TorC apocytochrome negatively autoregulates the trimethylamine N-oxide (TMAO) reductase operon in Escherichia coli

The trimethylamine N-oxide (TMAO) anaerobic respiratory system of Escherichia coli comprises a periplasmic terminal TMAO reductase (TorA) and a pentahaem c-type cytochrome (TorC), which is involved in electron transfer to TorA. The structural proteins are encoded by the torCAD operon whose expression is induced in the presence of TMAO through the TorS/TorR two-component system. By using a genomic library cloned into a multicopy plasmid, we identified TorC as a possible negative regulator of the tor operon. Interestingly, in trans overexpression of torC not only decreased the activity of a torA'-'lacZ fusion, but also dramatically reduced the amount of mature TorC cytochrome. This led us to propose that, after translocation, TorC apocytochrome downregulates the tor operon unless it is properly matured. In agreement with this hypothesis, we have shown that mini-Tn10 insertions within genes involved in the c-type cytochrome maturation pathway or haem biosynthesis decreased tor operon expression. Dithiothreitol (DTT), which reduces disulphide bonds and thus prevents the first step in c-type cytochrome formation, also strongly decreases the tor promoter activity. The DTT effect is TorC dependent, as it is abolished when torC is disrupted. In contrast, overexpression of the c-type cytochrome maturation (ccm ) genes relieved the tor operon of the negative control and allowed the bacteria to produce a higher amount of TorC holocytochrome. Therefore, the TorC negative autoregulation probably means that maturation of the c-type cytochrome is a limiting step for Tor system biogenesis. Genetic experiments have provided evidence that TorC control is mediated by the TorS/TorR two-component system and different from the tor anaerobic control. In our working model, TMAO and apoTorC bind to the periplasmic side of TorS, but TMAO activates TorS autophosphorylation, whereas apoTorC inhibits the TorS kinase activity.     

Systems healthcare: a holistic paradigm for tomorrow

Systems healthcare is a holistic approach to health premised on systems biology and medicine. The approach integrates data from molecules, cells, organs, the individual, families, communities, and the natural and man-made environment. Both extrinsic and intrinsic influences constantly challenge the biological networks associated with wellness. Such influences may dysregulate networks and allow pathobiology to evolve, resulting in early clinical presentation that requires astute assessment and timely intervention for successful mitigation. Herein, we describe the components of relevant biological systems and the nature of progression from at-risk to manifest disease. We illustrate the systems approach by examining two relevant clinical examples: Alzheimer’s and cardiovascular diseases. The implications of systems healthcare management are examined through the lens of economics, ethics, policy and the law. Finally, we propose the need to develop new educational paradigms to enhance the training of the health professional in an era of systems medicine.     

Modulation de la Réponse du Xyléme selon la Nature de l'Agression Vasculaire

Modulation of the xylem response to different types of vascular aggressions The evolution of cells lining the vessels in the stem xylem of carnation was compared in sham-stressed (s. e.), V. dabliae-infected (i V. d.) and P. cinerescens-infected (i P. c.) plants. All experimental stresses triggered ultrastructural changes leading to the appearance of new cell types. In parallel, vacuolar polyphenols were metabolized and dense-core vesicles appeared. These were early and independant phenomena. In all cases the reactions of carnation xylem were stronger against Verticillium than against Phialophora. Differences in vascular gummosis were disclosed whatever the criterion used (speed of installation, relative importance of the phenomenon, level of structural complexity, dynamics of appearance of the different structures). The possible relations between cell structures and gummous secretions were investigated by means of comparison of an efficient defence system (i V. d.) with a deficient one (i P. c.). All the criteria selected for analysis confirm that faced with a specific parasite the host response was disrupted. In other words, the biosynthetic pathways normally used by the plant after a fungal aggression were blocked, slowed or diverted. The differences in the responses of carnation to Verticillium and Phialophora give a picture of parasite specificity in agreement with the model recently proposed by de Wit (1981) for tomato/Cladosporium fulvum.     

Implications of feeding specialization on the recruitment processes and community structure of butterflyfishes

Synopsis When settling on coral reefs, fish larvae generally change from zooplanktivory to diverse forms of benthic feeding. Whereas food has not been reported to directly influence settlement, it is hypothesized that food resource might play a major role in the recruitment processes of butterflyfishes. Benthic feeding was found to occur immediatly after settlement, and was related to the degree of specialization of adult diets. Among obligate coral feeders scleractinian polyps were the exclusive diet of new recruits. In non-obligate corallivorous chaetodontids tentacles of sedentarian polychaetes were the preferred prey of juveniles for all the species studied, and represented on average 36.2% of their prey by weight. They formed a transitional food resource for these species which mainly fed on scleratinian polyps when adults (51.6% by weight). Among the chaetodontids studies, some recruited within adult home sites, whereas others exhibited size-specific distributions. The different patterns observed were not closely related to food specialization of the adults. The importance of food resources to the community structure of butterflyfishes on coral reefs is discussed.     

An integrative morphological and molecular diagnostics for Typhlodromus pyri (Acari: Phytoseiidae)

Tixier, M‐S., Okassa, M. & Kreiter, S. (2011). An integrative morphological and molecular diagnostics for Typhlodromus pyri (Acari: Phytoseiidae). —Zoologica Scripta, 41, 68–78. Phytoseiidae species are predators used in biological control programmes to limit mite pests out‐breaks in the world. Specific diagnostic is thus very important to ensure the success of pest management. This study aims to determine the species status of populations within the main species in vineyards and orchards: Typhlodromus (Typhlodromus) pyri, considering four molecular markers (COI, Cytb mtDNAs, 12SrRNA, ITSS) and 34 morphometrical characters. With the three mitochondrial DNA fragments considered, unexpected high genetic distances were observed between two groups, whereas both nuclear DNA and morphological analyses did not show such distinction. Furthermore, the GYMC and the 4 × rule tests emphasised the existence of a single species. Similarly, cross‐breeding experiments between specimens of the two groups showed no reproductive incompatibility. Therefore, despite the great intraspecific variation emphasised by the three mtDNA markers, we conclude that all the specimens considered belong to the same species. The present study clearly underlines the difficulty to conclude on species status using only mt markers and genetic distances, and stresses the necessity to apply multiple approaches for species definition. It also shows the confidence of the morphology for delineating this species.     

Brain Diurnal Levels of Adenosine 3', 5' Cyclic Monophasphate in C57 Bl/6 and Balb/C Mice

Adenosine 3', 5'-cyclic monophosphate (cAMP) was measured in whole brain of two inbred strains of mice (BALB/C and C57 BL/6) submitted to a lighting schedule consisting of 12 hr light (0700-1900) and 12 hr darkness (1900-0700). Different mean levels of cAMP were found in each strain. Furthermore, statistical analysis of diurnal brain cAMP fluctuations showed different nycthemeral rhythms in both strains. BALB/C was mainly characterized by the presence of very significant 0600 and 0800 harmonics and C57 BL/6 by an orthophase around 1700 hr.

Because both strains were studied under the same experimental conditions of light, temperature and food availability, these factors cannot account for the observed differences, which were thus tentatively interpreted in terms of genetic regulatory processes.     

5-Hydroxymethyluracil excretion, plasma tbars and plasma antioxidant vitamins in adriamycin-treated patients

The thymine oxidative lesion-5-hydroxymethyluracil (HMUra)—was measured in urine collected from cancer patients. These patients all received chemotherapy using Adriamycin. Adriamycin (ADR) intercalates DNA coils and interferes with normal cell metabolism through diverse biochemical mechanisms that may explain its different actions. The anticancer action of ADR could derive from its interaction with topoisomerase II, resulting in DNA nicking followed by DNA fragmentation and apoptosis. Side effects of ADR—mainly its cardiotoxicity—may derive from the fact that ADR generates superoxide and hydroxyl radicals in two ways: redox-cycling and a Haber-Weiss type reaction due to Fe-ADR complexes. The oxygen free radicals, particularly 'OH, are thought to be produced by ADR directly in genomic material and attack all its components. 5-Hydroxymethyluracil is a thymine lesion provoked by these attacks, and it has been proposed as a marker of DNA alterations. In this article, we report the results of a study involving 14 cancer patients treated with ADR. We found that urine HMUra is significantly increased by the anticancer therapy (HMUra (nmol/24 h): 74.4 9.46 vs. 96.3 8.74; p < .01), this increase reveals a higher risk of mutagenesis. Our study is the first to show an in vivo alteration of DNA by ADR. Results also show that thiobarbituric acid reactants increase significantly, and that the vitamin levels for retinol and a-tocopherol, which are antioxidant vitamins, are lower at the end of chemotherapy. We suggest to supplement these patients with vitamins A and E, and selenium to reduce the side effects of ADR.