Regulation of dissimilatory sulfur oxidation in the purple sulfur bacterium Allochromatium vinosum

In the purple sulfur bacterium Allochromatium vinosum, thiosulfate oxidation is strictly dependent on the presence of three periplasmic Sox proteins encoded by the soxBXAK and soxYZ genes. It is also well documented that proteins encoded in the dissimilatory sulfite reductase (dsr) operon, dsrABEFHCMKLJOPNRS, are essential for the oxidation of sulfur that is stored intracellularly as an obligatory intermediate during the oxidation of thiosulfate and sulfide. Until recently, detailed knowledge about the regulation of the sox genes was not available. We started to fill this gap and show that these genes are expressed on a low constitutive level in A. vinosum in the absence of reduced sulfur compounds. Thiosulfate and possibly sulfide lead to an induction of sox gene transcription. Additional translational regulation was not apparent. Regulation of soxXAK is probably performed by a two-component system consisting of a multi-sensor histidine kinase and a regulator with proposed di-guanylate cyclase activity. Previous work already provided some information about regulation of the dsr genes encoding the second important sulfur-oxidizing enzyme system in the purple sulfur bacterium. The expression of most dsr genes was found to be at a low basal level in the absence of reduced sulfur compounds and enhanced in the presence of sulfide. In the present work, we focused on the role of DsrS, a protein encoded by the last gene of the dsr locus in A. vinosum. Transcriptional and translational gene fusion experiments suggest a participation of DsrS in the post-transcriptional control of the dsr operon. Characterization of an A. vinosum ΔdsrS mutant showed that the monomeric cytoplasmic 41.1-kDa protein DsrS is important though not essential for the oxidation of sulfur stored in the intracellular sulfur globules

Atraumatic oral spray immunization with replication-deficient viral vector vaccines

The development of needle-free vaccines is one of the recently defined grand challenges in global health (H. Varmus, R. Klausner, R. Klausner, R. Zerhouni, T. Acharya, A. S. Daar, and P. A. Singer, Science 302:398-399, 2003). To explore whether a natural pathway to the inductive site of the mucosa-associated lymphatic tissue could be exploited for atraumatic immunization purposes, replication-deficient viral vector vaccines were sprayed directly onto the tonsils of rhesus macaques. Tonsillar immunization with viral vector vaccines encoding simian immunodeficiency virus (SIV) antigens induced cellular and humoral immune responses. Viral RNA levels after a stringent SIV challenge were reduced, providing a level of protection similar to that observed after systemic immunization with the same vaccines. Thus, atraumatic oral spray immunization with replication-deficient vectors can overcome the epithelial barrier, deliver the vaccine antigen to the mucosa-associated lymphatic tissue, and avoid induction of tolerance, providing a novel approach to circumvent acceptability problems of syringe and needle vaccines for children and in developing countries

A python tool to determine the thickness of the hydrate layer around clinker grains using SEM-BSE images

To accurately simulate the hydration process of cementitious materials, understanding the growth rate of C-S-H layers around clinker grains is crucial. Nonetheless, the thickness of the hydrate layer shows substantial variation around individual grains, depending on their surrounding. Consequently, it is not feasible to measure hydrate layers manually in a reliable and reproducible manner. To address this challenge, a software has been developed to statistically determine the C-S-H thickness, requiring minimal manual interventions for thresholding and for setting limits like particle size or circularity. This study presents a tool, which automatically identifies suitable clinker grains and and perform statistical measurements of their hydrate layer up to a specimen age of 28 days. The findings reveal a significant increase in the C-S-H layer, starting from 0.45 micrometer after 1 day and reaching 3.04 micrometer after 28 days. However, for older specimens, the measurement of the C-S-H layer was not feasible due to limited pore space and clinker grains.Comment: Paper for the 19th Euroseminar on Microscopy Applied to Building Materials in a special issue, 7 pages, 5 figures, 2 table

Eutergesundheits- und Stoffwechselstatus von Milchkühen in der Frühlaktation - was gibt den Ausschlag: Rasse oder Management?

Der Zeitraum der ansteigenden Milchleistung nach dem Kalben birgt ein höheres Risiko, dass die Tiere an Stoffwechselstörungen oder Mastitis erkranken. Die rechtlichen Regelungen für den ökologischen Landbau verschärfen dieses Risiko durch die Limitierung des Kraftfuttereinsatzes, fordern aber auch von den Landwirten mit Hilfe angepasster Rassen, dieses Problem anzugehen. Die vorliegende Studie zielte auf den Vergleich von zwei verschiedenen Rassen, die unter den gleichen Managementbedingungen gehalten wurden und einem Vergleich von zwei Betrieben, die zwar die gleiche Rasse hielten, sich aber im Management unterschieden. Es sollte geprüft werden ob die Rasse oder das Management entscheidender für den Eutergesundheits- und Stoffwechselstatus der Kühe in den ersten fünf Laktationswochen ist. Die Ergebnisse zeigten einen signifikanten Effekt der Energiebilanz und der Woche der Probenahme auf die getesteten Kriterien zur Einschätzung der Stoffwechselsituation (Fett-Eiweiß-Quotient FEQ, BHB-Konzentration der Milch, Glutamatdehydrogenase, nichtveresterte Fettsäuren). Hinsichtlich des FEQ und der BHB-Konzentration ergaben sich deutliche Effekte des Managements und der Rasse, wobei der managementeffekt deutlicher wurde. Der Zellgehalt des Gesamtgemelks zeigte Unterschiede zwischen den Herden, aber nicht zwischen den Rassen, die unter gleichen Bedingungen gehalten wurden

3-D reconstruction of anterior mantle-field techniques in Hodgkin's disease survivors: doses to cardiac structures

BACKGROUND: The long-term dose-effect relationship for specific cardiac structures in mediastinal radiotherapy has rarely been investigated. As part of an interdisciplinary project, the 3-D dose distribution within the heart was reconstructed in all long-term Hodgkin's disease survivors (n = 55) treated with mediastinal radiotherapy between 1978 and 1985. For dose reconstruction, original techniques were transferred to the CT data sets of appropriate test patients, in whom left (LV) and right ventricle (RV), left (LA) and right atrium (RA) as well as right (RCA), left anterior descending (LAD) and left circumflex (LCX) coronary arteries were contoured. Dose-volume histograms (DVHs) were generated for these heart structures and results compared between techniques. RESULTS: Predominant technique was an anterior mantle field (cobalt-60). 26 patients (47%) were treated with anterior mantle field alone (MF), 18 (33%) with anterior mantle field and monoaxial, bisegmental rotation boost (MF+ROT), 7 (13%) with anterior mantle field and dorsal boost (MF+DORS) and 4 (7%) with other techniques. Mean ± SD total mediastinal doses for MF+ROT (41.7 ± 3.5 Gy) and for MF+DORS (42.7 ± 7.4) were significantly higher than for MF (36.7 ± 5.2 Gy). DVH analysis documented relative overdosage to right heart structures with MF (median maximal dose to RV 129%, to RCA 127%) which was siginificantly reduced to 117% and 112%, respectively, in MF+ROT. Absolute doses in right heart structures, however, did not differ between techniques. Absolute LA doses were significantly higher in MF+ROT patients than in MF patients where large parts of LA were blocked. Median maximal doses for all techniques ranged between 48 and 52 Gy (RV), 44 and 46 Gy (LV), 47 and 49 Gy (RA), 38 and 45 Gy (LA), 46 and 50 Gy (RCA), 39 and 44 Gy (LAD) and 34 and 42 Gy (LCX). CONCLUSION: In patients irradiated with anterior mantle-field techniques, high doses to anterior heart portions were partly compensated by boost treatment from non-anterior angles. As the threshold doses for coronary artery disease, cardiomyopathy, pericarditis and valvular changes are assumed to be 30 to 40 Gy, cardiac toxicity must be anticipated in these patients. Thus, dose distributions in individual subjects should be correlated to the corresponding cardiovascular findings in these long-term survivors, e. g. by cardiovascular magnetic resonance imaging

C-S-H Pore Size Characterization Via a Combined Nuclear Magnetic Resonance (NMR)-Scanning Electron Microscopy (SEM) Surface Relaxivity Calibration.

A new method for the nuclear magnetic resonance (NMR) surface relaxivity calibration in hydrated cement samples is proposed. This method relies on a combined analysis of 28-d hydrated tricalcium silicate samples by scanning electron microscopy (SEM) image analysis and 1H-time-domain (TD)-NMR relaxometry. Pore surface and volume data for interhydrate pores are obtained from high resolution SEM images on surfaces obtained by argon broad ion beam sectioning. These data are combined with T2 relaxation times from 1H-TD-NMR to calculate the systems surface relaxivity according to the fast exchange model of relaxation. This new method is compared to an alternative method that employs sequential drying to calibrate the systems surface relaxivity

Exploring Influences on Theory of Mind Impairment in Opioid Dependent Patients

Theory of mind (ToM) is an aspect of social cognition impaired in different addictive disorders, including opioid addiction. This study aimed at replicating ToM deficits in opioid dependent patients undergoing opioid maintenance treatment (OMT) and exploring the influence of substance use related variables, executive functions and childhood maltreatment on ToM in opioid dependent patients. 66 opioid dependent patients were tested using the Movie for Assessment of Social Cognition (MASC) and compared with the data of healthy controls. Furthermore, the opioid dependent patients underwent testing for executive functions and filled in the Childhood Trauma Questionnaire (CTQ). Performance on the MASC was significantly poorer in the opioid dependence group than in the control group, even when recent additional drug use and psychiatric comorbidities were controlled for. No correlations were found between ToM and substance use related factors. Aspects of ToM performance in opioid dependent patients correlated significantly with different EF domains. ToM correlated significantly with the CTQ scales for physical maltreatment. The results confirm impaired ToM in opioid dependent patients and highlight executive functions and childhood maltreatment as influential factors. The lack of associations between ToM and substance use related variables and the association with childhood maltreatment suggest that ToM impairments might be a risk factor predating substance abuse.Peer Reviewe

Ultrafine carbon particles down-regulate CYP1B1 expression in human monocytes

Cytochrome P450 monoxygenases play an important role in the defence against inhaled toxic compounds and in metabolizing a wide range of xenobiotics and environmental contaminants. In ambient aerosol the ultrafine particle fraction which penetrates deeply into the lungs is considered to be a major factor for adverse health effects. The cells mainly affected by inhaled particles are lung epithelial cells and cells of the monocyte/macrophage lineage. RESULTS: In this study we have analyzed the effect of a mixture of fine TiO2 and ultrafine carbon black Printex 90 particles (P90) on the expression of cytochrome P450 1B1 (CYP1B1) in human monocytes, macrophages, bronchial epithelial cells and epithelial cell lines. CYP1B1 expression is strongly down-regulated by P90 in monocytes with a maximum after P90 treatment for 3 h while fine and ultrafine TiO2 had no effect. CYP1B1 was down-regulated up to 130-fold and in addition CYP1A1 mRNA was decreased 13-fold. In vitro generated monocyte-derived macrophages (MDM), epithelial cell lines, and primary bronchial epithelial cells also showed reduced CYP1B1 mRNA levels. Benzo[a]pyrene (BaP) is inducing CYB1B1 but ultrafine P90 can still down-regulate gene expression at 0.1 muM of BaP. The P90-induced reduction of CYP1B1 was also demonstrated at the protein level using Western blot analysis. CONCLUSION: These data suggest that the P90-induced reduction of CYP gene expression may interfere with the activation and/or detoxification capabilities of inhaled toxic compounds

A Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection

The intentional re-introduction of Variola virus (VARV), the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV) and Monkeypox virus (MPXV) cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus)