Ultra-weak reversible protein-protein interactions

Ultra-weak interactions (K(d)>100μM) between proteins have in the last decade become an increasing focus of attention in cell biology, especially in relation to cell-cell interactions and signalling processes. Methods for their quantitative definition are reviewed. NMR spectroscopy plays a major role in this area, as it not only can define interactions as weak or weaker than 3mM, but in favourable cases structural information concerning the complex can be yielded. Free solution technologies mostly fail when addressed to such systems. The AUC has the highest practical capability, but evaluation of the data to yield K(a) values is complicated by the presence of thermodynamic/hydrodynamic effects of a comparable order of magnitude. These effects can however be computationally removed by means of suitable algorithms, and K(d) values of up to 50mM can be characterised. The relative merits of velocity and equilibrium approaches are discussed, and both are shown to have particular advantages.     

Mammals of the northern Philippines: tolerance for habitat disturbance and resistance to invasive species in an endemic insular fauna

Aim Island faunas, particularly those with high levels of endemism, usually are considered especially susceptible to disruption from habitat disturbance and invasive alien species. We tested this general hypothesis by examining the distribution of small mammals along gradients of anthropogenic habitat disturbance in northern Luzon Island, an area with a very high level of mammalian endemism. Location Central Cordillera, northern Luzon Island, Philippines. Methods  Using standard trapping techniques, we documented the occurrence and abundance of 16 endemic and two non‐native species along four disturbance gradients where habitat ranged from mature forest to deforested cropland. Using regression analysis and AIC_c for model selection, we assessed the influence of four predictor variables (geographic range, elevational range, body size and diet breadth) on the disturbance tolerance of species. Results Non‐native species dominated areas with the most severe disturbance and were rare or absent in mature forest. Native species richness declined with increasing disturbance level, but responses of individual species varied. Elevational range (a measure of habitat breadth) was the best predictor of response of native species to habitat disturbance. Geographic range, body size and diet breadth were weakly correlated. Main conclusions The endemic small mammal fauna of northern Luzon includes species adapted to varying levels of natural disturbance and appears to be resistant to disruption by resident alien species. In these respects, it resembles a diverse continental fauna rather than a depauperate insular fauna. We conclude that the long and complex history of Luzon as an ancient member of the Philippine island arc system has involved highly dynamic ecological conditions resulting in a biota adapted to changing conditions. We predict that similar responses will be seen in other taxonomic groups and in other ancient island arc systems.     

Adult consequences of late adolescent alcohol consumption: a systematic review of cohort studies

Background

Although important to public policy, there have been no rigorous evidence syntheses of the long-term consequences of late adolescent drinking.

Methods and Findings

This systematic review summarises evidence from general population cohort studies of drinking between 15–19 years old and any subsequent outcomes aged 20 or greater, with at least 3 years of follow-up study. Fifty-four studies were included, of which 35 were assessed to be vulnerable to bias and/or confounding. The principal findings are: (1) There is consistent evidence that higher alcohol consumption in late adolescence continues into adulthood and is also associated with alcohol problems including dependence; (2) Although a number of studies suggest links to adult physical and mental health and social consequences, existing evidence is of insufficient quality to warrant causal inferences at this stage.

Conclusions

There is an urgent need for high quality long-term prospective cohort studies in order to better understand the public health burden that is consequent on late adolescent drinking, both in relation to adult drinking and more broadly. Reducing drinking during late adolescence is likely to be important for preventing long-term adverse consequences as well as protecting against more immediate harms. Please see later in the article for the Editors'' Summary     

Malaria's deadly grip: cytoadhesion of Plasmodium falciparum‐infected erythrocytes

Cytoadhesion of Plasmodium falciparum‐infected erythrocytes to host microvasculature is a key virulence determinant. Parasite binding is mediated by a large family of clonally variant adhesion proteins, termed P. falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by var genes and expressed at the infected erythrocyte surface. Although PfEMP1 proteins have extensively diverged under opposing selection pressure to maintain ligand binding while avoiding antibody‐mediated detection, recent work has revealed they can be classified into different groups based on chromosome location and domain composition. This grouping reflects functional specialization of PfEMP1 proteins for different human host and microvascular binding niches and appears to be maintained by gene recombination hierarchies. Inone extreme, a specific PfEMP1 variant is associated with placental binding and malaria during pregnancy, while other PfEMP1 subtypes appear to be specialized for infection of malaria naïve hosts. Here, we discuss recent findings on the origins and evolution of the var gene family, the structure–function of PfEMP1 proteins, and a distinct subset of PfEMP1 variants that have been associated with severe childhood malaria.     

