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51.
52.
Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium tuberculosis dormancy regulon 总被引:3,自引:0,他引:3
Kumar A Deshane JS Crossman DK Bolisetty S Yan BS Kramnik I Agarwal A Steyn AJ 《The Journal of biological chemistry》2008,283(26):18032-18039
The mechanisms that allow Mycobacterium tuberculosis (Mtb) to persist in human tissue for decades and to then abruptly cause disease are not clearly understood. Regulatory elements thought to assist Mtb to enter such a state include the heme two-component sensor kinases DosS and DosT and the cognate response regulator DosR. We have demonstrated previously that O(2), nitric oxide (NO), and carbon monoxide (CO) are regulatory ligands of DosS and DosT. Here, we show that in addition to O(2) and NO, CO induces the complete Mtb dormancy (Dos) regulon. Notably, we demonstrate that CO is primarily sensed through DosS to induce the Dos regulon, whereas DosT plays a less prominent role. We also show that Mtb infection of macrophage cells significantly increases the expression, protein levels, and enzymatic activity of heme oxygenase-1 (HO-1, the enzyme that produces CO), in an NO-independent manner. Furthermore, exploiting HO-1(+/+) and HO-1(-/-) bone marrow-derived macrophages, we demonstrate that physiologically relevant levels of CO induce the Dos regulon. Finally, we demonstrate that increased HO-1 mRNA and protein levels are produced in the lungs of Mtb-infected mice. Our data suggest that during infection, O(2), NO, and CO are being sensed concurrently rather than independently via DosS and DosT. We conclude that CO, a previously unrecognized host factor, is a physiologically relevant Mtb signal capable of inducing the Dos regulon, which introduces a new paradigm for understanding the molecular basis of Mtb persistence. 相似文献
53.
Enterocyte expression of the eotaxin and interleukin-5 transgenes induces compartmentalized dysregulation of eosinophil trafficking. 总被引:2,自引:0,他引:2
Anil Mishra Simon P Hogan Eric B Brandt Norbert Wagner Michael W Crossman Paul S Foster Marc E Rothenberg 《The Journal of biological chemistry》2002,277(6):4406-4412
Eosinophils accumulate in the gastrointestinal tract in a number of medical disorders, but the mechanisms involved are largely unknown. To understand the significance of cytokine expression by enterocytes, enterocyte transgenic mice that overexpressed the eosinophil-selective cytokines eotaxin and interleukin (IL)-5 were generated. Transgenic mice, generated by utilizing the rat intestinal fatty acid-binding protein promoter (Fabpi), overexpressed the mRNA for these cytokines in the small intestine. Overexpression of IL-5 resulted in marked increases of eosinophils in the bone marrow and blood, whereas eotaxin overexpression resulted in similar levels compared with nontransgenic control mice. In contrast, both IL-5 and eotaxin transgenic mice had significant accumulation of eosinophils in the gastrointestinal mucosa compared with control mice. Eotaxin-induced gastrointestinal eosinophilia was substantially higher than that induced by IL-5 and was especially prominent within the lamina propria of the villi. Interestingly, genetic rescue of eotaxin deficiency (by transgenic overexpression of eotaxin in eotaxin gene-targeted mice) resulted in significant restoration of gastrointestinal eosinophil levels. Finally, the intestinal eosinophilia induced by the eotaxin transgene was beta(7) integrin-dependent. Taken together, these results demonstrate that expression of eotaxin and IL-5 in intestinal epithelium induces compartmentalized dysregulation of eosinophil trafficking and the important role of the beta(7) integrin in gastrointestinal allergic responses. 相似文献
54.
