Zusammensetzung des Begleitinfiltrats und Koexpression von B-Zell-Transkriptionsfaktoren in follikulären Lymphomen

Follikuläre Lympome sind die zweithäufigsten Lymphome in der westlichen Welt, mit bisher nur schwer vorhersagbarem klinischen Verlauf. Da follikuläre Lymphome morphologisch Keimzentren immitieren, wurde im Rahmen dieser Arbeit der Einfluss von Regulationsfaktoren der physiologischen Keimzentrumsreaktion auf den Verlauf des follikulären Lymphoms untersucht. insbeondere wurde die Zusammensetzung des T-Zell-Begleitinfiltrats, sowie die Expression des Transkriptionsfaktors Mum1 untersucht

The Extended Star Formation History of the Andromeda Spheroid at 35 Kpc on the Minor Axis

Using the HST ACS, we have obtained deep optical images reaching well below the oldest main sequence turnoff in fields on the southeast minor-axis of the Andromeda Galaxy, 35 kpc from the nucleus. These data probe the star formation history in the extended halo of Andromeda -- that region beyond 30 kpc that appears both chemically and morphologically distinct from the metal-rich, highly-disturbed inner spheroid. The present data, together with our previous data for fields at 11 and 21 kpc, do not show a simple trend toward older ages and lower metallicities, as one might expect for populations further removed from the obvious disturbances of the inner spheroid. Specifically, the mean ages and [Fe/H] values at 11 kpc, 21 kpc, and 35 kpc are 9.7 Gyr and -0.65, 11.0 Gyr and -0.87, and 10.5 Gyr and -0.98, respectively. In the best-fit model of the 35 kpc population, one third of the stars are younger than 10 Gyr, while only ~10% of the stars are truly ancient and metal-poor. The extended halo thus exhibits clear evidence of its hierarchical assembly, and the contribution from any classical halo formed via early monolithic collapse must be small.Comment: Accepted for publication in The Astrophysical Journal Letters. 4 pages, latex, 2 color figure

Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research

The SPLASH Survey: A Spectroscopic Portrait of Andromeda's Giant Southern Stream

The giant southern stream (GSS) is the most prominent tidal debris feature in M31's stellar halo. The GSS is composed of a relatively metal-rich, high surface-brightness "core" and a lower metallicity, lower surface brightness "envelope." We present Keck/DEIMOS spectroscopy of red giant stars in six fields in the vicinity of M31's GSS and one field on Stream C, an arc-like feature on M31's SE minor axis at R=60 kpc. Several GSS-related findings and measurements are presented here. We present the innermost kinematical detection of the GSS core to date (R=17 kpc). This field also contains the continuation of a second kinematically cold component originally seen in a GSS core field at R=21 kpc. The velocity gradients of the GSS and the second component in the combined data set are parallel over a radial range of 7 kpc, suggesting a possible bifurcation in the line-of-sight velocities of GSS stars. We also present the first kinematical detection of substructure in the GSS envelope. Using kinematically identified samples, we show that the envelope debris has a ~0.7 dex lower mean photometric metallicity and possibly higher intrinsic velocity dispersion than the GSS core. The GSS is also identified in the field of the M31 dSph satellite And I; the GSS in this field has a metallicity distribution identical to that of the GSS core. We confirm the presence of two kinematically cold components in Stream C, and measure intrinsic velocity dispersions of ~10 and ~4 km/s. This compilation of the kinematical (mean velocity, intrinsic velocity dispersion) and chemical properties of stars in the GSS core and envelope, coupled with published surface brightness measurements and wide-area star-count maps, will improve constraints on the orbit and internal structure of the dwarf satellite progenitor.Comment: Accepted for publication in Ap

The Panchromatic Hubble Andromeda Treasury: Triangulum Extended Region (PHATTER). V. The Structure of M33 in Resolved Stellar Populations

We present a detailed analysis of the the structure of the Local Group flocculent spiral galaxy M33, as measured using the Panchromatic Hubble Andromeda Treasury Triangulum Extended Region (PHATTER) survey. Leveraging the multiwavelength coverage of PHATTER, we find that the oldest populations are dominated by a smooth exponential disk with two distinct spiral arms and a classical central bar $-$ completely distinct from what is seen in broadband optical imaging, and the first-ever confirmation of a bar in M33. We estimate a bar extent of $\sim$1 kpc. The two spiral arms are asymmetric in orientation and strength, and likely represent the innermost impact of the recent tidal interaction responsible for M33's warp at larger scales. The flocculent multi-armed morphology for which M33 is known is only visible in the young upper main sequence population, which closely tracks the morphology of the ISM. We investigate the stability of M33's disk, finding $Q{\sim}1$ over the majority of the disk. We fit multiple components to the old stellar density distribution and find that, when considering recent stellar kinematics, M33's bulk structure favors the inclusion of an accreted halo component, modeled as a broken power-law. The best-fit halo model has an outer power-law index of $-$3 and accurately describes observational evidence of M33's stellar halo from both resolved stellar spectroscopy in the disk and its stellar populations at large radius. Integrating this profile yields a total halo stellar mass of ${\sim}5{\times}10^8\ M_{\odot}$, giving a total stellar halo mass fraction of 16%, most of which resides in the innermost 2.5 kpc.Comment: 31 pages, 17 figures, 5 tables, Accepted for publication in Ap

Molecular Cytogenetic Profiling Reveals Similarities and Differences Between Localized Nodal and Systemic Follicular Lymphomas

Recently, we have developed novel highly promising gene expression (GE) classifiers discriminating localized nodal (LFL) from systemic follicular lymphoma (SFL) with prognostic impact. However, few data are available in LFL especially concerning hotspot genetic alterations that are associated with the pathogenesis and prognosis of SFL. A total of 144 LFL and 527 SFL, enrolled in prospective clinical trials of the German Low Grade Lymphoma Study Group, were analyzed by fluorescence in situ hybridization to detect deletions in chromosomes 1p, 6q, and 17p as well as BCL2 translocations to determine their impact on clinical outcome of LFL patients. The frequency of chromosomal deletions in 1p and 17p was comparable between LFL and SFL, while 6q deletions and BCL2 translocations more frequently occurred in SFL. A higher proportion of 1p deletions was seen in BCL2-translocation–positive LFL, compared with BCL2-translocation–negative LFL. Deletions in chromosomes 1p, 6q, and 17p predicted clinical outcome of patients with SFL in the entire cohort, while only deletions in chromosome 1p retained its negative prognostic impact in R-CHOP–treated SFL. In contrast, no deletions in one of the investigated genetic loci predicted clinical outcome in LFL. Likewise, the presence or absence of BCL2 translocations had no prognostic impact in LFL. Despite representing a genetic portfolio closely resembling SFL, LFL showed some differences in deletion frequencies. BCL2 translocation and 6q deletion frequency differs between LFL and SFL and might contribute to distinct genetic profiles in LFL and SFL

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049