Skeletal muscle creatine kinase MB alterations in women marathon runners

Total creatine kinase (CK) and CK MB activities were determined in gastrocnemius muscle and serum obtained from 14 female marathon runners. The level of CK MB in muscle increased significantly (p less than 0.05) after chronic exercise training from 5.3% to 10.5% of the total CK activity, but not after acute exercise (post-marathon 8.9%). No significant differences in total CK activities were detected. However, the total CK activity in the muscles were significantly (p less than 0.05) less than those previously reported from the muscle of men runners (1800 U/g, 3000 U/g respectively). No significant correlation existed between fiber type and muscle CK MB activity. Additionally, trace amounts of mitochondrial CK and CK BB were present in muscle homogenates. A significant correlation was observed in the increase in mean serum total CK (597 UL-1) and CK MB (23 UL-1) activities 24 h after the race (r = 0.97, p less than 0.05). These results suggest that gastrocnemius muscle in women adapts to training with increased CK MB activities and imply that skeletal muscle is the major source of elevated serum CK MB activities in women marathon runners.     

In vitro assembly of gap junctions

Gap junction structures were assembled in vitro from octyl-β- -glucopyranoside-solubilized components of lens fiber cell membranes. Individual pore structures (connexons), short double-membrane structures, and other amorphous material were evident in the solubilized mixture. Following the removal of the detergent by dialysis, these connexons associated to form single- and double-layered, two-dimensional hexagonal arrays (unit cell size a = B = 8.5 nm). The formation of larger arrays was dependent on the lipid-to-protein ratio and the presence of Mg²⁺ ions. Crystallographic analysis of electron micrographs revealed that lens junctional connexons consisted of six subunits surrounding a stain-filled channel. Upon further detergent treatment, in vitro assembled gap junctions were insoluble and formed three-dimensional stacks while other components were solubilized. SDS-PAGE and mass data from scanning transmission electron microscopy strongly suggest that a 38-kDa polypeptide, which is a processed form of the lens specific gap junction protein MP70, is a major component of the arrays. The in vitro assembly of gap junctions opens new avenues for the structural analysis of gap junctions and for the study of the intermolecular interactions of connexons during junctional assembly.     

Lifestyle Factors and Inflammation: Associations by Body Mass Index

Chronic inflammation, which is associated with obesity, may play a role in the etiology of several diseases. Thus, reducing inflammation may offer a disease-prevention strategy, particularly among the obese. Several modifiable factors have been associated with inflammation, including: dietary fiber intake, saturated fat intake, physical activity, smoking, alcohol, and use of certain supplements and medications (glucosamine, chondroitin, fish oil, vitamin E, statins and aspirin). To study whether these associations differ by body mass index (BMI), we used data on 9,895 adults included in the 1999–2004 cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted linear regression was used to evaluate the associations between modifiable factors and serum high-sensitivity C-reactive protein (hsCRP) concentrations across the following groups: underweight/normal weight (BMI<25 kg/m²), overweight (25-<30 kg/m²) and obese (30+ kg/m²). While several factors were significantly associated with decreased hsCRP among the normal weight or overweight groups (increased fiber intake, lower saturated fat intake, physical activity, not smoking, and use of chondroitin, fish oil and statins), only increasing dietary fiber intake and moderate alcohol consumption were associated with reduced hsCRP among the obese. Effect modification by BMI was statistically significant for the saturated fat-hsCRP and smoking-hsCRP associations. These results suggest that posited anti-inflammatory drugs and behaviors may be less strongly associated with inflammation among the obese than among lower weight persons.     

Sympatric divergence and clinal variation in multiple coloration traits of Ficedula flycatchers

Geographic variation in phenotypes plays a key role in fundamental evolutionary processes such as local adaptation, population differentiation and speciation, but the selective forces behind it are rarely known. We found support for the hypothesis that geographic variation in plumage traits of the pied flycatcher Ficedula hypoleuca is explained by character displacement with the collared flycatcher Ficedula albicollis in the contact zone. The plumage traits of the pied flycatcher differed strongly from the more conspicuous collared flycatcher in a sympatric area but increased in conspicuousness with increasing distance to there. Phenotypic differentiation (P_ST) was higher than that in neutral genetic markers (F_ST), and the effect of geographic distance remained when statistically controlling for neutral genetic differentiation. This suggests that a cline created by character displacement and gene flow explains phenotypic variation across the distribution of this species. The different plumage traits of the pied flycatcher are strongly to moderately correlated, indicating that they evolve non‐independently from each other. The flycatchers provide an example of plumage patterns diverging in two species that differ in several aspects of appearance. The divergence in sympatry and convergence in allopatry in these birds provide a possibility to study the evolutionary mechanisms behind the highly divergent avian plumage patterns.     

