Higher order structure of the PCM adjacent to the centriole

The centrosome is the major microtubule organizing center in most animal cells. This cytoplasmic organelle consists of two components : a mature centriole (or a pair of centrioles) and a mass of pericentriolar material (PCM). The PCM has been described as either a cloud of material that encases the entire centriole or as a cluster of proteins divided into two subsets, one that adheres to the lateral surface of the centriole and another that extends outward from this region as a cloud of material. In contrast to these protein distribution patterns, we demonstrated in a previous study that a subset of proteins present within the PCM is integrated together to form a tube (PCM tube) with an open and closed end that is duplicated in concert with centrosome duplication. The present study was undertaken to determine if this tubular conformation represents proteins that are confined to the surface of the centriole or if it represents a subset of proteins within the cloud of material that extends outward from the centriole. We document that : (1) the PCM tube represents a portion of the PCM directly associated with the centriole; (2) the PCM tube has a specific and reproducible relationship to the polar structure of the centriole; (3) the tube is a site of cytoplasmic microtubule organization, and has a structure that influences the initial pattern of microtubule assembly within the juxta-centriolar region; and (4) the PCM tube has a structural relationship with respect to the centriole, which allows the simultaneous expression of centriole- and PCM-based functions (e.g., ciliogenesis and cytoplasmic microtubule organization). Based on these findings, we propose a new model of the PCM at the centriole. This model highlights the role played by the proximal end of the centriole in the nucleation and organization of centriole-associated PCM, and indicates that the centrosome has an overall polarity in the region of the centriole.     

Identification of T-cell epitopes on E2 protein of rubella virus, as recognized by human T-cell lines and clones.

T-cell epitopes on the E2 protein of rubella virus were studied by using 15 overlapping synthetic peptides covering the E2 protein sequence. The most frequently recognized epitopes on E2 were E2-4 (residues 54 to 74), with 5 of 10 tested T-cell lines responding to it. Two CD4+ cytotoxic T-cell cloned isolated from one T-cell line responded strongly in proliferation assays with peptide E2-4 and were cytotoxic to target cells presenting the E2-4 determinant. Truncated peptides contained within the E2-4 peptide sequence were used to define the T-cell determinants. Results indicated that amino acid residues 54 to 65 were directly involved. Human cell lines with different HLA phenotypes were tested for the capacity to present the antigenic determinants. The results suggested that recognition of peptide E2-4 by T-cell clones was associated with HLA DR7.     

The size at reproduction of canopy tree species in central Africa

Size at reproduction is a key aspect of species life history that is relatively understudied for long‐lived tropical trees. Here, we quantified reproductive diameter for 31 major timber species across 11 sites in Cameroon, Congo, and Central African Republic. Specifically, we examined whether (1) between‐species variability is correlated with other species traits; (2) reproductive diameter varies within‐species among sites; (3) reproductive status varies with crown exposure; and (4) the minimum cutting diameter limits (MCDL) imposed by national forest regulations enable seed trees to persist after logging operations. Consistent with studies conducted elsewhere in the tropics, we found great variability in diameter at reproduction among species, which correlated with adult stature (maximum diameter and height). For some species, reproductive diameter thresholds substantially varied between sites, and crown exposure had a significant positive effect on reproductive status. Most MCDLs were found to be suitable, with trees having a high probability of being seed trees at MCDL. Our findings have implications for the sustainable management of production forests, and they highlight questionable MCDLs for some species and between‐site variation in reproductive diameter. The study also highlights the need for long‐term phenological monitoring of tree species spanning a large range of ecological strategies to address both theoretical (species life history, allocation trade‐offs) and practical questions (MCDL).     

