Fungal cyclooligomer depsipeptides: From classical biochemistry to combinatorial biosynthesis

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.This review surveys the biological activities and the iterative and recursive biosynthetic mechanisms of fungal cyclooligomer depsipeptides, and their structural diversification by various combinatorial biosynthetic methods

Metadata: how we relate to images

METADATA. HOW WE RELATE TO IMAGES Lethaby Gallery 10 Jan—3 Feb 2018 An exhibition organised by the International Research Group “Bilderfahrzeuge. Aby Warburg’s Legacy and the Future of Iconology” in collaboration with Central Saint Martins, University of the Arts London

Molecular Chromophore-DNA Architectures With Fullerenes: Optical Properties and Solar Cells

Supramolecular chemistry allows the construction of complex molecular architectures and the design of collective photophysical properties. DNA is an attractive template to build such supramolecular architectures due to its helical structure, the defined distances between the bases and the canonical base pairing that results in precise control of the chromophore position. The tailored properties of DNA-templated supramolecules eventually allow their implementation into optoelectronic applications. For the generation of free charge carriers from photo-generated excitons, fullerenes can be utilized. We synthesized two fullerene derivates, one of which binds by electrostatic interactions to single-stranded DNA, while the other contains two 2′-deoxyuridine moieties and assembles specifically along oligo-2′-deoxyadenosines (dA20) as DNA template. The DNA-directed assembly of both fullerenes in aqueous solution was investigated by UV/Vis absorbance and circular dichroism (CD) spectroscopy. The specific interactions with DNA make fullerenes with the 2′-deoxyuridine moieties a significantly better component for supramolecular DNA architectures. We studied the fluorescence quenching of both fullerenes with a DNA chromophore assembly. To investigate one of the key properties for optoelectronic applications, that is the supramolecular structure of the DNA-based assemblies in the solid phase, we characterized the CD of supramolecular chromophore-DNA architectures in thin films. Remarkably, the helical chirality of the chromophore assemblies that is induced by the DNA template is conserved even in the solid state. Upon implementation into organic solar cells, the external quantum efficiency measurements showed charge carrier generation on all three chromophore components of the DNA assemblies. The fullerenes with the 2′-deoxyuridine moieties enhance the quantum efficiency of the conversion process significantly, demonstrating the potential of DNA as structural element for ordering chromophores into functional π-systems, which may be employed in future organic solar cells

Use of long-term microdialysis subcutaneous glucose monitoring in the management of neonatal diabetes - A first case report

In neonatal diabetes mellitus (NDM), a rare genetic disorder, insulin therapy is required but the management is difficult. Frequent blood glucose determinations are necessary in most cases. Microdialysis subcutaneous glucose monitoring (MSGM) is feasible in neonates and has been proposed to reduce painful blood sampling and blood loss. We have applied long-term MSGM to a small-fordate female newborn with transient NDM. We found a good correlation of subcutaneous and blood glucose concentration over a wide range of values. MSGM enabled a reduction in blood glucose determinations during optimization of intravenous insulin treatment and initiation of continuous subcutaneous insulin infusion. We conclude that long-term MSGM is feasible and may reduce painful blood sampling and blood loss in NDM. Furthermore, long-term MSGM may hold a potential for avoiding hypoglycemic episodes and earlier discharge. Copyright (C) 2006 S. Karger AG, Basel

Comparison of 6 % hydroxyethyl starch and 5 % albumin for volume replacement therapy in patients undergoing cystectomy (CHART): study protocol for a randomized controlled trial

Background The use of artificial colloids is currently controversial, especially in Central Europe Several studies demonstrated a worse outcome in intensive care unit patients with the use of hydroxyethyl starch. This recently even led to a drug warning about use of hydroxyethyl starch products in patients admitted to the intensive care unit. The data on hydroxyethyl starch in non–critically ill patients are insufficient to support perioperative use. Methods/Design We are conducting a single-center, open-label, randomized, comparative trial with two parallel patient groups to compare human albumin 5 % (test drug) with hydroxyethyl starch 6 % 130/0.4 (comparator). The primary endpoint is cystatin C ratio, calculated as the ratio of the cystatin value at day 90 after surgery relative to the preoperative value. Secondary objectives are inter alia the evaluation of the influence of human albumin and hydroxyethyl starch on further laboratory chemical and clinical parameters, glycocalyx shedding, intensive care unit and hospital stay and acute kidney injury as defined by RIFLE criteria (risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage kidney disease) criteria. Discussion There is a general lack of evidence on the relative safety and effects of hydroxyethyl starch compared with human albumin for volume replacement in a perioperative setting. Previously conducted studies of surgical patients in which researchers have compared different hydroxyethyl starch products included too few patients to properly evaluate clinical important outcomes such as renal function. In the present study in a high-risk patient population undergoing a major surgical intervention, we will determine if perioperative fluid replacement with human albumin 5 % will have a long-term advantage over a third-generation hydroxyethyl starch 130/0.4 on the progression of renal dysfunction until 90 days after surgery

Primary Staging of Prostate Cancer Patients with [18F]PSMA-1007 PET/CT Compared with [68Ga]Ga-PSMA-11 PET/CT

Background: Hybrid imaging with prostate-specific membrane antigen (PSMA) is gaining importance as an increasingly meaningful tool for prostate cancer (PC) diagnostics and as a guide for therapy decisions. This study aims to investigate and compare the performance of [18F]PSMA1007 (18F-PSMA) and [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography ( 68Ga-PSMA) in the initial staging of PC patients. Methods: The data of 88 biopsy-proven patients were retrospectively evaluated. PSMA-avid lesions were compared with the histopathologic Gleason Score (GS) for prostate biopsies, and the results were plotted by receiver operating characteristic (ROC)-curve. Optimal maximum standardized uptake value (SUVmax) cut-off values were rated using the Youden index. Results: 18F-PSMA was able to distinguish GS ≤ 7a from ≥7b with a sensitivity of 62%, specificity of 85%, positive predictive value (PPV) of 92%, and accuracy of 67% for a SUVmax of 8.95, whereas sensitivity was 54%, specificity 91%, PPV 93%, and accuracy 66% for 68Ga-PSMA (SUVmax 8.7). Conclusions: Both methods demonstrated a high concordance of detected PSMA-avid lesions with histopathologically proven PC. 18F-PSMA and 68Ga-PSMA are both suitable for the characterization of primary PC with a comparable correlation of PSMA-avid lesions with GS. Neither method showed a superior advantage. Our calculated SUVmax thresholds may represent valuable parameters in clinical use to distinguish clinically significant PC (csPC) from non-csPC

Does 2D-Histologic identification of villous types of human placentas at birth enable sensitive and reliable interpretation of 3D structure?

INTRODUCTION: The villous tree of human placentas is a complex three-dimensional (3D) structure which enables fetomaternal exchange. Current concepts of microscopic analyses are based on the analysis of two-dimensional (2D) histologic sections. For this approach, the assessment of the stromal core of sectioned villi is of key importance. The classification of stromal properties of sectioned villi allows allocation of villous sections to villous types which are named by their expected position in villous trees (terminal, intermediate, and stem villi). METHOD: The present study takes these current concepts of placental histology as hypothesis and validates them against predetermined 3D positions of branches of villous trees. The 3D positions were determined prior to histologic sectioning using a recently introduced 3D-microscopic approach. Individual histologic sections of villi were classified by their stromal structures and inter rater variability of these histologic assessments were determined. RESULTS/DISSCUSSION: Inter rater variability was high and indicates substantial observer influence on the outcome of histologic assessments. Cross-match of villous types with the predetermined positions of villous branches of villous trees revealed substantial mismatch between the outcome of stromal classification and 3D-position of the sectioned villi in the placental villous trees.DFG, grant numbers INST 86/1495-1 FUGG, INST86/1452-1 LAGG.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.placenta.2015.10.00

Comparison of [18F]PSMA-1007 with [68Ga]Ga-PSMA-11 PET/CT in Restaging of Prostate Cancer Patients with PSA Relapse

This study aimed to compare the diagnostic performance of [18F]PSMA-1007 positron emission tomography/computed tomography (PET/CT) (18F-PSMA) and [68Ga]Ga-PSMA-11 PET/CT ( 68Ga-PSMA) by identifying prostate-specific antigen (PSA) threshold levels for optimal detecting recurrent prostate cancer (PC) and to compare both methods. Retrospectively, the study included 264 patients. The performances of 18F-PSMA and 68Ga-PSMA in relation to the pre-scan PSA were assessed by receiver operating characteristic (ROC) curve. 18F-PSMA showed PC-lesions in 87.5% (112/128 patients), while 68Ga-PSMA identified them in 88.9% (121/136). For 18F-PSMA biochemical recurrent (BCR) patients treated with radical prostatectomy (78/128, patient group: F-RP), a PSA of 1.08 ng/mL was found to be the optimal cut-off level for predicting positive and negative scans (AUC = 0.821; 95%, CI: 0.710–0.932), while for prostatectomized 68Ga-PSMA BCR-patients (89/136, patient group: Ga-RP), the cut-off was 1.84 ng/mL (AUC = 0.588; 95%, CI: 0.410–0.766). In patients with PSA < 1.08 ng/mL (F-RP) 76.3% and <1.84 ng/mL (Ga-RP) 78.6% scans were positive, whereas patients with PSA ≥ 1.08 ng/mL (F-RP) or 1.84 ng/mL (Ga-RP) had positive scan results in 100% and 91.5% (p < 0.001/p = 0.085). The identified PSA thresholds for PSMA-mappable PC lesions in BCR-patients (RP) showed a better separation for 18F-PSMA with regard to the distinguishing of positive and negative PC-lesions compared to 68Ga-PSMA. However, the two PSMA PET/CT tracers gave similar overall findings

Neutrophil gelatinase-associated lipocalin (NGAL) predicts response to neoadjuvant chemotherapy and clinical outcome in primary human breast cancer

In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In neoadjuvant chemotherapy (NACT) pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Immunohistochemistry was performed on tissue microarrays from 652 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression and intensity was evaluated separately. NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status, but not with other baseline parameters. NGAL expression did not correlate with pCR in the full population, however, NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status. In addition, strong NGAL expression correlated with higher pCR rates in node negative patients, patients with histological grade 1 or 2 tumors and a tumor size <40 mm. In univariate survival analysis, positive NGAL expression and strong staining intensity correlated with decreased disease-free survival (DFS) in the entire cohort and different subgroups, including HR positive patients. Similar correlations were found for intense staining and decreased overall survival (OS). In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS. The results show that in low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC