bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Reactivity of Highly Vibrationally Excited Molecules on Metal Surfaces
Authors: Hou H. , Huang Y. , Gulding S. J. , Rettner C. T. , Auerbach D. J. , Wodtke A. M.
Published: July 2002

The chemical dynamics of highly vibrationally excited molecules have been studied by measuring the quantum state–resolved scattering probabilities of nitric oxide (NO) molecules on clean and oxygen-covered copper (111) surfaces, where the incident NO was prepared in single quantum states with vibrational energies of as much as 300 kilojoules per mole. The dependence of vibrationally elastic and inelastic scattering on oxygen coverage strongly suggests that highly excited NO (
v
= 13 and 15) reacts on clean copper (111) with a probability of 0.87 ± 0.05, more than three orders of magnitude greater than the reaction probability of ground-state NO. Vibrational promotion of surface chemistry on metals (up to near-unit reaction probability) is possible despite the expected efficient relaxation of vibrational energy at metal surfaces.
Phylogenetic Classification and the Universal Tree
Authors: Doolittle W. Ford
Published: July 2002

From comparative analyses of the nucleotide sequences of genes encoding ribosomal RNAs and several proteins, molecular phylogeneticists have constructed a “universal tree of life,” taking it as the basis for a “natural” hierarchical classification of all living things. Although confidence in some of the tree's early branches has recently been shaken, new approaches could still resolve many methodological uncertainties. More challenging is evidence that most archaeal and bacterial genomes (and the inferred ancestral eukaryotic nuclear genome) contain genes from multiple sources. If “chimerism” or “lateral gene transfer” cannot be dismissed as trivial in extent or limited to special categories of genes, then no hierarchical universal classification can be taken as natural. Molecular phylogeneticists will have failed to find the “true tree,” not because their methods are inadequate or because they have chosen the wrong genes, but because the history of life cannot properly be represented as a tree. However, taxonomies based on molecular sequences will remain indispensable, and understanding of the evolutionary process will ultimately be enriched, not impoverished.
A Realizable Renewable Energy Future
Authors: Turner John A.
Published: July 2002

The ability of renewable resources to provide all of society's energy needs is shown by using the United States as an example. Various renewable systems are presented, and the issues of energy payback, carbon dioxide abatement, and energy storage are addressed. Pathways for renewable hydrogen generation are shown, and the implementation of hydrogen technologies into the energy infrastructure is presented. The question is asked, Should money and energy be spent on carbon dioxide sequestration, or should renewable resources be implemented instead.
Embryonic Stem Cell-Derived Glial Precursors: A Source of Myelinating Transplants
Authors: Brüstle Oliver , Jones Kimberly N. , Learish Randall D. , Karram Khalad , Choudhary Khalid , Wiestler Otmar D. , Duncan Ian D. , McKay Ronald D. G.
Published: July 2002

Self-renewing, totipotent embryonic stem (ES) cells may provide a virtually unlimited donor source for transplantation. A protocol that permits the in vitro generation of precursors for oligodendrocytes and astrocytes from ES cells was devised. Transplantation in a rat model of a human myelin disease shows that these ES cell–derived precursors interact with host neurons and efficiently myelinate axons in brain and spinal cord. Thus, ES cells can serve as a valuable source of cell type–specific somatic precursors for neural transplantation.
Heterostructures of Single-Walled Carbon Nanotubes and Carbide Nanorods
Authors: Zhang Y. , Ichihashi T. , Landree E. , Nihey F. , Iijima S.
Published: July 2002

A method based on a controlled solid-solid reaction was used to fabricate heterostructures between single-walled carbon nanotubes (SWCNTs) and nanorods or particles of silicon carbide and transition metal carbides. Characterization by high-resolution transmission electron microscopy and electron diffraction indicates that the heterostructures have well-defined crystalline interfaces. The SWCNT/carbide interface, with a nanometer-scale area defined by the cross section of a SWCNT bundle or of a single nanotube, represents the smallest heterojunction that can be achieved using carbon nanotubes, and it can be expected to play an important role in the future fabrication of hybrid nanodevices.
A Piston Model for Transmembrane Signaling of the Aspartate Receptor
Authors: Ottemann Karen M. , Xiao Wenzhong , Shin Yeon-Kyun , Koshland Daniel E.
Published: July 2002

To characterize the mechanism by which receptors propagate conformational changes across membranes, nitroxide spin labels were attached at strategic positions in the bacterial aspartate receptor. By collecting the electron paramagnetic resonance spectra of these labeled receptors in the presence and absence of the ligand aspartate, ligand binding was shown to generate an ∼1 angstrom intrasubunit piston-type movement of one transmembrane helix downward relative to the other transmembrane helix. The receptor-associated phosphorylation cascade proteins CheA and CheW did not alter the ligand-induced movement. Because the piston movement is very small, the ability of receptors to produce large outcomes in response to stimuli is caused by the ability of the receptor-coupled enzymes to detect small changes in the conformation of the receptor.
Optical Spatial Solitons and Their Interactions: Universality and Diversity
Authors: Stegeman George I. , Segev Mordechai
Published: July 2002

Spatial solitons, beams that do not spread owing to diffraction when they propagate, have been demonstrated to exist by virtue of a variety of nonlinear self-trapping mechanisms. Despite the diversity of these mechanisms, many of the features of soliton interactions and collisions are universal. Spatial solitons exhibit a richness of phenomena not found with temporal solitons in fibers, including effects such as fusion, fission, annihilation, and stable orbiting in three dimensions. Here the current state of knowledge on spatial soliton interactions is reviewed.
Species Diversity and Invasion Resistance in a Marine Ecosystem
Authors: Stachowicz John J. , Whitlatch Robert B. , Osman Richard W.
Published: July 2002

Theory predicts that systems that are more diverse should be more resistant to exotic species, but experimental tests are needed to verify this. In experimental communities of sessile marine invertebrates, increased species richness significantly decreased invasion success, apparently because species-rich communities more completely and efficiently used available space, the limiting resource in this system. Declining biodiversity thus facilitates invasion in this system, potentially accelerating the loss of biodiversity and the homogenization of the world's biota.
Ordered Bicontinuous Nanoporous and Nanorelief Ceramic Films from Self Assembling Polymer Precursors
Authors: Chan Vanessa Z.-H. , Hoffman James , Lee Victor Y. , Iatrou Hermis , Avgeropoulos Apostolos , Hadjichristidis Nikos , Miller Robert D. , Thomas Edwin L.
Published: July 2002

Three-dimensional ceramic nanostructured films were produced from silicon-containing triblock copolymer films exhibiting the double gyroid and inverse double gyroid morphologies (space group
Ia3d
). A one-step room-temperature oxidation process that used ozonolysis and ultraviolet irradiation effected both the selective removal of the hydrocarbon block and the conversion of the silicon-containing block to a silicon oxycarbide ceramic stable to 400°C. Depending on the relative volume fraction of the hydrocarbon block to the silicon- containing block, either nanoporous or nanorelief structures were fabricated with calculated interfacial areas of ∼40 square meters per gram and pore or strut sizes of ∼20 nanometers.
Impact of El Niño and Logging on Canopy Tree Recruitment in Borneo
Authors: Curran L. M. , Caniago I. , Paoli G. D. , Astianti D. , Kusneti M. , Leighton M. , Nirarita C. E. , Haeruman H.
Published: July 2002

Dipterocarpaceae, the dominant family of Bornean canopy trees, display the unusual reproductive strategy of strict interspecific mast-fruiting. During 1986–99, more than 50 dipterocarp species dispersed seed only within a 1- to 2-month period every 3 to 4 years during El Niño–Southern Oscillation events. Synchronous seed production occurred across extensive areas and was essential for satiating seed predators. Logging of dipterocarps reduced the extent and intensity of these reproductive episodes and exacerbated local El Niño conditions. Viable seed and seedling establishment have declined as a result of climate, logging, and predators. Since 1991, dipterocarps have experienced recruitment failure within a national park, now surrounded by logged forest.
Crystal Structure of
Thermotoga maritima
Ribosome Recycling Factor: A tRNA Mimic
Authors: Selmer Maria , Al-Karadaghi Salam , Hirokawa Go , Kaji Akira , Liljas Anders
Published: July 2002

Ribosome recycling factor (RRF), together with elongation factor G (EF-G), catalyzes recycling of ribosomes after one round of protein synthesis. The crystal structure of RRF was determined at 2.55 angstrom resolution. The protein has an unusual fold where domain I is a long three-helix bundle and domain II is a three-layer β/α/β sandwich. The molecule superimposes almost perfectly with a transfer RNA (tRNA) except that the amino acid–binding 3′ end is missing. The mimicry suggests that RRF interacts with the posttermination ribosomal complex in a similar manner to a tRNA, leading to disassembly of the complex. The structural arrangement of this mimicry is entirely different from that of other cases of less pronounced mimicry of tRNA so far described.
Organizing Principles for a Diversity of GABAergic Interneurons and Synapses in the Neocortex
Authors: Gupta Anirudh , Wang Yun , Markram Henry
Published: July 2002

A puzzling feature of the neocortex is the rich array of inhibitory interneurons. Multiple neuron recordings revealed numerous electrophysiological-anatomical subclasses of neocortical γ-aminobutyric acid–ergic (GABAergic) interneurons and three types of GABAergic synapses. The type of synapse used by each interneuron to influence its neighbors follows three functional organizing principles. These principles suggest that inhibitory synapses could shape the impact of different interneurons according to their specific spatiotemporal patterns of activity and that GABAergic interneuron and synapse diversity may enable combinatorial inhibitory effects in the neocortex.
Reaction of Plutonium Dioxide with Water: Formation and Properties of PuO
2+

x
Authors: Haschke John M. , Allen Thomas H. , Morales Luis A.
Published: July 2002

Results show that PuO

2+
x

, a high-composition (
x
≤ 0.27) phase containing Pu(VI), is the stable binary oxide in air. This nonstoichiometric oxide forms by reaction of dioxide with water and by water-catalyzed reaction of dioxide with oxygen. The PuO
2
+ H
2
O reaction rate is 0.27 nanomoles per meter squared per hour at 25°C; the activation energy at 25° to 350°C is 39 kilojoules per mole. Slow kinetics and a low lattice parameter–composition dependence for fluorite-related PuO
2+

x

are consistent with a failure to observe the phase in earlier studies. Perplexing aspects of plutonium oxide chemistry can now be explained.
Function of PI3Kγ in Thymocyte Development, T Cell Activation, and Neutrophil Migration
Authors: Sasaki Takehiko , Irie-Sasaki Junko , Jones Russell G. , Oliveira-dos-Santos Antonio J. , Stanford William L. , Bolon Brad , Wakeham Andrew , Itie Annick , Bouchard Dennis , Kozieradzki Ivona , Joza Nicholas , Mak Tak W. , Ohashi Pamela S. , Suzuki Akira , Penninger Josef M.
Published: July 2002

