Aufnahme und Metabolismus von 15N-markiertem Cyanamid durch Rebenstecklinge

Uptake and metabolism of 15N labelled cyanamide by cuttings of grapevine15N labelled cyanamide was taken up from nutrient solution by rooted grapevine cuttings. Precipitable N in shoots or roots contained up to 2/3 of total supplied 15N. Arginine concentrations were higher during cyanamide feeding than in controls and declined to control levels after transfer into cyanamide free nutrient solution. In arginine extracted from shoots and roots after hydrolysis with 6 M HCl and column chromatography, 6-7 % of l5N originating from cyanamide was recovered

MILLIMETER-WAVE SPECTROSCOPY AND GLOBAL ANALYSIS OF THE LOWEST EIGHT VIBRATIONAL STATES OF DEUTERATED HYDRAZOIC ACID (DN3)

Hydrazoic acid (chem{HN_3}) and chem{DN_3} have qualitatively different rotational spectra, owing in large part to a substantial difference in their emph{A} rotational constants (345 GHz for chem{DN_3} emph{vs} 611 GHz for chem{HN_3}). Like chem{HN_3}, chem{DN_3} has six fundamental vibrational modes, of which four are visible in our millimeter-wave spectra at room temperature. Between 240 and 450 GHz, many pure rotational transitions for the ground vibrational state, nub{5} (496 cm$^{-1}$), nub{6} (586 cm$^{-1}$), nub{4} (955 cm$^{-1}$), nub{3} (1197 cm$^{-1}$), the first overtones of nub{5} and nub{6}, and the combination nub{5}+nub{6} have been observed and assigned. Because chem{DN_3} is a light molecule, the rotational energy levels are widely spaced, leading to numerous interactions between rotational states of different vibrational modes. We have drawn on a wealth of previously published ro-vibrational data from high resolution FTIR spectrafootnote{J. Bendtsen and F. M. Nicolaisen, emph{J. Mol. Spectrosc.} textbf{125}, 14 (1987)}$^{,}$footnote{J. Bendtsen, F. Hegelund and F. M. Nicolaisen, emph{J. Mol. Spectrosc.} textbf{128}, 309 (1988)}$^{,}$footnote{J. Bendtsen and F. M. Nicolaisen, emph{J. Mol. Spectrosc.} textbf{145}, 123 (1991)}$^{,}$footnote{C. S. Hansen, J. Bendtsen and F. M. Nicolaisen, emph{J. Mol. Spectrosc.} textbf{175}, 239 (1996)} in our efforts to understand these perturbations. The centrifugal distortion interaction between nub{5} and the ground state of chem{DN_3} is less dramatic than in chem{HN_3} but still significant. chem{DN_3} shows the same set of Coriolis interactions as does chem{HN_3}, but again, their magnitude is generally smaller. In chem{DN_3} the nub{4} state is at slightly lower energy than 2nub{5}, instead of being nearly degenerate with nub{5}+nub{6} as is the case for chem{HN_3}. Therefore, there are strong local interactions between 2nub{5} and nub{4}, as well as between nub{3} and 2nub{6}. A notable advantage in solving the chem{DN_3} problem compared to chem{HN_3} is the substantial increase in the number and diversity of observable emph{b}-type lines in our frequency region. Furthermore, the smaller emph{A} value permits higher emph{K} states to be observed due to a more gradual decrease in state populations. Ground state observations have been extended through emph{K} = 11 and through emph{J} = 50. Pickett's SPFIT has been employed to carry out multi-state fits using combined datasets of our millimeter-wave data and the published FTIR data

Do-it-yourself genetic testing

We developed a computational screen that tests an individual's genome for mutations in the BRCA genes, despite the fact that both are currently protected by patents

Sex differences in zonulin in affective disorders and associations with current mood symptoms

Zonulin measurement was funded by Institut Allergosan (Graz, Austria).Introduction: The bidirectional connection between the brain and the gut within psychiatric entities has gained increasing scientific attention over the last years. As a regulator of intestinal permeability, zonulin acts as a key player on the interface of this interplay. Like several psychiatric disorders, intestinal permeability was associated with inflammation in previous findings. Methods: In this study we explored differences in zonulin serum levels in currently depressed (n = 55) versus currently euthymic (n = 37) individuals with an affective disorder. Further, we explored sex differences and possible influences on zonulin and affective symptoms like medication, age, body mass index, and smoking status. Results: Serum zonulin was significantly higher in females than in men independent from affective status (z = -2.412, p = .016). More specifically, females in the euthymic subgroup had higher zonulin levels than euthymic men (z = -2.114, p = .035). There was no difference in zonulin serum levels in individuals taking or not taking a specific psychopharmacotherapy. We found no correlation between zonulin serum levels and depression severity. Discussion: Increased serum zonulin levels as a proxy for increased intestinal permeability in women may indicate a state of elevated susceptibility for depression-inducing stimuli.Publisher PDFPeer reviewe

A visual and curatorial approach to clinical variant prioritization and disease gene discovery in genome-wide diagnostics

Background: Genome-wide data are increasingly important in the clinical evaluation of human disease. However, the large number of variants observed in individual patients challenges the efficiency and accuracy of diagnostic review. Recent work has shown that systematic integration of clinical phenotype data with genotype information can improve diagnostic workflows and prioritization of filtered rare variants. We have developed visually interactive, analytically transparent analysis software that leverages existing disease catalogs, such as the Online Mendelian Inheritance in Man database (OMIM) and the Human Phenotype Ontology (HPO), to integrate patient phenotype and variant data into ranked diagnostic alternatives. Methods: Our tool, “OMIM Explorer” (http://www.omimexplorer.com), extends the biomedical application of semantic similarity methods beyond those reported in previous studies. The tool also provides a simple interface for translating free-text clinical notes into HPO terms, enabling clinical providers and geneticists to contribute phenotypes to the diagnostic process. The visual approach uses semantic similarity with multidimensional scaling to collapse high-dimensional phenotype and genotype data from an individual into a graphical format that contextualizes the patient within a low-dimensional disease map. The map proposes a differential diagnosis and algorithmically suggests potential alternatives for phenotype queries—in essence, generating a computationally assisted differential diagnosis informed by the individual’s personal genome. Visual interactivity allows the user to filter and update variant rankings by interacting with intermediate results. The tool also implements an adaptive approach for disease gene discovery based on patient phenotypes. Results: We retrospectively analyzed pilot cohort data from the Baylor Miraca Genetics Laboratory, demonstrating performance of the tool and workflow in the re-analysis of clinical exomes. Our tool assigned to clinically reported variants a median rank of 2, placing causal variants in the top 1 % of filtered candidates across the 47 cohort cases with reported molecular diagnoses of exome variants in OMIM Morbidmap genes. Our tool outperformed Phen-Gen, eXtasy, PhenIX, PHIVE, and hiPHIVE in the prioritization of these clinically reported variants. Conclusions: Our integrative paradigm can improve efficiency and, potentially, the quality of genomic medicine by more effectively utilizing available phenotype information, catalog data, and genomic knowledge

Genomic sequencing in clinical trials

Human genome sequencing is the process by which the exact order of nucleic acid base pairs in the 24 human chromosomes is determined. Since the completion of the Human Genome Project in 2003, genomic sequencing is rapidly becoming a major part of our translational research efforts to understand and improve human health and disease. This article reviews the current and future directions of clinical research with respect to genomic sequencing, a technology that is just beginning to find its way into clinical trials both nationally and worldwide. We highlight the currently available types of genomic sequencing platforms, outline the advantages and disadvantages of each, and compare first- and next-generation techniques with respect to capabilities, quality, and cost. We describe the current geographical distributions and types of disease conditions in which these technologies are used, and how next-generation sequencing is strategically being incorporated into new and existing studies. Lastly, recent major breakthroughs and the ongoing challenges of using genomic sequencing in clinical research are discussed

Whole-Genome Sequencing of a Single Proband Together with Linkage Analysis Identifies a Mendelian Disease Gene

Although more than 2,400 genes have been shown to contain variants that cause Mendelian disease, there are still several thousand such diseases yet to be molecularly defined. The ability of new whole-genome sequencing technologies to rapidly indentify most of the genetic variants in any given genome opens an exciting opportunity to identify these disease genes. Here we sequenced the whole genome of a single patient with the dominant Mendelian disease, metachondromatosis (OMIM 156250), and used partial linkage data from her small family to focus our search for the responsible variant. In the proband, we identified an 11 bp deletion in exon four of PTPN11, which alters frame, results in premature translation termination, and co-segregates with the phenotype. In a second metachondromatosis family, we confirmed our result by identifying a nonsense mutation in exon 4 of PTPN11 that also co-segregates with the phenotype. Sequencing PTPN11 exon 4 in 469 controls showed no such protein truncating variants, supporting the pathogenicity of these two mutations. This combination of a new technology and a classical genetic approach provides a powerful strategy to discover the genes responsible for unexplained Mendelian disorders

Association of Carotid Plaque Lp-PLA2 with Macrophages and Chlamydia pneumoniae Infection among Patients at Risk for Stroke

BACKGROUND: We previously showed that the burden of Chlamydia pneumoniae in carotid plaques was significantly associated with plaque interleukin (IL)-6, and serum IL-6 and C-reactive protein (CRP), suggesting that infected plaques contribute to systemic inflammatory markers in patients with stroke risk. Since lipoprotein-associated phospholipase A2 (Lp-PLA(2)) mediates inflammation in atherosclerosis, we hypothesized that serum Lp-PLA(2) mass and activity levels and plaque Lp-PLA(2) may be influenced by plaque C. pneumoniae infection. METHODOLOGY/PRINCIPAL FINDINGS: Forty-two patients underwent elective carotid endarterectomy. Tissue obtained at surgery was stained by immunohistochemistry for Lp-PLA(2) grade, macrophages, IL-6, C. pneumoniae and CD4+ and CD8+ cells. Serum Lp-PLA(2) activity and mass were measured using the colorimetric activity method (CAM) and ELISA, respectively. Serum homocysteine levels were measured by HPLC. Eleven (26.2%) patients were symptomatic with transient ischemic attacks. There was no correlation between patient risk factors (smoking, coronary artery disease, elevated cholesterol, diabetes, obesity, hypertension and family history of genetic disorders) for atherosclerosis and serum levels or plaque grade for Lp-PLA(2). Plaque Lp-PLA(2) correlated with serum homocysteine levels (p = 0.013), plaque macrophages (p<0.01), and plaque C. pneumoniae (p<0.001), which predominantly infected macrophages, co-localizing with Lp-PLA(2). CONCLUSIONS: The significant association of plaque Lp-PLA(2) with plaque macrophages and C. pneumoniae suggests an interactive role in accelerating inflammation in atherosclerosis. A possible mechanism for C. pneumoniae in the atherogenic process may involve infection of macrophages that induce Lp-PLA(2) production leading to upregulation of inflammatory mediators in plaque tissue. Additional in vitro and in vivo research will be needed to advance our understanding of specific C. pneumoniae and Lp-PLA(2) interactions in atherosclerosis