Br - nanoconjugate enhances the antibacterial efficacy of nimboloide against Flavobacterium columnare infection in Labeo rohita: A nanoinformatics approach.

BACKGROUND: The bacterial pathogen, Flavobacterium columnare causes columnaris disease in Labeo rohita globally. Major effects of this bacterial infection include skin rashes and gill necrosis. Nimbolide, the key ingredient of the leaf extract of Azadirachta indica possesses anti-bacterial properties effective against many microorganisms. Nano-informatics plays a promising role in drug development and its delivery against infections caused by multi-drug-resistant bacteria. Currently, studies in the disciplines of dentistry, food safety, bacteriology, mycology, virology, and parasitology are being conducted to learn more about the wide anti-virulence activity of nimbolide. METHODS: The toxicity of nimbolide was predicted to determine its dosage for treating bacterial infection in Labeo rohita. Further, comparative 3-D structure prediction and docking studies are done for nimbolide conjugated nanoparticles with several key target receptors to determine better natural ligands against columnaris disease. The nanoparticle conjugates are being designed using in-silico approaches to study molecular docking interactions with the target receptor. RESULTS: Bromine conjugated nimbolide shows the best molecular interaction with the target receptors of selected species ie L rohita. Nimbolide comes under the class III level of toxic compound so, attempts are made to reduce the dosage of the compound without compromising its efficiency. Further, bromine is also used as a common surfactant and can eliminate heavy metals from wastewater. CONCLUSION: The dosage of bromine-conjugated nimbolide can be reduced to a non-toxic level and thus the efficiency of the Nimbolide can be increased. Moreover, it can be used to synthesize nanoparticle composites which have potent antibacterial activity towards both gram-positive and gram-negative bacteria. This material also forms a good coating on the surface and kills both airborne and waterborne bacteria.

Effect of Yoga Based Cardiac Rehabilitation on Blood Pressure Variability and Baroreflex Sensitivity: RCT in Patients Post MI.

To assess the effects of 12 weeks Yoga based Cardiac Rehabilitation program on Blood Pressure Variability and Baroreflex Sensitivity in Eighty patients post myocardial infarction. Randomized controlled trial with two parallel groups. A tertiary care institution in India. The Yoga group received 13 hospital-based structured yoga sessions in adjunct to the standard care. Control Group participants received enhanced standard care involving three brief educational sessions on importance of diet and physical activity. Beat to beat arterial pressure variability and baroreflex sensitivity was determined non-invasively. Baseline measurement was done at 3 weeks post Myocardial Infarction. The measurements were repeated at 13th week and at 26th week post MI. There was no significant difference between the groups in time domain indices of SBP variability. At 26th week post MI, after normalization the Low Frequency power increased in the yoga group as compared to the decrease in the standard care group (p = 0.02). Though the High Frequency power increased in both the groups, the magnitude of increase was higher in the standard care group (p = 0.005). However, the total power increased significantly in yoga group with a concurrent decrease in standard care group (p = < 0.001). The SBP All BRS was significantly different between the groups with an increase in the yoga group and a decline in standard care group (p = 0.003) at 13th week. A short-term Yoga based cardiac rehabilitation has additive effects in improving baroreflex sensitivity and dampening blood pressure variability post myocardial infarction in patients under optimal medication.The main trial is registered in Clinical Trials Registry-India (CTRI) (Ref. No: CTRI/2012/02/002408). In addition, CTRI has also been registered for the sub-study. (Ref. No: CTRI/2017/09/009925).

White light-emitting, biocompatible, water-soluble metallic magnesium nanoclusters for bioimaging applications.

