Biology subjects

Giri, B.

Publications and source records attributed to Giri, B..

13 recordsLinked to original sources

bioRxiv2026

Aberrant accumulation of α-synuclein might be linked with the progressive motor deficits in a mouse model of Angelman syndrome

Dysfunction of maternal UBE3A leads to Angelman syndrome (AS), which is characterized by significant intellectual and motor debilities. However, the molecular underpinnings of the behavioral deficits associated with UBE3A dysfunction remain obscure. In this study, we utilized a model mouse of AS and report, for the first time, that the aberrant accumulation of -synuclein may be linked to the development of AS. Firstly, we demonstrated a progressive deterioration of various motor functions in AS mice beginning from the early adolescent phase. Subsequently, we observed an age-dependent increase in the accumulation of both soluble and insoluble -synuclein, including its pathological variant (pSer129), in the striatum and substantia nigra dopaminergic neurons of AS mice. We also found that Ube3a interacts with -synuclein and promotes its proteasome-mediated degradation, as evidenced by decreased levels of K48-linked polyubiquitinated -synuclein in the brain samples of AS mice in comparison to wild-type animals. Finally, using an RT2 Profiler PCR Array that analysed 84 genes specifically related to dopamine and serotonin pathways, we identified altered transcript level of various genes in the striatal tissues of AS mice that are commonly associated with nigrostriatal dysfunctions in Parkinson's disease. These findings highlight -synuclein as a novel target of Ube3a and suggest that -synuclein pathology may contribute to the progressive motor and other behavioral abnormalities witnessed in AS mice.

neuroscience↗

bioRxiv2026

OsGGCT1 provides tolerance to Fusarium oxysporum in Arabidopsis thaliana by upregulating γ-glutamyl cycle

{gamma}-Glutamyl cyclotransferases (GGCTs) belongs to class of cytosolic enzymes that are responsible for glutathione (GSH) degradation under stress conditions. They regulate GSH homeostasis through the {gamma}-glutamyl cycle which is responsible for maintaining the synthesis of GSH as well as its breakdown, enabling recycling of its constituent amino acids. Although GGCTs have been implicated in enhancing heavy metal (HMs) tolerance in plants, their role in biotic stress remains largely unexplored. Previously, OsGGCT1 was identified as a gene strongly upregulated in Fusarium stress. In this study, the GGCT1 homolog from Oryza sativa japonica was characterized for its role in conferring tolerance to Fusarium oxysporum (F.O.). Similar to abiotic factors, biotic stresses significantly impact crop yield and productivity. The rhizosphere harbors diverse microbial communities, including harmful pathogens such as F. oxysporum. Fusarium causes wilt disease in a variety of plant species, such as: tomato, legumes, rice, and Arabidopsis thaliana. Our results demonstrate that overexpression of OsGGCT1 enhanced tolerance to F. oxysporum in A. thaliana, primarily by reducing fungal spore accumulation. Transgenic plants showed elevated expression of OsGGCT1 along with AtGSH1 and AtGSH2, reduced levels of reactive oxygen species (ROS), improved growth and photosynthetic performance and enhanced activities of the antioxidant enzymes. OsGGCT1 serves as a key component in maintaining GSH homeostasis by supporting glutamate (Glu) regeneration necessary for sustained GSH biosynthesis. Overall, these findings identify OsGGCT1 as an important constituent of the GSH-mediated detoxification pathway against Fusarium oxysporum and provide valuable molecular insights for developing Fusarium-tolerant rice varieties with reduced fungal accumulation.

plant biology↗

bioRxiv2026

Occurrence of (oo)cysts of Cryptosporidium and Giardia on vegetables across Nepal

