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Dwivedi, S.

Publications and source records attributed to Dwivedi, S..

14 recordsLinked to original sources

Whole-Genome Metagenomics Insights Revealed a Uranium Bio-remediating Cross-Domain Microbiome in the Dhala Impact Structure, India

Meteorite impact structures on earth represent unique terrestrial analogues of extreme planetary environments where fractured lithologies, hydrothermal alteration, elevated concentrations of radionuclides, and prolonged water-rock interactions create ecological niches for specialized microbial communities. The Palaeoproterozoic Dhala impact structure in north-central India is characterized by uranium-bearing impactites and possesses a very high concentration of Uranium (up to 99.5 ppm) that makes it a unique natural laboratory to investigate microbial adaptation to radioactive and metal-rich geological environments. In addition, the Dhala structure harbors specialized radiotoxic hydrothermal mineral phases such as coffinite and pitchblende, which show a globally distinct and biologically unexplored niche. The present investigation is the first in-depth, whole-genome metagenomic study of soil and water samples of uranium-rich sites from the Dhala structure, exploring the whole microbial community (Bacteria, Archaea, Eukaryotes, and Viruses) up to the species level present in the samples. The cross-domain metagenomics analysis identified a highly unique and resilient microbiome that consists of bacteria, archaea, eukaryotes, and viruses, coevolved under prolonged radiological and multiple metal stress. Functional metagenomic analysis revealed numerous metabolic adaptations responsible for their survival, homeostasis, and biomineralization in situ. The deep sequencing method further enabled the identification of 58 functional genes directly involved in uranium bioremediation. Furthermore, this study revealed important pathways for radionuclide reduction, cellular efflux, and biotransformation. Novel findings of the present study point out the in-depth evolutionary relations of biosphere-geosphere interaction within an ancient hypervelocity impact-generated ecosystem. In a nutshell, the Dhala extremophiles with novel genetic makeup present an untapped and promising reservoir for the development of eco-friendly, next-generation microbial bioremediation strategies to efficiently tackle the global anthropogenic contamination of uranium and the challenges of nuclear waste management. Thus, the present study establishes Dhala structure as an unparalleled site for environmental geomicrobiology, microbial evolution, and astrobiology.

genomics↗

Cooperation, privatization and cheating in microbial exoenzyme synthesis: theoretical analysis in view of biotechnological applications

This study presents a mathematical framework for investigating the dynamics of coexistence and competition among heterotrophic microbes across different time scales. Focusing on metabolic interactions, we examine how three strategies: public metabolizing, private metabolizing, and cheating, shape population behaviour. The framework integrates generalized Lotka-Volterra dynamics with evolutionary game theory to capture the effects of resource exchange, particularly glucose made available by public metabolizers and sucrose as a shared substrate driving population growth. Game-theoretic payoffs encode ecological costs and benefits, enabling analysis of frequency-dependent interactions among strategies. To capture evolutionary realism, we implement laboratory-inspired simulations in which strategies can switch between generations, mimicking mutation or phenotypic plasticity in microbial populations. These eco-evolutionary dynamics reveal conditions under which all three strategies coexist at interior equilibria and show how variation in growth advantages and, illustratively, phenotype-switching perturbations produce evolutionary shifts. Numerical analysis identifies ecological thresholds and fitness asymmetries that determine system robustness, long-term coexistence, and the persistence of a synthetic, cross-kingdom system linked by nutrient exchange. Together, these insights provide general principles for microbial coexistence and offer design guidelines for ecosystem engineering, biotechnological applications, and the construction of stable synthetic communities under ecological and evolutionary constraints.

ecology↗

Analyzing the dynamics in defense/counter-defense games among hosts and pathogens

