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101.
Generation and characterization of ecto-ADP-ribosyltransferase ART2.1/ART2.2-deficient mice
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Ohlrogge W Haag F Löhler J Seman M Littman DR Killeen N Koch-Nolte F 《Molecular and cellular biology》2002,22(21):7535-7542
This is the first study reporting the inactivation of a member of the mouse gene family of toxin-related ecto-ADP-ribosyltransferases (ARTs). Transfer of the ADP-ribose moiety from NAD onto extracellular arginine residues on T-cell membrane proteins is mediated by glycosylphosphatidylinositol-linked cell surface ARTs. Exposure of T cells to ecto-NAD blocks T-cell activation and induces T-cell apoptosis. To determine a possible role of ecto-ART2.1 and ART2.2 in these processes, we generated ART2.1/ART2.2 double-knockout mice. ART2-deficient mice were healthy and fertile and showed normal development of lymphoid organs. ART2-deficient T cells showed a dramatically reduced capacity to ADP-ribosylate cell surface proteins, indicating that most if not all ART activity on the T-cell surface can be attributed to the ART2s. Moreover, ART2-deficient T cells were completely resistant to NAD-induced apoptosis and partially resistant to NAD-mediated suppression of proliferation. These results demonstrate that the ART2 ectoenzymes are an essential component in the regulation of T-cell functions by extracellular NAD, e.g., following release of NAD upon lysis of cells in tissue injury and inflammation. 相似文献
102.
103.
CCR7 expression in developing thymocytes is linked to the CD4 versus CD8 lineage decision 总被引:1,自引:0,他引:1
Yin X Ladi E Chan SW Li O Killeen N Kappes DJ Robey EA 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(11):7358-7364
During thymic development, T cell progenitors undergo positive selection based on the ability of their T cell Ag receptors (TCR) to bind MHC ligands on thymic epithelial cells. Positive selection determines T cell fate, in that thymocytes whose TCR bind MHC class I (MHC-I) develop as CD8-lineage T cells, whereas those that bind MHC class II (MHC-II) develop as CD4 T cells. Positive selection also induces migration from the cortex to the medulla driven by the chemokine receptor CCR7. In this study, we show that CCR7 is up-regulated in a larger proportion of CD4(+)CD8(+) thymocytes undergoing positive selection on MHC-I compared with MHC-II. Mice bearing a mutation of Th-POK, a key CD4/CD8-lineage regulator, display increased expression of CCR7 among MHC-II-specific CD4(+)CD8(+) thymocytes. In addition, overexpression of CCR7 results in increased development of CD8 T cells bearing MHC-II-specific TCR. These findings suggest that the timing of CCR7 expression relative to coreceptor down-regulation is regulated by lineage commitment signals. 相似文献
104.
Pamela Opiyo W Richard Mukabana Ibrahim Kiche Evan Mathenge Gerry F Killeen Ulrike Fillinger 《Malaria journal》2007,6(1):1-20
Background
Capacity strengthening of rural communities, and the various actors that support them, is needed to enable them to lead their own malaria control programmes. Here the existing capacity of a rural community in western Kenya was evaluated in preparation for a larger intervention.Methods
Focus group discussions and semi-structured individual interviews were carried out in 1,451 households to determine (1) demographics of respondent and household; (2) socio-economic status of the household; (3) knowledge and beliefs about malaria (symptoms, prevention methods, mosquito life cycle); (4) typical practices used for malaria prevention; (5) the treatment-seeking behaviour and household expenditure for malaria treatment; and (6) the willingness to prepare and implement community-based vector control.Results
Malaria was considered a major threat to life but relevant knowledge was a chimera of scientific knowledge and traditional beliefs, which combined with socio-economic circumstances, leads to ineffective malaria prevention. The actual malaria prevention behaviour practiced by community members differed significantly from methods known to the respondents. Beside bednet use, the major interventions implemented were bush clearing and various hygienic measures, even though these are ineffective for malaria prevention. Encouragingly, most respondents believed malaria could be controlled and were willing to contribute to a community-based malaria control program but felt they needed outside assistance.Conclusion
Culturally sensitive but evidence-based education interventions, utilizing participatory tools, are urgently required which consider traditional beliefs and enable understanding of causal connections between mosquito ecology, parasite transmission and the diagnosis, treatment and prevention of disease. Community-based organizations and schools need to be equipped with knowledge through partnerships with national and international research and tertiary education institutions so that evidence-based research can be applied at the grassroots level. 相似文献105.
