CD98hc facilitates B cell proliferation and adaptive humoral immunity.

The proliferation of antigen-specific lymphocytes and resulting clonal expansion are essential for adaptive immunity. We report here that B cell-specific deletion of the heavy chain of CD98 (CD98hc) resulted in lower antibody responses due to total suppression of B cell proliferation and subsequent plasma cell formation. Deletion of CD98hc did not impair early B cell activation but did inhibit later activation of the mitogen-activated protein kinase Erk1/2 and downregulation of the cell cycle inhibitor p27. Reconstitution of CD98hc-deficient B cells with CD98hc mutants showed that the integrin-binding domain of CD98hc was required for B cell proliferation but that the amino acid-transport function of CD98hc was dispensable for this. Thus, CD98hc supports integrin-dependent rapid proliferation of B cells. We propose that the advantage of adaptive immunity favored the appearance of CD98hc in vertebrates

Report on identification of keystone species and processes across regional seas. DEVOTES FP7 Project

WP6, Deliverable 6.1, DEVOTES ProjectIn managing for marine biodiversity, it is worth recognising that, whilst every species contributes to biodiversity, each contribution is not of equal importance. Some have important effects and interactions, both primary and secondary, on other components in the community and therefore by their presence or absence directly affect the biodiversity of the community as a whole. Keystone species have been defined as species that have a disproportionate effect on their environment relative to their abundance. As such, keystone species might be of particular relevance for the marine biodiversity characterisation within the assessment of Good Environmental Status (GEnS), for the Marine Strategy Framework Directive (MSFD).The DEVOTES Keystone Catalogue and associated deliverable document is a review of potential keystone species of the different European marine habitats. The catalogue has 844 individual entries, which includes 210 distinct species and 19 groups classified by major habitat in the Baltic Sea, North East Atlantic, Mediterranean, Black Sea (EU Regional Seas) and Norwegian Sea (Non-­‐EU Sea). The catalogue and the report make use/cite 164 and 204 sources respectively. The keystones in the catalogue are indicated by models, by use as indicators, by published work (e.g. on traits and interactions with other species), and by expert opinion based on understanding of systems and roles of species/groups. A total of 74 species were considered to act as keystone predators, 79 as keystone engineers, 66 as keystone habitat forming species, while a few were thought of having multiple roles in their marine ecosystems. Benthic invertebrates accounted for 50% of the reported keystone species/groups, while macroalgae contributed 17% and fish12%. Angiosperms were consistently put forward as keystone habitat forming and engineering species in all areas. A significant number of keystones were invasive alien species.Only one keystone, the bivalve Mya arenaria, was common to all four EU regional seas. The Mediterranean Sea had the largest number of potential keystones (56% of the entries) with the least in the Norwegian Sea. There were very few keystones in deep waters (Bathyal-­‐Abyssal, 200+ m), with most reported in sublittoral shallow and shelf seabeds or for pelagic species in marine waters with few in reduced/variable salinity waters. The gaps in coverage and expertise in the catalogue are analysed at the habitat and sea level, within the MSFD biodiversity component groups and in light of knowledge and outputs from ecosystem models (Ecopath with Ecosim).The understanding of keystones is discussed as to when a species may be a dominant or keystone with respect to the definition term concerning ‘disproportionate abundance’, how important are the ‘disproportionate effects’ in relation to habitat formers and engineers, what separates a key predator and key prey for mid-­‐trophic range species and how context dependency makes a species a keystone. Keystone alien invasive species are reviewed and the use of keystone species model outputs investigated. In the penultimate sections of the review the current level of protection on keystone species and the possibilities for a keystone operational metric and their use in management and in GEnS assessments for the MSFD are discussed. The final section highlights the one keystone species and its interactions not covered in the catalogue but with the greatest impact on almost all marine ecosystems, Homo sapiens

R-Ras Regulates Migration through an Interaction with Filamin A in Melanoma Cells

