Determination of acetaldehyde in human blood

Summary A method for the determination of acetaldehyde in human plasma by headspace gas chromatography is described. Chloralhydrate, an inhibitor of aldehyde dehydrogenase, is immediately added to the blood sample to prevent a rapid disappearance of acetaldehyde in the erythrocytes.This work was supported by the Swiss National Science Foundation.The authors thank Miss Ch. Coullery and Miss E. Ernst for their technical assistance.     

Thymic major histocompatibility complex antigens and the alpha beta T-cell receptor determine the CD4/CD8 phenotype of T cells

T-cell receptors and T-cell subsets were analysed in T-cell receptor transgenic mice expressing alpha and beta T-cell receptor genes isolated from a male-specific, H-2Db-restricted CD4-8+ T-cell clone. The results indicate that the specific interaction of the T-cell receptor on immature thymocytes with thymic major histocompatibility complex antigens determines the differentiation of CD4+8+ thymocytes into either CD4+8- or CD4-8+ mature T cells.     

Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes

The mechanism of self-tolerance is studied in T-cell-receptor transgenic mice expressing a receptor in many of their T cells for the male (H-Y) antigen in the context of class I H-2Db MHC antigens. Autospecific T cells are deleted in male mice. The deletion affects only transgene-expressing cells with a relatively high surface-density of CD8 molecules, including nonmature CD4+ CD8+ thymocytes, and is not caused by anti-idiotype cells.     

近场光学显微术对凋亡HeLa细胞成像的探索

用扫描近场光学显微镜对凋亡的HeLa细胞进行了近场光学成像,得到优于光学衍射极限的光学分辨率.由于近场光学显微镜同时测量细胞表面形貌信息和透射光强信息,可以将细胞表面及其内部的物质结构特性和光学特性与空间位置相结合,获得凋亡细胞的结构信息与光学细节信息的对应关系.运用近场光谱方法在不同波长进行透射光谱成像时,不同波长的光在细胞内的传播与吸收所造成的光强分布存在显著差别,这种特性可以用于对细胞内不同组分的超高空间分辨率成像.结合近场光学成像和光谱成像结果,表明凋亡HeLa细胞内部为非均匀结构,并且其物质分布也极不均匀.研究表明,运用近场光学显微镜和近场光谱成像技术,不但提供优于衍射极限的高分辨本领,还可以提供生物细胞精细结构的更深层次的光学信息.     

Cyclotron resonance of composite fermions.

It is occasionally possible to interpret strongly interacting many-body systems within a single-particle framework by introducing suitable fictitious entities, or 'quasi-particles'. A notable recent example of the successful application of such an approach is for a two-dimensional electron system that is exposed to a strong perpendicular magnetic field. The conduction properties of the system are governed by electron-electron interactions, which cause the fractional quantum Hall effect. Composite fermions, electrons that are dressed with magnetic flux quanta pointing opposite to the applied magnetic field, were identified as apposite quasi-particles that simplify our understanding of the fractional quantum Hall effect. They precess, like electrons, along circular cyclotron orbits, but with a diameter determined by a reduced effective magnetic field. The frequency of their cyclotron motion has hitherto remained enigmatic, as the effective mass is no longer related to the band mass of the original electrons and is entirely generated from electron-electron interactions. Here we demonstrate enhanced absorption of a microwave field in the composite fermion regime, and interpret it as a resonance with the frequency of their circular motion. From this inferred cyclotron resonance, we derive a composite fermion effective mass that varies from 0.7 to 1.2 times that of the electron mass in vacuum as their density is tuned from 0.6 x 10(11) cm(-2) to 1.2 x 10(11) cm(-2).     

