Biology subjects

Niraula, S.

Publications and source records attributed to Niraula, S..

6 recordsLinked to original sources

bioRxiv2026

Shotgun metagenomic and untargeted metabolomic analysis of gut microbiome associated with peripheral artery disease

Background: While the human gut microbiome is a potentially important and modifiable risk factor for cardiovascular diseases, the links between the gut microbiome and peripheral artery disease (PAD) and its clinical subgroups (claudication and chronic limb-threatening ischemia; CLTI) are not well understood. Methods: We used shotgun metagenomics and untargeted metabolomics to analyze the fecal samples of people with PAD and age- and sex-matched non-PAD controls collected in a cross-sectional manner. We used functional prediction pathways, a network analysis, and weighted gene co-expression network analysis of metagenomic, metabolomics, and clinical data to better understand PAD-associated dysbiosis. Results: Alpha and beta diversity were similar between the PAD (n=78) and non-PAD (n=20) groups. Differentially abundant species were dominated by those belonging to the Lachnospiraceae, Ruminococcaceae and Enterobacteriaceae families. Fecal butyrate levels were reduced between the non-PAD and PAD groups, but differences were not statistically significant. There was significantly reduced alpha diversity in the samples of the CLTI compared to claudication subgroup. Abundance of multiple butyrate producers were greater in the claudication group compared to CLTI. Network analysis revealed 5 meta-modules, each with specific associations to PAD presentation and metabolomic profiles, and species that are both top module hubs and differentially abundant between groups. Community interconnectedness appears to increase in claudication, followed by community disintegration in CLTI. Conclusions: This metagenomic-metabolomic analysis of the gut microbiome of individuals with PAD, highlights the importance of studying functional capacity, diversity, and connectivity between species. Microbial modules may allow an integrative view of the microbial ecology relevant to presence and progression of PAD.

microbiology↗

bioRxiv2025

Generation and maintenance of apical rib-like actin fibers in epithelial support cells of the Drosophila eye

Heterogeneity and complexity of cytoskeletal structures, and how these are regulated, is poorly understood. Here we use cells of the Drosophila pupal eye as models to explore diversity in the actin cytoskeleton. We found that different F-actin structures emerge in primary (1{degrees}), secondary (2{degrees}), and tertiary (3{degrees}) pigment cells as they mature. 1{degrees} cells became characterized by dense accumulations of apical F-actin that we termed Apical Ribs of Actin Fibers (ARAFs). The formins Diaphanous and Dishevelled Associated Activator of Morphogenesis are essential for generation of ARAFs, which are connected into a network by -Actinin, the villin Quail, and Spectrins, and linked to the apical membrane by Quail and Spectrins. ARAFs are contractile, stress-fiber-like, and connect to adherens junctions. Impairing ARAFs indicated that this network maintains cortical tension and is crucial for 1{degrees}s to achieve their characteristic shapes. Our evaluation of the three-dimensional shape of 1{degrees}s reveals that ARAFs are essential for the rounding and elevation of the apical membrane. Hence, a toolkit of conserved actin regulatory proteins builds and maintains a network of apical stress fibers that governs the morphology of the cell. Summary StatementThis study describes a novel F-actin network that shapes the apical region of cells of the Drosophila eye and uncovers a set of proteins that build and maintain the network.

developmental biology↗

bioRxiv2023

Amyloid pathology impairs homeostatic inhibitory synaptic plasticity

Alzheimers disease patients and mouse models exhibit aberrant neuronal activity and altered excitatory-to-inhibitory synaptic ratio. Using multicolor two-photon microscopy, we test how amyloid pathology alters the structural dynamics of excitatory and inhibitory synapses and their adaptation to altered visual experience in vivo in the visual cortex. We show that the baseline dynamics of mature excitatory synapses and their adaptation to visual deprivation are not altered in amyloidosis. Likewise, the baseline dynamics of inhibitory synapses are not affected. In contrast, visual deprivation fails to induce inhibitory synapse loss in amyloidosis, a phenomenon observed in nonpathological conditions. Intriguingly, inhibitory synapse loss associated with visual deprivation in nonpathological mice is accompanied by the broadening of spontaneous but not visually evoked calcium transients. However, such broadening does not manifest in the context of amyloidosis. We also show that excitatory and inhibitory synapse loss is locally clustered under the nonpathological state. In contrast, a fraction of synapse loss is not locally clustered in amyloidosis, indicating an impairment in inhibitory synapse adaptation to changes in excitatory synaptic activity.

neuroscience↗

bioRxiv2023

Repeated passive visual experience modulates spontaneous and novelty-evoked neural activity.

