Significant differences in incubation times in sheep infected with bovine spongiform encephalopathy result from variation at codon 141 in the PRNP gene

The susceptibility of sheep to prion infection is linked to variation in the PRNP gene, which encodes the prion protein. Common polymorphisms occur at codons 136, 154 and 171. Sheep which are homozygous for the A<sub>136</sub>R<sub>154</sub>Q<sub>171</sub> allele are the most susceptible to bovine spongiform encephalopathy (BSE). The effect of other polymorphisms on BSE susceptibility is unknown. We orally infected ARQ/ARQ Cheviot sheep with equal amounts of BSE brain homogenate and a range of incubation periods was observed. When we segregated sheep according to the amino acid (L or F) encoded at codon 141 of the PRNP gene, the shortest incubation period was observed in LL141 sheep, whilst incubation periods in FF<sub>141</sub> and LF<sub>141</sub> sheep were significantly longer. No statistically significant differences existed in the expression of total prion protein or the disease-associated isoform in BSE-infected sheep within each genotype subgroup. This suggested that the amino acid encoded at codon 141 probably affects incubation times through direct effects on protein misfolding rates

Seguimiento de la diversidad de líquenes y cambio climático en Sierra Nevada (España)

Lichens are common organisms in high mountain zones, where they play an important role in ecosystem balance. In recent years, the increasing interest in understanding more about their interactions with abiotic factors has prompted several investigations, some of which have proved their value as bioindicators of climatic conditions. In this context, focusing on climatic change effects on high mountain vascular plants and supported by the Global Observation Research Initiative in Alpine Environments project (GLORIA), we have monitored for the first time the lichens biodiversity in Sierra Nevada with the intention of studying the alterations caused by the process of climatic change. The aim of this paper is to explain the monitoring experience developed on the massif and contribute to the first results from the biodiversity and statistical analysis of the sampling data.Los líquenes son organismos comunes en las zonas de alta montaña donde juegan un importante papel en el equilibrio de los ecosistemas. En los últimos años, el creciente interés por entender más acerca de sus interacciones con los factores abióticos ha motivado diversas investigaciones, algunas de las cuales han demostrado su valor como bioindicadores de las condiciones climáticas. En este contexto, centrándonos en los efectos del cambio climático en plantas vasculares de alta montaña y respaldados por el proyecto “Iniciativa para la investigación y el seguimiento global de los ambientes alpinos (GLORIA)”, se ha monitorizado por primera vez la diversidad de líquenes en Sierra Nevada con la intención de estudiar las posibles alteraciones que esta pueda sufrir causadas por el proceso de cambio climático. El objetivo de este artículo es el de dar a conocer la experiencia de seguimiento en el macizo y aportar los primeros resultados procedentes del análisis, tanto de la biodiversidad como estadístico, de los datos de muestreo

A single genomic region involving a putative chromosome rearrangement in flat oyster (Ostrea edulis) is associated with differential host resilience to the parasite Bonamia ostreae

European flat oyster (Ostrea edulis) is an ecologically and economically important marine bivalve, that has been severely affected by the intracellular parasite Bonamia ostreae. In this study, a flat oyster SNP array (~14,000 SNPs) was used to validate previously reported outlier loci for divergent selection associated with B. ostreae exposure in the Northeast Atlantic Area. A total of 134 wild and hatchery individuals from the North Sea, collected in naïve (NV) and long-term affected (LTA) areas, were analysed. Genetic diversity and differentiation were related to the sampling origin (wild vs. hatchery) when using neutral markers, and to bonamiosis status (NV vs. LTA) when using outlier loci for divergent selection. Two genetic clusters appeared intermingled in all sampling locations when using outlier loci, and their frequency was associated with their bonamiosis status. When both clusters were compared, outlier data sets showed high genetic divergence (FST > 0.25) unlike neutral loci (FST not ≠ 0). Moreover, the cluster associated with LTA samples showed much higher genetic diversity and significant heterozygote excess with outlier loci, but not with neutral data. Most outliers mapped on chromosome 8 (OE-C8) of the flat oyster genome, supporting a main genomic region underlying resilience to bonamiosis. Furthermore, differentially expressed genes previously reported between NV and LTA strains showed higher mapping density on OE-C8. A range of relevant immune functions were specifically enriched among genes annotated on OE-C8, providing hypotheses for resilience mechanisms to an intracellular parasite. The results suggest that marker-assisted selection could be applied to breed resilient strains of O. edulis to bonamiosis, if lower parasite load and/or higher viability of the LTA genetic cluster following B. ostreae infection is demonstratedBiotechnology and Biological Sciences Research Council. Grant Numbers: BBS/E/D/20002172, BB/S004181/1. Ministry of Agriculture, Nature and Food safety. Grant Numbers: BO43-18, KB33-004S

A single genomic region involving a putative chromosome rearrangement in flat oyster (Ostrea edulis) is associated with differential host resilience to the parasite Bonamia ostreae

