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

Cancer-associated epithelial cell adhesion molecule (EpCAM; CD326) enables epidermal Langerhans cell motility and migration in vivo

After activation, Langerhans cells (LC), a distinct subpopulation of epidermis-resident dendritic cells, migrate from skin to lymph nodes where they regulate the magnitude and quality of immune responses initiated by epicutaneously applied antigens. Modulation of LC-keratinocyte adhesion is likely to be central to regulation of LC migration. LC express high levels of epithelial cell adhesion molecule (EpCAM; CD326), a cell-surface protein that is characteristic of some epithelia and many carcinomas and that has been implicated in intercellular adhesion and metastasis. To gain insight into EpCAM function in a physiologic context in vivo, we generated conditional knockout mice with EpCAM-deficient LC and characterized them. Epidermis from these mice contained increased numbers of LC with normal levels of MHC and costimulatory molecules and T-cell-stimulatory activity in vitro. Migration of EpCAM-deficient LC from skin explants was inhibited, but chemotaxis of dissociated LC was not. Correspondingly, the ability of contact allergen-stimulated, EpCAM-deficient LC to exit epidermis in vivo was delayed, and strikingly fewer hapten-bearing LC subsequently accumulated in lymph nodes. Attenuated migration of EpCAM-deficient LC resulted in enhanced contact hypersensitivity responses as previously described in LC-deficient mice. Intravital microscopy revealed reduced translocation and dendrite motility in EpCAM-deficient LC in vivo in contact allergen-treated mice. These results conclusively link EpCAM expression to LC motility/migration and LC migration to immune regulation. EpCAM appears to promote LC migration from epidermis by decreasing LC-keratinocyte adhesion and may modulate intercellular adhesion and cell movement within in epithelia during development and carcinogenesis in an analogous fashion

Loss of Individual MicroRNAs Causes Mutant Phenotypes in Sensitized Genetic Backgrounds in \u3cem\u3eC. elegans\u3c/em\u3e

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate the translation and/or stability of their mRNA targets. Previous work showed that for most miRNA genes of C. elegans, single-gene knockouts did not result in detectable mutant phenotypes. This may be due, in part, to functional redundancy between miRNAs. However, in most cases, worms carrying deletions of all members of a miRNA family do not display strong mutant phenotypes. They may function together with unrelated miRNAs or with non-miRNA genes in regulatory networks, possibly to ensure the robustness of developmental mechanisms. To test this, we examined worms lacking individual miRNAs in genetically sensitized backgrounds. These include genetic backgrounds with reduced processing and activity of all miRNAs or with reduced activity of a wide array of regulatory pathways. With these two approaches, we identified mutant phenotypes for 25 out of 31 miRNAs included in this analysis. Our findings describe biological roles for individual miRNAs and suggest that the use of sensitized genetic backgrounds provides an efficient approach for miRNA functional analysis

A mammalian Wnt5a-Ror2-Vangl2 axis controls the cytoskeleton and confers cellular properties required for alveologenesis.

Alveolar formation increases the surface area for gas-exchange and is key to the physiological function of the lung. Alveolar epithelial cells, myofibroblasts and endothelial cells undergo coordinated morphogenesis to generate epithelial folds (secondary septa) to form alveoli. A mechanistic understanding of alveologenesis remains incomplete. We found that the planar cell polarity (PCP) pathway is required in alveolar epithelial cells and myofibroblasts for alveologenesis in mammals. Our studies uncovered a Wnt5a-Ror2-Vangl2 cascade that endows cellular properties and novel mechanisms of alveologenesis. This includes PDGF secretion from alveolar type I and type II cells, cell shape changes of type I cells and migration of myofibroblasts. All these cellular properties are conferred by changes in the cytoskeleton and represent a new facet of PCP function. These results extend our current model of PCP signaling from polarizing a field of epithelial cells to conferring new properties at subcellular levels to regulate collective cell behavior

Validating the use of intrinsic markers in body feathers to identify inter-individual differences in non-breeding areas of northern fulmars

Acknowledgments We thank Claire Deacon, Gareth Norton and Andrea Raab for help with laboratory work at the University of Aberdeen, and Barry Thornton and Gillian Martin for running stable isotope analysis at the James Hutton Institute. Thanks to all involved in the collection and processing of dead fulmars through the North Sea plastic pollution project at IMARES, with special thanks to Jens-Kjeld Jensen, Bergur Olsen and Elisa Bravo Rebolledo for samples from the Faroe Islands and Susanne Kühn for those from Iceland. Thanks to Orkney Islands Council for access to Eynhallow and to all the fieldworkers involved in deployment and recovery of the GLS tags. All ringing work was carried out under permit from the BTO, and feather sampling was carried out under licence from the Home Office. We are grateful to James Fox of Migrate Technologies for recovering data from GLS loggers which would not download, and Richard Phillips and Janet Silk of BAS for advice on GLS analysis. We thank Deborah Dawson of the NERC Biomolecular Analysis Facility, University of Sheffield and Stuart Piertney of University of Aberdeen for molecular sexing of the fulmars. Lucy Quinn was supported by a NERC Studentship and additional funding to support fieldwork was gratefully received from Talisman Energy (UK) Ltd. We thank Yves Cherel and two anonymous reviewers for their constructive comments on the manuscript.Peer reviewedPublisher PD

