Synthesen, Strukturen und Eigenschaften neuer Niobclusterverbindungen

Die Halogenidoliganden der festkörperchemisch gewonnenen Niobclusterverbindungen A4[Nb6Cl18] (A=K,Na,Rb) lassen sich in Lösung auf vielfältige Weise substituieren. In Hinblick auf die Verbesserung der Löslichkeit von Niobclusterverbindungen in organischen Lösungsmitteln wurden Ligandensubstitutionsreaktionen durchgeführt. Insgesamt wurden im Rahmendieser Arbeit 30 neue Niobclusterverbindungen synthetisiert. Diese wurden mit Hilfe der Einkristallröntgenstrukturanalyse charakterisiert und mittels IR-, Raman- und UV/Vis-spektroskopischen Methoden untersucht.Halogenidoligands of niobium cluster compounds A4[Nb6Cl18] (A=K,Na,Rb), which are gained via a solid state chemistry reaction, can be variously substituted in solution. Ligand substitution reactions have been carried out to improve the solubility of niobium cluster compounds in organic solvents. Within this work a total of 30 new niobium cluster compounds have been synthesised. They have been characterised by means of single-crystal X-ray structure analysis and further investigated by IR-, Raman- and UV/Vis-spectroscopic methods

Multi‐omics analysis reveals drivers of loss of β‐cell function after newly diagnosed autoimmune type 1 diabetes: An INNODIA multicenter study

Aims: Heterogeneity in the rate of beta-cell loss in newly diagnosed type 1 diabetes patients is poorly understood and creates a barrier to designing and interpreting disease-modifying clinical trials. Integrative analyses of baseline multi-omics data obtained after the diagnosis of type 1 diabetes may provide mechanistic insight into the diverse rates of disease progression after type 1 diabetes diagnosis. Methods: We collected samples in a pan-European consortium that enabled the concerted analysis of five different omics modalities in data from 97 newly diagnosed patients. In this study, we used Multi-Omics Factor Analysis to identify molecular signatures correlating with post-diagnosis decline in beta-cell mass measured as fasting C-peptide. Results: Two molecular signatures were significantly correlated with fasting C-peptide levels. One signature showed a correlation to neutrophil degranulation, cytokine signalling, lymphoid and non-lymphoid cell interactions and G-protein coupled receptor signalling events that were inversely associated with a rapid decline in beta-cell function. The second signature was related to translation and viral infection was inversely associated with change in beta-cell function. In addition, the immunomics data revealed a Natural Killer cell signature associated with rapid beta-cell decline. Conclusions: Features that differ between individuals with slow and rapid decline in beta-cell mass could be valuable in staging and prediction of the rate of disease progression and thus enable smarter (shorter and smaller) trial designs for disease modifying therapies as well as offering biomarkers of therapeutic effect

SHOX2 DNA Methylation is a Biomarker for the diagnosis of lung cancer based on bronchial aspirates

<p>Abstract</p> <p>Background</p> <p>This study aimed to show that SHOX2 DNA methylation is a tumor marker in patients with suspected lung cancer by using bronchial fluid aspirated during bronchoscopy. Such a biomarker would be clinically valuable, especially when, following the first bronchoscopy, a final diagnosis cannot be established by histology or cytology. A test with a low false positive rate can reduce the need for further invasive and costly procedures and ensure early treatment.</p> <p>Methods</p> <p>Marker discovery was carried out by differential methylation hybridization (DMH) and real-time PCR. The real-time PCR based HeavyMethyl technology was used for quantitative analysis of DNA methylation of SHOX2 using bronchial aspirates from two clinical centres in a case-control study. Fresh-frozen and Saccomanno-fixed samples were used to show the tumor marker performance in different sample types of clinical relevance.</p> <p>Results</p> <p>Valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 allowed to distinguish between malignant and benign lung disease, i.e. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses, at high specificity (68% sensitivity [95% CI 62-73%], 95% specificity [95% CI 91-97%]).</p> <p>Conclusions</p> <p>Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous.</p

Synthesis and Molecular Structure of tert-Butyl 4-(2-tert-butoxy-2-oxoethyl)piperazine-1-carboxylate

The crystal and molecular structure of tert-butyl 4-(2-tert-butoxy-2-oxoethyl)-piperazine-1-carboxylate is reported. The title compound crystallizes from a petroleum ether/ethyl acetate mixture in the monoclinic space group P 21/c with four molecules in the unit cell. The unit cell parameters are: a = 8.4007(2) Å, b = 16.4716(4) Å, c = 12.4876(3) Å; β = 90.948(1)° and V = 1727.71(7) Å3. Bond lengths and angles of this piperazine-carboxylate are typical

