Biology subjects

Dhiman, S.

Publications and source records attributed to Dhiman, S..

5 recordsLinked to original sources

bioRxiv2026

Combined Menin and XPO1 inhibition drive synergistic antileukemic activity in KMT2Ar and NPM1-m AML

Menin scaffolds the oncogenic histone-lysine-N-methyltransferase (KMT2A)-fusion protein (FP) complex in KMT2A-r and wild-type KMT2A complex in NPM1-m acute myeloid leukemia (AML). Menin inhibitors (MIs) are effective in KMT2A-r AML and NPM1-m AML. However, not all patients respond to MIs as monotherapy. In this preclinical study, we demonstrate that the MI ziftomenib, in combination with the XPO1 inhibitor selinexor, synergistically inhibited the growth of multiple KMT2A-r and NPM1-m AML cell lines (CI<1). The combination suppressed colony formation in primary CD34+ KMT2A-r progenitor cells without affecting normal stem cells. Robust apoptosis and decreased G2/M populations were also evident. The combination downregulated HOXA9 and MEIS1 while upregulating monocytic differentiation marker CD11b in both the AML molecular signatures. RNA sequencing and proteomic analysis in KMT2A-r revealed suppression of multiple bona fide menin-KMT2A target genes. Our mechanistic studies also identified a novel role of XPO1 in stabilizing menins binding to chromatin and its interactions with KMT2A and KMT2A/MLLT3. XPO1 inhibitor-mediated disruption of these interactions, particularly in combination with ziftomenib, synergistically impairs oncogenic transcriptional programs. In vivo, combination therapy improved survival in both MV4;11 and OCI-AML3 cell line and primary patient-derived KMT2A-r and NPM1-m AML xenograft models in NSG mice, effective even at reduced drug doses. These preclinical findings demonstrate that simultaneous inhibition of the menin-KMT2A interaction and XPO1 can be a more effective translational strategy for treating KMT2A-r and NPM1-m AML than MI monotherapy to deepen responses and delay/prevent relapses.

cancer biology↗

bioRxiv2023

Classification of bacterial nanowire proteins using Machine Learning and Feature Engineering model

Nanowires (NW) have been extensively studied for Shewanella spp. and Geobacter spp. and are mostly produced by Type IV pili or multiheme c-type cytochrome. Electron transfer via NW is the most studied mechanism in microbially induced corrosion, with recent interest in application in bioelectronics and biosensor. In this study, a machine learning (ML) based tool was developed to classify NW proteins. A manually curated 999 protein collection was developed as an NW protein dataset. Gene ontology analysis of the dataset revealed microbial NW is part of membranal proteins with metal ion binding motifs and plays a central role in electron transfer activity. Random Forest (RF), support vector machine (SVM), and extreme gradient boost (XGBoost) models were implemented in the prediction model and were observed to identify target proteins based on functional, structural, and physicochemical properties with 89.33%, 95.6%, and 99.99% accuracy. Dipetide amino acid composition, transition, and distribution protein features of NW are key important features aiding in the models high performance.

systems biology↗

bioRxiv2021

Deltamethrin contact exposure mediated toxicity and histopathological aberrations in tissue systems of cockroach species Periplaneta americana and Blatella germanica

