Biology subjects

Kar, S.

Publications and source records attributed to Kar, S..

8 recordsLinked to original sources

bioRxiv2018

Anemia Diagnosis on a Simple Paper-based Assay

In developing countries, the maternal and neonatal mortality rate is often affected by prenatal period anemia, a preventable and ubiquitous impairment attributed due to low hemoglobin (Hgb) concentration. We report the development of a simple, frugal (~ 0.02 $ per test), rapid and high fidelity paper-based colorimetric microfluidic device for point-of-care (POC) detection of anemia. We validate our findings with 32 blood samples collected from different patients covering a wide spectrum of anemia and subsequently, compare with standard pathological results measured using a hematology analyzer. POC based Hgb estimates are correlated with the pathological gold standard estimates of Hgb levels (r = 0.909), and the POC test method yielded similar sensitivity and specificity for detecting mild anemia (n = 8) (<11 g/dl) (sensitivity: 87.5%, specificity: 100 %) and for severe anemia (n = 3) (<7 g/dl) (sensitivity: 100 %, specificity: 100 %). The estimated Hgb levels are, within 1.5 g/dl from the pathological estimate, for 91 % of the blood samples. Results demonstrate the elevated efficacy and viability of this POC colorimetric diagnostic test, in comparison to the state-of-the-art complex and expensive diagnostic tests for anemia detection.

bioengineering↗

bioRxiv2018

Rapid Eye Movement sleep deprivation of rat generates ROS in the hepatocytes and make them more susceptible to oxidative stress

BackgroundRapid Eye Movement sleep deprivation (REMSD) of rats causes inflammation of the liver and apoptotic cell death of neurons and hepatocytes. Studies also suggest that REMSD are involved with muscle injury, cardiac injury and neurodegerative diseases.\n\nObjective and methodsThe aim of this research was to determine whether REMSD of rats would generate reactive oxygen species (ROS) and create oxidative stress in the hepatocytes. We selectively deprived the rats from REM sleep using the standard flower pot method.\n\nResultsWe observed that when rats were subjected to REMSD, the levels of ROS in the hepatocytes increased with the increase in the number of days of REMSD by [~]265%, but it returned towards normal levels after recovery sleep for 5 days ([~]36%) compared to controls. Nitric oxide synthase (iNOS) gene and protein was found elevated in hepatocytes in response to REM sleep loss as confirmed by real time PCR and western blot analysis compared to controls. The level of nitric oxide (NO) also increased by [~] 675% in the hepatocytes of REMSD rats as compared to that of control group of animals.\n\nDiscussionWe have analyzed the oxidative stress generated and potentiation of hepatocytes against oxidative stress in response to REMSD. Since, REM sleep is known to play an important role for survival of most animals and has important role in maintenance of body physiology. Hence, our findings that loss of REM sleep in hepatocytes of rats can affect the ROS levels and induce iNOS & NO circulation, while making them more susceptible to oxidative stress assumes significance.\n\nHighlights of the studyO_LIWe observed elevated levels of ROS in the hepatocytes of REM sleep deprived rats.\nC_LIO_LIThe hepatocytes of REMSD group of rats were found more susceptible to oxidative stress than that of control groups.\nC_LIO_LIWe found increased expression of iNOS gene and nitric oxide synthase protein in the hepatocytes of REMSD rats.\nC_LIO_LIWe observed that nitric oxide levels in the hepatocytes of REM sleep deprived rats increased positively with days of REMSD, but returned to its normal levels after 5 days of recovery sleep.\nC_LI

molecular biology↗

bioRxiv2018

Rapid eye movement sleep deprivation causes apoptotic cell-death of the hepatocytes in rat

IntroductionThe rapid eye movement sleep deprivation (REMSD) of rats relates with increased inflammations, acute phase response, oxidative damage, neuronal cell loss, and neurodegenerative diseases. Whereas, its role outside brain are not well studied. This study tried to explore the causal effect of REM sleep loss on hepatocytes.\n\nMethodsWe deprived the rats of REM sleep using standard flower pot method. We focused on liver to see the REMSD affects which controls most of the metabolic processes of the body.\n\nResultsWe report here that flower pot induced REMSD causes apoptotic cell death of hepatocytes (~10% by Annexin Assay & ~20% by TUNEL assay). This were further got alleviated up to extent after sleep recovery of 5 days (recovered approximately 8.0% by Annexin Assay & 14% by TUNEL assay). The gene expression and protein level profiling revealed the up-regulation of p53, Bax, Cytochrome c, Caspase 3, and Caspase 9. While, Bcl2 which is an anti-apoptotic protein were down-regulated in response to REMSD. Relentless recovery of 5 days affected the expression pattern of these genes/proteins.\n\nConclusionsOur study offer great pathological and physiological significance for sleep loss, by inferring the apoptotic cell-death in the hepatocytes of rat. This further signifies the functional and preventive role of REM sleep which is unique to mammals and avians with certain exceptions, as its loss can affect the natural well-being and survival of the individuals.\n\nHighlights of the studyO_LIWe observed significant apoptosis in the hepatocytes of REMSD group of rats.\nC_LIO_LIOur expression analysis confirmed altered expression for genes p53, Bcl2, Bax, and Caspase-3 after REMSD.\nC_LIO_LIProtein level analysis supported our gene expression results for p53, Bcl2, Bax, Caspase 3 and Caspase 9 after REMSD.\nC_LIO_LISleep recovery improved the respective genes and protein expression levels towards normalcy, signifying the functional role of REM sleep.\nC_LI

molecular biology↗

bioRxiv2018

Multi-Tissue Transcriptome-Wide Association Studies Identify 21 Novel Candidate Susceptibility Genes for High Grade Serous Epithelial Ovarian Cancer

