Biology subjects

Nair, M.

Publications and source records attributed to Nair, M..

14 recordsLinked to original sources

bioRxiv2026

Impact of opioid-based versus opioid-free anaesthesia on postoperative recovery, circulating inflammatory cytokines and brain-derived neurotrophic factor.

Background Opioid-free anaesthesia (OFA) has emerged as an alternative to opioid-based anaesthesia (OBA), but its benefit over OBA for postoperative quality of recovery (QoR) remains unclear. To address this question while limiting variability inherent in clinical studies, such as analgesic regimens and patient psychosocial factors, we investigated the effects of OFA versus OBA on postoperative recovery in a controlled preclinical mouse model. Methods Adult male and female C57BL/6J mice underwent laparotomy or sham procedures under isoflurane anaesthesia, and were randomly assigned to saline (control), fentanyl (OBA), or dexmedetomidine (OFA) as intraoperative analgesic adjuncts. All mice received multimodal postoperative analgesia, including carprofen. We adapted a standardised multidimensional recovery model using six behavioural endpoints reflecting human QoR domains: body weight, food intake, locomotor activity, mechanical sensitivity, sucrose preference, and social interaction. These endpoints were assessed on postoperative days 1, 2, 3, and 7. Plasma inflammatory cytokine and brain-derived neurotrophic factor (BDNF) concentrations were also measured in parallel as potential biological correlates of recovery. Results Over the study period, we observed no treatment effect across behavioural endpoints in laparotomised mice, including body weight (P=0.157), food intake (P=0.884), locomotor activity (P=0.864), mechanical sensitivity (P=0.628), sucrose preference (P=0.615), and social interaction (P=0.442). Composite QoR scores did not differ between OFA and OBA groups (P=0.569), with no differences in postoperative circulating inflammatory cytokine or BDNF concentrations. Conclusions Dexmedetomidine-based OFA and fentanyl-based OBA produced similar postoperative behavioural recovery, circulating inflammatory cytokine and BDNF trajectories in laparotomised mice receiving multimodal postoperative analgesia.

animal behavior and cognition↗

bioRxiv2026

A Wireless Wearable Platform for Intravenous Drug Self-Administration in Freely Behaving Rats

Studying how drugs act on neuronal circuits requires delivering them with temporal precision while behavior proceeds undisturbed, a combination that tethered infusion systems cannot provide. We developed WEARIT (Wireless Equipment for Autonomous Rat Infusion Tasks), a wearable, tetherless infusion platform that gives freely moving rats intravenous access under either remote or closed-loop operant control. The device houses a reservoir, miniaturized pump, rechargeable battery and Bluetooth circuitry in a 3D-printed enclosure worn on the back. By measuring spontaneous locomotion, amphetamine-induced hyperlocomotion and food-reinforced operant responding, we show that WEARIT leaves these behaviors unchanged. Remotely triggered fentanyl infusions yielded reliable delivery with physiological responses confirmed by pulse oximetry, and self-administration acquisition and dose-response functions were comparable to conventional tethered systems. WEARIT removes a longstanding constraint on intravenous pharmacology, opening self-administration paradigms to naturalistic and enriched environments and to concurrent imaging or optogenetic manipulation of the circuits engaged by drug reinforcement.

neuroscience↗

bioRxiv2026

Keloid transcriptomics reveal heterogeneity in fibroblast subtype enrichment, gene expression, and immune cell responses

Keloid disease (KD) is a fibroproliferative skin disorder resulting from abnormal scar formation that causes pain, itching, and decreased quality of life. While multiple KD transcriptomic studies exist, the influence of cell type composition on bulk tissue gene expression is unknown. We characterized fibroblast subtype and immune cell enrichment using bulk RNA-Seq of head and neck keloid and matched adjacent normal skin tissue (MANST) from 14 patients (10 African American and 4 European American). Cell type enrichment was calculated by single sample gene set enrichment analysis. Linear mixed-effects models were employed for 1) differential cell type enrichment across tissue, 2) tissue type-specific associations between fibroblast subtypes and immune cells, and 3) differentially expressed genes (DEGs) across tissue. Validation was conducted in an independent cohort of 8 African Americans. Three fibroblast subtypes and 14 immune cell types were differentially enriched across tissue type. Further, 17 tissue type-specific fibroblast subtype-immune cell enrichment associations were identified, with 14 exhibiting decreased association in keloid tissue relative to MANST. After adjustment for cell type enrichment, MIR31HG and NR4A2 were significant DEGs with the largest positive and negative fold-changes, respectively. By considering cell type enrichment, underlying keloid tissue-specific cell type and gene expression associations were revealed.