Gastrointestinal disorder caused by the ingestion of (oo)cysts of Cryptosporidium and Giardia is one of the major health problems in developing countries. Fruits and vegetables that are usually consumed unpeeled, poorly washed and or cooked and are the major modes of transmission. Frequent large-scale screening of the food samples is necessary to prevent outbreaks but screening of vegetables for such microbes is limited in Nepal. In this study, we used a smartphone microscopy system to study prevalence and quantification of (oo)cysts of Cryptosporidium and Giardia in 651 vegetable samples collected from nine major vegetable collection sites across Nepal. The overall prevalence rate of vegetable samples was 37.5% with at least with one of the parasites. We found that 23.2% samples were contaminated with Giardia and 33.3% samples were contaminated with Cryptosporidium. Among eight vegetable types, the prevalence rate was lowest in carrot (20%) and highest in spinach (48%). The prevalence rate of vegetable samples at different sites ranged from 13% in Dhading to 61% in Dhangadi. The contamination rate was 28% for winter, 43% for summer and 33% for monsoon seasons in samples collected from Kathmandu. These vegetables should be considered as a potential source of parasitic contamination in people. These vegetables can cause infection if consumed poorly washed and or cooked, posing a potential source of parasitic contamination in people.

microbiology↗

bioRxiv2025

Furrow tillage reduces soil carbon loss and enhances microbial metabolism

With increasing global carbon loss from agricultural fields, agricultural practices should be monitored with proper regulatory measures. To address three problems of minimising carbon loss, optimising soil fertility and enhancing soil microbiota together, this study has developed a new innovative "Furrow tillage" approach that affords a balance between conventional and conservative tillage. Based on two years of trials in rice fields at multiple sites, this practice has justifications from agronomy, geochemistry, crop physiology, and molecular microbiology. Furrow tillage illustrated low carbon loss, similar to no-tillage, while retaining high nutrient bioavailability, similar to deep tillage. Microbial diversity, molecular responses and metabolic activities showed that furrow tillage induced microbial interactions while allowing a better entrapment of carbon dioxide in the soil. The study used CO2 flux, spatial distribution, total and available elemental analysis, plant ultra-structural observations, microbial metagenomics, high-throughput sequencing and molecular modelling to establish an optimal soil-crop quality, microbial maintenance and reduce carbon loss through furrow tillage practice.

ecology↗

bioRxiv2025

Quantitative proteomics and phosphoproteomics analyses identify sex-biased protein ontologies of S. japonicum

Schistosoma japonicum (S. japonicum) is one of the major causative agents of human schistosomiasis in Asia. Identification of differentially expressed proteins (DEPs) between male and female worms could reveal critical signaling pathways that are involved in sexual maturation and egg production. In the study, quantitative proteome and phosphoproteome profiles were obtained from adult male and female worms of S. japonicum. A total of 2,710 unique proteins, including 2,055 proteins and 924 phosphorylated proteins, were identified. We identifed 252 ([~]12.5%) non-phosphorylated and 209 (11.7%) phosphorylated DEPs between males and females. Combined with the RNA sequencing (RNA-seq) results, 22 non-phosphorylated DEPs exhibited corresponding mRNA-level changes. Next, several identified non-phosphorylated DEPs were further shown to be involved in sex-biased biological processes, including vitellocyte development, oviposition, and parasite mobility by RNA interference, which were also supported by their cellular niches by analyzing previously published single-cell RNA seq data. Furthermore, we annotated 96 kinases of S. japonicum based on the obtained phosphorylated proteins, of which CMGC/MAPK, Atypical/RIO are significantly activated in males, while CAMK/CAMKL, AGC/DMPK, and STE/STE7 are activated in females. Finally, the potential drugs targeting these kinases were determined in silico, resulting in the identification of 28 S. japonicum kinases as potentially targetable by 30 FDA-approved drugs. Overall, our study provided a collection of evidence-based proteomic and phosphoproteomic resources of S. japonicum and identified sex-biased proteins, phosphopeptides, and kinases, which could serve as potentially effective targets for developing novel interventions against schistosomiasis.

microbiology↗

bioRxiv2025

Dysregulation of neuronal activity-dependent immediate early genes in a mouse model of Angelman syndrome

