An Isoniazid Based Schiff Base Sensor for Selective Detection of Pd2+ Ions.

Here, we developed a novel isoniazid based fluorescent probe (E)-N'-(thiophen-2-ylmethylene)isonicotinohydrazide (TINH) through simple condensation reaction and employed for selective detection of Pd2+ ions with a low detection limit of 4.102 × 10-11 M. Among the many existing cations, TINH bound Pd2+ ions with an association affinity of 9.794 × 105 M-1. Adding Pd2+ ions to ligand solution increased the absorption intensity in UV-Visible and quenched the emission intensity in fluorescence spectroscopic experiments. More importantly, this TINH complexed to Pd2+ ions in 1:1 stoichiometric ratio. To evaluate the stability of complexed system, pH experiments has been performed. The binding insights among the ligand and Pd2+ ions has been confirmed by IR spectroscopic and MASS spectrometric methods. Additionally, TINH also applied to real water samples for the identification and measurement of Pd2+ ions. Hence, this system could be highly applicable for detection of Pd2+ ions in environmental and industrial samples with in low detection range.

TRTools: a toolkit for genome-wide analysis of tandem repeats.

SUMMARY: A rich set of tools have recently been developed for performing genome-wide genotyping of tandem repeats (TRs). However, standardized tools for downstream analysis of these results are lacking. To facilitate TR analysis applications, we present TRTools, a Python library and suite of command line tools for filtering, merging and quality control of TR genotype files. TRTools utilizes an internal harmonization module, making it compatible with outputs from a wide range of TR genotypers. AVAILABILITY AND IMPLEMENTATION: TRTools is freely available at https://github.com/gymreklab/TRTools. Detailed documentation is available at https://trtools.readthedocs.io. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

New Insights into the Genetic Basis of Monge's Disease and Adaptation to High-Altitude.

Human high-altitude (HA) adaptation or mal-adaptation is explored to understand the physiology, pathophysiology, and molecular mechanisms that underlie long-term exposure to hypoxia. Here, we report the results of an analysis of the largest whole-genome-sequencing of Chronic Mountain Sickness (CMS) and nonCMS individuals, identified candidate genes and functionally validated these candidates in a genetic model system (Drosophila). We used PreCIOSS algorithm that uses Haplotype Allele Frequency score to separate haplotypes carrying the favored allele from the noncarriers and accordingly, prioritize genes associated with the CMS or nonCMS phenotype. Haplotypes in eleven candidate regions, with SNPs mostly in nonexonic regions, were significantly different between CMS and nonCMS subjects. Closer examination of individual genes in these regions revealed the involvement of previously identified candidates (e.g., SENP1) and also unreported ones SGK3, COPS5, PRDM1, and IFT122 in CMS. Remarkably, in addition to genes like SENP1, SGK3, and COPS5 which are HIF-dependent, our study reveals for the first time HIF-independent gene PRDM1, indicating an involvement of wider, nonHIF pathways in HA adaptation. Finally, we observed that down-regulating orthologs of these genes in Drosophila significantly enhanced their hypoxia tolerance. Taken together, the PreCIOSS algorithm, applied on a large number of genomes, identifies the involvement of both new and previously reported genes in selection sweeps, highlighting the involvement of multiple hypoxia response systems. Since the overwhelming majority of SNPs are in nonexonic (and possibly regulatory) regions, we speculate that adaptation to HA necessitates greater genetic flexibility allowing for transcript variability in response to graded levels of hypoxia.

Pyrazoles as Anti-inflammatory and Analgesic Agents: In-vivo and In-silico Studies.

BACKGROUND: Pyrazole is a well-known nucleus in the pharmacy field with a wide range of other activities in addition to anti-inflammatory and analgesic, i.e., anticonvulsant, antiviral, and anticancer activities. There are well-known marketed drugs having pyrazole moiety as celecoxib, and lonazolac as COX-II inhibitors. AIMS: We aim to synthesize better anti-inflammatory than existing ones. Thiophene is also known for its analgesic and anti-inflammatory action. Thus, the fusion of both gives better anti-inflammatory agents. In the present studies, derivatives from two series of pyrazole were prepared by reacting substituted chalcone (3a-3f) derivatives prepared from 2-acetyl thiophene. They substituted aromatic aldehydes with phenyl hydrazine to form (5a-5f) and with 2, 4-dinitro phenyl hydrazine giving compounds (6a-6f) separately. METHODS: Purified and characterized pyrazoles have been analyzed for in-vivo analgesic and anti-inflammatory activities by using standard methods. Compounds 5e, 5f, and 6d were proved to be potent analgesics and series (5a-5f) was found to have anti-inflammatory action, which was further validated using docking and ADME studies. RESULTS: The ADME profile of synthesized compounds was found to be satisfactory. CONCLUSION: The synthesized compounds can serve as lead for further drug designing.

Recent progress and major gaps in the vaccine development for African swine fever.

The swine industry across the globe is recently facing a devastating situation imparted by a highly contagious and deadly viral disease, African swine fever. The disease is caused by a DNA virus, the African swine fever virus (ASFV) of the genus Asfivirus. ASFV affects both wild boars and domestic pigs resulting in an acute form of hemorrhagic fever. Since the first report in 1921, the disease remains endemic in some of the African countries. However, the recent occurrence of ASF outbreaks in Asia led to a fresh and formidable challenge to the global swine production industry. Culling of the infected animals along with the implementation of strict sanitary measures remains the only options to control this devastating disease. Efforts to develop an effective and safe vaccine against ASF began as early as in the mid-1960s. Different approaches have been employed for the development of effective ASF vaccines including inactivated vaccines, subunit vaccines, DNA vaccines, virus-vectored vaccines, and live attenuated vaccines (LAVs). Inactivated vaccines are a non-feasible strategy against ASF due to their inability to generate a complete cellular immune response. However genetically engineered vaccines, such as subunit vaccines, DNA vaccines, and virus vector vaccines, represent tailored approaches with minimal adverse effects and enhanced safety profiles. As per the available data, gene deleted LAVs appear to be the most potential vaccine candidates. Currently, a gene deleted LAV (ASFV-G-∆I177L), developed in Vietnam, stands as the sole commercially available vaccine against ASF. The major barrier to the goal of developing an effective vaccine is the critical gaps in the knowledge of ASFV biology and the immune response induced by ASFV infection. The precise contribution of various hosts, vectors, and environmental factors in the virus transmission must also be investigated in depth to unravel the disease epidemiology. In this review, we mainly focus on the recent progress in vaccine development against ASF and the major gaps associated with it.

Unravelling the synergistic interaction of Thrips tabaci and newly recorded, Thrips parvispinus with Alternaria porri (Ellis.) Cif., inciting onion purple blotch.

Onion purple blotch is the most indispensable foliar disease of crop and has become a major concern for farmers and research fraternity. An attempt to investigate the role of injury in parasitism by Alternaria porri indicated that disease incidence and severity enhance considerably with injury. Thrips injured plants inoculated with A. porri presented 100% incidence and 52-72% severity while mechanically injured plants inoculated with A. porri showed 60-70% incidence and 28-34% severity. The uninjured plants showed considerably less disease incidence (30-40%) and severity (10-16%). Injured inoculated plants presented reduced leaf length and leaf area while the leaf diameter remained unaffected. The lesion number, lesion length and size was substantially enhanced with concomitant infestation of pest and pathogen. Thrips tabaci injury led to more pronounced symptoms of purple blotch compared to Thrips parvispinus injury. There was substantial decrease in photosynthetic rate and chlorophyll content with stress imposed on plant whilst the relative stress injury was enhanced. The induction of injury and inoculation of A. porri had an impact on the concentration of total phenolics, total soluble sugars, total proteins and hydrogen peroxide in onion leaves. A. porri combined with injury caused a more pronounced decrease in total soluble sugars and total protein content while enhancement in total phenolics and hydrogen peroxide content compared to uninjured plants. The dynamic nature of morpho-physiological and biochemical changes owing to stress conditions imposed on onion plant adds an extra layer of complexity in understanding the onion plant physiology and their ability to work out in response to challenging environment conditions.

Inference of multicomponent stress-strength reliability following Topp-Leone distribution using progressively censored data.

In this paper, the inference of multicomponent stress-strength reliability has been derived using progressively censored samples from Topp-Leone distribution. Both stress and strength variables are assumed to follow Topp-Leone distributions with different shape parameters. The maximum likelihood estimate along with the asymptotic confidence interval are developed. Boot-p and Boot-t confidence intervals are also constructed. The Bayes estimates under generalized entropy loss function based on gamma priors using Lindley's, Tierney-Kadane's approximation and Markov chain Monte Carlo methods are derived. A simulation study is considered to check the performance of various estimation methods and different censoring schemes. A real data study shows the applicability of the proposed estimation methods.

Precision medicine advancements in glioblastoma: A systematic review.

Background: Glioblastoma multiforme, commonly known as GBM or glioblastoma is a grade IV astrocytoma. Brain tumors are difficult to treat and lead to poor prognosis and survival in patients. Gliomas are categorized into four different grades among which GBM is the worst grade primary brain tumor with a survival of less than a year. The genomic heterogeneity of the brain tumor results in different profiles for patients diagnosed with glioblastoma. Precision medicine focuses on this specific tumor type and suggests specialized treatment for better prognosis and overall survival (OS). Purpose: With the recent advancements in Genome-Wide Studies (GWS) and various characterizations of brain tumors based on genetic, transcriptomic, proteomic, epigenetic, and metabolomics, this review discusses the advancements and opportunities of precision medicine therapeutics, drugs, and diagnosis methods based on the different profiles of glioblastoma. Methods: This review has exhaustively surveyed several pieces of works from various literature databases. Conclusion: It is evident that most primary brain tumors including glioblastoma require specific and precision therapeutics for better prognosis and OS. In present and future, molecular understanding and discovering specific therapies are essential for treatment in the field of neurooncology.

Dermatophytosis caused by Nannizzia nana (Microsporum nanum): a comprehensive review on a novel pathogen.

Keratinophilic fungi are mostly soil-inhabiting organisms with occasional infections in humans and animals. Even though most dermatophytes are host-adapted, cross-species infections are common by zoophilic and geophilic dermatophytes. N. nana is considered an etiological agent of ringworm in pigs but has also been isolated from other animals, including humans. However, it also possesses many characteristics of geophilic dermatophytes including the ability to grow in soil. N. nana produces characteristic pear-shaped macroconidia and usually exhibits an ectothrix pattern of hair infection. It has been isolated from dermatitis lesions as well as from soil. N. nana infections in pigs are not of much concern as far as economy or health is concerned. But it has been associated with onychomycosis and gonathritis in humans, which are significant in human medicine. The shift in the predominance of dermatophytes in humans and the ability to evolve into a potential tinea pathogen necessitates more understanding of the physiology and genetics of N. nana. In this review, we have attempted a detailed analysis of the studies about N. nana, emphasizing growth and cultural characters, physiology, isolation, infection in humans and animals, molecular characterization and antifungal susceptibility.

SNPs, short tandem repeats, and structural variants are responsible for differential gene expression across C57BL/6 and C57BL/10 substrains.

Mouse substrains are an invaluable model for understanding disease. We compared C57BL/6J, which is the most commonly used inbred mouse strain, with eight C57BL/6 and five C57BL/10 closely related inbred substrains. Whole-genome sequencing and RNA-sequencing analysis yielded 352,631 SNPs, 109,096 indels, 150,344 short tandem repeats (STRs), 3,425 structural variants (SVs), and 2,826 differentially expressed genes (DE genes) among these 14 strains; 312,981 SNPs (89%) distinguished the B6 and B10 lineages. These SNPs were clustered into 28 short segments that are likely due to introgressed haplotypes rather than new mutations. Outside of these introgressed regions, we identified 53 SVs, protein-truncating SNPs, and frameshifting indels that were associated with DE genes. Our results can be used for both forward and reverse genetic approaches and illustrate how introgression and mutational processes give rise to differences among these widely used inbred substrains.