Comparison of rapid laboratory tests for failure of passive transfer in the bovine

peer-reviewedBackground Failure of passive transfer of maternal immunity via colostrum can occur in the bovine, and a number of blood tests have been developed to test calves for this failure. It is not clear which test is most suitable for this purpose. The objective was to examine the most commonly used tests for failure of passive transfer and to decide which is most suitable for routine laboratory use. 126 serum samples were taken from calves of dairy cows after birth but prior to colostrum feeding, and at 48 h of age. Five different tests were compared against radial immunodiffusion which is considered the appropriate reference method. These tests were serum gamma-glutamyltransferase levels, serum protein levels, serum globulin levels, an enzyme linked immunosorbent assay and the zinc sulphate turbidity test. Results The tests examined displayed high sensitivity but widely varying specificity. Examination of the use of different cut-off points allowed some improvement in specificity at the expense of sensitivity, but the tests which had performed best at the original cut-off points still displayed the best performance. Gamma-glutamyltransferase levels as a measure of colostrum absorption returned, in this study, the best balance between sensitivity and specificity. The ELISA used in this study and serum globulin levels displayed performance similar to the gamma-glutamyltransferase levels. Serum total protein was less successful than others examined at providing both sensitivity and specificity but may, when performed via refractometer, be useful for on-farm testing. As currently performed the poor sensitivity for which the zinc sulphate turbidity test is most often criticized is evident. Modification of the cut-off point to increase specificity is less successful at balancing these parameters than the ELISA, gamma-glutamyltransferase levels, and globulin levels. Conclusions Gamma-glutamyltransferase levels, ELISA testing and circulating globulin levels performed best in detecting failure of passive transfer in serum samples, although all three had some practical considerations

Curating E-Mails; A life-cycle approach to the management and preservation of e-mail messages

E-mail forms the backbone of communications in many modern institutions and organisations and is a valuable type of organisational, cultural, and historical record. Successful management and preservation of valuable e-mail messages and collections is therefore vital if organisational accountability is to be achieved and historical or cultural memory retained for the future. This requires attention by all stakeholders across the entire life-cycle of the e-mail records. This instalment of the Digital Curation Manual reports on the several issues involved in managing and curating e-mail messages for both current and future use. Although there is no 'one-size-fits-all' solution, this instalment outlines a generic framework for e-mail curation and preservation, provides a summary of current approaches, and addresses the technical, organisational and cultural challenges to successful e-mail management and longer-term curation.

Globalisation of HR at Function Level: Exploring the Issues Through International Recruitment, Selection and Assessment Processes

Much of the debate around convergence-divergence is based around comparative analysis of HR systems. However, we need now to combine these insights with work in the field of IHRM on firm-level motivations to optimise, standardise and export HR models abroad. A series of the changes are being wrought on a range of IHRM functions – recruitment, global staffing, management development and careers, and rewards - by the process of globalisation highlighting the difference between globally standardised, optimised or localised HR processes. This paper reports on a study of firm-level developments in international recruitment, selection and assessment, drawing upon an analysis of four case studies each conducted in a different context. Organisations are building IHRM functions that are shifting from the management of expatriation towards supplementary services to the business aimed at facilitating the globalisation process, and this involves capitalising upon the fragmentation of international employees. As HR realigns itself in response to this process of within-function globalisation (building new alliances with other functions such as marketing and IS) the new activity streams that are being developed and the new roles and skills of the HR function carry important implications for the study of convergence and divergence of IHRM practice. Globalisation at firm level revolves around complexity, and this is evidenced in two ways: first, the range of theory that we have to draw upon, and the competing issues that surface depending on the level of analysis that is adopted; and second, the different picture that might emerge depending upon the level of analysis that is adopted. This paper shows that although the field of IHRM has traditionally drawn upon core theories such as the resource-based view of the firm, relational and social capital, and institutional theory, once the full range of resourcing options now open to IHRM functions are considered, it is evident that we need to incorporate both more micro theory, as well as insights from contingent fields in order to explain some of the new practices that are emerging