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The short-lived African killifishNothobranchius furzerilives in seasonal freshwater ponds and has evolved remarkable traits to survive in this limited environment. One of those traits is a genetic XX/XY sex-determination system, which ensures an equal distribution of both sexes. Comparisons of female and male genomic sequences identified the Y-chromosomal copy of the TGF-β family membergdf6as the candidate male sex-determining (SD) gene, which was namedgdf6Yin contrast to the X-chromosomal allelegdf6X. CRISPR/Cas9-mediated inactivation ofgdf6YinN. furzeriled to a complete male-to-female sex reversal in XY animals. The homozygous inactivation ofgdf6Xon the other hand led to a detrimental phenotype post-hatching. This phenotype was compensated bygdf6Y, revealing that the latter became the SD gene while retaining at least some of its originalgdf6function.Gdf6Yis expressed in testicular somatic cells already prior to hatching, where it represses the germ cell-intrinsic feminizing genefoxl2l. We have identified components of the TGF-β signaling pathway, especially the inhibitor of DNA binding genesid1/2/3, and the mRNA decay activatorzfp36l2, as Gdf6Y targets. We conclude that Gdf6Y exerts its function as the male sex-determining gene by suppressing female-specific genes in the developing gonad of maleN. furzeri. more...

The coordination of transcription through enhancers and promoters is a fundamental process that has a central role in development and disease 1–3. Convergent transcription, i.e., the collision of sense and antisense transcription, is ubiquitous in mammalian genomes 4–8 and believed to diminish RNA expression 9,10. Recently, antisense transcription downstream of promoters was found to be surprisingly prevalent 11–13. However, functional characteristics of promoters with convergent transcription are unknown. Here, we show that convergent transcription marks an unexpectedly cooperative promoter constellation we call super-promoters. By assessing transcriptional dynamic systems, we identified strongly cooperative constituent promoters that are connected through a distinct chromatin structure. Within these super-promoter constellations transcription factors can regulate both constituting promoters by binding to only one of them. Super-promoters comprise about a fourth of all active transcript starts and initiate 5’-overlapping antisense RNAs, an RNA class previously believed to be rare 4. Visualization of nascent RNA molecules provides evidence for convergent co-transcription at these loci. Our results demonstrate that super-promoters substantially expand the cis-regulatory repertoire and reveal limitations of the standing model of transcription interference. Together, our study revises the promoter architecture of many genes and calls for adjusting the promoter concept. more...

Teams sind formelle Gruppen, insoweit treffen die dort gemachten Ausfuhrungen uneingeschrankt auch auf das Verhalten und die Funktionsweise von Teams zu.

Selbstwertgefuhl entsteht aus der Wahrnehmung und Beurteilung der eigenen Person. Es ist damit das Ergebnis des Selbstbildes, das ein Mensch von sich hat, wohingegen die Wahrnehmung und Beurteilung durch andere das Fremdbild anhand bestimmter Kriterien zeichnen. more...

Die Gesundheit eines Menschen ist das hochste Gut. Wie an jedem Arbeitsplatz drohen auch Sicherheitsmitarbeitern vielfaltige Gefahren bei der Ausubung ihres Dienstes. Daher hat der Gesetzgeber verpflichtende Regeln festgelegt, um die Gesundheit von Arbeitnehmern an ihrem Arbeitsplatz bestmoglich zu schutzen. more...

Das Grundgesetz der Bundesrepublik Deutschland gehort als Verfassung unseres Landes zum Verfassungsrecht und steht als ranghochstes Gesetz uber allen anderen Rechtsnormen. Somit gibt es, wie bei einem Bilderrahmen, den rechtlichen Rahmen vor, in dem sich Recht, Gesetz und Burger bewegen. Im Gegensatz zu allen anderen Gesetzestexten ist es nicht in Paragrafen (§), sondern in Artikel (Art.) untergliedert. more...

