University of Marburg

About: University of Marburg is a education organization based out in Marburg, Germany. It is known for research contribution in the topics: Population & Gene. The organization has 23195 authors who have published 42907 publications receiving 1506069 citations. The organization is also known as: Philipps University of Marburg & Philipps-Universität.

Zur Kenntnis des Faktors F430 aus methanogenen Bakterien: Struktur des porphinoiden Ligandsystems

Abstract: Factor F430 from Methanogenic Bacteria: Structure of the Porphninoid Ligand System A structure is proposed for F430M, a non-cristalline methanolysis product of isolates of the nickel-containing, porphinoid factor F430 from Methanobacterium thermoautotrophicum. Crucial to the structure determination are five incorporation experiments with M. thermoautotrophicum (strain Marburg) in which the specifically mono-13C-labeled biosynthetic precursors (2-13C), (3-13C), (4-13C)-, (5-13C) ALA (ALA = δ-amino-levulinic acid) and L-(methyl-13C)methionine were incorporated into F430 with high efficiency. The 13C-NMR,-spectra of the specifically labeled F430M samples derived therefrom, together with the UV./VIS. spectral data of F430M, contain all the information necessary for the deduction of the constitution of the F430M chromophore, assuming the established pattern of porphinoid biosynthesis to be operative in F430 biosynthesis. 1H-NMR. spectroscopy and, in particular, 1H-NMR.-NOE-difference spectroscopy corroborates and completes the constitutional assignments and, furthermore, makes possible an almost complete derivation of the molecule's relative configuration. Schemes 3 and 4 summarize the results of 1H-NMR. spectroscopy, presenting them within the context of the proposed structure for F430M. The assignment of absolute configuration implied in the formula is given preference because of F430M's very close structural and (assumed) biosynthetic relationship to sirohydrochlorin and vitamin B12 (with respect to ring C, the assignment is based on degradative evidence). According to the proposed structure, the nickel complex F430M possesses an uroporphinoid (Type III) ligand skeleton with an additional carbocyclic ring and a chromophore system not previously encountered among natural porphinoids. It can be considered to be a (tetrahydro) derivative of the corphin system, combining structural elements of both porphyrins and corrins.

A mutation of the mitochondrial ABC transporter Sta1 leads to dwarfism and chlorosis in the Arabidopsis mutant starik

Abstract: A mutation in the Arabidopsis gene STARIK leads to dwarfism and chlorosis of plants with an altered morphology of leaf and cell nuclei. We show that the STARIK gene encodes the mitochondrial ABC transporter Sta1 that belongs to a subfamily of Arabidopsis half-ABC transporters. The severity of the starik phenotype is suppressed by the ectopic expression of the STA2 homolog; thus, Sta1 function is partially redundant. Sta1 supports the maturation of cytosolic Fe/S protein in Δatm1 yeast, substituting for the ABC transporter Atm1p. Similar to Atm1p-deficient yeast, mitochondria of the starik mutant accumulated more nonheme, nonprotein iron than did wild-type organelles. We further show that plant mitochondria contain a putative l-cysteine desulfurase. Taken together, our results suggest that plant mitochondria possess an evolutionarily conserved Fe/S cluster biosynthesis pathway, which is linked to the intracellular iron homeostasis by the function of Atm1p-like ABC transporters.

MYCN regulates oncogenic MicroRNAs in neuroblastoma.

