SNP characteristics predict replication success in association studies

Successful independent replication is the most direct approach for distinguishing real genotype–disease associations from false discoveries in genome-wide association studies (GWAS). Selecting SNPs for replication has been primarily based on P values from the discovery stage, although additional characteristics of SNPs may be used to improve replication success. We used disease-associated SNPs from more than 2,000 published GWASs to identify predictors of SNP reproducibility. SNP reproducibility was defined as a proportion of successful replications among all replication attempts. The study reporting association for the first time was considered to be discovery and all consequent studies targeting the same phenotype replications. We found that ?Log(P), where P is a P value from the discovery study, is the strongest predictor of the SNP reproducibility. Other significant predictors include type of the SNP (e.g., missense vs intronic SNPs) and minor allele frequency. Features of the genes linked to the disease-associated SNP also predict SNP reproducibility. Based on empirically defined rules, we developed a reproducibility score (RS) to predict SNP reproducibility independently of ?Log(P). We used data from two lung cancer GWAS studies as well as recently reported disease-associated SNPs to validate RS. Minus Log(P) outperforms RS when the very top SNPs are selected, while RS works better with relaxed selection criteria. In conclusion, we propose an empirical model to predict SNP reproducibility, which can be used to select SNPs for validation and prioritization.     

Effect of physostigmine and scopolamine on the memory functions of chess players

Six young trained chess players received 10 consecutive tasks comprising problematic play position at chess. Each subject was tested four times with drug orders balanced across subjects. Compared with saline placebo, physostigmine (20 microgram/kg i.v.) in the presence of peripheral muscarinic blockade (methylscopolamine 6 microgram/kg i.v.) impaired the performance of good players, but the amount of correct solutions was increased when the initial performance level was low. Scopolamine (6 microgram/kg i.v.) impaired the performance of all subjects, and saline placebo proved inactive. The effect of scopolamine together with physostigmine was about the average of the separate effects of these drugs. The subjects talked less, when mildly sedated, and felt nauseated after the physostigmine treatment. Antimuscarinics with and without physostigmine caused cycloplegia in all subjects.     

Local adaptation does not always predict high mating success

The hypothesis that adaptation to local environments can increase mating success was tested using ten replicate lines of Drosophila melanogaster adapted either to 16 °C or to 25 °C. Competitive mating trials at both temperatures were performed with males taken from a pair of lines, one adapted to each temperature. There was no average increase in mating success for males adapted to the local environment. Although one pair of lines showed the expected pattern, another pair showed the reverse pattern. More data are needed on this hypothesis, preferably with lines that have more strongly adapted to local environments.     

Physical characteristics that predict functional performance in Division I college football players

Strength and conditioning professionals who work with collegiate football players focus much of their time and effort on developing programs to enhance athletic performance. Although there has been much speculation, there is little scientific evidence to suggest which combination of physical characteristics best predicts athletic performance in this population. The purpose of this investigation was to examine the relationship among 6 physical characteristics and 3 functional measures in college football players. Data were gathered on 46 NCAA Division I college football players. The 3 response variables were 36.6-m sprint, 18.3-m shuttle run, and vertical jump. The 6 regressor variables were height, weight, percentage of body fat, hamstring length, bench press, and hang clean. A stepwise multiple regression analysis was performed to screen for variables that predict physical performance. Regression analysis revealed clear prediction models for the 36.6-m sprint and 18.3-m shuttle run. The results of this investigation will help strength and conditioning specialists better understand the variables that predict athletic performance in Division I college football players.     

Analytical functions to predict cosmic-ray neutron spectra in the atmosphere

Estimation of cosmic-ray neutron spectra in the atmosphere has been an essential issue in the evaluation of the aircrew doses and the soft-error rates of semiconductor devices. We therefore performed Monte Carlo simulations for estimating neutron spectra using the PHITS code in adopting the nuclear data library JENDL-High-Energy file. Excellent agreements were observed between the calculated and measured spectra for a wide altitude range even at the ground level. Based on a comprehensive analysis of the simulation results, we propose analytical functions that can predict the cosmic-ray neutron spectra for any location in the atmosphere at altitudes below 20 km, considering the influences of local geometries such as ground and aircraft on the spectra. The accuracy of the analytical functions was well verified by various experimental data.     

