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  • 1
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    Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alpha (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-01-15
    Description: Phosphoinositide 3-kinase (PI3K) activation has been implicated in many cellular responses, including fibroblast growth, transformation, survival, and chemotaxis. Although PI3K is activated by several agents that stimulate T and B cells, the role of PI3K in lymphocyte function is not clear. The mouse gene encoding the PI3K adapter subunit p85alpha and its splice variants p55alpha and p50alpha was disrupted. Most p85alpha-p55alpha-p50alpha-/- mice die within days after birth. Lymphocyte development and function was studied with the use of the RAG2-deficient blastocyst complementation system. Chimeric mice had reduced numbers of peripheral mature B cells and decreased serum immunoglobulin. The B cells that developed had diminished proliferative responses to antibody to immunoglobulin M, antibody to CD40, and lipopolysaccharide stimulation and decreased survival after incubation with interleukin-4. In contrast, T cell development and proliferation was normal. This phenotype is similar to defects observed in mice lacking the tyrosine kinase Btk.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fruman, D A -- Snapper, S B -- Yballe, C M -- Davidson, L -- Yu, J Y -- Alt, F W -- Cantley, L C -- R01 GM041890/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Jan 15;283(5400):393-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. dfruman@bidmc.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9888855" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD45/analysis ; Apoptosis ; B-Lymphocytes/cytology/enzymology/*immunology ; Catalytic Domain ; Cell Cycle ; Chimera ; Chromones/pharmacology ; Enzyme Inhibitors/pharmacology ; Female ; Gene Targeting ; Immunoglobulins/*blood ; *Lymphocyte Activation ; Lymphocyte Count ; Male ; Mice ; Mice, Inbred C57BL ; Morpholines/pharmacology ; Phosphatidylinositol 3-Kinases/antagonists & inhibitors/genetics/*metabolism ; Protein-Tyrosine Kinases/genetics/metabolism ; Spleen/immunology ; T-Lymphocytes/cytology/enzymology/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    Strontianite in coral skeletal aragonite (1997)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1997-03-07
    Description: An x-ray spectroscopic study of scleractinian coral skeletons indicated that, although some strontium substitutes for calcium in the aragonite structure, at concentrations of about 7500 parts per million, as much as 40 percent of the strontium resides in strontianite (SrCO3). A doublet peak in the Fourier transform of the extended x-ray absorption fine structure of the coral corresponded to six metal and 13 oxygen neighbors surrounding strontium at about 4.05 angstroms in strontium-substituted aragonite and at about 4.21 angstroms in strontianite. Thus, the mechanism of the temperature-sensitive partitioning of strontium between seawater and coral skeleton used for paleothermometry is unexpectedly complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Greegor, R B -- Pingitore, N E Jr -- Lytle, F W -- New York, N.Y. -- Science. 1997 Mar 7;275(5305):1452-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Boeing Company, Seattle, WA 98124, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9072808" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/analysis ; Calcium Carbonate/*analysis ; Carbonates/*analysis ; Cnidaria/*chemistry ; Fourier Analysis ; Spectrum Analysis ; Strontium/*analysis ; Temperature
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Thymocyte development in the absence of pre-T cell receptor extracellular immunoglobulin domains (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-05-23
    Description: Immature thymocytes express a pre-T cell receptor (pre-TCR) composed of the TCRbeta chain paired with pre-Talpha. Signals from this receptor are essential for passage of thymocytes through a key developmental checkpoint in the thymus. These signals were efficiently delivered in vivo by a truncated form of the murine pre-TCR that lacked all of its extracellular immunoglobulin domains. De novo expression of the truncated pre-TCR or an intact alphabetaTCR was sufficient to activate characteristic TCR signaling pathways in a T cell line. These findings support the view that recognition of an extracellular ligand is not required for pre-TCR function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Irving, B A -- Alt, F W -- Killeen, N -- New York, N.Y. -- Science. 1998 May 8;280(5365):905-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0414, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9572735" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/analysis ; Antigens, CD3/analysis/genetics ; DNA-Binding Proteins/genetics/metabolism ; Dimerization ; Gene Rearrangement, T-Lymphocyte ; Humans ; Immunoglobulins/chemistry ; Immunophenotyping ; Jurkat Cells ; Ligands ; Membrane Glycoproteins/chemistry/genetics/*physiology ; Mice ; Mice, Inbred Strains ; Mice, Transgenic ; NFATC Transcription Factors ; *Nuclear Proteins ; Receptors, Antigen, T-Cell, alpha-beta/chemistry/genetics/*physiology ; Signal Transduction ; T-Lymphocytes/cytology/*immunology/metabolism ; Transcription Factors/genetics/metabolism ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Attomole protein characterization by capillary electrophoresis-mass spectrometry (1996)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1996-08-30