Abstract: MYCN amplification is a common feature of aggressive tumour biology in neuroblastoma. The MYCN transcription factor has been demonstrated to induce or repress expression of numerous genes. MicroRNAs (miRNA) are a recently discovered class of short RNAs that repress translation and promote mRNA degradation by sequence-specific interaction with mRNA. Here, we sought to analyse the role of MYCN in regulation of miRNA expression. Using a miRNA microarray containing 384 different miRNAs and a set of 160 miRNA real-time PCR assays to validate the microarray results, 7 miRNAs were identified that are induced by MYCN in vitro and are upregulated in primary neuroblastomas with MYCN amplification. Three of the seven miRNAs belong to the miR-106a and miR-17 clusters, which have previously been shown to be regulated by c-Myc. The miR-17–92 polycistron also acts as an oncogene in haematopoietic progenitor cells. We show here that miR-221 is also induced by MYCN in neuroblastoma. Previous studies have reported miR-221 to be overexpressed in several other cancer entities, but its regulation has never before been associated with Myc. We present evidence of miRNA dysregulation in neuroblastoma. Additionally, we report miRNA induction to be a new mechanism of gene expression downregulation by MYCN. © 2007 Wiley-Liss, Inc.

Non‐pharmacological interventions for somatoform disorders and medically‐unexplained physical symptoms (MUPS) in adults

Abstract: Background Medically unexplained physical symptoms (MUPS) are physical symptoms for which no adequate medical explanation can be found after proper examination. The presence of MUPS is the key feature of conditions known as 'somatoform disorders'. Various psychological and physical therapies have been developed to treat somatoform disorders and MUPS. Although there are several reviews on non-pharmacological interventions for somatoform disorders and MUPS, a complete overview of the whole spectrum is missing. Objectives To assess the effects of non-pharmacological interventions for somatoform disorders (specifically somatisation disorder, undifferentiated somatoform disorder, somatoform disorders unspecified, somatoform autonomic dysfunction, pain disorder, and alternative somatoform diagnoses proposed in the literature) and MUPS in adults, in comparison with treatment as usual, waiting list controls, attention placebo, psychological placebo, enhanced or structured care, and other psychological or physical therapies. Search methods We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to November 2013. This register includes relevant randomised controlled trials (RCTs) from The Cochrane Library, EMBASE, MEDLINE, and PsycINFO. We ran an additional search on the Cochrane Central Register of Controlled Trials and a cited reference search on the Web of Science. We also searched grey literature, conference proceedings, international trial registers, and relevant systematic reviews. Selection criteria We included RCTs and cluster randomised controlled trials which involved adults primarily diagnosed with a somatoform disorder or an alternative diagnostic concept of MUPS, who were assigned to a non-pharmacological intervention compared with usual care, waiting list controls, attention or psychological placebo, enhanced care, or another psychological or physical therapy intervention, alone or in combination. Data collection and analysis Four review authors, working in pairs, conducted data extraction and assessment of risk of bias. We resolved disagreements through discussion or consultation with another review author. We pooled data from studies addressing the same comparison using standardised mean differences (SMD) or risk ratios (RR) and a random-effects model. Primary outcomes were severity of somatic symptoms and acceptability of treatment. Main results We included 21 studies with 2658 randomised participants. All studies assessed the effectiveness of some form of psychological therapy. We found no studies that included physical therapy.Fourteen studies evaluated forms of cognitive behavioural therapy (CBT); the remainder evaluated behaviour therapies, third-wave CBT (mindfulness), psychodynamic therapies, and integrative therapy. Fifteen included studies compared the studied psychological therapy with usual care or a waiting list. Five studies compared the intervention to enhanced or structured care. Only one study compared cognitive behavioural therapy with behaviour therapy.Across the 21 studies, the mean number of sessions ranged from one to 13, over a period of one day to nine months. Duration of follow-up varied between two weeks and 24 months. Participants were recruited from various healthcare settings and the open population. Duration of symptoms, reported by nine studies, was at least several years, suggesting most participants had chronic symptoms at baseline.Due to the nature of the intervention, lack of blinding of participants, therapists, and outcome assessors resulted in a high risk of bias on these items for most studies. Eleven studies (52% of studies) reported a loss to follow-up of more than 20%. For other items, most studies were at low risk of bias. Adverse events were seldom reported.For all studies comparing some form of psychological therapy with usual care or a waiting list that could be included in the meta-analysis, the psychological therapy resulted in less severe symptoms at end of treatment (SMD -0.34; 95% confidence interval (CI) -0.53 to -0.16; 10 studies, 1081 analysed participants). This effect was considered small to medium; heterogeneity was moderate and overall quality of the evidence was low. Compared with usual care, psychological therapies resulted in a 7% higher proportion of drop-outs during treatment (RR acceptability 0.93; 95% CI 0.88 to 0.99; 14 studies, 1644 participants; moderate-quality evidence). Removing one outlier study reduced the difference to 5%. Results for the subgroup of studies comparing CBT with usual care were similar to those in the whole group.Five studies (624 analysed participants) assessed symptom severity comparing some psychological therapy with enhanced care, and found no clear evidence of a difference at end of treatment (pooled SMD -0.19; 95% CI -0.43 to 0.04; considerable heterogeneity; low-quality evidence). Five studies (679 participants) showed that psychological therapies were somewhat less acceptable in terms of drop-outs than enhanced care (RR 0.93; 95% CI 0.87 to 1.00; moderate-quality evidence). Authors' conclusions When all psychological therapies included this review were combined they were superior to usual care or waiting list in terms of reduction of symptom severity, but effect sizes were small. As a single treatment, only CBT has been adequately studied to allow tentative conclusions for practice to be drawn. Compared with usual care or waiting list conditions, CBT reduced somatic symptoms, with a small effect and substantial differences in effects between CBT studies. The effects were durable within and after one year of follow-up. Compared with enhanced or structured care, psychological therapies generally were not more effective for most of the outcomes. Compared with enhanced care, CBT was not more effective. The overall quality of evidence contributing to this review was rated low to moderate.The intervention groups reported no major harms. However, as most studies did not describe adverse events as an explicit outcome measure, this result has to be interpreted with caution.An important issue was that all studies in this review included participants who were willing to receive psychological treatment. In daily practice, there is also a substantial proportion of participants not willing to accept psychological treatments for somatoform disorders or MUPS. It is unclear how large this group is and how this influences the relevance of CBT in clinical practice.The number of studies investigating various treatment modalities (other than CBT) needs to be increased; this is especially relevant for studies concerning physical therapies. Future studies should include participants from a variety of age groups; they should also make efforts to blind outcome assessors and to conduct follow-up assessments until at least one year after the end of treatment.

Carbon Monoxide Oxidation by Clostridium thermoaceticum and Clostridium formicoaceticum

Abstract: Cultures of Clostridium formicoaceticum and C. thermoaceticum growing on fructose and glucose, respectively, were shown to rapidly oxidize CO to CO(2). Rates up to 0.4 mumol min(-1) mg of wet cells(-1) were observed. Carbon monoxide oxidation by cell suspensions was found (i) to be dependent on pyruvate, (ii) to be inhibited by alkyl halides and arsenate, and (iii) to stimulate CO(2) reduction to acetate. Cell extracts catalyzed the oxidation of carbon monoxide with methyl viologen at specific rates up to 10 mumol min(-1) mg of protein(-1) (35 degrees C, pH 7.2). Nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide phosphate and ferredoxin from C. pasteurianum were ineffective as electron acceptors. The catalytic mechanism of carbon monoxide oxidation was "ping-pong," indicating that the enzyme catalyzing carbon monoxide oxidation can be present in an oxidized and a reduced form. The oxidized form was shown to react reversibly with cyanide, and the reduced form was shown to react reversibly with alkyl halides: cyanide inactivated the enzyme only in the absence of carbon monoxide, and alkyl halides inactivated it only in the presence of carbon monoxide. Extracts inactivated by alkyl halides were reactivated by photolysis. The findings are interpreted to indicate that carbon monoxide oxidation in the two bacteria is catalyzed by a corrinoid enzyme and that in vivo the reaction is coupled with the reduction of CO(2) to acetate. Cultures of C. acidi-urici and C. cylindrosporum growing on hypoxanthine were found not to oxidize CO, indicating that clostridia mediating a corrinoid-independent total synthesis of acetate from CO(2) do not possess a CO-oxidizing system.