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Objectives: Craniofacial fluctuating asymmetry (FA) refers to the random deviations from symmetry exhibited across the craniofacial complex and can be used as a measure of developmental instability for organisms with bilateral symmetry. This article addresses the lack of data on craniofacial FA in nonhuman primates by analyzing FA magnitude and variation in chimpanzees, gorillas, and macaques. We offer a preliminary investigation into how FA, as a proxy for developmental instability, varies within and among nonhuman primates. Materials and Methods: We generated 3D surface models of 121 crania from Pan troglodytes troglodytes, Gorilla gorilla gorilla, and Macaca fascicularis fascicularis. Using geometric morphometric techniques, the magnitude of observed FA was calculated and compared for each individual, sex, and taxon, along with the variation of FA across cranial regions and for each bilateral landmark. Results: Gorillas and macaques exhibited higher and more similar magnitudes of FA to each other than either taxon did to chimpanzees; variation in magnitude of FA followed this same trend. No significant differences were detected between sexes using pooled data across species, but sex did influence FA magnitude within taxa in gorillas. Further, variation in FA variance across cranial regions and by landmark was not distributed in any particular pattern. Conclusion: Possible environmentally induced causes for these patterns of FA magnitude include differences in growth rate and physiological stress experienced during life. Developmental stability may be greatest in chimpanzees in this sample. Additionally, these results point to appropriate landmarks for future FA analyses and may help suggest more urgent candidate taxa for conservation efforts. [ABSTRACT FROM AUTHOR]

Fluctuating asymmetry is a result of the organism's inability to develop in a certain way and exhibits disruptions in its early-stage developmental stability. The analysis of fluctuating asymmetry levels in anuran populations allows for a parallel assessment of the quality of the living environment. Meristic traits of anurans, such as colour marks (stripes and spots) on the backside of the body and limbs, are suitable for measuring levels of fluctuating asymmetry. The current study applies the method of fluctuating asymmetry in meristic morphological traits in adult individuals of B. viridis as a biomarker for assessment of the environmental quality of two semi-natural habitats - Halm Bunardzhik Hill (site 1) and Mladezhki Halm Hill (site 2), located in a highly urbanised area of Plovdiv City, Bulgaria. This study recorded low levels of fluctuating asymmetry for individuals of B. viridis from both sites: 0.27 (site 1) and 0.25 (site 2) for both studied hills, respectively. The low asymmetry levels reported for individuals of B. viridis from both sites indicated that their early stages of development had occurred under good environmental conditions, with a minimum risk of disturbances in their developmental stability. These results suggested that the environmental conditions at both sites were good at the time of the study. [ABSTRACT FROM AUTHOR]

It is generally believed that rice landraces with long culms are susceptible to lodging, and have not been utilized for breeding to improve lodging resistance. However, little is known about the structural culm strength of landraces and their beneficial genetic loci. Therefore, in this study, genome-wide association studies (GWAS) were performed using a rice population panel including Japanese rice landraces to identify beneficial loci associated with strong culms. As a result, the landraces were found to have higher structural culm strength and greater diversity than the breeding varieties. Genetic loci associated with strong culms were identified, and it was demonstrated that haplotypes with positive effects of those loci were present in a high proportion of these landraces. These results indicated that the utilization of the strong culm-associated loci present in Japanese rice landraces may further improve the lodging resistance of modern breeding varieties that have relied on semi-dwarfism. [ABSTRACT FROM AUTHOR]

Recent predictions on climate change indicate that high temperature episodes are expected to impact rice production and productivity worldwide. The present investigation was undertaken to assess the yield stability of 72 rice hybrids and their parental lines across three temperature regimes over two consecutive dry seasons using the additive main effect and multiplicative interaction (AMMI), genotype and genotype × environment interaction (GGE) stability model analysis. The combined ANOVA revealed that genotype × environment interaction (GEI) were significant due to the linear component for most of the traits studied. The AMMI and GGE biplot explained 57.2% and 69% of the observed genotypic variation for grain yield, respectively. Spikelet fertility was the most affected yield contributing trait and in contrast, plant height and tiller numbers were the least affected traits. In case of spikelet fertility, grain yield and other yield contributing traits, male parent contributed towards heat tolerance of the hybrids compared to the female parent. The parental lines G74 (IR58025B), G83 (IR40750R), G85 (C20R) and hybrids [G21 (IR58025A × KMR3); G3 (APMS6A × KMR3); G57 (IR68897A × KMR3) and G41 (IR79156A × RPHR1005)] were the most stable across the environments for grain yield. They can be considered as potential genotypes for cultivation under high temperature stress after evaluating under multi location trials. [ABSTRACT FROM AUTHOR]

Gene expression data obtained in large studies hold great promises for discovering disease signatures or subtypes through data analysis. It is also prone to technical variation, whose removal is essential to avoid spurious discoveries. Because this variation is not always known and can be confounded with biological signals, its removal is a challenging task. Here we provide a step-wise procedure and comprehensive analysis of the MINDACT microarray dataset. The MINDACT trial enrolled 6693 breast cancer patients and prospectively validated the gene expression signature MammaPrint for outcome prediction. The study also yielded a full-transcriptome microarray for each tumor. We show for the first time in such a large dataset how technical variation can be removed while retaining expected biological signals. Because of its unprecedented size, we hope the resulting adjusted dataset will be an invaluable tool to discover or test gene expression signatures and to advance our understanding of breast cancer. Laurent Jacob et al. develop a workflow and analytical pipeline to remove technical variation from the MINDACT microarray dataset. Their method preserved biological signals and the normalized datasets can be repurposed for the discovery of other biomarkers and signatures for breast cancer. [ABSTRACT FROM AUTHOR]

Abstract The robustness of biological systems against mutational and environmental perturbations is termed canalization. Because reducing phenotypic variability under environmental and genetic perturbations can be adaptive and facilitated by natural selection, it has been suggested that once canalization mechanisms have evolved to buffer the effects of environmental perturbations, they may act to buffer any and all sources of variation. Although whether canalization mechanisms are general or specific to the types of perturbation or phenotypic traits that they buffer is often addressed, the links between different canalization mechanisms remain unclear. In this review, three major sources of phenotypic variation, associated canalization concepts and indicators of the degree of canalization are first outlined. Then, the molecular bases of canalization mechanisms based on recent empirical studies are overviewed. Finally, the links between the underlying processes of different canalization mechanisms are explored. [ABSTRACT FROM AUTHOR]

Developmental instability provides a powerful monitoring tool to detect threats prior to population declines. Consequently, assessing the level of developmental instability by measuring fluctuating asymmetry (FA) of bilaterally symmetrical traits in association with environmental stress has become increasingly attractive. However, many studies failed in detecting a clear connection of FA to environmental stressors. Some of these may have suffered from large measurement error (ME) or the use of inappropriate methods. Here, we compared measurement accuracy and FA outcome from manual calliper measurements with those from non-destructive micro-3D-computed tomography (µCT) based skeletal measurements. Amphibians are assumed to be ideal models for measuring fluctuating asymmetry due to their sensitivity to environmental stress. For our study, we chose two bilateral, metric traits (femur and radio--ulna length) of the European Common Frog, Rana temporaria. Calliper measurements revealed meaningful FA estimates (i.e., FA exceeded ME) for radio-- ulna length only. In contrast, µCT-based measurements delivered meaningful FA estimates for both traits. ME was about twice as high for calliper measurements compared to µCT-based measurements, resulting in inflated levels of FA. Using callipers, we observed higher ME for femur measurements than for radio--ulna, meaning that ME strongly depended on the respective trait. When using µCT, however, we observed comparable ME between both traits. Our study revealed that analyses of developmental instability using manual measurements should be treated with caution. For smaller vertebrates we recommend skeletal measurements with µCT as a valuable alternative due to its greater reliability, thereby allowing for multi-trait analyses with equal accuracy. [ABSTRACT FROM AUTHOR]

The behavioral competence of captive‐bred individuals – an important source population for translocation programs – may differ from that of wild‐born individuals and these differences may influence post‐release survival. Some behaviors will be more robust, or developmentally stable, than others in the face of the environmental novelties of captivity. Here, we investigated developmental stability of foraging behavior by quantifying bamboo feeding behavior in captive‐bred and wild‐born giant pandas, Ailuropoda melanleuca. As an energy‐limited species adapted to a low‐nutrition diet, any reductions in feeding efficiency may compromise post‐release survival. Using video of 22 captive pandas, we measured several components of the panda's elaborate bamboo feeding behavior repertoire. We found that captive‐born and wild‐born pandas displayed the same repertoire of feeding behaviors, suggesting developmental stability in these motor patterns, but that they employed them differently with different parts of the bamboo. Captive‐born pandas devoted less time and effort to handling and chewing leaves while allocating more effort to the consumption of large culms than did wild‐born pandas. Captive‐born pandas also handled small culm and stripped small culms to prepare them for consumption less often than did wild‐born pandas. All of these behavioral differences indicate that wild‐born pandas in captivity behave in a manner more similar to wild pandas, and focus their behavioral effort on more nutritious bamboo. Thus, these aspects of captive‐born panda feeding behavior may be compromised, and were not developmentally stable in the captive environment. These behavioral differences are cause for concern and should be the subject of future study to determine whether they forecast compromised fitness in translocations. Evaluating developmental stability and behavioral competence should be a key component of captive‐release translocation programs, serving to guide pre‐release training and selection of individuals to be released. The behavioral competence of captive‐bred individuals may differ from that of wild‐born individuals and these differences may influence post‐release survival in translocation programs. We investigated developmental stability of foraging behavior by quantifying bamboo‐feeding behavior in captive‐bred and wild‐born giant pandas. Wild‐born pandas in captivity behaved in a manner more similar to wild pandas, and focused their behavioral effort on more nutritious bamboo, indicating that captive‐born panda feeding behavior may be compromised and that feeding behavior is influenced by development in a captive environment. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: More symmetric organisms are perceived as more attractive. Fluctuating asymmetry (FA) i.e. small, random deviations from perfect bilateral symmetry, is supposed to inform about developmental instability. According to the good genes hypothesis, a low level of FA is a putative cue to an organism's biological quality. An important aspect of this quality is the immune system functioning. The aim of this study was to evaluate the relationship between immune system functioning and body symmetry in healthy people. Materials and Methods: The composite body FA (cFA) was assessed on the basis of six bilateral traits (on hands and feet). The ISF was determined by many innate (total complement and lysozyme activity, neutrophils function) and adaptive immune parameters (T CD3 and B CD19 lymphocytes, total IgA and IgG and response to flu vaccine). A total of 98 men and 92 women were subjected to flu (among them 37 men and 30 women also to tetanus) vaccination. The blood samples were collected before and 4 weeks after the antigens exposure. Immunomodulatory factors: participant's age, body fat, and free testosterone level, were controlled. Results: Apart from the weak positive association between CD3 or CD19 and cFA in men, we found no association between the level of body symmetry and the rest of the analyzed immune parameters for both sexes. Discussion: Our results are the opposite of the good genes hypothesis prediction and suggest that in western, healthy populations, human mate preferences for more symmetric bodies are not related to immune competence. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The evaluation of developmental stability (DS) by measuring fluctuating asymmetry (FA), a bioindicator of general cumulative stress, is an approach that has often been used to characterize health status in past populations. New techniques of geometric morphometrics now enable a better appreciation of FA than before, with a more refined quantification of variation. The aim of our study is to determine the effectiveness of geometric morphometrics analyses of asymmetry in the human femur for the study of individual DS and inferring health status of human populations. Materials and methods: We conducted a comparative analysis between two diachronic populations of distinct and known health status. Two samples of 70 pairs of adult femurs from individuals of comparable age range and sex were selected and CT‐scanned. For each 3D reconstruction, two sets of 27 landmarks were digitized to quantify and minimize the effect of measurement error on the evaluation of FA. Results: While the measurement of FA in femoral centroid size seemed comparable between the samples, the amount of FA in femoral shape differed. Individuals who experienced high levels of environmental stress presented higher intra‐individual variation. In parallel, results did not reveal any significant differences in DS between sexes or age groups. Discussion: The geometric morphometrics analysis of femoral asymmetry was effective for distinguishing two populations. After considering various factors of influence, genetics and biomechanics seem to have a limited impact on the results. Expressing FA appears to be normal but dependent on the disturbances of DS produced by environmental stress. [ABSTRACT FROM AUTHOR]

Abstract: The evolution of phenotypic plasticity of plant traits may be constrained by costs and limits. However, the precise constraints are still unclear for many traits under different ecological contexts. In a glasshouse experiment, we grew ramets of 12 genotypes of a clonal plant Hydrocotyle vulgaris under the control (full light and no flood), shade and flood conditions and tested the potential costs and limits of plasticity in 13 morphological and physiological traits in response to light availability and flood variation. In particular, we used multiple regression and correlation analyses to evaluate potential plasticity costs, developmental instability costs and developmental range limits of each trait. We detected significant costs of plasticity in specific petiole length and specific leaf area in response to shade under the full light condition and developmental range limits in specific internode length and intercellular CO2 concentration in response to light availability variation. However, we did not observe significant costs or limits of plasticity in any of the 13 traits in response to flood variation. Our results suggest that the evolution of phenotypic plasticity in plant traits can be constrained by costs and limits, but such constraints may be infrequent and differ under different environmental contexts. [ABSTRACT FROM AUTHOR]

Beekeeping with the western honey bee ( Apis mellifera ) is important in tropical regions but scant information is available on the possible consequences of global warming for tropical beekeeping. We evaluated the effect of heat stress on developmental stability, the age at onset of foraging (AOF) and longevity in Africanized honey bees (AHBs) in the Yucatan Peninsula of Mexico, one of the main honey producing areas in the Neotropics, where high temperatures occur in spring and summer. To do so, we reared worker AHB pupae under a fluctuating temperature regime, simulating current tropical heatwaves, with a high temperature peak of 40.0 °C for 1 h daily across six days, and compared them to control pupae reared at stable temperatures of 34.0–35.5 °C. Heat stress did not markedly affect overall body size, though the forewing of heat-stressed bees was slightly shorter than controls. However, bees reared under heat stress showed significantly greater fluctuating asymmetry (FA) in forewing shape. Heat stress also decreased AOF and reduced longevity. Our results show that changes occur in the phenotype and behavior of honey bees under heat stress, with potential consequences for colony fitness. [ABSTRACT FROM AUTHOR]

The relationship between the general factor of intelligence ( g ) and handedness is investigated using a combined sample of 23511 respondents from three large databases: the NLSY’79 (US), NLSY’97 (US) and NCDS (UK). Dextrals – those who use their right hands were found to be 1.22 IQ points higher than sinistrals (left handers) after controlling for sex and age and correcting for sources of measurement error. To see if the association between IQ and handedness was strongest on the abilities that were the best measures of g, the method of correlated vectors was used to test for moderation. Across the three studies, g was found to very weakly negatively moderate the association between ability measure and handedness ( ρ  = −.023, K  = 3, N  = 23511), however in the NLSY’79, the coding speed subtest was an outlier in terms of the strength of its association with handedness. Its removal yielded indications of positive moderation in this dataset, which when aggregated boosted the overall vector correlation value to .539 ( K  = 3, N  = 23511), suggesting that g might be an important moderator of this relationship. Secondary analysis of secular trend data on the changing percentage of sinistrals in Western populations indicates that overall, sinistrality has increased, entailing a g decline of .106 points over 150 years (.006 points per decade). The secular increase in sinistrality is consistent with other data indicating long-term declines in developmental stability and may stem from some combination of increasing mutation load and environmental stress in Western populations. [ABSTRACT FROM AUTHOR]

The European golden jackal (Canis aureus moreoticus) is widespread in Bulgaria and it was assumed that the species had occupied almost the entire country with less manifested presence in highlands. The general aim of this investigation was to carry out comparative analysis at a population level of developmental stability of the jackal inhabiting in different habitats (POP_1, inhabiting Sakar-Strandzha region, POP_2 inhabiting the Upper Thracian Plain and POP_3 inhabiting the western part of the Sub-Balkan valleys), located along the presumable route of the species movement northwards and westwards in the country. The population levels of developmental stability were assessed through fluctuating asymmetry determined as minor non-directional deviations from bilateral symmetry in 10 morphological nonmetric skull characters. Looking at the fluctuating asymmetry as an indicator of environmental and genetic stress, there is no evidence of genetic depression by reproductive isolation in the studied populations. Moreover, there is no indication of relatively reduced developmental stability in any of the analyzed populations. In general, the results from the comparative population analysis of the craniological epigenetic fluctuating asymmetry in Bulgarian golden jackal with regard to the population developmental stability provided a substantial biological basis for their interpretation as biomonitor characteristics in a future biological monitoring of this species in the country. [ABSTRACT FROM AUTHOR]

Diversified bet-hedging ( DBH) by production of within-genotype phenotypic variance may evolve to maximize fitness in stochastic environments. Bet-hedging is generally associated with parental effects, but phenotypic variation may also develop throughout life via developmental instability ( DI). This opens for the possibility of a within-generation mechanism creating DBH during the lifetime of individuals. If so, DI could in fact be a plastic trait itself; if a fluctuating environment indicates uncertainty about future conditions, sensing such fluctuations could trigger DI as a DBH response. However, this possibility has received little empirical attention. Here, we test whether fluctuating environments may elicit such a response in the clonally reproducing crustacean Daphnia magna. Specifically, we exposed genetically identical individuals to two environments of different thermal stability (stable vs. pronounced daily realistic temperature fluctuations) and tested for effects on DI in body mass and metabolic rate shortly before maturation. Furthermore, we also estimated the genetic variation in DI. Interestingly, fluctuating temperatures did not affect body mass, but metabolic rate decreased. We found no evidence for plasticity in DI in response to environmental fluctuations. The lack of plasticity was common to all genotypes, and for both traits studied. However, we found considerable evolvability for DI, which implies a general evolutionary potential for DBH under selection for increased phenotypic variance. [ABSTRACT FROM AUTHOR]

Developmental instability (DI) has been proposed to relate negatively to aspects of evolutionary fitness, like mating success. One suggested indicator is fluctuating asymmetry (FA), random deviations from perfect symmetry in bilateral bodily traits. A meta-analytically robust negative association between FA and number of lifetime sexual partners has been previously shown in men and women. We examined the relationship between bodily FA across twelve traits and indicators of quantitative mating success in 284 individuals (141 males, age 19–30 years). Two further indicators of DI, minor physical anomalies (MPAs) and asymmetry in palmar atd angles, were also assessed. For men, no significant associations were detected, whereas for women, unexpected positive relationships of FA with the number of lifetime sexual partners and one-night stands emerged. Thus, in a large sample and using a more highly aggregated FA index, our study fails to replicate previous findings, though equivalence testing also did not support deviation from previous meta-analytic estimates, especially for men. No associations were found for MPAs and FA in atd angles in either sex. [ABSTRACT FROM AUTHOR]

To assess the prevalence of CYP3A5 genomic variances and their impact on tacrolimus (TAC) dosing requirements among kidney transplant recipients in eastern North Carolina, we conducted a single-center retrospective cohort study at a large tertiary care medical center. A total of 162 adults who received a kidney transplant between March 1, 2013, and February 28, 2015, and received oral TAC as part of their maintenance immunosuppression were enrolled. Of these patients, 85 patients expressed a genotype with a CYP3A5*1 variant ( C YP 3A5*1 group), and 77 patients expressed genotypes with other CYP3A5 variants (nonexpressor group). All patients were followed for 1 year posttransplantation. The primary end point was the TAC total daily dose ( TDD) required to achieve the first therapeutic trough level based on the presence or absence of the CYP3A5*1 variant. The prevalence of different CYP3A5 variants across race/ethnicities in the study cohort was determined by CYP3A5 genotyping for each patient. The C YP 3A5*1 and nonexpressor groups did not differ significantly with respect to sex, mean age, or mean weight. The CYP3A5*1 group was largely African American (93%, p≤0.0005) compared with other race/ethnicities. Among the CYP3A5*1 expressors compared with nonexpressors, the mean TAC TDD in milligrams at the first therapeutic TAC level was significantly higher (12 vs 8 mg/day, p≤0.001). Similarly, the mean TAC TDD in milligrams/kilogram was 50% greater among CYP3A5*1 expressors (0.15 vs 0.1 mg/kg/day, p≤0.0005). The predominant genotypic variants were CYP3A5*3/*3 (33%), CYP3A5*1/*3 (20%), and CYP3A5*1/*1 (19%). This study illustrates the prevalence of the CYP3A5*1 variant among African-American kidney transplant recipients and the effect of this gene expression on the TAC TDD. Patients with the CYP3A5*1 variant require higher TAC doses, on average, to achieve desirable drug levels. In addition, this study provides transplant clinicians with insight and support to dose TAC more aggressively in African-American kidney transplant recipients who may be at higher risk for both toxicities as well as poor clinical outcomes related to inadequate immunosuppression. [ABSTRACT FROM AUTHOR]

The light environment influences an animal's ability to forage, evade predators, and find mates, and consequently is known to drive local adaptation of visual systems. However, the light environment may also vary over fine spatial scales at which genetic adaptation is difficult. For instance, in aquatic systems, the available wavelengths of light change over a few metres depth. Do animals plastically adjust their visual system to such small-scale environmental light variation? Here, we show that in three-spine stickleback ( Gasterosteus aculeatus), opsin gene expression (an important determinant of colour vision) changes over a 2-m vertical gradient in nest depth. By experimentally altering the light environment using light filters to cover enclosures in a lake, we found that opsin expression can be adjusted on a short time frame (weeks) in response to the local light environment. This is to our knowledge the smallest spatial scale on which visual adjustments through opsin expression have been recorded in a natural setting along a continuously changing light environment. [ABSTRACT FROM AUTHOR]

