Biology subjects

Hauser, S.

Publications and source records attributed to Hauser, S..

4 recordsLinked to original sources

bioRxiv2022

Psychometric and subcortical neurometric measures of temporal discrimination in rhesus macaques

Temporal envelope fluctuations are abundant in nature and are critical for perception of complex sounds. While psychophysical sinusoidal amplitude modulation (SAM) processing studies have characterized the perception of SAM, and neurophysiological studies report a subcortical transformation from temporal to rate-based code, no studies have characterized this transformation in unanesthetized animals or in nonhuman primates. To address this, we recorded single-unit responses and compared derived neurometric measures in the cochlear nucleus (CN) and inferior colliculus (IC) to psychometric measures of modulation frequency (MF) discrimination in macaques. IC and CN neurons often exhibited tuned responses to SAM in their rate and spike-timing. Neurometric thresholds spanned a large range (2-200 Hz {Delta} MF). The lowest 40% of IC thresholds were less than or equal to psychometric thresholds, regardless of which code was used, while CN thresholds were greater than psychometric thresholds. Discrimination at 10-20 Hz could be explained by indiscriminately pooling 30 units in either structure, while discrimination at higher MFs was best explained by more selective pooling. This suggests that pooled brainstem activity was sufficient for AM discrimination. Psychometric and neurometric thresholds decreased as a function of stimulus duration, but IC and CN thresholds were greater and more variable than behavior at durations less than 500 ms. This slower subcortical temporal integration compared to behavior was consistent with a drift diffusion model which reproduced individual differences in performance and can constrain future neurophysiological studies of temporal integration. These measures provide an account of AM perception at the neurophysiological, computational, and behavioral levels. Significance statementListening in everyday environments tasks the brain with extracting information from sound envelopes. This process involves both sensory encoding and decision-making. Different neural codes for envelope representation have been well characterized in the auditory midbrain and cortex, but studies of the brainstem have usually been conducted in anesthetized rodents or cats. Moreover, these candidate neural codes have been studied in isolation from the decision-making process. In this study, we found that population activity in the primate subcortical auditory system contains sufficient information for discriminating sound envelope and applied a biologically plausible model of decision-making to sound envelope discrimination performance from rhesus macaques, a species with great phylogenetic and perceptual similarity to humans.

neuroscience↗

bioRxiv2021

Human KIR+CD8+ T cells target pathogenic T cells in Celiac disease and are active in autoimmune diseases and COVID-19

Previous reports show that Ly49+CD8+ T cells can suppress autoimmunity in mouse models of autoimmune diseases. Here we find a markedly increased frequency of CD8+ T cells expressing inhibitory Killer cell Immunoglobulin like Receptors (KIR), the human equivalent of the Ly49 family, in the blood and inflamed tissues of various autoimmune diseases. Moreover, KIR+CD8+ T cells can efficiently eliminate pathogenic gliadin-specific CD4+ T cells from Celiac disease (CeD) patients leukocytes in vitro. Furthermore, we observe elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 and influenza-infected patients, and this correlates with disease severity and vasculitis in COVID-19. Expanded KIR+CD8+ T cells from these different diseases display shared phenotypes and similar T cell receptor sequences. These results characterize a regulatory CD8+ T cell subset in humans, broadly active in both autoimmune and infectious diseases, which we hypothesize functions to control self-reactive or otherwise pathogenic T cells. One-Sentence SummaryHere we identified KIR+CD8+ T cells as a regulatory CD8+ T cell subset in humans that suppresses self-reactive or otherwise pathogenic CD4+ T cells.

immunology↗

bioRxiv2021

The crucial role of genome-wide genetic variation in conservation

The unprecedented rate of extinction calls for efficient use of genetics to help conserve biodiversity. Several recent genomic and simulation-based studies have argued that the field of conservation biology has placed too much focus on the conservation of genome-wide genetic variation, and that this approach should be replaced with another that focuses instead on managing the subset of functional genetic variation that is thought to affect fitness. Here, we critically evaluate the feasibility and likely benefits of this approach in conservation. We find that population genetics theory and empirical results show that the conserving genome-wide genetic variation is generally the best approach to prevent inbreeding depression and loss of adaptive potential from driving populations towards extinction. Focusing conservation efforts on presumably functional genetic variation will only be feasible occasionally, often misleading, and counterproductive when prioritized over genome-wide genetic variation. Given the increasing rate of habitat loss and other environmental changes, failure to recognize the detrimental effects of lost genome-wide variation on long-term population viability will only worsen the biodiversity crisis.

evolutionary biology↗

bioRxiv2020

Clinical metagenomics bioinformatics pipeline for the identification of hospital-acquired pneumonia pathogens antibiotic resistance genes from bronchoalveolar lavage samples

BackgroundShortening the time-to-result for pathogen detection and identification and antibiotic susceptibility testing for patients with Hospital-Acquired and Ventilator-Associated pneumonia (HAP-VAP) is of great interest. For this purpose, clinical metagenomics is a promising non-hypothesis driven alternative to traditional culture-based solutions: when mature, it would allow direct sequencing all microbial genomes present in a BronchoAlveolar Lavage (BAL) sample with the purpose of simultaneously identifying pathogens and Antibiotic Resistance Genes (ARG). In this study, we describe a new bioinformatics method to detect pathogens and their ARG with good accuracy, both in mono- and polymicrobial samples. MethodsThe standard approach (hereafter called TBo), that consists in taxonomic binning of metagenomic reads followed by an assembly step, suffers from lack of sensitivity for ARG detection. Thus, we propose a new bioinformatics approach (called TBwDM) with both models and databases optimized for HAP-VAP, that performs reads mapping against ARG reference database in parallel to taxonomic binning, and joint reads assembly. ResultsIn in-silico simulated monomicrobial samples, the recall for ARG detection increased from 51% with TBo to 97.3% with TBwDM; in simulated polymicrobial infections, it increased from 41.8% to 82%. In real sequenced BAL samples (mono and polymicrobial), detected pathogens were also confirmed by traditional culture approaches. Moreover, both recall and precision for ARG detection were higher with TBwDM than with TBo (35 points difference for recall, and 7 points difference for precision). ConclusionsWe present a new bioinformatics pipeline to identify pathogens and ARG in BAL samples from patients with HAP-VAP, with higher sensitivity for ARG recovery than standard approaches and the ability to link ARG to their host pathogens.

bioinformatics↗