Relationship between hypothermia and some chlorpromazine induced metabolic changes in mouse brain

Zusammenfassung Es wird gezeigt, dass Chlorpromazin keine Veränderung der Konzentration von Aminosäuren erzeugt, wohl aber die Inkorporation des Isotopen¹⁴C-Glukose im säurelöslichen Anteil des Mäusegehirns temperaturabhängig vermehrt.

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Governors' Research Scholar, Guy's Hospital Medical School.     

Differential inhibition of mitochondrial respiratory control by N-1-substituted, 3-, 4-substituted pyridinium halides

Summary Several N-1-alkyl-, 3-, and 4-carbamidopyridinium halides were synthesized and determined to be inhibitors of mitochondrial oxidative phosphorylation. L-Glutamate respiration was most depressed by N-1-dodecylpyridinium bromide whereas succinate respiration was most depressed by N-1-dodecylisonicotinamide bromide. Combination of inhibitors with mitochondrial sites may involve lipophilic interactions as modified by steric restrictions.     

Mutagenic insertion and chromosome engineering resource (MICER)

Embryonic stem cell technology revolutionized biology by providing a means to assess mammalian gene function in vivo. Although it is now routine to generate mice from embryonic stem cells, one of the principal methods used to create mutations, gene targeting, is a cumbersome process. Here we describe the indexing of 93,960 ready-made insertional targeting vectors from two libraries. 5,925 of these vectors can be used directly to inactivate genes with an average targeting efficiency of 28%. Combinations of vectors from the two libraries can be used to disrupt both alleles of a gene or engineer larger genomic changes such as deletions, duplications, translocations or inversions. These indexed vectors constitute a public resource (Mutagenic Insertion and Chromosome Engineering Resource; MICER) for high-throughput, targeted manipulation of the mouse genome.     

Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity

Autoimmune diseases are thought to result from imbalances in normal immune physiology and regulation. Here, we show that autoimmune disease susceptibility and resistance alleles on mouse chromosome 3 (Idd3) correlate with differential expression of the key immunoregulatory cytokine interleukin-2 (IL-2). In order to test directly that an approximately twofold reduction in IL-2 underpins the Idd3-linked destabilization of immune homeostasis, we show that engineered haplodeficiency of Il2 gene expression not only reduces T cell IL-2 production by twofold but also mimics the autoimmune dysregulatory effects of the naturally occurring susceptibility alleles of Il2. Reduced IL-2 production achieved by either genetic mechanism correlates with reduced function of CD4(+) CD25(+) regulatory T cells, which are critical for maintaining immune homeostasis.     

Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death

Mutations in ion channels involved in the generation and termination of action potentials constitute a family of molecular defects that underlie fatal cardiac arrhythmias in inherited long-QT syndrome. We report here that a loss-of-function (E1425G) mutation in ankyrin-B (also known as ankyrin 2), a member of a family of versatile membrane adapters, causes dominantly inherited type 4 long-QT cardiac arrhythmia in humans. Mice heterozygous for a null mutation in ankyrin-B are haploinsufficient and display arrhythmia similar to humans. Mutation of ankyrin-B results in disruption in the cellular organization of the sodium pump, the sodium/calcium exchanger, and inositol-1,4,5-trisphosphate receptors (all ankyrin-B-binding proteins), which reduces the targeting of these proteins to the transverse tubules as well as reducing overall protein level. Ankyrin-B mutation also leads to altered Ca2+ signalling in adult cardiomyocytes that results in extrasystoles, and provides a rationale for the arrhythmia. Thus, we identify a new mechanism for cardiac arrhythmia due to abnormal coordination of multiple functionally related ion channels and transporters.     

Activated CD8 binding to class I protein mediated by the T-cell receptor results in signalling

The CD8 glycoprotein of T cells bind nonpolymorphic regions of class I major histocompatibility complex proteins on target cells and these interactions promote antigen recognition and signalling by the T-cell receptor. Studies using artificial membranes indicated that effective CD8/class I interaction is critical for response by alloantigen-specific cytotoxic T lymphocytes when class I protein is the only ligand on the antigen-bearing surface. But significant CD8-mediated binding of cytotoxic T lymphocytes to non-antigenic class I protein could not be detected in the absence of the alloantigen. These apparently contradictory findings indicate that CD8 binding to class I protein might be activated through the T-cell receptor and the results reported here demonstrate that this is the case. Treatment of cytotoxic T lymphocytes with soluble anti-T-cell receptor antibody activates adhesion of the cytotoxic T lymphocytes to class I, but not class II proteins. The specificity of this binding implies that it is mediated by CD8 and blocking by anti-CD8 antibodies confirmed this. Furthermore, binding of CD8 to class I protein resulted in generation of an additional signal(s) necessary to initiate response at low T-cell receptor occupancy levels.     

以专业实验室评估为契机积极推进学生素质教育

教育的目的就是为了全面提高人的素质，为适应素质教育的需要，积极推进专业实验室评估势在必行。本文就我院当前形势，结合专业实验室评估的实际工作，对以专业实验室评估为契机积极推进学生素质教育进行了深入的剖析。