Etablierung und Charakterisierung der neuen cholangiozellulären Zelllinie CCC-5

Cholangiocellular carcinoma (CCC) is a rare tumor entity and the availability of systemic treatment is limited. Better knowledge of the tumor physiology might lead to an improved treatment. However, basic research is dependent on the availability of cell lines. As there are only few CCC cell lines disposable, we aimed to isolate new CCC cell lines from surgical samples. The cell line was established from a 59-year-old Caucasian male patient who suffered from malignant pleural effusion of a distal cholangiocellular carcinoma (CCC). The cell line was established by explant culture and further characterized with immunohistochemistry and Western blotting. We tested sensitivity towards commonly used chemotherapeutics. Immunohistochemistry and Western blotting showed expression of tumor markers typical for CCC cell lines. Analysis of sensitivity towards chemotherapeutics revealed that Irinotecan was the only agent with significant effect on cell proliferation. In conclusion the new cell line displays the typical characteristics of a CCC cell line. This new cell line might help to add new insights into this tumor entity and thereby help to find better treatment options for patients with CCC

Arginase Inhibition Reverses Monocrotaline-Induced Pulmonary Hypertension

Pulmonary hypertension (PH) is a heterogeneous disorder associated with a poor prognosis. Thus, the development of novel treatment strategies is of great interest. The enzyme arginase (Arg) is emerging as important player in PH development. The aim of the current study was to determine the expression of ArgI and ArgII as well as the effects of Arg inhibition in a rat model of PH. PH was induced in 35 Sprague–Dawley rats by monocrotaline (MCT, 60 mg/kg as single-dose). There were three experimental groups: sham-treated controls (control group, n = 11), MCT-induced PH (MCT group, n = 11) and MCT-induced PH treated with the Arg inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA; MCT/NorNoha group, n = 13). ArgI and ArgII expression was determined by immunohistochemistry and Western blot. Right ventricular systolic pressure (RVPsys) was measured and lung tissue remodeling was determined. Induction of PH resulted in an increase in RVPsys (81 ± 16 mmHg) compared to the control group (41 ± 15 mmHg, p = 0.002) accompanied by a significant elevation of histological sum-score (8.2 ± 2.4 in the MCT compared to 1.6 ± 1.6 in the control group, p < 0.001). Both, ArgI and ArgII were relevantly expressed in lung tissue and there was a significant increase in the MCT compared to the control group (p < 0.01). Arg inhibition resulted in a significant reduction of RVPsys to 52 ± 19 mmHg (p = 0.006) and histological sum-score to 5.8 ± 1.4 compared to the MCT group (p = 0.022). PH leads to increased expression of Arg. Arg inhibition leads to reduction of RVPsys and diminished lung tissue remodeling and therefore represents a potential treatment strategy in PH

Detection of Soluble ED-A +

Background and Aims. Fibronectin containing the extra domain A (ED-A+ Fn) was proven to serve as a valuable biomarker for cardiac remodeling. The study was aimed at establishing an ELISA to determine ED-A+ Fn in serum of heart failure patients. Methods. ED-A+ Fn was quantified in serum samples from 114 heart failure patients due to ischemic (ICM, n=44) and dilated (DCM, n=39) cardiomyopathy as well as hypertensive heart disease (HHD, n=31) compared to healthy controls (n=12). Results. In comparison to healthy volunteers, heart failure patients showed significantly increased levels of ED-A+ Fn (p<0.001). In particular in ICM patients there were significant associations between ED-A+ Fn serum levels and clinical parameters, for example, increased levels with rising NYHA class (p=0.013), a negative correlation with left ventricular ejection fraction (p=0.026, r: −0.353), a positive correlation with left atrial diameter (p=0.008, r: 0.431), and a strong positive correlation with systolic pulmonary artery pressure (p=0.002, r: 0.485). In multivariate analysis, ED-A+ Fn was identified as an independent predictor of an ischemic heart failure etiology. Conclusions. The current study could clearly show that ED-A+ Fn is a promising biomarker in cardiovascular diseases, especially in heart failure patients due to an ICM. We presented a valid ELISA method, which could be applied for further studies investigating the value of ED-A+ Fn

