bluuebunny/crossref_metadata_2025 huggingface dataset:
Stratospheric Harbingers of Anomalous Weather Regimes
Authors: Baldwin Mark P. , Dunkerton Timothy J.
Published: July 2002

Observations show that large variations in the strength of the stratospheric circulation, appearing first above ∼50 kilometers, descend to the lowermost stratosphere and are followed by anomalous tropospheric weather regimes. During the 60 days after the onset of these events, average surface pressure maps resemble closely the Arctic Oscillation pattern. These stratospheric events also precede shifts in the probability distributions of extreme values of the Arctic and North Atlantic Oscillations, the location of storm tracks, and the local likelihood of mid-latitude storms. Our observations suggest that these stratospheric harbingers may be used as a predictor of tropospheric weather regimes.
Erasing the World's Slow Stain: Strategies to Beat Multidrug-Resistant Tuberculosis
Authors: Dye Christopher , Williams Brian G. , Espinal Marcos A. , Raviglione Mario C.
Published: July 2002

Multidrug-resistant tuberculosis (MDR) is perceived as a growing hazard to human health worldwide. Judgments about the true scale of the problem, and strategies for containing it, need to come from a balanced appraisal of the epidemiological evidence. We conclude in this review that MDR is, and will probably remain, a locally severe problem; that epidemics can be prevented by fully exploiting the potential of standard short-course chemotherapy (SCC) based on cheap and safe first-line drugs; and that best-practice SCC may even reduce the incidence of MDR where it has already become endemic. On the basis of the available, imperfect data, we recommend a three-part response to the threat of MDR: widespread implementation of SCC as the cornerstone of good tuberculosis control, improved resistance testing and surveillance, and the careful introduction of second-line drugs after a sound evaluation of cost, effectiveness, and feasibility.
An Apolipoprotein Influencing Triglycerides in Humans and Mice Revealed by Comparative Sequencing
Authors: Pennacchio Len A. , Olivier Michael , Hubacek Jaroslav A. , Cohen Jonathan C. , Cox David R. , Fruchart Jean-Charles , Krauss Ronald M. , Rubin Edward M.
Published: July 2002

Comparison of genomic DNA sequences from human and mouse revealed a new apolipoprotein (APO) gene (
APOAV
) located proximal to the well-characterized
APOAI/CIII/AIV
gene cluster on human 11q23. Mice expressing a human
APOAV
transgene showed a decrease in plasma triglyceride concentrations to one-third of those in control mice; conversely, knockout mice lacking
Apoav
had four times as much plasma triglycerides as controls. In humans, single nucleotide polymorphisms (SNPs) across the
APOAV
locus were found to be significantly associated with plasma triglyceride levels in two independent studies. These findings indicate that APOAV is an important determinant of plasma triglyceride levels, a major risk factor for coronary artery disease.
Computer Networks As Social Networks
Authors: Wellman Barry
Published: July 2002

Computer networks are inherently social networks, linking people, organizations, and knowledge. They are social institutions that should not be studied in isolation but as integrated into everyday lives. The proliferation of computer networks has facilitated a deemphasis on group solidarities at work and in the community and afforded a turn to networked societies that are loosely bounded and sparsely knit. The Internet increases people's social capital, increasing contact with friends and relatives who live nearby and far away. New tools must be developed to help people navigate and find knowledge in complex, fragmented, networked societies.
Phosphatidic Acid-Mediated Mitogenic Activation of mTOR Signaling
Authors: Fang Yimin , Vilella-Bach Montserrat , Bachmann Rebecca , Flanigan Asa , Chen Jie
Published: July 2002

The mammalian target of rapamycin (mTOR) governs cell growth and proliferation by mediating the mitogen- and nutrient-dependent signal transduction that regulates messenger RNA translation. We identified phosphatidic acid (PA) as a critical component of mTOR signaling. In our study, mitogenic stimulation of mammalian cells led to a phospholipase D–dependent accumulation of cellular PA, which was required for activation of mTOR downstream effectors. PA directly interacted with the domain in mTOR that is targeted by rapamycin, and this interaction was positively correlated with mTOR's ability to activate downstream effectors. The involvement of PA in mTOR signaling reveals an important function of this lipid in signal transduction and protein synthesis, as well as a direct link between mTOR and mitogens. Furthermore, these studies suggest a potential mechanism for the in vivo actions of the immunosuppressant rapamycin.
The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses
Authors: Kandel Eric R.
Published: July 2002

One of the most remarkable aspects of an animal's behavior is the ability to modify that behavior by learning, an ability that reaches its highest form in human beings. For me, learning and memory have proven to be endlessly fascinating mental processes because they address one of the fundamental features of human activity: our ability to acquire new ideas from experience and to retain these ideas over time in memory. Moreover, unlike other mental processes such as thought, language, and consciousness, learning seemed from the outset to be readily accessible to cellular and molecular analysis. I, therefore, have been curious to know: What changes in the brain when we learn? And, once something is learned, how is that information retained in the brain? I have tried to address these questions through a reductionist approach that would allow me to investigate elementary forms of learning and memory at a cellular molecular level—as specific molecular activities within identified nerve cells.
Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations
Authors: Coussens Lisa M. , Fingleton Barbara , Matrisian Lynn M.
Published: July 2002

For at least 30 years, matrix metalloproteinases (MMPs) have been heralded as promising targets for cancer therapy on the basis of their massive up-regulation in malignant tissues and their unique ability to degrade all components of the extracellular matrix. Preclinical studies testing the efficacy of MMP suppression in tumor models were so compelling that synthetic metalloproteinase inhibitors (MPIs) were rapidly developed and routed into human clinical trials. The results of these trials have been disappointing. Here we review the studies that brought MPIs into clinical testing and discuss the design and outcome of the trials in light of new information about the cellular source, substrates, and mode of action of MMPs at different stages of tumor progression. The important lessons learned from the MPI experience may be of great value for future studies of MPIs and for cancer drug development in general.
Niobium-Zirconium Chronometry and Early Solar System Development
Authors: Schönbächler Maria , Rehkämper Mark , Halliday Alex N. , Lee Der-Chuen , Bourot-Denise Michèle , Zanda Brigitte , Hattendorf Bodo , Günther Detlef
Published: July 2002

Niobium-92 (92Nb) decays to zirconium-92 (92Zr) with a half-life of 36 million years and can be used to place constraints on the site ofp-process nucleosynthesis and the timing of early solar system processes. Recent results have suggested that the initial92Nb/93Nb of the solar system was high (>10−3). We report Nb-Zr internal isochrons for the ordinary chondrite Estacado (H6) and a clast of the mesosiderite Vaca Muerta, both of which define an initial92Nb/93Nb ratio of ∼10−5. Therefore, the solar system appears to have started with a ratio of <3 × 10−5, which implies that Earth's initial differentiation need not have been as protracted as recently suggested.
Induction of T Helper Type 2 Immunity by a Point Mutation in the LAT Adaptor
Authors: Aguado Enrique , Richelme Sylvie , Nuñez-Cruz Selene , Miazek Arkadiusz , Mura Anne-Marie , Richelme Mireille , Guo Xiao-Jun , Sainty Danielle , He Hai-Tao , Malissen Bernard , Malissen Marie
Published: July 2002

The transmembrane protein LAT (linker for activation of T cells) couples the T cell receptor (TCR) to downstream signaling effectors. Mice homozygous for a mutation of a single LAT tyrosine residue showed impeded T cell development. However, later they accumulated polyclonal helper T (T
H
) cells that chronically produced type 2 cytokines in large amounts. This exaggerated T
H
2 differentiation caused tissue eosinophilia and massive maturation of plasma cells secreting to immunoglobulins of the E and G1 isotypes. This paradoxical phenotype establishes an unanticipated inhibitory function for LAT that is critical for the differentiation and homeostasis of T
H
cells.
Fabrication of a Cylindrical Display by Patterned Assembly
Authors: Jacobs Heiko O. , Tao Andrea R. , Schwartz Alexander , Gracias David H. , Whitesides George M.
Published: July 2002

We demonstrate the patterned assembly of integrated semiconductor devices onto planar, flexible, and curved substrates on the basis of capillary interactions involving liquid solder. The substrates presented patterned, solder-coated areas that acted both as receptors for the components of the device during its assembly and as electrical connections during its operation. The components were suspended in water and agitated gently. Minimization of the free energy of the solder-water interface provided the driving force for the assembly. One hundred and thirteen GaAlAs light-emitting diodes with a chip size of 280 micrometers were fabricated into a prototype cylindrical display. It was also possible to assemble 1500 silicon cubes, on an area of 5 square centimeters, in less than 3 minutes, with a defect rate of ∼2%.
Tissue Engineering--Current Challenges and Expanding Opportunities
Authors: Griffith Linda G. , Naughton Gail
Published: July 2002

Tissue engineering can be used to restore, maintain, or enhance tissues and organs. The potential impact of this field, however, is far broader—in the future, engineered tissues could reduce the need for organ replacement, and could greatly accelerate the development of new drugs that may cure patients, eliminating the need for organ transplants altogether.
Melanopsin-Containing Retinal Ganglion Cells: Architecture, Projections, and Intrinsic Photosensitivity
Authors: Hattar S. , Liao H.-W. , Takao M. , Berson D. M. , Yau K.-W.
Published: July 2002

The primary circadian pacemaker, in the suprachiasmatic nucleus (SCN) of the mammalian brain, is photoentrained by light signals from the eyes through the retinohypothalamic tract. Retinal rod and cone cells are not required for photoentrainment. Recent evidence suggests that the entraining photoreceptors are retinal ganglion cells (RGCs) that project to the SCN. The visual pigment for this photoreceptor may be melanopsin, an opsin-like protein whose coding messenger RNA is found in a subset of mammalian RGCs. By cloning rat melanopsin and generating specific antibodies, we show that melanopsin is present in cell bodies, dendrites, and proximal axonal segments of a subset of rat RGCs. In mice heterozygous for tau-lacZ targeted to the melanopsin gene locus, β-galactosidase–positive RGC axons projected to the SCN and other brain nuclei involved in circadian photoentrainment or the pupillary light reflex. Rat RGCs that exhibited intrinsic photosensitivity invariably expressed melanopsin. Hence, melanopsin is most likely the visual pigment of phototransducing RGCs that set the circadian clock and initiate other non–image-forming visual functions.
A Phase Separation Model for the Nanopatterning of Diatom Biosilica
Authors: Sumper Manfred
Published: July 2002

Diatoms are encased in an intricately patterned wall that consists of amorphous silica. Species-specific fabrication of this ornate biomineral enables taxonomists to identify thousands of diatom species. The molecular mechanisms that control this nanofabrication and generate the diversity of patterns is not well understood. A simple model is described, in which repeated phase separation events during wall biogenesis are assumed to produce self-similar silica patterns in smaller and smaller scales. On the basis of this single assumption, the apparently complex patterns found in the valves of the diatom genus
Coscinodiscus
can be predicted. Microscopic analysis of valves in statu nascendi from three different
Coscinodiscus
species supports the conclusions derived from the model.
The Origin of Cu/Au Ratios in Porphyry-Type Ore Deposits
Authors: Halter Werner E. , Pettke Thomas , Heinrich Christoph A.
Published: July 2002