Angelman syndrome (AS) is a debilitating neurodevelopmental disorder triggered by impaired function of the maternal UBE3A gene, which codes a protein that functions as a ubiquitin ligase and transcriptional coactivator. Ube3a maternal deficient mice replicate many key behavioral deficits associated with AS; however, the underlying molecular mechanisms remain poorly understood. Using an RT2 Profiler PCR array that summarizes the expression of 84 genes regulating synaptic plasticity, we identified a number of dysregulated genes in the visual cortex of AS mice brains at postnatal day 25 (P25) compared to wild-type animals. In-depth analysis revealed that various immediate early genes (IEGs), like Arc, Egr1-4, and Homer, are dramatically down-regulated in the visual cortex of AS mice with regard to wild-type controls at P25. Moreover, the dark rearing of wild-type mice considerably decreased the levels of these IEGs to nearly the same level as those found in AS mice, along with the down-regulation of Ube3a. Furthermore, a significant reduction in the expression of these IEGs can also be observed in the hippocampus of AS mice. Finally, we demonstrate that the augmented activity of HDAC2 in the AS mice brain might be connected with the down-regulation of various IEGs and other synaptic plasticity-regulating genes. These findings indicate that the deregulated expression of neural activity-dependent IEGs could be linked with abnormal synaptic plasticity and associated behavioral deficits observed in AS mice.

neuroscience↗

bioRxiv2024

Extended Poisson Gaussian-Process Latent Variable Model for Unsupervised Neural Decoding

Dimension reduction on neural activity paves a way for unsupervised neural decoding by dissociating the measurement of internal neural state repetition from the measurement of external variable tuning. With assumptions only on the smoothness of latent dynamics and of internal tuning curves, the Poisson Gaussian-process latent variable model (P-GPLVM) (Wu et al., 2017) is a powerful tool to discover the low-dimensional latent structure for high-dimensional spike trains. However, when given novel neural data, the original model lacks a method to infer their latent trajectories in the learned latent space, limiting its ability for estimating the internal state repetition. Here, we extend the P-GPLVM to enable the latent variable inference of new data constrained by previously learned smoothness and mapping information. We also describe a principled approach for the constrained latent variable inference for temporally-compressed patterns of activity, such as those found in population burst events (PBEs) during hippocampal sharp-wave ripples, as well as metrics for assessing whether the inferred new latent variables are congruent with a previously learned manifold in the latent space. Applying these approaches to hippocampal ensemble recordings during active maze exploration, we replicate the result that P-GPLVM learns a latent space encoding the animals position. We further demonstrate that this latent space can differentiate one maze context from another. By inferring the latent variables of new neural data during running, certain internal neural states are observed to repeat, which is in accordance with the similarity of experiences encoded by its nearby neural trajectories in the training data manifold. Finally, repetition of internal neural states can be estimated for neural activity during PBEs as well, allowing the identification for replay events of versatile behaviors and more general experiences. Thus, our extension of the P-GPLVM framework for unsupervised analysis of neural activity can be used to answer critical questions related to scientific discovery.

neuroscience↗

bioRxiv2022

Smartphone-Operated Affordable PCR Thermal Cycler for the Detection of Antimicrobial Resistant Bacterial Genes

ObjectivesAntimicrobial resistance (AMR) is a global public health threat. Surveillance of AMR requires affordable, rapid, and user-friendly diagnostic method. Our aim was to develop a low-cost thermocycler to perform polymerase chain reaction (PCR). MethodsWe developed a smartphone-operated PCR thermal cycler using locally available recycled materials. The thermal cycler was used for the amplification for three bacterial genes - bla-TEM and bla-CTXM and 16s rRNA in human urine samples. The performance of custom-built thermal cycler was compared with the commercial one. ResultsThe thermal cycler was portable (<1kg weight), required 12 V power supply, 25 {micro}L of solution, and cost only USD50.0. Temperature and time conditions were instructed using a custom-built smartphone application. The ramping rate of was 0.23{degrees}C for heating and 0.43{degrees}C for cooling, set temperatures were within {+/-} 0.5 {degrees}C of target showing a good thermal stability. The antibiotic sensitivity test of human urine samples showed they were highly resistance and multi-resistant. Nearly 46 % (n=54) E. coli isolates were positive in ESBL screening test. The custom-built thermocycler was able to accurately predict the presence of bla-TEM and bla-CTXM genes (n=6). ConclusionsWe developed and demonstrated a portable, low-cost, easy-to-use, and smartphone-operated PCR thermal cycler. Since it is portable, it can be used in remote location and field settings, including places without stable power supply. The use of the thermal cycler system can be extended, beyond the detection of AMR genes, e.g., in clinical diagnosis, genetics, forensic analysis, and environmental protection.