Ultra-small (1.6 nm), water-soluble, white light-emitting (WLE), highly stable (∼8 months) BSA templated metallic (Mg0) nanoclusters (fluorescent magnesium nanoclusters = FMNCs) is developed using the green and facile route. Synthesis was facilitated by the reduction of magnesium salt, where template bovine serum albumin is utilized as a reducing agent and ascorbic acid act as a capping agent to impart stability in water, thereby obtaining stabilized Mg0nanoclusters In solution, stabilized Mg0nanoclusters produce white light (450-620 nm with FWHM ∼120 nm) upon 366 nm light excitation. This white light emission was found to have a CIE coordinate of 0.30, 0.33 [pure white light CIE (0.33, 0.33)]. Taking advantage of WLE and ultrasmall size, FMNCs were used forin vitrofluorescence imaging of HaCaT cell lines, yielding blue (τ= 2.94 ns, with a relative of QY = 1.2 % w.r.t QS), green (τ= 3.07 ns; relative quantum yield of 4.6% w.r.t R6G) and red (τ= 0.3 ns) images. Further, incubation of FMNCs with HEK293 (Human embryonic kidney cell) and cancerous MDA-MB-231 (Breast cancer cell line) human cell lines yielded 100 % cell viability. Current work is envisioned to contribute significantly in the area of science, engineering, and nanomedicine.

Isolation and characterization of hypoxia inducible heme oxygenase 1 (HMOX1) gene in Labeo rohita.

The HMOX1 gene plays role in several biological processes and is also responsive to hypoxia stress. Freshwater carp fish, Labeo rohita, is reported as hypoxia sensitive, but the information of annotated hypoxia genes in public domain is very scanty for this species. Here, an attempt was made to isolate and characterize HMOX1 gene in L. rohita using information from zebrafish. HMOX1 gene was obtained by mapping HMOX1 protein of zebrafish over assembled genome of L. rohita. Aligned region was used for designing primers for HMOX1 amplification. Eight overlapping sets of primers were designed for amplifying ~540 bp long successive overlapping fragments. Splicing of overlapping amplicons generated 3715 bp fragment that was confirmed as HMOX1 gene having full coding region with 6 exons between 184 and 2156 bp positions. HMOX1 characterization is an initiative for L. rohita genes annotation to support the characterization of new genes in the important species.

Evol2Circos: A web-based tool for genome synteny and collinearity analysis and its visualization in fishes.

The advent of high throughput next generation sequencing technologies and improved assembly algorithms have ensued in accumulation of voluminous genomic data in public domains. It has opened up entries for large scale comparative genome studies, especially the identification of conserved syntenic blocks among the species, facilitating the evolutionary importance of the conservation and variation in genomic organization. Synteny construction and visualization requires computational and bioinformatics skills to prepare input file for the synteny analysis pipeline. The syntenic information in fishes is still in juvenile stage and are scattered in different research domains. Here, we present a web-based tool 'Evol2Circos' to provide a user-friendly GUI- and web-based tool to analyse user specific data for synteny construction and visualization, and to facilitate the browsing of syntenic information of different fishes using the circos, bar, dual and dot plots. The information generated from the tool can also be used for further downstream analyses. Evol2Circos software tool is tested under Ubuntu Linux. The web-browser, source code, documentation, user manual, example dataset and scripts are available online at: 203.190.147.148/evole2circos/.

Production, characterization and antibacterial activity of silver nanoparticles produced by Fusarium oxysporum and monitoring of protein-ligand interaction through in-silico approaches.

The present study envisages biological production of silver nanoparticles using Fusarium oxysporum and in-silico identification of the antibacterial activity of the nanoparticles using protein-ligand interaction studies. The morphology of the nanoparticles was variable, with majority of them spherical in the size range 1-50 nm. For in-silico studies, two microorganisms, Escherichia coli and Pseudomonas aeruginosa were selected and metal docking was carried out using the licensed software SYBYL X 1.1.1. The ligand docked deeply into the binding pockets of the outer membrane proteins (OMPs) of both E. coli and P. aeruginosa. The results showed that silver may prove to be a strong antibacterial agent against both the pathogens, with the antibacterial action of silver being greater in the case of P. aeruginosa. The results obtained through in-silico studies were further validated by in-vitro approaches on both solid and liquid media to confirm the results obtained by in-silico analysis. The corroboration of in-silico and in-vitro results amply demonstrates the immense antibacterial potential of silver nanoparticles against the selected pathogens.

Isolation and characterization of hypoxia inducible gene connective tissue growth factor (CTGF) in Labeo rohita.

