Biology subjects

Srivastava, S.

Publications and source records attributed to Srivastava, S..

At least 127 records · Page 7Linked to original sources

bioRxiv2020

Temporal transcriptome profiling of Microchloropsis gaditana CCMP526 under hyper-saline conditions

Microalgae can tolerate a wide range of environmental conditions and have been exploited for their lipid and carbohydrate accumulating properties. The utility of this process could be further enhanced through understanding the critical gene regulatory networks that govern the acclimatization process. Advancements in systems biology and sequencing tools now enable us to obtain a genome-wide overview of gene expression under particular conditions of interest. Under salinity stress, Microchloropsis gaditana CCMP526, a commercially important alga has been previously reported to accumulate carbohydrate and lipid. To understand the mechanism of acclimatization, here we report a temporal transcriptomic analysis of M. gaditana under two different salinity levels (55 and 100 PSU). The short term (0, 1 and 6 h) and long term (24 and 72 h) responses of the salt-induced transcript pool were used to identify salinity-inducible genes using correspondence analysis. The transcript abundance of genes involved in triacylglycerol biosynthesis, membrane lipid modification, carbon assimilation and shunting, and osmolyte biosynthesis indicated that M. gaditana employs a two-stage acclimatization strategy during hypersaline conditions.

microbiology↗

bioRxiv2020

Exosomes Facilitate Transmission of SARS-CoV-2 Genome into Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

ABSTRACTThe novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a worldwide pandemic. Early data suggest that the prevalence and severity of COVID-19 appear to be higher among patients with underlying cardiovascular risk factors. Despite the expression of angiotensin-converting enzyme 2 (ACE2), a functional receptor for SARS-CoV-2 infection, in cardiomyocytes, there has been no conclusive evidence of direct viral infection although the presence of inflammation and viral genome within the hearts of COVID-19 patients have been reported. Here we transduced A549 lung epithelial cells with lentivirus overexpressing selected genes of the SARS-CoV-2. We then isolated extracellular vesicles (EVs) from the supernatant of A549 cells and detected the presence of viral RNA within the purified EVs. Importantly, we observed that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were able to actively uptake these EVs and viral genes were subsequently detected in the cardiomyocytes. Accordingly, uptake of EVs containing viral genes led to an upregulation of inflammation-related genes in hiPSC-CMs. Thus, our findings indicate that SARS-CoV-2 RNA-containing EVs represent an indirect route of viral RNA entry into cardiomyocytes.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cell biology↗

bioRxiv2020

Computational investigation for modelling the protein-protein interaction of TasA(28-261)with TapA(33-253); a decisive process in biofilm formation by Bacillus subtilis

Biofilms have significant role in microbial persistence, antibiotic resistance and chronic infections; consequently, there is a pressing need for development of novel "anti-biofilm strategies". One of the fundamental mechanisms involved in biofilm formation is protein-protein interactions of amyloid like proteins (ALPs) in extracellular matrix. Such interactions could be potential targets for development of novel anti-biofilm strategies; therefore, assessing the structural features of these interactions could be of great scientific value. Characterization of biomolecular interaction with conventional structure biology tools including X-Ray diffraction and Nuclear Magnetic Resonance is technically challenging, expensive and time-consuming. In contrast, modelling such interactions is time-efficient, economical and might provide deeper understanding of structural basis of interactions. Therefore, during the present study, protein-protein interaction of TasA(28-261)-TapA(33-253) (which is a decisive process for biofilm formation by Bacillus subtilis) was modeled using in silico approaches viz., molecular modelling, protein-protein docking and molecular dynamics simulations. Results identified amino-acid residues present within intrinsically disordered regions of both proteins to be critical for interaction. These results were further supported with PCA and FEL analyses. Results presented here represent novel finding and we hypothesize that aa identified during the present study could be targeted for inhibition of biofilm formation by B. subtilis.

bioinformatics↗

bioRxiv2020

The Ephrin receptor A2 and Roundabout Guidance Receptor 1 heterodimer: A potential theranostic for squamous cell carcinomas

Squamous cell carcinomas (SCC) of the lung (LSCC) and head and neck (HNSCC) are very prevalent with poor prognosis and limited treatment options. In both cancer types, Ephrin receptor A2 (EPHA2) is known to be overexpressed and exhibit opposing effects via two distinct signaling mechanisms. While it can inhibit cancer cell survival and migration by ligand-dependent signaling through tyrosine kinase phosphorylation at Y588 and Y772, it can promote tumor progression and cell migration in a ligand-independent manner via phosphorylation at S897. Variable ABnormal morphology (VAB-1) is the C. elegans ortholog of the human ephrin receptor (EPHR) that interacts genetically and biochemically in a dose-dependent manner with the axon guidance receptor, SAX3, the worm ortholog of ROBO. Double mutants of vab-1(EPHR)/sx-3(ROBO) are synthetic lethal, underscoring the interaction between the two signaling pathways which prompted us to investigate their role in SCC. Using biochemical and biophysical techniques, we show that EPHA2 and ROBO1 reside in the same complex and interact physically to form a functional heterodimer in LSCC and HNSCC. Furthermore, we show that treating squamous cells with the SLIT2, ligand of ROBO1, hinders phosphorylation of EPHA2 at S897, and thereby, attenuates cell proliferation. Interestingly, SLIT2 can interact with EPHA2 and attenuate the proliferation of cells that have low ROBO1 expression. Additionally, SLIT2 can act synergistically with the EPHA2 inhibitor, Ensartinib to attenuate cell growth in LSCC and HNSCC cells. Taken together, the data suggest that SLIT2 may serve as a novel therapeutic for LSCC and HNSCC. Here, we propose to stratify patients for treatment with SLIT2 and/or Ensartinib, based on their EPHA2 and ROBO1 expression levels in the diseased tissue. Thus 85% of LSCC cases can be treated with combination of SLIT2+Ensartinib and 55% of HNSCC cases can be treated with either SLIT2 or Ensartinib. Furthermore, EPHA2 and ROBO1 may represent novel theranostics in these two diseases. One sentence summaryHeterodimerization of EPHA2 and ROBO1 receptors attenuates growth of squamous cell carcinomas of the lung and head and neck.

cancer biology↗

bioRxiv2020

Structural basis to design multi-epitope vaccines against Novel Coronavirus 19 (COVID19) infection, the ongoing pandemic emergency: an in silico approach

The 2019 novel coronavirus (COVID19 / Wuhan coronavirus), officially named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a positive-sense single-stranded RNA coronavirus. SARS-CoV-2 causes the contagious COVID19 disease also known as 2019-nCoV acute respiratory disease and has led to the ongoing 2019-20 pandemic COVID19 outbreak. The effective counter measures against SARS-CoV-2 infection require the design and development of specific and effective vaccine candidate. In the present study, we have screened and shortlisted 38 CTL, 33 HTL and 12 B cell epitopes from the eleven Protein sequences of SARS-CoV-2 by utilizing different in silico tools. The screened epitopes were further validated for their binding with their respective HLA allele binders and TAP (Transporter associated with antigen processing) molecule by molecular docking. The shortlisted screened epitopes were further utilized to design novel two multi-epitope vaccines (MEVs) composed of CTL, HTL and B cell epitopes overlaps with potential to elicit humoral as well as cellular immune response against SARS-CoV-2. To enhance the immune response for our vaccine design, truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1 (Ov-ASP-1) has been utilized as an adjuvant at N terminal of both the MEVs. Further molecular models for both the MEVs were prepared and validated for their stable molecular interactions with Toll-Like Receptor 3 (TLR 3). The codon-optimized cDNA of both the MEVs were further analyzed for their potential of high level of expression in a human cell line. The present study is very significant in terms of molecular designing of prospective CTL and HTL vaccine against SARS-CoV-2 infection with the potential to elicit cellular as well as humoral immune response. (SARS-CoV-2), Coronavirus, Human Transporter associated with antigen processing (TAP), Toll-Like Receptor (TLR), Epitope, Immunoinformatics, Molecular Docking, Molecular dynamics simulation, Multi-epitope Vaccine Graphical abstractThe designed CTL (Cytotoxic T lymphocyte) and HTL (Helper T lymphocyte) multi-epitope vaccines (MEV) against COVID19 infection. Both the CTL and HTL MEV models show a very stable and well fit conformational complex formation tendency with the Toll like receptor 3. CTL and HTL MEVs: ribbon; Toll like receptor 3: gray cartoon; Adjuvant [truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1]: orange ribbon regions; Epitopes: cyan ribbons regions; 6xHis Tag: magenta ribbon regions. O_FIG O_LINKSMALLFIG WIDTH=87 HEIGHT=200 SRC="FIGDIR/small/019299v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@6cb749org.highwire.dtl.DTLVardef@1752d54org.highwire.dtl.DTLVardef@1f2fc16org.highwire.dtl.DTLVardef@18415a9_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2020

