bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic Genetic Analysis with Ordered Arrays of Yeast Deletion Mutants
Authors: Tong Amy Hin Yan , Evangelista Marie , Parsons Ainslie B. , Xu Hong , Bader Gary D. , Pagé Nicholas , Robinson Mark , Raghibizadeh Sasan , Hogue Christopher W. V. , Bussey Howard , Andrews Brenda , Tyers Mike , Boone Charles
Published: July 2002

In
Saccharomyces cerevisiae
, more than 80% of the ∼6200 predicted genes are nonessential, implying that the genome is buffered from the phenotypic consequences of genetic perturbation. To evaluate function, we developed a method for systematic construction of double mutants, termed synthetic genetic array (SGA) analysis, in which a query mutation is crossed to an array of ∼4700 deletion mutants. Inviable double-mutant meiotic progeny identify functional relationships between genes. SGA analysis of genes with roles in cytoskeletal organization (
BNI1
,
ARP2
,
ARC40
,
BIM1
), DNA synthesis and repair (
SGS1
,
RAD27
), or uncharacterized functions (
BBC1
,
NBP2
) generated a network of 291 interactions among 204 genes. Systematic application of this approach should produce a global map of gene function.
Sex-Biased Hatching Order and Adaptive Population Divergence in a Passerine Bird
Authors: Badyaev Alexander V. , Hill Geoffrey E. , Beck Michelle L. , Dervan Anne A. , Duckworth Renée A. , McGraw Kevin J. , Nolan Paul M. , Whittingham Linda A.
Published: July 2002

Most species of birds can lay only one egg per day until a clutch is complete, and the order in which eggs are laid often has strong and sex-specific effects on offspring growth and survival. In two recently established populations of the house finch (
Carpodacus mexicanus
) in Montana and Alabama, breeding females simultaneously adjusted the sex and growth of offspring in relation to their position in the laying order, thereby reducing the mortality of sons and daughters by 10 to 20% in both environments. We show experimentally that the reduction in mortality is produced by persistent and sex-specific maternal effects on the growth and morphology of offspring. These strong parental effects may have facilitated the rapid adaptive divergence among populations of house finches.
Stem Cell Self-Renewal Specified by JAK-STAT Activation in Response to a Support Cell Cue
Authors: Kiger Amy A. , Jones D. Leanne , Schulz Cordula , Rogers Madolyn B. , Fuller Margaret T.
Published: July 2002

Stem cells generate many differentiated, short-lived cell types, such as blood, skin, and sperm, throughout adult life. Stem cells maintain a long-term capacity to divide, producing daughter cells that either self-renew or initiate differentiation. Although the surrounding microenvironment or “niche” influences stem cell fate decisions, few signals that emanate from the niche to specify stem cell self-renewal have been identified. Here we demonstrate that the apical hub cells in the
Drosophila
testis act as a cellular niche that supports stem cell self-renewal. Hub cells express the ligand Unpaired (Upd), which activates the Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway in adjacent germ cells to specify self-renewal and continual maintenance of the germ line stem cell population.
The Medial Frontal Cortex and the Rapid Processing of Monetary Gains and Losses
Authors: Gehring William J. , Willoughby Adrian R.
Published: July 2002

We report the observation of neural processing that occurs within 265 milliseconds after outcome stimuli that inform human participants about gains and losses in a gambling task. A negative-polarity event-related brain potential, probably generated by a medial-frontal region in or near the anterior cingulate cortex, was greater in amplitude when a participant's choice between two alternatives resulted in a loss than when it resulted in a gain. The sensitivity to losses was not simply a reflection of detecting an error; gains did not elicit the medial-frontal activity when the alternative choice would have yielded a greater gain, and losses elicited the activity even when the alternative choice would have yielded a greater loss. Choices made after losses were riskier and were associated with greater loss-related activity than choices made after gains. It follows that medial-frontal computations may contribute to mental states that participate in higher level decisions, including economic choices.
Systematic Design of Pore Size and Functionality in Isoreticular MOFs and Their Application in Methane Storage
Authors: Eddaoudi Mohamed , Kim Jaheon , Rosi Nathaniel , Vodak David , Wachter Joseph , O'Keeffe Michael , Yaghi Omar M.
Published: July 2002

A strategy based on reticulating metal ions and organic carboxylate links into extended networks has been advanced to a point that allowed the design of porous structures in which pore size and functionality could be varied systematically. Metal-organic framework (MOF-5), a prototype of a new class of porous materials and one that is constructed from octahedral Zn-O-C clusters and benzene links, was used to demonstrate that its three-dimensional porous system can be functionalized with the organic groups –Br, –NH
2
, –OC
3
H
7
, –OC
5
H
11
, –C
2
H
4
, and –C
4
H
4
and that its pore size can be expanded with the long molecular struts biphenyl, tetrahydropyrene, pyrene, and terphenyl. We synthesized an isoreticular series (one that has the same framework topology) of 16 highly crystalline materials whose open space represented up to 91.1% of the crystal volume, as well as homogeneous periodic pores that can be incrementally varied from 3.8 to 28.8 angstroms. One member of this series exhibited a high capacity for methane storage (240 cubic centimeters at standard temperature and pressure per gram at 36 atmospheres and ambient temperature), and others the lowest densities (0.41 to 0.21 gram per cubic centimeter) for a crystalline material at room temperature.
An mRNA Surveillance Mechanism That Eliminates Transcripts Lacking Termination Codons
Authors: Frischmeyer Pamela A. , van Hoof Ambro , O'Donnell Kathryn , Guerrerio Anthony L. , Parker Roy , Dietz Harry C.
Published: July 2002

