Elevation gradients of European climate change in the regional climate model COSMO-CLM

A transient climate scenario experiment of the regional climate model COSMO-CLM is analyzed to assess the elevation dependency of 21st century European climate change. A focus is put on near-surface conditions. Model evaluation reveals that COSMO-CLM is able to approximately reproduce the observed altitudinal variation of 2m temperature and precipitation in most regions and most seasons. The analysis of climate change signals suggests that 21st century climate change might considerably depend on elevation. Over most parts of Europe and in most seasons, near-surface warming significantly increases with elevation. This is consistent with the simulated changes of the free-tropospheric air temperature, but can only be fully explained by taking into account regional-scale processes involving the land surface. In winter and spring, the anomalous high-elevation warming is typically connected to a decrease in the number of snow days and the snow-albedo feedback. Further factors are changes in cloud cover and soil moisture and the proximity of low-elevation regions to the sea. The amplified warming at high elevations becomes apparent during the first half of the 21st century and results in a general decrease of near-surface lapse rates. It does not imply an early detection potential of large-scale temperature changes. For precipitation, only few consistent signals arise. In many regions precipitation changes show a pronounced elevation dependency but the details strongly depend on the season and the region under consideration. There is a tendency towards a larger relative decrease of summer precipitation at low elevations, but there are exceptions to this as wel

F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in haemophilia A. It has been suggested that differences in the distribution of FVIII gene (F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Data from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1 + H2) and inhibitor risk among individuals of genetically determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and human leucocyte antigen (HLA) were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Haplotype 3 was associated with higher inhibitor risk among those genetically identified (N = 49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N = 223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Haplotype 3 was not an independent predictor of inhibitor risk. Furthermore, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual.Baxter BioScience Frederick National Laboratory for Cancer Research, National Institutes of Health (NIH) HHSN261200800001E Wyeth Research Fund at Malmo University Hospital NIH, National Institute of Child Health and Human Development R01-HD-41224 Bayer Inspiration Biopharmaceuticals, Inc. Grifols, Inc. Baxter Biogen Idec Biotest CSL Behring Grifols Inspiration Biopharmaceuticals NovoNordisk Octapharma Swedish Orphan Biovitrum Wyeth/Pfize

Targeted knock-down of miR21 primary transcripts using snoMEN vectors induces apoptosis in human cancer cell lines

We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2

The Highly Energetic Expansion of SN2010bh Associated with GRB 100316D

We present the spectroscopic and photometric evolution of the nearby (z = 0.059) spectroscopically confirmed type Ic supernova, SN 2010bh, associated with the soft, long-duration gamma-ray burst (X-ray flash) GRB 100316D. Intensive follow-up observations of SN 2010bh were performed at the ESO Very Large Telescope (VLT) using the X-shooter and FORS2 instruments. Owing to the detailed temporal coverage and the extended wavelength range (3000--24800 A), we obtained an unprecedentedly rich spectral sequence among the hypernovae, making SN 2010bh one of the best studied representatives of this SN class. We find that SN 2010bh has a more rapid rise to maximum brightness (8.0 +/- 1.0 rest-frame days) and a fainter absolute peak luminosity (L_bol~3e42 erg/s) than previously observed SN events associated with GRBs. Our estimate of the ejected (56)Ni mass is 0.12 +/- 0.02 Msun. From the broad spectral features we measure expansion velocities up to 47,000 km/s, higher than those of SNe 1998bw (GRB 980425) and 2006aj (GRB 060218). Helium absorption lines He I lambda5876 and He I 1.083 microm, blueshifted by ~20,000--30,000 km/s and ~28,000--38,000 km/s, respectively, may be present in the optical spectra. However, the lack of coverage of the He I 2.058 microm line prevents us from confirming such identifications. The nebular spectrum, taken at ~186 days after the explosion, shows a broad but faint [O I] emission at 6340 A. The light-curve shape and photospheric expansion velocities of SN 2010bh suggest that we witnessed a highly energetic explosion with a small ejected mass (E_k ~ 1e52 erg and M_ej ~ 3 Msun). The observed properties of SN 2010bh further extend the heterogeneity of the class of GRB supernovae.Comment: 37 pages and 12 figures (one-column pre-print format), accepted for publication in Ap

Depletion of soil carbon and aggregation after strong warming of a subarctic Andosol under forest and grassland cover

