Intra- and inter-individual genetic differences in gene expression

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.

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A statistical framework for genetic association studies of power curves in bird flight

How the power required for bird flight varies as a function of forward speed can be used to predict the flight style and behavioral strategy of a bird for feeding and migration. A U-shaped curve was observed between the power and flight velocity in many birds, which is consistent to the theoretical prediction by aerodynamic models. In this article, we present a general genetic model for fine mapping of quantitative trait loci (QTL) responsible for power curves in a sample of birds drawn from a natural population. This model is developed within the maximum likelihood context, implemented with the EM algorithm for estimating the population genetic parameters of QTL and the simplex algorithm for estimating the QTL genotype-specific parameters of power curves. Using Monte Carlo simulation derived from empirical observations of power curves in the European starling (Sturnus vulgaris), we demonstrate how the underlying QTL for power curves can be detected from molecular markers and how the QTL detected affect the most appropriate flight speeds used to design an optimal migration strategy. The results from our model can be directly integrated into a conceptual framework for understanding flight origin and evolution

Functional Mapping of Dynamic Traits with Robust t-Distribution

Functional mapping has been a powerful tool in mapping quantitative trait loci (QTL) underlying dynamic traits of agricultural or biomedical interest. In functional mapping, multivariate normality is often assumed for the underlying data distribution, partially due to the ease of parameter estimation. The normality assumption however could be easily violated in real applications due to various reasons such as heavy tails or extreme observations. Departure from normality has negative effect on testing power and inference for QTL identification. In this work, we relax the normality assumption and propose a robust multivariate -distribution mapping framework for QTL identification in functional mapping. Simulation studies show increased mapping power and precision with the distribution than that of a normal distribution. The utility of the method is demonstrated through a real data analysis

Enhancement of electrochemical activity of Raney-type NiZn coatings by modifying with PtRu binary deposits: Application for alkaline water electrolysis

This study presents electrochemical preparation and characterization of PtRu-modified Cu/Ni/NiZn electrodes (Cu/Ni/NiZn-PtRu) as cathode materials for alkaline water electrolysis. The electrodes were characterized using energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques. Their electrochemical activities as cathode materials for alkaline water electrolysis were evaluated with the help of current potential curves. The results showed that the PtRu-modified layers have porous structures with relatively low Pt and Ru chemical compositions. The modification of the alkaline leached Cu/Ni/NiZn surface by Pt and/or Ru enhances the electrochemical activity of the electrode. Their catalytic activity depends on the molar ratios of Pt and Ru; the PtRu binary deposit with the percentage weight ratio of approximately 56:44 exhibits the highest hydrogen evolution activity among the studied electrodes. The enhanced hydrogen evolution activity of the PtRu-modified electrodes was related to the porous surface and/or a possible synergistic effect between the metals. Copyright (c) 2015, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved

A Retrospective Cohort Study of the Potency of lipid-lowering therapy and Race-gender Differences in LDL cholesterol control

<p>Abstract</p> <p>Background</p> <p>Reasons for race and gender differences in controlling elevated low density lipoprotein (LDL) cholesterol may be related to variations in prescribed lipid-lowering therapy. We examined the effect of lipid-lowering drug treatment and potency on time until LDL control for black and white women and men with a baseline elevated LDL.</p> <p>Methods</p> <p>We studied 3,484 older hypertensive patients with dyslipidemia in 6 primary care practices over a 4-year timeframe. Potency of lipid-lowering drugs calculated for each treated day and summed to assess total potency for at least 6 and up to 24 months. Cox models of time to LDL control within two years and logistic regression models of control within 6 months by race-gender adjust for: demographics, clinical, health care delivery, primary/specialty care, LDL measurement, and drug potency.</p> <p>Results</p> <p>Time to LDL control decreased as lipid-lowering drug potency increased (P < 0.001). Black women (N = 1,440) received the highest potency therapy (P < 0.001) yet were less likely to achieve LDL control than white men (N = 717) (fully adjusted hazard ratio [HR] 0.66 [95% CI 0.56-0.78]). Black men (N = 666) and white women (N = 661) also had lower adjusted HRs of LDL control (0.82 [95% CI 0.69, 0.98] and 0.75 [95% CI 0.64-0.88], respectively) than white men. Logistic regression models of LDL control by 6 months and other sensitivity models affirmed these results.</p> <p>Conclusions</p> <p>Black women and, to a lesser extent, black men and white women were less likely to achieve LDL control than white men after accounting for lipid-lowering drug potency as well as diverse patient and provider factors. Future work should focus on the contributions of medication adherence and response to treatment to these clinically important differences.</p

Growth and weight status in treatment-naïve 12-16 year old adolescents with Alcohol Use Disorders in Cape Town, South Africa

