DNA Damage and Reactive Nitrogen Species are Barriers to Vibrio cholerae Colonization of the Infant Mouse Intestine

Ingested Vibrio cholerae pass through the stomach and colonize the small intestines of its host. Here, we show that V. cholerae requires at least two types of DNA repair systems to efficiently compete for colonization of the infant mouse intestine. These results show that V. cholerae experiences increased DNA damage in the murine gastrointestinal tract. Agreeing with this, we show that passage through the murine gut increases the mutation frequency of V. cholerae compared to liquid culture passage. Our genetic analysis identifies known and novel defense enzymes required for detoxifying reactive nitrogen species (but not reactive oxygen species) that are also required for V. cholerae to efficiently colonize the infant mouse intestine, pointing to reactive nitrogen species as the potential cause of DNA damage. We demonstrate that potential reactive nitrogen species deleterious for V. cholerae are not generated by host inducible nitric oxide synthase (iNOS) activity and instead may be derived from acidified nitrite in the stomach. Agreeing with this hypothesis, we show that strains deficient in DNA repair or reactive nitrogen species defense that are defective in intestinal colonization have decreased growth or increased mutation frequency in acidified nitrite containing media. Moreover, we demonstrate that neutralizing stomach acid rescues the colonization defect of the DNA repair and reactive nitrogen species defense defective mutants suggesting a common defense pathway for these mutants

Television pictures of Phobos: first results

In February-March 1989, 37 television images of the Martian satellite Phobos were obtained by the Phobos 2 spacecraft from distances of 200-1100 km. These images provide an important supplement to the TV data from the American Mariner 9 and Viking spacecraft in coverage of t4e surface of Phobos and in resolution in certain regions, in spectral range, and in range of phase angles. They make it possible to refine the figure and topographic and geological maps of the surface of Phobos, its spectral and angular reflective characteristics, the surface composition and texture, and characteristics of the orbital and librational motion

The Architecture of Cognitive Vulnerability to Depressive Symptoms in Adolescence: A Longitudinal Network Analysis Study

Rates of subclinical symptoms and full-blown depression significantly increase during adolescence. Hence, understanding how multiple cognitive risk factors are related to depression in adolescence is of major importance. For this purpose, we simultaneously considered multiple cognitive vulnerabilities, as proposed by three major cognitive theories for depression, namely Beck\u2019s cognitive theory, hopelessness theory, and response style theory. In this four-wave study, we investigated the architecture, interplay, and stability of cognitive vulnerability mechanisms, depressive symptoms, and stressors in a large group of adolescents over a period of one year (n = 469; mean age = 15\ua0years; 64% female). Network analysis was used to shed light on the structure of cognitive vulnerabilities in a data-driven fashion. Analyses revealed that different cognitive vulnerabilities were intertwined and automatic thoughts played the role of hub node in the network. Moreover, the interplay among cognitive vulnerabilities and depressive symptoms was already markedly stable in adolescence and did not change over a 12-month period. Finally, no evidence was found that cognitive vulnerabilities interacted with stressors, as proposed by diathesis-stress models. These findings advance our understanding of multiple cognitive risk factors for depression in adolescence

Photodynamic effects induced by meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin on isolated Sarcoma 180 ascites mitochondria

Using mitochondria isolated from Sarcoma 180 ascites tumour in Swiss mice as a model system, we have evaluated the ability of a novel porphyrin, meso-tetrakis [4- (carboxymethyleneoxy) phenyl] porphyrin (H(2)T4CPP), to induce damage on photosensitization. Oxidative damage to mitochondria, one of the primary and crucial targets of the photodynamic effect, is assessed by measuring products of lipid peroxidation such as thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LOOH), besides the loss of activity of the mitochondrial marker enzyme succinate dehydrogenase ( SDH). Analysis of product formation, the effect of deuteration and selective inhibition by scavengers of reactive oxygen species (ROS) show that the damage observed is due mainly to singlet oxygen (O-1(2)) and to a minor extent to hydroxyl radicals ((OH)-O-.). The O-1(2) generation and triplet lifetime of this porphyrin have also been estimated. Fluorescence spectroscopy, used to ascertain the binding of this porphyrin to the mitochondrial proteins, shows a rapid association within 0-2 h and a decline thereafter. Confocal microscopy reveals intracellular localisation of this porphyrin in cells in vitro. Our overall results suggest that the porphyrin H(2)T4CPP, due to its ability to bind to mitochondrial protein components and to generate ROS upon photoexcitation, may have potential applications in photodynamic therapy. (C) 1999 Elsevier Science S.A.

TECHNISCHE

The 3D Optical Systems Group at MIT investigates Nanostructured Origami TM 3D fabrication and assembly. The idea is to assemble complex hybrid (chemical or biological reactors, optical sensing, digital electronic logic, mechanical motion) systems in 3D by using exclusively 2D lithography technology. The 3D shape is obtained by folding the initial 2D membrane in a prescribed way, in a manner reminiscent of the Japanese art of origami (paper-folding). The patterning method (2D nanolithography, nanoimprinting and other techniques) as well as the actuation principle (Lorentz force actuation) which is responsible for initializing the folding process have already been developed and established. The knowledge of the dynamic folding process itself, needed to reach any desired 3D shape from a 2D initial state is to-date unexplored. Hence, the primary objective of this thesis is to determine the motions required to reach the goal (folded state) from a given initial state (unfolded). Hereto general folding operations will be analyzed and a new method to describe its kinematics for any arbitrary structure will be developed

Global and Regional Production Networks: A Theoretical and Practical Synthesis

Part 1: Knowledge-Based Performance ImprovementInternational audienceThe growth of research interest in networked production has brought up numerous important concepts aimed at production networks. Still the actual research object seems to be ambiguous, making the exact application of findings insufficient. It appears that there are two main notions of the term Production Network. The first meaning is derived by a single versus a multi-organizational perspective while the second meaning comes from a regional versus global view. Obviously indistinctness exists in this field of research and clarification of terms and concept is required. The objective of this paper is to give an overview of the existing theories in accordance with the industrial practice providing a model to bridge the academic theories to industrial practice

Ultrasound for the Detection of Inflammatory Abdominal Aortic Aneurysms: A Case and Validation Series

Inflammatory abdominal aortic aneurysms (iAAA) are a form of noninfectious aortitis in patients with abdominal aortic aneurysms (AAA). Ultrasound could help to detect iAAA early. This retrospective observational study assessed the potential of using ultrasound to detect iAAA in a case series of iAAA patients, and the diagnostic value of ultrasound to detect iAAA in consecutive patients in a follow-up for AAA, referred to as a feasibility study. In both studies, diagnosis of iAAA was based on a cuff surrounding the aneurysm using CT (golden standard). The case series included 13 patients (age 64 (61; 72) years; 100% male). The feasibility study included 157 patients (age 75 (67; 80) years; 84% male). In the case series, all iAAA patients showed a cuff surrounding the aortic wall on ultrasound. In the feasibility study with AAA patients, ultrasound yielded no cuff in 147 (93.6%; CT negative in all cases), a typic cuff in 8 (5.1%; CT positive in all cases), and an inconclusive cuff in 2 (1.3%; CT negative in both cases) patients. Sensitivity and specificity were 100% and 98.7%, respectively. This study indicates that iAAA can be identified with ultrasound, and safely ruled out. In positive ultrasound cases, additional CT imaging might still be warranted