Complete observation of all structural,conformational, and fibrillation transitions of monomeric globular proteins at submicellar sodium dodecyl sulfate concentrations

Although considerable information is available regarding protein–sodium dodecyl sulfate (SDS) interactions, it is still unclear as to how much SDS is needed to denature proteins. The role of protein charge and micellar surfactant concentration on amyloid fibrillation is also unclear. This study reports on equilibrium measurements of SDS interaction with six model proteins and analyzes the results to obtain a general understanding of conformational breakdown, reorganization and restructuring of secondary structure, and entry into the amyloid fibrillar state. Significantly, all of these responses are entirely resolved at much lower than the critical micellar concentration (CMC) of SDS. Electrostatic interaction of the dodecyl sulfate anion (DS⁻) with positive surface potential on the protein can completely unfold both secondary and tertiary structures, which is followed by protein chain restructuration to α-helices. All SDS-denatured proteins contain more α-helices than the corresponding native state. SDS interaction stochastically drives proteins to the aggregated fibrillar state.     

Estimation of Finite and Closed Population Size: An Inverse Sampling Approach with Unequal Recapture Probability

Based on capture-mark-recapture sampling methods the problem of estimating unknown population size was considered. The sampling started with the assumption that at the beginning of the experiment all the individuals were unmarked, and the unmarked individuals caught in each sample will be marked and returned to the original population before the next sample is drawn. It is also assumed that the population is closed by birth, death, emigration and immigration. Using a general inverse sampling approach, the unknown population size N is estimated by a maximum likelihood estimator (MLE), and a simple form for approximate MLE is obtained. The probability function for S (the minimum number of samples required to be drawn to have L (L ≥ 1) samples, each of which contains at least one marked individual) and the form for E[S] are also obtained. In addition, corrections and improvements of some previous works in this field are given.     

Altered infant feeding patterns in boys with acquired nonsyndromic cryptorchidism

BACKGROUND : Genetic and environmental factors likely influence susceptibility to nonsyndromic cryptorchidism, a common disease presenting at birth or in later childhood. We compared cases and controls to define differential risk factors for congenital versus acquired cryptorchidism. METHODS : We compared questionnaire and clinical data from cases of congenital cryptorchidism (n = 230), acquired cryptorchidism (n = 182) and hernia/hydrocele (n = 104) with a group of healthy male controls (n = 358). Potential predictor variables (p < 0.2 in univariable analysis) were included in stepwise multivariable logistic regression models. RESULTS : Temporary (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4–0.8) or exclusive (OR, 0.6; 95% CI, 0.4–0.9) breastfeeding was reduced and soy formula feeding increased (OR, 1.8; 95% CI, 1.2–2.9) in acquired but not congenital or hernia/hydrocele groups. The highest risk estimates were observed for primary soy formula feeding with limited or no breastfeeding (OR 2.5; 95% CI, 1.4–4.3; adjusted OR, 2.7; 95% CI, 1.4–5.4) in the acquired group. Primary feeding risk estimates were equivalent or strengthened when multivariable models were limited to age greater than 2 years, full‐term or not small for gestational age, or Caucasian subjects. Pregnancy complications and increased maternal exposure to cosmetic or household chemicals were not consistently associated with either form of cryptorchidism in these models. CONCLUSIONS : Our data support reduced breastfeeding and soy formula feeding as potential risk factors for acquired cryptorchidism. Although additional studies are needed, hormonally active components of breast milk and soy formula could influence the establishment of normal testis position in the first months of life, leading to apparent ascent of testes in childhood. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.     

Assigning and visualizing germline genes in antibody repertoires

Identifying the germline genes involved in immunoglobulin rearrangements is an essential first step in the analysis of antibody repertoires. Based on our prior work in analysing diverse recombinant viruses, we present IgSCUEAL (Immunoglobulin Subtype Classification Using Evolutionary ALgorithms), a phylogenetic approach to assign V and J regions of immunoglobulin sequences to their corresponding germline alleles, with D regions assigned using a simple pairwise alignment algorithm. We also develop an interactive web application for viewing the results, allowing the user to explore the frequency distribution of sequence assignments and CDR3 region length statistics, which is useful for summarizing repertoires, as well as a detailed viewer of rearrangements and region alignments for individual query sequences. We demonstrate the accuracy and utility of our method compared with sequence similarity-based approaches and other non-phylogenetic model-based approaches, using both simulated data and a set of evaluation datasets of human immunoglobulin heavy chain sequences. IgSCUEAL demonstrates the highest accuracy of V and J assignment amongst existing approaches, even when the reassorted sequence is highly mutated, and can successfully cluster sequences on the basis of shared V/J germline alleles.     

An analysis of heat effects in different subpopulations of Bangladesh

A substantial number of epidemiological studies have demonstrated an association between atmospheric conditions and human all-cause as well as cause-specific mortality. However, most research has been performed in industrialised countries, whereas little is known about the atmosphere–mortality relationship in developing countries. Especially with regard to modifications from non-atmospheric conditions and intra-population differences, there is a substantial research deficit. Within the scope of this study, we aimed to investigate the effects of heat in a multi-stratified manner, distinguishing by the cause of death, age, gender, location and socio-economic status. We examined 22,840 death counts using semi-parametric Poisson regression models, adjusting for a multitude of potential confounders. Although Bangladesh is dominated by an increase of mortality with decreasing (equivalent) temperatures over a wide range of values, the findings demonstrated the existence of partly strong heat effects at the upper end of the temperature distribution. Moreover, the study demonstrated that the strength of these heat effects varied considerably over the investigated subgroups. The adverse effects of heat were particularly pronounced for males and the elderly above 65 years. Moreover, we found increased adverse effects of heat for urban areas and for areas with a high socio-economic status. The increase in, and acceleration of, urbanisation in Bangladesh, as well as the rapid aging of the population and the increase in non-communicable diseases, suggest that the relevance of heat-related mortality might increase further. Considering rising global temperatures, the adverse effects of heat might be further aggravated.     

Phosphorylated Forms of Connexin43 Predominate in Rat Brain: Demonstration by Rapid Inactivation of Brain Metabolism

Abstract: The gap junction protein connexin43 (Cx43) has been reported to exist as several phosphorylated forms migrating at ˜43 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as well as an unphosphorylated 41-kDa form. In brain, Cx43 is expressed predominantly in astrocytes and is also expressed in several other cell types. Whereas the phosphorylated forms of Cx43 predominate in heart, several studies have indicated that high levels of the unphosphorylated form of Cx43 are present in brain. Various experiments in this report indicate that the 41-kDa molecular form in brain is a postmortem dephosphorylation product of phosphorylated Cx43. In rats killed by cranial high-energy microwave irradiation leading to rapid inactivation of brain metabolism, Cx43 in cerebral cortex was present almost exclusively as the 43-kDa phosphorylated form. Rapid dissection of brain followed by heat treatment or inclusion of phosphatase inhibitors during tissue homogenization also largely prevented the conversion of the 43-to the 41-kDa form. The 41-kDa species was generated after alkaline phosphatase digestion of the 43-kDa material obtained by immunoprecipitation from microwave-irradiated brain. Immunolabeling patterns and relative regional levels of Cx43 as seen by immunohistochemical and western blot detection were the same whether or not metabolism to the 41-kDa species was prevented. In developing rat brain, Cx43 levels in frontal cortex and brainstem increased with age, but the degree of dephosphorylation of the 43-to the 41-kDa form was greater at earlier ages in the brainstem. It appears that brain contains a phosphatase that may be involved in modulating the phosphorylation state of Cx43 and thus may regulate intercellular communication via astrocytic gap junctions.     

Association of Glutathione S-Transferase theta 1 and mu 1 Genes Polymorphisms with the Susceptibility of Myocardial Infarction in Bangladesh

Background:Myocardial infarction is one of the leading causes of morbidity and mortality worldwide. Oxidative stress plays a vital role in the pathogenesis of atherosclerosis leading to myocardial infarction and Glutathione S-transferases (GSTs) act as detoxifying enzymes to reduce oxidative stress. The aim of the present study was to investigate the associations of the GST (T1 & M1) gene polymorphism with the susceptibility of myocardial infarction in the Bangladeshi population.Methods:A case-control study on 100 cardiac patients with MI and 150 control subjects was conducted. The genotyping of GST (T1 & M1) gene was done using conventional Polymerase Chain Reaction.Results:The percentage of GSTM1 genotypes was significantly (p< 0.01) lower in patients compared to control subjects while the GSTT1 genotypes were not significantly different between the study subjects. The individual with GSTM1 null allele was at 2.5-fold increased risk {odds ratio (OR)= 2.5; 95 % confidence interval (95 % CI)= 1.4 to 4.3; p< 0.01} of experiencing MI while individual with either GSTM1 or GSTT1 genotypes was at lower risk. In the case of GST M1 and GST T1 combined genotype, patients having both null genotypes for GST M1 and GST T1 gene showed significantly (p< 0.01) higher risk of experiencing MI when compared to control subjects (OR= 3.5; 95% CI= 1.7–7.2; p< 0.001). Conclusion:Thus our recent study suggested that GSTM1 alone and GSTM1 and T1 in combination augments the risk of MI in Bangladeshi population. Key Words: Bangladesh, GST (T1 & M1), Myocardial infarction, PCR, Polymorphism