Biology subjects

Kumari, C.

Publications and source records attributed to Kumari, C..

9 recordsLinked to original sources

bioRxiv2026

Single-Cell Omics to Uncover Cell-Type-Specific Gene Regulatory Networks Driving Mucilage Production in Specialized Roots

Aerial roots of certain maize (Zea mays) and sorghum (Sorghum bicolor) genotypes secrete a carbohydrate-rich mucilage that sustains nitrogen-fixing bacteria, and the underground roots of most plants secrete mucilage at their tips. In both settings, border cells released from the root cap produce this mucilage, yet the genes controlling their formation remain largely unknown. We sequenced the RNA of about 23,000 nuclei from mucilage-secreting roots of maize, sorghum, and Medicago truncatula, sampled before and after secretion. Each species yielded 10 to 15 clusters, which we annotated with published markers and with new markers that we validated by in situ hybridization in the two cereals and by promoter-reporter fusions in M. truncatula. We then inferred modular and cell type-specific gene regulatory networks. Transcriptional programs diverged across the three species except in the quiescent center and the meristem, and in the clusters containing border cells, where a shared set of regulators emerged. Silencing three of five candidate regulators reduced border cell number, while silencing a partially overlapping set of three regulators reduced root diameter in M. truncatula. Silencing the C2H2 zinc finger protein MtrunA17_Chr1g0148421 also reduced border cell viability. A maize insertion mutant of bzip89 released fewer border cells than the wild type. These networks offer entry points for tuning mucilage production in cereal and legume crops.

plant biology↗

bioRxiv2026

Ribosome Processing Factor-2 Interacts with RPL10A to Regulate Selective Translation during Plant Immunity and Drought Stress

Processing of ribosomal RNA (rRNA) is essential for ribosome biogenesis, translation, plant development, and stress adaptation. Ribosome processing factor-2 (RPF2), which plays a role in the later stages of rRNA maturation, interacts with ribosomal protein L10A (RPL10A). RPF2 overexpression in Arabidopsis and Nicotiana benthamiana showed enhanced plant growth and trichome development due to increased gibberellic acid (GA) levels. Conversely, RPF2-silenced and mutant plants had a dwarf phenotype, reduced stomatal apertures, and decreased glucosinolate accumulation. RPF2 silenced and mutant plants also showed compromised nonhost disease resistance, whereas RPF2 overexpression lines exhibited enhanced disease resistance to both host and nonhost pathogens. RPL10A and RPF2 overexpression lines were sensitive to abscisic acid (ABA) and tolerant to drought, which is attributed to their unique roles in translation regulation. Despite having larger stomatal apertures, RPF2 overexpression plants displayed low pathogen multiplication rates and reduced water loss, indicating independent resistance mechanisms associated with ribosomal functions in translation regulation. Although both RPL10A and RPF2 proteins interact with each other and are involved in translation regulation, proteomic analysis suggests that they regulate the translation of distinct sets of genes during pathogen or drought stress. These findings indicate that RPF2 and RPL10A play independent roles in the regulation of unique protein translation.

plant biology↗

bioRxiv2025

Structural Validation of the Intermediate Leptomeningeal Layer in the Human Central Nervous System

Traditionally, the human central nervous system (CNS) is described as having three meningeal layers, from outer to inner: dura mater, arachnoid mater, and pia mater. The arachnoid and pia mater are called the leptomeninges, and the space between them is filled with cerebrospinal fluid (CSF). Using gross dissection, light microscopy, and ultrastructural analysis of fresh postmortem and cadaveric CNS specimens spanning fetal to adult ages (N=61), we demonstrate a fibrocellular intermediate leptomeningeal layer (ILL) from the cortex to the caudal end of the spinal cord. The ILL divides the subarachnoid space (SAS) into two distinct structural compartments, through which vessels and nerves pass. The ILL shows unique structural features, such as dips into the brains sulci and fissures, as a double-fold membrane that bears intra-layer trabeculae, carries vessels, and forms the perivascular sheath. Moreover, throughout the CNS, it appears to be a non-sieved barrier, characterized by the presence of tight and adherens junctions. ILL, predominantly in the spinal cord, contains macrophage-like cells, indicating its layer-specific immune properties. The ILL warrants recognition as a distinct human meningeal layer with potential barrier and immune functions. SignificanceO_ST_ABSAn Intermediate Leptomeningeal Layer encloses the Central Nervous System in HumansC_ST_ABSThe integrated analysis of our macroscopic, microscopic, and ultrastructural study provides robust support for an intermediate leptomeningeal layer (ILL) in the subarachnoid space (SAS) of the human central nervous system (CNS) along the entire neural axis. The ILL is a fibrocellular macroscopic structure, with restricted permeability, that divides the cerebrospinal fluid (CSF)-filled SAS into two distinct structural compartments. Uniquely, ILL revealed the presence of cells with macrophage-like properties, suggesting a possible role in immune surveillance. The ILL may redefine the established concept of protective coverings of CNS, CSF circulation dynamics, and the role of leptomeninges in health and disease, including drug delivery.

