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71.
Felgate H Giannopoulos G Sullivan MJ Gates AJ Clarke TA Baggs E Rowley G Richardson DJ 《Environmental microbiology》2012,14(7):1788-1800
Denitrifying bacteria convert nitrate (NO(3) (-) ) to dinitrogen (N(2) ) gas through an anaerobic respiratory process in which the potent greenhouse gas nitrous oxide (N(2) O) is a free intermediate. These bacteria can be grouped into classes that synthesize a nitrite (NO(2) (-) ) reductase (Nir) that is solely dependent on haem-iron as a cofactor (e.g. Paracoccus denitrificans) or a Nir that is solely dependent on copper (Cu) as a cofactor (e.g. Achromobacter xylosoxidans). Regardless of which form of Nir these groups synthesize, they are both dependent on a Cu-containing nitrous oxide reductase (NosZ) for the conversion of N(2) O to N(2) . Agriculture makes a major contribution to N(2) O release and it is recognized that a number of agricultural lands are becoming Cu-limited but are N-rich because of fertilizer addition. Here we utilize continuous cultures to explore the denitrification phenotypes of P.?denitrificans and A.?xylosoxidans at a range of extracellular NO(3) (-) , organic carbon and Cu concentrations. Quite distinct phenotypes are observed between the two species. Notably, P.?denitrificans emits approximately 40% of NO(3) (-) consumed as N(2) O under NO(3) (-) -rich Cu-deficient conditions, while under the same conditions A.?xylosoxidans releases approximately 40% of the NO(3) (-) consumed as NO(2) (-) . However, the denitrification phenotypes are very similar under NO(3) (-) -limited conditions where denitrification intermediates do not accumulate significantly. The results have potential implications for understanding denitrification flux in a range of agricultural environments. 相似文献
72.
Trevor J. Morin Teresa J. Broering Brett A. Leav Barbra M. Blair Kirk J. Rowley Elisabeth N. Boucher Yang Wang Peter S. Cheslock Michael Knauber David B. Olsen Steve W. Ludmerer Gyongyi Szabo Robert W. Finberg Robert H. Purcell Robert E. Lanford Donna M. Ambrosino Deborah C. Molrine Gregory J. Babcock 《PLoS pathogens》2012,8(8)
Hepatitis C virus (HCV) infection is a leading cause of liver transplantation and there is an urgent need to develop therapies to reduce rates of HCV infection of transplanted livers. Approved therapeutics for HCV are poorly tolerated and are of limited efficacy in this patient population. Human monoclonal antibody HCV1 recognizes a highly-conserved linear epitope of the HCV E2 envelope glycoprotein (amino acids 412–423) and neutralizes a broad range of HCV genotypes. In a chimpanzee model, a single dose of 250 mg/kg HCV1 delivered 30 minutes prior to infusion with genotype 1a H77 HCV provided complete protection from HCV infection, whereas a dose of 50 mg/kg HCV1 did not protect. In addition, an acutely-infected chimpanzee given 250 mg/kg HCV1 42 days following exposure to virus had a rapid reduction in viral load to below the limit of detection before rebounding 14 days later. The emergent virus displayed an E2 mutation (N415K/D) conferring resistance to HCV1 neutralization. Finally, three chronically HCV-infected chimpanzees were treated with a single dose of 40 mg/kg HCV1 and viral load was reduced to below the limit of detection for 21 days in one chimpanzee with rebounding virus displaying a resistance mutation (N417S). The other two chimpanzees had 0.5–1.0 log10 reductions in viral load without evidence of viral resistance to HCV1. In vitro testing using HCV pseudovirus (HCVpp) demonstrated that the sera from the poorly-responding chimpanzees inhibited the ability of HCV1 to neutralize HCVpp. Measurement of antibody responses in the chronically-infected chimpanzees implicated endogenous antibody to E2 and interference with HCV1 neutralization although other factors may also be responsible. These data suggest that human monoclonal antibody HCV1 may be an effective therapeutic for the prevention of graft infection in HCV-infected patients undergoing liver transplantation. 相似文献
73.
