Overhead photoselective shade films mitigate effects of climate change by arresting flavonoid and aroma composition degradation in wine

IntroductionOverhead photoselective shade films installed in vineyards improve berry composition in hot grape-growing regions. The aim of the study was to evaluate the flavonoid and aroma profiles and composition of wines from Cabernet Sauvignon grapes (Vitis vinifera L.) treated with partial solar radiation exclusion.MethodsExperimental design consisted in a randomized experiment with four shade films (D1, D3, D4, D5) with differing solar radiation spectra transmittance and compared to an uncovered control (C0) performed over two seasons (2021 and 2022) in Oakville (CA, USA). Berries were collected by hand at harvest and individual vinifications for each treatment and season were conducted in triplicates. Then, wine chemical composition, flavonoid and aromatic profiles were analyzed.ResultsThe wines from D4 treatment had greater color intensity and total phenolic index due to co-pigmentation with anthocyanins. Shade film wines D5 and D1 from the 2020 vintage demonstrated increased total anthocyanins in the hotter of the two experimental years. In 2021, reduced cluster temperatures optimized total anthocyanins in D4 wines. Reduced cluster temperatures modulated anthocyanin acylation, methylation and hydroxylation in shade film wines. Volatile aroma composition was analyzed using gas chromatography mass spectroscopy (GCMS) and D4 wines exhibited a more fruity and pleasant aroma profile than C0 wines.DiscussionResults provided evidence that partial solar radiation exclusion in the vineyard using overhead shade films directly improved flavonoid and aroma profiles of resultant wines under hot vintage conditions, providing a tool for combatting air temperatures and warmer growing conditions associated with climate change

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.We thank members of the Cambridge BioResource Scientific Advisory Board and Management Committee for their support of our study and the National Institute for Health Research Cambridge Biomedical Research Centre for funding. K.D. is funded as a HSST trainee by NHS Health Education England. M.F. is funded from the BLUEPRINT Grant Code HEALTH-F5-2011-282510 and the BHF Cambridge Centre of Excellence [RE/13/6/30180]. J.R.S. is funded by a MRC CASE Industrial studentship, co-funded by Pfizer. J.D. is a British Heart Foundation Professor, European Research Council Senior Investigator, and National Institute for Health Research (NIHR) Senior Investigator. S.M., S.T, M.H, K.M. and L.D. are supported by the NIHR BioResource-Rare Diseases, which is funded by NIHR. Research in the Ouwehand laboratory is supported by program grants from the NIHR to W.H.O., the European Commission (HEALTH-F2-2012-279233), the British Heart Foundation (BHF) to W.J.A. and D.R. under numbers RP-PG-0310-1002 and RG/09/12/28096 and Bristol Myers-Squibb; the laboratory also receives funding from NHSBT. W.H.O is a NIHR Senior Investigator. The INTERVAL academic coordinating centre receives core support from the UK Medical Research Council (G0800270), the BHF (SP/09/002), the NIHR and Cambridge Biomedical Research Centre, as well as grants from the European Research Council (268834), the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), Merck and Pfizer. DJR and DA were supported by the NIHR Programme ‘Erythropoiesis in Health and Disease’ (Ref. NIHR-RP-PG-0310-1004). N.S. is supported by the Wellcome Trust (Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH-F5-2011-282510). The INTERVAL study is funded by NHSBT and has been supported by the NIHR-BTRU in Donor Health and Genomics at the University of Cambridge in partnership with NHSBT. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health of England or NHSBT. D.G. is supported by a “la Caixa”-Severo Ochoa pre-doctoral fellowship

H2A.Z Demarcates Intergenic Regions of the Plasmodium falciparum Epigenome That Are Dynamically Marked by H3K9ac and H3K4me3

Epigenetic regulatory mechanisms and their enzymes are promising targets for malaria therapeutic intervention; however, the epigenetic component of gene expression in P. falciparum is poorly understood. Dynamic or stable association of epigenetic marks with genomic features provides important clues about their function and helps to understand how histone variants/modifications are used for indexing the Plasmodium epigenome. We describe a novel, linear amplification method for next-generation sequencing (NGS) that allows unbiased analysis of the extremely AT-rich Plasmodium genome. We used this method for high resolution, genome-wide analysis of a histone H2A variant, H2A.Z and two histone H3 marks throughout parasite intraerythrocytic development. Unlike in other organisms, H2A.Z is a constant, ubiquitous feature of euchromatic intergenic regions throughout the intraerythrocytic cycle. The almost perfect colocalisation of H2A.Z with H3K9ac and H3K4me3 suggests that these marks are preferentially deposited on H2A.Z-containing nucleosomes. By performing RNA-seq on 8 time-points, we show that acetylation of H3K9 at promoter regions correlates very well with the transcriptional status whereas H3K4me3 appears to have stage-specific regulation, being low at early stages, peaking at trophozoite stage, but does not closely follow changes in gene expression. Our improved NGS library preparation procedure provides a foundation to exploit the malaria epigenome in detail. Furthermore, our findings place H2A.Z at the cradle of P. falciparum epigenetic regulation by stably defining intergenic regions and providing a platform for dynamic assembly of epigenetic and other transcription related complexes

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Impact of Rootstock and Season on Red Blotch Disease Expression in Cabernet Sauvignon (V. vinifera).

Grapevine red blotch virus (GRBV), the causative agent of grapevine red blotch disease, is widespread across the United States and causes a delay in ripening events in grapes. This study evaluates the effects of GRBV on Cabernet Sauvignon grape berry composition, grafted on two different rootstocks (110R and 420A) in two seasons (2016 and 2017). Total soluble solids, acidity, and anthocyanin concentrations were monitored through ripening and at harvest. Phenolic and volatile compounds were also analyzed at harvest to determine genotypic and environmental influences on disease outcome. Sugar accumulation through ripening was lower in diseased fruit (RB (+)) than healthy fruit across rootstock and season. GRBV impact was larger in 2016 than 2017, indicating a seasonal effect on disease expression. In general, anthocyanin levels and volatile compound accumulation was lower in RB (+) fruit than healthy fruit. Total phenolic composition and tannin content was higher in RB (+) fruit than healthy fruit in only 110R rootstock. Overall, GRBV impacted Cabernet Sauvignon grape composition crafted on rootstock 110R more than those crafted on rootstock 420A

Correctly folded Pfs48/45 protein of Plasmodium falciparum elicits malaria transmission-blocking immunity in mice

Malaria kills >1 million people each year, in particular in sub-Saharan Africa. Although asexual forms are directly responsible for disease and death, sexual stages account for the transmission of Plasmodium parasites from human to the mosquito vector and therefore the spread of the parasite in the population. Development of a malaria vaccine is urgently needed to reduce morbidity and mortality. Vaccines against sexual stages of Plasmodium falciparum are meant to decrease the force of transmission and consequently reduce malaria burden. Pfs48/45 is specifically expressed in sexual stages and is a well established transmission-blocking (TB) vaccine candidate. However, production of correctly folded recombinant Pfs48/45 protein with display of its TB epitopes has been a major challenge. Here, we show the production of a properly folded Pfs48/45 C-terminal fragment by simultaneous coexpression with four periplasmic folding catalysts in Escherichia coli. This C-terminal fragment fused to maltose binding protein was produced at medium scale with >90% purity and a stability over at least a 9-month period. It induces uniform and high antibody titers in mice and elicits functional TB antibodies in standard membrane feeding assays in 90% of the immunized mice. Our data provide a clear perspective on the clinical development of a Pfs48/45-based TB malaria vaccine