In the dynamic interplay between hosts and pathogens, hosts may produce a defense compound that acts as a toxin to deter pathogen attack. Conversely, pathogens may evolve to produce a counter-defense enzyme, neutralizing the hosts toxin. This evolutionary arms race incurs costs for both parties, prompting adaptations and strategic shifts. We conceptualize this interaction as an asymmetric game, with hosts and pathogens as players, and their potential responses - defense, counter-defense, or inaction - as their strategic options. In this scenario, if the pathogens counter-defense enzyme is entirely effective, then the hosts toxin is rendered obsolete. However, should the host cease toxin production, the pathogens enzyme becomes redundant, ironically reinstating the toxins utility. This interaction leads to potential red-queen cycles in defense and counter-defense strategies under certain conditions, or a balanced, optimal production of toxin and enzymes by hosts and parasites, respectively. To explore this, we introduce a game-theoretical model incorporating replicator dynamics to examine temporal shifts in strategy from active (counter-)defense to non-(counter-)defense and back. In addition, we analyze compromise strategies and interpret them as bet-hedging-like. We provide a deterministic illustration of how partial defense and counter-defense generate a fitness-buffering structure in unpredictable environments and increase the geometric mean fitness of the population. In conclusion, our analysis supports the notion of continuous periodic adjustments in strategies, notably in the levels of defensive and counter-defensive measures.

systems biology↗

ViralMap: Predicting Features in Viral Proteins from Primary Sequence

Modern viral vaccines are designed to elicit an immune response against viral proteins that mediate infection, making those proteins important targets for characterization and engineering. To improve vaccine efficacy, the proteins often require changes to specific residues or domains to improve immunogenicity and induce a protective response. These engineering strategies vary significantly across viruses, and comprehensive and accurate protein sequence annotation is crucial for guiding vaccine design. The growing risk of novel pathogen emergence and initiatives such as the CEPI 100 Days Mission to rapidly counter "Disease X" threats heighten the need for tools that can convert viral protein sequences from newly characterized genomes or emerging variants into the annotation profiles required for antigen engineering. To address this, we developed ViralMap, a multi-label annotation model tailored for eukaryotic viral proteins. By leveraging ESM-2 language model representations, ViralMap simultaneously predicts ten distinct annotation classes spanning domain topology and localization, post-translational modifications, and structural features directly from primary sequences. The model achieves a residue-level precision-recall area under the curve (PR-AUC) of 0.75 or greater for seven of the ten classes and realizes predictive performance competitive with established tools across the eight benchmarked classes. Case studies on complex glycoproteins, including the SARS-CoV-2 spike and HIV-1 Env, illustrated the models ability to generalize across viral strains and to novel viral families not seen during training. By providing a unified, sequence-based framework for multi-label annotation, ViralMap offers a practical and scalable bridge from raw viral protein sequences to the annotation profiles required for antigen engineering.

bioinformatics↗

Macrophage migration inhibitory factor is a potential therapeutic target for cisplatin induced peripheral neuropathy in breast cancer

BackgroundCisplatin (CP) is an effective chemotherapy drug for several cancers. However, the use of CP is associated with peripheral neuropathy, a painful nerve disorder. Unfortunately, no therapies are available for CP-induced peripheral neuropathy (CisIPN). This study explored the role of a cytokine, the macrophage migration inhibitory factor (MIF), as a potential therapeutic target for CisIPN. MethodsThe role of neuroinflammation and MIF in CisIPN was evaluated in mice models of CisIPN, with and without breast cancer, after treatment with the anti-inflammatory drug Dexamethasone (Dex). Circulating MIF levels in animals were examined using ELISA. Pharmacological inhibition of MIF was achieved using the small molecule inhibitors, CPSI-1306 and ISO-1. Mechanical and thermal sensitivities of animals were assessed using von frey filament and cold acetone assays. Macrophage infiltration in peripheral nerve tissues was examined using CD68 and Iba-1 staining. ResultsOur results showed that Dex suppressed mechanical hyperalgesia in CisIPN animals, which was accompanied by downregulation of MIF. We also found that circulating MIF levels were increased in CisIPN animals. Furthermore, direct inhibition of MIF using CPSI-1306 and ISO-1 led to suppression of mechanical hyperalgesia, without compromising the anti-tumor efficacy of CP, in CisIPN animals. We did not find any significant change in macrophage infiltration in the peripheral nerve tissues of CisIPN animals. Immunostaining results indicated that sensory neurons in the DRGs and Schwann Cells in the sciatic nerves are potential sources for increased MIF in CisIPN. InterpretationOverall, our results strongly suggest that MIF is a promising therapeutic target for CisIPN.