Fecundity selection does not vary along a large geographical cline of trait means in a passerine bird

Local environmental and ecological conditions are commonly expected to result in local adaptation, although there are few examples of variation in phenotypic selection across continent‐wide spatial scales. We collected standardized data on selection with respect to the highly variable plumage coloration of pied flycatcher (Ficedula hypoleuca Pall.) males from 17 populations across the species' breeding range. The observed selection on multiple male coloration traits via the annual number of fledged young was generally relatively weak. The main aim of the present study, however, was to examine whether the current directional selection estimates are associated with distance to the sympatric area with the collared flycatcher (Ficedula albicollis Temminck), a sister species with which the pied flycatcher is showing character displacement. This pattern was expected because plumage traits in male pied flycatchers are changing with the distance to these areas of sympatry. However, we did not find such a pattern in current selection on coloration. There were no associations between current directional selection on ornamentation and latitude or longitude either. Interestingly, current selection on coloration traits was not associated with the observed mean plumage traits of the populations. Thus, there do not appear to be geographical gradients in current directional fecundity selection on male plumage ornamentation. The results of the present study do not support the idea that constant patterns in directional fecundity selection would play a major role in the maintenance of coloration among populations in this species. By contrast, the tendency for relatively weak mosaic‐like variation in selection among populations could reflect just a snapshot of temporally variable, potentially environment‐dependent, selection, as suggested by other studies in this system. Such fine‐grained variable selection coupled with gene flow could maintain extensive phenotypic variation across populations. © 2015 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, 114 , 808–827.     

Visualizing fusion of pseudotyped HIV-1 particles in real time by live cell microscopy

Merck's MK-0518, known as raltegravir, has recently become the first FDA-approved HIV-1 integrase (IN) inhibitor and has since risen to blockbuster drug status. Much research has in turn been conducted over the last few years aimed at recreating but optimizing the compound's interactions with the protein. Resulting me-too drugs have shown favorable pharmacokinetic properties and appear drug-like but, as expected, most have a highly similar interaction with IN to that of raltegravir. We propose that, based upon conclusions drawn from our docking studies illustrated herein, most of these me-too MK-0518 analogues may experience a low success rate against raltegravir-resistant HIV strains. As HIV has a very high mutational competence, the development of drugs with new mechanisms of inhibitory action and/or new active substituents may be a more successful route to take in the development of second- and third-generation IN inhibitors.     

Responses of domestic chicks (Gallus gallus domesticus) to multimodal aposematic signals

Many aposematic prey combine their visual warning signals withadditional signals. Together, these signals constitute a multimodalor multicomponent warning display. The additional signals arethought to increase the effects of the visual signals on predators.Olfactory signals are much emphasized, but later studies haveshown that also auditory signals like the buzzing of certaininsects might have multimodal effects. The wasp displays typicalvisual aposematic signals, black and yellow stripes, but doesalso emit a characteristic buzzing. We wanted to test if, andin what way, the visual and acoustic display of the wasp hasan aversive function on the predators. We therefore conducteda 12-trial discrimination-learning task on inexperienced chicksto study whether there are innate biases toward these signalsand how they affect the speed of avoidance learning. We alsoperformed three extinction-learning trials to study how memorablethe signals were to the chicks. We show that the visual signalsin the display of the wasp contribute to the protection frompredators but in different ways; the yellow color had an aversiveeffect on inexperienced predators, while the striped patternimproved the aversion learning. The sound did not enhance theinnate aversions but increased the aversion learning of stripesin green prey.     

ABCB1 genotypes and haplotypes in patients with dementia and age-matched non-demented control patients

Amyloid β is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26) and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age-matched controls. This study shows ABCB1 genotype frequencies to be comparable with described younger populations. To our knowledge this is the first study on ABCB1 genotypes in dementia. ABCB1 genotypes are presently not useful as a biomarker for dementia, as they were not significantly different between demented patients and age-matched control subjects.     

The ‘Antiretrovirals,Sexual Transmission Risk and Attitudes’ (ASTRA) Study. Design,Methods and Participant Characteristics

Life expectancy for people diagnosed with HIV has improved dramatically however the number of new infections in the UK remains high. Understanding patterns of sexual behaviour among people living with diagnosed HIV, and the factors associated with having condom-less sex, is important for informing HIV prevention strategies and clinical care. In addition, in view of the current interest in a policy of early antiretroviral treatment (ART) for all people diagnosed with HIV in the UK, it is of particular importance to assess whether ART use is associated with increased levels of condom-less sex. In this context the ASTRA study was designed to investigate current sexual activity, and attitudes to HIV transmission risk, in a large unselected sample of HIV-infected patients under care in the UK. The study also gathered background information on demographic, socio-economic, lifestyle and disease-related characteristics, and physical and psychological symptoms, in order to identify other key factors impacting on HIV patients and the behaviours which underpin transmission. In this paper we describe the study rationale, design, methods, response rate and the demographic characteristics of the participants. People diagnosed with HIV infection attending 8 UK HIV out-patient clinics in 2011-2012 were invited to participate in the study. Those who agreed to participate completed a confidential, self-administered pen-and-paper questionnaire, and their latest CD4 count and viral load test results were recorded. During the study period, 5112 eligible patients were invited to take part in the study and 3258 completed questionnaires were obtained, representing a response rate of 64% of eligible patients. The study includes 2248 men who have sex with men (MSM), 373 heterosexual men and 637 women. Future results from ASTRA will be a key resource for understanding HIV transmission within the UK, targeting prevention efforts, and informing clinical care of individuals living with HIV.