A Data-Independent-Acquisition-based proteomic approach towards understanding the acclimation strategy of Microchloropsis gaditana CCMP526 in hypersaline conditions

Salinity is one of the significant factors that affect growth and cellular metabolism, including photosynthesis and lipid accumulation, in microalgae and higher plants. Microchloropsis gaditana CCMP526 can acclimatize to different salinity levels by accumulating compatible solutes, carbohydrates, and lipids as an energy storage molecule. We used proteomics to understand the molecular basis for acclimation of M. gaditana to increased salinity levels (55 and 100 PSU (Practical Salinity Unit). Correspondence analysis (CA) was used for the identification of salinity-responsive proteins (SRPs). The highest number of altered proteins was observed in 100 PSU. Gene Ontology (GO) enrichment analysis revealed a separate path of acclimation for cells exposed to 55 and 100 PSU. Osmolyte and lipid biosynthesis was up-regulated in high saline conditions. However, concomitantly lipid oxidation pathways were also up-regulated at high saline conditions, providing acetyl-CoA for energy metabolism through the TCA cycle. Carbon fixation and photosynthesis were tightly regulated, while chlorophyll biosynthesis was affected under high salinity conditions. Importantly, temporal proteome analysis of salinity-challenged M. gaditana revealed vital salinity-responsive proteins which could be used for strain engineering for improved salinity resistance.

plant biology↗

bioRxiv2020

The novel reversible LSD1 inhibitor SP-2577 promotes anti-tumor immunity in SWItch/Sucrose-NonFermentable (SWI/SNF) complex mutated ovarian cancer

Chromatin remodeling SWItch/Sucrose-NonFermentable (SWI/SNF) complexes, initially identified in yeast 20 years ago, are evolutionarily conserved multi-subunit protein complexes that use the energy from hydrolysis of adenosine triphosphate (ATP) to remodel nucleosome structure and modulate transcription. Mutations in proteins of SWI/SNF complexes occur in 20% of human cancers including ovarian cancer (OC). Approximately 50% of ovarian clear cell carcinoma (OCCC) carries mutations in the SWI/SNF subunit ARID1A while small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is driven primarily by genetic inactivation of the SWI/SNF ATPase SMARCA4 (BRG1) alongside epigenetic silencing of the homolog ATPase SMARCA2 (BRM). Dual loss of these ATPases disrupts SWI/SNF chromatin remodeling activity and may also interfere with the function of other histone-modifying enzymes that associate with or are dependent on SWI/SNF activity. One such enzyme is lysine-specific histone demethylase 1 (LSD1/KDM1A) which regulates the chromatin landscape and gene expression by demethylating proteins, including histone H3. LSD1 associates with epigenetic complexes such as the nucleosome remodeling deacetylase complex (NuRD) and SWI/SNF to inhibit the transcription of genes involved in tumor suppression and cell differentiation. TGCA analysis of human cancers shows that LSD1 is highly expressed in SWI/SNF-mutated tumors. Further, SCCOHT and OCCC cell lines show low nM IC50s for the reversible LSD1 inhibitor SP-2577 (Seclidemstat, currently in clinical phase I trials), supporting that these SWI/SNF-deficient ovarian cancers are dependent on LSD1 activity. Recently, it has been also shown that inhibition of LSD1 stimulates interferon (IFN)-dependent anti-tumor immunity through induction of Endogenous Retroviruses Elements (ERVs) and may thereby overcome resistance to checkpoint blockade. Additionally, SCCOHTs have been shown to exhibit an immune-active tumor microenvironment with PD-L1 expression in both tumor and stromal cells that strongly correlated with T cell infiltration. Thus, in this study we investigated the ability of SP-2577 to promote anti-tumor immunity and T cell infiltration in SWI/SNF-mutant SCCOHT and OCCC models. Our data shows that the reversible LSD1 inhibitor SP-2577 stimulates IFN-dependent anti-tumor immunity in SCCOHT cells in vitro in a 3D immune-organoid platform. Additionally, SP-2577 promoted the expression of PD-L1 in both SCCOHT and OCCC models. Together our findings suggest that SP-2577 and checkpoint inhibitors as a therapeutic combination may induce or augment immunogenic responses in these tumors.