Genome-wide association studies (GWASs) have identified about 30 different susceptibility loci associated with high grade serous ovarian cancer (HGSOC) risk. We sought to identify potential susceptibility genes by integrating the risk variants at these regions with genetic variants impacting gene expression and splicing of nearby genes. We compiled gene expression and genotyping data from 2,169 samples for 6 different HGSOC-relevant tissue types. We integrated these data with GWAS data from 13,037 HGSOC cases and 40,941 controls, and performed a transcriptome-wide association study (TWAS) across >70,000 significantly heritable gene/exon features. We identified 24 transcriptome-wide significant associations for 14 unique genes, plus 90 significant exon-level associations in 20 unique genes. We implicated multiple novel genes at risk loci, e.g. LRRC46 at 19q21.32 (TWAS P=1x10-9) and a PRC1 splicing event (TWAS P=9x10-8) which was splice-variant specific and exhibited no eQTL signal. Functional analyses in HGSOC cell lines found evidence of essentiality for GOSR2, INTS1, KANSL1 and PRC1; with the latter gene showing levels of essentiality comparable to that of MYC. Overall, gene expression and splicing events explained 41% of SNP-heritability for HGSOC (s.e. 11%, P=2.5x10-4), implicated at least one target gene for 6/13 distinct genome-wide significant regions and revealed 2 known and 26 novel candidate susceptibility genes for HGSOC.\n\nSTATEMENT OF SIGNIFICANCEFor many ovarian cancer risk regions, the target genes regulated by germline genetic variants are unknown. Using expression data from >2,100 individuals, this study identified novel associations of genes and splicing variants with ovarian cancer risk; with transcriptional variation now explaining over one-third of the SNP-heritability for this disease.

genomics↗

bioRxiv2018

Disproportionate feedback interactions govern cell-type specific proliferation in mammalian cells

In mammalian cells, the critical decision to maintain quiescence over proliferation commitment in and around the G1-S transition depends on more than one intertwined feedback interaction, and is highly cell-type dependent. However, the precise role played by these individual feedback regulations, in order to generate such diverse nature of proliferation commitment, is still poorly understood. Herein, we propose a generic mathematical model of G1-S transition in mammalian cells that not only reconciles distinct single cell experimental observations in a cell-type specific manner, but also makes experimentally testable non-intuitive predictions. Intriguingly, The model analysis reveals that the feedback motifs responsible for the G1-S transition act in a disparate fashion to organize the cell-type specific proliferation response in different mammalian cells. The proposed model, in principle, can be effectively tuned to explore proliferation dynamics in a cell-type specific way to gain crucial insights about novel therapeutic intervention to prevent unwanted cellular proliferation.

systems biology↗

bioRxiv2017

Subtle alteration in microRNA dynamics accounts for differential nature of cellular proliferation

In the G1 phase of the mammalian cell cycle, a bi-stable steady state dynamics of the transcription factor E2F ensures that only a certain threshold level of the growth factor can induce a high expression level (on state) of E2F to initiate either normal or abnormal cellular proliferation or even apoptosis. A group of microRNAs known as the mir-17-92 cluster, which specifically inhibits E2F, can simultaneously influence the threshold level of growth factor required for E2F activation, and the corresponding expression level of E2F in the on state. However, mir-17-92 cluster can function as either oncogene or tumor suppressor in a cell-type specific manner for reasons that still remain illusive. Here we put forward a deterministic mathematical model for Myc/E2F/mir-17-92 network that demonstrates how the experimentally observed mir-17-92 mediated differential nature of the cellular proliferation can be reconciled by having conflicting steady state dynamics of E2F for different cell types. While a 2-D bifurcation study of the model rationalizes the reason behind the contrasting E2F dynamics, an intuitive sensitivity analysis of the model parameters predicts that by exclusively altering the mir-17-92 related part of the network, it is possible to experimentally manipulate the cellular proliferation in a cell-type specific fashion for therapeutic intervention.

systems biology↗

bioRxiv2017

P-values and confidence intervals: not fit for purpose?

DeclarationsCompeting interests: All authors have completed theunified competing interest form and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.\n\nThe lead author (the manuscripts guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted.\n\nEthical approval: not required\n\nDetails of funding: Not applicable\n\nStatement of independence of researchers from funders: Not applicable\n\nPatient involvement statement. Not applicable.\n\nData sharing statement: Not applicable.

scientific communication and education↗

bioRxiv2017

Deciphering the dynamical origin of mixed population during neural stem cell developmental lineage commitment

Neural stem cells (NSC's) often give rise to mixed population of cells during differentiation. However, the dynamical origin of these mixed states is poorly understood. In this article, our mathematical modeling study demonstrates that the bone morphogenetic protein 2 (BMP2) driven differential differentiation dynamics of NSC's in central and peripheral nervous systems essentially function through two distinct bi-stable switches that are mutually interconnected. Stochastic simulations of the model reveal that the mixed population originates due to the existence of these bistable switching regulations while the maintenance of such mixed states depends on the level of stochastic fluctuations of the system. Importantly, the model predicts that by individually altering the expression level of key regulatory proteins, the NSC's can be converted entirely to a preferred phenotype for BMP2 doses that earlier resulted into mixed population. Our findings show that efficient neuronal regeneration can be achieved by systematically maneuvering the differentiation dynamics.\n\nOne-sentence summaryUnraveling the differential dynamical origin, maintenance and escape route of mixed population in the midst of developmental fate commitment in central and peripheral nervous systems

systems biology↗