Phosphoinositide 3-kinases (PI3Ks) regulate fundamental cellular responses such as proliferation, apoptosis, cell motility, and adhesion. Viable gene-targeted mice lacking the p110 catalytic subunit of PI3Kγ were generated. We show that PI3Kγ controls thymocyte survival and activation of mature T cells but has no role in the development or function of B cells. PI3Kγ-deficient neutrophils exhibited severe defects in migration and respiratory burst in response to heterotrimeric GTP-binding protein (G protein)–coupled receptor (GPCR) agonists and chemotactic agents. PI3Kγ links GPCR stimulation to the formation of phosphatidylinositol 3,4,5-triphosphate and the activation of protein kinase B, ribosomal protein S6 kinase, and extracellular signal-regulated kinases 1 and 2. Thus, PI3Kγ regulates thymocyte development, T cell activation, neutrophil migration, and the oxidative burst.
Convergent Solutions to Binding at a Protein-Protein Interface
Authors: DeLano Warren L. , Ultsch Mark H. , de Abraham M. , Vos  , Wells James A.
Published: July 2002

The hinge region on the Fc fragment of human immunoglobulin G interacts with at least four different natural protein scaffolds that bind at a common site between the C
H2
and C
H3
domains. This “consensus” site was also dominant for binding of random peptides selected in vitro for high affinity (dissociation constant, about 25 nanomolar) by bacteriophage display. Thus, this site appears to be preferred owing to its intrinsic physiochemical properties, and not for biological function alone. A 2.7 angstrom crystal structure of a selected 13–amino acid peptide in complex with Fc demonstrated that the peptide adopts a compact structure radically different from that of the other Fc binding proteins. Nevertheless, the specific Fc binding interactions of the peptide strongly mimic those of the other proteins. Juxtaposition of the available Fc-complex crystal structures showed that the convergent binding surface is highly accessible, adaptive, and hydrophobic and contains relatively few sites for polar interactions. These are all properties that may promote cross-reactive binding, which is common to protein-protein interactions and especially hormone-receptor complexes.
Room Temperature Magnetic Quantum Cellular Automata
Authors: Cowburn R. P. , Welland M. E.
Published: July 2002

All computers process information electronically. A processing method based on magnetism is reported here, in which networks of interacting submicrometer magnetic dots are used to perform logic operations and propagate information at room temperature. The logic states are signaled by the magnetization direction of the single-domain magnetic dots; the dots couple to their nearest neighbors through magnetostatic interactions. Magnetic solitons carry information through the networks, and an applied oscillating magnetic field feeds energy into the system and serves as a clock. These networks offer a several thousandfold increase in integration density and a hundredfold reduction in power dissipation over current microelectronic technology.
Retinal Stem Cells in the Adult Mammalian Eye
Authors: Tropepe Vincent , Coles Brenda L. K. , Chiasson Bernard J. , Horsford D. Jonathan , Elia Andrew J. , McInnes Roderick R. , van der Kooy Derek
Published: July 2002

The mature mammalian retina is thought to lack regenerative capacity. Here, we report the identification of a stem cell in the adult mouse eye, which represents a possible substrate for retinal regeneration. Single pigmented ciliary margin cells clonally proliferate in vitro to form sphere colonies of cells that can differentiate into retinal-specific cell types, including rod photoreceptors, bipolar neurons, and Müller glia. Adult retinal stem cells are localized to the pigmented ciliary margin and not to the central and peripheral retinal pigmented epithelium, indicating that these cells may be homologous to those found in the eye germinal zone of other nonmammalian vertebrates.
How Animals Move: An Integrative View
Authors: Dickinson Michael H. , Farley Claire T. , Full Robert J. , Koehl M. A. R. , Kram Rodger , Lehman Steven
Published: July 2002

Recent advances in integrative studies of locomotion have revealed several general principles. Energy storage and exchange mechanisms discovered in walking and running bipeds apply to multilegged locomotion and even to flying and swimming. Nonpropulsive lateral forces can be sizable, but they may benefit stability, maneuverability, or other criteria that become apparent in natural environments. Locomotor control systems combine rapid mechanical preflexes with multimodal sensory feedback and feedforward commands. Muscles have a surprising variety of functions in locomotion, serving as motors, brakes, springs, and struts. Integrative approaches reveal not only how each component within a locomotor system operates but how they function as a collective whole.
Specification of
Drosophila
Hematopoietic Lineage by Conserved Transcription Factors
Authors: Lebestky Tim , Chang Ting , Hartenstein Volker , Banerjee Utpal
Published: July 2002

Two major classes of cells observed within the
Drosophila
hematopoietic repertoire are plasmatocytes/macrophages and crystal cells. The transcription factor Lz (Lozenge), which resembles human AML1 (acute myeloid leukemia– 1) protein, is necessary for the development of crystal cells during embryonic and larval hematopoiesis. Another transcription factor, Gcm (glial cells missing), has previously been shown to be required for plasmatocyte development. Misexpression of Gcm causes crystal cells to be transformed into plasmatocytes. The
Drosophila
GATA protein Srp (Serpent) is required for both Lz and Gcm expression and is necessary for the development of both classes of hemocytes, whereas Lz and Gcm are required in a lineage-specific manner. Given the similarities of Srp and Lz to mammalian GATA and AML1 proteins, observations in
Drosophila
are likely to have broad implications for understanding mammalian hematopoiesis and leukemias.
Receptors for Dopamine and Somatostatin: Formation of Hetero-Oligomers with Enhanced Functional Activity
Authors: Rocheville Magalie , Lange Daniela C. , Kumar Ujendra , Patel Shutish C. , Patel Ramesh C. , Patel Yogesh C.
Published: July 2002

