Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells

Cbl-b, a ring-type E3 ubiquitin protein ligase, is implicated in setting the threshold of T lymphocyte activation. The p85 regulatory subunit of phosphatidylinositol 3 kinase (PI3K) was identified as a substrate for Cbl-b. We have shown that Cbl-b negatively regulated p85 in a proteolysis-independent manner. Cbl-b is involved in the recruitment of p85 to CD28 and T cell antigen receptor zeta through its E3 ubiquitin ligase activity. The enhanced activation of Cbl-b(-/-) T cells was suppressed by the inhibition of PI3K. The results suggest a proteolysis-independent function for Cbl-b in the modification of protein recruitment.     

Persistence and amplification of St. Louis encephalitis virus in the Coachella Valley of California, 2000-2001

The introduction of a St. Louis encephalitis virus (SLE) genotype new to southeastern California during 2000 was followed by focal enzootic amplification in the Coachella Valley that was detected by seroconversions of 29 sentinel chickens in five of nine flocks of 10 chickens each, isolations of virus from 30 of 538 pools of 50 Culex tarsalis Coquillett females, and collection of 30 positive sera from 2,205 wild birds. This SLE strain over wintered successfully and then amplified during the summer of 2001, with 47 sentinel seroconversions in eight of nine flocks, 70 virus isolations from 719 pools of Cx. tarsalis and Cx. p. quinquefasciatus Say, and 40 positive sera from 847 wild birds. Human illness was not detected by passive case surveillance, despite issuance of a health alert during 2001. Virus amplification during both years was associated with above average temperatures conducive for extrinsic incubation and below average precipitation during spring associated with below average vector abundance. Seroconversions by sentinel chickens provided the timely detection of virus activity, with initial conversions detected before positive mosquito pools or wild bird infections. Vertical infection was not detected among Cx. tarsalis adults reared from immatures collected during the fall-winter of 2000, even though SLE over wintered successfully in this area. Early seroconversions by a sentinel chicken during February 2001 and a recaptured Gambel's quail in April 2001 provided evidence for transmission during winter and spring when ambient temperatures averaged below 17 degrees C, the threshold for SLE replication.     

Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next‐generation sequencing

Leukodystrophies are a heterogeneous group of heritable disorders characterized by abnormal brain white matter signal on magnetic resonance imaging (MRI) and primary involvement of the cellular components of myelin. Previous estimates suggest the incidence of leukodystrophies as a whole to be 1 in 7,000 individuals, however the frequency of specific diagnoses relative to others has not been described. Next generation sequencing approaches offer the opportunity to redefine our understanding of the relative frequency of different leukodystrophies. We assessed the relative frequency of all 30 leukodystrophies (associated with 55 genes) in more than 49,000 exomes. We identified a relatively high frequency of disorders previously thought of as very rare, including Aicardi Goutières Syndrome, TUBB4A‐related leukodystrophy, Peroxisomal biogenesis disorders, POLR3‐related Leukodystrophy, Vanishing White Matter, and Pelizaeus‐Merzbacher Disease. Despite the relative frequency of these conditions, carrier‐screening laboratories regularly test only 20 of the 55 leukodystrophy‐related genes, and do not test at all, or test only one or a few, genes for some of the higher frequency disorders. Relative frequency of leukodystrophies previously considered very rare suggests these disorders may benefit from expanded carrier screening.     

镁对在体兔缺血—再灌心脏的电生理效应

本实验通过结扎兔冠状动脉左室支复制动脉缺血－再灌注模型，应用心外膜接触电极记录单相动作电位，观察后除极电位在再灌注性心律失常中及镁离子的拮抗作用。结果表明，再灌性心律失常的５２．６％与早期后去极化有关。硫酸镁可终止及预防ＲＡ，对再灌中出现触发活动有抑制作用。     

司帕沙星对试验动物的一般药理研究

小鼠单次经口灌服司帕沙星4、20和100mg/kg后,动物的活动正常,未出现兴奋的抑制作用;小鼠单次经口灌服司帕沙星4、20和100mg/kg,与戊巴比妥钠镇静催眠无明显协同作用;给猫静脉注射司帕沙星4、16和64mg/kg,对动物呼吸和心血管系统无明显影响。     

Association of the CTLA-4 gene with rheumatoid arthritis in Chinese Han population

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is important for downregulation of T-cell activation, and CTLA-4 gene polymorphisms have been implicated as risk factors for rheumatoid arthritis (RA). Previous studies of the association between the +49 polymorphism of the CTLA-4 gene in RA have provided conflicting results. In order to determine association of the CTLA-4 gene with RA in Chinese Han population, we used denaturing gradient gel electrophoresis (DGGE) to genotype polymorphisms of four SNPs (MH30, +49, CT60 and JO31) of the CTLA-4 gene in 326 RA patients and 250 healthy controls. Furthermore, meta-analysis of all available studies relating +49 polymorphism to the risk of RA was performed to confirm the disease association. Among the SNPs examined, the genotype frequencies of CTLA-4 +49 and CT60 in RA patients differed significantly from controls (P=0.028 and 0.007). In addition, the distribution of four haplotypes constructed by these two SNPs was significantly different between patients and controls (chi(2)=10.58, d.f. =3, P=0.014). The meta-analysis also revealed that in both European and Asian populations, the CLTA-4 +49 G allele was associated with the risk of RA. These results suggested that the CTLA-4 gene might be involved in the susceptibility to RA in the Chinese Han population and both +49 and CT60 of CTLA-4 gene might be the causal variants in RA disease.     

高血压鼠动脉壁去甲肾上腺素含量及形态变化研究

取不同年龄组自发性高血压鼠的胸主动脉，颈劝脉和基底动脉，用高效液相色谱－电化学检测仪测定其去甲肾上腺素含量，并取脑软膜血管作超微结构观察，结果显示：各组高血压鼠动有脉壁去甲肾上腺素含量均下降，颈内动脉更明显；脑血管内弹性膜部分断裂，平滑肌细胞有空不包变性等。     

The Athletic Prevention Programming and Leadership Education (APPLE) Model: Developing Substance Abuse Prevention Programs

Alcohol and other drug (AOD) abuse affects every sector of society, and student-athletes are no exception. Because many factors affecting athletes do not affect other students, athletic departments commonly approach prevention through AOD education. Different educational approaches are described in this article, particularly the Athletic Prevention Programming and Leadership Education (APPLE) model. Project APPLE is designed to enable an athletic department to systematically analyze its AOD prevention in seven areas: recruitment practices, expectations and attitudes, education and AOD programs, policies, drug testing, discipline, and referral and counseling. Because athletic trainers often are involved in this process, this article should help them to design more effective AOD programs.