cancer biology↗

bioRxiv2019

RhoC modulates metabolic networks in cervical cancer by transcriptionally regulating the expression of genes involved in metabolism

In their quest for autonomy, tumor cells are known to reroute metabolic networks to aid their proliferation and survival. These metabolic alterations are governed by the tumor sub-population, thereby contributing towards an additional layer of complexity within the already heterogeneous tumor. For instance, bulk proliferative tumor cells rely on completely different pathways for their metabolic requirements as opposed to the stem-like metastatic cells. However, the molecular switch that drives these metabolic changes remains unknown. RhoC is a well-established contributor towards multiple aspects of tumor development including proliferation, EMT, migration, invasion and metastasis. A transcriptomics-based approach on a RhoC overexpressing cervical cancer cell line unveiled distinct metabolic signatures existent in these cells. Oxidative phosphorylation, TCA cycle, nucleic acid metabolism and fatty acid elongation were some of the specific pathways that emerged as up-regulated. This study therefore provides insight into the intricate metabolic circuitry functional in aggressive RhoC-high cells and thus proposes a pivotal role for RhoC in oncometabolism.

cancer biology↗

bioRxiv2019

Coessential Genetic Networks Reveal the Organization and Constituents of a Dynamic Cellular Stress Response

The interrelated programs essential for cellular fitness in the face of stress are critical to understanding tumorigenesis, neurodegeneration, and aging. However, modelling the combinatorial landscape of stresses experienced by diseased cells is challenging, leaving functional relationships within the global stress response network incompletely understood. Here, we leverage genome-scale fitness screening data from 625 cancer cell lines, each representing a unique biological context, to build a network of "coessential" gene relationships centered around master regulators of the response to proteotoxic, oxidative, hypoxic, and genotoxic stress. This approach organizes the stress response into functional modules, identifies genes connecting distinct modules, and reveals mechanisms underlying cellular dependence on individual modules. As an example of the power of this approach, we discover that the previously unannotated HAPSTR (C16orf72) promotes resilience to diverse stressors as a stress-inducible regulator of the E3 ligase HUWE1. Altogether, we present a broadly applicable framework and interactive tool (http://fireworks.mendillolab.org/) to interrogate biological networks using unbiased genetic screens.

genetics↗

bioRxiv2019

Isolation and molecular identification of pectinase producing Aspergillus species from different soil samples of Bhubaneswar regions

With the significant improvement of human civilization there is a spur in the urban, rural and industrial development, which has a profound effect on the surrounding natural environment. Increased utilization of natural resources is often associated with accumulation of waste materials whose management is crucial for sustainable development of life. Availability of different microorganisms in the soil facilitates the degradation of wastes through their potential enzymatic activities. Pectinase seems to be one of the important enzymes produced by a wide variety of microorganisms contained in the soil. It is mainly involved in maceration and rotting of plant extracts and debris by hydrolysis of 1,4-alpha glycosidic bonds of de-esterified pectate of plant call wall. In this paper we report molecular identification of some pectinase producing Aspergillus species selected from soil samples of five different zones of Bhubaneswar city using molecular biology and computational techniques. Among fifteen fungal isolates studied from these five zones Aspergillus parvisclerotigenus was potent for pectinase production next to Aspergillus niger in form of halozone of 0.6 mm. Its 28S rDNA sequence also had some significant identity (>90%) with different subspecies of Aspergillus. We hope that our findings will helpful in genetic manipulation for improvement of fungal strains of isolates. Again large scale use of the improved Aspergillus strains can degrade plant biomass & diverse industrial wastes which will reduce environmental pollution of capital urban like Bhubaneswar.

