Quantifying the Adaptive Potential of an Antibiotic Resistance Enzyme

For a quantitative understanding of the process of adaptation, we need to understand its “raw material,” that is, the frequency and fitness effects of beneficial mutations. At present, most empirical evidence suggests an exponential distribution of fitness effects of beneficial mutations, as predicted for Gumbel-domain distributions by extreme value theory. Here, we study the distribution of mutation effects on cefotaxime (Ctx) resistance and fitness of 48 unique beneficial mutations in the bacterial enzyme TEM-1 β-lactamase, which were obtained by screening the products of random mutagenesis for increased Ctx resistance. Our contributions are threefold. First, based on the frequency of unique mutations among more than 300 sequenced isolates and correcting for mutation bias, we conservatively estimate that the total number of first-step mutations that increase Ctx resistance in this enzyme is 87 [95% CI 75–189], or 3.4% of all 2,583 possible base-pair substitutions. Of the 48 mutations, 10 are synonymous and the majority of the 38 non-synonymous mutations occur in the pocket surrounding the catalytic site. Second, we estimate the effects of the mutations on Ctx resistance by determining survival at various Ctx concentrations, and we derive their fitness effects by modeling reproduction and survival as a branching process. Third, we find that the distribution of both measures follows a Fréchet-type distribution characterized by a broad tail of a few exceptionally fit mutants. Such distributions have fundamental evolutionary implications, including an increased predictability of evolution, and may provide a partial explanation for recent observations of striking parallel evolution of antibiotic resistance

Vitamin C and asthma in children: modification of the effect by age, exposure to dampness and the severity of asthma

Retraction: Clinical and Translational Allergy 2012, 2:6BACKGROUND: We previously found a significant benefit of vitamin C supplementation in asthmatic children. PURPOSE: To test whether the effect of vitamin C on asthma is heterogeneous over the participant population. METHODS: Egyptian asthmatic children between 7 and 10 years of age (n = 60) were included in the cross-over trial. They were administered 0.2 grams per day of vitamin C and placebo for separate 6-week periods. The variation in the vitamin C effect on two clinically relevant outcomes was analyzed: the childhood asthma control test (C-ACT), which measures the severity of asthma symptoms (the scale ranges from 0 to 27 points, < 20 points indicating unsatisfactory asthma control), and FEV1. We used linear modeling to examine the variation of the vitamin C effect in the subgroups. RESULTS: The effect of vitamin C on the C-ACT was significantly modified by age and baseline C-ACT levels. In the children aged 7.0-8.2 years with a baseline C-ACT of 18 to 19 points, vitamin C increased the C-ACT score by 4.2 points (95% CI: 3.3-5.3); whereas in the children aged 8.3-10 years who had a baseline C-ACT of 14 to 15 points, vitamin C increased the C-ACT score by only 1.3 points (95% CI: 0.1-2.5). The effect of vitamin C on the FEV1 levels was significantly modified by age and exposure to dampness. In the children aged 7.0-8.2 years with no exposure to dampness, vitamin C increased the FEV1 level by 37% (95% CI: 34-40%), whereas in the children aged 8.3-10 years with exposure to dampness or mold in their bedroom more than one year prior to the study, vitamin C increased the FEV1 level by only 21% (95% CI: 18-25%). CONCLUSIONS: We found strong evidence that the effect of vitamin C on asthmatic children is heterogeneous. Further research is needed to confirm our findings and identify the groups of children who would receive the greatest benefit from vitamin C supplementation.Peer reviewe

Internet Pathways in Suicidality: A Review of the Evidence

The general aim of this study was to review the scientific literature concerning the Internet and suicidality and to examine the different pathways by which suicidal risks and prevention efforts are facilitated through the Internet. An online literature search was conducted using the MEDLINE and Google Scholar databases. The main themes that were investigated included pathological Internet use and suicidality, pro-suicide websites, suicide pacts on the Internet, and suicide prevention via the Internet. Articles were screened based on the titles and abstracts reporting on the themes of interest. Thereafter, articles were selected based on scientific relevance of the study, and included for full text assessment. The results illustrated that specific Internet pathways increased the risk for suicidal behaviours, particularly in adolescents and young people. Several studies found significant correlations between pathological Internet use and suicidal ideation and non-suicidal self-injury. Pro-suicide websites and online suicide pacts were observed as high-risk factors for facilitating suicidal behaviours, particularly among isolated and susceptible individuals. Conversely, the evidence also showed that the Internet could be an effective tool for suicide prevention, especially for socially-isolated and vulnerable individuals, who might otherwise be unreachable. It is this paradox that accentuates the need for further research in this field

Horizontal gene transfer in silkworm, Bombyx mori

<p>Abstract</p> <p>Background</p> <p>The domesticated silkworm, <it>Bombyx mori</it>, is the model insect for the order Lepidoptera, has economically important values, and has gained some representative behavioral characteristics compared to its wild ancestor. The genome of <it>B. mori </it>has been fully sequenced while function analysis of <it>BmChi-h </it>and <it>BmSuc1 </it>genes revealed that horizontal gene transfer (HGT) maybe bestow a clear selective advantage to <it>B. mori</it>. However, the role of HGT in the evolutionary history of <it>B. mori </it>is largely unexplored. In this study, we compare the whole genome of <it>B. mori </it>with those of 382 prokaryotic and eukaryotic species to investigate the potential HGTs.</p> <p>Results</p> <p>Ten candidate HGT events were defined in <it>B. mori </it>by comprehensive sequence analysis using Maximum Likelihood and Bayesian method combining with EST checking. Phylogenetic analysis of the candidate HGT genes suggested that one HGT was plant-to- <it>B. mori </it>transfer while nine were bacteria-to- <it>B. mori </it>transfer. Furthermore, functional analysis based on expression, coexpression and related literature searching revealed that several HGT candidate genes have added important characters, such as resistance to pathogen, to <it>B. mori</it>.</p> <p>Conclusions</p> <p>Results from this study clearly demonstrated that HGTs play an important role in the evolution of <it>B. mori </it>although the number of HGT events in <it>B. mori </it>is in general smaller than those of microbes and other insects. In particular, interdomain HGTs in <it>B. mori </it>may give rise to functional, persistent, and possibly evolutionarily significant new genes.</p

Facebook's Mobile Career

At the end of its first decade, Facebook’s identity, popularity, and characteristics are shaped in important ways by its becoming a form of mobile media, as much as it as platform associated with Internet and social media. This paper seeks to explore and understand Facebook as the important force in mobile media and communication it now is. It draws upon and combines perspectives from technology production, design, and economy, as well as user adoption, consumption, practices, affect, emotion, and resistance. The paper discusses the beginnings of mobile Facebook, and the early adoption of mobile Facebook associated with the rise of smartphones. The second part of the paper explores Facebook’s integration with photography (with Instagram) and social games (such as Zynga’s Farmville). The paper argues that Facebook’s mobile career is an accomplishment that has distinctively melded evolving affordances, everyday use across a wide range of settings, as well as political economies, corporate strategy, and design.Australian Research Counci

Phosphate decreases urine calcium and increases calcium balance: A meta-analysis of the osteoporosis acid-ash diet hypothesis

<p>Abstract</p> <p>Background</p> <p>The acid-ash hypothesis posits that increased excretion of "acidic" ions derived from the diet, such as phosphate, contributes to net acidic ion excretion, urine calcium excretion, demineralization of bone, and osteoporosis. The public is advised by various media to follow an alkaline diet to lower their acidic ion intakes. The objectives of this meta-analysis were to quantify the contribution of phosphate to bone loss in healthy adult subjects; specifically, a) to assess the effect of supplemental dietary phosphate on urine calcium, calcium balance, and markers of bone metabolism; and to assess whether these affects are altered by the b) level of calcium intake, c) the degree of protonation of the phosphate.</p> <p>Methods</p> <p>Literature was identified through computerized searches regarding phosphate with surrogate and/or direct markers of bone health, and was assessed for methodological quality. Multiple linear regression analyses, weighted for sample size, were used to combine the study results. Tests of interaction included stratification by calcium intake and degree of protonation of the phosphate supplement.</p> <p>Results</p> <p>Twelve studies including 30 intervention arms manipulated 269 subjects' phosphate intakes. Three studies reported net acid excretion. All of the meta-analyses demonstrated significant decreases in urine calcium excretion in response to phosphate supplements whether the calcium intake was high or low, regardless of the degree of protonation of the phosphate supplement. None of the meta-analyses revealed lower calcium balance in response to increased phosphate intakes, whether the calcium intake was high or low, or the composition of the phosphate supplement.</p> <p>Conclusion</p> <p>All of the findings from this meta-analysis were contrary to the acid ash hypothesis. Higher phosphate intakes were associated with decreased urine calcium and increased calcium retention. This meta-analysis did not find evidence that phosphate intake contributes to demineralization of bone or to bone calcium excretion in the urine. Dietary advice that dairy products, meats, and grains are detrimental to bone health due to "acidic" phosphate content needs reassessment. There is no evidence that higher phosphate intakes are detrimental to bone health.</p

Physiological characteristics of dysphagia following thermal burn injury

The study aim was to document the acute physiological characteristics of swallowing impairment following thermal burn injury. A series of 19 participants admitted to a specialised burn centre with thermal burn injury were identified with suspected aspiration risk by a clinical swallow examination (CSE) conducted by a speech-language pathologist and referred to the study. Once medically stable, each then underwent more detailed assessment using both a CSE and fiberoptic evaluation of swallowing (FEES). FEES confirmed six individuals (32%) had no aspiration risk and were excluded from further analyses. Of the remaining 13, CSE confirmed that two had specific oral-phase deficits due to orofacial scarring and contractures, and all 13 had generalised oromotor weakness. FEES revealed numerous pharyngeal-phase deficits, with the major findings evident in greater than 50% being impaired secretion management, laryngotracheal edema, delayed swallow initiation, impaired sensation, inadequate movement of structures within the hypopharynx and larynx, and diffuse pharyngeal residue. Penetration and/or aspiration occurred in 83% (n = 10/12) of thin fluids trials, with a lack of response to the penetration/aspiration noted in 50% (n = 6/12 penetration aspiration events) of the cases. Most events occurred post swallow. Findings support the fact that individuals with dysphagia post thermal burn present with multiple risk factors for aspiration that appear predominantly related to generalised weakness and inefficiency and further impacted by edema and sensory impairments. Generalised oromotor weakness and orofacial contractures (when present) impact oral-stage swallow function. This study has identified a range of factors that may contribute to both oral- and pharyngeal-stage dysfunction in this clinical population and has highlighted the importance of using a combination of clinical and instrumental assessments to fully understand the influence of burn injury on oral intake and swallowing