bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature and Sperm Incorporation in Polyploid Salamanders
Authors: Bogart James P. , Elinson Richard P. , Licht Lawrence E.
Published: October 2006

Although most animals reproduce sexually, a number of all-female groups exist. Triploid hybrid salamanders appear to maintain themselves by using a male's sperm to activate their eggs, after which the sperm nucleus is eliminated (gynogenesis). The incidence of sperm nuclear incorporation in eggs of these salamanders depends on temperature. Triploid offspring derived gynogenetically are more frequent at lower temperature, whereas tetraploid offspring derived sexually are far more frequent at higher temperatures. Temperature-dependent variability in sperm nuclear incorporation helps explain the variability in reproductive modes reported for hybrid salamanders.
Cell Cycle-Dependent Regulation of Phosphorylation of the Human Retinoblastoma Gene Product
Authors: Mihara Koichiro , Cao Xiang-Rong , Yen Andrew , Chandler Suzanne , Driscoll Barbara , Murphree A. Linn , T'Ang Anne , Fung Yuen-Kai
Published: October 2006

The human retinoblastoma gene (
RB1
) encodes a protein (Rb) of 105 kilodaltons that can be phosphorylated. Analysis of Rb metabolism has shown that the protein has a half-life of more than 10 hours and is synthesized at all phases of the cell cycle. Newly synthesized Rb is not extensively phosphorylated (it is "underphosphorylated") in cells in the G
0
and G
1
phases but is phosphorylated at multiple sites at the G
1
/S boundary and in S phase. HL-60 cells that were induced to terminally differentiate by various chemicals lost their ability to phosphorylate newly synthesized Rb at multiple sites when cell growth was arrested. These findings suggest that underphosphorylated Rb may restrict cell proliferation.
Effect of Pressure on the Composition of the Lower Mantle End Member Fe
x
O
Authors: McCammon Catherine
Published: October 2006

The composition limits of Fe

x

O are sensitive to both pressure and temperature. Earlier studies have shown that Fe

x

O becomes highly nonstoichiometric when in equilibrium with metallic iron above 10 gigapascals, which is difficult to reconcile with available thermodynamic data. Experiments with a uniaxial split-sphere apparatus demonstrate that the iron content of Fe

x

O increases continuously at high pressure in excellent agreement with quantitative models and suggest that there is a discontinuity in the elastic properties of Fe

x

O above
x
= 0.95. On the basis of these results, it is inferred that the Earth's present lower mantle is not in equilibrium with metallic iron.
Metastability of Superconducting Compounds in the Y-Ba-Cu-O System
Authors: Brosha Eric L. , Davies Peter K. , Garzon Fernando H. , Raistrick Ian D.
Published: October 2006

Precision isothermal solution calorimetry was used to determine the standard-state enthalpy of formation of a number of phases in the Y-Ba-Cu-O system. An analysis of the data indicates that YBa
2
Cu
4
O
8
is thermodynamically metastable under ambient conditions. Taken together with the results from previous investigations, these data show that all of the superconducting compounds in the Y-Ba-Cu-O system are thermodynamically metastable at low temperatures.
Structure of Langmuir-Blodgett Films of Disk-Shaped Molecules Determined by Atomic Force Microscopy
Authors: Josefowicz Jack Y. , Maliszewskyj Nicholas C. , Idziak Stefan H. J. , Heiney Paul A. , McCauley John P. , Smith Amos B.
Published: October 2006

Monolayer Langmuir-Blodgett films of a discotic mesogen have been studied with atomic force microscopy (AFM). These measurements confirm the "edge on" arrangement for the disk-shaped molecules suggested by surface pressure—area isotherms and show that the molecules form columns that are separated by 17.7 angstroms ± 10 percent. Column alignment is found to be predominantly along the film deposition direction, with an angular spread of 35°. The AFM images also show that the mean disk separation within the columns is 5.1 ± 1.3 angstroms, in good agreement with x-ray diffraction (XRD) results. Room-temperature XRD measurements on bulk samples of the same material indicate a disordered-hexagonal liquid crystalline mesophase, with a column-to-column spacing of 19.9 ± 0.2 angstroms.
Banded Surface Flow Maintained by Convection in a Model of the Rapidly Rotating Giant Planets
Authors: Sun Zi-Ping , Schubert Gerald , Glatzmaier Gary A.
Published: October 2006

In three-dimensional numerical simulations of a rapidly rotating Boussinesq fluid shell, thermally driven convection in the form of columns parallel to the rotation axis generates an alternately directed mean zonal flow with a cylindrical structure. The mean structure at the outer spherical surface consists of a broad eastward flow at the equator and alternating bands of westward and eastward flows at higher latitudes in both hemispheres. The banded structure persists even though the underlying convective motions are time-dependent. These results, although still far from the actual motions seen on Jupiter and Saturn, provide support for theoretical suggestions that thermal convection can account for the remarkable banded flow structures on these planets.
X-ray Tomographic Study of Chemical Vapor Infiltration Processing of Ceramic Composites
Authors: Kinney J. H. , Breunig T. M. , Starr T. L. , Haupt D. , Nichols M. C. , Stock S. R. , Butts M. D. , Saroyan R. A.
Published: October 2006

The fabrication of improved ceramic-matrix composites will require a better understanding of processing variables and how they control the development of the composite microstructure. Noninvasive, high-resolution methods of x-ray tomography have been used to measure the growth of silicon carbide in a woven Nicalon-fiber composite during chemical vapor infiltration. The high spatial resolution allows one to measure the densification within individual fiber tows and to follow the closure of macroscopic pores in situ. The experiments provide a direct test of a recently proposed model that describes how the surface area available for matrix deposition changes during infiltration. The measurements indicate that this surface area is independent of the fiber architecture and location within the preform and is dominated by large-scale macroporosity during the final stages of composite consolidation. The measured surface areas are in good agreement with the theoretical model.
Stratospheric Chlorine Injection by Volcanic Eruptions: HCl Scavenging and Implications for Ozone
Authors: Tabazadeh A. , Turco R. P.
Published: October 2006

