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101.
Mutations affecting the biosynthesis of quinolinic acid, a precursor of nicotinamide adenine dinucleotide (NAD) in Escherichia coli K-12, are either near min 17 (nadA mutants) or near min 49 on the chromosome. These nad mutants all exhibit a phenotypic requirement for NAD or one of its immediate precursors. The mutants with lesions near min 49 can be separated into two groups based on in vitro complementation analysis. One group (nadB) exhibits complementation with nadA mutants, whereas the other group fails to do so. The latter group is tentatively designated nadR based on its regulation of the unlinked nadA gene. The nadR gene maps adjacent to nadB between purI and tyrA.  相似文献   
102.
The Tsaatan (or Dhuka) peoples of northern-western Mongolia are one of the few remaining reindeer-herding cultural groups in the world. Recently a disease condition that involves sudden death of reindeer and cases involving fever, lethargy, and pale mucous membranes has been reported. Examination of blood smears collected in the 2005 field season resulted in the identification of intra-erythrocytic inclusions resembling Anaplasma spp. in smears from clinically sick animals. Using universal polymerase chain reaction (PCR) primers for the amplification of the 60 kDa chaperonin gene (cpn60, also known as hsp60 or groEL), we detected sequences corresponding to Anaplasma ovis in reindeer blood samples. Species-specific PCR primers for A. ovis were designed and validated and used to screen blood samples from Mongolian reindeer. Screening of 66 blood samples collected in the 2006 field season resulted in the detection of A. ovis in 80% of the samples. Our results indicate a high prevalence of A. ovis in the Tsaatan reindeer herds and an association with clinical disease that is likely to be anaplasmosis. To our knowledge this is the first report of natural A. ovis infection in reindeer.  相似文献   
103.
This study examines thymic nurse cell (TNC) function during T-cell development. It has been suggested that TNCs function in the removal of nonfunctional and/or apoptotic thymocytes and do not participate in major histocompatibility complex restriction. We analyzed TNCs isolated from both normal C57BL/6 mice and C57BL/6 TgN (TCRHY) mice (HY-TCR transgenic mice). Using confocal microscopic analyses of TNCs isolated from C57BL/6 animals, we showed that 75%-78% of the enclosed thymocyte subset was viable, and 87%-90% of these cells expressed both CD4 and CD8. CD4 and CD8 also were expressed on TNC thymocytes isolated from both male and female HY-TCR transgenic mice. The transgenic female thymus was shown to have 17 times more TNCs per milligram of thymus than the transgenic male thymus. TNCs from HY-TCR transgenic females were 8-10 microm larger than transgenic male TNCs, and the female TNCs contained five times more thymocytes within intracytoplasmic vacuoles, with less than 4% apoptosis. However, more than 42% of the thymocytes within transgenic male TNCs were apoptotic. The large number and size of TNCs containing viable thymocytes in the female transgenic thymus suggest that TNC function is not limited to the removal of apoptotic thymocytes. We believe that the selective uptake of viable double-positive thymocytes by TNCs in C57BL/6 and HY-TCR transgenic female mice provides evidence that this interaction occurs during the process of major histocompatibility complex restriction.  相似文献   
104.
Abstract

Coupled geochemical speciation/transport models are being developed to assess potential transport of metal contaminants in the subsurface environment. In a test of the geochemical speciation portion of the effort, MINTEQA2 model predictions are compared with laboratory data concerning the pH dependent partitioning behavior of eight cationic contaminants (Ba, Be, Cd, Cu, Ni, Pb, Tl and Zn) on a sandy aquifer material in an oxidized environment. MINTEQA2 contains provisions for describing potential attenuation due to both mineral phase precipitation processes and adsorption processes resulting from amorphous iron oxides in aquifer materials (MIT Diffuse Layer Model). In the comparison, several trends were discerned. (1) Adsorptive processes tend to better describe the pH-dependent partitioning behavior of transition metals (especially Pb, Zn and Ni). (2) Cd behavior is better described by precipitation as a cadmium carbonate phase. (3) Cu behavior is not reasonably described by the model. (4) Ba and Be comparisons are poor (although presumably their partitioning behavior results from adsorptive and/or pH sensitive solid solution processes). (5) unlike the other elements, the behavior of Tl is relatively insensitive to pH.  相似文献   
105.
106.
Three isoprenoid diphosphate analogues of farnesyl diphosphate (FPP) where the diphosphate has been replaced by methylene diphosphonate and the negative charges masked by frangible pivaloyloxymethyl (POM) esters were prepared. Farnesyl methylenediphosphonate is a sub-micromolar substrate for protein farnesyl transferase. The tripivaloyloxymethyl esters of isoprenoid methylenediphosphonate have significantly increased lipophilicity and may act as important farnesyl diphosphate prodrugs.  相似文献   
107.
The skeletal muscle Ca(2+) release channel/ryanodine receptor (RyR1) contains approximately 50 thiols per subunit. These thiols have been grouped according to their reactivity/responsiveness toward NO, O(2), and glutathione, but the molecular mechanism enabling redox active molecules to modulate channel activity is poorly understood. In the case of NO, very low concentrations (submicromolar) activate RyR1 by S-nitrosylation of a single cysteine residue (Cys-3635), which resides within a calmodulin binding domain. S-Nitrosylation of Cys-3635 only takes place at physiological tissue O(2) tension (pO(2); i.e. approximately 10 mm Hg) but not at pO(2) approximately 150 mm Hg. Two explanations have been offered for the loss of RyR1 responsiveness to NO at ambient pO(2), i.e. Cys-3635 is oxidized by O(2) versus O(2) subserves an allosteric function (Eu, J. P., Sun, J. H., Xu, L., Stamler, J. S., and Meissner, G. (2000) Cell 102, 499-509). Here we report that the NO donors NOC-12 and S-nitrosoglutathione both activate RyR1 by release of NO but do so independently of pO(2). Moreover, NOC-12 activates the channel by S-nitrosylation of Cys-3635 and thereby reverses channel inhibition by calmodulin. In contrast, S-nitrosoglutathione activates RyR1 by oxidation and S-nitrosylation of thiols other than Cys-3635 (and calmodulin is not involved). Our results suggest that the effect of pO(2) on RyR1 S-nitrosylation is exerted through an allosteric mechanism.  相似文献   
108.
Cold weather exercise and airway cytokine expression.   总被引:4,自引:0,他引:4  
Athletes who perform repeated exercise while breathing cold air have a high prevalence of asthmalike chronic airway disease, but the mechanism linking such activity to airway inflammation is unknown. We used a novel animal model (exercising horses) to test the hypothesis that exercise-induced chronic airway disease is caused by exposure of intrapulmonary airways to unconditioned air, resulting in the upregulation of cytokine expression. Bronchoalveolar lavage fluid (BALF) was obtained from eight horses 5 h after submaximal exercise while they breathed room temperature or subfreezing air in a random crossover design. BALF total and differential nucleated cell counts were determined, and relative cytokine mRNA expression in BALF nucleated cells was quantified by real-time RT-PCR using primer and probe sequences specific for equine targets. There were no significant changes in total or differential cell concentrations between BALF recovered after warm and cold air exercise, although there was a strong trend toward increased concentrations of airway epithelial cells after cold air exercise (P = 0.0625). T(H)2 cytokines IL-4, IL-5, and IL-10 were preferentially upregulated after cold air exercise 12-, 9-, and 10-fold, respectively, compared with warm air exercise. Other cytokines (IL-2 and IL-6) were upregulated to a lesser extent (6- and 3-fold, respectively) or not at all (IL-1, IL-8, IFN-gamma, and TNF-alpha). These results suggest that cold weather exercise can lead to asthmalike airway disease through the local induction of cytokines typical of the T(H)2 phenotype.  相似文献   
109.
Among the more than 75 known variants of alpha(1)-proteinase inhibitor, a sub-population of rare, point mutations causing single amino acid replacements have been identified and classified as "at risk" alleles for development of pulmonary disease. In most cases, it is not clear how the amino acid replacements typical of these variants change the properties of the inhibitor to increase risk of disease in the affected individuals. To begin to address this question, we mutagenized a wild type alpha(1)-proteinase inhibitor cDNA to encode a panel of eight different point mutants reported to be associated with increased risk for development of pulmonary disease. These variants were then expressed in COS-l cells transiently transfected with plasmids containing the altered cDNAs. The effects of the mutations on the rates of secretion, cellular location, intracellular degradation, activity, stability, and tendency to aggregate were determined. Results of these studies show that, in some cases, the mutations affect the rate of secretion, the activity or both of these properties of alpha(1)-proteinase inhibitor in a manner consistent with its designation as an "at-risk" allele. In other cases, the mutations do not significantly change the properties of the inhibitor, suggesting that these may be normal variants and that their expression may not increase the risk of disease.  相似文献   
110.
Mammalian telomeres end in single-stranded, G-rich 3' overhangs resulting from both the "end-replication problem" (the inability of DNA polymerase to replicate the very end of the telomeres) and postreplication processing. Telomeric G-rich overhangs are precisely defined in ciliates; the length and the terminal nucleotides are fixed. Human telomeres have very long overhangs that are heterogeneous in size (35-600 nt), indicating that their processing must differ in some respects from model organisms. We developed telomere-end ligation protocols that allowed us to identify the terminal nucleotides of both the C-rich and the G-rich telomere strands. Up to approximately 80% of the C-rich strands terminate in CCAATC-5', suggesting that after replication a nuclease with high specificity or constrained action acts on the C strand. In contrast, the G-terminal nucleotide was less precise than Tetrahymena and Euplotes but still had a bias that changed as a function of telomerase expression.  相似文献   
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