    Description: Electrospray ionization with an ultralow flow rate (〈/=4 nanoliters per minute) was used to directly couple capillary electrophoresis with tandem mass spectrometry for the analysis and identification of biomolecules in mixtures. A Fourier transform mass spectrometer provided full spectra (〉30 kilodaltons) at a resolving power of approximately 60,000 for injections of 0.7 x 10(-18) to 3 x 10(-18) mole of 8- to 29-kilodalton proteins with errors of 〈1 dalton in molecular mass. Using a crude isolate from human blood, a value of 28,780.6 daltons (calculated, 28,780.4 daltons) was measured for carbonic anhydrase, representing 1 percent by weight of the protein in a single red blood cell. Dissociation of molecular ions from 9 x 10(-18) mole of carbonic anhydrase gave nine sequence-specific fragment ions, more data than required for unique retrieval of this enzyme from the protein database.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Valaskovic, G A -- Kelleher, N L -- McLafferty, F W -- 08-T2GM07273/GM/NIGMS NIH HHS/ -- GM16609/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Aug 30;273(5279):1199-202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Baker Laboratory, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8703047" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbonic Anhydrases/*analysis/chemistry ; Cattle ; Cytochrome c Group/analysis/chemistry ; Electrophoresis, Capillary/*methods ; Horses ; Humans ; Mass Spectrometry/*methods ; Molecular Weight ; Proteins/*analysis/chemistry ; Sensitivity and Specificity ; Spectroscopy, Fourier Transform Infrared ; Ubiquitins/analysis/chemistry
    Print ISSN: 0036-8075
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  • 5
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    Synaptic efficacy enhanced by glial cells in vitro (1997)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1997-09-12
    Description: In the developing nervous system, glial cells guide axons to their target areas, but it is unknown whether they help neurons to establish functional synaptic connections. The role of glial cells in synapse formation and function was studied in cultures of purified neurons from the rat central nervous system. In glia-free cultures, retinal ganglion cells formed synapses with normal ultrastructure but displayed little spontaneous synaptic activity and high failure rates in evoked synaptic transmission. In cocultures with neuroglia, the frequency and amplitude of spontaneous postsynaptic currents were potentiated by 70-fold and 5-fold, respectively, and fewer transmission failures occurred. Glial cells increased the action potential-independent quantal release by 12-fold without affecting neuronal survival. Thus, developing neurons in culture form inefficient synapses that require glial signals to become fully functional.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pfrieger, F W -- Barres, B A -- New York, N.Y. -- Science. 1997 Sep 12;277(5332):1684-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Stanford University, School of Medicine, Sherman Fairchild Science Building, 299 Campus Drive, Stanford, CA 94305-5125, USA. fpfrieg@mdc-berlin.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9287225" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Astrocytes/physiology ; Cell Survival ; Cells, Cultured ; Coculture Techniques ; Microglia/physiology ; Neuroglia/*physiology ; Oligodendroglia/physiology ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells/cytology/*physiology/ultrastructure ; Synapses/*physiology/ultrastructure ; *Synaptic Transmission
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Blocked Ras activation in anergic CD4+ T cells (1996)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1996-03-01
    Description: T cell anergy is a state of functional unresponsiveness characterized by the inability to produce interleukin-2 (IL-2) upon T cell receptor stimulation. The mitogen-activated protein kinases ERK-1 and ERK-2 and the guanosine triphosphate-binding protein p21ras were found to remain unactivated upon stimulation of anergic murine T helper cell 1 clones. The inability to activate the Ras pathway did not result from a defect in association among Shc, Grb-2, and murine Son of Sevenless, nor from a defect in their tyrosine phosphorylation. This block in Ras activation may lead to defective transactivation at activator protein 1 sites in anergic cells and may enable T cells to shut down IL-2 production selectively during anergy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fields, P E -- Gajewski, T F -- Fitch, F W -- New York, N.Y. -- Science. 1996 Mar 1;271(5253):1276-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ben May Institute, Department of Pathology, University of Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8638108" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Animals ; Antigens, CD4/immunology ; Calcium-Calmodulin-Dependent Protein Kinases/metabolism ; *Clonal Anergy ; Clone Cells ; GRB2 Adaptor Protein ; Guanine Nucleotide Exchange Factors ; Guanosine Triphosphate/metabolism ; Interleukin-2/biosynthesis ; Ionomycin/pharmacology ; Lymphocyte Activation ; Mice ; Mitogen-Activated Protein Kinase 1 ; Mitogen-Activated Protein Kinase 3 ; *Mitogen-Activated Protein Kinases ; Protein-Tyrosine Kinases/metabolism ; Proteins/metabolism ; Proto-Oncogene Proteins p21(ras)/*metabolism ; Receptors, Antigen, T-Cell/immunology ; *Signal Transduction ; Tetradecanoylphorbol Acetate/pharmacology ; Th1 Cells/*immunology/metabolism ; ras Guanine Nucleotide Exchange Factors
    Print ISSN: 0036-8075
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  • 7
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    Prospects for in utero human gene therapy (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-10-16
    Description: Gene therapy for the treatment of disease in children and adults is being actively pursued at many medical centers. However, a number of genetic disorders result in irreversible damage to the fetus before birth. In these cases, as well as for those with genetic diseases who may benefit from therapy before symptoms are manifested, in utero gene therapy (IUGT) could be beneficial. Although some successes with in utero gene transfer have been reported in animals, significant questions remain to be answered before IUGT clinical trials would be acceptable. This review analyzes the state of the art and delineates the studies that still need to be performed before it would be appropriate to consider human IUGT.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zanjani, E D -- Anderson, W F -- New York, N.Y. -- Science. 1999 Sep 24;285(5436):2084-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Veterans Administration Medical Center, University of Nevada, Reno, NV 89520, USA. zanjani@scs.unr.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10523208" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Fetal Diseases/*therapy ; *Fetus ; Gene Transfer Techniques ; Genetic Diseases, Inborn/*therapy ; *Genetic Therapy/adverse effects ; Genetic Vectors ; Germ Cells ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/cytology/physiology ; Humans ; Pregnancy
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Phylogenetic classification and the universal tree (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-06-26
    Description: From comparative analyses of the nucleotide sequences of genes encoding ribosomal RNAs and several proteins, molecular phylogeneticists have constructed a "universal tree of life," taking it as the basis for a "natural" hierarchical classification of all living things. Although confidence in some of the tree's early branches has recently been shaken, new approaches could still resolve many methodological uncertainties. More challenging is evidence that most archaeal and bacterial genomes (and the inferred ancestral eukaryotic nuclear genome) contain genes from multiple sources. If "chimerism" or "lateral gene transfer" cannot be dismissed as trivial in extent or limited to special categories of genes, then no hierarchical universal classification can be taken as natural. Molecular phylogeneticists will have failed to find the "true tree," not because their methods are inadequate or because they have chosen the wrong genes, but because the history of life cannot properly be represented as a tree. However, taxonomies based on molecular sequences will remain indispensable, and understanding of the evolutionary process will ultimately be enriched, not impoverished.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Doolittle, W F -- New York, N.Y. -- Science. 1999 Jun 25;284(5423):2124-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Canadian Institute for Advanced Research, Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada. ford@is.dal.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10381871" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Archaea/*classification/genetics ; Bacteria/*classification/genetics ; *Biological Evolution ; Eukaryotic Cells/*classification ; Genes, rRNA ; Genome ; *Phylogeny ; RNA, Ribosomal/chemistry/genetics ; *Recombination, Genetic
    Print ISSN: 0036-8075
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  • 9
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    Biospherian viewpoints (1997)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1997-02-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dempster, W F -- New York, N.Y. -- Science. 1997 Feb 28;275(5304):1247-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9064774" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arizona ; Atmosphere ; *Ecological Systems, Closed ; *Ecosystem ; Humans
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    Prevention of vascular and neural dysfunction in diabetic rats by C-peptide (1997)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1997-07-25
    Description: C-peptide, a cleavage product from the processing of proinsulin to insulin, has been considered to possess little if any biological activity other than its participation in insulin synthesis. Injection of human C-peptide prevented or attenuated vascular and neural (electrophysiological) dysfunction and impaired Na+- and K+-dependent adenosine triphosphate activity in tissues of diabetic rats. Nonpolar amino acids in the midportion of the peptide were required for these biological effects. Synthetic reverse sequence (retro) and all-D-amino acid (enantio) C-peptides were equipotent to native C-peptide, which indicates that the effects of C-peptide on diabetic vascular and neural dysfunction were mediated by nonchiral interactions instead of stereospecific receptors or binding sites.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ido, Y -- Vindigni, A -- Chang, K -- Stramm, L -- Chance, R -- Heath, W F -- DiMarchi, R D -- Di Cera, E -- Williamson, J R -- EY 06600/EY/NEI NIH HHS/ -- HL 39934/HL/NHLBI NIH HHS/ -- HL 58141/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1997 Jul 25;277(5325):563-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9228006" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Blood Circulation/drug effects ; Blood Glucose/metabolism ; C-Peptide/*chemistry/pharmacology/*therapeutic use ; Capillary Permeability/drug effects ; Circular Dichroism ; Diabetes Mellitus, Experimental/drug therapy/physiopathology ; Diabetic Angiopathies/*prevention & control ; Diabetic Neuropathies/*prevention & control ; Humans ; Male ; Molecular Sequence Data ; Neural Conduction/drug effects ; Peptide Fragments/pharmacology ; Protein Structure, Secondary ; Rats ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase/metabolism ; Stereoisomerism
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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