Exploiting multi-layered information to iteratively predict protein functions

BackgroundSimilarity based computational methods are a useful tool for predicting protein functions from protein–protein interaction (PPI) datasets. Although various similarity-based prediction algorithms have been proposed, unsatisfactory prediction results have occurred on many occasions. The purpose of this type of algorithm is to predict functions of an unannotated protein from the functions of those proteins that are similar to the unannotated protein. Therefore, the prediction quality largely depends on how to select a set of proper proteins (i.e., a prediction domain) from which the functions of an unannotated protein are predicted, and how to measure the similarity between proteins. Another issue with existing algorithms is they only believe the function prediction is a one-off procedure, ignoring the fact that interactions amongst proteins are mutual and dynamic in terms of similarity when predicting functions. How to resolve these major issues to increase prediction quality remains a challenge in computational biology.ResultsIn this paper, we propose an innovative approach to predict protein functions of unannotated proteins iteratively from a PPI dataset. The iterative approach takes into account the mutual and dynamic features of protein interactions when predicting functions, and addresses the issues of protein similarity measurement and prediction domain selection by introducing into the prediction algorithm a new semantic protein similarity and a method of selecting the multi-layer prediction domain. The new protein similarity is based on the multi-layered information carried by protein functions. The evaluations conducted on real protein interaction datasets demonstrated that the proposed iterative function prediction method outperformed other similar or non-iterative methods, and provided better prediction results.ConclusionsThe new protein similarity derived from multi-layered information of protein functions more reasonably reflects the intrinsic relationships among proteins, and significant improvement to the prediction quality can occur through incorporation of mutual and dynamic features of protein interactions into the prediction algorithm.     

Inflammatory response and neutrophil functions in players after a futsal match

Inflammatory response and neutrophil functions in players after a futsal match. J Strength Cond Res 26(9): 2507-2514, 2012-Futsal players suffer injuries resulting from muscle fatigue and contact or collision among players. Muscle lesions can be detected by measuring muscle lesion markers such as creatine kinase (CK) and lactate dehydrogenase (LDH) in plasma. After an initial lesion, there is an increase in the plasma levels of C-reactive protein (CRP) and proinflammatory cytokines. These mediators may activate neutrophils and contribute to tissue damage and increase susceptibility to invasive microorganisms. In this study, we investigated the effect of a futsal match on muscle lesion markers, cytokines, and CRP in elite players. The basal and stimulated neutrophil responsiveness after a match was also evaluated based on measurements of neutrophil necrosis, apoptosis, phagocytic capacity, reactive oxygen species (ROS) production, and cytokines (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-8, IL-1β, IL-10, and IL-1ra) production. Blood samples were taken from 16 players (26.4 ± 3.2 years, 70.2 ± 6.9 kg, 59.7 ± 5.1 ml·kg·min, sports experience of 4.4 ± 0.9 years) before and immediately after a match. Exercise increased the serum activities of CK (2.5-fold) and LDH (1.3-fold). Playing futsal also increased the serum concentrations of IL-6 (1.6-fold) and CRP (1.6-fold). The TNF-α, IL-1β, IL-8, IL-1ra, and IL-10 serum levels were not modified in the conditions studied. The futsal match induced neutrophil apoptosis, as indicated by phosphatidylserine externalization (6.0-fold). The exercise induced priming of neutrophils by increasing ROS (1.3-fold), TNF-α (5.8-fold), and IL-1β (4.8-fold) released in nonstimulated cells. However, in the stimulated condition, the exercise decreased neutrophil function, diminishing the release of ROS by phorbol myristate acetate-stimulated neutrophils (1.5-fold), and the phagocytic capacity (1.6-fold). We concluded that playing futsal induces inflammation, primes and activates neutrophils, and reduces the efficiency of neutrophil phagocytosis immediately after a match.     

