bluuebunny/crossref_metadata_2025 huggingface dataset:
β-Adrenergic Receptor Kinase: Primary Structure Delineates a Multigene Family
Authors: Benovic Jeffrey L. , DeBlasi Antonio , Stone W. Carl , Caron Marc G. , Lefkowitz Robert J.
Published: October 2006

The β-adrenergic receptor kinase (β-ARK), which specifically phosphorylates only the agonist-occupied form of the β-adrenergic and closely related receptors, appears to be important in mediating rapid agonist-specific (homologous) desensitization. The structure of this enzyme was elucidated by isolating clones from a bovine brain complementary DNA library through the use of oligonucleotide probes derived from partial amino acid sequence. The β-ARK cDNA codes for a protein of 689 amino acids (79.7 kilodaltons) with a protein kinase catalytic domain that bears greatest sequence similarity to protein kinase C and the cyclic adenosine monophosphate (cyclic AMP)-dependent protein kinase. When this clone was inserted into a mammalian expression vector and transfected into COS-7 cells, a protein that specifically phosphorylated the agonist-occupied form of the β
2
-adrenergic receptor and phosphorylated, much more weakly, the light-bleached form of rhodopsin was expressed. RNA blot analysis revealed a messenger RNA of four kilobases with highest amounts in brain and spleen. Genomic DNA blot analysis also suggests that β-ARK may be the first sequenced member of a multigene family of receptor kinases.
Germ-Line Transmission of a c-
abl
Mutation Produced by Targeted Gene Disruption in ES Cells
Authors: Schwartzberg Pamela L. , Goff Stephen P. , Robertson Elizabeth J.
Published: October 2006

A substitution mutation has been introduced into the c-
abl
locus of murine embryonic stem cells by homologous recombination between exogenously added DNA and the endogenous gene, and these cells have been used to generate chimeric mice. It is shown that the c-
abl
mutation was transmitted to progeny by several male chimeras. This work demonstrates the feasibility of germ-line transmission of a mutation introduced into a nonselectable autosomal gene by homologous recombination.
Variations in Strength and Slip Rate Along the San Andreas Fault System
Authors: Jones Craig H. , Wesnousky Steven G.
Published: October 2006

Convergence across the San Andreas fault (SAF) system is partitioned between strike-slip motion on the vertical SAF and oblique-slip motion on parallel dip-slip faults, as illustrated by the recent magnitude
M
s
= 6.0 Palm Springs,
M
s
= 6.7 Coalinga, and
M
s
= 7.1 Loma Prieta earthquakes. If the partitioning of slip minimizes the work done against friction, the direction of slip during these recent earthquakes depends primarily on fault dip and indicates that the normal stress coefficient and frictional coefficient (μ) vary among the faults. Additionally, accounting for the active dip-slip faults reduces estimates of fault slip rates along the vertical trace of the SAF by about 50 percent in the Loma Prieta and 100 percent in the North Palm Springs segments.
Conjugative Transfer by the Virulence System of
Agrobacterium tumefaciens
Authors: Beijersbergen Alice , Dulk-Ras Amke Den , Schilperoort Rob A. , Hooykaas Paul J. J.
Published: October 2006

Agrobacterium tumefaciens
transfers part of its Ti plasmid, the transferred DNA (T-DNA), to plant cells during tumor induction. Expression of this T-DNA in plant cells results in their transformation into tumor cells. There are similarities between the process of T-DNA transfer to plants and the process of bacterial conjugation. Here, the T-DNA transfer machinery mediated conjugation between bacteria. Thus, products of the Vir region of the Ti plasmid of
Agrobacterium tumefaciens
, normally involved in transfer of DNA from bacteria to plants, can direct the conjugative transfer of an IncQ plasmid between agrobacteria.
Small Earthquakes, Tectonic Forces
Authors: Hanks Thomas C.
Published: October 2006

Earthquake scaling and frequency-of-occurrence relations require that small earthquakes be just as important as larger ones in redistributing the forces that drive relative displacements across active faults of any dimension, including plate boundaries.
Molecular Cloning of Genes Under Control of the Circadian Clock in
Neurospora
Authors: Loros Jennifer J. , Denome Sylvia A , Dunlap Jay C.
Published: October 2006

To investigate the regulation of messenger RNA abundance by circadian clocks, genomic and complementary DNA libraries were screened with complementary DNA probes enriched, by means of sequential rounds of subtractive hybridization, for sequences complementary to transcripts specific to either early morning or early evening cultures of
Neurospora
. Only two morning-specific genes were identified through this protocol. RNA blot analysis verified that the abundance of the transcripts arising from these genes oscillates with a period of 21.5 hours in a clock wild-type strain and 29 hours in the long-period clock mutant strain
frq
7
. Genetic mapping through the use of restriction fragment length polymorphisms shows the two genes,
ccg-1
and
ccg-2
, to be unlinked. These data provide a view of the extent of clock control of gene expression.
Microaggregations of Oceanic Plankton Observed by Towed Video Microscopy
Authors: Davis Cabell S. , Gallager Scott M. , Solow Andrew R.
Published: October 2006

Oceanic plankton have been hypothesized to occur in micropatches (<10 meters) that can have a large impact on marine ecosystem dynamics. Towed video microscopy was used to unobtrusively determine distributions of oceanic plankton over a continuum of scales from microns to hundreds of meters. Distinct, taxa-specific aggregations measuring less than 20 centimeters were found for copepods but not for nonmotile (cyanobacterial colonies) or asexual (doliolid phorozooids) forms, which suggests that these small patches are related to mating. Significant patchiness was also found on larger scales and was correlated among taxa, indicating physical control. These video observations provide new insights into basic plankton ecology by allowing quantitative assessment of individual plankton in their natural, undisturbed state.
The Nature of the Metal-Metal Bond in Bimetallic Surfaces
Authors: Rodriguez José A. , Goodman D. Wayne
Published: October 2006