neuroscience↗

MYB transcription factor, NtMYB308, regulates anthocyanin and lignin content, and fungal tolerance in tobacco

Anthocyanins are secondary metabolites synthesized through the phenylpropanoid pathway. They attract pollinators, possess antioxidant properties that scavenge free radicals during environmental stress, and provide protection against various stress conditions. Lignin, another secondary metabolite, plays crucial roles in providing mechanical support, facilitating water and solute transport, and protecting against pathogens. MYB transcription factors, particularly R2R3 MYBs, are key regulators of secondary metabolism, especially within the phenylpropanoid pathway. These factors act as both activators and repressors. The N-terminal region of R2R3-MYB repressors contains a conserved bHLH-binding domain, while the C-terminal domain is divergent and includes an EAR repressor domain. R2R3-MYB proteins notably target sequences such as the MYB-response element and AC elements. In this study, we identified and characterized the Nicotiana MYB transcription factor, NtMYB308, and explored its regulatory function in anthocyanin and lignin biosynthesis in tobacco. Our Virus Induced Gene Silencing (VIGS) and Protein-DNA interaction studies suggest that NtMYB308 is a negative regulator of anthocyanin and lignin biosynthesis by binding to the promoters of genes involved in these pathways. To validate our findings, we developed CRISPR/Cas9-based knockout mutant plants of tobacco, NtMYB308CR, which showed up-regulation of anthocyanin and lignin biosynthesis. Conversely, NtMYB308 overexpression (NtMYB308OX) plants exhibited the opposite effect. Enhanced anthocyanin and lignin levels in NtMYB308CR plants provided tolerance against the fungus Alternaria solani, while NtMYB308OX lines were susceptible. This study advances our understanding of the regulatory mechanisms governing anthocyanin and lignin biosynthesis and their role in biotic stress in tobacco. One Sentence SummaryA R2R3 MYB transcription factor, NtMYB308, negatively regulates anthocyanin and lignin content, and fungal tolerance in tobacco.

plant biology↗

HY5 and COP1 function antagonistically in the light-dependent regulation of nicotine biosynthesis in tobacco

Nicotine constitutes approximately 90% of the total alkaloid content within the Nicotiana species, rendering it the most prevalent alkaloid. While the majority of genes responsible for nicotine biosynthesis express in root tissue, the influence of light on this process through shoot-to-root mobile ELONGATED HYPOCOTYL 5 (HY5) has been recognized. CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), a key regulator of light-associated responses, known for its role in modulating HY5 accumulation, remains largely unexplored in its relationship to light-dependent nicotine accumulation. Here, we identified NtCOP1, a COP1 homolog in Nicotiana tabacum, and demonstrated its ability to complement the cop1 mutant in Arabidopsis thaliana at molecular, morphological, and biochemical levels. Through the development of NtCOP1 overexpression (NtCOP1OX) plants, we observed a significant reduction in nicotine and flavonol content, inversely correlated with the down-regulation of nicotine and phenylpropanoid pathway. Conversely, CRISPR/Cas9-based knockout mutant plants (NtCOP1CR) exhibited an increase in nicotine levels. Further investigations, including yeast-two hybrid assays, grafting experiments, and western blot analyses, revealed that NtCOP1 modulates nicotine biosynthesis by targeting NtHY5, thereby impeding its transport from shoot-to-root. We conclude that the interplay between HY5 and COP1 functions antagonistically in the light-dependent regulation of nicotine biosynthesis in tobacco. HighlightCharacterization of CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) overexpressing and CRISPR/Cas9-based mutant plants suggests the intricate role of COP1 in modulating nicotine biosynthesis in tobacco.

plant biology↗

Abnormal trophoblast invasion in early onset preeclampsia: involvement of cystathionine β-synthase, specificity protein 1 and miR-22

IntroductionImpaired trophoblast invasion has been observed in early onset Preeclampsia patients (EOPE). Trophoblast cell invasion during human placentation is majorly regulated by the balance between MMPs 2, 9 and their inhibitors [tissue inhibitors of matrix metalloproteinases (TIMPs 1, 2)]. Exogenous NaHS (hydrogen sulphide donor) treatment was shown to significantly increase the expression levels of matrix metalloproteinases (MMPs 2, 9) in human bladder cancer EJ cells. Epigentically, the gene expression of hydrogen sulphide synthesising enzyme CBS (cystathionine {beta}-synthase) could be further regulated by various mi-RNAs via the transcription factors like Sp1. Specificity protein 1 (Sp1) has been identified as a target gene for miR-22 to regulate the invasion and metastasis of gastric cancer cells. However, the mechanism of MMPs regulation by either CBS, Sp1 and miRNA-22 in the pregnancies having EOPE is not known. Aims and ObjectivesTo determine and compare the expression of MMPs 2, 9, TIMPs 1, 2, CBS, Sp1 and miRNA-22 in EOPE patients and normotensive, non-proteinuric controls. Materials and methods100 pregnant women were enrolled from Department of Obstetrics and Gynaecology, AIIMS, New Delhi, India. EOPE women (n=50) after clinical diagnosis as per ACOG guidelines were enrolled as cases and normotensive, non-proteinuric pregnant women (n=50) were enrolled as controls. Protocol of the study was approved by Institute Ethics Committee, AIIMS, New Delhi. 5 ml of venous blood was collected from all the recruited women (2.5 ml in each EDTA and sera vial) followed by plasma and sera separation. Plasma samples were used subsequently to determine gene expression of MMPs 2, 9, TIMPs 1, 2, CBS, Sp1 and miRNA-22 by qRT-PCR and sera samples were used to estimate their protein levels by ELISA. Data were analyzed by STATA 14 and Graph Pad Prism 8. ResultsSignificantly down regulated expression of MMPs 2, 9, CBS and Sp1 whereas up regulated expression for that of TIMPs 1, 2 was observed in EOPE patients as compared to healthy pregnant women at both transcription and translation levels. Expression of miR-22 (pre miR-22 and miR-22-3p) was found to be significantly elevated in EOPE patients as compared to normotensive, non-proteinuric controls. ConclusionThis is the very first study of its kind which implicates that down regulated MMPs 2, 9, CBS, Sp1 levels and simultaneously upregulation of miR-22 expression in EOPE patients could have some association. In vitro experiments are needed to prove their association which if proven may provide a new, potential therapeutic target to treat early onset Preeclampsia.

developmental biology↗

MicroRNA-22, Specificity protein-1 and Cystathionine β-synthase in early onset Preeclampsia: significance in trophoblast invasion

IntroductionTrophoblast cell invasion during human placentation is majorly regulated by the balance between MMPs 2, 9 and their inhibitors [tissue inhibitors of matrix metalloproteinases (TIMPs 1, 2)]. Exogenous NaHS (hydrogen sulphide donor) treatment was shown to significantly increase the expression levels of matrix metalloproteinases (MMPs 2, 9) in human bladder cancer EJ cells. Epigentically, the gene expression of hydrogen sulphide synthesising enzyme CBS (cystathionine {beta}-synthase) could be further regulated by various mi-RNAs via the transcription factors like Sp1. Specificity protein 1 (Sp1) has been identified as a target gene for miR-22 to regulate the invasion and metastasis of gastric cancer cells. However, the mechanism of MMPs regulation by either CBS, Sp1 and miRNA-22 in the pregnancies having early onset preeclampsia is not known. Aim of the studyTo determine and compare the expression of MMPs 2, 9, TIMPs 1, 2, CBS, Sp-1 and miR-22 in early onset preeclamptic patients and normotensive, non-proteinuric controls at both transcription and translation levels. Materials and methods30 pregnant women were enrolled from Department of Obstetrics and Gynaecology, AIIMS, New Delhi, India. EOPE women (n=15) after clinical diagnosis as per ACOG guidelines were enrolled as cases and normotensive, non-proteinuric pregnant women (n=15) were enrolled as controls. Protocol of the study was approved by Institute Ethics Committee, AIIMS, New Delhi. 30 caesarean delivered placentae (15 each of patients and controls) were collected to analyse the mRNA and protein expression/levels of MMPs 2, 9, TIMPs 1, 2, CBS, and Sp1. Protein activity of MMP-2 and 9 was determined. Gene expression of miR-22 was observed in placentae of the recruited patients and controls. Data were analysed by STATA 14 and Graph Pad Prism 8. ResultsSignificantly reduced mRNA and protein expression/levels of MMPs 2, 9, CBS and Sp1 whereas elevated for those of TIMP-1 and TIMP-2 was observed in EOPE patients as compared to controls. Gelatinolytic activity of MMP-2 and 9 was also found significantly reduced in placentae from EOPE patients whereas gene expression of miR-22 was found significantly up regulated in the early onset preeclamptic patients in comparison to controls. ConclusionThis is the first study of its kind which implicates that insufficient trophoblastic invasion may be because of down regulation of MMPs 2, 9, CBS, Sp1 and concomitant up regulation of TIMPs 1, 2 and miR-22 in the early onset preeclamptic patients as compared to controls.

developmental biology↗

Role of MicroRNA-22 (miR-22)/Specificity protein 1 (Sp1)/Cystathionine beta-synthase (CBS) axis in regulating trophoblast invasion: an in vitro study

IntroductionPlacenta expresses many ubiquitous as well as specific miRNAs which regulate trophoblast cell differentiation, proliferation, apoptosis, invasion, migration, and angiogenesis. Aberrant miRNAs expression (miR-22) has been linked to pregnancy complications, such as preeclampsia. Specificity protein 1 (Sp1) was identified a direct target of miR-22 and an inverse linear correlation between expression of miR-22 and Sp1 mRNA in gastric tumour has been reported. Also, Sp1 has a critical and indispensable role in the regulation of cystathionine {beta}-synthase (H2S synthesizing enzyme). Exogenous H2S could promote cell proliferation and invasion by upregulating the expression of MMP-2 and MMP-9 in human bladder cancer EJ cells. Worldwide studies reported significant role of MMP-2 and MMP-9 in the regulation of trophoblast invasion. Aims and ObjectivesTo determine the role of MicroRNA-22 (miR-22)/Specificity protein 1 (Sp1)/Cystathionine {beta}-synthase (CBS) axis in regulating trophoblast invasion in the first-trimester trophoblast cells. Materials and methodsThe human first trimester trophoblast cell line (HTR-8/SVneo Cell line) was procured from American Type Culture Collection. Gain/Loss of function studies were conducted on HTR-8/SVneo cells and the expression of miR-22 (pre miR-22 and miR-22-3p), Sp1, CBS, MMP-2 and MMP-9 was observed. Invasion capacity of the cells was assessed by transwell invasion assay. Data were analyzed by STATA 14 and Graph Pad Prism 8. ResultsSignificantly down regulated regulated mRNA and protein expression of Sp1, CBS and and MMPs 2, 9 was observed when the cells were transfected with miR-22-3p mimic in comparison to miR-22-3p inhibitor transfected cells. Expression of CBS and MMPs 2, 9 was found to be significantly up regulated when the cells were transfected with Sp1 plasmid as compared to Sp1 inhibitor (2,4,5 trifluoroaniline) treated cells at both transcription and translation levels. MMP-2 and MMP-9 levels were found to be significantly elevated when the cells were subjected to NaHS [sodium hydrogen sulphide (H2S donor)] treatment as compared to AOAA (aminooxyacetic acid) treated cells. ConclusionThis is the first study which implies that miR-22 via targeting Sp1 must have influenced the mRNA and protein expression of CBS, MMP-2 and MMP-9 in order to regulate the trophoblast invasion.

developmental biology↗

Altered expression of MMP9 and TIMP1 leads to impaired placentation in early onset preeclamptic patients: a case control study

IntroductionMatrix metalloproteinases (MMPs) specifically MMP-9 is a key regulator of vascular and uterine spiral artery remodelling and its activity is controlled at multiple levels, including gene transcription, activation of its latent forms and endogenous inhibition by tissue inhibitors of metalloproteinases [TIMPs (specifically TIMP-1)]. Alteration in MMP-9 and TIMP-1 expression may contribute to uterine and vascular dysfunction leading to adverse pregnancy outcomes such as Preeclampsia (PE). Depending on time, PE is classified as early-onset preeclampsia, which is diagnosed before 34 weeks of gestation, or late-onset preeclampsia, which is diagnosed after 34 weeks. Early-onset preeclampsia (EOPE) is a severe obstetrics disease which threatens mother and foetus. Therefore, in the present study, we aimed to investigate the levels of MMP-9 and its inhibitor TIMP-1 in the placentae of EOPE patients and their maternal age matched normotensive, non-proteinuric controls at both mRNA and protein levels. MethodsA total of 30 caesarean delivered placentae (15 EOPE patients and 15 controls) were collected from Department of Obstetrics and Gynaecology, AIIMS, New Delhi after taking permission from Institute Ethics Committee. MMP-9 and TIMP-1 protein expression was observed by immunohistochemistry and immunofluorescence stainings. Gelatin Gel Zymography was done to evaluate MMP-9 activity and Western Blot was done for the quantification of MMP-9 and TIMP-1 proteins. mRNA levels of MMP-9 and TIMP-1 were determined by qRT-PCR ResultsImmunohistochemistry and Immunofluorescence staining discerned stronger expression of MMP-9 in normotensive placentae as compared to EOPE placentae whereas stronger expression of TIMP-1 was seen in EOPE placentae in comparison to those of normotensive placentae. Gelatin Gel Zymography reflected that MMP-9 activity was found elevated in maternal placental side in normotensive placentae as compared to EOPE placentae. Western Blot analysis revealed that protein expression of MMP-9 was elevated whereas for that of TIMP-1 was reduced in normotensive placentae in comparison to EOPE placentae. mRNA expression of MMP-9 was found up-regulated whereas for that of TIMP-1 was down-regulated in normotensive placentae as compared to EOPE placentae. ConclusionThe present study implies that aberrant functioning of MMP-9 and TIMP-1 in EOPE patients contribute to impaired placentation which might be relevant for possible future screening programs in order to predict and to design therapies for early onset preeclamptic patients.

developmental biology↗

Tobacco HY5, NtHY5, positively regulates flavonoid biosynthesis and enhances salt stress tolerance

Tobacco remains one of the most commercially important crops due to the parasympathomimetic alkaloid nicotine used in cigarettes. Most genes involved in nicotine biosynthesis are expressed in root tissues; however, their light-dependent regulation has not been studied. We identified the ELONGATED HYPOCOTYL 5 homolog, NtHY5, from Nicotiana tabacum and demonstrated its role in nicotine biosynthesis. We report the development of CRISPR/Cas9-based mutant plants, NtHY5CR, and show down-regulation of the nicotine biosynthetic pathway, whereas NtHY5 overexpression (NtHY5OX) plants show the opposite effect. Grafting experiments using wild type, NtHY5CR, and NtHY5OX indicated that NtHY5 moves from shoot-to-root to regulate nicotine biosynthesis in the root tissue. We conclude that shoot HY5, directly or through enhancing expression of the HY5 in the root, promotes nicotine biosynthesis. The CRISPR/Cas9-based mutants developed, in this study; with low nicotine accumulation in leaves could help people to overcome their nicotine addiction and the risk of death from tobacco use.

plant biology↗

How perception and attention participate in reading skill?

