bluuebunny/crossref_metadata_2025 huggingface dataset:
The Evolution of Species Interactions
Authors: Thompson John N.
Published: July 2002

Interactions between species are as evolutionarily malleable as the species themselves and have played a central role in the diversification and organization of life. This malleability creates complex geographic mosaics in interspecific interactions that can evolve rapidly over decades, blurring the distinction between evolutionary time and ecological time and making the study of coevolution crucial for human health and welfare.
Optical Vortices Crystals: Spontaneous Generation in Nonlinear Semiconductor Microcavities
Authors: Scheuer J. , Orenstein M.
Published: July 2002

Broad-area, vertical-cavity surface-emitting lasers were shown to switch their emission mode from the regular single or multilobed light fields to exhibit complex arrays of “dark beams.” Examination of these dark spot arrays revealed that they consist of multiple, closely packed optical vortices: optical fields that have phase singularities and show increased complexity as the injection current level is raised. Contrary to their complex appearance, most of these light distributions are not the result of a multimode (multiple-frequency) operation but exhibit single-frequency characteristics. The dark beam patterns can be described as emanating from a spontaneous process of transverse mode locking of nearly degenerate modes, assisted by the laser nonlinearity. Surprisingly, these patterns show high resemblance to patterns generated in other nonlinear scenarios that are completely different both in scale and in mechanism.
Deficient Cellular Immunity--Finding and Fixing the Defects
Authors: Greenberg Philip D. , Riddell Stanley R.
Published: July 2002

The critical role of cellular immunity in resistance to infectious diseases is glaringly revealed by life-threatening infections if T cell function is disrupted by an inherited or acquired immunodeficiency. Although treatment has historically focused on infectious complications, understanding of the cellular and molecular basis of immunodeficiency and technologies useful for enhancing cellular immunity have both been rapidly evolving. A new era of molecular and cellular therapy is emerging as approaches to correct abnormal genes, the loss of T cell subpopulations, and aberrant T cell homeostasis make the transition from bench to bedside.
The Selective Advantage of Low Relatedness
Authors: Cole Blaine J. , Wiernasz Diane C.
Published: July 2002

Relatedness within colonies of social Hymenoptera is often significantly lower than the outbred population maximum of 0.75. Several hypotheses address the widespread occurrence of low relatedness, but none have measured the covariation of colony fitness and relatedness. In a polyandrous harvester ant,
Pogonomyrmex occidentalis
, average within-colony relatedness in the population is low but highly variable among colonies, and relatedness is negatively correlated with colony growth rate. Differences in growth rate strongly influence survival and the onset of reproduction, leading to a 35-fold increase in fitness of fast-growing colonies. Benefits of a genetically diverse worker population may favor polyandry in this species.
Identification of a Mating Type-Like Locus in the Asexual Pathogenic Yeast
Candida albicans
Authors: Hull Christina M. , Johnson Alexander D.
Published: July 2002

Candida albicans
, the most prevalent fungal pathogen in humans, is thought to lack a sexual cycle. A set of
C. albicans
genes has been identified that corresponds to the master sexual cycle regulators a1, α1, and α2 of the
Saccharomyces cerevisiae
mating-type (
MAT
) locus. The
C. albicans
genes are arranged in a way that suggests that these genes are part of a mating type–like locus that is similar to the mating-type loci of other fungi. In addition to the transcriptional regulators a1, α1, and α2, the
C. albicans
mating type–like locus contains several genes not seen in other fungal
MAT
loci, including those encoding proteins similar to poly(A) polymerases, oxysterol binding proteins, and phosphatidylinositol kinases.
Stable Five- and Six-Coordinated Silicate Anions in Aqueous Solution
Authors: Kinrade Stephen D. , Del Nin Jeffrey W. , Schach Andrew S. , Sloan Todd A. , Wilson Krista L. , Knight Christopher T. G.
Published: July 2002

Addition of aliphatic polyols to aqueous silicate solutions is shown to yield high concentrations of stable polyolate complexes containing five- or six-coordinated silicon. Coordinating polyols require at least four hydroxy groups, two of which must be in
threo
configuration, and coordinate to silicon via hydroxy oxygens at chain positions on either side of the
threo
pair. The remarkable ease by which these simple sugar-like molecules react to form hypervalent silicon complexes in aqueous solution supports a long-standing supposition that such species play a significant role in the biological uptake and transport of silicon and in mineral diagenesis.
The Galilean Satellites
Authors: Showman Adam P. , Malhotra and Renu
Published: July 2002

