Substrate-specific function of the translocon-associated protein complex during translocation across the ER membrane

Although the transport of model proteins across the mammalian ER can be reconstituted with purified Sec61p complex, TRAM, and signal recognition particle receptor, some substrates, such as the prion protein (PrP), are inefficiently or improperly translocated using only these components. Here, we purify a factor needed for proper translocation of PrP and identify it as the translocon-associated protein (TRAP) complex. Surprisingly, TRAP also stimulates vectorial transport of many, but not all, other substrates in a manner influenced by their signal sequences. Comparative analyses of several natural signal sequences suggest that a dependence on TRAP for translocation is not due to any single physical parameter, such as hydrophobicity of the signal sequence. Instead, a functional property of the signal, efficiency of its post-targeting role in initiating substrate translocation, correlates inversely with TRAP dependence. Thus, maximal translocation independent of TRAP can only be achieved with a signal sequence, such as the one from prolactin, whose strong interaction with the translocon mediates translocon gating shortly after targeting. These results identify the TRAP complex as a functional component of the translocon and demonstrate that it acts in a substrate-specific manner to facilitate the initiation of protein translocation

Differing Mechanisms Underlie Sexual Size-Dimorphism in Two Populations of a Sex-Changing Fish

Variability in the density of groups within a patchy environment lead to differences in interaction rates, growth dynamics and social organization. In protogynous hermaphrodites there are hypothesised trade-offs among sex-specific growth, reproductive output and mortality. When differences in density lead to changes to social organization the link between growth and the timing of sex-change is predicted to change. The present study explores this prediction by comparing the social organisation and sex-specific growth of two populations of a protogynous tropical wrasse, Halichoeres miniatus, which differ in density. At a low density population a strict harem structure was found, where males maintained a tight monopoly of access and spawning rights to females. In contrast, at a high density population a loosely organised system prevailed, where females could move throughout multiple male territories. Otolith microstructure revealed the species to be annual and deposit an otolith check associated with sex-change. Growth trajectories suggested that individuals that later became males in both populations underwent a growth acceleration at sex-change. Moreover, in the high density population, individuals that later became males were those individuals that had the largest otolith size at hatching and consistently deposited larger increments throughout early larval, juvenile and female life. This study demonstrates that previous growth history and growth rate changes associated with sex change can be responsible for the sexual dimorphism typically found in sex-changing species, and that the relative importance of these may be socially constrained

Investigating the social value of the Ripon rivers flood alleviation scheme

This paper argues for an approach to flood alleviation design that considers the need not only for technical knowledge, but also a social perspective. It is predicted that more intense rainfall and rising sea levels will result in a greater number of people vulnerable to flood events. Flood alleviation design in the UK is often focused upon technical and cost-effective solutions, and consideration of social impact is seen as secondary. This paper examines how the social value of a UK flood alleviation scheme is perceived and discussed, by the local community and by those responsible for the design of the scheme, and exposes differences in perceptions both between and within these two groups. It recommends a future approach in which an understanding of the social value of a flood alleviation scheme is first co-produced with the community affected, enabling the design of a socially acceptable and successful project.The research presented in this paper is part of a larger study. The research is conducted with the aid of funding from an Engineering and Physical Sciences Research Council (EPSRC) iCASE doctoral award. Ove Arup and Partners also provide sponsorship as part of the award.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/jfr3.1217

Evaluating implicit feedback models using searcher simulations

In this article we describe an evaluation of relevance feedback (RF) algorithms using searcher simulations. Since these algorithms select additional terms for query modification based on inferences made from searcher interaction, not on relevance information searchers explicitly provide (as in traditional RF), we refer to them as implicit feedback models. We introduce six different models that base their decisions on the interactions of searchers and use different approaches to rank query modification terms. The aim of this article is to determine which of these models should be used to assist searchers in the systems we develop. To evaluate these models we used searcher simulations that afforded us more control over the experimental conditions than experiments with human subjects and allowed complex interaction to be modeled without the need for costly human experimentation. The simulation-based evaluation methodology measures how well the models learn the distribution of terms across relevant documents (i.e., learn what information is relevant) and how well they improve search effectiveness (i.e., create effective search queries). Our findings show that an implicit feedback model based on Jeffrey's rule of conditioning outperformed other models under investigation

Interacting with eHealth - Towards grand challenges for HCI

While health records are increasingly stored electronically, we, as citizens, have little access to this data about ourselves. We are not used to thinking of these official records either as ours or as useful to us. We increasingly turn to the Web, however, to query any ache, pain or health goal we may have before consulting with health care professionals. Likewise, for proactive health care such as nutrition or fitness, or to find fellow-sufferers for post diagnosis support, we turn to online resources. There is a potential disconnect between points at which professional and lay eHealth data and resources intersect for preventative or proactive health care. Such gaps in information sharing may have direct impact on practices we decide to take up, the care we seek, or the support professionals offer. In this panel, we consider several places within proactive, preventative health care in particular HCI has a role towards enhancing health knowledge discovery and health support interaction. Our goal is to demonstrate how now is the time for eHealth to come to the forefront of the HCI research agenda

Playing in the academic field: Non-native English-speaking academics in UK business schools

This paper draws on Bourdieu's concepts of field, habitus and capital to explore the ways in which working in English as a non-native language influences foreign academics' performance of academic habitus and the level of their symbolic capital necessary for the achievement of success within UK higher education. Empirically, it is based on interviews with 54 non-native English-speaking academics employed in UK business schools. Our findings point to advantages and disadvantages associated with being a non-native English-speaking academic, to strategies deployed by individuals to enhance their linguistic capital, and to the importance of language not merely as a tool of communication but as a key factor enabling individuals to perform academic habitus in the UK academic field. We reflect on whether, and if so, how, the UK academic field is changing as a result of the increased presence within it of non-UK-born academics and, in particular, the fact of their professional functioning in English as a non-native language

Identification and phylogenetic comparison of p53 in two distinct mussel species (Mytilus)

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 140 (2005): 237-250, doi:10.1016/j.cca.2005.02.011.The extent to which humans and wildlife are exposed to anthropogenic challenges is an important focus of environmental research. Potential use of p53 gene family marker(s) for aquatic environmental effects monitoring is the long-term goal of this research. The p53 gene is a tumor suppressor gene that is fundamental in cell cycle control and apoptosis. It is mutated or differentially expressed in about 50% of all human cancers and p53 family members are differentially expressed in leukemic clams. Here, we report the identification and characterization of the p53 gene in two species of Mytilus, Mytilus edulis and Mytilus trossulus, using RT-PCR with degenerate and specific primers to conserved regions of the gene. The Mytilus p53 proteins are 99.8% identical and closely related to clam (Mya) p53. In particular, the 3′ untranslated regions were examined to gain understanding of potential post-transcriptional regulatory pathways of p53 expression. We found nuclear and cytoplasmic polyadenylation elements, adenylate/uridylate-rich elements, and a K-box motif previously identified in other, unrelated genes. We also identified a new motif in the p53 3′UTR which is highly conserved across vertebrate and invertebrate species. Differences between the p53 genes of the two Mytilus species may be part of genetic determinants underlying variation in leukemia prevalence and/or development, but this requires further investigation. In conclusion, the conserved regions in these p53 paralogues may represent potential control points in gene expression. This information provides a critical first step in the evaluation of p53 expression as a potential marker for environmental assessment.AFM was supported by the Greater Vancouver Regional District, BC, Canada, and RLC was supported by STAR grant R82935901 from the Environmental Protection Agency (USA)