Biology subjects

Raju, V.

Publications and source records attributed to Raju, V..

4 recordsLinked to original sources

bioRxiv2025

Differential Burst dynamics of Slow and Fast gamma rhythms in Macaque primary visual cortex

Gamma oscillations have been ubiquitously observed across a wide spectrum of brain areas in multiple species. They tend to occur intermittently in the form of bursts, rather than being produced as sustained and continuous rhythmic activity. Recent studies have shown that large visual sinusoidal gratings elicit two distinct gamma rhythms, namely, slow ({approx} 20-35 Hz) and fast gamma ({approx} 40-65 Hz), in the primary visual cortex (V1) of non-human primates. However, their mechanisms of generation and potential functional role in cortical processing remain unclear. Details of their burst signatures could potentially provide crucial insights about how the two rhythms influence network dynamics. Therefore, we computed burst statistics (durations and latencies) of simultaneously induced slow and fast gamma rhythms in the local field potential (LFP) recorded from area V1 of two adult female bonnet monkeys using several burst estimation methods. We found that slow gamma rhythm exhibited significantly longer burst durations and longer latencies as compared to fast gamma. Slow gamma exhibited higher long-range synchrony compared to fast gamma, as estimated by coherence and weighted phase lag index (WPLI), which could aid in enhanced global coordination in neocortex. Interestingly, longer burst length of slow-gamma could be replicated in a recently-developed noisy Wilson-Cowan network model by simply changing the firing-rate time-constant of the corresponding inhibitory interneuronal population, which leads to both slower and longer bursts. These results are consistent with the hypothesis that the two oscillations are generated by different inter-neuronal classes that operate over different temporal and spatial scales of integration. Significance statementSlow ({approx} 20-35 Hz) and fast gamma ({approx} 40-65 Hz) are two distinct rhythms known to be induced by large visual gratings in the primary visual cortex (V1). Interestingly, gamma oscillations manifest in the form of transient and stochastic epochs, generally termed as "bursts". We estimated the durations of stimulus-induced slow and fast gamma bursts generated in the local field potential (LFP) recorded from V1 of monkeys. Slow gamma bursts had significantly longer durations and increased latency to onset compared to fast gamma, which was replicated in a noisy Wilson-Cowan model by changing the time-constant associated with inhibitory neuronal population. These results suggest that slow and fast gamma are generated by different inter-neuronal networks operating at different spatio-temporal scales.

neuroscience↗

bioRxiv2025

Big1 is a cell cycle regulator linking cell size to basal body number

Cell size control in dividing cells coordinates cell growth with cell division. In the ciliated protozoan, Tetrahymena, there is a tight link between cell size and the cytoskeletal assemblies at the cell cortex organized around basal bodies (BBs). BBs dictate the distribution of ciliary units governing cell motility and are organized into 18-22 ciliary rows. The number of BBs per cell remains remarkably consistent even when the number and lengths of ciliary rows vary. big1-1 mutant cells are large and have elevated numbers of BBs, providing a system to investigate links between BB number and cell size control. We discovered BIG1 encodes a protein with an RRM3 RNA-binding domain similar to the fission yeast meiotic entry gene, mei2. The big1-1 mutation is a predicted null allele. By extending the duration of specific cell cycle stages conducive to new BB assembly, big1-1 promotes cell size increases through BB amplification. In contrast, excess Big1 protein localizes to BBs and drives cells into premature cell division, resulting in small cells with fewer BBs. Thus, Tetrahymena Big1 localizes to BBs and controls cell cycle progression, indicating BBs and Big1 link cell growth to the cell division cycle.

cell biology↗

bioRxiv2024

Comparison of a novel potentiator of CFTR channel activity to ivacaftor in ameliorating mucostasis caused by cigarette smoke in primary human bronchial airway epithelial cells

BackgroundCystic Fibrosis causing mutations in the gene CFTR, reduce the activity of the CFTR channel protein, and leads to mucus aggregation, airway obstruction and poor lung function. A role for CFTR in the pathogenesis of other muco-obstructive airway diseases such as Chronic Obstructive Pulmonary Disease (COPD) has been well established. The CFTR modulatory compound, Ivacaftor (VX-770), potentiates channel activity of CFTR and certain CF-causing mutations and has been shown to ameliorate mucus obstruction and improve lung function in people harbouring these CF-causing mutations. A pilot trial of Ivacaftor supported its potential efficacy for the treatment of mucus obstruction in COPD. These findings prompted the search for CFTR potentiators that are more effective in ameliorating cigarette-smoke (CS) induced mucostasis. MethodsA novel small molecule potentiator (SK-POT1), previously identified in CFTR binding studies, was tested for its activity in augmenting CFTR channel activity using patch clamp electrophysiology in HEK-293 cells, a fluorescence-based assay of membrane potential in Calu-3 cells and in Ussing chamber studies of primary bronchial epithelial cultures. Addition of cigarette smoke extract (CSE) to the solutions bathing the apical surface of Calu-3 cells and primary bronchial airway cultures was used to model COPD. Confocal studies of the velocity of fluorescent microsphere movement on the apical surface of CSE exposed airway epithelial cultures, were used to assess the effect of potentiators on CFTR-mediated mucociliary movement. ResultsWe showed that SK-POT1, like VX-770, was effective in augmenting the cyclic AMP-dependent channel activity of CFTR. SK-POT-1 enhanced CFTR channel activity in airway epithelial cells previously exposed to CSE and ameliorated mucostasis on the surface of primary airway cultures. ConclusionTogether, this evidence supports the further development of SK-POT1 as an intervention in the treatment of COPD.

physiology↗

bioRxiv2021

Analysis of key genes and pathways associated with the pathogenesis of Type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is the most common endocrine disorder which poses a serious threat to human health. This investigation aimed to screen the candidate genes differentially expressed in T2DM by bioinformatics analysis. The expression profiling by high throughput sequencing of GSE81608 dataset was retrieved from the gene expression omnibus (GEO) database and analyzed to identify the differentially expressed genes (DEGs) between T2DM and normal controls. Then, Gene Ontology (GO) and pathway enrichment analysis, protein-protein interaction (PPI) network, modules, miRNA-hub gene regulatory network construction and TF-hub gene regulatory network construction, and topological analysis were performed. Receiver operating characteristic curve (ROC) analysis was also performed to verify the diagnostics value and expression of identified hub genes. A total of 927 DEGs (461 were up regulated and 466 down regulated genes) were identified in T2DM. GO and REACTOME results showed that DEGs mainly enriched in protein metabolic process, establishment of localization, metabolism of proteins and metabolism. The top centrality hub genes APP, MYH9, TCTN2, USP7, SYNPO, GRB2, HSP90AB1, UBC, HSPA5 and SQSTM1 were screened out as the critical genes among the DEGs from the PPI network, modules, miRNA-hub gene regulatory network construction and TF-hub gene regulatory network. ROC analysis provide diagnostics value of hub genes. This study identified key genes, signal pathways and therapeutic agents, which might help us, improve our understanding of the mechanisms of HGPS and identify some new therapeutic agents for T2DM.

bioinformatics↗