NASA's Galileo mission to Jupiter and improved Earth-based observing capabilities have allowed major advances in our understanding of Jupiter's moons Io, Europa, Ganymede, and Callisto over the past few years. Particularly exciting findings include the evidence for internal liquid water oceans in Callisto and Europa, detection of a strong intrinsic magnetic field within Ganymede, discovery of high-temperature silicate volcanism on Io, discovery of tenuous oxygen atmospheres at Europa and Ganymede and a tenuous carbon dioxide atmosphere at Callisto, and detection of condensed oxygen on Ganymede. Modeling of landforms seen at resolutions up to 100 times as high as those of Voyager supports the suggestion that tidal heating has played an important role for Io and Europa.
Seven-Transmembrane Proteins as Odorant and Chemosensory Receptors
Authors: Mombaerts Peter
Published: July 2002

The olfactory systems of various species solve the challenging problem of general molecular recognition in widely differing ways. Despite this variety, the molecular receptors are invariably G protein–coupled seven-transmembrane proteins, and are encoded by the largest gene families known to exist in a given animal genome. Receptor gene families have been identified in vertebrates and two invertebrate species, the nematode
Caenorhabditis elegans
and the fruit fly
Drosophila melanogaster
. The complexity of the odorant receptor repertoire is estimated in mouse and rat at 1000 genes, or 1 percent of the genome, surpassing that of the immunoglobulin and T cell receptor genes combined. Two distinct seven-transmembrane gene families may encode in rodents the chemosensory receptors of the vomeronasal organ, which is specialized in the detection of pheromones. Remarkably, these five receptor families have practically no sequence homology among them. Genetic manipulation experiments in mice imply that vertebrate odorant receptors may fulfill a dual role, also serving as address molecules that guide axons of olfactory sensory neurons to their precise target in the brain.
An Adenosine Deaminase that Generates Inosine at the Wobble Position of tRNAs
Authors: Gerber André P. , Keller Walter
Published: July 2002

Several transfer RNAs (tRNAs) contain inosine (I) at the first position of their anticodon (position 34); this modification is thought to enlarge the codon recognition capacity during protein synthesis. The tRNA-specific adenosine deaminase of
Saccharomyces cerevisiae
that forms I
34
in tRNAs is described. The heterodimeric enzyme consists of two sequence-related subunits (Tad2p/ADAT2 and Tad3p/ADAT3), both of which contain cytidine deaminase (CDA) motifs. Each subunit is encoded by an essential gene (
TAD2
and
TAD3
), indicating that I
34
is an indispensable base modification in elongating tRNAs. These results provide an evolutionary link between the CDA superfamily and RNA-dependent adenosine deaminases (ADARs/ADATs).
Impaired Immunoproteasome Assembly and Immune Responses in

PA28
−/−

Mice
Authors: Preckel Tobias , Fung-Leung Wai-Ping , Cai Zeling , Vitiello Antonella , Salter-Cid Luisa , Winqvist Ola , Wolfe Tom G. , Herrath Matthias Von , Angulo Ana , Ghazal Peter , Lee Jiing-Dwan , Fourie Anne M. , Wu Ying , Pang Jesse , Ngo Karen , Peterson Per A. , Früh Klaus , Yang Young
Published: July 2002

In vitro PA28 binds and activates proteasomes
.
It is shown here that mice with a disrupted
PA28b
gene lack PA28a and PA28b polypeptides, demonstrating that PA28 functions as a hetero-oligomer in vivo. Processing of antigenic epitopes derived from exogenous or endogenous antigens is altered in

PA28
–/–

mice. Cytotoxic T lymphocyte responses are impaired, and assembly of immunoproteasomes is greatly inhibited in mice lacking PA28. These results show that PA28 is necessary for immunoproteasome assembly and is required for efficient antigen processing, thus demonstrating the importance of PA28-mediated proteasome function in immune responses.
Microglial Activation Resulting from CD40-CD40L Interaction After β-Amyloid Stimulation
Authors: Tan Jun , Town Terrence , Paris Daniel , Mori Takashi , Suo Zhiming , Crawford Fiona , Mattson Mark P. , Flavell Richard A. , Mullan Michael
Published: July 2002

Alzheimer's disease (AD) has a substantial inflammatory component, and activated microglia may play a central role in neuronal degeneration. CD40 expression was increased on cultured microglia treated with freshly solublized amyloid-β (Aβ, 500 nanomolar) and on microglia from a transgenic murine model of AD (Tg APP
sw
). Increased tumor necrosis factor α production and induction of neuronal injury occurred when Aβ-stimulated microglia were treated with CD40 ligand (CD40L). Microglia from Tg APP
sw
mice deficient for CD40L demonstrated reduction in activation, suggesting that the CD40-CD40L interaction is necessary for Aβ-induced microglial activation. Finally, abnormal tau phosphorylation was reduced in Tg APP
sw
animals deficient for CD40L, suggesting that the CD40-CD40L interaction is an early event in AD pathogenesis.
A H
+
-Gated Urea Channel: The Link Between
Helicobacter pylori
Urease and Gastric Colonization
Authors: Weeks David L. , Eskandari Sepehr , Scott David R. , Sachs George
Published: July 2002

Acidic media trigger cytoplasmic urease activity of the unique human gastric pathogen
Helicobacter pylori.
Deletion of
ureI
prevents this activation of cytoplasmic urease that is essential for bacterial acid resistance. UreI is an inner membrane protein with six transmembrane segments as shown by in vitro transcription/translation and membrane separation. Expression of UreI in
Xenopus
oocytes results in acid-stimulated urea uptake, with a pH profile similar to activation of cytoplasmic urease. Mutation of periplasmic histidine 123 abolishes stimulation. UreI-mediated transport is urea specific, passive, nonsaturable, nonelectrogenic, and temperature independent. UreI functions as a H
+
-gated urea channel regulating cytoplasmic urease that is essential for gastric survival and colonization.
Creating a Protein-Based Element of Inheritance
Authors: Li Liming , Lindquist Susan
Published: July 2002

Proteins capable of self-perpetuating changes in conformation and function (known as prions) can serve as genetic elements. To test whether novel prions could be created by recombinant methods, a yeast prion determinant was fused to the rat glucocorticoid receptor. The fusion protein existed in different heritable functional states, switched between states at a low spontaneous rate, and could be induced to switch by experimental manipulations. The complete change in phenotype achieved by transferring a prion determinant from one protein to another confirms the protein-only nature of prion inheritance and establishes a mechanism for engineering heritable changes in phenotype that should be broadly applicable.
Mutations in
SDHD
, a Mitochondrial Complex II Gene, in Hereditary Paraganglioma
Authors: Baysal Bora E. , Ferrell Robert E. , Willett-Brozick Joan E. , Lawrence Elizabeth C. , Myssiorek David , Bosch Anne , Mey Andel van der , Taschner Peter E. M. , Rubinstein Wendy S. , Myers Eugene N. , Richard Charles W. , Cornelisse Cees J. , Devilee Peter , Devlin B.
Published: July 2002

Hereditary paraganglioma (PGL) is characterized by the development of benign, vascularized tumors in the head and neck. The most common tumor site is the carotid body (CB), a chemoreceptive organ that senses oxygen levels in the blood. Analysis of families carrying the
PGL1
gene, described here, revealed germ line mutations in the
SDHD
gene on chromosome 11q23.
SDHD
encodes a mitochondrial respiratory chain protein—the small subunit of cytochrome b in succinate-ubiquinone oxidoreductase (cybS). In contrast to expectations based on the inheritance pattern of PGL, the SDHD gene showed no evidence of imprinting. These findings indicate that mitochondria play an important role in the pathogenesis of certain tumors and that cybS plays a role in normal CB physiology.
Prevention of Acute Liver Failure in Rats with Reversibly Immortalized Human Hepatocytes
Authors: Kobayashi Naoya , Fujiwara Toshiyoshi , Westerman Karen A. , Inoue Yusuke , Sakaguchi Masakiyo , Noguchi Hirofumi , Miyazaki Masahiro , Cai Jin , Tanaka Noriaki , Fox Ira J. , Leboulch Philippe
Published: July 2002

Because of a critical shortage in suitable organs, many patients with terminal liver disease die each year before liver transplantation can be performed. Transplantation of isolated hepatocytes has been proposed for the temporary metabolic support of patients awaiting liver transplantation or spontaneous reversion of their liver disease. A major limitation of this form of therapy is the present inability to isolate an adequate number of transplantable hepatocytes. A highly differentiated cell line, NKNT-3, was generated by retroviral transfer in normal primary adult human hepatocytes of an immortalizing gene that can be subsequently and completely excised by Cre/Lox site-specific recombination. When transplanted into the spleen of rats under transient immunosuppression, reversibly immortalized NKNT-3 cells provided life-saving metabolic support during acute liver failure induced by 90% hepatectomy.
Natural NaAlSi
3
O
8
-Hollandite in the Shocked Sixiangkou Meteorite
Authors: Gillet Philippe , Chen Ming , Dubrovinsky Leonid , Goresy Ahmed El
Published: July 2002

