Search

AbstractInsulin receptor substrate 1(IRS1) is a signaling adapter protein encoded by the IRS1gene. This protein delivers signals from insulin and insulin-like growth factor-1(IGF-1) receptors to the phosphatidylinositol 3-kinases (P13K)/protein kinase B (Akt) and Extracellular signal-regulated kinases (Erk) - Mitogen-activated protein (MAP) kinase pathways, which regulate particular cellular processes. Mutations in this gene have been linked to type 2 diabetes mellitus, a heightened risk of insulin resistance, and an increased likelihood of developing a number of different malignancies. The structure and function of IRS1 could be severely compromised as a result of single nucleotide polymorphism (SNP) type genetic variants. In this study, we focused on identification of the most harmful non-synonymous SNPs (nsSNPs) of the IRS1gene as well as prediction of their structural and functional consequences. Six different algorithms made the initial prediction that 59 of the 1142 IRS1 nsSNPs would have a negative impact on the protein structure. In-depth evaluations detected 26 nsSNPs located inside the functional domains of IRS1. Following that, 16 nsSNPs were identified as more harmful based on conservation profile, hydrophobic interaction, surface accessibility, homology modelling, and inter-atomic interactions. Following an in-depth analysis of protein stability, M249T (rs373826433), I223T (rs1939785175) and V204G (rs1574667052) were identified as three most deleterious SNPs and were subjected to molecular dynamics simulation for further insights. These findings will help us understand the implications for disease susceptibility, cancer progression, and the efficacy of therapeutic development against IRS1gene mutants.Communicated by Ramaswamy H. Sarma

AbstractVibrio cholerae, the etiological agent of cholera, causes dehydration and severe diarrhea with the production of cholera toxin. Due to the acquired antibiotic resistance, V. choleraehas drawn attention to the establishment of novel medications to counteract the virulence and viability of the pathogen. Centella asiaticais a medicinal herb native to Bangladesh that has a wide range of medicinal and ethnobotanical applications including anti-bacterial properties. In the present investigation, a total of 25 bioactive phytochemicals of C. asiaticahave been screened virtually through molecular docking, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analyses, and molecular dynamics simulation. Our results revealed four lead compounds as Viridiflorol (−8.7 Kcal/mol), Luteolin (−8.1 Kcal/mol), Quercetin (−8.0 Kcal/mol) and, Geranyl acetate (−7.1 Kcal/mol) against V. choleraeToxin co-regulated pilus virulence regulatory protein (ToxT). All the lead compounds have been found to possess favorable pharmacokinetic, pharmacodynamics, and molecular dynamics properties. Toxicity analysis revealed satisfactory results with no major side effects. Molecular dynamics simulation was performed for 100 ns that revealed noteworthy conformational stability and structural compactness for all the lead compounds, especially for Quercetin. Target class prediction unveiled enzymes in most of the cases and some experimental and investigational drugs were found as structurally similar analogs of the lead compounds. These findings could aid in the development of novel therapeutics targeting Cholera disease and we strongly recommend in vitrotrials of our experimental findings.Communicated by Ramaswamy H. Sarma

AbstractThe SARS-CoV-2 has severely impacted the lives of people worldwide. Global concern is on the rise due to a large number of unexpected mutations in the viral genome, resulting in new variants. Nature-based bioactive phytochemicals hold great promise as inhibitors against pathogenic viruses. The current study was aimed at evaluating some bioactive antiviral phytochemicals against SARS-CoV-2 variants of concern. A total of 46 phytochemicals were screened against the pathogenic spike protein of Alpha, Beta, Delta, Gamma, and Omicron variants. In addition to molecular docking, screening for favorable pharmacokinetic and pharmacodynamic properties such as absorption, distribution, metabolism, excretion, and toxicity was undertaken. For each of the aforementioned five SARS-CoV-2 variants of concern, a 100 ns molecular dynamics simulation was run to assess the stability of the complexes between their respective spike protein receptor-binding domain and the best-selected compound. From our current investigation, the natural compound liquiritigenin turned out to be the most promising potential lead compound against almost all the variants. These findings could pave the way for the development of effective medications against SARS-CoV-2 variants. However, in vivotrials in future studies are necessary for further validation of our results.Communicated by Ramaswamy H. Sarma