Reading creates accessibility to the outer world information and is an integral skill for academic achievement. It involves visual perception, reasoning at symbolic level (text reading) and phonological processing. But does perception, visuospatial processing at pre-symbolic level affect reading skill? To understand and untangle the mechanism fifty children with reading problem (developmental dyslexia, DDC) and twentyfive age-matched typical readers (healthy controls, HC) were studied. In DDC, the variable-performance of non-symbolic visual search (pictorial-level) was associated with bilateral brain activity (functional MRI) of ventral stream (inferior occipital and fusiform) and greater involvement of frontal-prefrontal regions, suggesting the modified dorsal route-gating for figure-ground filtering. Performance variability in picture-concept reasoning (71.9% and significant group mean difference) and visuospatial-organization (51.3%) of DDC children indicate attentional or executive differences at nonsymbolic level. In symbolic discrimination performance, no significant difference observed for single alphabet or number (digit) reading but significant differences at word level for visual and phonological performance (considering orthographic differences), attributes to distractor-inhibition problems. Nonsymbolic to symbolic coding/decoding speed and writing error (copying) differences are suggestive of execution variability rather than motor coordination in DDC. In HC, the top-down dorsal route gating and hypoactivity induced in right frontal-anterior cingulate cortices, play a major role in reading by allocating spatial attention and inhibiting distractors. It has been elaborated in the "neurobiological model". How perception and attention participate in reading skill?O_ST_ABSResearch HighlightsC_ST_ABSO_LIVisuospatial attention, executive control (nonsymbolic level) and visual discrimination (symbolic level) performance contribute to reading. C_LIO_LIIn children with reading problems (dyslexia) pictorial visual processing task (fMRI) recruited higher activation in right hemispheric frontal, inferior parietal and anterior cingulate regions. C_LIO_LIBilateral activation of occipital-striate, extra-striate, fusiform for nonsymbolic is associated with significantly more errors at bigger-symbol-string, in dyslexia. C_LIO_LIAuditory discrimination differences in shallow-deep orthography. C_LIO_LICorrelation of non-symbolic executive and symbolic performances. C_LIO_LIRole of the prelexical visual perception and dorsal-route gating in reading skill explained as neurobiological model. C_LI

neuroscience↗

sFlt-1 (sVEGFR1) induces placental endoplasmic reticulum stress in trophoblast cell: implications for the complications in preeclampsia - an in vitro study

BackgroundThe concentration of sFlt-1, a major anti-angiogenic protein in maternal circulation has been seen to be raised in preeclamptic pregnancies. Endoplasmic reticulum (ER) stress represents one of the three (immunological, oxidative and ER stress) major stresses which placenta undergoes during pregnancies. The present study is designed to investigate the role of sFlt-1 in induction of ER stress in trophoblast cells.\n\nMaterials and MethodsMaternal serum levels of anti-angiogenic protein sFlt-1 and central regulator of unfolded protein response GRP78 was measured using sandwich ELISA. The expression of various ER stress markers (GRP78, eIF2, XBP1, ATF6 and apoptotic protein CHOP) were analyzed depending on various treatments given to the trophoblast cells using Immunofluorescence, western blot and q-RT PCR.\n\nResultsIncreased expression of ER stress markers (GRP78, eIF2, XBP1 ATF6 and apoptotic protein CHOP) was detected in the placental trophoblast cells treated with raised concentration of sFlt-1.\n\nConclusionSignificant upregulated expression of ER stress markers in trophoblast cells exposed with increased concentration of sFlt-1 suggested that it may be one of the anti-angiogenic factors present in maternal sera which not only contributes to oxidative stress but also may cause endoplasmic reticulum stress.

developmental biology↗