Shape: A 3D Modeling Tool for Astrophysics.

We present a flexible interactive 3D morpho-kinematical modeling application for astrophysics. Compared to other systems, our application reduces the restrictions on the physical assumptions, data type, and amount that is required for a reconstruction of an object's morphology. It is one of the first publicly available tools to apply interactive graphics to astrophysical modeling. The tool allows astrophysicists to provide a priori knowledge about the object by interactively defining 3D structural elements. By direct comparison of model prediction with observational data, model parameters can then be automatically optimized to fit the observation. The tool has already been successfully used in a number of astrophysical research projects.

Primary angioplasty for any patient with ST-elevation myocardial infarction? Guideline-adherent feasibility and impact on mortality in a rural infarction network.

AIMS: The aim of this study was to assess the guideline-adherent feasibility of area-wide primary angioplasty in rural German surroundings and its impact on reperfusion and outcome in patients with acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: All consecutive patients with acute STEMI (n = 347) admitted to any of the hospitals (5 non invasive and 1 invasive with established 24 h/7 days primary angioplasty service) in a 350.000 inhabitant rural area during the year 2002 (n = 184) and 2005 (n = 163) were included in this registry. In 2002, emergency medical services transferred acute STEMI patients to the nearest emergency room, where reperfusion therapy (fibrinolysis or primary angioplasty) was organised. In 2005, all patients were transferred directly to the cathlab bypassing any emergency room when possible. Primary angioplasty increased from 53 to 89% (p < 0.01), fibrinolysis decreased from 27 to 2% (p < 0.01) and the no revascularisation rate from 21 to 9% (p < 0.01). Onset of pain to balloon time in primary angioplasty was reduced from median 339 to 191 min (p < 0.01), median first medical contact to balloon time in 2005 was 101 min. Overall, 6-month mortality decreased from 19 to 10% (p = 0.03). CONCLUSIONS: After transition to a uniform primary angioplasty concept, an increase in overall reperfusion rates and a decrease in time delays could be observed in a rural German infarction network.

bZIP-Type transcription factors CREB and OASIS bind and stimulate the promoter of the mammalian transcription factor GCMa/Gcm1 in trophoblast cells.

One of the master regulators of placental cell fusion in mammals leading to multi-nucleated syncytiotrophoblasts is the transcription factor GCMa. Recently, we proved that the cAMP-driven protein kinase A signaling pathway is fundamental for up-regulation of GCMa transcript levels and protein stability. Here, we show that Transducer of Regulated CREB activity (TORC1), the human co-activator of cAMP response element-binding protein (CREB), but not a dominant-negative CREB mutant, significantly up-regulates the GCMa promoter. We identified potential cAMP response element (CRE)-binding sites within the GCMa promoter upstream of the transcriptional start site. Only the CRE site at -1337 interacted strongly with CREB in promoter mapping experiments. The characterization of GCMa promoter mutants and additional bZIP-type family members demonstrated that also old astrocyte specifically-induced substance (OASIS) is able to stimulate GCMa transcription. Knockdown of endogenous CREB or OASIS in BeWo cells decreased endogenous GCMa mRNA level and activity. Overexpression of TORC1 or OASIS in choriocarcinoma cells led to placental cell fusion, accompanied by placental expression of gap junction forming protein connexin-43. Further, we show that CREB expression is replaced by OASIS expression around E12.5 suggesting that a sequential order of bZIP-type family members ensures a high rate of GCMa transcription throughout placentation.

Identification of integrin-alpha4, Rb1, and syncytin a as murine placental target genes of the transcription factor GCMa/Gcm1.

Members of the GCM (glial cells missing) transcription factor family have been shown to act as master regulators in different cells during mammalian and fly development being responsible for processes including gliogenesis, hematopoiesis, placental formation, and development of the parathyroidea. In the central nervous system of flies, several target genes for GCM have been reported, namely repo, pointed, and tramtrack. In mammals, two GCM genes are known (GCMa and GCMb), but the knowledge of their target genes is very limited. Here, we present for the first time a global approach aimed to identify GCMa target genes. We found 66 genes up-regulated and 11 genes down-regulated in GCMa-deficient chorionic tissue of mice at embryonic day 9.5. Moreover, we verified by quantitative reverse transcription-PCR all 11 down-regulated genes. The two most strongly down-regulated genes, integrin-alpha4 and retinoblastoma (Rb1), were further analyzed by promoter studies. Additionally, we identified down-regulation of the murine syncytin A gene, which is fundamental for syncytiotrophoblast formation. Finally, we proved strong down-regulation of integrin-alpha4 and Rb1 transcript levels by in situ hybridization in murine GCMa-deficient placentae at embryonic day 9.5. Our data demonstrate for the first time that genes encoding key regulators of placental tissue formation and architecture are regulated by GCMa.

Casein kinase 2-dependent serine phosphorylation of MuSK regulates acetylcholine receptor aggregation at the neuromuscular junction.

The release of Agrin by motoneurons activates the muscle-specific receptor tyrosine kinase (MuSK) as the main organizer of subsynaptic specializations at the neuromuscular junction. MuSK downstream signaling is largely undefined. Here we show that protein kinase CK2 interacts and colocalizes with MuSK at post-synaptic specializations. We observed CK2-mediated phosphorylation of serine residues within the kinase insert (KI) of MuSK. Inhibition or knockdown of CK2, or exchange of phosphorylatable serines by alanines within the KI of MuSK, impaired acetylcholine receptor (AChR) clustering, whereas their substitution by residues that imitate constitutive phosphorylation led to aggregation of AChRs even in the presence of CK2 inhibitors. Impairment of AChR cluster formation after replacement of MuSK KI with KIs of other receptor tyrosine kinases correlates with potential CK2-dependent serine phosphorylation within KIs. MuSK activity was unchanged but AChR stability decreased in the presence of CK2 inhibitors. Muscle-specific CK2beta knockout mice develop a myasthenic phenotype due to impaired muscle endplate structure and function. This is the first description of a regulatory cross-talk between MuSK and CK2 and of a role for the KI of the receptor tyrosine kinase MuSK for the development of subsynaptic specializations.

Value of intravascular ultrasound for endovascular stent-graft placement in aortic dissection and aneurysm.

BACKGROUND: Endovascular stent-graft placement is a new concept for the treatment of aortic dissection and aneurysm. Intravascular ultrasound (IVUS) with established diagnostic features may be instrumental in guiding endovascular procedures. METHODS: We performed IVUS and digital angiography before, during, and after implantation of 47 stent grafts in 40 patients with Stanford type B dissection (26 patients, 28 stent grafts), thoracic aneurysm (9 patients, 11 stent grafts), and abdominal aneurysm (5 patients, 8 stent grafts). RESULTS: IVUS could clearly identify the aortic anatomy and differentiate between true and false lumen in all cases of dissection. In four patients with type B dissection extending from the thoracic to the abdominal aorta the true lumen was exclusively identified by IVUS, and thus, essential for safe execution of the procedure. In another patient stent-graft placement in the aorta was optimized by covering a second entry detected by IVUS, but undetected by angiography. The site of stent implantation, the true and false lumen, as well as entry and reentry were always identified in both thoracic and abdominal aorta. In comparison with angiography, IVUS information led to additional balloon molding due to incomplete stent apposition in seven cases. CONCLUSIONS: As an adjunctive imaging modality IVUS is likely to improve stent-graft placement in aortic type B dissection, especially in patients with abdominal extension.