Polymorphisms in the selectin gene cluster are associated with fertility and survival time in a population of Holstein Friesian cows

Selectins are adhesion molecules, which mediate attachment between leucocytes and endothelium. They aid extravasation of leucocytes from blood into inflamed tissue during the mammary gland’s response to infection. Selectins are also involved in attachment of the conceptus to the endometrium and subsequent placental development. Poor fertility and udder health are major causes for culling dairy cows. The three identified bovine selectin genes SELP, SELL and SELE are located in a gene cluster. SELP is the most polymorphic of these genes. Several SNP in SELP and SELE are associated with human vascular disease, while SELP SNP rs6127 has been associated with recurrent pregnancy loss in women. This study describes the results of a gene association study for SNP in SELP (n = 5), SELL (n = 2) and SELE (n = 1) with fertility, milk production and longevity traits in a population of 337 Holstein Friesian dairy cows. Blood samples for PCR-RFLP were collected at 6 months of age and animals were monitored until either culling or 2,340 days from birth. Three SNP in SELPEx4-6 formed a haplotype block containing a Glu/Ala substitution at rs42312260. This region was associated with poor fertility and reduced survival times. SELPEx8 (rs378218397) coded for a Val475Met variant locus in the linking region between consensus repeats 4 and 5, which may influence glycosylation. The synonymous SNP rs110045112 in SELEEx14 deviated from Hardy Weinberg equilibrium. For both this SNP and rs378218397 there were too few AA homozygotes present in the population and AG heterozygotes had significantly worse fertility than GG homozygotes. Small changes in milk production associated with some SNP could not account for the reduced fertility and only SELPEx6 showed any association with somatic cell count. These results suggest that polymorphisms in SELP and SELE are associated with the likelihood of successful pregnancy, potentially through compromised implantation and placental development

Mechanisms of T cell organotropism

F.M.M.-B. is supported by the British Heart Foundation, the Medical Research Council of the UK and the Gates Foundation

TET inducible expression of the α4β7-integrin ligand MAdCAM-1 on the blood-brain barrier does not influence the immunopathogenesis of experimental autoimmune encephalomyelitis

Inhibiting the α4 subunit of the integrin heterodimers α4β1 and α4β7 with the mab natalizumab is an effective treatment of multiple sclerosis (MS). Which of the two α4 heterodimers is involved in disease pathogenesis has, however, remained controversial. Whereas the development of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, is ameliorated in β7-integrin-deficient C57BL/6 mice, neutralizing antibodies against the β7-integrin subunit or the α4β7-integrin heterodimer fail to interfere with EAE pathogenesis in the SJL mouse. To facilitate α4β7-integrin-mediated immune-cell trafficking across the blood-brain barrier (BBB), we established transgenic C57BL/6 mice with endothelial cell-specific, inducible expression of the α4β7-integrin ligand mucosal addressin cell adhesion molecule (MAdCAM)-1 using the tetracycline (TET)-OFF system. Although TET-regulated MAdCAM-1 induced α4β7-integrin mediated interaction of α4β7(+) /α4β1(-) T cells with the BBB in vitro and in vivo, it failed to influence EAE pathogenesis in C57BL/6 mice. TET-regulated MAdCAM-1 on the BBB neither changed the localization of central nervous system (CNS) perivascular inflammatory cuffs nor did it enhance the percentage of α4β7-integrin(+) inflammatory cells within the CNS during EAE. In conclusion, our study demonstrates that ectopic expression of MAdCAM-1 at the BBB does not increase α4β7-integrin-mediated immune cell trafficking into the CNS during MOG(aa35-55)-induced EAE

SPASE metadata as a building block of a heliophysics science-enabling framework

International audienceHeliophysics and space weather research encompass the effects of solar output on practically the entire Solar System and are fundamentally cross-disciplinary. Cross-domain science investigations, such as in Sun-heliosphere interactions, solar wind-magnetosphere interactions, or magnetosphere-ionosphere coupling, often require the use of data, models, and other digital resources pertaining to different heliophysical domains: the Sun, the solar wind, the magnetosphere, the ionosphere, the thermosphere and the mesosphere. Due to differences in measurement platforms, techniques and instruments, heliophysics data obtained from different domains are diverse and complex, making the resource landscape difficult for untrained users to navigate. Without proper and adequate guidance from domain experts, it is often difficult for early-career scientists and non-domain experts to discover useful datasets and to know from where and how to obtain and understand the data they need to support their research. This paper describes the roles of metadata in providing the identification, location, access protocol, and detailed content description of a digital resource. More specifically, we point out that metadata written according to the Space Physics Archive Search and Extract (SPASE) metadata model are fully compatible with the FAIR principles so that digital resources described using the SPASE model can be uniformly Findable, Accessible, Interoperable, and Reusable. SPASE metadata can thus be the key element, the lingua franca so to speak, that enables unfettered information flow between data systems and services throughout the heliophysics data environment and lowers the understandability barrier of the resources to ensure their independent usability. After describing various components of the heliophysics data environment, their metadata requirements for effective operations, and some essential features of the SPASE metadata model, we then illustrate how metadata in SPASE can enable or facilitate the performance of different science tasks. The current status and future outlook of SPASE are also presented