bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerated Aging and Nucleolar Fragmentation in Yeast
sgs1
Mutants
Authors: Sinclair David A. , Mills Kevin , Guarente Leonard
Published: July 2002

The
SGS1
gene of yeast encodes a DNA helicase with homology to the human
WRN
gene. Mutations in
WRN
result in Werner's syndrome, a disease with symptoms resembling premature aging. Mutation of
SGS1
is shown to cause premature aging in yeast mother cells on the basis of a shortened life-span and the aging-induced phenotypes of sterility and redistribution of the Sir3 silencing protein from telomeres to the nucleolus. Further, in old
sgs1
cells the nucleolus is enlarged and fragmented
—
changes that also occur in old wild-type cells. These findings suggest a conserved mechanism of cellular aging that may be related to nucleolar structure.
Microbiology and Ecology of Filamentous Sulfur Formation
Authors: Taylor Craig D. , Wirsen Carl O.
Published: July 2002

A highly motile chemoautotrophic strain of hydrogen sulfide
–
oxidizing bacteria from coastal seawater produces solid sulfur filaments of dimensions 0.5 to 2.0 micrometers by 20 to 500 micrometers. Filamentous sulfur is rapidly produced by direct excretion by a vibrioid organism, and the newly produced filaments are thickened by the deposition of sulfur by other members of the population. Microscopic observations of the flocculent discharge material collected from diffuse-flow hydrothermal vents (9°N, East Pacific Rise) revealed that the material from this source is composed largely of filamentous sulfur of morphology nearly identical to that obtained in the model laboratory system.
STATs and Gene Regulation
Authors: Darnell James E.
Published: July 2002

STATs (signal transducers and activators of transcription) are a family of latent cytoplasmic proteins that are activated to participate in gene control when cells encounter various extracellular polypeptides. Biochemical and molecular genetic explorations have defined a single tyrosine phosphorylation site and, in a dimeric partner molecule, an Src homology 2 (SH2) phosphotyrosine-binding domain, a DNA interaction domain, and a number of protein-protein interaction domains (with receptors, other transcription factors, the transcription machinery, and perhaps a tyrosine phosphatase). Mouse genetics experiments have defined crucial roles for each known mammalian STAT. The discovery of a STAT in
Drosophila
, and most recently in
Dictyostelium discoideum
, implies an ancient evolutionary origin for this dual-function set of proteins.
Drug Abuse: Hedonic Homeostatic Dysregulation
Authors: Koob George F. , Moal Michel Le
Published: July 2002

Understanding the neurobiological mechanisms of addiction requires an integration of basic neuroscience with social psychology, experimental psychology, and psychiatry. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in compulsive drug use and a loss of control over drug-taking. Sensitization and counteradaptation are hypothesized to contribute to this hedonic homeostatic dysregulation, and the neurobiological mechanisms involved, such as the mesolimbic dopamine system, opioid peptidergic systems, and brain and hormonal stress systems, are beginning to be characterized. This framework provides a realistic approach to identifying the neurobiological factors that produce vulnerability to addiction and to relapse in individuals with a history of addiction.
The Endocrinology of Aging
Authors: Lamberts Steven W. J. , van den Beld Annewieke W. , van der Lely Aart-Jan
Published: July 2002

Most aging individuals die from atherosclerosis, cancer, or dementia; but in the oldest old, loss of muscle strength resulting in frailty is the limiting factor for an individual's chances of living an independent life until death. Three hormonal systems show decreasing circulating hormone concentrations during normal aging: (i) estrogen (in menopause) and testosterone (in andropause), (ii) dehydroepiandrosterone and its sulphate (in adrenopause), and (iii) the growth hormone/insulin-like growth factor I axis (in somatopause). Physical changes during aging have been considered physiologic, but there is evidence that some of these changes are related to this decline in hormonal activity. Hormone replacement strategies have been developed, but many of their aspects remain controversial, and increasing blood hormone levels in aging individuals to those found during mid-adult life has not been uniformly proven to be safe and of benefit.
Extinction and the Loss of Evolutionary History
Authors: Nee Sean , May Robert M.
Published: July 2002

Extinction episodes, such as the anthropogenic one currently under way, result in a pruned tree of life. But what fraction of the underlying evolutionary history survives when
k
of
n
species in a taxon are lost? This is relevant both to how species loss has translated into a loss of evolutionary history and to assigning conservation priorities. Here it is shown that approximately 80 percent of the underlying tree of life can survive even when approximately 95 percent of species are lost, and that algorithms that maximize the amount of evolutionary history preserved are not much better than choosing the survivors at random. Given the political, economic, and social realities constraining conservation biology, these findings may be helpful.
Direct Measurement of Distances and Angles in Biomolecules by NMR in a Dilute Liquid Crystalline Medium
Authors: Tjandra Nico , Bax Ad
Published: July 2002

In isotropic solution, internuclear dipolar couplings average to zero as a result of rotational diffusion. By dissolving macromolecules in a dilute aqueous nematic discotic liquid-crystalline medium containing widely spaced magnetically oriented particles, a tunable degree of solute alignment with the magnetic field can be created while retaining the high resolution and sensitivity of the regular isotropic nuclear magnetic resonance (NMR) spectrum. Dipolar couplings between
1
H-
1
H,
1
H-
13
C,
1
H-
15
N, and
13
C-
13
C pairs in such an oriented macromolecule no longer average to zero, and are readily measured. Distances and angles derived from dipolar couplings in human ubiquitin are in excellent agreement with its crystal structure. The approach promises to improve the accuracy of structures determined by NMR, and extend the size limit.
Warming Early Mars with Carbon Dioxide Clouds That Scatter Infrared Radiation
Authors: Forget François , Pierrehumbert Raymond T.
Published: July 2002

