First-generation linkage map for the European tree frog (Hyla arborea) with utility in congeneric species.

BACKGROUND: Western Palearctic tree frogs (Hyla arborea group) represent a strong potential for evolutionary and conservation genetic research, so far underexploited due to limited molecular resources. New microsatellite markers have recently been developed for Hyla arborea, with high cross-species utility across the entire circum-Mediterranean radiation. Here we conduct sibship analyses to map available markers for use in future population genetic applications. FINDINGS: We characterized eight linkage groups, including one sex-linked, all showing drastically reduced recombination in males compared to females, as previously documented in this species. Mapping of the new 15 markers to the ~200 My diverged Xenopus tropicalis genome suggests a generally conserved synteny with only one confirmed major chromosome rearrangement. CONCLUSIONS: The new microsatellites are representative of several chromosomes of H. arborea that are likely to be conserved across closely-related species. Our linkage map provides an important resource for genetic research in European Hylids, notably for studies of speciation, genome evolution and conservation.

A Qualitative Exploration of the Psychological Contents and Dynamics of Momentum in Sport

While studies on triggers and outcomes of Psychological Momentum (PM) exist, little is known about the dynamics by which PM emerges and develops over time. Based on video-assisted recalls of PM experiences in table tennis and swimming competitions, this research qualitatively explored the triggering processes, contents, and the development of PM over time. PM was found to be triggered by mechanisms of dissonance, consonance, or fear of not winning. During the PM experience, participants reported a variety of perceptions, affects and emotions, cognitions, and behaviors, and PM was found to develop through processes of amplification that sometimes ended with a reduction of efforts when the victory or defeat was perceived as certain. These findings are discussed in light of theories on self-regulation and reactance-helplessness. From a practical standpoint, achievement goal-based strategies are suggested, since mastery-approach goals were found to be endorsed to maintain positive PM and overcome negative PM

MAP/ERK kinase kinase 1 (MEKK1) mediates transcriptional repression by interacting with polycystic kidney disease-1 (PKD1) promoter-bound p53 tumor suppressor protein.

Mitogen-activated protein kinase (MAPK) cascades regulate a wide variety of cellular processes that ultimately depend on changes in gene expression. We have found a novel mechanism whereby one of the key MAP3 kinases, Mekk1, regulates transcriptional activity through an interaction with p53. The tumor suppressor protein p53 down-regulates a number of genes, including the gene most frequently mutated in autosomal dominant polycystic kidney disease (PKD1). We have discovered that Mekk1 translocates to the nucleus and acts as a co-repressor with p53 to down-regulate PKD1 transcriptional activity. This repression does not require Mekk1 kinase activity, excluding the need for an Mekk1 phosphorylation cascade. However, this PKD1 repression can also be induced by the stress-pathway stimuli, including TNFα, suggesting that Mekk1 activation induces both JNK-dependent and JNK-independent pathways that target the PKD1 gene. An Mekk1-p53 interaction at the PKD1 promoter suggests a new mechanism by which abnormally elevated stress-pathway stimuli might directly down-regulate the PKD1 gene, possibly causing haploinsufficiency and cyst formation.

Stored red blood cells: a changing universe waiting for its map(s).

The availability of stored red blood cells (RBCs) for transfusion remains an important aspect of the treatment of polytrauma, acute anemia or major bleedings. RBCs are prepared by blood banks from whole blood donations and stored in the cold in additive solutions for typically six weeks. These far from physiological storage conditions result in the so-called red cell storage lesion that is of importance both to blood bankers and to clinical practitioners. Here we review the current state of knowledge about the red cell storage lesion from a proteomic perspective. In particular, we describe the current models accounting for RBC aging and response to lethal stresses, review the published proteomic studies carried out to uncover the molecular basis of the RBC storage lesion, and conclude by suggesting a few possible proteomic studies that would provide further knowledge of the molecular alterations carried by RBCs stored in the cold for six weeks.

A road map toward a globally harmonized approach for occupational health surveillance and epidemiology in nanomaterial workers

OBJECTIVE: Few epidemiological studies have addressed the health of workers exposed to novel manufactured nanomaterials. The small current workforce will necessitate pooling international cohorts. METHOD: A road map was defined for a globally harmonized framework for the careful choice of materials, exposure characterization, identification of study populations, definition of health endpoints, evaluation of appropriateness of study designs, data collection and analysis, and interpretation of the results. RESULTS: We propose a road map to reach global consensus on these issues. The proposed strategy should ensure that the costs of action are not disproportionate to the potential benefits and that the approach is pragmatic and practical. CONCLUSIONS: We should aim to go beyond the collection of health complaints, illness statistics, or even counts of deaths; the manifestation of such clear endpoints would indicate a failure of preventive measures.

Gaining momentum: New options and opportunities for the treatment of advanced melanoma.

Before 2011, patients with advanced or metastatic melanoma had a particularly poor long-term prognosis. Since traditional treatments failed to confer a survival benefit, patients were preferentially entered into clinical trials of investigational agents. A greater understanding of the epidemiology and biology of disease has underpinned the development of newer therapies, including six agents that have been approved in the EU, US and/or Japan: a cytotoxic T-lymphocyte antigen-4 inhibitor (ipilimumab), two programmed cell death-1 receptor inhibitors (nivolumab and pembrolizumab), two BRAF inhibitors (vemurafenib and dabrafenib) and a MEK inhibitor (trametinib). The availability of these treatments has greatly improved the outlook for patients with advanced melanoma; however, a major consideration for physicians is now to determine how best to integrate these agents into clinical practice. Therapeutic decisions are complicated by the need to consider patient and disease characteristics, and individual treatment goals, alongside the different efficacy and safety profiles of agents with varying mechanisms of action. Long-term survival, an outcome largely out of reach with traditional systemic therapies, is now a realistic goal, creating the additional need to re-establish how clinical benefit is evaluated. In this review we summarise the current treatment landscape in advanced melanoma and discuss the promise of agents still in development. We also speculate on the future of melanoma treatment and discuss how combination and sequencing approaches may be used to optimise patient care in the future.

International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes.

A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.