Design,synthesis and evaluation of antiproliferative activity of melanoma-targeted histone deacetylase inhibitors

The clinical validation of histone deacetylase inhibition as a cancer therapeutic modality has stimulated interest in the development of new generation of potent and tumor selective histone deacetylase inhibitors (HDACi). With the goal of selective delivery of the HDACi to melanoma cells, we incorporated the benzamide, a high affinity melanin-binding template, into the design of HDACi to generate a new series of compounds 10a-b and 11a-b which display high potency towards HDAC1 and HDAC6. However, these compounds have attenuated antiproliferative activities relative to the untargeted HDACi. An alternative strategy furnished compound 14, a prodrug bearing the benzamide template linked via a labile bond to a hydroxamate-based HDACi. This pro-drug compound showed promising antiproliferative activity and warrant further study.     

Mortality incidence estimation using federal death certificate and natality data with an application to Tay–Sachs disease

For confidentiality reasons, US federal death certificate data are incomplete with regards to the dates of birth and death for the decedents, making calculation of total lifetime of a decedent impossible and thus estimation of mortality incidence difficult. This paper proposes the use of natality data and an imputation‐based method to estimate age‐specific mortality incidence rates in the face of this missing information. By utilizing previously determined probabilities of birth, a birth date and death date are imputed for every decedent in the dataset. Thus, the birth cohort of each individual is imputed, and the total on‐study time can be calculated. This idea is implemented in two approaches for estimation of mortality incidence rates. The first is an extension of a person‐time approach, while the second is an extension of a life table approach. Monte Carlo simulations showed that both approaches perform well in comparison to the ideal complete data methods, but that the person‐time method is preferred. An application to Tay–Sachs disease is demonstrated. It is concluded that the imputation methods proposed provide valid estimates of the incidence of death from death certificate data without the need for additional assumptions under which usual mortality rates provide valid estimates.     

Use of Composite Protein Database including Search Result Sequences for Mass Spectrometric Analysis of Cell Secretome

Mass spectrometric (MS) data of human cell secretomes are usually run through the conventional human database for identification. However, the search may result in false identifications due to contamination of the secretome with fetal bovine serum (FBS) proteins. To overcome this challenge, here we provide a composite protein database including human as well as 199 FBS protein sequences for MS data search of human cell secretomes. Searching against the human-FBS database returned more reliable results with fewer false-positive and false-negative identifications compared to using either a human only database or a human-bovine database. Furthermore, the improved results validated our strategy without complex experiments like SILAC. We expect our strategy to improve the accuracy of human secreted protein identification and to also add value for general use.     

Electrostatic Solitary Pulses in a Dusty Electronegative Magnetoplasma

The nonlinear characteristics of dust-electron-acoustic (DEA) waves in a dusty electronegative magnetoplasma system consisting of nonextensive hot electrons, inertial cold electrons, positively charged static ions, and negatively charged immobile dust grains has been investigated. In this observation, the well-known reductive perturbation technique is employed to determine different types of nonlinear dynamical equations, namely, magnetized Korteweg–de Vries (KdV), magnetized modified KdV (mKdV), and magnetized Gardner equations. The stationary solitary wave and double layer solution of these three equations, which describe the characteristics of solitary waves and double layers of DEA waves, are obtained and numerically analyzed. It is noticed that various plasma parameters (viz., hot electron nonextensivity, positive ion-to-cold electron number density ratio, dust-to-cold electron number density ratio, etc.) significantly affect the basic properties of DEA solitary waves (DEASWs) and Gardner solitons (GSs). The prodigious results found from this theoretical investigation may be useful for researchers to investigate the nonlinear structures in various space and laboratory plasmas.     

Phenotypic and Molecular Assessment of Wheat Genotypes Tolerant to Leaf Blight,Rust and Blast Diseases

Globally among biotic stresses, diseases like blight, rust and blast constitute prime constraints for reducing wheat productivity especially in Bangladesh. For sustainable productivity, the development of disease-resistant lines and high yielding varieties is vital and necessary. This study was conducted using 122 advanced breeding lines of wheat including 21 varieties developed by Bangladesh Wheat and Maize Research Institute (BAMRI) with aims to identify genotypes having high yield potential and resistance to leaf blight, leaf rust and blast diseases. These genotypes were evaluated for resistance against leaf blight and leaf rust at Dinajpur and wheat blast at Jashore under field condition. Out of 122 genotypes tested, 20 lines were selected as resistant to leaf blight based on the area under the diseases progress curve (AUDPC) under both irrigated timely sown (ITS) and irrigated late sown (ILS) conditions. Forty-two genotypes were found completely free from leaf rust infection, 59 genotypes were identified as resistant, and 13 genotypes were identified as moderately resistant to leaf rust. Eighteen genotypes were immune against wheat blast, 42 genotypes were categorized as resistant, and 26 genotypes were identified as moderately resistant to wheat blast. Molecular data revealed that the 16 genotypes showed a positive 2NS segment among the 18 immune genotypes selected against wheat blast under field conditions. The genotypes BAW 1322, BAW 1295, and BAW 1203 can be used as earlier maturing genotypes and the genotypes BAW 1372, BAW 1373, BAW 1297 and BAW 1364 can be used for lodging tolerant due to short plant height. The genotypes WMRI Gom 1, BAW 1349 and BAW 1350 can be selected for bold grain and the genotypes WMRI Gom 1, BAW 1297, BAW 1377 can be used as high yielder for optimum seeding condition but genotypes BAW 1377 and BAW 1366 can be used for late sown condition. The selected resistant genotypes against specific diseases can be used in the further breeding program to develop wheat varieties having higher disease resistance and yield potential.     

