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Wednesday, April 23, 2014

Guidelines for Investigating Causality of Sequence Variants in Human Disease

MacArthur DG, Manolio TA, Dimmock DP, et al. Guidelines for investigating causality of sequence variants in human disease. Nature 2014;508(7497):469-76.   http://www.nature.com/nature/journal/v508/n7497/full/nature13127.html    

The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed.

Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease.

Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality.

We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development.


96 Elephants: An Earth Day Moment of Zen


[Rats] Dose-Dependent Effects and Reversibility of Uterine Tissue And Fertility Caused By Nandrolone Decanoate

Belardin LB, Simao VA, Leite GA, Chuffa LG, Camargo IC. Dose-dependent effects and reversibility of the injuries caused by nandrolone decanoate in uterine tissue and fertility of rats. Birth Defects Res B Dev Reprod Toxicol 2014;101(2):168-77.   http://onlinelibrary.wiley.com/doi/10.1002/bdrb.21104/abstract   

This study is the first to investigate the effects of different doses of nandrolone decanoate (ND) upon uterine tissue and fertility, and if the reproductive alterations can be restored after cessation of the treatment.

Wistar female rats were treated with ND at doses of 1.87, 3.75, 7.5, and 15 mg/kg body weight, diluted in vehicle (n = 30/group), or received only mineral oil (control group, n = 45).

The animals were divided into three periods of study:
ND-treated receiving a daily subcutaneous injection for 15 consecutive days (1), and
treatment with ND followed by 30-day recovery (2), and
60-day recovery (3).

At the end of each period, five females per group were induced to death to histopathological analysis and the others were allowed to fertility evaluation (at 19th gestational day).

Animals that received ND followed by 30-day recovery exhibited persistent diestrous and marked suppression of reproductive capacity. Conversely, after 60-day recovery, only lowest doses females (1.87 and 3.75 mg/kg) exhibited restoration of normal estrous cyclicity.

Uterine weights were increased after ND treatment similarly to that of the controls after 60-day recovery. The ND-treated groups showed histopathological changes in the endometrium, myometrium, and perimetrium, and an increase in the thickness of both muscular and serous layers.

Notably, the recovery of uterine tissue after ND treatment was dose- and period-dependent.

We reported that administration of ND promoted damage in uterine tissue and fertility of rats, and the recovery periods were insufficient to restore all of the side effects caused by ND under a dose-dependent response.


Tuesday, April 22, 2014

Rolling Stones - Let It Bleed


The Evolution of Self-Control

MacLean EL, Hare B, Nunn CL, et al. The evolution of self-control. Proceedings of the National Academy of Sciences.   http://www.pnas.org/content/early/2014/04/16/1323533111.abstract   

Cognition presents evolutionary research with one of its greatest challenges. Cognitive evolution has been explained at the proximate level by shifts in absolute and relative brain volume and at the ultimate level by differences in social and dietary complexity.

However, no study has integrated the experimental and phylogenetic approach at the scale required to rigorously test these explanations. Instead, previous research has largely relied on various measures of brain size as proxies for cognitive abilities.

We experimentally evaluated these major evolutionary explanations by quantitatively comparing the cognitive performance of 567 individuals representing 36 species on two problem-solving tasks measuring self-control. Phylogenetic analysis revealed that absolute brain volume best predicted performance across species and accounted for considerably more variance than brain volume controlling for body mass.

This result corroborates recent advances in evolutionary neurobiology and illustrates the cognitive consequences of cortical reorganization through increases in brain volume. Within primates, dietary breadth but not social group size was a strong predictor of species differences in self-control. Our results implicate robust evolutionary relationships between dietary breadth, absolute brain volume, and self-control.

These findings provide a significant first step toward quantifying the primate cognitive phenome and explaining the process of cognitive evolution.


The Consequences of Climate Change (In Our Lifetimes)


Transcriptomic Profiling As A Screening Tool To Detect Trenbolone Treatment

Pegolo S, Cannizzo FT, Biolatti B, Castagnaro M, Bargelloni L. Transcriptomic profiling as a screening tool to detect trenbolone treatment in beef cattle. Res Vet Sci.   http://www.sciencedirect.com/science/article/pii/S0034528814000952   

The effects of steroid hormone implants containing trenbolone alone (Finaplix-H), combined with 17beta-oestradiol (17beta-E; Revalor-H), or with 17beta-E and dexamethasone (Revalor-H plus dexamethasone per os) on the bovine muscle transcriptome were examined by DNA-microarray.

Overall, large sets of genes were shown to be modulated by the different growth promoters (GPs) and the regulated pathways and biological processes were mostly shared among the treatment groups. Using the Prediction Analysis of Microarray program, GP-treated animals were accurately identified by a small number of predictive genes.

A meta-analysis approach was also carried out for the Revalor group to potentially increase the robustness of class prediction analysis. After data pre-processing, a high level of accuracy (90%) was obtained in the classification of samples, using 105 predictive gene markers.

Transcriptomics could thus help in the identification of indirect biomarkers for anabolic treatment in beef cattle to be applied for the screening of muscle samples collected after slaughtering.