GWAS of human bitter taste perception identifies new loci and reveals additional complexity of bitter taste genetics

Human perception of bitterness displays pronounced interindividual variation. This phenotypic variation is mirrored by equally pronounced genetic variation in the family of bitter taste receptor genes. To better understand the effects of common genetic variations on human bitter taste perception, we conducted a genome-wide association study on a discovery panel of 504 subjects and a validation panel of 104 subjects from the general population of São Paulo in Brazil. Correction for general taste-sensitivity allowed us to identify a SNP in the cluster of bitter taste receptors on chr12 (10.88- 11.24 Mb, build 36.1) significantly associated (best SNP: rs2708377, P = 5.31 × 10−13, r2 = 8.9%, β = −0.12, s.e. = 0.016) with the perceived bitterness of caffeine. This association overlaps with—but is statistically distinct from—the previously identified SNP rs10772420 influencing the perception of quinine bitterness that falls in the same bitter taste cluster. We replicated this association to quinine perception (P = 4.97 × 10−37, r2 = 23.2%, β = 0.25, s.e. = 0.020) and additionally found the effect of this genetic locus to be concentration specific with a strong impact on the perception of low, but no impact on the perception of high concentrations of quinine. Our study, thus, furthers our understanding of the complex genetic architecture of bitter taste perceptio

Sensitivity of Genome-Wide-Association Signals to Phenotyping Strategy: The PROP-TAS2R38 Taste Association as a Benchmark

Natural genetic variation can have a pronounced influence on human taste perception, which in turn may influence food preference and dietary choice. Genome-wide association studies represent a powerful tool to understand this influence. To help optimize the design of future genome-wide-association studies on human taste perception we have used the well-known TAS2R38-PROP association as a tool to determine the relative power and efficiency of different phenotyping and data-analysis strategies. The results show that the choice of both data collection and data processing schemes can have a very substantial impact on the power to detect genotypic variation that affects chemosensory perception. Based on these results we provide practical guidelines for the design of future GWAS studies on chemosensory phenotypes. Moreover, in addition to the TAS2R38 gene past studies have implicated a number of other genetic loci to affect taste sensitivity to PROP and the related bitter compound PTC. None of these other locations showed genome-wide significant associations in our study. To facilitate further, target-gene driven, studies on PROP taste perception we provide the genome-wide list of p-values for all SNPs genotyped in the current study

Towards detecting genotoxic chemicals in food packaging at thresholds of toxicological concern using bioassays with high-performance thin-layer chromatography

High-performance thin-layer chromatography (HPTLC)-bioassays are promising new methods for detecting bioactive chemicals in food packaging. Here, we test whether direct-acting genotoxic chemicals are detectable in food contact materials (FCM) using HPTLC-bioassays. First, an interactive worksheet lays out steps to calculate needed detection limits in (bio)analytical methods from regulatory limits, including thresholds of toxicological concern (TTC). Second, we show that the sensitivity of a HPTLC-genotoxicity assay to low doses of chemicals, including food contact chemicals, is greater than a standardized microtiter plate version and in vitro assays already reported. Third, using HPTLC, we detected genotoxicity in extracts of FCM, and not in simulated migrates of FCM. Applying the worksheet to calculate needed detection limits in FCM migrates, we observed that seven of ten genotoxic chemicals would be detectable with HPTLC if present at the regulatory 10 ppb limit and two of ten at TTC for adults. With development, HPTLC-bioassays might become the best option for supporting safety assessment of genotoxicants in food packaging

Genetic counselling legislation and practice in cancer in EU Member States

Background: Somatic and germline genetic alterations are significant drivers of cancer. Increasing integration of new technologies which profile these alterations requires timely, equitable and high-quality genetic counselling to facilitate accurate diagnoses and informed decision-making by patients and their families in preventive and clinical settings. This article aims to provide an overview of genetic counselling legislation and practice across European Union (EU) Member States to serve as a foundation for future European recommendations and action. Methods: National legislative databases of all 27 Member States were searched using terms relevant to genetic counselling, translated as appropriate. Interviews with relevant experts from each Member State were conducted to validate legislative search results and provide detailed insights into genetic counselling practice in each country. Results: Genetic counselling is included in national legislative documents of 22 of 27 Member States, with substantial variation in legal mechanisms and prescribed details (i.e. the ‘who, what, when and where’ of counselling). Practice is similarly varied. Workforce capacity (25 of 27 Member States) and genetic literacy (all Member States) were common reported barriers. Recognition and/or better integration of genetic counsellors and updated legislation and were most commonly noted as the ‘most important change’ which would improve practice. Conclusions: This review highlights substantial variability in genetic counselling across EU Member States, as well as common barriers notwithstanding this variation. Future recommendations and action should focus on addressing literacy and capacity challenges through legislative, regulatory and/or strategic approaches at EU, national, regional and/or local levels.</p

Early markers for myocardial ischemia and sudden cardiac death.

The post-mortem diagnosis of acute myocardial ischemia remains a challenge for both clinical and forensic pathologists. We performed an experimental study (ligation of left anterior descending coronary artery in rats) in order to identify early markers of myocardial ischemia, to further apply to forensic and clinical pathology in cases of sudden cardiac death. Using immunohistochemistry, Western blots, and gene expression analyses, we investigated a number of markers, selected among those which are currently used in emergency departments to diagnose myocardial infarction and those which are under investigation in basic research and autopsy pathology studies on cardiovascular diseases. The study was performed on 44 adult male Lewis rats, assigned to three experimental groups: control, sham-operated, and operated. The durations of ischemia ranged between 5 min and 24 h. The investigated markers were troponins I and T, myoglobin, fibronectin, C5b-9, connexin 43 (dephosphorylated), JunB, cytochrome c, and TUNEL staining. The earliest expressions (≤30 min) were observed for connexin 43, JunB, and cytochrome c, followed by fibronectin (≤1 h), myoglobin (≤1 h), troponins I and T (≤1 h), TUNEL (≤1 h), and C5b-9 (≤2 h). By this investigation, we identified a panel of true early markers of myocardial ischemia and delineated their temporal evolution in expression by employing new technologies for gene expression analysis, in addition to traditional and routine methods (such as histology and immunohistochemistry). Moreover, for the first time in the autopsy pathology field, we identified, by immunohistochemistry, two very early markers of myocardial ischemia: dephosphorylated connexin 43 and JunB

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Prävalenz, Ätiologie und Prognose von Husten in der Primärversorgung – eine systematische Übersichtsarbeit symptomevaluierender Studien

