The murine Nck SH2/SH3 adaptors are important for the development of mesoderm-derived embryonic structures and for regulating the cellular actin network

Mammalian Nck1 and Nck2 are closely related adaptor proteins that possess three SH3 domains, followed by an SH2 domain, and are implicated in coupling phosphotyrosine signals to polypeptides that regulate the actin cytoskeleton. However, the in vivo functions of Nck1 and Nck2 have not been defined. We have mutated the murine Nck1 and Nck2 genes and incorporated beta-galactosidase reporters into the mutant loci. In mouse embryos, the two Nck genes have broad and overlapping expression patterns. They are functionally redundant in the sense that mice deficient for either Nck1 or Nck2 are viable, whereas inactivation of both Nck1 and Nck2 results in profound defects in mesoderm-derived notochord and embryonic lethality at embryonic day 9.5. Fibroblast cell lines derived from Nck1(-/-) Nck2(-/-) embryos have defects in cell motility and in the organization of the lamellipodial actin network. These data suggest that the Nck SH2/SH3 adaptors have important functions in the development of mesodermal structures during embryogenesis, potentially linked to a role in cell movement and cytoskeletal organization.     

Structural basis for specific binding of the Gads SH3 domain to an RxxK motif-containing SLP-76 peptide: a novel mode of peptide recognition

The SH3 domain, which normally recognizes proline-rich sequences, has the potential to bind motifs with an RxxK consensus. To explore this novel specificity, we have determined the solution structure of the Gads T cell adaptor C-terminal SH3 domain in complex with an RSTK-containing peptide, representing its physiological binding site on the SLP-76 docking protein. The SLP-76 peptide engages four distinct binding pockets on the surface of the Gads SH3 domain and upon binding adopts a unique structure characterized by a right-handed 3(10) helix at the RSTK locus, in contrast to the left-handed polyproline type II helix formed by canonical proline-rich SH3 ligands. The structure, and supporting mutagenesis and peptide binding data, reveal a novel mode of ligand recognition by SH3 domains.     

A multiplexed set of microsatellite markers for discriminating <Emphasis Type="Italic">Acacia mangium</Emphasis>, <Emphasis Type="Italic">A. auriculiformis</Emphasis>, and their hybrid

In order to assist breeding and gene pool conservation in tropical Acacias, we aimed to develop a set of multipurpose SSR markers for use in both Acacia mangium and A. auriculiformis. A total of 51 SSR markers (developed in A. mangium and natural A. mangium x A. auriculiformis hybrid) were tested. A final set of 16 well-performing SSR markers were identified, six of which were species diagnostic. The markers were optimized for assay in four multiplex mixes and used to genotype range-wide samples of A. mangium, A. auriculiformis, and putative F₁ hybrids. Simulation analysis was used to investigate the power of the markers for identifying the pure species and their F₁, F₂, and backcross hybrids. The six species diagnostic markers were particularly powerful for detecting F₁ hybrids from pure species but could also discriminate the pure species from F₂ and backcross progenies in most cases (97 %). STRUCTURE analysis using all 16 markers was likewise able to distinguish these cross types and pure species sets. Both sets of markers had difficulties in distinguishing F₂ and backcross progenies. However, identifying F₁ from pure species is the current primary concern in countries where these species are planted. The SSR marker set also has direct application in DNA profiling (probability of identity?=?4.1?×?10^?13), breeding system analysis, and population genetics.     

Hearing Loss and Cognition: The Role of Hearing Aids,Social Isolation and Depression

Hearing loss is associated with poor cognitive performance and incident dementia and may contribute to cognitive decline. Treating hearing loss with hearing aids may ameliorate cognitive decline. The purpose of this study was to test whether use of hearing aids was associated with better cognitive performance, and if this relationship was mediated via social isolation and/or depression. Structural equation modelling of associations between hearing loss, cognitive performance, social isolation, depression and hearing aid use was carried out with a subsample of the UK Biobank data set (n = 164,770) of UK adults aged 40 to 69 years who completed a hearing test. Age, sex, general health and socioeconomic status were controlled for as potential confounders. Hearing aid use was associated with better cognition, independently of social isolation and depression. This finding was consistent with the hypothesis that hearing aids may improve cognitive performance, although if hearing aids do have a positive effect on cognition it is not likely to be via reduction of the adverse effects of hearing loss on social isolation or depression. We suggest that any positive effects of hearing aid use on cognition may be via improvement in audibility or associated increases in self-efficacy. Alternatively, positive associations between hearing aid use and cognition may be accounted for by more cognitively able people seeking and using hearing aids. Further research is required to determine the direction of association, if there is any direct causal relationship between hearing aid use and better cognition, and whether hearing aid use results in reduction in rates of cognitive decline measured longitudinally.     

Determinants of Unlawful File Sharing: A Scoping Review

We employ a scoping review methodology to consider and assess the existing evidence on the determinants of unlawful file sharing (UFS) transparently and systematically. Based on the evidence, we build a simple conceptual framework to model the psychological decision to engage in UFS, purchase legally or do nothing. We identify social, moral, experiential, technical, legal and financial utility sources of the decision to purchase or to file share. They interact in complex ways. We consider the strength of evidence within these areas and note patterns of results. There is good evidence for influences on UFS within each of the identified determinants, particularly for self-reported measures, with more behavioral research needed. There are also indications that the reasons for UFS differ across media; more studies exploring media other than music are required.     

Sacrifice as the ideal hunt: a cosmological explanation for the origin of reindeer domestication

The Siberian Northeast shows striking parallels between the cosmologies of hunters and reindeer herders. What may this tell us about the transformation from hunting to pastoralism? This article argues for a structural identity between hunting and sacrifice, and for the domestication of the reindeer as the result of hunters' efforts to use sacrifice to control the accidental variables of the hunt. Hunters can practise their ethos of ‘trust’ with prey only through highly controlled ritual enactments. We describe two: the famous bear festival of the Amur Gulf region and the consecrated reindeer of the Eveny. Both express the same overall logic by which sacrifice functions as an ideal hunt. The animal is involved in a relation not of domination but of trust, while also undergoing a process of taming. We therefore suggest that the reindeer's domestication may be based not only on ecological or economic adaptations, but also on cosmology.     

Modelling marine protected areas: insights and hurdles

Models provide useful insights into conservation and resource management issues and solutions. Their use to date has highlighted conditions under which no-take marine protected areas (MPAs) may help us to achieve the goals of ecosystem-based management by reducing pressures, and where they might fail to achieve desired goals. For example, static reserve designs are unlikely to achieve desired objectives when applied to mobile species or when compromised by climate-related ecosystem restructuring and range shifts. Modelling tools allow planners to explore a range of options, such as basing MPAs on the presence of dynamic oceanic features, and to evaluate the potential future impacts of alternative interventions compared with ‘no-action’ counterfactuals, under a range of environmental and development scenarios. The modelling environment allows the analyst to test if indicators and management strategies are robust to uncertainties in how the ecosystem (and the broader human–ecosystem combination) operates, including the direct and indirect ecological effects of protection. Moreover, modelling results can be presented at multiple spatial and temporal scales, and relative to ecological, economic and social objectives. This helps to reveal potential ‘surprises'', such as regime shifts, trophic cascades and bottlenecks in human responses. Using illustrative examples, this paper briefly covers the history of the use of simulation models for evaluating MPA options, and discusses their utility and limitations for informing protected area management in the marine realm.