The connective tissue growth factor gene plays important role in several biological processes and also responsive to hypoxia stress in fishes. The freshwater fish, Labeo rohita, highly cultured in Indian subcontinent for food, is reported as hypoxia sensitive but annotation and sequences of nuclear genes were not available for this species so far in the public domain, except some transcripts. In this study, an attempt was made for isolation and annotation of the CTGF gene in L. rohita using information of zebrafish from the same family. The CTGF gene sequence was obtained by aligning assembled genome of L. rohita, (NCBI BioProject ID: PRJNA437789), with the CTGF protein of zebrafish. Eight overlapping sets of forward and reverse primers from aligned region were designed for amplification of around 600 bp long successive overlapping fragments of CTGF gene in L. rohita. Assembly and annotation of overlapping fragments confirmed a complete 2421 bp long CTGF gene sequence with a full coding region that comprised of five exons between 308 and 1921 positions. This annotated CTGF gene sequence was submitted to GenBank (Acc. No. KY940466). Characterization of CTGF will be an initiative in identification of hypoxia response genes in L. rohita which may further help in understanding the mechanism of hypoxia tolerability in this species.

In silico identification and construction of microbial gene clusters associated with biodegradation of xenobiotic compounds.

Chemical substances not showing any importance in existence of biological systems and causing serious health hazards may be designated as Xenobiotic compound. Elimination or degradation of these unwanted substances is a major issue of concern for current time research. Process of biodegradation is a very important aspect of current research as discussed in current manuscript. Current study focuses on the detailed mining of data for the construction of microbial consortia for wide range of xenobiotics compounds. Intensive literature search was done for the construction of this library. Desired data was retrieved from NCBI in fasta format. Data was analysed through homology approaches by using BLAST. This homology based searched enriched with a great vision that not only bacterial population but many other cheap and potential sources are available for different xenobiotic degradation. Though it was focused that bacterial population covers a major part of biodegradation which is near about 90.6% but algae and fungi are also showing promising future in degradation of some important xenobiotic compounds. Analysis of data reveals that Pseudomonas putida has potential for degrading maximum compounds. Establishment of correlation through cluster analysis signifies that Pseudomonas putida, Aspergillus niger and Skeletonema costatum can have combined traits that can be used in finding out actual evolutionary relationship between these species. These findings may also givea new outcome in terms of much cheaper and eco-friendly source in the area of biodegradation of specified xenobiotic compounds.

WGSSAT: A High-Throughput Computational Pipeline for Mining and Annotation of SSR Markers From Whole Genomes.

Mining and characterization of Simple Sequence Repeat (SSR) markers from whole genomes provide valuable information about biological significance of SSR distribution and also facilitate development of markers for genetic analysis. Whole genome sequencing (WGS)-SSR Annotation Tool (WGSSAT) is a graphical user interface pipeline developed using Java Netbeans and Perl scripts which facilitates in simplifying the process of SSR mining and characterization. WGSSAT takes input in FASTA format and automates the prediction of genes, noncoding RNA (ncRNA), core genes, repeats and SSRs from whole genomes followed by mapping of the predicted SSRs onto a genome (classified according to genes, ncRNA, repeats, exonic, intronic, and core gene region) along with primer identification and mining of cross-species markers. The program also generates a detailed statistical report along with visualization of mapped SSRs, genes, core genes, and RNAs. The features of WGSSAT were demonstrated using Takifugu rubripes data. This yielded a total of 139 057 SSR, out of which 113 703 SSR primer pairs were uniquely amplified in silico onto a T. rubripes (fugu) genome. Out of 113 703 mined SSRs, 81 463 were from coding region (including 4286 exonic and 77 177 intronic), 7 from RNA, 267 from core genes of fugu, whereas 105 641 SSR and 601 SSR primer pairs were uniquely mapped onto the medaka genome. WGSSAT is tested under Ubuntu Linux. The source code, documentation, user manual, example dataset and scripts are available online at https://sourceforge.net/projects/wgssat-nbfgr.

