The natural resources of Bolinas Lagoon: their status and future

This publication is an integral part of the Department's high-priority inventory and assessment of coastal marshland and tideflat resources. It is intended as a guide for citizens, planners, administrators, and all others interested in the use and development of coastal lands and waters. Although the resources and problems of Bolinas Lagoon have probably been the subject of more biological and physical investigations than any small estuarine area of the California coast, many of the pertinent reports and information are not readily available to the public. Consequently, it is one purpose of this report to summarize the lagoon's history, ecological attractions, educational values and the problems facing its continued existence. At the same time, it should provide concerned citizens with a knowledge of the sources of additional and more specific information. Publication of this report is consistent with the obligation of the Department of Fish and Game to do everything in its power to protect and maintain the State's fish and wildlife resources. Therefore, its purpose transcends local issues on pollution and development, and the Department is, in fact, submitting a report to the people on the status and future of part of its inheritance and the dowry of coming generations. The report is the third of a scheduled series. It follows similar releases on Upper Newport Bay (Orange County) and Goleta Slough (Santa Barbara county) in March and June of 1970. Documentation of the resources of other critical areas is in progress. There will be future reports of this nature on Elkhorn Slough, Morro Bay, Tomales Bay, Humboldt Bay, and highly threatened marshlands in southern California. (137 pp.

High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP) receptor

The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein-coupled receptor (GPCR) that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structurefunction relationship of GPCRs. © 2014 Bill et al

Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: A phase III, randomized, open-label trial

INTRODUCTION: A multicenter, open-label phase III study was conducted to test whether sunitinib plus paclitaxel prolongs progression-free survival (PFS) compared with bevacizumab plus paclitaxel as first-line treatment for patients with HER2(-) advanced breast cancer. PATIENTS AND METHODS: Patients with HER2(-) advanced breast cancer who were disease free for 65 12 months after adjuvant taxane treatment were randomized (1:1; planned enrollment 740 patients) to receive intravenous (I.V.) paclitaxel 90 mg/m(2) every week for 3 weeks in 4-week cycles plus either sunitinib 25 to 37.5 mg every day or bevacizumab 10 mg/kg I.V. every 2 weeks. [corrected] RESULTS: The trial was terminated early because of futility in reaching the primary endpoint as determined by the independent data monitoring committee during an interim futility analysis. At data cutoff, 242 patients had been randomized to sunitinib-paclitaxel and 243 patients to bevacizumab-paclitaxel. Median PFS was shorter with sunitinib-paclitaxel (7.4 vs. 9.2 months; hazard ratio [HR] 1.63 [95% confidence interval (CI), 1.18-2.25]; 1-sided P = .999). At a median follow-up of 8.1 months, with 79% of sunitinib-paclitaxel and 87% of bevacizumab-paclitaxel patients alive, overall survival analysis favored bevacizumab-paclitaxel (HR 1.82 [95% CI, 1.16-2.86]; 1-sided P = .996). The objective response rate was 32% in both arms, but median duration of response was shorter with sunitinib-paclitaxel (6.3 vs. 14.8 months). Bevacizumab-paclitaxel was better tolerated than sunitinib-paclitaxel. This was primarily due to a high frequency of grade 3/4, treatment-related neutropenia with sunitinib-paclitaxel (52%) precluding delivery of the prescribed doses of both drugs. CONCLUSION: The sunitinib-paclitaxel regimen evaluated in this study was clinically inferior to the bevacizumab-paclitaxel regimen and is not a recommended treatment option for patients with advanced breast cance