microbiology↗

bioRxiv2019

A Non-genetic Mechanism for Chemoresistance in Lung Cancer: The Role of Integrin β4/Paxillin Axis

Tumor heterogeneity and cisplatin resistance are a major cause of tumor relapse and poor survival. Here we show that in lung adenocarcinoma (LUAD), paxillin (PXN) and integrin beta 4 (ITGB4) are associated with tumor progression, and cisplatin resistance. Silencing PXN and ITGB4 render cisplatin tolerant cells sensitive, and immunologically neutralizing ITGB4 improves sensitivity. The N-terminal half of PXN is intrinsically disordered and interacts with ITGB4 to regulate expression of USP1 and VDAC1 which are required for maintaining genomic stability and mitochondrial function in LUAD. By virtual screening an FDA-approved compound library, we identified compounds that interact with PXN in silico and attenuate cisplatin resistance in LUAD cells. RNAseq analysis identified a double negative feedback loop between ITGB4 and microRNA miR-1-3p, suggesting that bistability could lead to stochastic switching between cisplatin-sensitive and resistant states in these cells. The data highlight an alternate, non-genetic, mechanism underlying chemoresistance in lung cancer.

cancer biology↗

bioRxiv2019

Nutritive diet becomes unhealthy if taken in a wrong ratio: Scientific validation of Ayurvedic concept of \"incompatible diet\" (Virrudh Aahar)

Honey and ghee is an important constituent of our diet. Honey contain about 200 components in its which play an important role as antioxidative, anti-inflammatory, antimicrobial, wound healing and sunburn, etc. Ghee has also many essential constituents such as phospholipids, PUFA, fat- soluble vitamins, etc. It is mention in Charak Samhita that equal ratio of honey and ghee when taken in food become toxic to health. This study was designed to explore the mechanism of toxicity through the biochemical and histological parameter. For this study, 24 Charles foster rats were taken and divided into four groups (n=6) normal, honey, ghee, and honey+ghee (1:1). After 60 days rats were sacrificed. Weight loss, Hair loss and red patches on ear were found on honey+ghee fed rats. LFT, amadori test, AGE, UV, glucose, DPP-4 and LPO were found significantly increased in honey+ghee group. SOD, Catalase, GSH, ABTS+, GLP-1, GIP-1, ACB and HB were found significantly decreased in honey+ghee group. No changes were found in RFT. H&E show normal morphology in kidney, intestine, and pancreas but mild inflammation was found in liver tissue. We conclude that the equal mixture of honey and ghee shows toxic effect. Increased formation of hydroxymethyl furfural, amadori product, DPP-4 activity and low incretins (GLP-1, GIP-1) activity resulting high postprandial hyperglycemic response are collectively responsible for oxidative stress-mediated toxicity of the mixture of honey and ghee in equal ratio.

pharmacology and toxicology↗

bioRxiv2019

Histopathological study of different organs of charles foster strain rat under the exposure of Pueraria tuberosa.

The present study was undertaken to investigate the safe doses of Pueraria tuberosa water extract (PTWE) on different organs. The OECD guidelines 407 of repeated toxicity was followed with respect to the selection of dose and days for different organs. The selected doses of PTWE were 250, 500, 1000 and 2000 mg/kg b wt for 7, 14, 21 and 28 days. Haematoxylin and eosin staining was used to study the morphological alterations in heart, intestine, testis, adrenal gland and spleen. In the present study, no adverse alterations in cardiac fibers of the heart, size and shapes in crypts and villi of intestine, seminiferous tubules and spermatozoa count in testis, three zones of adrenal gland, and spleen were seen in all treated groups of PTWE. There were no adverse morphological alterations found in described organs. The PTWE are safe at 1000 mg/kg b wt. up to 28 days and 2000 mg/ kg b. wt up to 21 days, respectively.

pharmacology and toxicology↗

bioRxiv2019

Herbal tablet of Pueraria tuberosa water extract suppresses the alloxan induced liver damage and hyperglycemia in rats