Translation is an important mechanism to monitor the quality of messenger RNAs (mRNAs), as exemplified by the translation-dependent recognition and degradation of transcripts harboring premature termination codons (PTCs) by the nonsense-mediated mRNA decay (NMD) pathway. We demonstrate in yeast that mRNAs lacking all termination codons are as labile as nonsense transcripts. Decay of “nonstop” transcripts in yeast requires translation but is mechanistically distinguished from NMD and the major mRNA turnover pathway that requires deadenylation, decapping, and 5′-to-3′ exonucleolytic decay. These data suggest that nonstop decay is initiated when the ribosome reaches the 3′ terminus of the message. We demonstrate multiple physiologic sources of nonstop transcripts and conservation of their accelerated decay in mammalian cells. This process regulates the stability and expression of mRNAs that fail to signal translational termination.
Mechanical Circulatory Support--a Long and Winding Road
Authors: McCarthy Patrick M. , Smith William A.
Published: July 2002

The highly public reintroduction of the total artificial heart last year has prompted renewed interest in mechanical circulatory support systems for the treatment of end-stage heart disease.
Liquid-State NMR and Scalar Couplings in Microtesla Magnetic Fields
Authors: McDermott Robert , Trabesinger Andreas H. , Mück Michael , Hahn Erwin L. , Pines Alexander , Clarke John
Published: July 2002

We obtained nuclear magnetic resonance (NMR) spectra of liquids in fields of a few microtesla, using prepolarization in fields of a few millitesla and detection with a dc superconducting quantum interference device (SQUID). Because the sensitivity of the SQUID is frequency independent, we enhanced both signal-to-noise ratio and spectral resolution by detecting the NMR signal in extremely low magnetic fields, where the NMR lines become very narrow even for grossly inhomogeneous measurement fields. In the absence of chemical shifts, proton-phosphorous scalar (J) couplings have been detected, indicating the presence of specific covalent bonds. This observation opens the possibility for “pure J spectroscopy” as a diagnostic tool for the detection of molecules in low magnetic fields.
Electrochemistry and Electrogenerated Chemiluminescence from Silicon Nanocrystal Quantum Dots
Authors: Ding Zhifeng , Quinn Bernadette M. , Haram Santosh K. , Pell Lindsay E. , Korgel Brian A. , Bard Allen J.
Published: July 2002

Reversible electrochemical injection of discrete numbers of electrons into sterically stabilized silicon nanocrystals (NCs) (∼2 to 4 nanometers in diameter) was observed by differential pulse voltammetry (DPV) in
N
,
N
′-dimethylformamide and acetonitrile. The electrochemical gap between the onset of electron injection and hole injection—related to the highest occupied and lowest unoccupied molecular orbitals—grew with decreasing nanocrystal size, and the DPV peak potentials above the onset for electron injection roughly correspond to expected Coulomb blockade or quantized double-layer charging energies. Electron transfer reactions between positively and negatively charged nanocrystals (or between charged nanocrystals and molecular redox-active coreactants) occurred that led to electron and hole annihilation, producing visible light. The electrogenerated chemiluminescence spectra exhibited a peak maximum at 640 nanometers, a significant red shift from the photoluminescence maximum (420 nanometers) of the same silicon NC solution. These results demonstrate that the chemical stability of silicon NCs could enable their use as redox-active macromolecular species with the combined optical and charging properties of semiconductor quantum dots.
External Reflection from Omnidirectional Dielectric Mirror Fibers
Authors: Hart Shandon D. , Maskaly Garry R. , Temelkuran Burak , Prideaux Peter H. , Joannopoulos John D. , Fink Yoel
Published: July 2002

We report the design and fabrication of a multilayered macroscopic fiber preform and the subsequent drawing and optical characterization of extended lengths of omnidirectional dielectric mirror fibers with submicrometer layer thickness. A pair of glassy materials with substantially different indices of refraction, but with similar thermomechanical properties, was used to construct 21 layers of alternating refractive index surrounding a tough polymer core. Large directional photonic band gaps and high reflection efficiencies comparable to those of the best metallic reflectors were obtained. Potential applications of these fibers include woven fabrics for radiation barriers, spectral authentication of cloth, and filters for telecommunications.
Binary Asteroids in the Near-Earth Object Population
Authors: Margot J. L. , Nolan M. C. , Benner L. A. M. , Ostro S. J. , Jurgens R. F. , Giorgini J. D. , Slade M. A. , Campbell D. B.
Published: July 2002

Radar images of near-Earth asteroid 2000 DP107 show that it is composed of an ∼800-meter-diameter primary and an ∼300-meter-diameter secondary revolving around their common center of mass. The orbital period of 1.755 ± 0.007 days and semimajor axis of 2620 ± 160 meters constrain the total mass of the system to 4.6 ± 0.5 × 10
11
kilograms and the bulk density of the primary to 1.7 ± 1.1 grams per cubic centimeter. This system and other binary near-Earth asteroids have spheroidal primaries spinning near the breakup point for strengthless bodies, suggesting that the binaries formed by spin-up and fission, probably as a result of tidal disruption during close planetary encounters. About 16% of near-Earth asteroids larger than 200 meters in diameter may be binary systems.
Tropical Ocean-Atmosphere Interaction, the Pacific Cold Tongue, and the El Niño-Southern Oscillation
Authors: Jin F.-F.
Published: July 2002

