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Ischemic stroke is one of the leading causes of death and disability worldwide. Neurogenesis plays a crucial role in postischemic functional recovery. Alcohol dose-dependently affects the prognosis of ischemic stroke. We investigated the impact of light alcohol consumption (LAC) on neurogenesis under physiological conditions and following ischemic stroke. C57BL/6J mice (three months old) were fed with 0.7 g/kg/day ethanol (designed as LAC) or volume-matched water (designed as control) daily for eight weeks. To evaluate neurogenesis, the numbers of 5-bromo-2-deoxyuridine (BrdU)+/doublecortin (DCX)+ and BrdU+/NeuN+ neurons were assessed in the subventricular zone (SVZ), dentate gyrus (DG), ischemic cortex, and ischemic striatum. The locomotor activity was determined by the accelerating rotarod and open field tests. LAC significantly increased BrdU+/DCX+ and BrdU+/NeuN+ cells in the SVZ under physiological conditions. Ischemic stroke dramatically increased BrdU+/DCX+ and BrdU+/NeuN+ cells in the DG, SVZ, ischemic cortex, and ischemic striatum. The increase in BrdU+/DCX+ cells was significantly greater in LAC mice compared to the control mice. In addition, LAC significantly increased BrdU+/NeuN+ cells by about three folds in the DG, SVZ, and ischemic cortex. Furthermore, LAC reduced ischemic brain damage and improved locomotor activity. Therefore, LAC may protect the brain against ischemic stroke by promoting neurogenesis.

Helicobacter pylori (H. pylori) is a common gastric pathogen that infects approximately half of the world's population. Infection with H. pylori can lead to diverse pathological conditions, including chronic gastritis, peptic ulcer disease, and cancer. The latter is the most severe consequence of H. pylori infection. According to epidemiological studies, gastric infection with H. pylori is the strongest known risk factor for non-cardia gastric cancer (GC), which remains one of the leading causes of cancer-related deaths worldwide. However, it still remains to be poorly understood how host-microbe interactions result in cancer development in the human stomach. Here we focus on the H. pylori bacterial factors that affect the host ubiquitin proteasome system. We investigated E3 ubiquitin ligases SIVA1 and ULF that regulate p14ARF (p19ARF in mice) tumor suppressor. ARF plays a key role in regulation of the oncogenic stress response and is frequently inhibited during GC progression. Expression of ARF, SIVA1 and ULF proteins were investigated in gastroids, H. pylori-infected mice and human gastric tissues. The role of the H. pylori type IV secretion system was assessed using various H. pylori isogenic mutants. Our studies demonstrated that H. pylori infection results in induction of ULF, decrease in SIVA1 protein levels, and subsequent ubiquitination and degradation of p14ARF tumor suppressor. Bacterial CagA protein was found to sequentially bind to SIVA1 and ULF proteins. This process is regulated by CagA protein phosphorylation at the EPIYA motifs. Downregulation of ARF protein leads to inhibition of cellular apoptosis and oncogenic stress response that may promote gastric carcinogenesis.

Electrophilic aldehyde (4-hydroxynonenal; 4-HNE), formed after lipid peroxidation, is a mediator of mitochondrial dysfunction and implicated in both the pathogenesis and the progression of cardiovascular disease. Manganese superoxide dismutase (MnSOD), a nuclear-encoded antioxidant enzyme, catalyzes the dismutation of superoxide radicals (O2•-) in mitochondria. To study the role of MnSOD in the myocardium, we generated a cardiomyocyte-specific SOD2 (SOD2Δ) deficient mouse strain. Unlike global SOD2 knockout mice, SOD2Δ mice reached adolescence; however, they die at ~4 months of age due to heart failure. Ultrastructural analysis of SOD2Δ hearts revealed altered mitochondrial architecture, with prominent disruption of the cristae and vacuole formation. Noninvasive echocardiographic measurements in SOD2Δ mice showed dilated cardiomyopathic features such as decreased ejection fraction and fractional shortening along with increased left ventricular internal diameter. An increased incidence of ventricular tachycardia was observed during electrophysiological studies of the heart in SOD2Δ mice. Oxidative phosphorylation (OXPHOS) measurement using a Seahorse XF analyzer in SOD2Δ neonatal cardiomyocytes and adult cardiac mitochondria displayed reduced O2 consumption, particularly during basal conditions and after the addition of FCCP (H+ ionophore/uncoupler), compared to that in SOD2fl hearts. Measurement of extracellular acidification (ECAR) to examine glycolysis in these cells showed a pattern precisely opposite that of the oxygen consumption rate (OCR) among SOD2Δ mice compared to their SOD2fl littermates. Analysis of the activity of the electron transport chain complex identified a reduction in Complex I and Complex V activity in SOD2Δ compared to SOD2fl mice. We demonstrated that a deficiency of SOD2 increases reactive oxygen species (ROS), leading to subsequent overproduction of 4-HNE inside mitochondria. Mechanistically, proteins in the mitochondrial respiratory chain complex and TCA cycle (NDUFS2, SDHA, ATP5B, and DLD) were the target of 4-HNE adduction in SOD2Δ hearts. Our findings suggest that the SOD2 mediated 4-HNE signaling nexus may play an important role in cardiomyopathy.

Mitochondria are highly dynamic organelles that constantly undergo fission and fusion events to adapt to changes in the cellular environment. Aberrant mitochondrial fission has been associated with several types of cardiovascular dysfunction; inhibition of pathologically aberrant mitochondrial fission has been shown to be cardioprotective. Pathological fission is mediated by the excessive activation of GTPase dynamin-related protein 1 (Drp1), making it an attractive therapeutic target in numerous cardiovascular diseases. Mitochondrial division inhibitor (mdivi-1) is widely used small molecule reported to inhibit Drp1-dependent fission, elongate mitochondria, and mitigate injury. The purpose of our study was to understand the pleiotropic effects of mdivi-1 on mitochondrial dynamics, mitochondrial respiration, electron transport activities, and macro-autophagy. In this study, we found that mdivi-1 treatment decreased Drp1 expression, proteolytically cleaved L-OPA1, and altered the expression of OXPHOS complex proteins, resulting in increased superoxide production. The altered expression of OXPHOS complex proteins may be directly associated with decreased Drp1 expression, as Drp1 siRNA knockdown in cardiomyocytes showed similar effects. Results from an autophagy flux assay showed that mdivi-1 induced impaired autophagy flux that could be restored by Atg7 overexpression, suggesting that mdivi-1 mediated inhibition of macro-autophagy in cardiomyocytes. Treatment with mdivi-1 resulted in increased expression of p62, which is required for Atg7 overexpression-induced rescue of mdivi-1-mediated impaired autophagy flux. In addition, mdivi-1-dependent proteolytic processing of L-OPA1 was associated with increased mitochondrial superoxide production and altered expression of mitochondrial serine/proteases. Overall, the novel pleiotropic effect of mdivi-1 in cardiomyocytes included proteolytically cleaved L-OPA1, altered expression of OXPHOS complex proteins, and increased superoxide production, which together resulted in defects in mitochondrial respiration and inhibition of macro-autophagy.