Microanalysis of major and trace elements in sulfide and silicate melt inclusions by laser-ablation inductively coupled plasma mass spectrometry indicates a direct link between a magmatic sulfide liquid and the composition of porphyry-type ore deposits. Copper (Cu), gold (Au), and iron (Fe) are first concentrated in a sulfide melt during magmatic evolution and then released to an ore-forming hydrothermal fluid exsolved late in the history of a magma chamber. The composition of sulfide liquids depends on the initial composition and source of the magma, but it also changes during the evolution of the magma in the crust. Magmatic sulfide melts may exert the dominant direct control on the economic metal ratios of porphyry-type ore deposits.
Self-Representation in Nervous Systems
Authors: Churchland Patricia S.
Published: July 2002

The brain's earliest self-representational capacities arose as evolution found neural network solutions for coordinating and regulating inner-body signals, thereby improving behavioral strategies. Additional flexibility in organizing coherent behavioral options emerges from neural models that represent some of the brain's inner states as states of its body, while representing other signals as perceptions of the external world. Brains manipulate inner models to predict the distinct consequences in the external world of distinct behavioral options. The self thus turns out to be identifiable not with a nonphysical soul, but rather with a set of representational capacities of the physical brain.
Direct Recognition of Cytomegalovirus by Activating and Inhibitory NK Cell Receptors
Authors: Arase Hisashi , Mocarski Edward S. , Campbell Ann E. , Hill Ann B. , Lanier Lewis L.
Published: July 2002

Natural killer (NK) cells express inhibitory receptors for major histocompatibility complex (MHC) class I antigens, preventing attack against healthy cells. Mouse cytomegalovirus (MCMV) encodes an MHC-like protein (m157) that binds to an inhibitory NK cell receptor in certain MCMV-susceptible mice. In MCMV-resistant mice, this viral protein engages a related activating receptor (Ly49H) and confers host protection. These activating and inhibitory receptors are highly homologous, suggesting the possibility that one evolved from the other in response to selective pressure imposed by the pathogen.
How Did Replicating and Coding RNAs First Get Together?
Authors: Robertson Hugh D.
Published: July 2002

The RNA that codes for the delta hepatitis virus is made up of two parts: one that is like RNA viroids and one like a protein-coding sequence. In his Perspective, Robertson discusses the new findings by Brazas and Ganem (
p. 90
) in this issue of
Science
that there is a protein in liver cells that is strikingly like the protein coded for by the “protein-coding” part of the delta RNA. This leads Roberston to propose that this part of the delta RNA may have been “captured” from a normal cell, perhaps in the early prebiotic world, by the viroidlike RNA and might also explain the origin of introns.
Quantitative Image Analysis of HIV-1 Infection in Lymphoid Tissue
Authors: Haase Ashley T. , Henry Keith , Zupancic Mary , Sedgewick Gerald , Faust Russell A. , Melroe Holly , Cavert Winston , Gebhard Kristin , Staskus Katherine , Zhang Zhi-Qiang , Dailey Peter J. , Balfour Henry H. , Erice Alejo , Perelson Alan S.
Published: July 2002

Tracking human immunodeficiency virus-type 1 (HIV-1) infection at the cellular level in tissue reservoirs provides opportunities to better understand the pathogenesis of infection and to rationally design and monitor therapy. A quantitative technique was developed to determine viral burden in two important cellular compartments in lymphoid tissues. Image analysis and in situ hybridization were combined to show that in the presymptomatic stages of infection there is a large, relatively stable pool of virions on the surfaces of follicular dendritic cells and a smaller pool of productively infected cells. Despite evidence of constraints on HIV-1 replication in the infected cell population in lymphoid tissues, estimates of the numbers of these cells and the virus they could produce are consistent with the quantities of virus that have been detected in the bloodstream. The cellular sources of virus production and storage in lymphoid tissues can now be studied with this approach over the course of infection and treatment.
Bright Spots, Structure, and Magmatism in Southern Tibet from INDEPTH Seismic Reflection Profiling
Authors: Brown L. D. , Zhao Wenjin , Nelson K. D. , Hauck M. , Alsdorf D. , Ross A. , Cogan M. , Clark M. , Liu Xianwen , Che Jinkai
Published: July 2002

INDEPTH seismic reflection profiling shows that the decollement beneath which Indian lithosphere underthrusts the Himalaya extends at least 225 kilometers north of the Himalayan deformation front to a depth of ∼50 kilometers. Prominent reflections appear at depths of 15 to 18 kilometers near where the decollement reflector apparently terminates. These reflections extend north of the Zangbo suture to the Damxung graben of the Tibet Plateau. Some of these reflections have locally anomalous amplitudes (bright spots) and coincident negative polarities implying that they are produced by fluids in the crust. The presence of geothermal activity and high heat flow in the regions of these reflections and the tectonic setting suggest that the bright spots mark granitic magmas derived by partial melting of the tectonically thickened crust.
Inhibition of Adipogenesis Through MAP Kinase-Mediated Phosphorylation of PPARγ
Authors: Hu Erding , Kim Jae Bum , Sarraf Pasha , Spiegelman Bruce M.
Published: July 2002

