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Tripathi, R.

Publications and source records attributed to Tripathi, R..

8 recordsLinked to original sources

Dietary depletion of glutamine is atheroprotective

Heart attacks and strokes are late-stage complications of rupture of unstable atherosclerotic plaques. Stable plaques contain stabilizing matrix-producing fibrotic cells, largely smooth muscle cell (SMC)-derived. The molecular drivers of SMC phenotypic transitions to beneficial fibrotic or destabilizing inflammatory and calcifying phenotypes are unclear. Since atherosclerosis develops over decades, there is extensive interest in identifying dietary alterations that enhance plaque stability. We demonstrate that SMC acquire a fibrotic phenotype dependent on glutamine-derived metabolites supporting both catabolism and collagen synthesis. Moreover, dietary glutamine restriction decreases mortality of mice susceptible to atherosclerotic plaque rupture. Lesions from glutamine-restricted mice are smaller and have increased SMC investment. This study identifies dietary glutamine as a driver of cardiovascular mortality, suggesting a new strategy for reducing late-stage complications of atherosclerosis.

physiology↗

Zebrafish sleep displays distinct sub-states

Sleep is an essential and evolutionarily-conserved behavior. While mammals and several other species have been shown to exhibit well-defined sleep sub-states, some of which have been ascribed specific functions, it remains unclear to what extent such differentiation exists across the animal kingdom. Here we show, using long-term behavioral data combined with Hidden Markov Modeling, that larval zebrafish display distinct deep and light sleep sub-states. Although both states occur primarily at night, fish respond differently to sleep deprivation and arousing stimuli depending on which sleep sub-state they are in. Moreover, the proportions of deep and light sleep are selectively altered by genetic and pharmacological manipulations of melatonin, serotonin, and norepinephrine signaling, offering new insights into how these neuromodulators shape sleep architecture. These results support zebrafish as a tractable model for dissecting the regulation and function of sleep sub-states. More broadly, they demonstrate that structured, multi-state sleep is a conserved feature of vertebrate behavior.

neuroscience↗

A network based approach to identifying correlations between phylogeny, morphological traits and occurrence information of fish Species in US river basins.

The complex network framework has been successfully used to model interactions between entities in Complex Systems in the Biological Sciences such as Proteomics, Genomics, Neuroscience, and Ecology. Networks of organisms at different spatial scales and in different ecosystems have provided insights into community assembly patterns and emergent properties of ecological systems. In the present work, we investigate two questions pertaining to fish species assembly rules in US river basins, a) if morphologically similar fish species also tend to be phylogenetically closer, and b) to what extent are co-occurring species that are phylogentically close also morphologically similar? For the first question, we construct a network of Hydrologic Unit Code 8 (HUC8) regions as nodes with interaction strengths (edges) governed by the number of common species. For each of the modules of this network, which are found to be geographically separated, there is differential yet significant evidence that phylogenetic distance predicts morphological distance. For the second question, we construct and analyze nearest neighbor directed networks of species based on their morphological distances and phylogenetic distances. Through module detection on these networks and comparing the module-level mean phylogenetic distance and mean morphological distance with the number of basins of common occurrence of species in modules, we find that both phylogeny and morphology of species have significant roles in governing species co-occurrence, i.e. phylogenetically and morphologically distant species tend to co-exist more. In addition, between the two quantities (morphological distance and phylogentic distance), we find that morphological distance is a stronger determinant of species co-occurrences.

ecology↗

Mechanistic Neural Mass Modeling: from physiology to pathophysiological brain activity

Brain rhythms emerge from the mean-field activity of networks of neurons. There have been many efforts to build mathematical and computational embodiments in the form of discrete cell-group activities - termed neural masses - to understand particular the origins of evoked potentials, intrinsic patterns of activities such as theta, regulation of sleep, Parkinsons disease related dynamics, and instabilities such as seizure dynamics. As originally utilized, standard neural masses convert input through a sigmoidal function to a firing rate, and firing rate through a synaptic alpha function to other masses. Here we define a process to build almost from first principles (i.e. Hodgkin Huxley type models) mean field models of different neuron types that duplicate the stability, firing rate, and associated bifurcations as function of relevant slow variables - such as extracellular potassium - and synaptic current; and whose output is both firing rate and impact on the slow variables - such as transmembrane potassium flux. Small networks composed of just excitatory and inhibitory masses demonstrate expected dynamical states including stable firing, runaway excitation and depolarization block, and these transitions change in biologically observed ways with changes in extracellular potassium and excitatory-inhibitory balance.

neuroscience↗

Semecarpus anacardium Linn. leaf extract exhibits activities against breast cancer and prolongs the survival of tumor bearing mice

Semecarpus anacardium Linn. is commonly used in various traditional medicines from ancient times. The nuts have been described in Ayurveda medication systems to treat numerous clinical ailments. However, isolating phytochemical constituents from nuts remains challenging and exhibits cytotoxic effects on other cells. In this study, we have standardized procedures for isolating phytochemicals from the leaf extract. The ethyl acetate leaf extract selectively affects cancer cells in a dose-dependent manner (IC50: 0.57 g/ml in MCF-7 cells) in various cancer cell lines. Next, we examined if the extract incubation could induce cell cycle arrest and suppress cell migration in the cell culture model. Consistent with this idea, the leaf extract could potentially affect the aggressive migration nature of cancer cells. Moreover, oral administration of extract significantly restored tumor growth in mice. Together, these observations suggest the anti-cancer activities of S. anacardium leaf potential for both in vitro and in vivo models. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/898940v3_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@3fefborg.highwire.dtl.DTLVardef@594510org.highwire.dtl.DTLVardef@c525d2org.highwire.dtl.DTLVardef@1362978_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