neuroscience↗

bioRxiv2024

Aligning with the predecessors and counterarguments: A systematic review of the anatomical correlates for the newly discovered meningeal layer in the existing literature

A recent study reported the existence of a subarachnoid lymphatic-like membrane (SLYM) -an intermediate leptomeningeal layer between the arachnoid and pia mater in mice and human brains - dividing the subarachnoid space (SAS) into two functional compartments. Despite being a macroscopic structure, how it missed detection in previous studies is surprising. We systematically reviewed the published reports in animals and humans to explore whether prior descriptions of this meningeal layer have existed. An electronic search was conducted in PubMed/Medline, EMBASE, Google Scholar, Science Direct, and Web of Science databases using combinations of MeSH terms and keywords with Boolean operators from inception until 31st Dec 2023. We found at least eight studies that provided structural evidence of an intermediate leptomeningeal layer in the brain or spinal cord. However, unequivocal descriptions for this layer all along the central nervous system were scarce. Obscured names were used to describe it, i.e., the epipial layer, intermediate meningeal layer, intermediate lamella, and outer pial layer. Its microscopic/ultrastructural details closely resembled the SLYM. Further, we examined the counterarguments in current literature that are skeptical of this layers existence. Considering the significant physiological/clinical implications, exploring further structural and functional details of the new meningeal layer is a need of the hour.

neuroscience↗

bioRxiv2022

NRP1 and furin as putative mediators of SARS-CoV-2 entry into human brain cells

COVID-19 has prominent neurological manifestations including psychiatric symptoms, indicating significant synaptic pathology. Surprisingly, existing evidence suggests negligible expression of the key SARS-CoV-2 host cell entry mediators ACE2 and TMPRSS2 in human brain, which complicates understanding of the pathomechanisms of the neuropsychiatric manifestations in COVID-19. Recent studies suggested that an alternative host-cell entry receptor, NRP1, can mediate entry of furin cleaved SARS-CoV-2 spike proteins into the host cells. However, the role of NRP1 and furin in mediating SARS-CoV-2 entry in human brain cells has been least explored and remains a lacuna in the literature. We performed an in silico analysis of the transcriptomic and proteomic expressions of SARS-CoV-2 host-cell entry receptors and associated tissue proteases in human brain tissue, using the publically available databases. Based on the expression analysis, SARS-CoV-2 entry in human brain cells is likely to be mediated through NRP1 and furin. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/476893v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1c818baorg.highwire.dtl.DTLVardef@1cf7c0corg.highwire.dtl.DTLVardef@d92e19org.highwire.dtl.DTLVardef@61866a_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

Relevance of enriched expression of SARS-CoV-2 binding receptor ACE2 in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients

IntroductionCOVID-19 is caused by a new strain of coronavirus called SARS-coronavirus-2 (SARS-CoV-2), which is a positive sense single strand RNA virus. In humans, it binds to angiotensin converting enzyme 2 (ACE2) with the help a structural protein on its surface called the S-spike. Further, cleavage of the viral spike protein (S) by the proteases like transmembrane serine protease 2 (TMPRSS2) or Cathepsin L (CTSL) is essential to effectuate host cell membrane fusion and virus infectivity. COVID-19 poses intriguing issues with imperative relevance to clinicians. The pathogenesis of GI symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 are of particular relevance because they cannot be sufficiently explained from the existing knowledge of the viral diseases. Tissue specific variations of SARS-CoV-2 cell entry related receptors expression in healthy individuals can help in understanding the pathophysiological basis the aforementioned collection of symptoms. Materials and MethodsThe data were downloaded from the Human Protein Atlas available at (https://www.proteinatlas.org/humanproteome/sars-cov-2) and the tissue specific expressions (both mRNA and protein) of ACE2 and TMPRSS2 as yielded from the studies with RNA sequencing and immunohistochemistry (IHC) were analyzed as a function of the various components of the digestive tract. A digestive system specific functional enrichment map of ACE2 gene was created using g:profiler (https://biit.cs.ut.ee/gprofiler/gost) utility and the data were visualized using Cytoscape software, version 3.7.2 (https://cytoscape.org/). ResultsThe correlated expression (transcriptomic and proteomic) of ACE2 (to which SARS-CoV-2 binds through the S-spike) was found to be enriched in the lower gastrointestinal tract (GIT) (highest in small intestine, followed by colon and rectum), and was undetectable in the upper GIT components: mouth cavity (tongue, oral mucosa, and salivary glands), esophagus, and stomach. High expression of ACE2 was noted in the glandular cells as well as in the enterocytes in the lining epithelium (including brush border epithelium). Among other digestive system organs, Gall bladder (GB) showed high expression of ACE2 in glandular cells, while any protein expression was undetectable in liver and pancreas. TMPRSS2 was found enhanced in GIT and exocrine glands of pancreas, and co-localized with ACE2 in enterocytes. ConclusionsBased on the findings of this study and supportive evidence from the literature we propose that a SARS-CoV-2 binding with ACE2 mediates dysregulation of the sodium dependent nutrient transporters and hence may be a plausible basis for the digestive symptoms in COVID-19 patients. ACE2 mediated dysregulation of sodium dependent glucose transporter (SGLT1 or SLC5A1) in the intestinal epithelium also links it to the pathogenesis of diabetes mellitus which can be a possible reason for the associated mortality in COVID-19 patients with diabetes. High expression of ACE2 in mucosal cells of the intestine and GB make these organs potential sites for the virus entry and replication. Continued replication of the virus at these ACE2 enriched sites may be a basis for the disease recurrence reported in some, thought to be cured, patients. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

pathology↗

bioRxiv2020

Altered kinetics of circulating progenitor cells in cardiopulmonary bypass (CPB) associated vasoplegic patients: An observational study

Vasoplegia observed post cardiopulmonary bypass (CPB) is associated with substantial morbidity, multiple organ failure and mortality. Circulating counts of hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPC) are potential markers of neo-vascularization and vascular repair. However, the significance of changes in the circulating levels of these progenitors in perioperative CPB, and their association with post-CPB vasoplegia, are currently unexplored. We enumerated HSC and EPC counts, via flow cytometry, at different time-points during CPB in 19 individuals who underwent elective cardiac surgery. These 19 individuals were categorized into two groups based on severity of post-operative vasoplegia, a clinically insignificant vasoplegic Group 1 (G1) and a clinically significant vasoplegic Group 2 (G2). Differential changes in progenitor cell counts during different stages of surgery were compared across these two groups. Machine-learning classifiers (logistic regression and gradient boosting) were employed to determine if differential changes in progenitor counts could aid the classification of individuals into these groups. Enumerating progenitor cells revealed an early and significant increase in the circulating counts of CD34+ and CD34+CD133+ hematopoietic stem cells (HSC) in G1 individuals, while these counts were attenuated in G2 individuals. Additionally, EPCs (CD34+VEGFR2+) were lower in G2 individuals compared to G1. Gradient boosting outperformed logistic regression in assessing the vasoplegia grouping based on the fold change in circulating CD 34+ levels. Our findings indicate that a lack of early response of CD34+ cells and CD34+CD133+ HSCs might serve as an early marker for development of clinically significant vasoplegia after CPB.

physiology↗

bioRxiv2019

Transcriptomic Analysis of the Neurogenesis Signature suggests Continued but Minimal Neurogenesis in the Adult Human Hippocampus

PurposeSince immunohistological investigations have given rise to divergent perspectives about continued hippocampal neurogenesis in adult humans, a comprehensive transcriptomic analysis of the neurogenesis signature markers supplemented with insights from gliogenesis and apoptotic markers (in context to the developmental stages across age) may discern important aspects and may well be the appropriate methodology for resolving this conflict.\n\nMaterials and MethodsRNA expression data for the salient neurogenesis, gliogenesis, and apoptotic marker genes in post-mortem human hippocampal tissue of the Prenatal (n=15), Infant/Early childhood (n= 5), Adolescence (n=4), and Adulthood (n=6) ages were downloaded from Allen Brain Atlas database (http://www.brainspan.org/rnaseq). Gene expression data was categorized, median values were computed, and age group specific differential expression was statistically analyzed (the confidence level of 95%, p value [≤] 0.05 is used).\n\nResultsA sharp fall in prenatal to infant/early childhood expression was observed for all studied neurogenesis markers, except that for the post-mitotic late maturation (CALB1, CALB2, MAP2, NEUN, STMN2) which showed no significant differences in expression profiles. A continued post childhood decrease across advancing age was observed in the neural stem cells and progenitor markers with insignificant differences across close age groups. Uniquely, the postnatal sharp fall of KI67 and TBR2 continued across advancing age groups, reached near baseline until adolescent age. The immature granule cell, post mitotic early maturation, and late maturation markers showed a maintained or slightly increased (albeit insignificant) post childhood expression. The gliogenesis markers mostly showed a significant downregulation between prenatal and infant /early childhood age groups; this decline was persistent thereafter with insignificant differences between close age groups. A continued postnatal decrease occurred in apoptotic markers with observable, but insignificant, differences between adolescent and adult age.\n\nConclusionsOur findings indicate a possibility of continued but minimal neurogenesis in the adult human hippocampus. A significant part of the newborn cells in the neurogenic niche may be glial cells.\n\n(Findings of this study were first presented at the Annual Meeting of Society for Neuroscience (SFN), 3rd-7th November, 2018, San Diego, USA. https://abstractsonline.com/pp8/#!/4649/presentation/37213)\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=153 SRC=\"FIGDIR/small/664995v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (43K):\norg.highwire.dtl.DTLVardef@3268f3org.highwire.dtl.DTLVardef@18855bborg.highwire.dtl.DTLVardef@1b46bdaorg.highwire.dtl.DTLVardef@14b929_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract\n\nC_FIG HighlightsO_LIA varying but continued fall in expression was observed for all studied neurogenesis markers across advancing age groups, except that for the immature granule cells, early and post-mitotic late neuronal maturation markers.\nC_LIO_LIA continued postnatal sharp fall of progenitor markers KI67 and TBR2 reached near baseline until adolescent age.\nC_LIO_LIGliogenesis markers showed continued but insignificant fall in expression post infant/early childhood.\nC_LIO_LIApoptotic markers showed continued post infant/early childhood downfall but changes were negligible between adolescent and adult age.\nC_LI

neuroscience↗

bioRxiv2018

Predicting JNK1 Inhibitors Regulating Autophagy in Cancer using Random Forest Classifier

Autophagy (in Greek: self-eating) is the cellular process for delivery of heterogenic intracellular material to lysosomal digestion. Protein kinases are integral to the autophagy process, and when dysregulated or mutated cause several human diseases. Atg1, the first autophagy-related protein identified is a serine/threonine protein kinases (STPKs). mTOR (mammalian Target of Rapamycin), AMPK (AMP-activated protein kinase), Akt, MAPK (mitogen-activated protein kinase) and PKC (protein kinase C) are other STPKs which regulate various components/steps of autophagy, and are often deregulated in cancer. MAPK have three subfamilies - ERKs, p38, and JNKs. JNKs (c-Jun N-terminal Kinases) have three isoforms in mammals - JNK1, JNK2, and JNK3, each with distinct cellular locations and functions. JNK1 plays role in starvation induced activation of autophagy, and the context-specific role of autophagy in tumorigenesis establish JNK1 a challenging anticancer drug target. Since JNKs are closely related to other members of MAPK family (p38, MAP kinase and the ERKs), it is difficult to design JNK-selective inhibitors. Designing JNK isoform-selective inhibitors are even more challenging as the ATP-binding sites among all JNKs are highly conserved. Although limited informations are available to explore computational approaches to predict JNK1 inhibitors, it seems diificult to find literature exploring machine learning techniques to predict JNKs inhibitors. This study aims to apply machine learning to predict JNK1 inhibitors regulating autophagy in cancer using Random Forest (RF). Here, RF algorithm is used for two purposes- to select and rank the molecular descriptors calculated using PaDEL descriptor software and as clasifier. The descriptors are prioritized by calculating Variable Importance Measures (VIMs) using functions based on mean square error (IncMSE) and node purity (IncNodePurity) of RF. The classification models based on a set of 22 prioritized descriptors shows accuracy 86.36%, precision 88.27% and AUC (Area Under ROC curve) 0.8914. We conclude that machine learning-based compound classification using Random Forest is one of the ligand-based approach that can be opted for virtual screening of large compound library of JNK1 bioactives.\n\nAuthor SummaryOut of the three isoforms of JNKs (cJun N-terminal Kinases) in human (each with distinct cellular locations and functions), JNK1 plays role in starvation induced activation of autophagy. The role of JNK1 in autophagy modulation and dual role of autophagy in tumor cells makes JNK1 a promising anticancer drug target. Since JNKs are closely related to other members of MAPK (Mitogen-Activated Protein Kinases) family, it is difficult to design JNK selective inhibitors. Designing JNK isoformselective inhibitors are even more challenging as the ATP binding sites among all JNKs are highly conserved. Random forest classifier usually outperforms several other machine learning algorithms for classification and prediction tasks in diverse areas of research. In this work, we have used Random Forest algorithm for two purposes: (i) calculating variable importance measures to rank and select molecular features, and (ii) predicting JNK1 inhibitors regulating autophagy in cancer. We have used paDEL calculated molecular features of JNK1 bioactivity dataset from ChEMBL database to build classification models using random forest classifier. Our results show that by optimally selecting features from top 10% based on variable importance measure the classification accuracy is high, and the classification model proposed in this study can be integrated with drug design pipeline to virtually screen compound libraries for predicting JNK1 inhibitors.

bioinformatics↗