Tomá? Helikar Bryan Kowal Alex Madrahimov Manish Shrestha Jay Pedersen Kahani Limbu Ishwor Thapa Thaine Rowley Rahul Satalkar Naomi Kochi John Konvalina Jim A. Rogers 《PloS one》2012,7(10)
Computational modeling of biological processes is a promising tool in biomedical research. While a large part of its potential lies in the ability to integrate it with laboratory research, modeling currently generally requires a high degree of training in mathematics and/or computer science. To help address this issue, we have developed a web-based tool, Bio-Logic Builder, that enables laboratory scientists to define mathematical representations (based on a discrete formalism) of biological regulatory mechanisms in a modular and non-technical fashion. As part of the user interface, generalized “bio-logic” modules have been defined to provide users with the building blocks for many biological processes. To build/modify computational models, experimentalists provide purely qualitative information about a particular regulatory mechanisms as is generally found in the laboratory. The Bio-Logic Builder subsequently converts the provided information into a mathematical representation described with Boolean expressions/rules. We used this tool to build a number of dynamical models, including a 130-protein large-scale model of signal transduction with over 800 interactions, influenza A replication cycle with 127 species and 200+ interactions, and mammalian and budding yeast cell cycles. We also show that any and all qualitative regulatory mechanisms can be built using this tool. 相似文献
74.
Alvarez R Reading J King DF Hayes M Easterbrook P Farzaneh F Ressler S Yang F Rowley D Vyakarnam A 《Journal of virology》2008,82(1):471-486
Understanding why human immunodeficiency virus (HIV) preferentially infects some CD4+ CD45RO+ memory T cells has implications for antiviral immunity and pathogenesis. We report that differential expression of a novel secreted factor, ps20, previously implicated in tissue remodeling, may underlie why some CD4 T cells are preferentially targeted. We show that (i) there is a significant positive correlation between endogenous ps20 mRNA in diverse CD4 T-cell populations and in vitro infection, (ii) a ps20+ permissive cell can be made less permissive by antibody blockade- or small-interference RNA-mediated knockdown of endogenous ps20, and (iii) conversely, a ps20low cell can be more permissive by adding ps20 exogenously or engineering stable ps20 expression by retroviral transduction. ps20 expression is normally detectable in CD4 T cells after in vitro activation and interleukin-2 expansion, and such oligoclonal populations comprise ps20positive and ps20low/negative isogenic clones at an early differentiation stage (CD45RO+/CD25+/CD28+/CD57−). This pattern is altered in chronic HIV infection, where ex vivo CD4+ CD45RO+ T cells express elevated ps20. ps20 promoted HIV entry via fusion and augmented CD54 integrin expression; both of these effects were reversed by anti-ps20 antibody. We therefore propose ps20 to be a novel signature of HIV-permissive CD4 T cells that promotes infection in an autocrine and paracrine manner and that HIV has coopted a fundamental role of ps20 in promoting cell adhesion for its benefit. Disrupting the ps20 pathway may therefore provide a novel anti-HIV strategy. 相似文献
75.
Kawasaki disease (KD) has emerged as the most common cause of acquired heart disease in children in the developed world. The cause of KD remains unknown, although an as-yet unidentified infectious agent might be responsible. By determining the causative agent, we can improve diagnosis, therapy and prevention of KD. Recently, identification of an antigen-driven IgA response that was directed at cytoplasmic inclusion bodies in KD tissues has provided new insights that could unlock the mysteries of KD. 相似文献
76.
Rowley AH Baker SC Shulman ST Garcia FL Fox LM Kos IM Crawford SE Russo PA Hammadeh R Takahashi K Orenstein JM 《PloS one》2008,3(2):e1582
Background
Kawasaki Disease (KD) is the most common cause of acquired heart disease in children in developed nations. The KD etiologic agent is unknown but likely to be a ubiquitous microbe that usually causes asymptomatic childhood infection, resulting in KD only in genetically susceptible individuals. KD synthetic antibodies made from prevalent IgA gene sequences in KD arterial tissue detect intracytoplasmic inclusion bodies (ICI) resembling viral ICI in acute KD but not control infant ciliated bronchial epithelium. The prevalence of ICI in late-stage KD fatalities and in older individuals with non-KD illness should be low, unless persistent infection is common.Methods and Principal Findings
Lung tissue from late-stage KD fatalities and non-infant controls was examined by light microscopy for the presence of ICI. Nucleic acid stains and transmission electron microscopy (TEM) were performed on tissues that were strongly positive for ICI. ICI were present in ciliated bronchial epithelium in 6/7 (86%) late-stage KD fatalities and 7/27 (26%) controls ages 9–84 years (p = 0.01). Nucleic acid stains revealed RNA but not DNA within the ICI. ICI were also identified in lung macrophages in some KD cases. TEM of bronchial epithelium and macrophages from KD cases revealed finely granular homogeneous ICI.Significance
These findings are consistent with a previously unidentified, ubiquitous RNA virus that forms ICI and can result in persistent infection in bronchial epithelium and macrophages as the etiologic agent of KD. 相似文献77.
