severe disease and faster recovery. Our method may be used for other similar viruses, and these findings will contribute to the understanding of the dynamics of SARS-CoV-2 variants and the management of emerging variants.

bioinformatics↗

bioRxiv2020

A smartphone app for individual anesthetic calculation decreased anesthesia-related mortality in mice

Annually, millions of animals are used for experimental purposes. Despite the recommended anesthetic doses being well-known worldwide, the final amounts applied to mice could be different than those calculated. Here, we developed, tested, and validated a mobile app where researchers and operators were able to use personal devices to process body weight, calculate a master anesthetic cocktail, and then apply the individual volume to each mouse. Our objective was to refine anesthesia procedures using information technologies. Our data showed that the "Labinsane" mobile app decreased anesthetic-related deaths upon using weight-adjusted doses of ketamine and xylazine. Also, we validated that the Labinsane mobile app matched all calculations of anesthetic doses. To our knowledge, this is the first report with hundreds of anesthetized mice records and validation and implementation of a mobile app to solve an old but transversal challenge for researchers working with experimental mice.

pharmacology and toxicology↗