Malaria infection and feather growth rate predict reproductive success in house martins

Carry-over effects take place when events occurring in one season influence individual performance in a subsequent season. Blood parasites (e.g. Plasmodium and Haemoproteus) have strong negative effects on the body condition of their hosts and could slow the rate of feather growth on the wintering grounds. In turn, these winter moult costs could reduce reproductive success in the following breeding season. In house martins Delichon urbica captured and studied at a breeding site in Europe, we used ptilochronology to measure growth rate of tail feathers moulted on the winter range in Africa, and assessed infection status of blood parasites transmitted on the wintering grounds. We found a negative association between haemosporidian parasite infection status and inferred growth rate of tail feathers. A low feather growth rate and blood parasite infections were related to a delay in laying date in their European breeding quarters. In addition, clutch size and the number of fledglings were negatively related to a delayed laying date and blood parasite infection. These results stress the importance of blood parasites and feather growth rate as potentially mechanisms driving carry-over effects to explain fitness differences in wild populations of migratory birds.     

Executive functions of six-year-old boys with normal birth weight and gestational age

Impaired fetal development, reflected by low birth weight or prematurity, predicts an increased risk for psychopathology, especially attention deficit hyperactivity disorder (ADHD). Such effects cut across the normal range of birth weight and gestation. Despite the strength of existing epidemiological data, cognitive pathways that link fetal development to mental health are largely unknown. In this study we examined the relation of birth weight (>2500 g) and gestational age (37-41 weeks) within the normal range with specific executive functions in 195 Singaporean six-year-old boys of Chinese ethnicity. Birth weight adjusted for gestational age was used as indicator of fetal growth while gestational age was indicative of fetal maturity. Linear regression revealed that increased fetal growth within the normal range is associated with an improved ability to learn rules during the intra/extra-dimensional shift task and to retain visual information for short period of time during the delayed matching to sample task. Moreover, faster and consistent reaction times during the stop-signal task were observed among boys born at term, but with higher gestational age. Hence, even among boys born at term with normal birth weight, variations in fetal growth and maturity showed distinct effects on specific executive functions.     

Hormone levels predict individual differences in reproductive success in a passerine bird

Hormones mediate major physiological and behavioural components of the reproductive phenotype of individuals. To understand basic evolutionary processes in the hormonal regulation of reproductive traits, we need to know whether, and during which reproductive phases, individual variation in hormone concentrations relates to fitness in natural populations. We related circulating concentrations of prolactin and corticosterone to parental behaviour and reproductive success during both the pre-breeding and the chick-rearing stages in both individuals of pairs of free-living house sparrows, Passer domesticus. Prolactin and baseline corticosterone concentrations in pre-breeding females, and prolactin concentrations in pre-breeding males, predicted total number of fledglings. When the strong effect of lay date on total fledgling number was corrected for, only pre-breeding baseline corticosterone, but not prolactin, was negatively correlated with the reproductive success of females. During the breeding season, nestling provisioning rates of both sexes were negatively correlated with stress-induced corticosterone levels. Lastly, individuals of both sexes with low baseline corticosterone before and high baseline corticosterone during breeding raised the most offspring, suggesting that either the plasticity of this trait contributes to reproductive success or that high parental effort leads to increased hormone concentrations. Thus hormone concentrations both before and during breeding, as well as their seasonal dynamics, predict reproductive success, suggesting that individual variation in absolute concentrations and in plasticity is functionally significant, and, if heritable, may be a target of selection.     

Cues to fertility: perceived attractiveness and facial shape predict reproductive success

Attractive facial features in women are assumed to signal fertility, but whether facial attractiveness predicts reproductive success in women is still a matter of debate. We investigated the association between facial attractiveness at young adulthood and reproductive life history—number of children and pregnancies—in women of a rural community. For the analysis of reproductive success, we divided the sample into women who used contraceptives and women who did not. Introducing two-dimensional geometric morphometric methodology, we analysed which specific characteristics in facial shape drive the assessment of attractiveness and covary with lifetime reproductive success. A set of 93 (semi)landmarks was digitized as two-dimensional coordinates in postmenopausal faces. We calculated the degree of fluctuating asymmetry and regressed facial shape on facial attractiveness at youth and reproductive success. Among women who never used hormonal contraceptives, we found attractive women to have more biological offspring than less attractive women. These findings are not affected by sociodemographic variables. Postmenopausal faces corresponding to high reproductive success show more feminine features—facial characteristics previously assumed to be honest cues to fertility. Our findings support the notion that facial attractiveness at the age of mate choice predicts reproductive success and that facial attractiveness is based on facial characteristics, which seem to remain stable until postmenopausal age.     

