Results of soy-based meal replacement formula on weight, anthropometry, serum lipids & blood pressure during a 40-week clinical weight loss trial

BACKGROUND: To evaluate the intermediate-term health outcomes associated with a soy-based meal replacement, and to compare the weight loss efficacy of two distinct patterns of caloric restriction. METHODS: Ninety overweight/obese (28 < BMI ≤ 41 kg/m(2)) adults received a single session of dietary counseling and were randomized to either 12 weeks at 1200 kcal/day, 16 weeks at 1500 kcal/d and 12 weeks at 1800 kcal/d (i.e., the 12/15/18 diet group), or 28 weeks at 1500 kcal/d and 12 weeks at 1800 kcal/d (i.e., the 15/18 diet group). Weight, body fat, waist circumference, blood pressure and serum lipid concentrations were measured at 4-week intervals throughout the 40-week trial. RESULTS: Subjects in both treatments showed statistically significant improvements in outcomes. A regression model for weight change suggests that subjects with larger baseline weights tended to lose more weight and subjects in the 12/15/18 group tended to experience, on average, an additional 0.9 kg of weight loss compared with subjects in the 15/18 group. CONCLUSION: Both treatments using the soy-based meal replacement program were associated with significant and comparable weight loss and improvements on selected health variables

Genetic association analysis of the cardiovascular biomarker: N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP)

BACKGROUND: NT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we estimated the heritability of and examined genetic associations of SNPs in the BNP gene region with circulating NT-proBNP and prevalent CVD in 4,331 participants from the Long Life Family Study (LLFS). METHODS AND RESULTS: Genotypes of 10 SNPs from the NPPB and NPPA regions that encode BNP and A-type natriuretic peptide, respectively, were tested for association with NT-proBNP and prevalent cardiovascular disease and risk factors. We performed analyses using the Sequential Oligogenic Linkage Analysis (SOLAR) program to account for family relatedness, and adjusted all models for age, sex, and field center. The mean age of the LLFS was 69.8 years (range 24-110) with 55.4% females. NT-proBNP was significantly heritable (h2 = 0.21; P = 4x10-14), and the minor alleles of rs632793 (p\u3c0.001) and rs41300100 (p = 0.05) were independently associated with higher serum NT-proBNP levels. Additionally, the minor allele of rs632793 was significantly and consistently associated with lower prevalent CVD, including blood pressures, independent of NT-proBNP level (all P\u3c0.05). Results for prevalent CVD, but not NT-proBNP levels, showed significant interaction by familial generation. CONCLUSION: In this family-based study of subjects with exceptional longevity, we identified several allelic variants in the BNP gene region associated with NT-pro-BNP levels and prevalent CVD

Joint tests for quantitative trait loci in experimental crosses

Selective genotyping is common because it can increase the expected correlation between QTL genotype and phenotype and thus increase the statistical power of linkage tests (i.e., regression-based tests). Linkage can also be tested by assessing whether the marginal genotypic distribution conforms to its expectation, a marginal-based test. We developed a class of joint tests that, by constraining intercepts in regression-based analyses, capitalize on the information available in both regression-based and marginal-based tests. We simulated data corresponding to the null hypothesis of no QTL effect and the alternative of some QTL effect at the locus for a backcross and an F2 intercross between inbred strains. Regression-based and marginal-based tests were compared to corresponding joint tests. We studied the effects of random sampling, selective sampling from a single tail of the phenotypic distribution, and selective sampling from both tails of the phenotypic distribution. Joint tests were nearly as powerful as all competing alternatives for random sampling and two-tailed selection under both backcross and F2 intercross situations. Joint tests were generally more powerful for one-tailed selection under both backcross and F2 intercross situations. However, joint tests cannot be recommended for one-tailed selective genotyping if segregation distortion is suspected

Blood ties: ABO is a trans-species polymorphism in primates

The ABO histo-blood group, the critical determinant of transfusion incompatibility, was the first genetic polymorphism discovered in humans. Remarkably, ABO antigens are also polymorphic in many other primates, with the same two amino acid changes responsible for A and B specificity in all species sequenced to date. Whether this recurrence of A and B antigens is the result of an ancient polymorphism maintained across species or due to numerous, more recent instances of convergent evolution has been debated for decades, with a current consensus in support of convergent evolution. We show instead that genetic variation data in humans and gibbons as well as in Old World Monkeys are inconsistent with a model of convergent evolution and support the hypothesis of an ancient, multi-allelic polymorphism of which some alleles are shared by descent among species. These results demonstrate that the ABO polymorphism is a trans-species polymorphism among distantly related species and has remained under balancing selection for tens of millions of years, to date, the only such example in Hominoids and Old World Monkeys outside of the Major Histocompatibility Complex.Comment: 45 pages, 4 Figures, 4 Supplementary Figures, 5 Supplementary Table

Single-cell RNA transcriptome analysis of CNS immune cells reveals CXCL16/CXCR6 as maintenance factors for tissue-resident T cells that drive synapse elimination

