Computational Studies Show How the H463R Mutation Turns hKv1.5 into an Inactivation State.

The KCNA5 gene provides the code for the α-subunit of the potassium channel Kv1.5. The genetic variant H463R in the Kv1.5 channel has been reported to cause a functional loss in atrial fibrillation (AF) patients. Understanding the mutations at a molecular level is key to developing improved therapeutics concerning cardiac hKv1.5 and hKv1.4 channels. Molecular dynamics and umbrella sampling free energy simulations are an effective tool to understand the mutation's effect on ion conduction, which we have employed and found that the hKv1.5[H463R] mutation imposes an energy barrier on the ion conduction pathway compared to the wild-type channel's ion free energy and pore structure. These results imply that the arginine mutation associated with the AF disease in particular modulates the inactivation process of hKv1.5. Kv1.4, encoded by the KCNA4 gene, is also present in the heart. Therefore, we considered simulation studies of the equivalent H507R mutation in the hKv1.4 channel and found that the mutation slightly reduces the ion conduction barrier in the ion conduction pathway, making it insignificant.

Vitamin-A enriched yogurt through fortification of pumpkin (Cucurbita maxima): A potential alternative for preventing blindness in children.

Vitamin-A deficiency associated with night blindness in children is a global health problem that could be prevented or reduced by promoting the intake of ß-carotene in food. The fortification of ß-carotene in yogurt using pumpkin flesh (PF) could be a very cost-effective public health intervention. The current study aimed to analyze the proximate, functional, microbial, textural, and sensory properties of yogurt fortified with PF to evaluate its suitability as a ß-carotene enriched food. The research was conducted with three treatments, control set-type yogurt (CSY) with no PF, 15% PF-fortified set-type yogurt (15PFSY), and 20% PF-fortified set-type yogurts (20PFSY) followed by pumpkin pie spice and ground pumpkin seed to improve consumer acceptability. The fortified yogurt with 20PFSY and 15PFSY contained a higher amount of ß-carotene, protein, fiber, and ash, and lower carbohydrate, fat, and energy in compression with CSY, which might attract health-conscious people. In addition, viable bacterial count, firmness, consistency, cohesiveness, and viscosity index were found better in fortified yogurt. Based on reports of sensory panellists, 15PFSY achieved a significantly (p < 0.01) highest overall acceptability than 20PFSY and CSY. These findings suggest that pumpkin-fortified yogurt could be used widely as a nutrient-enriched fermented food. In addition, as a ß-carotene (vitamin-A) fortified yogurt, it could be a potential alternative to prevent or reduce blindness in children with minimal cost.

Zinc Biofortification through Basal Zinc Supply Reduces Grain Cadmium in Mung Beans: Metal Partitioning and Health Risks Assessment.

Grain zinc (Zn) biofortification with less cadmium (Cd) accumulation is of paramount importance from human health and environmental point of view. A pot experiment was carried out to determine the influence of Zn and Cd on their accumulations in Mung bean tissues (Vigna radiata) in two contrast soil types (Dermosol and Tenosol). The soil types with added Zn and Cd exerted a significant effect on translocation and accumulation of metals in different tissues. The accumulation of Zn and Cd was higher for Tenosol than that for Dermosol. At control, the concentration of Cd followed a pattern, e.g., root > stem > petiole > pod > leaflet > grain for both soils. A basal Zn supply (5 mg kg−1) increased the grain Zn concentration to a significant amount (up to 67%). It also reduced Cd accumulation in tissues, including grains (up to 34%). No non-carcinogenic effect was observed for either the children or the adults as the EDI and PTDI values were below the safety limit; however, the ILCR values exceeded the safety limit, indicating the possibility of some carcinogenic effects. Added Zn helped to reduce the carcinogenic and non-carcinogenic health risks on humans.

Full-length recombinant antibodies from Escherichia coli: production, characterization, effector function (Fc) engineering, and clinical evaluation.

