ABSTRACT
A 52-week feeding study in cynomolgus macaques was carried out to evaluate the safety of Bt rice Huahui 1 (HH1), a transgenic rice line expressing Cry1Ab/1Ac protein. Monkeys were fed a diet with 20% or 60% HH1 rice, 20% or 60% parental rice (Minghui 63, MH63), normal diet, normal diet spiked with purified recombinant Cry1Ab/1Ac fusion protein or bovine serum albumin (BSA) respectively. During the feeding trail, clinical observations were conducted daily, and multiple parameters, including body weight, body temperature, electrocardiogram, hematology, blood biochemistry, serum metabolome and gut microbiome were examined at regular intervals. Upon sacrifice, the organs were weighted, and the macroscopic, microscopic and electron microscopic examinations were performed. The results show no adverse or toxic effects of Bt rice HH1 or Cry1Ab/1Ac fusion protein on monkeys. Therefore, the present 52-week primate feeding study suggests that the transgenic rice containing Cry 1Ab/1Ac is equivalent to its parental rice line MH63.
Subject(s)
Bacterial Proteins/metabolism , Endotoxins/metabolism , Gastrointestinal Microbiome , Hemolysin Proteins/metabolism , Metabolome , Oryza/metabolism , Plants, Genetically Modified/metabolism , Animals , Bacillus thuringiensis Toxins , Cattle , Diet , Female , Food Safety , Macaca fascicularis , Male , Organ Size , Oryza/genetics , Plants, Genetically Modified/genetics , Proteomics , Risk Assessment , Serum Albumin, Bovine/metabolismABSTRACT
CD40, a member of tumour necrosis factor receptor (TNFR) superfamily, has a pivotal role in B-cell-mediated immunity through various effector pathways including AKT kinase, but the signal transduction of CD40-meidated AKT activation is poorly understood. Here we report that the neural precursor cell expressed developmentally downregulated protein 4 (NEDD4), homologous to E6-AP Carboxyl Terminus family E3 ubiquitin ligase, is a novel component of the CD40 signalling complex. It has a key role in CD40-mediated AKT activation and is involved in modulating immunoglobulin class switch through regulating the expression of activation-induced cytidine deaminase. NEDD4 constitutively interacts with CD40 and mediates K63-linked ubiquitination of TNFR-associated factor3 (TRAF3). The ubiquitination of TRAF3 by NEDD4 is critical for CD40-mediated AKT activation. Thus, NEDD4 is a previously unknown component of the CD40 signalling complex necessary for AKT activation.
Subject(s)
CD40 Antigens/metabolism , Endosomal Sorting Complexes Required for Transport/metabolism , Immunity, Cellular/immunology , Oncogene Protein v-akt/metabolism , Signal Transduction/immunology , TNF Receptor-Associated Factor 3/metabolism , Ubiquitin-Protein Ligases/metabolism , Animals , Flow Cytometry , Humans , Immunoprecipitation , Mass Spectrometry , Mice , Mice, Knockout , Nedd4 Ubiquitin Protein Ligases , RNA Interference , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , UbiquitinationABSTRACT
OBJECTIVE: To describe the epidemiological characteristics and related factors of SARS in Shanxi in order to provide scientific basis for prevention and control of severe acute respiratory syndrome (SARS). METHODS: Data on clinically-diagnosed SARS cases reported to Shanxi Center for Disease Control and Prevention through SARS reporting system of Shanxi province and epidemiological reports were collected from early March to 20 May, 2003. The characteristics of SARS distribution in time, place and population in Shanxi were described. The epidemiological characteristics and related influential factors were analyzed with EPI info 6.0 software. RESULTS: Since the first imported SARS case was diagnosed clinically on 7 March and till 20 May in Shanxi province, the number of cumulative clinically-diagnosed SARS cases were 445 with an attack rate of 1.34/10,000. 20 deaths occurred in that period with the mortality rate 4.49%. The number of cases increased from 28 March and formed the first peak. However, the number continued to increase until 18 April to have formed the second peak. Since then, the number of cases has gradually decreased gradually. Since 19 May, there has been no clinically-diagnosed cases being reported. SARS cases were mostly seen in urban areas of the city (83.82% of the total SARS cases) with sporadic cases found in rural areas. Students and medical staff and people from 20 - 59 years of age occupied the large part of the cases. Age specific mortality rate increased with age and the male/female ratio was 1:0.87. CONCLUSION: In Shanxi province, the SARS epidemic seemed to have had the following stages: importation of the first case, gradual increase of the number of cases to reach the peak and decreasing. Case identification at early stage as well as taking measures to decrease the chance of transmission were strategically crucial for controlling the spread of SARS virus in the community.