The tropical Pacific basin allows strong feedbacks among the trade winds, equatorial zonal sea surface temperature contrast, and upper ocean heat content. Coupled atmosphere-ocean dynamics produce both the strong Pacific cold tongue climate state and the El Niño-Southern Oscillation phenomenon. A simple paradigm of the tropical climate system is presented, capturing the basic physics of these two important aspects of the tropic Pacific and basic features of the climate states of the Atlantic and Indian ocean basins.
Visualization of Gene Expression in Living Adult
Drosophila
Authors: Calleja Manuel , Moreno Eduardo , Pelaz Soraya , Morata Ginés
Published: July 2002

To identify genes involved in the patterning of adult structures, Gal4-UAS (upstream activating site) technology was used to visualize patterns of gene expression directly in living flies. A large number of Gal4 insertion lines were generated and their expression patterns were studied. In addition to identifying several characterized developmental genes, the approach revealed previously unsuspected genetic subdivisions of the thorax, which may control the disposition of pattern elements. The boundary between two of these domains coincides with localized expression of the signaling molecule wingless.
Direct Imaging of the Atomic Configuration of Ultradispersed Catalysts
Authors: Nellist P. D. , Pennycook S. J.
Published: July 2002

Direct imaging of individual catalyst metal atoms on the insulating surface of an industrial support is demonstrated. Individual platinum and rhodium atoms ultradispersed on γ-Al
2
O
3
supports were imaged by high-resolution
Z
-contrast (atomic number
Z
) microscopy in a 300-kilovolt scanning transmission electron microscope. Within small clusters, the configuration of the metal atoms was seen to be constrained to match the surface structure of the γ-Al
2
O
3
, from which likely surface adsorption sites were deduced. A thin, extended raft of rhodium atoms was observed, mostly corresponding to one monolayer. Occasional two-atom features suggested partial dissolution into the top layers of the γ-Al
2
O
3
support.
Life with 6000 Genes
Authors: Goffeau A. , Barrell B. G. , Bussey H. , Davis R. W. , Dujon B. , Feldmann H. , Galibert F. , Hoheisel J. D. , Jacq C. , Johnston M. , Louis E. J. , Mewes H. W. , Murakami Y. , Philippsen P. , Tettelin H. , Oliver S. G.
Published: July 2002

The genome of the yeast
Saccharomyces cerevisiae
has been completely sequenced through a worldwide collaboration. The sequence of 12,068 kilobases defines 5885 potential protein-encoding genes, approximately 140 genes specifying ribosomal RNA, 40 genes for small nuclear RNA molecules, and 275 transfer RNA genes. In addition, the complete sequence provides information about the higher order organization of yeast's 16 chromosomes and allows some insight into their evolutionary history. The genome shows a considerable amount of apparent genetic redundancy, and one of the major problems to be tackled during the next stage of the yeast genome project is to elucidate the biological functions of all of these genes.
Hypertension Induced in Pregnant Mice by Placental Renin and Maternal Angiotensinogen
Authors: Takimoto Eriko , Ishida Junji , Sugiyama Fumihiro , Horiguchi Hisashi , Murakami Kazuo , Fukamizu Akiyoshi
Published: July 2002

Maternal hypertension is a common complication of pregnancy and its pathophysiology is poorly understood. This phenomenon was studied in an animal model by mating transgenic mice expressing components of the human renin-angiotensin system. When transgenic females expressing angiotensinogen were mated with transgenic males expressing renin, the pregnant females displayed a transient elevation of blood pressure in late pregnancy, due to secretion of placental human renin into the maternal circulation. Blood pressure returned to normal levels after delivery of the pups. Histopathologic examination revealed uniform enlargement of glomeruli associated with an increase in urinary protein excretion, myocardial hypertrophy, and necrosis and edema in the placenta. These mice may provide molecular insights into pregnancy-associated hypertension in humans.
Synaptic Activity and the Construction of Cortical Circuits
Authors: Katz L. C. , Shatz C. J.
Published: July 2002

Vision is critical for the functional and structural maturation of connections in the mammalian visual system. Visual experience, however, is a subset of a more general requirement for neural activity in transforming immature circuits into the organized connections that subserve adult brain function. Early in development, internally generated spontaneous activity sculpts circuits on the basis of the brain's “best guess” at the initial configuration of connections necessary for function and survival. With maturation of the sense organs, the developing brain relies less on spontaneous activity and increasingly on sensory experience. The sequential combination of spontaneously generated and experience-dependent neural activity endows the brain with an ongoing ability to accommodate to dynamically changing inputs during development and throughout life.
Cancer Cell Cycles
Authors: Sherr Charles J.
Published: July 2002

Uncontrolled cell proliferation is the hallmark of cancer, and tumor cells have typically acquired damage to genes that directly regulate their cell cycles. Genetic alterations affecting p16

INK4a

and cyclin D1, proteins that govern phosphorylation of the retinoblastoma protein (RB) and control exit from the G
1
phase of the cell cycle, are so frequent in human cancers that inactivation of this pathway may well be necessary for tumor development. Like the tumor suppressor protein p53, components of this “RB pathway,” although not essential for the cell cycle per se, may participate in checkpoint functions that regulate homeostatic tissue renewal throughout life.
Recalibrated Mariner 10 Color Mosaics: Implications for Mercurian Volcanism
Authors: Robinson Mark S. , Lucey Paul G.
Published: July 2002