The formation of a surface metal-metal bond can produce large perturbations in the electronic, chemical, and catalytic properties of a metal. Recent studies indicate that charge transfer is an important component in surface metal-metal bonds that involve dissimilar elements. The larger the charge transfer, the stronger the cohesive energy of the bimetallic bond. On a surface, the formation of a heteronuclear metal-metal bond induces a flow of electron density toward the element with the larger fraction of empty states in its valence band. This behavior is completely contrary to that observed in bulk alloys, indicating that the nature of a heteronuclear metal-metal bond depends strongly on the structural geometry of the bimetallic system.
Tuberculosis: Commentary on a Reemergent Killer
Authors: Bloom Barry R. , Murray Christopher J. L.
Published: October 2006

Tuberculosis remains the leading cause of death in the world from a single infectious disease, although there is little knowledge of the mechanisms of its pathogenesis and protection from it. After a century of decline in the United States, tuberculosis is increasing, and strains resistant to multiple antibiotics have emerged. This excess of cases is attributable to changes in the social structure in cities, the human immunodeficiency virus epidemic, and a failure in certain major cities to improve public treatment programs. The economic costs of not adequately addressing the problem of tuberculosis in this country are estimated from an epidemiological model.
The Yohkoh Mission for High-Energy Solar Physics
Authors: Acton L. , Bruner M. , Lemen J. , Tsuneta S. , Ogawara Y. , Nishimura J. , Bentley R. , Culhane L. , Canfield R. , Hudson H. , Doschek G. , Hiei E. , Hirayama T. , Kosugi T. , Watanabe T. , Lang J. , Makishima K. , Uchida Y.
Published: October 2006

The Japanese Yohkoh satellite is now in orbit observing the sun with a set of x-ray imagers and x-ray and gamma-ray spectrometers. The data from this successful mission provide new information on solar flares and the sun's corona. This paper discusses the Yohkoh observations and presents a sample of the first scientific results from the mission.
Budget Priorities of the Nation
Authors: Ooms Van Doom
Published: October 2006

Changes in the federal budget over the last several decades have raised current consumption at the expense of the investment needed for stronger economic growth. These changes have occurred in the budget's fiscal policy, which has reduced national saving and private investment; in its expenditure policy, which has emphasized short-term benefits rather than public investments; and in its transfer policy, which has not adequately addressed the increasing child poverty that threatens the productivity of our future labor force.
Spatial Patterns from Oscillating Microtubules
Authors: Mandelkow Eckhard , Mandelkow Eva-Maria , Hotani Hirokazu , Hess Benno , Müller Stefan C.
Published: October 2006

Microtubules are fibers of the cytoskeleton involved in the generation of cell shape and motility. They can be highly dynamic and are capable of temporal oscillations in their state of assembly. Solutions of tubulin (the subunit protein of microtubules) and guanosine triphosphate (GTP, the cofactor required for microtubule assembly and oscillations) can generate various dissipative structures. They include traveling waves of microtubule assembly and disassembly as well as polygonal networks. The results imply that cytoskeletal proteins can form dynamic spatial structures by themselves, even in the absence of cellular organizing centers. Thus the microtubule system could serve as a simple model for studying pattern formation by biomolecules in vitro.
Mediterranean Outflow Mixing and Dynamics
Authors: Price James F. , Baringer Molly O'Neil , Lueck Rolf G. , Johnson Gregory C. , Ambar Isabel , Parrilla Gregorio , Cantos Alain , Kennelly Maureen A. , Sanford Thomas B.
Published: October 2006

The Mediterranean Sea produces a salty, dense outflow that is strongly modified by entrainment as it first begins to descend the continental slope in the eastern Gulf of Cadiz. The current accelerates to 1.3 meters per second, which raises the internal Froude number above 1, and is intensely turbulent through its full thickness. The outflow loses about half of its density anomaly and roughly doubles its volume transport as it entrains less saline North Atlantic Central water. Within 100 kilometers downstream, the current is turned by the Coriolis force until it flows nearly parallel to topography in a damped geostrophic balance. The mixed Mediterranean outflow continues westward, slowly descending the continental slope until it becomes neutrally buoyant in the thermocline where it becomes an important water mass.
Crystal Structure and Optical Properties of Cd
32
S
14
(SC
6
H
5
)
36
. DMF
4
, a Cluster with a 15 Angstrom CdS Core
Authors: Herron N. , Calabrese J. C. , Farneth W. E. , Wang Y.
Published: October 2006

Recrystallization of the solid Cd
10
S
4
(SC
6
H
5
)
12
from a solution of pyridine and
N
,
N
-dimethylformamide (DMF) results in the formation of the cluster Cd
32
S
14
(SC
6
H
5
)
36
⋅DMF
4
as pale yellow cubes. The structure consists of an 82-atom CdS core that is a roughly spherical piece of the cubic sphalerite lattice ∼12 angstroms in diameter. The four corners of the lattice are capped by hexagonal wurtzite-like CdS units, which results in an overall tetrahedral cluster ∼15 angstroms in diameter. This cluster dissolves intact in tetrahydrofuran where its absorption spectrum reveals a sharp peak at 358 nanometers at room temperature and its emission spectra show a strong broad band at 500 nanometers.
Sound Velocities in Olivine at Earth Mantle Pressures
Authors: Zaug J. M. , Abramson E. H. , Brown J. M. , Slutsky L. J.
Published: October 2006

The independent elastic constants of an upper mantle mineral, San Carlos olivine [(Mg
1.8
Fe
0.2
)SiO
4
], were measured from 0 to 12.5 gigapascals. Evidence is offered in support of the proposition that the explicit temperature dependence of the bulk modulus is small over the range of temperatures and pressures thought to prevail above the 400-kilometer discontinuity, and thus the data can be extrapolated to estimate the properties of olivine under mantle conditions at a depth of 400 kilometers. In the absence of high-temperature data at high pressures, estimates are made of the properties of olivine under mantle conditions to a depth of 400 kilometers. In contrast with low-pressure laboratory data, the predicted covariance of shear and compressional velocities as a function of temperature nearly matches the seismically estimated value for the lower mantle.
Diamonds, Eclogites, and the Oxidation State of the Earth's Mantle
Authors: Luth Robert W.
Published: October 2006

The reaction dolomite + 2 coesite ⇄ diopside + 2 diamond + 2O
2
defines the coexistence of diamond and carbonate in mantle eclogites. The oxygen fugacity of this reaction is ∼1 log unit higher at a given temperature and pressure than the oxygen fugacities of the analogous reactions that govern the stability of diamond in peridotite. This difference allows diamond-bearing eclogite to coexist with peridotite containing carbonate or carbonate + diamond. This potential coexistence of diamond-bearing eclogite and carbonate-bearing peridotite can explain the presence of carbon-free peridotite interlayered with garnet pyroxenites that contain graphitized diamond in the Moroccan Beni Bousera massif at the Earth's surface and the preferential preservation of diamond-bearing eclogitic relative to peridotitic xenoliths in the Roberts Victor kimberlite.
The Cape Mendocino, California, Earthquakes of April 1992: Subduction at the Triple Junction
Authors: Oppenheimer D. , Eaton J. , Jayko A. , Lisowski M. , Marshall G. , Murray M. , Simpson R. , Stein R. , Beroza G. , Magee M. , Carver G. , Dengler L. , McPherson R. , Gee L. , Romanowicz B. , Gonzalez F. , Li W. H. , Satake K. , Somerville P. , Valentine D.
Published: October 2006

The 25 April 1992 magnitude 7.1 Cape Mendocino thrust earthquake demonstrated that the North America—Gorda plate boundary is seismogenic and illustrated hazards that could result from much larger earthquakes forecast for the Cascadia region. The shock occurred just north of the Mendocino Triple Junction and caused strong ground motion and moderate damage in the immediate area. Rupture initiated onshore at a depth of 10.5 kilometers and propagated up-dip and seaward. Slip on steep faults in the Gorda plate generated two magnitude 6.6 aftershocks on 26 April. The main shock did not produce surface rupture on land but caused coastal uplift and a tsunami. The emerging picture of seismicity and faulting at the triple junction suggests that the region is likely to continue experiencing significant seismicity.
Latest Pleistocene and Holocene Geomagnetic Paleointensity on Hawaii
Authors: Mankinen Edward A. , Champion Duane E.
Published: October 2006

Geomagnetic paleointensity determinations from radiocarbon-dated lava flows on the island of Hawaii provide an estimate of broad trends in paleointensity for Holocene time and offer a glimpse of intensity variations near the end of the last glacial period. When the data from Hawaii are compared with others worldwide, the intensity of the geomagnetic field seems to have been reduced from the Holocene average by about 35 percent between 45,000 and 10,000 years ago. A long-term reduction of this magnitude is compatible with reported increases in the production rate of cosmogenic nuclides during the same interval.
Identification of Complex Aromatic Molecules in Individual Interplanetary Dust Particles
Authors: Clemett Simon J. , Maechling Claude R. , Zare Richard N. , Swan Patrick D. , Walker Robert M.
Published: October 2006

Seventeen stratospherically collected particles—eight of which are classified as interplanetary dust particles (IDPs), seven of which are classified as probable terrestrial contaminants, and two of which have uncertain origins—were studied with a microprobe two-step laser mass spectrometer. Many polycyclic aromatic hydrocarbons (PAHs) and their alkylated derivatives were identified in two of the eight IDPs. The PAHs observed include a high-mass envelope not found in meteorites or terrestrial contaminants and prominent odd-mass peaks suggestive of nitrogen-containing functional groups attached to aromatic chromophores. In addition, the complexity of the IDP mass spectra has no precedence in previous studies of meteorite samples or their acid residues. Extensive checks were performed to demonstrate that the PAH signals are not caused by terrestrial contaminants.
The Manson Impact Structure:
40
Ar/
39
Ar Age and Its Distal Impact Ejecta in the Pierre Shale in Southeastern South Dakota
Authors: Izett G. A. , Cobban W. A. , Obradovich J. D. , Kunk M. J.
Published: October 2006

The
40
Ar/
39
Ar ages of a sanidine clast from a melt-matrix breccia of the Manson, Iowa, impact structure (MIS) indicate that the MIS formed 73.8 ± 0.3 million years ago (Ma) and is not coincident with the Cretaceous-Tertiary boundary (64.43 ± 0.05 Ma). The MIS sanidine is 9 million years older than
40
Ar/
39
Ar age spectra of MIS shock-metamorphosed microcline and melt-matrix breccia interpreted earlier to be 64 to 65 Ma. Grains of shock-metamorphosed quartz, feldspar, and zircon were found in the Crow Creek Member (upper Campanian) at a biostratigraphic level constrained by radiometric ages in the Pierre Shale of South Dakota that are consistent with the
40
Ar/
39
Ar age of 73.8 ± 0.3 Ma for MIS reported herein.
Carbon-Free Fullerenes: Condensed and Stuffed Anionic Examples in Indium Systems
Authors: Sevov Slavi C. , Corbett John D.
Published: October 2006

Condensed, well-ordered analogs of the fullerenes occur in the hexagonal phases Na
96
In
97
Z
2
(Z = nickel, palladium, or platinum). Large cages of In
74
(
D

3
h

) and M
60
(= In
48
Na
12
,
D

3
d

) share pentagonal faces to generate a double—hexagonal close-packed analog of NiAs. All these polyhedra are centered by partially disordered In
10
Z clusters within deltahedra of sodium atoms that cap all inner faces of the cages, namely, Z@In
10
@Na
39
@In
74
and Z@In
10
@Na
32
@Na
12
In
48
"onions." The highest filled bands in these compounds apparently involve localized electron pairs on surface features on In
74
-based layers. Structural and electronic relations between diamond and Naln (stuffed diamond structure) parallel those between certain fullerenes and Na
96
In
97
Z
2
and, presumably, other valence-driven intermetallic phases.
Controls on Geyser Periodicity
Authors: Ingebritsen S. E. , Rojstaczer S. A.
Published: October 2006

Geyser eruption frequency is not constant over time and has been shown to vary with small (≤10
–6
) strains induced by seismic events, atmospheric loading, and Earth tides. The geyser system is approximated as a permeable conduit of intensely fractured rock surrounded by a less permeable rock matrix. Numerical simulation of this conceptual model yields a set of parameters that controls geyser existence and periodicity. Much of the responsiveness to remote seismicity and other small strains in the Earth can be explained in terms of variations in permeability and lateral recharge rates.
Distributions of Phytoplankton Blooms in the Southern Ocean
Authors: Sullivan C. W. , Arrigo K. R. , McClain C. R. , Comiso J. C. , Firestone J.
Published: October 2006

A regional pigment retrieval algorithm for the Nimbus-7 Coastal Zone Color Scanner (CZCS) has been tested for the Southern Ocean. The pigment concentrations estimated with this algorithm agree to within 5 percent with in situ values and are more than twice as high as those previously reported. The CZCS data also revealed an asymmetric distribution of enhanced pigments in the waters surrounding Antarctica; in contrast, most surface geophysical properties are symmetrically distributed. The asymmetry is coherent with circumpolar current patterns and the availability of silicic acid in surface waters. Intense blooms (>1 milligram of pigment per cubic meter) that occur downcurrent from continental masses result from dissolved trace elements such as iron derived from shelf sediments and glacial melt.
The Economic Status of the Elderly
Authors: Hurd Michael D.
Published: October 2006

Augmented by public programs such as Social Security and Medicare, incomes of the elderly in the United States have grown more rapidly during the last several decades than have the incomes of other groups, so that on average the elderly are at least as well off as the nonelderly. Not all elderly, however, have done as well: widows, in particular, have high poverty rates. The economic prospects of the elderly during the next few decades are good because of the large work force from the baby-boom cohort. In the distant future a large fraction of the population will be elderly, which will probably lead to a deterioration in their economic status. Today, the main problems center on the distribution of economic resources among the elderly and on uncertainties such as costs of medical care.
Structure of Complex of Synthetic HIV-1 Protease with a Substrate-Based Inhibitor at 2.3 Å Resolution
Authors: Miller Maria , Schneider Jens , Sathyanarayana Bangalore K. , Toth Mihaly V. , Marshall Garland R. , Clawson Leigh , Selk Linda , Kent Stephen B. H. , Wlodawer Alexander
Published: October 2006

The structure of a complex between a peptide inhibitor with the sequence
N
-acetyl-Thr-Ile-Nle-ψ[ CH
2
-NH]-Nle-Gln-Arg.amide (Nle, norleucine) with chemically synthesized HIV-1 (human immunodeficiency virus 1) protease was determined at 2.3 Å resolution (
R
factor of 0.176). Despite the symmetric nature of the unliganded enzyme, the asymmetric inhibitor lies in a single orientation and makes extensive interactions at the interface between the two subunits of the homodimeric protein. Compared with the unliganded enzyme, the protein molecule underwent substantial changes, particularly in an extended region corresponding to the "flaps" (residues 35 to 57 in each chain), where backbone movements as large as 7 Å are observed.
Histamine H
1
Receptor-Mediated Guanosine 3′,5′-Monophosphate Formation by Cultured Mouse Neuroblastoma Cells
Authors: Richelson Elliott
Published: October 2006

Incubation of cultured mouse neuroblastoma cells with histamine caused a rapid and marked increase in the formation of guanosine 3′,5′-monophosphate (cyclic GMP) by these cells. Receptor agonists for H
1
, but not H
2
, caused this effect which was reduced by H
1
but not by H
2
or muscarinic acetylcholine receptor antagonists. These results indicate that activation of H
1
receptors in these cultured nerve cells stimulated cyclic GMP formation.
The Incremental Threshold of the Rod Visual System and Weber's Law
Authors: Sharpe Lindsay T. , Fach Clemens , Nordby Knut , Stockman Andrew
Published: October 2006

The incremental threshold of the isolated rod visual system is believed, under certain conditions, to obey Weber's law (that is, to increase in direct proportion to the intensity of the background). This relation was tested at several background wavelengths, over an intensity range for which the target was seen only by the rods. Although the slope on long-wavelength background approximates unity (that is, Weber's law on log-log coordinates), it averages less than 0.8 on short- and middle-wavelength backgrounds. This is the same value as that found for the thresholds of a typical, complete achromat—who lacks cone vision—regardless of background wavelength. These results force the conclusion that Weber's law for incremental threshold detection is achieved not by the rods alone but only by the rods acting together with the cones.
Catalytic Hydrolysis of Vasoactive Intestinal Peptide by Human Autoantibody
Authors: Paul Sudhir , Volle Deanna J. , Beach Carol M. , Johnson Donald R. , Powell Michael J. , Massey Richard J.
Published: October 2006

Vasoactive intestinal peptide (VIP) labeled with
125
I, [Tyr
10
-
125
I]VIP, can be hydrolyzed by immunoglobulin G (IgG) purified from a human subject, as judged by trichloroacetic acid precipitation and reversed-phase high-performance liquid chromatography (HPLC). The hydrolytic activity was precipitated by antibody to human IgG, it was bound by immobilized protein G and showed a molecular mass close to 150 kilodaltons by gel filtration chromatography, properties similar to those of authentic IgG. The Fab fragment, prepared from IgG by papain treatment, retained the VIP hydrolytic activity of the IgG. Peptide fragments produced by treatment of VIP with the antibody fraction were purified by reversed-phase HPLC and identified by fast atom bombardment-mass spectrometry and peptide sequencing. The scissile bond in VIP deduced from these experiments was Gln
16
-Met
17
. The antibody concentration (73.4 fmol per milligram of IgG) and the
K
d
(0.4 n
M
) were computed from analysis of VIP binding under conditions that did not result in peptide hydrolysis. Analysis of the antibody-mediated VIP hydrolysis at varying concentrations of substrate suggested conformity with Michaelis-Menton kinetics (
K
m
). The values for
K
m
(37.9 × 10
-9
M
) and the turnover number
k
cat
(15.6 min
-1
) suggested relatively tight VIP binding and a moderate catalytic efficiency of the antibody.
Number of Siblings and Educational Attainment
Authors: Blake Judith
Published: October 2006

Family background continues to be closely related to individuals' educational attainment in the United States. A notable change in one aspect of this background, number of siblings, is occurring as fertility is becoming extremely low. Examination of the negative relation between individuals' sibling number and years of schooling indicates that education among those with many siblings is disproportionately cut short before high school graduation. Because there is a strong negative relation between number of siblings and scores on tests measuring verbal ability, recent reductions in sibling number would be expected to contribute to enhanced verbal ability and increasing years of schooling for those born now in the United States.
Drug Prohibition in the United States: Costs, Consequences, and Alternatives
Authors: Nadelmann Ethan A.
Published: October 2006

"Drug legalization" increasingly merits serious consideration as both an analytical model and a policy option for addressing the "drug problem." Criminal justice approaches to the drug problem have proven limited in their capacity to curtail drug abuse. They also have proven increasingly costly and counterproductive. Drug legalization policies that are wisely implemented can minimize the risks of legalization, dramatically reduce the costs of current policies, and directly address the problems of drug abuse.
Drosophila
Nuclear Proteins Bind to Regions of Alternating C and T Residues in Gene Promoters
Authors: Gilmour David S.. , Thomas Claire , Elgin Sarah C. R..
Published: October 2006

Proteins from
Drosophila
nuclei that bind to regions of alternating C and T residues present in the promoters of the heat shock genes
hsp70
and
hsp26
and the histone genes
his3
and
his4
have been purified. These proteins bind to isolated linear DNA, and genomic footprinting analyses indicate that they are bound to DNA in nuclei. In supercoiled plasmids at low
p
H, some of these DNA sequences adopt triple-helical structures which, if they form in vivo, could significantly affect chromatin structure. The nuclear proteins described here, and not necessarily the deformed conformation of the DNA, may be responsible for maintaining a potentially inducible promoter structure before transcriptional activation.
Monoclonal Antibody-Mediated Tumor Regression by Induction of Apoptosis
Authors: Trauth Bernhard C. , Klas Christiane , Peters Anke M. J. , Matzku Siegfried , Möller Peter , Falk Werner , Debatin Klaus-Michael , Krammer Peter H.
Published: October 2006

To characterize cell surface molecules involved in control of growth of malignant lymphocytes, monoclonal antibodies were raised against the human B lymphoblast cell line SKW6.4. One monoclonal antibody, anti-APO-1, reacted with a 52-kilodalton antigen (APO-1) on a set of activated human lymphocytes, on malignant human lymphocyte lines, and on some patient-derived leukemic cells. Nanogram quantities of anti-APO-1 completely blocked proliferation of cells bearing APO-1 in vitro in a manner characteristic of a process called programmed cell death or apoptosis. Cell death was preceded by changes in cell morphology and fragmentation of DNA. This process was distinct from antibody- and complement-dependent cell lysis and was mediated by the antibody alone. A single intravenous injection of anti-APO-1 into
nu
/
nu
mice carrying a xenotransplant of a human B cell tumor induced regression of this tumor within a few days. Histological thin sections of the regressing tumor showed that anti-APO-1 was able to induce apoptosis in vivo. Thus, induction of apoptosis as a consequence of a signal mediated through cell surface molecules like APO-1 may be a useful therapeutic approach in treatment of malignancy.
Molecular Mechanisms and Forces Involved in the Adhesion and Fusion of Amphiphilic Bilayers
Authors: Helm Christiane A. , Israelachvili Jacob N. , McGuiggan Patricia M.
Published: October 2006

The surface forces apparatus technique was used for measuring the adhesion, deformation, and fusion of bilayers supported on mica surfaces in aqueous solutions. The most important force leading to the direct fusion of bilayers is the hydrophobic interaction, although the occurrence of fusion is not simply related to the force law between bilayers. Bilayers do not need to "overcome" some repulsive force barrier, such as hydration, before they can fuse. Instead, once bilayer surfaces come within about 1 nanometer of each other, local deformations and molecular rearrangements allow them to "bypass" these forces.
Decreased TRH Receptor mRNA Activity Precedes Homologous Downregulation: Assay in Oocytes
Authors: Oron Yoram , Straub Richard E. , Traktman Paula , Gershengorn Marvin C.
Published: October 2006

