Arginine-rich anti-vascular endothelial growth factor (anti-VEGF) hexapeptide inhibits collagen-induced arthritis and VEGF-stimulated productions of TNF-alpha and IL-6 by human monocytes

Vascular endothelial growth factor (VEGF) has been suggested to play a critical role in the pathogenesis of rheumatoid arthritis (RA). We previously identified a novel RRKRRR hexapeptide that blocked the interaction between VEGF and its receptor through the screening of peptide libraries. In this study, we investigated whether anti-VEGF peptide RRKRRR (dRK6) could suppress collagen-induced arthritis (CIA) and regulate the activation of mononuclear cells of RA patients. A s.c. injection of dRK6 resulted in a dose-dependent decrease in the severity and incidence of CIA and suppressed synovial infiltration of inflammatory cells in DBA/1 mice. In these mice, the T cell responses to type II collagen (CII) in lymph node cells and circulating IgG Abs to CII were also dose-dependently inhibited by the peptides. In addition, VEGF directly increased the production of TNF-alpha and IL-6 from human PBMC. Synovial fluid mononuclear cells of RA patients showed a greater response to VEGF stimulation than the PBMC of healthy controls. The major cell types responding to VEGF were monocytes. Moreover, anti-VEGF dRK6 inhibited the VEGF-induced production of TNF-alpha and IL-6 from synovial fluid mononuclear cells of RA patients and decreased serum IL-6 levels in CIA mice. In summary, we observed first that dRK6 suppressed the ongoing paw inflammation in mice and blocked the VEGF-induced production of proinflammatory cytokines. These data suggest that dRK6 may be an effective strategy in the treatment of RA, and could be applied to modulate various chronic VEGF-dependent inflammatory diseases.     

Geographical and altitudinal population genetic structure of two dung fly species with contrasting mobility and temperature preference

Local adaptation of populations requires some degree of spatio-temporal isolation. Previous studies of the two dung fly species Scathophaga stercoraria and Sepsis cynipsea have revealed low levels of geographic and altitudinal genetic differentiation in quantitative life history and morphological traits, but instead high degrees of phenotypic plasticity. These patterns suggest that gene flow is extensive despite considerable geographic barriers and large spatio-temporal variation in selection on body size and related traits. In this study we addressed this hypothesis by investigating genetic differentiation of dung fly populations throughout Switzerland based on the same 10 electrophoretic loci in each species. Overall, we found no significant geographic differentiation of populations for either species. This is inconsistent with the higher rates of gene flow expected due to better flying capacity of the larger S. stercoraria. However, heterozygote deficiencies within populations indicated structuring on a finer scale, seen for several loci in S. cynipsea, and for the locus PGM (Phosphoglucomutase) in S. stercoraria. Additionally, S. cynipsea showed a tendency towards a greater gene diversity at higher altitudes, mediated primarily by the locus MDH (malate dehydrogenase), at which a second allele was only present in populations above 1000 m. This may be caused by increased environmental stress at higher altitudes in this warm-adapted species. MDH might thus be a candidate locus subject to thermal selection in this species, but this remains to be corroborated by direct evidence. In S. stercoraria, no altitudinal variation was found.     

Radiation sensitivity of lymphocytes from healthy individuals and cancer patients as measured by the comet assay

Lymphocytes of healthy volunteers (n=24) and of tumour patients (n=30, 18 of whom had experienced severe side-effects) were irradiated with x-rays in vitro. DNA damage was analysed after 0.25–2 Gy and DNA repair after 2 Gy, and quantification of both endpoints was done by the comet assay. The individual differences in radiation-induced DNA damage as well as in the repair kinetics were observed to be striking for both healthy donors and tumour patients. After a repair time of 3 h, following 2 Gy x-irradiation, some of the healthy volunteers showed no residual DNA damage at all in their lymphocytes, whereas others revealed about 30%. There was no indication that our results were affected by either age, gender or smoking habits. Slow repair kinetics and high amounts of residual damage were characteristic for many but not all tumour patients who had experienced severe side-effects in their normal tissues during or after radiotherapy (n=18). Our conclusion is that those individuals showing poor DNA repair characteristics in the lymphocytes following in vitro irradiation, have a high probability of being radiosensitive. The opposite conclusion is not necessarily true: if repair is effective, this does not mean that the individual is radioresistant, because factors other than impaired repair may cause radiosensitivity. Received: 3 May 2000 / Accepted: 1 December 2000     

RNA-binding proteins in neurological diseases

Emerging studies support that RNA-binding proteins(RBPs)play critical roles in human biology and pathogenesis.RBPs are essential players in RNA processing and metabolism,including pre-mRNA splicing,polyadenylation,transport,surveillance,mRNA localization,mRNA stability control,translational control and editing of various types of RNAs.Aberrant expression of and mutations in RBP genes affect various steps of RNA processing,altering target gene function.RBPs have been associated with various diseases,including neurological diseases.Here,we mainly focus on selected RNA-binding proteins including Nova-1/Nova-2,HuR/HuB/HuC/HuD,TDP-43,Fus,Rbfox1/Rbfox2,QKI and FMRP,discussing their function and roles in human diseases.     

宁夏水稻选育品种遗传多样性和亲缘关系分析

选择31份宁夏近年来育成或审定的水稻品种(系),利用分布于12条染色体的36对SSR引物进行遗传多样性和遗传距离分析.共检测到159个等位基因,品种间不同位点等位基因数目不等,平均4.4个.Nei基因多样性指数变幅为0.031 7～0.844 4,平均为0.508 8.按育成或审定年份,把31份水稻分为3组,SSR分析...