CCR7 directs the migration of thymocytes into the thymic medulla 总被引:9,自引:0,他引:9
Developing thymocytes migrate from the cortex to the medulla of the thymus as a consequence of positive selection. This migration is likely to be essential for tolerance because it allows the developing cells to move into an environment that is optimal for negative selection. Guidance mechanisms that draw positively selected thymocytes into the medulla have not been clarified, but several studies have implicated chemokines in the process. CCR7, the receptor for the medullary chemokines CCL19 and CCL21, is induced on thymocytes during their positive selection. In this study we show that premature expression of CCR7 repositions CD4(+)CD8(+) double-positive cells into the medulla of transgenic mice. This repositioning of the thymocytes is accompanied by impairment of their development. The data show the involvement of CCR7 in medullary migration and emphasize the importance of proper thymocyte positioning for efficient T cell development. 相似文献
106.
In this otherwise insightful line of investigation, some aspects of rules of thumb (RoT) remain underspecified: their evolution and function, how they are selected for a task, how they are learned, and the dependence of their apparent simplicity on their embodiment and context. Theories of operant and respondent conditioning may serve as the theoretical framework required to flesh out those details. 相似文献
107.
Pea plants grown under controlled conditions for 28 days were sampled nine times during this growth period. On each sampling day 80 plants were harvested. Cotyledons were excised from 40 plants and the root-shoot axis allowed to continue growth. The other 40 plants were divided into roots, shoots, and cotyledons; the dry weights of alcohol-water extracts and residues from these organs were determined. Shoot lengths, numbers of nodes, buds, flowers, and fruits of 28-day-old plants, whose cotyledons were excised at different times, were determined. These data indicate that cotyledon excision after the 13th day has no apparent effect on seedling growth, whereas excision before the 13th day reduces growth. Glucose-U-C14 supplied to attached cotyledons of 6- and 16-day-old seedlings resulted in no major difference in the distribution pattern of recovered label throughout the plant even though 16-day-old cotyledons were depleted of their normal endogenous food reserve. 相似文献
108.
The phylogenetic position of the Pedetidae, represented by a single species
Pedetes capensis, is controversial, reflecting in part the retention of
both Hystricomorphous and Sciurognathous characteristics in this rodent. In
an attempt to clarify the species evolutionary relationships, mtDNA gene
sequences from 10 rodent species (representing seven families) were
analyzed using phenetic, parsimony, and maximum-likelihood methods of
phylogenetic inference; the rabbit, Oryctolagus cuniculus (Order
Lagomorpha), and cow, Bos taurus (Order Artiodactyla), were used as
outgroups. Investigation of 714 base pairs of the protein-coding cytochrome
b gene indicate strong base bias at the third codon position with
significant rate heterogeneity evident between the three structural domains
of this gene. Similar analyses conducted on 816 base pairs of the 12S rRNA
gene revealed a transversion bias in the loop sections of all taxa. The
cytochrome b gene sequences proved useful in resolving associations between
closely related species but failed to produce consistent tree topologies at
the family level. In contrast, phylogenetic analysis of the 12S rRNA gene
resulted in strong support for the clustering of
Pedetidae/Heteromyidae/Geomyidae and Muridae in one clade to the exclusion
of the Hystricidae/Thryonomyidae and Sciuridae, a finding which is
concordant with studies of rodent fetal membranes as well as reproductive
and other anatomical features.
相似文献
109.
Zacharia Mtema Joel Changalucha Sarah Cleaveland Martin Elias Heather M. Ferguson Jo E. B. Halliday Daniel T. Haydon Gurdeep Jaswant Rudovick Kazwala Gerry F. Killeen Tiziana Lembo Kennedy Lushasi Alpha D. Malishee Rebecca Mancy Matthew Maziku Eberhard M. Mbunda Geofrey J. M. Mchau Roderick Murray-Smith Kristyna Rysava Khadija Said Maganga Sambo Elizabeth Shayo Lwitiko Sikana Sunny E Townsend Honorathy Urassa Katie Hampson 《PLoS medicine》2016,13(4)
110.
A generic schema and data collection forms applicable to diverse entomological studies of mosquitoes
Samson?S.?KiwareEmail author Tanya?L.?Russell Zacharia?J.?Mtema Alpha?D.?Malishee Prosper?Chaki Dickson?Lwetoijera Javan?Chanda Dingani?Chinula Silas?Majambere John?E.?Gimnig Thomas?A.?Smith Gerry?F.?Killeen 《Source code for biology and medicine》2016,11(1):4