Adipocyte differentiation is an important component of obesity and other metabolic diseases. This process is strongly inhibited by many mitogens and oncogenes. Several growth factors that inhibit fat cell differentiation caused mitogen-activated protein (MAP) kinase-mediated phosphorylation of the dominant adipogenic transcription factor peroxisome proliferator-activated receptor γ (PPARγ) and reduction of its transcriptional activity. Expression of PPARγ with a nonphosphorylatable mutation at this site (serine-112) yielded cells with increased sensitivity to ligand-induced adipogenesis and resistance to inhibition of differentiation by mitogens. These results indicate that covalent modification of PPARγ by serum and growth factors is a major regulator of the balance between cell growth and differentiation in the adipose cell lineage.
Activation of Interferon-γ Inducing Factor Mediated by Interleukin-1β Converting Enzyme
Authors: Gu Yong , Kuida Keisuke , Tsutsui Hiroko , Ku George , Hsiao Kathy , Fleming Mark A. , Hayashi Nobuki , Higashino Kazuya , Okamura Haruki , Nakanishi Kenji , Kurimoto Masashi , Tanimoto Tadao , Flavell Richard A. , Sato Vicki , Harding Matthew W. , Livingston David J. , Su Michael S.-S.
Published: July 2002

The interleukin-1β (IL-1β) converting enzyme (ICE) processes the inactive IL-1β precursor to the proinflammatory cytokine. ICE was also shown to cleave the precursor of interferon-γ inducing factor (IGIF) at the authentic processing site with high efficiency, thereby activating IGIF and facilitating its export. Lipopolysaccharide-activated ICE-deficient (ICE
−/−
) Kupffer cells synthesized the IGIF precursor but failed to process it into the active form. Interferon-γ and IGIF were diminished in the sera of ICE
−/−
mice exposed to
Propionibacterium acnes
and lipopolysaccharide. The lack of multiple proinflammatory cytokines in ICE
−/−
mice may account for their protection from septic shock.
Circadian Rhythms in Rapidly Dividing Cyanobacteria
Authors: Kondo Takao , Mori Tetsuya , Lebedeva Nadya V. , Aoki Setsuyuki , Ishiura Masahiro , Golden Susan S.
Published: July 2002

The long-standing supposition that the biological clock cannot function in cells that divide more rapidly than the circadian cycle was investigated. During exponential growth in which the generation time was 10 hours, the profile of bioluminescence from a reporter strain of the cyanobacterium
Synechococcus
(species PCC 7942) matched a model based on the assumption that cells proliferate exponentially and the bioluminescence of each cell oscillates in a cosine fashion. Some messenger RNAs showed a circadian rhythm in abundance during continuous exponential growth with a doubling time of 5 to 6 hours. Thus, the cyanobacterial circadian clock functions in cells that divide three or more times during one circadian cycle.
Chaotic Dynamics in an Insect Population
Authors: Costantino R. F. , Desharnais R. A. , Cushing J. M. , Dennis Brian
Published: July 2002

A nonlinear demographic model was used to predict the population dynamics of the flour beetleTriboliumunder laboratory conditions and to establish the experimental protocol that would reveal chaotic behavior. With the adult mortality rate experimentally set high, the dynamics of animal abundance changed from equilibrium to quasiperiodic cycles to chaos as adult-stage recruitment rates were experimentally manipulated. These transitions in dynamics corresponded to those predicted by the mathematical model. Phase-space graphs of the data together with the deterministic model attractors provide convincing evidence of transitions to chaos.
Transmission of the BSE Agent to Mice in the Absence of Detectable Abnormal Prion Protein
Authors: Lasmézas Corinne I. , Deslys Jean-Philippe , Robain Olivier , Jaegly Alexandre , Beringue Vincent , Peyrin Jean-Michel , Fournier Jean-Guy , Hauw Jean-Jacques , Rossier Jean , Dormont Dominique
Published: July 2002

The agent responsible for transmissible spongiform encephalopathies (TSEs) is thought to be a malfolded, protease-resistant version (PrPres) of the normal cellular prion protein (PrP). The interspecies transmission of bovine spongiform encephalopathy (BSE) to mice was studied. Although all of the mice injected with homogenate from BSE-infected cattle brain exhibited neurological symptoms and neuronal death, more than 55 percent had no detectable PrPres. During serial passage, PrPres appeared after the agent became adapted to the new host. Thus, PrPres may be involved in species adaptation, but a further unidentified agent may actually transmit BSE.
Modeling the Exchanges of Energy, Water, and Carbon Between Continents and the Atmosphere
Authors: Sellers P. J. , Dickinson R. E. , Randall D. A. , Betts A. K. , Hall F. G. , Berry J. A. , Collatz G. J. , Denning A. S. , Mooney H. A. , Nobre C. A. , Sato N. , Field C. B. , Henderson-Sellers A.
Published: July 2002

Atmospheric general circulation models used for climate simulation and weather forecasting require the fluxes of radiation, heat, water vapor, and momentum across the land-atmosphere interface to be specified. These fluxes are calculated by submodels called land surface parameterizations. Over the last 20 years, these parameterizations have evolved from simple, unrealistic schemes into credible representations of the global soil-vegetation-atmosphere transfer system as advances in plant physiological and hydrological research, advances in satellite data interpretation, and the results of large-scale field experiments have been exploited. Some modern schemes incorporate biogeochemical and ecological knowledge and, when coupled with advanced climate and ocean models, will be capable of modeling the biological and physical responses of the Earth system to global change, for example, increasing atmospheric carbon dioxide.
Detection and Characterization of the Cumulene Carbenes H
2
C
5
and H
2
C
6
Authors: McCarthy M. C. , Travers M. J. , Kovács A. , Chen Wei , Novick Stewart E. , Gottlieb C. A. , Thaddeus P.
Published: July 2002