Lipid Phosphate phosphatase 3 (LPP3), encoded by the Plpp3 gene, is an enzyme that dephosphorylates the bioactive lipid mediator lysophosphatidic acid (LPA). To study the role of LPP3 in the myocardium, we generated a cardiac specific Plpp3 deficient mouse strain. Although these mice were viable at birth in contrast to global Plpp3 knockout mice, they showed increased mortality ~ 8 months. LPP3 deficient mice had enlarged hearts with reduced left ventricular performance as seen by echocardiography. Cardiac specific Plpp3 deficient mice had longer ventricular effective refractory periods compared to their Plpp3 littermates. We observed that lack of Lpp3 enhanced cardiomyocyte hypertrophy based on analysis of cell surface area. We found that lack of Lpp3 signaling was mediated through the activation of Rho and phospho-ERK pathways. There are increased levels of fetal genes Natriuretic Peptide A and B (Nppa and Nppb) expression indicating myocardial dysfunction. These mice also demonstrate mitochondrial dysfunction as evidenced by a significant decrease (P < 0.001) in the basal oxygen consumption rate, mitochondrial ATP production, and spare respiratory capacity as measured through mitochondrial bioenergetics. Histology and transmission electron microscopy of these hearts showed disrupted sarcomere organization and intercalated disc, with a prominent disruption of the cristae and vacuole formation in the mitochondria. Our findings suggest that LPA/LPP3-signaling nexus plays an important role in normal function of cardiomyocytes. Keywords: Heart failure, Lipid phosphate phosphatase, Lysophosphatidic acid

This study aimed to generate predictive models for growth, sporulation, and ochratoxin A (OTA) production under abiotic climatic variables, including temperatures (15–35 °C) and water activity levels (0.99–0.90 aw) by Aspergillus ochraceus group. The data were divided into three sets: one for training, one for testing, and the third one for model validation. Optimum growth occurred at 0.95 aw and 25 °C and 0.95 aw and 30 °C for A. westerdijkiae and A. steynii, respectively. Significantly improved A. westerdijkiae and A. steynii spore production occurred at 0.95 aw and 20 °C and 0.90 aw and 35 °C, respectively. A. steynii and A. westerdijkiae produced the majority of OTA at 35 °C and 0.95 aw and 25–30 °C at 0.95–0.99 aw, respectively. The accuracy of the third-order polynomial regression model reached 96% in growth cases, 94.7% in sporulation cases, and 90.9% in OTA production cases; the regression coefficients (R2) ranged from 0.8819 to 0.9978 for the Aspergillus ochraceus group. A reliable agreement was reached between the predicted and observed growth, sporulation, and OTA production. The effects of abiotic climatic variables on growth, sporulation, and OTA production of A. ochraceus group have been effectively defined, and the models generated were responsible for adequately predicted and validated models against data from other strains within A. ochraceus group that had been published in the literature under the current treatments. These models could be successfully implemented to predict fungal growth and OTA contamination on food matrices for these strains under these conditions.

Estrogen receptor α (ERα) is the key transcriptional driver in a large proportion of breast cancers. We report that APOBEC3B (A3B) is required for regulation of gene expression by ER and acts by causing C-to-U deamination at ER binding regions. We show that these C-to-U changes lead to the generation of DNA strand breaks through activation of base excision repair (BER) and to repair by non-homologous end-joining (NHEJ) pathways. We provide evidence that transient cytidine deamination by A3B aids chromatin modification and remodelling at the regulatory regions of ER target genes that promotes their expression. A3B expression is associated with poor patient survival in ER+ breast cancer, reinforcing the physiological significance of A3B for ER action.

We identified ubiquitin-like with PHD and RING finger domain 1 (UHRF1) as a binding factor for DNA interstrand crosslink (ICL) lesions through affinity purification of ICL-recognition activities. UHRF1 is recruited to DNA lesions in vivo and binds directly to ICL-containing DNA. UHRF1-deficient cells display increased sensitivity to a variety of DNA damages. We found that loss of UHRF1 led to retarded lesion processing and reduced recruitment of ICL repair nucleases to the site of DNA damage. UHRF1 interacts physically with both ERCC1 and MUS81, two nucleases involved in the repair of ICL lesions. Depletion of both UHRF1 and components of the Fanconi anemia (FA) pathway resulted in increased DNA damage sensitivity compared to defect of each mechanism alone. These results suggest that UHRF1 promotes recruitment of lesion-processing activities via its affinity to recognize DNA damage and functions as a nuclease recruitment scaffold in parallel to the FA pathway.

Peroxisome proliferator-activated receptor Gamma (PPARγ), a ligand-activated transcription factor, has a role in various cellular functions as well as glucose homeostasis, lipid metabolism, and prevention of oxidative stress. The activators of PPARγ are already widely used in the treatment of diabetes mellitus. The cardioprotective effect of PPARγ activation has been studied extensively over the years making them potential therapeutic targets in diseases associated with cardiovascular disorders. However, they are also associated with adverse cardiovascular events such as congestive heart failure and myocardial infarction. This review aims to discuss the role of PPARγ in the various cardiovascular diseases and summarize the current knowledge on PPARγ agonists from multiple clinical trials. Finally, we also review the new PPARγ agonists under development as potential therapeutics with reduced or no adverse effects.

Candida albicans, a human fungal pathogen, undergoes morphogenetic changes that are associated with virulence. We report here that GAL102 in C. albicans encodes a homolog of dTDP-glucose 4,6-dehydratase, an enzyme that affects cell wall properties as well as virulence of many pathogenic bacteria. We found that GAL102 deletion leads to greater sensitivity to antifungal drugs and cell wall destabilizing agents like Calcofluor white and Congo red. The mutant also formed biofilms consisting mainly of hyphal cells that show less turgor. The NMR analysis of cell wall mannans of gal102 deletion strain revealed that a major constituent of mannan is missing and the phosphomannan component known to affect virulence is greatly reduced. We also observed that there was a substantial reduction in the expression of genes involved in biofilm formation but increase in the expression of genes encoding glycosylphosphatidylinositol-anchored proteins in the mutant. These, along with altered mannosylation of cell wall proteins together might be responsible for multiple phenotypes displayed by the mutant. Finally, the mutant was unable to grow in the presence of resident peritoneal macrophages and elicited a weak pro-inflammatory cytokine response in vitro. Similarly, this mutant elicited a poor serum pro-inflammatory cytokine response as judged by IFNγ and TNFα levels and showed reduced virulence in a mouse model of systemic candidiasis. Importantly, an Ala substitution for a conserved Lys residue in the active site motif YXXXK, that abrogates the enzyme activity also showed reduced virulence and increased filamentation similar to the gal102 deletion strain. Since inactivating the enzyme encoded by GAL102 makes the cells sensitive to antifungal drugs and reduces its virulence, it can serve as a potential drug target in combination therapies for C. albicans and related pathogens.

Abstract Long intergenic non-coding RNAs (lincRNAs) are emerging as regulators of protein-coding genes (PCGs) in many plant and animal developmental processes and stress responses. In this study, we characterize the genome-wide lincRNAs in potatoes responsive to a vascular bacterial disease presumably caused by Candidatus Liberibacter solanacearum (CLso). Approximately 4397 lincRNAs were detected in healthy and infected potato plants at various stages of zebra chip (ZC) disease progression. Of them, ~65% (2844) were novel lincRNAs, and less than 1% (9) were orthologs of Arabidopsis and rice based on reciprocal BLAST analysis, suggesting species-specific expansion. Among the proximal lincRNAs within 50 kbp from a PCG, ~49% were transcribed from the same strand, while ~39% and ~15% followed convergent (head-to-head) and divergent (tail-to-tail) orientations, respectively. Approximately 30% (1308) were differentially expressed following CLso infection, with substantial changes occurring 21 days after infection (DAI). Weighted Gene Co-expression Network Analysis (WGCNA) of lincRNAs and PCGs identified 46 highly correlated lincRNA–PCG pairs exhibiting co-up or co-downregulation. Furthermore, overexpression of selected lincRNAs in transgenic potato hairy roots resulted in perturbation of neighboring PCG expression and conferred tolerance to CLso infection. Our results provide novel insights into potato lincRNAs’ identity, expression dynamics, and functional relevance to CLso infection.