Comparative Transcriptomics Data Profiling Reveals E2F Targets as an Important Biological Pathway Overexpressed in Intellectual Disability Disorder.

Intellectual disability (ID) is an early childhood neurodevelopmental disorder that is characterized by impaired intellectual functioning and adaptive behavior. It is one of the major concerns in the field of neurodevelopmental disorders across the globe. Diversified approaches have been put forward to overcome this problem. Among all these approaches, high throughput transcriptomic analysis has taken an important dimension. The identification of genes causing ID rapidly increased over the past 3 to 5 years owing to the use of sophisticated high throughput sequencing platforms. Early monitoring and preventions are much important for such disorder as their progression occurs during fetal development. This study is an attempt to identify differentially expressed genes (DEGs) and upregulated biological processes involved in development of ID patients through comparative analysis of available transcriptomics data. A total of 7 transcriptomic studies were retrieved from National Center for Biotechnology Information (NCBI) and were subjected to quality check and trimming prior to alignment. The normalization and differential expression analysis were carried out using DESeq2 and EdgeR packages of Rstudio to identify DEGs in ID. In progression of the study, functional enrichment analysis of the results obtained from both DESeq2 and EdgeR was done using gene set enrichment analysis (GSEA) tool to identify major upregulated biological processes involved in ID. Our findings concluded that monitoring the level of E2F targets, estrogen, and genes related to oxidative phosphorylation, DNA repair, and glycolysis during the developmental stage of an individual can help in the early detection of ID disorder.

RNA-Seq data analysis reveals novel nonsense mutations in the NPR3 gene leading to the progression of intellectual disability disorder.

Intellectual disability (ID) is a progressive disorder that affects around 1-3% of the world's population. The heterogeneity of intellectual disability makes it difficult to diagnose as a complete disease. Genetic factors and major mutations play a noticeable role in the development and progression of ID. There is a high need to explore novel variants that may lead to new insights into the progressive aspects of ID. In the current course of study, 31 samples of ID from different studies available on GEO (GSE77742, GSE74263, GSE90682, GSE98476, GSE108887, GSE145710, and PRJEB21964) datasets were taken for the study. These datasets were analyzed for differential gene expression and single nucleotide polymorphism (SNPs). The SNPs of high impact were compared with the differentially expressed genes. Comparison leads to the identification of the priority gene ie NPR3 gene. The identified priority gene further was evaluated for the effect of the mutation using a Mutation Taster. Structure comparison analysis of the wild and mutated proteins of the NPR3 gene was further carried out by UCSF Chimera. Structural analysis reveals the anomalies in protein expression affecting the regulations of the NPR3 gene. These findings identified a novel nonsense mutation (E222*) in the downregulated NPR3 gene that leads to anomalies in the regulation of its protein expression. This missense mutation reveals a major role in causing ID. Our study concludes that the decrease in the expression of the NPR3 gene causes delayed sensory, motor, and physiological functions of the human brain leading to neurodevelopmental delay that causes ID.

In Silico Analysis Predicts Mutational Consequences of CITED2, NUDT4, and Ar18B in Patients with Bipolar Disorder.

Bipolar disorder is a mood-related disorder, which can be portrayed as extreme shifts in energy, mood, and activity levels which can also be characterized by manic highs and depressive lows that can be often misdiagnosed as unipolar disorder due to primitive diagnostics techniques based on clinical assessments as well as diagnostic complexities arising due to its heterogeneous nature and overlapping symptoms with conditions like schizophrenia. leading to delays in treatment Strong evidence in support of genetic and epigenetic aspects of bipolar disorder, including mechanisms such as compromised hypothalamic-pituitary-adrenal axis, immune-inflammatory imbalances, oxidative stress, and mitochondrial dysfunction are found. Moreover, some previous research has already stated the role of genes like CITED2, NUDT4, and Arl8B in these processes. The primary goal of this study is to investigate the involvement of the genes in exploring and validating their potential as biomarkers for bipolar disorder. In silico tools like MutationTaster, PolyPhen2, SIFT, GTEx, PhenoScanner, and RegulomeDB were used to perform mutational and gene expression analyses. Results revealed potentially dangerous mutations caused in CITED2, NUDT4, and Arl8B, those which can have diverse outcomes. RegulomeDB, GTEx, and PhenoScanner reveal the involvement of these genes in various brain regions highlighting their relevance to bipolar disorder. This analysis suggests the potential utility of CITED2, NUDT4, and Arl8B as diagnostic markers hence shedding light on their roles to elaborate the molecular range of bipolar disorder. The study also contributes to providing valuable insights into the genetic and molecular basis of bipolar disorders.

