The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance

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Precise Gene Editing Preserves Hematopoietic Stem Cell Function following Transient p53-Mediated DNA Damage Response

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Effect of Polymer Crystallinity in P3HT:PCBM Solar Cells on Band Gap Trap States and Apparent Recombination Order

The non‐geminate recombination of charge carriers in polymer‐fullerene solar cells has been modeled in the last few years with a trap‐assisted recombination model, which states that the apparent recombination order depends on the concentration of trapped charges tailing into the band gap. Higher concentrations of trapped charges lead to higher apparent recombination orders. In this work, the mass fraction f of highly crystalline nanofibrillar P3HT to the total P3HT content in P3HT:PCBM solar cells is consistently varied, controlling the temperature of a nanofibers‐P3HT casting dispersion. A systematic study of the apparent recombination order, measured with a transient photovoltage technique, as a function of f is presented. A correlation is shown between the apparent recombination order, the P3HT crystallinity, and the trap concentration in the band gap measured with an admittance spectroscopy technique.     

Detection of Haplotypes Associated with Prenatal Death in Dairy Cattle and Identification of Deleterious Mutations in GART,SHBG and SLC37A2

The regular decrease of female fertility over time is a major concern in modern dairy cattle industry. Only half of this decrease is explained by indirect response to selection on milk production, suggesting the existence of other factors such as embryonic lethal genetic defects. Genomic regions harboring recessive deleterious mutations were detected in three dairy cattle breeds by identifying frequent haplotypes (>1%) showing a deficit in homozygotes among Illumina Bovine 50k Beadchip haplotyping data from the French genomic selection database (47,878 Holstein, 16,833 Montbéliarde, and 11,466 Normande animals). Thirty-four candidate haplotypes (p<10⁻⁴) including previously reported regions associated with Brachyspina, CVM, HH1, and HH3 in Holstein breed were identified. Haplotype length varied from 1 to 4.8 Mb and frequencies from 1.7 up to 9%. A significant negative effect on calving rate, consistent in heifers and in lactating cows, was observed for 9 of these haplotypes in matings between carrier bulls and daughters of carrier sires, confirming their association with embryonic lethal mutations. Eight regions were further investigated using whole genome sequencing data from heterozygous bull carriers and control animals (45 animals in total). Six strong candidate causative mutations including polymorphisms previously reported in FANCI (Brachyspina), SLC35A3 (CVM), APAF1 (HH1) and three novel mutations with very damaging effect on the protein structure, according to SIFT and Polyphen-2, were detected in GART, SHBG and SLC37A2 genes. In conclusion, this study reveals a yet hidden consequence of the important inbreeding rate observed in intensively selected and specialized cattle breeds. Counter-selection of these mutations and management of matings will have positive consequences on female fertility in dairy cattle.     

Factors affecting reproduction of Woodpigeons Columba palumbus in North African forests: 1. Nest habitat selection

Capsule Woodpigeon Columba palumbus nest-tree selection is affected by human disturbance, grazing and tree characteristics.

Aims To determine the characteristics of trees used for nesting by Woodpigeons under two levels of grazing and disturbance in a Holm oak Middle Atlas forest, Morocco.

Methods Woodpigeon nest-tree selection was investigated in highly disturbed and less-disturbed sites over two years (2010 and 2011). The features of nest-tree characteristics were determined by comparing the characteristics of trees used for nesting to those of randomly selected trees.

Results Tree physical characteristics, grazing intensity and level of human disturbance were the main factors determining selection for nest-trees. Woodpigeons chose nesting trees that were greater in height, larger in DBH, lower in base of the live crown, in denser stands and at greater distance from tracks.

Conclusions Forest management for Woodpigeon nest habitat selection should focus on controlling the access of vehicles especially trucks, introducing a rotating system of forest utilization for grazing and maintaining (without extending) the cereal crops. These recommendations may assist land managers to plan for continued persistence of this species in Middle Atlas forests.     

Heating as a rapid purification method for recovering correctly-folded thermotolerant VH and VHH domains

Background  

Recombinant antibodies from Camelidae (VHHs) are potentially useful tools for both basic research and biotechnological applications because of their small size, robustness, easy handling and possibility to refold after chemio-physical denaturation. Their heat tolerance is a particularly interesting feature because it has been recently related to both high yields during recombinant expression and selective purification of folded protein.     

HADDOCK versus HADDOCK: new features and performance of HADDOCK2.0 on the CAPRI targets

Here we present version 2.0 of HADDOCK, which incorporates considerable improvements and new features. HADDOCK is now able to model not only protein-protein complexes but also other kinds of biomolecular complexes and multi-component (N > 2) systems. In the absence of any experimental and/or predicted information to drive the docking, HADDOCK now offers two additional ab initio docking modes based on either random patch definition or center-of-mass restraints. The docking protocol has been considerably improved, supporting among other solvated docking, automatic definition of semi-flexible regions, and inclusion of a desolvation energy term in the scoring scheme. The performance of HADDOCK2.0 is evaluated on the targets of rounds 4-11, run in a semi-automated mode using the original information we used in our CAPRI submissions. This enables a direct assessment of the progress made since the previous versions. Although HADDOCK performed very well in CAPRI (65% and 71% success rates, overall and for unbound targets only, respectively), a substantial improvement was achieved with HADDOCK2.0.     

Mitochondrial proteases and cancer

Mitochondria are a major source of intracellular reactive oxygen species, the production of which increases with cancer. The deleterious effects of reactive oxygen species may be responsible for the impairment of mitochondrial function observed during various pathophysiological states associated with oxidative stress and cancer. These organelles are also targets of oxidative damage (oxidation of mitochondrial DNA, lipids, protein). An important factor for protein maintenance in the presence of oxidative stress is enzymatic reversal of oxidative modifications and/or protein degradation. Failure of these processes is likely a critical component of the cancer process. Mitochondrial proteases degrade misfolded and non-assemble polypeptides, thus performing quality control surveillance in the organelle. Mitochondrial proteases may be directly involved in cancer development as recently shown for HtrA2/Omi or may regulate crucial mitochondrial molecule such as cytochrome c oxidase 4 a subunit of the cytochrome c oxidase complex degraded by the Lon protease. Thus, the role of mitochondrial proteases is further addressed in the context of oxidative stress and cancer.     

Should We Abandon the t-Test in the Analysis of Gene Expression Microarray Data: A Comparison of Variance Modeling Strategies

High-throughput post-genomic studies are now routinely and promisingly investigated in biological and biomedical research. The main statistical approach to select genes differentially expressed between two groups is to apply a t-test, which is subject of criticism in the literature. Numerous alternatives have been developed based on different and innovative variance modeling strategies. However, a critical issue is that selecting a different test usually leads to a different gene list. In this context and given the current tendency to apply the t-test, identifying the most efficient approach in practice remains crucial. To provide elements to answer, we conduct a comparison of eight tests representative of variance modeling strategies in gene expression data: Welch''s t-test, ANOVA [1], Wilcoxon''s test, SAM [2], RVM [3], limma [4], VarMixt [5] and SMVar [6]. Our comparison process relies on four steps (gene list analysis, simulations, spike-in data and re-sampling) to formulate comprehensive and robust conclusions about test performance, in terms of statistical power, false-positive rate, execution time and ease of use. Our results raise concerns about the ability of some methods to control the expected number of false positives at a desirable level. Besides, two tests (limma and VarMixt) show significant improvement compared to the t-test, in particular to deal with small sample sizes. In addition limma presents several practical advantages, so we advocate its application to analyze gene expression data.