Virtaul screening of MAP-Tau protein inhibitors from Semecarpus anacardium Linn. leaf extract for cancer prevention

Semecarpus anacardium is a well known Indian medicinal plant with various medicinal properties like hypoglycemic, antioxidant, anticancer, anti-inflammatory, anti-geriatric, antimicrobial and hair growth promoter, etc. The molecular mechanism of metabolites from fruiting bodies of S. anacardium against cancer has been described but anticancerous properties in its leaves are still unknown. The leaves were extracted in petroleum ether, ethyl acetate and methanol and assayed for anticancer activity using MTT assay. The active extract was evaluated for mode of cell death induction using EtBr-AO double staining and analyzed for phytochemical constituents using GC-MS, followed by molecular docking studies for exploration of possibility for anticancer agents and Drugability. In this study, ethyl acetate extract of leaf was found potent cytotoxic in MCF-7 cells and also induced apoptosis. It has also found the SLE is safe for normal cells. The molecular docking studies were done to explore the probable mechanism of action of the extract which showed 9 compounds are targeting the microtubule-associated protein tau (MAPT). MAPT promotes assembling and prevents disassembling to arrest the cell cycle. The overexpression of MAPT induces chemoresistance to cancerous cells against conventional drugs like paclitaxel. We have identified 17 compounds from ethyl acetate extract of S. anacardium leaves and drawn its chemical structure by using chembiodraw software to transform into pdb format. Further, the compounds have been subjected for molecular docking study to investigate its interactive efficiency with MAPT protein. The compound 13 had higher interactive potential to MAPT with binding energy -31.75 kcal/mol and lowest binding energy (-15.44 kcal/mol) was observed in compound 6. The present study suggested that the compounds from leaves of S. anacardium could be alternative approach of conventional drug for cancer treatment with cost effective and less side effect.

bioinformatics↗

Temperature and polarity based evolutionary model of the ribosomal complex in Thermus thermophilus and Escherichia coli.

The ribosome is considered a molecular fossil of the RNA world and is the oldest molecular machinery of living cells responsible for translating genetic information encoded by messenger RNA(mRNA) to proteins. Currently not much is known regarding how these proteins were assembled and the potential biogeochemical environment that could have shaped their evolution. In order to answer these questions, a comprehensive analysis of the amino acid frequencies of 30S and 50S ribosomal sub-units occurring in thermophile Thermus thermophilus and mesophile Escherichia coli was performed. The amino acid frequencies in proteins are believed to have been shaped by their pre-biotic abundances in the universe and by heavy bombardment of meteorites on planet earth (4.5-3.8 Ga). Absence of amino acid residues such as cysteine and tryptophan in T.thermophilus and E.coli proteins hints towards the evolution of small and large subunits prior to the origin of metabolic pathways of amino acid synthesis possibly under anoxic and sulphur free conditions. Moreover, an underrepresentation of readily oxidizable amino acids such as methionine, tyrosine and histidine, indicates that these proteins could have evolved in a more reducing environment as was prevalent on early earth. A comparison of amino acid biases with universal UNIPROT estimates, indicates arginine and lysine overrepresentation, linking a role of these amino acids in ribosomal RNA binding and stabilization corresponding to the RNA world hypothesis whereby RNA molecules drove the assembly of living systems. The continuing prevalence of these amino acid biases in modern proteins reflects the functional stability of ancient proteins constructed during billions of years of evolution and provides glimpses into the evolution of the ancient amino acid code. Step-wise accretion models involving increasing complexity of the amino acid code and the ribosomal sub-units are proposed for T.thermophilus and E.coli, providing potential insights regarding the origin of ribosomes in a temperature dependent and polar environment.

biochemistry↗

Preparation of Organ Scaffolds by Decellularization of Pancreas and Re-functionalization

Extracellular matrix of each tissue is unique in composition, architecture and finer details that support the very identity of the organ by regulating the status/character of the cells within it. Tissue engineering centers around creating a niche similar to the natural one, with a purpose of developing an organ/oid. In this study, whole organ decellularization of pancreas was attempted followed by reseeding it with adult mesenchymal stem cells. Decellularization completely removes cells leaving behind extracellular matrix rich scaffold. After reseeding, mesenchymal stem cells differentiate into pancreas specific cells. Upon transplantation of recellularized pancreas in streptozotocin induced diabetic mice, this organ was capable of restoring its histomorphology and normal functioning. Restoration of endocrine islets, the exocrine acinar region, and vascular network was seen in transplanted pancreas. The entire process of functional recovery took about 20 days when the mice demonstrated glucoregulation, though none achieved gluconormalization. Transplanted mice upon feeding show insulin and c-peptide in circulation. This process demonstrates that natural scaffolds of soft organs can be refunctionalized using recipients cells to counter immune problems arising due to organ transplantation.

cell biology↗