molecular biology↗

bioRxiv2021

Estimation of the Acetylcholinesterase activity of honey bees in Nepal

Decline in honey bee colonies possess a serious threat to biodiversity and agriculture. Prior detection of the stresses with the help of biomarkers and their management ensures honey bees survivability. Acetylcholinesterase (AChE) is a promising biomarker to monitor exposure of honey bees towards environmental pollutants. In this preliminary study, we measured AChE activity in forager honey bees collected from six districts of Nepal, Kathmandu, Bhaktapur, Lalitpur, Chitwan, Rupandehi and Pyuthan during autumn and winter seasons. We estimated AChE tissue and specific activities from bees heads using commercial kit based on Ellman assay and protein concentration using Lowry assay. In total, we collected 716 foragers belonging to A. cerana, A. mellifera and A. dorsata. A significant increase in all three parameters measured: AChE tissue activity, AChE specific activity and protein concentration was observed in winter samples. Both AChE tissue and specific activities were lower in A. mellifera compared to either A. cerana or A. dorsata. Protein concentration was higher in A. mellifera than in A. dorsata and lower than in A. cerana. We show correlation between both AChE tissue and specific activities and protein concentration across season and species and discuss possible factors contributing to the observations. Our results clearly indicate the presence of stress in the winter which is manifested through overexpression of the AChE. We recommend a detailed study to determine the factors accountable for the stresses for better management of honey bees in Nepal.

ecology↗

bioRxiv2020

A smartphone microscope method for simultaneous detection of (oo)cyst of Cryptosporodium and Giardia

Gastrointestinal disorders caused by ingestion of (oo)cysts of Cryptosporodium and Giardia is one of the major health problems in developing countries. We developed a smartphone based microscopic assay method to screen (oo)cysts of Cryptosporodium and Giardia contamination in vegetable and water samples. We used sapphire ball lens as the major imaging element to modify a smartphone as a microscope. Imaging parameters such as field of view and magnification, and image contrast under different staining and illumination conditions were measured. The smartphone microscope method consisting of ball lens of 1 mm diameter, white LED as illumination source and Lugolss iodine staining provided magnification and contrast capable of distinguishing (oo)cysts of Crypstopsporodium and Giardia in the same sample. The analytical performance of the method was tested by spike recovery experiments. The spiking recovery experiments performed on cabbage, carrot, cucumber, radish, tomatoes, and water resulted 26.8{+/-}10.3, 40.1{+/-}8.5, 44.4{+/-}7.3, 47.6{+/-}11.3, 49.2 {+/-}10.9, and 30.2{+/-}7.9% recovery for Cryptosporodium, respectively and 10.2{+/-}4.0, 14.1{+/-}7.3, 24.2{+/-}12.1, 23.2{+/-}13.7, 17.1{+/-}13.9, and 37.6{+/-}2.4 % recovery for Giardia, respectively. These recovery results were found to be similar when compared with the commercial brightfield and fluorescence microscopes. We tested the smartphone microscope system for detecting (oo)cysts on 7 types of vegetable (n=196) and river water (n=18) samples. Forty two percent vegetable and thirty-nine percent water samples were found to be contaminated with Cryptosporodium oocyst. Similarly, thirty one percent vegetable and thirty three percent water samples were contaminated with Giardia cyst. This study showed that the developed method can be a cheaper alternative for simultaneous detection of (oo)cysts in vegetable and water samples.

pathology↗

bioRxiv2019

Neural Mediators of Altered Perceptual Choice and Confidence Using Social Information

