Shell Disease Syndrome Is Associated with Reduced and Shifted Epibacterial Diversity on the Carapace of the Crustacean Cancer pagurus

Crustaceans increasingly suffer from the black spot shell disease syndrome, which principally results from bacterial breakdown of their chitinous exoskeleton. Since Cancer pagurus is highly susceptible to this disease, we compared the bacterial communities of black spot affected and non-affected areas of the carapace by amplicon sequencing of 16S rRNA genes and 16S rRNA. Within each spot, bacterial communities of affected areas were less diverse compared to communities from non-affected areas. Communities of different affected spots were, however, more divergent from each other, compared to those of different nonaffected areas. This indicates a reduced and shifted microbial community composition caused by the black spot disease. Different communities found in black spots likely indicate different stages of the disease. In affected areas, Flavobacteriaceae rose up to one of the most abundant and active families, due to massive increase of Aquimarina spp., suggesting a significant role in shell disease syndrome. We isolated 75 bacterial strains from diseased and healthy areas, which primarily affiliated with Proteobacteria and Bacteroidetes, thus reflecting the dominant phyla detected by amplicon sequencing. The ability to degrade chitin was mainly found for Gammaproteobacteria and Aquimarina spp. within the Flavobacteriia, while the ability to use N-acetylglucosamine, the monomer of the polysaccharide chitin, was observed for most isolates, including many Alphaproteobacteria. Furthermore, one third of the isolates showed antagonistic properties. The combination of bacterial community analysis and the physiological properties of the isolates provides insights into a functional complex epibacterial community on the carapace of C. pagurus. Importance In recent years, the shell disease syndrome was detected for several ecologically and economically important crustacean species. Large proportions of populations are affected, e.g., >60% of the widely distributed species Cancer pagurus in different North Sea areas. Bacteria play a significant role in the development of different forms of shell disease, all characterized by microbial chitinolytic degradation of the outer shell. By comparing the bacterial communities of healthy and diseased areas of the shell of C. pagurus we could demonstrate that the disease causes a reduced bacterial diversity within affected areas, a phenomenon co-occurring also with many other diseases. Furthermore, the community composition dramatically changed, with some taxa rising to high relative abundances and showing increased activity, indicating a strong participation in shell disease. Characterization of bacterial isolates obtained from affected and non-affected spots provided deeper insights in their physiological properties and thus the possible role within the microbiome

Hochauflösende Kartierung der Virusresistenzgene rym11 und Ryd3 in Gerste (Hordeum vulgare L.)

Zusammenfassung Zwei landwirtschaftlich bedeutende Resistenzgene der Gerste (Hordeum vulgare L.), - rym11, welches Resistenz gegen die Gelbmosaikvirose [Barley mild mosaic virus (BaMMV), Barley yellow mosaic virus (BaYMV)] bedingt, und Ryd3, das gegen die viröse Gelbverzwergung [Barley yellow dwarf virus (BYDV)] wirksam ist, sollen mittels hochauflösender Kartierungspopulationen von jeweils 5000 F2-Pflanzen kartiert und isoliert werden. Zu diesem Zweck werden die aus den Kartierungspopulationen entstandenen und für das jeweilige Zielintervall genetisch fixierten, segmental rekombinanten Inzuchtlinien (RIL) einer ausgiebigen Markeranalyse sowie einer wiederholten Virustestung sowohl im Gewächshaus als auch im Feld unterzogen. Für rym11 sind 5102, für Ryd3 3213 der F2-Pflanzen analysiert worden. Für beide Populationen liegen erste phänotypische Daten vor und mehrere mit dem jeweiligen Resistenzgen eng gekoppelte Marker konnten kartiert werden. Stichwörter: Gerste, Resistenz, Gelbmosaikvirose, viröse Gelbverzwergung, rym11, Ryd3, RIL, Kartierung   Abstract Two important resistance genes of barley (Hordeum vulgare L.) - rym11, which confers resistance against the Barley yellow mosaic virus complex [Barley mild mosaic virus (BaMMV), Barley yellow mosaic virus (BaYMV)] and Ryd3, which is effective against Barley yellow dwarf [Barley yellow dwarf virus (BYDV)] - are to be mapped at high resolution by analyzing 5000 F2-plants each as a prerequisite for isolating these genes via a map based cloning approach. For this purpose segmental recombinant inbreed lines (RIL), originated from the mapping populations and genetically fixed for the respective target interval, undergo an extensive marker analysis as well as repeated virus testing both in the greenhouse and in the field. For rym11 5102 and for Ryd3 3213 F2-plants have been analysed up to now. For both populations first phenotypic data is present and several closely linked markers could be mapped. Keywords: Barley, resistance, Barley yellow mosaic virus complex, Barley yellow dwarf, rym11, Ryd3, RIL, mappin

Thinopyrum-Arten als Donoren von Resistenzen gegen wichtige Pathogene im Winterweizen (Triticum aestivum L.)

Zusammenfassung In bekannten Kulturformen des Weizens (Triticum aestivum L.) werden immer seltener neue Resistenzen gegen wirtschaftlich bedeutende Krankheiterreger (Oculimacula spp, Fusarium culmorum, Puccina triticina und Barley yellow dwarf Virus) identifiziert. Die Identifikation von Resistenzgenen aus der Wildtypform Thinopyrum spp. und deren anschließende Nutzung in der Weizenzüchtung ist somit Ziel dieses Projekts. Für ein markergestütztes Rückkreuzungsprogramm stehen zwei Translokationslinien, PI583794 und PI611939, als Träger einer Thinopyrum- Introgession auf Chromosom 4D, sowie 3 Weizensorten (Boomer, Esket und Mirage) zur Verfügung. Für die phänotypische Charakterisierung wurden diese Linien auf ihre Resistenz gegen die genannten Erreger getestet. Parallel dazu erfolgte die genotypische Charakterisierung. Mit den spezifischen Primern STSJ15 und 2P1/2P2 konnte die Introgression nachgewiesen werden. Zur Bestimmung der Größe des Introgressionsfragments wurden ausgewählte Genotypen der BC1F1 und BC2F1mit polymorphen SSRs analysiert, um auf diese Weise Genotypen zu identifizieren, welche ein möglichst kleines Introgessionsfragment aufweisen, jedoch resistent sind. Stichwörter: Weizen (Triticum aestivum L.), Thinopyrum intermedium, Thinopyrum ponticum, Oculimacula spp, Fusarium culmorum, Puccina triticina, Barley yellow dwarf Virus, PI583794, PI611939, STSJ15, 2P1/2P2   Abstract In order to broaden the genetic base in Triticum aestivum against economically important pathogens (Oculimacula spp, Fusarium culmorum, Puccina triticina and Barley yellow dwarf virus) wheat translocation lines carrying a chromosomal segment derived from Thinopyrum spp are tested for resistance and analyzed by molecular techniques. Two introgression lines PI583794 and PI611939 as carriers of the Thinopyrum-fragment, as well as 3 wheat cultivars (Boomer, Esket and Mirage) are used for a marker-assisted back crossing program. For the phenotypic characterization, these lines were tested for resistance against these above mentioned pathogens. In addition to the genotypic characterization was carried out using Thinopyrum specific primers STSJ15 and 2P1/2P2 to identify the introgression.. To define the size of the introgressions-fragments selected genotypes of the BC1F1 and BC2F1 were tested with polymorphic microsatellites (SSRs) in order to identify those genotyes carrying only a small fragment of Thinopyrum spp. but still being resistant. Keywords: wheat (Triticum aestivum L.), Thinopyrum intermedium, Thinopyrum ponticum, Oculimacula spp, Fusarium culmorum, Puccina triticina, Barley yellow dwarf, PI583794; PI611939, STSJ15, 2P1/2P

X-chromosome and kidney function:evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements

X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.</p

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Abstract: Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Variant annotation was supported by software resources provided via the Caché Campus program of the InterSystems GmbH to Alexander Teumer

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms