bluuebunny/crossref_metadata_2025 huggingface dataset:
Thorium-Uranium Fractionation by Garnet: Evidence for a Deep Source and Rapid Rise of Oceanic Basalts
Authors: LaTourrette T. Z. , Kennedy A. K. , Wasserburg G. J.
Published: October 2006

Mid-ocean ridge basalts (MORBs) and ocean island basalts (OIBs) are derived by partial melting of the upper mantle and are marked by systematic excesses of thorium-230 activity relative to the activity of its parent, uranium-238. Experimental measurements of the distribution of thorium and uranium between the melt and solid residue show that, of the major phases in the upper mantle, only garnet will retain uranium over thorium. This sense of fractionation, which is opposite to that caused by clinopyroxene-melt partitioning, is consistent with the thorium-230 excesses observed in young oceanic basalts. Thus, both MORBs and OIBs must begin partial melting in the garnet stability field or below about 70 kilometers. A calculation shows that the thorium-230—uranium-238 disequilibrium in MORBs can be attributed to dynamic partial melting beginning at 80 kilometers with a melt porosity of 0.2 percent or more. This result requires that melting beneath ridges occurs in a wide region and that the magma rises to the surface at a velocity of at least 0.9 meter per year.
Lattice Effect of Strong Electron Correlation: Implication for Ferroelectricity and Superconductivity
Authors: Egami T. , Ishihara S. , Tachiki M.
Published: October 2006

Much theoretical work has been devoted to understanding the role of strong electron correlations in high-temperature superconductivity mainly through magnetic interactions, but the possible role of electron correlation in ferroelectricity of metal oxides has not received attention. Diagonalization of a simple many-body, tight-binding Hamiltonian shows that the electron-lattice interaction is dramatically enhanced in some cases by strong electron correlation because of deformation-induced charge transfer. This effect may be closely related to ferroelectricity and superconductivity in transition metal oxides.
Deep and Bottom Water of the Weddell Sea's Western Rim
Authors: Gordon Arnold L. , Huber Bruce A. , Hellmer Hartmut H. , Ffield Amy
Published: October 2006

Oceanographic observations from the Ice Station Weddell 1 show that the western rim of the Weddell Gyre contributes to Weddell Sea Bottom Water. A thin (< 300 meters), highly oxygenated benthic layer is composed of a low-salinity type of bottom water overlying a high-salinity component. This complex layering disappears near 66°S because of vertical mixing and further inflow from the continental margin. The bottom water flowing out of the western rim is a blend of the two types. Additionally, the data show that a narrow band of warmer Weddell Deep Water hugged the continental margin as it flowed into the western rim, providing the continental margin with the salt required for bottom-water production.
Isotopic Evidence for Reduced Productivity in the Glacial Southern Ocean
Authors: Shemesh A. , Macko S. A. , Charles C. D. , Rau G. H.
Published: October 2006

Records of carbon and nitrogen isotopes in biogenic silica and carbon isotopes in planktonic foraminifera from deep-sea sediment cores from the Southern Ocean reveal that the primary production during the last glacial maximum was lower than Holocene productivity. These observations conflict with the hypothesis that the low atmospheric carbon dioxide concentrations were introduced by an increase in the efficiency of the high-latitude biological pump. Instead, different oceanic sectors may have had high glacial productivity, or alternative mechanisms that do not involve the biological pump must be considered as the primary cause of the low glacial atmospheric carbon dioxide concentrations.
Active Optics, Adaptive Optics, and Laser Guide Stars
Authors: Hubin N. , Noethe L.
Published: October 2006

Optical astronomy is crucial to our understanding of the universe, but the capabilities of ground-based telescopes are severely limited by the effects of telescope errors and of the atmosphere on the passage of light. Recently, it has become possible to construct inbuilt corrective devices that can compensate for both types of degradations as observations are conducted. For full use of the newly emerged class of 8-meter telescopes, such active corrective capabilities, known as active and adaptive optics, are essential. Some physical limitations in the adaptive optics field can be overcome by artificially created reference stars, called laser guide stars. These new technologies have lately been applied with success to some medium and very large telescopes.
Satellite Radar Interferometry for Monitoring Ice Sheet Motion: Application to an Antarctic Ice Stream
Authors: Goldstein Richard M. , Engelhardt Hermann , Kamb Barclay , Frolich Richard M.
Published: October 2006

Satellite radar interferometry (SRI) provides a sensitive means of monitoring the flow velocities and grounding-line positions of ice streams, which are indicators of response of the ice sheets to climatic change or internal instability. The detection limit is about 1.5 millimeters for vertical motions and about 4 millimeters for horizontal motions in the radar beam direction. The grounding line, detected by tidal motions where the ice goes afloat, can be mapped at a resolution of ∼0.5 kilometer. The SRI velocities and grounding line of the Rutford Ice Stream, Antarctica, agree fairly well with earlier ground-based data. The combined use of SRI and other satellite methods is expected to provide data that will enhance the understanding of ice stream mechanics and help make possible the prediction of ice sheet behavior.
Macrophage Inflammatory Protein-1: a Prostaglandin-Independent Endogenous Pyrogen
Authors: Davatelis George , Wolpe Stephen D. , Sherry Barbara , Dayer J.-M. , Chicheportiche Rachel , Cerami Anthony
Published: October 2006

Macrophage inflammatory protein-1 (MIP-1) produced a monophasic fever of rapid onset whose magnitude was equal to or greater than that of fevers produced with either recombinant human cachectin (or tumor necrosis factor) or recombinant human interleukin-1. However, in contrast to these two endogenous pyrogens, the fever induced by MIP-1 was not inhibited by the cyclooxygenase inhibitor ibuprofen. Thus, MIP-1 may participate in the febrile response that is not mediated through prostaglandin synthesis and clinically cannot be ablated by cyclooxygenase inhibitors.
Chromosome 17 Deletions and p53 Gene Mutations in Colorectal Carcinomas
Authors: Baker Suzanne J. , Fearon Eric R. , Nigro Janice M. , Hamilton Stanley R. , Preisinger Ann C. , Jessup J. Milburn , vanTuinen Peter , Ledbetter David H. , Barker David F. , Nakamura Yusuke , White Ray , Vogelstein Bert
Published: October 2006

Previous studies have demonstrated that allelic deletions of the short arm of chromosome 17 occur in over 75% of colorectal carcinomas. Twenty chromosome 17p markers were used to localize the common region of deletion in these tumors to a region contained within bands 17p12 to 17p13.3. This region contains the gene for the transformation-associated protein p53. Southern and Northern blot hybridization experiments provided no evidence for gross alterations of the p53 gene or surrounding sequences. As a more rigorous test of the possibility that p53 was a target of the deletions, the p53 coding regions from two tumors were analyzed; these two tumors, like most colorectal carcinomas, had allelic deletions of chromosome 17p and expressed considerable amounts of p53 messenger RNA from the remaining allele. The remaining p53 allele was mutated in both tumors, with an alanine substituted for valine at codon 143 of one tumor and a histidine substituted for arginine at codon 175 of the second tumor. Both mutations occurred in a highly conserved region of the p53 gene that was previously found to be mutated in murine p53 oncogenes. The data suggest that p53 gene mutations may be involved in colorectal neoplasia, perhaps through inactivation of a tumor suppressor function of the wild-type p53 gene.
Delay of Gratification in Children
Authors: Mischel Walter , Shoda Yuichi , Rodriguez Monica L.
Published: October 2006

To function effectively, individuals must voluntarily postpone immediate gratification and persist in goal-directed behavior for the sake of later outcomes. The present research program analyzed the nature of this type of future-oriented self-control and the psychological processes that underlie it. Enduring individual differences in self-control were found as early as the preschool years. Those 4-year-old children who delayed gratification longer in certain laboratory situations developed into more cognitively and socially competent adolescents, achieving higher scholastic performance and coping better with frustration and stress. Experiments in the same research program also identified specific cognitive and attentional processes that allow effective self-regulation early in the course of development. The experimental results, in turn, specified the particular types of preschool delay situations diagnostic for predicting aspects of cognitive and social competence later in life.
Electrospray Ionization for Mass Spectrometry of Large Biomolecules
Authors: Fenn John B. , Mann Matthias , Meng Chin Kai , Wong Shek Fu , Whitehouse Craig M.
Published: October 2006

Electrospray ionization has recently emerged as a powerful technique for producing intact ions in vacuo from large and complex species in solution. To an extent greater than has previously been possible with the more familiar "soft" ionization methods, this technique makes the power and elegance of mass spectrometric analysis applicable to the large and fragile polar molecules that play such vital roles in biological systems. The distinguishing features of electrospray spectra for large molecules are coherent sequences of peaks whose component ions are multiply charged, the ions of each peak differing by one charge from those of adjacent neighbors in the sequence. Spectra have been obtained for biopolymers including oligonucleotides and proteins, the latter having molecular weights up to 130,000, with as yet no evidence of an upper limit.
S Phase of the Cell Cycle
Authors: Laskey Ronald A. , Fairman Micaela P. , Blow J. Julian
Published: October 2006

In each cell cycle the complex structure of the chromosome must be replicated accurately. In the last few years there have been major advances in understanding eukaryotic chromosome replication. Patterns of replication origins have been mapped accurately in yeast chromosomes. Cellular replication proteins have been identified by fractionating cell extracts that replicate viral DNA templates in vitro. Cell-free systems that initiate eukaryotic DNA replication in vitro have demonstrated the importance of complex nuclear architecture in the control of DNA replication. Although the events of S phase were relatively neglected for many years, knowledge of DNA replication is now advancing rapidly in step with other phases of the cell cycle.
The Anticodon Contains a Major Element of the Identity of Arginine Transfer RNAs
Authors: Schulman LaDonne H. , Pelka Heike
Published: October 2006

The contribution of the anticodon to the discrimination between cognate and noncognate tRNAs by
Escherichia coli
Arg-tRNA synthetase has been investigated by in vitro synthesis and aminoacylation of elongator methionine tRNA (tRNA
m
Met
) mutants. Substitution of the Arg anticodon CCG for the Met anticodon CAU leads to a dramatic increase in Arg acceptance by tRNA
m
Met
. A nucleotide (A20) previously identified by others in the dihydrouridine loop of tRNA
Arg
s makes a smaller contribution to the conversion of tRNA
m
Met
identity from Met to Arg. The combined anticodon and dihydrouridine loop mutations yield a tRNA
m
Met
derivative that is aminoacylated with near-normal kinetics by the Arg-tRNA synthetase.
Neural Integration of Information Specifying Structure from Stereopsis and Motion
Authors: Nawrot Mark , Blake Randolph
Published: October 2006

When one views a two-dimensional parallel projection of dots on the surface of a rotating globe, the direction of rotation is ambiguous, and the perceived direction of rotation of the two-dimensional figure is unstable over time. Stability can be temporarily induced by adaptation to a three-dimensional globe with a direction of rotation unambiguously specified by stereo disparity; adaptation causes the two-dimensional figure to appear to rotate in the direction opposite that experienced during stereoscopic adaptation. This adaptation effect is selective for axis of rotation but is not shape-specific. It does depend on simultaneous stimulation by multiple depth planes defined by elements moving in different directions. Evidently information about stereopsis and information about structure from motion are integrated within a common neural site in the brain.
Switching of a Neuron from One Network to Another by Sensory-Induced Changes in Membrane Properties
Authors: Hooper Scott L. , Moulins Maurice
Published: October 2006

A neuron that is an integral member of the pyloric neural network of the lobster stomatogastric nervous system leaves this network and instead fires exclusively with another stomatogastric nervous system network, the cardiac sac network, whenever the cardiac sac network is active. This switch is associated with the neuron losing, in a long-lasting fashion, regenerative oscillatory membrane properties that underlie its participation in the pyloric network. Functional membership of neurons in central networks is thus not fixed, and long-lasting neuromodulatory influences, controlled at least in part by sensory inputs, can switch neurons from one network to another.
Scaling Body Support in Mammals: Limb Posture and Muscle Mechanics
Authors: Biewener Andrew A.
Published: October 2006

The scaling of bone and muscle geometry in mammals suggests that peak stresses (ratio of force to cross-sectional area) acting in these two support elements increase with increasing body size. Observations of stresses acting in the limb bones of different sized mammals during strenuous activity, however, indicate that peak bone stress is independent of size (maintaining a safety factor of between 2 and 4). It appears that similar peak bone stresses and muscle stresses in large and small mammals are achieved primarily by a size-dependent change in locomotor limb posture: small animals run with crouched postures, whereas larger species run more upright. By adopting an upright posture, large animals align their limbs more closely with the ground reaction force, substantially reducing the forces that their muscles must exert (proportional to body mass
0.74
) and hence, the forces that their bones must resist, to counteract joint moments. This change in limb posture to maintain locomotor stresses within safe limits, however, likely limits the maneuverability and accelerative capability of large animals.
Introduction of Human DNA into Mouse Eggs by Injection of Dissected Chromosome Fragments
Authors: Richa Jean , Lo Cecilia W.
Published: October 2006

A procedure has been developed for introducing exogenous DNA into mouse eggs by injection of chromosome fragments. Chromosome fragments were dissected from human metaphase spreads and microinjected into the pronuclei of fertilized mouse eggs. Many of the injected eggs subsequently exhibited normal pre- and postimplantation development. Embryos obtained from eggs injected with centromeric fragments retained human centromeric DNA as demonstrated by in situ hybridization analysis. From eggs injected with noncentromeric fragments, a mouse was obtained whose tail tissue exhibited the presence of human DNA. This procedure should facilitate incorporation of very large (more than 10 megabases) DNA fragments into cells and embryos without the need for cloned sequences.
Peptide Binding and Release by Proteins Implicated as Catalysts of Protein Assembly
Authors: Flynn Gregory C. , Chappell Thomas G. , Rothman James E.
Published: October 2006

Two members of the hsp70 family, termed hsc70 and BiP, have been implicated in promoting protein folding and assembly processes in the cytoplasm and the lumen of the endoplasmic reticulum, respectively. Short hydrophilic (8 to 25 residues) synthetic peptides have now been tested as possible mimics of polypeptide chain substrates to help define an enzymatic basis for these activities. Both BiP and hsc70 have specific peptide binding sites. Peptide binding elicits hydrolysis of adenosine triphosphate, with the subsequent release of bound peptide.
Spontaneous Vesicle Formation in Aqueous Mixtures of Single-Tailed Surfactants
Authors: Kaler Eric W. , Murthy A. Kamalakara , Rodriguez Beatriz E. , Zasadzinski Joseph A. N.
Published: October 2006

Spontaneous, single-walled, equilibrium vesicles can be prepared from aqueous mixtures of simple, commercially available, single-tailed cationic and anionic surfactants. Vesicle size, surface charge, or permeability can be readily adjusted by varying the ratio of anionic to cationic surfactant. Vesicle formation apparently results from the production of anion-cation surfactant pairs that then act as double-tailed zwitterionic surfactants. These vesicles are quite stable in comparison to conventional vesicles prepared by mechanical disruption of insoluble liquid crystalline dispersions.
Identification of Nuclear Receptors for VIP on a Human Colonic Adenocarcinoma Cell Line
Authors: Omary M. Bisher , Kagnoff Martin F.
Published: October 2006

Vasoactive intestinal peptide (VIP) is a neuropeptide with broad tissue distribution. Although its precise function is unknown, it is thought to exert its effect, at least in part, by interacting with cell surface receptors. Nuclear receptors for VIP have now been identified by specific binding of
125
I-labeled VIP to nuclei of a human colonic adenocarcinoma cell line (HT29) and by cross-linking of
125
I-labeled VIP to its receptor on intact nuclei. In contrast,
125
I-labeled transferrin shows only background binding to nuclei but significant binding to intact cells. Purity of the isolated nuclei was further substantiated by electron microscopy. The apparent molecular sizes of the VIP—cross-linked nuclear and cell surface receptors are similar but not identical.
Tat Protein from Human Immunodeficiency Virus Forms a Metal-Linked Dimer
Authors: Frankel Alan D. , Bredt David S. , Pabo Carl O.
Published: October 2006

Tat, the transactivating protein from HIV, forms a metal-linked dimer with metal ions bridging cysteine-rich regions from each monomer. This novel arrangement is distinct from the "zinc finger" domain observed in other eukaryotic regulatory proteins. Ultraviolet absorption spectra show that Tat binds two Zn
2+
or two Cd
2+
ions per monomer, and electrophoresis of the Tat-metal complexes demonstrates that the protein forms metal-linked dimers. Partial proteolysis and circular dichroism spectra suggest that metal binding has its primary effects in the cysteine-rich region and relatively little effect on the folding of other regions. These results suggest new directions for biological studies and new approaches to drug design.
Yeast HAP2 and HAP3: Transcriptional Activators in a Heteromeric Complex
Authors: Hahn Steven , Guarente Leonard
Published: October 2006

Transcription of the yeast
CYC1
gene (iso-1-cytochrome c) is regulated in part by the upstream activation site UAS2. Activity of UAS2 requires both the HAP2 and HAP3 activators, which bind to UAS2 in an interdependent manner. To distinguish whether these factors bound to UAS2 cooperatively or formed a complex in the absence of DNA, HAP2 and HAP3 were tagged by gene fusion to LexA and β-galactosidase, respectively, and purified through four chromatographic steps. The copurification of LexA-HAP2, HAP3 β-galactosidase, and UAS2 binding activity shows that HAP2 and HAP3 associate in the absence of DNA to form a multisubunit activation complex.
The Interplay Between Chemistry and Biology in the Design of Enzymatic Catalysts
Authors: Schultz P. G.
Published: October 2006

Chemists and biologists are focusing considerable effort on the development of efficient, highly selective catalysts for the synthesis or modification of complex molecules. Two approaches are described here, the generation of catalytic antibodies and hybrid enzymes, which exploit the binding and catalytic machinery of nature in catalyst design. Characterization of these systems is providing additional insight into the mechanisms of molecular recognition and catalysis which may, in turn, lead to the design of tailor-made catalysts for applications in chemistry, biology, and medicine.
Toxic DNA Damage by Hydrogen Peroxide Through the Fenton Reaction in Vivo and in Vitro
Authors: Imlay James A. , Chin Sherman M. , Linn Stuart
Published: October 2006

Exposure of
Escherichia coli
to low concentrations of hydrogen peroxide results in DNA damage that causes mutagenesis and kills the bacteria, whereas higher concentrations of peroxide reduce the amount of such damage. Earlier studies indicated that the direct DNA oxidant is a derivative of hydrogen peroxide whose formation is dependent on cell metabolism. The generation of this oxidant depends on the availability of both reducing equivalents and an iron species, which together mediate a Fenton reaction in which ferrous iron reduces hydrogen peroxide to a reactive radical. An in vitro Fenton system was established that generates DNA strand breaks and inactivates bacteriophage and that also reproduces the suppression of DNA damage by high concentrations of peroxide. The direct DNA oxidant both in vivo and in this in vitro system exhibits reactivity unlike that of a free hydroxyl radical and may instead be a ferryl radical.
Requirement for Glycine in Activation of NMDA-Receptors Expressed in
Xenopus
Oocytes
Authors: Kleckner Nancy W. , Dingledine Raymond
Published: October 2006

Receptors for
N
-methyl-D-aspartate (NMDA) are involved in many plastic and pathological processes in the brain. Glycine has been reported to potentiate NMDA responses in neurons and in
Xenopus
oocytes injected with rat brain messenger RNA. Glycine is now shown to be absolutely required for activation of NMDA receptors in oocytes. In voltage-clamped oocytes, neither perfusion nor rapid pressure application of NMDA onto messenger RNA-injected oocytes caused a distinct ionic current without added glycine. When glycine was added, however, NMDA evoked large inward currents. The concentration of glycine required to produce a half-maximal response was 670 nanomolar, and the glycine dose-response curve extrapolated to zero in the absence of glycine. Several analogs of glycine could substitute for glycine, among which D-serine and D-alanine were the most effective. The observation that D-amino acids are effective will be important in developing drugs targeted at the glycine site.
Coding of Two Sphingolipid Activator Proteins (SAP-1 and SAP-2) by Same Genetic Locus
Authors: O'Brien John S. , Kretz Keith A. , Dewji Nazneen , Wenger David A. , Esch Fred , Fluharty Arvan L.
Published: October 2006

Several complementary DNAs (cDNAs) coding for sphingolipid activator protein-2 (SAP-2) were isolated from a λgt-11 human hepatoma library by means of polyclonal antibodies. The nucleotide sequence of the largest cDNA was colinear with the derived amino acid sequence of SAP-2 and with the nucleotide sequence of the cDNA coding for the 70-kilodalton precursor of SAP-1 (SAP precursor cDNA). The coding sequence for mature SAP-2 was located 3′ to that coding for SAP-1 in the SAP precursor cDNA. Both SAP-1 and SAP-2 appeared to be derived by proteolytic processing from a common precursor that is coded by a genetic locus on human chromosome 10. Two other domains similar to SAP-1 and SAP-2 were also identified in SAP precursor protein. Each of the four domains was approximately 80 amino acid residues long, had nearly identical placement of cysteine residues, potential glycosylation sites, and proline residues. Each domain also contained internal amino acid sequences capable of forming amphipathic helices separated by helix breakers to give a cylindrical hydrophobic domain that is probably stabilized by disulfide bridges. Protein immunoblotting experiments indicated that SAP precursor protein (70 kilodaltons) as well as immunoreactive SAP-like proteins of intermediate sizes (65, 50, and 31 kilodaltons) are present in most human tissues.
The Effect of Histone Gene Deletions on Chromatin Structure in
Saccharomyces cerevisiae
Authors: Norris David , Dunn Barbara , Osley Mary Ann
Published: October 2006

As a way of studying nucleosome assembly and maintenance in
Saccharomyces cerevisiae
, mutants bearing deletions or duplications of the genes encoding histones H2A and H2B were analyzed. Previous genetic analysis had shown that only one of these mutants exhibited dramatic and pleiotropic phenotypes. This mutant was also the only one that contained disrupted chromatin, suggesting that the original phenotypes were attributable to alterations in chromosome structure. The chromatin disruption in the mutant, however, did not extend over the entire genome, but rather was localized to specific regions. Thus, while the arrangement of nucleosomes over the
HIS4
and
GAL1
genes, the telomeres, and the long terminal repeats (δ sequences) of Ty retrotransposons appeared essentially normal, nucleosomes over the
CYH2
and
UBI4
genes and the centromere of chromosome III were dramatically disrupted. The observation that the mutant exhibited localized chromatin disruptions implies that the assembly or maintenance of nucleosomes differs over different parts of the yeast genome.
Two Forms of Autosomal Chronic Granulomatous Disease Lack Distinct Neutrophil Cytosol Factors
Authors: Nunoi Hiroyuki , Rotrosen Daniel , Gallin John I. , Malech Harry L.
Published: October 2006

Chronic granulomatous diseases of childhood (CGD) are a group of disorders of phagocytic cell superoxide (O
2
⋅
-
) production (respiratory burst). Anion exchange chromatography separated from normal neutrophil cytosol a 47-kilodalton neutrophil cytosol factor, NCF-1, that restored activity to defective neutrophil cytosol from most patients with autosomally inherited CGD in a cell-free O
2
⋅
-
-generating system. A 65-kilodalton factor, NCF-2, restored activity to defective neutrophil cytosol from one patient with autosomal CGD. NCF-1, NCF-2, and a third cytosol fraction, NCF-3, were inactive alone or in pairs, but together replaced unfractionated cytosol in cell-free O
2
⋅
-
generation. Neutrophils deficient in NCF-1, but not NCF-2, did not phosphorylate the 47-kilodalton protein. It is proposed that NCF-1, NCF-2, and NCF-3 are essential for generation of O
2
⋅
-
by phagocytic cells and that genetic abnormalities of these cytosol components can result in the CGD phenotype.
Positron Emission Tomography: Human Brain Function and Biochemistry
Authors: Phelps Michael E. , Mazziotta John C.
Published: October 2006

Positron emission tomography (PET) is an analytical imaging technique that provides a way of making in vivo measurements of the anatomical distribution and rates of specific biochemical reactions. This ability of PET to measure and image dynamic biochemistry builds a bridge between the basic and clinical neurosciences founded on the commonality of the types of measurements made. Clinical findings with PET in humans are suggesting hypotheses that can be tested rigorously in the basic science laboratory.
Choline Acetyltransferase Activity in Striatum of Neonatal Rats Increased by Nerve Growth Factor
Authors: Mobley William C. , Rutkowski J. Lynn , Tennekoon Gihan I. , Buchanan Karen , Johnston Michael V.
Published: October 2006

Some neurodegenerative disorders may be caused by abnormal synthesis or utilization of trophic molecules required to support neuronal survival. A test of this hypothesis requires that trophic agents specific for the affected neurons be identified. Cholinergic neurons in the corpus striatum of neonatal rats were found to respond to intracerebroventricular administration of nerve growth factor with prominent, dose-dependent, selective increases in choline acetyltransferase activity. Cholinergic neurons in the basal forebrain also respond to nerve growth factor in this way. These actions of nerve growth factor may indicate its involvement in the normal function of forebrain cholinergic neurons as well as in neurodegenerative disorders involving such cells.
Transplantation of Fetal Hematopoietic Stem Cells in Utero: The Creation of Hematopoietic Chimeras
Authors: Flake Alan W. , Harrison Michael R. , Adzick N. Scott , Zanjani Esmail D.
Published: October 2006

Transplantation of normal, immature, fetal hematopoietic cells into a preimmune fetal recipient with a congenital hemoglobinopathy may allow partial reconstitution of normal hemoglobin production without the complications associated with postnatal bone marrow transplantation (immunosuppression and the occurrence of graft versus host disease). In order to test this hypothesis the naturally occurring polymorphism at the β-hemoglobin locus of the sheep was used as a marker for engraftment and hematopoietic chimerism. Intraperitoneal injection of allogeneic fetal stem cells into normal fetal lambs resulted in hematopoietic chimerism in three of four surviving recipients. This chimerism has been sustained for 6 months after birth and 9 months after engraftment, without evidence of graft versus host disease, and without the use of immunosuppressive therapy.
Isolation of a New Virus, HBLV, in Patients with Lymphoproliferative Disorders
Authors: Salahuddin S. Zaki , Ablashi Dharam V. , Markham Phillip D. , Josephs Steven F. , Sturzenegger Susi , Kaplan Mark , Halligan Gregory , Biberfeld Peter , Wong-Staal Flossie , Kramarsky Bernhard , Gallo Robert C.
Published: October 2006

A novel human B-lymphotropic virus (HBLV) was isolated from the peripheral blood leukocytes of six individuals: two HTLV-III seropositive patients from the United States (one with AIDS-related lymphoma and one with dermatopathic lymphadenopathy), three HTLV-III seronegative patients from the United States (one with angioimmunoblastic lymphadenopathy, one with cutaneous T-cell lymphoma, and one with immunoblastic lymphoma), and one HTLV-III seronegative patient with acute lymphocytic leukemia from Jamaica. All six isolates were closely related by antigenic analysis, and sera from all six virus-positive patients reacted immunologically with each virus isolate. In contrast, only four sera from 220 randomly selected healthy donors and none from 12 AIDS patients without associated lymphoma were seropositive. The virus selectively infected freshly isolated human B cells and converted them into large, refractile mono- or binucleated cells with nuclear and cytoplasmic inclusion bodies. HBLV is morphologically similar to viruses of the herpesvirus family but is readily distinguishable from the known human and nonhuman primate herpesviruses by host range, in vitro biological effects, and antigenic features.
Zinc Selectively Blocks the Action of
N
-Methyl-D-Aspartate on Cortical Neurons
Authors: Peters S. , Koh J. , Choi D. W.
Published: October 2006

Large amounts of zinc are present in synaptic vesicles of mammalian central excitatory boutons and may be released during synaptic activity, but the functional significance of the metal for excitatory neurotransmission is currently unknown. Zinc (10 to 1000 micromolar) was found to have little intrinsic membrane effect on cortical neurons, but invariably produced a zinc concentration-dependent, rapid-onset, reversible, and selective attenuation of the membrane responses to
N
-methyl-D-aspartate, homocysteate, or quinolinate. In contrast, zinc generally potentiated the membrane responses to quisqualate or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and often did not affect the response to kainate. Zinc also attenuated
N
-methyl-D-aspartate receptor-mediated neurotoxicity but not quisqualate or kainate neurotoxicity. The ability of zinc to specifically modulate postsynaptic neuronal responses to excitatory amino acid transmitters, reducing
N
-methyl-D-aspartate receptor-mediated excitation while often increasing quisqualate receptor-mediated excitation, is proposed to underlie its normal function at central excitatory synapses and furthermore could be relevant to neuronal cell loss in certain disease states.
Adrenal Medulla Grafts Enhance Recovery of Striatal Dopaminergic Fibers
Authors: Bohn Martha C. , Cupit Lisa , Marciano Frederick , Gash Don M.
Published: October 2006

The drug, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), depletes striatal dopamine levels in primates and certain rodents, including mice, and produces parkinsonian-like symptoms in humans and nonhuman primates. To investigate the consequences of grafting adrenal medullary tissue into the brain of a rodent model of Parkinson's disease, a piece of adult mouse adrenal medulla was grafted unilaterally into mouse striatum 1 week after MPTP treatment. This MPTP treatment resulted in the virtual disappearance of tyrosine hydroxylase-immunoreactive fibers and severely depleted striatal dopamine levels. At 2, 4, and 6 weeks after grafting, dense tyrosine hydroxylase-immunoreactive fibers were observed in the grafted striatum, while only sparse fibers were seen in the contralateral striatum. In all cases, tyrosine hydroxylase-immunoreactive fibers appeared to be from the host rather than from the grafts, which survived poorly. These observations suggest that, in mice, adrenal medullary grafts exert a neurotrophic action in the host brain to enhance recovery of dopaminergic neurons. This effect may be relevant to the symptomatic recovery in Parkinson's disease patients who have received adrenal medullary grafts.
Synthetic Peptide Immunoassay Distinguishes HIV Type 1 and HIV Type 2 Infections
Authors: Gnann John W. , McCormick Joseph B. , Mitchell Sheila , Nelson Jay A. , Oldstone Michael B. A.
Published: October 2006

Efforts to solve the epidemiologic puzzle of AIDS in Africa are complicated by the presence of multiple human retroviruses. Simple serologic tests that unambiguously distinguish among infections by these retroviruses are essential. To that end, a partially conserved immunoreactive epitope was identified in the transmembrane glycoproteins of human immunodeficiency viruses (HIV) types 1 and 2. Synthetic peptides derived from these conserved domains were used in sensitive and specific immunoassays that detect antibodies in sera from patients infected with HIV-1 or HIV-2. By making single amino acid substitutions in the HIV-1 peptide, it was possible to demonstrate HIV-1 strain-specific antibody responses to this epitope. Such custom-designed peptides synthesized from this domain are likely to detect newly discovered HIV types, define infection with specific HIV strains, and allow detection of group-common antibodies.
Clonal Analysis of Human Colorectal Tumors
Authors: Fearon Eric R. , Hamilton Stanley R. , Vogelstein Bert
Published: October 2006

The clonal composition of human colorectal tumors was studied by means of restriction fragment length polymorphisms (RFLPs). First, X-linked RFLPs were used to examine the pattern of X chromosome inactivation in colorectal tumors of females. All 50 tumors examined showed monoclonal patterns of X chromosome inactivation; these tumors included 20 carcinomas as well as 30 adenomas of either familial or spontaneous type. Second, RFLPs of autosomes were used as clonal markers to detect the somatic loss or gain of specific chromosomal sequences in colorectal tumors. Among other changes, it was found that somatic loss of chromosome 17p sequences occurred in over 75 percent of the carcinomas examined, but such loss was rare in adenomas. These data support a monoclonal origin for colorectal neoplasms, and suggest that a gene on the short arm of chromosome 17 may be associated with progression from the benign to the malignant state.
Molecular Cloning of a Feline Leukemia Virus That Induces Fatal Immunodeficiency Disease in Cats
Authors: Overbaugh Julie , Donahue Peter R. , Quackenbush Sandra L. , Hoover Edward A. , Mullins James I.
Published: October 2006

A replication-defective variant of feline leukemia virus was molecularly cloned directly from infected tissue and found to induce a rapid and fatal immunodeficiency syndrome in cats. Studies with cloned viruses also showed that subtle mutational changes would convert a minimally pathogenic virus into one that would induce an acute form of immunodeficiency. The data suggest that acutely pathogenic viruses may be selected against by current methods for isolation of the human and simian immunodeficiency viruses.
Cryopreservation, Culture, and Transplantation of Human Fetal Mesencephalic Tissue into Monkeys
Authors: Redmond D. E. , Naftolin F. , Collier T. J. , Leranth C. , Robbins R. J. , Sladek C. D. , Roth R. H. , Sladek J. R.
Published: October 2006

Studies in animals suggest that fetal neural grafts might restore lost neurological function in Parkinson's disease. In monkeys, such grafts survive for many months and reverse signs of parkinsonism, without attendant graft rejection. The successful and reliable application of a similar transplantation procedure to human patients, however, will require neural tissue obtained from human fetal cadavers, with demonstrated cellular identity, viability, and biological safety. In this report, human fetal neural tissue was successfully grafted into the brains of monkeys. Neural tissue was collected from human fetal cadavers after 9 to 12 weeks of gestation and cryopreserved in liquid nitrogen. Viability after up to 2 months of storage was demonstrated by cell culture and by transplantation into monkeys. Cryopreservation and storage of human fetal neural tissue would allow formation of a tissue bank. The stored cells could then be specifically tested to assure their cellular identity, viability, and bacteriological and virological safety before clinical use. The capacity to collect and maintain viable human fetal neural tissue would also facilitate research efforts to understand the development and function of the human brain and provide opportunities to study neurological diseases.
Increased Expression of DNA Cointroduced with Nuclear Protein in Adult Rat Liver
Authors: Kaneda Yasufumi , Iwai Kunimitsu , Uchida Tsuyoshi
Published: October 2006

DNA and nuclear proteins were transferred into cells simultaneously at more than 95% efficiency by means of vesicle complexes. The DNA was rapidly transported into the nuclei of cultured cells, and its expression reached a maximum within 6 to 8 hours after its introduction. Moreover, when the plasmid DNA and nuclear protein were cointroduced into nondividing cells in rat liver by injection into the portal veins of adult rats, the plasmid DNA was carried into liver cell nuclei efficiently by nuclear protein. The expression of the DNA in adult rat liver, on introduction of the DNA with nuclear protein, was more than five times as great as with nonnuclear protein.
Specific Recognition of Cruciform DNA by Nuclear Protein HMG1
Authors: Bianchi Marco E. , Beltrame Monica , Paonessa Giacomo
Published: October 2006

Cruciform DNA, a non-double helix form of DNA, can be generated as an intermediate in genetic recombination as well as from palindromic sequences under the effect of supercoiling. Eukaryotic cells are equipped with a DNA-binding protein that selectively recognizes cruciform DNA. Biochemical and immunological data showed that this protein is HMG1, an evolutionarily conserved, essential, and abundant component of the nucleus. The interaction with a ubiquitous protein points to a critical role for cruciform DNA conformations.
Direct Measurements of Sliding Between Outer Doublet Microtubules in Swimming Sperm Flagella
Authors: Brokaw Charles J.
Published: October 2006

The relative motion of 40-nanometer gold beads bound to the exposed outer doublet microtubules of demembranated sea urchin sperm flagella has been observed and photographed during adenosine triphosphate (ATP)-reactivated swimming. This direct demonstration and measure of sliding displacements between outer doublet microtubules in actively bending flagella verifies the original sliding microtubule model for ciliary bending that was established by electron microscopy of fixed cilia and provides a new, functional measure for the diameter of the flagellar axoneme of 132 ± 8 nanometers.
Control of Directionality in Lambda Site Specific Recombination
Authors: Bushman Wade , Thompson John F. , Vargas Lina , Landy Arthur
Published: October 2006

The simple relation between the substrates and products of site-specific recombination raises questions about the control of directionality often observed in this class of DNA transactions. For bacteriophage lambda, viral integration and excision proceed by discrete pathways, and DNA substrates with the intrinsic property of recombining in only one direction can be constructed. These pathways display an asymmetric reliance on a complex array of protein binding sites, and they respond differently to changes in the concentrations of the relevant proteins. The
Escherichia coli
protein integration host factor (IHF) differentially affects integrative and excisive recombination, thereby influencing directionality. A four- to eightfold increase in intracellular IHF coincides with the transition from exponential to stationary phase; this provides a mechanism for growth phase-dependent regulation of recombination that makes the cellular physiology an intrinsic part of the recombination reaction.
Selectivity of Intracellular Proteolysis: Protein Substrates Activate the ATP-Dependent Protease (La)
Authors: Waxman Lloyd , Goldberg Alfred L.
Published: October 2006

A critical enzyme in protein breakdown in
Escherichia coli
is protease La (the
lon
gene product), which hydrolyzes proteins and adenosine triphosphate (ATP) in a coupled process. The mechanism of this process was studied with fluorogenic tripeptides. Although proteins and peptides are degraded at the same active site, protein substrates enhance the ability of the enzyme to degrade these peptides two- to tenfold. Proteins that are not substrates had little or no effect. Thus, protein substrates must bind to protease La at two sites, the active site and an allosteric site whose occupancy enhances proteolytic activity. This effect did not require that the proteins themselves be degraded. Proteins could induce peptide breakdown even in the absence of ATP, and proteins and ATP had additive effects in stimulating peptidase activity. A multistep cyclical mechanism is proposed in which the binding of the substrate and ATP activates the protease. The enzyme can then cleave a peptide bond, but is inactivated through ATP hydrolysis. Such a mechanism may help account for the selectivity of protein breakdown and prevent inappropriate or excessive proteolysis in vivo.
The
trans
Golgi Network: Sorting at the Exit Site of the Golgi Complex
Authors: Griffiths Gareth , Simons Kai
Published: October 2006

The Golgi complex is a series of membrane compartments through which proteins destined for the plasma membrane, secretory vesicles, and lysosomes move sequentially. A model is proposed whereby these three different classes of proteins are sorted into different vesicles in the last Golgi compartment, the
trans
Golgi network. This compartment corresponds to a tubular reticulum on the
trans
side of the Golgi stack, previously called Golgi endoplasmic reticulum lysosomes (GERL).
α
2
-Antiplasmin Enschede: Alanine Insertion and Abolition of Plasmin Inhibitory Activity
Authors: Holmes W. E. , Lijnen H. R. , Nelles L. , Kluft C. , Nieuwenhuis H. K. , Rijken D. C. , Collen D.
Published: October 2006

An abnormal α2-antiplasmin that is associated with a serious bleeding tendency has been found in a Dutch family and is referred to as α2-antiplasmin Enschede. This abnormal α2-antiplasmin is converted from an inhibitor of plasmin to a substrate. The molecular defect of α2-antiplasmin Enschede, as revealed by sequencing of cloned genomic DNA fragments, consists of an alanine insertion near the active site region of the molecule. Substitution of this fragment into complementary DNA for a wild-type α2-antiplasmin yields a translation product with physical and functional properties typical of the abnormal α2-antiplasmin Enschede. The naturally occurring mutant may serve as a model for investigating the structures that determine the properties of an inhibitor versus those of a substrate in serine protease inhibitors.
Immunotherapy of the Nonobese Diabetic Mouse: Treatment with an Antibody to T-Helper Lymphocytes
Authors: Shizuru Judith A. , Taylor-Edwards Cariel , Banks Beth Ann , Gregory Anita K. , Fathman C. Garrison
Published: October 2006

Spontaneous diabetes mellitus was blocked in nonobese diabetic mice by treatment with a monoclonal antibody against the L3T4 determinant present on the surface of T-helper lymphocytes. Sustained treatment with the monoclonal antibody led to cessation of the lymphocytic infiltration associated with the destruction of the insulin-producing β cells. Moreover, the mice remained normoglycemic after the antibody therapy was stopped. These studies indicate that immunotherapy with monoclonal antibodies to the lymphocyte subset may not only halt the progression of diabetes, but may lead to long-term reversal of the disease after therapy has ended.
cDNA Expression Cloning of the IL-1 Receptor, a Member of the Immunoglobulin Superfamily
Authors: Sims John E. , March Caril J. , Cosman David , Widmer Michael B. , MacDonald H. Robson , McMahan Catherine J. , Grubin Catherine E. , Wignall Janis M. , Jackson Jana L. , Call Susan M. , Friend Della , Alpert Alan R. , Gillis Steven , Urdal David L. , Dower Steven K.
Published: October 2006

Interleukin-1 alpha and -1 beta (IL-1α and IL-1β) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis. A direct expression strategy was used to clone the receptor for IL-1 from mouse T cells. The product of the cloned complementary DNA binds both IL-1α and IL-1β in a manner indistinguishable from that of the native T cell IL-1 receptor. The extracellular, IL-1 binding portion of the receptor is 319 amino acids in length and is composed of three immunoglobulin-like domains. The cytoplasmic portion of the receptor is 217 amino acids long.
Synthetic CD4 Peptide Derivatives That Inhibit HIV Infection and Cytopathicity
Authors: Lifson Jeffrey D. , Hwang Kou M. , Nara Peter L. , Fraser Blair , Padgett Mary , Dunlop Nancy M. , Eiden Lee E.
Published: October 2006

Synthetic peptide segments of the CD4 molecule were tested for their ability to inhibit infection of CD4
+
cells by the human immunodeficiency virus (HIV) and to inhibit HIV-induced cell fusion. A peptide mixture composed of CD4(76-94), and synthesis side products, blocked HIV-induced cell fusion at a nominal concentration of 125 micromolar. Upon high-performance liquid chromatography, the antisyncytial activity of the peptide mixture was found not in the fraction containing the peptide CD4(76-94) itself, but in a side fraction containing derivatized peptide products generated in the automated synthesis. Derivatized deletion and substitution peptides in the region CD4(76-94) were used to demonstrate sequence specificity, a requirement for benzyl derivatization, and a core seven-residue fragment required for antisyncytial activity. A partially purified
S
-benzyl-CD4(83-94) peptide mixture inhibited HIV-induced cell fusion at a nominal concentration of ≤32 micromolar. Derivatized CD4 peptides blocked cell fusion induced by several HIV isolates and by the simian immunodeficiency virus, SIV, and blocked infection in vitro by four HIV-1 isolates with widely variant envelope gene sequences. Purified CD4(83-94) dibenzylated at cysteine 86 and glutamate 87 possessed antisyncytial activity at 125 micromolar. Derivatization may specifically alter the conformation of CD4 holoreceptor peptide fragments, increasing their antiviral efficacy.