Wie eingangs beschrieben, machen viele Einsatzszenarien ein gemeinsames Handeln mit unterschiedlichen Kraften notwendig. Dabei haben alle diese Krafte eigene Einsatzgrundsatze, Informations- und Kommunikationswege und Befugnisse. Alle Aktivitaten der unterschiedlichen Bereiche mussen unter Berucksichtigung der verschiedenen Einsatzgrundsatze und Befugnisse koordiniert und die Informations- und Kommunikationswege zusammengefuhrt werden. more...

We present a time-series analysis of the asynchronous polar CD Ind, using fast cadence TESS photometry. A similar analysis is performed using ground based photometry of BY Cam. These asynchronous polars show remarkably similar light curves and enigmatic timing characteristics. A pair of competing models for the assignment of the white dwarf spin period have been presented for both binaries. TESS allows for the breaking of this degeneracy by providing continuous coverage over several beat-cycles. The CD Ind light curve displays a super-orbital period of 7.2 days due to beat-phased modulation of the accretion rate onto a permanently visible spot. This (main) accretion region is active for 3/4 of the beat-cycle. The dominant photometric signal is at 109.654(4) min and is identified as a side-band related to the white dwarf spin and the binary orbit, analogous to that found in BY Cam. We obtain the white dwarf spin period of CD Ind as 110.820(5) min and an orbital period of 111.952(8) min. The TESS light curve supports a pole-switching scenario for CD Ind, with a total of 4 alternating, and oppositely positioned accretion regions. This inclination of CD Ind is estimated as i = 65 ° ± 10 ° . One accretion region remains in view of the observer at all times. In addition, two pulsed accretion spots each accrete for just less than 1/2 of the beat-cycle. These alternating spots are orthogonal to the main accretion region (which is always in view), and are found to be roughly 180 ° apart in longitude. Finally, since the mean flux drops by a factor of 2 for about 1/4 of the beat-cycle and the dominant accretion region turns off during this time, we hypothesize the existence of a fourth (permanently hidden) accretion region opposite to the one permanently in view. Photometric models for the 2- and 4-pole accretion configurations are developed and only the 4-pole model is consistent with the observed periodogram for CD Ind. We conclude that complex magnetic fields affect accretion flow onto these white dwarf stars. In particular, the magnetic field of the white dwarf in both of these binaries is inconsistent with either a centered or an offset dipole configuration. more...

Accurate modeling of the reaction rate of char particles is decisive for precise computational fluid dynamics simulations of gasifiers. Pore diffusion limits the reaction rate at medium temperatures and strongly depends on the pore size. In most of the present research, pore diffusion is either completely neglected or modeled with a single mean pore size. This work introduces a particle model with two pore sizes. Large pores transport the reactant gases into the particle and distribute them to small pores, in which the heterogeneous reactions take place. This approach is compared with a simpler model with a single mean pore size. The particle and the small pores are discretized by an appropriate number of elements, which allows an exact numerical calculation of the concentration profile for nth-order reactions. Both models are implemented into a two-dimensional computational fluid dynamics simulation of a lab-scale fixed bed gasifier. Simulations and experiments are carried out for 1.362 mm, 0.815 mm, and 0.458 mm sized particles, which are gasified with carbon dioxide and steam at 1200 °C and 1.1 bar total pressure. The reactant gases can penetrate smaller particles more easily. However, the measured product gas flow is independent of the particle size although the reactions take place under pore diffusion limitation. Only the proposed model with two pore sizes is able to reproduce the experiments adequately. However, it causes a significant extra computational effort. more...

In recent years, our web-atlas at www.TargetGeneReg.org has enabled many researchers to uncover new biological insights and to identify novel regulatory mechanisms that affect p53 and the cell cycle – signaling pathways that are frequently dysregulated in diseases like cancer. Here, we provide a substantial upgrade of the database that comprises an extension to include non-coding genes and the transcription factors ΔNp63 and RFX7. TargetGeneReg 2.0 combines gene expression profiling and transcription factor DNA binding data to determine, for each gene, the response to p53, ΔNp63, and cell cycle signaling. It can be used to dissect common, cell type, and treatment-specific effects, identify the most promising candidates, and validate findings. We demonstrate the increased power and more intuitive layout of the resource using realistic examples. more...