Abstract Connectome studies have shown how Alzheimer’s disease (AD) disrupts functional and structural connectivity among brain regions. But the molecular basis of such disruptions is less studied, with most genomic/transcriptomic studies performing within-brain-region analyses. To inspect how AD rewires the correlation structure among genes in different brain regions, we performed an Inter-brain-region Differential Correlation (Inter-DC) analysis of RNA-seq data from Mount Sinai Brain Bank on four brain regions (frontal pole, superior temporal gyrus, parahippocampal gyrus and inferior frontal gyrus, comprising 264 AD and 372 control human post-mortem samples). An Inter-DC network was assembled from all pairs of genes across two brain regions that gained (or lost) correlation strength in the AD group relative to controls at FDR 1%. The differentially correlated (DC) genes in this network complemented known differentially expressed genes in AD, and likely reflects cell-intrinsic changes since we adjusted for cell compositional effects. Each brain region used a distinctive set of DC genes when coupling with other regions, with parahippocampal gyrus showing the most rewiring, consistent with its known vulnerability to AD. The Inter-DC network revealed master dysregulation hubs in AD (at genes ZKSCAN1, SLC5A3, RCC1, IL17RB, PLK4, etc.), inter-region gene modules enriched for known AD pathways (synaptic signaling, endocytosis, etc.), and candidate signaling molecules that could mediate region-region communication. The Inter-DC network generated in this study is a valuable resource of gene pairs, pathways and signaling molecules whose inter-brain-region functional coupling is disrupted in AD, thereby offering a new perspective of AD etiology.

Brain tumor (BT) is an awful disease and one of the foremost causes of death in human beings. BT develops mainly in 2 stages and varies by volume, form, and structure, and can be cured with special clinical procedures such as chemotherapy, radiotherapy, and surgical mediation. With revolutionary advancements in radiomics and research in medical imaging in the past few years, computer-aided diagnostic systems (CAD), especially deep learning, have played a key role in the automatic detection and diagnosing of various diseases and significantly provided accurate decision support systems for medical clinicians. Thus, convolution neural network (CNN) is a commonly utilized methodology developed for detecting various diseases from medical images because it is capable of extracting distinct features from an image under investigation. In this study, a deep learning approach is utilized to extricate distinct features from brain images in order to detect BT. Hence, CNN from scratch and transfer learning models (VGG-16, VGG-19, and LeNet-5) are developed and tested on brain images to build an intelligent decision support system for detecting BT. Since deep learning models require large volumes of data, data augmentation is used to populate the existing dataset synthetically in order to utilize the best fit detecting models. Hyperparameter tuning was conducted to set the optimum parameters for training the models. The achieved results show that VGG models outperformed others with an accuracy rate of 99.24%, average precision of 99%, average recall of 99%, average specificity of 99%, and average f 1-score of 99% each. The results of the proposed models compared to the other state-of-the-art models in the literature show better performance of the proposed models in terms of accuracy, sensitivity, specificity, and f 1-score. Moreover, comparative analysis shows that the proposed models are reliable in that they can be used for detecting BT as well as helping medical practitioners to diagnose BT.

Selenium, an essential micronutrient with potent anticancer and antioxidant properties, the inorganic form of selenium is highly toxic, while organic and elemental nanoforms are more bioavailable and less toxic and have gained attention owing to their dietary and clinical relevance. This study aims to optimize conditions for the biosynthesis and production of elemental selenium nanoparticles for selenium supplements using marine microalgae, Nannochloropsis oceanica CASA CC201. The 10 mM precursor solution treated with 1 % of the algal extract (10:1 ratio of precursor and algal extract, respectively) was shown to be the optimal concentration for synthesizing highly stable selenium nanoparticles with a size of 183 nm and a zeta potential of −38.5 mV. AFM and TEM analysis suggest that the spherical-shaped nanoparticles with smooth surfaces were polydispersely distributed. The nanoparticles are well characterized using various analytical and advanced techniques, including Raman spectroscopy and X-ray photoelectron spectroscopy. FT-IR analyses reveal the presence of microalgae proteins and peptides as stabilizing and fabricating agents of Se-NPs to further understand the mode of bioreduction. The synthesized elemental nanoform (Se0) has been validated for its biological functions, showing enhanced radical scavenging activity (74 % in a concentration-dependent manner). Subsequently, algal-mediated selenite reduction and nanoparticle synthesis is an eco-friendly, non-toxic, and sustainable method for the large-scale production of highly stable Se-NPs for niche applications as dietary and feed supplements.

Background: Literature indicates that L-carnosine may be deficient in autism spectrum disorder (ASD) children. The aim of the present study was to estimate the level of L-carnosine in plasma and correlate it with the Autism Treatment Evaluation Checklist (ATEC) and Childhood Autism Rating Scale 2nd Edition, Standard Version (CARS2-ST) scores. To measure L-carnosine level, a bio-analytical method was developed using reverse phase high- liquid chromatography and validated as per International Conference on Harmonization guidelines. Method: Children were supplemented with L-carnosine (10–15 mg/kg) along with standard care therapies for 2 months. Before and after supplementation, scores on the ATEC, CARS2-ST, BEARS sleep screening tool, 6-item Gastrointestinal Severity Index, and Parental Stress Scale were evaluated, and L-carnosine was measured at the end of the trial. Results: The calibration curve was linear in the range of 100–600 ng/mL (R2 = 0.998). The level of L-carnosine quantified was 33.7 ± 0.2 ng/mL. There was no significant difference found in any of the outcome measures (p > 0.05). Conclusions: Despite the fact that L-carnosine is detectable in the blood, it was found to be ineffective in the management of ASD in children. Clinical Trial Registration: The study was registered in the Clinical Trial Registry-India, registration number: CTRI/2019/07/020102.

Heat stress is a major threat to global crop production, and understanding its impact on plant fertility is crucial for developing climate-resilient crops. Despite the known negative effects of heat stress on plant reproduction, the underlying molecular mechanisms remain poorly understood. Here, we investigated the impact of elevated temperature on centromere structure and chromosome segregation during meiosis in Arabidopsis thaliana. Consistent with previous studies, heat stress leads to a decline in fertility and micronuclei formation in pollen mother cells. Our results reveal that elevated temperature causes a decrease in the amount of centromeric histone and the kinetochore protein BMF1 at meiotic centromeres with increasing temperature. Furthermore, we show that heat stress increases the duration of meiotic divisions and prolongs the activity of the spindle assembly checkpoint during meiosis I, indicating an impaired efficiency of the kinetochore attachments to spindle microtubules. Our analysis of mutants with reduced levels of centromeric histone suggests that weakened centromeres sensitize plants to elevated temperature, resulting in meiotic defects and reduced fertility even at moderate temperatures. These results indicate that the structure and functionality of meiotic centromeres in Arabidopsis are highly sensitive to heat stress, and suggest that centromeres and kinetochores may represent a critical bottleneck in plant adaptation to increasing temperatures.

