Late Quaternary sea-level history and the antiquity of mammoths (\u3ci\u3eMammuthus exilis\u3c/i\u3e and \u3ci\u3eMammuthus columbi\u3c/i\u3e), Channel Islands National Park, California, USA

Fossils of Columbian mammoths (Mammuthus columbi) and pygmymammoths (Mammuthus exilis) have been reported from Channel Islands National Park, California. Most date to the last glacial period (Marine Isotope Stage [MIS] 2), but a tusk of M. exilis (or immature M. columbi) was found in the lowest marine terrace of Santa Rosa Island. Uranium-series dating of corals yielded ages from 83.8 ± 0.6 ka to 78.6 ± 0.5 ka, correlating the terrace withMIS 5.1, a time of relatively high sea level.Mammoths likely immigrated to the islands by swimming during the glacial periodsMIS 6 (~150 ka) orMIS 8 (~250 ka),when sea levelwas lowand the island–mainland distance was minimal, as during MIS 2. Earliest mammoth immigration to the islands likely occurred late enough in the Quaternary that uplift of the islands and the mainland decreased the swimming distance to a range that could be accomplished by mammoths. Results challenge the hypothesis that climate change, vegetation change, and decreased land area from sea-level rise were the causes of mammoth extinction at the Pleistocene/ Holocene boundary on the Channel Islands. Pre-MIS 2 mammoth populations would have experienced similar or even more dramatic changes at the MIS 6/5.5 transition

Targeting the latent human cytomegalovirus reservoir for T-cell-mediated killing with virus-specific nanobodies.

Funder: Department of HealthLatent human cytomegalovirus (HCMV) infection is characterized by limited gene expression, making latent HCMV infections refractory to current treatments targeting viral replication. However, reactivation of latent HCMV in immunosuppressed solid organ and stem cell transplant patients often results in morbidity. Here, we report the killing of latently infected cells via a virus-specific nanobody (VUN100bv) that partially inhibits signaling of the viral receptor US28. VUN100bv reactivates immediate early gene expression in latently infected cells without inducing virus production. This allows recognition and killing of latently infected monocytes by autologous cytotoxic T lymphocytes from HCMV-seropositive individuals, which could serve as a therapy to reduce the HCMV latent reservoir of transplant patients

Antinuclear antibodies in primary pulmonary hypertension

The association of positive antinuclear antibodies with the clinical and hemodynamic features of 43 patients with primary pulmonary hypertension and 16 patients with secondary pulmonary hypertension was investigated. Each patient had determinations of antinuclear antibodies using a KB cell substrate immunofluorescent test. Of the patients with primary pulmonary hypertension, 40% had positive antinuclear antibodies at titers of 1:80 dilutions or greater. There were no differences between patients with primary pulmonary hypertension and positive antinuclear antibodies compared with those with negative antinuclear antibodies in relation to clinical or hemodynamic status. A 6% incidence raie of antinuclear antibodies was found in patients with secondary pulmonary hypertension, similar to that in the normal population.The clinical, hemodynamic, serologic and histologic similarity between patients with primary pulmonary hypertension and those with unexplained pulmonary hypertension associated with collagen vascular disorders suggests that primary pulmonary hypertension in some patients may represent a collagen vascular disease confined to the lungs. The frequency of positive antinuclear antibody tests would place primary pulmonary hypertension between rheumatoid arthritis and scleroderma in the spectrum of collagen vascular diseases. Further studies are necessary, however, before one might expect that immunosuppressive therapy would be beneficial to these patients

University of California Research Seminar Network: A Prospectus

By webcasting the hundreds of seminars presented in the University of California system each week, UC educators hope to enhance the exchange of scientific information for their campuses and create the foundation for an international research seminar network

A Physical Model for z~2 Dust Obscured Galaxies

We present a physical model for the origin of z~2 Dust-Obscured Galaxies (DOGs), a class of high-redshift ULIRGs selected at 24 micron which are particularly optically faint (24/R>1000). By combining N-body/SPH simulations of high redshift galaxy evolution with 3D polychromatic dust radiative transfer models, we find that luminous DOGs (with F24 > 0.3 mJy at z~2 are well-modeled as extreme gas-rich mergers in massive (~5x10^12-10^13 Msun) halos, with elevated star formation rates (~500-1000 Msun/yr) and/or significant AGN growth (Mdot > 0.5 Msun/yr), whereas less luminous DOGs are more diverse in nature. At final coalescence, merger-driven DOGs transition from being starburst dominated to AGN dominated, evolving from a "bump" to a power-law shaped mid-IR (IRAC) spectral energy distribution (SED). After the DOG phase, the galaxy settles back to exhibiting a "bump" SED with bluer colors and lower star formation rates. While canonically power-law galaxies are associated with being AGN-dominated, we find that the power-law mid-IR SED can owe both to direct AGN contribution, as well as to a heavily dust obscured stellar bump at times that the galaxy is starburst dominated. Thus power-law galaxies can be either starburst or AGN dominated. Less luminous DOGs can be well-represented either by mergers, or by massive ($M_{\rm baryon} ~5x10^11 Msun) secularly evolving gas-rich disc galaxies (with SFR > 50 Msun/yr). By utilising similar models as those employed in the SMG formation study of Narayanan et al. (2010), we investigate the connection between DOGs and SMGs. We find that the most heavily star-forming merger driven DOGs can be selected as Submillimetre Galaxies (SMGs), while both merger-driven and secularly evolving DOGs typically satisfy the BzK selection criteria.Comment: Accepted by MNRAS; major changes include better description of dependency on ISM specification and updated models allowing dust to evolve with metallicity

Oxygen Activation and Radical Transformations in Heme Proteins and Metalloporphyrins

As a result of the adaptation of life to an aerobic environment, nature has evolved a panoply of metalloproteins for oxidative metabolism and protection against reactive oxygen species. Despite the diverse structures and functions of these proteins, they share common mechanistic grounds. An open-shell transition metal like iron or copper is employed to interact with O_2 and its derived intermediates such as hydrogen peroxide to afford a variety of metal–oxygen intermediates. These reactive intermediates, including metal-superoxo, -(hydro)peroxo, and high-valent metal–oxo species, are the basis for the various biological functions of O_2-utilizing metalloproteins. Collectively, these processes are called oxygen activation. Much of our understanding of the reactivity of these reactive intermediates has come from the study of heme-containing proteins and related metalloporphyrin compounds. These studies not only have deepened our understanding of various functions of heme proteins, such as O2 storage and transport, degradation of reactive oxygen species, redox signaling, and biological oxygenation, etc., but also have driven the development of bioinorganic chemistry and biomimetic catalysis. In this review, we survey the range of O_2 activation processes mediated by heme proteins and model compounds with a focus on recent progress in the characterization and reactivity of important iron–oxygen intermediates. Representative reactions initiated by these reactive intermediates as well as some context from prior decades will also be presented. We will discuss the fundamental mechanistic features of these transformations and delineate the underlying structural and electronic factors that contribute to the spectrum of reactivities that has been observed in nature as well as those that have been invented using these paradigms. Given the recent developments in biocatalysis for non-natural chemistries and the renaissance of radical chemistry in organic synthesis, we envision that new enzymatic and synthetic transformations will emerge based on the radical processes mediated by metalloproteins and their synthetic analogs

Human marginal zone B cell development from early T2 progenitors.

B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2, and T3 stages to become naive B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgMhi and IgMlo developmental trajectories. IgMhi T2 cells have higher expression of α4β7 integrin and lower expression of IL-4 receptor (IL4R) compared with the IgMlo branch and are selectively recruited into gut-associated lymphoid tissue. IgMhi T2 cells also share transcriptomic features with marginal zone B cells (MZBs). Lineage progression from T1 cells to MZBs via an IgMhi trajectory is identified by pseudotime analysis of scRNA-sequencing data. Reduced frequency of IgMhi gut-homing T2 cells is observed in severe SLE and is associated with reduction of MZBs and their putative IgMhi precursors. The collapse of the gut-associated MZB maturational axis in severe SLE affirms its existence in health