Field Guide to Exhumed Major Faults in Southern California

This field guide provides an overview of exposures and provides a field trip guide to localities of exhumed faults in southern California. We focus on exposures of faults that are documented or inferred to be exhumed from seismogenic depths. The goal of this guidebook is to provide geoscientists who are interested in fault zone mechanics and earthquake processes a summary of the results of the work on these sites

Ceramide remodeling and risk of cardiovascular events and mortality

BackgroundRecent studies suggest that circulating concentrations of specific ceramide species may be associated with coronary risk and mortality. We sought to determine the relations between the most abundant plasma ceramide species of differing acyl chain lengths and the risk of coronary heart disease (CHD) and mortality in community‐based samples. Methods and ResultsWe developed a liquid chromatography/mass spectrometry assay to quantify plasma C24:0, C22:0, and C16:0 ceramides and ratios of these very–long‐chain/long‐chain ceramides in 2642 FHS (Framingham Heart Study) participants and in 3134 SHIP (Study of Health in Pomerania) participants. Over a mean follow‐up of 6 years in FHS, there were 88 CHD and 90 heart failure (HF) events and 239 deaths. Over a median follow‐up time in SHIP of 5.75 years for CHD and HF and 8.24 years for mortality, there were 209 CHD and 146 HF events and 377 deaths. In meta‐analysis of the 2 cohorts and adjusting for standard CHD risk factors, C24:0/C16:0 ceramide ratios were inversely associated with incident CHD (hazard ratio per average SD increment, 0.79; 95% confidence interval, 0.71–0.89; P<0.0001) and inversely associated with incident HF (hazard ratio, 0.78; 95% confidence interval, 0.61–1.00; P=0.046). Moreover, the C24:0/C16:0 and C22:0/C16:0 ceramide ratios were inversely associated with all‐cause mortality (C24:0/C16:0: hazard ratio, 0.60; 95% confidence interval, 0.56–0.65; P<0.0001; C22:0/C16:0: hazard ratio, 0.65; 95% confidence interval, 0.60–0.70; P<0.0001). ConclusionsThe ratio of C24:0/C16:0 ceramides in blood may be a valuable new biomarker of CHD risk, HF risk, and all‐cause mortality in the community

Paenibacillus melissococcoides sp. nov., isolated from a honey bee colony affected by European foulbrood disease.

A novel, facultatively anaerobic, Gram-stain-positive, motile, endospore-forming bacterium of the genus Paenibacillus, designated strain 2.1T, was isolated from a colony of Apis mellifera affected by European foulbrood disease in Switzerland. The rod-shaped cells of strain 2.1T were 2.2–6.5 μm long and 0.7–1.1 μm wide. Colonies of strain 2.1T were orange-pigmented under oxic growth conditions on solid basal medium at 35–37 °C. Strain 2.1T showed catalase and cytochrome c oxidase activity. Its polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, aminophospholipid and phospholipid. The only respiratory quinone was menaquinone 7, and the major cellular fatty acids were anteiso-C15 : 0, anteiso-C17 : 0, iso-C15 : 0, iso-C17 : 0 and palmitic acid (C16 : 0), which is consistent with other members of the genus Paenibacillus. The G+C content of the genomic DNA of strain 2.1T was 53.3 mol%. Phylogenetic analyses based on the 16S rRNA gene sequence similarity showed that strain 2.1T was closely related to Paenibacillus dendritiformis LMG 21716T (99.7 % similarity) and Paenibacillus thiaminolyticus DSM 7262T (98.8 %). The whole-genome average nucleotide identity between strain 2.1T and the type strains of P. dendritiformis and P. thiaminolyticus was 92 and 91 %, respectively, and thus lower than the 95 % threshold value for delineation of genomic prokaryotic species. Based on the results of phylogenetic, genomic, phenotypic and chemotaxonomic analyses we propose the name Paenibacillus melissococcoides sp. nov. for this novel Paenibacillus species. The type strain is 2.1T (=CCOS 2000T=DSM 113619T=LMG 32539T)

FGFR2 signaling underlies p63 oncogenic function in squamous cell carcinoma

Oncogenic transcription factors drive many human cancers, yet identifying and therapeutically targeting the resulting deregulated pathways has proven difficult. Squamous cell carcinoma (SCC) is a common and lethal human cancer, and relatively little progress has been made in improving outcomes for SCC due to a poor understanding of its underlying molecular pathogenesis. While SCCs typically lack somatic oncogene-activating mutations, they exhibit frequent overexpression of the p53-related transcription factor p63. We developed an in vivo murine tumor model to investigate the function and key transcriptional programs of p63 in SCC. Here, we show that established SCCs are exquisitely dependent on p63, as acute genetic ablation of p63 in advanced, invasive SCC induced rapid and dramatic apoptosis and tumor regression. In vivo genome-wide gene expression analysis identified a tumor-survival program involving p63-regulated FGFR2 signaling that was activated by ligand emanating from abundant tumor-associated stroma. Correspondingly, we demonstrate the therapeutic efficacy of extinguishing this signaling axis in endogenous SCCs using the clinical FGFR2 inhibitor AZD4547. Collectively, these results reveal an unanticipated role for p63-driven paracrine FGFR2 signaling as an addicting pathway in human cancer and suggest a new approach for the treatment of SCC

Zoledronic acid in metastatic chondrosarcoma and advanced sacrum chordoma: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Chondrosarcomas and chordomas are usually chemoresistant bone tumors and may have a poor prognosis when advanced. They are usually associated with worsening pain difficult to control.</p> <p>Patients and Methods</p> <p>Zoledronic acid was used in a 63-year-old man with metastatic chondrosarcoma and in a 66-year-old woman with a diagnosis of sacrum chordoma both reporting severe pain related to tumor.</p> <p>Results</p> <p>In the first case, zoledronic acid was able to maintain pain control despite disease progression following chemotherapy, in the other case, zoledronic acid only produced significant clinical benefit.</p> <p>Conclusion</p> <p>Control of pain associated with bone tumors such as chondrosarcoma and chondroma may significantly improve from use of zoledronic acid, independently from tumor response to other treatments. Evaluation on larger series are needed to confirm the clinical effect of this bisphosphonate on such tumors.</p