Single-stranded DNA-binding proteins regulate the abundance of LIM domain and LIM domain-binding proteins.

The LIM domain-binding protein Ldb1 is an essential cofactor of LIM-homeodomain (LIM-HD) and LIM-only (LMO) proteins in development. The stoichiometry of Ldb1, LIM-HD, and LMO proteins is tightly controlled in the cell and is likely a critical determinant of their biological actions. Single-stranded DNA-binding proteins (SSBPs) were recently shown to interact with Ldb1 and are also important in developmental programs. We establish here that two mammalian SSBPs, SSBP2 and SSBP3, contribute to an erythroid DNA-binding complex that contains the transcription factors Tal1 and GATA-1, the LIM domain protein Lmo2, and Ldb1 and binds a bipartite E-box-GATA DNA sequence motif. In addition, SSBP2 was found to augment transcription of the Protein 4.2 (P4.2) gene, a direct target of the E-box-GATA-binding complex, in an Ldb1-dependent manner and to increase endogenous Ldb1 and Lmo2 protein levels, E-box-GATA DNA-binding activity, and P4.2 and beta-globin expression in erythroid progenitors. Finally, SSBP2 was demonstrated to inhibit Ldb1 and Lmo2 interaction with the E3 ubiquitin ligase RLIM, prevent RLIM-mediated Ldb1 ubiquitination, and protect Ldb1 and Lmo2 from proteasomal degradation. These results define a novel biochemical function for SSBPs in regulating the abundance of LIM domain and LIM domain-binding proteins.

Die frühe hebräische Geschichtsschreibung und die Historien Herodots - zwei Paar Stiefel?

In der Vergangenheit ist vielfach behauptet worden, dass die Hebräische Bibel und die Historien Herodots in ganz verschiedene literarische bzw. konzeptionelle Kategorien gehören. Ein Textvergleich soll klären, ob diese These haltbar ist. Der Tagungsbeitrag gibt Einblick in grundsätzliche Überlegungen im Zuge der Präzisierung des methodischen Zugriffs und der Fragestellung. Es werden zunächst kurz verschiedene Begründungen für die Verneinung von Historiographie im Tanach beleuchtet (Christian Meier, Erhard Blum, Philip Davies) und dann kurz die Schwierigkeiten bei der Definition von antiker Geschichtsschreibung dargestellt, die im Ergebnis für das Offenhalten von Kategorien- und Genregrenzen sprechen. Möglicherweise kann beim Umgang mit dieser etwas diffusen Situation die Kategorienbildung in der Prototypensemantik helfen. Ausgehend von einer Liste von Elementen, die nicht als ‚KO-Kriterien‘ für antike Geschichtsschreibung in Frage kommen wird kurz erläutert, warum Geschichtsschreibung und mythisches Erzählen in frühen historiographischen Texten miteinander kompatibel sind. Kurze Beispiele zeigen, dass Herodots Verhältnis zu mythischen und religiösen Vorstellungen keineswegs einheitlich ist, und dass diese Tradition einen der Bezugsrahmen seines Werks ausmacht. Diese Einsichten schlagen sich in den methodischen Überlegungen nieder. Ein wichtiger Ausgangspunkt ist hier die Annahme der Andersartigkeit der antiken Historiographie und ihrer Auffassung von der Arbeit und Aufgabe eines Historikers. In der Forschung sind zu meinem oder ähnlichen Themen verschiedene methodische Ansätze gewählt worden; so das Ausgehen von modernen oder antiken Geschichts- bzw. Literaturtheorien oder die Rekonstruktion des Umgangs der Autoren mit ihren Quellen. Demgegenüber bietet eine literaturwissenschaftlich-vergleichende Erzähltextanalyse gewisse Vorteile. Damit die Auswahl der Vergleichshinsichten nicht willkürlich erfolgt, brauchen komparatistische Textanalysen trotzdem ein theoretisches Konzept oder zumindest einen übergeordneten Leitgedanken. Hier scheint mir das Herausarbeiten der jeweils spezifischen ‚historischen Wahrheit‘ der Texte fruchtbar zu sein.

The HARPS search for southern extra-solar planets

The vast diversity of planetary systems detected to date is defying our capability of understanding their formation and evolution. Well-defined volume-limited surveys are the best tool at our disposal to tackle the problem, via the acquisition of robust statistics of the orbital elements. We are using the HARPS spectrograph to conduct our survey of ≈850 nearby solar-type stars, and in the course of the past nine years we have monitored the radial velocity of HD 103774, HD 109271, and BD-061339. In this work we present the detection of five planets orbiting these stars, with msin   (i) between 0.6 and 7 Neptune masses, four of which are in two multiple systems, comprising one super-Earth and one planet within the habitable zone of a late-type dwarf. Although for strategic reasons we chose efficiency over precision in this survey, we have the capability to detect planets down to the Neptune and super-Earth mass range as well as multiple systems, provided that enough data points are made available.

Victoria en Germania. Tomás Luis de Victoria y la historiografía alemana hasta principios del siglo XX

Es war bisher unbekannt, dass die deutschsprachige Musikhistoriographie dem Komponisten Tomás Luis de Victoria relativ viel Beachtung geschenkt hat. Als iberischer Counterpart des Heroen Palestrina spielt er bei der Gestaltung eines Geschichtsbildes der musikalischen Renaissance daher eine viel wichtigere Rolle als bisher vermutet. Die Auseinandersetzung deutscher Musikwissenschaftler mit Victoria spielte eine zentrale Rolle bei der Würdigung des Komponisten durch die spanische Historiographie.

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the "REGISTRY" cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis.

Suicidal ideation in a European Huntington's disease population.

BACKGROUND Previous studies indicate increased prevalences of suicidal ideation, suicide attempts, and completed suicide in Huntington's disease (HD) compared with the general population. This study investigates correlates and predictors of suicidal ideation in HD. METHODS The study cohort consisted of 2106 HD mutation carriers, all participating in the REGISTRY study of the European Huntington's Disease Network. Of the 1937 participants without suicidal ideation at baseline, 945 had one or more follow-up measurements. Participants were assessed for suicidal ideation by the behavioural subscale of the Unified Huntington's Disease Rating Scale (UHDRS). Correlates of suicidal ideation were analyzed using logistic regression analysis and predictors were analyzed using Cox regression analysis. RESULTS At baseline, 169 (8.0%) mutation carriers endorsed suicidal ideation. Disease duration (odds ratio [OR]=0.96; 95% confidence interval [CI]: 0.9-1.0), anxiety (OR=2.14; 95%CI: 1.4-3.3), aggression (OR=2.41; 95%CI: 1.5-3.8), a previous suicide attempt (OR=3.95; 95%CI: 2.4-6.6), and a depressed mood (OR=13.71; 95%CI: 6.7-28.0) were independently correlated to suicidal ideation at baseline. The 4-year cumulative incidence of suicidal ideation was 9.9%. Longitudinally, the presence of a depressed mood (hazard ratio [HR]=2.05; 95%CI: 1.1-4.0) and use of benzodiazepines (HR=2.44; 95%CI: 1.2-5.0) at baseline were independent predictors of incident suicidal ideation, whereas a previous suicide attempt was not predictive. LIMITATIONS As suicidal ideation was assessed by only one item, and participants were a selection of all HD mutation carriers, the prevalence of suicidal ideation was likely underestimated. CONCLUSIONS Suicidal ideation in HD frequently occurs. Assessment of suicidal ideation is a priority in mutation carriers with a depressed mood and in those using benzodiazepines.

Latrepirdine stimulates autophagy and reduces accumulation of α-synuclein in cells and in mouse brain

Latrepirdine (Dimebon; dimebolin) is a neuroactive compound that was associated with enhanced cognition, neuroprotection and neurogenesis in laboratory animals, and has entered phase II clinical trials for both Alzheimer's disease and Huntington's disease (HD). Based on recent indications that latrepirdine protects cells against cytotoxicity associated with expression of aggregatable neurodegeneration-related proteins, including Aβ42 and γ-synuclein, we sought to determine whether latrepirdine offers protection to Saccharomyces cerevisiae. We utilized separate and parallel expression in yeast of several neurodegeneration-related proteins, including α-synuclein (α-syn), the amyotrophic lateral sclerosis-associated genes TDP43 and FUS, and the HD-associated protein huntingtin with a 103 copy-polyglutamine expansion (HTT gene; htt-103Q). Latrepirdine effects on α-syn clearance and toxicity were also measured following treatment of SH-SY5Y cells or chronic treatment of wild-type mice. Latrepirdine only protected yeast against the cytotoxicity associated with α-syn, and this appeared to occur via induction of autophagy. We further report that latrepirdine stimulated the degradation of α-syn in differentiated SH-SY5Y neurons, and in mouse brain following chronic administration, in parallel with elevation of the levels of markers of autophagic activity. Ongoing experiments will determine the utility of latrepirdine to abrogate α-syn accumulation in transgenic mouse models of α-syn neuropathology. We propose that latrepirdine may represent a novel scaffold for discovery of robust pro-autophagic/anti-neurodegeneration compounds, which might yield clinical benefit for synucleinopathies including Parkinson's disease, Lewy body dementia, rapid eye movement (REM) sleep disorder and/or multiple system atrophy, following optimization of its pro-autophagic and pro-neurogenic activities.

Cognitive Interventions with Children with Special Needs - Transfer effects and multidisciplinary perspectives

Our last study with regularly developed children demonstrated a positive effect of working memory training on cognitive abilities. Building upon these findings, the aim of this multidisciplinary study is to investigate the effects of training of core functions with children who are suffering from different learning disabilities, like AD/HD, developmental dyslexia or specific language impairment. In addition to working memory training (BrainTwister), we apply a perceptual training, which concentrates on auditory-visual matching (Audilex), as well as an implicit concept learning task. We expect differential improvements of mental capacities, specifically of executive functions (working memory, attention, auditory and visual processing), scholastic abilities (language and mathematical skills), as well as of problem solving. With that, we hope to find further directions regarding helpful and individually adapted interventions in educational settings. Interested parties are invited to discuss and comment the design, the research question, and the possibilities in recruiting the subjects.

The biomechanics of the hip joint using new diagnostic aspects in the field of hip joint dysplasia. Constructive criticism of hip dysplasia diagnosis and present marketable breeding methods with an outlook on future perspectives and possibilities. Part I

In absence of basic canine hip biomechanics, a specific, consequent three dimensional concept to evaluate the coxofemoral joint was developed for the dog. With the help of a new method to radiologically demonstrate the hip in a physiological standing position several new clinically relevant aspects could be further investigated. For example the breed specific anatomical differences in the hip, and dynamics and the background on "iatrogenic luxations" in HD diagnostics could be shown. The caudal luxation and the growth abnormalities of the hip and their consequences on the whole leg (antetorsion syndrome) as a consequence of inadequate breeding could be demonstrated.

UNDERSTANDING TRENDS ASSOCIATED WITH CLOUDS IN IRRADIATED EXOPLANETS

Unlike previously explored relationships between the properties of hot Jovian atmospheres, the geometric albedo and the incident stellar flux do not exhibit a clear correlation, as revealed by our re-analysis of Q0-Q14 Kepler data. If the albedo is primarily associated with the presence of clouds in these irradiated atmospheres, a holistic modeling approach needs to relate the following properties: the strength of stellar irradiation (and hence the strength and depth of atmospheric circulation), the geometric albedo (which controls both the fraction of starlight absorbed and the pressure level at which it is predominantly absorbed), and the properties of the embedded cloud particles (which determine the albedo). The anticipated diversity in cloud properties renders any correlation between the geometric albedo and the stellar flux weak and characterized by considerable scatter. In the limit of vertically uniform populations of scatterers and absorbers, we use an analytical model and scaling relations to relate the temperature-pressure profile of an irradiated atmosphere and the photon deposition layer and to estimate whether a cloud particle will be lofted by atmospheric circulation. We derive an analytical formula for computing the albedo spectrum in terms of the cloud properties, which we compare to the measured albedo spectrum of HD 189733b by Evans et al. Furthermore, we show that whether an optical phase curve is flat or sinusoidal depends on whether the particles are small or large as defined by the Knudsen number. This may be an explanation for why Kepler-7b exhibits evidence for the longitudinal variation in abundance of condensates, while Kepler-12b shows no evidence for the presence of condensates despite the incident stellar flux being similar for both exoplanets. We include an "observer's cookbook" for deciphering various scenarios associated with the optical phase curve, the peak offset of the infrared phase curve, and the geometric albedo.

Veterinary hemodialysis: advances in management and technology.

