Population genetics of selected species of sharks

Molecular genetic techniques were used to elucidate genetic population structure in three species of sharks, the coastal sandbar shark (Carcharhinus plumbeus) and Atlantic sharpnose shark (Rhizoprionodon terraenovae), and the pelagic shortfin mako (Isurus oxyrinchus). Allozyme analysis and analysis of restriction fragment length polymorphisms (RFLP) of mitochondrial DNA (mtDNA) were used to test the null hypothesis that the mid-Atlantic Bight and the Gulf of Mexico sandbar sharks consist of a single gene pool. RFLP analysis of mtDNA was used to determine the pattern and level of genetic divergence in the sandbar shark between the western North Atlantic and the Eastern Indian Ocean, and within the entire species range of the cosmopolitan shortfin mako and the Atlantic sharpnose shark. No significant genetic divergence was detected in the sandbar shark between the mid-Atlantic Bight and Gulf of Mexico. Genetic variation was extremely low but homogeneously distributed. A significant degree of genetic divergence was detected between North Atlantic and Australian sandbar sharks. All Australian sandbar shark mtDNAs were fixed for alleles other than those detected in the North Atlantic. The hypothesis that the shortfin mako comprises a single panmictic population was rejected. The overall probability of drawing samples with such disparate allele frequencies from a single gene pool was &\u3c&0.001. The only barrier to gene flow detected appeared to be the equatorial Atlantic. Samples from Brazil, Australia, and California were not significantly different from each other, however all three were significantly different from the North Atlantic sample. The shortfin mako exhibited a considerably higher level of genetic variation than the sandbar shark. The Atlantic sharpnose shark did not exhibit significant differences in allele frequency throughout its range. The level of genetic variation detected in mtDNA was intermediate to that of the sandbar shark and the shortfin mako

Mitochondrial DNA Diversity And Divergence Among Sharpnose Sharks, Rhizoprionodon Terraenovae, From The Gulf Of Mexico And Mid-Atlantic Bight

The Atlantic sharpnose shark, Rhizoprionodon terraenovae, is a small coastal shark that is harvested in both directed and nondirected fisheries throughout its range. Because pups of this species are found both along the southeastern U.S. Atlantic coast and the Gulf of Mexico, it is possible that multiple isolated breeding stocks exist. Restriction fragment length polymorphism analysis of mitochondrial DNA was used to test the hypothesis that Atlantic sharpnose sharks from the U.S. Atlantic coast and the western Gulf of Mexico have identical mitochondrial haplotype frequencies and therefore no apparent genetic stock structure. Seven mitochondrial haplotypes were detected among 52 individuals. The distribution of haplotypes between samples did not differ significantly from homogeneity (P=0.694), indicating that the null hypothesis of a single breeding population could not be rejected

Comparative Analysis of Sea Scallop Escapement/Retention and Resulting Economic Impacts

During the months of June and September 1988, gear experiments were conducted aboard the F/V Carolina Dawn and Carolina Capes. The primary objective of the experiments was to assess the technical efficiency and size selectivity of 3.5-inch ring dredges relative to the current commercially-used 3.0-inch ring dredges. Secondary objectives were to analyze the economic and regulatory ramifications of using 3.5-inch ring dredges to control the age-at-capture and enhance the yield-per- recruit

Probing molecular ordering in the nematic phases of para-linked bimesogen dimers through NMR studies of flexible prochiral solutes

The quadrupolar splittings of perdeuteriated n-decane dissolved in nematic phases formed by mesogenic dimers of the CBnCB series, for n = 7,9,10,11, are measured throughout the entire temperature range of these phases. These results are reported together with related measurements using the common nematic phase of 5CB as a solvent for n-decane. The data obtained from the 13C spectra of the cyanobiphenyl mesogenic units of the monomeric and dimeric solvent molecules yield the order parameter of those units. The information obtained from this set of experiments is used to elucidate the structure of the low temperature (NX) and the high temperature (N) nematic phases of CBnCB dimers with n = 7,9,11. The polar twisted nematic (NPT) model is found to provide a consistent description not only of our experimental results but also of NMR measurements previously reported in the literature for these phases. These findings suggest that the high temperature nematic (N) is not a common, locally uniaxial and apolar nematic, but rather a nematic phase consisting of NPT clusters. The twist-bend (NTB) model, often identified with the NX phase, is shown to be inadequate to account even qualitatively for crucial features of the experimental findings

Evidence of Limited Recruitment of Pallid Sturgeon in the Lower Missouri River

Pallid Sturgeon Scaphirhynchus albus are endemic to the Missouri and Mississippi river basins and are rare throughout their range. The species was listed as federally endangered with little to no evidence of natural recruitment. Since population augmentation was initiated as a recovery objective in the early 1990s, thousands of hatchery-origin Pallid Sturgeon have been stocked in the lower Missouri River (Gavins Point Dam [river kilometer 1,305.1] to the confluence of the Mississippi River [river kilometer 0.0]). Efforts to discriminate natural reproduction and recruitment of wild-origin Pallid Sturgeon from hatchery-origin fish has been hampered by tag loss in hatchery-origin sturgeon, inconsistent documentation of hatchery parental crosses, and the failure to collect tissue samples for genotyping all broodstock. However, the recent reconstruction of missing parental genotypes from known hatchery-origin progeny and from cryopreserved milt made it possible to examine Pallid Sturgeon recruitment. Therefore, our objectives were to 1) determine the likelihood that unmarked Pallid Sturgeon captured from the lower Missouri River were the result of natural recruitment and 2) examine the length distribution of wild- and hatchery-origin fish to determine if a difference exists by origin and examine the life-stage distribution. Genetic analysis showed that from 2003 to 2015, 358 ‘‘presumptive wild-origin’’ Pallid Sturgeon were captured in the lower Missouri River and the comparison between the length distributions of wild- and hatchery-origin fish did not provide any additional clarification into potential wildorigin fish. Low recruitment may be due to a small breeding population, high mortality of early life stages, hybridization with Shovelnose Sturgeon Scaphirhynchus platorynchus, or transport of drifting free embryos or larvae into inhospitable habitats. Determining what factors are limiting recruitment is the important next step for the recovery of Pallid Sturgeon in the lower Missouri River

Brief Report: Safety and Antitumor Activity of Alectinib Plus Atezolizumab From a Phase 1b Study in Advanced ALK-Positive NSCLC

INTRODUCTION: Alectinib is a preferred first-line treatment option for advanced ALK-positive NSCLC. Combination regimens of alectinib with immune checkpoint inhibitors are being evaluated for synergistic effects. METHODS: Adults with treatment-naive, stage IIIB/IV, or recurrent ALK-positive NSCLC were enrolled into a two-stage phase 1b study. Patients received alectinib 600 mg (twice daily during cycle 1 and throughout each 21-d cycle thereafter) plus atezolizumab 1200 mg (d8 of cycle 1 and then d1 of each 21-d cycle). Primary objectives were to evaluate safety and tolerability of alectinib plus atezolizumab. Secondary objectives included assessments of antitumor activity. RESULTS: In total, 21 patients received more than or equal to 1 dose of alectinib or atezolizumab. As no dose-limiting toxicities were observed in stage 1 (n = 7), the starting dose and schedule were continued into stage 2 (n = 14). Median duration of follow-up was 29 months (range: 1-39). Grade 3 treatment-related adverse events occurred in 57% of the patients, most often rash (19%). No grade 4 or 5 treatment-related adverse events were reported. Confirmed objective response rate was 86% (18 of 21; 95% confidence interval [CI]: 64-97). Median progression-free survival was not estimable (NE) (95% CI: 13 mo-NE), neither was median overall survival (95% CI: 33 mo-NE). CONCLUSIONS: The combination of alectinib and atezolizumab is feasible, but increased toxicity was found compared with the individual agents. With small sample sizes and relatively short follow-up, definitive conclusions regarding antitumor activity cannot be made

Genetic Heterogeneity in a Cyclical Forest Pest, the Southern Pine Beetle, Dendroctonus frontalis, is Differentiated Into East and West Groups in the Southeastern United States

The southern pine beetle, Dendroctonus frontalis Zimmerman (Coleoptera: Curculionidae) is an economically important pest species throughout the southeastern United States, Arizona, Mexico, and Central America. Previous research identified population structure among widely distant locations, yet failed to detect population structure among national forests in the state of Mississippi. This study uses microsatellite variation throughout the southeastern United States to compare the southern pine beetle's pattern of population structure to phylogeographic patterns in the region, and to provide information about dispersal. Bayesian clustering identified east and west genetic groups spanning multiple states. The east group had lower heterozygosity, possibly indicating greater habitat fragmentation or a more recent colonization. Significant genetic differentiation (θST = 0.01, p < 0.0001) followed an isolation-by-distance pattern (r = 0.39, p < 0.001) among samples, and a hierarchical AMOVA indicated slightly more differentiation occurred between multi-state groups. The observed population structure matches a previously identified phylogeographic pattern, division of groups along the Appalachian Mountain/Apalachicola River axis. Our results indicate that the species likely occurs as a large, stable metapopulation with considerable gene flow among subpopulations. Also, the relatively low magnitude of genetic differentiation among samples suggests that southern pine beetles may respond similarly to management across their range

ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer:ANSELMA

BACKGROUND: Now that immunotherapy plus chemotherapy (CT) is one standard option in first-line treatment of advanced non-small cell lung cancer (NSCLC), there exists a medical need to assess the efficacy of second-line treatments (2LT) with antiangiogenics (AA). We performed an individual patient data meta-analysis to validate the efficacy of these combinations as 2LT. METHODS: Randomised trials of AA plus standard 2LT compared to 2LT alone that ended accrual before 2015 were eligible. Fixed-effect models were used to compute pooled hazard ratios (HRs) for overall survival (OS, main end-point), progression-free survival (PFS) and subgroup analyses. RESULTS: Sixteen trials were available (8,629 patients, 64% adenocarcinoma). AA significantly prolonged OS (HR = 0.93 [95% confidence interval {CI}: 0.89; 0.98], p = 0.005) and PFS (0.80 [0.77; 0.84], p < 0.0001) compared with 2LT alone. Absolute 1-year OS and PFS benefit for AA were +1.8% [-0.4; +4.0] and +3.5% [+1.9; +5.1], respectively. The OS benefit of AA was higher in younger patients (HR = 0.87 [95% CI: 0.76; 1.00], 0.89 [0.81; 0.97], 0.94 [0.87; 1.02] and 1,04 [0.93; 1.17] for patients <50, 50-59, 60-69 and ≥ 70 years old, respectively; trend test: p = 0.02) and in patients who started AA within 9 months after starting the first-line therapy (0.88 [0.82; 0.99]) than in patients who started AA later (0.99 [0.91; 1.08]) (interaction: p = 0.03). Results were similar for PFS. AA increased the risk of hypertension (p < 0.0001), but not the risk of pulmonary thromboembolic events (p = 0.21). CONCLUSIONS: In the 2LT of advanced NSCLC, adding AA significantly prolongs OS and PFS, but the benefit is clinically limited, mainly observed in younger patients and after shorter time since the start of first-line therapy