bluuebunny/crossref_metadata_2025 huggingface dataset:
A Gene Map of the Human Genome
Authors: Schuler G. D. , Boguski M. S. , Stewart E. A. , Stein L. D. , Gyapay G. , Rice K. , White R. E. , Rodriguez-Tomé P. , Aggarwal A. , Bajorek E. , Bentolila S. , Birren B. B. , Butler A. , Castle A. B. , Chiannilkulchai N. , Chu A. , Clee C. , Cowles S. , Day P. J. R. , Dibling T. , Drouot N. , Dunham I. , Duprat S. , East C. , Edwards C. , Fan J.-B. , Fang N. , Fizames C. , Garrett C. , Green L. , Hadley D. , Harris M. , Harrison P. , Brady S. , Hicks A. , Holloway E. , Hui L. , Hussain S. , Louis-Dit-Sully C. , Ma J. , MacGilvery A. , Mader C. , Maratukulam A. , Matise T. C. , McKusick K. B. , Morissette J. , Mungall A. , Muselet D. , Nusbaum H. C. , Page D. C. , Peck A. , Perkins S. , Piercy M. , Qin F. , Quackenbush J. , Ranby S. , Reif T. , Rozen S. , Sanders C. , She X. , Silva J. , Slonim D. K. , Soderlund C. , Sun W.-L. , Tabar P. , Thangarajah T. , Vega-Czarny N. , Vollrath D. , Voyticky S. , Wilmer T. , Wu X. , Adams M. D. , Auffray C. , Walter N. A. R. , Brandon R. , Dehejia A. , Goodfellow P. N. , Houlgatte R. , Hudson J. R. , Ide S. E. , Iorio K. R. , Lee W. Y. , Seki N. , Nagase T. , Ishikawa K. , Nomura N. , Phillips C. , Polymeropoulos M. H. , Sandusky M. , Schmitt K. , Berry R. , Swanson K. , Torres R. , Venter J. C. , Sikela J. M. , Beckmann J. S. , Weissenbach J. , Myers R. M. , Cox D. R. , James M. R. , Bentley D. , Deloukas P. , Lander E. S. , Hudson T. J.
Published: July 2002

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at
http://www.ncbi.nlm.nih.gov/SCIENCE96/
.
Accessing Genetic Information with High-Density DNA Arrays
Authors: Chee Mark , Yang Robert , Hubbell Earl , Berno Anthony , Huang Xiaohua C. , Stern David , Winkler Jim , Lockhart David J. , Morris Macdonald S. , Fodor Stephen P. A.
Published: July 2002

Rapid access to genetic information is central to the revolution taking place in molecular genetics. The simultaneous analysis of the entire human mitochondrial genome is described here. DNA arrays containing up to 135,000 probes complementary to the 16.6-kilobase human mitochondrial genome were generated by light-directed chemical synthesis. A two-color labeling scheme was developed that allows simultaneous comparison of a polymorphic target to a reference DNA or RNA. Complete hybridization patterns were revealed in a matter of minutes. Sequence polymorphisms were detected with single-base resolution and unprecedented efficiency. The methods described are generic and can be used to address a variety of questions in molecular genetics including gene expression, genetic linkage, and genetic variability.
Apomixis--The Asexual Revolution
Authors: Calzada Jean-Philippe Vielle , Crane Charles F. , Stelly David M.
Published: July 2002

Apomixis is an asexual reproductive process in plants whereby seeds that are exact genetic replicas of the maternal genetic material are produced. Vielle Calzada, Crane, and Stelly argue that this process, if understood and harnessed, will revolutionize genetic engineering and seed production for agriculturally important crops.
An Explanation for Symmetry-Induced Isotopic Fractionation in Ozone
Authors: Gellene Gregory I.
Published: July 2002

Application of a theory of nuclear symmetry-based reaction restrictions to the O
2
+ O → O
3
reaction provides a potential explanation for the symmetry-induced isotopic enrichment observed for laboratory and atmospherically produced O
3
. Within this theory, the rate of formation of O
3
from collisions of O and isotopically homonuclear O
2
depends on whether the O
2
molecule is in an
f
(allowed) or an
e
(restricted) parity label state. The restriction can be relaxed by various potential energy surface coupling terms, and the assumption that approximately 78 percent of the restricted O
2
(e)
levels produce O
3
with the same efficiency as the allowed O
2
(
f
) levels can account for laboratory-observed isotopic fractionation. In particular, the theory explains the special enhanced formation of the completely asymmetric isotopomer
16
O
17
O
18
O.
Chaos in Neuronal Networks with Balanced Excitatory and Inhibitory Activity
Authors: van Vreeswijk C. , Sompolinsky H.
Published: July 2002

Neurons in the cortex of behaving animals show temporally irregular spiking patterns. The origin of this irregularity and its implications for neural processing are unknown. The hypothesis that the temporal variability in the firing of a neuron results from an approximate balance between its excitatory and inhibitory inputs was investigated theoretically. Such a balance emerges naturally in large networks of excitatory and inhibitory neuronal populations that are sparsely connected by relatively strong synapses. The resulting state is characterized by strongly chaotic dynamics, even when the external inputs to the network are constant in time. Such a network exhibits a linear response, despite the highly nonlinear dynamics of single neurons, and reacts to changing external stimuli on time scales much smaller than the integration time constant of a single neuron.
Grain Growth Rates of MgSiO
3
Perovskite and Periclase Under Lower Mantle Conditions
Authors: Yamazaki Daisuke , Kato Takumi , Ohtani Eiji , Toriumi Mitsuhiro
Published: July 2002

The grain growth rates of MgSiO
3
perovskite and periclase in aggregates have been determined at 25 gigapascals and 1573 to 2173 kelvin. The average grain size (
G
) was fitted to the rate equation, and the grain growth rates of perovskite and periclase were
G
10.6
= 1 × 10
−57.4
t
exp(−320.8/
RT
) and
G
10.8
= 1 × 10
−62.3
t
exp(−247.0/
RT
), respectively, where
t
is the time,
R
is the gas constant, and
T
is the absolute temperature. These growth rates provide insight into the mechanism for grain growth in minerals relevant to the Earth's lower mantle that will ultimately help define the rheology of the lower mantle.
Induction of Apoptosis by ASK1, a Mammalian MAPKKK That Activates SAPK/JNK and p38 Signaling Pathways
Authors: Ichijo Hidenori , Nishida Eisuke , Irie Kenji , Dijke Peter ten , Saitoh Masao , Moriguchi Tetsuo , Takagi Minoru , Matsumoto Kunihiro , Miyazono Kohei , Gotoh Yukiko
Published: July 2002

Mitogen-activated protein (MAP) kinase cascades are activated in response to various extracellular stimuli, including growth factors and environmental stresses. A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively. Overexpression of ASK1 induced apoptotic cell death, and ASK1 was activated in cells treated with tumor necrosis factor-α (TNF-α). Moreover, TNF-α-induced apoptosis was inhibited by a catalytically inactive form of ASK1. ASK1 may be a key element in the mechanism of stress- and cytokine-induced apoptosis.
Hillslope Evolution by Bedrock Landslides
Authors: Densmore Alexander L. , Anderson Robert S. , McAdoo Brian G. , Ellis Michael A.
Published: July 2002

Bedrock landsliding is a dominant geomorphic process in a number of high-relief landscapes, yet is neglected in landscape evolution models. A physical model of sliding in beans is presented, in which incremental lowering of one wall simulates baselevel fall and generates slides. Frequent small slides produce irregular hillslopes, on which steep toes and head scarps persist until being cleared by infrequent large slides. These steep segments are observed on hillslopes in high-relief landscapes and have been interpreted as evidence for increases in tectonic or climatic process rates. In certain cases, they may instead reflect normal hillslope evolution by landsliding.
Giant Friedel Oscillations on the Beryllium(0001) Surface
Authors: Sprunger P. T. , Petersen L. , Plummer E. W. , Lægsgaard E. , Besenbacher F.
Published: July 2002

Large-amplitude electron density oscillations were observed on a Be(0001) surface by means of variable-temperature scanning tunneling microscopy. Fourier transforms of the images showed a ring of radius 2
k
F
, where
k
F
is the Fermi wave vector of the Be(0001) surface state. This wavelength was expected from Friedel oscillations caused by electronic screening of surface defects, but the amplitude of the waves for energies near the Fermi energy was anomalously large and inconsistent with the Friedel concept of screening. The enhanced amplitude of the waves must be a many-body effect, either in the electron gas (possibly an incipient charge density wave) or in the response of the lattice (electron-phonon coupling).
Dopamine Neuron Agenesis in Nurr1-Deficient Mice
Authors: Zetterström Rolf H. , Solomin Ludmila , Jansson Lottie , Hoffer Barry J. , Olson Lars , Perlmann Thomas
Published: July 2002

Dopamine neurons of the substantia nigra and ventral tegmental area regulate movement and affective behavior and degenerate in Parkinson’s disease. The orphan nuclear receptor Nurr1 was shown to be expressed in developing dopamine neurons before the appearance of known phenotypic markers for these cells. Mice lacking Nurr1 failed to generate midbrain dopaminergic neurons, were hypoactive, and died soon after birth. Nurr1 expression continued into adulthood, and brains of heterozygous animals, otherwise apparently healthy, contained reduced dopamine levels. These results suggest that putative Nurr1 ligands may be useful for treatment of Parkinson’s disease and other disorders of midbrain dopamine circuitry.
Early Forest Soils and Their Role in Devonian Global Change
Authors: Retallack Gregory J.
Published: July 2002

A paleosol in the Middle Devonian Aztec Siltstone of Victoria Land, Antarctica, is the most ancient known soil of well-drained forest ecosystems. Clay enrichment and chemical weathering of subsurface horizons in this and other Devonian forested paleosols culminate a long-term increase initiated during the Silurian. From Silurian into Devonian time, red clayey calcareous paleosols show a greater volume of roots and a concomitant decline in the density of animal burrows. These trends parallel the decline in atmospheric carbon dioxide determined from isotopic records of pedogenic carbonate in these same paleosols. The drawdown of carbon dioxide began well before the Devonian appearance of coals, large logs, and diverse terrestrial plants and animals, and it did not correlate with temporal variation in volcanic or metamorphic activity. The early Paleozoic greenhouse may have been curbed by the evolution of rhizospheres with an increased ratio of primary to secondary production and by more effective silicate weathering during Silurian time.
High-Power Infrared (8-Micrometer Wavelength) Superlattice Lasers
Authors: Scamarcio Gaetano , Capasso Federico , Sirtori Carlo , Faist Jerome , Hutchinson Albert L. , Sivco Deborah L. , Cho Alfred Y.
Published: July 2002

A quantum-cascade long-wavelength infrared laser based on superlattice active regions has been demonstrated. In this source, electrons injected by tunneling emit photons corresponding to the energy gap (minigap) between two superlattice conduction bands (minibands). A distinctive design feature is the high oscillator strength of the optical transition. Pulsed operation at a wavelength of about 8 micrometers with peak powers ranging from ∼0.80 watt at 80 kelvin to 0.2 watt at 200 kelvin has been demonstrated in a superlattice with 1-nanometer-thick AlInAs barriers and 4.3-nanometer-thick GaInAs quantum wells grown by molecular beam epitaxy. These results demonstrate the potential of strongly coupled superlattices as infrared laser materials for high-power sources in which the wavelength can be tailored by design.
Accessible Solitons
Authors: Snyder Allan W. , Mitchell D. John
Published: July 2002

Solitons are ubiquitous. Their description involves abstruse mathematics and is limited to a two-dimensional idealization. A nonlocal model is presented that provides a radical simplification and allows for an elegant description of soliton collisions, interactions, and deformations in two and three dimensions. The model reveals an intimate connection between solitons and the linear harmonic oscillator. It foreshadows a photonic switch in which a bright beam can steer a distant dim beam, and it predicts the existence of noncircularly symmetric solitons.
Cannabinoid and Heroin Activation of Mesolimbic Dopamine Transmission by a Common µ
1
Opioid Receptor Mechanism
Authors: Tanda Gianluigi , Pontieri Francesco E. , Chiara Gaetano Di
Published: July 2002

The effects of the active ingredient of
Cannabis
, Δ
9
-tetrahydrocannabinol (Δ
9
-THC), and of the highly addictive drug heroin on in vivo dopamine transmission in the nucleus accumbens were compared in Sprague-Dawley rats by brain microdialysis. Δ
9
-THC and heroin increased extracellular dopamine concentrations selectively in the shell of the nucleus accumbens; these effects were mimicked by the synthetic cannabinoid agonist WIN55212-2. SR141716A, an antagonist of central cannabinoid receptors, prevented the effects of Δ
9
-THC but not those of heroin. Naloxone, a generic opioid antagonist, administered systemically, or naloxonazine, an antagonist of μ
1
opioid receptors, infused into the ventral tegmentum, prevented the action of cannabinoids and heroin on dopamine transmission. Thus, Δ
9
-THC and heroin exert similar effects on mesolimbic dopamine transmission through a common μ
1
opioid receptor mechanism located in the ventral mesencephalic tegmentum.
Multiple Trophic Levels of a Forest Stream Linked to Terrestrial Litter Inputs
Authors: Wallace J. B. , Eggert S. L. , Meyer J. L. , Webster J. R.
Published: July 2002

The importance of terrestrial-aquatic linkages was evaluated by a large-scale, 3-year exclusion of terrestrial leaf litter inputs to a forest stream. Exclusion of leaf litter had a strong bottom-up effect that was propagated through detritivores to predators. Most invertebrate taxa in the predominant habitat declined in either abundance, biomass, or both, compared with taxa in a nearby reference stream. However, fauna in moss habitats changed little, indicating that different food webs exist in habitats of different geomorphology. Thus, the ecosystem-level consequences of excluding detrital inputs to an ecosystem were demonstrated. Inputs of riparian detritus are essential for conservation or restoration of diverse stream food webs.
Mid- to Late Pleistocene Ice Drift in the Western Arctic Ocean: Evidence for a Different Circulation in the Past
Authors: Bischof Jens F. , Darby Dennis A.
Published: July 2002

The provenance of ice-rafted debris (IRD) in four Arctic sediment cores implies that icebergs from the northwestern Laurentide ice sheets drifted across the western Arctic Ocean along the 180°–0° meridian toward Fram Strait during mid- to late Pleistocene deglaciations within the last 700,000 years. This iceberg drift was different from the present-day Beaufort Gyre circulation and resembled a dislocated transpolar drift (TPD). Sea ice mainly followed the iceberg trajectories but also frequently drifted from the Russian shelves eastward into the Amerasian Basin.
Biotic Control over the Functioning of Ecosystems
Authors: Chapin F. Stuart , Walker Brian H. , Hobbs Richard J. , Hooper David U. , Lawton John H. , Sala Osvaldo E. , Tilman David
Published: July 2002

Changes in the abundance of species
—
especially those that influence water and nutrient dynamics, trophic interactions, or disturbance regime
—
affect the structure and functioning of ecosystems. Diversity is also functionally important, both because it increases the probability of including species that have strong ecosystem effects and because it can increase the efficiency of resource use. Differences in environmental sensitivity among functionally similar species give stability to ecosystem processes, whereas differences in sensitivity among functionally different species make ecosystems more vulnerable to change. Current global environmental changes that affect species composition and diversity are therefore profoundly altering the functioning of the biosphere.
Hopes for the Future: Restoration Ecology and Conservation Biology
Authors: Dobson Andy P. , Bradshaw A. D. , Baker A. J. M.
Published: July 2002

Conversion of natural habitats into agricultural and industrial landscapes, and ultimately into degraded land, is the major impact of humans on the natural environment, posing a great threat to biodiversity. The emerging discipline of restoration ecology provides a powerful suite of tools for speeding the recovery of degraded lands. In doing so, restoration ecology provides a crucial complement to the establishment of nature reserves as a way of increasing land for the preservation of biodiversity. An integrated understanding of how human population growth and changes in agricultural practice interact with natural recovery processes and restoration ecology provides some hope for the future of the environment.
Iron-Sulfur Clusters: Nature's Modular, Multipurpose Structures
Authors: Beinert Helmut , Holm Richard H. , Münck Eckard
Published: July 2002

Iron-sulfur proteins are found in all life forms. Most frequently, they contain Fe
2
S
2
, Fe
3
S
4
, and Fe
4
S
4
clusters. These modular clusters undergo oxidation-reduction reactions, may be inserted or removed from proteins, can influence protein structure by preferential side chain ligation, and can be interconverted. In addition to their electron transfer function, iron-sulfur clusters act as catalytic centers and sensors of iron and oxygen. Their most common oxidation states are paramagnetic and present significant challenges for understanding the magnetic properties of mixed valence systems. Iron-sulfur clusters now rank with such biological prosthetic groups as hemes and flavins in pervasive occurrence and multiplicity of function.
Variability in Radiocarbon Ages of Individual Organic Compounds from Marine Sediments
Authors: Eglinton Timothy I. , Benitez-Nelson Bryan C. , Pearson Ann , McNichol Ann P. , Bauer James E. , Druffel Ellen R. M.
Published: July 2002

Organic carbon (OC) from multiple sources can be delivered contemporaneously to aquatic sediments. The influence of different OC inputs on carbon-14–based sediment chronologies is illustrated in the carbon-14 ages of purified, source-specific (biomarker) organic compounds from near-surface sediments underlying two contrasting marine systems, the Black Sea and the Arabian Sea. In the Black Sea, isotopic heterogeneity of
n
-alkanes indicated that OC was contributed from both fossil and contemporary sources. Compounds reflecting different source inputs to the Arabian Sea exhibit a 10,000-year range in conventional carbon-14 ages. Radiocarbon measurements of biomarkers of marine photoautotrophy enable sediment chronologies to be constructed independent of detrital OC influences.
Seed Banks and Molecular Maps: Unlocking Genetic Potential from the Wild
Authors: Tanksley Steven D. , McCouch Susan R.
Published: July 2002

Nearly a century has been spent collecting and preserving genetic diversity in plants. Germplasm banks—living seed collections that serve as repositories of genetic variation—have been established as a source of genes for improving agricultural crops. Genetic linkage maps have made it possible to study the chromosomal locations of genes for improving yield and other complex traits important to agriculture. The tools of genome research may finally unleash the genetic potential of our wild and cultivated germplasm resources for the benefit of society.
Hypermethylated
SUPERMAN
Epigenetic Alleles in
Arabidopsis
Authors: Jacobsen Steven E. , Meyerowitz Elliot M.
Published: July 2002

Mutations in the
SUPERMAN
gene affect flower development in
Arabidopsis
. Seven heritable but unstable
sup
epi-alleles (the
clark kent
alleles) are associated with nearly identical patterns of excess cytosine methylation within the
SUP
gene and a decreased level of
SUP
RNA. Revertants of these alleles are largely demethylated at the
SUP
locus and have restored levels of
SUP
RNA. A transgenic
Arabidopsis
line carrying an antisense methyltransferase gene, which shows an overall decrease in genomic cytosine methylation, also contains a hypermethylated
sup
allele. Thus, disruption of methylation systems may yield more complex outcomes than expected and can result in methylation defects at known genes. The
clark kent
alleles differ from the antisense line because they do not show a general decrease in genomic methylation.
Corona Formation and Heat Loss on Venus by Coupled Upwelling and Delamination
Authors: Smrekar Suzanne E. , Stofan Ellen R.
Published: July 2002

Coronae are volcanotectonic features that are unique to Venus and are interpreted to be small-scale upwellings. A model in which upwelling causes delamination at the edge of the plume head, along with deformation of a preexisting depleted mantle layer, produced the full range of topographic forms of coronae. If half of the coronae are active, delamination of the lower lithosphere could account for about 10 percent of Venus' heat loss, with another 15 percent due to upwelling. Delamination may occur in other geologic environments and could account for some of Venus' heat loss “deficit.”
Explosive Basaltic Volcanism from Cerro Negro Volcano: Influence of Volatiles on Eruptive Style
Authors: Roggensack Kurt , Hervig Richard L. , McKnight Steven B. , Williams Stanley N.
Published: July 2002

The 1992 and 1995 basaltic eruptions of Cerro Negro volcano, Nicaragua, had contrasting eruptive styles. Although they were nearly identical in composition, the 1992 eruption was explosive, producing a 7-kilometer-high sustained ash column, whereas the 1995 eruption was essentially effusive. The differences in water and carbon dioxide contents of melt inclusions from the two eruptions define minimum saturation pressures and show how decompression of initially similar magmas influences eruptive style. Before eruption, the explosive 1992 magma retained water and carbon dioxide while ascending to a moderate crustal level (about 6 kilometers), whereas the nonexplosive 1995 magma lost all carbon dioxide by degassing during ascent to shallow crustal levels (about 1 to 2 kilometers).
Fossilized Metazoan Embryos from the Earliest Cambrian
Authors: Bengtson Stefan , Zhao Yue
Published: July 2002

Small globular fossils known as
Olivooides
and
Markuelia
from basal Cambrian rocks in China and Siberia, respectively, contain directly developing embryos of metazoans. Fossilization is due to early diagenetic phosphatization. A nearly full developmental sequence of
Olivooides
can be observed, from late embryonic stages still within an egg membrane, to hatched specimens belonging to several ontogenetic stages. Earlier cleavage stages also occur, but cannot be identified to taxon.
Olivooides
shows similarities to coronate scyphozoans and to their probable Paleozoic representatives, the conulariids.
Markuelia
eggs contain looped embryos of a segmented worm with short, conical processes covering the body.
Global Sea Floor Topography from Satellite Altimetry and Ship Depth Soundings
Authors: Smith Walter H. F. , Sandwell David T.
Published: July 2002

A digital bathymetric map of the oceans with a horizontal resolution of 1 to 12 kilometers was derived by combining available depth soundings with high-resolution marine gravity information from the Geosat and ERS-1 spacecraft. Previous global bathymetric maps lacked features such as the 1600-kilometer-long Foundation Seamounts chain in the South Pacific. This map shows relations among the distributions of depth, sea floor area, and sea floor age that do not fit the predictions of deterministic models of subsidence due to lithosphere cooling but may be explained by a stochastic model in which randomly distributed reheating events warm the lithosphere and raise the ocean floor.
Rapid Colorectal Adenoma Formation Initiated by Conditional Targeting of the
Apc
Gene
Authors: Shibata Hiroyuki , Toyama Kaoru , Shioya Hisashi , Ito Masaki , Hirota Morihisa , Hasegawa Sumitaka , Matsumoto Hiroshi , Takano Hiroshi , Akiyama Tetsu , Toyoshima Kumao , Kanamaru Ryunosuke , Kanegae Yumi , Saito Izumu , Nakamura Yusuke , Shiba Kiyotaka , Noda Tetsuo
Published: July 2002

Familial adenomatous polyposis coli (FAP) is a disease characterized by the development of multiple colorectal adenomas, and affected individuals carry germline mutations in the
APC
gene. With the use of a conditional gene targeting system, a mouse model of FAP was created that circumvents the embryonic lethality of Apc deficiency and directs
Apc
inactivation specifically to the colorectal epithelium.
loxP
sites were inserted into the introns around
Apc
exon 14, and the resultant mutant allele (
Apc

580S

) was introduced into the mouse germline. Mice homozygous for
Apc

580S

were normal; however, upon infection of the colorectal region with an adenovirus encoding the Cre recombinase, the mice developed adenomas within 4 weeks. The adenomas showed deletion of
Apc
exon 14, indicating that the loss of Apc function was caused by Cre-
loxP–
mediated recombination.
Conductance of a Molecular Junction
Authors: Reed M. A. , Zhou C. , Muller C. J. , Burgin T. P. , Tour J. M.
Published: July 2002

Molecules of benzene-1,4-dithiol were self-assembled onto the two facing gold electrodes of a mechanically controllable break junction to form a statically stable gold-sulfur-aryl-sulfur-gold system, allowing for direct observation of charge transport through the molecules. Current-voltage measurements at room temperature demonstrated a highly reproducible apparent gap at about 0.7 volt, and the conductance-voltage curve showed two steps in both bias directions. This study provides a quantative measure of the conductance of a junction containing a single molecule, which is a fundamental step in the emerging area of molecular-scale electronics.
A Genomic Perspective on Protein Families
Authors: Tatusov Roman L. , Koonin Eugene V. , Lipman David J.
Published: July 2002

In order to extract the maximum amount of information from the rapidly accumulating genome sequences, all conserved genes need to be classified according to their homologous relationships. Comparison of proteins encoded in seven complete genomes from five major phylogenetic lineages and elucidation of consistent patterns of sequence similarities allowed the delineation of 720 clusters of orthologous groups (COGs). Each COG consists of individual orthologous proteins or orthologous sets of paralogs from at least three lineages. Orthologs typically have the same function, allowing transfer of functional information from one member to an entire COG. This relation automatically yields a number of functional predictions for poorly characterized genomes. The COGs comprise a framework for functional and evolutionary genome analysis.
Environment and Cancer: Who Are Susceptible?
Authors: Perera Frederica P.
Published: July 2002

Acting in concert with individual susceptibility, environmental factors such as smoking, diet, and pollutants play a role in most human cancer. However, new molecular evidence indicates that specific groups—characterized by predisposing genetic traits or ethnicity, the very young, and women—may have heightened risk from certain exposures. This is illustrated by molecular epidemiologic studies of environmental carcinogens such as polycyclic aromatic hydrocarbons and aromatic amines. Individual genetic screening for rare high-risk traits or for more common, low-penetrant susceptibility genes is problematic and not routinely recommended. However, knowledge of the full spectrum of both genetic and acquired susceptibility in the population will be instrumental in developing health and regulatory policies that increase protection of the more susceptible groups from risks of environmental carcinogens. This will necessitate revision of current risk assessment methodologies to explicitly account for individual variation in susceptibility to environmental carcinogens.
Age and Origin of the Moon
Authors: Lee Der-Chuen , Halliday Alex N. , Snyder Gregory A. , Taylor Lawrence A.
Published: July 2002

The age and origin of the moon have been studied with the use of the recently developed short-lived hafnium-tungsten chronometer (
182
Hf-
182
W, half-life of nine million years). The tungsten isotopic compositions of 21 lunar samples range from chondritic to slightly radiogenic (ɛ
W
= −0.50 ± 0.60 to +6.75 ± 0.42). This heterogeneity may have been inherited from material excavated from Earth and the putative impactor, but it is more likely the result of late radioactive decay within the moon itself; in this case, the moon formed 4.52 to 4.50 billion years ago, and its mantle has since remained poorly mixed.
Recovery of Replication-Competent HIV Despite Prolonged Suppression of Plasma Viremia
Authors: Wong Joseph K. , Hezareh Marjan , Günthard Huldrych F. , Havlir Diane V. , Ignacio Caroline C. , Spina Celsa A. , Richman Douglas D.
Published: July 2002

In evaluating current combination drug regimens for treatment of human immunodeficiency virus (HIV) disease, it is important to determine the existence of viral reservoirs. After depletion of CD8 cells from the peripheral blood mononuclear cells (PBMCs) of both patients and normal donors, activation of patient CD4 lymphocytes with immobilized antibodies to CD3 and CD28 enabled the isolation of virus from PBMCs of six patients despite the suppression of their plasma HIV RNA to fewer than 50 copies per milliliter for up to 2 years. Partial sequencing of HIV pol revealed no new drug resistance mutations or discernible evolution, providing evidence for viral latency rather than drug failure.
Identification of a Reservoir for HIV-1 in Patients on Highly Active Antiretroviral Therapy
Authors: Finzi Diana , Hermankova Monika , Pierson Theodore , Carruth Lucy M. , Buck Christopher , Chaisson Richard E. , Quinn Thomas C. , Chadwick Karen , Margolick Joseph , Brookmeyer Ronald , Gallant Joel , Markowitz Martin , Ho David D. , Richman Douglas D. , Siliciano Robert F.
Published: July 2002