Geomorphic evidence that Mars was warm enough to support flowing water about 3.8 billion years ago presents a continuing enigma that cannot be explained by conventional greenhouse warming mechanisms. Model calculations show that the surface of early Mars could have been warmed through a scattering variant of the greenhouse effect, resulting from the ability of the carbon dioxide ice clouds to reflect the outgoing thermal radiation back to the surface. This process could also explain how Earth avoided an early irreversible glaciation and could extend the size of the habitable zone on extrasolar planets around stars.
Modulating Irrelevant Motion Perception by Varying Attentional Load in an Unrelated Task
Authors: Rees Geraint , Frith Christopher D. , Lavie Nilli
Published: July 2002

Lavie's theory of attention proposes that the processing load in a relevant task determines the extent to which irrelevant distractors are processed. This theory was tested by asking participants in a study to perform linguistic tasks of low or high load while ignoring irrelevant visual motion in the periphery of the display. Although task and distractor were unrelated, both functional imaging of motion-related activity in cortical area V5 and psychophysical measures of the motion aftereffect showed reduced motion processing during high load in the linguistic task. These findings fulfill the prediction that perception of irrelevant distractors depends on the relevant processing load.
Spontaneous Formation of Macroscopic Chiral Domains in a Fluid Smectic Phase of Achiral Molecules
Authors: Link Darren R. , Natale Giorgio , Shao Renfan , Maclennan Joseph E. , Clark Noel A. , Körblova Eva , Walba David M.
Published: July 2002

A smectic liquid-crystal phase made from achiral molecules with bent cores was found to have fluid layers that exhibit two spontaneous symmetry-breaking instabilities: polar molecular orientational ordering about the layer normal and molecular tilt. These instabilities combine to form a chiral layer structure with a handedness that depends on the sign of the tilt. The bulk states are either antiferroelectric-racemic, with the layer polar direction and handedness alternating in sign from layer to layer, or antiferroelectric-chiral, which is of uniform layer handedness. Both states exhibit an electric field–induced transition from antiferroelectric to ferroelectric.
Ultraviolet-Induced Cell Death Blocked by a Selenoprotein from a Human Dermatotropic Poxvirus
Authors: Shisler Joanna L. , Senkevich Tatiana G. , Berry Marla J. , Moss Bernard
Published: July 2002

Selenium, an essential trace element, is a component of prokaryotic and eukaryotic antioxidant proteins. A candidate selenoprotein homologous to glutathione peroxidase was deduced from the sequence of molluscum contagiosum, a poxvirus that causes persistent skin neoplasms in children and acquired immunodeficiency syndrome (AIDS) patients. Selenium was incorporated into this protein during biosynthesis, and a characteristic stem-loop structure near the end of the messenger RNA was required for alternative selenocysteine decoding of a potential UGA stop codon within the open reading frame. The selenoprotein protected human keratinocytes against cytotoxic effects of ultraviolet irradiation and hydrogen peroxide, providing a mechanism for a virus to defend itself against environmental stress.
Unconventional Myosins in Cell Movement, Membrane Traffic, and Signal Transduction
Authors: Mermall Valerie , Post Penny L. , Mooseker Mark S.
Published: July 2002

In the past few years genetic, biochemical, and cytolocalization data have implicated members of the myosin superfamily of actin-based molecular motors in a variety of cellular functions including membrane trafficking, cell movements, and signal transduction. The importance of myosins is illustrated by the identification of myosin genes as targets for disease-causing mutations. The task at hand is to decipher how the multitude of myosins function at both the molecular and cellular level—a task facilitated by our understanding of myosin structure and function in muscle.
Temperature and Surface-Ocean Water Balance of the Mid-Holocene Tropical Western Pacific
Authors: Gagan Michael K. , Ayliffe Linda K. , Hopley David , Cali Joseph A. , Mortimer Graham E. , Chappell John , McCulloch Malcolm T. , Head M. John
Published: July 2002

Skeletal Sr/Ca and
18
O/
16
O ratios in corals from the Great Barrier Reef, Australia, indicate that the tropical ocean surface ∼5350 years ago was 1°C warmer and enriched in
18
O by 0.5 per mil relative to modern seawater. The results suggest that the temperature increase enhanced the evaporative enrichment of
18
O in seawater. Transport of part of the additional atmospheric water vapor to extratropical latitudes may have sustained the
18
O/
16
O anomaly. The reduced glacial-Holocene shift in seawater
18
O/
16
O ratio produced by the mid-Holocene
18
O enrichment may help to reconcile the different temperature histories for the last deglaciation given by coral Sr/Ca thermometry and foraminiferal oxygen-isotope records.
Carbonic Acid in the Gas Phase and Its Astrophysical Relevance
Authors: Hage Wolfgang , Liedl Klaus R. , Hallbrucker Andreas , Mayer Erwin
Published: July 2002

In outer space, high-energy irradiation of cryogenic ice mixtures of abundant water and carbon dioxide is expected to form solid carbonic acid. Experiments and thermodynamic analyses show that crystalline carbonic acid sublimates without decomposition. Free-energy considerations based on highly accurate molecular quantum mechanics, in combination with vapor pressures resulting from experimental sublimation rates, suggest that in the gas phase, a monomer and dimer of carbonic acid are in equilibrium, comparable to that of formic acid. Gaseous carbonic acid could be present in comets, on Mars and outer solar system bodies, in interstellar icy grains, and in Earth's upper atmosphere.
Control of Alternative Splicing of Potassium Channels by Stress Hormones
Authors: Xie Jiuyong , McCobb David P.
Published: July 2002

Many molecular mechanisms for neural adaptation to stress remain unknown. Expression of alternative splice variants of
Slo,
a gene encoding calcium- and voltage-activated potassium channels, was measured in rat adrenal chromaffin tissue from normal and hypophysectomized animals. Hypophysectomy triggered an abrupt decrease in the proportion of Slo transcripts containing a “STREX” exon. The decrease was prevented by adrenocorticotropic hormone injections. In
Xenopus
oocytes, STREX variants produced channels with functional properties associated with enhanced repetitive firing. Thus, the hormonal stress axis is likely to control the excitable properties of epinephrine-secreting cells by regulating alternative splicing of Slo messenger RNA.
Cathepsin L: Critical Role in Ii Degradation and CD4 T Cell Selection in the Thymus
Authors: Nakagawa Terry , Roth Wera , Wong Phillip , Nelson Andrew , Farr Andrew , Deussing Jan , Villadangos Jose A. , Ploegh Hidde , Peters Christoph , Rudensky Alexander Y.
Published: July 2002

Degradation of invariant chain (Ii) is a critical step in major histocompatibility complex class II–restricted antigen presentation. Cathepsin L was found to be necessary for Ii degradation in cortical thymic epithelial cells (cTECs), but not in bone marrow (BM)–derived antigen-presenting cells (APCs). Consequently, positive selection of CD4
+
T cells was reduced. Because different cysteine proteinases are responsible for specific Ii degradation steps in cTECs and BM-derived APCs, the proteolytic environment in cells mediating positive and negative selection may be distinct. The identification of a protease involved in class II presentation in a tissue-specific manner suggests a potential means of manipulating CD4
+
T cell responsiveness in vivo.
Imaging the Deep Seismic Structure Beneath a Mid-Ocean Ridge: The MELT Experiment
Authors: Team The MELT Seismic
Published: July 2002

The Mantle Electromagnetic and Tomography (MELT) Experiment was designed to distinguish between competing models of magma generation beneath mid-ocean ridges. Seismological observations demonstrate that basaltic melt is present beneath the East Pacific Rise spreading center in a broad region several hundred kilometers across and extending to depths greater than 100 kilometers, not just in a narrow region of high melt concentration beneath the spreading center, as predicted by some models. The structure of the ridge system is strongly asymmetric: mantle densities and seismic velocities are lower and seismic anisotropy is stronger to the west of the rise axis.
Phase Velocities of Rayleigh Waves in the MELT Experiment on the East Pacific Rise
Authors: Forsyth Donald W. , Webb Spahr C. , Dorman LeRoy M. , Shen Yang
Published: July 2002

The phase velocities of Rayleigh waves increase more rapidly with distance from the East Pacific Rise (EPR) axis than is predicted by models of conductive cooling of the lithosphere. Low velocities near the axis are probably caused by partial melt at depths of 20 to 70 kilometers in a zone several hundred kilometers wide. The lowest velocities are offset to the west of the EPR. Wave propagation is anisotropic; the fast direction is approximately perpendicular to the ridge, parallel to the spreading direction. Anisotropy increases from a minimum near the axis to 3 percent or more on the flanks.
Integrated Optoelectronic Devices Based on Conjugated Polymers
Authors: Sirringhaus Henning , Tessler Nir , Friend Richard H.
Published: July 2002

An all-polymer semiconductor integrated device is demonstrated with a high-mobility conjugated polymer field-effect transistor (FET) driving a polymer light-emitting diode (LED) of similar size. The FET uses regioregular poly(hexylthiophene). Its performance approaches that of inorganic amorphous silicon FETs, with field-effect mobilities of 0.05 to 0.1 square centimeters per volt second and ON-OFF current ratios of >10
6
. The high mobility is attributed to the formation of extended polaron states as a result of local self-organization, in contrast to the variable-range hopping of self-localized polarons found in more disordered polymers. The FET-LED device represents a step toward all-polymer optoelectronic integrated circuits such as active-matrix polymer LED displays.
Proton Transfer Pathways in Bacteriorhodopsin at 2.3 Angstrom Resolution
Authors: Luecke Hartmut , Richter Hans-Thomas , Lanyi Janos K.
Published: July 2002

Photoisomerization of the retinal of bacteriorhodopsin initiates a cyclic reaction in which a proton is translocated across the membrane. Studies of this protein promise a better understanding of how ion pumps function. Together with a large amount of spectroscopic and mutational data, the atomic structure of bacteriorhodopsin, determined in the last decade at increasing resolutions, has suggested plausible but often contradictory mechanisms. X-ray diffraction of bacteriorhodopsin crystals grown in cubic lipid phase revealed unexpected two-fold symmetries that indicate merohedral twinning along the crystallographic
c
axis. The structure, refined to 2.3 angstroms taking this twinning into account, is different from earlier models, including that most recently reported. One of the carboxyl oxygen atoms of the proton acceptor Asp
85
is connected to the proton donor, the retinal Schiff base, through a hydrogen-bonded water and forms a second hydrogen bond with another water. The other carboxyl oxygen atom of Asp
85
accepts a hydrogen bond from Thr
89
. This structure forms the active site. The nearby Arg
82
is the center of a network of numerous hydrogen-bonded residues and an ordered water molecule. This network defines the pathway of the proton from the buried Schiff base to the extracellular surface.
Synthesis of Macroporous Minerals with Highly Ordered Three-Dimensional Arrays of Spheroidal Voids
Authors: Holland Brian T. , Blanford Christopher F. , Stein Andreas
Published: July 2002