bioinformatics↗

bioRxiv2026

The Herbicide Glyphosate Promotes Hypertension via Gut Microbiota-Mediated Mechanisms

Glyphosate, the active ingredient in herbicide Roundup, is the most widely used environmental contaminant that has been extensively studied for its potential carcinogenic effects. In the US alone, a staggering 81% of the US population [≥]6 years of age is exposed to glyphosate. Notably, this coincides with the alarming rise in the incidence of hypertension, the single largest risk factor for global mortality through cardiovascular diseases. Here we asked if there is a link between glyphosate exposure and hypertension, the premise being that glyphosate targets the shikimate pathway present in gut microbiota coupled with more recent knowledge that gut microbiota causally regulate blood pressure. We hypothesized that glyphosate elevates hypertension through microbiota-mediated mechanisms and document a highly concerning detrimental effect of glyphosate by demonstrating a causal link between oral glyphosate exposure and significant elevation in blood pressure. Gut microbiota was identified as the central mediator of this effect. Mechanistically, glyphosate-mediated elevation in blood pressure was through disruption of both gut-liver and gut-vascular homeostasis via FXR-signaling and accumulation of the microbial metabolite shikimic acid, respectively. Together, these findings underscore the need to reconsider the unabated use of this herbicide, which adversely affects a cardinal sign of health.

physiology↗

bioRxiv2026

Altered immune and treatment response gene expression signatures among poverty-exposed children with B-ALL

Children diagnosed with cancer typically receive standardized treatment regimens. Despite highly protocolized care, children living in poverty experience a greater risk of cancer relapse and higher mortality compared to their more affluent peers.1,2 Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer, and children with ALL exposed to poverty are more likely to experience early relapse.3 Using single-cell RNA sequencing to analyze leukemic blasts and their microenvironment at diagnosis we found that poverty-exposed patients with standard-risk B-ALL exhibit transcriptional signatures of steroid resistance at time of diagnosis. Additionally, we observe increased expression of inflammatory signatures in myeloid cells and reduced effector signatures in CD8+ T-cells in children with B-ALL living in poverty. Further investigation of the mechanisms underlying these associations may identify opportunities for risk-adapted therapeutic strategies to improve disease outcomes in pediatric ALL.

cancer biology↗

bioRxiv2025

Evaluating the potential of cross-species neutralization of anti-PfCyRPA and anti-PfRIPR Monoclonal Antibodies

PfCyRPA and PfRIPR are promising next-generation malaria blood-stage vaccine candidate antigens that play an essential role in erythrocyte invasion of Plasmodium falciparum. CyRPA and RIPR orthologs are present in all human-infecting Plasmodium species, suggesting the potential for a cross-species vaccine. Using Growth Inhibition Assays (GIA), this study investigates seven anti-PfCyRPA and three anti-PfRIPR monoclonal antibodies targeting P. falciparum for their inhibitory activity against P. knowlesi, a non-falciparum species that contributes to a significant burden of zoonotic disease in South-East Asia, shares some biological features with Plasmodium vivax, and has a robust in vitro culture system. Despite their efficacy against P. falciparum and partially conserved epitopes, these antibodies exhibited minimal inhibition of P. knowlesi. Understanding the antigenic diversity and immune mechanisms across Plasmodium species is critical for advancing pan-species vaccine strategies.

immunology↗

bioRxiv2025

Microbial source tracking using metagenomic analysis from Cochin Estuary

Microbial source tracking (MST) and metagenomics offer powerful insights into microbial ecosystems and pollution sources. This pilot study used metagenomics to identify microbial pollution sources in the Cochin Estuary (CE), a vital coastal ecosystem in southwest India. The CE faces significant microbial pollution, necessitating effective tracking for conservation. Bacterial community analysis via high-throughput sequencing was conducted to determine fecal pollution sources in CE waters. Samples included human, cow, dog, and goat feces, along with sewage, slaughterhouse, and domestic waste, alongside 24 water samples from eight sites across monsoon and non-monsoon seasons. DNA extraction and 16S rRNA (V3-V4) sequencing via Illumina MiSeq enabled MST analysis. Results indicated that sewage and domestic waste were the predominant contaminants, contributing to 50% of bacterial communities. Downstream sites were more polluted than upstream areas. Proteobacteria dominated estuarine waters, whereas Firmicutes and Bacteroidetes were prevalent in source samples. This study highlights the need for targeted remediation to protect the CEs environmental health. Importance of the studyThis study is essential for addressing microbial pollution in the Cochin Estuary (CE), a crucial Ramsar site facing contamination threats. Beyond identifying pollution sources, it provides valuable insights into seasonal variations in microbial composition, highlighting differences between monsoon (wet) and non-monsoon (dry) periods. It emphasizes the role of environmental factors such as conductivity, temperature, dissolved oxygen (DO), and salinity in shaping microbial communities. The study also employs advanced statistical tools like non-metric multidimensional scaling (NMDS) and principal coordinates analysis (PCoA) to assess microbial diversity and pollution patterns. Additionally, it underscores the significance of next-generation sequencing (NGS) in high-resolution microbial source tracking (MST). By integrating environmental parameters and microbial analysis, the study offers a comprehensive approach for monitoring estuarine health. These findings are crucial for policymakers, aiding in the development of targeted wastewater management and pollution mitigation strategies to protect CEs biodiversity and ecological balance.

microbiology↗

bioRxiv2023

Androgen Receptor driven gene score identifies tumors with Epithelial to Mesenchymal Transition features in triple negative breast cancer

BackgroundAndrogen receptor (AR) is considered marker associated with better prognosis within hormone receptor positive tumors. Its role in triple negative tumors however is controversial showing both better and worse prognosis and different methods are used for identification of AR driven tumors. Conflicting results could be due to intrinsic molecular differences or scoring method for AR positivity. We attempted to develop an AR driven gene score and examined its utility in subtypes of breast cancer (BC). MethodsA bioinformatic pipeline was constructed and applied on publicly available microarray data sets obtained from AR positive BC cell lines treated with dihydrotestosterone (DHT). Expression levels of genes identified through the pipeline along with set of epithelial mesenchymal transition (EMT) markers, proliferation associated genes and enzymes involved in intracrinal androgen metabolism was evaluated in a cohort of Indian Breast cancer patients. Tumors were divided into AR high and low based on the gene score and association with clinical parameters, circulating androgens, disease free survival, proliferation and EMT markers were examined, all results were further validated in external public datasets. ResultsAR driven gene score was calculated as average expression of the 6 genes selected through bioinformatic analysis. 53% (133/249) tumors were classified as AR high by the gene score and had significantly better clinical parameters such as higher age, smaller tumor size, lower grade and lower proliferation. Tumors with high AR driven gene score had significantly better disease-free survival (mean survival time of 86.13 vs 72.69 months, log rank p=0.032) when compared to the AR low tumors. A subset analysis within TNBC (N=66) showed 36% (24/66) were AR high and had significantly higher expression of EMT markers (p=0.024). Though circulating levels of total testosterone was not different between the groups, intratumoral levels of 5 alfa reductase (SRD5A1) was significantly high in tumors with high AR driven score. ConclusionRole of AR in breast cancer is debatable and difficult to decipher with protein detection alone. Our results support the context dependent function of AR in driving better prognosis, while identifying its role in driving EMT within TNBC tumors.

cancer biology↗

bioRxiv2021

Resting state functional connectivity in relapsing remitting multiple sclerosis with mild disability - a data driven, whole brain multivoxel pattern analysis study

BackgroundMultivoxel pattern analysis (MVPA) has emerged as a powerful unbiased approach for generating seed regions of interest (ROIs) in resting-state functional connectivity (RSFC) analysis in a data-driven manner. Studies exploring RSFC in multiple sclerosis have produced diverse and often incongruent results. ObjectivesThe aim of the present study was to investigate RSFC differences between persons with relapsing-remitting multiple sclerosis (RRMS) and healthy controls (HC). MethodsWe performed a whole-brain connectome-wide MVPA in 50 RRMS patients with expanded disability status scale [≤]4 and 50 age and gender-matched HCs. ResultsSignificant group differences were noted in RSFC in three clusters distributed in the following regions; anterior cingulate gyrus, right middle frontal gyrus, and frontal medial cortex. Whole-brain seed-to-voxel RSFC characterization of these clusters as seed ROIs revealed network-specific abnormalities, specifically in the anterior cingulate cortex and the default mode network. ConclusionsThe network-wide RSFC abnormalities we report agree with the previous findings in RRMS, the cognitive and clinical implications of which are discussed herein. IMPACT STATEMENTThis study investigated resting state functional connectivity (RSFC) in relapsing remitting multiple sclerosis (RRMS) persons with mild disability (expanded disability status scale [≤]4). Whole-brain connectome-wide multivoxel pattern analysis (MVPA) was used for assessing RSFC. Compared to healthy controls (HC), we were able to identify three regions of interest for significant differences in connectivity patterns, which were then extracted as a mask for whole-brain seed-to-voxel analysis. A reduced connectivity was noted in the RRMS group, particularly in the anterior cingulate cortex and the default mode network regions, providing insights into the RSFC abnormalities in RRMS.