The hollandite high-pressure polymorph of plagioclase has been identified in shock-induced melt veins of the Sixiangkou L6 chondrite. It is intimately intergrown with feldspathic glass within grains previously thought to be “maskelynite.” The crystallographic nature of the mineral was established by laser micro-Raman spectroscopy and x-ray diffraction. The mineral is tetragonal with the unit cell parameters
a
= 9.263 ± 0.003 angstroms and
c
= 2.706 ± 0.003 angstroms. Its occurrence with the liquidus pair majorite-pyrope solid solution plus magnesiowüstite sets constraints on the peak pressures that prevailed in the shock-induced melt veins. The absence of a calcium ferrite–structured phase sets an upper bound for the crystallization of the hollandite polymorph near 23 gigapascals.
Single-Molecule Study of Transcriptional Pausing and Arrest by
E. coli
RNA Polymerase
Authors: John R. , Davenport  , Wuite Gijs J. L. , Landick Robert , Bustamante Carlos
Published: July 2002

Using an optical-trap/flow-control video microscopy technique, we followed transcription by single molecules of
Escherichia coli
RNA polymerase in real time over long template distances. These studies reveal that RNA polymerase molecules possess different intrinsic transcription rates and different propensities to pause and stop. The data also show that reversible pausing is a kinetic intermediate between normal elongation and the arrested state. The conformational metastability of RNA polymerase revealed by this single-molecule study of transcription has direct implications for the mechanisms of gene regulation in both bacteria and eukaryotes.
Carbon Isotopic Evidence for Methane Hydrate Instability During Quaternary Interstadials
Authors: Kennett James P. , Cannariato Kevin G. , Hendy Ingrid L. , Behl Richard J.
Published: July 2002

Large (about 5 per mil) millennial-scale benthic foraminiferal carbon isotopic oscillations in the Santa Barbara Basin during the last 60,000 years reflect widespread shoaling of sedimentary methane gradients and increased outgassing from gas hydrate dissociation during interstadials. Furthermore, several large, brief, negative excursions (up to –6 per mil) coinciding with smaller shifts (up to –3 per mil) in depth-stratified planktonic foraminiferal species indicate massive releases of methane from basin sediments. Gas hydrate stability was modulated by intermediate-water temperature changes induced by switches in thermohaline circulation. These oscillations were likely widespread along the California margin and elsewhere, affecting gas hydrate instability and contributing to millennial-scale atmospheric methane oscillations.
Translating Biomolecular Recognition into Nanomechanics
Authors: Fritz J. , Baller M. K. , Lang H. P. , Rothuizen H. , Vettiger P. , Meyer E. , -J. Güntherodt H. , Gerber Ch. , Gimzewski J. K.
Published: July 2002

We report the specific transduction, via surface stress changes, of DNA hybridization and receptor-ligand binding into a direct nanomechanical response of microfabricated cantilevers. Cantilevers in an array were functionalized with a selection of biomolecules. The differential deflection of the cantilevers was found to provide a true molecular recognition signal despite large nonspecific responses of individual cantilevers. Hybridization of complementary oligonucleotides shows that a single base mismatch between two 12-mer oligonucleotides is clearly detectable. Similar experiments on protein A–immunoglobulin interactions demonstrate the wide-ranging applicability of nanomechanical transduction to detect biomolecular recognition.
Cardiovascular Evidence for an Intermediate or Higher Metabolic Rate in an Ornithischian Dinosaur
Authors: Fisher Paul E. , Russell Dale A. , Stoskopf Michael K. , Barrick Reese E. , Hammer Michael , Kuzmitz Andrew A.
Published: July 2002

Computerized tomography scans of a ferruginous concretion within the chest region of an ornithischian dinosaur reveal structures that are suggestive of a four-chambered heart and a single systemic aorta. The apparently derived condition of the cardiovascular system in turn suggests the existence of intermediate-to-high metabolic rates among dinosaurs.
A High-Affinity Iron Permease Essential for
Candida albicans
Virulence
Authors: Ramanan Narendrakumar , Wang Yue
Published: July 2002

Microbial pathogens must compete with the iron-withholding defense systems of their host to acquire this essential nutrient. Here, two high-affinity iron permease genes,
CaFTR1
and
CaFTR2
, were isolated.
CaFTR1
expression was induced under iron-limited conditions and repressed when iron supply was sufficient, whereas the expression of
CaFTR2
was regulated in a reversed manner. Mutants lacking
CaFTR1
but not
CaFTR2
exhibited a severe growth defect in iron-deficient medium and were unable to establish systemic infection in mice. Thus, CaFTR1-mediated iron-uptake mechanism constitutes a virulence factor of
Candida albicans
and may be a target for the development of anti-
Candida
therapies.
Selectivity for 3D Shape That Reveals Distinct Areas Within Macaque Inferior Temporal Cortex
Authors: Janssen Peter , Vogels Rufin , Orban Guy A.
Published: July 2002