Greater concern about hypoglycemia in Type 2 diabetics is the need of the hour-findings from a prospective, single-center, observational study.

CONTEXT: Hypoglycemia is a well-recognized adverse effect in the treatment of type 1 diabetes mellitus. For patients of type 2 diabetes mellitus (T2DM) on stabilized treatment with the current oral antidiabetic drugs, occurrence of hypoglycemia is considerably less well studied. The current study was undertaken to understand the extent of this problem in elderly Indian patients. OBJECTIVES PRIMARY OBJECTIVE: Assessment of incidence of hypoglycemia in patients of T2DM on stable treatment. SECONDARY OBJECTIVES: 1. Estimation of incidence of episodes of severe hypoglycemia in patients. 2. Correlation of presence of hypoglycemia with treatment modality. SETTINGS AND DESIGN: This study was conducted as an open label, single-center observational study at a multispecialty tertiary care hospital. MATERIALS AND METHODS: The study participants consisted of 50 elderly confirmed patients of either gender suffering from T2DM undergoing treatment and follow-up in the hospital for at least 12 weeks. After a brief training session and enrolment, the patients were asked to report to study site every month for next 2 months. Parameters recorded were plasma glucose levels, HbA1c levels, treatment regimen, body mass index, possible hypoglycemic episode based on symptoms and self-monitoring of blood glucose, and quality of life based on questionnaire score. STATISTICAL ANALYSIS: Descriptive and other statistics were used to analyze the hypoglycemic episodes experienced by the patients for correlation with medicines and the effect of hypoglycemia on their quality of life. RESULTS: Total of nine hypoglycemic episodes were recorded. Severe hypoglycemia did not occur in any patient. Patient on insulin reported significantly more hypoglycemia. Quality of life is not much different in patients using insulin in T2DM.

The impact of short tandem repeat variation on gene expression.

Short tandem repeats (STRs) have been implicated in a variety of complex traits in humans. However, genome-wide studies of the effects of STRs on gene expression thus far have had limited power to detect associations and provide insights into putative mechanisms. Here, we leverage whole-genome sequencing and expression data for 17 tissues from the Genotype-Tissue Expression Project to identify more than 28,000 STRs for which repeat number is associated with expression of nearby genes (eSTRs). We use fine-mapping to quantify the probability that each eSTR is causal and characterize the top 1,400 fine-mapped eSTRs. We identify hundreds of eSTRs linked with published genome-wide association study signals and implicate specific eSTRs in complex traits, including height, schizophrenia, inflammatory bowel disease and intelligence. Overall, our results support the hypothesis that eSTRs contribute to a range of human phenotypes, and our data should serve as a valuable resource for future studies of complex traits.

A reference haplotype panel for genome-wide imputation of short tandem repeats.

Short tandem repeats (STRs) are involved in dozens of Mendelian disorders and have been implicated in complex traits. However, genotyping arrays used in genome-wide association studies focus on single nucleotide polymorphisms (SNPs) and do not readily allow identification of STR associations. We leverage next-generation sequencing (NGS) from 479 families to create a SNP + STR reference haplotype panel. Our panel enables imputing STR genotypes into SNP array data when NGS is not available for directly genotyping STRs. Imputed genotypes achieve mean concordance of 97% with observed genotypes in an external dataset compared to 71% expected under a naive model. Performance varies widely across STRs, with near perfect concordance at bi-allelic STRs vs. 70% at highly polymorphic repeats. Imputation increases power over individual SNPs to detect STR associations with gene expression. Imputing STRs into existing SNP datasets will enable the first large-scale STR association studies across a range of complex traits.