Decreased thermal tolerance under recurrent heat stress conditions explains summer mass mortality of the blue mussel Mytilus edulis

Extreme events such as heat waves have increased in frequency and duration over the last decades. Under future climate scenarios, these discrete climatic events are expected to become even more recurrent and severe. Heat waves are particularly important on rocky intertidal shores, one of the most thermally variable and stressful habitats on the planet. Intertidal mussels, such as the blue mussel Mytilus edulis, are ecosystem engineers of global ecological and economic importance, that occasionally suffer mass mortalities. This study investigates the potential causes and consequences of a mass mortality event of M. edulis that occurred along the French coast of the eastern English Channel in summer 2018. We used an integrative, climatological and ecophysiological methodology based on three complementary approaches. We first showed that the observed mass mortality (representing 49 to 59% of the annual commercial value of local recreational and professional fisheries combined) occurred under relatively moderate heat wave conditions. This result indicates that M. edulis body temperature is controlled by non-climatic heat sources instead of climatic heat sources, as previously reported for intertidal gastropods. Using biomimetic loggers (i.e. 'robomussels'), we identified four periods of 5 to 6 consecutive days when M. edulis body temperatures consistently reached more than 30 °C, and occasionally more than 35 °C and even more than 40 °C. We subsequently reproduced these body temperature patterns in the laboratory to infer M. edulis thermal tolerance under conditions of repeated heat stress. We found that thermal tolerance consistently decreased with the number of successive daily exposures. These results are discussed in the context of an era of global change where heat events are expected to increase in intensity and frequency, especially in the eastern English Channel where the low frequency of commercially exploitable mussels already questions both their ecological and commercial sustainability.Funding Agency French Ministere de l'Enseignement Superieur et de la Recherche Region Hauts-de-France European Funds for Regional Economical Development Pierre Hubert Curien PESSOA Felloswhip Fundacao para a Ciencia e Tecnologia (FCT-MEC, Portugal) IF/01413/2014/CP1217/CT0004 National Research Foundation - South Africa 64801 South African Research Chairs Initiative (SARChI) of the Department of Science and Technology National Research Foundation - South Africainfo:eu-repo/semantics/publishedVersio

Effect of field exposure to 38-year-old residual petroleum hydrocarbons on growth, condition index, and filtration rate of the ribbed mussel, Geukensia demissa

Author Posting. © The Author(s), 2007. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Environmental Pollution 154 (2008): 312-319, doi:10.1016/j.envpol.2007.10.008.In September 1969, the Florida barge spilled 700,000 L of No. 2 fuel oil into the salt marsh sediments of Wild Harbor, MA. Today a substantial amount, approximately 100 kg, of moderately degraded petroleum remains within the sediment and along eroding creek banks. The ribbed mussels, Geukensia demissa, which inhabit the salt marsh creek bank, are exposed to the spilled oil. Examination of short-term exposure was done with transplantation of G. demissa from a control site, Great Sippewissett marsh, into Wild Harbor. We examined the effects of long-term exposure with transplantation of mussels from Wild Harbor into Great Sippewissett. Both the short- and long-term exposure transplants exhibited slower growth rates, shorter mean shell lengths, lower condition indices, and decreased filtration rates. Our results add new knowledge about long-term consequences of spilled oil, a dimension that should be included when assessing oil-impacted areas and developing management plans designed to restore, rehabilitate, or replace impacted areas.This work is the result of research sponsored by NOAA National Sea Grant College Program Office, Department of Commerce, under Grant No. NA16RG2273, Woods Hole Oceanographic Institution Sea Grant Project No. R/P-73. Additional support was provided by funding from the NSF-funded Research Experience for Undergraduates program, award 0453292, an Office of Naval Research Young Investigator Award (N00014-04-01-0029) to C. Reddy

The importance of turbulent kinetic energy on transport of juvenile clams (Mya arenaria)

Soft-shell clam, Mya arenaria, culture on the east coast of Canada is characterized by high loss following seeding. To evaluate the importance of passive transport due to currents, an experimental flume study was designed. The purpose was to measure the effects of hydrodynamic conditions, substrate, and clam size on dispersal in controlled laboratory condition and to interpret these results in relation to field measurements. Unidirectional currents with gradual increasing velocities (0 to 60 cm s(-1)) were applied to three substrates (muddy sand, medium sand, and coarse sand) in which clams from one of three size classes (10, 15, and 20 mm) had burrowed. We also examined the resulting effects of turbulent kinetic energy on the erosion of medium-grain sand and clams from the three size classes. Turbulent energy was created with a homemade device acting on the unidirectional currents. Nearly 95% of buried clams (all substrates and size classes together) were unaffected by unidirectional currents of up to 60 cm s(-1), but only 10% withstood turbulent kinetic energy of 10.1 J m(-3), a level that is lower than that measured in the field during an autumnal storm. The transport of clams was found to be directly related to substrate erosion-levels. (C) 2010 Elsevier B.V. All rights reserved

Pharmacogenomic analysis from a phase III study of pemetrexed plus carboplatin (PC) versus etoposide plus carboplatin (EC) in chemonaive patients (pts) with extensive-stage disease small cell lung cancer (ED-SCLC)

8030 Background: We have reported results of a randomized phase III trial in chemonaive patients with ED-SCLC comparing PC to EC. Study enrollment was closed for futility but pharmacogenomic endpoints were not reported. Here we report the results of immunohistochemistry (IHC) analysis from tumor tissues and single nucleotide polymorphism (SNP) analysis of selected genes implicated in pemetrexed, carboplatin, or etoposide activity. Methods: Proteins studied by validated IHC on Benchmark XT were thymidylate synthase (TS), excision repair cross complementing-1 (ERCC1), glycinamide ribonucleotide formyl transferase (GARFT), and folylpolyglutamate synthetase (FPGS). SNP data from whole blood were genotyped by massArray mass spectrometry from 611 samples. One hundred fifty-eight SNPs were genotyped for TS, FPGS, γ-glutamyl hydrolase (GGH), methylene tetrahydrofolate reductase (MTHFR), folate receptor- α (FR-α), solute carrier 19A1 (SLC19A1) and adjacent regions. Allele frequency and Hardy-Weinberg equilibrium were calculated for each SNP. Results: Of 408 tissue samples (from 908 enrolled pts) available for IHC, 336 samples were assayed for &gt; 1 assay target. The IHC analyses showed improved OS in the EC arm relative to the PC arm for patients with low TSnuclear (12.9 vs 7.5 month, p &lt; 0.001, interaction p value = 0.017). There was no differential treatment effect within the PC arm for low vs. high TS. High vs low ERCC1 levels did not predict outcome following C exposure. GARFT was not associated with outcome by treatment. SNP rs2838952 (adjacent to SLC19A1) was significant for improved OS (HR = 0.590, p = 0.01) in both study arms. SNP rs12379987 (FPGS) was significantly associated with treatment for OS (interaction p value = 0.036). Exploratory analyses found associations between additional SNPs and PFS within and across treatments. Conclusions: Pharmacogenomic analyses of tumor samples show that low TSnuclear expression correlates with OS in the EC arm. Two germline SNPs in regions including FPGS and SLC19A1 were associated with better OS. Further analysis of these pharmacogenomic results is ongoing. [Table: see text] </jats:p

Randomized, Phase II, Placebo-Controlled, Double- Blind Study With and Without Enzastaurin in Combination With Paclitaxel and Carboplatin As First-Line Treatment Followed by Maintenance Treatment in Advanced Ovarian Cancer

Purpose Enzastaurin is an oral serine/threonine kinase inhibitor antitumor agent. Our phase II trial tested the efficacy and safety of enzastaurin added to a standard carboplatin/paclitaxel chemotherapy regimen in patients with newly diagnosed advanced ovarian cancer. Patients and Methods This was a randomized, placebo-controlled study in patients with International Federation of Gynecology and Obstetrics stage IIB to IV ovarian, fallopian tube, or peritoneal epithelial carcinoma. Patients were randomly assigned to six cycles of chemotherapy (paclitaxel/carboplatin +/- enzastaurin [PCE/PC]) followed by maintenance therapy (enzastaurin/placebo). Primary end point was progression-free survival (PFS). Secondary measures included response rate, safety assessment, and translational research. Results A total of 142 patients were randomly assigned to PCE (n = 69) or PC (n = 73). Patients in the PCE group had a 3.7-month longer median PFS compared with patients in the PC group; this was not statistically significant (hazard ratio [HR], 0.80; 95% CI, 0.50 to 1.29; P = .37). Safety profiles of the treatment arms were comparable. Frequency of discontinuation because of adverse events was similar (PCE, 11.9%; PC, 9.7%). Multivariate analyses confirmed the importance of optimal debulking with regard to PFS (debulking optimal v suboptimal: HR, 0.51; 95% CI, 0.30 to 0.85; P = .009). HR for covariate stage (stage IIB to IIIB v IIIC to IV) was not statistically significant (0.75; 95% CI, 0.38 to 1.47; P = .40). Translational research of immunohistochemistry protein assays did not identify any markers significantly associated with treatment difference regarding PFS. Conclusion The PCE combination increased PFS, but it was not significantly superior to PC in this phase II stud

Translational research (TR) results from pointbreak: A randomized, open-label, phase III study of pemetrexed (Pem)+carboplatin (Cb)+bevacizumab (Bev) followed by maintenance pem+bev (Pem Arm) versus paclitaxel (Pac)+cb+bev followed by maintenance bev (Pac Arm) in patients (pts) with stage IIIB or IV nonsquamous non-small cell lung cancer (ns-NSCLC).

8086 Background: Results of PointBreak were previously reported. Correlative tissue TR results are presented. Methods: Of 939 pts in the intent-to-treat population (ITT), 211 (22.5%) signed TR consent forms and had evaluable samples. Specimens were analyzed for: Epidermal Growth Factor Receptor (EGFR) mutations by polymerase chain reaction (n=132); thyroid transcription factor-1 (TTF-1) (n=205), thymidylate synthase (TS) (n=189), and folate receptor-alpha (FR-α) (n=180) by immunohistochemistry (IHC) (H-scores range, 0-300). H scores were dichotomized based on positive (&gt;0)/negative (=0) cutpoint. Adjusted Cox/logistic regression determined correlations between overall survival (OS), progression-free survival (PFS), response rate (RR), and dichotomous IHC markers. A 2-sided test with α = 0.05 and 0.1 evaluated treatment and interaction effects, respectively. Results: Median (m) OS and mPFS were similar in the ITT and TR populations for both arms. 11/132 (8.3%) pts had activating EGFR mutations. For TS or FR-α, no significant between-arm differences in OS, PFS and RR were seen. 139/205 (67.8%) pts had positive TTF-1 (TTF-1+). TTF-1+ pts, compared with TTF-1-, independent of treatment, had significantly longer mOS (14.9 vs 8.7 mos, HR 0.48, p&lt;0.001), mPFS (6.9 vs 4.5 mos, HR 0.62, p=0.006), and higher RR (38.9% vs 19.7%, OR 2.68, p=0.008). For TTF-1+ pts, compared with Pac arm, Pem arm had longer mOS (17.6 vs 12.8 mos, HR=0.7, p=0.08; interaction p=0.12) and mPFS (7.3 vs 5.8 mos, HR=0.78, p=0.20; interaction p=0.261); although not statistically significant. Conclusions: The number of pts with EGFR mutations was too small to draw conclusions. No significant between-arm differences for TS and FR-α were seen. Longer survival in TTF-1+ pts suggests TTF-1 expression is prognostic. Additional studies will be needed to better understand trends favoring pem for survival among TTF-1+ pts and other prognostic and/or predictive relationships of these markers. Clinical trial information: NCT00762034. </jats:p