The origins of the anomalous warming in the California coastal ocean and San Francisco Bay during 2014-2016

During 2014 exceptionally warm water temperatures developed across a wide area off the California coast and within San Francisco Bay (SFB) and persisted into 2016. Observations and numerical model output are used to document this warming and determine its origins. The coastal warming was mostly confined to the upper 100 m of the ocean and was manifested strongly in the two leading modes of upper ocean (0-100 m) temperature variability in the extratropical eastern Pacific. Observations suggest that the coastal warming in 2014 propagated into nearshore regions from the west while later indicating a warming influence that propagated from south to north into the region associated with the 2015-2016 El Nino event. An analysis of the upper ocean (0-100 m) heat budget in a Regional Ocean Modeling System (ROMS) simulation confirmed this scenario. The results from a set of sensitivity runs with the model in which the lateral boundary conditions varied supported the conclusions drawn from the heat budget analysis. Concerning the warming in the SFB, an examination of the observations and the heat budget in an unstructured-grid numerical model simulation suggested that the warming during the second half of 2014 and early 2016 originated in the adjacent California coastal ocean and propagated through the Golden Gate into the Bay. The finding that the coastal and Bay warming are due to the relatively slow propagation of signals from remote sources raises the possibility that such warming events may be predictable many months or even several seasons in advance. Plain Language Summary The origins of the exceptionally warm water temperatures that developed off the California coast and in San Francisco Bay were studied using observations and computer model experiments. The coastal warming was mostly confined to the upper ocean. The coastal warming in 2014 was found to have moved into coastal waters from further offshore in the northeastern Pacific. Warming persisted into 2015-2016 as a warming influence from the south associated with the 2015-16 El Nino event in the tropical Pacific Ocean. The model experiments suggested confirmed that propagation of the warming signals from the west and north into the California coastal ocean and suggested that the warming in San Francisco Bay was found to have originated primarily in the adjacent California coastal ocean. The finding that the coastal and Bay warming are due to the relatively slow propagation of signals from remote sources raises the possibility that such warming events may be predictable many months or even several seasons in advance

Real-world COVID-19 vaccine effectiveness against the Omicron BA.2 variant in a SARS-CoV-2 infection-naive population

The SARS-CoV-2 Omicron variant has demonstrated enhanced transmissibility and escape of vaccine-derived immunity. Although first-generation vaccines remain effective against severe disease and death, robust evidence on vaccine effectiveness (VE) against all Omicron infections, irrespective of symptoms, remains sparse. We used a community-wide serosurvey with 5,310 subjects to estimate how vaccination histories modulated risk of infection in infection-naive Hong Kong during a large wave of Omicron BA.2 epidemic in January-July 2022. We estimated that Omicron infected 45% (41-48%) of the local population. Three and four doses of BNT162b2 or CoronaVac were effective against Omicron infection 7 days after vaccination (VE of 48% (95% credible interval 34-64%) and 69% (46-98%) for three and four doses of BNT162b2, respectively; VE of 30% (1-66%) and 56% (6-97%) for three and four doses of CoronaVac, respectively). At 100 days after immunization, VE waned to 26% (7-41%) and 35% (10-71%) for three and four doses of BNT162b2, and to 6% (0-29%) and 11% (0-54%) for three and four doses of CoronaVac. The rapid waning of VE against infection conferred by first-generation vaccines and an increasingly complex viral evolutionary landscape highlight the necessity for rapidly deploying updated vaccines followed by vigilant monitoring of VE

Genome-Wide Analysis of DNA Methylation and Fine Particulate Matter Air Pollution in Three Study Populations: KORA F3, KORA F4, and the Normative Aging Study

BACKGROUND: Epidemiological studies have reported associations between particulate matter (PM) concentrations and cancer and respiratory and cardiovascular diseases. DNA methylation has been identified as a possible link but so far it has only been analyzed in candidate sites. OBJECTIVES: We studied the association between DNA methylation and short-and mid-term air pollution exposure using genome-wide data and identified potential biological pathways for-additional investigation. METHODS: We collected whole blood samples from three independent studies-KORA F3 (2004-2005) and F4 (2006-2008) in Germany, and the Normative Aging Study (1999-2007) in the United States-and measured genome-wide DNA methylation proportions with the Illumina 450k BeadChip. PM concentration was measured daily at fixed monitoring stations and three different trailing averages were considered and regressed against DNA methylation: 2-day, 7-day and 28-day. Meta-analysis was performed to pool the study-specific results. RESULTS: Random-effect meta-analysis revealed 12 CpG (cytosine-guanine dinucleotide) sites as associated with PM concentration (1 for 2-day average, 1 for 7-day, and 10 for 28-day) at a genome-wide Bonferroni significance level (p 0.05 and I-2< 0.5: the site from the 7-day average results and 3 for the 28-day average. Applying false discovery rate, p-value < 0.05 was observed in 8 and 1,819 additional CpGs at 7- and 28-day average PM2.5 exposure respectively. CONCLUSION: The PM-related CpG sites found in our study suggest novel plausible systemic pathways linking ambient PM exposure to adverse health effect through variations in DNA methylation

