Oceanographic drivers of deep-sea coral species distribution and community assembly on seamounts, islands, atolls, and reefs within the Phoenix Islands Protected Area

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Auscavitch, S. R., Deere, M. C., Keller, A. G., Rotjan, R. D., Shank, T. M., & Cordes, E. E. Oceanographic drivers of deep-sea coral species distribution and community assembly on seamounts, islands, atolls, and reefs within the Phoenix Islands Protected Area. Frontiers in Marine Science, 7, (2020): 42, doi:10.3389/fmars.2020.00042.The Phoenix Islands Protected Area, in the central Pacific waters of the Republic of Kiribati, is a model for large marine protected area (MPA) development and maintenance, but baseline records of the protected biodiversity in its largest environment, the deep sea (>200 m), have not yet been determined. In general, the equatorial central Pacific lacks biogeographic perspective on deep-sea benthic communities compared to more well-studied regions of the North and South Pacific Ocean. In 2017, explorations by the NOAA ship Okeanos Explorer and R/V Falkor were among the first to document the diversity and distribution of deep-water benthic megafauna on numerous seamounts, islands, shallow coral reef banks, and atolls in the region. Here, we present baseline deep-sea coral species distribution and community assembly patterns within the Scleractinia, Octocorallia, Antipatharia, and Zoantharia with respect to different seafloor features and abiotic environmental variables across bathyal depths (200–2500 m). Remotely operated vehicle (ROV) transects were performed on 17 features throughout the Phoenix Islands and Tokelau Ridge Seamounts resulting in the observation of 12,828 deep-water corals and 167 identifiable morphospecies. Anthozoan assemblages were largely octocoral-dominated consisting of 78% of all observations with seamounts having a greater number of observed morphospecies compared to other feature types. Overlying water masses were observed to have significant effects on community assembly across bathyal depths. Revised species inventories further suggest that the protected area it is an area of biogeographic overlap for Pacific deep-water corals, containing species observed across bathyal provinces in the North Pacific, Southwest Pacific, and Western Pacific. These results underscore significant geographic and environmental complexity associated with deep-sea coral communities that remain in under-characterized in the equatorial central Pacific, but also highlight the additional efforts that need to be brought forth to effectively establish baseline ecological metrics in data deficient bathyal provinces.Funding for this work was provided by NOAA Office of Ocean Exploration and Research (Grant No. NA17OAR0110083) to RR, EC, TS, and David Gruber

Identification of an HIV-1 mutation in spacer peptide 1 that stabilizes the immature CA-SP1 lattice

Upon release of HIV-1 particles from the infected cell, the viral protease cleaves the Gag polyprotein at specific sites, triggering maturation. During this process, which is essential for infectivity, the capsid protein (CA) reassembles into a conical core. Maturation inhibitors (MIs) block HIV-1 maturation by interfering with protease-mediated CA-spacer peptide 1 (CA-SP1) processing, concomitantly stabilizing the immature CA-SP1 lattice; virions from MI-treated cells retain an immature-like CA-SP1 lattice, whereas mutational abolition of cleavage at the CA-SP1 site results in virions in which the CA-SP1 lattice converts to a mature-like form. We previously reported that propagation of HIV-1 in the presence of MI PF-46396 selected for assembly-defective, compound-dependent mutants with amino acid substitutions in the major homology region (MHR) of CA. Propagation of these mutants in the absence of PF-46396 resulted in the acquisition of second-site compensatory mutations. These included a Thr-to-Ile substitution at SP1 residue 8 (T8I), which results in impaired CA-SP1 processing. Thus, the T8I mutation phenocopies PF-46396 treatment in terms of its ability to rescue the replication defect imposed by the MHR mutations and to impede CASP1 processing. Here, we use cryo-electron tomography to show that, like MIs, the T8I mutation stabilizes the immature-like CA-SP1 lattice. These results have important implications for the mechanism of action of HIV-1 MIs; they also suggest that T8I may provide a valuable tool for structural definition of the CA-SP1 boundary region, which has thus far been refractory to highresolution analysis, apparently because of conformational flexibility in this region of Gag. IMPORTANCE HIV-1 maturation involves dissection of the Gag polyprotein by the viral protease and assembly of a conical capsid enclosing the viral ribonucleoprotein. Maturation inhibitors (MIs) prevent the final cleavage step at the site between the capsid protein (CA) and spacer peptide 1 (SP1), apparently by binding at this site and denying the protease access. Additionally, MIs stabilize the immature-like CA-SP1 lattice, preventing release of CA into the soluble pool. We previously found that T8I, a mutation in SP1, rescues a PF-46396-dependent CA mutant and blocks CA-SP1 cleavage. In this study, we imaged T8I virions by cryo-electron tomography and showed that T8I mutants, like MI-treated virions, contain an immature CA-SP1 lattice. These results lay the groundwork needed to understand the structure of the CA-SP1 interface region and further illuminate the mechanism of action of MIs