Using the centipede model species Strigamia maritima as a subject of study, we illustrate the potential of geometric morphometrics for investigating the development and evolution of segmentation, with a specific focus on post-embryonic segmental patterning. We show how these techniques can contribute detailed descriptive data for comparative purposes, but also precious information on some features of the developmental system that are considered relevant for the evolvability of a segmented body architecture, such as developmental stability and canalization. Morphometric analyses allow to separately investigate several sources of phenotypic variation along a segmented body axis, like constitutive and random segment heteronomy, both within and among individuals. Specifically, in S. maritima , the segmental pattern of ventral sclerite shapes mirrors that of their bilateral fluctuating asymmetry and among-individual variation in associating the most anterior and most posterior segments in diverging from the central ones. Also, among segments, there seems to be a correlation between fluctuating asymmetry and shape variation among individuals, suggesting that canalization and developmental stability are somehow associated. Overall, these associations might stem from a joint influence of the segmental position on the two processes of developmental buffering. [ABSTRACT FROM AUTHOR]

Genotype by environment interaction (G × E) in dairy cattle productive traits has been shown to exist, but current genetic evaluation methods do not take this component into account. As several environmental descriptors (e.g., climate, farming system) are known to vary within the United States, not accounting for the G × E could lead to reranking of bulls and loss in genetic gain. Using test-day records on milk yield, somatic cell score, fat, and protein percentage from all over the United States, we computed within herd-year-season daughter yield deviations for 1,087 Holstein bulls and regressed them on genetic and environmental information to estimate variance components and to assess prediction accuracy. Genomic information was obtained from a 50k SNP marker panel. Environmental effect inputs included herd (160 levels), geographical region (7 levels), geographical location (2 variables), climate information (7 variables), and management conditions of the herds (16 total variables divided in 4 subgroups). For each set of environmental descriptors, environmental, genomic, and G × E components were sequentially fitted. Variance components estimates confirmed the presence of G × E on milk yield, with its effect being larger than main genetic effect and the environmental effect for some models. Conversely, G × E was moderate for somatic cell score and small for milk composition. Genotype by environment interaction, when included, partially eroded the genomic effect (as compared with the models where G × E was not included), suggesting that the genomic variance could at least in part be attributed to G × E not appropriately accounted for. Model predictive ability was assessed using 3 crossvalidation schemes (new bulls, incomplete progeny test, and new environmental conditions), and performance was compared with a reference model including only the main genomic effect. In each scenario, at least 1 of the models including G × E was able to perform better than the reference model, although it was not possible to find the overall best-performing model that included the same set of environmental descriptors. In general, the methodology used is promising in accounting for G × E in genomic predictions, but challenges exist in identifying a unique set of covariates capable of describing the entire variety of environments. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is characterized by progressive cognitive decline and memory loss. Environmental factors and gene-environment interactions (GXE) may increase AD risk, accelerate cognitive decline, and impair learning and memory. However, there is currently little direct evidence supporting this hypothesis. Methods: In this study, we assessed for a GXE between lead and ApoE4 on cognitive behavior using transgenic knock-in (KI) mice that express the human Apolipoprotein E4 allele (ApoE4-KI) or Apolipoprotein E3 allele (ApoE3-KI). We exposed 8-week-old male and female ApoE3-KI and ApoE4-KI mice to 0.2% lead acetate via drinking water for 12 weeks and assessed for cognitive behavior deficits during and after the lead exposure. In addition, we exposed a second (cellular) cohort of animals to lead and assessed for changes in adult hippocampal neurogenesis as a potential underlying mechanism for lead-induced learning and memory deficits. Results: In the behavior cohort, we found that lead reduced contextual fear memory in all animals; however, this decrease was greatest and statistically significant only in lead-treated ApoE4-KI females. Similarly, only lead-treated ApoE4-KI females exhibited a significant decrease in spontaneous alternation in the T-maze. Furthermore, all lead-treated animals developed persistent spatial working memory deficits in the novel object location test, and this deficit manifested earlier in ApoE4-KI mice, with female ApoE4-KI mice exhibiting the earliest deficit onset. In the cellular cohort, we observed that the maturation, differentiation, and dendritic development of adult-born neurons in the hippocampus was selectively impaired in lead-treated female ApoE4-KI mice. Conclusions: These data suggest that GXE between ApoE4 and lead exposure may contribute to cognitive impairment and that impaired adult hippocampal neurogenesis may contribute to these deficits in cognitive behavior. Together, these data suggest a role for GXE and sex differences in AD risk. [ABSTRACT FROM AUTHOR]

Aims: Serial invasive endomyocardial biopsies (EMB) remain the gold standard for acute cellular rejection (ACR) diagnosis. However histological grading has several limitations. We aimed to explore the value of myocardial Gene Expression Profiling (GEP) for diagnosing and identifying predictive biomarkers of ACR. Methods: A case-control study nested within a retrospective heart transplant patients cohort included 126 patients with median (IQR) age 50 (41–57) years and 111 (88%) males. Among 1157 EMB performed, 467 were eligible (i.e, corresponding to either ISHLT grade 0 or ≥3A), among which 36 were selected for GEP according to the grading: 0 (CISHLT, n = 13); rejection ≥3A (RISHLT, n = 13); 0 one month before ACR (BRISHLT, n = 10). Results: We found 294 genes differentially expressed between CISHLT and RISHLT, mainly involved in immune activation, and inflammation. Hierarchical clustering showed a clear segregation of CISHLT and RISHLT groups and heterogeneity of GEP within RISHLT. All EMB presented immune activation, but some RISHLT EMB were strongly subject to inflammation, whereas others, closer to CISHLT, were characterized by structural modifications with lower inflammation level. We identified 15 probes significantly different between BRISHLT and CISHLT, including the gene of the muscular protein TTN. This result suggests that structural alterations precede inflammation in ACR. Linear Discriminant Analysis based on these 15 probes was able to identify the histological status of every 36 samples. Conclusion: Myocardial GEP is a helpful method to accurately diagnose ACR, and predicts rejection one month before its histological occurrence. These results should be considered in cardiac allograft recipients’ care. [ABSTRACT FROM AUTHOR]

Background: Organisms can rapidly adapt to their environment when colonizing a new habitat, and this could occur by changing protein sequences or by altering patterns of gene expression. The importance of gene expression in driving local adaptation is increasingly being appreciated, and cis-regulatory elements (CREs), which control and modify the expression of the nearby genes, are predicted to play an important role. Here we investigate genetic variation in gene expression in immune-challenged Drosophila melanogaster from temperate and tropical or sub-tropical populations in Australia and United States. Results: We find parallel latitudinal changes in gene expression, with genes involved in immunity, insecticide resistance, reproduction, and the response to the environment being especially likely to differ between latitudes. By measuring allele-specific gene expression (ASE), we show that cis-regulatory variation also shows parallel latitudinal differences between the two continents and contributes to the latitudinal differences in gene expression. Conclusions: Both Australia and United States were relatively recently colonized by D. melanogaster, and it was recently shown that introductions of both African and European flies occurred, with African genotypes contributing disproportionately to tropical populations. Therefore, both the demographic history of the populations and local adaptation may be causing the patterns that we see. [ABSTRACT FROM AUTHOR]

Environmental influences shape phenotypes within and across generations, often through DNA methylations that modify gene expression. Methylations were proposed to mediate caste and task allocation in some eusocial insects, but how an insect's environment affects DNA methylation in its offspring is yet unknown. We characterized parental effects on methylation profiles in the polyembryonic parasitoid wasp Copidosoma koehleri, as well as methylation patterns associated with its simple caste system. We used methylation-sensitive amplified fragment length polymorphism ( MS- AFLP) to compare methylation patterns, among (1) reproductive and soldier larvae; and (2) offspring (larvae, pupae, and adults) of wasps that were reared at either high or low larval density and mated in the four possible combinations. Methylation frequencies were similar across castes, but the profiles of methylated fragments differed significantly. Parental rearing density did not affect methylation frequencies in the offspring at any developmental stage. Principal coordinate analysis indicated no significant differences in methylation profiles among the four crossbreeding groups and the three developmental stages. Nevertheless, a clustering analysis, performed on a subset of the fragments, revealed similar methylation patterns in larvae, pupae, and adults in two of the four parental crosses. Nine fragments were methylated at two cytosine sites in all larvae, and five others were methylated at two sites in all adults. Thus, DNA methylations correlate with within-generation phenotypic plasticity due to caste. However, their association with developmental stage and with transgenerational epigenetic effects is not clearly supported. [ABSTRACT FROM AUTHOR]

Developmental stability and canalization describe the ability of developmental systems to minimize phenotypic variation in the face of stochastic micro-environmental effects, genetic variation and environmental influences. Canalization is the ability to minimize the effects of genetic or environmental effects, whereas developmental stability is the ability to minimize the effects of micro-environmental effects within individuals. Despite much attention, the mechanisms that underlie these two components of phenotypic robustness remain unknown. We investigated the genetic structure of phenotypic robustness in the collaborative cross ( CC) mouse reference population. We analysed the magnitude of fluctuating asymmetry ( FA) and among-individual variation of cranial shape in reciprocal crosses among the eight parental strains, using geometric morphometrics and a diallel analysis based on a Bayesian approach. Significant differences among genotypes were found for both measures, although they were poorly correlated at the level of individuals. An overall positive effect of inbreeding was found for both components of variation. The strain CAST/EiJ exerted a positive additive effect on FA and, to a lesser extent, among-individual variance. Sex- and other strain-specific effects were not significant. Neither FA nor among-individual variation was associated with phenotypic extremeness. Our results support the existence of genetic variation for both developmental stability and canalization. This finding is important because robustness is a key feature of developmental systems. Our finding that robustness is not related to phenotypic extremeness is consistent with theoretical work that suggests that its relationship to stabilizing selection is not straightforward. [ABSTRACT FROM AUTHOR]

Microarray gene expression data sets are jointly analyzed to increase statistical power. They could either be merged together or analyzed by meta-analysis. For a given ensemble of data sets, it cannot be foreseen which of these paradigms, merging or meta-analysis, works better. In this article, three joint analysis methods, Z-score normalization, ComBat and the inverse normal method (meta-analysis) were selected for survival prognosis and risk assessment of breast cancer patients. The methods were applied to eight microarray gene expression data sets, totaling 1324 patients with two clinical endpoints, overall survival and relapse-free survival. The performance derived from the joint analysis methods was evaluated using Cox regression for survival analysis and independent validation used as bias estimation. Overall, Z-score normalization had a better performance than ComBat and meta-analysis. Higher Area Under the Receiver Operating Characteristic curve and hazard ratio were also obtained when independent validation was used as bias estimation. With a lower time and memory complexity, Z-score normalization is a simple method for joint analysis of microarray gene expression data sets. The derived findings suggest further assessment of this method in future survival prediction and cancer classification applications. [ABSTRACT FROM AUTHOR]

Gene expression measurements represent the most important source of biological data used to unveil the interaction and functionality of genes. In this regard, several data mining and machine learning algorithms have been proposed that require, in a number of cases, some kind of data discretization to perform the inference. Selection of an appropriate discretization process has a major impact on the design and outcome of the inference algorithms, as there are a number of relevant issues that need to be considered. This study presents a revision of the current state-of-the-art discretization techniques, together with the key subjects that need to be considered when designing or selecting a discretization approach for gene expression data. [ABSTRACT FROM AUTHOR]

With the advent of high - throughput technologies large amount of protein - protein interaction data are available. Many researchers studied this data and predicted the importance of essential proteins in disease diagnosis,cosmetic development and drug design. Knockout experiments consumed more time and money while predicting the essential protein and this motivated computational biologists to develop algorithms and mathematical model to predict essential proteins. Early algorithms were based on topological properties. However the major setback to these algorithms were the unreliability of protein data. To overcome this, newly developed algorithms tried to incorporate biological properties along with the topological properties. In this study we introduce a new algorithm called,UDoGeC,Unified Domain and Gene Expression Centrality Method,which combines both the domain and gene expression profiles together. This algorithm is based on the assumption that an essential protein tends to form densely populated clusters and these clusters are strongly co-expressed. If that protein has rarely occurring domains than in other protein we predict it as essential otherwise non - essential. Finally a comparison study with three other centrality methods DC, UDoNC and PeC is performed to evaluate the performance of this newly suggested algorithm.The results were promising that UDoGeC showed better performance in various aspects. [ABSTRACT FROM AUTHOR]

Background: Medicago sativa (alfalfa) is a low-input forage and potential bioenergy crop, and improving its yield and quality has always been a focus of the alfalfa breeding industry. Transgenic alfalfa plants overexpressing a precursor of alfalfa microRNA156 (MsmiR156) were recently generated by our group. These plants (miR156OE) showed enhanced biomass yield, reduced internodal length, increased shoot branching and trichome density, and a delay in flowering time. Transcripts of three SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) genes (MsSPL6, MsSPL12, and MsSPL13) were found to be targeted for cleavage by MsmiR156 in alfalfa. Results: To further illustrate the molecular mechanisms underlying the effects of miR156 in alfalfa, two miR156OE genotypes (A11a and A17) were subjected to Next Generation RNA Sequencing with Illumina HiSeq. More than 1.11 billion clean reads were obtained from our available sequenced samples. A total of 160,472 transcripts were generated using Trinity de novo assembly and 4,985 significantly differentially expressed genes were detected in miR156OE plants A1 1a and A17 using the Medicago truncatula genome as reference. A total of 17 genes (including upregulated, downregulated, and unchanged) were selected for quantitative real-time PCR (qRT-PCR) validation, which showed that gene expression levels were largely consistent between qRT-PCR and RNA-Seq data. In addition to the established SPL genes MsSPL6, MsSPL12 and MsSPL13, four new SPLs; MsSPL2, MsSPL3, MsSPL4 and MsSPL9 were also down-regulated significantly in both miR156OE plants. These seven SPL genes belong to genes phylogeny clades VI, IV, VIII, V and VII, which have been reported to be targeted by miR156 in Arabidopsis thaliana. The gene ontology terms characterized electron transporter, starch synthase activity, sucrose transport, sucrose-phosphate synthase activity, chitin binding, sexual reproduction, flavonoid biosynthesis and lignin catabolism correlate well to the phenotypes of miR1 56OE alfalfa plants. Conclusions: This is the first report of changes in global gene expression in response to miR1 56 overexpression in alfalfa. The discovered miR156-targeted SPL genes belonging to different clades indicate miR1 56 plays fundamental and multifunctional roles in regulating alfalfa plant development. [ABSTRACT FROM AUTHOR]

To study the effects of polyphenolic extract from involucres of Castanea mollissima Blume (PICB), a novel approach using gene expression by real time polymerase chain reaction (real-time PCR) coupled with metabolomic profiling technique was established to explain the mechanism of PICB on heat-stressed broiler chicks. Four thousand 28-day-old male Arbor Acres (AA) broilers were randomly assigned to 5 groups (4 replicates / group, 20 chicks / replicate), in which group 1 was normal control group fed with basic ration; groups 2, 3, 4, and 5 were fed with the basic ration with a supplementation of 0.2% Vitamin C (VC), or 0.2%, 0.3%, or 0.4% of PICB respectively. After 1 wk of adaptation, heat stress was applied for 7 consecutive days. On d 3 and d 7 of heat stress, the chicks were sacrificed and sampled. The mRNA expression of heat stress protein 70 (HSP70), glutathione peroxidase (GSH-Px), ornithine decarboxylase (ODC), epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) were detected by real-time PCR using samples from jejunum mucosa. The serum and jejunum mucosa metabolomic profiles of PICB group showing best antioxidative effects and control group at d 3 were studied using the method of the gas chromatography – time of flight mass spectrometry (GT-TOF-MS), followed by principal component analysis and partial least squares-discriminate analysis. Potential biomarkers were found using Student's t-test. The results showed mRNA expressions of HSP70, GSH-Px, ODC, EGF, and EGFR were altered by the supplementation of PICB. PICB exhibited antioxidative and growth promoting effects, and 0.3% PICB supplementation level exhibited the best. Three metabolites in the serum and 5 in the jejunum mucosa were identified as potential biomarkers. They were considered to be in accordance with antioxidative and growth promoting effects of PICB, which involved in the energy metabolism (sorbitol, palmitic acid), carbohydrate metabolism, amino acids metabolism (serine, L-ornithine), glutathione metabolism (glutamate, L-ornithine), GnRH signaling pathway (inositol), etc. These findings provided novel insights into our understanding of molecular mechanism of PICB effects on heat-stressed chicks. [ABSTRACT FROM AUTHOR]

Lack of regulation of microRNAs (miRNAs) expression has been observed in some autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. G2013, as a novel non-steroidal anti-inflammatory drug (NSAID) with the immunomodulatory property, has been shown the positive effects in multiple sclerosis and anti-ageing experimental models. This research aimed to study the inhibitory effect of G2013 on miR-155 gene expression using HEK-Blue hTLR4 and Null2 cell lines. Total RNA was extracted from the treated and control cells. cDNA was made for miRNA and expression levels of miR-155 were detected by quantitative Real-time PCR using a specific primer together with U6 as the internal reference gene. A non-significant reduction was observed in the gene expression level of miR-155 in the HEK-Blue hTLR4 and Null2 cell lines under the influence of a low dose of G2013. In contrast, adding lipopolysaccharide (LPS) to the mentioned cells led to a significant increase in miR-155 expression, whereas addition of LPS four hours after exposing the cells with G2013 could not increase the expression level of this miRNA (P < 0.05). Collectively, this research showed that G2013, as a novel NSAID with immunomodulatory property is able to significantly decrease the gene expression of miR-155 following stimulation by LPS. [ABSTRACT FROM AUTHOR]

The neurogenin (Ngn) transcription factors control early neurogenesis and neurite outgrowth in mammalian cortex. In contrast to their proneural activity, their function in neurite growth is poorly understood. Drosophila has a single predicted Ngn homolog, Tap, of unknown function. Here we show that Tap is not a proneural protein in Drosophila but is required for proper axonal growth and guidance of neurons of the mushroom body, a neuropile required for associative learning and memory. Genetic and expression analyses suggest that Tap inhibits excessive axonal growth by fine regulation of the levels of the Wnt signaling adaptor protein Dishevelled. [ABSTRACT FROM AUTHOR]

Disrupted in schizophrenia 1 (DISC1) is known as a high susceptibility gene for schizophrenia. Recent studies have indicated that schizophrenia might be caused by glia defects and dysfunction. However, there is no direct evidence of a link between the schizophrenia gene DISC1 and gliogenesis defects. Thus, an investigation into the involvement of DISC1 (a ubiquitously expressed brain protein) in astrogenesis during the late stage of mouse embryonic brain development is warranted. Here, we show that suppression of DISC1 expression represses astrogenesis in vitro and in vivo, and that DISC1 overexpression substantially enhances the process. Furthermore, mouse and human DISC1 overexpression rescued the astrogenesis defects caused by DISC1 knockdown. Mechanistically, DISC1 activates the RAS/MEK/ERK signaling pathway via direct association with RASSF7. Also, the pERK complex undergoes nuclear translocation and influences the expression of genes related to astrogenesis. In summary, our results demonstrate that DISC1 regulates astrogenesis by modulating RAS/MEK/ERK signaling via RASSF7 and provide a framework for understanding how DISC1 dysfunction might lead to neuropsychiatric diseases. [ABSTRACT FROM AUTHOR]

ERP measures may index genetic risk for psychopathology before disorder onset in adolescence, but little is known about their developmental rank-order stability during this period of significant brain maturation. We studied ERP stability in 48 pairs of identical twins (age 14-16 years) tested 1 year apart. Trial-averaged voltage waveforms were extracted from electroencephalographic recordings from oddball/novelty, go/no-go, and flanker tasks, and 16 amplitude measures were examined. Members of twin pairs were highly similar, whether based on ERP amplitude measures (intraclass correlation [ICC] median = .64, range = .44-.86) or three factor scores (all ICCs ≥ .69) derived from them. Stability was high overall, with 69% of the 16 individual measures generating stability coefficients exceeding .70 and all factor scores showing stability above .75. Measures from 10 difference waveforms calculated from paired conditions within tasks were also examined, and were associated with lower twin similarity (ICC median = .52, .38-.64) and developmental stability (only 30% exceeding .70). In a supplemental analysis, we found significant developmental stability for error-related negativity (range = .45-.55) and positivity (.56-.70) measures when average waveforms were based on one or more trials, and that these values were equivalent to those derived from averages using the current field recommendation, which requires six or more trials. Overall, we conclude that the studied brain measures are largely stable over 1 year of mid- to late adolescence, likely reflecting familial etiologic influences on brain functions pertaining to cognitive control and salience recognition. [ABSTRACT FROM AUTHOR]

Summary Human cowpox virus (CPXV) infections are rare, but can result in severe and sometimes fatal outcomes. The majority of recent cases were traced back to contacts with infected domestic cats or pet rats. The aim of the present study was to evaluate a three-dimensional (3D) skin model as a possible replacement for animal experiments. We monitored CPXV lesion formation, viral gene expression and cell cycle patterns after infection of 3D skin cultures with two CPXV strains of different pathogenic potential: a recent pet rat isolate (RatPox09) and the reference Brighton red strain. Infected 3D skin cultures exhibited histological alterations that were similar to those of mammal skin infections, but there were no differences in gene expression patterns and tissue damage between the two CPXV strains in the model system. In conclusion, 3D skin cultures reflect the development of pox lesions in the skin very well, but seem not to allow differentiation between more or less virulent virus strains, a distinction that is made possible by experimental infection in suitable animal models. [ABSTRACT FROM AUTHOR]

Does a modular body organization present a challenge for developmental control? We investigate the idea of a possible developmental cost of modularity by examining the relationship between modularity and developmental stability in a multi-segmented arthropod taxon: the geophilomorph centipedes. In a sample of eight species, we tested the correlation between developmental stability, estimated from measures of translational fluctuating asymmetry, and the number of trunk segments and some other morphological traits, both at the species and individual levels. We found sizeable differences in size and shape patterns of variation at the level of species. However, we did not find any clear evidence of correlation between fluctuating asymmetry and the number of trunk segments or the other morphological traits considered. Thus, our results provide no support to the idea of a possible trade-off between the cardinality of a modular system and the level of developmental precision in the phenotypic expression of its modules. The results of this exploratory study invite further investigations of patterns of translational fluctuating asymmetry in segmented animals and other modular organisms, as these have the potential to reveal features of developmental stability that cannot be captured by the study of bilateral asymmetry alone. [ABSTRACT FROM AUTHOR]