Hemodialysis (HD) is a renal replacement therapy that can enable recovery of patients in acute kidney failure and prolong survival for patients with end-stage kidney failure. HD is also uniquely suited for management of refractory volume overload and removal of certain toxins from the bloodstream. Over the last decade, veterinary experience with HD has deepened and refined and its geographic availability has increased. As awareness of the usefulness and availability of dialytic therapy increases among veterinarians and pet owners and the number of veterinary dialysis facilities increases, dialytic management will become the standard of advanced care for animals with severe intractable uremia.

Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin-basophil axis.

BACKGROUND Exposure to food allergens through a disrupted skin barrier has been recognized as a potential factor in the increasing prevalence of food allergy. OBJECTIVE We sought to test the immunologic mechanisms by which epicutaneous sensitization to food allergens predisposes to intestinal food allergy. METHODS Mice were epicutaneously sensitized with ovalbumin or peanut on an atopic dermatitis-like skin lesion, followed by intragastric antigen challenge. Antigen-specific serum IgE levels and T(H)2 cytokine responses were measured by ELISA. Expression of type 2 cytokines and mast cell proteases in the intestine were measured by using real-time PCR. Accumulation of basophils in the skin and mast cells in the intestine was examined by using flow cytometry. In vivo basophil depletion was achieved by using diphtheria toxin treatment of Baso-DTR mice. For cell-transfer studies, the basophil population was expanded in vivo by means of hydrodynamic tail vein injection of thymic stromal lymphopoietin (TSLP) cDNA plasmid. RESULTS Sensitization to food allergens through an atopic dermatitis-like skin lesion is associated with an expansion of TSLP-elicited basophils in the skin that promote antigen-specific T(H)2 cytokine responses, increased antigen-specific serum IgE levels, and accumulation of mast cells in the intestine, promoting the development of intestinal food allergy. Critically, disruption of TSLP responses or depletion of basophils reduced the susceptibility to intestinal food allergy, whereas transfer of TSLP-elicited basophils into intact skin promoted disease. CONCLUSION Epicutaneous sensitization on a disrupted skin barrier is associated with accumulation of TSLP-elicited basophils, which are necessary and sufficient to promote antigen-induced intestinal food allergy.

Siege und Niederlagen, Irrtümer und Erkenntnisse nach 30 Jahren Geschlechtergeschichte. Eine Bilanz

Die Geschlechtergeschichte blickt mittlerweile auf eine mehr als fünf Jahrzehnte überspannende Entwicklung zurück. Wenn Geschlechtergeschichte inzwischen auch bis in die Schulbücher und in die Einführungen zum Geschichtsstudium Eingang gefunden hat, nimmt sie im Fach dennoch weiterhin eine ambivalente Position ein: Sie war einerseits an wichtigen theoretischen Entwicklungen maßgeblich beteiligt (Alltagsgeschichte, historische Anthropologie, linguistic turn, cultural turn, postcolonial turn), andererseits haftet ihr bis heute der Ruch der politisch gefärbten und daher tendenziösen und „unsoliden“ Wissenschaft an. Im Panel soll es darum gehen, wichtige Stationen der Entwicklung der Geschlechtergeschichte (von der Frauen- zur Geschlechtergeschichte, von der feministischen zur akademischen Forschung, von der Etablierung zur Kritik der Kategorie Geschlecht, vom Um-Schreiben der Geschichte zur Historiographie der Geschlechtergeschichte usw.) nachzuvollziehen sowie die wichtigsten Erträge der geschlechtergeschichtlichen Forschung zu beleuchten und Felder zu benennen, in denen die geschlechtergeschichtliche Forschung die Geschichtswissenschaft insgesamt beeinflusst und verändert hat. Dies soll in zwei Etappen realisiert werden: Im ersten Panel sollen wichtige Leistungen der Geschlechtergeschichte innerhalb der Geschichtswissenschaft beleuchtet und deren Rezeption innerhalb der pluralisierten geschichtswissenschaftlichen Ansätze diskutiert werden. In einem zweiten Schritt sollen wichtige Entwicklungen innerhalb der Geschlechtergeschichte themen- bzw. problemspezifisch präsentiert und diskutiert werden. Dies soll in Form einer round table-Diskussion erfolgen. Dabei richtet sich der Blick v.a. auf den bundesdeutschen Raum, ohne aber internationale Entwicklungen dabei außer Acht zu lassen.