Promiscuous Interactions of gp78 E3 Ligase CUE Domain with Polyubiquitin Chains

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Highlights? The ubiquitin ligase gp78 recruits ubiquitinated substrates via its CUE domain ? gp78CUE:Ub complex reveals a large set of specific interactions ? gp78CUE binds to both distal and proximal moities of diubiquitin in a similar fashion ? The gp78CUE domain binds to K48- and K63-linked diubiquitin equally well     

Visual pigments of marine carnivores: pinnipeds, polar bear, and sea otter

Rod and cone visual pigments of 11 marine carnivores were evaluated. Rod, middle/long-wavelength sensitive (M/L) cone, and short-wavelength sensitive (S) cone opsin (if present) sequences were obtained from retinal mRNA. Spectral sensitivity was inferred through evaluation of known spectral tuning residues. The rod pigments of all but one of the pinnipeds were similar to those of the sea otter, polar bear, and most other terrestrial carnivores with spectral peak sensitivities (λ_max) of 499 or 501 nm. Similarly, the M/L cone pigments of the pinnipeds, polar bear, and otter had inferred λ_max of 545 to 560 nm. Only the rod opsin sequence of the elephant seal had sensitivity characteristic of adaptation for vision in the marine environment, with an inferred λ_max of 487 nm. No evidence of S cones was found for any of the pinnipeds. The polar bear and otter had S cones with inferred λ_max of ∼440 nm. Flicker-photometric ERG was additionally used to examine the in situ sensitivities of three species of pinniped. Despite the use of conditions previously shown to evoke cone responses in other mammals, no cone responses could be elicited from any of these pinnipeds. Rod photoreceptor responses for all three species were as predicted by the genetic data.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Identification of a mutation in the para-sodium channel gene of the cattle tick Rhipicephalus (Boophilus) microplus associated with resistance to synthetic pyrethroid acaricides

Resistance against synthetic pyrethroid (SP) products for the control of cattle ticks in Australia was detected in the field in 1984, within a very short time of commercial introduction. We have identified a mutation in the domain II S4-5 linker of the para-sodium channel that is associated with resistance to SPs in the cattle tick Rhipicephalus (Boophilus) microplus from Australia. The cytosine to adenine mutation at position 190 in the R. microplus sequence AF134216, results in an amino acid substitution from leucine in the susceptible strain to isoleucine in the resistant strain. A similar mutation has been shown to confer SP resistance in the whitefly, Bemisia tabaci, but has not been described previously in ticks. A diagnostic quantitative PCR assay has been developed using allele-specific Taqman^® minor groove-binding (MGB) probes. Using the assay to screen field and laboratory populations of ticks showed that homozygote allelic frequencies correlated highly with the survival percentage at the discriminating concentration of cypermethrin.     

Static and dynamic human flexor tendon–pulley interaction

The aim of the study was to investigate the influence of a preceding flexion or extension movement on the static interaction of human finger flexor tendons and pulleys concerning flexion torque being generated. Six human fresh frozen cadaver long fingers were mounted in an isokinetic movement device for the proximal interphalangeal (PIP) joint. During flexion and extension movement both flexor tendons were equally loaded with 40 N while the generated moment was depicted simultaneously at the fingertip. The movement was stopped at various positions of the proximal interphalangeal joint to record dynamic and static torque. The static torque was always greater after a preceding extension movement compared to a preceding flexion movement in the corresponding same position of the joint. This applied for the whole arc of movement of 0–105°. The difference between static extension and flexion torque was maximal 11% in average at about 83° of flexion. Static torque was always smaller than dynamic torque during extension movement and always greater than dynamic torque during flexion movement. The kind of preceding movement therefore showed an influence to the torque being generated in the proximal interphalangeal joint. The effect could be simulated on a mechanical finger device.     

Fatness-Associated FTO Gene Variant Increases Mortality Independent of Fatness – in Cohorts of Danish Men

Background

The A-allele of the single nucleotide polymorphism (SNP), rs9939609, in the FTO gene is associated with increased fatness. We hypothesized that the SNP is associated with morbidity and mortality through the effect on fatness.

Methodology/Principal Findings

In a population of 362,200 Danish young men, examined for military service between 1943 and 1977, all obese (BMI≥31.0 kg/m²) and a random 1% sample of the others were identified. In 1992–94, at an average age of 46 years, 752 of the obese and 876 of the others were re-examined, including measurements of weight, fat mass, height, and waist circumference, and DNA sampling. Hospitalization and death occurring during the following median 13.5 years were ascertained by linkage to national registers. Cox regression analyses were performed using a dominant effect model (TT vs. TA or AA). In total 205 men died. Mortality was 42% lower (p = 0.001) with the TT genotype than in A-allele carriers. This phenomenon was observed in both the obese and the randomly sampled cohort when analysed separately. Adjustment for fatness covariates attenuated the association only slightly. Exploratory analyses of cause-specific mortality and morbidity prior to death suggested a general protective effect of the TT genotype, whereas there were only weak associations with disease incidence, except for diseases of the nervous system.

Conclusion

Independent of fatness, the A-allele of the FTO SNP appears to increase mortality of a magnitude similar to smoking, but without a particular underlying disease pattern barring an increase in the risk of diseases of the nervous system.     

Rapid Global Expansion of the Fungal Disease Chytridiomycosis into Declining and Healthy Amphibian Populations

The fungal disease chytridiomycosis, caused by Batrachochytrium dendrobatidis, is enigmatic because it occurs globally in both declining and apparently healthy (non-declining) amphibian populations. This distribution has fueled debate concerning whether, in sites where it has recently been found, the pathogen was introduced or is endemic. In this study, we addressed the molecular population genetics of a global collection of fungal strains from both declining and healthy amphibian populations using DNA sequence variation from 17 nuclear loci and a large fragment from the mitochondrial genome. We found a low rate of DNA polymorphism, with only two sequence alleles detected at each locus, but a high diversity of diploid genotypes. Half of the loci displayed an excess of heterozygous genotypes, consistent with a primarily clonal mode of reproduction. Despite the absence of obvious sex, genotypic diversity was high (44 unique genotypes out of 59 strains). We provide evidence that the observed genotypic variation can be generated by loss of heterozygosity through mitotic recombination. One strain isolated from a bullfrog possessed as much allelic diversity as the entire global sample, suggesting the current epidemic can be traced back to the outbreak of a single clonal lineage. These data are consistent with the current chytridiomycosis epidemic resulting from a novel pathogen undergoing a rapid and recent range expansion. The widespread occurrence of the same lineage in both healthy and declining populations suggests that the outcome of the disease is contingent on environmental factors and host resistance.