Polymorphisms within the canine MLPH gene are associated with dilute coat color in dogs

BACKGROUND Pinschers and other dogs with coat color dilution show a characteristic pigmentation phenotype. The fur colors are a lighter shade, e.g. silvery grey (blue) instead of black and a sandy color (Isabella fawn) instead of red or brown. In some dogs the coat color dilution is sometimes accompanied by hair loss and recurrent skin inflammation, the so called color dilution alopecia (CDA) or black hair follicular dysplasia (BHFD). In humans and mice a comparable pigmentation phenotype without any documented hair loss is caused by mutations within the melanophilin gene (MLPH). RESULTS We sequenced the canine MLPH gene and performed a mutation analysis of the MLPH exons in 6 Doberman Pinschers and 5 German Pinschers. A total of 48 sequence variations was identified within and between the breeds. Three families of dogs showed co-segregation for at least one polymorphism in an MLPH exon and the dilute phenotype. No single polymorphism was identified in the coding sequences or at splice sites that is likely to be causative for the dilute phenotype of all dogs examined. In 18 German Pinschers a mutation in exon 7 (R199H) was consistently associated with the dilute phenotype. However, as this mutation was present in homozygous state in four dogs of other breeds with wildtype pigmentation, it seems unlikely that this mutation is truly causative for coat color dilution. In Doberman Pinschers as well as in Large Munsterlanders with BHFD, a set of single nucleotide polymorphisms (SNPs) around exon 2 was identified that show a highly significant association to the dilute phenotype. CONCLUSION This study provides evidence that coat color dilution is caused by one or more mutations within or near the MLPH gene in several dog breeds. The data on polymorphisms that are strongly associated with the dilute phenotype will allow the genetic testing of Pinschers to facilitate the breeding of dogs with defined coat colors and to select against Large Munsterlanders carrying BHFD.

Health-Related Quality of Life of Young Adults Treated with Recombinant Human Growth Hormone during Childhood.

BACKGROUND Since recombinant human growth hormone (rhGH) became available in 1985, the spectrum of indications has broadened and the number of treated patients increased. However, long-term health-related quality of life (HRQoL) after childhood rhGH treatment has rarely been documented. We assessed HRQoL and its determinants in young adults treated with rhGH during childhood. METHODOLOGY/PRINCIPAL FINDINGS For this study, we retrospectively identified former rhGH patients in 11 centers of paediatric endocrinology, including university hospitals and private practices. We sent a questionnaire to all patients treated with rhGH for any diagnosis, who were older than 18 years, and who resided in Switzerland at time of the survey. Three hundred participants (58% of 514 eligible) returned the questionnaire. Mean age was 23 years; 56% were women; 43% had isolated growth hormone deficiency, or idiopathic short stature; 43% had associated diseases or syndromes, and 14% had growth hormone deficiency after childhood cancer. Swiss siblings of childhood cancer survivors and the German norm population served as comparison groups. HRQoL was assessed using the Short Form-36. We found that the Physical Component Summary of healthy patients with isolated growth hormone deficiency or idiopathic short stature resembled that of the control group (53.8 vs. 54.9). Patients with associated diseases or syndromes scored slightly lower (52.5), and former cancer patients scored lowest (42.6). The Mental Component Summary was similar for all groups. Lower Physical Component Summary was associated with lower educational level (coeff. -1.9). Final height was not associated with HRQoL. CONCLUSIONS/SIGNIFICANCE In conclusion, HRQoL after treatment with rhGH in childhood depended mainly on the underlying indication for rhGH treatment. Patients with isolated growth hormone deficiency/idiopathic short stature or patients with associated diseases or syndromes had HRQoL comparable to peers. Patients with growth hormone deficiency after childhood cancer were at high risk for lower HRQoL. This reflects the general impaired health of this vulnerable group, which needs long-term follow-up.

Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol.