Because the output of volatile chlorine during a major volcanic event can greatly exceed the annual anthropogenic emissions of chlorine to the atmosphere, the fate of volcanic chlorine must be known. Although numerous observations have shown that volcanoes do not significantly contribute to the stratospheric chlorine burden, no quantitative explanation has been published. Hydrogen chloride (HCl) scavenging processes during the early phases of a volcanic eruption are discussed. A plume dynamics and thermodynamics model is used to show that HCl removal in condensed supercooled water can reduce HCl vapor concentrations by up to four orders of magnitude, preventing substantial stratospheric chlorine injection.
Atmosphere-Surface Exchange Measurements
Authors: Dabberdt W. F. , Lenschow D. H. , Horst T. W. , Zimmerman P. R. , Oncley S. P. , Delany A. C.
Published: October 2006

The exchange of various trace species and energy at the earth's surface plays an important role in climate, ecology, and human health and welfare. Surface exchange measurements can be difficult to obtain yet are important to understand physical processes, assess environmental and global change impacts, and develop robust parameterizations of atmospheric processes. The physics and turbulent structure of the atmospheric boundary layer are reviewed as they contribute to dry surface exchange rates (fluxes). Micrometeorological, budget, and enclosure techniques used to measure or estimate surface fluxes are described, along with their respective advantages and limitations. Various measurement issues (such as site characteristics, sampling considerations, sensor attributes, and flow distortion) impact on the ability to obtain representative surface-based and airborne flux data.
A Picture of the Moon's Atmosphere
Authors: Flynn Brian , Mendillo Michael
Published: October 2006

Atomic sodium is a useful tracer of the tenuous lunar atmosphere because of its high efficiency in scattering sunlight at the D
1
(5896 angstroms) and D
2
(5890 angstroms) wavelengths. In 1988, Earth-based instruments revealed the presence of sodium at a density of less than 50 atoms per cubic centimeter at lunar altitudes below 100 kilometers. Telescopic observations that are made with a coronograph technique to block out the disk of the moon allow a true picture of the circumlunar atmosphere to be obtained and show the presence of sodium out to a distance of several lunar radii. The distribution of sodium has a solar zenith angle dependence, suggesting that most of the sodium that reaches great altitudes is liberated from the moon's surface by solar photons (by heating or sputtering) or by solar wind impact, in contrast to a source driven by uniform micrometeor bombardment.
A Solid Sulfur Cathode for Aqueous Batteries
Authors: Peramunage Dharmasena , Licht Stuart
Published: October 2006

Because of its high resistivity and subsequent low electroactivity, sulfur is not normally considered a room-temperature battery cathode. An elemental sulfur cathode has been made with a measured capacity of over 900 ampere⋅hours per kilogram, more than 90 percent of the theoretical storage capacity of solid sulfur at room temperature, accessed by means of a lightweight, highly conductive, aqueous polysulfide interface through the electrocatalyzed reaction S + H
2
O + 2e
-
→ HS
-
+ OH
-
. This solid sulfur cathode was first used in a battery with an aluminum anode for an overall discharge reaction 2Al + 3S + 3OH
-
+ 3H
2
O → 2Al(OH)
3
+ 3HS
-
, giving a cell potential of 1.3 volts. The theoretical specific energy of the aluminum-sulfur battery (based on potassium salts) is 910 watt⋅hours per kilogram with an experimental specific energy of up to 220 watt⋅hours per kilogram.
A 5000-Year Record of Extreme Floods and Climate Change in the Southwestern United States
Authors: Ely Lisa L. , Enzel Yehouda , Baker Victor R. , Cayan Daniel R.
Published: October 2006

A 5000-year regional paleoflood chronology, based on flood deposits from 19 rivers in Arizona and Utah, reveals that the largest floods in the region cluster into distinct time intervals that coincide with periods of cool, moist climate and frequent El Niño events. The floods were most numerous from 4800 to 3600 years before present (B.P.), around 1000 years B.P., and after 500 years B.P., but decreased markedly from 3600 to 2200 and 800 to 600 years B.P. Analogous modern floods are associated with a specific set of anomalous atmospheric circulation conditions that were probably more prevalent during past flood epochs.
Scale Transformation of Magnetic "Bubble" Arrays: Coupling of Topological Disorder and Polydispersity
Authors: Seul M. , Murray C. A.
Published: October 2006

The evolution of disorder in response to period adaptation in a hexagonal magnetic bubble array is shown to arise from the proliferation of dislocations and to proceed by means of intermediate states of steadily decreasing hexatic order to an amorphous final state. Remarkably, each dislocation core imposes a size adjustment on bubbles decorating its constituent pair of five- and sevenfold coordinated sites. Topological disorder thus induces intrinsic polydispersity and converts the initially unimodal size distribution into a trimodal one. This intimate interplay between geometry and topology provides an explicit mechanism by which structural disorder arises as a result of frustration.
Evidence Suggesting Superconductivity at 250 K in a Sequentially Deposited Cuprate Film
Authors: Laguës Michel , Xie Xiao Ming , Tebbji Hassan , Xu Xiang Zhen , Mairet Vincent , Hatterer Christophe , Beuran Cristian F. , Deville-Cavellin Catherine
Published: October 2006

An artificial cuprate compound belonging to the BiSrCaCuO family with eight adjacent CuO
2
layers in each building block was deposited on a single crystal of SrTiO
3
by sequentially imposed layer epitaxy. This compound undergoes a five order of magnitude resistivity drop with an onset near 280 kelvin and an offset at 250 kelvin. It exhibits a diamagnetic variation of susceptibility and magnetization below 290 kelvin. Additional observed features, such as strongly nonlinear conductivity, suggests superconductivity as a plausible explanation of the properties of this compound.
Evidence of the Growth Plate and the Growth of Long Bones in Juvenile Dinosaurs
Authors: Barreto Claudia , Albrecht Ralph M. , Bjorling Dale E. , Horner John R. , Wilsman Norman J.
Published: October 2006

Histological and ultrastructural evaluation of the ends of long bones of juvenile dinosaurs from the Upper Cretaceous Two Medicine Formation of Montana revealed the preservation of growth plates. Growth plates are discs of cartilage present near the ends of growing long bones that generate bone elongation. Comparison of the fossils with modern taxa demonstrated homology of the growth plate in birds and dinosaurs. The presence of an avian-type growth plate in dinosaurs adds a shared derived anatomical character corroborating inclusion of birds within the Dinosauria. Additionally, possession of a growth plate, which in birds is capable of producing rapid determinate long bone growth, implies that an avian developmental pattern may have been present in these dinosaurs.
Receptor-Mediated Drug Delivery to Macrophages in Chemotherapy of Leishmaniasis
Authors: Mukhopadhyay Amitabha , Chaudhuri Gautam , Arora Sunil K. , Sehgal Shobha , Basu Sandip K.
Published: October 2006

Methotrexate coupled to maleylated bovine serum albumin was taken up efficiently through the "scavenger" receptors present on macrophages and led to selective killing of intracellular
Leishmania mexicana amazonensis
amastigotes in cultured hamster peritoneal macrophages. The drug conjugate was nearly 100 times as effective as free methotrexate in eliminating the intracellular parasites. Furthermore, in a model of experimental cutaneous leishmaniasis in hamsters, the drug conjugate brought about more than 90% reduction in the size of footpad lesions within 11 days. In contrast, the free drug at a similar concentration did not significantly affect lesion size. These studies demonstrate the potential of receptor-mediated drug delivery in the therapy of macrophage-associated diseases.
Interleukin-2 Receptor β Chain Gene: Generation of Three Receptor Forms by Cloned Human α and β Chain cDNA's
Authors: Hatakeyama Masanori , Tsudo Mitsuru , Minamoto Seijiro , Kono Takeshi , Doi Takeshi , Miyata Takashi , Miyasaka Masayuki , Taniguchi Tadatsugu
Published: October 2006

Interleukin-2 (IL-2) binds to two distinct receptor molecules, the IL-2 receptor α (IL-2Rα, p55) chain and the newly identified IL-2 receptor β (IL-2Rβ, p70-75) chain. The cDNA encoding the human IL-2Rβ chain has now been isolated. The overall primary structure of the IL-2Rβ chain shows no apparent homology to other known receptors. Unlike the IL-2Rα chain, the IL-2Rβ chain has a large cytoplasmic region in which a functional domain (or domains) mediating an intracellular signal transduction pathway (or pathways) may be embodied. The cDNA-encoded β chain binds and internalizes IL-2 when expressed on T lymphoid cells but not fibroblast cells. Furthermore, the cDNA gives rise to the generation of high-affinity IL-2 receptor when co-expressed with the IL-2Rα chain cDNA.
Cocaine Receptors on Dopamine Transporters Are Related to Self-Administration of Cocaine
Authors: Ritz Mary C. , Lamb R. J.. , Goldberg Steven R. , Kuhar Michael J.
Published: October 2006

Although cocaine binds to several sites in the brain, the biochemical receptor mechanism or mechanisms associated with its dependence producing properties are unknown. It is shown here that the potencies of cocaine-like drugs in self-administration studies correlate with their potencies in inhibiting [
3
H]mazindol binding to the dopamine transporters in the rat striatum, but not with their potencies in binding to a large number of other presynaptic and postsynaptic binding sites. Thus, the cocaine receptor related to substance abuse is proposed to be the one associated with dopamine uptake inhibition.
Physiological Role of Silent Receptors of Atrial Natriuretic Factor
Authors: Maack Thomas , Suzuki Muneya , Almeida Fernando A. , Nussenzveig D. , Scarborough Robert M. , McEnroe Glenn A. , Lewicki John A.
Published: October 2006

A ring-deleted analog of atrial natriuretic factor—des[Gln
18
, Ser
19
, Gly
20
, Leu
21
, Gly
22
] ANF
4-23
-NH
2
(C-ANF
4-23
)—binds with high affinity to approximately 99% of ANF receptors in the isolated perfused rat kidney. In this preparation, C-ANF
4-23
is devoid of detectable renal effects and does not antagonize any of the known renal hemodynamic and natriuretic actions of biologically active ANF
1-28
. In contrast, both C-ANF
4-23
and ANF
1-28
increase sodium excretion and decrease blood pressure in intact anesthetized rats. This apparent contradiction is resolved by the finding that the ring-deleted analog markedly increases plasma levels of endogenous immunoreactive ANF in the rat. The results show that the majority of the renal receptors of ANF are biologically silent. This new class of receptors may serve as specific peripheral storage-clearance binding sites, acting as a hormonal buffer system to modulate plasma levels of ANF.
Monocyte-Derived Human B-Cell Growth Factor Identified as Interferon-β
2
(BSF-2, IL-6)
Authors: Tosato Giovanna , Seamon Kenneth B. , Goldman Neil D. , Sehgal Pravinkumar B. , May Lester T. , Washington Glennelle C. , Jones Karen D. , Pike Sandra E.
Published: October 2006

Soluble products of either Epstein-Barr virus (EBV)-infected B cells or activated monocytes promote the proliferation of EBV-infected B cells and permit their growth at low cell densities. This suggests that growth factors are important for B-cell immortalization by EBV. In this study, a monocyte-derived factor that promotes the growth of EBV-infected B cells was purified and identified as interferon-β
2
(IFN-β
2
), which is also known as 26-kilodalton protein, B-cell differentiation factor (BSF-2), and interleukin-6 (IL-6). The purified protein has a specific activity of approximately 4 β 10
7
units per milligram of protein in assays of B-cell growth. Thus, IFN-β
2
/BSF-2 is a B-cell growth factor that promotes the proliferation of human B cells infected with EBV.
The Elastin Receptor: A Galactoside-Binding Protein
Authors: Hinek Aleksander , Wrenn David S. , Mecham Robert P. , Barondes Samuel H.
Published: October 2006

The elastin receptor complex contains a component of 67 kilodaltons that binds to a glycoconjugate affinity column containing β-galactoside residues and is eluted from this column with lactose. This protein component is also released from the surface of cultured chondroblasts by incubation with lactose, and its association with immobilized elastin is inhibited by lactose. Since lactose also blocks elastic fiber formation by cultured chondroblasts, the galactoside-binding property of the elastin receptor is implicated in this process.
An Origin Unwinding Activity Regulates Initiation of DNA Replication During Mammalian Cell Cycle
Authors: Roberts James M. , D'Urso Gennaro
Published: October 2006

An in vitro assay was developed to study the positive factors that regulate the onset of DNA replication during the mammalian cell cycle. Extracts prepared from cells at defined positions in the cell cycle were used to examine the replication of SV40 DNA in a cell free system. Extracts prepared from S phase cells were ten times more efficient at initiating replication at the SV40 origin than were extracts from G
1
cells, whereas elongation rates were similar in G
1
and S reactions. At a discrete point in the cell cycle, just before the cell's entry into S, an activity appeared that was required, in conjunction with SV40 T antigen, for site specific initiation at the SV40 origin. This factor had a role in unwinding DNA at the replication origin.
HIV-Infected Cells Are Killed by rCD4-Ricin A Chain
Authors: Till Mark A. , Ghetie Victor , Gregory Timothy , Patzer Eric J. , Porter James P. , Uhr Jonathan W. , Capon Daniel J. , Vitetta Ellen S.
Published: October 2006

The gp120 envelope glycoprotein of the human immunodeficiency virus (HIV), which is expressed on the surface of many HIV-infected cells, binds to the cell surface molecule CD4. Soluble derivatives of recombinant CD4 (rCD4) that bind gp120 with high affinity are attractive vehicles for targeting a cytotoxic reagent to HIV-infected cells. Soluble rCD4 was conjugated to the active subunit of the toxin ricin. This conjugate killed HIV-infected H9 cells but was 1/1000 as toxic to uninfected H9 cells (which do not express gp120) and was not toxic to Daudi cells (which express major histocompatibility class II antigens, the putative natural ligand for cell surface CD4). Specific killing of infected cells can be blocked by rgp120, rCD4, or a monoclonal antibody to the gp120 binding site on CD4.
Regulation of the Erythropoietin Gene: Evidence That the Oxygen Sensor Is a Heme Protein
Authors: Goldberg Mark A. , Dunning Susan P. , Bunn H. Franklin
Published: October 2006

Erythropoietin (Epo), the hormone that stimulates red blood cell production, is synthesized in the kidney and liver in response to hypoxia. The human hepatoma cell line Hep3B regulates its production of Epo in a physiologic manner. Either hypoxia or cobalt chloride markedly increases expression of Epo mRNA as well as production of biologically active and immunologically distinct Epo protein. New protein synthesis is required before the induction of increased levels of hypoxia- or cobalt-induced Epo mRNA. Hypoxia, cobalt chloride, and nickel chloride appear to stimulate Epo production through a common pathway. The inhibition of Epo production at low partial pressures of oxygen by carbon monoxide provides evidence that a heme protein is integrally involved in the oxygen-sensing mechanism. This hypothesis is further supported by the finding that when heme synthesis is blocked, hypoxia-, cobalt-, and nickel-induced Epo production are all markedly inhibited. A model is proposed in which a ligand-dependent conformational change in a heme protein accounts for the mechanism by which hypoxia as well as cobalt and nickel stimulate the production of Epo.
Pharmacological Induction of Use-Dependent Receptive Field Modifications in the Visual Cortex
Authors: Greuel Joachim M. , Luhmann Heiko J. , Singer Wolf
Published: October 2006

Lasting modifications of the receptive fields of neurons in the visual cortex can be induced by pairing visual stimuli with iontophoretic application of the neuromodulators acetylcholine and noradrenaline or the excitatory amino acids
N
-methyl-D-aspartate (NMDA) and L-glutamate. The modifications are obtained in less than 1 hour and persist for more than 40 minutes. Thus, acetylcholine and norepinephrine have a permissive role in use-dependent neuronal plasticity. These results support the notion of a postsynaptic threshold for neuronal malleability that differs from that of sodium-dependent action potentials.
In Vivo Administration of Anti-CD3 Prevents Malignant Progressor Tumor Growth
Authors: Ellenhorn Joshua D. I. , Hirsch Raphael , Schreiber Hans , Bluestone Jeffrey A.
Published: October 2006

Malignant progressor tumors are only weakly immunogenic and can evade host recognition and rejection. One approach to therapy involves activation of the host antitumor cellular effector mechanisms. Since monoclonal antibodies to CD3 (anti-CD3) can activate T cells in vitro, an attempt was made to determine if tumor immunity could be achieved by the administration of anti-CD3 in vivo. T lymphocytes from mice injected with anti-CD3 showed increased interleukin-2 receptor (IL-2R) expression, increased proliferation to recombinant IL-2 (rIL-2), and enhanced reactivity in both an allogeneic mixed lymphocyte reaction and a mixed lymphocyte tumor culture. Malignant tumor growth in treated mice was also examined. The anti-CD3 treatment prevented tumor outgrowth that would have killed untreated animals and also stimulated an in vivo response against a malignant progressor tumor providing lasting tumor immunity.
Molecular Sorting in the Secretory Pathway
Authors: Chung Koong-Nah , Walter Peter , Aponte Gregory W. , Moore Hsiao-Ping H.
Published: October 2006

Proteins can be secreted from animal cells by either a constitutive or a regulated pathway; those destined for regulated secretion are actively sorted into dense-core secretory granules. Although sorting is generally assumed to be accomplished by specific carriers, the nature of these carriers remains elusive. In this study, peptide hormones were used as affinity ligands to purify a set of 25-kilodalton proteins from canine pancreatic tissue. Their ligand specificities and patterns of expression have the characteristics of sorting carriers.
Epithelial Cell Surfaces Induce
Salmonella
Proteins Required for Bacterial Adherence and Invasion
Authors: Finlay B. Brett , Heffron Fred , Falkow Stanley
Published: October 2006

Salmonella
bacteria are capable of entering (invading) and multiplying within eukaryotic cells. Stable adherence to and invasion of epithelial cells by
S. choleraesuis
and
S. typhimurium
were found to require de novo synthesis of several new bacterial proteins. This inducible event appears to be a coordinately regulated system dependent on trypsin- and neuraminidase-sensitive structures present on the epithelial cell surface. Mutants of
S. choleraesuis
and
S. typhimurium
were unable to synthesize these proteins and did not stably adhere to nor invade eukaryotic cells. Two such
S. typhimurium
mutants were avirulent in mice, an indication that these proteins are required for
Salmonella
virulence.
Isotypic Exclusion of γδ T Cell Receptors in Transgenic Mice Bearing a Rearranged β-Chain Gene
Authors: Fenton Robert G. , Marrack Philippa , Kappler John W. , Kanagawa O. , Seidman J. G.
Published: October 2006

The rearrangement of T cell antigen receptor β- and γ-chain gene segments was studied in transgenic mice that bear a functional β-chain gene. Virtually all CD3-positive T cells derived from transgenic mice express β chains containing the transgene-encoded V
β
8.2 variable region on their surfaces and do not express endogenous β-chain variable regions. Expression of endogenous V
β
genes is inhibited at the level of somatic recombination during thymic ontogeny. Furthermore, rearrangements of the TCR γ-chain genes are also markedly inhibited in these transgenic animals. Hence expression of the TCR β transgene has led to allelic exclusion of αβ receptors and isotypic exclusion of γδ T cell receptors.
Antibodies to Peptides Detect New Hepatitis B Antigen: Serological Correlation with Hepatocellular Carcinoma
Authors: Moriarty Ann M. , Alexander Hannah , Lerner Richard A. , Thornton George B.
Published: October 2006

The expression of a previously unidentified gene product, encoded by the hepatitis B virus (HBV) genome, has been achieved with a recombinant SV40 expression vector. Antibodies against synthetic peptides representing defined regions of this protein were used to screen cells infected with recombinant virus as well as tissues naturally infected with HBV. A 24,000-dalton protein (p24) was detected in cells infected with recombinant virus and a 28,000-dalton protein (p28) was detected in tissues infected with HBV. The peptides or recombinant-derived protein were used as antigens to screen sera from individuals infected with HBV. Specific antibodies were detected predominantly in sera from patients with hepatocellular carcinoma. The presence of p28 in tissues infected with HBV and the appearance of specific antibodies in infectious sera establish the existence of an additional marker for HBV infection.
Expression of
Plasmodium falciparum
Circumsporozoite Proteins in
Escherichia coli
for Potential Use in a Human Malaria Vaccine
Authors: Young James F. , Hockmeyer Wayne T. , Gross Mitchell , Ballou W. Ripley , Wirtz Robert A. , Trosper James H. , Beaudoin Richard L. , Hollingdale Michael R. , Miller Louis H. , Diggs Carter L. , Rosenberg Martin
Published: October 2006

The circumsporozoite (CS) protein of the human malaria parasite
Plasmodium falciparum
may be the most promising target for the development of a malaria vaccine. In this study, proteins composed of 16, 32, or 48 tandem copies of a tetrapeptide repeating sequence found in the CS protein were efficiently expressed in the bacterium
Escherichia coli
. When injected into mice, these recombinant products resulted in the production of high titers of antibodies that reacted with the authentic CS protein on live sporozoites and blocked sporozoite invasion of human hepatoma cells in vitro. These CS protein derivatives are therefore candidates for a human malaria vaccine.
A Large Deletion Within the T-Cell Receptor Beta-Chain Gene Complex in New Zealand White Mice
Authors: Kotzin Brian L. , Barr Virginia L. , Palmer Edward
Published: October 2006

The T-cell receptor β-chain gene complex contains a duplication of D
β
, J
β
, and C
β
gene segments in mice and man. When DNA from many inbred strains of mice was screened an unusual allele of the beta locus was identified in New Zealand White (NZW) mice. This allele is distinguished by the deletion of an 8.8-kilobase segment of DNA containing C
β1
, D
β2
and the J
β2
cluster. Despite the fact that all NZW T-cell receptors must be derived from a single set of β-chain gene segments, this strain has functional T cells and is phenotypically normal. This deletion of T-cell receptor β-chain segments occurs in a strain known to contribute to lupus-like autoimmune disease.
Characterization of gp41 as the Transmembrane Protein Coded by the HTLV-III/LAV Envelope Gene
Authors: Veronese Fulvia DiMarzo , DeVico Anthony L. , Copeland Terry D. , Oroszlan Stephen , Gallo Robert C. , Sarngadharan M. G.
Published: October 2006

Radiolabeled amino acid sequencing was used to characterize gp41, an antigen of HTLV-III/LAV, the virus believed to be the etiological agent of the acquired immune deficiency syndrome. This antigen is the one most commonly detected in immunoblot assays by sera of patients with AIDS or AIDS-related complex (ARC) and other individuals infected with HTLV-III/LAV. A mouse monoclonal antibody that was reactive with gp41 precipitated a 160-kilodalton protein (gp160) in addition to gp41, but did not precipitate a 120-kilodalton protein (gp120) from extracts of metabolically labeled cells producing HTLV-III. Extracts of infected cells that had been labeled with tritiated leucine or isoleucine were immunoprecipitated with the monoclonal antibody. The immunoprecipitates were fractionated by polyacrylamide gel electrophoresis and the p41 was eluted from the gel bands and subjected to amino-terminal radiolabeled amino acid sequencing by the semiautomated Edman degradation. Leucine residues occurred in cycles 7, 9, 12, 26, 33, and 34 among 40 cycles and isoleucine occurred in cycle 4 among 24 cycles analyzed. Comparison of the data with the deduced amino acid sequence of the
env
gene product of HTLV-III precisely placed gp41 in the COOH-terminal region of the
env
gene product. Gp160 is thus the primary
env
gene product and it is processed into gp120 and gp41.
Deletion in Cysteine-Rich Region of LDL Receptor Impedes Transport to Cell Surface in WHHL Rabbit
Authors: Yamamoto Tokuo , Bishop Richard W. , Brown Michael S. , Goldstein Joseph L. , Russell David W.
Published: October 2006

The Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal with familial hypercholesterolemia, produces a mutant receptor for plasma low-density lipoprotein (LDL) that is not transported to the cell surface at a normal rate. Cloning and sequencing of complementary DNA's from normal and WHHL rabbits, shows that this defect arises from an in-frame deletion of 12 nucleotides that eliminates four amino acids from the cysteine-rich ligand binding domain of the LDL receptor. A similar mutation, detected by S1 nuclease mapping of LDL receptor messenger RNA, occurred in a patient with familial hypercholesterolemia whose receptor also fails to be transported to the cell surface. These findings suggest that animal cells may have fail-safe mechanisms that prevent the surface expression of improperly folded proteins with unpaired or improperly bonded cysteine residues.
The Role of Individual Cysteine Residues in the Structure and Function of the v-
sis
Gene Product
Authors: Giese N. A. , Robbins K. C. , Aaronson S. A.
Published: October 2006

The v-
sis
oncogene encodes a platelet-derived growth factor (PDGF)-related product whose transforming activity is mediated by its functional interaction with the PDGF receptor. PDGF, as well as processed forms of the v-
sis
gene product, is a disulfide-linked dimer with eight conserved cysteine residues in the minimum region necessary for biologic activity. Site-directed mutagenesis of the v-
sis
gene revealed that each conserved cysteine residue was required directly or indirectly for disulfide-linked dimer formation. However, substitution of serine for cysteine codons at any of four positions had no detrimental effect on transforming activity of the encoded v-
sis
protein. These results establish that interchain disulfide bonds are not essential in order for this protein to act as a functional ligand for the PDGF receptor. The remaining four substitutions of serine for cysteine each inactivated transforming function of the molecule. In each case this was associated with loss of a conformation shown to involve intramolecular disulfide bonds. These studies provide insight into the role of individual cysteine residues in determining the structure of the
sis
/PDGF molecule critical for biological activity.
A Novel Instrument for Separating Large DNA Molecules with Pulsed Homogeneous Electric Fields
Authors: Clark Steven M. , Lai Eric , Birren Bruce W. , Hood Leroy
Published: October 2006

A new instrument has been developed for the electrophoretic separation of large DNA molecules that can independently regulate the voltage of each of 24 electrodes and allow the magnitude, orientation, homogeneity, and duration of the electric field to be precisely controlled. Each parameter can be varied at any time during the electrophoretic process. Thus distinct sets of conditions can be combined to optimize the separation of various fragment sizes in a single run. Independent control of electrode voltage allows all of the fields to be generated with electrodes arranged in a closed contour, independent of a particular geometry. This device increases both the resolution in any size range and the speed of separation, especially for DNA molecules larger than 3 megabases.
A Continuous Cell-Free Translation System Capable of Producing Polypeptides in High Yield
Authors: Spirin Alexander S. , Baranov Vladimir I. , Ryabova Lubov' A. , Ovodov Sergey , Alakhov Yuly B.
Published: October 2006

A cell-free translation system has been constructed that uses a continuous flow of the feeding buffer [including amino acids, adenosine triphosphate (ATP), and guanosine triphosphate (GTP)] through the reaction mixture and a continuous removal of a polypeptide product. Both prokaryotic (
Escherichia coli
) and eukaryotic (wheat embryos,
Triticum sp.
) versions of the system have been tested. In both cases the system has proven active for long times, synthesizing polypeptides at a high constant rate for tens of hours. With the use of MS2 phage RNA or brome mosaic virus RNA 4 as templates, 100 copies of viral coat proteins per RNA were synthesized for 20 hours in the prokaryotic or eukaryotic system, respectively. With synthetic calcitonin messenger RNA, 150 to 300 copies of calcitonin polypeptide were produced per messenger RNA in both types of continuous translation systems for 40 hours.
Light Stimulates Tyrosine Hydroxylase Activity and Dopamine Synthesis in Retinal Amacrine Neurons
Authors: Iuvone P. Michael , Galli C. L. , Garrison-Gund C. K. , Neff N. H.
Published: October 2006

Retinal dopamine-containing amacrine neurons are rapidly activated by light, as shown by an increase in the rate of dopamine formation in vivo and a concomitant increase in the activity of tyrosine hydroxylase, measured in vitro with a subsaturating concentration of pteridine cofactor. Activation of tyrosine hydroxylase also occurs when isolated eyes from rats killed in the dark are exposed to a strobe light. Studies of amacrine neurons should provide basic data about the biochemical processing of visual information, as well as the physiological presynaptic regulatory mechanisms of dopamine-containing neurons.
Fertilization Events Induced by Neurotransmitters After Injection of mRNA in
Xenopus
Eggs
Authors: Kline Douglas , Simoncini Luciana , Mandel Gail , Maue Robert A. , Kado Raymond T. , Jaffe Laurinda A.
Published: October 2006

Fertilization initiates in the egg a dramatic increase in intracellular calcium that opens ion channels and causes exocytosis. To explore the possibility that these events might involve a receptor-mediated pathway, receptors for serotonin or acetylcholine (M1 muscarinic) were expressed in the
Xenopus
egg; serotonin or acetylcholine then could initiate a series of responses similar to those normally initiated by sperm. Thus, there may be an endogenous receptor in the egg membrane that is activated by sperm, and the serotonin or M1 muscarinic receptor may replace the sperm receptor in this pathway.
Hormone Conjugated with Antibody to CD3 Mediates Cytotoxic T Cell Lysis of Human Melanoma Cells
Authors: Liu Margaret Ann , Nussbaum Samuel R. , Eisen Herman N.
Published: October 2006

Cytotoxic T lymphocytes can be activated by antibodies to their antigen-specific receptor complex (TCR-CD3) to destroy target cells, regardless of the specificity of the cytotoxic T cells. A novel hormone-antibody conjugate, consisting of an analog of melanocyte-stimulating hormone chemically coupled to a monoclonal antibody to CD3, the invariant component of the T cell receptor complex, was used to target human melanoma cells for destruction by human cytotoxic T lymphocytes that bear no specificity for the tumor cells. As targeting components of such anti-CD3 conjugates, hormones or growth factors are expected to prove more effective than antibodies to tumor-associated antigens in focusing the destructive activity of cytotoxic T cells on tumor target cells.
Intraventricular Carbachol Mimics the Effects of Light on the Circadian Rhythm in the Rat Pineal Gland
Authors: Zatz Martin , Brownstein Michael J.
Published: October 2006

Environmental lighting regulates numerous circadian rhythms, including the cycle in pineal serotonin
N
-acetyltransferase activity. Brief exposure of rats to light can shift the phase of this enzyme's circadian rhythm. Light also rapidly reduces nocturnal enzyme activity. Intraventricular injections of carbachol, a cholinergic agonist, can mimic both of these effects. Light and carbachol presumably act on the suprachiasmatic nucleus of the hypothalamus. These experiments demonstrate the feasibility of using a neuropharmacologic approach to the mechanisms underlying mammalian circadian rhythms.
Modulation of Folding Pathways of Exported Proteins by the Leader Sequence
Authors: Park Soonhee , Liu Gseping , Topping Traci B. , Cover William H. , Randall Linda L.
Published: October 2006

Leader peptides that function to direct export of proteins through membranes have some common features but exhibit a remarkable sequence diversity. Thus there is some question whether leader peptides exert their function through conventional stereospecific protein-protein interaction. Here it is shown that the leader peptides retarded the folding of precursor maltose-binding protein and ribose-binding protein from
Escherichia coli
. This kinetic effect may be crucial in allowing precursors to enter the export pathway.
erg
, a Human
ets
-Related Gene on Chromosome 21: Alternative Splicing, Polyadenylation, and Translation
Authors: Rao Veena N. , Papas Takis S. , Reddy E. Shyam P.
Published: October 2006

The avian acute leukemia virus E26 induces a mixed erythroid-myeloid leukemia in chickens and carries two distinct oncogenes, v-
myb
and v-
ets
. Recently, a novel gene named
erg
, closely related to the v-
ets
oncogene, was identified in human COLO 320 cells and the nucleotide sequence of its approximately 5.0-kilobase transcript,
erg
1 was determined. In the present study, the nucleotide sequence of the alternatively spliced transcript,
erg
2, was found to differ from
erg
1 by a splicing event that causes a coding frameshift near the amino terminus, resulting in an additional 99-amino acid insertion at the amino-terminus. Expression of complementary DNAs for the two transcripts in vitro resulted in synthesis of polypeptides of approximately 41 and 52 kilodaltons, suggesting the use of alternative translation initiation codons in the case of
erg
proteins. The
erg
gene was localized by somatic cell genetic analysis to human chromosome 21. It is proposed that alternative sites of splicing and polyadenylation, together with alternative sites of translation initiation, allow the synthesis of two related polypeptides from a single
erg
gene transcriptional unit.
Molecular Cloning of Odorant-Binding Protein: Member of a Ligand Carrier Family
Authors: Pevsner Jonathan , Reed Randall R. , Feinstein Paul G. , Snyder Solomon H.
Published: October 2006

Odorant-binding protein (OBP) is found in nasal epithelium, and it selectively binds odorants. Three complementary DNAs encoding rat odorant-binding protein have now been cloned and sequenced. One clone contains an open reading frame predicted to encode an 18,091-dalton protein. RNA blot analysis confirms the localization of OBP messenger RNA in the nasal epithelium. This OBP has 33 percent amino acid identity to α
2
-microglobulin, a secreted plasma protein. Other members of an α
2
-microglobulin superfamily bind and transport hydrophobic ligands. Thus, OBP probably binds and carries odorants within the nasal epithelium to putative olfactory receptors.
Selective Activation of Transcription by a Novel CCAAT Binding Factor
Authors: Maity Sankar N. , Golumbek Paul T. , Karsenty Gerard , de Crombrugghe Benoit
Published: October 2006

A novel CCAAT binding factor (CBF) composed of two different subunits has been extensively purified from rat liver. Both subunits are needed for specific binding to DNA. Addition of this purified protein to nuclear extracts of NIH 3T3 fibroblasts stimulates transcription from several promoters including the α2(I) collagen, the α1(I) collagen, the Rous sarcoma virus long terminal repeat (RSV-LTR), and the adenovirus major late promoter. Point mutations in the CCAAT motif that show either no binding or a decreased binding of CBF likewise abolish or reduce activation of transcription by CBF. Activation of transcription requires, therefore, the specific binding of CBF to its recognition sites.
Primary Rat Embryo Cells Transformed by One or Two Oncogenes Show Different Metastatic Potentials
Authors: Pozzatti Rudy , Muschel Ruth , Williams Jeanne , Padmanabhan Raji , Howard Bruce , Liotta Lance , Khoury George
Published: October 2006

Second-passage rat embryo cells were transfected with a neomycin resistance gene and the activated form of the c-Ha-
ras
I gene, or with these two genes plus the adenovirus type 2 E1a gene. Foci of morphologically transformed cells were observed in both cases; however, the frequency of transformation was at least ten times higher with two oncogenes than with the
ras
gene alone. All the transformed cell lines gave rise to rapidly growing tumors when injected subcutaneously into nude mice. All but one of the cell lines transformed by the
ras
oncogene alone formed metastatic nodules in the lungs of animals that had been injected subcutaneously with transformed cells. When transformed cells were injected intravenously, all the
ras
single-gene transformants gave rise to many metastatic lung nodules. In contrast, cell lines transformed with
ras
and E1a did not generate metastases after subcutaneous injection and gave rise to very few metastatic lung nodules after intravenous injection. These data demonstrate that a fully malignant cell with metastatic potential, as measured in an immunodeficient animal, can be obtained from early passage embryo cells by the transfection of the
ras
oncogene alone.
Double-Labeled Metabolic Maps of Memory
Authors: John E. R. , Tang Y. , Brill A. B. , Young R. , Ono K.
Published: October 2006

The physical changes representing a memory are believed to be localized to specific neurons, widely distributed in multiple parallel pathways in the brain. 2-Fluorodeoxyglucose, labeled with two discriminable radioactive tracers, was used to construct quantitative metabolic maps in split-brain cats during a visual task. One side of the brain served to estimate the metabolic variability of nonspecific influences. The other side was used to map metabolic changes related to the presence of previously learned visual cues, as well as changes related to nonspecific influences, in the same periods of time. When the two sides were compared, between 5 million and 100 million neurons (depending upon the significance level selected) were identified in which activity increased during presentation of the familiar cues. The wide distribution of these neurons throughout the brain is compatible with prior evidence of a distributed memory system. However, the large number of neurons involved is difficult to reconcile with theories in which individual neurons are dedicated to specific memories.
Construction of a Novel Oncogene Based on Synthetic Sequences Encoding Epidermal Growth Factor
Authors: Stern D. F. , Hare D. L. , Cecchini M. A. , Weinberg R. A.
Published: October 2006

The autocrine model postulates that constitutive release of a mitogenic growth factor can lead to uncontrolled proliferation and cell transformation. A synthetic polynucleotide encoding epidermal growth factor conferred a tumorigenic phenotype on cells. These cells were transformed through the action of an autocrine circuit having an extracellular component.
Leishmaniasis and Malaria: New Tools for Epidemiologic Analysis
Authors: Wirth Dyann F. , Rogers William O. , Barker Robert , Dourado Heitor , Suesebang Laksami , Albuquerque Bernardino
Published: October 2006

Parasitic diseases are still prevalent in many parts of the world, causing both human suffering and economic loss. Recent developments in biotechnology, such as the use of monoclonal antibodies and recombinant DNA, have the potential for providing both more extensive and detailed information on the parasite in the infected human and in insect vectors. New methods of detection, both in man and insect vectors, have been developed for two parasitic diseases, leishmaniasis and malaria. These new methodologies will be important in epidemiologic studies on the prevalence and transmission of these parasitic diseases.
A Tunnel in the Large Ribosomal Subunit Revealed by Three-Dimensional Image Reconstruction
Authors: Yonath A. , Leonard K. R. , Wittmann H. G.
Published: October 2006

A better understanding of the molecular mechanism of protein biosynthesis depends on the availability of a reliable model for the ribosome particle. The application of a diffraction technique, namely, three-dimensional image reconstruction from two-dimensional sheets of the large ribosomal subunits of
Bacillus stearothermophilus
at a resolution of 30 angstroms is described. The resulting three-dimensional model shows at least four projecting arms, arranged radially near the presumed interface with the 30
S
subunit. The projecting arms are positioned around a cleft, which turns into a tunnel with a length of 100 to 120 angstroms and a diameter of up to 25 angstroms. This tunnel spans the particle and may provide the path taken by the nascent polypeptide chain.