Although several antibody fragments and antibody fragment-fusion proteins produced in Escherichia coli (E. coli) are approved as therapeutics for various human diseases, a full-length monoclonal or a bispecific antibody produced in E. coli has not yet been approved. The past decade witnessed substantial progress in expression of full-length antibodies in the E. coli cytoplasm and periplasm, as well as in cell-free expression systems. The equivalency of E. coli-produced aglycosylated antibodies and their mammalian cell-produced counterparts, with respect to biochemical and biophysical properties, including antigen binding, in vitro and in vivo serum stability, pharmacokinetics, and in vivo serum half-life, has been demonstrated. Extensive engineering of the Fc domain of aglycosylated antibodies enables recruitment of various effector functions, despite the lack of N-linked glycans. This review summarizes recent research, preclinical advancements, and clinical development of E. coli-produced aglycosylated therapeutic antibodies as monoclonal, bispecific, and antibody-drug conjugates for use in autoimmune, oncology, and immuno-oncology areas.Abbreviations: ADA Anti-drug antibody; ADCC Antibody-dependent cellular cytotoxicity; ADCP Antibody-dependent cellular phagocytosis; ADC Antibody-drug conjugate; aFc Aglycosylated Fc; AMD Age-related macular degeneration aTTP Acquired thrombotic thrombocytopenic purpura; BCMA B-cell maturation antigen; BLA Biologics license application; BsAb Bispecific antibody; C1q Complement protein C1q; CDC Complement-dependent cytotoxicity; CDCC Complement-dependent cellular cytotoxicity; CDCP Complement-dependent cellular phagocytosis; CEX Cation exchange chromatography; CFPS Cell-free protein expression; CHO Chinese Hamster Ovary; CH1-3 Constant heavy chain 1-3; CL Constant light chain; DLBCL Diffuse large B-cell lymphoma; DAR Drug antibody ratio; DC Dendritic cell; dsFv Disulfide-stabilized Fv; EU European Union; EGFR Epidermal growth factor receptor; E. coli Escherichia coli; EpCAM Epithelial cell adhesion molecule; Fab Fragment antigen binding; FACS Fluorescence activated cell sorting; Fc Fragment crystallizable; FcRn Neonatal Fc receptor; FcÉ£Rs Fc gamma receptors; FDA Food and Drug Administration; FL-IgG Full-length immunoglobulin; Fv Fragment variable; FolRαa Folate receptor alpha; gFc Glycosylated Fc; GM-CSF Granulocyte macrophage-colony stimulating factor; GPx7 Human peroxidase 7; HCL Hairy cell leukemia; HIV Human immunodeficiency virusl; HER2 Human epidermal growth factor receptor 2; HGF Hepatocyte growth factor; HIC Hydrophobic interaction chromatography; HLA Human leukocyte antigen; IBs Inclusion bodies; IgG1-4 Immunoglobulin 1-4; IP Intraperitoneal; ITC Isothermal titration calorimetry; ITP Immune thrombocytopenia; IV Intravenous; kDa Kilodalton; KiH Knob-into-Hole; mAb Monoclonal antibody; MAC Membrane-attack complex; mCRC Metastatic colorectal cancer; MM Multipl myeloma; MOA Mechanism of action; MS Mass spectrometry; MUC1 Mucin 1; MG Myasthenia gravis; NB Nanobody; NK Natural killer; nsAA Nonstandard amino acid; NSCLC Non-small cell lung cancer; P. aeruginosa Pseudomonas aeruginosa; PD-1 Programmed cell death 1; PD-L1 Programmed cell death-ligand 1; PDI Protein disulfide isomerase; PECS Periplasmic expression cytometric screening; PK Pharmacokinetics; P. pastoris Pichia pastoris; PTM Post-translational modification; Rg Radius of gyration; RA Rheumatoid arthritis; RT-PCR Reverse transcription polymerase chain reaction; SAXS Small angle X-ray scattering; scF Single chain Fv; SCLC Small cell lung cancer; SDS-PAGE Sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SEC Size exclusion chromatography; SEED Strand-exchange engineered domain; sRNA Small regulatory RNA; SRP Signal recognition particle; T1/2 Half-life; Tagg Aggregation temperature; TCR T cell receptor; TDB T cell-dependent bispecific; TF Tissue factor; TIR Translation initiation region; Tm Melting temperature; TNBC Triple-negative breast cancer; TNF Tumor necrosis factor; TPO Thrombopoietin; VEGF Vascular endothelial growth factor; vH Variable heavy chain; vL Variable light chain; vWF von Willebrand factor; WT Wild type.