Ligand-induced decrease in cell-surface receptor number (homologous downregulation) is often due to rapid receptor internalization. Thyrotropin-releasing hormone (TRH), however, causes a slow downregulation of TRH receptors (TRH-Rs), with a half-time of approximately 12 hours, in GH
3
rat pituitary cells. The mechanism of TRH-R downregulation was studied by monitoring TRH-evoked depolarizing currents in
Xenopus
oocytes injected with GH
3
cell RNA as a bioassay for TRH-R messenger RNA (mRNA) activity. In GH
3
cells, TRH caused a rapid decrease in TRH-R mRNA activity to 15 percent of control within 3 hours. Because the half-life of TRH-R mRNA activity in control cells was approximately 3 hours, the rapid decrease in mRNA activity was not due to inhibition of mRNA synthesis alone and may represent a post-transcriptional effect.
Activation of the HIV-1 LTR by T Cell Mitogens and the Trans-Activator Protein of HTLV-I
Authors: Siekevitz Miriam , Josephs Steven F. , Dukovich Mitchell , Peffer Nancy , Wong-Staal Flossie , Greene Warner C.
Published: October 2006

To investigate the mechanism by which immune activation augments replication of the human immunodeficiency virus type 1 (HIV-1) in infected T cells, four different classes of T cell mitogens were evaluated for their effects on the HIV-1 long terminal repeat (LTR). Phytohemagglutinin (PHA), a mitogenic lectin; phorbol 12-myristic 13-acetate, a tumor promoter; ionomycin, a calcium ionophore; and
tat
-1, the trans-activator protein from the human T cell leukemia/lymphoma virus type I (HTLV-I) each stimulated the HIV-1 LTR. Studies of deleted forms of the LTR supported a central role in these responses for the HIV-1 enhancer, which alone was sufficient for mitogen inducibility, but also suggested that other 5′ positive and negative regulatory elements contribute to the overall magnitude of the response. Synergistic activation of the HIV-1 LTR (up to several thousandfold) was observed with combinations of these mitogens and the HIV-1—derived
tat
-III protein. Cyclosporin A, an immunosuppressive agent, inhibited PHA-mediated activation of the HIV-1 LTR but was without effect in the presence of the other mitogens. Thus, HIV-1 gene expression and replication appear to be regulated, via the HIV-1 LTR, by the same mitogenic signals that induce T cell activation.
A Novel Putative Tyrosine Kinase Receptor Encoded by the
eph
Gene
Authors: Hirai Hisamaru , Maru Yoshiro , Hagiwara Koichi , Nishida Junji , Takaku Fumimaro
Published: October 2006

Growth factors and their receptors are involved in the regulation of cell proliferation and also play a key role in oncogenesis. In this study, a novel putative kinase receptor gene, termed
eph
, has been identified and characterized by molecular cloning. Its primary structure is similar to that of tyrosine kinase receptors thus far cloned and includes a cysteine-rich region in the extracellular domain. However, other features of the sequence distinguish the
eph
gene product from known receptors with tyrosine kinase activity. Thus the
eph
protein may define a new class of these molecules. The
eph
gene is overexpressed in several human carcinomas, suggesting that this gene may be involved in the neoplastic process of some tumors.
Antagonistic Adrenergic-Muscarinic Regulation of M Current in Smooth Muscle Cells
Authors: Sims Stephen M. , Singer Joshua J. , Walsh John V.
Published: October 2006

The β-adrenergic agonist isoproterenol and analogs of adenosine 3′,5′-monophosphate (cAMP) induced a potassium current, M current, in freshly dissociated gastric smooth muscle cells. Muscarinic agonists suppress this current, apparently by acting at a locus downstream from regulation of cAMP levels by adenylate cyclase and phosphodiesterase. Thus, M current can be induced by an agent and regulated in antagonistic fashion by β-adrenergic and muscarinic systems.
Alterations in L-Glutamate Binding in Alzheimer's and Huntington's Diseases
Authors: Greenamyre J. Timothy , Penney John B. , Young Anne B. , D'Amato Constance J. , Hicks Samuel P. , Shoulson Ira
Published: October 2006

Brain sections from patients who had died with senile dementia of the Alzheimer's type (SDAT), Huntington's disease (HD), or no neurologic disease were studied by autoradiography to measure sodium-independent L-[
3
H] glutamate binding. In brain sections from SDAT patients, glutamate binding was normal in the caudate, putamen, and claustrum but was lower than normal in the cortex. The decreased cortical binding represented a reduction in numbers of binding sites, not a change in binding affinity, and appeared to be the result of a specific decrease in numbers of the low-affinity quisqualate binding site. No significant changes in cortical binding of other ligands were observed. In brains from Huntington's disease patients, glutamate binding was lower in the caudate and putamen than in the same regions of brains from control and SDAT patients but was normal in the cortex. It is possible that development of positron-emitting probes for glutamate receptors may permit diagnosis of SDAT in vivo by means of positron emission tomographic scanning.
Pavlovian Conditioning of Rat Mucosal Mast Cells to Secrete Rat Mast Cell Protease II
Authors: MacQueen Glenda , Marshall Jean , Perdue Mary , Siegel Shepard , Bienenstock John
Published: October 2006

Antigen (egg albumin) injections, which stimulate mucosal mast cells to secrete mediators, were paired with an audiovisual cue. After reexposure to the audiovisual cue, a mediator (rat mast cell protease II) was measured with a sensitive and specific assay. Animals reexposed to only the audiovisual cue released a quantity of protease not significantly different from animals reexposed to both the cue and the antigen; these groups released significantly more protease than animals that had received the cue and antigen in a noncontingent manner. The results support a role for the central nervous system as a functional effector of mast cell function in the allergic state.
Gating of Retinal Transmission by Afferent Eye Position and Movement Signals
Authors: Lal Ratneshwar , Friedlander Michael J.
Published: October 2006

Vision in most vertebrates is an active process that requires the brain to combine retinal signals with information about eye movement. Eye movement information may feed forward from the motor control areas of the brain or feed back from the extrinsic eye muscles. Feedback signals elicited by passive eye movement selectively gate retinal outflow at the first relay, the dorsal lateral geniculate nucleus. The gating predominantly facilitates retinogeniculate transmission immediately after eye movement and inhibits transmission when a new steady-state eye position is achieved. These two gating effects are distributed in a complementary fashion across the dorsal lateral geniculate nucleus such that the spatiotemporal activity profile could contribute to object detection and localization.
Sequence-Specific Peptide Cleavage Catalyzed by an Antibody
Authors: Iverson Brent L. , Lerner Richard A.
Published: October 2006

Monoclonal antibodies have been induced that are capable of catalyzing specific hydrolysis of the Gly-Phe bond of peptide substrates at neutral
p
H with a metal complex cofactor. The antibodies were produced by immunizing with a Co(III) triethylenetetramine (trien)-peptide hapten. These antibodies as a group are capable of binding trien complexes of not only Co(III) but also of numerous other metals. Six peptides were examined as possible substrates with the antibodies and various metal complexes. Two of these peptides were cleaved by several of the antibodies. One antibody was studied in detail, and cleavage was observed for the substrates with the trien complexes of Zn(II), Ga(III), Fe(III), In(III), Cu(II), Ni(II), Lu(III), Mg(II), or Mn(II) as cofactors. A turnover number of 6 × 10
-4
per second was observed for these substrates. These results demonstrate the feasibility of the use of cofactor-assisted catalysis in an antibody binding site to accomplish difficult chemical transformations.
β Amyloid Gene Duplication in Alzheimer's Disease and Karyotypically Normal Down Syndrome
Authors: Delabar Jean-Maurice , Goldgaber Dmitry , Lamour Yvon , Nicole Annie , Huret Jean-Louis , de Grouchy Jean , Brown Paul , Gajdusek D. Carleton , Sinet Pierre-Marie
Published: October 2006

With the recently cloned complementary DNA probe, λAm4 for the chromosome 21 gene encoding brain amyloid polypeptide (β amyloid protein) of Alzheimer's disease, leukocyte DNA from three patients with sporadic Alzheimer's disease and two patients with karyotypically normal Down syndrome was found to contain three copies of this gene. Because a small region of chromosome 21 containing the
ets
-2 gene is duplicated in patients with Alzheimer's disease, as well as in karyotypically normal Down syndrome, duplication of a subsection of the critical segment of chromosome 21 that is duplicated in Down syndrome may be the genetic defect in Alzheimer's disease.
Trans
-Acting Transcriptional Regulation of Human T-Cell Leukemia Virus Type III Long Terminal Repeat
Authors: Sodroski Joseph , Rosen Craig , Wong-Staal Flossie , Salahuddin S. Zaki , Popovic Mikulas , Arya Suresh , Gallo Robert C. , Haseltine William A.
Published: October 2006

Human T-cell leukemia virus type III (HTLV-III) was recently identified as the probable etiologic agent of the acquired immune deficiency syndrome (AIDS). Here it is shown that, in human T-cell lines infected with HTLV-III, gene expression directed by the long terminal repeat sequence of this virus is stimulated by more than two orders of magnitude compared to matched uninfected cells. The rate of transcription of the HTLV-III long terminal repeat is more than 1000 times that of the SV40 early promoter in one infected cell line. Thus, HTLV-III, like HTLV-I, HTLV-II, and the bovine leukemia virus, is characterized by
trans
-activation of transcription in infected cells. The efficiency of
trans
-activation in the case of HTLV-III may account, at least in part, for the virulent nature of HTLV-III infection.
Genetic Basis for Species Vulnerability in the Cheetah
Authors: O'Brien S. J. , Roelke M. E. , Marker L. , Newman A. , Winkler C. A. , Meltzer D. , Colly L. , Evermann J. F. , Bush M. , Wildt D. E.
Published: October 2006

A population genetic survey of over 200 structural loci previously revealed that the South African cheetah (
Acinonyx jubatus jubatus
) has an extreme paucity of genetic variability, probably as a consequence of a severe population bottleneck in its recent past. The genetic monomorphism of the species is here extended to the major histocompatibility complex, since 14 reciprocal skin grafts between unrelated cheetahs were accepted. The apparent consequences of such genetic uniformity to the species include (i) great difficulty in captive breeding, (ii) a high degree of juvenile mortality in captivity and in the wild, and (iii) a high frequency of spermatozoal abnormalities in ejaculates. The species vulnerability of the cheetah was demonstrated by an epizootic of coronavirus-associated feline infectious peritonitis in an Oregon breeding colony in 1983. Exposure and spread of the coronavirus, which has a very low morbidity in domestic cats (approximately 1 percent), has decimated a heretofore productive and healthy captive population. The extreme genetic monomorphism, especially at the major histocompatibility complex, and the apparent hypersensitivity of the cheetah to a viral pathogen may be related, and provide a biological basis for understanding the adaptive significance of abundant genetic variation in outbred mammalian species.
Major Glycoprotein Antigens That Induce Antibodies in AIDS Patients Are Encoded by HTLV-III
Authors: Allan J. S. , Coligan J. E. , Barin F. , McLane M. F. , Sodroski J. G. , Rosen C. A. , Haseltine W. A. , Lee T. H. , Essex M.
Published: October 2006

Antibodies from the serum of patients with the acquired immune deficiency syndrome (AIDS) or with the AIDS-related complex and from the serum of seropositive healthy homosexuals, recognize two major glycoproteins in cells infected with human T-cell lymphotropic virus type III (HTLV III). These glycoproteins, gp160 and gp120, are encoded by the 2.5-kilobase open reading frame located in the 3′ end of the HTLV-III genome, as determined by amino terminus sequence analysis of the radiolabeled forms of these proteins. It is hypothesized that gp160 and gp120 represent the major species of virus-encoded envelope gene products for HTLV-III.
Virus Envelope Protein of HTLV-III Represents Major Target Antigen for Antibodies in AIDS Patients
Authors: Barin F. , McLane M. F. , Allan J. S. , Lee T. H. , Groopman J. E. , Essex M.
Published: October 2006

In this study, two glycoproteins (gp160 and gp120) that are encoded by human T-cell lymphoma virus type III (HTLV-III) were the antigens most consistently recognized by antibodies found in patients with the acquired immune deficiency syndrome (AIDS) and with the AIDS-related complex (ARC) and in healthy homosexual males. The techniques used to detect the glycoproteins were radioimmunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (RIP/SDS-PAGE). Although most antibody-positive samples from ARC patients and from healthy homosexual males also reacted with the virus core protein p24, less than half of the AIDS patients revealed a positive band with p24 under the same conditions. The ability to detect antibodies against a profile of both the major
env
gene encoded antigens and the
gag
gene encoded antigens suggests that the RIP/SDS-PAGE may be a valuable confirmatory assay for establishing the presence or absence of antibodies to HTLV-III in human serum samples.
Expression in Brain of a Messenger RNA Encoding a Novel Neuropeptide Homologous to Calcitonin Gene-Related Peptide
Authors: Amara Susan G. , Arriza Jeffrey L. , Leff Stuart E. , Swanson Larry W. , Evans Ronald M. , Rosenfeld Michael G.
Published: October 2006

As a consequence of alternative RNA processing events, a single rat gene can generate messenger RNA's (mRNA's) encoding either calcitonin or a neuropeptide referred to as alpha-type calcitonin gene-related peptide (α-CGRP). An mRNA product of a related gene has been identified in rat brain and thyroid encoding the protein precursor of a peptide differing from α-CGRP by only a single amino acid. The RNA encoding this peptide, which is referred to as β-CGRP, appears to be the only mature transcript of the β-CGRP gene. Hybridization histochemistry reveals a similar distribution of α- and β-CGRP mRNA's, but their relative levels of expression vary in different cranial nerve nuclei. Thus β-CGRP is a new member of a family of related genes with potential functions in regulating the transduction of sensory and motor information.
Strategies and Applications of in Vitro Mutagenesis
Authors: Botstein David , Shortle David
Published: October 2006

The many mutagenesis strategies made possible by the availability of cloned genes have been outlined in the context of how each strategy lends itself to the answering of different kinds of biological questions.
Site-Specific Increased Phosphorylation of pp60

v-
src

After Treatment of RSV-Transformed Cells with a Tumor Promoter
Authors: Purchio A. F. , Shoyab M. , Gentry L. E.
Published: October 2006

When vole cells that had been transformed by Rous sarcoma virus were treated with the tumor-promoting phorbol ester 12-
O
-tetradecanoyl-13-acetate (TPA), specific phosphorylation of pp60

v-
src

was increased. Partial V8 protease mapping indicated that the increased phosphorylation occurred exclusively on serine residues located in the amino terminus of the molecule. Treatment of cells with dimethyl sulfoxide or 4α-phorbol-12,13-didecanoate did not elicit this response. Two-dimensional tryptic phosphopeptide mapping of pp60

v-
src

immunoprecipitated from untreated and TPA-treated cells indicated that a specific tryptic amino-terminal peptide was hyperphosphorylated.
Tissue-Specific Expression in Transgenic Mice of a Fused Gene Containing RSV Terminal Sequences
Authors: Overbeek Paul A. , Lai Sing-Ping , Van Quill Kurtis R. , Westphal Heiner
Published: October 2006

Transgenic mice were generated with pRSV-CAT, a chimeric gene construct containing the long terminal repeat of Rous sarcoma virus (RSV) linked to the bacterial gene encoding chloramphenicol acetyltransferase (CAT). CAT expression, detected in adult animals of five independent strains, was preferentially directed to organs rich in tendon, bone, and muscle. This pattern reflects the disease specificity of the intact virus and suggests that the tissue tropism of RSV is determined at least in part by the presence of endogenous tissue-specific factors that can promote expression of genetic information linked to the long terminal repeat. In two of the mouse strains, insertion of the pRSV-CAT DNA resulted in developmental abnormalities. One of these strains was characterized by a dominant trait of embryonic lethality, the other by a recessive trait of fused toes in all four feet.
Receptor-Coupled Activation of Phosphoinositide-Specific Phospholipase C by an N Protein
Authors: Smith Charles D. , Cox C. Christine , Snyderman Ralph
Published: October 2006

Cleavage of phosphatidylinositol 4,5-bisphosphate by phospholipase C results in the production of two important second messengers: inositol-1,4,5-trisphosphate and 1,2-diacylglycerol. Although several receptors promote this cleavage, the molecular details of phospholipase C activation have remained unresolved. In this study, occupancy of a Ca
2+
-mobilizing receptor, the oligopeptide chemoattractant receptor on human polymorphonuclear leukocyte plasma membranes, was found to lead to the activation of a guanine nucleotide regulatory (N) protein by guanosine 5′-triphosphate. The activated N protein then stimulated a polyphosphoinositide-specific phospholipase C by reducing the Ca
2+
requirement for expression of this activity from superphysiological to normal intracellular concentrations. Therefore, the N protein-mediated activation of phospholipase C may be a key step in the pathway of cellular activation by chemoattractants and certain other hormones.