Regular fat and reduced fat dairy products show similar associations with markers of adolescent cardiometabolic health

Reduced fat dairy products are generally recommended for adults and children over the age of two years. However, emerging evidence suggests that dairy fat may not have detrimental health effects. We aimed to investigate prospective associations between consumption of regular versus reduced fat dairy products and cardiometabolic risk factors from early to late adolescence. In the West Australian Raine Study, dairy intake was assessed using semi-quantitative food frequency questionnaires in 860 adolescents at 14 and 17-year follow-ups; 582 of these also had blood biochemistry at both points. Using generalized estimating equations, we examined associations with cardiometabolic risk factors. Models incorporated reduced fat and regular fat dairy together (in serves/day) and were adjusted for a range of factors including overall dietary pattern. In boys, there was a mean reduction in diastolic blood pressure of 0.66 mmHg (95% CI 0.23–1.09) per serve of reduced fat dairy and an independent, additional reduction of 0.47 mmHg (95% CI 0.04–0.90) per serve of regular fat dairy. Each additional serve of reduced fat dairy was associated with a 2% reduction in HDL-cholesterol (95% CI 0.97–0.995) and a 2% increase in total: HDL-cholesterol ratio (95% CI 1.002–1.03); these associations were not observed with regular fat products. In girls, there were no significant independent associations observed in fully adjusted models. Although regular fat dairy was associated with a slightly better cholesterol profile in boys, overall, intakes of both regular fat and reduced fat dairy products were associated with similar cardiometabolic associations in adolescents

The statistical properties of solar wind temperature parameters near 1 AU

We present a long-duration ($\sim$10 years) statistical analysis of the temperatures, plasma betas, and temperature ratios for the electron, proton, and alpha-particle populations observed by the \emph{Wind} spacecraft near 1 AU. The mean(median) scalar temperatures are $T{\scriptstyle_{e, tot}}$ $=$ 12.2(11.9) eV, $T{\scriptstyle_{p, tot}}$ $=$ 12.7(8.6) eV, and $T{\scriptstyle_{\alpha, tot}}$ $=$ 23.9(10.8) eV. The mean(median) total plasma betas are $\beta{\scriptstyle_{e, tot}}$ $=$ 2.31(1.09), $\beta{\scriptstyle_{p, tot}}$ $=$ 1.79(1.05), and $\beta{\scriptstyle_{\alpha, tot}}$ $=$ 0.17(0.05). The mean(median) temperature ratios are $\left(T{\scriptstyle_{e}}/T{\scriptstyle_{p}}\right){\scriptstyle_{tot}}$ $=$ 1.64(1.27), $\left(T{\scriptstyle_{e}}/T{\scriptstyle_{\alpha}}\right){\scriptstyle_{tot}}$ $=$ 1.24(0.82), and $\left(T{\scriptstyle_{\alpha}}/T{\scriptstyle_{p}}\right){\scriptstyle_{tot}}$ $=$ 2.50(1.94). We also examined these parameters during time intervals that exclude interplanetary (IP) shocks, times within the magnetic obstacles (MOs) of interplanetary coronal mass ejections (ICMEs), and times that exclude MOs. The only times that show significant alterations to any of the parameters examined are those during MOs. In fact, the only parameter that does not show a significant change during MOs is the electron temperature. Although each parameter shows a broad range of values, the vast majority are near the median. We also compute particle-particle collision rates and compare to effective wave-particle collision rates. We find that, for reasonable assumptions of wave amplitude and occurrence rates, the effect of wave-particle interactions on the plasma is equal to or greater than the effect of Coulomb collisions. Thus, wave-particle interactions should not be neglected when modeling the solar wind.Comment: 23 pages, 3 figures, 6 tables, submitted to Astrophys. J. Suppl. on Jan. 30, 201

Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity

Prosurvival Bcl-2–like proteins, like Bcl-w, are thought to function on organelles such as the mitochondrion and to be targeted to them by their hydrophobic COOH-terminal domain. We unexpectedly found, however, that the membrane association of Bcl-w was enhanced during apoptosis. In healthy cells, Bcl-w was loosely attached to the mitochondrial membrane, but it was converted into an integral membrane protein by cytotoxic signals that induce binding of BH3-only proteins, such as Bim, or by the addition of BH3 peptides to lysates. As the structure of Bcl-w has revealed that its COOH-terminal domain occupies the hydrophobic groove where BH3 ligands bind, displacement of that domain by a BH3 ligand would displace the hydrophobic COOH-terminal residues, allowing their insertion into the membrane. To determine whether BH3 ligation is sufficient to induce the enhanced membrane affinity, or to render Bcl-w proapoptotic, we mimicked their complex by tethering the Bim BH3 domain to the NH2 terminus of Bcl-w. The chimera indeed bound avidly to membranes, in a fashion requiring the COOH-terminal domain, but neither promoted nor inhibited apoptosis. These results suggest that ligation of a proapoptotic BH3-only protein alters the conformation of Bcl-w, enhances membrane association, and neutralizes its survival function

Observations of Arp 220 using Herschel-SPIRE: An Unprecedented View of the Molecular Gas in an Extreme Star Formation Environment

We present Herschel SPIRE-FTS observations of Arp~220, a nearby ULIRG. The FTS continuously covers 190 -- 670 microns, providing a good measurement of the continuum and detection of several molecular and atomic species. We detect luminous CO (J = 4-3 to 13-12) and water ladders with comparable total luminosity; very high-J HCN absorption; OH+, H2O+, and HF in absorption; and CI and NII. Modeling of the continuum yields warm dust, with T = 66 K, and an unusually large optical depth of ~5 at 100 microns. Non-LTE modeling of the CO shows two temperature components: cold molecular gas at T ~ 50 K and warm molecular gas at T ~1350 K. The mass of the warm gas is 10% of the cold gas, but dominates the luminosity of the CO ladder. The temperature of the warm gas is in excellent agreement with H2 rotational lines. At 1350 K, H2 dominates the cooling (~20 L_sun/M_sun) in the ISM compared to CO (~0.4 L_sun/M_sun). We found that only a non-ionizing source such as the mechanical energy from supernovae and stellar winds can excite the warm gas and satisfy the energy budget of ~20 L_sun/M_sun. We detect a massive molecular outflow in Arp 220 from the analysis of strong P-Cygni line profiles observed in OH+, H2O+, and H2O. The outflow has a mass > 10^{7} M_sun and is bound to the nuclei with velocity < 250 km/s. The large column densities observed for these molecular ions strongly favor the existence of an X-ray luminous AGN (10^{44} ergs/s) in Arp 220.Comment: Accepted in ApJ on September 1, 201

Developmentally regulated Tcf7l2 splice variants mediate transcriptional repressor functions during eye formation

Tcf7l2 mediates Wnt/b-Catenin signalling during development and is implicated in cancer and type-2 diabetes. The mechanisms by which Tcf7l2 and Wnt/b-Catenin signalling elicit such a diversity of biological outcomes are poorly understood. Here, we study the function of zebrafish tcf7l2 alternative splice variants and show that only variants that include exon five or an analogous human tcf7l2 variant can effectively provide compensatory repressor function to restore eye formation in embryos lacking tcf7l1a/tcf7l1b function. Knockdown of exon five specific tcf7l2 variants in tcf7l1a mutants also compromises eye formation, and these variants can effectively repress Wnt pathway activity in reporter assays using Wnt target gene promoters. We show that the repressive activities of exon5-coded variants are likely explained by their interaction with Tle co-repressors. Furthermore, phosphorylated residues in Tcf7l2 coded exon5 facilitate repressor activity. Our studies suggest that developmentally regulated splicing of tcf7l2 can influence the transcriptional output of the Wnt pathway

IGG3 Subclass Antibodies Recognize Antigenically Drifted Influenza Viruses and SARS-CoV-2 Variants Through Efficient Bivalent Binding

The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here, we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2, or IgG3. We found that many influenza virus-specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed as IgG3 bound and neutralized antigenically drifted influenza viruses more effectively. We obtained similar results using a panel of SARS-CoV-2-specific mAbs and the antigenically advanced B.1.351 and BA.1 strains of SARS-CoV-2. We found that a licensed therapeutic mAb retained neutralization breadth against SARS-CoV-2 variants when expressed as IgG3, but not IgG1. These data highlight that IgG subclasses are not only important for fine-tuning effector functionality but also for binding and neutralization of antigenically drifted viruses

Effective fisheries management instrumental in improving fish stock status

Marine fish stocks are an important part of the world food system and are particularly important for many of the poorest people of the world. Most existing analyses suggest overfishing is increasing, and there is widespread concern that fish stocks are decreasing throughout most of the world. We assembled trends in abundance and harvest rate of stocks that are scientifically assessed, constituting half of the reported globalmarine fish catch. For these stocks, on average, abundance is increasing and is at proposed target levels. Compared with regions that are intensively managed, regions with less-developed fisheries management have, on average, 3-fold greater harvest rates and half the abundance as assessed stocks. Available evidence suggests that the regions without assessments of abundance have little fisheries management, and stocks are in poor shape. Increased application of area-appropriate fisheries science recommendations and management tools are still needed for sustaining fisheries in places where they are lacking.Fil: Hilborn, Ray. University of Washington; Estados UnidosFil: Amoroso, Ricardo Oscar. University of Washington; Estados UnidosFil: Anderson, Christopher M.. University of Washington; Estados UnidosFil: Baum, Julia K.. University of Victoria; CanadáFil: Branch, Trevor A.. University of Washington; Estados UnidosFil: Costello, Christopher. University of California at Santa Barbara; Estados UnidosFil: de Moor, Carryn L.. University of Cape Town; SudáfricaFil: Faraj, Abdelmalek. Einstitut National de Recherche Halieutique; MarruecosFil: Hively, Daniel. University of Washington; Estados UnidosFil: Jensen, Olaf P.. Rutgers University; Estados UnidosFil: Kurota, Hiroyuki. Japan Fisheries Research and Education Agency; JapónFil: Little, L. Richard. Csiro Oceans and Atmosphere; AustraliaFil: Mace, Pamela. Ministry for Primary Industries; Nueva ZelandaFil: McClanahan, Tim. Wildlife Conservation Society; Estados UnidosFil: Melnychuk, Michael C.. University of Washington; Estados UnidosFil: Minto, Cóilín. Galway-Mayo Institute of Technology; IrlandaFil: Osio, Giacomo Chato. Joint Research Centre (JRC); Italia. DG Maritime Affairs and Fisheries, European Commission; BélgicaFil: Pons, Maite. University of Washington; Estados UnidosFil: Parma, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Segurado, Susana. Sustainable Fisheries Partnership; Estados UnidosFil: Szuwalski, Cody S.. University of California at Santa Barbara; Estados UnidosFil: Wilson, Jono R.. University of California at Santa Barbara; Estados Unidos. The Nature Conservancy; Estados UnidosFil: Ye, Yimin. Food and Agriculture Organization of the United Nations; Itali