AimTo study the protective response of herbal formulation (tablets) of Pueraria tuberosa water extract (PTAB) on alloxan induced rat diabetic model.\n\nMethodologyAlloxan (120 mg/kg bw) was injected intraperitonially. Rats were divided into three groups: group 1 as normal, group 2 as diabetic control and group 3 were given PTAB upto 14 days. Blood glucose and liver function tests were done using their respective kits. Hematoxylene and eosin staining was done to evaluate the morphological changes in liver tissues. Through immunohistochemistry, we have checked the protein expression of VEGF, MMP9 and ki67.\n\nResultPTAB significantly decreases blood glucose level in a time dependent manner up to 14 days. As compared to diabetic control, PTAB decreases SGOT, SGPT and alkaline phosphates after 14 days of treatment. In diabetic control, the morphology of liver tissues were found damaged due to deformed hepatocytes and dilated lobules. Most of the hepatocytes after PTAB treatment were comparatively found similar to normal rats tissues, along with dilated blood vessels and normalized liver lobules. In addition to these results, PTAB suppresses the expressions of VEGF and MMP 9.\n\nConclusionPTAB was found to act as an effective hypoglycemic agent. In addition to this, PTAB also found to inhibit inflammation and apoptosis of liver. Thus, can be taken as a potential drug in liver diseases.

pharmacology and toxicology↗

bioRxiv2019

Anti-oxidant, anti-apoptotic, anti-hypoxic and anti-inflammatory conditions induced by PTY-2 against STZ-induced stress in islets

Background and AimEarlier assessment of Pueraria tuberosa tubers has shown anti-diabetic effects through incretin mimetic action and DPP-IV inhibition. The aim of this work was to further explore the protective role of aqueous extract of Pueraria tuberosa against streptozotocin (STZ)-induced pancreatic stress in rats.\n\nMethodsDiabetes was induced with STZ (65 mg/kg body weight) in Charles foster male rats. After 60 days of STZ administration, animals with blood glucose levels > 200 g/dL were considered as diabetic. All the rats were later divided into three groups: Group-1 (STZ untreated normal rats), Group-2 (Diabetic control), and Group-3 (PTY-2 [50 mg/100 g bw treatment for next 10 days to diabetic rats). The rats were then sacrificed at the 10th day of treatment accordingly.\n\nResultsSTZ treatment led to an increase in expression of MMP-9, Tnf , HIF-1, VEGF, IL-6, PKC {varepsilon}, NF-kB, and Caspase-3. Reverse transcriptase Polymerase Chain Reaction (PCR), IHC and western blot analysis showed an increase in the expressions of superoxide dismutase (SOD) and Nephrin, and a decrease in the expressions of NF-kB, PKC {varepsilon}, TNF- MMP-9, HIF-1, VEGF, Caspase 3 and IL-6 after 10 days of PTY-2 treatment.\n\nConclusionThe results show that PTY-2 favorably changed the expression of NF-kB, PKC {varepsilon}, TNF , MMP 9, HIF-1, VEGF, IL-6, Caspase3, Nephrin and SOD in cases of STZ-induced pancreatic stress. Further evaluation of PTY-2 might be helpful in establishing its role in the management of diabetes mellitus.\n\nHighlightsO_LIPTY 2 act as a protective herbal drug against STZ induced islet stress.\nC_LIO_LIPTY 2 upregulates protective and downregulates harmful markers.\nC_LIO_LIThis study composed of four pathway through which PTY 2 acts on pancreas.\nC_LI\n\nGRAPHICAL ABSTRACT\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC=\"FIGDIR/small/670364v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (69K):\norg.highwire.dtl.DTLVardef@14b1f18org.highwire.dtl.DTLVardef@e6a1f2org.highwire.dtl.DTLVardef@19225b0org.highwire.dtl.DTLVardef@1e87bf5_HPS_FORMAT_FIGEXP M_FIG Mechanism of action of PTY 2 against STZ induced islet stress.\n\nC_FIG

pharmacology and toxicology↗

bioRxiv2019

PTY 2 As DPP-IV Inhibitor Prevents Intestinal Cell’s Apoptosis

Enhanced DPP-IV expression is found to get enhanced in various intestinal diseases. PTY-2 has already been known to have DPP-IV inhibitory potential. This inhibition has not yet been studied at mRNA level. Increased incretin secretion due to DPP-IV inhibition could lead to suppression of stress & intestinal cells apoptosis. Through histological analysis, we have found morphological damage of intestine after STZ injection (65 mg/kg bw) to male Charles foster rats. mRNA expressions were analyzed by PCR and apoptosis of cells was checked through tunnel assay & Bcl 2 expression. The number and length of villi get reduced in STZ induced diabetic control, but these damages have been getting reversed after the PTY-2 treatment for 10 days. The expression of SOD was found to get reduced while that of DPP-IV was enhanced in diabetic control group along with significant intestinal cell apoptosis. PTY-2 treatment reduces the stress by upregulating the expression of SOD and through downregulation of DPP-IV mRNA expression. These recoveries by PTY-2 leads to suppression of intestinal cells apoptosis. These short studies explain the protective action of PTY-2 against STZ induced intestinal damage. Hence, PTY-2 could be taken as an herbal treatment against intestinal disorders in case of chronic diabetes.

pharmacology and toxicology↗

bioRxiv2019

Intestinal peroxisomal fatty acid β-oxidation regulates neural serotonin signaling through a feedback mechanism

The ability to coordinate behavioral responses with metabolic status is fundamental to the maintenance of energy homeostasis. In numerous species including C. elegans and mammals, neural serotonin signaling regulates a range of food-related behaviors. However, the mechanisms that integrate metabolic information with serotonergic circuits are poorly characterized. Here, we identify metabolic, molecular, and cellular components of a circuit that links peripheral metabolic state to serotonin-regulated behaviors in C. elegans. We find that blocking the entry of fatty acyl-CoAs into peroxisomal {beta}-oxidation in the intestine results in blunting of the effects of neural serotonin signaling on feeding and egg-laying behaviors. Comparative genomics and metabolomics revealed that interfering with intestinal peroxisomal {beta}-oxidation results in a modest global transcriptional change but significant changes to the metabolome, including a large number of changes in ascaroside and phospholipid species, some of which affect feeding behavior. We also identify body cavity neurons and an ether-a-go-go related (EAG) potassium channel that functions in these neurons as key cellular components of the circuitry linking peripheral metabolic signals to regulation of neural serotonin signaling. These data raise the possibility that the effects of serotonin on satiety may have their origins in feedback, homeostatic metabolic responses from the periphery.

physiology↗

bioRxiv2019

Investigating metabolic interactions in a microbial co-culture through integrated modelling and experiments

Microbial co-cultures have been used in several biotechnological applications. Within these co-cultures, the micro-organisms tend to interact with each other and perform complex actions vis-a-vis a single organism. Investigating metabolic interactions in microbial co-cultures is crucial in designing microbial consortia tailored for specific applications. In this study, we present a pipeline integrating modelling and experimental approaches to understand metabolic interactions between organisms in a community. We define a new index named Metabolic Support Index (MSI), which quantifies the benefits derived by each organism in the presence of the other when grown as a co-culture. We computed MSI for several experimentally demonstrated co-culture systems and showed that MSI, as a metric, accurately identifies the organism that derives the maximum benefit. We also computed MSI for a commonly used yeast co-culture consisting of Saccharomyces cerevisiae and Pichia stipitis and observed that the latter derives higher benefit from the interaction. Further, we designed two-stage experiments to study mutual interactions and showed that P. stipitis indeed derives the maximum benefit from the interaction, as shown from our computational predictions. Also, using our previously developed computational tool MetQuest, we identified all the metabolic exchanges happening between these organisms by analysing the pathways spanning the two organisms. By analysing the HPLC profiles and studying the isotope labelling, we show that P. stipitis consumes the ethanol produced by S. cerevisiae when grown on glucose-rich medium under aerobic conditions, as also indicated by our in silico pathway analyses. Our approach represents an important step in understanding metabolic interactions in microbial communities through an integrating framework of modelling and experiments.

systems biology↗