Production of amphiregulin and recovery from influenza is greater in males than females

Abstract Background Amphiregulin (AREG) is an epidermal growth factor that is a significant mediator of tissue repair at mucosal sites, including in the lungs during influenza A virus (IAV) infection. Previous research illustrates that males of reproductive ages experience less severe disease and recover faster than females following infection with IAV. Methods Whether males and females differentially produce and utilize AREG for pulmonary repair after IAV infection was investigated using murine models on a C57BL/6 background and primary mouse and human epithelial cell culture systems. Results Following sublethal infection with 2009 H1N1 IAV, adult female mice experienced greater morbidity and pulmonary inflammation during the acute phase of infection as well as worse pulmonary function during the recovery phase of infection than males, despite having similar virus clearance kinetics. As compared with females, AREG expression was greater in the lungs of male mice as well as in primary respiratory epithelial cells derived from mouse and human male donors, in response to H1N1 IAVs. Internalization of the epidermal growth factor receptor (EGFR) was also greater in respiratory epithelial cells derived from male than female mice. IAV infection of Areg knock-out (Areg −/−) mice eliminated sex differences in IAV pathogenesis, with a more significant role for AREG in infection of male compared to female mice. Deletion of Areg had no effect on virus replication kinetics in either sex. Gonadectomy and treatment of either wild-type or Areg −/− males with testosterone improved the outcome of IAV as compared with their placebo-treated conspecifics. Conclusions Taken together, these data show that elevated levels of testosterone and AREG, either independently or in combination, improve resilience (i.e., repair and recovery of damaged tissue) and contribute to better influenza outcomes in males compared with females

A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age.

Early-onset breast cancer (EOBC) causes substantial loss of life and productivity, creating a major burden among women worldwide. We analyzed 1,265,548 Hapmap3 single-nucleotide polymorphisms (SNP) among a discovery set of 3,523 EOBC incident cases and 2,702 population control women ages ≤ 51 years. The SNPs with smallest P values were examined in a replication set of 3,470 EOBC cases and 5,475 control women. We also tested EOBC association with 19,684 genes by annotating each gene with putative functional SNPs, and then combining their P values to obtain a gene-based P value. We examined the gene with smallest P value for replication in 1,145 breast cancer cases and 1,142 control women. The combined discovery and replication sets identified 72 new SNPs associated with EOBC (P < 4 × 10(-8)) located in six genomic regions previously reported to contain SNPs associated largely with later-onset breast cancer (LOBC). SNP rs2229882 and 10 other SNPs on chromosome 5q11.2 remained associated (P < 6 × 10(-4)) after adjustment for the strongest published SNPs in the region. Thirty-two of the 82 currently known LOBC SNPs were associated with EOBC (P < 0.05). Low power is likely responsible for the remaining 50 unassociated known LOBC SNPs. The gene-based analysis identified an association between breast cancer and the phosphofructokinase-muscle (PFKM) gene on chromosome 12q13.11 that met the genome-wide gene-based threshold of 2.5 × 10(-6). In conclusion, EOBC and LOBC seem to have similar genetic etiologies; the 5q11.2 region may contain multiple distinct breast cancer loci; and the PFKM gene region is worthy of further investigation. These findings should enhance our understanding of the etiology of breast cancer

Changes in North Sea macrofauna communities and species distribution between 1986 and 2000

The North Sea Benthos Project 2000 was initiated as a follow-up to the 1986 ICES North Sea Benthos Survey with the major aim to identify changes in the macrofauna species distribution and community structure in the North Sea and their likely causes. The results showed that the large-scale spatial distribution of macrofauna communities in the North Sea hardly changed between 1986 and 2000, with the main divisions at the 50 m and 100 m depth contours. Water temperature and salinity as well as wave exposure, tidal stress and primary production were influential environmental factors on a large (North Sea-wide) spatial scale. The increase in abundance and regional changes in distribution of various species with a southern distribution in the North Sea in 2000 were largely associated with an increase in sea surface temperature, primary production and, thus, food supply. This can be most likely related to the North Sea hydro-climate change in the late 1980s influenced by the variability in the North Atlantic Oscillation (NAO). Only one cold-temperate species decreased in abundance in 2000 at most of the stations. Indications for newly established populations of offshore non-native species were not found. Differences in macrofauna community structure on localised spatial scales were predominantly found north of the 50 m depth contour off the British coast along the Flamborough Head Front towards the Dogger Bank, off the coast of Jutland and at the Frisian Front. These changes were most likely attributed to stronger frontal systems in 2000 caused by the increased inflow of Atlantic water masses in relation to the hydro-climate change in the late 1980s