Tony Hickey Jules Devaux Vijay Rajagopal Amelia Power David Crossman 《Biophysical reviews》2022,14(1):403
In the Carboniferous, insects evolved flight. Intense selection drove for high performance and approximately 100 million years later, Hymenoptera (bees, wasps and ants) emerged. Some species had proportionately small wings, with apparently impossible aerodynamic challenges including a need for high frequency flight muscles (FMs), powered exclusively off aerobic pathways and resulting in extreme aerobic capacities. Modern insect FMs are the most refined and form large dense blocks that occupy 90% of the thorax. These can beat wings at 200 to 230 Hz, more than double that achieved by standard neuromuscular systems. To do so, rapid repolarisation was circumvented through evolution of asynchronous stimulation, stretch activation, elastic recoil and a paradoxically slow Ca2+ reuptake. While the latter conserves ATP, considerable ATP is demanded at the myofibrils. FMs have diminished sarcoplasmic volumes, and ATP is produced solely by mitochondria, which pack myocytes to maximal limits and have very dense cristae. Gaseous oxygen is supplied directly to mitochondria. While FMs appear to be optimised for function, several unusual paradoxes remain. FMs lack any significant equivalent to the creatine kinase shuttle, and myofibrils are twice as wide as those of within cardiomyocytes. The mitochondrial electron transport systems also release large amounts of reactive oxygen species (ROS) and respiratory complexes do not appear to be present at any exceptional level. Given that the loss of the creatine kinase shuttle and elevated ROS impairs heart function, we question how do FM shuttle adenylates at high rates and tolerate oxidative stress conditions that occur in diseased hearts? 相似文献
55.
Synopsis Apparatus and methods are described and illustrated for flushing and retaining gut contents from large, living fishes with water supplied by a 12 volt portable pump. 相似文献
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58.
Neural mechanisms in disorders of movement 总被引:2,自引:0,他引:2
1. Experimental models of ballism, chorea and Parkinson's disease have been developed in the primate, and the underlying neural mechanisms which mediate these disorders of movement have been investigated using the 2-deoxyglucose uptake technique. 2. In ballism, the subthalamic nucleus is either lesioned or underactive. Because of the excitatory nature of subthalamic efferent fibres, this leads to abnormal underactivity of neurons in the medical segment of the globus pallidus which project to the ventral anterior and ventral lateral nuclei of the thalamus, and to the pedunculopontine nucleus of the caudal midbrain. 3. In chorea, there is underactivity of GABAergic striatal (putaminal) neurons which project to the lateral segment of the globus pallidus. This leads to overacting of lateral pallidal neurons and, thus, physiological inhibition of the subthalamic nucleus. Common neural mechanisms, therefore, underlie the appearance of dyskinesia in ballism and chorea. 4. In parkinsonism, there is overactivity of putaminal neurons projecting to the lateral pallidal segment. This results in excessive inhibition of lateral pallidal neurons and, as a consequence, disinhibition of the subthalamic nucleus. Overactivity of the subthalamic nucleus provides excessive drive upon medial pallidal neurons projecting to thalamic and pedunculopontine nuclei. 相似文献
59.
Young excised coleoptiles from dark grown wheat have their cell growth promoted by gibberellic acid (GA3 ), while sections from older coleoptiles have their cell growth promoted by auxin. The GA3 response has a much longer lag period than that of auxin. Neither GA3 nor auxin has any effect on 14 C-leucine and 14 C-uridine incorporation and uptake after 1 h, indicating that the lag in growth stimulation following GA3 application is not associated with changes in protein or RNA synthesis. Following a 6 h incubation there are small increases in 14 C-leucine and 14 C-uridine incorporation in response to both GA3 and auxin, and in the case of auxin this is associated with increased uptake. Studies on protein and RNA turnover using pulse-chase experiments have shown that both GA3 and auxin have no effect on protein and RNA stability. There are, however, developmental changes in RNA and protein synthesis that should be considered in any explanation of the mechanism of action of these hormones on cell growth. Young GA3 -sensitive tissue has high rates of RNA synthesis and low protein and RNA turnover, while auxin-sensitive tissue has low rates of RNA synthesis, slightly higher rates of RNA turnover and much higher rates of protein turnover. The evidence overall favours more effective utilisation by GA3 and auxin of a basal control level of RNA and protein synthesis and turnover in coleoptile tissue. 相似文献
60.
High-resolution genetic map of the Lv resistance locus in tomato 总被引:3,自引:0,他引:3
J. Chunwongse S. Doganlar C. Crossman J. Jiang S. D. Tanksley 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1997,95(1-2):220-223
Bulked segregant analysis and high-resolution mapping were used to pinpoint the position of the Lv gene for resistance to Leveillula taurica in tomato. Mapping in an F2, corresponding to more than 3800 gametes, indicates that Lv is positioned within the 0.84-cM interval defined by the RFLP markers CT121 and CT129, with the closest marker, CT121, being
only 0.16 cM from the gene. The tight linkage of these markers demonstrates their usefulness in marker-assisted breeding for
Lv, and the high-resolution map provides a starting a starting point for positional cloning of this resistance gene.
Received: 25 February 1997 / Accepted: 21 March 1997 相似文献