Pharmacophore-Assisted Covalent Docking Identifies a Potential Covalent Inhibitor for Drug-Resistant Genotype 3 Variants of Hepatitis C Viral NS3/4A Serine Protease.

The emergence of drug-resistance-inducing mutations in Hepatitis C virus (HCV) coupled with genotypic heterogeneity has made targeting NS3/4A serine protease difficult. In this work, we investigated the mutagenic variations in the binding pocket of Genotype 3 (G3) HCV NS3/4A and evaluated ligands for efficacious inhibition. We report mutations at 14 positions within the ligand-binding residues of HCV NS3/4A, including H57R and S139P within the catalytic triad.

Association of epilepsy and neurological impairments with homozygous recessive missense mutations found in the genes responsible for ganglioside biosynthesis () and calcium voltage-gated channels () - insights through molecular dynamic simulations.

With over 2.2 million cases, the incidence rate of epilepsy in Pakistan is far higher than the rest of the world due primarily to the frequent, traditionally imposed cousin marriages. In the present study, comprehensive whole exome sequencing (WES) analyses of a three-generation family with four affected members presenting 'unexplained' childhood absence epilepsy (CAE), seizures and dementia, was performed in a quest to identify heritable, epilepsy-causal gene variants to better aid in carrier screening and genetic counselling.

Fingerprinting hyperglycemia using predictive modelling approach based on low-cost routine CBC and CRP diagnostics.

Hyperglycemia is an outcome of dysregulated glucose homeostasis in the human body and may induce chronic elevation of blood glucose levels. Lifestyle factors such as overnutrition, physical inactivity, and psychosocials coupled with systemic low-grade inflammation have a strong negative impact on glucose homeostasis, in particular, insulin sensitivity. Together, these factors contribute to the pathophysiology of diabetes (DM) and expanding landscape of its prevalence regionally and globally.

NMR-Based Metabolomics: A New Paradigm to Unravel Defense-Related Metabolites in Insect-Resistant Cotton Variety through Different Multivariate Data Analysis Approaches.

Cotton () is an economically important crop and is widely cultivated around the globe. However, the major problem of cotton is its high vulnerability to biotic and abiotic stresses. It has been around three decades since the cotton plant was genetically engineered with genes encoding insecticidal proteins (mainly Cry proteins) with an aim to protect it against insect attack.

The Solvation of the CheY Phosphorylation Site Mapped by XFMS.

The CheY protein belongs to a large bacterial response regulator superfamily. X-ray hydroxy radical foot-printing with mass spectroscopy (XFMS) has shown that allosteric activation of CheY by its motor target triggers a concerted internalization of aromatic sidechains. We reanalyzed the XFMS data to compare polar versus non-polar CheY residue positions.

Navigating Multi-Scale Cancer Systems Biology Towards Model-Driven Clinical Oncology and Its Applications in Personalized Therapeutics.

Rapid advancements in high-throughput omics technologies and experimental protocols have led to the generation of vast amounts of scale-specific biomolecular data on cancer that now populates several online databases and resources. Cancer systems biology models built using this data have the potential to provide specific insights into complex multifactorial aberrations underpinning tumor initiation, development, and metastasis. Furthermore, the annotation of these single- and multi-scale models with patient data can additionally assist in designing personalized therapeutic interventions as well as aid in clinical decision-making.

Expression of cyanobacterial genes enhanced CO assimilation and biomass production in transgenic .

Background: Photosynthesis is a key process in plants that is compromised by the oxygenase activity of Rubisco, which leads to the production of toxic compound phosphoglycolate that is catabolized by photorespiratory pathway. Transformation of plants with photorespiratory bypasses have been shown to reduce photorespiration and enhance plant biomass. Interestingly, engineering of a single gene from such photorespiratory bypasses has also improved photosynthesis and plant productivity.

H-NMR-Based Metabolomics: An Integrated Approach for the Detection of the Adulteration in Chicken, Chevon, Beef and Donkey Meat.

Meat is a rich source of energy that provides high-value animal protein, fats, vitamins, minerals and trace amounts of carbohydrates. Globally, different types of meats are consumed to fulfill nutritional requirements. However, the increasing burden on the livestock industry has triggered the mixing of high-price meat species with low-quality/-price meat.

A Personalized Therapeutics Approach Using an Reveals Optimal Chemo- and Targeted Therapy Combinations for Colorectal Cancer.

models of biomolecular regulation in cancer, annotated with patient-specific gene expression data, can aid in the development of novel personalized cancer therapeutic strategies. is a well-established animal model that is increasingly being employed to evaluate such preclinical personalized cancer therapies. Here, we report five Boolean network models of biomolecular regulation in cells lining the midgut epithelium and annotate them with colorectal cancer patient-specific mutation data to develop an (DPM).

PERCEPTRON: an open-source GPU-accelerated proteoform identification pipeline for top-down proteomics.

PERCEPTRON is a next-generation freely available web-based proteoform identification and characterization platform for top-down proteomics (TDP). PERCEPTRON search pipeline brings together algorithms for (i) intact protein mass tuning, (ii) de novo sequence tags-based filtering, (iii) characterization of terminal as well as post-translational modifications, (iv) identification of truncated proteoforms, (v) in silico spectral comparison, and (vi) weight-based candidate protein scoring. High-throughput performance is achieved through the execution of optimized code via multiple threads in parallel, on graphics processing units (GPUs) using NVidia Compute Unified Device Architecture (CUDA) framework.

Trends in antimicrobial resistance amongst pathogens isolated from blood and cerebrospinal fluid cultures in Pakistan (2011-2015): A retrospective cross-sectional study.

While antimicrobial resistance (AMR) continues to be a major public health problem in Pakistan, data regarding trends of resistance among pathogenic bacteria remains scarce, with few studies presenting long-term trends in AMR. This study was therefore designed to analyze long-term AMR trends at a national level in Pakistan. We report here results of a comprehensive analysis of resistance, among pathogens isolated from blood and cerebrospinal fluid (CSF), between 2011 and 2015.

Host biomarkers for monitoring therapeutic response in extrapulmonary tuberculosis.

Purpose: The aim of this study was to explore the utility of inflammatory biomarkers in the peripheral blood to predict response to treatment in extrapulmonary tuberculosis (EPTB).

Methods: A Luminex xMAP-based multiplex immunoassay was used to measure 40 inflammatory biomarkers in un-stimulated plasma of 91 EPTB patients (48 lymphadenitis, and 43 pleuritis) before and at 2 and 6 months of treatment.

Results: Overall a significant change was observed in 28 inflammatory biomarkers with treatment in EPTB patients.

An evaluation of lipid profile and pro-inflammatory cytokines as determinants of cardiovascular disease in those with diabetes: a study on a Mexican American cohort.

Sedentary life styles coupled with high-calorie diets and unhealthy social habits such as smoking, have put an ever-increasing number of people at risk of cardiovascular disorders (CVD), worldwide. A concomitant increase in the prevalence of type 2-diabetes (hyperglycemia), a risk factor for CVD, has further contributed towards escalating CVD-related mortalities. The increase in number of cases of type 2-diabetes underscores the importance of early diagnosis of cardiovascular disease in those with diabetes.

CRISPR-Cas13a mediated targeting of hepatitis C virus internal-ribosomal entry site (IRES) as an effective antiviral strategy.

Hepatitis C is an inflammatory liver disease caused by the single-stranded RNA (ssRNA) hepatitis C virus (HCV). The genetic diversity of the virus and quasispecies produced during replication have resulted in viral resistance to direct-acting antivirals (DAAs) as well as impediments in vaccine development. The recent adaptation of CRISPR-Cas as an alternative antiviral approach has demonstrated degradation of viral nucleic acids in eukaryotes.

A cyanobacterial photorespiratory bypass model to enhance photosynthesis by rerouting photorespiratory pathway in C plants.

Plants employ photosynthesis to produce sugars for supporting their growth. During photosynthesis, an enzyme Ribulose 1,5 bisphosphate carboxylase/oxygenase (Rubisco) combines its substrate Ribulose 1,5 bisphosphate (RuBP) with CO to produce phosphoglycerate (PGA). Alongside, Rubisco also takes up O and produce 2-phosphoglycolate (2-PG), a toxic compound broken down into PGA through photorespiration.

Estimation of hepatitis C prevalence in the Punjab province of Pakistan: A retrospective study on general population.

Background: Hepatitis C virus (HCV) infections are amongst the leading public health concerns in Pakistan with a high disease burden. Despite the availability of effective antiviral treatments in the country the disease burden in general population has not lowered. This could be attributed to the asymptomatic nature of this infection that results in lack of diagnosis until the late symptomatic stage.

Evolution of efficacious pangenotypic hepatitis C virus therapies.

Hepatitis C compromises the quality of life of more than 350 million individuals worldwide. Over the last decade, therapeutic regimens for treating hepatitis C virus (HCV) infections have undergone rapid advancements. Initially, structure-based drug design was used to develop molecules that inhibit viral enzymes.

Reduced metabolites of nitroaromatics are distributed in the environment via the food chain.

Increased industrial processes have introduced emerging toxic pollutants into the environment. Phytoremediation is considered to be a very useful, economical and ecofriendly way of controlling these pollutants, however, certain pollutants can potentially travel through the food chain and accumulate at hazardous levels. Four isomers of dinitrotoluenes (DNT) were investigated and observed their potential toxicity towards A.

ATLANTIS - Attractor Landscape Analysis Toolbox for Cell Fate Discovery and Reprogramming.

Boolean modelling of biological networks is a well-established technique for abstracting dynamical biomolecular regulation in cells. Specifically, decoding linkages between salient regulatory network states and corresponding cell fate outcomes can help uncover pathological foundations of diseases such as cancer. Attractor landscape analysis is one such methodology which converts complex network behavior into a landscape of network states wherein each state is represented by propensity of its occurrence.

Expression of Cucumber mosaic virus suppressor 2b alters FWA methylation and its siRNA accumulation in Arabidopsis thaliana.

The Cucumber mosaic virus (CMV) suppressor 2b co-localizes with AGO4 in cytoplasmic and nuclear fractions of Arabidopsis thaliana Biochemical fractionation of A. thaliana cellular extracts revealed that 2b and AGO4 coexist in multiple size exclusions. 2b transgenic A.

Starvation-Induced Dietary Behaviour in Drosophila melanogaster Larvae and Adults.

Drosophila melanogaster larvae are classified as herbivores and known to feed on non-carnivorous diet under normal conditions. However, when nutritionally challenged these larvae exhibit cannibalistic behaviour by consuming a diet composed of larger conspecifics. Herein, we report that cannibalism in Drosophila larvae is confined not only to scavenging on conspecifics that are larger in size, but also on their eggs.

ELECANS--an integrated model development environment for multiscale cancer systems biology.

Motivation: Computational multiscale models help cancer biologists to study the spatiotemporal dynamics of complex biological systems and to reveal the underlying mechanism of emergent properties.

Results: To facilitate the construction of such models, we have developed a next generation modelling platform for cancer systems biology, termed 'ELECANS' (electronic cancer system). It is equipped with a graphical user interface-based development environment for multiscale modelling along with a software development kit such that hierarchically complex biological systems can be conveniently modelled and simulated by using the graphical user interface/software development kit combination.