INTRODUCTION Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function. METHODS AND ANALYSIS Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to ≤0.5 (decimal system) and an onset of symptoms within 10 days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33 000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30 months. ETHICS AND DISSEMINATION TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki, local laws and ICH-GCP. TRIAL REGISTRATION NUMBER NCT01962571.

La reconstrucción histórica en el "Revisionismo" de David Irving

En este trabajo se plantea, más allá de examinar las tesis principales del "revisionismo", la propia naturaleza del conocimiento histórico. ¿Son válidas todas las interpretaciones de un hecho histórico? ¿Se trata en tales casos de "otra lectura", de una "versión alternativa", es decir, de otra apreciación de los datos disponibles? ¿Cómo saber cuando hay mala interpretación deliberada o falsificación de la evidencia? ¿Puede detectarse si la argumentación tendenciosa es deshonesta? El "revisionismo histórico" se ha definido a sí mismo como una corriente historiográfica que ofrece otra versión de Hitler y su régimen. Cerca de una veintena de autores, desde los años cuarenta del siglo XX, se adscriben en esta tendencia, algunos de los cuales han desplegado una sostenida actividad y han logrado una llamativa repercusión en los medios de difusión. Este es el caso de David Irving. Autor de más de treinta libros, artículos, conferencias y discursos dedicados al III Reich, ha pasado largos años de su vida rastreando y estudiando archivos alemanes. Pero muy lejos de constituir un nuevo enfoque historiográfico del nazismo, el "revisionismo" de David Irving está imbuido de política e ideología y sus métodos de trabajo incluyen la adulteración y la distorsión intencional de la historia.

Masterchronology on Arctica islandica from Spiekeroog

Sclerochronological records of interannual shell growth variability were established for eight modern shells (26 to 163 years of age) of the bivalve Arctica islandica, which were sampled at one site in the inner German Bight. The records indicate generally low synchrony between individuals. Spectral analysis of the whole 163-yr masterchronology indicated a cyclic pattern with a period of 5 and 7 years. The masterchronology correlated poorly to time series of environmental parameters over the last 90 years. High environmental variability in time and space of the dynamic and complex German Bight hydrographic system results in an extraordinarily high noise' level in the shell growth pattern of Arctica islandica.

