High-resolution melt curve analysis: An approach for variant detection in the TPO gene of congenital hypothyroid patients in Bangladesh.

TPO (Thyroid Peroxidase) is known to be one of the major genes involved in congenital hypothyroid patients with thyroid dyshormonogenesis. The present study aims to validate high-resolution melting (HRM) curve analysis as a substitute method for Sanger sequencing, focusing on the frequently observed non-synonymous mutations c.1117G>T, c.

Transcriptomes of cervical cancer provide novel insights into dysregulated pathways, potential therapeutic targets, and repurposed drugs.

Cervical cancer ranks as the fourth most prevalent gynaecological malignancy and is a significant contributor to mortality among women globally. With the exception of HPV-mediated oncogenesis, the molecular etiology of the disease is poorly understood, and there is a critical dearth of knowledge concerning cancer that is not caused by HPV. Moreover, none of the options presently accessible for the treatment of cancers specifically target cervical cancer.

Role of the redox state of the Pirin-bound cofactor on interaction with the master regulators of inflammation and other pathways.

Persistent cellular stress induced perpetuation and uncontrolled amplification of inflammatory response results in a shift from tissue repair toward collateral damage, significant alterations of tissue functions, and derangements of homeostasis which in turn can lead to a large number of acute and chronic pathological conditions, such as chronic heart failure, atherosclerosis, myocardial infarction, neurodegenerative diseases, diabetes, rheumatoid arthritis, and cancer. Keeping the vital role of balanced inflammation in maintaining tissue integrity in mind, the way to combating inflammatory diseases may be through identification and characterization of mediators of inflammation that can be targeted without hampering normal body function. Pirin (PIR) is a non-heme iron containing protein having two different conformations depending on the oxidation state of the iron.

The pectinolytic activity of Burkholderia cepacia and its application in the bioscouring of cotton knit fabric.

Background: Enzymatic catalysis in different industrial applications is often preferred over chemical methods due to various advantages, such as higher specificity, greater efficiency, and less environmental footprint. Pectinases are a group of enzymes that catalyze the degradation of pectic compounds, the key components of plant middle lamella and the primary cell wall. Pectinases have found applications in multiple industrial processes, including cotton bioscouring, fruit juice extraction and its clarification, plant fiber degumming, paper making, plant biomass liquefaction, and saccharification, among others.

Correction: Heterogeneous expression of CFTR in insulin-secreting β-cells of the normal human islet.

[This corrects the article DOI: 10.1371/journal.pone.

Disease-associated metabolic pathways affected by heavy metals and metalloid.

Increased exposure to environmental heavy metals and metalloids and their associated toxicities has become a major threat to human health. Hence, the association of these metals and metalloids with chronic, age-related metabolic disorders has gained much interest. The underlying molecular mechanisms that mediate these effects are often complex and incompletely understood.

A comprehensive in silico exploration of the impacts of missense variants on two different conformations of human pirin protein.

Background: Pirin, a member of the cupin superfamily, is an iron-binding non-heme protein. It acts as a coregulator of several transcription factors, especially the members of NFκB transcription factor family. Based on the redox state of its iron cofactor, it can assume two different conformations and thereby act as a redox sensor inside the nucleus.

TTN as a candidate gene for distal arthrogryposis type 10 pathogenesis.

Background: Arthrogryposis is a medical term used to describe congenital contractures which often affect multiple limbs. Distal arthrogryposis (DA) is one of the major categories of arthrogryposis that primarily affects the distal parts of the body, i.e.

A comprehensive in silico analysis of the deleterious nonsynonymous SNPs of human FOXP2 protein.

FOXP2 encodes the forkhead transcription factor that plays a significant role in language development. Single nucleotide polymorphisms in FOXP2 have been linked to speech- language disorder, autism, cancer and schizophrenia. So, scrutinizing the functional SNPs to better understand their association in disease is an uphill task.

Use of relevancy and complementary information for discriminatory gene selection from high-dimensional gene expression data.

With the advent of high-throughput technologies, life sciences are generating a huge amount of varied biomolecular data. Global gene expression profiles provide a snapshot of all the genes that are transcribed in a cell or in a tissue under a particular condition. The high-dimensionality of such gene expression data (i.

Effects of arsenic and heavy metals on metabolic pathways in cells of human origin: Similarities and differences.

Various anthropogenic and natural events over the years have gradually increased human exposure to various heavy metals. Several of these heavy metals including cadmium, mercury, nickel, chromium, and the metalloid arsenic among others, have created major public health concerns for their high level of toxicities. Identification of the general as well as the differentially affected cellular metabolic pathways will help understanding the molecular mechanism of different heavy metal-induced toxicities.

Disparities in COVID-19 severities and casualties across ethnic groups around the globe and patterns of ACE2 and PIR variants.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mediated Coronavirus disease-19 (COVID-19) has affected millions of individuals around all corners of the globe. Symptoms and severities of infection with this highly contagious virus vary among individuals and there is disparity in the number of COVID-19-related casualties across different ethnic groups. The primary receptor for SARS-CoV-2 entry into the host cells is angiotensin-converting enzyme 2 (ACE2).

Common genetic variants and pathways in diabetes and associated complications and vulnerability of populations with different ethnic origins.

Diabetes mellitus is a complex and heterogeneous metabolic disorder which is often pre- or post-existent with complications such as cardiovascular disease, hypertension, inflammation, chronic kidney disease, diabetic retino- and nephropathies. However, the frequencies of these co-morbidities vary among individuals and across populations. It is, therefore, not unlikely that certain genetic variants might commonly contribute to these conditions.

