Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans

The functional interaction of BAFF and APRIL with TNF receptor superfamily members BAFFR, TACI and BCMA is crucial for development and maintenance of humoral immunity in mice and humans. Using a candidate gene approach, we identified homozygous and heterozygous mutations in TNFRSF13B, encoding TACI, in 13 individuals with common variable immunodeficiency. Homozygosity with respect to mutations causing the amino acid substitutions S144X and C104R abrogated APRIL binding and resulted in loss of TACI function, as evidenced by impaired proliferative response to IgM-APRIL costimulation and defective class switch recombination induced by IL-10 and APRIL or BAFF. Family members heterozygous with respect to the C104R mutation and individuals with sporadic common variable immunodeficiency who were heterozygous with respect to the amino acid substitutions A181E, S194X and R202H had humoral immunodeficiency. Although signs of autoimmunity and lymphoproliferation are evident, the human phenotype differs from that of the Tnfrsf13b-/- mouse model.     

Influence of chlorpromazine on nuclear and cytoplasmic uptake of35S-methionine

Résumé Des rats ont été traités avec de la chlorpromazine et ont reçu en suite une seule injection de³⁵S-méthionine. Des radioautographies des coupes histologiques ont montré que la chlorpromazine a un effect inhibitoire dans la synthèse de la protéine nucléaire et cytoplasmatique. Les cellules qui ont une grande vitesse de synthèse protéique sont les plus affectées.

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This investigation was supported by grants from the Rockefeller Foundation and Conselho Nacional de Pesquisas.

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The authors wish to acknowledge the help of Prof. L. C. U.Junqueira for criticism and encouragement, and MissEdna Freymüller for her skilled technical assistance.     

抗氧化剂抑制内皮细胞表面的白细胞粘附不依赖其抗氧化活性

氧张力是炎症反应、再灌注损伤和动脉粥样硬化形成的致病因素。这些病变的共同点是内皮细胞表面的白细胞粘附增加。我们用几种抗氧化剂：ＤＣＩ,Ｃｈｒｙｓｉｎ,ＰＤＴＣ和Ｐｒｏｂｕｃｏｌ在流动条件下（切变力在０６～２４ｄｙｎ／ｃｍ２）实验其对内皮细胞表面白细胞粘附的影响,用化学发光法分析这几种抗氧化剂的抗氧化活性。结果显示：ＰＤＴＣ和Ｐｒｏｂｕｃｏｌ对外周血有核细胞氧自由基的产生没有抑制作用,Ｃｈｒｙｓｉｎ可轻度抑制,ＤＣＩ可明显抑制活性氧的产生。相反,ＰＤＴＣ（最大半抑制量８×１０－４ｍｏｌ和Ｃｈｒｙｓｉｎ最大半抑制量５×１０－５ｍｏｌ）可抑制细胞对经ＴＮＦα刺激的人脐带静脉内皮细胞（ＨＵＶＥＣ）的粘附。ＤＣＩ和Ｐｒｏｂｕｃｏｌ对各种切变力范围的细胞粘附无作用。抗氧化剂对内皮细胞表面的白细胞粘附的抑制作用不能单用其抗氧性特性来解释。可能的作用机理是这类物质直接作用转录因子ＮＦ－ｋＢ的结果     

Preface

正The ever increasing concerns over energy security due to the depletion of fossil fuel give rise to heightened interest in and greater effort towards more sustainable energy supply and utilisation.In the meantime,the climate change as a result of CO2emission from fossil fuel use is undoubtedly another key driver for renewable energy development.Unfortunately,renewable energy such as solar,hydroelectric,wind and geothermal only constitutes a very small     

基于碳纳米管阵列/无机物片层交替结构具有能量吸收特性的杂化复合材料

将二维的层状纳米结构与有一维的碳纳米管阵列组合,形成多级有序的三维纳米结构材料,可获得许多奇特的材料性能.所以,如能大规模地在纳米尺度上实现材料的规整组装将会极大地提高材料的性能,拓展纳米材料的应用.众所周知,如果高分子插层到无机片层材料中,就会显著提高复合物的强度.但是这种填充进去的高分子的有序度往往难以控制.如果能够在二维片     

Rapid and recent origin of species richness in the Cape flora of South Africa.

The Cape flora of South Africa grows in a continental area with many diverse and endemic species. We need to understand the evolutionary origins and ages of such 'hotspots' to conserve them effectively. In volcanic islands the timing of diversification can be precisely measured with potassium-argon dating. In contrast, the history of these continental species is based upon an incomplete fossil record and relatively imprecise isotopic palaeotemperature signatures. Here we use molecular phylogenetics and precise dating of two island species within the same clade as the continental taxa to show recent speciation in a species-rich genus characteristic of the Cape flora. The results indicate that diversification began approximately 7-8 Myr ago, coincident with extensive aridification caused by changes in ocean currents. The recent origin of endemic species diversity in the Cape flora shows that large continental bursts of speciation can occur rapidly over timescales comparable to those previously associated with oceanic island radiations.     

Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria.

The gene products involved in mammalian mitochondrial DNA (mtDNA) maintenance and organization remain largely unknown. We report here a novel mitochondrial protein, Twinkle, with structural similarity to phage T7 gene 4 primase/helicase and other hexameric ring helicases. Twinkle colocalizes with mtDNA in mitochondrial nucleoids. Screening of the gene encoding Twinkle in individuals with autosomal dominant progressive external ophthalmoplegia (adPEO), associated with multiple mtDNA deletions, identified 11 different coding-region mutations co-segregating with the disorder in 12 adPEO pedigrees of various ethnic origins. The mutations cluster in a region of the protein proposed to be involved in subunit interactions. The function of Twinkle is inferred to be critical for lifetime maintenance of human mtDNA integrity.