Grapevine genotype susceptibility to Xylella fastidiosa does not predict vector transmission success

For vector-borne diseases, interactions between vector, host, and pathogen can influence patterns of disease spread. In particular, previous studies suggest that host genotype may influence disease dynamics because of differences in susceptibility to the pathogen and, therefore, subsequent vector transmission efficiency from these plants. We tested this hypothesis by using the pathogenic bacterium Xylella fastidiosa, the etiological agent of Pierce's disease in grapevines, and its leafhopper vector Homalodisca vitripennis (Germar). Pathogen infection level and transmission efficiency among several widely cultivated red and white wine, table, and raisin grape cultivars, were compared with the expectation that vector transmission rate would differ among cultivars, because of underlying differences in susceptibility to infection. The 14 grapevine genotypes evaluated showed significant differences among cultivars in the populations of X. fastidiosa that developed in petioles. 'Flame seedless' hosted the highest bacterial populations, between 1.81 and 2.05 times higher than the least susceptible 'Merlot', 'Crimson seedless', 'Grenache Noir', and 'Rubired'. Although the transmission rate of X. fastidiosa by H. vitripennis varied substantially (zero to 33%), it was not significantly different among cultivars. These results suggest that either the relationship between vine infection level and transmission is weaker than previously reported, or innate differences in vector preference among cultivars confounded any effects of vine susceptibility to infection.     

Portage connectivity does not predict establishment success of canoe-mediated dispersal for crustacean zooplankton

Although community structure may be largely determined by local abiotic and biotic conditions under moderate levels of dispersal, anthropogenic activities can enhance dispersal rates far beyond what would otherwise occur in natural systems. We investigated the potential impact of recreational canoeing on crustacean zooplankton community structure in Killarney Provincial Park, Canada, where canoes that are transported between lakes via portage routes may enhance zooplankton community connectivity by providing a dispersal “short-cut.” We conducted a study to (1) quantify zooplankton attachment to canoe hulls after paddling through a lake and assess the importance of canoes to overall seasonal dispersal within a lake relative to other means of dispersal, (2) test the prediction that zooplankton survivorship is negatively correlated with portage duration using a mesocosm experiment, and (3) test whether variation in lake community composition was better explained by models based on reduced portage-corrected distances or true edge-to-edge distances between lakes along popular canoe routes. Here, we report the findings that canoes have the potential to act as frequent dispersal vectors, but appear to have little impact on community structure in portage-connected lakes. Substantial numbers of adult zooplankton became attached to canoe hulls and were able to establish viable populations even after exposure to portage conditions for 30 min. However, canoe-mediated dispersal only accounted for a very small proportion (<1% in this case) of overall seasonal dispersal. Moreover, environmental variables explained the greatest amount of variation in community composition among park lakes. Nevertheless, this study indicates that canoe dispersal could be more effective for specific species such as Sida crystallina than is evident by analysis of entire communities and could facilitate the spread of invasive species amenable to attaching to boat hulls. Thus, the debate about whether community composition is more strongly influenced by local environmental conditions or regional dispersal may vary depending on the scale of consideration (i.e., individual species vs. whole community).     

Voice and handgrip strength predict reproductive success in a group of indigenous african females

Evolutionary accounts of human traits are often based on proxies for genetic fitness (e.g., number of sex partners, facial attractiveness). Instead of using proxies, actual differences in reproductive success is a more direct measure of Darwinian fitness. Certain voice acoustics such as fundamental frequency and measures of health such as handgrip strength correlate with proxies of fitness, yet there are few studies showing the relation of these traits to reproduction. Here, we explore whether the fundamental frequency of the voice and handgrip strength account for differences in actual reproduction among a population of natural fertility humans. Our results show that both fundamental frequency and handgrip strength predict several measures of reproductive success among a group of indigenous Namibian females, particularly amongst the elderly, with weight also predicting reproductive outcomes among males. These findings demonstrate that both hormonally regulated and phenotypic quality markers can be used as measures of Darwinian fitness among humans living under conditions that resemble the evolutionary environment of Homo sapiens. We also argue that these findings provide support for the Grandmother Hypothesis.