Data from PhD thesis

The ocean quahog, Arctica islandica is the longest-lived non-colonial animal known to science. A maximum individual age of this bivalve of 405 years has been found in a population off the north western coast of Iceland. Conspicuously shorter maximum lifespan potentials (MLSPs) were recorded from other populations of A. islandica in European waters (e.g. Kiel Bay: 30 years, German Bight: 150 years) which experience wider temperature and salinity fluctuations than the clams from Iceland. The aim of my thesis was to identify possible life-prolonging physiological strategies in A. islandica and to examine the modulating effects of extrinsic factors (e.g. seawater temperature, food availability) and intrinsic factors (e.g. species-specific behavior) on these strategies. Burrowing behavior and metabolic rate depression (MRD), tissue-specific antioxidant and anaerobic capacities as well as cell-turnover (= apoptosis and proliferation) rates were investigated in A. islandica from Iceland and the German Bight. An inter-species comparison of the quahog with the epibenthic scallop Aequipecten opercularis (MLSP = 8-10 years) was carried out in order to determine whether bivalves with short lifespans and different lifestyles also feature a different pattern in cellular maintenance and repair. The combined effects of a low-metabolic lifestyle, low oxidative damage accumulation, and constant investment into cellular protection and tissue maintenance, appear to slow-down the process of physiological aging in A. islandica and to afford the extraordinarily long MLSP in this species. Standard metabolic rates were lower in A. islandica when compared to the shorter-lived A. opercularis. Furthermore, A. islandica regulate mantle cavity water PO2 to mean values < 5 kPa, a PO2 at which the formation of reactive oxygen species (ROS) in isolated gill tissues of the clams was found to be 10 times lower than at normoxic conditions (21 kPa). Burrowing and metabolic rate depression (MRD) in Icelandic specimens were more pronounced in winter, possibly supported by low seawater temperature and food availability, and seem to be key energy-saving and life-prolonging parameters in A. islandica. The signaling molecule nitric oxide (NO) may play an important role during the onset of MRD in the ocean quahog by directly inhibiting cytochome-c-oxidase at low internal oxygenation upon shell closure. In laboratory experiments, respiration of isolated A. islandica gills was completely inhibited by chemically produced NO at low experimental PO2 <= 10 kPa. During shell closure, mantle cavity water PO2 decreased to 0 kPa for longer than 24 h, a state in which ROS production is supposed to subside. Compared to other mollusk species, onset of anaerobic metabolism is late in A. islandica in the metabolically reduced state. Increased accumulation of the anaerobic metabolite succinate was initially detected in the adductor muscle of the clams after 3.5 days under anoxic incubation or in burrowed specimens. A ROS-burst was absent in isolated gill tissue of the clams following hypoxia (5 kPa)-reoxygenation (21 kPa). Accordingly, neither the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), nor the specific content of the ROS-scavenger glutathione (GSH) was enhanced in different tissues of the ocean quahog after 3.5 days of self-induced or forced hypoxia/anoxia to prepare for an oxidative burst. While reduced ROS formation compared to routine levels lowers oxidative stress during MRD and also during surfacing, the general preservation of high cellular defense and the efficient removal and replacement of damaged cells over lifetime seem to be of crucial importance in decelerating the senescent decline in tissues of A. islandica. Along with stable antioxidant protection over 200 years of age, proliferation rates and apoptosis intensities in most investigated tissues of the ocean quahog were low, but constant over 140 years of age. Accordingly, age-dependent accumulations of protein and lipid oxidation products are lower in A. islandica tissues when compared to the shorter-lived bivalve A. opercularis. The short-lived swimming scallop is a model bivalve species representing the opposite life and aging strategy to A. islandica. In this species permanently high energy throughput, reduced investment into antioxidant defense with age, and higher accumulation of oxidation products are met by higher cell turnover rates than in the ocean quahog. The only symptoms of physiological change over age ever found in A. islandica were decreasing cell turnover rates in the heart muscle over a lifetime of 140 years. This may either indicate higher damage levels and possibly ongoing loss of functioning in the heart of aging clams, or, the opposite, lower rates of cell damage and a reduced need for cell renewal in the heart tissue of A. islandica over lifetime. Basic physiological capacities of different A. islandica populations, measured at controlled laboratory conditions, could not explain considerable discrepancies in population specific MLSPs. For example, levels of tissue-specific antioxidant capacities and cell turnover rates were similarly high in individuals from the German Bight and from Iceland. Rather than genetic differences, the local impacts of environmental conditions on behavioral and physiological traits in the ocean quahog seem to be responsible for differences in population-specific MLSPs.

Database of Ice-Rich Yedoma Permafrost (IRYP)

Vast portions of Arctic and sub-Arctic Siberia, Alaska and the Yukon Territory are covered by ice-rich silty to sandy deposits that are containing large ice wedges, resulting from syngenetic sedimentation and freezing. Accompanied by wedge-ice growth in polygonal landscapes, the sedimentation process was driven by cold continental climatic and environmental conditions in unglaciated regions during the late Pleistocene, inducing the accumulation of the unique Yedoma deposits up to >50 meters thick. Because of fast incorporation of organic material into syngenetic permafrost during its formation, Yedoma deposits include well-preserved organic matter. Ice-rich deposits like Yedoma are especially prone to degradation triggered by climate changes or human activity. When Yedoma deposits degrade, large amounts of sequestered organic carbon as well as other nutrients are released and become part of active biogeochemical cycling. This could be of global significance for future climate warming as increased permafrost thaw is likely to lead to a positive feedback through enhanced greenhouse gas fluxes. Therefore, a detailed assessment of the current Yedoma deposit coverage and its volume is of importance to estimate its potential response to future climate changes. We synthesized the map of the coverage and thickness estimation, which will provide critical data needed for further research. In particular, this preliminary Yedoma map is a great step forward to understand the spatial heterogeneity of Yedoma deposits and its regional coverage. There will be further applications in the context of reconstructing paleo-environmental dynamics and past ecosystems like the mammoth-steppe-tundra, or ground ice distribution including future thermokarst vulnerability. Moreover, the map will be a crucial improvement of the data basis needed to refine the present-day Yedoma permafrost organic carbon inventory, which is assumed to be between 83±12 (Strauss et al., 2013, doi:10.1002/2013GL058088) and 129±30 (Walter Anthony et al., 2014, doi:10.1038/nature13560) gigatonnes (Gt) of organic carbon in perennially-frozen archives. Hence, here we synthesize data on the circum-Arctic and sub-Arctic distribution and thickness of Yedoma for compiling a preliminary circum-polar Yedoma map. For compiling this map, we used (1) maps of the previous Yedoma coverage estimates, (2) included the digitized areas from Grosse et al. (2013) as well as extracted areas of potential Yedoma distribution from additional surface geological and Quaternary geological maps (1.: 1:500,000: Q-51-V,G; P-51-A,B; P-52-A,B; Q-52-V,G; P-52-V,G; Q-51-A,B; R-51-V,G; R-52-V,G; R-52-A,B; 2.: 1:1,000,000: P-50-51; P-52-53; P-58-59; Q-42-43; Q-44-45; Q-50-51; Q-52-53; Q-54-55; Q-56-57; Q-58-59; Q-60-1; R-(40)-42; R-43-(45); R-(45)-47; R-48-(50); R-51; R-53-(55); R-(55)-57; R-58-(60); S-44-46; S-47-49; S-50-52; S-53-55; 3.: 1:2,500,000: Quaternary map of the territory of Russian Federation, 4.: Alaska Permafrost Map). The digitalization was done using GIS techniques (ArcGIS) and vectorization of raster Images (Adobe Photoshop and Illustrator). Data on Yedoma thickness are obtained from boreholes and exposures reported in the scientific literature. The map and database are still preliminary and will have to undergo a technical and scientific vetting and review process. In their current form, we included a range of attributes for Yedoma area polygons based on lithological and stratigraphical information from the original source maps as well as a confidence level for our classification of an area as Yedoma (3 stages: confirmed, likely, or uncertain). In its current version, our database includes more than 365 boreholes and exposures and more than 2000 digitized Yedoma areas. We expect that the database will continue to grow. In this preliminary stage, we estimate the Northern Hemisphere Yedoma deposit area to cover approximately 625,000 km². We estimate that 53% of the total Yedoma area today is located in the tundra zone, 47% in the taiga zone. Separated from west to east, 29% of the Yedoma area is found in North America and 71 % in North Asia. The latter include 9% in West Siberia, 11% in Central Siberia, 44% in East Siberia and 7% in Far East Russia. Adding the recent maximum Yedoma region (including all Yedoma uplands, thermokarst lakes and basins, and river valleys) of 1.4 million km² (Strauss et al., 2013, doi:10.1002/2013GL058088) and postulating that Yedoma occupied up to 80% of the adjacent formerly exposed and now flooded Beringia shelves (1.9 million km², down to 125 m below modern sea level, between 105°E - 128°W and >68°N), we assume that the Last Glacial Maximum Yedoma region likely covered more than 3 million km² of Beringia. Acknowledgements: This project is part of the Action Group "The Yedoma Region: A Synthesis of Circum-Arctic Distribution and Thickness" (funded by the International Permafrost Association (IPA) to J. Strauss) and is embedded into the Permafrost Carbon Network (working group Yedoma Carbon Stocks). We acknowledge the support by the European Research Council (Starting Grant #338335), the German Federal Ministry of Education and Research (Grant 01DM12011 and "CarboPerm" (03G0836A)), the Initiative and Networking Fund of the Helmholtz Association (#ERC-0013) and the German Federal Environment Agency (UBA, project UFOPLAN FKZ 3712 41 106).

Puente de ferrocarril sobre el Mittellandkanal en Braunschweig

The bridge over the Mittellandkanal is located in the municipality of Braunschweig, a city of Low Saxony located in Mid-North Germany, between Berlin and Hannover, 50 km away from this last city. The city of Braunschwig has 248.867 inhabitants (December 2010). The orography of the zone is practically even, with some slopes in the surrounding area, with a no important variation of the ground elevation, characterized by a big uniformity and a great visual quality. In this zone the canal flows from west to east, from the Dortmundkanal until the Elbe river, so it has a length of 325,3 km. The normal flora from the zone is farmland with some little forests not very big and not very important. But the Mittellandkanal lies at the North of Brauschweig, that means that in the zone of the canal there is a change between the urban area and the rural area. For this reason in the zone of the bridge we start to find farmlands and forest, however the constructions and buildings are still present in this area. The railway line that is going to be built will unite the North-center of Germany with the North-East of Germany because some of the following factors: •Overstress of the only existing line in the moment that connects Berlin with the North-East extreme of Germany. •No direct connection with the North-Easth Germany with other important German cities from South and West of Germany. •Replacement of the old existing one way line in the area that has to be renewed. •Modernization of the old railway lines of Germany. Schedule order by the European Union and the German Government. The actual lines of the zone do not have the necessary conditions and characteristics to satisfy the demand of the travelers that want to travel all over Germany with the railway avoiding using other transports like plan or car. For these reasons the necessity of the replacement of the old railway line and the aim to create a union with the North-East Germany that has a deficit of transport infrastructures and connections with the rest of the country and Europe. Although the new railway line provokes some disadvantages when constructing it is indispensable to build this railway line. The pass of the railway line through Braunschweig has not been random. The zone Braunschweig-Wolfsburg is a very industrialized area because of some companies like Wolkswagen and too because this zone is an important pass of important line from Berlin, South and East Germany. For all of these reasons the railway line goes through Braunschweig and connects to the city of Wolfsburg first, and after the North-East Germany zone.

Desarrollo de la radio en el marco de las rivalidades político-militares de principios del siglo XX

A lo largo de este proyecto, se analizarán los comienzos de la radio en las primeras décadas del siglo XX, teniendo como objetivo describir el desarrollo científico-tecnológico y las rivalidades político-militares de las potencias europeas de Reino Unido y Alemania. En primer lugar se verán los precursores de la radio que existían anteriormente al surgimiento de la radiotelegrafía como la telegrafía óptica, la telegrafía eléctrica o el teléfono. Al igual que los primeros investigadores, como James Clerk Maxwell o Heinrich Rudolf Hertz, gracias a los cuales el origen de la radio fue posible. También se analizará el contexto histórico-político de Reino Unido y Alemania donde se muestran las características de las dos grandes potencias del momento, el Imperio Británico y el Imperio Alemán. Además, la cada vez mayor importancia de la telegrafía sin hilos, hará necesaria una organización internacional, dando lugar a las Conferencias Internacionales de Radiotelegrafía y que enfrentarán a estas dos potencias por defender sus intereses. Guillermo Marconi, por parte de Reino Unido, y Telefunken, por parte de Alemania, serán las principales marcas comerciales de radiotelegrafía, no solo en sus respectivos países, sino también en el resto del mundo. Entre ambas compañías se verán las rivalidades por la incesante lucha de patentes, el desarrollo tecnológico y el control de los mercados. También se tratará el enfrentamiento directo que se produjo en la Primera Guerra Mundial, donde la radio jugaría un papel fundamental. Por último, se analizarán los comienzos de la radiodifusión en la segunda década del siglo XX, donde la radio ya estaba consolidada como uno de los medios de comunicación más importante de la época, capaz de llegar a todos los rincones del planeta y perfectamente integrada en la sociedad del momento. ABSTRACT. Throughout this project, it will be analyzed the beginning of the radio in the first decades of the XX century, having as goal to describe the scientific-technological development and the political-militaries opponents of the European’s countries, United kingdom and Germany. Firstly, it will be shown the radio’s precursors before the origin of the wireless telegraphy, like: optical telegraphy, electric telegraphy or telephone. Moreover, it will show the first researchers like: Clerk Maxwell or Heinrich Hertz, thanks to them, the origin of the radio was possible. In addition, it will analyze the historical-political context of United Kingdom and Germany, where it is shown the main features of the Britain Empire and the German Empire. Moreover, the importance of the telegraphy without wire will make necessary and international organization, resulting the International Conferences of Wireless Telegraphy and it will put together these main countries in order to protect their interests. Guglielmo Marconi, by United Kingdom, and Telefunken, by Germany, they will be the main commercials brand of the wireless telegraphy, not only in their countries, but also in all over the world. Between both companies will be seen the main competitions for their patens, the technology development and the market’s control. Moreover, it will be dealt the direct conflict in the First World of War, where the radio has a fundamental role. Finally, it will be analyze the beginning of the wireless broadcasting in the second decade of the XX century, where the radio was established as one of the most important media of the age, able to arrive at every places of the world and it was perfectly integrated in the society of that moment.

A weak link? Germany in the Euro-Atlantic security system. OSW Point of View Number 47, January 2015

The political, military and economic parameters of German power influence the vision of the international order that Berlin favours. Politically, Germany is a regional power in the EU with considerable diplomatic potential. Economically, it is the world's third largest power with growing global trade and investment links. At the same time, Germany's military potential is limited and the German strategic culture makes the country sceptical about the use of military instruments. Berlin is thus essentially interested in maintaining peace and stability, both in Europe and globally, and in developing diplomatic mechanisms to manage regional and global crises and conflicts. The German preference for dialogue and compromise in conflict situations in the regional and global dimensions may increasingly pose a risk to maintaining the cohesion and credibility of NATO – both from the perspective of the USA and Germany’s allies from Central-Eastern and Northern Europe.

Turkey makes a mockery of Europe’s claim to uphold democratic values. EPC Commentary, 16 March 2016

The 7 March EU-Turkey migration crisis summit took place three days after the Turkish authorities seized Feza media group, which includes Turkey’s largest circulation daily Zaman and its English language sister paper Today’s Zaman. The seizure was the latest development in the worst crackdown on fundamental rights and freedoms Turkey has witnessed in decades. Yet because Turkey is vital in dealing with the migration/refugee crisis, the EU’s response was meek to say the least. For the first time since the Cold War – when Turkey was key in shoring up Europe’s security – Ankara has found itself in a particular position of strength. Turkey has skillfully exploited the EU’s and particularly German Chancellor Angela Merkel’s urgent need to find a way out of the crisis.

Turkey makes a mockery of Europe's claim to uphold democratic values. EPC Commentary, 16 March 2016

The 7 March EU-Turkey migration crisis summit took place three days after the Turkish authorities seized Feza media group, which includes Turkey’s largest circulation daily Zaman and its English language sister paper Today’s Zaman. The seizure was the latest development in the worst crackdown on fundamental rights and freedoms Turkey has witnessed in decades. Yet because Turkey is vital in dealing with the migration/refugee crisis, the EU’s response was meek to say the least. For the first time since the Cold War – when Turkey was key in shoring up Europe’s security – Ankara has found itself in a particular position of strength. Turkey has skillfully exploited the EU’s and particularly German Chancellor Angela Merkel’s urgent need to find a way out of the crisis.

Eins in's andere : Für die reifere jugend gesammelt.

Mode of access: Internet.

Oud-nederlandsche liederen uit den Nederlandtschen gedenck-clanck, 1626. Met toelichting en klavierbegeleiding van A. D. Loman.

Pl. no. L.R.25.

Marietta's song : from the opera The dead city = Mariettas Lied zur Laute /

For medium voice and piano; German and English words.