Biology subjects

Saraf, S.

Publications and source records attributed to Saraf, S..

9 recordsLinked to original sources

bioRxiv2026

Glutamine Metabolism Supports α cell Mass and Glucagon Secretion

The liver- cell axis is a finely tuned biological rheostat that regulates whole body amino acid availability. Pancreatic cells secrete glucagon that regulates amino acid catabolism through gluconeogenesis and ureagenesis, yet the mechanisms linking amino acid levels to cell growth and function are not fully understood. Here, we identify glutaminase, the enzyme that catalyzes glutamine catabolism, as a critical cell regulator. Glutaminase is highly enriched in cells across species. cell expression of glutaminase is required for nutrient-dependent mTORC1 activation, suppression of AMPK signaling, and sustained expression of the glutamine transporter SLC38A5. This establishes a feed-forward loop linking glutamine metabolism to amino acid sensing and growth. Reduced glutaminase activity impairs dynamic glucagon secretion in response to low glucose and amino acids. Together, these findings highlight the importance of glutamine metabolism in cell growth and hormone secretion and suggest it may play a role in cell adaptation to hyperaminoacidemia.

physiology↗

bioRxiv2025

Variations in neuronal selectivity create efficient representational geometries for perception

A complete understanding of population coding requires connecting multiple levels of neural processing: individual responses, population representations, and behavior. We link these by relating the distribution of neuronal tuning properties to a populations representational geometry and its efficiency for perceptual tasks. We use theory, analysis of recordings from macaque primary visual cortex (V1), and simulations to reveal how diversity of tuning amplitude and bandwidth enhances the population code for visual discrimination and identification. Both types of diversity drive different, but complementary changes to the representational geometry. Amplitude diversity increases the Euclidean distance between the responses to different stimuli, while bandwidth diversity creates a larger angular distance between them. The first utilizes the range of firing rates available to neurons, and the second exploits the high-dimensional nature of population responses. Population codes can be improved using these two different geometric changes, and amplitude and bandwidth diversity provide biological mechanisms for doing so. HighlightsO_LI- Perceptual performance is improved both by increased diversity of response amplitude and increased diversity of tuning bandwidth. C_LIO_LI- Both kinds of diversity improve visual discrimination and identification. C_LIO_LI- Amplitude diversity improves discrimination more, and bandwidth diversity improves identification more. C_LIO_LI- Representational geometry reveals the mechanisms of these effects. C_LI

neuroscience↗

bioRxiv2025

Interactions of Natural Compounds and Biomolecules with Hepatitis C Virus RNA Untranslated Regions: Exploring Structural Modifications to Advance Pathogenesis Understanding and Antiviral Strategy Design

Hepatitis C virus (HCV), a 10 kb positive-strand RNA virus, primarily infects liver cells and is a major cause of liver cirrhosis, which can progress to hepatocellular carcinoma. The HCV RNA untranslated regions (UTRs) adopt topologies that serve as binding sites for host proteins and miRNAs, crucial for viral replication and pathogenesis. However, the precise interactors and mechanisms of these interactions remain unclear. This study investigates the architectural landscape of HCV UTRs alone and in the presence of various interactors. Structural analysis reveals stable HCV UTR topologies, but significant alterations occur upon interaction with miRNAs and phytochemicals, potentially critical for viral pathogenicity. Additionally, proteins SRSF7 and AKAP8L are identified as novel interactors, which could have implication in host immune evasion and enhanced virulence. These findings highlight new miRNAs, proteins, and small molecules as interactors of HCV UTRs, offering insights into HCV infectivity and therapeutic targets for antiviral interventions.