Neutrophil Myeloperoxidase-Mediated N-Demethylation of Quetiapine Leads to N-Desalkylquetiapine, a Pharmacologically Active Cytochrome P450 Metabolite.

The atypical antipsychotic drugs, quetiapine and clozapine, are associated with idiosyncratic drug reactions (such as agranulocytosis or neutropenia) that are thought to involve reactive metabolites. Neutrophil myeloperoxidase (MPO) metabolism of quetiapine is not well-studied, but is metabolized by cytochrome P450. Based on structural similarity to clozapine, we hypothesized that quetiapine can be metabolized by MPO and that there is overlap between cytochrome P450 and MPO metabolism of quetiapine. The interaction of quetiapine and clozapine with MPO and MPO chlorination activity was studied using UV-vis spectrophotometry. The metabolites were characterized using liquid chromatography-mass spectrometry (LC-MS), and electron paramagnetic resonance (EPR) spectroscopy was used for detecting drug-catalyzed glutathione oxidation. In the presence of quetiapine, MPO compound II accumulated for about 7.5 min, whereas in the presence of clozapine, MPO compound II was not observed as it was rapidly reduced back to the resting state. Increasing quetiapine concentrations resulted in a decrease in MPO chlorination activity, while the opposite result was found in the case of clozapine. UV-vis spectral studies showed no change when quetiapine was oxidized in the absence and presence of chloride anion (Cl-, to catalyze chlorination reactions). Significant changes, however, were observed in the same assay with clozapine, where Cl- appeared to hinder the rate of clozapine metabolism. The MPO-catalyzed hydroxylated and dealkylated metabolites of quetiapine and hydroxylated metabolites of clozapine were observed from the LC-MS analyses, particularly when Cl- was included in the reaction. In addition, hydroxylated, dealkylated, and a proposed sulfoxide metabolite of quetiapine were also observed in the reaction catalyzed by human microsomes/NADPH. Lastly, compared to quetiapine, clozapine metabolism by MPO/H2O2 and glutathione produced more glutathionyl radicals using EPR spin trapping. In conclusion, MPO/H2O2/Cl- was shown to metabolize quetiapine to S-oxidation and P450-like dealkylation products, and quetiapine metabolites were generally less reactive than clozapine.

Patients' Satisfaction on the Service Quality of Upazila Health Complex in Bangladesh.

This article attempts to measure the state of satisfaction of patients over the quality of health care as well as identify the crucial factors that affect the patients' satisfaction in Upazila Health Complex (UHC). The quantitative approach was used following a structured questionnaire survey method. Four hundred visitors of 2 UHCs in Meherpur district were randomly selected as respondents for the study. The Statistical Package for Social Science IBM version 24 and R software (version 4.0.2) were used to run descriptive statistics, χ2 test, confirmatory factor analysis, and principal component analysis for quantitative data analysis. The data reveal that the overall satisfaction score is (2.75 ± 0.943). A 3-dimension model of service quality is found to have a significant relationship with patients' satisfaction at the rural level. Care providers' attitude and responsiveness in service delivery are found to be the most vital factor, while the tangibles and accessibility factors moderately influence the patient's satisfaction on the service quality at UHCs.

Interactions of the antioxidant enzymes NAD(P)H: Quinone oxidoreductase 1 (NQO1) and NRH: Quinone oxidoreductase 2 (NQO2) with pharmacological agents, endogenous biochemicals and environmental contaminants.

NAD(P)H: Quinone Oxidoreductase 1 (NQO1) is an antioxidant enzyme that catalyzes the two-electron reduction of several different classes of quinone-like compounds (quinones, quinone imines, nitroaromatics, and azo dyes). One-electron reduction of quinone or quinone-like metabolites is considered to generate semiquinones to initiate redox cycling that is responsible for the generation of reactive oxygen species and oxidative stress and may contribute to the initiation of adverse drug reactions and adverse health effects. On the other hand, the two-electron reduction of quinoid compounds appears important for drug activation (bioreductive activation) via chemical rearrangement or autoxidation. Two-electron reduction decreases quinone levels and opportunities for the generation of reactive species that can deplete intracellular thiol pools. Also, studies have shown that induction or depletion (knockout) of NQO1 were associated with decreased or increased susceptibilities to oxidative stress, respectively. Moreover, another member of the quinone reductase family, NRH: Quinone Oxidoreductase 2 (NQO2), has a significant functional and structural similarity with NQO1. The activity of both antioxidant enzymes, NQO1 and NQO2, becomes critically important when other detoxification pathways are exhausted. Therefore, this article summarizes the interactions of NQO1 and NQO2 with different pharmacological agents, endogenous biochemicals, and environmental contaminants that would be useful in the development of therapeutic approaches to reduce the adverse drug reactions as well as protection against quinone-induced oxidative damage. Also, future directions and areas of further study for NQO1 and NQO2 are discussed.

Gender Differences in Service Quality of Upazila Health Complex in Bangladesh.

The gender-based differences in satisfaction on the service quality of the Upazila Health Complex (UHC) in Bangladesh are assessed in this paper using the SERVQUAL model. Two Upazila, field administrative unit of Bangladesh, of Meherpur district of Bangladesh, were selected to conduct the study. The study used a quantitative approach, primarily using the survey method. The research found that the perception of male and female on service quality of UHC varies significantly. Though they have a similar perception of reliability dimension, females still have a comparatively more positive perception of accessibility, tangibles, empathy, and responsiveness dimensions to UHC than male service receivers. The regression result showed that responsiveness is the key factor to bring satisfaction in service, while empathy and accessibility moderately influence service receivers' satisfaction. The findings will be useful for policymakers, public health stakeholders, earnest learners, practitioners, and academia.

Reviewing the world's edible mushroom species: A new evidence-based classification system.

Wild mushrooms are a vital source of income and nutrition for many poor communities and of value to recreational foragers. Literature relating to the edibility of mushroom species continues to expand, driven by an increasing demand for wild mushrooms, a wider interest in foraging, and the study of traditional foods. Although numerous case reports have been published on edible mushrooms, doubt and confusion persist regarding which species are safe and suitable to consume. Case reports often differ, and the evidence supporting the stated properties of mushrooms can be incomplete or ambiguous. The need for greater clarity on edible species is further underlined by increases in mushroom-related poisonings. We propose a system for categorizing mushroom species and assigning a final edibility status. Using this system, we reviewed 2,786 mushroom species from 99 countries, accessing 9,783 case reports, from over 1,100 sources. We identified 2,189 edible species, of which 2,006 can be consumed safely, and a further 183 species which required some form of pretreatment prior to safe consumption or were associated with allergic reactions by some. We identified 471 species of uncertain edibility because of missing or incomplete evidence of consumption, and 76 unconfirmed species because of unresolved, differing opinions on edibility and toxicity. This is the most comprehensive list of edible mushrooms available to date, demonstrating the huge number of mushrooms species consumed. Our review highlights the need for further information on uncertain and clash species, and the need to present evidence in a clear, unambiguous, and consistent manner.

Dynamics of COVID-19 transmission in Dhaka and Chittagong: Two business hubs of Bangladesh.

BACKGROUND: Having inadequate health care systems and poor socio-economic infrastructure, Bangladesh has been braving to contain the impact of current COVID-19 pandemic since March, 2020. To curb the diffusion of COVID-19, the local government has responded to the outbreak by enforcing a set of restricted measures on economic and social activities across the country. OBJECTIVES: Here, we aim to assess the propagation of COVID-19 by estimating the coronavirus active cases and mortality rate in two major business hubs of Bangladesh, namely Dhaka and Chittagong city under flexible lockdown conditions. METHODS: We apply a data-driven forecasting model using Susceptible, Exposed, Infected, Recovered and Deaths status through time to deal with coronavirus outbreak. RESULTS: The epidemiological model forecasts the dire consequences for Dhaka city with 2400 death cases at the end of December, 2020, whereas Chittagong city might experience 14% more deaths than Dhaka if the severe restrictions are not implemented to control the pandemic. CONCLUSION: Although lockdown has a positive impact in reducing the diffusion of COVID-19, it is disastrous for human welfare and national economies. Therefore, a unidirectional decision by the policymakers might cost a very high price on either way for a lower-middle-income country, Bangladesh. In this study, we suggest a fair trade-off between public health and the economy to avoid enormous death tolls and economic havoc in Bangladesh.

Molecular simulation of the Kv7.4[ΔS269] mutant channel reveals that ion conduction in the cavity is perturbed due to hydrophobic gating.

Mutations in the voltage-gated potassium channel Kv7.4 (encoded as KCNQ4) lead to the early onset of non-syndromic hearing loss, which is significant during language acquisition. The deletion of the S269 pore residue (genetic Δ mutation) in Kv7.4 has been reported to be associated with hearing loss. So far, there is no mechanistic understanding of how this mutation modulates channel function. To understand the role of S269 in ion conduction, we performed molecular dynamics simulations for both wild type and ΔS269 mutant channels. Simulations indicate that the ΔS269 mutation suppresses the fluctuations in the neighboring Y269 residue and thereby consolidates the ring formed by I307 and F310 residues in the adjacent S6 helixes in the cavity region. We show that the long side chains of I307 near the entrance to the cavity form a hydrophobic gate. Comparison of the free energy profiles of a cavity ion in Kv7.4 and Kv7.4[ΔS269] channels reveals a sizable energy barrier in the latter case, which suppresses ion conduction. Thus the simulation studies reveal that the hydrophobic gate resulting from the ΔS269 mutation appears to be responsible for sensorineural hearing loss.

Beneficial effects of probiotic and phytobiotic as growth promoter alternative to antibiotic for safe broiler production.

OBJECTIVES: Drug residues in poultry products could lead to the development of antibiotic-resistant bacteria as in any living animal and human alike. Extensive use of antibiotics in animals to promote growth rate, increase feed efficiency, and for prevention of intestinal infections has led to the development of resistant bacteria in the gastrointestinal tract. The present study was conducted to evaluate the effects of biological supplementation of probiotic, phytobiotic, and their combination over antibiotic on growth performance, microbial load, and hematological parameters in Broiler. MATERIALS AND METHODS: Sixty-five broiler chicken were divided into five groups (12 birds in each group), namely, group A (basal diet), group B (antibiotic, Renamycin 100®), group C (phytobiotic, Galibiotic®), group D (probiotic, Bio-Top®), and group E (combination, Galibiotic®+Galibiotic®) and five were sacrificed for baseline data on day 0. RESULTS: Average final live weight gain was highest in group D (probiotic) than other groups. The feed conversion ratio was highest in group A and lowest in the probiotic group (group C). Blood samples were collected on 14th and 28th day for hematological studies. The mean hematology values regarding the total erythrocyte count, hemoglobin concentration, packed cell volume, and erythrocyte sedimentation rate differed significantly (p < 0.05) among groups. The pH of all the treatment groups was significantly decreased compared to the control group (p < 0.05) where group C was significantly (p < 0.05) lower than all other groups. Highest total viable cell count was observed in control (group A) and total coliform count in phytobiotic (group C) was significantly lower than in other treatment groups (p < 0.05). CONCLUSION: It may conclude that biological supplements have a significant positive impact on growth performance, hematological parameters, and gut microbial load in broiler chicken of which the probiotic showing the best effects. Supplementation of probiotic in feed could be one of the best candidates as an alternative to antibiotics as growth promoter for safe broiler production.

Dose-dependent response to phytobiotic supplementation in feed on growth, hematology, intestinal pH, and gut bacterial load in broiler chicken.

OBJECTIVE: The present study was aimed to evaluate dose-dependent effects of phytobiotic (Galibiotic) supplements in feed on growth performance, hematological parameters, intestinal pH, and gut bacterial population in broiler chick. MATERIALS AND METHODS: A total of 50 ten day old broiler chicks were divided into five groups, namely, Group A as control (without galibiotic), Group B (galibiotic at 1 gm/kg feed), Group C (galibiotic at 2 gm/kg feed), Group D (galibiotic at 5 gm/kg feed), and Group E (galibiotic at 10 gm/kg feed). All the birds were reared for 42 days and samples were collected before and after sacrifice. RESULTS: Live body weights showed no significant differences between the groups but overall feed conversion ratios (FCRs) of treatment groups were significantly low in Group E having the lowest. Blood samples collected for hematology differed significantly (p < 0.01) among the different groups. Intestinal pH was lower in treatment groups with Group E having the lowest. Cecal total viable count was highest in Group A and lowest in Group E. The cecal coliform count was low in all the treatment groups. CONCLUSION: Along with previously published report, it may conclude that the phytobiotic could be used as an alternative to antibiotics due to positive growth performance, lower FCR, carcass quality, and improved gut health of broiler chicks.

Plant hormone effects on isoprene emission from tropical tree in Ficus septica.

Plant hormones and the circadian rhythm have been implicated in coordinated control of isoprene emission in plants. To gain insights into the signalling networks, foliar application of plant hormones was conducted in a native emitter, Ficus septica. Spraying of 50 µM jasmonic acid (JA) gradually decreased isoprene emission by 88% compared with initial levels within 5 days, and emission increased after relief from JA application. We further explored the molecular regulatory mechanism of isoprene emission by analysing photosynthetic rate, gene expression of 2-C-methyl-D-erythrytol 4-phosphate (MEP) pathway, hormone signalling and circadian rhythm processes, and metabolite pool sizes of MEP pathway. Results show that isoprene emission strongly correlated with isoprene synthase (IspS) gene expression and IspS protein levels over the period of JA treatment, indicating transcriptional and possible translational modulation of IspS by JA. Application of JA coordinately modulated genes in the auxin, cytokinin (CK), and circadian rhythm signal transduction pathways. Among the transcriptional factors analysed, MYC2 (JA) and LHY (circadian clock) negatively correlated with isoprene emission. Putative cis-elements predicted on IspS promoter (G-box for MYC2 and circadian for LHY) supports our proposal that isoprene emission is regulated by coordinated transcriptional modulation of IspS gene by phytohormone and circadian rhythm signalling.

Toward Cell Membrane Biomimetic Lipidic Cubic Phases: A High-Throughput Exploration of Lipid Compositional Space.

The bicontinuous lipidic cubic phase (LCP), which is based on the fundamental structure of the lipid bilayer, is increasingly used in a range of applications including drug delivery, in meso crystallization of membrane proteins, biosensors, and biofuel cells. The majority of LCPs investigated to date have been formulated from a single lipid or a combination of two lipids in water. Such systems lack tunability, with only a narrow range of lattice parameters adopted. In addition, the lipid bilayer of these materials lacks the complexity of natural cell membranes, which are composed of hundreds of different lipids and which may be essential to retaining the functionality of proteins embedded within them. In this work, we investigate the phase behavior of quaternary lipid-water systems consisting of three different lipids (monoolein-cholesterol-phospholipid) and water using a combination of experimental and simulation techniques. This study provides a large library of lipidic materials with bilayer compositions, which more effectively mimic the native cell membrane and significantly increased tunability based on nanostructural parameters such as lattice parameter, aqueous channel size, and bilayer thickness. Importantly, the library contained several extremely swollen cubic phases with a maximum lattice parameter of up to 342.5 Å. Many of these cubic phases were successfully dispersed into highly swollen cubosomes. The swollen cubic phases described in this article contain only uncharged lipids and are therefore particularly useful for applications with a high salt concentration, including encapsulation of larger therapeutic proteins and peptides for in vivo delivery, or for the crystallization of large membrane proteins such as GPCRs.(1).