The hypothesis that quiescent CD4
+
T lymphocytes carrying proviral DNA provide a reservoir for human immunodeficiency virus–type 1 (HIV-1) in patients on highly active antiretroviral therapy (HAART) was examined. In a study of 22 patients successfully treated with HAART for up to 30 months, replication-competent virus was routinely recovered from resting CD4
+
T lymphocytes. The frequency of resting CD4
+
T cells harboring latent HIV-1 was low, 0.2 to 16.4 per 10
6
cells, and, in cross-sectional analysis, did not decrease with increasing time on therapy. The recovered viruses generally did not show mutations associated with resistance to the relevant antiretroviral drugs. This reservoir of nonevolving latent virus in resting CD4
+
T cells should be considered in deciding whether to terminate treatment in patients who respond to HAART.
The
18
O/
16
O and
17
O/
16
O Ratios in Atmospheric Nitrous Oxide: A Mass-Independent Anomaly
Authors: Cliff Steven S. , Thiemens Mark H.
Published: July 2002

Measurements of the oxygen isotope ratios (
18
O/
16
O and
17
O/
16
O) in atmospheric nitrous oxide (N
2
O) from La Jolla, Pasadena, and the White Mountain Research Station (elevation, 3801 meters) in California and the White Sands Missile Range in New Mexico show that N
2
O has a mass-independent composition. These data suggest the presence of a previously undefined atmospheric process. The La Jolla samples can be explained by a mixing between an atmospherically derived source of mass-independent N
2
O and biologically derived mass-dependent N
2
O. Possible origins of the mass-independent anomaly in N
2
O are discussed.
Isotopic Fractionation of Stratospheric Nitrous Oxide
Authors: Yung Yuk L. , Miller Charles E.
Published: July 2002

We propose an isotopic fractionation mechanism, based on photolytic destruction, to explain the
15
N/
14
N and
18
O/
16
O fractionation of stratospheric nitrous oxide (N
2
O) and reconcile laboratory experiments with atmospheric observations. The theory predicts that (i) the isotopomers
15
N
14
N
16
O and
14
N
15
N
16
O have very different isotopic fractionations in the stratosphere, and (ii) laboratory photolysis experiments conducted at 205 nanometers should better simulate the observed isotopic fractionation of stratospheric N
2
O. Modeling results indicate that there is no compelling reason to invoke a significant chemical source of N
2
O in the middle atmosphere and that individual N
2
O isotopomers might be useful tracers of stratospheric air parcel motion.
Requirement of NF-κB Activation to Suppress p53-Independent Apoptosis Induced by Oncogenic Ras
Authors: Mayo Marty W. , Wang Cun-Yu , Cogswell Patricia C. , Rogers-Graham Kelley S. , Lowe Scott W. , Der Channing J. , Baldwin Albert S.
Published: July 2002

The
ras
proto-oncogene is frequently mutated in human tumors and functions to chronically stimulate signal transduction cascades resulting in the synthesis or activation of specific transcription factors, including Ets, c-Myc, c-Jun, and nuclear factor kappa B (NF-κB). These Ras-responsive transcription factors are required for transformation, but the mechanisms by which these proteins facilitate oncogenesis have not been fully established. Oncogenic Ras was shown to initiate a p53-independent apoptotic response that was suppressed through the activation of NF-κB. These results provide an explanation for the requirement of NF-κB for Ras-mediated oncogenesis and provide evidence that Ras-transformed cells are susceptible to apoptosis even if they do not express the p53 tumor-suppressor gene product.
Sequence-Specific and Phosphorylation-Dependent Proline Isomerization: A Potential Mitotic Regulatory Mechanism
Authors: Yaffe Michael B. , Schutkowski Mike , Shen Minhui , Zhou Xiao Zhen , Stukenberg P. Todd , Rahfeld Jens-Ulrich , Xu Jian , Kuang Jian , Kirschner Marc W. , Fischer Gunter , Cantley Lewis C. , Lu Kun Ping
Published: July 2002

Pin1 is an essential and conserved mitotic peptidyl-prolyl isomerase (PPIase) that is distinct from members of two other families of conventional PPIases, cyclophilins and FKBPs (FK-506 binding proteins). In response to their phosphorylation during mitosis, Pin1 binds and regulates members of a highly conserved set of proteins that overlaps with antigens recognized by the mitosis-specific monoclonal antibody MPM-2. Pin1 is here shown to be a phosphorylation-dependent PPIase that specifically recognizes the phosphoserine-proline or phosphothreonine-proline bonds present in mitotic phosphoproteins. Both Pin1 and MPM-2 selected similar phosphorylated serine-proline–containing peptides, providing the basis for the specific interaction between Pin1 and MPM-2 antigens. Pin1 preferentially isomerized proline residues preceded by phosphorylated serine or threonine with up to 1300-fold selectivity compared with unphosphorylated peptides. Pin1 may thus regulate mitotic progression by catalyzing sequence-specific and phosphorylation-dependent proline isomerization.
Signaling Through Scaffold, Anchoring, and Adaptor Proteins
Authors: Pawson Tony , Scott John D.
Published: July 2002

The process by which extracellular signals are relayed from the plasma membrane to specific intracellular sites is an essential facet of cellular regulation. Many signaling pathways do so by altering the phosphorylation state of tyrosine, serine, or threonine residues of target proteins. Recently, it has become apparent that regulatory mechanisms exist to influence where and when protein kinases and phosphatases are activated in the cell. The role of scaffold, anchoring, and adaptor proteins that contribute to the specificity of signal transduction events by recruiting active enzymes into signaling networks or by placing enzymes close to their substrates is discussed.
Footwall Refrigeration Along a Detachment Fault: Implications for the Thermal Evolution of Core Complexes
Authors: Morrison Jean , Anderson J. Lawford
Published: July 2002

Oxygen isotope compositions of epidote and quartz from chloritic breccias that underlie the detachment fault in the metamorphic core complex of the Whipple Mountains yielded quartz-epidote fractionations that range from 4.1 to 6.4 per mil and increase systematically toward the fault. These fractionations give mean temperatures that decrease from ∼432°C at 50 meters below the fault to ∼350°C at 12 meters below the fault. This extreme thermal gradient of 82°C over 38 meters (2160°C per kilometer) is best explained by advective heat extraction by means of circulating surface-derived fluids. Models of lithospheric extension consider only conductive cooling resulting from tectonic denudation and thus require revision to include fluid-induced fault-zone refrigeration.
Rho GTPases and the Actin Cytoskeleton
Authors: Hall Alan
Published: July 2002

The actin cytoskeleton mediates a variety of essential biological functions in all eukaryotic cells. In addition to providing a structural framework around which cell shape and polarity are defined, its dynamic properties provide the driving force for cells to move and to divide. Understanding the biochemical mechanisms that control the organization of actin is thus a major goal of contemporary cell biology, with implications for health and disease. Members of the Rho family of small guanosine triphosphatases have emerged as key regulators of the actin cytoskeleton, and furthermore, through their interaction with multiple target proteins, they ensure coordinated control of other cellular activities such as gene transcription and adhesion.
Images of Interlayer Josephson Vortices in Tl
2
Ba
2
CuO
6+
δ
Authors: Moler Kathryn A. , Kirtley John R. , Hinks D. G. , Li T. W. , Xu Ming
Published: July 2002

The strength of the interlayer Josephson tunneling in layered superconductors is an essential test of the interlayer tunneling model as a mechanism for superconductivity, as well as a useful phenomenological parameter. A scanning superconducting quantum interference device (SQUID) microscope was used to image interlayer Josephson vortices in Tl
2
Ba
2
CuO
6+
δ
and to obtain a direct measure of the interlayer tunneling in a high–transition temperature superconductor with a single copper oxide plane per unit cell. The measured interlayer penetration depth, λ
c
, is ∼20 micrometers, about 20 times the penetration depth required by the interlayer tunneling model.
Rejoining of DNA by the RAG1 and RAG2 Proteins
Authors: Melek Meni , Gellert Martin , van Gent Dik C.
Published: July 2002

Assembly of immunoglobulin and T cell receptor genes from separate gene segments [V(D)J recombination] begins with DNA double-strand breakage by the RAG1 and RAG2 proteins, acting at a pair of recombination signal sequences (RSSs). Here, the RAG proteins are shown to reverse the cleavage reaction by joining an RSS to a broken coding sequence end. These “hybrid joints” have also been found in lymphoid cells, even when the normal pathway of DNA double-strand break repair is inactive, and can now be explained by this activity of the RAG proteins.
Visualization of Single RNA Transcripts in Situ
Authors: Femino Andrea M. , Fay Fredric S. , Fogarty Kevin , Singer Robert H.
Published: July 2002

Fluorescence in situ hybridization (FISH) and digital imaging microscopy were modified to allow detection of single RNA molecules. Oligodeoxynucleotide probes were synthesized with five fluorochromes per molecule, and the light emitted by a single probe was calibrated. Points of light in exhaustively deconvolved images of hybridized cells gave fluorescent intensities and distances between probes consistent with single messenger RNA molecules. Analysis of β-actin transcription sites after serum induction revealed synchronous and cyclical transcription from single genes. The rates of transcription initiation and termination and messenger RNA processing could be determined by positioning probes along the transcription unit. This approach extends the power of FISH to yield quantitative molecular information on a single cell.
The Biochemical Basis of an All-or-None Cell Fate Switch in
Xenopus
Oocytes
Authors: Ferrell James E. , Machleder Eric M.
Published: July 2002

Xenopus
oocytes convert a continuously variable stimulus, the concentration of the maturation-inducing hormone progesterone, into an all-or-none biological response—oocyte maturation. Here evidence is presented that the all-or-none character of the response is generated by the mitogen-activated protein kinase (MAPK) cascade. Analysis of individual oocytes showed that the response of MAPK to progesterone or Mos was equivalent to that of a cooperative enzyme with a Hill coefficient of at least 35, more than 10 times the Hill coefficient for the binding of oxygen to hemoglobin. The response can be accounted for by the intrinsic ultrasensitivity of the oocyte's MAPK cascade and a positive feedback loop in which the cascade is embedded. These findings provide a biochemical rationale for the all-or-none character of this cell fate switch.
Replication Checkpoint Enforced by Kinases Cds1 and Chk1
Authors: Boddy Michael N. , Furnari Beth , Mondesert Odile , Russell Paul
Published: July 2002

Cdc2, the kinase that induces mitosis, is regulated by checkpoints that couple mitosis to the completion of DNA replication and repair. The repair checkpoint kinase Chk1 regulates Cdc25, a phosphatase that activates Cdc2. Effectors of the replication checkpoint evoked by hydroxyurea (HU) are unknown. Treatment of fission yeast with HU stimulated the kinase Cds1, which appears to phosphorylate the kinase Wee1, an inhibitor of Cdc2. The protein kinase Cds1 was also required for a large HU-induced increase in the amount of Mik1, a second inhibitor of Cdc2. HU-induced arrest of cell division was abolished in
cds1 chk1
cells. Thus, Cds1 and Chk1 appear to jointly enforce the replication checkpoint.
U/Pb Zircon Geochronology and Tempo of the End-Permian Mass Extinction
Authors: Bowring S. A. , Erwin D. H. , Jin Y. G. , Martin M. W. , Davidek K. , Wang W.
Published: July 2002

The mass extinction at the end of the Permian was the most profound in the history of life. Fundamental to understanding its cause is determining the tempo and duration of the extinction. Uranium/lead zircon data from Late Permian and Early Triassic rocks from south China place the Permian-Triassic boundary at 251.4 ± 0.3 million years ago. Biostratigraphic controls from strata intercalated with ash beds below the boundary indicate that the Changhsingian pulse of the end-Permian extinction, corresponding to the disappearance of about 85 percent of marine species, lasted less than 1 million years. At Meishan, a negative excursion in δ
13
C at the boundary had a duration of 165,000 years or less, suggesting a catastrophic addition of light carbon.
Salts on Europa's Surface Detected by Galileo's Near Infrared Mapping Spectrometer
Authors: McCord T. B. , Hansen G. B. , Fanale F. P. , Carlson R. W. , Matson D. L. , Johnson T. V. , Smythe W. D. , Crowley J. K. , Martin P. D. , Ocampo A. , Hibbitts C. A. , Granahan J. C. ,   the NIMS Team
Published: July 2002

Reflectance spectra in the 1- to 2.5-micrometer wavelength region of the surface of Europa obtained by Galileo's Near Infrared Mapping Spectrometer exhibit distorted water absorption bands that indicate the presence of hydrated minerals. The laboratory spectra of hydrated salt minerals such as magnesium sulfates and sodium carbonates and mixtures of these minerals provide a close match to the Europa spectra. The distorted bands are only observed in the optically darker areas of Europa, including the lineaments, and may represent evaporite deposits formed by water, rich in dissolved salts, reaching the surface from a water-rich layer underlying an ice crust.
Optimizing Sound Features for Cortical Neurons
Authors: deCharms R. Christopher , Blake David T. , Merzenich Michael M.
Published: July 2002

The brain's cerebral cortex decomposes visual images into information about oriented edges, direction and velocity information, and color. How does the cortex decompose perceived sounds? A reverse correlation technique demonstrates that neurons in the primary auditory cortex of the awake primate have complex patterns of sound-feature selectivity that indicate sensitivity to stimulus edges in frequency or in time, stimulus transitions in frequency or intensity, and feature conjunctions. This allows the creation of classes of stimuli matched to the processing characteristics of auditory cortical neurons. Stimuli designed for a particular neuron's preferred feature pattern can drive that neuron with higher sustained firing rates than have typically been recorded with simple stimuli. These data suggest that the cortex decomposes an auditory scene into component parts using a feature-processing system reminiscent of that used for the cortical decomposition of visual images.
Coupled
186
Os and
187
Os Evidence for Core-Mantle Interaction
Authors: Brandon Alan D. , Walker Richard J. , Morgan John W. , Norman Marc D. , Prichard Hazel M.
Published: July 2002

Osmium isotopic analyses of picritic lavas from Hawaii show enrichments in the osmium-186/osmium-188 ratio (
186
Os/
188
Os) of 0.008 to 0.018%, relative to a chondritic upper mantle, that are positively correlated with enrichments in
187
Os/
188
Os of 5.4 to 9.0%. The most viable mechanism to produce these coupled
186
Os and
187
Os enrichments is by addition of 0.5 to 1 weight percent of outer core metal to a portion of the D" layer and subsequent upwelling of the mixture. These data suggest that some plumes originate at the core-mantle boundary and that Os isotopes may be used to distinguish plumes derived from shallow versus deep mantle sources.
Giant Electrostriction and Relaxor Ferroelectric Behavior in Electron-Irradiated Poly(vinylidene fluoride-trifluoroethylene) Copolymer
Authors: Zhang Q. M. , Bharti Vivek , Zhao X.
Published: July 2002

An exceptionally high electrostrictive response (∼4 percent) was observed in electron-irradiated poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] copolymer. The material exhibits typical relaxor ferroelectric behavior, suggesting that the electron irradiation breaks up the coherent polarization domain (all-trans chains) in normal ferroelectric P(VDF-TrFE) copolymer into nanopolar regions (nanometer-size, all-trans chains interrupted by trans and gauche bonds) that transform the material into a relaxor ferroelectric. The expanding and contracting of these polar regions under external fields, coupled with a large difference in the lattice strain between the polar and nonpolar phases, generate an ultrahigh strain response.
p115 RhoGEF, a GTPase Activating Protein for Gα
12
and Gα
13
Authors: Kozasa Tohru , Jiang Xuejun , Hart Matthew J. , Sternweis Pamela M. , Singer William D. , Gilman Alfred G. , Bollag Gideon , Sternweis Paul C.
Published: July 2002

Members of the regulators of G protein signaling (RGS) family stimulate the intrinsic guanosine triphosphatase (GTPase) activity of the α subunits of certain heterotrimeric guanine nucleotide–binding proteins (G proteins). The guanine nucleotide exchange factor (GEF) for Rho, p115 RhoGEF, has an amino-terminal region with similarity to RGS proteins. Recombinant p115 RhoGEF and a fusion protein containing the amino terminus of p115 had specific activity as GTPase activating proteins toward the α subunits of the G proteins G
12
and G
13
, but not toward members of the G
s
, G
i
, or G
q
subfamilies of Gα proteins. This GEF may act as an intermediary in the regulation of Rho proteins by G
13
and G
12
.