The anterior part of the macaque inferior temporal cortex, area TE, occupies a large portion of the temporal lobe and is critical for object recognition. Thus far, no relation between anatomical subdivisions of TE and neuronal selectivity has been described. Here, we present evidence that neurons selective for three-dimensional (3D) shape are concentrated in the lower bank of the superior temporal sulcus, whereas neurons in lateral TE are generally unselective for 3D shape, though equally selective for 2D shape. These findings reveal that TE consists of at least two distinct areas, one of which processes a specific object property.
A Structural Model of Transcription Elongation
Authors: Korzheva Nataliya , Mustaev Arkady , Kozlov Maxim , Malhotra Arun , Nikiforov Vadim , Goldfarb Alex , Darst Seth A.
Published: July 2002

The path of the nucleic acids through a transcription elongation complex was tracked by mapping cross-links between bacterial RNA polymerase (RNAP) and transcript RNA or template DNA onto the x-ray crystal structure. In the resulting model, the downstream duplex DNA is nestled in a trough formed by the β′ subunit and enclosed on top by the β subunit. In the RNAP channel, the RNA/DNA hybrid extends from the enzyme active site, along a region of the β subunit harboring rifampicin resistance mutations, to the β′ subunit “rudder.” The single-stranded RNA is then extruded through another channel formed by the β-subunit flap domain. The model provides insight into the functional properties of the transcription complex.
Ferromagnetism Stabilized by Lattice Distortion at the Surface of the
p
-Wave Superconductor Sr
2
RuO
4
Authors: Matzdorf R. , Fang Z. , Ismail  , Zhang Jiandi , Kimura T. , Tokura Y. , Terakura K. , Plummer E. W.
Published: July 2002

Ferromagnetic (FM) spin fluctuations are believed to mediate the spin-triplet pairing for the
p
-wave superconductivity in Sr
2
RuO
4
. Our experiments show that, at the surface, a bulk soft-phonon mode freezes into a static lattice distortion associated with an in-plane rotation of the RuO
6
octahedron. First-principle calculations confirm this structure and predict a FM ground state at the surface. This coupling between structure and magnetism in the environment of broken symmetry at the surface allows a reconsideration of the coupling mechanism in the bulk.
Isotopic Evidence for Variations in the Marine Calcium Cycle Over the Cenozoic
Authors: De La Rocha Christina L. , DePaolo Donald J.
Published: July 2002

Significant variations in the isotopic composition of marine calcium have occurred over the last 80 million years. These variations reflect deviations in the balance between inputs of calcium to the ocean from weathering and outputs due to carbonate sedimentation, processes that are important in controlling the concentration of carbon dioxide in the atmosphere and, hence, global climate. The calcium isotopic ratio of paleo-seawater is an indicator of past changes in atmospheric carbon dioxide when coupled with determinations of paleo-pH.
Remobilization in the Cratonic Lithosphere Recorded in Polycrystalline Diamond
Authors: Jacob D. E. , Viljoen K. S. , Grassineau N. , Jagoutz E.
Published: July 2002

Polycrystalline diamonds (framesites) from the Venetia kimberlite in South Africa contain silicate minerals whose isotopic and trace element characteristics document remobilization of older carbon and silicate components to form the framesites shortly before kimberlite eruption. Chemical variations within the garnets correlate with carbon isotopes in the diamonds, indicating contemporaneous formation. Trace element, radiogenic, and stable isotope variations can be explained by the interaction of eclogites with a carbonatitic melt, derived by remobilization of material that had been stored for a considerable time in the lithosphere. These results indicate more recent formation of diamonds from older materials within the cratonic lithosphere.
Relation Between Population Density and Body Size in Stream Communities
Authors: Schmid P. E. , Tokeshi M. , Schmid-Araya J. M.
Published: July 2002

The existence of a general relation between population density and body size in animal assemblages has been debated because of known biases and ambiguities in the published data and data handling. Using new comprehensive data sets from two geographically separated stream communities that encompass 448 and 260 invertebrate taxa with a wide range of body sizes, we show that an inverse proportionality between density and body size is a consistent feature in these communities. The scaling across taxa is not statistically different between the two systems, indicating a convergent pattern of communities. Variation in the regression slope among different taxonomic groups indicates that these communities are not governed universally by a single ecological or energetic rule.
Radio Science Results During the NEAR-Shoemaker Spacecraft Rendezvous with Eros
Authors: Yeomans D. K. , Antreasian P. G. , Barriot J.-P. , Chesley S. R. , Dunham D. W. , Farquhar R. W. , Giorgini J. D. , Helfrich C. E. , Konopliv A. S. , McAdams J. V. , Miller J. K. , Owen W. M. , Scheeres D. J. , Thomas P. C. , Veverka J. , Williams B. G.
Published: July 2002

