The evolution of domain-content in bacterial genomes

Background  

Across all sequenced bacterial genomes, the number of domains n _c in different functional categories c scales as a power-law in the total number of domains n, i.e. , with exponents α _c that vary across functional categories. Here we investigate the implications of these scaling laws for the evolution of domain-content in bacterial genomes and derive the simplest evolutionary model consistent with these scaling laws.     

Impact of social support intensity on walking in the severely obese: a randomized clinical trial

Objective: There are few established methods for promoting physical activity (PA) in the severely obese. Because social support is a potential method for promoting PA, we compared mean steps/day during 18 weeks in severely obese outpatients receiving either standard support (SS) or added support (AS). Methods and Procedures: Eighty severely obese outpatients from an obesity clinic were invited; 66 provided written consent, 55 were randomized, and 42 were included in final analyses (9 men, 33 women; age 44.4 ± 13.1 years; BMI 41.9 ± 5.5 kg/m²). All participants received a pedometer and a walking promotion booklet. In addition to SS, the AS group received ten 2‐h group counseling sessions aimed at increasing weekly accumulated steps, every second week during the study. Each participant was asked to complete a 7‐day walking diary every second week (10 observations). Results: Baseline steps/day was 6,912 for the AS group and 5,311 for the SS group (P = 0.023). Data at 18 weeks showed that the AS group recorded 10,136 steps/day and the SS group 6,118 steps/day (P = 0.024). There was no allocation × time interaction (P = 0.46). During the follow‐up period as a whole, the AS group recorded 1,794 more steps/day than the SS group (P = 0.0074). Discussion: The AS group recorded more steps/day than the SS group, reaching a mean level of ～10,000 steps/day. However, the nonsignificant interaction between allocation × time suggests that this difference was present already at baseline and did not increase during follow‐up.     

Programming obesity and poor fitness: the long-term impact of childhood television

Objective: To assess whether the long‐term effects of childhood television viewing on BMI and cardiorespiratory fitness are mediated by adult viewing. Methods and Procedures: This prospective study included an unselected birth cohort of 1,037 participants (535 men) born in Dunedin, New Zealand in 1972/1973. Hours of television viewing on weekdays were reported at ages 5, 7, 9, 11, 13, 15, and 32 years. BMI and cardiorespiratory fitness were measured at age 32 years. Results: Both childhood and adult television viewing times were significantly associated with higher BMI and lower cardiorespiratory fitness at age 32 years. Childhood television viewing was a better predictor of adult BMI and fitness than adult viewing and remained a significant predictor of these outcomes after adjusting for adult viewing time. After adjusting for adult viewing, the odds (95% confidence interval) of adult obesity increased by a factor of 1.25 (1.01, 1.53) and poor fitness increased by a factor of 1.40 (1.16, 1.70) for each hour of mean weekday television viewing during childhood. Discussion: The association between childhood television viewing and obesity and poor fitness in adulthood is not mediated by adult viewing. The detrimental health effects of watching too much television during childhood persist into adulthood. Attempts to reduce adult obesity and poor fitness by modifying television viewing habits need to begin in childhood.     

Contrasting Microbial Community Assembly Hypotheses: A Reconciling Tale from the Río Tinto

Background

The Río Tinto (RT) is distinguished from other acid mine drainage systems by its natural and ancient origins. Microbial life from all three domains flourishes in this ecosystem, but bacteria dominate metabolic processes that perpetuate environmental extremes. While the patchy geochemistry of the RT likely influences the dynamics of bacterial populations, demonstrating which environmental variables shape microbial diversity and unveiling the mechanisms underlying observed patterns, remain major challenges in microbial ecology whose answers rely upon detailed assessments of community structures coupled with fine-scale measurements of physico-chemical parameters.

Methodology/Principal Findings

By using high-throughput environmental tag sequencing we achieved saturation of richness estimators for the first time in the RT. We found that environmental factors dictate the distribution of the most abundant taxa in this system, but stochastic niche differentiation processes, such as mutation and dispersal, also contribute to observed diversity patterns.

Conclusions/Significance

We predict that studies providing clues to the evolutionary and ecological processes underlying microbial distributions will reconcile the ongoing debate between the Baas Becking vs. Hubbell community assembly hypotheses.     

A comparative structural bioinformatics analysis of the insulin receptor family ectodomain based on phylogenetic information

The insulin receptor (IR), the insulin-like growth factor 1 receptor (IGF1R) and the insulin receptor-related receptor (IRR) are covalently-linked homodimers made up of several structural domains. The molecular mechanism of ligand binding to the ectodomain of these receptors and the resulting activation of their tyrosine kinase domain is still not well understood. We have carried out an amino acid residue conservation analysis in order to reconstruct the phylogeny of the IR Family. We have confirmed the location of ligand binding site 1 of the IGF1R and IR. Importantly, we have also predicted the likely location of the insulin binding site 2 on the surface of the fibronectin type III domains of the IR. An evolutionary conserved surface on the second leucine-rich domain that may interact with the ligand could not be detected. We suggest a possible mechanical trigger of the activation of the IR that involves a slight 'twist' rotation of the last two fibronectin type III domains in order to face the likely location of insulin. Finally, a strong selective pressure was found amongst the IRR orthologous sequences, suggesting that this orphan receptor has a yet unknown physiological role which may be conserved from amphibians to mammals.     

The male sex pheromone of the butterfly Bicyclus anynana: towards an evolutionary analysis

Background

Female sex pheromones attracting mating partners over long distances are a major determinant of reproductive isolation and speciation in Lepidoptera. Males can also produce sex pheromones but their study, particularly in butterflies, has received little attention. A detailed comparison of sex pheromones in male butterflies with those of female moths would reveal patterns of conservation versus novelty in the associated behaviours, biosynthetic pathways, compounds, scent-releasing structures and receiving systems. Here we assess whether the African butterfly Bicyclus anynana, for which genetic, genomic, phylogenetic, ecological and ethological tools are available, represents a relevant model to contribute to such comparative studies.

Methodology/Principal Findings

Using a multidisciplinary approach, we determined the chemical composition of the male sex pheromone (MSP) in the African butterfly B. anynana, and demonstrated its behavioural activity. First, we identified three compounds forming the presumptive MSP, namely (Z)-9-tetradecenol (Z9-14:OH), hexadecanal (16:Ald ) and 6,10,14-trimethylpentadecan-2-ol (6,10,14-trime-15-2-ol), and produced by the male secondary sexual structures, the androconia. Second, we described the male courtship sequence and found that males with artificially reduced amounts of MSP have a reduced mating success in semi-field conditions. Finally, we could restore the mating success of these males by perfuming them with the synthetic MSP.

Conclusions/Significance

This study provides one of the first integrative analyses of a MSP in butterflies. The toolkit it has developed will enable the investigation of the type of information about male quality that is conveyed by the MSP in intraspecific communication. Interestingly, the chemical structure of B. anynana MSP is similar to some sex pheromones of female moths making a direct comparison of pheromone biosynthesis between male butterflies and female moths relevant to future research. Such a comparison will in turn contribute to understanding the evolution of sex pheromone production and reception in butterflies.     

AMPK α1 Activation Is Required for Stimulation of Glucose Uptake by Twitch Contraction,but Not by H2O2, in Mouse Skeletal Muscle

Background

AMPK is a promising pharmacological target in relation to metabolic disorders partly due to its non-insulin dependent glucose uptake promoting role in skeletal muscle. Of the 2 catalytic α-AMPK isoforms, α₂ AMPK is clearly required for stimulation of glucose transport into muscle by certain stimuli. In contrast, no clear function has yet been determined for α₁ AMPK in skeletal muscle, possibly due to α-AMPK isoform signaling redundancy. By applying low-intensity twitch-contraction and H₂O₂ stimulation to activate α₁ AMPK, but not α₂ AMPK, in wildtype and α-AMPK transgenic mouse muscles, this study aimed to define conditions where α₁ AMPK is required to increase muscle glucose uptake.

Methodology/Principal Findings

Following stimulation with H₂O₂ (3 mM, 20 min) or twitch-contraction (0.1 ms pulse, 2 Hz, 2 min), signaling and 2-deoxyglucose uptake were measured in incubated soleus muscles from wildtype and muscle-specific kinase-dead AMPK (KD), α₁ AMPK knockout or α₂ AMPK knockout mice. H₂O₂ increased the activity of both α₁ and α₂ AMPK in addition to Akt phosphorylation, and H₂O₂-stimulated glucose uptake was not reduced in any of the AMPK transgenic mouse models compared with wild type. In contrast, twitch-contraction increased the activity of α₁ AMPK, but not α₂ AMPK activity nor Akt or AS160 phosphorylation. Glucose uptake was markedly lower in α₁ AMPK knockout and KD AMPK muscles, but not in α₂ AMPK knockout muscles, following twitch stimulation.

Conclusions/Significance

These results provide strong genetic evidence that α₁ AMPK, but not α₂ AMPK, Akt or AS160, is necessary for regulation of twitch-contraction stimulated glucose uptake. To our knowledge, this is the first report to show a major and essential role of α₁ AMPK in regulating a physiological endpoint in skeletal muscle. In contrast, AMPK is not essential for H₂O₂-stimulated muscle glucose uptake, as proposed by recent studies.     

The conserved salt bridge in human alpha-defensin 5 is required for its precursor processing and proteolytic stability

Mammalian alpha-defensins, expressed primarily in leukocytes and epithelia, play important roles in innate and adaptive immune responses to microbial infection. Six invariant cysteine residues forming three indispensable disulfide bonds and one Gly residue required structurally for an atypical beta-bulge are totally conserved in the otherwise diverse sequences of all known mammalian alpha-defensins. In addition, a pair of oppositely charged residues (Arg/Glu), forming a salt bridge across a protruding loop in the molecule, is highly conserved. To investigate the structural and functional roles of the conserved Arg(6)-Glu(14) salt bridge in human alpha-defensin 5 (HD5), we chemically prepared HD5 and its precursor proHD5 as well as their corresponding salt bridge-destabilizing analogs E14Q-HD5 and E57Q-proHD5. The Glu-to-Gln mutation, whereas significantly reducing the oxidative folding efficiency of HD5, had no effect on the folding of proHD5. Bovine trypsin productively and correctly processed proHD5 in vitro but spontaneously degraded E57Q-proHD5. Significantly, HD5 was resistant to trypsin treatment, whereas E14Q-HD5 was highly susceptible. Further, degradation of E14Q-HD5 by trypsin was initiated by the cleavage of the Arg(13)-Gln(14) peptide bond in the loop region, a catastrophic proteolytic event resulting directly in quick digestion of the whole defensin molecule. The E14Q mutation did not alter the bactericidal activity of HD5 against Staphylococcus aureus but substantially enhanced the killing of Escherichia coli. By contrast, proHD5 and E57Q-proHD5 were largely inactive against both strains at the concentrations tested. Our results confirm that the primary function of the conserved salt bridge in HD5 is to ensure correct processing of proHD5 and subsequent stabilization of mature alpha-defensin in vivo.