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Contains fulltext : 294362.pdf (Publisher’s version ) (Open Access), BACKGROUND: Heterozygous, large-scale deletions at 14q24.3-31.1 affecting the neurexin-3 gene have been associated with neurodevelopmental disorders such as autism. Both "de novo" occurrences and inheritance from a healthy parent suggest incomplete penetrance and expressivity, especially in autism spectrum disorder. NRXN3 encodes neurexin-3, a neuronal cell surface protein involved in cell recognition and adhesion, as well as mediating intracellular signaling. NRXN3 is expressed in two distinct isoforms (alpha and beta) generated by alternative promoters and splicing. MM/Results: Using exome sequencing, we identified a monoallelic frameshift variant c.159_160del (p.Gln54AlafsTer50) in the NRXN3 beta isoform (NM_001272020.2) in a 5-year-old girl with developmental delay, autism spectrum disorder, and behavioral issues. This variant was inherited from her mother, who did not have any medical complaints. DISCUSSION: This is the first detailed report of a loss-of-function variant in NRXN3 causing an identical phenotype, as reported for heterozygous large-scale deletions in the same genomic region, thereby confirming NRXN3 as a novel gene for neurodevelopmental disorders with autism.

Contains fulltext : 300179.pdf (Publisher’s version ) (Open Access), Two siblings showed increased galactose and galactose-related metabolites in neonatal screening. Diagnostic workup did not reveal abnormalities in any of the known disease-causing enzymes involved in galactose metabolism. Using whole-exome sequencing, we identified a homozygous missense variant in PPA1 encoding the cytosolic pyrophosphatase 1 (PPA1), c.557C>T (p.Thr186Ile). The enzyme activity of PPA1 was determined using a colorimetric assay, and the protein content was visualized via western blotting in skin fibroblasts from one of the affected individuals. The galactolytic activity of the affected fibroblasts was determined by measuring extracellular acidification with a Seahorse XFe96 analyzer. PPA1 activity decreased to 22% of that of controls in the cytosolic fraction of homogenates from patient fibroblasts. PPA1 protein content decreased by 50% according to western blot analysis, indicating a reduced stability of the variant protein. The extracellular acidification rate was reduced in patient fibroblasts when galactose was used as a substrate. Untargeted metabolomics of blood samples revealed an elevation of other metabolites related to pyrophosphate metabolism. Besides hyperbilirubinemia in the neonatal period in one child, both children were clinically unremarkable at the ages of 3 and 14 years, respectively. We hypothesize that the observed metabolic derangement is a possible mild manifestation of PPA1 deficiency. Unresolved abnormalities in galactosemia screening might result in the identification of more individuals with PPA1 deficiency, a newly discovered inborn metabolic disorder (IMD).

Models can be applied to extrapolate consequences of climate change for complex ecological systems in the future. The acknowledged systems’ behaviour at present is projected into the future considering climate projection data. Such an approach can be used to addresses the future activity and density of the castor bean tick Ixodes ricinus, the most widespread tick species in Europe. It is an important vector of pathogens causing Lyme borreliosis and tick-borne encephalitis. The population dynamics depend on several biotic and abiotic factors. Such complexity makes it difficult to predict the future dynamics and density of I. ricinus and associated health risk for humans. The objective of this study is to force ecological models with high-resolution climate projection data to extrapolate I. ricinus tick density and activity patterns into the future. We used climate projection data of temperature, precipitation, and relative humidity for the period 1971–2099 from 15 different climate models. Tick activity was investigated using a climate-driven cohort-based population model. We simulated the seasonal population dynamics using climate data between 1971 and 2099 and observed weather data since 1949 at a specific location in southern Germany. We evaluated derived quantities of local tick ecology, e.g. the maximum questing activity of the nymphal stage. Furthermore, we predicted spatial density changes by extrapolating a German-wide tick density model. We compared the tick density of the reference period (1971–2000) with the counter-factual densities under the near-term scenario (2012–2041), mid-term scenario (2050–2079) and long-term scenario (2070–2099). We found that the nymphal questing peak would shift towards early seasons of the year. Also, we found high spatial heterogeneity across Germany, with predicted hotspots of up to 2,000 nymphs per 100 m2 and coldspots with constant density. As our results suggest extreme changes in tick behaviour and density, we discuss wh

Contains fulltext : 229600.pdf (Publisher’s version ) (Closed access)

Biting midges (Diptera, Ceratopogonidae) of the genus Culicoides are important vectors of pathogens causing diseases in free living and production animals and can lead to large economic losses in many European countries. In Europe, Culicoides imicola and the Obsoletus group are considered to be the main vectors of bluetongue virus that mostly affects ruminants such as cattle and sheep. Spatio-temporal modelling of vector distribution and abundance allows us to identify high risk areas for virus transmission and can aid in applying effective surveillance and control measures. We used presence-absence and monthly abundance data of Culicoides from 1005 sites across 9 countries (Spain, France, Denmark, Poland, Switzerland, Austria, Poland, Sweden, Norway) collected between the years 2007 and 2013. The dataset included information on the vector species abundance (number of specimens caught per night), GPS coordinates of each trap, start and end dates of trapping. We used 120 environmental predictor variables together with Random Forest machine learning algorithms to predict the overall species distribution (probability of occurrence) and monthly abundance in Europe. We generated maps for every month of the year, to visualize the abundance of C. imicola and Obsoletus group in Europe as well as distribution maps showing the probability of occurrence. We were able to create predictive maps of both Culicoides sp. occurrence and abundance using Random Forest models, and although the variance was large, the predicted abundance values for each site had a positive correlation with the observed abundance. We found relatively large spatial variations in probability of occurrence and abundance for both C. imicola and the Obsoletus group. For C. imicola probability of occurrence and abundance was higher in southern Spain, where as the Obsoletus group had higher probability of occurrence and abundance in central and northern Europe such as France and Germany. Temp

Over 11 000 L of kerosene was deposited on the surface of Rabots glaciar on the Kebnekaise Massif, northern Sweden, following the crash of a Royal Norwegian Air Force aircraft in March 2012. An environmental monitoring programme was subsequently commissioned, including a series of dye tracing experiments during the 2013 melt season, conducted to investigate the transport of pollutants through the glacier hydrological system. This experimental set-up provided a basis from which we could gain new insight into the internal hydrological system of Rabots glaciar. Results of dye tracing experiments reveal a degree of homogeneity in the topology of the drainage system throughout July and August, with an increase in efficiency as the season progresses, as reflected by decreasing temporary storage and dispersivity. Early onset of melting likely led to formation of an efficient, discrete drainage system early in the melt season, subject to decreasing sinuosity and braiding as the season progressed. Four distinct meltwater flow regimes are identified to summarize the temporal and spatial evolution of the system. Analysis of turbidity-discharge hysteresis further supports the formation of discrete, efficient drainage, with clockwise diurnal hysteresis suggesting easy mobilization of readily available sediments in channels. Dye injection immediately downstream of the pollution source zone reveals prolonged storage of dye followed by fast, efficient release. Twinned with a low dye recovery, and supported by sporadic detection of hydrocarbons in the proglacial river, we suggest that meltwater, and thus pollutants in solution, may be released periodically through an efficient, and likely pressurized, hydrological system within the upper reaches of the glacier.

Serratia sp. strain ATCC 39006 is a Gram-negative bacterium and a member of the Enterobacteriaceae that produces various bioactive secondary metabolites, including the tripyrrole red pigment prodigiosin and the β-lactam antibiotic 1-carbapenen-2-em-3-carboxylic acid (a carbapenem). This strain is the only member of the Enterobacteriaceae known to naturally produce gas vesicles, as flotation organelles. Here we present the genome sequence of this strain, which has served as a model for analysis of the biosynthesis and regulation of antibiotic production.

MUTAGEN is a free prokaryotic annotation system. It offers the advantages of genome comparison, graphical sequence browsers, search facilities and open-source for user-specific adjustments. The web-interface allows several users to access the system from standard desktop computers. The Sulfolobus acidocaldarius genome, and several plasmids and viruses have so far been analysed and annotated using MUTAGEN.

Small tight trapping and guiding potentials can be created for neutral atoms moving microns above surfaces patterned with nanofabricated charged and current-carrying structures. Surfaces holding such structures form atom chips which, for coherent matter w, Addresses: Brugger K, Innsbruck Univ, Inst Expt Phys, A-6020 Innsbruck, Austria. Innsbruck Univ, Inst Expt Phys, A-6020 Innsbruck, Austria. Innsbruck Univ, Inst Theoret Phys, A-6020 Innsbruck, Austria. ECT, I-38050 Trent, Italy. Univ Uppsala, Dept Quantum

Atoms can be trapped and guided using nanofabricated wires on surfaces, achieving the scales required by quantum information proposals. These atom chips form the basis for robust and widespread application of cold atoms ranging from atom optics to fundame, Addresses: Bartenstein M, Innsbruck Univ, Inst Expt Phys, A-6020 Innsbruck, Austria. Innsbruck Univ, Inst Expt Phys, A-6020 Innsbruck, Austria. Free Univ Berlin, Inst Expt Phys, D-14195 Berlin, Germany. Innsbruck Univ, Inst Theoret Phys, A-6020 Innsbruck