Cockroach species Periplaneta americana and Blatella germanica potentially survive in locations close to human activity. Besides spoiling food material, cockroaches also transfer pathogens of different diseases among human. Since the insecticides have been used extensively to control cockroaches, information on their insecticide susceptibility and toxicity at cellular level may be crucial. In the study, deltamethrin toxicity as well as the deltamethrin-mediated cytomorphological changes in brain, ovary and midgut of the two important cockroach species has been assessed. Different concentrations [0.00025% (0.0025mg/ml), 0.0025% (0.025mg/ml), 0.025 (0.25mg/ml), 0.25% (2.5mg/ml), 0.5% (5mg/ml), 1% (10mg/ml)] of deltamethrin in acetone were used to expose test species in WHO bottle assay. Knockdown was recorded after 5 min interval while delayed mortality was observed after 24 hr. Brain, ovary and gut were dissected post 1 hr exposure and 24 hr holding (for 0.25%, 0.5% and 1% concentration), and tissues were processed for microscopic analysis. Deltamethrin exposed cockroaches and dissected tissues were used to estimate deltamethrin using HPLC. At 0.00025% (lowest concentration), the percentage knock-down observed was 66.7% for P. americana and 80% B. germanica respectively (R2= 0.78; p=0.0001) in 1 hr. KDT50 value was found to be 8.7 min (95% CI: 7.3-10.2), while KDT99 was 20.7 min (95% CI: 16.0-35.7) in P. americana at 1% concentration. Whereas, the KDT50 and KDT99 values for B. germanica were 7.4 min (95% CI: 5.4-9.1) and 27.4 min (95% CI: 18.2-80.0) at similar concentration. LD50 and LD95 values (for 60 min standard exposure) were 0.0006 % (95% CI: 0.00-0.001) and 0.034% (95% CI: 0.013-0.49) respectively for P. americana, while these values were 0.0005 (95% CI: 0.00-0.001) and 0.04 (95% CI: 0.01-0.23) for B. germanica. Exposure to 1% deltamethrin induced considerable toxic effect in the epithelial cells in the midgut. HPLC estimated 0.21{+/-}0.05 mg (95% CI - 0.18-0.25; CoV 23.9%) deltamethrin in P. americana post 1% exposure. Even short term exposure of low concentration of synthetic pyrethroid deltamethrin displayed immediate knockdown and delayed mortality in both the test species. Considerable histological damage was observed in both the insects at 1% exposure. In India, resistance to deltamethrin may have been reported among different insects due its extensive use, however the formulations such as insecticide paints, attractant baits etc. developed using deltamethrin as active ingredient could be useful in cockroach control operations.

zoology↗

bioRxiv2021

PyDesigner: A Pythonic Implementation of the DESIGNER Pipeline for Diffusion Tensor and Diffusional Kurtosis Imaging

PyDesigner is an open-source and containerized Python software package, adapted from the DESIGNER pipeline, for diffusion weighted magnetic resonance imaging preprocessing and tensor estimation. PyDesigner combines tools from FSL and MRtrix3 to reduce the effects of signal noise and imaging artifacts on multiple diffusion measures that can be derived from the diffusion and kurtosis tensors. This publication describes the main features of PyDesigner and highlights its ease of use across platforms, while examining its accuracy and robustness in deriving commonly used diffusion and kurtosis metrics.

neuroscience↗

bioRxiv2020

Potential malaria vector Anopheles minimus (species A) still persisting in North East India

BackgroundVector borne infectious diseases affect two third of the worlds human population and cause mortality in millions each year. Malaria remains one of the major killers in the Indian sub-continent and transmitted uninterruptedly by many efficient vectors and their sibling species. In North East India (NE), Anopheles minimus has been recognized as an important vector which shares majority of malaria cases. This study primarily focuses on to recognize the presence and distribution of sibling species of An. minimus in certain endemic area of NE India. MethodsAnopheles species were collected and identified using available morphological keys. The genomic DNA was extracted from the mosquito specimen and used to perform species specific PCR (ss PCR) for molecular identification of major malaria vector An. minimus sibling species ResultMorphological identification suggested the presence of An. minimus sl in low density in the study area. The specimen of An. minimus subjected to ss PCR confirmed the prevalence of only one sibling species namely, An. minimus A in Sialmari and Chandubi. ConclusionThough in low density, but malaria vector An. minimus is still present in certain endemic areas of NE India. The ss PCR assay employed presently suggested that An. minimus sibling species A is prevailing in the region. Presently used ss PCR assay was simpler, faster, cheaper and more readily interpreted than earlier assays. This information could be useful in understanding of current prevalence and distribution of An. minimus sibling species complex in NE region of India.

ecology↗