A molecular atlas of cell types and zonation in the brain vasculature

Cerebrovascular disease is the third most common cause of death in developed countries, but our understanding of the cells that compose the cerebral vasculature is limited. Here, using vascular single-cell transcriptomics, we provide molecular definitions for the principal types of blood vascular and vessel-associated cells in the adult mouse brain. We uncover the transcriptional basis of the gradual phenotypic change (zonation) along the arteriovenous axis and reveal unexpected cell type differences: a seamless continuum for endothelial cells versus a punctuated continuum for mural cells. We also provide insight into pericyte organotypicity and define a population of perivascular fibroblast-like cells that are present on all vessel types except capillaries. Our work illustrates the power of single-cell transcriptomics to decode the higher organizational principles of a tissue and may provide the initial chapter in a molecular encyclopaedia of the mammalian vasculature.Peer reviewe

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Characterization of resting state dynamics in monkey motor cortex

Nowadays, modeling studies of cortical network dynamics aim to include realistic assumptions on structural and functional properties of the corresponding neurons [1,2]. Such models often do not consider functional aspects but rather describe the “ground”, “idle”, or “resting state” of the cortical network, typically characterized as asynchronous irregular spiking [2]. However, for model validation, i.e., for a concrete comparison of experimental versus model data aiming at a more realistic model, one needs to compare this cortical state to the corresponding experimental data. Therefore we performed a “resting state” experiment (this term is adapted from human fMRI studies where it is defined as brain activity observed when the subject is at rest [3]). We recorded the neuronal activity from macaque monkey motor cortex with a chronically implanted 4x4mm2 100 electrode Utah Array (Blackrock Microsystems) for 15min, while the monkey was sitting in a chair without any task or given stimulus. This is in contrast to most neurophysiological studies that focus on a task- or stimulus-specific analysis [e.g. 4]. Based on a video recording of the monkey during the neuronal recording, we differentiate between “resting” intervals and intervals when the monkey spontaneously moved.The goal of this study is to thoroughly characterize the simultaneous spiking activity recorded from 146 single units during resting state. To enable a detailed comparison to simulated spiking data, we subdivide the single units into putative excitatory and inhibitory neurons based on their spike shapes [5]. We apply common statistical measures, e.g., firing rate, (local) coefficient of variation for single unit characterization, and we also compute the pairwise fine temporal correlation by correlation coefficients. These measures are calculated in two ways: averaged over time and single units, as well as averaged over time but separately for each single unit (except for the correlation coefficients). Comparing the distributions of these measures from the two behavioral states we do not find any difference – when averaging over single units. However, when focusing on non-averaged, single unit data we notice that some neurons increase their firing rates systematically when the monkey moves compared to rest, whereas others decrease or do not change their rates. Thus, there was seemingly no difference on the population level, but significant differences on the level of individual neurons. Moreover, we observe a strong correlation between a few neuronal units, independent of their cortical distance, while others show lower or no correlation. Our next steps are to characterize if such findings are particularly different for excitatory and inhibitory neurons. Further, we aim to study the underlying network mechanisms. One possibility would be to re-consider the balancing effects of inhibition and recurrence [5,6]

The Influence of Pretherapeutic and Preoperative Sarcopenia on Short-Term Outcome after Esophagectomy

By introducing minimally invasive surgery the rate of postoperative morbidity in esophageal cancer patients could be reduced. But esophagectomy is still associated with a relevant risk of postoperative morbidity and mortality. Patients often present with nutritional deficiency and sarcopenia even at time of diagnosis. This study focuses on the influence of skeletal muscle index (SMI) on postoperative morbidity and mortality. Fifty-two patients were included in this study. SMI was measured using computer tomographic images at the time of diagnosis and before surgery. Then, SMI and different clinicopathological and demographic features were correlated with postoperative morbidity. There was no correlation between SMI before neoadjuvant therapy (p = 0.5365) nor before surgery (p = 0.3530) with the short-term postoperative outcome. Regarding cholesterol level before surgery there was a trend for a higher risk of complications with lower cholesterol levels (p = 0.0846). Our findings suggest that a low preoperative SMI does not necessarily predict a poor postoperative outcome in esophageal cancer patients after esophagectomy but that there are many factors that influence the nutritional status of cancer patients. To improve nutritional status, cancer patients at our clinic receive specialized nutritional counselling during neoadjuvant treatment as well as after surgery

Männlichkeit(en) zwischen Politisierung und Pathologisierung. Anlass für eine kritisch-emanzipatorische Bildung

Mokros N, Pangritz J. Männlichkeit(en) zwischen Politisierung und Pathologisierung. Anlass für eine kritisch-emanzipatorische Bildung. In: Bechtel T, Girnus L, Grün-Neuhof J, Prehm F, Vogt J, eds. Why focus on gender? Gender und intersektionale Perspektiven in der politischen Bildung. Gender in politischer Bildungs- und Transferforschung . Frankfurt am Main: Wochenschau Verlag; In Press