Antibiotic resistance is a major crisis that the modern world is confronting. This review highlights the abundance of different types of antibiotic resistance genes (ARGs) in two major reservoirs in the environment, namely hospital and municipal wastewater, which is an unforeseen threat to human lives across the globe. The review helps understand the current state of affairs and the whereabouts on the dissemination of ARGs in both these environments. The various traditional wastewater treatment methods, such as chlorination and UV treatment, and modern methods, such as electrochemical oxidation, are discussed, and the gaps in these technologies are highlighted. The need for the development of newer techniques for wastewater treatment with enhanced efficiency is urgently underscored. Nanomaterial applications for ARG removal were observed to be less explored. This has been discussed, and prospective nanomaterials and nanocomposites for these applications are proposed.

Targeted gene therapy may revolutionize disease treatment by precisely treating genetic defects. This method targets particular cells or tissues with therapeutic genes to treat a variety of genetic problems, including cancer, hereditary diseases, and viral infections. Viral, nonviral, and genome editing techniques such as CRISPR-Cas9 are used for targeted gene therapy to fix or modify disease-causing genes with minimal off-target effects. The issues of vector immunogenicity, off-target mutations, and gene delivery to target cells persist despite tremendous progress. The successful implementation of targeted gene therapy is further hindered by hereditary illness complexity and genetic background diversity. These difficulties require multidisciplinary cooperation, novel vector design, and thorough preclinical and clinical assessments. The long-term and unforeseen effects of gene editing must also be considered from an ethical viewpoint. Targeted gene therapy has considerable therapeutic promise, but more research and technological advances are needed to overcome limitations and develop safe and successful clinical treatments.

Toxin–antitoxin (TA) systems are widespread bacterial immune systems that confer protection against various environmental stresses. TA systems have been classified into eight types (I–VIII) based on the nature and mechanism of action of the antitoxin. Type III TA systems consist of a noncoding RNA antitoxin and a protein toxin, forming a ribonucleoprotein (RNP) TA complex that plays crucial roles in phage defence in bacteria. Type III TA systems are present in the human gut microbiome and several pathogenic bacteria and, therefore, could be exploited for a novel antibacterial strategy. Due to the inherent toxicity of the toxin for E. coli, it is challenging to overexpress and purify free toxins from E. coli expression systems. Therefore, protein toxin is typically co-expressed and co-purified with antitoxin RNA as an RNP complex from E. coli for structural and biophysical studies. Here, we have optimized the co-expression and purification method for ToxIN type III TA complexes from E. coli that results in the purification of TA RNP complex and, often, free antitoxin RNA and free active toxin in quantities required for the biophysical and structural studies. This protocol can also be adapted to purify isotopically labelled (e.g., uniformly 15N- or 13C-labelled) free toxin proteins, free antitoxin RNAs, and TA RNPs, which can be studied using multidimensional nuclear magnetic resonance (NMR) spectroscopy methods.Key features• Detailed protocol for the large-scale purification of ToxIN type III toxin–antitoxin complexes from E. coli.• The optimized protocol results in obtaining milligrams of TA RNP complex, free toxin, and free antitoxin RNA.• Commercially available plasmid vectors and chemicals are used to complete the protocol in five days after obtaining the required DNA clones.• The purified TA complex, toxin protein, and antitoxin RNA are used for biophysical experiments such as NMR, ITC, and X-ray crystallography.Graphical overview

Summary: Macrophages release soluble mediators following efferocytic clearance of apoptotic cells to facilitate intercellular communication and promote the resolution of inflammation. However, whether inflammation resolution is modulated by extracellular vesicles (EVs) and vesicular mediators released by efferocytes is not known. We report that efferocyte-derived EVs express prosaposin, which binds to macrophage GPR37 to increase expression of the efferocytosis receptor Tim4 via an ERK-AP1-dependent signaling axis, leading to increased macrophage efferocytosis efficiency and accelerated resolution of inflammation. Neutralization and knockdown of prosaposin or blocking GRP37 abrogates the pro-resolution effects of efferocyte-derived EVs in vivo. Administration of efferocyte-derived EVs in a murine model of atherosclerosis is associated with an increase in lesional macrophage efferocytosis efficiency and a decrease in plaque necrosis and lesional inflammation. Thus, we establish a critical role for efferocyte-derived vesicular mediators in increasing macrophage efferocytosis efficiency and accelerating the resolution of inflammation and tissue injury.

With the evolution of multicellularity, communication among cells in different tissues and organs became pivotal to life. Molecular basis of such communication has long been studied, but genome-wide screens for genes and other biomolecules mediating tissue-tissue signaling are lacking. To systematically identify inter-tissue mediators, we present a novel computational approach MultiCens (Multilayer/Multi-tissue network Centrality measures). Unlike single-layer network methods, MultiCens can distinguish within- vs. across-layer connectivity to quantify the "influence" of any gene in a tissue on a query set of genes of interest in another tissue. MultiCens enjoys theoretical guarantees on convergence and decomposability, and performs well on synthetic benchmarks. On human multi-tissue datasets, MultiCens predicts known and novel genes linked to hormones. MultiCens further reveals shifts in gene network architecture among four brain regions in Alzheimer's disease. MultiCens-prioritized hypotheses from these two diverse applications, and potential future ones like "Multi-tissue-expanded Gene Ontology" analysis, can enable whole-body yet molecular-level systems investigations in humans.

Caromiobenella helgolandica (Claus, 1863), a presumedly widespread monstrilloid copepod, is reported for the first time from Saudi waters of the Arabian Gulf; only females were found in zooplankton samples collected from Tarut Bay in the Arabian Gulf. Caromiobenella Jeon, Lee, & Soh, 2018 is a recently described genus that is distinguished by having modified male antennules. The nauplii of monstrilloid copepods are endoparasitic on molluscs and polychaetes, while the adults are free-living reproductive forms. This study is an unprecedented record of C. helgolandica from the Arabian Gulf region.

This study aims to increase Bacillus and Streptomyces antagonistic activity against the root rot and wilt diseases of pulses caused by Macrophomina phaseolina and Fusarium oxysporum f. sp. udum, respectively. To increase antagonistic action, Bacillus subtilis BRBac4, Bacillus siamensis BRBac21, and Streptomyces cavourensis BRAcB10 were subjected to random mutagenesis using varying doses of gamma irradiation (0.5–3.0 kGy). Following the irradiation, 250 bacterial colonies were chosen at random for each antagonistic strain and their effects against pathogens were evaluated in a plate assay. The ERIC, BOX, and random amplified polymorphic studies demonstrated a clear distinction between mutant and wild-type strains. When mutants were compared to wild-type strains, they showed improved plant growth-promoting characteristics and hydrolytic enzyme activity. The disease suppression potential of the selected mutants, B. subtilis BRBac4-M6, B. siamensisi BRBac21-M10, and S. cavourensis BRAcB10-M2, was tested in green gram, black gram, and red gram. The combined inoculation of B. siamensis BRBac21-M10 and S. cavourensis BRAcB10-M2 reduced the incidence of root rot and wilt disease. The same treatment also increased the activity of the defensive enzymes peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase. These findings suggested that gamma-induced mutation can be exploited effectively to improve the biocontrol characteristics of Bacillus and Streptomyces. Following the field testing, a combined bio-formulation of these two bacteria may be utilised to address wilt and root-rot pathogens in pulses.

With the rapid growth of the COVID-19 (coronavirus disease 2019) pandemic across the globe, therapeutic attention must be directed to fight the novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). However, developing new antiviral drugs and vaccines is time-consuming, so one of the best solutions to tackle this virus at present is to repurpose ready-to-use drugs. This paper proposes the repurposing of the Food and Drug Administration (FDA)-approved, purchasable, and naturally occurring drugs for preventive and therapeutic use. We propose to design a dual-inhibitor for the SARS-CoV-2 cysteine proteases—3 Chemotrypsin-like protease or main protease (3CLpro or Mpro) and Papain-like protease (PLpro) responsible for processing the translated polyprotein chain from the viral RNA yielding functional viral proteins. For virtual screening, an unbiased blind docking was performed from which the top nine dual-targeting inhibitors for 3CLpro and PLpro were selected. The nine repurposed drugs, block the catalytic dyad (His41 and Cys145) of 3CLpro as well as the catalytic triad (Cys111, His272, and Asp286) of PLpro. Repurposing known drugs will not only pave the way for rapid in-vitro and in-vivo studies to battle the SARS-CoV-2 but will also expedite the quest for a potent anti-coronaviral drug.

Sex is a biological variable in experimental models. In our previous diisopropylfluorophosphate (DFP) studies, female rats required a higher dose of DFP to achieve a somewhat similar severity of status epilepticus (SE) as males. In those studies, male and female rats were bought separately from the same vendor, housed in different rooms, and the DFP used was from different batches. We had also shown that surgery for epidural electrodes implantation reduces the threshold for SE. Our recent study in the soman (GD) model using a mixed-sex cohort of rats housed individually but in the same room showed that females achieved significantly higher SE severity than males for the same dose of GD. In this study, we demonstrate that housing the mixed-sex cohorts in the same room and treating them with DFP (4 mg/kg, s.c.) from the same pool, though from different batches, yielded reproducible SE severity in both sexes and both telemetry (surgery) and non-telemetry (non-surgery) groups. We conducted experiments in four mixed-sex cohorts of adult Sprague-Dawley rats. In females, the surgery for implanting the telemetry devices reduced the latency to convulsive seizure (CS) and increased SE severity compared to non-telemetry females. However, there were no sex differences in latency or SE severity within telemetry or non-telemetry groups. Once animals reached CS stage ≥3, they remained in CS stage in both sexes until midazolam was administered. Midazolam (3 mg/kg, i.m.) treatment 1-one-hour post-DFP significantly reduced epileptiform spikes in both sexes. The mortality was only 2% in 24 h. Irrespective of sex or stage of estrous cycle or surgery, the animals had continuous convulsive SE for ∼40 min. In telemetry rats, electrographic changes correlated with behavioral seizures. However, there was a significant difference in SE severity and the latency between directly-observed behavioral CS and EEG-based CS quantification in both sexes. Overall, these results suggest that housing both sexes in the same room and treating with DFP in a mixed-sex cohort from the same pool of reagents will minimize variability in SE severity. Such rigorous experiments will yield better outcomes while testing disease-modifying agents in epilepsy models.

Tilapia is a widely cultured species native to Africa; these fish are prolific breeders and constitute an economically important fish species supplying higher-quality protein. To meet the global food demand and achieve the UN’s Sustainable Developmental Goals (SDG), the aquaculture industry has conceived of productive solutions with the potential for adaptability, palatability, and profitability. Tilapia may play a vital role with respect to the possibility for sustainability in the nutrition and aquaculture sectors. India contributes to the promotion of aquacultural practices through a structural framework focused on agricultural, environmental, geographical, and socio-economic factors that provide opportunities for tilapia farming. Globally, the Indian aquaculture sector is currently the second largest in terms of aquacultural production but is moving toward different species that meet SDG and facilitate international marketing opportunities. The farming of aquacultural species with innovative technology constitutes an efficient use of resources. Productive research on feeding, disease management, construction, and layout helps overcome the challenges faced in aquaculture. These focused and sustained factors of the aquaculture industry offer a latent contribution to global food security. This review reports on the state of the art, the challenges regarding tilapia aquaculture in India, and the Indian government’s schemes, missions, subsidies, projects and funding related to tilapia production.

Traditional watermarking methods can remove a watermark from an image, making it possible to see the copyright information about the image owner or to estimate similarities using techniques such as bit error rate and normalized correlation. Deep learning is another examination field in AI, and is utilized to develop a deep network to extract objective elements and afterwards distinguish the general environment. To assure the robustness and security of computerized image watermarking, we propose a novel algorithm using convolutional generative adversarial neural networks. This research proposed a novel technique in digital watermarking, with data hiding based on segmentation and classification, using deep learning techniques. The used input images are medical images, including Magnetic Resonance Images (MRI) and Computed Tomography (CT) images, which have been processed for noise removal, smoothening and normalization. The processed image has been watermarked using the Singular Value Decomposition-based discrete wavelet transform quantization model, being segmented and classified using convolutional generative adversarial neural networks. The experimental analysis has been carried out in terms of bit error rate, Structural Similarity Index Measure (SSIM), Normalized Cross-Correlation (NCC), training accuracy, and validation accuracy. This achieved an attained bit error rate of 71%, an SSIM of 56%, a Normalized Cross-Correlation of 71%, a training accuracy of 98%, and a validation accuracy of 95%.

Fetal alcohol spectrum disorder (FASD) results from prenatal ethanol exposure. The zebrafish (Danio rerio) is an outstanding in vivo FASD model. Early development produced the three germ layers and embryonic axes patterning. A critical pluripotency transcriptional gene circuit of sox2, pou5f1 (oct4; recently renamed pou5f3), and nanog maintain potency and self-renewal. Ethanol affects sox2 expression, which functions with pou5f1 to control target gene transcription. Various genes, like elf3, may interact and regulate sox2, and elf3 knockdown affects early development. Downstream of the pluripotency transcriptional circuit, developmental signaling activities regulate morphogenetic cell movements and lineage specification. These activities are also affected by ethanol exposure. Hedgehog signaling is a critical developmental signaling pathway that controls numerous developmental events, including neural axis specification. Sonic hedgehog activities are affected by embryonic ethanol exposure. Activation of sonic hedgehog expression is controlled by TGF-ß family members, Nodal and Bmp, during dorsoventral (DV) embryonic axis establishment. Ethanol may perturb TGF-ß family receptors and signaling activities, including the sonic hedgehog pathway. Significantly, experiments show that activation of sonic hedgehog signaling rescues some embryonic ethanol exposure effects. More research is needed to understand how ethanol affects early developmental signaling and morphogenesis.

Phospholipids (PLs) are amphiphilic molecules that are in charge of controlling what goes in or out of the cell, keeping up the structure and numerous associated functions. These primary molecules are not only the integral part but also a vastly diverse group of molecules present in microorganisms, plants, and animals. PLs provide rigidity, signal transduction, energy to cells. PLs such as lecithins are molecules of future food, medicine and cosmetic industry. PLs are used in fat and oil refining and these are also used as carriers in drug and drug delivery system. Of course, challenges are there in the assay of phospholipids because of their availability of hydrophobic and hydrophilic components in the same environment. This review is mainly focused to unveil the function, characteristics, features and applications of PLs in various fields.

Rice (Oryza sativa L.) plants are simultaneously encountered by environmental stressors, most importantly salinity stress. Salinity is the major hurdle that can negatively impact growth and crop yield. Understanding the salt stress and its associated complex trait mechanisms for enhancing salt tolerance in rice plants would ensure future food security. The main aim of this review is to provide insights and impacts of molecular-physiological responses, biochemical alterations, and plant hormonal signal transduction pathways in rice under saline stress. Furthermore, the review highlights the emerging breakthrough in multi-omics and computational biology in identifying the saline stress-responsive candidate genes and transcription factors (TFs). In addition, the review also summarizes the biotechnological tools, genetic engineering, breeding, and agricultural practicing factors that can be implemented to realize the bottlenecks and opportunities to enhance salt tolerance and develop salinity tolerant rice varieties. Future studies pinpointed the augmentation of powerful tools to dissect the salinity stress-related novel players, reveal in-depth mechanisms and ways to incorporate the available literature, and recent advancements to throw more light on salinity responsive transduction pathways in plants. Particularly, this review unravels the whole picture of salinity stress tolerance in rice by expanding knowledge that focuses on molecular aspects.

Alzheimer’s disease (AD) in elderly adds substantially to socioeconomic burden necessitating early diagnosis. While recent studies in rodent models of AD have suggested diagnostic and therapeutic value for gamma rhythms in brain, the same has not been rigorously tested in humans. In this case-control study, we recruited a large population (N = 244; 106 females) of elderly (>49 years) subjects from the community, who viewed large gratings that induced strong gamma oscillations in their electroencephalogram (EEG). These subjects were classified as healthy (N = 227), mild cognitively impaired (MCI; N = 12), or AD (N = 5) based on clinical history and Clinical Dementia Rating scores. Surprisingly, stimulus-induced gamma rhythms, but not alpha or steady-state visually evoked responses, were significantly lower in MCI/AD subjects compared to their age- and gender-matched controls. This reduction was not due to differences in eye movements or baseline power. Our results suggest that gamma could be used as a potential screening tool for MCI/AD in humans.

To understand the spread of SARS-CoV2, in August and September 2020, the Council of Scientific and Industrial Research (India) conducted a serosurvey across its constituent laboratories and centers across India. Of 10,427 volunteers, 1058 (10.14%) tested positive for SARS-CoV2 anti-nucleocapsid (anti-NC) antibodies, 95% of which had surrogate neutralization activity. Three-fourth of these recalled no symptoms. Repeat serology tests at 3 (n = 607) and 6 (n = 175) months showed stable anti-NC antibodies but declining neutralization activity. Local seropositivity was higher in densely populated cities and was inversely correlated with a 30-day change in regional test positivity rates (TPRs). Regional seropositivity above 10% was associated with declining TPR. Personal factors associated with higher odds of seropositivity were high-exposure work (odds ratio, 95% confidence interval, p value: 2.23, 1.92–2.59,

Coronavirus disease (COVID-19) has emerged as a fast-paced epidemic in late 2019 which is disrupting life-saving immunization services. SARS-CoV-2 is a highly transmissible virus and an infectious disease that has caused fear among people across the world. The worldwide emergence and rapid expansion of SARS-CoV-2 emphasizes the need for exploring innovative therapeutic approaches to combat SARS-CoV-2. The efficacy of some antiviral drugs such as remdesivir, favipiravir, umifenovir, etc., are still tested against SARS-CoV-2. Additionally, there is a large global effort to develop vaccines for the protection against COVID-19. Because vaccines seem the best solution to control the pandemic but time is required for its development, pre-clinical/clinical trials, approval from FDA and scale-up. The nano-based approach is another promising approach to combat COVID-19 owing to unique physicochemical properties of nanomaterials. Peptide based vaccines emerged as promising vaccine candidates for SARS-CoV-2. The study emphasizes the current therapeutic approaches against SARS-CoV-2 and some of the potential candidates for SARS-CoV-2 treatment which are still under clinical studies for their effectiveness against SARS-CoV-2. Overall, it is of high importance to mention that clinical trials are necessary for confirming promising drug candidates and effective vaccines and the safety profile of the new components must be evaluated before translation of in vitro studies for implementation in clinical use.

Chitosan is a rather attractive material, especially because of its bio-origins as well as generation from exoskeletal waste. As the mantle has been effectively transferred from chitin to chitosan, so has it been extrapolated to in-house synthesized novel chitosan derivatives. This review comprehensively lists the available novel chitosan derivatives (ChDs) and summarizes their biological applications. The fact that chitosan derivatives do comprise multifaceted biological applications is attested by the voluminous reports on their varied contributions. However, this review points out to the fact that there has been selective focus on bio functions such as antifungal, antioxidant, antibacterial, whereas other biomedical applications and antiviral applications remain relatively less explored. With their current functionality record, there is definitely no doubt that the plethora of synthesized ChDs will have a profound impact on the unexplored biological aspects. This review points out this lacuna as room for future exploration.

Introduction: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease caused by increasing breathing passage obstruction which completely disrupts human homeostasis. Some patients require lung transplantation or long-term oxygen therapy. COPD is one of the noxious diseases and its fourth leading cause of death around the globe. There is an immediate need for potential drug development to tackle this serious disease. Folk medicines are used to combat complex diseases that have shown effectiveness in the treatment of breathing diseases. Vitex negundo L. is an ethnobotanically important medicinal plant used for various ailments and modulates human cellular events. This shrub has diverse specialized metabolites and is being used as complementary medicine in various countries. Though systems-level understanding is there on the mode of action, the multi-target treatment strategy for COPD is still a bottleneck. Methods: In this investigation, systems pharmacology, cheminformatics, and molecular docking analyses were performed to unravel the multi-targeted mechanisms of V. negundo L. potential bioactives to combat COPD. Results: Cheminformatics analysis combined with the target mining process identified 86 specialized metabolites and their corresponding 1300 direct human receptors, which were further imputed and validated systematically. Furthermore, molecular docking approaches were employed to evaluate the potential activity of identified potential compounds. In addition, pharmacological features of these bioactives were compared with available COPD drugs to recognize potential compounds that were found to be more efficacious with higher bioactive scores. Conclusions: The present study unravels the druggable targets and identifies the bioactive compounds present in V. negundo L., that may be utilized for potential treatment against COPD. However, further in vivo analyses and clinical trials of these molecules are essential to deciphering their efficacy.

Objective: To synthesize bio-inspired gold nanoparticles (AuNPs) using the leaf extract of Justicia adhatoda and evaluate the anti-cancer activity on human lung cancer cell line (A549). Methods: Synthesis of AuNPs was done using an aqueous leaf extract of Justicia adhatoda as a green route. The bio-synthesized AuNPs were confirmed and characterized by using various spectral studies such as UV-Vis spectrum, Scanning Electron Microscope with EDAX, Transmission Electron Microscope, Fourier Transmission Infrared Spectroscope analysis and Surface Enhanced Raman Spectroscopy. The cell viability was determined by MTT reduction assay. In addition, cytomorphology and the nuclear morphological study of A549 cell line was observed under fluorescence microscope. Results: UV-Vis spectrum showed surface plasmon resonance peak at 547 nm, scanning electron microscope and transmission electron microscope studies showed the monodispersed spherical shape and its average size in the range of 40.1 nm was noticed. Fourier Transmission Infrared Spectroscope analysis confirmed that the C=O group of amino acids of proteins had strong ability to bind with the surface of nanoparticle. Interestingly, our results also demonstrated inhibited proliferation of A549 cell line by MTT (IC50 value: 80 μg/mL). Cell morphology was observed and cell death was caused by apoptosis as revealed by propidium iodide staining. Conclusions: The current study proves the anticancer potential of bio-synthesized AuNPs. Thus, synthesized AuNPs can be used for the treatment of human lung cancer cell (A549) and it can be exploited for drug delivery in future.