We determined the mass of asteroid 433 Eros, its lower order gravitational harmonics, and rotation state, using ground-based Doppler and range tracking of the Near Earth Asteroid Rendezvous (NEAR)–Shoemaker spacecraft and images of the asteroid's surface landmarks. The mass of Eros is (6.687 ± 0.003) × 10
18
grams, which, coupled with our volume estimate, implies a bulk density of 2.67 ± 0.03 grams per cubic centimeter. The asteroid appears to have a uniform density distribution. The right ascension and declination of the rotation pole are 11.37 ± 0.05 and 17.22 ± 0.05 degrees, respectively, and at least over the short term, the rotation state of Eros is stable with no measurable free precession of the spin pole. Escape velocities on the surface vary from 3.1 to 17.2 meters per second. The dynamical environment of Eros suggests that it is covered with regolith and that one might expect material transport toward the deepest potential wells in the saddle and 5.5-kilometer crater regions.
Activation of the DNA Replication Checkpoint Through RNA Synthesis by Primase
Authors: Michael W. Matthew , Ott Robert , Fanning Ellen , Newport John
Published: July 2002

When DNA replication is inhibited during the synthesis (S) phase of the cell cycle, a signaling pathway (checkpoint) is activated that serves to prevent mitosis from initiating before completion of replication. This replication checkpoint acts by down-regulating the activity of the mitotic inducer cdc2-cyclin B. Here, we report the relation between chromatin structure and induction of the replication checkpoint. Chromatin was competent to initiate a checkpoint response only after the DNA was unwound and DNA polymerase α had been loaded. Checkpoint induction did not require new DNA synthesis on the unwound template strand but did require RNA primer synthesis by primase. These findings identify the RNA portion of the primer as an important component of the signal that activates the replication checkpoint.
The Quiet Revolution: Biodiversity Informatics and the Internet
Authors: Bisby Frank A.
Published: July 2002

The massive development of biodiversity-related information systems on the Internet has created much that appears exciting but chaotic, a diversity to match biodiversity itself. This richness and the arrays of new sources are counterbalanced by the maddening difficulty in knowing what is where, or of comparing like with like. But quietly, behind the first waves of exuberance, biologists and computer scientists have started to pull together in a rising tide of coherence and organization. The fledgling field of biodiversity informatics looks set to deliver major advances that could turn the Internet into a giant global biodiversity information system.
NMDA Receptor-Dependent Synaptic Reinforcement as a Crucial Process for Memory Consolidation
Authors: Shimizu Eiji , Tang Ya-Ping , Rampon Claire , Tsien Joe Z.
Published: July 2002

The hippocampal CA1 region is crucial for converting new memories into long-term memories, a process believed to continue for week(s) after initial learning. By developing an inducible, reversible, and CA1-specific knockout technique, we could switch
N
-methyl-
d
-aspartate (NMDA) receptor function off or on in CA1 during the consolidation period. Our data indicate that memory consolidation depends on the reactivation of the NMDA receptor, possibly to reinforce site-specific synaptic modifications to consolidate memory traces. Such a synaptic reinforcement process may also serve as a cellular means by which the new memory is transferred from the hippocampus to the cortex for permanent storage.
Oxygen Activation and Reduction in Respiration: Involvement of Redox-Active Tyrosine 244
Authors: Proshlyakov Denis A. , Pressler Michelle A. , DeMaso Catherine , Leykam Joseph F. , DeWitt David L. , Babcock Gerald T.
Published: July 2002

Cytochrome oxidase activates and reduces O
2
to water to sustain respiration and uses the energy released to drive proton translocation and adenosine 5′-triphosphate synthesis. A key intermediate in this process,
P
, lies at the junction of the O
2
-reducing and proton-pumping functions. We used radioactive iodide labeling followed by peptide mapping to gain insight into the structure of
P
. We show that the cross-linked histidine 240–tyrosine 244 (His
240
-Tyr
244
) species is redox active in
P
formation, which establishes its structure as Fe
IV
=O/Cu
B
2+
-H
240
-Y
244
·. Thus, energy transfer from O
2
to the protein moiety is used as a strategy to avoid toxic intermediates and to control energy utilization in subsequent proton-pumping events.
Photoactivated Fluorescence from Individual Silver Nanoclusters
Authors: Peyser Lynn A. , Vinson Amy E. , Bartko Andrew P. , Dickson Robert M.
Published: July 2002

