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11.
The T cell coreceptors CD4 and CD8 both associate via their cytoplasmic tails with the N-terminus of the Src-family tyrosine kinase Lck. These interactions require zinc and are critical for T cell development and activation. We examined the folding and solution structures of ternary CD4-Lck-Zn2+ and CD8alpha-Lck-Zn2+ complexes. The coreceptor tails and the Lck N-terminus are unstructured in isolation but assemble in the presence of zinc to form compactly folded heterodimeric domains. The cofolded complexes have similar "zinc clasp" cores that are augmented by distinct structural elements. A dileucine motif required for clathrin-mediated endocytosis of CD4 is masked by Lck. 相似文献
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Weng AP Ferrando AA Lee W Morris JP Silverman LB Sanchez-Irizarry C Blacklow SC Look AT Aster JC 《Science (New York, N.Y.)》2004,306(5694):269-271
Very rare cases of human T cell acute lymphoblastic leukemia (T-ALL) harbor chromosomal translocations that involve NOTCH1, a gene encoding a transmembrane receptor that regulates normal T cell development. Here, we report that more than 50% of human T-ALLs, including tumors from all major molecular oncogenic subtypes, have activating mutations that involve the extracellular heterodimerization domain and/or the C-terminal PEST domain of NOTCH1. These findings greatly expand the role of activated NOTCH1 in the molecular pathogenesis of human T-ALL and provide a strong rationale for targeted therapies that interfere with NOTCH signaling. 相似文献
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SUMMARY To determine whether oral cobalt supplements could modify the clinical onset of annual ryegrass toxicity, groups (n = 5) of sheep were dosed orally with 0, 4 or 16 mg cobalt/day. After 3 weeks on this treatment, toxic ryegrass seed was added to their feed to provide 0, 0.15 and 0.30 mg corynetoxins/kg body weight, daily. Sheep receiving cobalt ingested 30% more toxin than did unsupplemented sheep before clinical signs developed (P = 0.03). There was no significant difference between groups receiving 4 and 16 mg cobalt. The results showed that cobalt delayed, but did not prevent, the onset of clinical signs of annual ryegrass toxicity. 相似文献
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J. W. PLANT B.V.SC HELEN M. ACLAND B.V.SC G. P. GARD B.V.SC Ph.D. 《Australian veterinary journal》1976,52(2):57-63
A condition resembling border disease has been transmitted by the inoculation of pregnant ewes with material from affected lambs. Forty-nine merino ewes, mated to merino rams 7 to 87 days previously, were inoculated with an homogenate of brain, spinal cord and spleen from affected lambs. Mummified foetuses, abortions and stillbirths were observed, and lambs with hairy birth coats were born to ewes inoculated between days 12 to 70 of gestation. A mucosal disease virus (MDV), present in the original material, was recovered from the aborted foetuses and lambs. Attempts to induce passive protection using bovine anti-serum to the C24V strain of MDV were not successful. The condition was also transmitted by inoculation of pregnant ewes with a cell culture supernatant prepared from tissue cultures that had been inoculated with an organ homogenate pool. MDV was present in the supernatant and was recovered from aborted foetuses and lambs. It is suggested that a condition in sheep in Australia resembling border disease is due to the infection of the pregnant ewe by a mucosal disease virus. 相似文献
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C Alexopoulos GC Fthenakis A Burriel E Bourtzi-Hatzopoulou SK Kritas A Sbiraki SC Kyriakis 《Reproduction in domestic animals》2003,38(3):187-192
The objective of this study was to assess the effects of in‐feed chlortetracycline (CTC) as a measure of preventing or minimizing infectious problems of reproductive failure in gilts and sows. In a farm of 400 Large White × Landrace gilts and sows with a clinical history of porcine respiratory and reproductive syndrome (PRRS) virus, the animals were treated with CTC. Treatment consisted of 10 g CTC sow/day for 15 days every 3 months. It improved the health status of sows by decreasing post‐farrowing clinical mastitis and vaginal discharges, abortions, return‐to‐oestrus and irregular return‐to‐oestrus rates. These beneficial effects had a positive impact on the performance of the litter. More piglets were born live and weaned. These positive effects improved with repeated use of CTC. The serological evidence of PRRS virus, Leptospira spp. and Chlamydia spp. and the subsequent beneficial use of the antimicrobial agent indicate that reproductive failure, possibly resulting from the bacterial agents can be controlled with in‐feed use of broad spectrum antimicrobials. 相似文献
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