X-ray Damage to CF3CO2-Terminated Organic Monolayers on Si/Au: Principal Effect of Electrons

The relative importance of x-rays alone and of x-ray-generated primary and secondary electrons in damaging organic materials was explored by use of self-assembled monolayers (SAMs) on multilayer thin-film supports. The substrates were prepared by the deposit of thin films of silicon (0, 50, 100, and 200 angstroms) on thick layers of gold (2000 angstroms). These systems were supported on chromium-primed silicon wafers. Trifluoroacetoxy-terminated SAMs were assembled on these substrates, and the samples were irradiated with common fluxes of monochromatic aluminum K(alpha) x-rays. The fluxes and energy distributions of the electrons generated by interactions of the x-rays with the various substrates, however, differed. The substrates that emitted a lower flux of electrons exhibited a slower loss of fluorine from the SAMs. This observation indicated that the electrons-and not the x-rays themselves-were largely responsible for the damage to the organic monolayer.     

Beta-adrenergic-receptor localization by light microscopic autoradiography

beta-Receptors were identified in rat brain by a light microscopic autoradiographic technique. The procedure involved binding 3H-labeled dihydroalprenolol to beta-receptors in intact slide-mounted tissue sections and generating autoradiograms by the apposition of emulsion-coated cover slips, Biochemical analysis of the binding indicated that these conditions provided a high degree of selective labeling of beta-receptors. High densities of receptors were found in superficial layers of the cerebral cortex, throughout the caudate-putamen, in the periventricular nucleus of the thalamus, in the molecular layer of the cerebellum, and in other areas. These results are in agreement with other electrophysiological and histochemical data. This radiohistochemical approach should be an important addition to other methods for mapping functional catecholamine neuronal pathways and sites of hormonal action.     

High-resolution autoradiography of intracellular plutonium

Intracellular incorporation of polymeric plutonium injected into mice was demonstrated in liver and spleen by electron-microscopic auto-radiography. The observations are not inconsistent with other evidence indicating the association of plutonium with lysosomal components. Early results with a quantitative electron-microscopic technique may lead to microdosimetry of cells and cellular components.     

Electron microscopy and autoradiography

The combined techniques of electron microscopy and autoradiography were used for the purpose of differentiating radioactive from nonradioactive particles collected on membrane filters. Newer methods of processing the membrane filters and applying the nuclear emulsion have resulted in an improvement in the qualitative nature of the procedure.     

A G protein mutant that inhibits thrombin and purinergic receptor activation of phospholipase A2

The stimulation of phospholipase A2 by thrombin and type 2 (P2)-purinergic receptor agonists in Chinese hamster ovary cells is mediated by the G protein Gi. To delineate alpha chain regulatory regions responsible for control of phospholipase A2, chimeric cDNAs were constructed in which different lengths of the alpha subunit of Gs (alpha s) were replaced with the corresponding sequence of the Gi alpha subunit (alpha i2). When a carboxyl-terminal chimera alpha s-i(38), which has the last 38 amino acids of alpha s substituted with the last 36 residues of alpha i2, was expressed in Chinese hamster ovary cells, the receptor-stimulated phospholipase A2 activity was inhibited, although the chimera could still activate adenylyl cyclase. Thus, alpha s-i(38) is an active alpha s, but also a dominant negative alpha i molecule, indicating that the last 36 amino acids of alpha i2 are a critical domain for G protein regulation of phospholipase A2 activity.     

Locus of the alpha-chain of the T-cell receptor is split by chromosome translocation in T-cell leukemias

Mouse lymphoma cells were hybridized with two human acute T-cell leukemias with a t(11;14) (p13;q11) translocation and the segregated hybrids were examined for the presence of the DNA segments coding for the constant (C) and the variable (V) regions of the alpha chain (C alpha and V alpha) of the T-cell receptor. The C alpha segment was translocated to the involved chromosome 11 (11p+) while the V alpha segment remained on the involved chromosome 14 (14q-). The data indicate that the locus for the alpha chain of the T-cell receptor is split by the chromosomal breakpoint between the V alpha and the C alpha gene segments, and that the V alpha segments are proximal to the C alpha segment within chromosome band 14q11.2.     

Estradiol-concentrating neurons: topography in the hypothalamus by dry-mount autoradiography

Serial section autoradiograms were prepared of different planes of the hypothalamus and diencephalon of immature female, immature male, and ovariectomized mature rats injected with 6,7-(3)H-estradiol-17 beta. Known causes of diffusion and redistribution of the label, such as fixation, embedding, and thawing, were eliminated by the use of an autoradiographic technique based on the dry-mounting of freeze-dried sections. Neurons that concentrate estradiol exist in distinct and definable anatomical areas that are independent of the sex and hormonal state of the animals. Distribution of these neurons follows known terminations of the stria terminalis, which supports the concept of an endocrine amygdaloid-hypothalamic-hypophysial axis.     

Type I and type II GABAA-benzodiazepine receptors produced in transfected cells

GABAA (gamma-aminobutyric acid A)-benzodiazepine receptors expressed in mammalian cells and assembled from one of three different alpha subunit variants (alpha 1, alpha 2, or alpha 3) in combination with a beta 1 and a gamma 2 subunit display the pharmacological properties of either type I or type II receptor subtypes. These receptors contain high-affinity binding sites for benzodiazepines. However, CL 218 872, 2-oxoquazepam, and methyl beta-carboline-3-carboxylate (beta-CCM) show a temperature-modulated selectivity for alpha 1 subunit-containing receptors. There were no significant differences in the binding of clonazepam, diazepam, Ro 15-1788, or dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) to all three recombinant receptors. Receptors containing the alpha 3 subunit show greater GABA potentiation of benzodiazepine binding than receptors containing the alpha 1 or alpha 2 subunit, indicating that there are subtypes within the type II class. Thus, diversity in benzodiazepine pharmacology is generated by heterogeneity of the alpha subunit of the GABAA receptor.     

Transmitter sensitivity of neurons assayed by autoradiography

Ionic conductance channels that are opened by activating nicotinic acetylcholine receptors at synapses of sympathetic neurons are permeable to small organic amines. Uptake of a tritium-labeled amine through these channels can be measured by autoradiography. This provides a simple and direct way to assess the sensitivity of individual neurons to acetylcholine without using microelectrodes.     

云芝化学成分研究

 从真菌云芝子实体中分离鉴定了6个化合物和1个混合物,分别为：(22E,24R)-ergosta-7,22-dien-3β-ol（1）、 (22E, 24R)-ergosta-6,22-dien-3β,5α,8α-triol（2）、5α,6α-epoxy-(22E,24R)-ergosta-8,22-dien-3β,7α-diol（3）、二十四碳酸（4）、二十六碳酸（5）和α,α-trehalose（6）;混合物可推测主要由russulamide（7）、ascolipid C（8）、ascolipid D（9）组成。除化合物1外,其余化合物均为该种首次分离得到。     

Production of alpha 1,3-galactosyltransferase-deficient pigs

The enzyme alpha1,3-galactosyltransferase (alpha1,3GT or GGTA1) synthesizes alpha1,3-galactose (alpha1,3Gal) epitopes (Galalpha1,3Galbeta1,4GlcNAc-R), which are the major xenoantigens causing hyperacute rejection in pig-to-human xenotransplantation. Complete removal of alpha1,3Gal from pig organs is the critical step toward the success of xenotransplantation. We reported earlier the targeted disruption of one allele of the alpha1,3GT gene in cloned pigs. A selection procedure based on a bacterial toxin was used to select for cells in which the second allele of the gene was knocked out. Sequencing analysis demonstrated that knockout of the second allele of the alpha1,3GT gene was caused by a T-to-G single point mutation at the second base of exon 9, which resulted in inactivation of the alpha1,3GT protein. Four healthy alpha1,3GT double-knockout female piglets were produced by three consecutive rounds of cloning. The piglets carrying a point mutation in the alpha1,3GT gene hold significant value, as they would allow production of alpha1,3Gal-deficient pigs free of antibiotic-resistance genes and thus have the potential to make a safer product for human use.     

Silent hemoglobin alpha genes in apes: potential source of thalassemia

Small quantities of unusual hemoglobins were found in 1 of 37 chimpanzees and 2 of 6 gorillas. In each genus these hemoglobins contain unique alpha chains that differ from the ordinary by eight to nine scattered amino acid changes. The unusual chains arise from a hitherto undetected hemoglobin (3)alpha locus. No (3)alpha products are found in most apes; accordingly, (3)alpha is considered synthetically inactive in all but a few reversion mutants. Indirect evidence that the inactive (3)alpha locus is juxtaposed to an active alpha locus together with the supposition that (3)alpha exists in man provides a setting wherein thalassemia might be produced by nonhomologous recombination between two loci.     

Functional expression of a new pharmacological subtype of brain nicotinic acetylcholine receptor

A new type of agonist-binding subunit of rat neuronal nicotinic acetylcholine receptors (nAChRs) was identified. Rat genomic DNA and complementary DNA encoding this subunit (alpha 2) were cloned and analyzed. Complementary DNA expression studies in Xenopus oocytes revealed that the injection of messenger RNAs (mRNAs) for alpha 2 and beta 2 (a neuronal nAChR subunit) led to the generation of a functional nAChR. In contrast to the other known neuronal nAChRs, the receptor produced by the injection of alpha 2 and beta 2 mRNAs was resistant to the alpha-neurotoxin Bgt3.1. In situ hybridization histochemistry showed that alpha 2 mRNA was expressed in a small number of regions, in contrast to the wide distribution of the other known agonist-binding subunits (alpha 3 and alpha 4) mRNAs. These results demonstrate that the alpha 2 subunit differs from other known agonist-binding alpha-subunits of nAChRs in its distribution in the brain and in its pharmacology.     

Two G protein oncogenes in human endocrine tumors

Somatic mutations in a subset of growth hormone (GH)-secreting pituitary tumors convert the gene for the alpha polypeptide chain (alpha s) of Gs into a putative oncogene, termed gsp. These mutations, which activate alpha s by inhibiting its guanosine triphosphatase (GTPase) activity, are found in codons for either of two amino acids, each of which is completely conserved in all known G protein alpha chains. The likelihood that similar mutations would activate other G proteins prompted a survey of human tumors for mutations that replace either of these two amino acids in other G protein alpha chain genes. The first gene so far tested, which encodes the alpha chain of Gi2, showed mutations that replaced arginine-179 with either cysteine or histidine in 3 of 11 tumors of the adrenal cortex and 3 of 10 endocrine tumors of the ovary. The mutant alpha i2 gene is a putative oncogene, referred to as gip2. In addition, gsp mutations were found in 18 of 42 GH-secreting pituitary tumors and in an autonomously functioning thyroid adenoma. These findings suggest that human tumors may harbor oncogenic mutations in various G protein alpha chain genes.     

1 -Antitrypsin deficiency: a variant with no detectable 1 -antitrypsin

No alpha(1)-antitrypsin could be detected in the serum of a 24-year-old man with advanced pulmonary emphysema by agarose electrophoresis, immnuno-electrophoresis, double diffusion in agarose gel, or alpha(1)-antitrypsin genetic typing by a combination of starch-gel electrophoresis and crossed antigen-antibody electrophoresis. A circulating alpha(1)-antitrypsin inactivator could not be demonstrated. Evidence was obtained in family members of genetic transmission of this new alpha(1)-antitrypsin variant.     

Measuring the surface dynamics of glassy polymers

The motion of polymer chain segments cooled below the glass transition temperature slows markedly; with sufficient cooling, segmental motion becomes completely arrested. There is debate as to whether the chain segments near the free surface, or in thin films, are affected in the same way as the bulk material. By partially embedding and then removing gold nanospheres, we produced a high surface coverage of well-defined nanodeformations on a polystyrene surface; to probe the surface dynamics, we measured the time-dependent relaxation of these surface deformations as a function of temperature from 277 to 369 kelvin. Surface relaxation was observed at all temperatures, providing strong direct evidence for enhanced surface mobility relative to the bulk. The deviation from bulk alpha relaxation became more pronounced as the temperature was decreased below the bulk glass transition temperature. The temperature dependence of the relaxation time was much weaker than that of the bulk alpha relaxation of polystyrene, and the process exhibited no discernible temperature dependence between 277 and 307 kelvin.     

可见光响应氮杂化TiO2-N薄膜对水源水体的杀菌作用

以尿素为氮源,采用Sol-gel法及浸渍-提拉法制备氮杂化TiO2-N薄膜,并运用正交试验法优化TiO2-N薄膜的最佳制备条件;利用AFM分析技术对TiO2-N薄膜表面形貌进行表征;在太阳光光催化反应器中,探讨TiO2-N薄膜对饮用水供水水源水体中大肠菌群的杀菌作用。结果表明,热处理条件是影响TiO2-N薄膜制备的关键因素,各个影响因素的主次顺序为热处理温度〉停留温度〉热处理时间,在最佳条件下制备的TiO2-N薄膜,在太阳光作用下光解30min时,对饮用水供水水源水体中大肠菌群的杀菌率达到57.7%以上;Ag的协同掺杂（Ag-TiO2-N）或在TiO2-N薄膜表面的沉积（Ag/TiO2-N）,显著提高了TiO2-N薄膜的杀菌作用,对大肠菌群的杀菌率可达90%以上。     

MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha

Phosphorylation of mitogen-activated protein kinases (MAPKs) on specific tyrosine and threonine sites by MAP kinase kinases (MAPKKs) is thought to be the sole activation mechanism. Here, we report an unexpected activation mechanism for p38alpha MAPK that does not involve the prototypic kinase cascade. Rather it depends on interaction of p38alpha with TAB1 [transforming growth factor-beta-activated protein kinase 1 (TAK1)-binding protein 1] leading to autophosphorylation and activation of p38alpha. We detected formation of a TRAF6-TAB1-p38alpha complex and showed stimulus-specific TAB1-dependent and TAB1-independent p38alpha activation. These findings suggest that alternative activation pathways contribute to the biological responses of p38alpha to various stimuli.     

Molecular and neuronal substrate for the selective attenuation of anxiety

Benzodiazepine tranquilizers are used in the treatment of anxiety disorders. To identify the molecular and neuronal target mediating the anxiolytic action of benzodiazepines, we generated and analyzed two mouse lines in which the alpha2 or alpha3 GABAA (gamma-aminobutyric acid type A) receptors, respectively, were rendered insensitive to diazepam by a knock-in point mutation. The anxiolytic action of diazepam was absent in mice with the alpha2(H101R) point mutation but present in mice with the alpha3(H126R) point mutation. These findings indicate that the anxiolytic effect of benzodiazepine drugs is mediated by alpha2 GABAA receptors, which are largely expressed in the limbic system, but not by alpha3 GABAA receptors, which predominate in the reticular activating system.