European flat oyster (Ostrea edulis) is an ecologically and economically important marine bivalve, that has been severely affected by the intracellular parasite Bonamia ostreae. In this study, a flat oyster SNP array (~14,000 SNPs) was used to validate previously reported outlier loci for divergent selection associated with B. ostreae exposure in the Northeast Atlantic Area. A total of 134 wild and hatchery individuals from the North Sea, collected in naïve (NV) and long-term affected (LTA) areas, were analysed. Genetic diversity and differentiation were related to the sampling origin (wild vs. hatchery) when using neutral markers, and to bonamiosis status (NV vs. LTA) when using outlier loci for divergent selection. Two genetic clusters appeared intermingled in all sampling locations when using outlier loci, and their frequency was associated with their bonamiosis status. When both clusters were compared, outlier data sets showed high genetic divergence (FST > 0.25) unlike neutral loci (FST not ≠ 0). Moreover, the cluster associated with LTA samples showed much higher genetic diversity and significant heterozygote excess with outlier loci, but not with neutral data. Most outliers mapped on chromosome 8 (OE-C8) of the flat oyster genome, supporting a main genomic region underlying resilience to bonamiosis. Furthermore, differentially expressed genes previously reported between NV and LTA strains showed higher mapping density on OE-C8. A range of relevant immune functions were specifically enriched among genes annotated on OE-C8, providing hypotheses for resilience mechanisms to an intracellular parasite. The results suggest that marker-assisted selection could be applied to breed resilient strains of O. edulis to bonamiosis, if lower parasite load and/or higher viability of the LTA genetic cluster following B. ostreae infection is demonstratedBiotechnology and Biological Sciences Research Council. Grant Numbers: BBS/E/D/20002172, BB/S004181/1. Ministry of Agriculture, Nature and Food safety. Grant Numbers: BO43-18, KB33-004S

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion

Genome wide association mapping for arabinoxylan content in a collection of tetraploid wheats

BACKGROUND: Arabinoxylans (AXs) are major components of plant cell walls in bread wheat and are important in bread-making and starch extraction. Furthermore, arabinoxylans are components of soluble dietary fibre that has potential health-promoting effects in human nutrition. Despite their high value for human health, few studies have been carried out on the genetics of AX content in durum wheat. RESULTS: The genetic variability of AX content was investigated in a set of 104 tetraploid wheat genotypes and regions attributable to AX content were identified through a genome wide association study (GWAS). The amount of arabinoxylan, expressed as percentage (w/w) of the dry weight of the kernel, ranged from 1.8% to 5.5% with a mean value of 4.0%. The GWAS revealed a total of 37 significant marker-trait associations (MTA), identifying 19 quantitative trait loci (QTL) associated with AX content. The highest number of MTAs was identified on chromosome 5A (seven), where three QTL regions were associated with AX content, while the lowest number of MTAs was detected on chromosomes 2B and 4B, where only one MTA identified a single locus. Conservation of synteny between SNP marker sequences and the annotated genes and proteins in Brachypodium distachyon, Oryza sativa and Sorghum bicolor allowed the identification of nine QTL coincident with candidate genes. These included a glycosyl hydrolase GH35, which encodes Gal7 and a glucosyltransferase GT31 on chromosome 1A; a cluster of GT1 genes on chromosome 2B that includes TaUGT1 and cisZog1; a glycosyl hydrolase that encodes a CelC gene on chromosome 3A; Ugt12887 and TaUGT1genes on chromosome 5A; a (1,3)-β-D-glucan synthase (Gsl12 gene) and a glucosyl hydrolase (Cel8 gene) on chromosome 7A. CONCLUSIONS: This study identifies significant MTAs for the AX content in the grain of tetraploid wheat genotypes. We propose that these may be used for molecular breeding of durum wheat varieties with higher soluble fibre content.Ilaria Marcotuli, Kelly Houston, Robbie Waugh, Geoffrey B. Fincher, Rachel A. Burton, Antonio Blanco, Agata Gadalet

The role of pulmonary arterial stiffness in COPD

AbstractCOPD is the second most common cause of pulmonary hypertension, and is a common complication of severe COPD with significant implications for both quality of life and mortality. However, the use of a rigid diagnostic threshold of a mean pulmonary arterial pressure (mPAP) of ≥25mHg when considering the impact of the pulmonary vasculature on symptoms and disease is misleading. Even minimal exertion causes oxygen desaturation and elevations in mPAP, with right ventricular hypertrophy and dilatation present in patients with mild to moderate COPD with pressures below the threshold for diagnosis of pulmonary hypertension. This has significant implications, with right ventricular dysfunction associated with poorer exercise capability and increased mortality independent of pulmonary function tests.The compliance of the pulmonary artery (PA) is a key component in decoupling the right ventricle from the pulmonary bed, allowing the right ventricle to work at maximum efficiency and protecting the microcirculation from large pressure gradients. PA stiffness increases with the severity of COPD, and correlates well with the presence of exercise induced pulmonary hypertension. A curvilinear relationship exists between PA distensibility and mPAP and pulmonary vascular resistance (PVR) with marked loss of distensibility before a rapid rise in mPAP and PVR occurs with resultant right ventricular failure. This combination of features suggests PA stiffness as a promising biomarker for early detection of pulmonary vascular disease, and to play a role in right ventricular failure in COPD. Early detection would open this up as a potential therapeutic target before end stage arterial remodelling occurs

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta