Biology subjects

Bal, M.

Publications and source records attributed to Bal, M..

6 recordsLinked to original sources

bioRxiv2026

Evidence of residual Brugia malayi infection in TAS-III cleared areas of coastal Odisha: Findings from Molecular Xenomonitoring

BackgroundLymphatic filariasis (LF), caused by Wuchereria (W) bancrofti, Brugia malayi and Brugia (B) timori, remains a major public health problem known for its disfiguring and debilitating effects despite notable progress under the Global Program to Eliminate Lymphatic Filariasis (GPELF). Following recent national directives (2024) restructuring implementation units (IUs) to the block level, all TAS-cleared blocks now require re-evaluation using night blood surveys (NBS) or filarial test strip (FTS) kits. Molecular Xenomonitoring (MX) is recommended as a post-validation surveillance method for detecting active LF transmission in vectors. Therefore, an exploratory study was conducted in two coastal districts of Odisha, namely Jagatsinghpur and Puri, which cleared TAS-III, to investigate the presence of B. malayi and W. bancrofti infections in filaria-transmitting vectors. Methodology/Principal FindingsAdult female mosquitoes were collected from three villages across Jagatsinghpur and Puri districts during March-April 2025. Species were identified morphologically, segregated and pooled. The pooled samples were screened for the presence of filarial DNA using species-specific PCR assays. Of 1,518 collected adult female mosquitoes, 22.6% were Culex quinquefasciatus, 18.3% were Mansonia (Mn) annulifera, and 4.3% were Mansonia uniformis. Among 33 pools screened, six pools were positive for B. malayi DNA (18.18% pool positivity; infection rate 2.88%, 95% CI: 1.23-5.74), in Mn. annulifera, whereas W. bancrofti was not detected. Conclusions/SignificanceThe study provides the first molecular confirmation of B. malayi infection in Mn. annulifera, indicating a persistent Brugian transmission in Odisha even after the implementation of mass drug administration. The Study highlights MX as a sensitive, non-invasive surveillance tool for detecting residual infection in post-MDA and post-TAS settings. The study underscores the need for a standardized MX protocol and integration with entomological monitoring to sustain national LF elimination targets by 2027. Author SummaryLymphatic filariasis is a mosquito-borne disease that can cause severe, disfiguring swelling of the limbs and other lasting disabilities, and it remains a serious public health problem in India. National programmes in India are actively working to eliminate it by giving preventive medicines to communities, conducting surveys to confirm that transmission has ceased, and once an area passes, this treatment is withdrawn. However, it is not always clear whether the parasite has truly disappeared or is still lingering at very low levels. In this study, we searched for the parasite directly inside mosquitoes, an approach that does not require collecting blood from people. We sampled mosquitoes from two coastal districts of Odisha, India, that had already passed the required surveys and stopped treatment. We found the parasite Brugia malayi in Mansonia mosquitoes, the first time this has been shown using this molecular method in the region, although the more common filarial parasite was not detected. Our findings show that transmission can smoulder on even after an area is judged free of disease. Because India has no available rapid field test for this particular parasite, we argue that examining mosquitoes should become a routine safeguard for the countrys elimination effort.

zoology↗

bioRxiv2024

Statins attenuate Wnt/β-catenin signaling by targeting SATB family proteins in colorectal cancer

Colorectal cancer is the second leading cause of cancer-related deaths worldwide, highlighting the need for improved treatments and advanced molecular research. A recent therapeutic approach focuses on repurposing drugs to target dysregulated pathways involved in tumorigenesis. Among these, statins, commonly known for lowering cholesterol, have attracted attention for their potential anti-cancer properties. Here, we provide direct evidence for the same by assessing the impact of statin treatment on lipid, transcript, and protein levels. Our findings reveal that statins specifically target key components of the Wnt/{beta}-catenin pathway, a major factor in adenoma formation, including the SATB (Special AT-rich Binding protein) family proteins. While SATB1 is recognized as a regulator of tumorigenesis, particularly under Wnt signaling, SATB2 appears to exert an opposing role. We demonstrate that statin treatment reciprocally alters the expression pattern of these proteins. Furthermore, a human clinical trial evaluating statins as an anti-cancer therapy supports the hypothesis that differential expression of SATB proteins is crucial in tumorigenic outcomes. In conclusion, this modulation by statin treatment suggests promising new therapeutic avenues through drug repurposing.

cancer biology↗

bioRxiv2022

Insulin receptor substrate 4 deficiency mediates the insulin effect on the epithelial magnesium channel TRPM6 and causes hypomagnesemia

The kidney is the key regulator of magnesium (Mg2+) homeostasis in the human body. In the distal convoluted tubule (DCT), the apical epithelial magnesium (Mg2+) channel TRPM6, determines how much Mg2+ is excreted in the urine. To better understand the regulation of human renal Mg2+ absorption we identified novel, potential interaction partners of TRPM6 by pursuing a liquid chromatography - tandem mass spectrometry (LC-MS/MS) proteomics approach. We found insulin receptor substrate 4 (IRS4) enriched with TRPM6 tagged to glutathione S-transferase (TRPM6-GST) but not GST control. Physical interaction between IRS4 and TRPM6 was confirmed by co-immunoprecipitation. Applying microdissection of mouse tubules, we detected Irs4 mRNA expression mostly in the DCT and to a lower degree in the proximal tubule and thick ascending limb of Henle. Given the overall low abundance of Irs4 mRNA along the tubule we investigated the phenotype of Irs4 knockout mice (Irs4-/-). These Irs4-/- mice displayed significantly higher urinary and fecal Mg2+ losses and lower blood Mg2+ levels than wild-type (WT) mice. Claudin-16, claudin-19, and Hnf1b mRNA and Claudin-16 and Trpm6 protein expression was significantly higher in kidneys of 3 month old Irs4-/- mice consistent with a compensatory mechanism to conserve Mg2+. Applying whole-cell patch-clamp recording we confirmed the stimulatory role of insulin on TRPM6 channel activity and showed that IRS4 targets the two TRPM6 phosphorylation sites T1391 and S1583 to enhance TRPM6 current density. To test the effect of Mg2+ deficiency on metabolism, we performed glucose and insulin tolerance studies, which were mildly abnormal in Irs4-/- mice. SIGNIFICANCE STATEMENTMagnesium (Mg2+) is the second most abundant intracellular cation but the regulation of Mg2+ homeostasis is not well understood. The kidney is the key organ for regulating Mg2+ homeostasis. Insulin is a known stimulator of the apical epithelial Mg2+channel TRPM6. We present a novel modifier of Mg2+ absorption with insulin receptor substrate 4 (IRS4) which illuminates further, how insulin activates the TRPM6 channel and modifies Mg2+ homeostasis. Applying protein biochemistry, tubular microdissection, whole mouse physiology, and patch-clamp recording, we demonstrate that IRS4 mediates the stimulatory effect of insulin by enhancing phosphorylation of two specific TRPM6 residues. Irs4-/- mice develop increased urinary and stool Mg2+ losses, lower serum Mg2+ concentration, and display mild impairment in glucose and insulin tolerance.

physiology↗

bioRxiv2021

Local adaptations of Mediterranean sheep and goats through an integrative approach

In a context of climate change, identifying the genes underlying adaptations to extreme environments is essential. Small ruminants are adapted to a wide variety of habitats and thus, are promising study models. Here, we considered 17 goat and 25 sheep local Mediterranean breeds, in Italy, France and Spain. We proposed, and empirically tested a new methodology to highlight selection signatures in relation to the environments. Based on historical archives, we selected the breeds potentially most linked to a territory and defined their original geographical cradle, including transhumant pastoral areas. For both species, the cradles were arranged along latitudinal gradient of aridity and altitude. Then we used the programs PCAdapt and LFMM. Considering cradles, instead of current GPS coordinates, markedly improved the sensitivity of the LFMM analyses. All the results combined with a systematic literature review, revealed a set of genes with potentially key adaptive roles. Some of these genes, have been found implicated in lipid metabolism (SUCLG2, BMP2), hypoxia/heat stress (UBE2R2/UBAP2), lung function (BMPR2), seasonal patterns (SOX2, DPH6) or neuronal function (TRPC4, TRPC6). For the intergenic region between PCDH9 and KLH1, as well as NBEA, identified in both species, the adaptive role could be strong. We found for RXFP2, associated with sheep horn development, and MSRB3 and SLC26A4, both associated with hearing of sheep, a strong association with the environment gradient. We conclude that our new methodology, which considers breeds in their historical, environmental and anthropological context, provides novel and essential information on local breeds and their unique adaptations.

evolutionary biology↗

bioRxiv2020

A Novel Machine Learning Approach Uncovers New and Distinctive Inhibitors for Cyclin-Dependent Kinase 9

We present a novel combination of generative and predictive machine learning models for discovering unique protein inhibitors. The new method is assessed on its ability to generate unique inhibitors for the cancer associated protein kinase, CDK9. We validate our method by performing biochemical assays, attaining a hit rate of more than 10%, demonstrating the method to be a notable improvement upon a more standard, and somewhat naive approach. Moreover, we imposed the additional challenge of finding inhibitors that are readily synthesized. Importantly, two new inhibitors are found, with one being distinct from reported CDK9 inhibitors. We discuss the results in the context of modern machine learning principles and the desire expressed by the rational drug design community to secure molecules that are structurally different, yet with high binding affinities, to structurally determined protein targets.

bioinformatics↗

bioRxiv2019

Detection and identification of bacterial spp. from culture negative surgical site infection patients using molecular tool.

Surgical site infection (SSI) is the most common post operative infections, that sometimes cause postoperative morbidity, mortality and increase in hospital costs. Managing surgical site infections, with negative culture report in routine diagnosis is a common dilemma in microbiology. The present study was carried out to know the presence and frequencies of various bacteria in wound aspirates/ swabs of some culture negative surgical site infection patients attending a tertiary care hospital of eastern India with molecular methods. Ninety seven (97) patients with post-operative SSI whose wound swabs/ aspirate were negative in the conventional aerobic culture after 48 hrs of incubation were taken for finding the presence and identification of any bacteria in sample with 16S rRNA gene specific broad PCR and submitted to NCBI. Of the 97 patients, 16S rRNA based broad range PCR assay could able to identify the presence of bacterial pathogen in 53(54.63%) cases, out of which 29 isolates were of viable but non-culturable bacteria(VBNC), 07 were of obligatory anaerobes and 13 were of unculturable bacteria, 04 were with polybacterial infections. Some measures should be taken in the microbiology laboratory along with conventional culture, for better patient care such as, culture plates should be allowed to incubate for an additional 3 - 4 days that will allow the growth any fastidious bacteria, anaerobic culture system should be developed along with aerobic system, and molecular diagnosis by 16S broad range PCR should be performed routinely.

microbiology↗