We generated four independent transgenic mouse lines that showed severe melanosis of the whole body by introducing the ret oncogene fused to the mouse metallothionein (MT)‐I promoter‐enhancer (MT/ret). Whereas melanogenesis was accelerated without distinct proliferative disorders in one line, melanocytic tumours frequently developed in the other three lines. Northern hybridization and in situ hybridization analyses showed that tumour cells and non‐tumorous melanin‐producing cells expressed the transgene at high levels. The aberrant melanogenesis and tumour development were influenced by genetic and environmental factors. Furthermore, crossbreeding experiments between the transgenic mice and Wv mice suggested that the ret gene product can partially compensate for the defect of melanocyte development in Wv mice. This is a novel mammalian model in which melanosis and melanocytic tumours develop stepwise, triggered by a single transgene.
The swamp type of the Asian water buffalo is assumed to have been domesticated by about 4000 years BP, following the introduction of rice cultivation. Previous localizations of the domestication site were based on mitochondrial DNA (mtDNA) variation within China, accounting only for the maternal lineage. We carried out a comprehensive sampling of China, Taiwan, Vietnam, Laos, Thailand, Nepal and Bangladesh and sequenced the mtDNA Cytochrome b gene and control region and the Y-chromosomal ZFY, SRY and DBY sequences. Swamp buffalo has a higher diversity of both maternal and paternal lineages than river buffalo, with also a remarkable contrast between a weak phylogeographic structure of river buffalo and a strong geographic differentiation of swamp buffalo. The highest diversity of the swamp buffalo maternal lineages was found in south China and north Indochina on both banks of the Mekong River, while the highest diversity in paternal lineages was in the China/Indochina border region. We propose that domestication in this region was later followed by introgressive capture of wild cows west of the Mekong. Migration to the north followed the Yangtze valley as well as a more eastern route, but also involved translocations of both cows and bulls over large distances with a minor influence of river buffaloes in recent decades. Bayesian analyses of various migration models also supported domestication in the China/Indochina border region. Coalescence analysis yielded consistent estimates for the expansion of the major swamp buffalo haplogroups with a credibility interval of 900 to 3900 years BP. The spatial differentiation of mtDNA and Y-chromosomal haplotype distributions indicates a lack of gene flow between established populations that is unprecedented in livestock.
Four Asian elephants were confirmed to be infected with Mycobacterium tuberculosis by bacterial culture, other diagnostic procedures, and sequencing of 16S–23S rDNA internal transcribed spacer region, 16S rRNA, and gyrase B gene sequences. Genotyping showed that the infectious agents originated from 4 sources in Thailand. To identify infections, a combination of diagnostic assays is essential.
Y-chromosomal variation in the water buffalo was analysed by sequencing of DBY, ZFY and SRY gene segments. A clear separation of the paternal lineages of the river and swamp types parallels the differences between their maternal lineages and nuclear DNA. Sequence divergence was found to be comparable to the divergence of taurine cattle and zebu, and this divergence predated domestication, confirming that river and swamp buffalo originated from different wild populations. Within a sample of 23 Thai swamp buffaloes, we identified four haplotypes with different geographical distributions, two of which were shared by Thai wild buffaloes.
A CD30 ligand (CD30L, CD153) is a type II membrane-associated glycoprotein belonging to the TNF family. To illustrate the potential role of CD30L in CD4+ Th1 cell responses, we investigated the fate of Ag-specific CD4+ T cells in CD30L-deficient (CD30L−/−) mice after Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection. The number of bacteria was significantly higher in organs of CD30L−/− mice than in wild-type (WT) mice 4 wk postinfection. The numbers of purified protein derivative- or Ag85B-specific-IFN-γ-producing-CD4+ T cells in spleen, lung, or peritoneal exudate cells were significantly fewer in CD30L−/− mice than in WT mice. During the infection, CD30L was expressed mainly by CD44+CD3+CD4+ T cells but not by CD3+CD8+ T cells, B cells, dendritic cells, or macrophages. Costimulation with agonistic anti-CD30 mAb or coculturing with CD30L-transfected P815 cells restored IFN-γ production by CD4+ T cells from BCG-infected CD30L−/− mice. Coculturing with CD30L+/+CD4+ T cells from BCG-infected WT mice also restored the number of IFN-γ+CD30L−/−CD4+ T cells. When transferred into the CD30L+/+ mice, Ag-specific donor CD30L−/− CD4+ T cells capable of producing IFN-γ were restored to the compared level seen in CD30L+/+ CD4+ T cells on day 10 after BCG infection. When naive CD30L+/+ T cells were transferred into CD30L−/− mice, IFN-γ-producing-CD4+ Th1 cells of donor origin were normally generated following BCG infection, and IFN-γ-producing-CD30L−/−CD4+ Th1 cells of host origin were partly restored. These results suggest that CD30L/CD30 signaling executed by CD30+ T-CD30L+ T cell interaction partly play a critical role in augmentation of Th1 response capable of producing IFN-γ against BCG infection.
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