Somatostatin and dopamine are two major neurotransmitter systems that share a number of structural and functional characteristics. Somatostatin receptors and dopamine receptors are colocalized in neuronal subgroups, and somatostatin is involved in modulating dopamine-mediated control of motor activity. However, the molecular basis for such interaction between the two systems is unclear. Here, we show that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-oligomerization to create a novel receptor with enhanced functional activity. Our results provide evidence that receptors from different G protein (heterotrimeric guanine nucleotide binding protein)–coupled receptor families interact through oligomerization. Such direct intramembrane association defines a new level of molecular crosstalk between related G protein–coupled receptor subfamilies.
Chaperone Selection During Glycoprotein Translocation into the Endoplasmic Reticulum
Authors: Molinari Maurizio , Helenius Ari
Published: July 2002

A variety of molecular chaperones and folding enzymes assist the folding of newly synthesized proteins in the endoplasmic reticulum. Here we investigated why some glycoproteins interact with the molecular chaperone BiP, and others with the calnexin/calreticulin pathway. The folding of Semliki forest virus glycoproteins and influenza hemagglutinin was studied in living cells. The initial choice of chaperone depended on the location of N-linked glycans in the growing nascent chain. Direct interaction with calnexin and calreticulin without prior interaction with BiP occurred if glycans were present within about 50 residues of the protein's NH
2
-terminus.
Rocks from the Mantle Transition Zone: Majorite-Bearing Xenoliths from Malaita, Southwest Pacific
Authors: Collerson Kenneth D. , Hapugoda Sarath , Kamber Balz S. , Williams Quentin
Published: July 2002

Rocks containing high-pressure mineral assemblages derived from the mantle transition zone between depths of about 400 and 670 kilometers occur as xenoliths and megacrysts on the island of Malaita in the southwest Pacific on the Ontong Java Plateau. Observed ultrahigh pressure mineral chemistries include majorite, calcium- and magnesium-perovskite, aluminous silicate phases, and microdiamond. Based on an empirical barometer, majoritic garnets in these xenoliths record pressures of up to 22 gigapascal. The occurrence of material with perovskite chemistry and several enigmatic aluminous phases indicates pressures of up to 27 gigapascal. Samples were brought to the surface at about 34 million years ago by potassic ultramafic magmas, which evidently originated in the lower mantle.
Negative Poisson's Ratios for Extreme States of Matter
Authors: Baughman Ray H. , Dantas Socrates O. , Stafström Sven , Zakhidov Anvar A. , Mitchell Travis B. , Dubin Daniel H. E.
Published: July 2002

Negative Poisson's ratios are predicted for body-centered-cubic phases that likely exist in white dwarf cores and neutron star outer crusts, as well as those found for vacuumlike ion crystals, plasma dust crystals, and colloidal crystals (including certain virus crystals). The existence of this counterintuitive property, which means that a material laterally expands when stretched, is experimentally demonstrated for very low density crystals of trapped ions. At very high densities, the large predicted negative and positive Poisson's ratios might be important for understanding the asteroseismology of neutron stars and white dwarfs and the effect of stellar stresses on nuclear reaction rates. Giant Poisson's ratios are both predicted and observed for highly strained coulombic photonic crystals, suggesting possible applications of large, tunable Poisson's ratios for photonic crystal devices.
Coherent High- and Low-Latitude Climate Variability During the Holocene Warm Period
Authors: deMenocal Peter , Ortiz Joseph , Guilderson Tom , Sarnthein Michael
Published: July 2002

A faunal record of sea-surface temperature (SST) variations off West Africa documents a series of abrupt, millennial-scale cooling events, which punctuated the Holocene warm period. These events evidently resulted from increased southward advection of cooler temperate or subpolar waters to this subtropical location or from enhanced regional upwelling. The most recent of these events was the Little Ice Age, which occurred between 1300 to 1850 A.D., when subtropical SSTs were reduced by 3° to 4°C. These events were synchronous with Holocene changes in subpolar North Atlantic SSTs, documenting a strong, in-phase link between millennial-scale variations in high- and low-latitude climate during the Holocene.
Calcium Sensitivity of Glutamate Release in a Calyx-Type Terminal
Authors: Bollmann Johann H. , Sakmann Bert , Borst J. Gerard G.
Published: July 2002

Synaptic efficacy critically depends on the presynaptic intracellular calcium concentration ([Ca
2+
]
i
). We measured the calcium sensitivity of glutamate release in a rat auditory brainstem synapse by laser photolysis of caged calcium. A rise in [Ca
2+
]
i
to 1 micromolar readily evoked release. An increase to >30 micromolar depleted the releasable vesicle pool in <0.5 millisecond. A comparison with action potential–evoked release suggested that a brief increase of [Ca
2+
]
i
to ∼10 micromolar would be sufficient to reproduce the physiological release pattern. Thus, the calcium sensitivity of release at this synapse is high, and the distinction between phasic and delayed release is less pronounced than previously thought.
Suppression of Mutations in Mitochondrial DNA by tRNAs Imported from the Cytoplasm
Authors: Kolesnikova O. A. , Entelis N. S. , Mireau H. , Fox T. D. , Martin R. P. , Tarassov I. A.
Published: July 2002

Mitochondrial import of a cytoplasmic transfer RNA (tRNA) in yeast requires the preprotein import machinery and cytosolic factors. We investigated whether the tRNA import pathway can be used to correct respiratory deficiencies due to mutations in the mitochondrial DNA and whether this system can be transferred into human cells. We show that cytoplasmic tRNAs with altered aminoacylation identity can be specifically targeted to the mitochondria and participate in mitochondrial translation. We also show that human mitochondria, which do not normally import tRNAs, are able to internalize yeast tRNA derivatives in vitro and that this import requires an essential yeast import factor.
Triple Vortex Ring Structure in Superfluid Helium II
Authors: Kivotides Demosthenes , Barenghi Carlo F. , Samuels David C.
Published: July 2002

Superfluids such as helium II consist of two interpenetrating fluids: the normal fluid and the superfluid. The helium II vortex ring has generally been considered merely as a superfluid object, neglecting any associated motion of the normal fluid. We report a three-dimensional calculation of the coupled motion of the normal-fluid and superfluid components, which shows that the helium II vortex ring consists of a superfluid vortex ring accompanied by two coaxial normal-fluid vortex rings of opposite polarity. The three vortex rings form a coherent, dissipative structure.
Förster Energy Transfer in an Optical Microcavity
Authors: Andrew Piers , Barnes William L.
Published: July 2002

By studying the transfer of excitation energy between dye molecules confined within an optical microcavity, we demonstrate experimentally that Förster energy transfer is influenced by the local photonic mode density. Locating donor and acceptor molecules at well-defined positions allows the transfer rate to be determined as a function of both mutual separation and cavity length. The results show that the Förster transfer rate depends linearly on the donor emission rate and hence photonic mode density, providing the potential to control energy transfer by modification of the optical environment.
Resistance Spikes at Transitions Between Quantum Hall Ferromagnets
Authors: De Poortere E. P. , Tutuc E. , Papadakis S. J. , Shayegan M.
Published: July 2002

We report a manifestation of first-order magnetic transitions in two-dimensional electron systems. This phenomenon occurs in aluminum arsenide quantum wells with sufficiently low carrier densities and appears as a set of hysteretic spikes in the resistance of a sample placed in crossed parallel and perpendicular magnetic fields, each spike occurring at the transition between states with different partial magnetizations. Our experiments thus indicate that the presence of magnetic domains at the transition starkly increases dissipation, an effect also suspected in other ferromagnetic materials. Analysis of the positions of the transition spikes allows us to deduce the change in exchange-correlation energy across the magnetic transition, which in turn will help improve our understanding of metallic ferromagnetism.
Ultrahigh-Density Nanowire Arrays Grown in Self-Assembled Diblock Copolymer Templates
Authors: Thurn-Albrecht T. , Schotter J. , Kästle G. A. , Emley N. , Shibauchi T. , Krusin-Elbaum L. , Guarini K. , Black C. T. , Tuominen M. T. , Russell T. P.
Published: July 2002

We show a simple, robust, chemical route to the fabrication of ultrahigh-density arrays of nanopores with high aspect ratios using the equilibrium self-assembled morphology of asymmetric diblock copolymers. The dimensions and lateral density of the array are determined by segmental interactions and the copolymer molecular weight. Through direct current electrodeposition, we fabricated vertical arrays of nanowires with densities in excess of 1.9 × 10
11
wires per square centimeter. We found markedly enhanced coercivities with ferromagnetic cobalt nanowires that point toward a route to ultrahigh-density storage media. The copolymer approach described is practical, parallel, compatible with current lithographic processes, and amenable to multilayered device fabrication.
Evidence for Genetic Linkage of Alzheimer's Disease to Chromosome 10q
Authors: Bertram Lars , Blacker Deborah , Mullin Kristina , Keeney Devon , Jones Jennifer , Basu Sanjay , Yhu Stephen , McInnis Melvin G. , Go Rodney C. P. , Vekrellis Konstantinos , Selkoe Dennis J. , Saunders Aleister J. , Tanzi Rudolph E.
Published: July 2002

Recent studies suggest that insulin-degrading enzyme (IDE) in neurons and microglia degrades Aβ, the principal component of β-amyloid and one of the neuropathological hallmarks of Alzheimer's disease (AD). We performed parametric and nonparametric linkage analyses of seven genetic markers on chromosome 10q, six of which map near the
IDE
gene, in 435 multiplex AD families. These analyses revealed significant evidence of linkage for adjacent markers (D10S1671, D10S583, D10S1710, and D10S566), which was most pronounced in late-onset families. Furthermore, we found evidence for allele-specific association between the putative disease locus and marker D10S583, which has recently been located within 195 kilobases of the
IDE
gene.
Linkage of Plasma Aβ42 to a Quantitative Locus on Chromosome 10 in Late-Onset Alzheimer's Disease Pedigrees
Authors: Ertekin-Taner Nilufer , Graff-Radford Neill , Younkin Linda H. , Eckman Christopher , Baker Matthew , Adamson Jennifer , Ronald James , Blangero John , Hutton Michael , Younkin Steven G.
Published: July 2002

Plasma Aβ42 (amyloid β42 peptide) is invariably elevated in early-onset familial Alzheimer's disease (AD), and it is also increased in the first-degree relatives of patients with typical late-onset AD (LOAD). To detect LOAD loci that increase Aβ42, we used plasma Aβ42 as a surrogate trait and performed linkage analysis on extended AD pedigrees identified through a LOAD patient with extremely high plasma Aβ. Here, we report linkage to chromosome 10 with a maximal lod score of 3.93 at 81 centimorgans close to D10S1225. Remarkably, linkage to the same region was obtained independently in a genome-wide screen of LOAD sibling pairs. These results provide strong evidence for a novel LOAD locus on chromosome 10 that acts to increase Aβ.
Distinct Roles for TBP and TBP-Like Factor in Early Embryonic Gene Transcription in
Xenopus
Authors: Veenstra Gert Jan C. , Weeks Daniel L. , Wolffe Alan P.
Published: July 2002

