bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of Rock, Metals, and Ices in Callisto
Authors: Anderson J. D. , Schubert G. , Jacobson R. A. , Lau E. L. , Moore W. B. , Sjogren W. L.
Published: July 2002

Radio Doppler data from a single encounter (C3) of the Galileo spacecraft with Callisto, the outermost Galilean moon of Jupiter, indicated that Callisto was probably undifferentiated. Now, similar data from a second encounter (C9) corroborate this conclusion, but more accurate data from a third encounter (C10) indicate that the rock and ice within Callisto have partially, but not completely, separated. Callisto may be differentiated into a rock-metal core less than 25 percent of Callisto's radius, an outer layer of clean ice less than 350 km thick, and a middle layer of mixed rock and ice. Models in which ice and rock are mixed all the way to the center of Callisto are also consistent with the data.
Planar Patterned Magnetic Media Obtained by Ion Irradiation
Authors: Chappert C. , Bernas H. , Ferré J. , Kottler V. , Jamet J.-P. , Chen Y. , Cambril E. , Devolder T. , Rousseaux F. , Mathet V. , Launois H.
Published: July 2002

By ion irradiation through a lithographically made resist mask, the magnetic properties of cobalt-platinum simple sandwiches and multilayers were patterned without affecting their roughness and optical properties. This was demonstrated on arrays of 1-micrometer lines by near- and far-field magnetooptical microscopy. The coercive force and magnetic anisotropy of the irradiated regions can be accurately controlled by the irradiation fluence. If combined with high-resolution lithography, this technique holds promise for ultrahigh-density magnetic recording applications.
Edge Effects and the Extinction of Populations Inside Protected Areas
Authors: Woodroffe Rosie , Ginsberg Joshua R.
Published: July 2002

Theory predicts that small populations may be driven to extinction by random fluctuations in demography and loss of genetic diversity through drift. However, population size is a poor predictor of extinction in large carnivores inhabiting protected areas. Conflict with people on reserve borders is the major cause of mortality in such populations, so that border areas represent population sinks. The species most likely to disappear from small reserves are those that range widely—and are therefore most exposed to threats on reserve borders—irrespective of population size. Conservation efforts that combat only stochastic processes are therefore unlikely to avert extinction.
Reproductive Dominance of Pasture Trees in a Fragmented Tropical Forest Mosaic
Authors: Aldrich Preston R. , Hamrick J. L.
Published: July 2002

Tropical forest fragmentation threatens biodiversity, yet basic information on population responses for major groups such as plants is lacking. Hypervariable genetic markers were used to reconstruct a population-level pedigree in fragmented tropical forest for the tree
Symphonia globulifera
. Though seedlings occurred only in remnant forest, the pedigree showed that most seedlings had been produced by sequentially fewer adults in pasture, creating a genetic bottleneck. The pedigree also implicated shifts in the foraging of animals that disperse pollen and seed in a secondary constriction of the bottleneck. These results suggest that tropical conservation strategies should anticipate complex, cryptic responses to fragmentation.
Complete Structure of the 11-Subunit Bovine Mitochondrial Cytochrome bc
1
Complex
Authors: Iwata So , Lee Joong W. , Okada Kengo , Lee John Kyongwon , Iwata Momi , Rasmussen Bjarne , Link Thomas A. , Ramaswamy S. , Jap Bing K.
Published: July 2002

Mitochondrial cytochrome bc
1
complex performs two functions: It is a respiratory multienzyme complex and it recognizes a mitochondrial targeting presequence. Refined crystal structures of the 11-subunit bc
1
complex from bovine heart reveal full views of this bifunctional enzyme. The “Rieske” iron-sulfur protein subunit shows significant conformational changes in different crystal forms, suggesting a new electron transport mechanism of the enzyme. The mitochondrial targeting presequence of the “Rieske” protein (subunit 9) is lodged between the two “core” subunits at the matrix side of the complex. These “core” subunits are related to the matrix processing peptidase, and the structure unveils how mitochondrial targeting presequences are recognized.
Specific Covalent Labeling of Recombinant Protein Molecules Inside Live Cells
Authors: Griffin B. Albert , Adams Stephen R. , Tsien Roger Y.
Published: July 2002

Recombinant proteins containing four cysteines at the
i
,
i
+ 1,
i
+ 4, and
i
+ 5 positions of an α helix were fluorescently labeled in living cells by extracellular administration of 4′,5′-bis(1,3,2-dithioarsolan-2-yl)fluorescein. This designed small ligand is membrane-permeant and nonfluorescent until it binds with high affinity and specificity to the tetracysteine domain. Such in situ labeling adds much less mass than does green fluorescent protein and offers greater versatility in attachment sites as well as potential spectroscopic and chemical properties. This system provides a recipe for slightly modifying a target protein so that it can be singled out from the many other proteins inside live cells and fluorescently stained by small nonfluorescent dye molecules added from outside the cells.
Mitochondria and Apoptosis
Authors: Green Douglas R. , Reed John C.
Published: July 2002

REVIEW

A variety of key events in apoptosis focus on mitochondria, including the release of caspase activators (such as cytochrome c), changes in electron transport, loss of mitochondrial transmembrane potential, altered cellular oxidation-reduction, and participation of pro- and antiapoptotic Bcl-2 family proteins. The different signals that converge on mitochondria to trigger or inhibit these events and their downstream effects delineate several major pathways in physiological cell death.
Response of Flexible Polymers to a Sudden Elongational Flow
Authors: Smith Douglas E. , Chu Steven
Published: July 2002

Individual polymers at thermal equilibrium were exposed to an elongational flow producing a high strain rate, and their dynamics were recorded with video fluorescence microscopy. The flow was turned on suddenly so that the entire evolution of molecular conformation could be observed without initial perturbations. The rate of stretching of individual molecules is highly variable and depends on the molecular conformation that develops during stretching. This variability is due to a dependence of the dynamics on the initial, random equilibrium conformation of the polymer coil. The increasing appearance at high strain rates of slowly unraveling hairpin folds is an example of nonergodic dynamics, which can occur when a statistical mechanical system is subjected to nonadiabatic, or “sudden,” external forces.
An Antimicrobial Activity of Cytolytic T Cells Mediated by Granulysin
Authors: Stenger Steffen , Hanson Dennis A. , Teitelbaum Rachel , Dewan Puneet , Niazi Kayvan R. , Froelich Christopher J. , Ganz Tomas , Thoma-Uszynski Sybille , Melián Agustı́n , Bogdan Christian , Porcelli Steven A. , Bloom Barry R. , Krensky Alan M. , Modlin Robert L.
Published: July 2002

Cytolytic T lymphocytes (CTLs) kill intracellular pathogens by a granule-dependent mechanism. Granulysin, a protein found in granules of CTLs, reduced the viability of a broad spectrum of pathogenic bacteria, fungi, and parasites in vitro. Granulysin directly killed extracellular
Mycobacterium tuberculosis
, altering the membrane integrity of the bacillus, and, in combination with perforin, decreased the viability of intracellular
M. tuberculosis
. The ability of CTLs to kill intracellular
M. tuberculosis
was dependent on the presence of granulysin in cytotoxic granules, defining a mechanism by which T cells directly contribute to immunity against intracellular pathogens.
Increased Vascularization in Mice Overexpressing Angiopoietin-1
Authors: Suri Chitra , McClain Joyce , Thurston Gavin , McDonald Donald M. , Zhou Hao , Oldmixon Eben H. , Sato Thomas N. , Yancopoulos George D.
Published: July 2002

The angiopoietins and members of the vascular endothelial growth factor (VEGF) family are the only growth factors thought to be largely specific for vascular endothelial cells. Targeted gene inactivation studies in mice have shown that VEGF is necessary for the early stages of vascular development and that angiopoietin-1 is required for the later stages of vascular remodeling. Here it is shown that transgenic overexpression of angiopoietin-1 in the skin of mice produces larger, more numerous, and more highly branched vessels. These results raise the possibility that angiopoietins can be used, alone or in combination with VEGF, to promote therapeutic angiogenesis.
A Physical Map of 30,000 Human Genes
Authors: Deloukas P. , Schuler G. D. , Gyapay G. , Beasley E. M. , Soderlund C. , Rodriguez-Tomé P. , Hui L. , Matise T. C. , McKusick K. B. , Beckmann J. S. , Bentolila S. , Bihoreau M.-T. , Birren B. B. , Browne J. , Butler A. , Castle A. B. , Chiannilkulchai N. , Clee C. , Day P. J. R. , Dehejia A. , Dibling T. , Drouot N. , Duprat S. , Fizames C. , Fox S. , Gelling S. , Green L. , Harrison P. , Hocking R. , Holloway E. , Hunt S. , Keil S. , Lijnzaad P. , Louis-Dit-Sully C. , Ma J. , Mendis A. , Miller J. , Morissette J. , Muselet D. , Nusbaum H. C. , Peck A. , Rozen S. , Simon D. , Slonim D. K. , Staples R. , Stein L. D. , Stewart E. A. , Suchard M. A. , Thangarajah T. , Vega-Czarny N. , Webber C. , Wu X. , Hudson J. , Auffray C. , Nomura N. , Sikela J. M. , Polymeropoulos M. H. , James M. R. , Lander E. S. , Hudson T. J. , Myers R. M. , Cox D. R. , Weissenbach J. , Boguski M. S. , Bentley D. R.
Published: July 2002

A map of 30,181 human gene–based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (
www.ncbi.nlm.nih.gov/genemap
) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.
Spontaneous Emission Spectrum in Double Quantum Dot Devices
Authors: Fujisawa Toshimasa , Oosterkamp Tjerk H. , van der Wiel Wilfred G. , Broer Benno W. , Aguado Ramón , Tarucha Seigo , Kouwenhoven Leo P.
Published: July 2002

A double quantum dot device is a tunable two-level system for electronic energy states. A dc electron current was used to directly measure the rates for elastic and inelastic transitions between the two levels. For inelastic transitions, energy is exchanged with bosonic degrees of freedom in the environment. The inelastic transition rates are well described by the Einstein coefficients, relating absorption with stimulated and spontaneous emission. The most effectively coupled bosons in the specific environment of the semiconductor device used here were acoustic phonons. The experiments demonstrate the importance of vacuum fluctuations in the environment for quantum dot devices and potential design constraints for their use for preparing long-lived quantum states.
A Tough, Thermally Conductive Silicon Carbide Composite with High Strength up to 1600°C in Air
Authors: Ishikawa Toshihiro , Kajii Shinji , Matsunaga Kenji , Hogami Toshihiko , Kohtoku Yasuhiko , Nagasawa Toshio
Published: July 2002

