Endogenous retroviruses

Xenotransplantation is defined by the PHS as any procedure that involves the transplantation, implantation or infusion into a human recipient of either (a) live cells, tissues or organs from a nonhuman animal source, or (b) human body fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman animal cells, tissues or organs (Public Health Service Guideline on Infectious Disease Issues in Xenotransplantation). Use of pigs for human xenotransplantation raises concerns about the risks of transfer of infectious agents from the pig cells to xenotransplantation recipients. The observation that the porcine germline harbors genetic loci encoding porcine endogenous retroviruses (PERVs) that are in some cases infectious for human cells has resulted in renewed scientific interest in PERVs. However, in spite of the past 10 years of investigation, the actual risk for PERV infection, replication, and pathogenic outcome in human recipients of xenotransplantation products is still undefined. (Part of a Multi-author Review)     

Age differences at marriage and divorce

This article explores the age difference of marrying and divorcing couples, calculated by subtracting the wife's age from the husband's. Age difference is of interest in the study of families and partnership behaviour. It is also important because of its link with broader socio-demographic changes, such as population ageing, delayed fertility and the provision of care. The main finding is that between 1963 and 2005, the distribution of age differences for all marriages is very similar in each year to the distribution of age differences for the subset of couples who married in that year, but have since divorced. While there is some evidence of small variations in the proportion of marriages that end in divorce by age difference, there does not seem to be evidence of a strong association.     

Taxonomic revision of the seasonal killifish genus Nothobranchius from Zanzibar,East Africa (Cyprinodontoidei: Aplocheilidae)

Nothobranchius guentheri and Nothobranchius melanospilus, the two seasonal killifishes of the genus Nothobranchius occurring in Zanzibar Island, Tanzania, were involved in past taxonomical mistakes and are still misidentified in museum collections. A historical review is herein presented and both species are redescribed on the basis of type material and recent collections. Nothobranchius guentheri, a popular aquarium fish, is endemic to Zanzibar, and N. melanospilus, geographically widespread in East Africa, occurring both in Zanzibar and in continental river basins. These species are distinguished by a series of morphological features not previously reported in the literature, including pre-dorsal length and relative position of the anterior portion of the dorsal-fin skeletal support and vertebrae; number of gill-rakers of the first branchial arch, caudal-fin rays, scales of the longitudinal series, series of scales around caudal peduncle, and vertebrae; frontal squamation; and arrangement and number of neuromasts of the supraorbital series. The present taxonomic revision comprising N. guentheri and N. melanospilus, the oldest species names of the genus in the East African biodiversity hotspot, is important to improve the knowledge of the genus in a region where its taxonomy is still problematic     

The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens.

Macrophages orchestrate innate immunity by phagocytosing pathogens and coordinating inflammatory responses. Effective defence requires the host to discriminate between different pathogens. The specificity of innate immune recognition in Drosophila is mediated by the Toll family of receptors; Toll mediates anti-fungal responses, whereas 18-wheeler mediates anti-bacterial defence. A large number of Toll homologues have been identified in mammals, and Toll-like receptor 4 is critical in responses to Gram-negative bacteria. Here we show that Toll-like receptor 2 is recruited specifically to macrophage phagosomes containing yeast, and that a point mutation in the receptor abrogates inflammatory responses to yeast and Gram-positive bacteria, but not to Gram-negative bacteria. Thus, during the phagocytosis of pathogens, two classes of innate immune receptors cooperate to mediate host defence: phagocytic receptors, such as the mannose receptor, signal particle internalization, and the Toll-like receptors sample the contents of the vacuole and trigger an inflammatory response appropriate to defence against the specific organism.     

Participation of DNA repair in the response to 5-fluorouracil

The anti-metabolite 5-fluorouracil (5-FU) is employed clinically to manage solid tumors including colorectal and breast cancer. Intracellular metabolites of 5-FU can exert cytotoxic effects via inhibition of thymidylate synthetase, or through incorporation into RNA and DNA, events that ultimately activate apoptosis. In this review, we cover the current data implicating DNA repair processes in cellular responsiveness to 5-FU treatment. Evidence points to roles for base excision repair (BER) and mismatch repair (MMR). However, mechanistic details remain unexplained, and other pathways have not been exhaustively interrogated. Homologous recombination is of particular interest, because it resolves unrepaired DNA intermediates not properly dealt with by BER or MMR. Furthermore, crosstalk among DNA repair pathways and S-phase checkpoint signaling has not been examined. Ongoing efforts aim to design approaches and reagents that (i) approximate repair capacity and (ii) mediate strategic regulation of DNA repair in order to improve the efficacy of current anticancer treatments. Received 08 September 2008; received after revision 25 September 2008; accepted 03 October 2008     

The proportion of marriages ending in divorce

Even though cohabitation has become more prevalent in the last few decades, the majority of the adult population is married, and marriage is associated with a number of factors, such as educational outcom and health. Understanding the marrie population is also an important part of understanding partnering behaviour and family formation and dissolution. The length of marriages and whether they are ended by death or divorce is therefore of interest t demographers and policy maker     

Rheumatoid arthritis susceptibility loci at chromosomes 10p15, 12q13 and 22q13

The WTCCC study identified 49 SNPs putatively associated with rheumatoid arthritis at P = 1 x 10(-4) - 1 x 10(-5) (tier 3). Here we show that three of these SNPs, mapping to chromosome 10p15 (rs4750316), 12q13 (rs1678542) and 22q13 (rs3218253), are also associated (trend P = 4 x 10(-5), P = 4 x 10(-4) and P = 4 x 10(-4), respectively) in a validation study of 4,106 individuals with rheumatoid arthritis and an expanded reference group of 11,238 subjects, confirming them as true susceptibility loci in individuals of European ancestry.     

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.     

Topological surface states and flat bands in the kagome superconductor CsV3Sb5

Exotic quantum phenomena may appear in material systems with multiple orders or phases,where the mutual interactions can give rise to new physics beyond that of...