BACKGROUND: Emerging RNA viruses that target the central nervous system (CNS) lead to cognitive sequelae in survivors. Studies in humans and mice infected with West Nile virus (WNV), a re-emerging RNA virus associated with learning and memory deficits, revealed microglial-mediated synapse elimination within the hippocampus. Moreover, CNS-resident memory T (T METHODS: Here, we examined immune cells within the murine WNV-recovered forebrain using single-cell RNA sequencing to identify putative ligand-receptor pairs involved in intercellular communication between T cells and microglia. Clustering and differential gene analyses were followed by protein validation and genetic and antibody-based approaches utilizing an established murine model of WNV recovery in which microglia and complement promote ongoing hippocampal synaptic loss. RESULTS: Profiling of host transcriptome immune cells at 25 days post-infection in mice revealed a shift in forebrain homeostatic microglia to activated subpopulations with transcriptional signatures that have previously been observed in studies of neurodegenerative diseases. Importantly, CXCL16/CXCR6, a chemokine signaling pathway involved in T CONCLUSIONS: We provide a comprehensive assessment of the role of CXCL16/CXCR6 as an interaction link between microglia and CD

Facemasks, Hand Hygiene, and Influenza among Young Adults: A Randomized Intervention Trial

Limited vaccine availability and the potential for resistance to antiviral medications have led to calls for establishing the efficacy of non-pharmaceutical measures for mitigating pandemic influenza. Our objective was to examine if the use of face masks and hand hygiene reduced rates of influenza-like illness (ILI) and laboratory-confirmed influenza in the natural setting. A cluster-randomized intervention trial was designed involving 1,178 young adults living in 37 residence houses in 5 university residence halls during the 2007–2008 influenza season. Participants were assigned to face mask and hand hygiene, face mask only, or control group during the study. Discrete-time survival models using generalized estimating equations to estimate intervention effects on ILI and confirmed influenza A/B infection over a 6-week study period were examined. A significant reduction in the rate of ILI was observed in weeks 3 through 6 of the study, with a maximum reduction of 75% during the final study week (rate ratio [RR] = 0.25, [95% CI, 0.07 to 0.87]). Both intervention groups compared to the control showed cumulative reductions in rates of influenza over the study period, although results did not reach statistical significance. Generalizability limited to similar settings and age groups. Face masks and hand hygiene combined may reduce the rate of ILI and confirmed influenza in community settings. These non-pharmaceutical measures should be recommended in crowded settings at the start of an influenza pandemic

Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

The Searsville Lake Site (California, USA) as a candidate Global Boundary Stratotype Section and Point for the Anthropocene Series

Cores from Searsville Lake within Stanford University’s Jasper Ridge Biological Preserve, California, USA, are examined to identify a potential GSSP for the Anthropocene: core JRBP2018-VC01B (944.5 cm-long) and tightly correlated JRBP2018-VC01A (852.5 cm-long). Spanning from 1900 CE ± 3 years to 2018 CE, a secure chronology resolved to the sub-annual level allows detailed exploration of the Holocene-Anthropocene transition. We identify the primary GSSP marker as first appearance of 239,240Pu (372–374 cm) in JRBP2018-VC01B and designate the GSSP depth as the distinct boundary between wet and dry season at 366 cm (6 cm above the first sample containing 239,240Pu) and corresponding to October-December 1948 CE. This is consistent with a lag of 1–2 years between ejection of 239,240Pu into the atmosphere and deposition. Auxiliary markers include: first appearance of 137Cs in 1958; late 20th-century decreases in δ15N; late 20th-century elevation in SCPs, Hg, Pb, and other heavy metals; and changes in abundance and presence of ostracod, algae, rotifer, and protozoan microfossils. Fossil pollen document anthropogenic landscape changes related to logging and agriculture. As part of a major university, the Searsville site has long been used for research and education, serves users locally to internationally, and is protected yet accessible for future studies and communication about the Anthropocene. PLAIN WORD SUMMARY: The Global Boundary Stratotype Section and Point (GSSP) for the proposed Anthropocene Series/Epoch is suggested to lie in sediments accumulated over the last ~120 years in Searsville Lake, Woodside, California, USA. The site fulfills all of the ideal criteria for defining and placing a GSSP. In addition, the Searsville site is particularly appropriate to mark the onset of the Anthropocene, because it was anthropogenic activities–the damming of a watershed–that created a geologic record that now preserves the very signals that can be used to recognize the Anthropocene worldwide

Elemental energy spectra of cosmic rays measured by CREAM-II

We present new measurements of the energy spectra of cosmic-ray (CR) nuclei from the second flight of the balloon-borne experiment CREAM (Cosmic Ray Energetics And Mass). The instrument (CREAM-II) was comprised of detectors based on different techniques (Cherenkov light, specific ionization in scintillators and silicon sensors) to provide a redundant charge identification and a thin ionization calorimeter capable of measuring the energy of cosmic rays up to several hundreds of TeV. The data analysis is described and the individual energy spectra of C, O, Ne, Mg, Si and Fe are reported up to ~ 10^14 eV. The spectral shape looks nearly the same for all the primary elements and can be expressed as a power law in energy E^{-2.66+/-0.04}. The nitrogen absolute intensity in the energy range 100-800 GeV/n is also measured.Comment: 4 pages, 3 figures, presented at ICRC 2009, Lodz, Polan

Measurements of cosmic-ray energy spectra with the 2nd CREAM flight

During its second Antarctic flight, the CREAM (Cosmic Ray Energetics And Mass) balloon experiment collected data for 28 days, measuring the charge and the energy of cosmic rays (CR) with a redundant system of particle identification and an imaging thin ionization calorimeter. Preliminary direct measurements of the absolute intensities of individual CR nuclei are reported in the elemental range from carbon to iron at very high energy.Comment: 4 pages, 3 figures, presented at XV International Symposium on Very High Energy Cosmic Ray Interactions (ISVHECRI 2008