The present study was carried out to analyze the potential of fungi isolated from the rhizosphere of soybean, brinjal, tomato, and potato plants. The density of fungi varied in the pot soil and rhizosphere after Paecilomyces formosus MD12 treatment. The P. formosus MD12 population was 6.3 ± 0.13 × 104 CFU g−1 in the pot planted with brinjal, and the population increased in the rhizosphere (6.72 ± 0.41 × 104 CFU g−1). P. formosus MD12 was cultured in the production medium, and the supernatant was used for egg inhibition studies on a root-knot nematode parasite, Meloidogyne incognita. It was revealed that maximum egg inhibition (94.7 ± 6.2%) was obtained at 100% concentration of extract. The culture supernatant from P. formosus MD12 affected the development of M. incognita juvenile, and the mortality rate was maximum after 96 h (95 ± 6%). Mortality was reduced when treated with 25%, 50%, and 75% supernatant. At 1 × 107 mL−1 of spore suspension, we found reductions of 71.6 ± 3.3% nematode populations in the soil, 60.7 ± 2.2% from the root, and 63.6 ± 2.4% egg mass compared with the control in the pot experiment. The culture supernatant applied at the 10% level showed a maximum mean reduction of the nematode population in roots (72.4 ± 2.2%), soil (77.9 ± 2.5%), and egg masses (73.2 ± 1.5%), respectively. The presence of P. formosus MD12 in a soil environment could antagonize nematode parasites and improve soil amendment. The P. formosus MD12 strain showed good biocontrol ability against the root-knot nematode, M. incognita, under in vitro and green house experimental condition.

Understanding the regulatory networks underlying lineage differentiation and fate determination of human bone marrow stromal cells (hBMSC) is a prerequisite for their therapeutic use. The goal of the current study was to unravel the novel role of the low-density lipoprotein receptor-related protein 3 (LRP3) in regulating the osteogenic and adipogenic differentiation of immortalized hBMSCs. Gene expression profiling revealed significantly higher LRP3 levels in the highly osteogenic hBMSC clone imCL1 than in the less osteogenic clone imCL2, as well as a significant upregulation of LRP3 during the osteogenic induction of the imCL1 clone. Data from functional and gene expression assays demonstrated the role of LRP3 as a molecular switch promoting hBMSC lineage differentiation into osteoblasts and inhibiting differentiation into adipocytes. Interestingly, microRNA (miRNA) expression profiling identified miR-4739 as the most under-represented miRNA (−36.11 fold) in imCL1 compared to imCL2. The TargetScan prediction algorithm, combined with functional and biochemical assays, identified LRP3 mRNA as a novel target of miR-4739, with a single potential binding site for miR-4739 located in the LRP3 3′ UTR. Regulation of LRP3 expression by miR-4739 was subsequently confirmed by qRT-PCR, western blotting, and luciferase assays. Over-expression of miR-4739 mimicked the effects of LRP3 knockdown on promoting adipogenic and suppressing osteogenic differentiation of hBMSCs. Hence, we report for the first time a novel biological role for the LRP3/hsa-miR-4739 axis in balancing osteogenic and adipocytic differentiation of hBMSCs. Our data support the potential utilization of miRNA-based therapies in regenerative medicine.

The Hippo pathway effectors YAP and TAZ act as nuclear sensors of mechanical signals in response to extracellular matrix (ECM) cues. However, the identity and nature of regulators in the ECM and the precise pathways relaying mechanoresponsive signals into intracellular sensors remain unclear. Here, we uncover a functional link between the ECM proteoglycan Agrin and the transcriptional co-activator YAP. Importantly, Agrin transduces matrix and cellular rigidity signals that enhance stability and mechanoactivity of YAP through the integrin-focal adhesion- and Lrp4/MuSK receptor-mediated signaling pathways. Agrin antagonizes focal adhesion assembly of the core Hippo components by facilitating ILK-PAK1 signaling and negating the functions of Merlin and LATS1/2. We further show that Agrin promotes oncogenesis through YAP-dependent transcription and is clinically relevant in human liver cancer. We propose that Agrin acts as a mechanotransduction signal in the ECM.

Matcha tea is a traditional Japanese tea that is said to possess ten times higher bioactive components and polyphenols than that of conventional green teas. Matcha is remotely popular among the global community and meagerly researched and infamous among the scientific population. It is the powdered form of green tea leaves that are directly suspended in hot water and drunk without filtration. Matcha is said to be one of the richest antioxidant sources naturally available. This review summarizes the available research publications related to matcha and compares the research accomplishments of green tea and matcha researchers. The fact that green tea is backed up by 35,000 publications while matcha has merely 54 publications to its credit is highlighted in this review for the first time. The future of matcha for tapping its enormous antioxidant activity and health potentials remains connected to the volume of scientific awareness and enhanced research attention in this area. If green tea has so much to offer towards human health and welfare, there is certainly room for more benefits from matcha, which is yet to be disclosed. As public awareness cannot be won without scientific approval, this review seeks that this gap may be bridged using essential knowledge gained from matcha applications and allied research.

Microbial natural biocides have attracted much more attention in recent years in order to avoid the unrestricted use of chemical biocides in the environment. The aim of this study is to analyze the antibacterial and antifungal activities of secondary metabolites and growth promoting, nematicidal, and soil enzyme activity mediated by Trichoderma hamatum FB10. The bactericidal and fungicidal activities were performed using cell-free extract. Results revealed that the selected strain exert antibacterial activity against Acidovorax avenae, Erutimacarafavora, and Xanthomonas campestris. The selected fungal strain FB10 showed antagonistic activity against fungal pathogens such as, S. sclerotiorum, Rhizoctonia solani, Alternaria radicina, Alternaria citri, and Alternaria dauci. Among the bacterial pathogens, A. avenae showed least MIC (30 ± 2.5 µg/mL) and MBC (70 ± 1.25 µg/mL) values. T. hamatum FB10 strain synthesized bioactive volatile secondary metabolite, which effectively inhibited the growth of bacteria and fungi and indicated the presence of 6-pentyl-alpha-pyrone as the major compound (67.05%). The secondary metabolite synthesized by T. hamatum FB10 showed nematicidal activity against M. incognita eggs. Egg hatch inhibition was 78 ± 2.6% and juvenile stage mortality rate was 89 ± 2.5% when the strain FB10 was treated with nematode. The cell free extract of T. hamatum FB10 showed protease, amylase, cellulase, chitinase, glucanase activities. T. hamatum FB10 inoculated with green gram increased 11% plant height, compared to the control. The fresh weight of the experimental group inoculated with T. hamatum FB10 increased 33.6% more compared to the control group. The green gram seedlings inoculated with T. hamatum FB10 increased 18% more dry weight than control group. Soil enzymes such as, urease, phosphatase, catalase and saccharase were improved in the soil inoculated with T. hamatum FB10. These biochemical components play potent role in soil fertility, energy conversion, and in soil organic matter conversion.

Glycobiology is gaining paramount importance for its influence on diseases as a consequence of a fundamental understanding of the underlying processes involved in them. Cancer is still posing threats to human health and welfare and therapies are perpetually being sought. Glycans are selectively attached to proteins and lipids during glycosylation, and these hold anchorage positions in many important biological processes involved in cancer through their altered expression or activity upon malignant transformation. Aberrant glycosylation is well established as a hallmark of cancer, linked to tumor development and metastasis. The analytical inputs and milestones achieved and the characterization and detection of glycosylation in cancer have been summarized in this review. The milestones achieved in cancer research through inputs from glycosylation have been highlighted. With almost 70% of biopharmaceuticals being glycoproteins and almost 80% of cancer biomarkers being glycan in origin, glycosylation has a lot of say in cancer prognosis and diagnosis. The future of glycosylation in cancer and the lacunae in the smooth channelization of state-of-the-art technologies for taking this research knowledge from bench top to bedside (actual clinical settings) is speculated upon. The incorporation of cross-disciplinary integrated approaches and nano-instrumentation sophistications are proposed for achieving scaling up.

