Description: We report on observations of dense shelf water overflows and Antarctic Bottom Water (AABW) formation along the continental margin of the Adelie and George V Land coast between 140°E and 149°E. Vertical sections and bottom layer water mass properties sampled during two RVIB Nathaniel B Palmer hydrographic surveys (NBP00-08, December 2000/January 2001 and NBP04-08, October 2004) describe the spreading of cold, dense shelf water on the continental slope and rise from two independent source regions. The primary source region is the Adelie Depression, exporting high-salinity dense shelf water through the Adelie Sill at 143°E. An additional eastern source region of lower-salinity dense shelf water from the Mertz Depression is identified for the first time from bottom layer properties northwest of the Mertz Sill and Mertz Bank (146°E-148°E) that extend as far as the Buffon Channel (144.75°E) in summer. Regional analysis of satellite-derived ice production estimates over the entire region from 1992 to 2005 suggests that up to 40% of the total ice production for the region occurs over the Mertz Depression and therefore this area is likely to make a significant contribution to the total dense shelf water export. Concurrent time series from bottom-mounted Microcats and ADCP instruments from the Mertz Polynya Experiment (April 1998 to May 1999) near the Adelie Sill and on the upper continental slope (1150 m) and lower continental rise (3250 m) to the north describe the seasonal variability in downslope events and their interaction with the ambient water masses. The critical density for shelf water to produce AABW is examined and found to be 27.85 kg/m**3 from the Adelie Depression and as low as 27.80 kg/m**3 from the Mertz Depression. This study suggests previous dense shelf water export estimates based on the flow through the Adelie Sill alone are conservative and that other regions around East Antarctica with similar ice production to the Mertz Depression could be contributing to the total AABW in the Australian-Antarctic Basin.

Description: Activation of the hepatocyte growth factor (HGF)–Met pathway evokes dynamic biological responses that support the morphogenesis, regeneration and survival of cells and tissues. A characterization of conditional Met knockout mice indicates that the HGF–Met pathway plays important roles in the regeneration, protection and homeostasis of cells such as hepatocytes, renal tubular cells and neurons. Preclinical studies in disease models have indicated that recombinant HGF protein and expression plasmid for HGF are biological drug candidates for the treatment of patients with diseases or injuries that involve impaired tissue function. The phase-I and phase-I/II clinical trials of the intrathecal administration of HGF protein for the treatment of patients with amyotrophic lateral sclerosis and spinal cord injury, respectively, are ongoing. Biological actions of HGF that promote the dynamic movement, morphogenesis and survival of cells also closely participate in invasion-metastasis and resistance to the molecular-targeted drugs in tumour cells. Different types of HGF–Met pathway inhibitors are now in clinical trials for treatment of malignant tumours. Basic research on HGF and Met has lead to drug discoveries in regenerative medicine and tumour biology.

Description: Although many α- and some β-proteobacterial species are symbiotic with legumes, the evolutionary origin of nitrogen-fixing nodulation remains unclear. We examined α- and β-proteobacteria whose genomes were sequenced using large-scale phylogenetic profiling and revealed the evolutionary origin of two nodulation genes. These genes, nodI and nodJ ( nodIJ ), play key roles in the secretion of Nod factors, which are recognized by legumes during nodulation. We found that only the nodulating β-proteobacteria, including the novel strains isolated in this study, possess both nodIJ and their paralogous genes (DRA-ATPase/permease genes). Contrary to the widely accepted scenario of the α-proteobacterial origin of rhizobia, our exhaustive phylogenetic analysis showed that the entire nodIJ clade is included in the clade of Burkholderiaceae DRA-ATPase/permease genes, that is, the nodIJ genes originated from gene duplication in a lineage of the β-proteobacterial family. After duplication, the evolutionary rates of nodIJ were significantly accelerated relative to those of homologous genes, which is consistent with their novel function in nodulation. The likelihood analyses suggest that this accelerated evolution is not associated with changes in either nonsynonymous/synonymous substitution rates or transition/transversion rates, but rather, in the GC content. Although the low GC content of the nodulation genes has been assumed to reflect past horizontal transfer events from donor rhizobial genomes with low GC content, no rhizobial genome with such low GC content has yet been found. Our results encourage a reconsideration of the origin of nodulation and suggest new perspectives on the role of the GC content of bacterial genes in functional adaptation.

Description: Background Hyaluronan (HA) metabolism in skin fibroblasts is mediated by HYBID ( HY aluronan B inding protein I nvolved in hyaluronan D epolymerisation, KIAA1199) and HA synthases 1/2 (HAS1/2). However, photoageing-dependent changes in HA and their molecular mechanisms, and the relationship between HA metabolism and clinical symptoms in photoaged skin remain elusive. Objectives We examined amount, size and tissue distribution of HA and expression levels of HYBID and HAS1/2 in photoaged skin, and analysed their relationships to the degree of photoageing. Methods Photoageing-dependent changes of HA were investigated by studying skin biopsies isolated from photoprotected and photoexposed areas of the same donors, and the relationship between HA and photoageing symptoms such as skin wrinkling and sagging was examined. Results Skin biopsy specimens showed that amount and size of HA are decreased in the photoexposed skin compared to the photoprotected skin, and this was accompanied by increased expression of HYBID and decreased expression of HAS1/2 , respectively. Histologically, HA staining in the papillary dermis was decreased in photoexposed skin, showing reverse correlation with HYBID expression. HYBID expression in the photoexposed skin directly correlated with skin roughness and sagging parameters, and reduced HA staining in the papillary dermis in the photoexposed skin positively correlated with these symptoms. Conclusions These data demonstrate that imbalance between HYBID-mediated HA degradation and HAS-mediated HA synthesis may contribute to enhanced HA catabolism in the photoaged skin, and suggest that HYBID-mediated HA reduction in the papillary dermis is related to skin wrinkling and sagging of photoaged skin. This article is protected by copyright. All rights reserved.

Description: Although immune checkpoint inhibitors (ICI) significantly improve the survival of advanced melanoma, more than half of the patients received no benefit. To predict outcomes, efforts to associate baseline peripheral blood biomarkers were started in patients given treatment with ipilimumab. Among the most critical markers is an increased neutrophil-to-lymphocyte ratio (NLR), which negatively correlates with outcome. Although several baseline factors have been reported to correlate with outcome in patients treated with nivolumab/pembrolizumab (eosinophil count, lymphocyte count, lactate dehydrogenase [LDH], and c-reactive protein [CRP]), a positive link between NLR and outcome has yet to be shown. This article is protected by copyright. All rights reserved.