Biology subjects

Kashyap, M.

Publications and source records attributed to Kashyap, M..

6 recordsLinked to original sources

bioRxiv2024

Cued probabilistic expectations do not modulate grating-evoked event-related potentials in the visual system

We can rapidly learn recurring patterns that occur within our sensory environments. This knowledge allows us to form expectations about future sensory events. Several influential predictive coding models posit that, when a stimulus matches our expectations, the activity of feature-selective neurons in visual cortex will be suppressed relative to when that stimulus is unexpected. However, after accounting for known critical confounds, there is currently scant evidence for these hypothesised effects from studies recording electrophysiological neural activity. To provide a strong test for expectation effects on stimulus-evoked responses in visual cortex, we performed a probabilistic cueing experiment while recording electroencephalographic (EEG) data. Participants (n=48) learned associations between visual cues and subsequently presented gratings. A given cue predicted the appearance of a certain grating orientation with 10%, 25%, 50%, 75%, or 90% validity. We did not observe any stimulus expectancy effects on grating-evoked event-related potentials. Multivariate classifiers trained to discriminate between grating orientations performed better when classifying 10% compared to 90% probability gratings. However, classification performance did not substantively differ across any other stimulus expectancy conditions. Our findings provide very limited evidence for modulations of prediction error signalling by probabilistic expectations as specified in contemporary predictive coding models.

neuroscience↗

bioRxiv2023

Production of single-cell-protein (SCP)/poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) matrices through fermentation of archaea Haloferax mediterranei

The idea of in-situ integrating poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) sieves in a single-cell protein (SCP) represents a promising approach to enhance the properties of microbial biomass as protein alternatives. Archaea SCP/PHBV matrix was successfully produced with a concentration of 8.0 {+/-} 0.1 g L-1 and a productivity of 11.1 mg L-1 h-1 using Haloferax mediterranei. This was achieved by employing 30 g L-1 of enzymatically hydrolyzed bread waste (BW) and 200 g L-1 of red sea salt at 42 {degrees}C and with shaking at 150 rpm for 3 days. The amino acid profile of the SCP/PHBV matrix revealed a total amino acid content of 358 g kg-1, including 147 g kg-1 of essential amino acids. The protein quality of the H. mediterranei SCP/PHBV matrix was assessed using the in-vitro enzyme digestion method, indicating a high-quality protein with an in-vitro digestibility value of 0.91 and a protein digestibility-corrected amino acid score (PDCAAS) of 0.78. The PHBV component (36.0 {+/-} 6.3% w/w) in the SCP/PHBV matrix consisted of a copolymer of 3-hydroxybutyrate and 3- hydroxyvalerate in a 91:9 mol% ratio, respectively. The simultaneous production of PHBV polymeric sieves within the H. mediterranei SCP/PHBV matrix provides an alternative protein source with enhanced physicochemical and thermal properties. HighlightsO_LISCP/PHBV matrices were produced from wasted bread by archaea H. mediterranei. C_LIO_LIThis is the first report that explored the production and properties of SCP/PHBV. C_LIO_LIThe presence of PHBV in SCP affected its physicochemical and thermal properties. C_LIO_LISCP/PHBV with high-quality protein was achieved with a PDCAAS value of 0.78. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/571855v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@773447org.highwire.dtl.DTLVardef@94a96org.highwire.dtl.DTLVardef@1ffdfb8org.highwire.dtl.DTLVardef@1b8e27a_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

Development of Corynebacterium glutamicum as a monoterpene production platform

Monoterpenes are commonly known for their role in the flavors and fragrances industry and are also gaining attention for other uses like insect repellant and as potential renewable fuels for aviation. Corynebacterium glutamicum, a Generally Recognized as Safe microbe, has been a choice organism in industry for the annual million ton-scale bioproduction of amino acids for more than 50 years; however, efforts to produce monoterpenes in C. glutamicum have remained relatively limited. In this study, we report a further expansion of the C. glutamicum biosynthetic repertoire through the development and optimization of a mevalonate-based monoterpene platform. In the course of our plasmid design iterations, we increased flux through the mevalonate-based bypass pathway, measuring isoprenol production as a proxy for monoterpene precursor abundance and demonstrating the highest reported titers in C. glutamicum to date at nearly 1500 mg/L. Our designs also evaluated the effects of backbone, promoter, and GPP synthase homolog origin on monoterpene product titers. Monoterpene production was further improved by disrupting competing pathways for isoprenoid precursor supply and by implementing a biphasic production system to prevent volatilization. With this platform, we achieved 321.1 mg/L of geranoids, 723.6 mg/L of 1,8-cineole, and 227.8 mg/L of linalool. Furthermore, we determined that C. glutamicum first oxidizes geraniol through an aldehyde intermediate before it is asymmetrically reduced to citronellol. Additionally, we demonstrate that the aldehyde reductase, AdhC, possesses additional substrate promiscuity for acyclic monoterpene aldehydes. HighlightsO_LIDesign of a mevalonate-based monoterpene production platform in C. glutamicum C_LIO_LIHighest production titers of geranoids, eucalyptol, and linalool reported in C. glutamicum to date C_LIO_LIIdentification of citronellal as an intermediate in the reduction of geraniol to citronellol by C. glutamicum C_LI

synthetic biology↗

bioRxiv2023

Metabolic alterations unravel the materno fetal immune responses with disease severity in pregnant women infected with SARS-CoV-2