Eisenia fetida is a terrestrial organism, which can be used to diagnose sub-lethal concentrations of PFOA by using molecular biomarkers. In order to identify potential molecular biomarkers, we have exposed E. fetida to 10 mg/kg of PFOA in soil for 8 months. The mRNA isolation, sequencing, transcriptome assembly followed by differential gene expression studies have revealed that genes that are involved in apoptotic process, reproduction, calcium signalling, neuronal development and lipid metabolism are predominantly affected. Highly specific genes that are altered by PFOA can be further validated and used as biomarker to detect sub-lethal concentrations of PFOA in the soil. [ABSTRACT FROM AUTHOR]

Background: Tobacco-smoke is the major etiological factor related to lung cancer. However, other important factor is chronic wood smoke exposure (WSE). Approximately 30 % of lung cancer patients in Mexico have a history of WSE, and present different clinical, pathological and molecular characteristics compared to tobacco related lung cancer, including differences in mutational profiles. There are several molecular alterations identified in WSE associated lung cancer, however most studies have focused on the analysis of changes in several pathogenesis related proteins.Methods: Our group evaluated gene expression profiles of primary lung adenocarcinoma, from patients with history of WSE or tobacco exposure. Differential expression between these two groups were studied through gene expression microarrays.Results: Results of the gene expression profiling revealed 57 statistically significant genes (p < 0.01). The associated biological functional pathways included: lipid metabolism, biochemistry of small molecules, molecular transport, cell morphology, function and maintenance. A highlight of our analysis is that three of the main functional networks represent 37 differentially expressed genes out of the 57 found. These hubs are related with ubiquitin C, GABA(A) receptor-associated like protein; and the PI3K/AKT and MEK/ERK signaling pathways.Conclusion: Our results reflect the intrinsic biology that sustains the development of adenocarcinoma related to WSE and show that there is a different gene expression profile of WSE associated lung adenocarcinoma compared to tobacco exposure, suggesting that they arise through different carcinogenic mechanisms, which may explain the clinical and mutation profile divergences between both lung adenocarcinomas. [ABSTRACT FROM AUTHOR]

Clinical human cytomegalovirus (HCMV) strains invariably mutate when propagated in vitro. Mutations in gene RL13 are selected in all cell types, whereas in fibroblasts mutants in the UL128 locus (UL128L; genes UL128, UL130, and UL131A) are also selected. In addition, sporadic mutations are selected elsewhere in the genome in all cell types. We sought to investigate conditions under which HCMV can be propagated without incurring genetic defects. Bacterial artificial chromosomes (BACs) provide a stable, genetically defined source of viral genome. Viruses were generated from BACs containing the genomes of strains TR, TB40, FIX, and Merlin, as well as from Merlin-BAC recombinants containing variant nucleotides in UL128L from TB40-BAC4 or FIX-BAC. Propagation of viruses derived from TR-BAC, TB40-BAC4, and FIX-BAC in either fibroblast or epithelial cells was associated with the generation of defects around the prokaryotic vector, which is retained in the unique short (US) region of viruses. This was not observed for Merlin-BAC, from which the vector is excised in derived viruses; however, propagation in epithelial cells was consistently associated with mutations in the unique long b' (UL/b') region, all impacting on gene UL141. Viruses derived from Merlin-BAC in fibroblasts had mutations in UL128L, but mutations occurred less frequently with recombinants containing UL128L nucleotides from TB40-BAC4 or FIX-BAC. Viruses derived from a Merlin-BAC derivative in which RL13 and UL128L were either mutated or repressed were remarkably stable in fibroblasts. Thus, HCMV containing a wildtype gene complement can be generated in vitro by deriving virus from a self-excising BAC in fibroblasts and repressing RL13 and UL128L. [ABSTRACT FROM AUTHOR]

The g -loss predicted based on genetic selection is smaller than that observed across various ratio-scale measures of cognitive ability. The difference may result in part from the accumulation of deleterious mutations across generations, reducing g via their effects on developmental stability/fitness. Previously published secular trend data on a developmental stability measure, craniofacial fluctuating asymmetry (FA) size, for white US males and females covering 14 and 15 decades respectively, are re-analysed. When the secular increases in FA size are rescaled as declines in latent developmental stability, and multiplied by the validity and reliability adjusted developmental stability- g correlation, g -losses of −.16 points per decade are predicted for the males, females and the combined sample. Predicted fitness losses due to mutation accumulation may account for 30% of the generational decline (−.05 points per decade), indicating only a small role for mutations in secular g -loss. The remaining 70% (−.11 points per decade) may result from developmental stability disrupting environmental change, such as increased exposure to pollutants. Adding these to the g -loss due to selection (re-estimated at −.54 points per decade) yields a combined decadal loss of −.70 points. Additional adjustments for replacement migration and the generation length- g interaction yield a larger magnitude decadal g -loss of − 1.25 points. [ABSTRACT FROM AUTHOR]

The present investigation was carried out during kharif 2012 at the Agricultural Research Station, Gulbarga and other four locations located in north eastern dry zone (Zone 2) of Karnataka, to know the stability of the nineteen advanced genotypes of pigeonpea. Highly significant differences among genotypes were observed for all the characters except number of pods per plant, number of seeds per pod and seed yield per plant. The variance due to Genotype x Environment found significant for the characters like days to 80% pod maturity and number of seeds per pod. Environment (linear) interaction component was significant for all the traits. The variance due to pooled deviation (non- linear) was highly significant for all the characters except for number of seeds per pod which reflect considerable genetic diversity in the material. Out of 19 genotypes studied two entries viz., GRG-109 and GRG-107 were consistent and high yielding compared to local checks. [ABSTRACT FROM AUTHOR]

Research suggests that fast life history strategy (LHS) may be a primary driver of substance use among young adults. However, a recent study reported that (a) young adult fast LHS did not subsume all theorized indicators of LHS during this period and (b) fast LHS among parents did not predict young adult fast LHS or liability for use of common substances. In this study, we used structural equations and national data to test whether these findings generalized to adolescence. In addition, given that LHS and substance use share genetic and neuropsychological bases, we examined whether fast LHS could explain the developmental stability of substance use. Overall, our results extend the findings discussed above and suggest that fast LHS fully explains the developmental stability of substance use among youth. We discuss implications for life history models, research applying life history theory and substance use, and substance abuse prevention and treatment. [ABSTRACT FROM AUTHOR]

The role of sex and androgen receptors (ARs) for social preference and social memory is rather unknown. In this study of mice we compared males, females and males lacking ARs specifically in the nervous system, ARNesDel, with respect to social preference, assessed with the three-chambered apparatus test, and social recognition, assessed with the social discrimination procedure. In the social discrimination test we also evaluated the tentative importance of the sex of the stimulus animal. Novel object recognition and olfaction were investigated to complement the results from the social tests. Gene expression analysis was performed to reveal molecules involved in the effects of sex and androgens on social behaviors. All three test groups showed social preference in the three-chambered apparatus test. In both social tests an AR- independent sexual dimorphism was seen in the persistence of social investigation of female conspecifics, whereas the social interest toward male stimuli mice was similar in all groups. Male and female controls recognized conspecifics independent of their sex, whereas ARNesDelmales recognized female but not male stimuli mice. Moreover, the non-social behaviors were not affected by AR deficiency. The gene expression analyses of hypothalamus and amygdala indicated that Oxtr, Cd38, Esr1, Cyp19a1, Ucn3, Crh, and Gtf2i were differentially expressed between the three groups. In conclusion, our results suggest that ARs are required for recognition of male but not female conspecifics, while being dispensable for social investigation toward both sexes. In addition, the AR seems to regulate genes related to oxytocin, estrogen and William's syndrome. [ABSTRACT FROM AUTHOR]