Two cumulene carbenes, H
2
C
5
and H
2
C
6
, were detected in a supersonic molecular beam by Fourier transform microwave spectroscopy. Their rotational and leading centrifugal distortion constants were determined with high accuracy, such that the entire radio spectrum can now be calculated. Like the known carbenes H
2
C
3
and H
2
C
4
, both molecules have singlet electronic ground states and linear carbon-chain backbones. They can be produced in sufficiently high concentrations in the laboratory that their electronic spectra, expected to lie in the visible, should be readily detectable by laser spectroscopy. The microwave spectra of other, more exotic isomers may be detectable as well.
Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering
Authors: Nie Shuming , Emory Steven R.
Published: July 2002

Optical detection and spectroscopy of single molecules and single nanoparticles have been achieved at room temperature with the use of surface-enhanced Raman scattering. Individual silver colloidal nanoparticles were screened from a large heterogeneous population for special size-dependent properties and were then used to amplify the spectroscopic signatures of adsorbed molecules. For single rhodamine 6G molecules adsorbed on the selected nanoparticles, the intrinsic Raman enhancement factors were on the order of 10
14
to 10
15
, much larger than the ensemble-averaged values derived from conventional measurements. This enormous enhancement leads to vibrational Raman signals that are more intense and more stable than single-molecule fluorescence.
Muscular Force in Running Turkeys: The Economy of Minimizing Work
Authors: Roberts Thomas J. , Marsh Richard L. , Weyand Peter G. , Taylor C. Richard
Published: July 2002

During running, muscles and tendons must absorb and release mechanical work to maintain the cyclic movements of the body and limbs, while also providing enough force to support the weight of the body. Direct measurements of force and fiber length in the lateral gastrocnemius muscle of running turkeys revealed that the stretch and recoil of tendon and muscle springs supply mechanical work while active muscle fibers produce high forces. During level running, the active muscle shortens little and performs little work but provides the force necessary to support body weight economically. Running economy is improved by muscles that act as active struts rather than working machines.
A Neural Substrate of Prediction and Reward
Authors: Schultz Wolfram , Dayan Peter , Montague P. Read
Published: July 2002

The capacity to predict future events permits a creature to detect, model, and manipulate the causal structure of its interactions with its environment. Behavioral experiments suggest that learning is driven by changes in the expectations about future salient events such as rewards and punishments. Physiological work has recently complemented these studies by identifying dopaminergic neurons in the primate whose fluctuating output apparently signals changes or errors in the predictions of future salient and rewarding events. Taken together, these findings can be understood through quantitative theories of adaptive optimizing control.
Tyrosine Phosphorylation of Transmembrane Ligands for Eph Receptors
Authors: Brückner Katja , Pasquale Elena B. , Klein Rüdiger
Published: July 2002

Axonal pathfinding in the nervous system is mediated in part by cell-to-cell signaling events involving members of the Eph receptor tyrosine kinase (RTK) family and their membrane-bound ligands. Genetic evidence suggests that transmembrane ligands may transduce signals in the developing embryo. The cytoplasmic domain of the transmembrane ligand Lerk2 became phosphorylated on tyrosine residues after contact with the Nuk/Cek5 receptor ectodomain, which suggests that Lerk2 has receptorlike intrinsic signaling potential. Moreover, Lerk2 is an in vivo substrate for the platelet-derived growth factor receptor, which suggests crosstalk between Lerk2 signaling and signaling cascades activated by tyrosine kinases. It is proposed that transmembrane ligands of Eph receptors act not only as conventional RTK ligands but also as receptorlike signaling molecules.
Attentional Activation of the Cerebellum Independent of Motor Involvement
Authors: Allen Greg , Buxton Richard B. , Wong Eric C. , Courchesne Eric
Published: July 2002

The cerebellum traditionally has been viewed as a neural device dedicated to motor control. Although recent evidence shows that it is involved in nonmotor operations as well, an important question is whether this involvement is independent of motor control and motor guidance. Functional magnetic resonance imaging was used to demonstrate that attention and motor performance independently activate distinct cerebellar regions. These findings support a broader concept of cerebellar function, in which the cerebellum is involved in diverse cognitive and noncognitive neurobehavioral systems, including the attention and motor systems, in order to anticipate imminent information acquisition, analysis, or action.
Tropospheric Air Pollution: Ozone, Airborne Toxics, Polycyclic Aromatic Hydrocarbons, and Particles
Authors: Finlayson-Pitts Barbara J. , Pitts James N.
Published: July 2002

Tropospheric air pollution has impacts on scales ranging from local to global. Reactive intermediates in the oxidation of mixtures of volatile organic compounds (VOCs) and oxides of nitrogen (NO
x
) play central roles: the hydroxyl radical (OH), during the day; the nitrate radical (NO
3
), at night; and ozone (O
3
), which contributes during the day and night. Halogen atoms can also play a role during the day. Here the implications of the complex VOC-NO
x
chemistry for O
3
control are discussed. In addition, OH, NO
3
, and O
3
are shown to play a central role in the formation and fate of airborne toxic chemicals, mutagenic polycyclic aromatic hydrocarbons, and fine particles.
A Similarity Between Viral Defense and Gene Silencing in Plants
Authors: Ratcliff Frank , Harrison Bryan D. , Baulcombe David C.
Published: July 2002