Crystal structure of 2-(diphenylphosphanyl)phenyl 4-(hydroxymethyl)benzoate

The title compound, C26H21O3P, was obtained as by-product due to the hydrolysis of the desired tosylated compound. The dihedral angles between the three aromatic rings attached to the P atom lie in the range 78.1 (1)–87.6 (1)°. The hydroxymethyl group is disordered between two conformations in a 0.719 (9):0.281 (9) ratio. The hydroxy H atom is not involved in intermolecular interactions, while the hydroxy O atom serves as a donor for weak C—H...O hydrogen bonds, which link the molecules into chains propagating in [0-11]

A novel method for sensitive and specific detection of DNA methylation biomarkers based on DNA restriction during PCR cycling

DNA methylation is an important epigenetic mechanism involved in fundamental biological processes such as development, imprinting, and carcino-genesis. For these reasons, DNA methylation represents a valuable source for cancer biomarkers. Methods for the sensitive and specific detection of methylated DNA are a prerequisite for the implementation of DNA biomarkers into clinical routine when early detection based on the analysis of body fluids is desired. Here, a novel technique is presented for the detection of DNA methylation biomarkers, based on real-time PCR of bisulfite-treated template with enzymatic digestion of background DNA during amplification using the heat-stable enzyme Tsp509I. An assay for the lung cancer methylation biomarker BARHL2 was used to show clinical and analytical performance of the method in comparison with methylation-specific PCR technology. Both technologies showed comparable performance when analyzing technical DNA mixtures and bronchial lavage samples from 75 patients suspected of having lung cancer. The results demonstrate that the approach is useful for sensitive and specific detection of a few copies of methylated DNA in samples with a high background of unmethylated DNA, such as in clinical samples from body fluids

Alterations to the urinary metabolome following semi-controlled short exposures to ultrafine particles at a major airport.

21 healthy, non-smoking volunteers (aged 19-27 years) were repeatedly (2-5 visits) exposed for 5h to ambient air at Amsterdam Airport Schiphol, while performing intermittent, moderate exercise. Pre- to-post exposure changes in urinary metabolite concentrations were assessed via 1H NMR spectroscopy and related to total and source-specific particle number concentrations (PNC) using linear mixed effects models

Alterations to the urinary metabolome following semi-controlled short exposures to ultrafine particles at a major airport

BACKGROUND: Inflammation, oxidative stress and reduced cardiopulmonary function following exposure to ultrafine particles (UFP) from airports has been reported but the biological pathways underlying these toxicological endpoints remain to be explored. Urinary metabolomics offers a robust method by which changes in cellular pathway activity can be characterised following environmental exposures. OBJECTIVE: We assessed the impact of short-term exposures to UFP from different sources at a major airport on the human urinary metabolome. METHODS: 21 healthy, non-smoking volunteers (aged 19-27 years) were repeatedly (2-5 visits) exposed for 5h to ambient air at Amsterdam Airport Schiphol, while performing intermittent, moderate exercise. Pre- to-post exposure changes in urinary metabolite concentrations were assessed via 1H NMR spectroscopy and related to total and source-specific particle number concentrations (PNC) using linear mixed effects models. RESULTS: Total PNC at the exposure site was on average, 53,500 particles/cm3 (range 10,500-173,200) and associated with significant reductions in urinary taurine (-0.262 AU, 95% CI: -0.507 to -0.020) and dimethylamine concentrations (-0.021 AU, 95% CI: -0.040 to -0.067). Aviation UFP exposure accounted for these changes, with the reductions in taurine and dimethylamine associating with UFP produced during both aircraft landing and take-off. Significant reductions in pyroglutamate concentration were also associated with aviation UFP specifically, (-0.005 AU, 95% CI: -0.010 - <0.000) again, with contributions from both landing and take-off UFP exposure. While non-aviation UFPs induced small changes to the urinary metabolome, their effects did not significantly impact the overall response to airport UFP exposure. DISCUSSION: Following short-term exposures at a major airport, aviation-related UFP caused the greatest changes to the urinary metabolome. These were consistent with a heightened antioxidant response and altered nitric oxide synthesis. Although some of these responses could be adaptive, they appeared after short-term exposures in healthy adults. Further study is required to determine whether long-term exposures induce injurious effects

(3R*,5&amp;#8242;S*)-6,7-Dimethoxy-3-(4&amp;#8242;-methoxy-6&amp;#8242;-methyl-5&amp;#8242;,6&amp;#8242;,7&amp;#8242;,8&amp;#8242;-tetrahydro-1,3-dioxolo[4,5-g]isoquinolin-5&amp;#8242;-yl)isobenzofuran-1(3H)-one (racemic &amp;#945;-noscapine)

In the racemic title compound, C22H23NO7, the dihedral angle between the fused ring systems is 51.87&amp;#8197;(6)&amp;#176;. Two of the methoxy groups are disordered over two orientations in 0.688&amp;#8197;(5):0.312&amp;#8197;(5) and 0.672&amp;#8197;(15):0.328&amp;#8197;(15) ratios. In the crystal, weak C&amp;#8212;H...O interactions link the molecules