Identification of an ADAMTS2 frameshift variant in a cat family with Ehlers-Danlos syndrome.

We investigated four European domestic shorthair kittens with skin lesions consistent with the dermatosparaxis type of the Ehlers-Danlos syndrome (EDS), a connective tissue disorder. The kittens were sired by the same tomcat, but were born by three different mothers. The kittens had easily torn skin resulting in non-healing skin wounds. Both clinically and histologically, the skin showed thin epidermis in addition to inflammatory changes. Changes in collagen fibers were visible in electron micrographs. The complete genome of an affected kitten was sequenced. A one base pair duplication leading to a frameshift in the candidate gene ADAMTS2 was identified, p.(Ser235fs*3). All four affected cats carried the frameshift duplication in a homozygous state. Genotypes at this variant showed perfect co-segregation with the autosomal recessive EDS phenotype in the available family. The mutant allele did not occur in 48 unrelated control cats. ADAMTS2 loss-of-function variants cause autosomal recessive forms of EDS in humans, mice, dogs, cattle and sheep. The available evidence from our investigation together with the functional knowledge on ADAMTS2 in other species allow to classify the identified ADAMTS2 variant as pathogenic and most likely causative variant for the observed EDS

Genetic variants in PPARGC1B and CNTN4 are associated with thromboxane A2 formation and with cardiovascular event free survival in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

BACKGROUND AND AIMS: Elevated urinary 11-dehydro thromboxane B2 (TxB2), a measure of thromboxane A2 formation in vivo, predicts future atherothrombotic events. To further understand this relationship, the genetic determinants of 11-dehydro TxB2 and their associations with cardiovascular morbidity were investigated in this study. METHODS: Genome-wide and targeted genetic association studies of urinary 11-dehydro TxB2 were conducted in 806 Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) participants. RESULTS: The strongest associations were in PPARGC1B (rs4235745, rs32582, rs10515638) and CNTN4 (rs10510230, rs4684343), these 5 single nucleotide polymorphisms (SNPs) were independently associated with 11-dehydro TxB2 formation. Haplotypes of 11-dehydro TxB2 increasing alleles for both PPARGC1B and CNTN4 were significantly associated with 11-dehydro TxB2, explaining 5.2% and 4.5% of the variation in the whole cohort, and 8.8% and 7.9% in participants not taking aspirin, respectively. In a second ASCOT population (n = 6199), addition of these 5 SNPs significantly improved the covariate-only Cox proportional hazards model for cardiovascular events (chisq = 14.7, p=0.01). Two of the risk alleles associated with increased urinary 11-dehydro TxB2 were individually associated with greater incidences of cardiovascular events - rs10515638 (HR = 1.31, p=0.01) and rs10510230 (HR = 1.25, p=0.007); effect sizes were larger in those not taking aspirin. CONCLUSIONS: PPARGC1B and CNTN4 genotypes are associated with elevated thromboxane A2 formation and with an excess of cardiovascular events. Aspirin appears to blunt these associations. If specific protection of PPARGC1B and CNTN4 variant carriers by aspirin is confirmed by additional studies, PPARGC1B and CNTN4 genotyping could potentially assist in clinical decision making regarding the use of aspirin in primary prevention

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.Peer reviewe

Dobutamine stress echocardiography ischemia as a predictor of the placebo-controlled efficacy of percutaneous coronary intervention in stable coronary artery disease: the stress echo-stratified analysis of ORBITA

BACKGROUND: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina).METHODS: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling.RESULTS: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score (Pinteraction=0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina (Pinteraction=0.116), physical limitation (Pinteraction=0.461), quality of life (Pinteraction=0.689), EuroQOL 5 quality-of-life score (Pinteraction=0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class (Pinteraction=0.693), and treadmill exercise time (Pinteraction=0.426).CONCLUSIONS: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Att systematiskt hantera kunskap vid planering av ny infrastruktur : En fallstudie om skyfallsskador på riksväg 90 i Kramfors kommun

Natural disasters are becoming more common due to climate change and it is important to adapt the society and its infrastructure to withstand events such as extreme rainfall. Precipitation is an important climatic factor affecting the transport and annually generates the cost of millions in damages, over the past 40 years heavy rain has increased and will continue to increase in the future. The extreme rainfall that occurred in Kramfors municipality in September 2013 led to flooding and destroyed several roads, including highway 90, which recently both had been rebuilt and given a new stretch of road. Extreme rainfall had also occurred in the municipality earlier.   The aim of the thesis was to examine how the Swedish Transport Administration handles new knowledge gained after natural disasters and how this is used in the planning of new roads. From the aim of the study a case study was used as a method. Information was sought from reports, official documents and government investigations in order to see how the Swedish Transport Administration’s work looks like and to find studies about the incident on highway 90. There were also conducted interviews with informants within the Swedish Transport Administration to find out how the planning and investigation of roads looks like, and to get information about the work of national highway 90. Within the Swedish Transport Administration lessons are learned from natural disasters and events in the past, but learning is mainly individual - based and internally. There is no system in the Swedish Transport Administration to manage new information or collect past experiences. New knowledge and new conditions are used in the investigation and planning of roads, but depends on which people work with those. The planning of highway 90 follows the regulations and plans to be followed, but with additional information on past events and climate adaptation in those, the damages caused by the extreme rain on highway 90 could perhaps have been avoided.  Naturolyckor blir allt vanligare i samband med klimatförändringar och det är viktigt att anpassa samhället och dess infrastruktur för att motstå händelser som exempelvis skyfall. Nederbörd är en viktig klimatfaktor som påverkar transportsystemet och som årligen genererar i miljonbelopp i form av skador. Under de senaste 40 åren har andelen skyfall ökat och det kommer att öka mer i framtiden. Skyfallet som drabbade Kramfors kommun i september 2013 medförde översvämningar och flera förstörda vägar. Bland annat skadades riksväg 90 som nyligen både byggts om och fått en ny vägsträcka. Skyfall har också tidigare inträffat i kommunen.   Syftet med examensarbetet var att undersöka hur man på Trafikverket hanterar ny kunskap som man fått efter att naturolyckor inträffat och hur man använder denna vid planering av nya vägar. Utifrån syftet valdes fallstudien som metod. Information söktes från rapporter, myndighetsdokument och statliga utredningar för att kunna se hur Trafikverkets arbete ser ut och för att hitta utredningar runt händelsen på riksväg 90. Vidare utfördes intervjuer med informanter inom Trafikverket för att ta reda på hur arbetet med planering och utredning av vägar ser ut, samt för att få information runt arbetet med riksväg 90.   Inom Trafikverket dras lärdom av naturolyckor och tidigare händelser, men lärandet är främst personbaserat och internt. Det finns inget system inom Trafikverket för att hantera ny kunskap eller samla in tidigare erfarenheter. Ny kunskap och nya förutsättningar används vid utredning och planering av vägar, men det påverkas av vilka personer som genomför dessa. Planeringen av riksväg 90 gjordes i enighet med de regelverk och planer som ska följas, men med ytterligare information om tidigare händelser och klimatanpassning i dessa hade kanske de skadorna som uppkom vid skyfallet på riksväg 90 kunnat undvikas