Gene silencing in plants, in which an endogenous gene is suppressed by introduction of a related transgene, has been used for crop improvement. Observations that viruses are potentially both initiators and targets of gene silencing suggested that this phenomenon may be related to natural defense against viruses. Supporting this idea, it was found that nepovirus infection of nontransgenic plants induces a resistance mechanism that is similar to transgene-induced gene silencing.
Regulatory Phosphorylation of AMPA-Type Glutamate Receptors by CaM-KII During Long-Term Potentiation
Authors: Barria Andres , Muller Dominique , Derkach Victor , Griffith Leslie C. , Soderling Thomas R.
Published: July 2002

Long-term potentiation (LTP), a cellular model of learning and memory, requires calcium-dependent protein kinases. Induction of LTP increased the phosphorus-32 labeling of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)–type glutamate receptors (AMPA-Rs), which mediate rapid excitatory synaptic transmission. This AMPA-R phosphorylation appeared to be catalyzed by Ca2+- and calmodulin-dependent protein kinase II (CaM-KII): (i) it correlated with the activation and autophosphorylation of CaM-KII, (ii) it was blocked by the CaM-KII inhibitor KN-62, and (iii) its phosphorus-32 peptide map was the same as that of GluR1 coexpressed with activated CaM-KII in HEK-293 cells. This covalent modulation of AMPA-Rs in LTP provides a postsynaptic molecular mechanism for synaptic plasticity.
Forests as Human-Dominated Ecosystems
Authors: Noble Ian R. , Dirzo Rodolfo
Published: July 2002

Forests are human-dominated ecosystems. Many of the seemingly lightly managed or unmanaged forests are actually in use for agroforestry or for hunting and gathering. Agroforestry does reduce biodiversity, but it can also act as an effective buffer to forest clearance and conversion to other land uses, which present the greatest threat to forested ecosystems. In forests used for logging, whole-landscape management is crucial. Here, emphasis is placed on areas of intensive use interspersed with areas for conservation and catchment purposes. Management strategies for sustainable forestry are being developed, but there is a need for further interaction among foresters, ecologists, community representatives, social scientists, and economists.
The Influence of Functional Diversity and Composition on Ecosystem Processes
Authors: Tilman David , Knops Johannes , Wedin David , Reich Peter , Ritchie Mark , Siemann Evan
Published: July 2002

Humans are modifying both the identities and numbers of species in ecosystems, but the impacts of such changes on ecosystem processes are controversial. Plant species diversity, functional diversity, and functional composition were experimentally varied in grassland plots. Each factor by itself had significant effects on many ecosystem processes, but functional composition and functional diversity were the principal factors explaining plant productivity, plant percent nitrogen, plant total nitrogen, and light penetration. Thus, habitat modifications and management practices that change functional diversity and functional composition are likely to have large impacts on ecosystem processes.
Binding of Neuroligins to PSD-95
Authors: Irie M. , Hata Y. , Takeuchi M. , Ichtchenko K. , Toyoda A. , Hirao K. , Takai Y. , Rosahl T. W. , Südhof T. C.
Published: July 2002

PSD-95 is a component of postsynaptic densities in central synapses. It contains three PDZ domains that localize
N
-methyl-
d
-aspartate receptor subunit 2 (NMDA2 receptor) and K
+
channels to synapses. In mouse forebrain, PSD-95 bound to the cytoplasmic COOH-termini of neuroligins, which are neuronal cell adhesion molecules that interact with β-neurexins and form intercellular junctions. Neuroligins bind to the third PDZ domain of PSD-95, whereas NMDA2 receptors and K
+
channels interact with the first and second PDZ domains. Thus different PDZ domains of PSD-95 are specialized for distinct functions. PSD-95 may recruit ion channels and neurotransmitter receptors to intercellular junctions formed between neurons by neuroligins and β-neurexins.
Measurements of the Cretaceous Paleolatitude of Vancouver Island: Consistent with the Baja-British Columbia Hypothesis
Authors: Ward Peter D. , Hurtado José M. , Kirschvink Joseph L. , Verosub Kenneth L.
Published: July 2002

A previously unsampled outcrop of gently dipping or flat-lying Upper Cretaceous sedimentary strata in the Vancouver Island region, which contains unaltered aragonitic mollusk fossils, yielded a stable remanent magnetization that is biostratigraphically consistent with Cretaceous magnetochrons 33R, 33N, and 32R. These results, characterized by shallow inclinations, indicate an Upper Cretaceous paleolatitude of about 25 ± 3 degrees north, which is equivalent to that of modern-day Baja California. These findings are consistent with the Baja–British Columbia hypothesis, which puts the Insular Superterrane well south of the Oregon-California border in the Late Cretaceous.
Increased Compressibility of Pseudobrookite-Type MgTi2O5Caused by Cation Disorder
Authors: Hazen Robert M. , Yang Hexiong
Published: July 2002

Compressibilities were determined for four pseudobrookite-type magnesium titanate (MgTi2O5) samples with different degrees of Mg-Ti disorder. Compressibilities ofaandcaxes in disordered MgTi2O5were 10% and 7% greater, respectively, than those of a relatively ordered sample. The estimated bulk moduli for fully ordered and disordered MgTi2O5are 167 ± 1 and 158 ± 1 gigapascals, respectively. This difference is an order of magnitude greater than that predicted by bulk modulus–volume systematics. Cation order, in addition to composition and structure information, is thus important when documenting the elasticity of crystalline phases. Elastic constants of mantle silicates that are subject to pressure-induced cation ordering must be reevaluated.
Implications of Satellite OH Observations for Middle Atmospheric H
2
O and Ozone
Authors: Summers M. E. , Conway R. R. , Siskind D. E. , Stevens M. H. , Offermann D. , Riese M. , Preusse P. , Strobel D. F. , Russell J. M.
Published: July 2002