The original publication is available at http://www.nutritionj.com/Publication of this article was funded by the Stellenbosch University Open Access Fund.Abstract: Background Heavy alcohol consumption during adolescence has many known harmful health and social consequences and is strongly associated with numerous health risk behaviours. The consequences of heavy alcohol use during adolescence on nutritional status, specifically growth and weight status are largely unknown at this time. Methods Substance use, anthropometric indices of growth and weight, dietary energy intake and physical activity in heavy drinking adolescents (meeting DSM-IV criteria for alcohol use disorders) and matched light/non-drinking control adolescents were assessed. Results Lifetime alcohol dose, measured in standard drinks of alcohol, was orders of magnitude higher in adolescents with alcohol use disorders (AUDs) compared to controls. The AUDs group was selected to represent relatively 'pure' AUDs, with minimal other drug use and no psychiatric diagnoses. The growth and weight status of adolescents with AUDs were generally comparable to that of controls, and is in line with the growth and weight status of the South African adolescent population. A greater proportion of overweight/obese females was found in both groups, with this percentage tending to be greater, although not significantly so, in the AUDs group. Adolescent females with AUDs had increased odds of being overweight/obese compared to controls, after adjustment for smoking, physical activity and energy intake. Conclusion Anthropometric indices of growth and weight status of participants in the Control and AUD groups were generally comparable. Female adolescents with AUDs may have an increased risk of being overweight/obese compared to adolescent females without AUDs. The presence of an AUD in our adolescent sample was associated with higher energy intake. Longitudinal studies are needed to elucidate the effects of heavy alcohol use on energy balance, growth and weight status in adolescents as they age. Nonetheless, the current study contributes to our understanding of the impacts of heavy alcohol consumption on important aspects of adolescent development.Publishers' versio

Re-Patterning Sleep Architecture in Drosophila through Gustatory Perception and Nutritional Quality

Organisms perceive changes in their dietary environment and enact a suite of behavioral and metabolic adaptations that can impact motivational behavior, disease resistance, and longevity. However, the precise nature and mechanism of these dietary responses is not known. We have uncovered a novel link between dietary factors and sleep behavior in Drosophila melanogaster. Dietary sugar rapidly altered sleep behavior by modulating the number of sleep episodes during both the light and dark phase of the circadian period, independent of an intact circadian rhythm and without affecting total sleep, latency to sleep, or waking activity. The effect of sugar on sleep episode number was consistent with a change in arousal threshold for waking. Dietary protein had no significant effect on sleep or wakefulness. Gustatory perception of sugar was necessary and sufficient to increase the number of sleep episodes, and this effect was blocked by activation of bitter-sensing neurons. Further addition of sugar to the diet blocked the effects of sweet gustatory perception through a gustatory-independent mechanism. However, gustatory perception was not required for diet-induced fat accumulation, indicating that sleep and energy storage are mechanistically separable. We propose a two-component model where gustatory and metabolic cues interact to regulate sleep architecture in response to the quantity of sugar available from dietary sources. Reduced arousal threshold in response to low dietary availability may have evolved to provide increased responsiveness to cues associated with alternative nutrient-dense feeding sites. These results provide evidence that gustatory perception can alter arousal thresholds for sleep behavior in response to dietary cues and provide a mechanism by which organisms tune their behavior and physiology to environmental cues

Genome Wide Analysis of Inbred Mouse Lines Identifies a Locus Containing Ppar-γ as Contributing to Enhanced Malaria Survival

The genetic background of a patient determines in part if a person develops a mild form of malaria and recovers, or develops a severe form and dies. We have used a mouse model to detect genes involved in the resistance or susceptibility to Plasmodium berghei malaria infection. To this end we first characterized 32 different mouse strains infected with P. berghei and identified survival as the best trait to discriminate between the strains. We found a locus on chromosome 6 by linking the survival phenotypes of the mouse strains to their genetic variations using genome wide analyses such as haplotype associated mapping and the efficient mixed-model for association. This new locus involved in malaria resistance contains only two genes and confirms the importance of Ppar-γ in malaria infection

Using hippocampal microRNA expression differences between mouse inbred strains to characterise miRNA function

Micro-RNAs (miRNAs) are short, single-stranded, noncoding RNAs that are involved in the regulation of protein-coding genes at the level of messenger RNA (mRNA). They are involved in the regulation of numerous traits, including developmental timing, apoptosis, immune function, and neuronal development. To better understand how the expression of the miRNAs themselves is regulated, we looked for miRNA expression differences among four mouse inbred strains, A/J, BALB/cJ, C57BL/6J, and DBA/2J, in one tissue, the hippocampus. A total of 166 miRNA RT-PCR assays were used to screen RNA pools for each strain. Twenty miRNA species that were markedly different between strains were further investigated using eight individual samples per strain, and 11 miRNAs showed significant differences across strains (p < 0.05). This is the first observation of miRNA expression differences across inbred mice strains. We conducted an in silico correlation analysis of the expression of these differentially expressed miRNAs with phenotype data and mRNA expression to better characterise the effects of these miRNAs on both phenotype and the regulation of mRNA expression. This approach has allowed us to nominate miRNAs that have potential roles in anxiety, exploration, and learning and memory