molecular biology↗

bioRxiv2025

A pan-gene catalogue of Asian cultivated rice

The rice genome underpins fundamental research and breeding, but the Nipponbare (japonica) reference does not fully encompass the genetic diversity of Asian rice. To address this gap, the Rice Population Reference Panel (RPRP) was developed, comprising high-quality assemblies of 16 rice cultivars to represent japonica, indica, aus, and aromatic varietal groups. The RPRP has been consistently annotated, supported by extensive experimental data and here we report the computational assignment, characterization and dissemination of stably identified pan-genes. We identified 25,178 core pan-genes shared across all cultivars, alongside cultivar-specific and family-enriched genes. Core genes exhibit higher gene expression and proteomic evidence, higher confidence protein domains and AlphaFold structures, while cultivar-specific genes were enriched for domains under selective breeding pressure, such as for disease resistance. This resource, integrated into public databases, enables researchers to explore genetic and functional diversity via a population-aware "reference guide" across rice genomes, advancing both basic and applied research.

genomics↗

bioRxiv2023

Building pangene sets from plant genome alignments confirms presence-absence variation

Consistent gene annotation in crops is becoming harder as genomes for new cultivars are frequently published. Gene sets from recently sequenced accessions have different gene identifiers to those on the reference accession, and might be of higher quality due to technical advances. For these reasons there is a need to define pangenes, which represent all known syntenic orthologues for a gene model and can be linked back to the original annotation sources. A pangene set effectively summarizes our current understanding of the coding potential of a crop and can be used to inform gene model annotation in new cultivars. Here we present an approach (get_pangenes) to identify and analyze pangenes that is not biased towards the reference annotation. The method involves computing Whole Genome Alignments (WGA), which are used to estimate gene model overlaps. After a benchmark on Arabidopsis, rice, wheat and barley datasets, we find that minimap2 performs better than the GSAlign WGA algorithm. Our results show that pangenes recapitulate known phylogeny-based orthologies while adding extra core gene models in rice. More importantly, get_pangenes can also produce clusters of genome segments (gDNA) that overlap with gene models annotated in other cultivars. By lifting-over CDS sequences, gDNA clusters can help refine gene models across individuals and confirm or reject observed gene Presence-Absence Variation. A collection of flowering-related genes from the barley pangenome are discussed in detail. Documentation and source code are available at https://github.com/Ensembl/plant-scripts.

genomics↗

bioRxiv2022

Genomic and phenotypic analyses suggest moderate fitness differences among Zika virus lineages

RNA viruses have short generation times and high mutation rates, allowing them to undergo rapid molecular evolution during epidemics. However, the extent of RNA virus phenotypic evolution within epidemics and the resulting effects on fitness and virulence remain mostly unknown. Here, we screened the 2015-2016 Zika epidemic in the Americas for lineage-specific fitness differences. We engineered a library of recombinant viruses representing twelve major Zika virus lineages and used them to measure replicative fitness within disease-relevant human primary cells and live mosquitoes. We found that two of these lineages conferred significant in vitro replicative fitness changes among human primary cells, but we did not find fitness changes in Aedes aegypti mosquitoes. Additionally, we found evidence for elevated levels of positive selection among five amino acid sites that define major Zika virus lineages. While our work suggests that Zika virus may have acquired several phenotypic changes during a short time scale, these changes were relatively moderate and do not appear to have enhanced virulence or transmission during the epidemic.

evolutionary biology↗

bioRxiv2020

Two sides of a coin: a Zika virus mutation selected in pregnant rhesus macaques promotes fetal infection in mice but at a cost of reduced fitness in nonpregnant macaques and diminished transmissibility by vectors