AbstractBreast cancer (BC) is the second most prevalent cancer worldwide. Estrogen receptor beta (ERβ) is an essential protein of breast cells to suppress estrogen-induced uncontrolled proliferation. Thus, small molecules that can modulate and enhance ERβ expression would be an effective agent to suppress BC development. Studies showed that cannabinoid (CB), specifically delta-9-tetrahydrocannabinol (Del9THC), can increase the expression of ERβ and inhibits BC cell proliferation. In this study, less psychoactive and structurally similar analogs of Del9THC were chosen as drug candidates and ERβ was targeted as a therapeutic receptor. Delta-8-tetrahydrocannabinol (Del8THC) and delta-4-isotetrahydrocannabinol (Del4isoTHC) were the drug candidates selected on the basis of literature reports, absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, medicinal chemistry profile, and physicochemical features. Molecular docking simulations were carried out to determine ligand receptor interactions and binding affinity based on free binding energy. To get a better drug, the structural modification was done on Del8THC and generated a new CB analog called Cannabinoid A. Finally, molecular interaction analysis revealed that two CBs and one of their analog interact with the active site residues of ERβ. Therefore, this study revealed a new way to discover novel drug(s) for BC patients.Communicated by Ramaswamy H. Sarma

Introduction: Many emerging and reemerging pathogens have been identified as major public health threats in Bangladesh. Collection, transportation, and storage of infectious materials and management of generated waste from diagnosing those diseases require strict adherence to biosafety and biosecurity practices. Such activities in Bangladesh need substantial development.Methods: A novel multipronged approach was followed to create awareness and provide resources to strengthen nationwide biosafety and biosecurity status. The approach included, but was not limited to, developing resource persons (RPs), developing laboratories’ baseline assessment tools, training assessors, conducting assessments, organizing awareness and training programs, identifying laboratories dealing with biohazards, developing a biosafety cabinet certification program, developing a Web site, and developing customized biosafety and biosecurity guidelines.Results: Currently, 133 RPs and 29 assessors are available in Bangladesh. The RPs organized 8 divisional awareness programs and trained about 3,000 professionals. Assessors conducted baseline assessments of 18 key laboratories, and RPs identified 127 laboratories in Bangladesh dealing with biohazards. NSF-accredited certifiers are now certifying biosafety cabinets in Bangladesh. Guidelines were developed and disseminated to the members. Those RPs who were organizing activities under the program are now organizing biosafety and biosecurity training sessions as academic activities.Conclusions: There is a shift from no biosafety and biosecurity practice toward a growing culture of biosafety and biosecurity practices in research and diagnostics in Bangladesh. To sustain the momentum of this development and to further strengthen the program, allocation of necessary resources and strong leadership support from the government of Bangladesh and donor groups are indispensable.

Introduction:Many emerging and reemerging pathogens have been identified as major public health threats in Bangladesh. Collection, transportation, and storage of infectious materials and management of generated waste from diagnosing those diseases require strict adherence to biosafety and biosecurity practices. Such activities in Bangladesh need substantial development.Methods:A novel multipronged approach was followed to create awareness and provide resources to strengthen nationwide biosafety and biosecurity status. The approach included, but was not limited to, developing resource persons (RPs), developing laboratories’ baseline assessment tools, training assessors, conducting assessments, organizing awareness and training programs, identifying laboratories dealing with biohazards, developing a biosafety cabinet certification program, developing a Web site, and developing customized biosafety and biosecurity guidelines.Results:Currently, 133 RPs and 29 assessors are available in Bangladesh. The RPs organized 8 divisional awareness programs and trained about 3,000 professionals. Assessors conducted baseline assessments of 18 key laboratories, and RPs identified 127 laboratories in Bangladesh dealing with biohazards. NSF-accredited certifiers are now certifying biosafety cabinets in Bangladesh. Guidelines were developed and disseminated to the members. Those RPs who were organizing activities under the program are now organizing biosafety and biosecurity training sessions as academic activities.Conclusions:There is a shift from no biosafety and biosecurity practice toward a growing culture of biosafety and biosecurity practices in research and diagnostics in Bangladesh. To sustain the momentum of this development and to further strengthen the program, allocation of necessary resources and strong leadership support from the government of Bangladesh and donor groups are indispensable.

Evolution of hepatitis B virus (HBV) is a mystery and caused mainly by genomic mutations as well as recombination. Viral evolution may be responsible for increasing disease severity and render resistance to the existing treatment processes. HBV/C2 strain is associated with chronicity, which may progress to the liver cirrhosis and hepatocellular carcinoma. Furthermore, HBV/C2 strain is highly prevalent in the chronic hepatitis B patients in Bangladesh. Hence, the molecular evolution of that strain and its disease pattern need to be uncovered. Herein, the purpose of this study is to determine the potential mutations of HBV complete genome sequences isolated in Bangladesh and the molecular evolution of HBV/C2 strain. Mutation analysis of the total 57 complete genome sequences of HBV in Bangladesh revealed that 42.11%, 12.28%, 7.02% and 3.51% of the strains were vaccine resistant, HBsAg detection escape, HBV immunoglobulin escape, multi-drug resistant respectively. Furthermore, of the vaccine resistant strains, 16.67% were observed resistant to both vaccine, HBsAg detection and immunoglobulin escape. Bayesian skyline analysis with 462 HBV/C2 strains from 2000 to 2017 revealed the evolution of the strain was in nineteenth century with two rapid sharp increases in the genetic diversity at the end of the twentieth century and then a sudden decrease in the early twenty-first century as observed in C and X gene analysis. This study may help researchers and clinicians to get a better knowledge about the emergence and evolution of HBV/C2 strain that may help to find a proper treatment strategy against hepatitis B.

Overproduction of reactive oxygen species intervenes zinc metabolism and promotes the onset of diabetes and related complications. Metallothionein (MT) are proteins conferring protection to cells against the toxic effects of reactive oxygen species. Polymorphism in the MT1Agene particularly rs8052394 (+1245 A/G) was shown to be associated with Type 2 Diabetes Mellitus (T2DM) in several populations around the globe. Given the high frequency of T2DM in Bangladesh, the current case-control study (n = 300) explored the association of this polymorphism with the onset of T2DM in the Bangladeshi population. The genotyping of the samples was done by polymerase chain reaction (PCR) and followed by restriction fragment length polymorphism (RFLP). Before that, the deleterious effect of this non-synonymous single nucleotide polymorphism (SNP) was predicted through the bioinformatics approach. Upon analysis, homozygous polymorphic genotype was found absent in the studied population and overall allele frequency of A and G was observed as 86% and 14% respectively. Although the higher frequency of the heterozygous (AG) polymorphic genotype was observed in the cases compared to the control, the difference was not statistically significant (p = 0.059), which indicates this polymorphism is not associated with T2DM in the Bangladeshi population.However, significant (p = 0.024) typical T2DM age distribution of the heterozygous polymorphic genotype was observed in the studied population. Before making a conclusion regarding the association between this SNP and T2DM in the Bangladeshi population, a large-scale study of rs8052394 is necessary.

Tenualosa ilishais an important fish in the Indian Ocean regions and the most profitable fishery in Bangladesh. A total of 160 T. ilisha(∼250 gm) were collected from Chandpur (riverine), Noakhali (estuarine), Patuakhali and Cox's Bazar (marine). Besides, forty Hilsha kelee(outgroup) samples were collected from Bagerhat (estuarine) region of Bangladesh. Cytochrome bregion of mtDNA of all samples were amplified by PCR. Forty-two PCR products of T. ilishaand six H. keleewere sequenced to investigate their genetic structures. A total of 305 polymorphic sites with 23 haplotypes were found in T. ilisha. A network of these haplotypes was constructed along with molecular differentiation of T. ilishaand H. keleeby phylogenetic analysis. High genetic variability (0.902) and low nucleotide diversity (0.193) were found among four populations. Analysis of molecular variance showed significantly different population structure (Fst 0.025, p < 0.001). Our study revealed a high genetic variability and distinct population structure in the T. ilishapopulations. Moreover, the non-significant negative value of Tajima's D for Chandpur, Noakhali and Patuakhali populations and negative Fu (FS) value for Noakhali population suggested a recent population expansion of hilsa.

Dengue fever is the most widespread mosquito-borne viral disease caused by the four serotypes of Dengue virus that belong to the Genus Flavivirus(family Flaviviridae). The diversity of serotype makes the diseases fatal with the possibility to be infected four times and makes complications in the antiviral drug discovery process. In this study, we analyzed the genomic diversity along with phylogenetical relations of the complete genome of four dengue virus serotypes found in different regions in the world. Viral pathogen and its host (human, mosquito) protein–protein interactions (PPIs) have been performed to reveal the connection between the proteins of host and pathogen. The analysis revealed that DENV3 and DENV1 strains are closely related, whereas the other 2 strains (DENV2 and DENV4) are distinctly related. DENV-2 serotype has been supposed to be more virulent, because more epidemics of dengue hemorrhagic fever have been associated with it than with the other serotypes. PPIs between dengue virus proteins obtained from Bangladesh regions and its host revealed that dengue–human PPIs are more prevail in DENV2 and DENV3 serotypes, whereas dengue–mosquito PPIs are most predominant in DENV1 serotype. Moreover, precursor miRNAs and their respective mature miRNAs are also predicted that may provide more clear insight into dengue virus pathogenesis. The present analysis provides detailed pictures of the origin, evolution, and genetic mutations of the dengue virus serotypes. This study can facilitate one stepping stone in the development and production of preventive, affordable, and safe antiviral medications.