Recalibration of Mariner 10 color image data allows the identification of distinct color units on the mercurian surface. We analyze these data in terms of opaque mineral abundance, iron content, and soil maturity and find color units consistent with the presence of volcanic deposits on Mercury's surface. Additionally, materials associated with some impact craters have been excavated from a layer interpreted to be deficient in opaque minerals within the crust, possibly analogous to the lunar anorthosite crust. These observations suggest that Mercury has undergone complex differentiation like the other terrestrial planets and the Earth's moon.
Mathematical and Computational Challenges in Population Biology and Ecosystems Science
Authors: Levin Simon A. , Grenfell Bryan , Hastings Alan , Perelson Alan S.
Published: July 2002

Mathematical and computational approaches provide powerful tools in the study of problems in population biology and ecosystems science. The subject has a rich history intertwined with the development of statistics and dynamical systems theory, but recent analytical advances, coupled with the enhanced potential of high-speed computation, have opened up new vistas and presented new challenges. Key challenges involve ways to deal with the collective dynamics of heterogeneous ensembles of individuals, and to scale from small spatial regions to large ones. The central issues—understanding how detail at one scale makes its signature felt at other scales, and how to relate phenomena across scales—cut across scientific disciplines and go to the heart of algorithmic development of approaches to high-speed computation. Examples are given from ecology, genetics, epidemiology, and immunology.
An Explanation for Earth's Long-Term Rotational Stability
Authors: Richards Mark A. , Ricard Yannick , Lithgow-Bertelloni Carolina , Spada Giorgio , Sabadini Roberto
Published: July 2002

Paleomagnetic data show less than ∼1000 kilometers of motion between the paleomagnetic and hotspot reference frames—that is, true polar wander—during the past 100 million years, which implies that Earth's rotation axis has been very stable. This long-term rotational stability can be explained by the slow rate of change in the large-scale pattern of plate tectonic motions during Cenozoic and late Mesozoic time, provided that subducted lithosphere is a major component of the mantle density heterogeneity generated by convection. Therefore, it is unnecessary to invoke other mechanisms, such as sluggish readjustment of the rotational bulge, to explain the observed low rate of true polar wander.
Still life, a Protein in Synaptic Terminals ofDrosophilaHomologous to GDP-GTP Exchangers
Authors: Sone Masaki , Hoshino Mikio , Suzuki Emiko , Kuroda Shinya , Kaibuchi Kozo , Nakagoshi Hideki , Saigo Kaoru , Nabeshima Yo-ichi , Hama Chihiro
Published: July 2002

The morphology of axon terminals changes with differentiation into mature synapses. A molecule that might regulate this process was identified by a screen ofDrosophilamutants for abnormal motor activities. Thestill life(sif) gene encodes a protein homologous to guanine nucleotide exchange factors, which convert Rho-like guanosine triphosphatases (GTPases) from a guanosine diphosphate-bound inactive state to a guanosine triphosphate-bound active state. The SIF proteins are found adjacent to the plasma membrane of synaptic terminals. Expression of a truncated SIF protein resulted in defects in neuronal morphology and induced membrane ruffling with altered actin localization in human KB cells. Thus, SIF proteins may regulate synaptic differentiation through the organization of the actin cytoskeleton by activating Rho-like GTPases.
Nuclear Export of NF-ATc Enhanced by Glycogen Synthase Kinase-3
Authors: Beals Chan R. , Sheridan Colleen M. , Turck Christoph W. , Gardner Phyllis , Crabtree Gerald R.
Published: July 2002

The transcription factor NF-AT responds to Ca
2+
-calcineurin signals by translocating to the nucleus, where it participates in the activation of early immune response genes. Calcineurin dephosphorylates conserved serine residues in the amino terminus of NF-AT, resulting in nuclear import. Purification of the NF-AT kinase revealed that it is composed of a priming kinase activity and glycogen synthase kinase-3 (GSK-3). GSK-3 phosphorylates conserved serines necessary for nuclear export, promotes nuclear exit, and thereby opposes Ca
2+
-calcineurin signaling. Because GSK-3 responds to signals initiated by Wnt and other ligands, NF-AT family members could be effectors of these pathways.
Supramolecular Materials: Self-Organized Nanostructures
Authors: Stupp S. I. , LeBonheur V. , Walker K. , Li L. S. , Huggins K. E. , Keser M. , Amstutz A.
Published: July 2002

Miniaturized triblock copolymers have been found to self-assemble into nanostructures that are highly regular in size and shape. Mushroom-shaped supramolecular structures of about 200 kilodaltons form by crystallization of the chemically identical blocks and self-organize into films containing 100 or more layers stacked in a polar arrangement. The polar supramolecular material exhibits spontaneous second-harmonic generation from infrared to green photons and has an adhesive tape–like character with nonadhesive-hydrophobic and hydrophilic-sticky opposite surfaces. The films also have reasonable shear strength and adhere tenaciously to glass surfaces on one side only. The regular and finite size of the supramolecular units is believed to be mediated by repulsive forces among some of the segments in the triblock molecules. A large diversity of multifunctional materials could be formed from regular supramolecular units weighing hundreds of kilodaltons.
Ozone Pollution in the Rural United States and the New NAAQS
Authors: Chameides W. L. , Saylor R. D. , Cowling E. B.
Published: July 2002

The U.S. Environmental Protection Agency (EPA) has recently proposed a new National Ambient Air Quality Standard (NAAQS) for ozone, based on an 8-hour averaged concentration of 0.08 part per million. An analysis of ozone data gathered in 1995 by the Southern Oxidants Study Spatial Ozone Network (SON) and EPA’s Clean Air Status and Trends Network (CASTNet) indicates that promulgation of this new standard will bring large parts of the rural eastern United States into nonattainment. This in turn will necessitate a major change in the nation’s pollution control strategies.
Disordered Biopyriboles, Amphibole, and Talc in the Allende Meteorite: Products of Nebular or Parent Body Aqueous Alteration?
Authors: Brearley Adrian J.
Published: July 2002

Transmission electron microscope observations of the Allende carbonaceous chondrite provided evidence of widespread hydrous phases replacing enstatite in chondrules. Calcic amphibole and talc occur in thin (less than 0.3 micrometer) crosscutting veins and as alteration products of primary chondrule glass in contraction cracks within the enstatite. In addition, talc and disordered biopyriboles were found replacing enstatite grains along cracks and fractures. Although rare hydrous phases have been reported in calcium- and aluminum-rich inclusions in the Allende meteorite, these observations suggest that aqueous fluids played a much more significant role in the mineralogical and geochemical evolution of Allende than has previously been thought.
Tin-Based Amorphous Oxide: A High-Capacity Lithium-Ion-Storage Material
Authors: Idota Yoshio , Kubota Tadahiko , Matsufuji Akihiro , Maekawa Yukio , Miyasaka Tsutomu
Published: July 2002

A high-capacity lithium-storage material in metal-oxide form has been synthesized that can replace the carbon-based lithium intercalation materials currently in extensive use as the negative electrode (anode) of lithium-ion rechargeable batteries. This tin-based amorphous composite oxide (TCO) contains Sn(II)-O as the active center for lithium insertion and other glass-forming elements, which make up an oxide network. The TCO anode yields a specific capacity for reversible lithium adsorption more than 50 percent higher than those of the carbon families that persists after charge-discharge cycling when coupled with a lithium cobalt oxide cathode. Lithium-7 nuclear magnetic resonance measurements evidenced the high ionic state of lithium retained in the charged state, in which TCO accepted 8 moles of lithium ions per unit mole.
Hyperplasia of Lymphatic Vessels in VEGF-C Transgenic Mice
Authors: Jeltsch Michael , Kaipainen Arja , Joukov Vladimir , Meng Xiaojuan , Lakso Merja , Rauvala Heikki , Swartz Melody , Fukumura Dai , Jain Rakesh K. , Alitalo Kari
Published: July 2002

No growth factors specific for the lymphatic vascular system have yet been described. Vascular endothelial growth factor (VEGF) regulates vascular permeability and angiogenesis, but does not promote lymphangiogenesis. Overexpression of VEGF-C, a ligand of the VEGF receptors VEGFR-3 and VEGFR-2, in the skin of transgenic mice resulted in lymphatic, but not vascular, endothelial proliferation and vessel enlargement. Thus, VEGF-C induces selective hyperplasia of the lymphatic vasculature, which is involved in the draining of interstitial fluid and in immune function, inflammation, and tumor metastasis. VEGF-C may play a role in disorders involving the lymphatic system and may be of potential use in therapeutic lymphangiogenesis.
Structural Insights into the Evolution of an Antibody Combining Site
Authors: Wedemayer Gary J. , Patten Phillip A. , Wang Leo H. , Schultz Peter G. , Stevens Raymond C.
Published: July 2002

The crystal structures of a germline antibody Fab fragment and its complex with hapten have been solved at 2.1 Å resolution. These structures are compared with the corresponding crystal structures of the affinity-matured antibody, 48G7, which has a 30,000 times higher affinity for hapten as a result of nine replacement somatic mutations. Significant changes in the configuration of the combining site occur upon binding of hapten to the germline antibody, whereas hapten binds to the mature antibody by a lock-and-key fit mechanism. The reorganization of the combining site that was nucleated by hapten binding is further optimized by somatic mutations that occur up to 15 Å from bound hapten. These results suggest that the binding potential of the primary antibody repertoire may be significantly expanded by the ability of germline antibodies to adopt more than one combining-site configuration, with both antigen binding and somatic mutation stabilizing the configuration with optimal hapten complementarity.
Chemical Coupling Between Atmospheric Ozone and Particulate Matter
Authors: Meng Z. , Dabdub D. , Seinfeld J. H.
Published: July 2002

A major fraction of ambient particulate matter arises from atmospheric gas-to-particle conversion. Attempts to reduce particulate matter levels require control of the same organic and nitrogen oxide (NO

x

) emissions that are precursors to urban and regional ozone formation. Modeling of the gas-aerosol chemical interactions that govern levels of particulate components showed that control of gas-phase organic and NO

x

precursors does not lead to proportionate reductions of the gas-phase–derived components of atmospheric particles. The chemical coupling between ozone and particulate matter has implications for strategies to achieve the new ozone and particulate matter standards proposed by the U.S. Environmental Protection Agency.
Evolution of a Strain of CJD That Induces BSE-Like Plaques
Authors: Manuelidis Laura , Fritch William , Xi You-Gen
Published: July 2002

Bovine spongiform encephalopathy (BSE) has become a public health issue because a recently evolved BSE agent has infected people, yielding an unusual form of Creutzfeld-Jakob disease (CJD). A new CJD agent that provokes similar amyloid plaques and cerebellar pathology was serially propagated. First-passage rats showed obvious clinical signs and activated microglia but had negligible PrP-res (the more protease-resistant form of host PrP) or cerebellar lesions. Microglia and astrocytes may participate in strain selection because the agent evolved, stabilized, and reproducibly provoked BSE-like disease in subsequent passages. Early vacuolar change involving activated microglia and astrocytes preceded significant PrP-res accumulation by more than 50 days. These studies reveal several inflammatory host reactions to an exogenous agent.
The Ras-RasGAP Complex: Structural Basis for GTPase Activation and Its Loss in Oncogenic Ras Mutants
Authors: Scheffzek Klaus , Ahmadian Mohammad Reza , Kabsch Wolfgang , Wiesmüller Lisa , Lautwein Alfred , Schmitz Frank , Wittinghofer Alfred
Published: July 2002

The three-dimensional structure of the complex between human H-Ras bound to guanosine diphosphate and the guanosine triphosphatase (GTPase)–activating domain of the human GTPase-activating protein p120
GAP
(GAP-334) in the presence of aluminum fluoride was solved at a resolution of 2.5 angstroms. The structure shows the partly hydrophilic and partly hydrophobic nature of the communication between the two molecules, which explains the sensitivity of the interaction toward both salts and lipids. An arginine side chain (arginine-789) of GAP-334 is supplied into the active site of Ras to neutralize developing charges in the transition state. The switch II region of Ras is stabilized by GAP-334, thus allowing glutamine-61 of Ras, mutation of which activates the oncogenic potential, to participate in catalysis. The structural arrangement in the active site is consistent with a mostly associative mechanism of phosphoryl transfer and provides an explanation for the activation of Ras by glycine-12 and glutamine-61 mutations. Glycine-12 in the transition state mimic is within van der Waals distance of both arginine-789 of GAP-334 and glutamine-61 of Ras, and even its mutation to alanine would disturb the arrangements of residues in the transition state.
Crystal Structure of Mouse CD1: An MHC-Like Fold with a Large Hydrophobic Binding Groove
Authors: Zeng Z.-H. , Castaño A. R. , Segelke B. W. , Stura E. A. , Peterson P. A. , Wilson I. A.
Published: July 2002

CD1 represents a third lineage of antigen-presenting molecules that are distantly related to major histocompatibility complex (MHC) molecules in the immune system. The crystal structure of mouse CD1d1, corresponding to human CD1d, at 2.8 Å resolution shows that CD1 adopts an MHC fold that is more closely related to that of MHC class I than to that of MHC class II. The binding groove, although significantly narrower, is substantially larger because of increased depth and it has only two major pockets that are almost completely hydrophobic. The extreme hydrophobicity and shape of the binding site are consistent with observations that human CD1b and CD1c can present mycobacterial cell wall antigens, such as mycolic acid and lipoarabinomannans. However, mouse CD1d1 can present very hydrophobic peptides, but must do so in a very different way from MHC class Ia and class II molecules.
Natural Occurrence of MgSiO
3
-Ilmenite and Evidence for MgSiO
3
-Perovskite in a Shocked L Chondrite
Authors: Sharp Thomas G. , Lingemann Cornelia M. , Dupas Catherine , Stöffler Dieter
Published: July 2002

Shock-induced melt veins in the Acfer 040 L5-6 (S6) chondrite contain a previously unknown set of high pressure phases consisting of amorphous grains similar in composition to majorite, MgSiO
3
-ilmenite, and ringwoodite. The amorphous grains have compositions that are similar to those of synthetic MgSiO
3
-perovskites from chemically complex systems and are inferred to be MgSiO
3
-perovskite that crystallized from the melt at high pressure and temperature and subsequently amorphized after pressure release. The ilmenite represents a natural occurrence of a potentially important mineral in Earth's mantle. The MgSiO
3
-perovskite–MgSiO
3
-ilmenite–ringwoodite assemblage is not predicted by phase equilibria studies, but appears to result from crystallization of a melt at pressures above 26 gigapascals.
Human Domination of Earth's Ecosystems
Authors: Vitousek Peter M. , Mooney Harold A. , Lubchenco Jane , Melillo Jerry M.
Published: July 2002

Human alteration of Earth is substantial and growing. Between one-third and one-half of the land surface has been transformed by human action; the carbon dioxide concentration in the atmosphere has increased by nearly 30 percent since the beginning of the Industrial Revolution; more atmospheric nitrogen is fixed by humanity than by all natural terrestrial sources combined; more than half of all accessible surface fresh water is put to use by humanity; and about one-quarter of the bird species on Earth have been driven to extinction. By these and other standards, it is clear that we live on a human-dominated planet.
The Management of Fisheries and Marine Ecosystems
Authors: Botsford Louis W. , Castilla Juan Carlos , Peterson Charles H.
Published: July 2002

The global marine fish catch is approaching its upper limit. The number of overfished populations, as well as the indirect effects of fisheries on marine ecosystems, indicate that management has failed to achieve a principal goal, sustainability. This failure is primarily due to continually increasing harvest rates in response to incessant sociopolitical pressure for greater harvests and the intrinsic uncertainty in predicting the harvest that will cause population collapse. A more holistic approach incorporating interspecific interactions and physical environmental influences would contribute to greater sustainability by reducing the uncertainty in predictions. However, transforming the management process to reduce the influence of pressure for greater harvest holds more immediate promise.
Bcl-2: Prolonging Life in a Transgenic Mouse Model of Familial Amyotrophic Lateral Sclerosis
Authors: Kostic Vladimir , Jackson-Lewis Vernice , de Bilbao Fabienne , Dubois-Dauphin Michel , Przedborski Serge
Published: July 2002

Mutations in the gene encoding copper/zinc superoxide dismutase enzyme produce an animal model of familial amyotrophic lateral sclerosis (FALS), a fatal disorder characterized by paralysis. Overexpression of the proto-oncogenebcl-2delayed onset of motor neuron disease and prolonged survival in transgenic mice expressing the FALS-linked mutation in which glycine is substituted by alanine at position 93. It did not, however, alter the duration of the disease. Overexpression ofbcl-2also attenuated the magnitude of spinal cord motor neuron degeneration in the FALS-transgenic mice.
Dual Role of Phosphatidylinositol-3,4,5-trisphosphate in the Activation of Protein Kinase B
Authors: Stokoe David , Stephens Leonard R. , Copeland Terry , Gaffney Piers R. J. , Reese Colin B. , Painter Gavin F. , Holmes Andrew B. , McCormick Frank , Hawkins Phillip T.
Published: July 2002

Protein kinase B (PKB) is a proto-oncogene that is activated in signaling pathways initiated by phosphoinositide 3-kinase. Chromatographic separation of brain cytosol revealed a kinase activity that phosphorylated and activated PKB only in the presence of phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P
3
]. Phosphorylation occurred exclusively on threonine-308, a residue implicated in activation of PKB in vivo. PtdIns(3,4,5)P
3
was determined to have a dual role: Its binding to the pleckstrin homology domain of PKB was required to allow phosphorylation by the upstream kinase and it directly activated the upstream kinase.
Climate and Ocean Dynamics and the Lead Isotopic Records in Pacific Ferromanganese Crusts
Authors: Christensen John N. , Halliday Alex N. , Godfrey Linda V. , Hein James R. , Rea David K.
Published: July 2002

As hydrogenous iron-manganese crusts grow, at rates of millimeters per million years, they record changes in the lead isotopic composition of ambient seawater. Time-resolved lead isotopic data for cut slabs of two central Pacific iron-manganese crusts that have been growing since about 50 million years ago were measured in situ by laser ablation, multiple-collector, inductively coupled plasma mass spectrometry. The lead isotopic compositions have remained remarkably uniform over the past 30 million years, but the record of small variations corresponds with other paleoceanographic indicators of climate change, including weathering and glaciation. This implies that despite the short residence time of lead in the oceans, global mechanisms may influence lead isotopic compositions in the central Pacific, far from continental inputs, because of changes in weathering, ocean circulation, and degree of mixing. Thus lead isotopic data could be used to probe climate-driven changes in ocean circulation through time.
Superconductivity up to 126 Kelvin in Interstitially Doped Ba2Can-1CunOx[02(n-1)n-Ba]
Authors: Chu C. W. , Xue Y. Y. , Du Z. L. , Sun Y. Y. , Gao L. , Wu N. L. , Cao Y. , Rusakova I. , Ross K.
Published: July 2002

A new high-temperature superconducting compound system, Ba2Can–1CunOx[02(n–1)n–Ba] interstitially doped with calcium or (Ca,Cu) has been identified to exhibit a transition temperature up to 126 kelvin, the highest for a superconductor without a volatile toxic element. 02(n–1)n–Ba has body-centered tetragonal symmetry and an unusual charge-reservoir block. The compounds offer interesting opportunities for high-temperature superconductivity science and technology.
Fuzzy Nanoassemblies: Toward Layered Polymeric Multicomposites
Authors: Decher Gero
Published: July 2002

Multilayer films of organic compounds on solid surfaces have been studied for more than 60 years because they allow fabrication of multicomposite molecular assemblies of tailored architecture. However, both the Langmuir-Blodgett technique and chemisorption from solution can be used only with certain classes of molecules. An alternative approach—fabrication of multilayers by consecutive adsorption of polyanions and polycations—is far more general and has been extended to other materials such as proteins or colloids. Because polymers are typically flexible molecules, the resulting superlattice architectures are somewhat fuzzy structures, but the absence of crystallinity in these films is expected to be beneficial for many potential applications.
Selective Expression of the Eotaxin Receptor CCR3 by Human T Helper 2 Cells
Authors: Sallusto Federica , Mackay Charles R. , Lanzavecchia Antonio
Published: July 2002

There is growing evidence that T helper cell subsets (T
H
1 and T
H
2) can be differentially recruited to promote different types of inflammatory reactions. Murine T
H
1 but not T
H
2 cells are recruited through P- and E-selectin into inflamed tissues, where they induce delayed-type hypersensitivity reactions. The human eotaxin-receptor CCR3, originally described on eosinophils and basophils, was also found to be expressed by T
H
2 cells. An antibody to CCR3 was used to isolate T cells from peripheral blood that give rise to T
H
2-polarized cell lines and to identify T
H
2 cells derived from naı̈ve T cells in vitro. Eotaxin stimulated increases in intracellular calcium and chemotaxis of CCR3
+
T cells. The attraction of T
H
2 cells by eotaxin could represent a key mechanism in allergic reactions, because it promotes the allergen-driven production of interleukin-4 and interleukin-5 necessary to activate basophils and eosinophils.
A Pervasive Millennial-Scale Cycle in North Atlantic Holocene and Glacial Climates
Authors: Bond Gerard , Showers William , Cheseby Maziet , Lotti Rusty , Almasi Peter , deMenocal Peter , Priore Paul , Cullen Heidi , Hajdas Irka , Bonani Georges
Published: July 2002

Evidence from North Atlantic deep sea cores reveals that abrupt shifts punctuated what is conventionally thought to have been a relatively stable Holocene climate. During each of these episodes, cool, ice-bearing waters from north of Iceland were advected as far south as the latitude of Britain. At about the same times, the atmospheric circulation above Greenland changed abruptly. Pacings of the Holocene events and of abrupt climate shifts during the last glaciation are statistically the same; together, they make up a series of climate shifts with a cyclicity close to 1470 ± 500 years. The Holocene events, therefore, appear to be the most recent manifestation of a pervasive millennial-scale climate cycle operating independently of the glacial-interglacial climate state. Amplification of the cycle during the last glaciation may have been linked to the North Atlantic's thermohaline circulation.
Results from the Mars Pathfinder Camera
Authors: Smith P. H. , Bell J. F. , Bridges N. T. , Britt D. T. , Gaddis L. , Greeley R. , Keller H. U. , Herkenhoff K. E. , Jaumann R. , Johnson J. R. , Kirk R. L. , Lemmon M. , Maki J. N. , Malin M. C. , Murchie S. L. , Oberst J. , Parker T. J. , Reid R. J. , Sablotny R. , Soderblom L. A. , Stoker C. , Sullivan R. , Thomas N. , Tomasko M. G. , Ward W. , Wegryn E.
Published: July 2002

Images of the martian surface returned by the Imager for Mars Pathfinder (IMP) show a complex surface of ridges and troughs covered by rocks that have been transported and modified by fluvial, aeolian, and impact processes. Analysis of the spectral signatures in the scene (at 440- to 1000-nanometer wavelength) reveal three types of rock and four classes of soil. Upward-looking IMP images of the predawn sky show thin, bluish clouds that probably represent water ice forming on local atmospheric haze (opacity ∼0.5). Haze particles are about 1 micrometer in radius and the water vapor column abundance is about 10 precipitable micrometers.
The Chemical Composition of Martian Soil and Rocks Returned by the Mobile Alpha Proton X-ray Spectrometer: Preliminary Results from the X-ray Mode
Authors: Rieder R. , Economou T. , Wänke H. , Turkevich A. , Crisp J. , Brückner J. , Dreibus G. , McSween H. Y.
Published: July 2002

The alpha proton x-ray spectrometer (APXS) on board the rover of the Mars Pathfinder mission measured the chemical composition of six soils and five rocks at the Ares Vallis landing site. The soil analyses show similarity to those determined by the Viking missions. The analyzed rocks were partially covered by dust but otherwise compositionally similar to each other. They are unexpectedly high in silica and potassium, but low in magnesium compared to martian soils and martian meteorites. The analyzed rocks are similar in composition to terrestrial andesites and close to the mean composition of Earth's crust. Addition of a mafic component and reaction products of volcanic gases to the local rock material is necessary to explain the soil composition.
Natural Variation in a
Drosophila
Clock Gene and Temperature Compensation
Authors: Sawyer Lesley A. , Hennessy J. Michael , Peixoto Alexandre A. , Rosato Ezio , Parkinson Helen , Costa Rodolfo , Kyriacou Charalambos P.
Published: July 2002

The threonine-glycine (Thr-Gly) encoding repeat within the clock gene
period
of
Drosophila melanogaster
is polymorphic in length. The two major variants
(Thr-Gly)17
and
(Thr-Gly)20
are distributed as a highly significant latitudinal cline in Europe and North Africa. Thr-Gly length variation from both wild-caught and transgenic individuals is related to the flies' ability to maintain a circadian period at different temperatures. This phenomenon provides a selective explanation for the geographical distribution of Thr-Gly lengths and gives a rare glimpse of the interplay between molecular polymorphism, behavior, population biology, and natural selection.
Expansion and Length-Dependent Fragility of CTG Repeats in Yeast
Authors: Freudenreich Catherine H. , Kantrow Sara M. , Zakian Virginia A.
Published: July 2002

Expansion of DNA trinucleotide repeats (TNRs) is the causative mutation in a growing number of human genetic diseases. Large expansions of a CTG tract were obtained and shown by genetic and physical assays to be length-dependent sites of chromosome breakage in
Saccharomyces cerevisiae
. Deletion of
RAD27
, which encodes a nuclease involved in Okazaki fragment processing, caused length-dependent destabilization of CTG tracts and a substantial increase in expansion frequency. The genetic assay described here can be used to evaluate other factors that induce TNR expansion or chromosome fragility in humans.
Activation of the OxyR Transcription Factor by Reversible Disulfide Bond Formation
Authors: Zheng Ming , Åslund Fredrik , Storz Gisela
Published: July 2002

The OxyR transcription factor is sensitive to oxidation and activates the expression of antioxidant genes in response to hydrogen peroxide in
Escherichia coli
. Genetic and biochemical studies revealed that OxyR is activated through the formation of a disulfide bond and is deactivated by enzymatic reduction with glutaredoxin 1 (Grx1). The gene encoding Grx1 is regulated by OxyR, thus providing a mechanism for autoregulation. The redox potential of OxyR was determined to be –185 millivolts, ensuring that OxyR is reduced in the absence of stress. These results represent an example of redox signaling through disulfide bond formation and reduction.
Formation of a Magmatic-Hydrothermal Ore Deposit: Insights with LA-ICP-MS Analysis of Fluid Inclusions
Authors: Audétat Andreas , Günther Detlef , Heinrich Christoph A.
Published: July 2002

The physical and chemical mechanism of ore precipitation in the Yankee Lode tin deposit (Mole Granite, Australia) was quantified by direct trace-element microanalysis of fluid inclusions. Laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) was used to measure element concentrations in a series of fluid inclusions representing the fluid before, during, and after the deposition of cassiterite (SnO
2
). Tin precipitation was driven by mixing of hot magmatic brine with cooler meteoric water. At the same time, a separate magmatic vapor phase selectively transported copper and boron into the liquid mixture.