BackgroundPregnancy being immune compromised state, COVID-19 disease poses high risk of premature delivery and threat to fetus. Plasma metabolome regulates immune cellular responses and we aimed to analyze the plasma secretome, metabolome and immune cells in COVID-19 positive pregnant mother and cord blood. MethodsCOVID-19 RT-PCR positive pregnant females (n=112) asymptomatic (n=82), or with mild (n=21) or moderate (n=9) disease and control healthy pregnant (n=10) females were included. Mothers blood and cord blood (n=80) was analysed for untargeted metabolome profiling and plasma cytokines by high-resolution mass spectrometry (MS) and multiplex cytokine bead array. Immune scan in mothers was done using flow cytometry. ResultsIn asymptomatic SARS-CoV-2 infection, --the amino acid metabolic pathways such as glycine, serine, L-lactate and threonine metabolism was upregulated, riboflavin and tyrosine metabolism, downregulated. In mild to moderate disease, the pyruvate and NAD+ metabolism (energy metabolic pathways) were mostly altered. In addition to raised TNF-, IFN-, IFN-{gamma}, IL-6 cytokine storm, IL-9 was increased in both mothers and neonates. Pyruvate and NAD+ metabolic pathways along with IL-9 and IFN-{gamma} had impact on non-classical monocytes, increased CD4 T cells and B cells but depleted CD8+ T cells. Cord blood mimicked the mothers metabolomic profiles by showing altered valine, leucine, isoleucine, glycine, serine, threonine in asymptomatic and NAD+ and riboflavin metabolism in mild and moderate disease subjects. ConclusionsOur results demonstrate a graduated immune-metabolomic interplay in mother and fetus in pregnant females with different degrees of severity of COVID-19 disease. IL-9 and IFN- {gamma} regulated pyruvate, lactate TCA metabolism and riboflavin metabolism with context to disease severity are hall marks of this materno-fetal metabolome. HighlightsO_LISARS-CoV-2 infection alters energy consumption metabolic pathways during pregnancy. C_LIO_LIPregnant women with mild to moderate COVID-19 show increased energy demands, and consume stored glucose by upregulating pyruvate and NAD+ metabolism. C_LIO_LIIncreased TNF- and IL-9 in mild COVID-19 disease involve TCA cycle to produce lactate and consume stored glucose by up regulating pyruvate and nicotinamide and nicotinate metabolism. C_LIO_LIWith mild to moderate disease, raised IL-9 and TNF-, decreased riboflavin pathway, exhaustion of T and B cells cause pathogenesis. C_LIO_LICord blood mimics the metabolic profile of mothers peripheral blood, SARS- CoV-2 infection reshapes immune-metabolic profiles of mother-infant dyad. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=141 HEIGHT=200 SRC="FIGDIR/small/540101v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@657cc3org.highwire.dtl.DTLVardef@e1e76forg.highwire.dtl.DTLVardef@12153f2org.highwire.dtl.DTLVardef@10e5332_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2020

Evolutionary genetics of Drosophila melanogaster immunity: role of the X chromosome and sex-specific dominance

Intralocus Sexual Conflict (IaSC) ensues when males and females of the same species experience divergent selection on shared traits. A large number of traits have been implicated in IaSC and there is growing evidence for sexual antagonism associated with immunity. X chromosomes are thought to be hotspots of sexually antagonistic genetic variation and have been shown to harbour substantial immunity-related genetic variation. Here, using interpopulation crosses and cytogenetic cloning, we investigated the role of the X chromosome in improved immune response of laboratory populations of the fruit-fly Drosophila melanogaster selected against systemic infection by Pseudomonas entomophila. We could not detect any contribution of the X chromosome in the evolved immune response of our selected populations. However, we found strong evidence of sex-specific dominance related to immunity in our populations. Our results indicate that alleles that confer a superior immune response to the selected populations are, on average, partially dominant in females but partially recessive in males. We argue that sex-specific dominance over immunity evolved as a by-product of sexually antagonistic selection in the wild ancestors of our populations. We also highlight sex-specific dominance as a potential mechanism of sex differences in immunity, with population-level sex differences primarily driven by sex differences in heterozygotes.

evolutionary biology↗

bioRxiv2019

Development and Validation of Phenotype Classifiers across Multiple Sites in the Observational Health Sciences and Informatics (OHDSI) Network

ObjectiveAccurate electronic phenotyping is essential to support collaborative observational research. Supervised machine learning methods can be used to train phenotype classifiers in a high-throughput manner using imperfectly labeled data. We developed ten phenotype classifiers using this approach and evaluated performance across multiple sites within the Observational Health Sciences and Informatics (OHDSI) network.\n\nMaterials and MethodsWe constructed classifiers using the Automated PHenotype Routine for Observational Definition, Identification, Training and Evaluation (APHRODITE) R-package, an open-source framework for learning phenotype classifiers using datasets in the OMOP CDM. We labeled training data based on the presence of multiple mentions of disease-specific codes. Performance was evaluated on cohorts derived using rule-based definitions and real-world disease prevalence. Classifiers were developed and evaluated across three medical centers, including one international site.\n\nResultsCompared to the multiple mentions labeling heuristic, classifiers showed a mean recall boost of 0.43 with a mean precision loss of 0.17. Performance decreased slightly when classifiers were shared across medical centers, with mean recall and precision decreasing by 0.08 and 0.01, respectively, at a site within the USA, and by 0.18 and 0.10, respectively, at an international site.\n\nDiscussion and ConclusionWe demonstrate a high-throughput pipeline for constructing and sharing phenotype classifiers across multiple sites within the OHDSI network using APHRODITE. Classifiers exhibit good portability between sites within the USA, however limited portability internationally, indicating that classifier generalizability may have geographic limitations, and consequently, sharing the classifier-building recipe, rather than the pre-trained classifiers, may be more useful for facilitating collaborative observational research.

bioinformatics↗