Feeding ecology of broadbill swordfish (Xiphias gladius) in the California current

Funding: Support for our study includes salary funding from the NOAA Fisheries’ Office of Science and Technology and contract funds from the Cooperative Institute for Marine, Earth, and Atmospheric Systems. The National Observer Program within NOAA Fisheries’ Office of Science and Technology carried out sample collection. While the study fits the scope of work under the coauthors’ performance plans, they received no specific funding for this work. The funders had no role in study design, analysis, decision to publish, or preparation of the manuscript. Acknowledgments This work would not have been possible without the assistance and samples provided by the NMFS Southwest Region Fishery Observer Program and the participating drift gillnet fishermen. We thank several assistant volunteers who helped process the stomach samples. Alexandra Stohs provided research assistance. Mark Lowry, Eric Hochberg and John Hyde helped identify some prey specimens. John Field, Chugey Sepulveda and Scott Aalbers offered science feedback. Barbara Muhling helped create the map. Kristen Koch, Annie Yau, Brad Erisman, Heidi Dewar, Stephanie Flores, Crystal Dombrow, Elan Portner and Ruben Bergtraun provided useful comments on the draft. Debra Losey assisted with library research. We also thank Hiroshi Ohizumi and two anonymous reviewers for their careful critiques that helped improve the manuscript.Peer reviewedPublisher PD

Effective Menin inhibitor-based combinations against AML with MLL rearrangement or NPM1 mutation (NPM1c)

Treatment with Menin inhibitor (MI) disrupts the interaction between Menin and MLL1 or MLL1-fusion protein (FP), inhibits HOXA9/MEIS1, induces differentiation and loss of survival of AML harboring MLL1 re-arrangement (r) and FP, or expressing mutant (mt)-NPM1. Following MI treatment, although clinical responses are common, the majority of patients with AML with MLL1-r or mt-NPM1 succumb to their disease. Pre-clinical studies presented here demonstrate that genetic knockout or degradation of Menin or treatment with the MI SNDX-50469 reduces MLL1/MLL1-FP targets, associated with MI-induced differentiation and loss of viability. MI treatment also attenuates BCL2 and CDK6 levels. Co-treatment with SNDX-50469 and BCL2 inhibitor (venetoclax), or CDK6 inhibitor (abemaciclib) induces synergistic lethality in cell lines and patient-derived AML cells harboring MLL1-r or mtNPM1. Combined therapy with SNDX-5613 and venetoclax exerts superior in vivo efficacy in a cell line or PD AML cell xenografts harboring MLL1-r or mt-NPM1. Synergy with the MI-based combinations is preserved against MLL1-r AML cells expressing FLT3 mutation, also CRISPR-edited to introduce mtTP53. These findings highlight the promise of clinically testing these MI-based combinations against AML harboring MLL1-r or mtNPM1

Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1

Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse. Utilizing single-cell RNA-Seq, ChiP-Seq, ATAC-Seq, RNA-Seq, RPPA, and mass cytometry (CyTOF) analyses, present pre-clinical studies elucidate gene-expression correlates of MI efficacy in AML cells harboring MLL1-r or mtNPM1. Notably, MI-mediated genome-wide, concordant, log2 fold-perturbations in ATAC-Seq and RNA-Seq peaks were observed at the loci of MLL-FP target genes, with upregulation of mRNAs associated with AML differentiation. MI treatment also reduced the number of AML cells expressing the stem/progenitor cell signature. A protein domain-focused CRISPR-Cas9 screen in MLL1-r AML cells identified targetable co-dependencies with MI treatment, including BRD4, EP300, MOZ and KDM1A. Consistent with this, in vitro co-treatment with MI and BET, MOZ, LSD1 or CBP/p300 inhibitor induced synergistic loss of viability of AML cells with MLL1-r or mtNPM1. Co-treatment with MI and BET or CBP/p300 inhibitor also exerted significantly superior in vivo efficacy in xenograft models of AML with MLL1-r. These findings highlight novel, MI-based combinations that could prevent escape of AML stem/progenitor cells following MI monotherapy, which is responsible for therapy-refractory AML relapse

National Oceanic and Atmospheric Administration Report 190

Abstract: Statistical guidelines are described for the development of a pilot scientific observer sampling program to collect turtle interactions data from the Hawaii longline fishery. The best available data are presented and potential sources of variability in longline turtle take rates are discussed. A stratified sampling design for a pilot survey is developed based on time and target species. An array of sample size choices for the pilot program is presented covering a range of tolerance levels and confidence levels for estimation of total turtle take

Reproductive ecology and scientific inference of steepness: a fundamental metric of population dynamics and strategic fisheries management

The relationship between the biomass of reproductively mature individuals (spawning stock) and the resulting offspring added to the population (recruitment), the stock–recruitment relationship, is a fundamental and challenging problem in all of population biology. The steepness of this relationship is commonly defined as the fraction of recruitment from an unfished population obtained when the spawning stock biomass is 20% of its unfished level. Since its introduction about 20 years ago, steepness has become widely used in fishery management, where it is usually treated as a statistical quantity. Here, we investigate the reproductive ecology of steepness, using both unstructured and age‐structured models. We show that if one has sufficient information to construct a density‐independent population model (maximum per capita productivity and natural mortality for the unstructured case or maximum per capita productivity, natural mortality and schedules of size and maturity at age for the structured model) then one can construct a point estimate for steepness. Thus, steepness cannot be chosen arbitrarily. If one assumes that the survival of recruited individuals fluctuates within populations, it is possible, by considering the early life history, to construct a prior distribution for steepness from this same demographic information. We develop the ideas for both compensatory (Beverton–Holt) and over‐compensatory (Ricker) stock–recruitment relationships. We illustrate our ideas with an example concerning bluefin tuna (Thunnus thynnus/orientalis, Scombridae). We show that assuming that steepness is unity when recruitment is considered to be environmentally driven is not biologically consistent, is inconsistent with a precautionary approach, and leads to the wrong scientific inference (which also applies for assigning steepness any other single value)

Spatiotemporal analysis of lobster trap catches: Impacts of trap fishing on community structure

Volume: 543Start Page: 217End Page: 23

National Oceanic and Atmospheric Administration Report 344

Report on "estimate body size at sexual maturity for Hawaiian spiny lobster and slipper lobster using all available fishery independent research catch data from 1986 to 2001." (pg. 1