Regulation of the MAD1 promoter by G-CSF

MAD family proteins are transcriptional repressors that antagonize the functions of MYC oncoproteins. In particular, MAD1 has been demonstrated to interfere with MYC-induced proliferation, transformation and apoptosis. The MAD1 gene is expressed in distinct patterns, mainly associated with differentiation and quiescence. We observed that MAD1 is directly activated by G-CSF in promyelocytic cell lines. To investigate the transcriptional regulation of the human MAD1 gene, we have cloned and characterized its promoter. A region of high homology between the MAD1 orthologs of human, mouse and rat contains the core promoter, marked by open chromatin, high GC content and the lack of a TATA box. Using deletion constructs we identified two CCAAT-boxes occupied by C/EBPα and β in the homology region that mediate responsiveness to G-CSF receptor signaling. The necessary signals include the activation of STAT3 and the RAS/RAF/ERK pathway. STAT3 does not bind directly to promoter DNA, but is recruited by C/EBPβ. In summary, our studies provide a first analysis of the MAD1 promoter and suggest STAT3 functions as a C/EBPβ cofactor in the regulation of the MAD1 gene. Our findings provide the base for the characterization of additional signal transduction pathways that control the expression of MAD1

Retrospective, controlled observational case study of patients with central retinal vein occlusion and initially low visual acuity treated with an intravitreal dexamethasone implant

Background Patients with initially low visual acuity were excluded from the therapy approval studies for retinal vein occlusion. But up to 28 % of patients presenting with central retinal vein occlusion have a baseline BCVA of less than 34 ETDRS letters (0.1). The purpose of our study was to assess visual acuity and central retinal thickness in patients suffering from central retinal vein occlusion and low visual acuity (<0.1) in comparison to patients with visual acuity (≥0.1) treated with Dexamethasone implant 0.7 mg for macular edema. Methods Retrospective, controlled observational case study of 30 eyes with macular edema secondary to central retinal vein occlusion, which were treated with a dexamethasone implantation. Visual acuity, central retinal thickness and intraocular pressure were measured monthly. Analyses were performed separately for eyes with visual acuity <0.1 and ≥0.1. Results Two months post intervention, visual acuity improved only marginally from 0.05 to 0.07 (1 month; p = 0,065) and to 0.08 (2 months; p = 0,2) in patients with low visual acuity as compared to patients with visual acuity ≥0.1 with an improvement from 0.33 to 0.47 (1 month; p = 0,005) and to 0.49 (2 months; p = 0,003). The central retinal thickness, however, was reduced in both groups, falling from 694 to 344 μm (1 month; p = 0.003,) to 361 μm (2 months; p = 0,002) and to 415 μm (3 months; p = 0,004) in the low visual acuity group and from 634 to 315 μm (1 month; p < 0,001) and to 343 μm (2 months; p = 0,001) in the visual acuity group ≥0.1. Absence of visual acuity improvement was related to macular ischemia. Conclusions In patients with central retinal vein occlusion and initially low visual acuity, a dexamethasone implantation can lead to an important reduction of central retinal thickness but may be of limited use to increase visual acuity

Ti/Al multi-layered sheets: Accumulative roll bonding (Part A)

Co-deformation of Al and Ti by accumulative roll bonding (ARB) with intermediate heat treatments is utilized to prepare multi-layered Ti/Al sheets. These sheets show a high specific strength due to the activation of various hardening mechanisms imposed during deformation, such as: hardening by grain refinement, work hardening and phase boundary hardening. The latter is even enhanced by the confinement of the layers during deformation. The evolution of the microstructure with a special focus on grain refinement and structural integrity is traced, and the correlation to the mechanical properties is shown

German Catalysis Society Meeting: Exploring the Various Facets of Catalysis

Tradition is tradition: Already for the 52nd time the Annual Meeting of the German Catalysis Society (GeCatS) took place from March 13th to 15th, 2019. Following its long‐standing tradition, the meeting was organized in the Neue Weimarhalle in the beautiful city of Weimar, Thuringia

German Catalysis Society Meeting: Exploring the Various Facets of Catalysis

Tradition is tradition: Already for the 52nd time the Annual Meeting of the German Catalysis Society (GeCatS) took place from March 13th to 15th, 2019. Following its long‐standing tradition, the meeting was organized in the Neue Weimarhalle in the beautiful city of Weimar, Thuringia

Entsiegelungspotenziale zur Wiederherstellung von Bodenfunktionen und zur Klimaanpassung: Vorschläge für eine verbesserte Nutzung aus fachlicher, rechtlicher und förderpolitischer Sicht

Entsiegelungsmaßnahmen können zum Bodenschutz und zur Bereitstellung von Ökosystemleistungen, zur Klimaanpassung sowie zu Land Degradation Neutrality (SDG 15.3) beitragen. Dem hohen Nutzen von Entsiegelungsmaßnahmen stehen allerdings die geringe Verfügbarkeit von Entsiegelungspotenzialen sowie diverse Umsetzungshemmnisse für Entsiegelungsmaßnahmen gegenüber. Aus rechtlicher Sicht gibt es verschiedene Instrumente, um Entsiegelungspotenziale zu aktivieren. Entsprechende Vorschriften sind in den Bereichen des Bau- und Bodenschutzrechts, aber auch des Wasser-, Naturschutz- und Planungsrechts zu finden. Die gesetzlichen Regelungen müssen aber besser umgesetzt und optimiert werden, um tatsächlich zu mehr Entsiegelungen in der Praxis beizutragen. Aus förderpolitischer Sicht sind vor allem Förderprogramme auf kommunaler und Landesebene, ergänzend auch auf Bundes- und EU-Ebene, relevant. Neben den Programmkulissen Städtebauförderung, Klimaanpassung, Brachenabriss und Quartiersaufwertung kann auf ein breites Spektrum informeller Anreizinstrumente, bspw. Beratungsangebote, zurückgegriffen werden