Outlier SNPs enable food traceability of the southern rock lobster, Jasus edwardsii

Recent advances in next-generation sequencing have enhanced the resolution of population genetic studies of non-model organisms through increased marker generation and sample throughput. Using double digest restriction site-associated DNA sequencing (ddRADseq), we investigated the population structure of the commercially important southern rock lobster, Jasus edwardsii, in Australia and New Zealand with the aim of identifying a panel of SNP markers that could be used to trace country of origin. Four ddRADseq libraries comprising a total of 88 individuals were sequenced on the Illumina MiSeq platform, and demultiplexed reads were used to create a reference catalog of loci. Individual reads were then mapped to the reference catalog, and variant calling was performed. We have characterized two single-nucleotide polymorphism (SNP) panels comprised in total of 656 SNPs. The first panel contained 535 neutral SNPs and the second, 121 outlier SNPs that were characteristic of being putatively under selection. Both neutral and outlier SNP panels showed significant differentiation between the two countries, with the outlier loci demonstrating much larger F(ST) values (F(ST) outlier SNP panel = 0.134, P < 0.0001; F(ST) neutral SNP panel = 0.022, P < 0.0001). Assignment tests performed with the outlier SNP panel allocated 100 % of the individuals to country of origin, demonstrating the usefulness of these markers for food traceability of J. edwardsii

Elastic properties of B-C-N films grown by N2-reactive sputtering from boron carbide targets

The following article appeared in Journal of Applied Physics 114.21 (2013): 213508 and may be found at http://scitation.aip.org/content/aip/journal/jap/114/21/10.1063/1.4837655Boron-carbon-nitrogen films were grown by RF reactive sputtering from a B4C target and N2 as reactive gas. The films present phase segregation and are mechanically softer than boron carbide films (a factor of more than 2 in Young's modulus). This fact can turn out as an advantage in order to select buffer layers to better anchor boron carbide films on substrates eliminating thermally induced mechanical tensions.This work has been supported by Spanish MINECO under contracts MAT2009-08786 and MAT2012-37276- C03-01 as well as by the Madrid Regional Government though contract S2009/MAT-1756

P82 238. ¿Es segura la reintervención dejando los injertos arteriales permeables sin clampar?

ObjetivoEl objetivo de no dañar la arteria mamaria evitando su disección y clampaje supone un reto para la protección miocárdica debido al lavado de la cardioplejía.Presentamos nuestra experiencia en reintervenciones sin disecar ni clampar los injertos arteriales.Material y métodosDesde septiembre de 2000 hasta febrero de 2010 se realizaron 29 reintervenciones en 28 pacientes, (89,7% varones), edad media 73,17±7,38años. Las causas de reoperación fueron: progresión de valvulopatía 17 pacientes (58,6%), endocarditis 10 (34,4%), disfunción protésica no estructural 2 (6,9%). La mediana del EuroS-CORE logístico fue 14,84 (4-77,25). La cirugía fue urgente en 7 pacientes. Se realizó sustitución valvular aórtica aislada en 18 y se asoció revascularización en 4, sustitución/plastia mitral en 4, sustitución de aorta en 2; sustitución mitral aislada en 1.La protección miocárdica se realizó con cardioplejía hemática con esmolol, K+ y Mg+, administrándola siempre que no dificultaba el trabajo quirúrgico (intervalos nunca > 20min). Temperatura sistémica media 32,26±3,23 °C.ResultadosLa mediana del tiempo de circulación extracorpórea (CEC) fue 153 (91-494) y de clampaje 103 (71-430)min. Presentaron infarto postoperatorio 1 paciente (3,4%) y síndrome de bajo gasto postoperatorio 2 pacientes (6,5%). La mediana de troponina I postoperatoria fue 7,03ng/ml (1,84-109,5). La mortalidad hospitalaria fue 3 pacientes (10,3%) (cirugía urgente por endocarditis). Las causas de mortalidad fueron: daño neurológico irreversible (1 paciente), sepsis y bajo gasto (2 pacientes). La mediana de estancia hospitalaria fue 7 (1-33) días.ConclusiónEn nuestra experiencia, sin clampar los injertos arteriales y con la estrategia descrita, la protección miocárdica parece adecuada y la mortalidad hospitalaria aceptable

Human pluripotent stem cell modeling of alveolar type 2 cell dysfunction caused by ABCA3 mutations

Mutations in ATP-binding cassette A3 (ABCA3), a phospholipid transporter critical for surfactant homeostasis in pulmonary alveolar type II epithelial cells (AEC2s), are the most common genetic causes of childhood interstitial lung disease (chILD). Treatments for patients with pathological variants of ABCA3 mutations are limited, in part due to a lack of understanding of disease pathogenesis resulting from an inability to access primary AEC2s from affected children. Here, we report the generation of AEC2s from affected patient induced pluripotent stem cells (iPSCs) carrying homozygous versions of multiple ABCA3 mutations. We generated syngeneic CRISPR/Cas9 gene-corrected and uncorrected iPSCs and ABCA3-mutant knockin ABCA3:GFP fusion reporter lines for in vitro disease modeling. We observed an expected decreased capacity for surfactant secretion in ABCA3-mutant iPSC-derived AEC2s (iAEC2s), but we also found an unexpected epithelial-intrinsic aberrant phenotype in mutant iAEC2s, presenting as diminished progenitor potential, increased NFκB signaling, and the production of pro-inflammatory cytokines. The ABCA3:GFP fusion reporter permitted mutant-specific, quantifiable characterization of lamellar body size and ABCA3 protein trafficking, functional features that are perturbed depending on ABCA3 mutation type. Our disease model provides a platform for understanding ABCA3 mutation-mediated mechanisms of alveolar epithelial cell dysfunction that may trigger chILD pathogenesis

Gangrena de Fournier en paciente obeso con COVID-19: reporte de caso

La Gangrena de Fournier (GF) es una fascitis necrotizante que afecta los planos superficiales. Se presenta frecuentemente en hombres entre 50 y 79 años con una elevada tasa de mortalidad, la cual aumenta con la presencia de factores de riesgo destacándose entre ellos la diabetes y obesidad. Se reporta el caso de un paciente obeso diagnosticado con COVID-19 antes del ingreso y tratado con corticoides, que acude por aparente celulitis escrotal que evoluciona a GF, la cual fue diagnosticada 2 días luego de la hospitalización. Se le realiza intervención quirúrgica inmediata, previa cobertura antibiótica. La COVID-19 no tuvo relevancia clínica en la evolución y pronóstico de la GF; sin embargo, fueron las terapias desmesuradas las que influyeron negativamente. A pesar de ello, el paciente evolucionó favorablemente hasta su recuperación total. Palabras clave: Gangrena de Fournier, obesidad, COVID-19 (MeSH) DOI: http://dx.doi.org/10.17268/rmt.2020.v16i01.1

Human iPSC-hepatocyte modeling of alpha-1 antitrypsin heterozygosity reveals metabolic dysregulation and cellular heterogeneity

Individuals homozygous for the “Z” mutation in alpha-1 antitrypsin deficiency are known to be at increased risk for liver disease. It has also become clear that some degree of risk is similarly conferred by the heterozygous state. A lack of model systems that recapitulate heterozygosity in human hepatocytes has limited the ability to study the impact of a single Z alpha-1 antitrypsin (ZAAT) allele on hepatocyte biology. Here, we describe the derivation of syngeneic induced pluripotent stem cells (iPSCs) engineered to determine the effects of ZAAT heterozygosity in iPSC-hepatocytes (iHeps). We find that heterozygous MZ iHeps exhibit an intermediate disease phenotype and share with ZZ iHeps alterations in AAT protein processing and downstream perturbations including altered endoplasmic reticulum (ER) and mitochondrial morphology, reduced mitochondrial respiration, and branch-specific activation of the unfolded protein response in cell subpopulations. Our model of MZ heterozygosity thus provides evidence that a single Z allele is sufficient to disrupt hepatocyte homeostatic function.This work was supported by an Alpha-1 Foundation John W. Walsh Translational Research Award (to J.E.K.); a CJ Martin Early Career Fellowship from the Australian National Health and Medical Research Council (to R.B.W.); NIH grant R01HL095993 (to D.N.K.); and NIH grants R01DK101501 (to A.A.W.) and R01DK117940 (to A.N.H. and A.A.W.). iPSC distribution and disease modeling is supported by NIH grants U01TR001810 (to D.N.K. and A.A.W.) and N0175N92020C00005 (to D.N.K.); and by The Alpha-1 Project (TAP), a wholly owned subsidiary of the Alpha-1 Foundation (to D.N.K. and A.A.W.)

High-accuracy determination of the neutron flux in the new experimental area n_TOF-EAR2 at CERN

A new high flux experimental area has recently become operational at the n_TOF facility at CERN. This new measuring station, n_TOF-EAR2, is placed at the end of a vertical beam line at a distance of approximately 20m from the spallation target. The characterization of the neutron beam, in terms of flux, spatial profile and resolution function, is of crucial importance for the feasibility study and data analysis of all measurements to be performed in the new area. In this paper, the measurement of the neutron flux, performed with different solid-state and gaseous detection systems, and using three neutron-converting reactions considered standard in different energy regions is reported. The results of the various measurements have been combined, yielding an evaluated neutron energy distribution in a wide energy range, from 2meV to 100MeV, with an accuracy ranging from 2%, at low energy, to 6% in the high-energy region. In addition, an absolute normalization of the n_TOF-EAR2 neutron flux has been obtained by means of an activation measurement performed with 197Au foils in the beam.Peer reviewe

Joining forces to strengthen community seedbanks worldwide

Community seedbanks and emerging networks of community seedbanks contribute to the conservation and sustainable use of plant genetic resources for food and agriculture. Community seedbanks can secure improved access to and availability of diverse, locally adapted crops and varieties and enhance related indigenous knowledge and skills in plant management including seed selection, treatment, storage, multiplication and distribution. Two events were held in July 2018 in Rome, Italy to bring together representatives of organizations supporting community seedbanks from Africa, Asia, Europe and Latin America. This brief presents achievements, challenges, lessons learned and new opportunities in their countries and reflects on prospects of community seedbanks and their networks

Loss-of-Function Genomic Variants Highlight Potential Therapeutic Targets for Cardiovascular Disease

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of the protein. This includes ZNF529:p.K405X, which is associated with decreased low-density-lipoprotein (LDL) cholesterol (P = 1.3 × 10−8) without being associated with liver enzymes or non-fasting blood glucose. Silencing of ZNF529 in human hepatoma cells results in upregulation of LDL receptor and increased LDL uptake in the cells. This suggests that inhibition of ZNF529 or its gene product should be prioritized as a novel candidate drug target for treating dyslipidemia and associated CVD