21 research outputs found
Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy
We review HB stars in a broad astrophysical context, including both variable
and non-variable stars. A reassessment of the Oosterhoff dichotomy is
presented, which provides unprecedented detail regarding its origin and
systematics. We show that the Oosterhoff dichotomy and the distribution of
globular clusters (GCs) in the HB morphology-metallicity plane both exclude,
with high statistical significance, the possibility that the Galactic halo may
have formed from the accretion of dwarf galaxies resembling present-day Milky
Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the
second-parameter problem is presented. A technique is proposed to estimate the
HB types of extragalactic GCs on the basis of integrated far-UV photometry. The
relationship between the absolute V magnitude of the HB at the RR Lyrae level
and metallicity, as obtained on the basis of trigonometric parallax
measurements for the star RR Lyrae, is also revisited, giving a distance
modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are
studied. Finally, the conductive opacities used in evolutionary calculations of
low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and
Space Scienc
A delicate balance between antibody evasion and ACE2 affinity for Omicron BA.2.75
Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused successive global waves of infection. These variants, with multiple mutations in the spike protein, are thought to facilitate escape from natural and vaccine-induced immunity and often increase in affinity for ACE2. The latest variant to cause concern is BA.2.75, identified in India where it is now the dominant strain, with evidence of wider dissemination. BA.2.75 is derived from BA.2 and contains four additional mutations in the receptor-binding domain (RBD). Here, we perform an antigenic and biophysical characterization of BA.2.75, revealing an interesting balance between humoral evasion and ACE2 receptor affinity. ACE2 affinity for BA.2.75 is increased 9-fold compared with BA.2; there is also evidence of escape of BA.2.75 from immune serum, particularly that induced by Delta infection, which may explain the rapid spread in India, where where there is a high background of Delta infection. ACE2 affinity appears to be prioritized over greater escape
Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses
In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent mAb binding shifting to 3 clusters, 2 corresponding to early-pandemic binding hotspots. The RBD mutations in recent variants map close to these binding sites and knock out or severely knock down neutralization activity of all but 1 potent mAb. This recent mAb escape corresponds with large falls in neutralization titer of vaccine or BA.1, BA.2, or BA.4/5 immune serum
Pathogenic Germline Variants in 10,389 Adult Cancers
We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer. A pan-cancer analysis identifies hundreds of predisposing germline variants
Spatial Distribution of Carbon in the Subsurface of Riparian Zones
Soil C supplies vary spatially within and among riparian wetlands. Understanding this variability is essential to assessments of C-dependent riparian wetland functions such as water quality enhancement and C storage. In this study, we examined the distribution of C with depth across the riparian landscape. Our objectives were to describe the spatial distribution of various C forms in the subsurface of riparian wetlands, and to identify the watershed, landscape, and soil characteristics that govern the distribution of these forms. Twenty-two riparian sites, mapped as alluvial or outwash soils, were examined along first-through fourth-order streams. Soils were described from pits and auger borings along transects established perpendicular to the stream. Roots and buried A horizons represent the majority of C in the subsurface, representing an important source of C for riparian zone functions. Buried A horizons and C-rich lenses, indicative of alluvial soils, were identified in 21 of the 22 sites. Higher order riparian zones tended to have greater quantities of alluvium. Roots were generally distributed to the greatest depths close to the streams where alluvial deposits were thickest. All first-, second-, and third-order riparian zones were mapped as outwash soils on county-scale soil surveys. These sites, however, contained predominantly alluvial soils, suggesting that soil surveys at the 1:15,840 scale are inadequate for identifying alluvial soils along lower order streams. To assess the best predictors of alluvium distribution within riparian zones, 11 watershed characteristics were examined. A forward stepwise regression revealed that watershed size and floodplain width are two of the most important indicators of the quantity, width, and depth of alluvium, and subsequently subsurface C, within glaciated riparian zones. © Soil Science Society of America
Subsurface Transport of Heavy Metals Mediated by Biosolid Colloids in Waste-Amended Soils
Effect of 4-(4-Chlorobenzyl)pyridine on Rat Hepatic Microsomal Cytochrome P450 and Drug-Metabolizing Enzymes in Vivo and in Vitro.
A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer
Precision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. We found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. We developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations. We demonstrated large gains in overlap between resources across variants, diseases and drugs as a result of this harmonization. We subsequently demonstrated improved matching between a patient cohort and harmonized interpretations of potential clinical significance, observing an increase from an average of 33% per individual knowledgebase to 57% in aggregate. Our analyses illuminate the need for open, interoperable sharing of variant interpretation data. We also provide a freely available web interface (search.cancervariants.org) for exploring the harmonized interpretations from these six knowledgebases.We acknowledge the contributions from members of GA4GH and specifically the Genotype to Phenotype Task Team for their numerous contributions leading to this study. We thank the VICC knowledgebase partners for their input in construction of the meta-knowledgebase and drafting of the paper, M. McCoy for his assistance in proofreading the manuscript and J. McMichael for his work in restyling Fig. 1. A.H.W. was supported by NIH National Cancer Institute (NCI) award F32CA206247 and National Human Genome Research Institute (NHGRI) award K99HG010157. B.W. was supported by NIH NHGRI award U54HG007990, NIH NCI R01CA180778 and Intel SRA-16-037. D.T.R. is a participant in the Berlin Institute of Health—Charité Clinical Scientist Program funded by the Charité—Universitätsmedizin Berlin and the Berlin Institute of Health, and was supported by grant nos. 031L0030E and 031L0023 awarded by the German Federal Ministry of Education and Research. D.I.R. and S.M. are supported by ClinGen, through the NHGRI awards U41HG006834, U41HG009649, U41HG009650 and U01HG007437. T.A. was supported by an award from Academy of Finland (grant no. 330857), Cancer Society of Finland. M.H. was supported by the Monarch Initiative NIH Office of Director award R24OD011883. J. Gao, D.C. and N.S. were supported by NIH NCI award P30CA008748. N.L.B. acknowledges funding from the European Research Council (consolidator grant 682398). M.L. was supported through the Medical Research Council—Cancer Research UK Stratification in Colorectal Cancer Program grant and Health Data Research UK Substantive Site grant. M.G. was supported by NIH NHGRI award R00HG007940 and a V Scholar Award from the V Foundation for Cancer Research. O.L.G., M.G. and the CIViC knowledgebase were supported by the NIH NCI awards U01CA209936 and U24CA237719 and a Cancer Moonshot funding opportunity, specifically an Activities to Promote Technology Research Collaborations for Cancer Research (Administrative Support) award
Pines
Pinus is the most important genus within the Family Pinaceae and also within the gymnosperms by the number of species (109 species recognized by Farjon 2001) and by its contribution to forest ecosystems. All pine species are evergreen trees or shrubs. They are widely distributed in the northern hemisphere, from tropical areas to northern areas in America and Eurasia. Their natural range reaches the equator only in Southeast Asia. In Africa, natural occurrences are confined to the Mediterranean basin. Pines grow at various elevations from sea level (not usual in tropical areas) to highlands. Two main regions of diversity are recorded, the most important one in Central America (43 species found in Mexico) and a secondary one in China. Some species have a very wide natural range (e.g., P. ponderosa, P. sylvestris). Pines are adapted to a wide range of ecological conditions: from tropical (e.g., P. merkusii, P. kesiya, P. tropicalis), temperate (e.g., P. pungens, P. thunbergii), and subalpine (e.g., P. albicaulis, P. cembra) to boreal (e.g., P. pumila) climates (Richardson and Rundel 1998, Burdon 2002). They can grow in quite pure stands or in mixed forest with other conifers or broadleaved trees. Some species are especially adapted to forest fires, e.g., P. banksiana, in which fire is virtually essential for cone opening and seed dispersal. They can grow in arid conditions, on alluvial plain soils, on sandy soils, on rocky soils, or on marsh soils. Trees of some species can have a very long life as in P. longaeva (more than 3,000 years)