When does female multiple mating evolve to adjust inbreeding? : Effects of inbreeding depression, direct costs, mating constraints, and polyandry as a threshold trait

Ackowledgements: This work was funded by a European Research Council Starting Grant to JMR. All simulations were performed using the Maxwell computing cluster at the University of AberdeenPeer reviewedPublisher PD

Evolution of precopulatory and post-copulatory strategies of inbreeding avoidance and associated polyandry

Acknowledgments This work was funded by a European Research Council Starting Grant to JMR. Computer simulations were performed using the Maxwell Computing Cluster at the University of Aberdeen. We thank Matthew E. Wolak and two anonymous reviewers for very helpful comments.Peer reviewedPublisher PD

Proton momentum distribution in a protein hydration shell

The momentum distribution of protons in the hydration shell of a globular protein has been measured through deep inelastic neutron scattering at 180 and 290 K, below and above the crossover temperature T-c=1.23T(g), where T-g=219 K is the glass transition temperature. It is found that the mean kinetic energy of the water hydrogens shows no temperature dependence, but the measurements are accurate enough to indicate a sensible change of momentum distribution and effective potential felt by protons, compatible with the transition from a single to a double potential well. This could support the presence of tunneling effects even at room temperature, playing an important role in biological function

Ebolavirus and Marburgvirus: insight the Filoviridae family

Ebolavirus and Marburgvirus (belonging to the Filoviridae family) emerged four decades ago and cause epidemics of haemorrhagic fever with high case-fatality rates. The genome of filoviruses encodes seven proteins. No significant homology is observed between filovirus proteins and any known macromolecule. Moreover, Marburgvirus and Ebolavirus show significant differences in protein homology. The natural maintenance cycle of filoviruses is unknown, the natural reservoir, the mode of transmission, the epidemic disease generation, and temporal dynamics are unclear. Lastly, Ebolavirus and Marburgvirus are considered as potential biological weapons. Vaccine appears the unique therapeutic frontier. Here, molecular and clinical aspects of filoviral haemorrhagic fevers are summarized

Variation in parent-offspring kinship in socially monogamous systems with extra-pair reproduction and inbreeding

ACKNOWLEDGMENTS We thank the Tsawout and Tseycum First Nations bands for allowing access to Mandarte; everyone who contributed to long-term data collection; Lukas Keller and Ryan Germain for helpful discussions; and the European Research Council, UK Royal Society, National Sciences and Engineering Research Council of Canada and Swiss National Science Foundation for their invaluable support. DATA ARCHIVING Data are available from the Dryad Digital Repository: http://dx.doi.org/10.5061/dryad.4r383.Peer reviewedPublisher PD

An ATM/Chk2-mediated DNA damage responsive signaling pathway suppresses Epstein-Barr virus transformation of primary human B cells

SummaryEpstein-Barr virus (EBV), an oncogenic herpesvirus that causes human malignancies, infects and immortalizes primary human B cells in vitro into indefinitely proliferating lymphoblastoid cell lines, which represent a model for EBV-induced tumorigenesis. The immortalization efficiency is very low, suggesting that an innate tumor suppressor mechanism is operative. We identify the DNA damage response (DDR) as a major component of the underlying tumor suppressor mechanism. EBV-induced DDR activation was not due to lytic viral replication, nor did the DDR marks colocalize with latent episomes. Rather, a transient period of EBV-induced hyperproliferation correlated with DDR activation. Inhibition of the DDR kinases ATM and Chk2 markedly increased transformation efficiency of primary B cells. Further, the viral latent oncoprotein EBNA3C was required to attenuate the EBV-induced DDR. We propose that heightened oncogenic activity in early cell divisions activates a growth-suppressive DDR that is attenuated by viral latency products to induce cell immortalization

Improving the forecast for biodiversity under climate change

Acknowledgments: This paper originates from the “Ecological Interactions and Range Evolution Under Environmental Change” and “RangeShifter” working groups, supported by the Synthesis Centre of the German Centre for Integrative Biodiversity Research (DFG-FZT-118), DIVERSITAS, and its core projects bioDISCOVERY and bioGENESIS. Supported by the Canada Research Chair, Natural Sciences and Engineering Research Council of Canada, and Quebec Centre for Biodiversity Science (A.G.); the University of Florida Foundation (R.D.H.); KU Leuven Research Fund grant PF/2010/07, ERA-Net BiodivERsA TIPPINGPOND, and Belspo IAP SPEEDY (L.D.M.); European Union Biodiversity Observation Network grant EU-BON-FP7-308454 (J.-B.M. and G.P.); KU Leuven Research Fund (J.P.); and NSF grants DEB-1119877 and PLR-1417754 and the McDonnell Foundation (M.C.U.).Peer reviewedPostprin

Targeting oncogenic Src homology 2 domain-containing phosphatase 2 (SHP2) by inhibiting its protein-protein interactions

We developed a new class of inhibitors of protein-protein interactions of the SHP2 phosphatase, which is pivotal in cell signaling and represents a central target in the therapy of cancer and rare diseases. Currently available SHP2 inhibitors target the catalytic site or an allosteric pocket but lack specificity or are ineffective for disease-associated SHP2 mutants. Considering that pathogenic lesions cause signaling hyperactivation due to increased levels of SHP2 association with cognate proteins, we developed peptide-based molecules with nanomolar affinity for the N-terminal Src homology domain of SHP2, good selectivity, stability to degradation, and an affinity for pathogenic variants of SHP2 that is 2-20 times higher than for the wild-type protein. The best peptide reverted the effects of a pathogenic variant (D61G) in zebrafish embryos. Our results provide a novel route for SHP2-targeted therapies and a tool for investigating the role of protein-protein interactions in the function of SHP2