Titania, zirconia, and alumina samples with periodic three-dimensional arrays of macropores were synthesized from the corresponding metal alkoxides, using latex spheres as templates. In a fast, single-step reaction, the monomeric alkoxide precursors permeate the array of bulk polystyrene spheres and condense in air at room temperature. Close packed, open-pore structures with 320- to 360-nanometer voids are obtained after calcination of the organic component at 575°C. The examples presented demonstrate the compositional diversity possible with this technique. The resulting highly structured ceramics could have applications in areas ranging from quantum electronics to photocatalysis to battery materials.
Impact of a Catastrophic Hurricane on Island Populations
Authors: Spiller David A. , Losos Jonathan B. , Schoener Thomas W.
Published: July 2002

Lizard and spider populations were censused immediately before and after Hurricane Lili on islands differentially affected by the storm surge. The results support three general propositions. First, the larger organisms, lizards, are more resistant to the immediate impact of moderate disturbance, whereas the more prolific spiders recover faster. Second, extinction risk is related to population size when disturbance is moderate but not when it is catastrophic. Third, after catastrophic disturbance, the recovery rate among different types of organisms is related to dispersal ability. The absence of the poorer dispersers, lizards, from many suitable islands is probably the result of long-lasting effects of catastrophes.
Alteration of Oceanic Volcanic Glass: Textural Evidence of Microbial Activity
Authors: Fisk Martin R. , Giovannoni Stephen J. , Thorseth Ingunn H.
Published: July 2002

The subsurface biosphere may constitute as much as 50 percent of Earth's biomass. Direct and indirect evidence suggests that an extensive biosphere exists in the rocks below the sea floor. This survey of basalts of the Atlantic, Pacific, and Indian Oceans supports the hypothesis that bacteria have colonized much of the upper oceanic crust, which has a volume estimated at 10
18
cubic meters. Although this is the largest habitat on Earth, its low abundance of bacteria constitutes much less than 1 percent of Earth's biomass.
Dimensionality-Driven Insulator-to-Metal Transition in the Bechgaard Salts
Authors: Vescoli V. , Degiorgi L. , Henderson W. , Grüner G. , Starkey K. P. , Montgomery L. K.
Published: July 2002

Optical experiments were conducted on a series of organic linear chain conductors with different values of the interchain single-electron transfer integral

t
b

, which quantifies the degree of anisotropy. Electron-electron interactions together with Umklapp scattering resulted in a correlation gap and an insulating state for small

t
b

. An insulator-to-metal transition was observed when

t
b

exceeded a critical value, on the order of the correlation gap
E
gap
. The absence of a plasma edge on the insulator side of the transition for polarization perpendicular to the chains suggests that the electrons are confined to the chains. The optical features of the metallic state, when contrasted with the magnetic properties, are suggestive of spin-charge separation.
Metallic CsI at Pressures of up to 220 Gigapascals
Authors: Eremets M. I. , Shimizu K. , Kobayashi T. C. , Amaya K.
Published: July 2002

Direct electrical transport measurements in a diamond anvil cell provide evidence for the metallization of cesium iodide (CsI) at a pressure of 115 gigapascals. A drop in the temperature dependence of the resistance was found at pressures above 180 gigapascals, indicating that the CsI was superconductive. The superconductivity changed under the influence of a magnetic field to a lower critical temperature and disappeared above 0.3 tesla. The highest critical temperature at which superconductivity was observed was 2 kelvin, and the critical temperature decreased with increasing pressure.
Metapopulation Dynamics, Abundance, and Distribution in a Microecosystem
Authors: Gonzalez A. , Lawton J. H. , Gilbert F. S. , Blackburn T. M. , Evans-Freke I.
Published: July 2002

The experimental fragmentation of landscapes of a natural ecosystem resulted in declines in the abundance and distribution of most species in the multispecies animal community inhabiting the landscapes and the extinction of many species. These declines caused the deterioration of the positive interspecific relation between local population abundance and distributional extent in this community. However, when patches were connected by habitat corridors, an immigration “rescue effect” arrested declines in both abundance and distribution and maintained the observed positive relation between them. These results demonstrate the importance of metapopulation dynamics and landscape connectivity for the persistence of populations in fragmented landscapes.
Organic Carbon Fluxes and Ecological Recovery from the Cretaceous-Tertiary Mass Extinction
Authors: D'Hondt Steven , Donaghay Percy , Zachos James C. , Luttenberg Danielle , Lindinger Matthias
Published: July 2002

Differences between the carbon isotopic values of carbonates secreted by planktic and benthic organisms did not recover to stable preextinction levels for more than 3 million years after the Cretaceous-Tertiary mass extinction. These decreased differences may have resulted from a smaller proportion of marine biological production sinking to deep water in the postextinction ocean. Under this hypothesis, marine production may have recovered shortly after the mass extinction, but the structure of the open-ocean ecosystem did not fully recover for more than 3 million years.
Long-Term Agroecosystem Experiments: Assessing Agricultural Sustainability and Global Change
Authors: Rasmussen Paul E. , Goulding Keith W. T. , Brown James R. , Grace Peter R. , Janzen H. Henry , Körschens Martin
Published: July 2002

Long-term agroecosystem experiments can be defined as large-scale field experiments more than 20 years old that study crop production, nutrient cycling, and environmental impacts of agriculture. They provide a resource for evaluating biological, biogeochemical, and environmental dimensions of agricultural sustainability; for predicting future global changes; and for validating model competence and performance. A systematic assessment is needed to determine the merits of all known experiments and to identify any that may exist in tropical and subtropical environments. The establishment of an international network to coordinate data collection and link sites would facilitate more precise prediction of agroecosystem sustainability and future global change.
Binding of Hepatitis C Virus to CD81
Authors: Pileri Piero , Uematsu Yasushi , Campagnoli Susanna , Galli Giuliano , Falugi Fabiana , Petracca Roberto , Weiner Amy J. , Houghton Michael , Rosa Domenico , Grandi Guido , Abrignani Sergio
Published: July 2002

Chronic hepatitis C virus (HCV) infection occurs in about 3 percent of the world's population and is a major cause of liver disease. HCV infection is also associated with cryoglobulinemia, a B lymphocyte proliferative disorder. Virus tropism is controversial, and the mechanisms of cell entry remain unknown. The HCV envelope protein E2 binds human CD81, a tetraspanin expressed on various cell types including hepatocytes and B lymphocytes. Binding of E2 was mapped to the major extracellular loop of CD81. Recombinant molecules containing this loop bound HCV and antibodies that neutralize HCV infection in vivo inhibited virus binding to CD81 in vitro.
Cardiovascular Failure in Mouse Embryos Deficient in VEGF Receptor-3
Authors: Dumont Daniel J. , Jussila Lotta , Taipale Jussi , Lymboussaki Athina , Mustonen Tuija , Pajusola Katri , Breitman Martin , Alitalo Kari
Published: July 2002

Vascular endothelial growth factor (VEGF) is a key regulator of blood vessel development in embryos and angiogenesis in adult tissues. Unlike VEGF, the related VEGF-C stimulates the growth of lymphatic vessels through its specific lymphatic endothelial receptor VEGFR-3. Here it is shown that targeted inactivation of the gene encoding VEGFR-3 resulted in defective blood vessel development in early mouse embryos. Vasculogenesis and angiogenesis occurred, but large vessels became abnormally organized with defective lumens, leading to fluid accumulation in the pericardial cavity and cardiovascular failure at embryonic day 9.5. Thus, VEGFR-3 has an essential role in the development of the embryonic cardiovascular system before the emergence of the lymphatic vessels.
Grassland Vegetation Changes and Nocturnal Global Warming
Authors: Alward Richard D. , Detling James K. , Milchunas Daniel G.
Published: July 2002

Global minimum temperatures (
T
MIN
) are increasing faster than maximum temperatures, but the ecological consequences of this are largely unexplored. Long-term data sets from the shortgrass steppe were used to identify correlations between
T
MIN
and several vegetation variables. This ecosystem is potentially sensitive to increases in
T
MIN
. Most notably, increased spring
T
MIN
was correlated with decreased net primary production by the dominant C
4
grass (
Bouteloua gracilis
) and with increased abundance and production by exotic and native C
3
forbs. Reductions in
B. gracilis
may make this system more vulnerable to invasion by exotic species and less tolerant of drought and grazing.
β-Arrestin-Dependent Formation of β
2
Adrenergic Receptor-Src Protein Kinase Complexes
Authors: Luttrell L. M. , Ferguson S. S. G. , Daaka Y. , Miller W. E. , Maudsley S. , Della Rocca G. J. , Lin F.-T. , Kawakatsu H. , Owada K. , Luttrell D. K. , Caron M. G. , Lefkowitz R. J.
Published: July 2002

The Ras-dependent activation of mitogen-activated protein (MAP) kinase pathways by many receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) requires the activation of Src family tyrosine kinases. Stimulation of β
2
adrenergic receptors resulted in the assembly of a protein complex containing activated c-Src and the receptor. Src recruitment was mediated by β-arrestin, which functions as an adapter protein, binding both c-Src and the agonist-occupied receptor. β-Arrestin 1 mutants, impaired either in c-Src binding or in the ability to target receptors to clathrin-coated pits, acted as dominant negative inhibitors of β
2
adrenergic receptor–mediated activation of the MAP kinases Erk1 and Erk2. These data suggest that β-arrestin binding, which terminates receptor–G protein coupling, also initiates a second wave of signal transduction in which the “desensitized” receptor functions as a critical structural component of a mitogenic signaling complex.
Visible Quantum Cutting in LiGdF
4
:Eu
3+
Through Downconversion
Authors: Wegh René T. , Donker Harry , Oskam Koenraad D. , Meijerink Andries
Published: July 2002

For mercury-free fluorescent lamps and plasma display panels, alternative luminescent materials are required for the efficient conversion of vacuum ultraviolet radiation to visible light. Quantum cutting involving the emission of two visible photons for each vacuum ultraviolet photon absorbed is demonstrated in Eu
3+
-doped LiGdF
4
with the concept of downconversion. Upon excitation of Gd
3+
with a high-energy photon, two visible photons can be emitted by Eu
3+
through an efficient two-step energy transfer from Gd
3+
to Eu
3+
, with a quantum efficiency that approaches 200 percent.
Elongation of Oligopeptides in a Simulated Submarine Hydrothermal System
Authors: Imai Ei-ichi , Honda Hajime , Hatori Kuniyuki , Brack André , Matsuno Koichiro
Published: July 2002

Oligomerization of a peptide was attempted in a flow reactor that simulated a submarine hydrothermal system. When fluid containing glycine repeatedly circulated through the hot and cold regions in the reactor, oligopeptides were made from glycine. When divalent ions (such as copper ions) were added under acidic conditions, oligoglycine was elongated up to hexaglycine. This observation suggests that prebiotic monomers could have oligomerized in the vicinity of submarine hydrothermal vents on primitive Earth.
Single-Channel Recording of a Store-Operated Ca
2+
Channel in Jurkat T Lymphocytes
Authors: Kerschbaum Hubert H. , Cahalan Michael D.
Published: July 2002

In T lymphocytes, a store-operated calcium ion (Ca
2+
) entry mechanism termed the calcium release–activated Ca
2+
channel (CRAC channel) underlies the sustained or oscillatory intracellular calcium concentration signal required for interleukin-2 gene expression and cell proliferation. The use of sodium ions as a current carrier enabled single-channel recordings of CRAC channels during activation, inactivation, and blockade of current in the presence of divalent cations. A large conductance of 36 to 40 picosiemens indicates that 100 to 400 CRAC channels are present in T lymphocytes.
Reciprocal Control of T Helper Cell and Dendritic Cell Differentiation
Authors: Rissoan Marie-Clotilde , Soumelis Vassili , Kadowaki Norimitsu , Grouard Geraldine , Briere Francine , Malefyt René de Waal , Liu Yong-Jun
Published: July 2002

It is not known whether subsets of dendritic cells provide different cytokine microenvironments that determine the differentiation of either type-1 T helper (T
H
1) or T
H
2 cells. Human monocyte (pDC1)–derived dendritic cells (DC1) were found to induce T
H
1 differentiation, whereas dendritic cells (DC2) derived from CD4
+
CD3
–
CD11c
–
plasmacytoid cells (pDC2) induced T
H
2 differentiation by use of a mechanism unaffected by interleukin-4 (IL-4) or IL-12. The T
H
2 cytokine IL-4 enhanced DC1 maturation and killed pDC2, an effect potentiated by IL-10 but blocked by CD40 ligand and interferon-γ. Thus, a negative feedback loop from the mature T helper cells may selectively inhibit prolonged T
H
1 or T
H
2 responses by regulating survival of the appropriate dendritic cell subset.
Lu-Hf Isotope Systematics of Garnet Pyroxenites from Beni Bousera, Morocco: Implications for Basalt Origin
Authors: Blichert-Toft Janne , Albarède Francis , Kornprobst Jacques
Published: July 2002

Six garnet pyroxenites from Beni Bousera, Morocco, yield a mean lutetium-hafnium age of 25 ± 1 million years ago and show a wide range in hafnium isotope compositions (ɛ
Hf
= –9 to +42 25 million years ago), which exceeds that of known basalts (0 to +25). Therefore, primary melts of garnet pyroxenites cannot be the source of basalts. The upper mantle may be an aggregate of pyroxenites that were left by the melting of oceanic crust at subduction zones and peridotites that were contaminated by the percolation of melts from these pyroxenites. As a consequence, the concept of geochemical heterogeneities as passive tracers is inadequate. Measured lutetium-hafnium partitioning of natural minerals requires a reassessment of some experimental work relevant to mantle melting in the presence of garnet.
Regulation of β-Catenin Signaling by the B56 Subunit of Protein Phosphatase 2A
Authors: Seeling Joni M. , Miller Jeffrey R. , Gil Rosario , Moon Randall T. , White Ray , Virshup David M.
Published: July 2002

Dysregulation of Wnt–β-catenin signaling disrupts axis formation in vertebrate embryos and underlies multiple human malignancies. The adenomatous polyposis coli (APC) protein, axin, and glycogen synthase kinase 3β form a Wnt-regulated signaling complex that mediates the phosphorylation-dependent degradation of β-catenin. A protein phosphatase 2A (PP2A) regulatory subunit, B56, interacted with APC in the yeast two-hybrid system. Expression of B56 reduced the abundance of β-catenin and inhibited transcription of β-catenin target genes in mammalian cells and
Xenopus
embryo explants. The B56-dependent decrease in β-catenin was blocked by oncogenic mutations in β-catenin or APC, and by proteasome inhibitors. B56 may direct PP2A to dephosphorylate specific components of the APC-dependent signaling complex and thereby inhibit Wnt signaling.
Geochemical Consequences of Increased Atmospheric Carbon Dioxide on Coral Reefs
Authors: Kleypas Joan A. , Buddemeier Robert W. , Archer David , Gattuso Jean-Pierre , Langdon Chris , Opdyke Bradley N.
Published: July 2002

A coral reef represents the net accumulation of calcium carbonate (CaCO
3
) produced by corals and other calcifying organisms. If calcification declines, then reef-building capacity also declines. Coral reef calcification depends on the saturation state of the carbonate mineral aragonite of surface waters. By the middle of the next century, an increased concentration of carbon dioxide will decrease the aragonite saturation state in the tropics by 30 percent and biogenic aragonite precipitation by 14 to 30 percent. Coral reefs are particularly threatened, because reef-building organisms secrete metastable forms of CaCO
3
, but the biogeochemical consequences on other calcifying marine ecosystems may be equally severe.
Regulation of Mammalian Circadian Behavior by Non-rod, Non-cone, Ocular Photoreceptors
Authors: Freedman Melanie S. , Lucas Robert J. , Soni Bobby , von Schantz Malcolm , Muñoz Marta , David-Gray Zoë , Foster Russell
Published: July 2002

Circadian rhythms of mammals are entrained by light to follow the daily solar cycle (photoentrainment). To determine whether retinal rods and cones are required for this response, the effects of light on the regulation of circadian wheel-running behavior were examined in mice lacking these photoreceptors. Mice without cones (
cl
) or without both rods and cones (
rdta/cl
) showed unattenuated phase-shifting responses to light. Removal of the eyes abolishes this behavior. Thus, neither rods nor cones are required for photoentrainment, and the murine eye contains additional photoreceptors that regulate the circadian clock.
Phylogenetic Perspectives in Innate Immunity
Authors: Hoffmann Jules A. , Kafatos Fotis C. , Janeway Charles A. , Ezekowitz R. A. B.
Published: July 2002

The concept of innate immunity refers to the first-line host defense that serves to limit infection in the early hours after exposure to microorganisms. Recent data have highlighted similarities between pathogen recognition, signaling pathways, and effector mechanisms of innate immunity in
Drosophila
and mammals, pointing to a common ancestry of these defenses. In addition to its role in the early phase of defense, innate immunity in mammals appears to play a key role in stimulating the subsequent, clonal response of adaptive immunity.
Type III Secretion Machines: Bacterial Devices for Protein Delivery into Host Cells
Authors: Galán Jorge E. , Collmer Alan
Published: July 2002

Several Gram-negative pathogenic bacteria have evolved a complex protein secretion system termed type III to deliver bacterial effector proteins into host cells that then modulate host cellular functions. These bacterial devices are present in both plant and animal pathogenic bacteria and are evolutionarily related to the flagellar apparatus. Although type III secretion systems are substantially conserved, the effector molecules they deliver are unique for each bacterial species. Understanding the biology of these devices may allow the development of novel prevention and therapeutic approaches for several infectious diseases.
Carbon Nanotube Actuators
Authors: Baughman Ray H. , Cui Changxing , Zakhidov Anvar A. , Iqbal Zafar , Barisci Joseph N. , Spinks Geoff M. , Wallace Gordon G. , Mazzoldi Alberto , De Rossi Danilo , Rinzler Andrew G. , Jaschinski Oliver , Roth Siegmar , Kertesz Miklos
Published: July 2002

Electromechanical actuators based on sheets of single-walled carbon nanotubes were shown to generate higher stresses than natural muscle and higher strains than high-modulus ferroelectrics. Like natural muscles, the macroscopic actuators are assemblies of billions of individual nanoscale actuators. The actuation mechanism (quantum chemical–based expansion due to electrochemical double-layer charging) does not require ion intercalation, which limits the life and rate of faradaic conducting polymer actuators. Unlike conventional ferroelectric actuators, low operating voltages of a few volts generate large actuator strains. Predictions based on measurements suggest that actuators using optimized nanotube sheets may eventually provide substantially higher work densities per cycle than any previously known technology.
Identification of a Nuclear Receptor for Bile Acids
Authors: Makishima Makoto , Okamoto Arthur Y. , Repa Joyce J. , Tu Hua , Learned R. Marc , Luk Alvin , Hull Mitchell V. , Lustig Kevin D. , Mangelsdorf David J. , Shan Bei
Published: July 2002

Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7α-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid–binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport.
Bile Acids: Natural Ligands for an Orphan Nuclear Receptor
Authors: Parks Derek J. , Blanchard Steven G. , Bledsoe Randy K. , Chandra Gyan , Consler Thomas G. , Kliewer Steven A. , Stimmel Julie B. , Willson Timothy M. , Zavacki Ann Marie , Moore David D. , Lehmann Jürgen M.
Published: July 2002

Bile acids regulate the transcription of genes that control cholesterol homeostasis through molecular mechanisms that are poorly understood. Physiological concentrations of free and conjugated chenodeoxycholic acid, lithocholic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H4), an orphan nuclear receptor. As ligands, these bile acids and their conjugates modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1. These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis.
Broadly Protective Vaccine for
Staphylococcus aureus
Based on an in Vivo-Expressed Antigen
Authors: McKenney David , Pouliot Kimberly L. , Wang Ying , Murthy Vivek , Ulrich Martina , Döring Gerd , Lee Jean C. , Goldmann Donald A. , Pier Gerald B.
Published: July 2002

Vaccines based on preferential expression of bacterial antigens during human infection have not been described.
Staphylococcus aureus
synthesized poly-
N
-succinyl β-1-6 glucosamine (PNSG) as a surface polysaccharide during human and animal infection, but few strains expressed PNSG in vitro. All
S. aureus
strains examined carried genes for PNSG synthesis. Immunization protected mice against kidney infections and death from strains that produced little PNSG in vitro. Nonimmune infected animals made antibody to PNSG, but serial in vitro cultures of kidney isolates yielded mostly cells that did not produce PNSG. PNSG is a candidate for use in a vaccine to protect against
S. aureus
infection.
SHRIMP Uranium-Lead Dating of Diagenetic Xenotime in Siliciclastic Sedimentary Rocks
Authors: McNaughton Neal J. , Rasmussen Birger , Fletcher Ian R.
Published: July 2002

Diagenetic xenotime is common in siliciclastic sedimentary rocks, where it starts to form on detrital zircon shortly after sediment deposition. It is possible to estimate the age of sedimentary rocks by in situ uranium-lead analysis of that xenotime. Two Proterozoic sandstone units from northwestern Australia, previously constrained to the age interval of 1790 to 750 million years ago, have diagenetic xenotime ages of 1704 ± 7 and 1704 ± 14 million years ago. This method has potential for dating sedimentary sequences of all ages but should be especially valuable for refining the Precambrian time scale.
Ploidy Regulation of Gene Expression
Authors: Galitski Timothy , Saldanha Alok J. , Styles Cora A. , Lander Eric S. , Fink Gerald R.
Published: July 2002

Microarray-based gene expression analysis identified genes showing ploidy-dependent expression in isogenic
Saccharomyces cerevisiae
strains that varied in ploidy from haploid to tetraploid. These genes were induced or repressed in proportion to the number of chromosome sets, regardless of the mating type. Ploidy-dependent repression of some G
1
cyclins can explain the greater cell size associated with higher ploidies, and suggests ploidy-dependent modifications of cell cycle progression. Moreover, ploidy regulation of the
FLO11
gene had direct consequences for yeast development.
Requirement of Rsk-2 for Epidermal Growth Factor-Activated Phosphorylation of Histone H3
Authors: Sassone-Corsi Paolo , Mizzen Craig A. , Cheung Peter , Crosio Claudia , Monaco Lucia , Jacquot Sylvie , Hanauer André , Allis C. David
Published: July 2002

During the immediate-early response of mammalian cells to mitogens, histone H3 is rapidly and transiently phosphorylated by one or more unidentified kinases. Rsk-2, a member of the pp90rsk family of kinases implicated in growth control, was required for epidermal growth factor (EGF)–stimulated phosphorylation of H3.
RSK-2
mutations in humans are linked to Coffin-Lowry syndrome (CLS). Fibroblasts derived from a CLS patient failed to exhibit EGF-stimulated phosphorylation of H3, although H3 was phosphorylated during mitosis. Introduction of the wild-type
RSK-2
gene restored EGF-stimulated phosphorylation of H3 in CLS cells. In addition, disruption of the
RSK-2
gene by homologous recombination in murine embryonic stem cells abolished EGF-stimulated phosphorylation of H3. H3 appears to be a direct or indirect target of Rsk-2, suggesting that chromatin remodeling might contribute to mitogen-activated protein kinase–regulated gene expression.
Salt Tolerance Conferred by Overexpression of a Vacuolar Na
+
/H
+
Antiport in
Arabidopsis
Authors: Apse Maris P. , Aharon Gilad S. , Snedden Wayne A. , Blumwald Eduardo
Published: July 2002

Agricultural productivity is severely affected by soil salinity. One possible mechanism by which plants could survive salt stress is to compartmentalize sodium ions away from the cytosol. Overexpression of a vacuolar Na
+
/H
+
antiport from
Arabidopsis thaliana
in
Arabidopsis
plants promotes sustained growth and development in soil watered with up to 200 millimolar sodium chloride. This salinity tolerance was correlated with higher-than-normal levels of
AtNHX1
transcripts, protein, and vacuolar Na
+
/H
+
(sodium/proton) antiport activity. These results demonstrate the feasibility of engineering salt tolerance in plants.
Dual Function of the Selenoprotein PHGPx During Sperm Maturation
Authors: Ursini Fulvio , Heim Sabina , Kiess Michael , Maiorino Matilde , Roveri Antonella , Wissing Josef , Flohé Leopold
Published: July 2002

The selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) changes its physical characteristics and biological functions during sperm maturation. PHGPx exists as a soluble peroxidase in spermatids but persists in mature spermatozoa as an enzymatically inactive, oxidatively cross-linked, insoluble protein. In the midpiece of mature spermatozoa, PHGPx protein represents at least 50 percent of the capsule material that embeds the helix of mitochondria. The role of PHGPx as a structural protein may explain the mechanical instability of the mitochondrial midpiece that is observed in selenium deficiency.
Trends in the Vertical Distribution of Ozone
Authors: Randel William J. , Stolarski Richard S. , Cunnold Derek M. , Logan Jennifer A. , Newchurch M. J. , Zawodny Joseph M.
Published: July 2002

Analyses of satellite, ground-based, and balloon measurements allow updated estimates of trends in the vertical profile of ozone since 1979. The results show overall consistency among several independent measurement systems, particularly for northern hemisphere midlatitudes where most balloon and ground-based measurements are made. Combined trend estimates over these latitudes for the period 1979–96 show statistically significant negative trends at all altitudes between 10 and 45 km, with two local extremes: −7.4 ± 2.0% per decade at 40 km and −7.3 ± 4.6% per decade at 15 km altitude. There is a strong seasonal variation in trends over northern midlatitudes in the altitude range of 10 to 18 km, with the largest ozone loss during winter and spring. The profile trends are in quantitative agreement with independently measured trends in column ozone, the amount of ozone in a column above the surface. The vertical profiles of ozone trends provide a fingerprint for the mechanisms of ozone depletion over the last two decades.
Synergy Between Tumor Suppressor
APC
and the β-Catenin-Tcf4 Target
Tcf1
Authors: Roose Jeroen , Huls Gerwin , Beest Moniek van , Moerer Petra , Horn Karin van der , Goldschmeding Roel , Logtenberg Ton , Clevers Hans
Published: July 2002

Mutations in APC or β-catenin inappropriately activate the transcription factor Tcf4, thereby transforming intestinal epithelial cells. Here it is shown that one of the target genes of Tcf4 in epithelial cells is
Tcf1
. The most abundant Tcf1 isoforms lack a β-catenin interaction domain.
Tcf1
−/−
mice develop adenomas in the gut and mammary glands. Introduction of a mutant APC allele into these mice substantially increases the number of these adenomas. Tcf1 may act as a feedback repressor of β-catenin–Tcf4 target genes and thus may cooperate with APC to suppress malignant transformation of epithelial cells.
The Root of Angiosperm Phylogeny Inferred from Duplicate Phytochrome Genes
Authors: Mathews Sarah , Donoghue Michael J.
Published: July 2002

An analysis of duplicate phytochrome genes (
PHYA
and
PHYC
) is used to root the angiosperms, thereby avoiding the inclusion of highly diverged outgroup sequences. The results unambiguously place the root near
Amborella
(one species, New Caledonia) and resolve water lilies (Nymphaeales, ∼70 species, cosmopolitan), followed by
Austrobaileya
(one species, Australia), as early branches. These findings bear directly on the interpretation of morphological evolution and diversification within angiosperms.