The net loss of soil organic carbon (SOC) from terrestrial ecosystems is a likely consequence of global warming and may affect key soil functions. The strongest changes in temperature are expected to occur at high northern latitudes, with forest and tundra as prevailing land cover types. However, specific soil responses to warming in different ecosystems are currently understudied. In this study, we used a natural geothermal soil warming gradient (0–17.5 °C warming intensity) in an Icelandic spruce forest on Andosol to assess changes in the SOC content between 0 and 10 cm (topsoil) and between 20 and 30 cm (subsoil) after 10 years of soil warming. Five different SOC fractions were isolated, and their redistribution and the amount of stable aggregates were assessed to link SOC to changes in the soil structure. The results were compared to an adjacent, previously investigated warmed grassland. Soil warming depleted the SOC content in the forest soil by -2:7 g kg-1 °C-1 (-3:6%°C-1) in the topsoil and -1:6 g kg-1 °C-1 (-4:5%°C-1) in the subsoil. The distribution of SOC in different fractions was significantly altered, with particulate organic matter and SOC in sand and stable aggregates being relatively depleted and SOC attached to silt and clay being relatively enriched in warmed soils. The major reason for this shift was aggregate breakdown: the topsoil aggregate mass proportion was reduced from 60:7+_2:2% in the unwarmed reference to 28:9+_4:6% in the most warmed soil. Across both depths, the loss of one unit of SOC caused a depletion of 4.5 units of aggregated soil, which strongly affected the bulk density (an R2 value of 0.91 and p < 0:001 when correlated with SOC, and an R2 value of 0.51 and p < 0:001 when correlated with soil mass in stable aggregates). The proportion of water-extractable carbon increased with decreasing aggregation, which might indicate an indirect protective effect of aggregates larger than 63 μm on SOC. Topsoil changes in the total SOC content and fraction distribution were more pronounced in the forest than in the adjacent warmed grassland soils, due to higher and more labile initial SOC. However, no ecosystem effect was observed on the warming response of the subsoil SOC content and fraction distribution. Thus, whole profile differences across ecosystems might be small. Changes in the soil structure upon warming should be studied more deeply and taken into consideration when interpreting or modelling biotic responses to warming

A cAMP-binding ectoprotein in the yeast Saccharomyces cerevisiae

tides 10, 593-595

Phenotypic insights into ADCY5-associated disease

BACKGROUND: Adenylyl cyclase 5 (ADCY5) mutations is associated with heterogenous syndromes: familial dyskinesia and facial myokymia; paroxysmal chorea and dystonia; autosomal-dominant chorea and dystonia; and benign hereditary chorea. We provide detailed clinical data on 7 patients from six new kindreds with mutations in the ADCY5 gene, in order to expand and define the phenotypic spectrum of ADCY5 mutations. METHODS: In 5 of the 7 patients, followed over a period of 9 to 32 years, ADCY5 was sequenced by Sanger sequencing. The other 2 unrelated patients participated in studies for undiagnosed pediatric hyperkinetic movement disorders and underwent whole-exome sequencing. RESULTS: Five patients had the previously reported p.R418W ADCY5 mutation; we also identified two novel mutations at p.R418G and p.R418Q. All patients presented with motor milestone delay, infantile-onset action-induced generalized choreoathetosis, dystonia, or myoclonus, with episodic exacerbations during drowsiness being a characteristic feature. Axial hypotonia, impaired upward saccades, and intellectual disability were variable features. The p.R418G and p.R418Q mutation patients had a milder phenotype. Six of seven patients had mild functional gain with clonazepam or clobazam. One patient had bilateral globus pallidal DBS at the age of 33 with marked reduction in dyskinesia, which resulted in mild functional improvement. CONCLUSION: We further delineate the clinical features of ADCY5 gene mutations and illustrate its wide phenotypic expression. We describe mild improvement after treatment with clonazepam, clobazam, and bilateral pallidal DBS. ADCY5-associated dyskinesia may be under-recognized, and its diagnosis has important prognostic, genetic, and therapeutic implications. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Warming shifts the biomass distribution of soil microarthropod communities

Climate warming is often more detrimental to large body sized organisms than small body sized organisms. Yet, how such differential effects of warming at organismal levels affect aggregate community properties, such as community biomass, remains little understood. Here, using geothermally warmed sub-Arctic grassland soils, we investigate how total biomass (product of density and individual body mass) of two major groups of soil microarthropods (Collembola and mites), which are composed of both large and small body sized species, shift in warmed soils when warmed by ∼3–∼6 °C. Our results show that total biomass of Collembola significantly decreased in warmed soils predominantly due to a decline in the density of large body sized species. In contrast, total mite biomass showed a unimodal response to warming. As a result, there was a shift towards mite biomass dominated microarthropod communities in warmed soils. Within Collembola, the deep soil living eu-edaphic functional group declined the most in total biomass, whereas the unimodal response in mites was most pronounced in oribatid mites. Our study highlights that warming induced shifts in total community biomass of soil microarthropods are likely due to greater detrimental effects of warming on several large body sized Collembola