Molecular regulatory mechanism of isoprene emission under short-term drought stress in the tropical tree Ficus septica.

Isoprene is emitted by many plants and is thought to function as an antioxidant under stressful conditions. However, the detailed regulatory mechanism of isoprene emission in relation to the antioxidant system remains unclear. Therefore, in this study, we explored the molecular regulatory mechanism of isoprene emission under short-term drought stress in the tropical tree Ficus septica Burm.f. We found that the soil moisture content gradually decreased from 55% on Day 1 (D1) to 23% (wilting point) on D5 after withholding water for 4 days and then returning to the initial level following re-watering on D6. On D5, drought-stressed plants had more than twofold higher isoprene emission and 90.6% lower photosynthesis rates, 99.5% lower stomatal conductance and 82.3% lower transpiration rates than well-watered control plants. It was also estimated that the isoprene concentration inside the leaf greatly increased on D5 due to the increased isoprene emission rate and reduced stomatal conductance. Among the traits related to the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway, which is responsible for isoprene biosynthesis, the isoprene synthase (IspS) protein level was positively correlated with the isoprene emission rate in stressed plants. The transcripts of the antioxidant genes peroxidase 2 (POD2), POD4, copper-zinc superoxide dismutase 2 (Cu-ZnSOD2) and manganese superoxide dismutase 1 (Mn-SOD1) also increased during the drying period, while those of ascorbate peroxidase 1 (APX1) decreased. However, there was only a weak correlation between isoprene emission and antioxidant enzyme gene expression, indicating that the regulation of isoprene biosynthesis is not directly linked to the antioxidant defense network in drought-stressed F. septica. These findings suggest that the post-transcriptional regulation of IspS led to the observed change in isoprene emission rate, which enhanced the quenching of reactive oxygen species (ROS) and, in combination with the increased antioxidant enzyme activity, conferred tolerance to drought stress in this species.

Arsenic and Other Elemental Concentrations in Mushrooms from Bangladesh: Health Risks.

Mushroom cultivation has been increasing rapidly in Bangladesh. Arsenic (As) toxicity is widespread in the world and Bangladesh faces the greatest havoc due to this calamity. Rice is the staple food in Bangladesh and among all the crops grown, it is considered to be the main cause of As poisoning to its population after drinking water. Consequently, rice straw, an important growing medium of mushrooms in Bangladesh, is known to have high As content. The objective of this study was, therefore, to determine the concentrations of As in mushrooms cultivated in Bangladesh and to assess the health risk as well. It also considered other elements, including Cd, Cr, Co, Cu, Pb, Mn, Hg, Ni, and Zn concentrations in mushrooms from Bangladesh. The mean concentrations (mg/kg) of As, Cd, Cr, Co, Cu, Pb, Mn, Hg, Ni, and Zn in mushrooms were 0.51, 0.38, 0.28, 0.01, 13.7, 0.31, 11.7, 0.12, 0.28, and 53.5, respectively. Based on the dietary intake of mushrooms, the weekly intakes of As, Cd, Cr, Co, Cu, Pb, Mn, Hg, Ni, and Zn from mushrooms for adults were 0.0042, 0.0030, 0.0024, 0.0001, 0.1125, 0.0019, 0.1116, 0.0011, 0.0023, and 0.4734 mg, respectively. Due to the low concentrations of As and other trace elements observed in mushrooms from Bangladesh, as well as relatively lower consumption of this food in people’s diet, it can be inferred that consumption of the species of mushrooms analysed will cause no toxicological risk.

Computational Study of the Loss-of-Function Mutations in the Kv1.5 Channel Associated with Atrial Fibrillation.