neuroscience↗

bioRxiv2020

A miR-137-related biological pathway of risk for Schizophrenia is associated with human brain emotion processing

Genome-Wide-Association studies have involved miR-137 in schizophrenia. However, the biology underlying this statistical evidence is unclear. Statistical polygenic risk for schizophrenia is associated with working memory, while other biological evidence involves miR-137 in emotion processing. We investigated the function of miR-137 target schizophrenia risk genes in humans. We identified a prefrontal co-expression pathway of schizophrenia-associated miR-137 targets and validated the association with miR-137 expression in neuroblastoma cells. Alleles predicting greater co-expression of this pathway were associated with greater prefrontal activation during emotion processing in two independent cohorts of healthy volunteers (N1=222; N2=136). Statistical polygenic risk for schizophrenia was instead associated with prefrontal activation during working memory. A co-expression pathway links miR-137 and its target genes to emotion processing and risk for schizophrenia. Low prefrontal miR-137 expression may be related with SCZ risk via increased expression of target risk genes, itself associated with increased prefrontal activation during emotion processing.

neuroscience↗

bioRxiv2020

PTPN11/SHP2 negatively regulates growth in breast epithelial cells: implications on tumorigenesis

PTPN11/SHP2, a non-receptor protein tyrosine phosphatase is a prominent target of the receptor tyrosine kinase that participates in positive feedback signalling of the human epidermal growth factor receptors and helps in growth and migration. PTPN11/SHP2 is widely believed to be an oncoprotein, although its possible tumor-suppressor role is also reported. Our analysis of breast cancer metadata shows, PTPN11/SHP2 copy number loss in luminal A subtype is correlated to poor disease-specific survival and late-stage cancer at diagnosis. Analysis of the level 4 Reverse Phase Protein Array (RPPA) data available on the TCGA database resulted in positive correlations between the lower expression levels of constitutively active variant, the phospho-SHP2-Y542, of PTPN11/SHP2 and larger tumor size and lymph node positivity. We experimentally examined possible negative regulation of growth by PTPN11/SHP2 using MCF10A, a normal breast epithelial cell line. Knock-down of PTPN11/SHP2 resulted in increased cell migration, cell shape changes to mesenchymal morphology, and increased survival in cells treated with epirubicin, a DNA-damaging drug. However, it did not alter the rate of cell proliferation. It is possible that PTPN11/SHP2 might function as a tumor suppressor by potentiating proliferating cells with increased cell migration and resistance to apoptosis. Statement of SignificanceMolecules like PTPN11/SHP2, among many others that show dual specificity in tumorigenesis in the same tissue depending on the upstream signaling cues, present challenges in the field of targeted drug therapy. This study puts forth the importance of understanding the mechanism of one of the two outcomes and thereby helps better clinical management of a subgroup of cancer.

cancer biology↗

bioRxiv2020

Characterisation of the Renal Cortical Transcriptome Following Roux-en-Y Gastric Bypass Surgery in Experimental Diabetic Kidney Disease.

IntroductionRoux-en-Y Gastric Bypass Surgery (RYGB) reduces albuminuria and the long-term incidence of end-stage renal disease in patients with obesity and diabetes. Preclinical modelling in experimental diabetic kidney disease (DKD) demonstrates that improvements in glomerular structure likely underpin these findings. Research Design & MethodsIn adult male Zucker Diabetic Fatty (ZDF) rats, we profiled the effect of RYGB on weight and metabolic control as well biochemical, structural and ultrastructural indices of diabetic renal injury. Furthermore, we sequenced the renal cortical transcriptome in these rats and used bioinformatic pathway analyses to characterise the transcriptional alterations governing the renal reparative response to RYGB ResultsIn parallel with improvements in weight and metabolic control, RYGB reduced albuminuria, glomerulomegaly, podocyte stress, and podocyte foot process effacement. Pathway analysis of RYGB-induced transcriptomic changes in the renal cortex highlighted correction of disease-associated alterations in fibrosis, inflammation and biological oxidation pathways. RYGB reversed disease-associated changes in the expression of TGF-{beta} superfamily genes that strongly correlated with improvements in structural measures of glomerulopathy. ConclusionsImproved glomerular structure in ZDF rats following RYGB is underpinned by pathway level changes, including interruption of the TGF-{beta} driven pro-fibrotic programme. Our data provide an important layer of experimental support for clinical evidence demonstrating that RYGB arrests renal damage in patients with obesity and Type 2 Diabetes. KEY MESSAGESO_LIWhat is already known about this subject? O_LIRYGB is an effective treatment for obesity and type 2 diabetes and longitudinal cohort studies have demonstrated its albuminuria lowering effect and evidence of longer term reno-protection. C_LIO_LIStudies in pre-clinical models of diabetic kidney disease have described favourable changes in measures of renal structure and ultrastructure following RYGB. C_LI C_LIO_LIWhat are the new findings? O_LIThe present study directly correlates structural and ultrastructural improvements in the ZDF rat kidney following RYGB with corrective shifts in the global renal transcriptome. C_LIO_LIChronic renal remodelling responses in experimental DKD that are governed by TGF-{beta} signalling are interrupted and reversed by RYGB. C_LI C_LIO_LIHow might these results change the focus of research or clinical practice? O_LIThese data will support further interrogation of RYGB specific shifts in the renal transcriptome with a view to identifying tractable targets for treatment response biomarkers and bariatric mimetic based diet and pharmacotherapy based interventions. C_LI C_LI

molecular biology↗

bioRxiv2019

Three complete genome sequences of Penguin megrivirus from ornithogenic soil, Adelie penguin and Weddell seal of Antarctica

We report the complete genome sequences of Penguin megriviruses from three different sources from Antarctica namely feces of Adelie penguin, feces of Weddell seal and ornithogenic soil. Phylogenetic analysis indicates the prevalence of very similar viruses in different sources of Antarctic environment. These genome sequences aid to understand the evolution of megriviruses in Antarctic ecology and reveal their place in global megrivirus phylogeny.

microbiology↗

bioRxiv2019

ZIKA VIRUS INFECTION DURING PREGNANCY AND INDUCED BRAIN PATHOLOGY IN BECLIN1-DEFICIENT MOUSE MODEL

We investigated the role of the autophagy protein, Beclin1, in the replication and disease of Zika virus (ZIKV) in pregnant dams and their offspring using Beclin1-deficient (Atg6+/-) and wild-type (Atg6+/+) mouse model infected with the Honduran (R103451), Puerto Rican (PRVABC59), and the Uganda (MR766) strains of ZIKV. Pregnant dams infected subcutaneously at embryonic stage (E)9 showed viral RNA in serum harvested at E13 and in various organs removed postmortem at E17. Subcutaneous infections with ZIKV also showed the vertical transmission of ZIKV from the placenta to embryos removed postmortem at E17. From the three isolates, R103451-infected Atg6+/- dams had the lowest mortality rate while 30 % of their offspring containing the hemizygous beclin1 allele (Atg6+/-) were smaller in size and had smaller and underdeveloped brain. Growth impairment in the pups became noticeable after two weeks post-birth. After 21-days, pups were sacrificed and brain tissues removed postmortem showed expression of the envelope (E) and the non-structural (NS)-1 proteins, along with signs of neuronal injury, despite an absence in viral RNA detection. A significant decrease in the mRNA expression levels of the insulin-like growth factor-1 (IGF-1) by 8-fold and a decrease in the mRNA expression levels of several microcephaly related genes along with an increase in the secretion of several inflammatory molecules may have contributed to the observed phenotype. Since autophagy regulates cytokines and chemokines production, a dysregulation in this pathway may have further exacerbated the pathology of ZIKV. IMPORTANCEPups delivered from ZIKV-infected dams showed significant growth impairments in the body and the brain. We believe that the reduction in insulin growth factor together with the increase secretion of inflammatory molecules may have triggered neuronal injury and the downregulation of the microcephalic genes, while reduced expression of the autophagy protein, Beclin1 further exacerbated the pathology. Although the mechanism is still unknown, the autophagy pathway seems to play a key role in ZIKV pathology. It is therefore of great significance to study the role of autophagy during viral infection with the goal to identify potential targets for anti-ZIKV therapeutic intervention.

immunology↗