Temperature Effects on Mechanical Properties of Zinc Dithiophosphate Tribofilms

Nanoindentation tests were performed at several temperatures (24 to 80degC) on one antiwear zinc dialkyl-dithiophosphate (ZDTP) tribofilm using a Nanoindenter XP (R) entirely set into a climatic chamber. Mechanical properties of the tribofilm were determined using a simple model. AFM observations were conducted to estimate the order of magnitude of the film's thickness. The effect of applied pressure on the elastic properties was demonstrated and taken into account in the present analysis. The use of the F/S^2 parameter, independent of contact geometry, revealed a hardness dependency upon temperature. Furthermore, careful AFM observations of the residual pile-up produced by plastic flow around the indents pointed out the evolution of the film deformation process with temperature

Cytonuclear interactions remain stable during allopolyploid evolution despite repeated whole-genome duplications in Brassica

Several plastid macromolecular protein complexes are encoded by both nuclear and plastid genes. Therefore, cytonuclear interactions are held in place to prevent genomic conflicts that may lead to incompatibilities. Allopolyploidy resulting from hybridization and genome doubling of two divergent species can disrupt these fine-tuned interactions, as newly formed allopolyploid species confront biparental nuclear chromosomes with a uniparentally inherited plastid genome. To avoid any deleterious effects of unequal genome inheritance, preferential transcription of the plastid donor over the other donor has been hypothesized to occur in allopolyploids. We used Brassica as a model to study the effects of paleopolyploidy in diploid parental species, as well as the effects of recent and ancient allopolyploidy in Brassica napus, on genes implicated in plastid protein complexes. We first identified redundant nuclear copies involved in those complexes. Compared with cytosolic protein complexes and with genome-wide retention rates, genes involved in plastid protein complexes show a higher retention of genes in duplicated and triplicated copies. Those redundant copies are functional and are undergoing strong purifying selection. We then compared transcription patterns and sequences of those redundant gene copies between resynthesized allopolyploids and their diploid parents. The neopolyploids showed no biased subgenome expression or maternal homogenization via gene conversion, despite the presence of some non-synonymous substitutions between plastid genomes of parental progenitors. Instead, subgenome dominance was observed regardless of the maternal progenitor. Our results provide new insights on the evolution of plastid protein complexes that could be tested and generalized in other allopolyploid species

The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease

Objective To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease

Male Attractiveness Is Influenced by UV Wavelengths in a Newt Species but Not in Its Close Relative

Background: Functional communication in the UV range has been reported in Invertebrates and all major groups of Vertebrates but Amphibians. Although perception in this wavelength range has been shown in a few species, UV signalling has not been demonstrated in this group. One reason may be that in lentic freshwater habitats, litter decomposition generates dissolved organic carbon that absorbs UV radiation and thus hinders its use for visual signalling. We tested the effect of male UV characteristics on female sexual preference in two newt species that experience contrasting levels of UV water transmission when breeding. Methodology/Principal Findings: We analysed water spectral characteristics of a sample of breeding ponds in both species. We quantified male ventral coloration and measured male attractiveness under two lighting conditions (UV present, UV absent) using a no-choice female preference design. UV transmission was higher in Lissotriton vulgaris breeding sites. Male UV patterns also differed between experimental males of the two species. We observed a first common peak around 333 nm, higher in L. vulgaris, and a second peak around 397 nm, more frequent and higher in L. helveticus. Male attractiveness was significantly reduced in L. vulgaris when UV was not available but not in L. helveticus. Male attractiveness depended on the hue of the first UV peak in L. vulgaris. Conclusion/Significance: Our study is the first report of functional UV-based communication in Amphibians. Interestingly

Mechanisms of NK Cell-Macrophage Bacillus anthracis Crosstalk: A Balance between Stimulation by Spores and Differential Disruption by Toxins

NK cells are important immune effectors for preventing microbial invasion and dissemination, through natural cytotoxicity and cytokine secretion. Bacillus anthracis spores can efficiently drive IFN-γ production by NK cells. The present study provides insights into the mechanisms of cytokine and cellular signaling that underlie the process of NK-cell activation by B. anthracis and the bacterial strategies to subvert and evade this response. Infection with non-toxigenic encapsulated B. anthracis induced recruitment of NK cells and macrophages into the mouse draining lymph node. Production of edema (ET) or lethal (LT) toxin during infection impaired this cellular recruitment. NK cell depletion led to accelerated systemic bacterial dissemination. IFN-γ production by NK cells in response to B. anthracis spores was: i) contact-dependent through RAE-1-NKG2D interaction with macrophages; ii) IL-12, IL-18, and IL-15-dependent, where IL-12 played a key role and regulated both NK cell and macrophage activation; and iii) required IL-18 for only an initial short time window. B. anthracis toxins subverted both NK cell essential functions. ET and LT disrupted IFN-γ production through different mechanisms. LT acted both on macrophages and NK cells, whereas ET mainly affected macrophages and did not alter NK cell capacity of IFN-γ secretion. In contrast, ET and LT inhibited the natural cytotoxicity function of NK cells, both in vitro and in vivo. The subverting action of ET thus led to dissociation in NK cell function and blocked natural cytotoxicity without affecting IFN-γ secretion. The high efficiency of this process stresses the impact that this toxin may exert in anthrax pathogenesis, and highlights a potential usefulness for controlling excessive cytotoxic responses in immunopathological diseases. Our findings therefore exemplify the delicate balance between bacterial stimulation and evasion strategies. This highlights the potential implication of the crosstalk between host innate defences and B. anthracis in initial anthrax control mechanisms

Delivery dilemmas: How drug cryptomarket users identify and seek to reduce their risk of detection by law enforcement

© 2016 Background Cryptomarkets represent an important drug market innovation by bringing buyers and sellers of illegal drugs together in a ‘hidden’ yet public online marketplace. We ask: How do cryptomarket drug sellers and buyers perceive the risks of detection and arrest, and attempt to limit them? Methods We analyse selected texts produced by vendors operating on the first major drug cryptomarket, Silk Road (N = 600) alongside data extracted from the marketplace discussion forum that include buyer perspectives. We apply Fader's (2016) framework for understanding how drug dealers operating ‘offline’ attempt to reduce the risk of detection and arrest: visibility reduction, charge reduction and risk distribution. Results We characterize drug transactions on cryptomarkets as ‘stretched’ across time, virtual and physical space, and handlers, changing the location and nature of risks faced by cryptomarket users. The key locations of risk of detection and arrest by law enforcement were found in ‘offline’ activities of cryptomarket vendors (packaging and delivery drop-offs) and buyers (receiving deliveries). Strategies in response involved either creating or disrupting routine activities in line with a non-offending identity. Use of encrypted communication was seen as ‘good practice’ but often not employed. ‘Drop shipping’ allowed some Silk Road vendors to sell illegal drugs without the necessity of handling them. Conclusion Silk Road participants neither viewed themselves as immune to, nor passively accepting of, the risk of detection and arrest. Rational choice theorists have viewed offending decisions as constrained by limited access to relevant information. Cryptomarkets as ‘illicit capital’ sharing communities provide expanded and low-cost access to information enabling drug market participants to make more accurate assessments of the risk of apprehension. The abundance of drug market intelligence available to those on both sides of the law may function to speed up innovation in illegal drug markets, as well as necessitate and facilitate the development of law enforcement responses

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe