Biology subjects

M, N.

Publications and source records attributed to M, N..

8 recordsLinked to original sources

bioRxiv2025

AKNA drives neural stem cell fate transition through differential localization and coordinating the modulation of chromatin from H3K27me3 to H3K27ac

Neuronal stem cells (NSCs) play pivotal role in adult neurogenesis, however, detail mechanisms of obtaining pluripotency or undergoing differentiation remain unknown. Herein, how AT-hook protein AKNA regulates pluripotency and stemness in neuroblastoma cells is demonstrated by gene knockdown, immunofluorescence, chromatin immunoprecipitation (ChIP), localization of AKNA, signaling interactions and transcriptional activity. AKNA was abundant and mostly nuclear during induction of pluripotency and its knockdown reduced stemness, even in presence of other pluripotency factors, including OCT4 and SOX2. During the course of induction of differentiation, AKNA remain localized in the cytosol, essential for regulated differentiation. Cytosolic retention of AKNA is possibly driven by FAK signaling. In the nucleus, AKNA promotes KDM6B demethylase for H3K27me3 demethylation to H3K27, and subsequently promotes CBP/p300 to acetylate H3K27 to H3K27ac deposition on promoter region of respective genes to trigger their transcription. Data obtained from knockdown and overexpression of AKNA and KDM6B further reinforce its importance that, they physically interact to drive pluripotency and stemness. These findings establish AKNA as a critical regulator for NSCs fate determination in association with epigenetic modifiers and signaling pathway, offering potential targets for neuroblastoma therapies and regenerative medicines for neurodegenerative diseases.

molecular biology↗

bioRxiv2023

A novel glideosome-associated protein S14 coordinates sporozoite gliding motility and infectivity in mosquito and mammalian hosts

Plasmodium sporozoites are the infective forms of the malaria parasite in the vertebrate host. Gliding motility allows sporozoites to migrate and invade the salivary gland and hepatocytes. Invasion is powered by an actin-myosin motor complex linked to glideosome. However, the gliding complex and the role of several glideosome-associated proteins (GAPs) are poorly understood. In silico analysis of a novel protein, S14, which is uniquely upregulated in salivary gland sporozoites, suggested its association with glideosome-associated proteins. We confirmed S14 expression in sporozoites using real-time PCR. Further, the S14 gene was endogenously tagged with 3XHA-mCherry to study expression and localization. We found its expression and localization on the inner membrane of sporozoites. By targeted gene deletion, we demonstrate that S14 is essential for sporozoite gliding motility, salivary gland, and hepatocyte invasion. The gliding and invasion-deficient S14 KO sporozoites showed normal expression and organization of IMC and surface proteins. Using in silico and the yeast two-hybrid system, we showed the interaction of S14 with the glideosome-associated proteins GAP45 and MTIP. Together, our data show that S14 is a glideosome-associated protein and plays an essential role in sporozoite gliding motility, which is critical for the invasion of the salivary gland, hepatocyte, and malaria transmission.

microbiology↗

bioRxiv2023

Genetic diversity and evidence of recombination of Horsegram yellow mosaic virus infecting pole bean (Phaseolus vulgaris L.) from South India

The yellow mosaic disease (YMD) caused by begomoviruses is a major constraint for the production of pole bean (Phaseolus vulgaris L.) in India. Survey was carried out in the eastern dry zone of Karnataka during 2019-20 to record the incidence of yellow mosaic disease in pole bean which revealed the ubiquitous prevalence of YMD in pole bean ranging from 6.02 to 80.74 per cent. Leaf samples collected (symptomatic and asymptomatic) were subjected for begomovirus detection using specific primers. Twelve samples, representing all the 12 taluks in the surveyed region were considered for full genome amplification by RCA, cloned and sequenced. Genome length of 12 current isolates ranged from 2718 - 2744 and 2668 - 2671 nucleotides for DNA-A and DNA-B, respectively. Sequence analysis using Sequence Demarcation Tool (SDT) showed >91 per cent nucleotide identity of current isolates (DNA-A) with other horsegram yellow mosaic virus (HgYMV) isolates available in the GenBank. As per existing ICTV criteria, all the current isolates can be considered as strains of HgYMV. Further, DNA-B associated with all the 12 isolates also shared >91 per cent nucleotide identity with DNA-B of HgYMV isolates, indicating absence of component re-assortment in HgYMV. Variation in the pairwise nucleotide identity and phylogenetic analysis confirmed the existence of new strains within the current HgYMV isolates. GC plot analysis reveals potential recombination in the low GC rich regions. Further, recombination breakpoint analysis indicated intra-species recombination in both DNA-A and DNA-B, which might have driven the origin of new strains in HgYMV. This is the first comprehensive study on begomoviruses ioslates associated with the yellow mosaic disease of pole bean based on complete genome sequencing in the world.

molecular biology↗

bioRxiv2022

dnaE2 expression promotes genetic diversity and bacterial persistence in mycobacterial biofilms

The complex cellular architecture and the microenvironments within the biofilm give rise to a population that is both physiologically and genetically heterogeneous. Transcriptome analysis of Mycobacterium smegmatis in biofilm culture and its transition phase into planktonic growth was performed to identify the genetic basis of heterogeneity in the biofilm. While there was an increase in the expression of mycobacterial mutasome consisting of dnaE2, imuA, and imuB in the biofilm, the mutation burden was less compared to the planktonic culture. Deletion of dnaE2 causes lower mutation frequency and bacterial fitness in comparison to the parental strain in biofilm culture. The expression of dnaE2 contributes to a slower bacterial growth rate, potentially promoting persister formation. Our study uncovers the multiple benefits of dnaE2 expression in biofilm such as increasing genetic diversity and reducing growth rate; both of which are necessary for mycobacterial survival and adaptation.

