Analyzing the effects of surface distribution of pores in cell electroporation for a cell membrane containing cholesterol

This paper presents a model and numerical analysis (simulations) of transmembrane potential induced in biological cell membrane under the influence of externally applied electric field (i.e., electroporation). This model differs from the established models of electroporation in two distinct ways. Firstly, it incorporates the presence of cholesterol (~20% mole-fraction) in biological membrane. Secondly, it considers the distribution of pores as a function of the variation of transmembrane potential from one region of the cell to another. Formulation is based on the role of membrane tension and electrical forces in the formation of pores in a cell membrane, which is considered as an infinitesimally thin insulator. The model has been used to explore the process of creation and evolution of pores and to determine the number and size of pores as a function of applied electric field (magnitude and duration). Results show that the presence of cholesterol enhances poration by changing the membrane tension. Analyses indicate that the number of pores and average pore radii differ significantly from one part of the cell to the other. While some regions of the cell membrane undergo rapid and dense poration, others remain unaffected. The method can be a useful tool for a more realistic prediction of pore formation in cells subjected to electroporation.Comment: 11 pages, 3 figures. v2: added new references, grammatical changes, corrected typo

Trend analysis and forecasting coconut production in Assam

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An open label study to determine the effects of an oral proteolytic enzyme system on whey protein concentrate metabolism in healthy males

<p>Abstract</p> <p>Background</p> <p>Current research suggests that protein intake of 1.5 – 2.8 g/kg/day (3.5 times the current recommended daily allowance) is effective and safe for individuals trying to increase or maintain lean muscle mass. To achieve these levels of daily protein consumption, supplementing the diet with processed whey protein concentrate (WPC) in liquid form has become a popular choice for many people. Some products have a suggested serving size as high as 50 g of protein. However, due to possible inhibition of endogenous digestive enzymes from over-processing and rapid small intestine transit time, the average amount of liquid WPC that is absorbed may be only 15 g. The combined effect of these factors may contribute to incomplete digestion, thereby limiting the absorption rate of protein before it reaches the ceacum and is eliminated as waste. The purpose of this study was to determine if Aminogen^®, a patented blend of digestive proteases from <it>Aspergillus niger </it>and <it>Aspergillus oryzae</it>, would significantly increase the in-vivo absorption rate of processed WPC over control values. It also investigated if any increase would be sufficient to significantly alter nitrogen (N2) balance and C-reactive protein (CRP) levels over control values as further evidence of increased WPC absorption rate.</p> <p>Methods</p> <p>Two groups of healthy male subjects were assigned a specified balanced diet before and after each of two legs of the study. Subjects served as their own controls. In the first leg each control group (CG) was dosed with 50 g of WPC following an overnight fast. Nine days later each test group (TG) was dosed following an overnight fast with 50 g of WPC containing either 2.5 g (A2.5) or 5 g (A5) of Aminogen^®. Blood samples were collected during each leg at 0 hr, 0.5 hr, 1 hr, 2 hr, 3 hr, 3.5 hr and 4 hr for amino acid (AA) and CRP analyses. The following 18 AAs were quantified: alanine, arginine, aspartic acid, cysteine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine and valine. Urine was collected for 24 hours from 0 hr for total N2 analysis. Results are expressed as means ± SEM. All significance and power testing on results was done at a level of alpha = 0.05. Area under the concentration time curve (AUC) was calculated using the trapezoidal rule. One-way analysis of variance (ANOVA-1) was done between CGs, between TGs and between time points. One-way repeated measures analysis of variance (ANOVA-1-RM) was done to compare CGs and TGs. Two-way analysis of variance (ANOVA-2) was performed on total serum amino acid (TSAA) levels, urine N2 levels and CRP levels between each CG and TG.</p> <p>Results</p> <p>After baseline subtraction the mean AUC was significantly (p ≤ 0.05) greater in each TG compared the corresponding CG. Comparison of the mean AUC between each TG and each CG was not significantly different. Total serum amino acid (TSAA) levels were significantly greater in each TG compared the corresponding CG. They were also significantly different between each TG but not between each CG. All individual serum amino acid (ISAA) levels in TG-A2.5 except glycine, histidine, methionine and serine were significantly higher than in CG-A2.5 at 4 hr. All ISAA levels in TG-A5 except methionine and serine were significantly higher than in CG-A5 at 4 hr. The N2 balance was significantly higher in each TG compared to the corresponding CG, but not significantly different between each CG and between each TG. Significant differences in CRP levels are reported between each TG compared to the corresponding CG, but not significantly different between each TG and between each CG.</p> <p>Conclusion</p> <p>A patented blend of digestive proteases (Aminogen^®) increased the absorption rate of processed WPC over controls, as measured by statistically significant increases in AUC, TSAA levels, ISAA levels and N2 balance. Significant decreases in CRP levels and fluxes in AA levels are also reported.</p

Transmission dynamics of novel influenza A/H1N1 2009 outbreak in a residential school in India

Transmission dynamics of an outbreak of novel influenza A/H1N1 (2009) in June-July 2009 in a residential school in Maharashtra, India has been studied. A mathematical model of the type susceptible-exposedinfectious- asymptomatic-recovered has been adopted for the purpose. Analyses of epidemiological data revealed that close clustering within population resulted in high transmissibility with basic reproduction number R0 = 2.61 and transmission rate (β) being 0.001566. Model has successfully described the dynamics of transmission in a residential school setting and helped in ascertaining the epidemiological parameters for asymptomatic cases and the effectiveness of the control measures. Our study presents a framework for studying similar outbreaks of influenza involving clustered populations

Oral Delivery of Bioencapsulated Proteins Across Blood–Brain and Blood–Retinal Barriers

Delivering neurotherapeutics to target brain-associated diseases is a major challenge. Therefore, we investigated oral delivery of green fluorescence protein (GFP) or myelin basic protein (MBP) fused with the transmucosal carrier cholera toxin B subunit (CTB), expressed in chloroplasts (bioencapsulated within plant cells) to the brain and retinae of triple transgenic Alzheimer\u27s disease (3×TgAD) mice, across the blood–brain barriers (BBB) and blood–retinal barriers (BRB). Human neuroblastoma cells internalized GFP when incubated with CTB-GFP but not with GFP alone. Oral delivery of CTB-MBP in healthy and 3×TgAD mice shows increased MBP levels in different regions of the brain, crossing intact BBB. Thioflavin S–stained amyloid plaque intensity was reduced up to 60% by CTB-MBP incubation with human AD and 3×TgAD mice brain sections ex vivo. Amyloid loads were reduced in vivo by 70% in hippocampus and cortex brain regions of 3×TgAD mice fed with bioencapsulated CTB-MBP, along with reduction in the ratio of insoluble amyloid β 42 (Aβ42) to soluble fractions. CTB-MBP oral delivery reduced Aβ42 accumulation in retinae and prevented loss of retinal ganglion cells in 3×TgAD mice. Lyophilization of leaves increased CTB-MBP concentration by 17-fold and stabilized it during long-term storage in capsules, facilitating low-cost oral delivery of therapeutic proteins across the BBB and BRB

Molecular and Antigenic Characterization of Reassortant H3N2 Viruses from Turkeys with a Unique Constellation of Pandemic H1N1 Internal Genes

Triple reassortant (TR) H3N2 influenza viruses cause varying degrees of loss in egg production in breeder turkeys. In this study we characterized TR H3N2 viruses isolated from three breeder turkey farms diagnosed with a drop in egg production. The eight gene segments of the virus isolated from the first case submission (FAV-003) were all of TR H3N2 lineage. However, viruses from the two subsequent case submissions (FAV-009 and FAV-010) were unique reassortants with PB2, PA, nucleoprotein (NP) and matrix (M) gene segments from 2009 pandemic H1N1 and the remaining gene segments from TR H3N2. Phylogenetic analysis of the HA and NA genes placed the 3 virus isolates in 2 separate clades within cluster IV of TR H3N2 viruses. Birds from the latter two affected farms had been vaccinated with a H3N4 oil emulsion vaccine prior to the outbreak. The HAl subunit of the H3N4 vaccine strain had only a predicted amino acid identity of 79% with the isolate from FAV-003 and 80% for the isolates from FAV-009 and FAV-0010. By comparison, the predicted amino acid sequence identity between a prototype TR H3N2 cluster IV virus A/Sw/ON/33853/2005 and the three turkey isolates from this study was 95% while the identity between FAV-003 and FAV-009/10 isolates was 91%. When the previously identified antigenic sites A, B, C, D and E of HA1 were examined, isolates from FAV-003 and FAV-009/10 had a total of 19 and 16 amino acid substitutions respectively when compared with the H3N4 vaccine strain. These changes corresponded with the failure of the sera collected from turkeys that received this vaccine to neutralize any of the above three isolates in vitro

Prevalence and changes in chronic diseases among South Korean farmers: 1998 to 2005

<p>Abstract</p> <p>Background</p> <p>Epidemiologic studies have suggested a unique pattern of disease among farmers in Western countries, but limited information is available about the magnitude of disease prevalence and their changes over time in Asian farmers. The aim of this study was to compare the prevalence and changes in chronic diseases among farmers with those of other occupational groups in South Korea.</p> <p>Methods</p> <p>Using data from three consecutive cross-sectional national surveys: the Korean National Health and Nutrition Examination Survey 1998 (n = 39,060), 2001 (n = 37,769), and 2005 (n = 34,145), we calculated age and gender-standardized prevalence of chronic diseases by the direct method and compared the prevalence changes from 1998 to 2005.</p> <p>Results</p> <p>Female farmers had significantly higher chronic disease prevalence than other occupational groups in all three surveys. Arthritis was the most prevalent chronic disease among farmers for both men and women. Compared with other populations, farmers demonstrated a higher prevalence of arthritis and intervertebral disc disorders. Farmers showed higher prevalence changes for intervertebral disc disorders than other occupational workers.</p> <p>Conclusion</p> <p>Our findings support that South Korean farmers have a distinct pattern of diseases prevalence from other populations. More detailed studies investigating the risk of musculoskeletal diseases and intensive intervention efforts to reduce the prevalence these diseases, particularly among female farmers, are required.</p

Understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of Group B Streptococcus

The pilus 2a backbone protein (BP-2a) is one of the most structurally and functionally characterized components of a potential vaccine formulation against Group B Streptococcus. It is characterized by six main immunologically distinct allelic variants, each inducing variant-specific protection. To investigate the molecular determinants driving the variant immunogenic specificity of BP-2a, in terms of single residue contributions, we generated six monoclonal antibodies against a specific protein variant based on their capability to recognize the polymerized pili structure on the bacterial surface. Three mAbs were also able to induce complement-dependent opsonophagocytosis killing of live GBS and target the same linear epitope present in the structurally defined and immunodominant domain D3 of the protein. Molecular docking between the modelled scFv antibody sequences and the BP-2a crystal structure revealed the potential role at the binding interface of some non-conserved antigen residues. Mutagenesis analysis confirmed the necessity of a perfect balance between charges, size and polarity at the binding interface to obtain specific binding of mAbs to the protein antigen for a neutralizing response

Mapping child growth failure across low- and middle-income countries

Childhood malnutrition is associated with high morbidity and mortality globally1. Undernourished children are more likely to experience cognitive, physical, and metabolic developmental impairments that can lead to later cardiovascular disease, reduced intellectual ability and school attainment, and reduced economic productivity in adulthood2. Child growth failure (CGF), expressed as stunting, wasting, and underweight in children under five years of age (0�59 months), is a specific subset of undernutrition characterized by insufficient height or weight against age-specific growth reference standards3�5. The prevalence of stunting, wasting, or underweight in children under five is the proportion of children with a height-for-age, weight-for-height, or weight-for-age z-score, respectively, that is more than two standard deviations below the World Health Organization�s median growth reference standards for a healthy population6. Subnational estimates of CGF report substantial heterogeneity within countries, but are available primarily at the first administrative level (for example, states or provinces)7; the uneven geographical distribution of CGF has motivated further calls for assessments that can match the local scale of many public health programmes8. Building from our previous work mapping CGF in Africa9, here we provide the first, to our knowledge, mapped high-spatial-resolution estimates of CGF indicators from 2000 to 2017 across 105 low- and middle-income countries (LMICs), where 99 of affected children live1, aggregated to policy-relevant first and second (for example, districts or counties) administrative-level units and national levels. Despite remarkable declines over the study period, many LMICs remain far from the ambitious World Health Organization Global Nutrition Targets to reduce stunting by 40 and wasting to less than 5 by 2025. Large disparities in prevalence and progress exist across and within countries; our maps identify high-prevalence areas even within nations otherwise succeeding in reducing overall CGF prevalence. By highlighting where the highest-need populations reside, these geospatial estimates can support policy-makers in planning interventions that are adapted locally and in efficiently directing resources towards reducing CGF and its health implications. © 2020, The Author(s)