Although genome-wide association studies (GWASs) have discovered numerous novel genetic variants associated with many complex traits and diseases, those genetic variants typically explain only a small fraction of phenotypic variance. Factors that account for phenotypic variance include environmental factors and gene-by-environment interactions (GEIs). Recently, several studies have conducted genome-wide gene-by-environment association analyses and demonstrated important roles of GEIs in complex traits. One of the main challenges in these association studies is to control effects of population structure that may cause spurious associations. Many studies have analyzed how population structure influences statistics of genetic variants and developed several statistical approaches to correct for population structure. However, the impact of population structure on GEI statistics in GWASs has not been extensively studied and nor have there been methods designed to correct for population structure on GEI statistics. In this paper, we show both analytically and empirically that population structure may cause spurious GEIs and use both simulation and two GWAS datasets to support our finding. We propose a statistical approach based on mixed models to account for population structure on GEI statistics. We find that our approach effectively controls population structure on statistics for GEIs as well as for genetic variants. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the expression levels and biological functions of microRNA-202 (miR-202) in patients with esophageal squamous cell carcinoma (ESCC). A total of 60 patients with ESCC and 30 healthy individuals were enrolled and reverse transcription-quantitative polymerase chain reaction was performed to measure the expression levels of miR-202. In order to investigate the effects of miR-202 expression levels on the proliferative, migratory and invasive abilities of ESCC cells, methylthiazolyl-tetrazolium bromide proliferation, in vitro scratch and Transwell® chamber assays were performed. Expression levels of miR-202 were significantly decreased in the peripheral blood of patients with ESCC, which is associated with the degree of cell differentiation and lymph node metastasis (P<0.05). Following miR-202 transfection, cell proliferation was significantly inhibited (P<0.05). Cell migration and invasion was also significantly inhibited by miR-202 transfection (P<0.05). The results of the present study demonstrated that the expression of miR-202 inhibited the proliferation, migration and invasion of ESCC cells. Furthermore, low expression levels of miR-202 were detected in the peripheral blood of patients with ESCC, which is associated with the development, invasion and metastasis of ESCC. [ABSTRACT FROM AUTHOR]

Responses of human neutrophils to TNF-α are complex and multifactorial. Exposure of human neutrophils to TNF-α in vitro primes the respiratory burst, delays apoptosis and induces the expression of several genes including chemokines, and TNF-α itself. This study aimed to determine the impact of TNF-α exposure on the expression of neutrophil genes and proteins that regulate apoptosis. Quantitative PCR and RNA-Seq, identified changes in expression of several apoptosis regulating genes in response to TNF-α exposure. Up-regulated genes included TNF-α itself, and several anti-apoptotic genes, including BCL2A1, CFLAR (cFLIP) and TNFAIP3, whose mRNA levels increased above control values by between 4-20 fold ( n = 3, P < 0.05). In contrast, the expression of pro-apoptotic genes, including CASP8, FADD and TNFRSF1A and TNFRSF1B, were significantly down-regulated following TNF-α treatment. These changes in mRNA levels were paralleled by decreases in protein levels of caspases 8 and 10, TRADD, FADD, TNFRSF1A and TNFRSF1B, and increased cFLIP protein levels, as detected by western blotting. These data indicate that when neutrophils are triggered by TNF-α exposure, they undergo molecular changes in transcriptional expression to up-regulate expression of specific anti-apoptotic proteins and concomitantly decrease expression of specific proteins involved in death receptor signaling which will alter their function in TNF-α rich environments. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) are small conserved RNA that regulate gene expression. Bioinformatic analysis of miRNA profiles during mouse lung development indicated a role for multiple miRNA, including miRNA-489. miR-489 increased on completion of alveolar septation [postnatal day 42 (P42)], associated with decreases in its conserved target genes insulin-like growth factor-1 (Igf1) and tenascin C (Tnc). We hypothesized that dysregulation of miR-489 and its target genes Igf1 and Tnc contribute to hyperoxia-induced abnormal lung development. C57BL/6 mice were exposed to normoxia (21%) or hyperoxia (85% O2) from P4 to P14, in combination with intranasal locked nucleic acid against miR-489 to inhibit miR-489, cytomegalovirus promoter (pCMV)-miR-489 to overexpress miR-489, or empty vector. Hyperoxia reduced miR-489 and increased Igf1 and Tnc. Locked nucleic acid against miR-489 improved lung development during hyperoxia and did not alter it during normoxia, whereas miR-489 overexpression inhibited lung development during normoxia. The 3= untranslated region in vitro reporter studies confirmed Igf1 and Tnc as targets of miR-489. While miR-489 was of epithelial origin and present in exosomes, its targets Igf1 and Tnc were produced by fibroblasts. Infants with bronchopulmonary dysplasia (BPD) had reduced lung miR-489 and increased Igf1 and Tnc compared with normal preterm or term infants. These results suggest increased miR-489 is an inhibitor of alveolar septation. During hyperoxia or BPD, reduced miR-489 and increased Igf1 and Tnc may be inadequate attempts at compensation. Further inhibition of miR-489 may permit alveolar septation to proceed. The use of specific miRNA antagonists or agonists may be a therapeutic strategy for inhibited alveolarization, such as in BPD. [ABSTRACT FROM AUTHOR]

Background: Many algorithms have been developed to infer the topology of gene regulatory networks from gene expression data. These methods typically produce a ranking of links between genes with associated confidence scores, after which a certain threshold is chosen to produce the inferred topology. However, the structural properties of the predicted network do not resemble those typical for a gene regulatory network, as most algorithms only take into account connections found in the data and do not include known graph properties in their inference process. This lowers the prediction accuracy of these methods, limiting their usability in practice. Results: We propose a post-processing algorithm which is applicable to any confidence ranking of regulatory interactions obtained from a network inference method which can use, inter alia, graphlets and several graph-invariant properties to re-rank the links into a more accurate prediction. To demonstrate the potential of our approach, we re-rank predictions of six different state-of-the-art algorithms using three simple network properties as optimization criteria and show that Netter can improve the predictions made on both artificially generated data as well as the DREAM4 and DREAM5 benchmarks. Additionally, the DREAM5 E.coli. community prediction inferred from real expression data is further improved. Furthermore, Netter compares favorably to other post-processing algorithms and is not restricted to correlation-like predictions. Lastly, we demonstrate that the performance increase is robust for a wide range of parameter settings. Netter is available at http://bioinformatics.intec.ugent.be. Conclusions: Network inference from high-throughput data is a long-standing challenge. In this work, we present Netter, which can further refine network predictions based on a set of user-defined graph properties. Netter is a flexible system which can be applied in unison with any method producing a ranking from omics data. It can be tailored to specific prior knowledge by expert users but can also be applied in general uses cases. Concluding, we believe that Netter is an interesting second step in the network inference process to further increase the quality of prediction. [ABSTRACT FROM AUTHOR]