For the first time, the developmental events in the course of complicated exine structure establishment have been traced in detail with transmission electron microscope in the representative of Acer. A new look at unfolding events is suggested using the knowledge of a boundary field, colloid science. Our purpose was to find out whether the sequence of sporoderm developmental events represents, in essence, the sequence of self-assembling micellar mesophases, initiated by genomically given physicochemical parameters and induced by surfactant glycoproteins at increasing concentration. Indeed, the first units observed in the periplasmic space are globular ones (=spherical micelles) which become arranged into rod-like units (=cylindrical micelles). Then, twisted clusters of rodlets form a layer of procolumellae (middle micellar mesophase). The tectum emerges as an untwisting and merging of distal ends of procolumellae (distal untwist of micelle clusters). In the end of tetrad period, when a hydrophilic–hydrophobic switch occurs in the periplasmic space, the contrast reversal of the columellae corresponds to the change of normal micelles to reverse ones. The initiation of the foot layer and the endexine lamellae, with their typical central “white lines”, corresponds to the next—“neat”—mesophase, with its typical central gaps between layers. Aperture sites during development show all the main micellar mesophases and their transitional forms. The data received have supported our previous hypothesis. 相似文献
78.
The effects of glucose, sulfated cholecystokinin-octapeptide (CCK-8), or carbachol on insulin secretory dynamics were studied in pancreatic islets isolated from 1- and 3-day-old neonatal rats. When challenged with glucose, 1-day islets responded with a definite first phase and elevated secretion during the latter part of the stimulation period; 3-day islets had a first phase and a rising, sustained second phase. The presence of stimulatory concentrations of CCK-8 or carbachol in addition to glucose caused dramatic changes in the release pattern in both islet populations. In 1-day islets, carbachol stimulated mainly first phase secretion whereas CCK-8 enhanced first phase release and produced a definite second phase response. The two secretagogues increased significantly both phases of release in 3-day islets with no differences between the two agents in their effects. These results indicate that CCK-8 and carbachol differentially stimulate neonatal insulin secretion, possibly through different steps in the stimulus-secretion pathway. They also suggest that the cellular mechanism for second phase release is present in 1-day islets and can be activated by CCK-8. 相似文献
79.
A. J. Cowley R. D. Wynne K. Stainer L. Fullwood J. M. Rowley J. R. Hampton 《BMJ (Clinical research ed.)》1988,297(6642):169-173
There is no single, simple test with which to evaluate new treatments for heart failure. Various methods need to be used, and a study of both the acute haemodynamic and longer term symptomatic effects of flosequinan, a new direct acting arteriolar and venous vasodilator, was therefore carried out in patients with heart failure. In one group of patients flosequinan increased cardiac output and caused a fall in pulmonary capillary wedge pressure, both effects lasting for 24 hours. In a double blind, placebo controlled study in another group flosequinan improved mean exercise tolerance from 9.9 to 12.7 minutes after four weeks of treatment. The drug also reduced perceived exertion during submaximal exercise and increased calf and therefore skeletal muscle blood flow. It reduced plasma renin activity and noradrenaline concentrations. Flosequinan possesses all the important properties of a drug likely to be of value in the treatment of heart failure. 相似文献
80.
Identificaton of a translocation with quinacrine fluorescence in a patient with acute leukemia 总被引:9,自引:0,他引:9
J D Rowley 《Annales de génétique》1973,16(2):109-112