Atrial fibrillation (AF) is a heart disease caused by defective ion channels in the atria, which affect the action potential (AP) duration and disturb normal heart rhythm. Rapid firing of APs in neighboring atrial cells is a common mechanism of AF, and therefore, therapeutic approaches have focused on extending the AP duration by inhibiting the K+ channels involved in repolarization. Of these, Kv1.5 that carries the I Kur current is a promising target because it is expressed mainly in atria and not in ventricles. In genetic studies of AF patients, both loss-of-function and gain-of-function mutations in Kv1.5 have been identified, indicating that either decreased or increased I Kur currents could trigger AF. Blocking of already downregulated Kv1.5 channels could cause AF to become chronic. Thus, a molecular-level understanding of how the loss-of-function mutations in Kv1.5 affect I Kur would be useful for developing new therapeutics. Here, we perform molecular dynamics simulations to study the effect of three loss-of-function mutations in the pore domain of Kv1.5 on ion permeation. Comparison of the pore structures and ion free energies in the wild-type and mutant Kv1.5 channels indicates that conformational changes in the selectivity filter could hinder ion permeation in the mutant channels.

Molecular characterization of cytosolic cysteine synthase in Mimosa pudica.

In the cysteine and mimosine biosynthesis process, O-acetyl-L-serine (OAS) is the common substrate. In the presence of O-acetylserine (thiol) lyase (OASTL, cysteine synthase) the reaction of OAS with sulfide produces cysteine, while with 3-hydroxy-4-pyridone (3H4P) produces mimosine. The enzyme OASTL can either catalyze Cys synthesis or both Cys and mimosine. A cDNA for cytosolic OASTL was cloned from M. pudica for the first time containing 1,410 bp nucleotides. The purified protein product from overexpressed bacterial cells produced Cys only, but not mimosine, indicating it is Cys specific. Kinetic studies revealed that pH and temperature optima for Cys production were 6.5 and 50 °C, respectively. The measured Km, Kcat, and Kcat Km-1 values were 159 ± 21 µM, 33.56 s-1, and 211.07 mM-1s-1 for OAS and 252 ± 25 µM, 32.99 s-1, and 130.91 mM-1s-1 for Na2S according to the in vitro Cys assay. The Cy-OASTL of Mimosa pudica is specific to Cys production, although it contains sensory roles in sulfur assimilation and the reduction network in the intracellular environment of M. pudica.

Determination of heavy metals in the soils of tea plantations and in fresh and processed tea leaves: an evaluation of six digestion methods.

BACKGROUND: The aim of this study was to determine the levels of cadmium (Cd), chromium (Cr), lead (Pb), arsenic (As) and selenium (Se) in (1) fresh tea leaves, (2) processed (black) tea leaves and (3) soils from tea plantations originating from Bangladesh. METHODS: Graphite furnace atomic absorption spectrometry (GF-AAS) was used to evaluate six digestion methods, (1) nitric acid, (2) nitric acid overnight, (3) nitric acid-hydrogen peroxide, (4) nitric-perchloric acid, (5) sulfuric acid, and (6) dry ashing, to determine the most suitable digestion method for the determination of heavy metals in the samples. RESULTS: The concentration ranges of Cd, Pb, As and Se in fresh tea leaves were from 0.03-0.13, 0.19-2.06 and 0.47-1.31 µg/g, respectively while processed tea contained heavy metals at different concentrations: Cd (0.04-0.16 µg/g), Cr (0.45-10.73 µg/g), Pb (0.07-1.03 µg/g), As (0.89-1.90 µg/g) and Se (0.21-10.79 µg/g). Moreover, the soil samples of tea plantations also showed a wide range of concentrations: Cd (0.11-0.45 µg/g), Pb (2.80-66.54 µg/g), As (0.78-4.49 µg/g), and Se content (0.03-0.99 µg/g). Method no. 2 provided sufficient time to digest the tea matrix and was the most efficient method for recovering Cd, Cr, Pb, As and Se. Methods 1 and 3 were also acceptable and can be relatively inexpensive, easy and fast. The heavy metal transfer factors in the investigated soil/tea samples decreased as follows: Cd > As > Se > Pb. CONCLUSION: Overall, the present study gives current insights into the heavy metal levels both in soils and teas commonly consumed in Bangladesh.