Although fetal death is now understood to be a severe outcome of congenital Zika syndrome, the role of viral genetics is still unclear. We sequenced Zika virus (ZIKV) from a rhesus macaque fetus that died after inoculation and identified a single intra-host mutation, M1404I, in the ZIKV polyprotein, located in NS2B. Targeted sequencing flanking position 1404 in 9 additional macaque mothers and their fetuses identified M1404I at sub-consensus frequency in the majority (5 of 9, 56%) of animals and some of their fetuses. Despite its repeated presence in pregnant macaques, M1404I occurs rarely in humans since 2015. Since the primary ZIKV transmission cycle is human-mosquito-human, mutations in one host must be retained in the alternate host to be perpetuated. We hypothesized that ZIKV I1404 increases fitness in non-pregnant macaques and pregnant mice but is less efficiently transmitted by vectors, explaining its low frequency in humans during outbreaks. By examining competitive fitness relative to M1404, we observed that I1404 produced lower viremias in non-pregnant macaques and was a weaker competitor in tissues. In pregnant wildtype mice ZIKV I1404 increased the magnitude and rate of placental infection and conferred fetal infection, contrasting with M1404, which was not detected in fetuses. Although infection and dissemination rates were not different, Ae. aegypti transmitted ZIKV I1404 more poorly than M1404. Our data highlight the complexity of arbovirus mutation-fitness dynamics, and suggest that intrahost ZIKV mutations capable of augmenting fitness in pregnant vertebrates may not necessarily spread efficiently via mosquitoes during epidemics. IMPORTANCEAlthough Zika virus infection of pregnant women can result in congenital Zika syndrome, the factors that cause the syndrome in some but not all infected mothers are still unclear. We identified a mutation that was present in some ZIKV genomes in experimentally inoculated pregnant rhesus macaques and their fetuses. Although we did not find an association between the presence of the mutation and fetal death, we performed additional studies with it in non-pregnant macaques, pregnant mice, and mosquitoes. We observed that the mutation increased the ability of the virus to infect mouse fetuses but decreased its capacity to produce high levels of virus in the blood of non-pregnant macaques and to be transmitted by mosquitoes. This study shows that mutations in mosquito-borne viruses like ZIKV that increase fitness in pregnant vertebrates may not spread in outbreaks when they compromise transmission via mosquitoes and fitness in non-pregnant hosts.

microbiology↗

bioRxiv2019

Correlations in population dynamics in multi-component networks

This is a theoretical study of correlations in spiking activity between neuronal populations. We focus on the spike firing of entire local populations without regard to the identities of the neurons that fire the spikes, and show that such a population-level metric is more robust than correlations between pairs of neurons. Between any source and target populations, there is an intrinsic response time characterized by the phase-shift that maximizes the correlation between their spiking. We find that the alignment of gamma-band rhythms contributes significantly to the positive correlations between populations. Hence, the correlation metric sheds light on the transference of gamma rhythms between populations; the effectiveness of such transference has been hypothesized to be connected to communication between brain regions. We investigate the dependence of correlations on connectivity and degree of synchrony, and consider multi-component network motifs with configurations known to occur in real cortex, studying the correlations between components that are directly or indirectly connected, by single or multiple pathways, with or without feedback. Mechanistic explanations are offered for many of the phenomena observed.

neuroscience↗

bioRxiv2018

International travelers and genomics uncover a ‘hidden’ Zika outbreak

The ongoing Zika epidemic in the Americas has challenged public health surveillance, response, and control systems. Even as the epidemic appears to be near its end in the Americas, it is unclear whether substantial Zika virus transmission may still be ongoing. This issue is exacerbated by large discrepancies in local case reporting and significant delays in detecting outbreaks due to surveillance gaps. To uncover locations with lingering outbreaks in the Americas, we investigated travel-associated Zika cases diagnosed in the United States and Europe to identify signatures of transmission dynamics that were not captured by local reporting. We found that a large and unreported Zika outbreak occurred in Cuba during 2017, a year after peak transmission in neighboring countries, with cases still appearing in 2018. By sequencing Zika virus from infected travelers, we show that the 2017 outbreak in Cuba was sparked by long-lived lineages of Zika virus introduced from multiple places in the Americas a year prior. Our data suggest that while aggressive mosquito control in Cuba may initially have been effective at mitigating Zika virus transmission, in the absence of vaccines, herd immunity, or strong international coordination, such control measures may need to be maintained to be effective. Our study highlights how Zika virus may still be silently spreading in the Americas and provides a framework for more accurately understanding outbreak dynamics.

epidemiology↗