Fluorescence microscopy of nanoscale silver oxide (Ag
2
O) reveals strong photoactivated emission for excitation wavelengths shorter than 520 nanometers. Although blinking and characteristic emission patterns demonstrate single-nanoparticle observation, large-scale dynamic color changes were also observed, even from the same nanoparticle. Identical behavior was observed in oxidized thin silver films that enable Ag
2
O particles to grow at high density from silver islands. Data were readily written to these films with blue excitation; stored data could be nondestructively read with the strong red fluorescence resulting from green (wavelengths longer than 520 nanometers) excitation. The individual luminescent species are thought to be silver nanoclusters that are photochemically generated from the oxide.
Fluid Control in Multichannel Structures by Electrocapillary Pressure
Authors: Prins M. W. J. , Welters W. J. J. , Weekamp J. W.
Published: July 2002

We demonstrate control of fluid motion in three-dimensional structures with thousands of microchannels. Fluids are manipulated via an electrocapillary pressure, originating from electrostatic control of the solid/fluid interfacial tension in the microchannels. Reversible fluid displacement has been achieved for all channel orientations with respect to gravity. The velocities of several centimeters per second are nearly two orders of magnitude higher than the velocities demonstrated by other electrofluidic actuation principles.
Apoptotic Molecular Machinery: Vastly Increased Complexity in Vertebrates Revealed by Genome Comparisons
Authors: Aravind L. , Dixit Vishva M. , Koonin Eugene V.
Published: July 2002

A comparison of the proteins encoded in the recently (nearly) completed human genome to those from the fly and nematode genomes reveals a major increase in the complexity of the apoptotic molecular machinery in vertebrates, in terms of both the number of proteins involved and their domain architecture. Several components of the apoptotic system are shared by humans and flies, to the exclusion of nematodes, which seems to support the existence of a coelomate clade in animal evolution. A considerable repertoire of apoptotic protein domains was detected in Actinomycetes and Cyanobacteria, which suggests a major contribution of horizontal gene transfer to the early evolution of apoptosis.
Effect of Subinhibitory Concentrations of Macrolides on Expression of Flagellin inPseudomonas aeruginosaandProteus mirabilis
Authors: Kawamura-Sato Kumiko , Iinuma Yoshitsugu , Hasegawa Tadao , Horii Toshinobu , Yamashino Takafumi , Ohta Michio
Published: July 2002

In the present study we showed by molecular analysis that the inhibition of motility by macrolides inProteus mirabilisandPseudomonas aeruginosawas well correlated with the loss of the expression of flagellin. Erythromycin, clarithromycin, and azithromycin at subinhibitory concentrations (sub-MICs) suppressed the expression of flagellin dose dependently. Azithromycin had the strongest inhibitory effect on the expression ofP. aeruginosaflagellin, whereas 16-membered rokitamycin had only a weak inhibitory effect. These results indicate the potential effectiveness of sub-MICs of erythromycin, clarithromycin, and azithromycin for the treatment of patients withP. mirabilisandP. aeruginosainfections.
ACI-1 from
Acidaminococcus fermentans
: Characterization of the First β-Lactamase in Anaerobic Cocci
Authors: Galán J. C. , Reig M. , Navas A. , Baquero F. , Blázquez J.
Published: July 2002

Acidaminococcus fermentans
belongs to the group of strictly anaerobic gram-negative cocci. All previously described
Acidaminococcus
strains are susceptible to β-lactam antibiotics. An
A. fermentans
strain (RYC-MR95) resistant to penicillin and expanded-spectrum cephalosporin (amoxicillin and cefotaxime MICs, 64 μg/ml) was isolated from a human perianal abscess. A fragment encoding a β-lactamase from genomic DNA was cloned in
Escherichia coli
K-12 strain HB101, and the recombinant strain expressed resistance to amoxicillin (MIC, 1,024 μg/ml) and cefotaxime (MIC, 4 μg/ml). Clavulanic acid decreased the MICs to 8 and 0.03 μg/ml, respectively. Analysis of the nucleotide sequence revealed a new class A β-lactamase, ACI-1. In accordance with its biochemical properties, we propose to assign ACI-1 to functional group 2be. The ACI-1 enzyme (estimated pI 4.3) had <50% amino acid identity with any other class A β-lactamases, the closest being ROB-1 from
Haemophilus influenzae
(44%). ACI-1 was closer to class A β-lactamases from some gram-positive organisms (41 to 44% amino acid identity with
Bacillus
β-lactamases) than to most class A enzymes from gram-negative organisms (TEM-1, 24.6%). The
aci1
gene had a G+C content of 42.1%, in contrast with 56% G+C content for genomic DNA from
A. fermentans
, thus suggesting that
aci1
may have been obtained by horizontal gene transfer.
In Vitro Susceptibilities of
Capnocytophaga
Isolates to β-Lactam Antibiotics and β-Lactamase Inhibitors
Authors: Jolivet-Gougeon Anne , Buffet Anne , Dupuy Cécile , Sixou Jean-Louis , Bonnaure-Mallet Martine , David Sandrine , Cormier Michel
Published: July 2002