Hintergrund: Husten ist einer der häufigsten Beratungsanlässe in der Primärversorgung. Für eine evidenzbasierte Entscheidungsfindung benötigen Hausärztinnen und Hausärzte Setting-spezifisches Wissen über die Häufigkeit, die Prätestwahrscheinlichkeiten zugrunde liegender Erkrankungsbilder und den Verlauf eines Symptoms. In der vorliegenden systematischen Übersichtsarbeit und Metaanalyse symptomevaluierender Studien wurden daher Studien zur Prävalenz/Inzidenz, Ätiologie und Prognose des Symptoms Husten in der Primärversorgung ausgewertet. Die Daten wurden sowohl für Erwachsene, Patient*innen aller Altersgruppen als auch für Kinder erhoben. Methoden: Entsprechend eines vorab definierten Algorithmus erfolgte eine systematische Literatursuche in den Datenbanken MEDLINE und EMBASE bis einschließlich November 2019 bzw. Januar 2020. Im Sinne einer Schneeballsuche wurden die anhängigen Literaturverzeichnisse der eingeschlossenen Studien gescreent. Eingeschlossen wurden englische, französische und deutsche Originalarbeiten mit unselektierten Studienkollektiven von Patient*innen, welche aufgrund von Husten eine hausärztliche Praxis konsultierten. Zwei unabhängige Reviewer*innen beurteilten Ein- und Ausschlusskriterien sowie die methodische Qualität der Studien. Die Effektschätzer sowie die Varianz zwischen den jeweiligen Einzelstudien (Between-Study Variance) wurden in Forest Plots dargestellt. Für eine Metaanalyse innerhalb geeigneter Subgruppen - sofern im Rahmen der Heterogenität vertretbar - verwendeten wir das Random Effects Model. Ergebnisse: Dreiundsiebzig Publikationen erfüllten die Einschlusskriterien. Sechzig Veröffentlichungen entsprechend 31 Studien enthielten Daten zu Erwachsenen bzw. Patient*innen aller Altersgruppen, davon 22 Studien mit Schätzern zur Prävalenz/Inzidenz, zwölf zur Ätiologie und vier zur Prognose. Bei den Kindern ließen sich 20 einschlägige Veröffentlichungen (19 Studien) identifizieren, hiervon enthielten 14 Studien Daten zur Prävalenz/Inzidenz, fünf zur Ätiologie und eine Studie zur Prognose. Die Prävalenzschätzer für Erwachsene und Patient*innen aller Altersgruppen lagen bei 3,8-4,2% in westlicher Primärversorgung und bei 10,3-13,8% in Afrika, Asien und Südamerika. Die entsprechenden Inzidenzen wurden mit 12,5% (westliche Primärversorgung) bzw. 6,3-6,5% (Afrika, Asien und Südamerika) bestimmt. Husten war bei Kindern häufiger als bei Erwachsenen, mit niedrigen Prävalenzen bei Jugendlichen und im Sommer: Die Prävalenzschätzer lagen zwischen 4,7-23,3% (Beratungsanlässe) und bis zu 60% bezogen auf Patient*innen oder Konsultationen. In westlichen Ländern wurde akuter Husten sowohl bei Erwachsenen als auch bei Kindern vor allem durch obere Atemwegsinfektionen und Bronchitis verursacht, gefolgt von Influenza und Asthma. Abwendbar gefährliche Verläufe wie Pneumonie, COPD, Herzinsuffizienz und Verdacht auf eine maligne Erkrankung lagen im Niedrigprävalenzbereich. Zu subakutem und chronischem Husten bei Erwachsenen und Kindern fanden sich nur wenige Daten. Zugrunde liegende Ätiologien von Husten über zwei Wochen bei Kindern waren wiederkehrende Atemwegsinfektionen (27,7%), Asthma (bis zu 50,4%) und Pertussis (37,2%). 40,2-67% der Erwachsenen und Patient*innen aller Altersgruppen mit akutem Husten berichteten eine Genesung nach zwei Wochen und 79% nach vier Wochen. Die mittlere Zeit bis zur Genesung lag zwischen neun und elf Tagen. 21,1-35% der Patient*innen rekonsultierten, 0-1,3% wurden im Krankenhaus aufgenommen, niemand verstarb. Die Gesamthustendauer bei Kindern mit subakutem und chronischem Husten lag zwischen 24 und 192 Tagen, zwei Monate nach Symptombeginn husteten noch 62,3%. Diskussion: Die Prävalenz und Inzidenz von Husten sind hoch und regional unterschiedlich. Die Ergebnisse dieser Arbeit stützen die Empfehlungen gängiger Leitlinien bezüglich eines abwartenden Offenhaltens bei akutem Husten, da dieser überwiegend durch selbstlimitierende Atemwegsinfekte verursacht wird. Bei chronischem Husten ist bei Kindern eine Genese durch Asthma oder Pertussis zu bedenken. Weitere hochqualitative Forschung zu ätiologischen Prätestwahrscheinlichkeiten wird benötigt, da sich nur wenige Daten insbesondere zur Ätiologie von subakutem und chronischem Husten in westlicher Primärversorgung fanden. Um die Evidenz bezüglich der Entscheidung zwischen einem abwartenden Offenhalten vs. der Einleitung weiterer Diagnostik, Überweisung oder Therapie zu verbessern, sind prognostische Studien zum Symptom Husten in der Primärversorgung notwendig. Essentiell sind dabei standardisierte Outcomes, eine ausreichende Länge der Follow-Up-Periode und eine unselektierte Studienpopulation. Die epidemiologischen Daten dieser Arbeit wurden vor dem Ausbruch der COVID-19-Pandemie erhoben. Es wird interessant sein, sie mit zukünftiger Forschung der Post-Pandemie-Ära zu vergleichen