microbiology↗

bioRxiv2022

Single session of rTMS enhances brain metastability and intrinsic ignition

BackgroundEmerging evidence support the view that brain stimulation might improve essential tremor (ET) by altering brain networks and facilitating plasticity. Yet, we are still missing a mechanistic explanation of the whole brain dynamics underlying these plasticity defining changes. MethodIn this study, we explored the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) over left primary motor cortex (L-M1) on functional connectivity dynamics (FCD) in patients with ET. Resting-state fMRI (RsfMRI) was acquired before and after a single session of rTMS in 30 patients with ET and compared with RsfMRI of 20 age and gender matched healthy controls (HCs). We have measured the effect of brain stimulation using network topological re-organization through whole brain integration and segregation, brain stability and capacity of neural propagation through metastability and intrinsic ignition. ResultsPatients with ET had altered FCD measures compared to controls. After a single session rTMS, the brain connectivity measures approached normality and patients with ET revealed significantly higher integration, lower segregation with higher metastability and increased intrinsic ignition. ConclusionBrain metastability and intrinsic ignition measures could be valuable tools in appreciating mechanisms of brain stimulation in ET and other neurological diseases.

neuroscience↗

bioRxiv2022

ASM-3D: An attentional search model fashioned after what andwhere/how pathways for target search in 3D environment

We propose a biologically inspired attentional search model for target search in a 3D environment, which has two separate channels for object classification, analogous to the "what" pathway in the human visual system, and for prediction of the next location of the camera, analogous to the "where" pathway. We generated 3D Cluttered Cube datasets that consist of an image on one vertical face, and clutter images on the other faces. The camera goes around each cube on a circular orbit centered on the cube and determines the identity of the image and the face on which it is located. The images pasted on the cube faces were drawn from three: MNIST handwriting digit, QuickDraw, and RGB MNIST handwriting digit datasets. The attentional input of 3 concentric cropped windows resembling the high-resolution central fovea and low-resolution periphery of the retina, flows through a Classifier Network and a Camera Motion Network. The Classifier Network classifies the current view into one of the classes or clutter. The Camera Motion Network predicts the cameras next position on the orbit (varying the azimuthal angle or {theta}). Here the camera performs one of three actions: move right, move left, or dont move. The Camera-Position Network adds the cameras current{theta} information into the higher features level of the Classifier Network and the Camera Motion Network. The Camera Motion Network is trained using Q-learning where the reward is 1 if the classifier network gives the correct classification, otherwise 0. Total loss is computed by adding the mean square loss of temporal difference and cross entropy loss. Then the total loss is backpropagated using Adam optimizer. Results on two grayscale image datasets and one RGB image dataset show that the proposed model is successfully able to discover the desired search pattern to find the target face on the cube, and also classify the target face accurately.

neuroscience↗

bioRxiv2020

Spatial separation of Streptomyces aerial mycelium during fermentation enhances secondary metabolite production

Conditioning of morphology is an effective technique to enhance secondary metabolite production by Streptomyces. Here we report a novel conditioning method employing glass marbles in batch cultures to enhance secondary metabolite production by Streptomyces sp. The marbles seem to spatially separate aerial and submerged mycelia in the flask which was necessary for the qualitative and quantitative enhancement of metabolite production of secondary metabolites. The method also offers shorter incubation period compared to conventional methods for effective production. Further, using a combination of this method and response surface methodology we could enhance the production of antimycobacterial molecules chrysomycin A and B significantly. ImportanceRediscovery of existing molecules and lack of techniques to induce production of secondary metabolites are the major bottlenecks associated with drug discovery of novel bioactive molecules from Streptomyces, the major source of marketable drugs today. We found a new method to increase the diversity and quantity of secondary metabolites in two Streptomyces species. This method thus enhances the chance of finding novel active principles from Streptomyces.

microbiology↗

bioRxiv2018

Activation of Multiple Signalling Pathways by P152Lp53 Mutant Reveals New Gain-of-function Implicating Tumorigenesis

TP53 is the most frequently mutated tumor suppressor gene in context of all varieties of cancer, yet biochemical characterization of several reported mutations with probable biological significance have not been accomplished. We have identified a relatively rare proline to leucine mutation (P152L) in p53 in an Indian oral cancer patient sample at the fade end of its DNA binding domain (DBD). Although P152Lp53 DBD potentially binds to DNA, the full length protein is completely devoid of DNA binding ability at its cognate site. Interestingly, P152Lp53 can efficiently tetramerize. Significantly, this mutant when expressed in p53 null cell line, was found to induce cell mobility, proliferation, and invasion as compared to vector control. Also, enhanced tumorigenic potential was observed when cells expressing P152Lp53 were xenografted into nude mice, the mechanistic details of which were also investigated upon where several of the pathways were found to be upregulated such as Cell-Cell/Cell-ECM signalling, EGFR signalling, Rho-GTPase signalling. Taken together, this study establishes P152Lp53 as a new gain of function mutant.

cancer biology↗