Chemical compositions at Mars landing sites subject to Mars Odyssey Gamma Ray Spectrometer constraints

The Mars Odyssey Gamma Ray Spectrometer (GRS) is the first instrument suite to return elemental abundances throughout the midlatitudes of Mars. Concentrations of Cl, Fe, H, K, Si, and Th have been determined to tens of centimeter depths as mass fractions with reasonable confidence. Comparing such data with, or normalizing them to, in situ compositional data is difficult due to issues such as dramatic differences in spatial resolution; difficulties in convolving densities, abundances, and compositions of different regolith components; and a limited number of elements observed in common. We address these concerns in the context of the GRS, using Si at Pathfinder to normalize remote data. In addition, we determine representative in situ compositions for Spirit (both with and without Columbia Hills rocks), Opportunity, and Viking 1 landing sites using GRS-derived H content to hydrate the soil component. Our estimate of the Si mass fraction at Pathfinder, with 13% areal fraction of rocks, is 21%. The composition of major elements, such as Si and Fe, is similar across the four landing sites, while minor elements show significant variability. Areal dominance of soil at all four landing sites causes representative compositions to be driven by the soil component, while proportionally large uncertainties of bulk densities dominate the net uncertainties. GRS compositional determinations compare favorably with the in situ estimates for Cl and K, and for Si by virtue of the normalization. However, the GRS-determined Fe content at each landing site is consistently higher than the in situ value. Copyright 2007 by the American Geophysical Union

Anatomical localization of progenitor cells in human breast tissue reveals enrichment of uncommitted cells within immature lobules

Introduction: Lineage tracing studies in mice have revealed the localization and existence of lineage-restricted mammary epithelial progenitor cells that functionally contribute to expansive growth during puberty and differentiation during pregnancy. However, extensive anatomical differences between mouse and human mammary tissues preclude the direct translation of rodent findings to the human breast. Therefore, here we characterize the mammary progenitor cell hierarchy and identify the anatomic location of progenitor cells within human breast tissues. Methods: Mammary epithelial cells (MECs) were isolated from disease-free reduction mammoplasty tissues and assayed for stem/progenitor activity in vitro and in vivo. MECs were sorted and evaluated for growth on collagen and expression of lineages markers. Breast lobules were microdissected and individually characterized based on lineage markers and steroid receptor expression to identify the anatomic location of progenitor cells. Spanning-tree progression analysis of density-normalized events (SPADE) was used to identify the cellular hierarchy of MECs within lobules from high-dimensional cytometry data. Results: Integrating multiple assays for progenitor activity, we identified the presence of luminal alveolar and basal ductal progenitors. Further, we show that Type I lobules of the human breast were the least mature, demonstrating an unrestricted pattern of expression of luminal and basal lineage markers. Consistent with this, SPADE analysis revealed that immature lobules were enriched for basal progenitor cells, while mature lobules consisted of increased hierarchal complexity of cells within the luminal lineages. Conclusions: These results reveal underlying differences in the human breast epithelial hierarchy and suggest that with increasing glandular maturity, the epithelial hierarchy also becomes more complex. Electronic supplementary material The online version of this article (doi:10.1186/s13058-014-0453-3) contains supplementary material, which is available to authorized users

Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial.

BackgroundAdjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC.MethodsWe did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC. We enrolled patients from across the US National Clinical Trials Network, including patients from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) affiliates in Europe and from the Canadian Cancer Trials Group, within 6-12 weeks of surgery. The chemotherapy regimen for each patient was selected before randomisation and administered intravenously; it consisted of four 21-day cycles of cisplatin (75 mg/m2 on day 1 in all regimens) in combination with investigator's choice of vinorelbine (30 mg/m2 on days 1 and 8), docetaxel (75 mg/m2 on day 1), gemcitabine (1200 mg/m2 on days 1 and 8), or pemetrexed (500 mg/m2 on day 1). Patients in the bevacizumab group received bevacizumab 15 mg/kg intravenously every 21 days starting with cycle 1 of chemotherapy and continuing for 1 year. We randomly allocated patients (1:1) to group A (chemotherapy alone) or group B (chemotherapy plus bevacizumab), centrally, using permuted blocks sizes and stratified by chemotherapy regimen, stage of disease, histology, and sex. No one was masked to treatment assignment, except the Data Safety and Monitoring Committee. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00324805.FindingsBetween June 1, 2007, and Sept 20, 2013, 1501 patients were enrolled and randomly assigned to the two treatment groups: 749 to group A (chemotherapy alone) and 752 to group B (chemotherapy plus bevacizumab). 383 (26%) of 1458 patients (with complete staging information) had stage IB, 636 (44%) had stage II, and 439 (30%) had stage IIIA disease (stage of disease data were missing for 43 patients). Squamous cell histology was reported for 422 (28%) of 1501 patients. All four cisplatin-based chemotherapy regimens were used: 377 (25%) patients received vinorelbine, 343 (23%) received docetaxel, 283 (19%) received gemcitabine, and 497 (33%) received pemetrexed. At a median follow-up of 50·3 months (IQR 32·9-68·0), the estimated median overall survival in group A has not been reached, and in group B was 85·8 months (95% CI 74·9 to not reached); hazard ratio (group B vs group A) 0·99 (95% CI 0·82-1·19; p=0·90). Grade 3-5 toxicities of note (all attributions) that were reported more frequently in group B (the bevacizumab group) than in group A (chemotherapy alone) were overall worst grade (ie, all grade 3-5 toxicities; 496 [67%] of 738 in group A vs 610 [83%] of 735 in group B), hypertension (60 [8%] vs 219 [30%]), and neutropenia (241 [33%] vs 275 [37%]). The number of deaths on treatment did not differ between the groups (15 deaths in group A vs 19 in group B). Of these deaths, three in group A and ten in group B were considered at least possibly related to treatment.InterpretationAddition of bevacizumab to adjuvant chemotherapy did not improve overall survival for patients with surgically resected early-stage NSCLC. Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for patients with resected early-stage NSCLC.FundingNational Cancer Institute of the National Institutes of Health

