The Amateur Sky Survey Mark III Project

The Amateur Sky Survey (TASS) is a loose confederation of amateur and professional astronomers. We describe the design and construction of our Mark III system, a set of wide-field drift-scan CCD cameras which monitor the celestial equator down to thirteenth magnitude in several passbands. We explain the methods by which images are gathered, processed, and reduced into lists of stellar positions and magnitudes. Over the period October, 1996, to November, 1998, we compiled a large database of photometric measurements. One of our results is the "tenxcat" catalog, which contains measurements on the standard Johnson-Cousins system for 367,241 stars; it contains links to the light curves of these stars as well.Comment: 20 pages, including 4 figures; additional JPEG files for Figures 1, 2. Submitted to PAS

Aspirin, but Not Tirofiban Displays Protective Effects in Endotoxin Induced Lung Injury

Background Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. Recruitment of neutrophils into the lungs, regarded as a key mechanism in progression of ALI, depends on signaling between neutrophils and platelets. Consequently we explored the effect of platelet-targeted aspirin and tirofiban treatment in endotoxin induced acute lung injury Methods C57Bl/6 mice were exposed to aerosolized LPS (500 mu g/ml) for 30min and treated with Aspirin (100 mu g/g bodyweight via intraperitoneal injection, 30 min before or 1 hour after LPS inhalation) or Tirofiban (0.5 mu g/g bodyweight via tail vein injection 30 min before or 1 hour after LPS inhalation). The count of alveolar, interstitial, and intravascular neutrophils was assessed 4h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and protein content in the BAL fluid. Results Aspirin both before and after LPS inhalation reduced neutrophil influx into the lung and lung permeability indicating the protective role of Aspirin in ALI. Tirofiban, however, did not alter neutrophil recruitment after LPS inhalation. Release of platelet-derived chemokines CCL5 and PF4 and neutrophil extracellular traps was reduced by Aspirin but not by Tirofiban. Conclusion Aspirin, but not Tirofiban reduces neutrophil recruitment and displays protective effects during endotoxin induced lung injury

Plasmacytoid predendritic cells initiate psoriasis through interferon-α production

Psoriasis is one of the most common T cell–mediated autoimmune diseases in humans. Although a role for the innate immune system in driving the autoimmune T cell cascade has been proposed, its nature remains elusive. We show that plasmacytoid predendritic cells (PDCs), the natural interferon (IFN)-α–producing cells, infiltrate the skin of psoriatic patients and become activated to produce IFN-α early during disease formation. In a xenograft model of human psoriasis, we demonstrate that blocking IFN-α signaling or inhibiting the ability of PDCs to produce IFN-α prevented the T cell–dependent development of psoriasis. Furthermore, IFN-α reconstitution experiments demonstrated that PDC-derived IFN-α is essential to drive the development of psoriasis in vivo. These findings uncover a novel innate immune pathway for triggering a common human autoimmune disease and suggest that PDCs and PDC-derived IFN-α represent potential early targets for the treatment of psoriasis

Diagnostic challenges in a child with early onset desmoplastic medulloblastoma and homozygous variants in MSH2 and MSH6

International audienceConstitutional mismatch repair deficiency (CMMRD) is an autosomal recessively inherited childhood cancer susceptibility syndrome caused by biallelic germline mutations in one of the mismatch repair (MMR

IFABP levels predict visceral malperfusion in the first hours after open thoracoabdominal aortic repair

IntroductionIntestinal ischemia after open thoracoabdominal aortic repairs, is a rare but devastating complication, associated with high mortality. Notoriously challenging to diagnose, visceral malperfusion necessitates immediate surgical attention. Intestinal fatty acid-binding protein (IFABP) has been proposed as a biomarker for the diagnosis of intestinal wall damage. In this prospectively conducted, observational study we evaluated the diagnostic capacity of IFABP levels in patients' serum and their correlation with visceral malperfusion.Methods23 patients undergoing open thoracoabdominal aortic repairs were included in this study and 8 of them were diagnosed postoperatively with visceral malperfusion—defined as a partial or complete thrombotic occlusion of the superior mesenteric artery and/or the coeliac trunk. IFABP levels and laboratory parameters often associated with intestinal ischemia (leucocytes, CRP, PCT and lactate) were measured at baseline, directly postoperatively, and at 12, 24 and 48 h after surgery. Postoperative visceral malperfusion—as revealed in CT angiography—was assessed and the predictive ability of IFABP levels to detect visceral malperfusion was evaluated with receiver-operator curve analysis.ResultsPatients with visceral malperfusion had a relevant risk for a fatal outcome (p = .001). IFABP levels were significantly elevated directly postoperatively and at 12 h after surgery in cases of visceral malperfusion. High IFABP concentrations in serum detected visceral malperfusion accurately during the first 12 h after surgery, with the maximum diagnostic ability achieved immediately after surgery (AUC 1, Sensitivity 100%, Specificity 100%, p < .001).ConclusionWe conclude, that IFABP measurements during the first postoperative hours after open thoracoabdominal aortic surgery can be a valuable tool for reliable and timely detection of visceral malperfusion

Loss of Pax5 exploits sca1-BCR-ABLp190 susceptibility to confer the metabolic shift essential for pB-ALL

Preleukemic clones carrying BCR-ABLp190 oncogenic lesions are found in neonatal cord blood, where the majority of preleukemic carriers do not convert into precursor B-cell acute lymphoblastic leukemia (pB-ALL). However, the critical question of how these preleukemic cells transform into pB-ALL remains undefined. Here, we model a BCR-ABLp190 preleukemic state and show that limiting BCR-ABLp190 expression to hematopoietic stem/progenitor cells (HS/PC) in mice (Sca1-BCR-ABLp190) causes pB-ALL at low penetrance, which resembles the human disease. pB-ALL blast cells were BCR-ABL–negative and transcriptionally similar to pro-B/pre-B cells, suggesting disease onset upon reduced Pax5 functionality. Consistent with this, double Sca1-BCR-ABLp190+Pax5+/− mice developed pB-ALL with shorter latencies, 90% incidence, and accumulation of genomic alterations in the remaining wild-type Pax5 allele. Mechanistically, the Pax5-deficient leukemic pro-B cells exhibited a metabolic switch toward increased glucose utilization and energy metabolism. Transcriptome analysis revealed that metabolic genes (IDH1, G6PC3, GAPDH, PGK1, MYC, ENO1, ACO1) were upregulated in Pax5-deficient leukemic cells, and a similar metabolic signature could be observed in human leukemia. Our studies unveil the first in vivo evidence that the combination between Sca1-BCR-ABLp190 and metabolic reprogramming imposed by reduced Pax5 expression is sufficient for pB-ALL development. These findings might help to prevent conversion of BCR-ABLp190 preleukemic cells.J. Hauer has been supported by the German Cancer Aid (Project 110997 and Translational Oncology Program 70112951), the German Jose Carreras Foundation (DJCLS 02R/2016), the Kinderkrebsstiftung (2016/17), and the "Elterninitiative Kinderkrebstiftung e.V." S. Ginzel has been supported by a scholarship of the Hochschule Bonn-Rhein-Sieg. M. Muschen is an HHMI Faculty Scholar (HHMI- € 55108547) and supported by NIH/NCI through an Outstanding Investigator Award (R35CA197628, R01CA137060, R01CA157644, R01CA172558, R01CA213138) to M. Muschen, a Wellcome Trust Senior Investigator Award, € the Leukemia and Lymphoma Society, the Norman and Sadie Lee Foundation (for Pediatric Cancer, to M. Muschen), and the Dr. Ralph and Marian € Falk Medical Research Trust (to M. Muschen), Cancer Research Institute € through a Clinic and Laboratory Integration Program grant (to M. Muschen) € and the California Institute for Regenerative Medicine (CIRM) through DISC2-10061. A. Borkhardt has been supported by the German Children's Cancer Foundation and the Federal Ministry of Education and Research, Bonn, Germany. Research in I. Sanchez-García's group is partially supported by FEDER and by MINECO (SAF2012-32810, SAF2015-64420-R, and Red de Excelencia Consolider OncoBIO SAF2014-57791-REDC), Instituto de Salud Carlos III (PIE14/00066), ISCIII- Plan de Ayudas IBSAL 2015 Proyectos Integrados (IBY15/00003), by Junta de Castilla y Leon (BIO/SA51/15, CSI001U14, UIC-017, and CSI001U16), Fundacion Inocente Inocente and by the ARIMMORA project [European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 282891]. I. Sanchez-García's lab is a member of the EuroSyStem and the DECIDE Network funded by the European Union under the FP7 program. A. Borkhardt and I. Sanchez-García have been supported by the German Carreras Foundation (DJCLS R13/26). Research in C. Vicente-Duenas's ~ group is partially supported by FEDER, Ministerio de Economía y Competitividad ("Miguel Servet" Grant - CP14/00082 - AES 2013-2016) and (PI17/00167) from the Instituto de Salud Carlos III. A. Martín-Lorenzo and G. Rodríguez-Hernandez were supported by FSE-Conserjería de Educacion de la Junta de Castilla y Leon (CSI001-13 and CSI001-15, respectively). F. Auer was supported by a Deutsche Forschungsgemeinschaft (DFG) fellowship (AU 525/1-1)

The Maastricht Acquisition Platform for Studying Mechanisms of Cell–Matrix Crosstalk (MAPEX):An Interdisciplinary and Systems Approach towards Understanding Thoracic Aortic Disease

Current management guidelines for ascending thoracic aortic aneurysms (aTAA) recommend intervention once ascending or sinus diameter reaches 5–5.5 cm or shows a growth rate of &gt;0.5 cm/year estimated from echo/CT/MRI. However, many aTAA dissections (aTAAD) occur in vessels with diameters below the surgical intervention threshold of &lt;55 mm. Moreover, during aTAA repair surgeons observe and experience considerable variations in tissue strength, thickness, and stiffness that appear not fully explained by patient risk factors. To improve the understanding of aTAA pathophysiology, we established a multi-disciplinary research infrastructure: The Maastricht acquisition platform for studying mechanisms of tissue–cell crosstalk (MAPEX). The explicit scientific focus of the platform is on the dynamic interactions between vascular smooth muscle cells and extracellular matrix (i.e., cell–matrix crosstalk), which play an essential role in aortic wall mechanical homeostasis. Accordingly, we consider pathophysiological influences of wall shear stress, wall stress, and smooth muscle cell phenotypic diversity and modulation. Co-registrations of hemodynamics and deep phenotyping at the histological and cell biology level are key innovations of our platform and are critical for understanding aneurysm formation and dissection at a fundamental level. The MAPEX platform enables the interpretation of the data in a well-defined clinical context and therefore has real potential for narrowing existing knowledge gaps. A better understanding of aortic mechanical homeostasis and its derangement may ultimately improve diagnostic and prognostic possibilities to identify and treat symptomatic and asymptomatic patients with existing and developing aneurysms.</p