Aufhebung der Thermothyrin-A-Sekretion der Schilddrüse durch Fütterung mit Methylthiouracil

Summary G. Mansfeld demonstrated that in the serum of overheated animals a substance (thermothyrine A) is present which, injected into normal animals, decreases O₂-consumption. Serum of thyroidectomized animals has no effect.Dogs and rabbits were treated daily with 0.10 g per kg methylthiouracil during 4 weeks, and were than subjected for 5 hours to a temperature of 34–35° C which raised their body temperature by 0.5–1.5° C. 2.5 cm³ of serum obtained at the end of the 5 hours period failed to reduce O₂-consumption of normal rats, while sera of untreated dogs and rabbits produced after similar exposure to high temperature a fall of O₂-consumption by 14–48%. It is therefore evident that methylthiouracil not only inhibits the formation of thyroxine but of thermothyrine A as well.The fact that thermothyrine A contains no iodine proves conclusively that the action of thiouracil compounds cannot be exclusively an inhibition of iodinization.     

Positive selection of antigen-specific T cells in thymus by restricting MHC molecules

Thymus-derived lymphocytes (T cells) recognize antigen in the context of class I or class II molecules encoded by the major histocompatibility complex (MHC) by virtue of the heterodimeric alpha beta T-cell receptor (TCR). CD4 and CD8 molecules expressed on the surface of T cells bind to nonpolymorphic portions of class II and class I MHC molecules and assist the TCR in binding and possibly in signalling. The analysis of T-cell development in TCR transgenic mice has shown that the CD4/CD8 phenotype of T cells is determined by the interaction of the alpha beta TCR expressed on immature CD4+8+ thymocytes with polymorphic domains of thymic MHC molecules in the absence of nominal antigen. Here we provide direct evidence that positive selection of antigen-specific, class I MHC-restricted CD4-8+ T cells in the thymus requires the specific interaction of the alpha beta TCR with the restricting class I MHC molecule.     

Enhanced susceptibility of T lymphocytes to oxidative stress in the absence of the cellular prion protein

The cellular prion glycoprotein (PrP^C) is ubiquitously expressed but its physiologic functions remain enigmatic, particularly in the immune system. Here, we demonstrate in vitro and in vivo that PrP^C is involved in T lymphocytes response to oxidative stress. By monitoring the intracellular level of reduced glutathione, we show that PrP^−/− thymocytes display a higher susceptibility to H₂O₂ exposure than PrP^+/+ cells. Furthermore, we find that in mice fed with a restricted diet, a regimen known to increase the intracellular level of ROS, PrP^−/− thymocytes are more sensitive to oxidative stress. PrP^C function appears to be specific for oxidative stress, since no significant differences are observed between PrP^−/− and PrP^+/+ mice exposed to other kinds of stress. We also show a marked evolution of the redox status of T cells throughout differentiation in the thymus. Taken together, our results clearly ascribe to PrP^C a protective function in thymocytes against oxidative stress.     

Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes

Genome-wide association studies have revealed that common noncoding variants in MTNR1B (encoding melatonin receptor 1B, also known as MT(2)) increase type 2 diabetes (T2D) risk(1,2). Although the strongest association signal was highly significant (P < 1 × 10(-20)), its contribution to T2D risk was modest (odds ratio (OR) of ～1.10-1.15)(1-3). We performed large-scale exon resequencing in 7,632 Europeans, including 2,186 individuals with T2D, and identified 40 nonsynonymous variants, including 36 very rare variants (minor allele frequency (MAF) <0.1%), associated with T2D (OR = 3.31, 95% confidence interval (CI) = 1.78-6.18; P = 1.64 × 10(-4)). A four-tiered functional investigation of all 40 mutants revealed that 14 were non-functional and rare (MAF < 1%), and 4 were very rare with complete loss of melatonin binding and signaling capabilities. Among the very rare variants, the partial- or total-loss-of-function variants but not the neutral ones contributed to T2D (OR = 5.67, CI = 2.17-14.82; P = 4.09 × 10(-4)). Genotyping the four complete loss-of-function variants in 11,854 additional individuals revealed their association with T2D risk (8,153 individuals with T2D and 10,100 controls; OR = 3.88, CI = 1.49-10.07; P = 5.37 × 10(-3)). This study establishes a firm functional link between MTNR1B and T2D risk.