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Panwar, V.

Publications and source records attributed to Panwar, V..

6 recordsLinked to original sources

Autonomous learning of pathologists' cancer grading rules

Deep learning reveals that tissue morphology contains rich pathophysiological information beyond human understanding. However, approaches to convert these spatially distributed signals into subcellular insights informing disease mechanisms are lacking. We introduce Delta-Marches, an interpretability-first approach that nominates distinguishing morphological features rather than explaining existing models' decisions. Delta-Marches simulates idealized morphological changes between classes by coupling latent-space traversals with generative AI. Comparing each image to its class-shifted counterpart allows feature extractors to infer the most affected aspects, reducing sample-to-sample variability and resolving transformations at subcellular resolution. Prototyped in renal carcinoma grading, Delta-Marches generates realistic grade transitions and pinpoints tumor-cell nuclear phenotypes as key determinants. It also reveals reduced vasculature with increasing grade, a known pattern absent from standard rubrics. Applied to dysplastic progression in colorectal tissue, it recovers glandular remodeling and goblet-cell loss, generalizing across tissue types and scales. These results show Delta-Marches parses complex image phenotypes and catalyzes hypothesis generation.

bioinformatics↗

In silico codon optimization of the variant antigen-encoding genes of diverse strains of Zika Virus

AbstractWith the recent emergence of the coronavirus pandemic, the scare for other viral pandemics is on the rise. Already having caused an epidemic in 2015-16, Zika virus (ZIKV) poses a threat for potential havoc. Thus, there is an urgent need to produce drugs and vaccines for the same as no approved vaccinations exist for the virus as of now. With the optimization of codon usage, the process of vaccine development can be accelerated and efficacy can be ensured. ZIKV genome has 3 structural genes (envelope, capsid and membrane which is obtained from pre membrane) and 7 nonstructural genes (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). We have used these 10 genes in 5 different strains of ZIKV for in silico DNA optimization in Escherichia coli. The mean CAI, GC% and AT% of wild-type DNA and optimized DNA of each were compared. It was observed that the CAI and GC% had increased in optimized DNA as compared to wild- type while the opposite was seen for AT%. The results show that codon optimization helps in efficient expression of proteins in the host. These could be used in the development of biotherapeutics. The ideal genes to be overexpressed in development of biotherapeutics are the membrane precursor (prM) and envelope (E) genes as the results have shown.

bioinformatics↗

Monocot-specific miR528 act as the post-transcriptional regulator of strigolactone signaling via Dwarf 3 in rice

miRNAs are a critical component of regulatory mechanisms involved in plant growth, development, and stress response including phytohormone action. The role of miRNAs in regulating the strigolactone (SL) signaling in plants is still unexplored. Here we report that miR528 impacts the SL signaling via the post-transcriptional regulation of Dwarf 3 (OsD3). Comparative miRNome analysis under drought conditions in flag leaf, inflorescence, and roots uncovered the tissue-biased unique stress response of miR528 in drought-tolerant N22 (down in inflorescence and roots; up in flag leaf). Consequently, its target, OsD3 which encodes for the F-BOX/LRR-REPEAT MAX2 HOMOLOG and is a critical component of the rice SL signaling pathway exhibit opposite expression to miR528 in all three tissues. Interestingly, OsD3 is a rice-specific target of miR528. miR528 overexpression plants exhibited early heading, increment in the number of tillers, flag leaf length, and width, number of panicle branches, grain per panicle, effective grains per panicle, seed length, and photosynthesis rate. miR528 overexpression plants exhibited similar traits to Osd3 mutants including high tiller number, root architecture under low nitrogen conditions, and moderate insensitivity to GR24 and TIS1 levels in addition to shared transcriptional regulation. Furthermore, SL (GR24) negatively impacts the miR528 transcription. The impact of the miR528:D3 module is also reflected in the D53-mediated downstream signaling involving IPA1 regulon.

plant biology↗

Investigations on regulation of miRNAs in rice reveal cyt signal transduction regulated miRNAs