The TATA-binding protein (TBP) is believed to function as a key component of the general transcription machinery. We tested the role of TBP during the onset of embryonic transcription by antisense oligonucleotide–mediated turnover of maternal TBP messenger RNA. Embryos without detectable TBP initiated gastrulation but died before completing gastrulation. The expression of many genes transcribed by RNA polymerase II and III was reduced; however, some genes were transcribed with an efficiency identical to that of TBP-containing embryos. Using a similar antisense strategy, we found that the TBP-like factor TLF/TRF2 is essential for development past the mid-blastula stage. Because TBP and a TLF factor play complementary roles in embryonic development, our results indicate that although similar mechanistic roles exist in common, TBP and TLF function differentially to control transcription of specific genes.
A Ribonucleotide Reductase Homolog of Cytomegalovirus and Endothelial Cell Tropism
Authors: Brune Wolfram , Ménard Carine , Heesemann Jürgen , Koszinowski Ulrich H.
Published: July 2002

Human cytomegalovirus infects vascular tissues and has been associated with atherogenesis and coronary restenosis. Although established laboratory strains of human cytomegalovirus have lost the ability to grow on vascular endothelial cells, laboratory strains of murine cytomegalovirus retain this ability. With the use of a forward-genetic procedure involving random transposon mutagenesis and rapid phenotypic screening, we identified a murine cytomegalovirus gene governing endothelial cell tropism. This gene,
M45
, shares sequence homology to ribonucleotide reductase genes. Endothelial cells infected with M45-mutant viruses rapidly undergo apoptosis, suggesting that a viral strategy to evade destruction by cellular apoptosis is indispensable for viral growth in endothelial cells.
SUB1, an
Arabidopsis
Ca
2+
-Binding Protein Involved in Cryptochrome and Phytochrome Coaction
Authors: Guo Hongwei , Mockler Todd , Duong Hien , Lin Chentao
Published: July 2002

Cryptochromes and phytochromes are the major photosensory receptors in plants and often regulate similar photomorphogenic responses. The molecular mechanisms underlying functional interactions of cryptochromes and phytochromes remain largely unclear. We have identified an
Arabidopsis
photomorphogenic mutant,
sub1
, which exhibits hypersensitive responses to blue light and far-red light. Genetic analyses indicate that
SUB1
functions as a component of a cryptochrome signaling pathway and as a modulator of a phytochrome signaling pathway. The
SUB1
gene encodes a Ca
2+
-binding protein that suppresses light-dependent accumulation of the transcription factor HY5.
Reaction-Controlled Phase-Transfer Catalysis for Propylene Epoxidation to Propylene Oxide
Authors: Zuwei Xi , Ning Zhou , Yu Sun , Kunlan Li
Published: July 2002

The epoxidation of olefins with H
2
O
2
was performed with a tungsten-containing catalyst. This insoluble catalyst forms soluble active species by the action of H
2
O
2
, and when the H
2
O
2
is used up, the catalyst precipitates for easy recycling. Thus, the advantages of both homogeneous and heterogeneous catalysts are combined in one system through reaction-controlled phase transfer of the catalyst. When coupled with the 2-ethylanthraquinone/2-ethylanthrahydroquinone redox process for H
2
O
2
production, O
2
can be used for the epoxidation of propylene to propylene oxide with 85% yield based on 2-ethylanthrahydroquinone without any co-products. This approach avoids the problematic co-products normally associated with the industrial production of propylene oxide.
Global Cooling After the Eruption of Mount Pinatubo: A Test of Climate Feedback by Water Vapor
Authors: Soden Brian J. , Wetherald Richard T. , Stenchikov Georgiy L. , Robock Alan
Published: July 2002

The sensitivity of Earth's climate to an external radiative forcing depends critically on the response of water vapor. We use the global cooling and drying of the atmosphere that was observed after the eruption of Mount Pinatubo to test model predictions of the climate feedback from water vapor. Here, we first highlight the success of the model in reproducing the observed drying after the volcanic eruption. Then, by comparing model simulations with and without water vapor feedback, we demonstrate the importance of the atmospheric drying in amplifying the temperature change and show that, without the strong positive feedback from water vapor, the model is unable to reproduce the observed cooling. These results provide quantitative evidence of the reliability of water vapor feedback in current climate models, which is crucial to their use for global warming projections.
Epidemiological Survey of Amoxicillin-Clavulanate Resistance and Corresponding Molecular Mechanisms in
Escherichia coli
Isolates in France: New Genetic Features of
bla
TEM
Genes
Authors: Leflon-Guibout V. , Speldooren V. , Heym B. , Nicolas-Chanoine M.-H.
Published: July 2002

Amoxicillin-clavulanate resistance (MIC >16 μg/ml) and the corresponding molecular mechanisms were prospectively studied in
Escherichia coli
over a 3-year period (1996 to 1998) in 14 French hospitals. The overall frequency of resistant
E. coli
isolates remained stable at about 5% over this period. The highest frequency of resistant isolates (10 to 15%) was observed, independently of the year, among
E. coli
isolated from lower respiratory tract samples, and the isolation rate of resistant strains was significantly higher in surgical wards than in medical wards in 1998 (7.8 versus 2.8%). The two most frequent mechanisms of resistance for the 3 years were the hyperproduction of the chromosomal class C β-lactamase (48, 38.4, and 39.7%) and the production of inhibitor-resistant TEM (IRT) enzymes (30.4, 37.2, and 41.2%). By using the single-strand conformational polymorphism–PCR technique and sequencing methods, we determined that 59 IRT enzymes corresponded to previously described IRT enzymes whereas 8 were new. Three of these new enzymes derived from TEM-1 by only one amino acid substitution (Ser130Gly, Arg244Gly, and Asn276Asp), whereas three others derived by two amino acid substitutions (Met69Leu and Arg244Ser, Met69Leu and Ile127Val, and Met69Val and Arg275Gln). The two remaining new IRTs showed three amino acid substitutions (Met69Val, Trp165Arg, and Asn276Asp and Met69Ile, Trp165Cys, and Arg275Gln). New genetic features were also found in
bla
TEM
genes, namely,
bla
TEM-1B
with either the promoters
Pa
and
Pb
,
P4
, or a promoter displaying a C→G transversion at position 3 of the −35 consensus sequence and new
bla
TEM
genes, notably one encoding TEM-1 but possessing the silent mutations originally described in
bla
TEM-2
and then in some
bla
TEM
-encoding IRT enzymes.
Short-Term Exposure to Membrane-Active Antibiotics Inhibits
Cryptosporidium parvum
Infection in Cell Culture
Authors: Giacometti Andrea , Cirioni Oscar , Del Prete Maria Simona , Barchiesi Francesco , Scalise Giorgio
Published: July 2002