Understanding how individuals utilize social information while making perceptual decisions and how it affects their decision confidence is crucial in a society. Till date, very little is known about perceptual decision making in humans under the influence of social cues and the associated neural mediators. The present study provides empirical evidence of how individuals get manipulated by social cues while performing a face/car identification task. Subjects were significantly influenced by what they perceived as decisions of other subjects while the cues in reality were manipulated independently from the stimulus. Subjects in general tend to increase their decision confidence when their individual decision and social cues coincide, while their confidence decreases when cues conflict with their individual judgments often leading to reversal of decision. Using a novel statistical model, it was possible to rank subjects based on their propensity to be influenced by social cues. This was subsequently corroborated by analysis of their neural data. Neural time series analysis revealed no significant difference in decision making using social cues in the early stages unlike neural expectation studies with predictive cues. Multivariate pattern analysis of neural data alludes to a potential role of frontal cortex in the later stages of visual processing which appeared to code the effect of social cues on perceptual decision making. Specifically medial frontal cortex seems to play a role in facilitating perceptual decision preceded by conflicting cues.

neuroscience↗

bioRxiv2019

Targeting tumor intrinsic metabolic node in pancreatic cancer causes tumor regression, remodels extracellular matrix and sensitizes to anti-PD1 therapy.

Pancreatic ductal adenocarcinoma (PDAC) is considered to be a highly immunosuppressive and heterogenous neoplasm. Despite improved knowledge regarding the genetic background of the tumor and better understanding of the tumor microenvironment, immune checkpoint inhibitor therapy (targeting CTLA-4, PD-1, PD-L1) has not been very successful against PDAC.\n\nThe robust desmoplastic stroma, along with an extensive extracellular matrix (ECM) that is rich in hyaluronan, plays an integral role in this immune evasion. Hexosamine biosynthesis pathway (HBP), a shunt pathway of glycolysis, is a metabolic node in cancer cells that can promote survival pathways on one hand and influence the hyaluronan synthesis in the ECM on the other. The rate-limiting enzyme of the pathway, glutamine-fructose amidotransferase (GFAT1), uses glutamine and fructose 6-phosphate to eventually synthesize UDP-GlcNAc.\n\nIn the current manuscript, we target this glutamine-utilizing enzyme by a small molecule glutamine analog (6-diazo-5-oxo-L-norleucine or DON). Our results show that DON decreases the self-renewal potential and metastatic ability of tumor cell. Further, treatment with DON results in a decrease in hyaluronan and collagen in the tumor microenvironment, leading to an extensive remodeling of the ECM. this in turn, increases CD8+ cytotoxic T-cells infiltration, and makes the tumors tumors more amenable and sensitive to anti-PD1 therapy.

cancer biology↗

bioRxiv2018

O-GlcNAc modification of oncogenic transcription factor Sox2 promotes protein stability and regulates self-renewal in pancreatic cancer

Pancreatic cancer is among the 3rd leading cause of cancer related deaths in the United States along with a 5-year survival rate of 7%. The aggressive biology of the disease is responsible for such dismal outcome and is manifested by an increase in self-renewal capacity of the cancer cells, which leads to an increased rate of tumor-recurrence, contributing to poor prognosis. Transcription factor SOX2 maintains a critical balance between differentiation and \"stemness\" and is thus tightly regulated within a cell. In cancer, SOX2 is aberrantly \"turned-on\" leading to activation of self-renewal pathways in cancer. Regulation of Sox2 in cancer is poorly understood. In the current study, we show for the first time that in pancreatic cancer, Sox2 is modified by addition of O-GlcNAc moiety, catalyzed by OGT (O-GlcNAc Transferase) at S246. This activates Sox2 transcriptional activity by stabilizing the protein in the nucleus. A CRISPR-OGT knockout in pancreatic cancer cell line S2VP10 resulted in a delayed tumor initiation. We further showed that mutation of this site (S246A) prevents the modification of Sox2 and its downstream activity. Our study also demonstrated that targeting OGT in vivo with a small molecule inhibitor OSMI, results in decreased tumor burden, delayed tumor progression and a decreased expression of SOX2 in pancreatic cancer cells. Our study highlights for the first time that that the O-GlcNAc transferase dependent SOX2 glycosylation has a profound effect on the transcriptional activity of SOX2 and is instrumental in determining self-renewal in pancreatic cancer.\n\nSignificanceOur study highlights for the first time that that the O-GlcNAc transferase dependent SOX2 glycosylation determines self-renewal in pancreatic cancer which is responsible for tumor initiation.

cancer biology↗