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Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.
Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families as well as 438 subjects from an independent, sporadic BD case-control cohort were analysed. Polygenic risk scores (PRS) for BD, schizophrenia, and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had significantly higher PRS for all three psychiatric disorders than the independent controls, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and sporadic BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses, therefore, demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. The PRS explained only part of the observed phenotypic variance and rare variants might have also contributed to disease development.
S1P and its receptors have been reported to play important roles in the development of renal fibrosis. Although S1P5 has barely been investigated so far, there are indications that it can influence inflammatory and fibrotic processes. Here, we report the role of S1P5 in renal inflammation and fibrosis. Male S1P5 knockout mice and wild-type mice on a C57BL/6J background were fed with an adenine-rich diet for 7 days or 14 days to induce tubulointerstitial fibrosis. The kidneys of untreated mice served as respective controls. Kidney damage, fibrosis, and inflammation in kidney tissues were analyzed by real-time PCR, Western blot, and histological staining. Renal function was assessed by plasma creatinine ELISA. The S1P5 knockout mice had better renal function and showed less kidney damage, less proinflammatory cytokine release, and less fibrosis after 7 days and 14 days of an adenine-rich diet compared to wild-type mice. S1P5 knockout ameliorates tubular damage and tubulointerstitial fibrosis in a model of adenine-induced nephropathy in mice. Thus, targeting S1P5 might be a promising goal for the pharmacological treatment of kidney diseases.
String theory suggests the existence of a minimum length scale. An exciting quantum mechanical implication of this feature is a modification of the uncertainty principle. In contrast to the conventional approach, this generalised uncertainty principle does not allow to resolve space–time distances below the Planck length. In models with extra dimensions, which are also motivated by string theory, the Planck scale can be lowered to values accessible by ultra high energetic cosmic rays (UHECRs) and by future colliders, i.e., Mf≈ 1 TeV. It is demonstrated that in this novel scenario, short distance physics below 1/Mf is completely cloaked by the uncertainty principle. Therefore, Planckian effects could be the final physics discovery at future colliders and in UHECRs. As an application, we predict the modifications to the e+e−→f+f− cross-sections.
Plants, fungi and algae are important components of global biodiversity and are fundamental to all ecosystems. They are the basis for human well-being, providing food, materials and medicines. Specimens of all three groups of organisms are accommodated in herbaria, where they are commonly referred to as botanical specimens.The large number of specimens in herbaria provides an ample, permanent and continuously improving knowledge base on these organisms and an indispensable source for the analysis of the distribution of species in space and time critical for current and future research relating to global biodiversity. In order to make full use of this resource, a research infrastructure has to be built that grants comprehensive and free access to the information in herbaria and botanical collections in general. This can be achieved through digitization of the botanical objects and associated data.The botanical research community can count on a long-standing tradition of collaboration among institutions and individuals. It agreed on data standards and standard services even before the advent of computerization and information networking, an example being the Index Herbariorum as a global registry of herbaria helping towards the unique identification of specimens cited in the literature.In the spirit of this collaborative history, 51 representatives from 30 institutions advocate to start the digitization of botanical collections with the overall wall-to-wall digitization of the flat objects stored in German herbaria. Germany has 70 herbaria holding almost 23 million specimens according to a national survey carried out in 2019. 87% of these specimens are not yet digitized. Experiences from other countries like France, the Netherlands, Finland, the US and Australia show that herbaria can be comprehensively and cost-efficiently digitized in a relatively short time due to established workflows and protocols for the high-throughput digitization of flat objects.Most of the herbaria are part of a university (34), fewer belong to municipal museums (10) or state museums (8), six herbaria belong to institutions also supported by federal funds such as Leibniz institutes, and four belong to non-governmental organizations. A common data infrastructure must therefore integrate different kinds of institutions.Making full use of the data gained by digitization requires the set-up of a digital infrastructure for storage, archiving, content indexing and networking as well as standardized access for the scientific use of digital objects. A standards-based portfolio of technical components has already been developed and successfully tested by the Biodiversity Informatics Community over the last two decades, comprising among others access protocols, collection databases, portals, tools for semantic enrichment and annotation, international networking, storage and archiving in accordance with international standards. This was achieved through the funding by national and international programs and initiatives, which also paved the road for the German contribution to the Global Biodiversity Information Facility (GBIF).Herbaria constitute a large part of the German botanical collections that also comprise living collections in botanical gardens and seed banks, DNA- and tissue samples, specimens preserved in fluids or on microscope slides and more. Once the herbaria are digitized, these resources can be integrated, adding to the value of the overall research infrastructure. The community has agreed on tasks that are shared between the herbaria, as the German GBIF model already successfully demonstrates.We have compiled nine scientific use cases of immediate societal relevance for an integrated infrastructure of botanical collections. They address accelerated biodiversity discovery and research, biomonitoring and conservation planning, biodiversity modelling, the generation of trait information, automated image recognition by artificial intelligence, automated pathogen detection, contextualization by interlinking objects, enabling provenance research, as well as education, outreach and citizen science.We propose to start this initiative now in order to valorize German botanical collections as a vital part of a worldwide biodiversity data pool.