A sintered silicon carbide fiber–bonded ceramic, which consists of a highly ordered, close-packed structure of very fine hexagonal columnar fibers with a thin interfacial carbon layer between fibers, was synthesized by hot-pressing plied sheets of an amorphous silicon-aluminum-carbon-oxygen fiber prepared from an organosilicon polymer. The interior of the fiber element was composed of sintered β-silicon carbide crystal without an obvious second phase at the grain boundary and triple points. This material showed high strength (over 600 megapascals in longitudinal direction), fibrous fracture behavior, excellent high-temperature properties (up to 1600°C in air), and high thermal conductivity (even at temperatures over 1000°C).
Coral Record of Equatorial Sea-Surface Temperatures During the Penultimate Deglaciation at Huon Peninsula
Authors: McCulloch Malcolm T. , Tudhope Alexander W. , Esat Tezer M. , Mortimer Graham E. , Chappell John , Pillans Bradley , Chivas Allan R. , Omura Akio
Published: July 2002

Uplifted coral terraces at Huon Peninsula, Papua New Guinea, preserve a record of sea level, sea-surface temperature, and salinity from the penultimate deglaciation. Remnants have been found of a shallow-water reef that formed during a pause, similar to the Younger Dryas, in the penultimate deglaciation at 130,000 ± 2000 years ago, when sea level was 60 to 80 meters lower than it is today.
Porites
coral, which grew during this period, has oxygen isotopic values and strontium/calcium ratios that indicate that sea-surface temperatures were much cooler (22° ± 2°C) than either Last Interglacial or present-day tropical temperatures (29° ± 1°C). These observations provide further evidence for a major cooling of the equatorial western Pacific followed by an extremely rapid rise in sea level during the latter stages of Termination II.
Light-Gap Disturbances, Recruitment Limitation, and Tree Diversity in a Neotropical Forest
Authors: Hubbell S. P. , Foster R. B. , O'Brien S. T. , Harms K. E. , Condit R. , Wechsler B. , Wright S. J. , de Lao S. Loo
Published: July 2002

Light gap disturbances have been postulated to play a major role in maintaining tree diversity in species-rich tropical forests. This hypothesis was tested in more than 1200 gaps in a tropical forest in Panama over a 13-year period. Gaps increased seedling establishment and sapling densities, but this effect was nonspecific and broad-spectrum, and species richness per stem was identical in gaps and in nongap control sites. Spatial and temporal variation in the gap disturbance regime did not explain variation in species richness. The species composition of gaps was unpredictable even for pioneer tree species. Strong recruitment limitation appears to decouple the gap disturbance regime from control of tree diversity in this tropical forest.
Chemical Analysis of Polar Stratospheric Cloud Particles
Authors: Schreiner Jochen , Voigt Christiane , Kohlmann Andreas , Arnold Frank , Mauersberger Konrad , Larsen Niels
Published: July 2002

A balloon-borne gondola carrying a particle analysis system, a backscatter sonde, and pressure and temperature sensors was launched from Kiruna, Sweden, on 25 January 1998. Measurements within polar stratospheric cloud layers inside the Arctic polar vortex show a close correlation between large backscatter ratios and enhanced particle-related water and nitric acid signals at low temperatures. Periodic structures in the data indicate the presence of lee waves. The H
2
O/HNO
3
molar ratios are consistently found to be above 10 at atmospheric temperatures between 189 and 192 kelvin. Such high ratios indicate ternary solution particles of H
2
O, HNO
3
, and H
2
SO
4
rather than the presence of solid hydrates.
A 0.5-Million-Year Record of Millennial-Scale Climate Variability in the North Atlantic
Authors: McManus Jerry F. , Oppo Delia W. , Cullen James L.
Published: July 2002

Long, continuous, marine sediment records from the subpolar North Atlantic document the glacial modulation of regional climate instability throughout the past 0.5 million years. Whenever ice sheet size surpasses a critical threshold indicated by the benthic oxygen isotope (δ
18
O) value of 3.5 per mil during each of the past five glaciation cycles, indicators of iceberg discharge and sea-surface temperature display dramatically larger amplitudes of millennial-scale variability than when ice sheets are small. Sea-surface temperature oscillations of 1° to 2°C increase in size to approximately 4° to 6°C, and catastrophic iceberg discharges begin alternating repeatedly with brief quiescent intervals. The glacial growth associated with this amplification threshold represents a relatively small departure from the modern ice sheet configuration and sea level. Instability characterizes nearly all observed climate states, with the exception of a limited range of baseline conditions that includes the current Holocene interglacial.
Evolutionary and Preservational Constraints on Origins of Biologic Groups: Divergence Times of Eutherian Mammals
Authors: Foote Mike , Hunter John P. , Janis Christine M. , Sepkoski J. John
Published: July 2002

Some molecular clock estimates of divergence times of taxonomic groups undergoing evolutionary radiation are much older than the groups' first observed fossil record. Mathematical models of branching evolution are used to estimate the maximal rate of fossil preservation consistent with a postulated missing history, given the sum of species durations implied by early origins under a range of species origination and extinction rates. The plausibility of postulated divergence times depends on origination, extinction, and preservation rates estimated from the fossil record. For eutherian mammals, this approach suggests that it is unlikely that many modern orders arose much earlier than their oldest fossil records.
Acoel Flatworms: Earliest Extant Bilaterian Metazoans, Not Members of Platyhelminthes
Authors: Ruiz-Trillo Iñaki , Riutort Marta , Littlewood D. Timothy J. , Herniou Elisabeth A. , Baguñà Jaume
Published: July 2002

Because of their simple organization the Acoela have been considered to be either primitive bilaterians or descendants of coelomates through secondary loss of derived features. Sequence data of 18
S
ribosomal DNA genes from non–fast evolving species of acoels and other metazoans reveal that this group does not belong to the Platyhelminthes but represents the extant members of the earliest divergent Bilateria, an interpretation that is supported by recent studies on the embryonic cleavage pattern and nervous system of acoels. This study has implications for understanding the evolution of major body plans, and for perceptions of the Cambrian evolutionary explosion.
Rapid Dendritic Morphogenesis in CA1 Hippocampal Dendrites Induced by Synaptic Activity
Authors: Maletic-Savatic M. , Malinow R. , Svoboda K.
Published: July 2002

Activity shapes the structure of neurons and their circuits. Two-photon imaging of CA1 neurons expressing enhanced green fluorescent protein in developing hippocampal slices from rat brains was used to characterize dendritic morphogenesis in response to synaptic activity. High-frequency focal synaptic stimulation induced a period (longer than 30 minutes) of enhanced growth of small filopodia-like protrusions (typically less than 5 micrometers long). Synaptically evoked growth was long-lasting and localized to dendritic regions close (less than 50 micrometers) to the stimulating electrode and was prevented by blockade of
N
-methyl-
d
-aspartate receptors. Thus, synaptic activation can produce rapid input-specific changes in dendritic structure. Such persistent structural changes could contribute to the development of neural circuitry.
Extensive 200-Million-Year-Old Continental Flood Basalts of the Central Atlantic Magmatic Province
Authors: Marzoli Andrea , Renne Paul R. , Piccirillo Enzo M. , Ernesto Marcia , Bellieni Giuliano , Min Angelo De
Published: July 2002

The Central Atlantic Magmatic Province (CAMP) is defined by tholeiitic basalts that crop out in once-contiguous parts of North America, Europe, Africa, and South America and is associated with the breakup of Pangea.
40
Ar/
39
Ar and paleomagnetic data indicate that CAMP magmatism extended over an area of 2.5 million square kilometers in north and central Brazil, and the total aerial extent of the magmatism exceeded 7 million square kilometers in a few million years, with peak activity at 200 million years ago. The magmatism coincided closely in time with a major mass extinction at the Triassic-Jurassic boundary.
Rbx1, a Component of the VHL Tumor Suppressor Complex and SCF Ubiquitin Ligase
Authors: Kamura T. , Koepp D. M. , Conrad M. N. , Skowyra D. , Moreland R. J. , Iliopoulos O. , Lane W. S. , Kaelin W. G. , Elledge S. J. , Conaway R. C. , Harper J. W. , Conaway J. W.
Published: July 2002

The von Hippel–Lindau (VHL) tumor suppressor gene is mutated in most human kidney cancers. The VHL protein is part of a complex that includes Elongin B, Elongin C, and Cullin-2, proteins associated with transcriptional elongation and ubiquitination. Here it is shown that the endogenous VHL complex in rat liver also includes Rbx1, an evolutionarily conserved protein that contains a RING-H2 fingerlike motif and that interacts with Cullins. The yeast homolog of Rbx1 is a subunit and potent activator of the Cdc53-containing SCF
Cdc4
ubiquitin ligase required for ubiquitination of the cyclin-dependent kinase inhibitor Sic1 and for the G
1
to S cell cycle transition. These findings provide a further link between VHL and the cellular ubiquitination machinery.
Self-Assembly of Disk-Shaped Molecules to Coiled-Coil Aggregates with Tunable Helicity
Authors: Engelkamp H. , Middelbeek S. , J. M. R. , Nolte
Published: July 2002

A disk-shaped molecule with chiral tails is shown to form long fibers of molecular diameter and micrometer length by self-assembly in chloroform. The molecules are derived from crown ethers and contain a phthalocyanine ring. In the fibers, they have a clockwise, staggered orientation that leads to an overall right-handed helical structure. These structures, in turn, self-assemble to form coiled-coil aggregates with left-handed helicity. Addition of potassium ions to the fibers leaves their structure intact but blocks the transfer of the chirality from the tails to the cores, leading to loss of the helicity of the fibers. These tunable chiral materials have potential in optoelectronic applications and as components in sensor devices.
Specific Coupling of NMDA Receptor Activation to Nitric Oxide Neurotoxicity by PSD-95 Protein
Authors: Sattler Rita , Xiong Zhigang , Lu Wei-Yang , Hafner Mathias , MacDonald John F. , Tymianski Michael
Published: July 2002

The efficiency with which
N
-methyl-
d
-aspartate receptors (NMDARs) trigger intracellular signaling pathways governs neuronal plasticity, development, senescence, and disease. In cultured cortical neurons, suppressing the expression of the NMDAR scaffolding protein PSD-95 (postsynaptic density–95) selectively attenuated excitotoxicity triggered via NMDARs, but not by other glutamate or calcium ion (Ca
2+
) channels. NMDAR function was unaffected, because receptor expression, NMDA currents, and
45
Ca
2+
loading were unchanged. Suppressing PSD-95 blocked Ca
2+
-activated nitric oxide production by NMDARs selectively, without affecting neuronal nitric oxide synthase expression or function. Thus, PSD-95 is required for efficient coupling of NMDAR activity to nitric oxide toxicity, and imparts specificity to excitotoxic Ca
2+
signaling.
Early Animal Evolution: Emerging Views from Comparative Biology and Geology
Authors: Knoll Andrew H. , Carroll Sean B.
Published: July 2002

The Cambrian appearance of fossils representing diverse phyla has long inspired hypotheses about possible genetic or environmental catalysts of early animal evolution. Only recently, however, have data begun to emerge that can resolve the sequence of genetic and morphological innovations, environmental events, and ecological interactions that collectively shaped Cambrian evolution. Assembly of the modern genetic tool kit for development and the initial divergence of major animal clades occurred during the Proterozoic Eon. Crown group morphologies diversified in the Cambrian through changes in the genetic regulatory networks that organize animal ontogeny. Cambrian radiation may have been triggered by environmental perturbation near the Proterozoic-Cambrian boundary and subsequently amplified by ecological interactions within reorganized ecosystems.
Real-Time Tracking of Memory Formation in the Human Rhinal Cortex and Hippocampus
Authors: Fernández Guillén , Effern Arndt , Grunwald Thomas , Pezer Nico , Lehnertz Klaus , Dümpelmann Matthias , Roost Dirk Van , Elger Christian E.
Published: July 2002

A fundamental question about human memory is which brain structures are involved, and when, in transforming experiences into memories. This experiment sought to identify neural correlates of memory formation with the use of intracerebral electrodes implanted in the brains of patients with temporal lobe epilepsy. Event-related potentials (ERPs) were recorded directly from the medial temporal lobe (MTL) as the patients studied single words. ERPs elicited by words subsequently recalled in a memory test were contrasted with ERPs elicited by unrecalled words. Memory formation was associated with distinct but interrelated ERP differences within the rhinal cortex and the hippocampus, which arose after about 300 and 500 milliseconds, respectively. These findings suggest that declarative memory formation is dissociable into subprocesses and sequentially organized within the MTL.
The Age of the Carbonates in Martian Meteorite ALH84001
Authors: Borg Lars E. , Connelly James N. , Nyquist Larry E. , Shih Chi-Y. , Wiesmann Henry , Reese Young
Published: July 2002

The age of secondary carbonate mineralization in the martian meteorite ALH84001 was determined to be 3.90 ± 0.04 billion years by rubidium-strontium (Rb-Sr) dating and 4.04 ± 0.10 billion years by lead-lead (Pb-Pb) dating. The Rb-Sr and Pb-Pb isochrons are defined by leachates of a mixture of high-graded carbonate (visually estimated as ∼5 percent), whitlockite (trace), and orthopyroxene (∼95 percent). The carbonate formation age is contemporaneous with a period in martian history when the surface is thought to have had flowing water, but also was undergoing heavy bombardment by meteorites. Therefore, this age does not distinguish between aqueous and impact origins for the carbonates.
A Subclass of Ras Proteins That Regulate the Degradation of IκB
Authors: Fenwick Craig , Na Soon-Young , Voll Reinhard E. , Zhong Haihong , Im Suhn-Young , Lee Jae Woon , Ghosh Sankar
Published: July 2002

Small guanosine triphosphatases, typified by the mammalian Ras proteins, play major roles in the regulation of numerous cellular pathways. A subclass of evolutionarily conserved Ras-like proteins was identified, members of which differ from other Ras proteins in containing amino acids at positions 12 and 61 that are similar to those present in the oncogenic forms of Ras. These proteins, κB-Ras1 and κB-Ras2, interact with the PEST domains of IκBα and IκBβ [inhibitors of the transcription factor nuclear factor kappa B (NF-κB)] and decrease their rate of degradation. In cells, κB-Ras proteins are associated only with NF-κB:IκBβ complexes and therefore may provide an explanation for the slower rate of degradation of IκBβ compared with IκBα.
Conservation and Novelty in the Evolution of Cell Adhesion and Extracellular Matrix Genes
Authors: Hutter Harald , Vogel Bruce E. , Plenefisch John D. , Norris Carolyn R. , Proenca Rui B. , Spieth John , Guo Chaobo , Mastwal Surjeet , Zhu Xiaoping , Scheel † Jochen , Hedgecock Edward M.
Published: July 2002

New proteins and modules have been invented throughout evolution. Gene “birth dates” in
Caenorhabditis elegans
range from the origins of cellular life through adaptation to a soil habitat. Possibly half are “metazoan” genes, having arisen sometime between the yeast-metazoan and nematode-chordate separations. These include basement membrane and cell adhesion molecules implicated in tissue organization. By contrast, epithelial surfaces facing the environment have specialized components invented within the nematode lineage. Moreover, interstitial matrices were likely elaborated within the vertebrate lineage. A strategy for concerted evolution of new gene families, as well as conservation of adaptive genes, may underlie the differences between heterochromatin and euchromatin.
Molecular Architecture and Evolution of a Modular Spider Silk Protein Gene
Authors: Hayashi Cheryl Y. , Lewis Randolph V.
Published: July 2002

Spider flagelliform silk is one of the most elastic natural materials known. Extensive sequencing of spider silk genes has shown that the exons and introns of the flagelliform gene underwent intragenic concerted evolution. The intron sequences are more homogenized within a species than are the exons. This pattern can be explained by extreme mutation and recombination pressures on the internally repetitive exons. The iterated sequences within exons encode protein structures that are critical to the function of silks. Therefore, attributes that make silks exceptional biomaterials may also hinder the fixation of optimally adapted protein sequences.
Seismic Images of the Far Side of the Sun
Authors: Lindsey C. , Braun and D. C.
Published: July 2002

Images of an active region on the far side of the sun were derived by applying seismic holography to recent helioseismic observations from space. Active regions are the centers of energetic phenomena such as solar flares and coronal mass ejections, whose resulting electromagnetic and particle radiation interfere with telecommunications and power transmissions on Earth and can pose significant hazards to astronauts and spacecraft. Synoptic seismic imaging of far-side solar activity will now allow anticipation of the appearance of large active regions more than a week ahead of their arrival on the east solar limb.
Monolithic Microfabricated Valves and Pumps by Multilayer Soft Lithography
Authors: Unger Marc A. , Chou Hou-Pu , Thorsen Todd , Scherer Axel , Quake Stephen R.
Published: July 2002

Soft lithography is an alternative to silicon-based micromachining that uses replica molding of nontraditional elastomeric materials to fabricate stamps and microfluidic channels. We describe here an extension to the soft lithography paradigm, multilayer soft lithography, with which devices consisting of multiple layers may be fabricated from soft materials. We used this technique to build active microfluidic systems containing on-off valves, switching valves, and pumps entirely out of elastomer. The softness of these materials allows the device areas to be reduced by more than two orders of magnitude compared with silicon-based devices. The other advantages of soft lithography, such as rapid prototyping, ease of fabrication, and biocompatibility, are retained.
A Structural Framework for Deciphering the Link Between I-A
g7
and Autoimmune Diabetes
Authors: Corper Adam L. , Stratmann Thomas , Apostolopoulos Vasso , Scott Christopher A. , Garcia K. Christopher , Kang Angray S. , Wilson Ian A. , Teyton Luc
Published: July 2002

Susceptibility to murine and human insulin-dependent diabetes mellitus correlates strongly with major histocompatibility complex (MHC) class II I-A or HLA-DQ alleles that lack an aspartic acid at position β57. I-A
g7
lacks this aspartate and is the only class II allele expressed by the nonobese diabetic mouse. The crystal structure of I-A
g7
was determined at 2.6 angstrom resolution as a complex with a high-affinity peptide from the autoantigen glutamic acid decarboxylase (GAD) 65. I-A
g7
has a substantially wider peptide-binding groove around β57, which accounts for distinct peptide preferences compared with other MHC class II alleles. Loss of Asp
β57
leads to an oxyanion hole in I-A
g7
that can be filled by peptide carboxyl residues or, perhaps, through interaction with the T cell receptor.
Forming Supramolecular Networks from Nanoscale Rods in Binary, Phase-Separating Mixtures
Authors: Peng Gongwen , Qiu Feng , Ginzburg Valeriy V. , Jasnow David , Balazs Anna C.
Published: July 2002

Simulations show that when low-volume fractions of nanoscale rods are immersed in a binary, phase-separating blend, the rods self-assemble into needle-like, percolating networks. The interconnected network arises through the dynamic interplay of phase-separation between the fluids, through preferential adsorption of the minority component onto the mobile rods, and through rod-rod repulsion. Such cooperative effects provide a means of manipulating the motion of nanoscopic objects and directing their association into supramolecular structures. Increasing the rod concentration beyond the effective percolation threshold drives the system to self-assemble into a lamellar morphology, with layers of wetted rods alternating with layers of the majority-component fluid. This approach can potentially yield organic/inorganic composites that are ordered on nanometer scales and exhibit electrical or structural integrity.
Atomic Structure of PDE4: Insights into Phosphodiesterase Mechanism and Specificity
Authors: Xu Robert X. , Hassell Anne M. , Vanderwall Dana , Lambert Millard H. , Holmes William D. , Luther Michael A. , Rocque Warren J. , Milburn Michael V. , Zhao Yingdong , Ke Hengming , Nolte Robert T.
Published: July 2002

Cyclic nucleotides are second messengers that are essential in vision, muscle contraction, neurotransmission, exocytosis, cell growth, and differentiation. These molecules are degraded by a family of enzymes known as phosphodiesterases, which serve a critical function by regulating the intracellular concentration of cyclic nucleotides. We have determined the three-dimensional structure of the catalytic domain of phosphodiesterase 4B2B to 1.77 angstrom resolution. The active site has been identified and contains a cluster of two metal atoms. The structure suggests the mechanism of action and basis for specificity and will provide a framework for structure-assisted drug design for members of the phosphodiesterase family.
Pattern of Marine Mass Extinction Near the Permian-Triassic Boundary in South China
Authors: Jin Y. G. , Wang Y. , Wang W. , Shang Q. H. , Cao C. Q. , Erwin D. H.
Published: July 2002

The Meishan section across the Permian-Triassic boundary in South China is the most thoroughly investigated in the world. A statistical analysis of the occurrences of 162 genera and 333 species confirms a sudden extinction event at 251.4 million years ago, coincident with a dramatic depletion of δ
13
C
carbonate
and an increase in microspherules.
Therapeutic Approaches to Bone Diseases
Authors: Rodan Gideon A. , Martin T. John
Published: July 2002

The strength and integrity of our bones depends on maintaining a delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts. As we age or as a result of disease, this delicate balancing act becomes tipped in favor of osteoclasts so that bone resorption exceeds bone formation, rendering bones brittle and prone to fracture. A better understanding of the biology of osteoclasts and osteoblasts is providing opportunities for developing therapeutics to treat diseases of bone. Drugs that inhibit the formation or activity of osteoclasts are valuable for treating osteoporosis, Paget's disease, and inflammation of bone associated with rheumatoid arthritis or periodontal disease. Far less attention has been paid to promoting bone formation with, for example, growth factors or hormones, an approach that would be a valuable adjunct therapy for patients receiving inhibitors of bone resorption.
Cholera Dynamics and El Niño-Southern Oscillation
Authors: Pascual Mercedes , Rodó Xavier , Ellner Stephen P. , Colwell Rita , Bouma Menno J.
Published: July 2002

Analysis of a monthly 18-year cholera time series from Bangladesh shows that the temporal variability of cholera exhibits an interannual component at the dominant frequency of El Niño–Southern Oscillation (ENSO). Results from nonlinear time series analysis support a role for both ENSO and previous disease levels in the dynamics of cholera. Cholera patterns are linked to the previously described changes in the atmospheric circulation of south Asia and, consistent with these changes, to regional temperature anomalies.
How Snapping Shrimp Snap: Through Cavitating Bubbles
Authors: Versluis Michel , Schmitz Barbara , von der Heydt Anna , Lohse Detlef
Published: July 2002

The snapping shrimp (
Alpheus heterochaelis
) produces a loud snapping sound by an extremely rapid closure of its snapper claw. One of the effects of the snapping is to stun or kill prey animals. During the rapid snapper claw closure, a high-velocity water jet is emitted from the claw with a speed exceeding cavitation conditions. Hydrophone measurements in conjunction with time-controlled high-speed imaging of the claw closure demonstrate that the sound is emitted at the cavitation bubble collapse and not on claw closure. A model for the bubble dynamics based on a Rayleigh-Plesset–type equation quantitatively accounts for the time dependence of the bubble radius and for the emitted sound.
Flashing Superluminal Components in the Jet of the Radio Galaxy 3C120
Authors: Gómez José-Luis , Marscher Alan P. , Alberdi Antonio , Jorstad Svetlana G. , Garcı́a-Miró Cristina
Published: July 2002

A 16-month sequence of radio images of the active galaxy 3C120 with the Very Long Baseline Array reveals a region in the relativistic jet where superluminal components flash on and off over time scales of months, while the polarization angle rotates. This can be explained by interaction between the jet and an interstellar cloud located about 8 parsecs from the center of the galaxy. The cloud, which rotates the polarization direction and possibly eclipses a section of the jet, represents a “missing link” between the ultradense broad–emission-line clouds closer to the center and the lower density narrow–emission-line clouds seen on kiloparsec scales.
The History of South American Tropical Precipitation for the Past 25,000 Years
Authors: Baker Paul A. , Seltzer Geoffrey O. , Fritz Sherilyn C. , Dunbar Robert B. , Grove Matthew J. , Tapia Pedro M. , Cross Scott L. , Rowe Harold D. , Broda James P.
Published: July 2002

Long sediment cores recovered from the deep portions of Lake Titicaca are used to reconstruct the precipitation history of tropical South America for the past 25,000 years. Lake Titicaca was a deep, fresh, and continuously overflowing lake during the last glacial stage, from before 25,000 to 15,000 calibrated years before the present (cal yr B.P.), signifying that during the last glacial maximum (LGM), the Altiplano of Bolivia and Peru and much of the Amazon basin were wetter than today. The LGM in this part of the Andes is dated at 21,000 cal yr B.P., approximately coincident with the global LGM. Maximum aridity and lowest lake level occurred in the early and middle Holocene (8000 to 5500 cal yr B.P.) during a time of low summer insolation. Today, rising levels of Lake Titicaca and wet conditions in Amazonia are correlated with anomalously cold sea-surface temperatures in the northern equatorial Atlantic. Likewise, during the deglacial and Holocene periods, there were several millennial-scale wet phases on the Altiplano and in Amazonia that coincided with anomalously cold periods in the equatorial and high-latitude North Atlantic, such as the Younger Dryas.
Deregulation of the Arginine Deiminase (
arc
) Operon in Penicillin-Tolerant Mutants of
Streptococcus gordonii
Authors: Caldelari I. , Loeliger B. , Langen H. , Glauser M. P. , Moreillon P.
Published: July 2002

Penicillin tolerance is an incompletely understood phenomenon that allows bacteria to resist drug-induced killing. Tolerance was studied with independent
Streptococcus gordonii
mutants generated by cyclic exposure to 500 times the MIC of penicillin. Parent cultures lost 4 to 5 log
10
CFU/ml of viable counts/24 h. In contrast, each of four independent mutant cultures lost ≤2 log
10
CFU/ml/24 h. The mutants had unchanged penicillin-binding proteins but contained increased amounts of two proteins with respective masses of ca. 50 and 45 kDa. One mutant (Tol1) was further characterized. The two proteins showing increased levels were homologous to the arginine deiminase and ornithine carbamoyl transferase of other gram-positive bacteria and were encoded by an operon that was >80% similar to the arginine-deiminase (
arc
) operon of these organisms. Partial nucleotide sequencing and insertion inactivation of the
S. gordonii arc
locus indicated that tolerance was not a direct consequence of
arc
alteration. On the other hand, genetic transformation of tolerance by Tol1 DNA always conferred
arc
deregulation. In nontolerant recipients,
arc
was repressed during exponential growth and up-regulated during postexponential growth. In tolerant transformants,
arc
was constitutively expressed. Tol1 DNA transformed tolerance at the same rate as transformation of a point mutation (10
−2
to 10
−3
). The tolerance mutation mapped on a specific chromosomal fragment but was physically distant from
arc
. Importantly,
arc
deregulation was observed in most (6 of 10) of additional independent penicillin-tolerant mutants. Thus, although not exclusive, the association between
arc
deregulation and tolerance was not fortuitous. Since penicillin selection mimicked the antibiotic pressure operating in the clinical environment,
arc
deregulation might be an important correlate of naturally occurring tolerance and help in understanding the mechanism(s) underlying this clinically problematic phenotype.
Effects of Antiviral Usage on Transmission Dynamics of Herpes Simplex Virus Type 1 and on Antiviral Resistance: Predictions of Mathematical Models
Authors: Lipsitch Marc , Bacon Teresa H. , Leary Jeffry J. , Antia Rustom , Levin Bruce R.
Published: July 2002

Herpes simplex virus type 1 (HSV-1) causes recurrent herpes labialis (RHL), a common disease afflicting up to 40% of adults worldwide. Mathematical models are used to analyze the effect of antiviral treatment on the transmission of, and the prevalence of drug resistance in, HSV-1 in the United States. Three scenarios are analyzed: no antiviral use, the current level of use, and a substantial increase in nucleoside analogue use, such as might occur if topical penciclovir were available over-the-counter for the treatment of RHL. A basic model predicts that present level of nucleoside analogue use has a negligible effect on HSV-1 transmission and that even if use of topical penciclovir for (RHL) increased substantially, the overall prevalence of infectious HSV-1 is unlikely to be reduced by more than 5%. An expanded model, which allows for acquired resistance and includes immunocompromised hosts and other more realistic features, predicts that current antiviral use is unlikely to lead to any noticeable increase in resistance. If antiviral use increases, the resulting rise in resistance in the population will depend primarily on the probability that immunocompetent hosts will acquire permanent resistance upon treatment. This probability is known to be small, but its exact value remains uncertain. If acquired resistance occurs less than once per 2,500 treated episodes, then in the community at large, the frequency of HSV-1 resistance is predicted to increase slowly, if at all (remaining below 0.5% for >50 years), even with extensive nucleoside analogue use. If acquired resistance emerges in 1 of 625 treated episodes (the maximum of an approximate 95% confidence interval derived from the results of several studies of resistance in treated hosts), then the prevalence of infection with resistant HSV-1 could rise from about 0.2% to 1.5 to 3% within 50 years. The limitations of existing data on acquired resistance and the potential impact of acquired resistance if it occurs are discussed, and strategies are suggested for enhancing information on acquired resistance. The predictions of this model contrast with the more rapid increases in antimicrobial resistance anticipated by models and observed for other pathogenic bacteria and viruses. The reasons for these contrasting predictions are discussed.
Cloning and Characterization of SmeDEF, a Novel Multidrug Efflux Pump from
Stenotrophomonas maltophilia
Authors: Alonso Ana , Martínez José L.
Published: July 2002

Stenotrophomonas maltophilia
is a nosocomial bacterial pathogen intrinsically resistant to several antibiotics. The mechanisms involved in this intrinsic multiresistance phenotype are poorly understood. A library of chromosomal DNA from a spontaneous multidrug-resistant
S. maltophilia
D457R mutant (A. Alonso and J. L. Martinez, Antimicrob. Agents Chemother. 41:1140–1142, 1997) was screened for complementation of erythromycin susceptibility on an antibiotic-hypersusceptible
Escherichia coli ΔacrAB
strain. Cloning and further analysis revealed that a 6-kbp region constituting a transcriptional unit was capable of complementing the antibiotic-susceptible phenotype of an
E. coli ΔacrAB
strain. We identified three open reading frames,
smeD
,
smeE
and
smeF
, which code for members of the membrane fusion protein, resistance nodulation division, and outer membrane factor families, respectively. Drug susceptibility assays indicated that the SmeDEF system cloned in
E. coli
mediates resistance to a wide range of antibiotics. Ethidium bromide and norfloxacin accumulation experiments in the presence and in the absence of carbonyl cyanide
m
-chlorophenylhydrazone showed that this system constitutes a drug efflux pump dependent on the membrane proton motive force. The presence of high levels of
smeDEF
mRNA in the multiresistant D457R mutant was consistent with the high levels of SmeF (formerly Omp54) observed in the same strain. In contrast, transcription levels of
smeDEF
in the D457 strain were tiny, which correlates with the low levels of SmeF observed for this strain. Also, for both the D457 and D457R strains, we observed growth phase-dependent regulation in which the highest level of transcription corresponded to early exponential phase, with transcription decreasing throughout the growth curve to undetectable levels at 24 h.
Effect of Ceftazidime on Systemic Cytokine Concentrations in Rats
Authors: Alkharfy Khalid M. , Kellum John A. , Frye Reginald F. , Matzke Gary R.
Published: July 2002

The effect of a single dose of ceftazidime on circulating concentrations of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in a rat model of sepsis was studied. IL-6 concentrations were significantly elevated (100 to 200 times the baseline) 6 h after ceftazidime administration in both septic and nonseptic (control) rats. TNF-α concentrations increased significantly in nonseptic (∼40 times the baseline) rats but not septic (∼2 to 3 times the baseline) rats. Ceftazidime administration was not associated with an increase in endotoxin concentrations. These findings suggest that ceftazidime modulation of proinflammatory cytokine concentrations may be independent of its antimicrobial properties.