Sexual conflict and the function of genitalic claws in guppies (Poecilia reticulata)

Poeciliid fish, freshwater fish with internal fertilization, are known for the diversity of structures on the male intromittent organ, the gonopodium. Prominent among these, in some species, is a pair of claws at its tip. We conducted a manipulative study of these claws in the guppy, Poecilia reticulata, to determine if these aid in transferring sperm to resistant females. We compared the sperm transfer rates of clawed versus surgically declawed males attempting to mate with either receptive or unreceptive (i.e. resistant) females. Our analyses demonstrate that the gonopodial claws function to increase sperm transfer to unreceptive females during uncooperative matings but not during receptive matings. Up to threefold more sperm were transferred to unreceptive females by clawed than declawed males. These data suggest that the claw is a sexually antagonistic trait, functioning to aid in transferring sperm to resistant females, and implicate sexual conflict as a selective force in the diversification of the gonopodium in the Poeciliidae.     

Disconnecting Mitochondrial Content from Respiratory Chain Capacity in PGC-1-Deficient Skeletal Muscle

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Acquired defects in CFTR-dependent β-adrenergic sweat secretion in chronic obstructive pulmonary disease

Rationale

Smoking-induced chronic obstructive pulmonary disease (COPD) is associated with acquired systemic cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Recently, sweat evaporimetry has been shown to efficiently measure β-adrenergic sweat rate and specifically quantify CFTR function in the secretory coil of the sweat gland.

Objectives

To evaluate the presence and severity of systemic CFTR dysfunction in smoking-related lung disease using sweat evaporimetry to determine CFTR-dependent sweat rate.

Methods

We recruited a cohort of patients consisting of healthy never smokers (N = 18), healthy smokers (12), COPD smokers (25), and COPD former smokers (12) and measured β-adrenergic sweat secretion rate with evaporative water loss, sweat chloride, and clinical data (spirometry and symptom questionnaires).

Measurements and main results

β-adrenergic sweat rate was reduced in COPD smokers (41.9 ± 3.4, P < 0.05, ± SEM) and COPD former smokers (39.0 ± 5.4, P < 0.05) compared to healthy controls (53.6 ± 3.4). Similarly, sweat chloride was significantly greater in COPD smokers (32.8 ± 3.3, P < 0.01) and COPD former smokers (37.8 ± 6.0, P < 0.01) vs. healthy controls (19.1 ± 2.5). Univariate analysis revealed a significant association between β-adrenergic sweat rate and female gender (β = 0.26), age (−0.28), FEV₁% (0.35), dyspnea (−0.3), and history of smoking (−0.27; each P < 0.05). Stepwise multivariate regression included gender (0.39) and COPD (−0.43) in the final model (R² = 0.266, P < 0.0001).

Conclusions

β-adrenergic sweat rate was significantly reduced in COPD patients, regardless of smoking status, reflecting acquired CFTR dysfunction and abnormal gland secretion in the skin that can persist despite smoking cessation. β-adrenergic sweat rate and sweat chloride are associated with COPD severity and clinical symptoms, supporting the hypothesis that CFTR decrements have a causative role in COPD pathogenesis.     

Genome sequences for five strains of the emerging pathogen Haemophilus haemolyticus

We report the first whole-genome sequences for five strains, two carried and three pathogenic, of the emerging pathogen Haemophilus haemolyticus. Preliminary analyses indicate that these genome sequences encode markers that distinguish H. haemolyticus from its closest Haemophilus relatives and provide clues to the identity of its virulence factors.