MicroRNAs are critical components of the multi-dimensional regulatory networks in eukaryotic systems. They regulate a spectrum of developmental and metabolic processes in both plants and animals. Thus, it is quite apparent that the transcription, processing as well as activity of the miRNAs themselves is very dynamically regulated. One of the most important and universally implicated signalling molecule is [Ca2+]cyt. It is known to regulate a plethora of developmental and metabolic processes in both plants and animals, however their impact on the regulation of miRNA expression is relatively less explored. The current study employed a combination of internal and external calcium channel inhibitors, to establish that [Ca2+]cyt signatures actively regulate miRNA expression in rice. Involvement of [Ca2+]cyt in regulation of miRNA expression was further confirmed by treatment with calcimycin, the calcium ionophore. Modulation of the cytosolic calcium levels was also found to regulate the drought responsive expression as well as ABA mediated response of miRNA genes in rice seedlings. The study further establishes the role of calmodulins and Calmodulin-binding Transcription Activators (CAMTAs) as important components of the signal transduction schema that regulates miRNA expression. Yeast-one-hybrid assay established that OsCAMTA4 & 6 are involved in the transcriptional regulation of miR156a and miR167h. Thus, the study was able to clearly establish that [Ca2+]cyt is actively involved in regulating expression of miRNA genes both under control and stress conditions.

plant biology↗

Pathogenic bacteria grown in iron and zinc milieu exhibit magnetotaxis

The growing number of multiple drug resistant (MDR) bacteria and the dwindling pipeline of new antibiotics are driving us towards a post-antibiotic era in which even common infections would become difficult to treat. To address this, an antibiotic-free strategy that can combat multiple bacteria is recommended. Most of the proposed approaches nevertheless have several limitations, including bacterial targeting. To overcome such limitations, the proposed strategy employs the bacterial machinery to self-destruct. Herein, the biosynthesis of magnetic nanoparticle (MNP) is reported for the first time in multiple pathogenic bacteria, including MDR bacteria. The intracellular MNPs composed of superparamagnetic zinc ferrites were formed in presence of iron and zinc precursors. Exposure of the treated bacteria/biofilms to an alternating magnetic field (AMF) exhibited hyperthermia (5-6{degrees}C) and a dramatic decrease in bacterial viability, suggesting the MNPs therapeutic potential. Likewise, the bacteria existing in vivo biosynthesize the MNPs by mining these elements from the host. To determine its therapeutic efficacy, the infected tissues were exposed directly to AMF. A 3-4 log reduction in bacterial burden, as compared to antibiotics treatment, confirmed the significance of using naturally existing MNPs to combat bacterial infections. The proposed broad-spectrum approach can therefore aid in overcoming the challenges facing anti-bacterial therapies.

microbiology↗

The vesicular trafficking system component MIN7 is required for minimizing Fusarium graminearum infection

Plants have developed intricate defense mechanisms, referred to as innate immunity, to defend themselves against a wide range of pathogens. Plants often respond rapidly to pathogen attack by the synthesis and delivery of various antimicrobial compounds, proteins and small RNA in membrane vesicles to the primary infection sites. Much of the evidence regarding the importance of vesicular trafficking in plant-pathogen interactions comes from the studies involving model plants whereas this process is relatively understudied in crop plants. Here we assessed whether the vesicular trafficking system components previously implicated in immunity in Arabidopsis thaliana play a role in the interaction with Fusarium graminearum, a fungal pathogen notoriously famous for its ability to cause Fusarium head blight (FHB) disease in wheat. Among the analyzed vesicular trafficking mutants, two independent T-DNA insertion mutants in the AtMin7 gene displayed a markedly enhanced susceptibility to F. graminearum. Earlier studies identified this gene, encoding an ARF-GEF protein, as a target for the HopM1 effector of the bacterial pathogen Pseudomonas syringae pv. tomato, which destabilizes AtMIN7 leading to its degradation and weakening host defenses. To test whether this key vesicular trafficking component may also contribute to defense in crop plants, we identified the candidate TaMin7 genes in wheat and knocked-down their expression through Virus induced gene silencing. Wheat plants in which TaMIN7 were silenced displayed significantly more FHB disease. This suggests that disruption of MIN7 function in both model and crop plants compromises the trafficking of innate immunity signals or products resulting in hyper-susceptibility to various pathogens. One sentence summaryDisruption of an ARF-GEF protein encoding gene AtMin7 in Arabidopsis thaliana and silencing of the orthologous gene in wheat result in hyper susceptibility to the fungal pathogen Fusarium graminearum.

plant biology↗