Changes in cell adhesion and migration in the tumor microenvironment are key in the initiation and progression of metastasis. R-Ras is one of several small GTPases that regulate cell adhesion and migration on the extracellular matrix, however the mechanism has not been completely elucidated. Using a yeast two-hybrid approach we sought to identify novel R-Ras binding proteins that might mediate its effects on integrins.We identified Filamin A (FLNa) as a candidate interacting protein. FLNa is an actin-binding scaffold protein that also binds to integrin β1, β2 and β7 tails and is associated with diverse cell processes including cell migration. Indeed, M2 melanoma cells require FLNa for motility. We further show that R-Ras and FLNa interact in co-immunoprecipitations and pull-down assays. Deletion of FLNa repeat 3 (FLNaΔ3) abrogated this interaction. In M2 melanoma cells active R-Ras co-localized with FLNa but did not co-localize with FLNa lacking repeat 3. Thus, activated R-Ras binds repeat 3 of FLNa. The functional consequence of this interaction was that active R-Ras and FLNa coordinately increased cell migration. In contrast, co-expression of R-Ras and FLNaΔ3 had a significantly reduced effect on migration. While there was enhancement of integrin activation and fibronectin matrix assembly, cell adhesion was not altered. Finally, siRNA knockdown of endogenous R-Ras impaired FLNa-dependent fibronectin matrix assembly.These data support a model in which R-Ras functionally associates with FLNa and thereby regulates integrin-dependent migration. Thus in melanoma cells R-Ras and FLNa may cooperatively promote metastasis by enhancing cell migration

Modeling the distribution of a wide-ranging invasive species using the sampling efforts of expert and citizen scientists

1- Results for the models calibrated with <i>Weigted Pts</i> pseudo-absences for the paper 'Modelling the distribution of a wide-ranging invasive species using the sampling efforts of expert and citizen scientists'.<div>2- Final figure of the probability of distribution of rabbits in black and white.</div><div>3- Final figure of the probability of distribution of rabbits in ASC format.<br></div

Beyond knowing nature: Contact, emotion, compassion, meaning, and beauty are pathways to nature connection

Feeling connected to nature has been shown to be beneficial to wellbeing and pro-environmental behaviour. General nature contact and knowledge based activities are often used in an attempt to engage people with nature. However the specific routes to nature connectedness have not been examined systematically. Two online surveys (total n = 321) of engagement with, and value of, nature activities structured around the nine values of the Biophila Hypothesis were conducted. Contact, emotion, meaning, and compassion, with the latter mediated by engagement with natural beauty, were predictors of connection with nature, yet knowledge based activities were not. In a third study (n = 72), a walking intervention with activities operationalising the identified predictors, was found to significantly increase connection to nature when compared to walking in nature alone or walking in and engaging with the built environment. The findings indicate that contact, emotion, meaning, compassion, and beauty are pathways for improving nature connectedness. The pathways also provide alternative values and frames to the traditional knowledge and identification routes often used by organisations when engaging the public with nature.N/

Human Endometrial CD98 Is Essential for Blastocyst Adhesion

BACKGROUND: Understanding the molecular basis of embryonic implantation is of great clinical and biological relevance. Little is currently known about the adhesion receptors that determine endometrial receptivity for embryonic implantation in humans. METHODS AND PRINCIPAL FINDINGS: Using two human endometrial cell lines characterized by low and high receptivity, we identified the membrane receptor CD98 as a novel molecule selectively and significantly associated with the receptive phenotype. In human endometrial samples, CD98 was the only molecule studied whose expression was restricted to the implantation window in human endometrial tissue. CD98 expression was restricted to the apical surface and included in tetraspanin-enriched microdomains of primary endometrial epithelial cells, as demonstrated by the biochemical association between CD98 and tetraspanin CD9. CD98 expression was induced in vitro by treatment of primary endometrial epithelial cells with human chorionic gonadotropin, 17-β-estradiol, LIF or EGF. Endometrial overexpression of CD98 or tetraspanin CD9 greatly enhanced mouse blastocyst adhesion, while their siRNA-mediated depletion reduced the blastocyst adhesion rate. CONCLUSIONS: These results indicate that CD98, a component of tetraspanin-enriched microdomains, appears to be an important determinant of human endometrial receptivity during the implantation window

Aberrant Herpesvirus-Induced Polyadenylation Correlates With Cellular Messenger RNA Destruction

Inhibition of host cell gene expression by the human herpesvirus KSHV occurs via a novel mechanism involving polyadenylation-linked RNA turnover