The cystic fibrosis transmembrane conductance regulator (CFTR): three-dimensional structure and localization of a channel gate

Cystic fibrosis affects about 1 in 2500 live births and involves loss of transmembrane chloride flux due to a lack of a membrane protein channel termed the cystic fibrosis transmembrane conductance regulator (CFTR). We have studied CFTR structure by electron crystallography. The data were compared with existing structures of other ATP-binding cassette transporters. The protein was crystallized in the outward facing state and resembled the well characterized Sav1866 transporter. We identified regions in the CFTR map, not accounted for by Sav1866, which were potential locations for the regulatory region as well as the channel gate. In this analysis, we were aided by the fact that the unit cell was composed of two molecules not related by crystallographic symmetry. We also identified regions in the fitted Sav1866 model that were missing from the map, hence regions that were either disordered in CFTR or differently organized compared with Sav1866. Apart from the N and C termini, this indicated that in CFTR, the cytoplasmic end of transmembrane helix 5/11 and its associated loop could be partly disordered (or alternatively located).     

Complete genome sequence of the dog commensal and human pathogen Capnocytophaga canimorsus strain 5

Capnocytophaga canimorsus is a commensal Gram-negative bacterium, originally isolated from a dog's mouth, that causes septicemia in humans. C. canimorsus has the unusual ability to feed on host cells, including phagocytes. This capacity depends on surface-exposed glycan-foraging systems. Here we present the first complete genome sequence of a C. canimorsus strain (Cc5).     

Reproductive constraints,not environmental conditions,shape the ontogeny of sex‐specific mass–size allometry in roe deer

In polygynous mammals, sex‐specific patterns of body growth are linked to divergent selection pressures on male and female body size, resulting in sexual dimorphism (SD). For males, reproductive success is generally linked to body size, hence, males should prioritise early growth. For females, reproductive success is linked to resource availability, so they may adopt a more conservative growth tactic. Using longitudinal monitoring of known‐age animals in two contrasting populations and an allometric approach to disentangle the relative contribution of structural size and physiological condition to SD, we addressed these issues in the weakly polygynous roe deer. Despite very different environmental conditions, we found remarkably similar patterns in the two populations in the mass–size allometric relationship at each life history stage, suggesting that relative allocation to structural size and physiological condition is highly constrained. SD in structural size (indexed by hind foot length) involved sex‐specific growth trajectories governed by a single mass–size allometric relationship during the juvenile stage, such that males were both bigger and heavier than females. In contrast, SD in physiological condition (indexed by the allometric relationship between body mass and hind foot length, expressed as body mass for a given body size) developed markedly during the sub‐adult stage in relation to sex differences in the timing of first reproduction. Among adults, males were heavier for a given size than females, suggesting that, relative to females, males express a capital breeder tactic, accumulating fat reserves to offset reproductive costs. By the senescent stage, SD in physiological condition had disappeared, with both sexes governed by a single allometric relationship, suggesting more rapid senescence in males than females. Individuals born into poor cohorts were generally lighter for a given size, indicating growth priority for skeletal size over physiological condition in both sexes. However, sex differences in cohort effects among sub‐adults resulted in lower size‐specific SD in poor cohorts, indicating that body condition of sub‐adult females is buffered against environmental harshness. We conclude that sex‐differences in reproductive tactics impose constraints on the ontogeny of SD in roe deer, leading to sex‐specific trajectories in structural size and physiological condition.     

Metagenomic analysis of the viral communities in fermented foods

Viruses are recognized as the most abundant biological components on Earth, and they regulate the structure of microbial communities in many environments. In soil and marine environments, microorganism-infecting phages are the most common type of virus. Although several types of bacteriophage have been isolated from fermented foods, little is known about the overall viral assemblages (viromes) of these environments. In this study, metagenomic analyses were performed on the uncultivated viral communities from three fermented foods, fermented shrimp, kimchi, and sauerkraut. Using a high-throughput pyrosequencing technique, a total of 81,831, 70,591 and 69,464 viral sequences were obtained from fermented shrimp, kimchi and sauerkraut, respectively. Moreover, 37 to 50% of these sequences showed no significant hit against sequences in public databases. There were some discrepancies between the prediction of bacteriophages hosts via homology comparison and bacterial distribution, as determined from 16S rRNA gene sequencing. These discrepancies likely reflect the fact that the viral genomes of fermented foods are poorly represented in public databases. Double-stranded DNA viral communities were amplified from fermented foods by using a linker-amplified shotgun library. These communities were dominated by bacteriophages belonging to the viral order Caudovirales (i.e., Myoviridae, Podoviridae, and Siphoviridae). This study indicates that fermented foods contain less complex viral communities than many other environmental habitats, such as seawater, human feces, marine sediment, and soil.     

The design of a reflectionless arterial prosthesis

We propose a new technique to characterize a reflectionless arterial prosthesis. The corresponding transmission and reflection coefficients are determined from the geometric and the elastic properties of the arterial wall, and the interaction between the latter and the prosthesis are studied accordingly.     

Identification of a novel prostate cancer susceptibility variant in the KLK3 gene transcript

Genome-wide association studies (GWAS) have identified more than 30 prostate cancer (PrCa) susceptibility loci. One of these (rs2735839) is located close to a plausible candidate susceptibility gene, KLK3, which encodes prostate-specific antigen (PSA). PSA is widely used as a biomarker for PrCa detection and disease monitoring. To refine the association between PrCa and variants in this region, we used genotyping data from a two-stage GWAS using samples from the UK and Australia, and the Cancer Genetic Markers of Susceptibility (CGEMS) study. Genotypes were imputed for 197 and 312 single nucleotide polymorphisms (SNPs) from HapMap2 and the 1000 Genome Project, respectively. The most significant association with PrCa was with a previously unidentified SNP, rs17632542 (combined P?=?3.9?×?10(-22)). This association was confirmed by direct genotyping in three stages of the UK/Australian GWAS, involving 10,405 cases and 10,681 controls (combined P?=?1.9?×?10(-34)). rs17632542 is also shown to be associated with PSA levels and it is a non-synonymous coding SNP (Ile179Thr) in KLK3. Using molecular dynamic simulation, we showed evidence that this variant has the potential to introduce alterations in the protein or affect RNA splicing. We propose that rs17632542 may directly influence PrCa risk.