Recommendations for school-going students post CoVid-19 in Bangladesh

The CoVid-19 pandemic caused by SARS-CoV-2 has taken more lives than any other pandemic so far, with non-pharmacological interventions such as lockdown, school closures, and travel bans, especially social distance, abounding around the world. With limited resources, these interventions pose the ultimate challenge to the education system in developing countries like Bangladesh, especially in providing uninterrupted education for all children in rural areas, where a significant number of students are enrolled in this area. However, the initiative to close schools for an extended period has affected children physically, emotionally, socially, and in various ways. Noteworthy, it demands to reopen to protect the future of children. Schools have reopened in many countries around the world. It is of interest to document recommendations for school-going students post CoVid-19 in Bangladesh using evidence-based data, information, and knowledge. We document such data in the context of Bangladesh to take such policy initiatives.     

An altered camelid-like single domain anti-idiotypic antibody fragment of HM-1 killer toxin: acts as an effective antifungal agent

Phage-display and competitive panning elution leads to the identification of minimum-sized antigen binders together with conventional antibodies from a mouse cDNA library constructed from HM-1 killer toxin neutralizing monoclonal antibody (nmAb-KT). Antigen-specific altered camelid-like single-domain heavy chain antibody (scFv K2) and a conventional antibody (scFv K1) have been isolated against the idiotypic antigen nmAb-KT. The objectives of the study were to examine (1) their properties as compared to conventional antibodies and also (2) their antifungal activity against different pathogenic and non-pathogenic fungal species. The alternative small antigen-binder, i.e., the single-domain heavy chain antibody, was originated from a conventional mouse scFv phage library through somatic hyper-mutation while selection against antigen. This single-domain antibody fragment was well expressed in bacteria and specifically bound with the idiotypic antigen nmAb-KT and had a high stability and solubility. Experimental data showed that the binding affinity for this single-domain antibody was 272-fold higher (K _d = 1.07 × 10⁻¹⁰ M) and antifungal activity was three- to fivefold more efficient (IC₅₀ = 0.46 × 10⁻⁶ to 1.17 × 10⁻⁶ M) than that for the conventional antibody (K _d = 2.91 × 10⁻⁸ M and IC₅₀ = 2.14 × 10⁻⁶ to 3.78 × 10⁻⁶ M). The derived single-domain antibody might be an ideal scaffold for anti-idiotypic antibody therapy and the development of smaller peptides or peptide mimetic drugs due to their less complex antigen-binding site. We expect that such single-domain synthetic antibodies will find their way into a number of biotechnological or medical applications.     

Electrostatic solitary structures in a magnetized nonextensive plasma with q-distributed electrons

A rigorous theoretical investigation has been made of obliquely propagating electrostatic solitary structures in a magnetized plasma, taking into account the effect of nonextensive electrons. By employing the reductive perturbation method, the basic characteristics of obliquely propagating ion-acoustic (IA) solitary waves (SWs) in a cold magnetized electron-ion plasma (consisting of inertial ions and noninertial q-distributed electrons) have been addressed. The Korteweg-de Vries equation is derived and its numerical solution is obtained. It has been shown that the effects of electron nonextensivity and external magnetic field significantly modify the natures of the small but finite-amplitude IA SWs. The present analysis may be useful to understand and demonstrate the dynamical properties of IA SWs in different astrophysical and cosmological scenarios (viz. stellar polytropes, hadronic matter, quark-gluon plasma, protoneutron stars, dark-matter halos, etc.).     

Dynamics of Japanese Encephalitis Virus Transmission among Pigs in Northwest Bangladesh and the Potential Impact of Pig Vaccination

Background

Japanese encephalitis (JE) virus infection can cause severe disease in humans, resulting in death or permanent neurologic deficits among survivors. Studies indicate that the incidence of JE is high in northwestern Bangladesh. Pigs are amplifying hosts for JE virus (JEV) and a potentially important source of virus in the environment. The objectives of this study were to describe the transmission dynamics of JEV among pigs in northwestern Bangladesh and estimate the potential impact of vaccination to reduce incidence among pigs.

Methodology/Principal Findings

We conducted a comprehensive census of pigs in three JE endemic districts and tested a sample of them for evidence of previous JEV infection. We built a compartmental model to describe JEV transmission dynamics in this region and to estimate the potential impact of pig vaccination. We identified 11,364 pigs in the study area. Previous JEV infection was identified in 30% of pigs with no spatial differences in the proportion of pigs that were seropositive across the study area. We estimated that JEV infects 20% of susceptible pigs each year and the basic reproductive number among pigs was 1.2. The model suggest that vaccinating 50% of pigs each year resulted in an estimated 82% reduction in annual incidence in pigs.

Conclusions/Significance

The widespread distribution of historic JEV infection in pigs suggests they may play an important role in virus transmission in this area. Future studies are required to understand the contribution of pig infections to JE risk in humans and the potential impact of pig vaccination on human disease.