Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity

Alzheimer's disease is characterized by cerebral deposits of amyloid beta-protein (AP) as senile plaque core and vascular amyloid, and a complementary DNA encoding a precursor of this protein (APP) has been cloned from human brain. From a cDNA library of a human glioblastoma cell line, we have isolated a cDNA identical to that previously reported, together with a new cDNA which contains a 225-nucleotide insert. The sequence of the 56 amino acids at the N-terminal of the protein deduced from this insert is highly homologous to the basic trypsin inhibitor family, and the lysate from COS-1 cells transfected with the longer APP cDNA showed an increased inhibition of trypsin activity. Partial sequencing of the genomic DNA encoding APP showed that the 225 nucleotides are located in two exons. At least three messenger RNA species, apparently transcribed from a single APP gene by alternative splicing, were found in human brain. We suggest that protease inhibition by the longer APP(s) could be related to aberrant APP catabolism.     

金纳米薄膜面向导热系数的实验研究

基于电子束物理气相沉积法制备纳米薄膜的悬浮工艺，采用一维稳态恒热流加热法实验测量了80—300K厚度为23nm金薄膜的面向导热系数．研究表明金纳米薄膜的面向导热系数有非常显著的尺寸效应：金纳米薄膜的面向导热系数大大低于体材料的值，并且导热系数随温度的升高而增大，这一趋势与体材料导热系数的温度依赖性相反；同时，金纳米薄膜的Lorenz数大约为体材料值的3倍，并且随着温度的升高有减小的趋势，表明Wiedemann-Franz定律对于金纳米薄膜不再适用．     

Receptor binding and internalization of immobilized transcobalamin II by mouse leukaemia cells

Membrane transport of vitamin B12 (cyanocobalamin; Cbl) into mammalian cells is mediated by the serum protein transcobalamin II (TCII). In mouse leukaemia L1210 cells, TCII-Cbl binds to membrane receptors in a rapid, temperature-independent step and is internalized by a slow, temperature-dependent process. To delineate the location of receptors on these cells, we have constructed a visual probe by covalently coupling purified TCII-Cbl to submicrometre latex particles (minibeads). We report here that when L1210 cells are incubated with minibeads containing TCII-Cbl at 4 degrees C and examined by scanning electron microscopy (SEM), the particles are found attached predominantly to microvilli. Incubation of the cells at 37 degrees C results in the internalization of the minibeads. As visualized by transmission electron microscopy (TEM), this endocytotic process seems to occur in clathrin-coated pits and vesicles at the cell surface.     

Primary structure of the receptor for calcium channel blockers from skeletal muscle

The complete amino-acid sequence of the receptor for dihydropyridine calcium channel blockers from rabbit skeletal muscle is predicted by cloning and sequence analysis of DNA complementary to its messenger RNA. Structural and sequence similarities to the voltage-dependent sodium channel suggest that in the transverse tubule membrane of skeletal muscle the dihydropyridine receptor may act both as voltage sensor in excitation-contraction coupling and as a calcium channel.     

Cloning of complementary DNA encoding T-cell replacing factor and identity with B-cell growth factor II

Proliferation and maturation of antigen-stimulated B cells are regulated by several soluble factors derived from macrophages and T cells. These soluble factors are functionally divided into two groups: B-cell growth factor (BCGF), thought to be involved in B-cell proliferation; and B-cell differentiation factor (BCDF), responsible for maturation of activated B cells into immunoglobulin-secreting cells. This classification needs to be re-examined in the light of the recent cloning of complementary DNA encoding IgG1 induction factor (interleukin-4, IL-4) from the 2.19 mouse T-cell line. Recombinant IL-4 has BCGF and BCDF activities and affects B cells, T cells and mast cells (refs 7, 8; our unpublished data). Another well-characterized B-cell factor is T-cell replacing factor (TRF), which, when secreted by the murine T-cell hybridoma B151K12, is defined by two activities: induction of IgM secretion by BCL1 leukaemic B-cell line; and induction of secondary anti-dinitrophenol (DNP) immunoglobulin G (IgG) synthesis in vitro by DNP-prime B cells. Although TRF from B151K12 was classified as BCDF, purified TRF has BCGF-II activity. To elucidate the molecular properties of TRF we isolated cDNA encoding TRF from the 2.19 T-cell line and report here the structure and multiple activities of this lymphokine.     

Molecular distinction between fetal and adult forms of muscle acetylcholine receptor

Distinct classes of acetylcholine receptor channels are formed when Xenopus oocytes are injected with combinations of the bovine alpha-, beta-, gamma- and delta- or the alpha-, beta-, gamma- and epsilon-subunit-specific messenger RNAs. The conductance and gating properties of the two classes of channels, in conjunction with the developmental changes in the muscular contents of the mRNAs, suggest that replacement of the gamma-subunit by the epsilon-subunit is responsible for the functional alteration of the receptor during muscle development.     

Alpha-amylase inhibitor increases plasma 3-hydroxybutyric acid in food-restricted rats

The effect on energy metabolism of delayed absorption of starch by inhibition of -amylase was examined by considering levels of plasma glucose and 3-hydroxybutyric acid (3-OHBA) in rats. Addition of -amylase inhibitor (AI) to a high starch diet delayed the plasma glucose response after feeding: peak plasma glucose levels in the control group occurred 15 min after feeding, whereas in the AI group this peak did not occur until 30 min after. The total plasma glucose response was not different between the two groups. Plasma 3-OHBA levels 1 day after food restriction increased approximately five-fold in both groups. After 3 days of food restriction, the AI group maintained the same level of plasma 3-OHBA as after 1 day of food restriction, while the control group showed significantly decreased levels of 3-OHBA. After 3 days of food restriction, plasma insulin levels were significantly decreased in the AI group compared with the corresponding levels of the control group and with levels before the restriction. There was no significant difference in body weight between the two groups. These findings suggest that delayed hyperglycemia due to delayed absorption of starch following AI loading may attenuate insulin secretion, leading to altered metabolism of 3-OHBA during the delayed response to energy deficit.     

Estradiol treatment reduces a cytosol androgen binding protein in male rat liver

Summary The in vivo treatment of male rats with estradiol-17 resulted in a significant decrease in liver cytosol of the protein which binds specifically androstenedione and testosterone.Acknowledgment. This investigation was supported by a grant to N. S. from the Iwate-Keiryokai Medical University Research Foundation.