This report provides the first record of the exotic sucker fish P. pardalis from the Cauvery river system, Tamilnadu state, India. Information on the assumed presence of this invasive species based on sightings of a hitherto unknown species by local people and fishermen in stretches of Cauvery river have been confirmed by our study. Sailfin sucker fishes are popular among pet traders and aquarists in south east Asian countries and have been regarded as invaders worldwide. Occurrence of P. pardalis in newer habitats due to its potential invasion in the South Indian waters issues threat to native fauna.

Abstract Using expression profiles from postmortem prefrontal cortex samples of 624 dementia patients and non‐demented controls, we investigated global disruptions in the co‐regulation of genes in two neurodegenerative diseases, late‐onset Alzheimer's disease (AD) and Huntington's disease (HD). We identified networks of differentially co‐expressed (DC) gene pairs that either gained or lost correlation in disease cases relative to the control group, with the former dominant for both AD and HD and both patterns replicating in independent human cohorts of AD and aging. When aligning networks of DC patterns and physical interactions, we identified a 242‐gene subnetwork enriched for independent AD/HD signatures. This subnetwork revealed a surprising dichotomy of gained/lost correlations among two inter‐connected processes, chromatin organization and neural differentiation, and included DNA methyltransferases, DNMT1 and DNMT3A, of which we predicted the former but not latter as a key regulator. To validate the inter‐connection of these two processes and our key regulator prediction, we generated two brain‐specific knockout (KO) mice and show that Dnmt1 KO signature significantly overlaps with the subnetwork (P = 3.1 × 10−12), while Dnmt3a KO signature does not (P = 0.017).

Although much is known about the molecular players in insulin signaling, there is scant information about transcriptional regulation of its key components. We now find that NUCKS is a transcriptional regulator of the insulin signaling components, including the insulin receptor (IR). Knockdown of NUCKS leads to impaired insulin signaling in endocrine cells. NUCKS knockout mice exhibit decreased insulin signaling and increased body weight/fat mass along with impaired glucose tolerance and reduced insulin sensitivity, all of which are further exacerbated by a high-fat diet (HFD). Genome-wide ChIP-seq identifies metabolism and insulin signaling as NUCKS targets. Importantly, NUCKS is downregulated in individuals with a high body mass index and in HFD-fed mice, and conversely, its levels increase upon starvation. Altogether, NUCKS is a physiological regulator of energy homeostasis and glucose metabolism that works by regulating chromatin accessibility and RNA polymerase II recruitment to the promoters of IR and other insulin pathway modulators.

Autism spectrum disorder (ASD) refers to a group of childhood neurodevelopmental disorders with polygenic etiology. The expression of many genes implicated in ASD is tightly regulated by various factors including microRNAs (miRNAs), a class of noncoding RNAs ∼22 nucleotides in length that function to suppress translation by pairing with ‘miRNA recognition elements’ (MREs) present in the 3′untranslated region (3′UTR) of target mRNAs. This emphasizes the role played by miRNAs in regulating neurogenesis, brain development and differentiation and hence any perturbations in this regulatory mechanism might affect these processes as well. Recently, single nucleotide polymorphisms (SNPs) present within 3′UTRs of mRNAs have been shown to modulate existing MREs or even create new MREs. Therefore, we hypothesized that SNPs perturbing miRNA-mediated gene regulation might lead to aberrant expression of autism-implicated genes, thus resulting in disease predisposition or pathogenesis in at least a subpopulation of ASD individuals. We developed a systematic computational pipeline that integrates data from well-established databases. By following a stringent selection criterion, we identified 9 MRE-modulating SNPs and another 12 MRE-creating SNPs in the 3′UTR of autism-implicated genes. These high-confidence candidate SNPs may play roles in ASD and hence would be valuable for further functional validation.

With the rising awareness on environmental issues and the increasing risks through industrial development, clean up remediation measures have become the need of the hour. Bioremediation has become increasingly popular owing to its environmentally friendly approaches and cost effectiveness. Polychlorinated biphenyls (PCBs) are an alarming threat to human welfare as well as the environment. They top the list of hazardous xenobiotics. The multiple effects these compounds render to the niche is not unassessed. Bioremediation does appear promising, with myco remediation having a clear edge over bacterial remediation. In the following review, the inputs of white-rot fungi in PCB remediation are examined and the lacunae in the practical application of this versatile technology highlighted. The unique abilities of Pleurotus ostreatus and its deliverables with respect to removal of PCBs are presented. The need for improvising P. ostreatus-mediated remediation is emphasized.

Quantifying heterogeneity in gene expression among single cells can reveal information inaccessible to cell-population averaged measurements. However, the expression level of many genes in single cells fall below the detection limit of even the most sensitive technologies currently available. One proposed approach to overcome this challenge is to measure random pools of k cells (e.g., 10) to increase sensitivity, followed by computational "deconvolution" of cellular heterogeneity parameters (CHPs), such as the biological variance of single-cell expression levels. Existing approaches infer CHPs using either single-cell or k-cell data alone, and typically within a single population of cells. However, integrating both single- and k-cell data may reap additional benefits, and quantifying differences in CHPs across cell populations or conditions could reveal novel biological information. Here we present a Bayesian approach that can utilize single-cell, k-cell, or both simultaneously to infer CHPs within a single condition or their differences across two conditions. Using simulated as well as experimentally generated single- and k-cell data, we found situations where each data type would offer advantages, but using both together can improve precision and better reconcile CHP information contained in single- and k-cell data. We illustrate the utility of our approach by applying it to jointly generated single- and k-cell data to reveal CHP differences in several key inflammatory genes between resting and inflammatory cytokine-activated human macrophages, delineating differences in the distribution of 'ON' versus 'OFF' cells and in continuous variation of expression level among cells. Our approach thus offers a practical and robust framework to assess and compare cellular heterogeneity within and across biological conditions using modern multiplexed technologies.

The Rajiv Gandhi National Park encompasses a rich biodiversity of both flora and fauna and is regarded as one of the richest protected areas in Asia. It is a part of Nilgiri Biosphere Reserve and covers foot-hills of the Brahmagiri hill ranges in the Western Ghats, which is one of the world’s biodiversity hotspots and epicenter of Indian endemics harbouring species-rich-habitats and supporting a high biodiversity. This is evident in its flowering plants diversity brought to focus during the present study. The National Park spreads over an area of 643.39 km2, harbours 1337 species, 14 subspecies and 34 varieties of Angiosperms distributed over 754 genera and 152 families. Notably 110 species of these are endemic. A complete inventory of all the recorded species is provided here.

We do not need to rehearse the grim story of the global rise of antibiotic resistant microbes. But what if it were possible to control the rate with which antibiotic resistance evolves by de novo mutation? It seems that some bacteria may already do exactly that: they modify the rate at which they mutate to antibiotic resistance dependent on their biological environment. In our recent study [Krašovec, et al. Nat. Commun. (2014), 5, 3742] we find that this modification depends on the density of the bacterial population and cell-cell interactions (rather than, for instance, the level of stress). Specifically, the wild-type strains of Escherichia coli we used will, in minimal glucose media, modify their rate of mutation to rifampicin resistance according to the density of wild-type cells. Intriguingly, the higher the density, the lower the mutation rate (Figure 1). Why this novel density-dependent ‘mutation rate plasticity’ (DD-MRP) occurs is a question at several levels. Answers are currently fragmentary, but involve the quorum-sensing gene luxS and its role in the activated methyl cycle.