Behavioural syndrome in a solitary predator is independent of body size and growth rate.

Models explaining behavioural syndromes often focus on state-dependency, linking behavioural variation to individual differences in other phenotypic features. Empirical studies are, however, rare. Here, we tested for a size and growth-dependent stable behavioural syndrome in the juvenile-stages of a solitary apex predator (pike, Esox lucius), shown as repeatable foraging behaviour across risk. Pike swimming activity, latency to prey attack, number of successful and unsuccessful prey attacks was measured during the presence/absence of visual contact with a competitor or predator. Foraging behaviour across risks was considered an appropriate indicator of boldness in this solitary predator where a trade-off between foraging behaviour and threat avoidance has been reported. Support was found for a behavioural syndrome, where the rank order differences in the foraging behaviour between individuals were maintained across time and risk situation. However, individual behaviour was independent of body size and growth in conditions of high food availability, showing no evidence to support the state-dependent personality hypothesis. The importance of a combination of spatial and temporal environmental variation for generating growth differences is highlighted

Comparative effectiveness of lifestyle interventions on cardiovascular risk factors among a Dutch overweight working population: A randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Overweight (Body Mass Index [BMI] ≥ 25 kg/m²) and obesity (BMI≥ 30 kg/m²) are associated with increased cardiovascular risk, posing a considerable burden to public health. The main aim of this study was to investigate lifestyle intervention effects on cardiovascular risk factors in healthy overweight employees.</p> <p>Methods</p> <p>Participants were 276 healthy overweight employees (69.2% male; mean age 44.0 years [SD 9.2]; mean BMI 29.7 kg/m²[SD 3.1]). They were randomized to one of two intervention groups receiving a six month lifestyle intervention with behavior counseling by phone (phone group) or e-mail (Internet group), or to a control group receiving usual care. Body weight, height, waist circumference, sum of skinfolds, blood pressure, total cholesterol level and predicted aerobic fitness were measured at baseline, at 6 and at 24 months. Regression analyses included the 141 participants with complete data.</p> <p>Results</p> <p>At 6 months a significant favorable effect on total cholesterol level (-0.2 mmol/l, 95%CI -0.5 to -0.0) was observed in the phone group and a trend for improved aerobic fitness (1.9 ml/kg/min, 95%CI -0.2 to 3.9) in the Internet group. At two years, favorable trends for body weight (-2.1 kg, 95%CI -4.4 to 0.2) and aerobic fitness (2.3 ml/kg/min, 95%CI -0.2 to 4.8) were observed in the Internet group.</p> <p>Conclusions</p> <p>The intervention effects were independent of the used communication mode. However short-term results were in favor of the phone group and long-term results in favor of the internet group. Thus, we found limited evidence for our lifestyle intervention to be effective in reducing cardiovascular risk in a group of apparently healthy overweight workers.</p> <p>Trial registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN04265725">ISRCTN04265725</a></p

Evaluating the Effects of Cutoffs and Treatment of Long-range Electrostatics in Protein Folding Simulations

The use of molecular dynamics simulations to provide atomic-level descriptions of biological processes tends to be computationally demanding, and a number of approximations are thus commonly employed to improve computational efficiency. In the past, the effect of these approximations on macromolecular structure and stability has been evaluated mostly through quantitative studies of small-molecule systems or qualitative observations of short-timescale simulations of biological macromolecules. Here we present a quantitative evaluation of two commonly employed approximations, using a test system that has been the subject of a number of previous protein folding studies–the villin headpiece. In particular, we examined the effect of (i) the use of a cutoff-based force-shifting technique rather than an Ewald summation for the treatment of electrostatic interactions, and (ii) the length of the cutoff used to determine how many pairwise interactions are included in the calculation of both electrostatic and van der Waals forces. Our results show that the free energy of folding is relatively insensitive to the choice of cutoff beyond 9 Å, and to whether an Ewald method is used to account for long-range electrostatic interactions. In contrast, we find that the structural properties of the unfolded state depend more strongly on the two approximations examined here

Etk/Bmx Regulates Proteinase-Activated-Receptor1 (PAR1) in Breast Cancer Invasion: Signaling Partners, Hierarchy and Physiological Significance

BACKGROUND: While protease-activated-receptor 1 (PAR(1)) plays a central role in tumor progression, little is known about the cell signaling involved. METHODOLOGY/PRINCIPAL FINDINGS: We show here the impact of PAR(1) cellular activities using both an orthotopic mouse mammary xenograft and a colorectal-liver metastasis model in vivo, with biochemical analyses in vitro. Large and highly vascularized tumors were generated by cells over-expressing wt hPar1, Y397Z hPar1, with persistent signaling, or Y381A hPar1 mutant constructs. In contrast, cells over-expressing the truncated form of hPar1, which lacks the cytoplasmic tail, developed small or no tumors, similar to cells expressing empty vector or control untreated cells. Antibody array membranes revealed essential hPar1 partners including Etk/Bmx and Shc. PAR(1) activation induces Etk/Bmx and Shc binding to the receptor C-tail to form a complex. Y/A mutations in the PAR(1) C-tail did not prevent Shc-PAR(1) association, but enhanced the number of liver metastases compared with the already increased metastases obtained with wt hPar1. We found that Etk/Bmx first binds via the PH domain to a region of seven residues, located between C378-S384 in PAR(1) C-tail, enabling subsequent Shc association. Importantly, expression of the hPar1-7A mutant form (substituted A, residues 378-384), which is incapable of binding Etk/Bmx, resulted in inhibition of invasion through Matrigel-coated membranes. Similarly, knocking down Etk/Bmx inhibited PAR(1)-induced MDA-MB-435 cell migration. In addition, intact spheroid morphogenesis of MCF10A cells is markedly disrupted by the ectopic expression of wt hPar1. In contrast, the forced expression of the hPar1-7A mutant results in normal ball-shaped spheroids. Thus, by preventing binding of Etk/Bmx to PAR(1) -C-tail, hPar1 oncogenic properties are abrogated. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration that a cytoplasmic portion of the PAR(1) C-tail functions as a scaffold site. We identify here essential signaling partners, determine the hierarchy of binding and provide a platform for therapeutic vehicles via definition of the critical PAR(1)-associating region in the breast cancer signaling niche

Dissolved organic carbon transformations and microbial community response to variations in recharge waters in a shallow carbonate aquifer

© 2016, The Author(s). In carbonate aquifers, dissolved organic carbon from the surface drives heterotrophic metabolism, generating CO2 in the subsurface. Although this has been a proposed mechanism for enhanced dissolution at the water table, respiration rates and their controlling factors have not been widely evaluated. This study investigates the composition and concentration of dissolved organic carbon (DOC) reaching the water table from different recharge pathways on a subtropical carbonate island using a combination of DOC concentration measurements, fluorescence and absorption characterisation. In addition, direct measurements of the microbial response to the differing water types were made. Interactions of rainfall with the vegetation, via throughfall and stemflow, increase the concentration of DOC. The highest DOC concentrations are associated with stemflow, overland recharge and dissolution hole waters which interact with bark lignin and exhibit strong terrestrial-derived characteristics. The groundwater samples exhibit the lowest concentrations of DOC and are comprised of refractory humic-like organic matter. The heterotrophic response seems to be controlled by the concentration of DOC in the sample. The terrestrially sourced humic-like matter in the stemflow and dissolution hole samples was highly labile, thus increasing the amount of biologically produced CO2 to drive dissolution. Based on the calculated respiration rates, microbial activity could enhance carbonate dissolution, increasing porosity generation by a maximum of 1%kyr−1 at the top of the freshwater lens

Acidithiobacillus ferrooxidans metabolism: from genome sequence to industrial applications

<p>Abstract</p> <p>Background</p> <p><it>Acidithiobacillus ferrooxidans </it>is a major participant in consortia of microorganisms used for the industrial recovery of copper (bioleaching or biomining). It is a chemolithoautrophic, γ-proteobacterium using energy from the oxidation of iron- and sulfur-containing minerals for growth. It thrives at extremely low pH (pH 1–2) and fixes both carbon and nitrogen from the atmosphere. It solubilizes copper and other metals from rocks and plays an important role in nutrient and metal biogeochemical cycling in acid environments. The lack of a well-developed system for genetic manipulation has prevented thorough exploration of its physiology. Also, confusion has been caused by prior metabolic models constructed based upon the examination of multiple, and sometimes distantly related, strains of the microorganism.</p> <p>Results</p> <p>The genome of the type strain <it>A. ferrooxidans </it>ATCC 23270 was sequenced and annotated to identify general features and provide a framework for <it>in silico </it>metabolic reconstruction. Earlier models of iron and sulfur oxidation, biofilm formation, quorum sensing, inorganic ion uptake, and amino acid metabolism are confirmed and extended. Initial models are presented for central carbon metabolism, anaerobic metabolism (including sulfur reduction, hydrogen metabolism and nitrogen fixation), stress responses, DNA repair, and metal and toxic compound fluxes.</p> <p>Conclusion</p> <p>Bioinformatics analysis provides a valuable platform for gene discovery and functional prediction that helps explain the activity of <it>A. ferrooxidans </it>in industrial bioleaching and its role as a primary producer in acidic environments. An analysis of the genome of the type strain provides a coherent view of its gene content and metabolic potential.</p

