Asbestos contamination of parenteral drugs   总被引：1，自引：0，他引：1  

W J Nicholson  C J Maggiore  I J Selikoff 《Science (New York, N.Y.)》1972,177(44):171-173

Chrysotile asbestos has been found in approximately one third of the samples from two sets of 17 widely used parenteral drugs.  相似文献   

Replacements of Pro86 in phage T4 lysozyme extend an alpha-helix but do not alter protein stability   总被引：10，自引：0，他引：10  

T Alber  J A Bell  D P Sun  H Nicholson  J A Wozniak  S Cook  B W Matthews 《Science (New York, N.Y.)》1988,239(4840):631-635

To investigate the relation between protein stability and the predicted stabilities of individual secondary structural elements, residue Pro86 in an alpha-helix in phage T4 lysozyme was replaced by ten different amino acids. The x-ray crystal structures of seven of the mutant lysozymes were determined at high resolution. In each case, replacement of the proline resulted in the formation of an extended alpha-helix. This involves a large conformational change in residues 81 to 83 and smaller shifts that extend 20 angstroms across the protein surface. Unexpectedly, all ten amino acid substitutions marginally reduce protein thermostability. This insensitivity of stability to the amino acid at position 86 is not simply explained by statistical and thermodynamic criteria for helical propensity. The observed conformational changes illustrate a general mechanism by which proteins can tolerate mutations.  相似文献   

Science and technology in government     

Nicholson RS  Abelson PH 《Science (New York, N.Y.)》1993,260(5107):471

  相似文献   

Preferred centripetal conduction of dendritic spikes in alligator Purkinje cells     

R Llinás  C Nicholson  W Precht 《Science (New York, N.Y.)》1969,163(863):184-187

Dendritic action potentials in alligator Purkinje cells tend to have a unidirectional preference which favors centripetal over centrifugal propagation. This unidirectional tendency funnels the peripherally evoked dendritic spikes into the lower dendrites and soma of these cells, and it allows the peripheral dendritic branches to operate to a certain extent as partially independent functional units.  相似文献   

Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease     

Outeiro TF  Kontopoulos E  Altmann SM  Kufareva I  Strathearn KE  Amore AM  Volk CB  Maxwell MM  Rochet JC  McLean PJ  Young AB  Abagyan R  Feany MB  Hyman BT  Kazantsev AG 《Science (New York, N.Y.)》2007,317(5837):516-519

The sirtuins are members of the histone deacetylase family of proteins that participate in a variety of cellular functions and play a role in aging. We identified a potent inhibitor of sirtuin 2 (SIRT2) and found that inhibition of SIRT2 rescued alpha-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. Genetic inhibition of SIRT2 via small interfering RNA similarly rescued alpha-synuclein toxicity. Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease. The results suggest a link between neurodegeneration and aging.  相似文献   

Elucidation of the small RNA component of the transcriptome   总被引：3，自引：0，他引：3  

Lu C  Tej SS  Luo S  Haudenschild CD  Meyers BC  Green PJ 《Science (New York, N.Y.)》2005,309(5740):1567-1569

Small RNAs play important regulatory roles in most eukaryotes, but only a small proportion of these molecules have been identified. We sequenced more than two million small RNAs from seedlings and the inflorescence of the model plant Arabidopsis thaliana. Known and new microRNAs (miRNAs) were among the most abundant of the nonredundant set of more than 75,000 sequences, whereas more than half represented lower abundance small interfering RNAs (siRNAs) that match repetitive sequences, intergenic regions, and genes. Individual or clusters of highly regulated small RNAs were readily observed. Targets of antisense RNA or miRNA did not appear to be preferentially associated with siRNAs. Many genomic regions previously considered featureless were found to be sites of numerous small RNAs.  相似文献   

Mutations in dynein link motor neuron degeneration to defects in retrograde transport     

Hafezparast M  Klocke R  Ruhrberg C  Marquardt A  Ahmad-Annuar A  Bowen S  Lalli G  Witherden AS  Hummerich H  Nicholson S  Morgan PJ  Oozageer R  Priestley JV  Averill S  King VR  Ball S  Peters J  Toda T  Yamamoto A  Hiraoka Y  Augustin M  Korthaus D  Wattler S  Wabnitz P  Dickneite C  Lampel S  Boehme F  Peraus G  Popp A  Rudelius M  Schlegel J  Fuchs H  Hrabe de Angelis M  Schiavo G  Shima DT  Russ AP  Stumm G  Martin JE  Fisher EM 《Science (New York, N.Y.)》2003,300(5620):808-812

Degenerative disorders of motor neurons include a range of progressive fatal diseases such as amyotrophic lateral sclerosis (ALS), spinal-bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA). Although the causative genetic alterations are known for some cases, the molecular basis of many SMA and SBMA-like syndromes and most ALS cases is unknown. Here we show that missense point mutations in the cytoplasmic dynein heavy chain result in progressive motor neuron degeneration in heterozygous mice, and in homozygotes this is accompanied by the formation of Lewy-like inclusion bodies, thus resembling key features of human pathology. These mutations exclusively perturb neuron-specific functions of dynein.  相似文献   

Immunology. Exposing thy self     

Ohashi PS 《Science (New York, N.Y.)》2002,298(5597):1348-1349

  相似文献   

Modulation of postendocytic sorting of G protein-coupled receptors   总被引：1，自引：0，他引：1  

Whistler JL  Enquist J  Marley A  Fong J  Gladher F  Tsuruda P  Murray SR  Von Zastrow M 《Science (New York, N.Y.)》2002,297(5581):615-620

Recycling of the mu opioid receptor to the plasma membrane after endocytosis promotes rapid resensitization of signal transduction, whereas targeting of the delta opioid receptor (DOR) to lysosomes causes proteolytic down-regulation. We identified a protein that binds preferentially to the cytoplasmic tail of the DOR as a candidate heterotrimeric GTP-binding protein (G protein)-coupled receptor-associated sorting protein (GASP). Disruption of the DOR-GASP interaction through receptor mutation or overexpression of a dominant negative fragment of GASP inhibited receptor trafficking to lysosomes and promoted recycling. The GASP family of proteins may modulate lysosomal sorting and functional down-regulation of a variety of G protein-coupled receptors.  相似文献   

Genetics. Toward a new vocabulary of human genetic variation     

Sankar P  Cho MK 《Science (New York, N.Y.)》2002,298(5597):1337-1338

  相似文献