Red wine and components flavonoids inhibit UGT2B17 in vitro

Background The metabolism and excretion of the anabolic steroid testosterone occurs by glucuronidation to the conjugate testosterone glucuronide which is then excreted in urine. Alterations in UGT glucuronidation enzyme activity could alter the rate of testosterone excretion and thus its bioavailability. The aim of this study is to investigate if red wine, a common dietary substance, has an inhibitory effect on UGT2B17. Methods Testosterone glucuronidation was assayed using human UGT2B17 supersomes with quantification of unglucuronidated testosterone over time using HPLC with DAD detection. The selected red wine was analysed using HPLC and the inhibitory effects of the wine and phenolic components were tested independently in a screening assay. Further analyses were conducted for the strongest inhibitors at physiologically relevant concentrations. Control experiments were conducted to determine the effects of the ethanol on UGT2B17. Results Over the concentration range of 2 to 8% the red wine sample inhibited the glucuronidation of testosterone by up to 70% over 2 hours. The ethanol content had no significant effect. Three red wine phenolics, identified by HLPC analyses, also inhibited the enzyme by varying amounts in the order of quercetin (72%), caffeic acid (22%) and gallic acid (9%); using a ratio of phenolic:testosterone of 1:2.5. In contrast p-coumaric acid and chlorogenic acid had no effect on the UGT2B17. The most active phenolic was selected for a detailed study at physiologically relevant concentrations, and quercetin maintained inhibitory activity of 20% at 2 M despite a ten-fold excess of testosterone. Conclusion This study reports that in an in vitro supersome-based assay, the key steroid-metabolising enzyme UGT2B17 is inhibited by a number of phenolic dietary substances and therefore may reduce the rate of testosterone glucuronidation in vivo. These results highlight the potential interactions of a number of common dietary compounds on testosterone metabolism. Considering the variety of foodstuffs that contain flavonoids, it is feasible that diet can elevate levels of circulating testosterone through reduction in urinary excretion. These results warrant further investigation and extension to a human trial to delineate the healt

Characterization of polyploid wheat genomic diversity using a high-density 90,000 single nucleotide polymorphism array

High-density single nucleotide polymorphism (SNP) genotyping arrays are a powerful tool for studying genomic patterns of diversity, inferring ancestral relationships between individuals in populations and studying marker-trait associations in mapping experiments. We developed a genotyping array including about 90,000 gene-associated SNPs and used it to characterize genetic variation in allohexaploid and allotetraploid wheat populations. The array includes a significant fraction of common genome-wide distributed SNPs that are represented in populations of diverse geographical origin. We used density-based spatial clustering algorithms to enable high-throughput genotype calling in complex data sets obtained for polyploid wheat. We show that these model-free clustering algorithms provide accurate genotype calling in the presence of multiple clusters including clusters with low signal intensity resulting from significant sequence divergence at the target SNP site or gene deletions. Assays that detect low-intensity clusters can provide insight into the distribution of presence-absence variation (PAV) in wheat populations. A total of 46 977 SNPs from the wheat 90K array were genetically mapped using a combination of eight mapping populations. The developed array and cluster identification algorithms provide an opportunity to infer detailed haplotype structure in polyploid wheat and will serve as an invaluable resource for diversity studies and investigating the genetic basis of trait variation in wheat.Shichen Wang, Debbie Wong, Kerrie Forrest, Alexandra Allen, Shiaoman Chao, Bevan E. Huang, Marco Maccaferri, Silvio Salvi, Sara G. Milner, Luigi Cattivelli, Anna M. Mastrangelo, Alex Whan, Stuart Stephen, Gary Barker, Ralf Wieseke, Joerg Plieske, International Wheat Genome Sequencing Consortium, Morten Lillemo, Diane Mather, Rudi Appels, Rudy Dolferus, Gina Brown-Guedira, Abraham Korol, Alina R. Akhunova, Catherine Feuillet, Jerome Salse, Michele Morgante, Curtis Pozniak, Ming-Cheng Luo, Jan Dvorak, Matthew Morell, Jorge Dubcovsky, Martin Ganal, Roberto Tuberosa, Cindy Lawley, Ivan Mikoulitch, Colin Cavanagh, Keith J. Edwards, Matthew Hayden, and Eduard Akhuno

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice

Search for neutral MSSM Higgs bosons decaying to a pair of tau leptons in pp collisions

Peer reviewe