A cell culture system and double fluorogenic staining were used to study the susceptibility of
Cryptosporidium parvum
to membrane-active antibiotics. Buforin II and magainin II exerted a cytotoxic effect on sporozoites but did not consistently affect oocyst viability. Lasalocid and nigericin demonstrated less activity against sporozoites but reduced the infectivity of oocysts.
Correlation between the Resistance Genotype Determined by Multiplex PCR Assays and the Antibiotic Susceptibility Patterns of
Staphylococcus aureus
and
Staphylococcus epidermidis
Authors: Martineau Francis , Picard François J. , Lansac Nicolas , Ménard Christian , Roy Paul H. , Ouellette Marc , Bergeron Michel G.
Published: July 2002

Clinical isolates of
Staphylococcus aureus
(a total of 206) and
S. epidermidis
(a total of 188) from various countries were tested with multiplex PCR assays to detect clinically relevant antibiotic resistance genes associated with staphylococci. The targeted genes are implicated in resistance to oxacillin (
mecA
), gentamicin [
aac
(6′)-
aph
(2")], and erythromycin (
ermA
,
ermB
,
ermC
, and
msrA
). We found a nearly perfect correlation between genotypic and phenotypic analysis for most of these 394 strains, showing the following correlations: 98% for oxacillin resistance, 100% for gentamicin resistance, and 98.5% for erythromycin resistance. The discrepant results were (i) eight strains found to be positive by PCR for
mecA
or
ermC
but susceptible to the corresponding antibiotic based on disk diffusion and (ii) six strains of
S. aureus
found to be negative by PCR for
mecA
or for the four erythromycin resistance genes targeted but resistant to the corresponding antibiotic. In order to demonstrate in vitro that the eight susceptible strains harboring the resistance gene may become resistant, we subcultured the susceptible strains on media with increasing gradients of the antibiotic. We were able to select cells demonstrating a resistant phenotype for all of these eight strains carrying the resistance gene based on disk diffusion and MIC determinations. The four oxacillin-resistant strains negative for
mecA
were PCR positive for
blaZ
and had the phenotype of β-lactamase hyperproducers, which could explain their borderline oxacillin resistance phenotype. The erythromycin resistance for the two strains found to be negative by PCR is probably associated with a novel mechanism. This study reiterates the usefulness of DNA-based assays for the detection of antibiotic resistance genes associated with staphylococcal infections.
Role of Putative Loops 2 and 3 in Imipenem Passage through the Specific Porin OprD of
Pseudomonas aeruginosa
Authors: Ochs Martina M. , Bains Manjeet , Hancock Robert E. W.
Published: July 2002

Mutant proteins with eight amino acid deletions in putative surface loops 2 and 3 of the imipenem-specific porin OprD of
Pseudomonas aeruginosa
failed to reconstitute imipenem susceptibility in an
oprD
-deficient background. The loop 3 deletion prevented the ability of imipenem to inhibit KCl conductance through the OprD channel, as previously shown for a loop 2 deletion. This suggests that both loops 2 and 3 have a role in imipenem binding to the OprD channel.
Studies of In Vitro Activities of Voriconazole and Itraconazole against
Aspergillus
Hyphae Using Viability Staining
Authors: Lass-Flörl Cornelia , Nagl Markus , Speth Cornelia , Ulmer Hanno , Dierich Manfred P. , Würzner Reinhard
Published: July 2002

The minimal fungicidal concentrations (MFCs) of voriconazole and itraconazole for five clinical isolates each of
Aspergillus terreus
,
Aspergillus fumigatus
,
Aspergillus flavus
, and
Aspergillus niger
were determined by a broth macrodilution method. Conidial suspensions as inocula were compared to hyphae as inocula since the invasive form of aspergillosis is manifested by the appearance of hyphal structures. In addition, cell viability staining with the dye FUN-1 was performed to assess time-dependent damage of hyphae exposed to various concentrations of the antifungal agents. With conidial inocula the MFC ranges of voriconazole were 0.5 to 4 μg/ml and those of itraconazole were 0.25 to 2 μg/ml, whereas the MFCs (2 to >16 μg/ml) with hyphal inocula were substantially higher (P < 0.01) for both itraconazole and voriconazole. Only minor differences between the tested antifungals were observed since 16 of 20 and 17 of 20 of the isolates of
Aspergillus
spp. tested appeared to be killed by voriconazole and itraconazole, respectively. The results of FUN-1 viability staining correlated closely to colony counts, but various time- and dose-dependent levels of viability of hyphae were also observed. In conclusion, our study demonstrates the importance of the type of inoculum used to test antifungals and the applicability of FUN-1 staining as a rapid and sensitive method for assaying the viability of hyphae.
Complexity and Diversity of
Klebsiella pneumoniae
Strains with Extended-Spectrum β-Lactamases Isolated in 1994 and 1996 at a Teaching Hospital in Durban, South Africa
Authors: Essack Sabiha Y. , Hall Lucinda M. C. , Pillay Devadas G. , McFadyen Margaret Lynn , Livermore David M.
Published: July 2002