The Lantern Vol. 16, No. 3, Spring 1948

• Not So Light • Babba\u27s Luck • Winter Night • God Hath Wrought • Less Than Trivia • What is Progress? • Betrayal • The Key • Journey From a Star • War and Peace • Experiment in Prose Poetry • Dawn • Eternal Question • My Gift • Jazz Fantasy • M.W. Witmerhttps://digitalcommons.ursinus.edu/lantern/1045/thumbnail.jp

A Memetic Analysis of a Phrase by Beethoven: Calvinian Perspectives on Similarity and Lexicon-Abstraction

This article discusses some general issues arising from the study of similarity in music, both human-conducted and computer-aided, and then progresses to a consideration of similarity relationships between patterns in a phrase by Beethoven, from the first movement of the Piano Sonata in A flat major op. 110 (1821), and various potential memetic precursors. This analysis is followed by a consideration of how the kinds of similarity identified in the Beethoven phrase might be understood in psychological/conceptual and then neurobiological terms, the latter by means of William Calvin’s Hexagonal Cloning Theory. This theory offers a mechanism for the operation of David Cope’s concept of the lexicon, conceived here as a museme allele-class. I conclude by attempting to correlate and map the various spaces within which memetic replication occurs

Observation of an Isotope Shift in the Superconducting Transition Temperature of La\u3csub\u3e1.85\u3c/sub\u3eSr\u3csub\u3e0.15\u3c/sub\u3eCuO\u3csub\u3e4\u3c/sub\u3e

An oxygen isotope shift is observed in superconducting La1.85Sr0.15CuO4 when 18O is substituted partially for 16O; the superconducting transition temperature Tc is lowered by 0.3 to 1.0 K in different samples. We examine these results using conventioanl phonon-mediated BCS theory and conclude that, for La1.85Sr0.15CuO4, phonons play an important role in the pairing mechanism

The NQO1*2/*2 polymorphism is associated with poor overall survival in patients following resection of stages II and IIIa non-small cell lung cancer

NAD(P)H:quinone oxidoreductase 1 (NQO1), is a cytosolic flavoenzyme that catalyzes the two-electron reduction of quinones into hydroquinones. A polymorphism (NQO1*2) alters enzymatic activity of NQO1 resulting in diminished NQO1 activity. Malignancies with NQO1*2 may be resistant to radiation and chemotherapy with resulting poorer survival. NQO1 allele was evaluated in subjects enrolled in ECOG 3590, a randomized comparison of radiation (RT) vs radiation and chemotherapy with cisplatin/etoposide (RCT) in patients with completely resected stages II and IIIa NSCLC. Overall survival was estimated using the Kaplan-Meier method and compared via the log-rank test. Cox models were used to assess the impact of covariates on outcomes. Among 152 patients with assessable samples, 24 (16%) had NQO1*2. Median follow-up was 139 months. The presence of NQO1*2/*2 was associated with decreased overall survival (OS) (median in the heterozygote/wild-type group 42.3 vs. 33.5 months in the variant group, p=0.04). In a multivariable Cox model, variant NQO1 (HR=1.58, p=0.05), age <60 (HR=0.67, p=0.04), PS 1 (HR=1.47, p=0.05), cardiovascular disease (HR=1.93, p=0.003) and alkaline phosphatase <100 mg/ml (HR=0.59, p=0.005) were all significant predictors of OS. NQO1*2/*2 may be an independent predictor of poor overall survival in individuals with resected stages II and IIIa NSCLC. Although the basis for the NQO1 association with decreased survival requires additional evaluation, NQO1 may represent a biomarker for guiding individualized therapy