Satellite observations by the Middle Atmosphere High Resolution Spectrograph Investigation (MAHRSI) have produced global measurements of hydroxyl (OH) in the atmosphere. These observations reveal a sharp peak in OH density near an altitude of 65 to 70 km and are thus consistent with observations from the Halogen Occultation Experiment (HALOE) on the NASA Upper Atmosphere Research Satellite (UARS), which showed an unexplained H
2
O layer at the same level. Analysis of stratopause (about 50 kilometers) OH measurements and coincident ozone observations from the Cryogenic Infrared Spectrometers and Telescopes for the Atmosphere (CRISTA) experiment reveals that the catalytic loss of ozone attributable to odd-hydrogen chemistry is less than that predicted with standard chemistry. Thus, the dominant portion of the ozone deficit problem in standard models is a consequence of overestimation of the OH density in the upper stratosphere and lower mesosphere.
Phosphorylation of Sic1p by G
1
Cdk Required for Its Degradation and Entry into S Phase
Authors: Verma R. , Annan R. S. , Huddleston M. J. , Carr S. A. , Reynard G. , Deshaies R. J.
Published: July 2002

G
1
cyclin-dependent kinase (Cdk)–triggered degradation of the S-phase Cdk inhibitor Sic1p has been implicated in the transition from G
1
to S phase in the cell cycle of budding yeast. A multidimensional electrospray mass spectrometry technique was used to map G
1
Cdk phosphorylation sites in Sic1p both in vitro and in vivo. A Sic1p mutant lacking three Cdk phosphorylation sites did not serve as a substrate for Cdc34p-dependent ubiquitination in vitro, was stable in vivo, and blocked DNA replication. Moreover, purified phosphoSic1p was ubiquitinated in cyclin-depleted G
1
extract, indicating that a primary function of G
1
cyclins is to tag Sic1p for destruction. These data suggest a molecular model of how phosphorylation and proteolysis cooperate to bring about the G
1
/S transition in budding yeast.
Regulation of Gliogenesis in the Central Nervous System by the JAK-STAT Signaling Pathway
Authors: Bonni Azad , Sun Yi , Nadal-Vicens Mireya , Bhatt Ami , Frank David A. , Rozovsky Irina , Stahl Neil , Yancopoulos George D. , Greenberg Michael E.
Published: July 2002

A mechanism by which members of the ciliary neurotrophic factor (CNTF)–leukemia inhibitory factor cytokine family regulate gliogenesis in the developing mammalian central nervous system was characterized. Activation of the CNTF receptor promoted differentiation of cerebral cortical precursor cells into astrocytes and inhibited differentiation of cortical precursors along a neuronal lineage. Although CNTF stimulated both the Janus kinase–signal transducer and activator of transcription (JAK-STAT) and Ras–mitogen-activated protein kinase signaling pathways in cortical precursor cells, the JAK-STAT signaling pathway selectively enhanced differentiation of these precursors along a glial lineage. These findings suggest that cytokine activation of the JAK-STAT signaling pathway may be a mechanism by which cell fate is controlled during mammalian development.
Interleukin-3-Induced Phosphorylation of BAD Through the Protein Kinase Akt
Authors: Peso Luis del , González-Garcı́a Maribel , Page Carmen , Herrera Román , Nuñez Gabriel
Published: July 2002

BAD is a distant member of the Bcl-2 family that promotes cell death. Phosphorylation of BAD prevents this. BAD phosphorylation induced by interleukin-3 (IL-3) was inhibited by specific inhibitors of phosphoinositide 3-kinase (PI 3-kinase). Akt, a survival-promoting serine-threonine protein kinase, was activated by IL-3 in a PI 3-kinase–dependent manner. Active, but not inactive, forms of Akt were found to phosphorylate BAD in vivo and in vitro at the same residues that are phosphorylated in response to IL-3. Thus, the proapoptotic function of BAD is regulated by the PI 3-kinase–Akt pathway.
Belated Decision in the Hilbert-Einstein Priority Dispute
Authors: Corry Leo , Renn Jürgen , Stachel John
Published: July 2002

According to the commonly accepted view, David Hilbert completed the general theory of relativity at least 5 days before Albert Einstein submitted his conclusive paper on this theory on 25 November 1915. Hilbert's article, bearing the date of submission 20 November 1915 but published only on 31 March 1916, presents a generally covariant theory of gravitation, including field equations essentially equivalent to those in Einstein's paper. A close analysis of archival material reveals that Hilbert did not anticipate Einstein. The first set of proofs of Hilbert's paper shows that the theory he originally submitted is not generally covariant and does not include the explicit form of the field equations of general relativity.
Nuclear Accumulation of NFAT4 Opposed by the JNK Signal Transduction Pathway
Authors: Chow Chi-Wing , Rincón Mercedes , Cavanagh Julie , Dickens Martin , Davis Roger J.
Published: July 2002

The nuclear factor of activated T cells (NFAT) group of transcription factors is retained in the cytoplasm of quiescent cells. NFAT activation is mediated in part by induced nuclear import. This process requires calcium-dependent dephosphorylation of NFAT caused by the phosphatase calcineurin. The c-Jun amino-terminal kinase (JNK) phosphorylates NFAT4 on two sites. Mutational removal of the JNK phosphorylation sites caused constitutive nuclear localization of NFAT4. In contrast, JNK activation in calcineurin-stimulated cells caused nuclear exclusion of NFAT4. These findings show that the nuclear accumulation of NFAT4 promoted by calcineurin is opposed by the JNK signal transduction pathway.
Arabidopsis
NPH1: A Protein Kinase with a Putative Redox-Sensing Domain
Authors: Huala Eva , Oeller Paul W. , Liscum Emmanuel , Han In-Seob , Larsen Elise , Briggs Winslow R.
Published: July 2002

The
NPH1
(nonphototropic hypocotyl 1) gene encodes an essential component acting very early in the signal-transduction chain for phototropism.
Arabidopsis NPH1
contains a serine-threonine kinase domain and LOV1 and LOV2 repeats that share similarity (36 to 56 percent) with
Halobacterium salinarium
Bat,
Azotobacter vinelandii
NIFL,
Neurospora crassa
White Collar–1,
Escherichia coli
Aer, and the Eag family of potassium-channel proteins from
Drosophila
and mammals. Sequence similarity with a known (NIFL) and a suspected (Aer) flavoprotein suggests that NPH1 LOV1 and LOV2 may be flavin-binding domains that regulate kinase activity in response to blue light–induced redox changes.
Discrete Start Sites for DNA Synthesis in the YeastARS1Origin
Authors: Bielinsky Anja-Katrin , Gerbi Susan A.
Published: July 2002

Sites of DNA synthesis initiation have been detected at the nucleotide level in a yeast origin of bidirectional replication with the use of replication initiation point mapping. TheARS1origin ofSaccharomyces cerevisiaeshowed a transition from discontinuous to continuous DNA synthesis in an 18–base pair region (nucleotides 828 to 845) from within element B1 toward B2, adjacent to the binding site for the origin recognition complex, the putative initiator protein.
Entering the Century of the Environment: A New Social Contract for Science
Authors: Lubchenco Jane
Published: July 2002

As the magnitude of human impacts on the ecological systems of the planet becomes apparent, there is increased realization of the intimate connections between these systems and human health, the economy, social justice, and national security. The concept of what constitutes “the environment” is changing rapidly. Urgent and unprecedented environmental and social changes challenge scientists to define a new social contract. This contract represents a commitment on the part of all scientists to devote their energies and talents to the most pressing problems of the day, in proportion to their importance, in exchange for public funding. The new and unmet needs of society include more comprehensive information, understanding, and technologies for society to move toward a more sustainable biosphere—one which is ecologically sound, economically feasible, and socially just. New fundamental research, faster and more effective transmission of new and existing knowledge to policy- and decision-makers, and better communication of this knowledge to the public will all be required to meet this challenge.
Possible Production of High-Energy Gamma Rays from Proton Acceleration in the Extragalactic Radio Source Markarian 501
Authors: Mannheim K.
Published: July 2002

The active galaxy Markarian 501 was discovered with air-Cerenkov telescopes at photon energies of 10 tera–electron volts. Such high energies may indicate that the gamma rays from Markarian 501 are due to the acceleration of protons rather than electrons. Furthermore, the observed absence of gamma ray attenuation due to electron-positron pair production in collisions with cosmic infrared photons implies a limit of 2 to 4 nanowatts per square meter per steradian for the energy flux of an extragalactic infrared radiation background at a wavelength of 25 micrometers. This limit provides important clues about the epoch of galaxy formation.
Photometry and Spectroscopy of the GRB 970508 Optical Counterpart
Authors: Castro-Tirado Alberto J. , Gorosabel Javier , Benı́tez Narciso , Wolf Christian , Fockenbrock Ralf , Martı́nez-González Enrique , Kristen Helmuth , Broeils Adrick , Pedersen Holger , Greiner Jochen , Costa Enrico , Feroci Marco , Piro Luigi , Frontera Filippo , Nicastro Luciano , Palazzi Eliana , Bartolini Corrado , Guarnieri Adriano , Masetti Nicola , Piccioni Adalberto , Mignoli Marco , Wold Magrethe , Lacy Mark , Birkle Kurt , Broadhurst Tom , Brandt Søren , Lund Niels
Published: July 2002

An optical transient within the error box of the gamma ray burst GRB 970508 was imaged 4 hours after the event. It displayed a strong ultraviolet excess, and reached maximum brightness 2 days later. The optical spectra did not show any emission lines, and no variations on time scales of minutes were observed for 1 hour during the decline phase. According to the fireball and afterglow models, the intensity should rise monotonically before the observed optical maximum, but the data indicate that another physical mechanism may be responsible for the constant phase seen during the first hours after the burst.
Sphingosine-1-Phosphate as a Ligand for the G Protein-Coupled Receptor EDG-1
Authors: Lee Menq-Jer , Van Brocklyn James R. , Thangada Shobha , Liu Catherine H. , Hand Arthur R. , Menzeleev Ramil , Spiegel Sarah , Hla Timothy
Published: July 2002

The sphingolipid metabolite sphingosine-1–phosphate (SPP) has been implicated as a second messenger in cell proliferation and survival. However, many of its biological effects are due to binding to unidentified receptors on the cell surface. SPP activated the heterotrimeric guanine nucleotide binding protein (G protein)–coupled orphan receptor EDG-1, originally cloned as
Endothelial Differentiation Gene
–
1
. EDG-1 bound SPP with high affinity (dissociation constant = 8.1 nM) and high specificity. Overexpression of EDG-1 induced exaggerated cell-cell aggregation, enhanced expression of cadherins, and formation of well-developed adherens junctions in a manner dependent on SPP and the small guanine nucleotide binding protein Rho.