β-Lactamase production was investigated in cultures of 25
Klebsiella pneumoniae
isolates isolated at a hospital in Durban, South Africa, in 1994 and 1996. Twenty of these isolates gave ceftazidime MIC/ceftazidime plus clavulanate MIC ratios of ≥8, implying production of extended-spectrum β-lactamases (ESBLs), and DNA sequencing identified an ESBL gene (
bla
TEM-53
) in a further two isolates. Pulsed-field gel electrophoresis (PFGE) defined 4 distinct strains among the 12 isolates collected in 1994 and 9 distinct strains among the 13 isolates collected in 1996. In three cases, multiple isolates from single patients varied in their PFGE profiles and antibiograms, implying mixed colonization or infection. Isoelectric focusing and DNA hybridization found both TEM and SHV enzymes and their genes in all 25 isolates. Many isolates had multiple identical or different β-lactamase gene variants, with at least 84
bla
SHV
and
bla
TEM
gene copies among the 25 organisms. Sequencing identified the genes for the SHV-1, -2, and -5 enzymes and for four new SHV types (SHV-19, -20, -21, and -22). These new SHV variants had novel mutations remote from sites known to affect catalytic activity. Sequencing also found the genes for TEM-1, TEM-53, and one novel type, TEM-63. All the isolates had multiple and diverse plasmids. These complex and diverse patterns of ESBL production and strain epidemiology are far removed from the concept of an ESBL outbreak and suggest a situation in which ESBL production has become endemic and in which evolution is generating a wide range of enzyme combinations. This complexity and diversity complicates patient management and the design of antibiotic use policies.
Incidence of Class 1 and 2 Integrases in Clinical and Commensal Bacteria from Livestock, Companion Animals, and Exotics
Authors: Goldstein Cathy , Lee Margie D. , Sanchez Susan , Hudson Charlene , Phillips Brad , Register Brad , Grady Michael , Liebert Cynthia , Summers Anne O. , White David G. , Maurer John J.
Published: July 2002

Many pathogenic and commensal organisms are multidrug resistant due to exposure to various antibiotics. Often, this antimicrobial resistance is encoded by integrons that occur on plasmids or that are integrated into the bacterial chromosome. Integrons are commonly associated with bacterial genera in the family
Enterobacteriaceae
. We determined that class 1 integrases were present in approximately 46% of the isolates from the family
Enterobacteriaceae
; class 2 integrases were present only among
Escherichia coli
and
Salmonella
isolates. Seven percent of veterinary isolates were positive for class 3 integrase by DNA-DNA hybridization but could not be confirmed to be positive by PCR. None of the veterinary isolates possessed the class 4 integrase gene. The distribution of these integrase genes was variable within the members of the family
Enterobacteriaceae
when some or all integrase classes were absent from a particular genus. There was also considerable variability in the distribution of these integrases within a species, depending on the animal host. Unlike the class 1 integrases, the other integrase class,
intI2
, appears to be more restricted in its distribution among the members of the family
Enterobacteriaceae
. There is also considerable variability in the distribution of the class 1 integrases within
E. coli
strains isolated from different food animals. The class 1 integrases are the most widely disseminated of the four classes among the members of the family
Enterobacteriaceae
from both the clinical and normal flora of animals. This is the first report to closely examine the distribution of class 2 integrases in members of the family
Enterobacteriaceae
isolated in the United States.
Anti-Human Immunodeficiency Virus Activity of YK-FH312 (a Betulinic Acid Derivative), a Novel Compound Blocking Viral Maturation
Authors: Kanamoto Taisei , Kashiwada Yoshiki , Kanbara Kenji , Gotoh Kazuyo , Yoshimori Manabu , Goto Toshiyuki , Sano Kouichi , Nakashima Hideki
Published: July 2002

Betulinic acid, a triterpenoid isolated from the methyl alcohol extract of the leaves of
Syzigium claviflorum
, was found to have a potent inhibitory activity against human immunodeficiency virus type 1 (HIV-1). Betulinic acid derivatives were synthesized to enhance the anti-HIV activity. Among the derivatives, 3-
O
-(3′,3′-dimethylsuccinyl) betulinic acid, designated YK-FH312, showed the highest activity against HIV-induced cytopathic effects in HIV-1-infected MT-4 cells. To determine the step(s) of HIV replication affected by YK-FH312, a syncytium formation inhibition assay in MOLT-4/HIV-1
IIIB
and MOLT-4 coculture, a multinuclear-activation-of-galactosidase-indicator (MAGI) assay in MAGI-CCR5 cells, electron microscopic observation, and a time-of-addition assay were performed. In the syncytium formation inhibition assay or in the MAGI assay for de novo infection, the compound did not show inhibitory effects against HIV replication. Conversely, no virions were detected in HIV-1-infected cell cultures treated with YK-FH312 either by electron microscopic observation or by viral yield in the supernatant. In accordance with a p24 enzyme-linked immunosorbent assay of culture supernatant in the time-of-addition assay, YK-FH312 inhibited virus expression in the supernatant when it was added 18 h postinfection. However, Western blot analysis of the cells in the time-of-addition assay revealed that the production of viral proteins in the cells was not inhibited completely by YK-FH312. These results suggest that YK-FH312 might affect the step(s) of virion assembly and/or budding of virions, and this is a novel mechanism of action of an anti-HIV compound.