A novel high-throughput system, called the stacked slice-gel system for separation and reactions (4SR), was developed for the analysis of DNA/RNA and protein/peptide. The system provides a novel three-dimensional gel electrophoresis approach that exploits the property of stacked slice gels. It allows multiple samples simultaneously to react as well as to be separated, offering a two-dimensional (m × n) sample loading system. For this purpose, high-throughput multi-micro vessels (MMVs) containing variable numbers of wells (100 wells in this paper) have been used, which are made of 25 mm square-size polyacrylamide gels. Furthermore, after electrophoretic separation, a slice gel containing a desired sample can be easily removed and proceeded to the next step. Different biological reactions as well as successive separation of products were effectively carried out dealing with DNA/RNA and protein/peptide. It shows that this system has a diversity of potentials to be developed.

A novel high-throughput system, called the stacked slice-gel system for separation and reactions (4SR), was developed for the analysis of DNA/RNA and protein/peptide. The system provides a novel three-dimensional gel electrophoresis approach that exploits the property of stacked slice gels. It allows multiple samples simultaneously to react as well as to be separated, offering a two-dimensional (m × n) sample loading system. For this purpose, high-throughput multi-micro vessels (MMVs) containing variable numbers of wells (100 wells in this paper) have been used, which are made of 25 mm square-size polyacrylamide gels. Furthermore, after electrophoretic separation, a slice gel containing a desired sample can be easily removed and proceeded to the next step. Different biological reactions as well as successive separation of products were effectively carried out dealing with DNA/RNA and protein/peptide. It shows that this system has a diversity of potentials to be developed.

Abstract: In this paper, we have examined the filamentation instability of laser radiation in a GaAs sample in the negative differential resistivity region. A dc electric field is applied to assist the laser beam transferring electrons in the conduction band from the lower valley to upper satellite valleys, i.e. in increasing the effective mass of electrons. The instability causes the space charge perturbations in the microwave range of frequencies. The nonlinearity arises through the energy dependence of the effective mass and the ponderomotive force on the electrons. The instability has finite frequency and possesses large growth rate which is greatly influenced by the dc electric field.

Abstract: Using the fluid model for the nonlinear response of ions, we have studied the nonlinear scattering of an electromagnetic ion cyclotron wave off the ion acoustic wave in a plasma. The low frequency nonlinearity arises through the parallel ponderomotive force on ions and the high frequency nonlinearity arises through the nonlinear current density of ions. For a typical nonisothermal plasma (T e/T i∼10) the threshold for this instability in a uniform plasma is ∼1mW/cm2. At power densities ≳102 W/cm2, the growth rate for backscatter turns out to be ∼104s−1.

In this work we have studied the filamentation instability of a higher-power electromagnetic ion cyclotron wave in a hot, collisionless and homogeneous magnetoplasma. Fluid equations have been employed to find the nonlinear response of electrons and ions. The low-frequency nonlinearity arises through the transverse ponderomotive force on electrons and ions and the high-frequency nonlinearity arises through the nonlinear current densities of electrons and ions. It is noticed that the ion nonlinearity dominates over the electron nonlinearity for pump waves of ion cyclotron range of frequencies. For typical plasma parameters and a considerable power density (∼10 kW cm−2) of the incident wave the growth rate of the filamentation instability is significantly high (∼106rad s−1).

This paper presents a theoretical investigation of the nonlinear excitation of electrostatic waves at the difference frequency of two electromagnetic ion cyclotron waves in a hot, collisionless and homogeneous magnetoactive plasma. The nonlinearity arises through the ponderomotive force on electrons and ions in the plasma. It is noticed that the power conversion efficiency of the excited waves depends drastically on the external static magnetic field.

We developed a method for selective purification of DNA using the cationic detergent, cetyltrimethylammonium bromide (CTAB), accompanied with urea and controlled high-salt (NaCl) concentration. This method is effective for rapid separation of DNA fragments from artifacts such as PCR primer dimers or ligation adapters. The CTAB-associated purification completely removed the short PCR artifacts and primers, as well as enzymes and buffer, while recovering a sufficient quantity of amplicons for subsequent experiments such as preparation of libraries. This method could also be applied to the fractionation of nucleic acids generated by other types of reactions.

A rapid small-scale peptide synthesis method was developed based on in vitro translation system. It enables us to obtain peptides within a day. Comparing the biological activity of in vitro synthesized peptides with that of chemically synthesized ones, the activity of both peptides was confirmed to be equivalent. The recovered peptides were assumed correct in their sequence through MS analysis and estimated to be more than pmoles/run. Moreover, this method could produce highly hydrophobic peptide, otherwise unavailable.