Transcriptional responses to glucose in Saccharomyces cerevisiae strains lacking a functional protein kinase A

Background The pattern of gene transcripts in the yeast Saccharomyces cerevisiae is strongly affected by the presence of glucose. An increased activity of protein kinase A (PKA), triggered by a rise in the intracellular concentration of cAMP, can account for many of the effects of glucose on transcription. In S. cerevisiae three genes, TPK1, TPK2, and TPK3, encode catalytic subunits of PKA. The lack of viability of tpk1 tpk2 tpk3 triple mutants may be suppressed by mutations such as yak1 or msn2/msn4. To investigate the requirement for PKA in glucose control of gene expression, we have compared the effects of glucose on global transcription in a wild-type strain and in two strains devoid of PKA activity, tpk1 tpk2 tpk3 yak1 and tpk1 tpk2 tpk3 msn2 msn4. Results We have identified different classes of genes that can be induced -or repressed- by glucose in the absence of PKA. Representative examples are genes required for glucose utilization and genes involved in the metabolism of other carbon sources, respectively. Among the genes responding to glucose in strains devoid of PKA some are also controlled by a redundant signalling pathway involving PKA activation, while others are not affected when PKA is activated through an increase in cAMP concentration. On the other hand, among genes that do not respond to glucose in the absence of PKA, some give a full response to increased cAMP levels, even in the absence of glucose, while others appear to require the cooperation of different signalling pathways. We show also that, for a number of genes controlled by glucose through a PKA-dependent pathway, the changes in mRNA levels are transient. We found that, in cells grown in gluconeogenic conditions, expression of a small number of genes, mainly connected with the response to stress, is reduced in the strains lacking PKA. Conclusions In S. cerevisiae, the transcriptional responses to glucose are triggered by a variety of pathways, alone or in combination, in which PKA is often involved. Redundant signalling pathways confer a greater robustness to the response to glucose, while cooperative pathways provide a greater flexibility.BT/BiotechnologyApplied Science

Design of the Balance@Work project: systematic development, evaluation and implementation of an occupational health guideline aimed at the prevention of weight gain among employees

<p>Abstract</p> <p>Background</p> <p>Occupational health professionals may play an important role in preventive health promotion activities for employees. However, due to a lack of knowledge and evidence- and practice based methods and strategies, interventions are hardly being implemented by occupational physicians to date. The aim of the Balance@Work project is to develop, evaluate, and implement an occupational health guideline aimed at the prevention of weight gain among employees.</p> <p>Methods</p> <p>Following the guideline development protocol of the Netherlands Society of Occupational Medicine and the Intervention Mapping protocol, the guideline was developed based on literature, interviews with relevant stakeholders, and consensus among an expert group. The guideline consists of an individual and an environmental component. The individual component includes recommendations for occupational physicians on how to promote physical activity and healthy dietary behavior based on principles of motivational interviewing. The environmental component contains an obesogenic environment assessment tool. The guideline is evaluated in a randomised controlled trial among 20 occupational physicians. Occupational physicians in the intervention group apply the guideline to eligible workers during 6 months. Occupational physicians in the control group provide care as usual. Measurements take place at baseline and 6, 12, and 18 months thereafter. Primary outcome measures include waist circumference, daily physical activity and dietary behavior. Secondary outcome measures include sedentary behavior, determinants of behavior change, body weight and body mass index, cardiovascular disease risk profile, and quality of life. Additionally, productivity, absenteeism, and cost-effectiveness are assessed.</p> <p>Discussion</p> <p>Improving workers' daily physical activity and dietary behavior may prevent weight gain and subsequently improve workers' health, increase productivity, and reduce absenteeism. After an effect- and process evaluation the guideline will be adjusted and, after authorisation, published. Together with several implementation aids, the published guideline will be disseminated broadly by the Netherlands Society of Occupational Medicine.</p> <p>Trial Registration</p> <p>ISRCTN73545254/NTR1190</p