Setu: a pipeline for the robust assembly of SARS-CoV-2 genomes.

Setu is an efficient pipeline integrating currently available open source bioinformatic tools to perform rapid de novo assembly to assist tracking of severe acute respiratory syndrome coronavirus 2 genome evolution in clinical data, being particularly useful for institutions with limited computing resources or personnel not familiar with bioinformatic pipelines.

Correlation between acne and insulin resistance; experience from central India.

Introduction: Acne is a common dermatological condition primarily seen in teenage and adolescent patients and is a major concern for cosmological issues. Along with environmental factors, the proliferation of basal keratinocytes in the sebaceous-pilosebaceous unit, abnormal desquamation of follicular corneocytes, and metabolic abnormalities play a significant role in the pathogenesis of acne development. Aim: To study the causal relation between acne vulgaris and insulin resistance by calculating Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and identify the relation between insulin resistance and the severity of acne. Materials and Methods: This was a retrospective study, where the data of patients with persistent Acne Vulgaris who were referred to the Endocrine department for evaluation of the hormonal and metabolic causes for acne vulgaris were analysed. The patient's clinical records were evaluated in whom there was no significant hormonal or metabolic abnormality identified known to cause persistent acne were included after proper consent and HOMA-IR was calculated. Results: Of several patients with persistent acne, 150 patients were included in our study with the male-to-female ratio was 23:27. The mean age of patients was 33.2 years. The mean HOMA-IR in our acne patients was 1.62 ranging from 0.9-3.7. Sixty four (42.67%) patients had HOMA-IR more than 2.0, thereby suggesting insulin resistance. Conclusion: Our study suggests the prevalence of insulin resistance in 42.67% of patients with acne, thereby providing the possibility of use of insulin modifiers as an adjunct acne treatment and stratifying the possible risk of metabolic syndrome in patients with acne. Also recommended is the control of dietary factors and lifestyle modification for the management of acne with insulin resistance.

Chitosan nanoplatform for the co-delivery of palbociclib and ultra-small magnesium nanoclusters: dual receptor targeting, therapy and imaging.

Theranostic nanoparticles have gained significant attention in cancer diagnosis and therapy. In this study, estrone (ES) and folic acid (FA) functionalized single and dual receptor targeted theranostic chitosan nanoparticles were developed for breast cancer imaging and therapy. These nanoparticles (NPs) were loaded with palbociclib (PB) and ultra-small magnesium nanoclusters (UMN). The developed nontargeted theranostic NPs (PB-UMN-CS-NPs), estrogen receptor targeted theranostic NPs (PB-UMN-CS-ES-NPs), folate receptor targeted theranostic NPs (PB-UMN-CS-FA-NPs), and dual targeted theranostic NPs (PB-UMN-CS-ES-FA-NPs) have particle sizes of 178.4 ± 1.21 nm, 181.6± 1.35 nm, 185.1± 1.33 nm, and 198.2± 1.43 nm with surface charges of +19.02± 0.382 mV, +13.89±0.410 mV, +16.72±0.527 mV and +15.23±0.377 mV, respectively. Cytotoxicity studies on estrogen receptor (ER) and folate receptor (FR) expressing breast cancer cells revealed that dual-targeted theranostic NPs (PB-UMN-CS-FA-ES-NPs) were more effective, inhibiting cell growth by 54.17 and 42.23 times in MCF-7 and T-47D cells compared to free PB, respectively. Additionally, developed NPs were capable of inhibiting the cell cycle progression of MCF-7 cells from the G1 phase to the S phase more efficiently compared to free PB. Ultrasound and photoacoustic (USG/PA) imaging demonstrated that dual targeted theranostic NPs were capable of effectively reducing hypoxic tumor volume and significantly suppressing tumor vascularity compared to free PB, nontargeted, FR targeted and ER targeted NPs. Moreover, in vivo optical imaging demonstrated tumor specific accumulation of the dual-targeted theranostic NPs. Furthermore, in vitro hemocompatibility and histopathological studies confirmed the biocompatibility of developed nanoformulations.

Molecular docking approaches and its significance in assessing the antioxidant properties in different compounds.

In the last few years, the significance of antioxidant compounds and their properties has attracted great interest from the scientific community. The role of an antioxidant in managing & regulating oxidative stress and also in the protection of the human body from severe adverse effects due to excess release of free radicles or reactive oxygen species (ROS) is remarkable. From aiding protection & combating severe illnesses such as cancer, neurodegeneration, aging, and diabetes to being a vital part of the treatment of SARs-CoV-19 is of great importance. Therefore, the study of anti-oxidants is of great importance in human sustenance. Additionally, molecular docking techniques and their various mathematical features help in understanding the molecular interactions of anti-oxidants based on their lowest binding energy. The evaluation of the binding score between two constituent molecules will provide insight as to the binding process and also suggest possible novel therapeutic targets for the treatment of diseases. In this chapter, we will discuss the significance of molecular docking techniques in the study of antioxidant compounds.

Deployment of in-silico analysis to reveal the antibacterial profiles of Allium sativum against Aeromonas hydrophila.

The key challenges in aquaculture are the emergence of antimicrobial resistance in fish cultivation due to the frequent use of antibiotics. Over the past three decades, this led to a major threat in the persistence of multidrug-resistant bacteria. Aeromonas hydrophila is a Gram-negative bacterium, a common causative agent of motile bacterial septicemia in fisheries. Combining these two key factors of the presented narrative, the essential type II topoisomerase enzyme 'DNA gyrase' (encoded by the gyrA and gyrB genes) as a potential drug target in Aeromonas hydrophila was taken, retrieve its sequence from UniProtKB (Id-A0KKQ2), constructs the 3-D structure using SWISS-MODEL (in absence of the experimental structure), and performs an in-silico screening of selected drug-like compounds (25 antibacterial phytochemicals) most of which are bioactive compounds of A. sativum through molecular docking. Quercetin a derivative of A. sativum was observed as a more potent drug molecule than other studied molecules based on ligand binding energy as docking score -7.812, showed highly encouraging results, supported by a study using structural dynamics of the receptor-ligand complex for a duration of 100 ns by Molecular Dynamic Simulations and confirm binding stability with MM-GBSA calculations. This study also provides theoretical grounds for drug discovery against other pathogenic bacteria posing threats to the ecosystem. Switching to herbal products is the best way to combat the plurality of problems to avoid seen or unseen post-treatment side effects.Communicated by Ramaswamy H. Sarma.

COVID Variants, Villain and Victory: A Bioinformatics Perspective.

The SARS-CoV-2 virus, a novel member of the Coronaviridae family, is responsible for the viral infection known as Coronavirus Disease 2019 (COVID-19). In response to the urgent and critical need for rapid detection, diagnosis, analysis, interpretation, and treatment of COVID-19, a wide variety of bioinformatics tools have been developed. Given the virulence of SARS-CoV-2, it is crucial to explore the pathophysiology of the virus. We intend to examine how bioinformatics, in conjunction with next-generation sequencing techniques, can be leveraged to improve current diagnostic tools and streamline vaccine development for emerging SARS-CoV-2 variants. We also emphasize how bioinformatics, in general, can contribute to critical areas of biomedicine, including clinical diagnostics, SARS-CoV-2 genomic surveillance and its evolution, identification of potential drug targets, and development of therapeutic strategies. Currently, state-of-the-art bioinformatics tools have helped overcome technical obstacles with respect to genomic surveillance and have assisted in rapid detection, diagnosis, and delivering precise treatment to individuals on time.