Die auf dem ACDM-Modell beruhenden numerischen Simulationen der gravitativen Strukturbildung sind auf Skalen M >> 10 hoch 10 M sehr erfolgreich, insbesondere konvergieren die Verfahren hinsichtlich des vorhergesagten Masseanteils der Halos an der Gesamtmasse von Galaxien. Jedoch konvergieren die Simulationen nicht bezüglich der lokalen Überdichten von CDM in den Halos, vielmehr setzt sich gravitative Strukturbildung auf immer kleinere Skalen fort. Numerisch kann keine Massen-Schwelle berechnet werden, unterhalb derer keine CDM-Strukturen mehr gravitativ gebildet werden. Die Kenntnis der lokalen Überdichten in den CDM-Wolken und die Verteilung der CDM-Wolken ist jedoch für Experimente zum direkten und indirekten Nachweis von CDM-Teilchen essentiell. Aus den lokalen Überdichten folgen für Experimente zum direkten Nachweis die einfallende Stromdichten der CDM-Teilchen und für Experimente zum indirekten Nachweis die Stromdichte der Annihilationsprodukte. Außerdem können die lokalen Überdichten als Gravitationslinsen wirken. In dieser Arbeit werden Massen Schwellen analytisch berechnet, unterhalb derer akustische Störungen in CDM nicht mehr zur gravitativen Strukturbildung beitragen können. Das Massen-Spektrum von lokalen Überdichten ist nach unten durch zwei unterschiedliche Mechanismen beschränkt: (1) Während der kinetischen Entkopplung formieren sich Nichtgleichgewichtsprozesse, die sich kollektiv als Reihungsphänomene konstituieren. Im lineare Regime sind dies die Volumenviskosität, die Scherungsviskosität und die Wärmeleitung. Die dissipativen Prozesse deponieren Energie und Impuls der akustischen Störungen in die Ebene senkrecht zur Ausbreitungsrichtung der Störungen und schmieren diese so aus. (II) Nach dem kinetischen Entkopplungsprozeß strömt CDM frei auf Geodäten. Dies ermöglicht einen Strom von Teilchen von überdichten in unterdichte Regionen, so daß die Amplituden der lokalen Überdichten weiter gedämpft werden. Die lokalen Transportkoeffizienten in (1) werden durch einen legitimen Vergleich von hydrodynamischer und kinetischer Beschreibung schwach dissipativer Prozesse gewonnen. Dissipative Prozesse induzieren eine Dämpfungsmasse Mc ungefähr gleich 10 hoch minus 9 M in SUSY-CDM und beschränken damit das Spektrum akustischer Störungen in SUSY-CDM. Freies Strömen (II) von CDM-Teilchen auf Geodäten induziert eine weitere Dämpfungsmasse M fs ungefähr gleich 10 hoch minus 6 M in SUSY-CDM, wobei das berechnete M d als Anfangswert dient. Die berechneten Schwellen liefern konsistente Schranken für numerische Simulationen, die weit unterhalb des momentanen numerischen Auflösungsvermögens liegen. Weiterhin folgt aus den Schwellen die Masse der ersten rein gravitativ gebundenen CDM-Wolken. Aus diesen bilden sich im Rahmen der hierarchischen Strukturbildung größere Substrukturen bis hin zu den heute vorhandenen CDM-Halos.