Familiarity creates subjective memory of repeated innocuous experiences, reduces neural and behavioral responsiveness to those experiences, and enhances novelty detection. The neural correlates of the internal model of familiarity and the cellular mechanisms of enhanced novelty detection following multi-day repeated passive experience remain elusive. Using the mouse visual cortex as a model system, we test how the repeated passive experience of a 45{degrees} orientation-grating stimulus for multiple days alters spontaneous and non-familiar stimuli evoked neural activity in neurons tuned to familiar or non-familiar stimuli. We found that familiarity elicits stimulus competition such that stimulus selectivity reduces in neurons tuned to the familiar 45{degrees} stimulus; it increases in those tuned to the 90{degrees} stimulus but does not affect neurons tuned to the orthogonal 135{degrees} stimulus. Furthermore, neurons tuned to orientations 45{degrees} apart from the familiar stimulus dominate local functional connectivity. Interestingly, responsiveness to natural images, which consists of familiar and non-familiar orientations, increases subtly in neurons that exhibit stimulus competition. We also show the similarity between familiar grating stimulus-evoked and spontaneous activity increases, indicative of an internal model of altered experience.

neuroscience↗

bioRxiv2022

Unusual Morphological Changes of Rugositalea oryzae, A Novel Wrinkled Bacterium Isolated from The Rice Rhizosphere, Under Nutrient Stress

Bacterial cell morphology might result from natural selection to gain a competitive advantage under environmentally stressful conditions such as nutrient limitation. A bacterial strain YC6860T isolated from the rhizosphere of rice (Oryza sativa L.) showed pleomorphic behavior with smooth cell morphology and wrinkled surface rods depending upon nutritional conditions. Based on scanning and transmission electron microscopy studies, we hypothesized that the surface-to-volume ratio of cells increases with decreasing nutrient concentrations. The transition from smooth to wrinkled cell surface morphology could be one of the adaptation strategies by which YC6860T maximizes its ability to access available nutrients. To characterize the properties of the wrinkled strain, we performed taxonomic and phylogenetic analyses. 16S rRNA gene sequencing results showed that the strain represented a novel, deep-rooting lineage within the order Rhizobiales with the highest similarity of 94.2% to Pseudorhodoplanes sinuspersici RIPI 110T. Whole genome sequencing was also performed to characterize its genetic features. The strain YC6860T might belong to a new genus, named Rugositalea, and a new species, named Rugositalea oryzae, In addition, taxonomic analysis showed that YC6860T is Gram-negative, aerobic, and rod-shaped with large regular wrinkles resembling a delicate twist of fusilli, measuring 0.5-0.6 {micro}m in width and 1.5-1.6 {micro}m in length under nutrient-limiting conditions. This unique cell structure with regular rugosity could be the first finding that has not been reported in the existing bacterial morphology.

microbiology↗

bioRxiv2020

The carboxyl-terminus of RAN translated GGGGCC nucleotide repeat expansions modulates toxicity in models of ALS/FTD

An intronic hexanucleotide repeat expansion in C9ORF72 causes familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This repeat is thought to elicit toxicity through RNA mediated protein sequestration and repeat-associated non-AUG (RAN) translation of dipeptide repeat proteins (DPRs). We generated a series of transgenic Drosophila models expressing GGGGCC (G4C2) repeats either inside of an artificial intron within a GFP reporter or within the 5 UTR of GFP placed in different downstream reading frames. Expression of 484 intronic repeats elicited minimal alterations in eye morphology, viability, longevity, or larval crawling but did trigger RNA foci formation, consistent with prior reports. In contrast, insertion of repeats into the 5 UTR elicited differential toxicity that was dependent on the reading frame of GFP relative to the repeat. Greater toxicity correlated with a short and unstructured carboxyl terminus in the glycine-arginine (GR) RAN protein reading frame. This change in C-terminal sequence triggered nuclear accumulation of all three RAN DPRs. A similar differential toxicity and dependence on the GR carboxyl terminus was observed when repeats were expressed in rodent neurons. The presence of the native carboxyl-termini across all three reading frames was partly protective. Taken together, these findings suggest that carboxyl terminal sequences outside of the repeat region may alter the behavior and toxicity of dipeptide repeat proteins derived from GGGGCC repeats.

genetics↗