Effects of intima stiffness and plaque morphology on peak cap stress

Background  

Rupture of the cap of a vulnerable plaque present in a coronary vessel may cause myocardial infarction and death. Cap rupture occurs when the peak cap stress exceeds the cap strength. The mechanical stress within a cap depends on the plaque morphology and the material characteristics of the plaque components. A parametric study was conducted to assess the effect of intima stiffness and plaque morphology on peak cap stress.     

Strategies for the production of cell wall‐deconstructing enzymes in lignocellulosic biomass and their utilization for biofuel production

Microbial cell wall‐deconstructing enzymes are widely used in the food, wine, pulp and paper, textile, and detergent industries and will be heavily utilized by cellulosic biorefineries in the production of fuels and chemicals. Due to their ability to use freely available solar energy, genetically engineered bioenergy crops provide an attractive alternative to microbial bioreactors for the production of cell wall‐deconstructing enzymes. This review article summarizes the efforts made within the last decade on the production of cell wall‐deconstructing enzymes in planta for use in the deconstruction of lignocellulosic biomass. A number of strategies have been employed to increase enzyme yields and limit negative impacts on plant growth and development including targeting heterologous enzymes into specific subcellular compartments using signal peptides, using tissue‐specific or inducible promoters to limit the expression of enzymes to certain portions of the plant or certain times, and fusion of amplification sequences upstream of the coding region to enhance expression. We also summarize methods that have been used to access and maintain activity of plant‐generated enzymes when used in conjunction with thermochemical pretreatments for the production of lignocellulosic biofuels.     

A Comparison of the Adaptive Immune Response between Recovered Anthrax Patients and Individuals Receiving Three Different Anthrax Vaccines

Several different human vaccines are available to protect against anthrax. We compared the human adaptive immune responses generated by three different anthrax vaccines or by previous exposure to cutaneous anthrax. Adaptive immunity was measured by ELISPOT to count cells that produce interferon (IFN)-γ in response to restimulation ex vivo with the anthrax toxin components PA, LF and EF and by measuring circulating IgG specific to these antigens. Neutralising activity of antisera against anthrax toxin was also assayed. We found that the different exposures to anthrax antigens promoted varying immune responses. Cutaneous anthrax promoted strong IFN-γ responses to all three antigens and antibody responses to PA and LF. The American AVA and Russian LAAV vaccines induced antibody responses to PA only. The British AVP vaccine produced IFN-γ responses to EF and antibody responses to all three antigens. Anti-PA (in AVA and LAAV vaccinees) or anti-LF (in AVP vaccinees) antibody titres correlated with toxin neutralisation activities. Our study is the first to compare all three vaccines in humans and show the diversity of responses against anthrax antigens.     

Liquid chromatographic and spectrofluorimetric assays of empagliflozin: Applied to degradation kinetic study and content uniformity testing

Stability‐indicating high‐performance liquid chromatography (HPLC) and spectrofluorimetric methods were developed for determination of empagliflozin (EGF). EGF was subjected to oxidation, wet heat, photo‐degradation, acid hydrolysis and alkali hydrolysis. The alkaline degradation pathway was subjected to a kinetics study as the major product obtained after stress conditions. Arrhenius plots were constructed and the activation energies of the degradation process were calculated. HPLC was used for the kinetic study as it enabled simultaneous determination of EGF and the degradation product while the spectrofluorimetric assay was applied to content uniformity testing due to its higher sensitivity and lower limit of detection (LOD). Isocratic chromatographic elution was attained for HPLC on a Intersil® C₁₈ column (150 mm × 4 mm, 5 μm), using a mobile phase of acetonitrile–potassium dihydrogen phosphate buffer pH 4, (50:50, v/v) at a flow rate of 1 ml/min with ultraviolet (UV) detection at 225 nm. The relative fluorescence intensity was recorded by spectrofluorimeter applying synchronous mode using ?λ = 70 nm at 297.6 nm. Linearity ranges were found to be 5–50 μg/ml and 50–1000 ng/ml for HPLC and spectrofluorimetric methods, respectively.     

Complex selection on a regulator of social cognition: Evidence of balancing selection,regulatory interactions and population differentiation in the prairie vole Avpr1a locus

Adaptive variation in social behaviour depends upon standing genetic variation, but we know little about how evolutionary forces shape genetic diversity relevant to brain and behaviour. In prairie voles (Microtus ochrogaster), variants at the Avpr1a locus predict expression of the vasopressin 1a receptor in the retrosplenial cortex (RSC), a brain region that mediates spatial and contextual memory; cortical V1aR abundance in turn predicts diversity in space use and sexual fidelity in the field. To examine the potential contributions of adaptive and neutral forces to variation at the Avpr1a locus, we explore sequence diversity at the Avpr1a locus and throughout the genome in two populations of wild prairie voles. First, we refine results demonstrating balancing selection at the locus by comparing the frequency spectrum of variants at the locus to a random sample of the genome. Next, we find that the four single nucleotide polymorphisms that predict high V1aR expression in the RSC are in stronger linkage disequilibrium than expected by chance despite high recombination among intervening variants, suggesting that epistatic selection maintains their association. Analysis of population structure and a haplotype network for two populations revealed that this excessive LD was unlikely to be due to admixture alone. Furthermore, the two populations differed considerably in the region shown to be a regulator of V1aR expression despite the extremely low levels of genomewide genetic differentiation. Together, our data suggest that complex selection on Avpr1a locus favours specific combinations of regulatory polymorphisms, maintains the resulting alleles at population‐specific frequencies, and may contribute to unique patterns of spatial cognition and sexual fidelity among populations.     

Higher‐order assemblies of oligomeric cargo receptor complexes form the membrane scaffold of the Cvt vesicle

Selective autophagy is the mechanism by which large cargos are specifically sequestered for degradation. The structural details of cargo and receptor assembly giving rise to autophagic vesicles remain to be elucidated. We utilize the yeast cytoplasm‐to‐vacuole targeting (Cvt) pathway, a prototype of selective autophagy, together with a multi‐scale analysis approach to study the molecular structure of Cvt vesicles. We report the oligomeric nature of the major Cvt cargo Ape1 with a combined 2.8 Å X‐ray and negative stain EM structure, as well as the secondary cargo Ams1 with a 6.3 Å cryo‐EM structure. We show that the major dodecameric cargo prApe1 exhibits a tendency to form higher‐order chain structures that are broken upon interaction with the receptor Atg19 in vitro. The stoichiometry of these cargo–receptor complexes is key to maintaining the size of the Cvt aggregate in vivo. Using correlative light and electron microscopy, we further visualize key stages of Cvt vesicle biogenesis. Our findings suggest that Atg19 interaction limits Ape1 aggregate size while serving as a vehicle for vacuolar delivery of tetrameric Ams1.     

The Relevance of a Novel Quantitative Assay to Detect up to 40 Major Streptococcus pneumoniae Serotypes Directly in Clinical Nasopharyngeal and Blood Specimens

For epidemiological and surveillance purposes, it is relevant to monitor the distribution and dynamics of Streptococcus pneumoniae serotypes. Conventional serotyping methods do not provide rapid or quantitative information on serotype loads. Quantitative serotyping may enable prediction of the invasiveness of a specific serotype compared to other serotypes carried. Here, we describe a novel, rapid multiplex real-time PCR assay for identification and quantification of the 40 most prevalent pneumococcal serotypes and the assay impacts in pneumonia specimens from emerging and developing countries. Eleven multiplex PCR to detect 40 serotypes or serogroups were optimized. Quantification was enabled by reference to standard dilutions of known bacterial load. Performance of the assay was evaluated to specifically type and quantify S. pneumoniae in nasopharyngeal and blood samples from adult and pediatric patients hospitalized with pneumonia (n = 664) from five different countries. Serogroup 6 was widely represented in nasopharyngeal specimens from all five cohorts. The most frequent serotypes in the French, South African, and Brazilian cohorts were 1 and 7A/F, 3 and 19F, and 14, respectively. When both samples were available, the serotype in blood was always present as carriage with other serotypes in the nasopharynx. Moreover, the ability of a serotype to invade the bloodstream may be linked to its nasopharyngeal load. The mean nasopharyngeal concentration of the serotypes that moved to the blood was 3 log-fold higher than the ones only found in the nasopharynx. This novel, rapid, quantitative assay may potentially predict some of the S. pneumoniae serotypes invasiveness and assessment of pneumococcal serotype distribution.     

Son preference in Bangladesh: an emerging barrier to fertility regulation

This study investigates the effect of son preference on contraceptive use and desire for additional children using national level survey data from Bangladesh for the years 1969 and 1979. National probability samples of ever married women between the ages of 10 and 50 were selected and stratified by urban-rural residence. Specifically, the study focuses on contraceptive use and desire for additional children and separates the effect of sex preference from that of high parity on fertility control. Son preference has a negative effect on contraceptive use and a positive effect on the desire for additional children regardless of socioeconomic and demographic characteristics. This advese effect of son preference on fertility regulation seemed to have persisted over the years. Relevent socioeconomic conditions in Bangladesh are described. In 1979, the effect of sex composition on contraceptive use or desire for additional children varied by parity. The negative effect of fewer living sons on contraceptive use and its positive effect on desire for additional children was higher in parities between 2 and 4 than in other parities. The effect of sex composition was stronger on desire for additional children than on contraceptive usage. In 1969, however, there was no consistent positive relationship between sex composition and contraceptive use. The relationship between sex composition and desire for more children was positive. Among women of parities 2 to 4, an excess of daughters continued to have a major positive effect on desire for additional children, and a negative effect on contraceptive use, after controlling for other sociodemographic variables. For parities 1 and 5 or above, the effect was either weak or inconsistent.