Mutant <Emphasis Type="Italic">TP53</Emphasis> G245C and R273H promote cellular malignancy in esophageal squamous cell carcinoma

Background

TP53 gene mutations occur in more than 50% of human cancers and the vast majority of these mutations in human cancers are missense mutations, which broadly occur in DNA binding domain (DBD) (Amino acids 102–292) and mainly reside in six “hotspot” residues. TP53 G245C and R273H point mutations are two of the most frequent mutations in tumors and have been verified in several different cancers. In the previous study of the whole genome sequencing (WGS), we found some mutations of TP53 DBD in esophageal squamous cell carcinoma (ESCC) clinical samples. We focused on two high-frequent mutations TP53 p.G245C and TP53 p.R273H and investigated their oncogenic roles in ESCC cell lines, p53-defective cell lines H1299 and HCT116 p53?/?.

Results

MTS and colony formation assays showed that mutant TP53 G245C and R273H increased cell vitality and proliferation. Flow cytometry results revealed inhibition of ultraviolet radiation (UV)- and ionizing radiation (IR)- induced apoptosis and disruption of TP53-mediated cell cycle arrest after UV, IR and Nocodazole treatment. Transwell assays indicated that mutant TP53 G245C and R273H enhanced cell migration and invasion abilities. Moreover, western blot revealed that they were able to suppress the expression of TP53 downstream genes in the process of apoptosis and cell cycle arrest induced by UV, which suggests that these two mutations can influence apoptosis and growth arrest might be due, at least in part, to down-regulate the expression of P21, GADD45α and PARP.

Conclusions

These results indicate that mutant TP53 G245C and R273H can lead to more aggressive phenotypes and enhance cancer cell malignancy, which further uncover TP53 function in carcinogenesis and might be useful in clinical diagnosis and therapy of TP53 mutant cancers.

     

多因素影响白花前胡甲素和乙素含量分析

目的:研究在不同采收期、栽培环境、抽薹前后和组织部位的白花前胡甲素和乙素含量的变化规律.方法:采用高效液相色谱法测定不同采收时期栽培白花前胡甲素及乙素含量.结果:前胡甲素及乙素含量累积规律是根>茎>叶;二年生前胡甲素含量显著高于一年生,南坡前胡甲素显著高于其他坡向;抽薹前后的前胡甲素和乙素含量无显著差异.结论:高效液相...     

Proteolytic conversion of hepatitis B virus e antigen precursor to end product occurs in a postendoplasmic reticulum compartment.

At least two proteolytic events are involved in the biogenesis of hepatitis B virus e antigen. The first proteolytic event removes the signal peptide and results in the translocation of the precursor protein, P22, into the lumen of the endoplasmic reticulum (ER). The second proteolytic event removes the carboxy-terminal arginine-rich sequence of P22 and converts it to the 16-kDa hepatitis B virus e antigen end product. In contrast to the first proteolytic event, the second proteolytic event is suppressed by brefeldin A, a chemical that inhibits the transport of protein from the ER to the Golgi apparatus. In subcellular fractionation experiments, P22 was detected in both the ER and the Golgi fractions, but P16 was detected only in the Golgi fraction. On the basis of these results, we conclude that the conversion of P22 to P16 occurs ina post-ER compartment, mostly likely the Golgi apparatus.     

^14C—菲在“植物—火山石—营养液—空气”系统中的迁移和转化

利用放射性同位素示踪技术,研究^14C－菲在“植物－火山石－营养液－空气”封闭系统中的迁移转化。结果表明,菲在该系统中降解较快,实验进行到23d时,营养液中的放射性含量仅为施入时的25％,实验结束（46d）时,^14C放射性在该系统各部分间的分布顺序为根（38.55%）＞挥发性有机代谢产物（VOCs,17.68%）＞火山石（14.35%）＞CO2（11.42%0＞茎（2％）;植物体内的放射性物质主要以结合态（根4.68%,茎叶0.68%）与植物组织结合和以极性代谢产物（根23.14%;茎0.78%）形式存在。     

Safety and Immunogenicity of the Malaria Vaccine Candidate MSP3 Long Synthetic Peptide in 12–24 Months-Old Burkinabe Children

Background

A Phase Ia trial in European volunteers of the candidate vaccine merozoite surface protein 3 (MSP3), a Plasmodium falciparum blood stage membrane, showed that it induces biologically active antibodies able to achieve parasite killing in vitro, while a phase Ib trial in semi-immune adult volunteers in Burkina Faso confirmed that the vaccine was safe.The aim of this study was to assess the safety and immunogenicity of this vaccine candidate in children aged 12–24 months living in malaria endemic area of Burkina Faso.

Methods

The study was a double-blind, randomized, controlled, dose escalation phase Ib trial, designed to assess the safety, reactogenicity and immunogenicity of three doses of either 15 or 30 µg of MSP3-LSP adsorbed on aluminum hydroxide in 45 children 12 to 24 months of age randomized into three equal groups. Each group received 3 vaccine doses (on days 0, 28 and 56) of either 15 µg of MSP3-LSP, 30 µg of MSP3-LSP or of the Engerix B hepatitis B vaccine. Children were visited at home daily for the 6 days following each vaccination to solicit symptoms which might be related to vaccination. Serious adverse events occurring during the study period (1 year) were recorded. Antibody responses to MSP3-LSP were measured on days 0, 28, 56 and 84.

Results

All 45 enrolled children received three MSP3 vaccine doses. No serious adverse events were reported. Most of the adverse events reported were mild to moderate in severity. The only reported local symptoms with grade 3 severity were swelling and induration, with an apparently dose related response. All grade 3 adverse events resolved without any sequelae. Both MSP3 doses regimens were able to elicit high levels of anti-MSP3 specific IgG1 and IgG3 antibodies in the volunteers with very little or no increase in IgG2, IgG4 and IgM classes: i.e. vaccination induced predominantly the isotypes involved in the monocyte-dependent mechanism of P. falciparum parasite-killing.

Conclusion

Our results support the promise of MSP3-LSP as a malaria vaccine candidate, both in terms of tolerability and of immunogenicity. Further assessment of the efficacy of this vaccine is recommended.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00452088","term_id":"NCT00452088"}}NCT00452088     

Association of CVD Candidate Gene Polymorphisms with Ischemic Stroke and Cerebral Hemorrhage in Chinese Individuals

Background

Contribution of cardiovascular disease related genetic risk factors for stroke are not clearly defined. We performed a genetic association study to assess the association of 56 previously characterized gene variants in 34 candidate genes from cardiovascular disease related biological pathways with ischemic stroke and cerebral hemorrhage in a Chinese population.

Methods

There were 1280 stroke patients (1101 with ischemic stroke and 179 with cerebral hemorrhage) and 1380 controls in the study. The genotypes for 56 polymorphisms of 34 candidate genes were determined by the immobilized probe approach and the associations of gene polymorphisms with ischemic stroke and cerebral hemorrhage were performed by logistic regression under an allelic model.

Results

After adjusting for age, sex, BMI and hypertension status by logistic regression analysis, we found that NPPA rs5063 was significantly associated with both ischemic stroke (odds ratio [OR] 0.69; 95% confidence interval [CI], 0.52 to 0.90; P = 0.006) and cerebral hemorrhage(OR = 0.39; 95%CI, 0.19 to 0.78; P = 0.007). In addition, MTHFR rs1801133 also was associated with cerebral hemorrhage (OR = 1.48; 95%CI, 1.16 to1.89; P = 0.001) but not with ischemic stroke (OR = 1.08; 95%CI, 0.96 to1.22; P = 0.210). After false discovery rate (FDR) correction, the association of NPPA rs5063 and MTHFR rs1801133 with cerebral hemorrhage remained significant.

Conclusions

The NPPA rs5063 is associated with reduced risk for cerebral hemorrhage and MTHFR rs1801133 is associated with increased risk of cerebral hemorrhage in a Chinese population.