Aspartame, acesulfame K and sucralose- influence on the metabolism of .

Gut microbes play a crucial role in the maintenance of human health. Components in the diet of the host affect their metabolism and diversity. Here, we investigated the influences of three commonly used non-caloric artificial sweeteners-aspartame, acesulfame K and sucralose-on the growth and metabolism of an omnipresent gut microbe c K-12.

Heterogeneous expression of CFTR in insulin-secreting β-cells of the normal human islet.

Cystic fibrosis (CF) is due to mutations in the CF-transmembrane conductance regulator (CFTR) and CF-related diabetes (CFRD) is its most common co-morbidity, affecting ~50% of all CF patients, significantly influencing pulmonary function and longevity. Yet, the complex pathogenesis of CFRD remains unclear. Two non-mutually exclusive underlying mechanisms have been proposed in CFRD: i) damage of the endocrine cells secondary to the severe exocrine pancreatic pathology and ii) intrinsic β-cell impairment of the secretory response in combination with other factors.

Heterogeneity in the distribution of 159 drug-response related SNPs in world populations and their genetic relatedness.

Interethnic variability in drug response arises from genetic differences associated with drug metabolism, action and transport. These genetic variations can affect drug efficacy as well as cause adverse drug reactions (ADRs). We retrieved drug-response related single nucleotide polymorphism (SNP) associated data from databases and analyzed to elucidate population specific distribution of 159 drug-response related SNPs in twenty six populations belonging to five super-populations (African, Admixed Americans, East Asian, European and South Asian).

Non-Caloric Artificial Sweeteners Modulate the Expression of Key Metabolic Genes in the Omnipresent Gut Microbe Escherichia coli.

The human gut is inhabited by several hundred different bacterial species. These bacteria are closely associated with our health and well-being. The composition of these diverse commensals is influenced by our dietary intakes.

Mutation Spectrum in TPO Gene of Bangladeshi Patients with Thyroid Dyshormonogenesis and Analysis of the Effects of Different Mutations on the Structural Features and Functions of TPO Protein through Approach.

Although thyroid dyshormonogenesis (TDH) accounts for 10-20% of congenital hypothyroidism (CH), the molecular etiology of TDH is unknown in Bangladesh. Thyroid peroxidase (TPO) is most frequently associated with TDH and the present study investigated the spectrum of TPO mutations in Bangladeshi patients and analyzed the effects of mutations on TPO protein structure through approach. Sequencing-based analysis of TPO gene revealed four mutations in 36 diagnosed patients with TDH including three nonsynonymous mutations, namely, p.

Interaction of rs316019 variants of SLC22A2 with metformin and other drugs- an analysis.

Metformin is one of the first-line and most widely prescribed drugs to treat type 2 diabetes (T2D). Its clearance from circulation is mostly facilitated by SLC22A2 (OCT2) in the renal cells. SLC22A2 is a polyspecific organic cation transporter and mediate transport of structurally unrelated endogenous and exogenous compounds including many drugs.

Age-Specific Cut-off Values of Amino Acids and Acylcarnitines for Diagnosis of Inborn Errors of Metabolism Using Liquid Chromatography Tandem Mass Spectrometry.

Liquid Chromatography tandem mass spectrometry (LC-MS/MS) is used for the diagnosis of more than 30 inborn errors of metabolisms (IEMs). Accurate and reliable diagnosis of IEMs by quantifying amino acids (AAs) and acylcarnitines (ACs) using LC-MS/MS systems depend on the establishment of age-specific cut-offs of the analytes. This study aimed to (1) determine the age-specific cut-off values of AAs and ACs in Bangladesh and (2) validate the LC-MS/MS method for diagnosis of the patients with IEMs.

High resolution melting curve analysis targeting the HBB gene mutational hot-spot offers a reliable screening approach for all common as well as most of the rare beta-globin gene mutations in Bangladesh.

Background: Bangladesh lies in the global thalassemia belt, which has a defined mutational hot-spot in the beta-globin gene. The high carrier frequencies of beta-thalassemia trait and hemoglobin E-trait in Bangladesh necessitate a reliable DNA-based carrier screening approach that could supplement the use of hematological and electrophoretic indices to overcome the barriers of carrier screening. With this view in mind, the study aimed to establish a high resolution melting (HRM) curve-based rapid and reliable mutation screening method targeting the mutational hot-spot of South Asian and Southeast Asian countries that encompasses exon-1 (c.

The neuronal KCl co-transporter 2 (Slc12a5) modulates insulin secretion.

Intracellular chloride concentration ([Cl]) in pancreatic β-cells is kept above electrochemical equilibrium due to the predominant functional presence of Cl loaders such as the NaK2Cl co-transporter 1 (Slc12a2) over Clextruders of unidentified nature. Using molecular cloning, RT-PCR, Western blotting, immunolocalization and in vitro functional assays, we establish that the "neuron-specific" KCl co-transporter 2 (KCC2, Slc12a5) is expressed in several endocrine cells of the pancreatic islet, including glucagon secreting α-cells, but particularly in insulin-secreting β-cells, where we provide evidence for its role in the insulin secretory response. Three KCC2 splice variants were identified: the formerly described KCC2a and KCC2b along with a novel one lacking exon 25 (KCC2a-S25).