The susceptibilities of 43 pharyngeal isolates of
Capnocytophaga
to beta-lactam antibiotics, alone or in combination with beta-lactamase inhibitors, were tested by an agar dilution method. The 34 beta-lactamase-positive strains were highly resistant to beta-lactams, but the intrinsic activities of clavulanate, tazobactam, and sulbactam against
Capnocytophaga
, even beta-lactamase producers, indicates that these beta-lactamase inhibitors could be used for empirical treatment of neutropenic patients with oral sources of infection.
Comparative In Vitro Activities of Daptomycin and Vancomycin against Resistant Gram-Positive Pathogens
Authors: Snydman D. R. , Jacobus N. V. , McDermott L. A. , Lonks J. R. , Boyce J. M.
Published: July 2002

The in vitro activity of daptomycin against 224 current gram-positive clinical isolates including vancomycin-resistant
Enterococcus faecium
(VREF), methicillin-resistant
Staphylococcus aureus
(MRSA), methicillin-resistant
Staphylococcus
spp. (MRSS), and penicillin-resistant
Streptococcus pneumoniae
(PRSP) was evaluated. The MICs at which 90% of isolates are inhibited for daptomycin and vancomycin, respectively, were as follows: MRSA, 1 and 2 μg/ml; MRSS, 1 and 4 μg/ml; PRSP, 1 and 0.5 μg/ml; and VREF, 2 and >64 μg/ml. Daptomycin was bactericidal against 82% of 17 VREF isolates. The antibacterial activity of daptomycin was strongly dependent on the calcium concentration of the medium. Daptomycin was active against all gram-positive cocci tested.
Molecular Genetic Analysis of Nucleotide Polymorphisms Associated with Ethambutol Resistance in Human Isolates of
Mycobacterium tuberculosis
Authors: Ramaswamy Srinivas V. , Amin Amol G. , Göksel Servet , Stager Charles E. , Dou Shu-Jun , El Sahly Hana , Moghazeh Soraya L. , Kreiswirth Barry N. , Musser James M.
Published: July 2002

Ethambutol (EMB) is a central component of drug regimens used worldwide for the treatment of tuberculosis. To gain insight into the molecular genetic basis of EMB resistance, approximately 2 Mb of five chromosomal regions with 12 genes in 75 epidemiologically unassociated EMB-resistant and 33 EMB-susceptible
Mycobacterium tuberculosis
strains isolated from human patients were sequenced. Seventy-six percent of EMB-resistant organisms had an amino acid replacement or other molecular change not found in EMB-susceptible strains. Thirty-eight (51%) EMB-resistant isolates had a resistance-associated mutation in only 1 of the 12 genes sequenced. Nineteen EMB-resistant isolates had resistance-associated nucleotide changes that conferred amino acid replacements or upstream potential regulatory region mutations in two or more genes. Most isolates (68%) with resistance-associated mutations in a single gene had nucleotide changes in
embB
, a gene encoding an arabinosyltransferase involved in cell wall biosynthesis. The majority of these mutations resulted in amino acid replacements at position 306 or 406 of EmbB. Resistance-associated mutations were also identified in several genes recently shown to be upregulated in response to exposure of
M. tuberculosis
to EMB in vitro, including genes in the
iniA
operon. Approximately one-fourth of the organisms studied lacked mutations inferred to participate in EMB resistance, a result indicating that one or more genes that mediate resistance to this drug remain to be discovered. Taken together, the results indicate that there are multiple molecular pathways to the EMB resistance phenotype.
In Vitro Activities of Ketoconazole, Econazole, Miconazole, and
Melaleuca alternifolia
(Tea Tree) Oil against
Malassezia
Species
Authors: Hammer K. A. , Carson C. F. , Riley T. V.
Published: July 2002

The in vitro activities of ketoconazole, econazole, miconazole, and tea tree oil against 54
Malassezia
isolates were determined by agar and broth dilution methods. Ketoconazole was more active than both econazole and miconazole, which showed very similar activities.
M. furfur
was the least susceptible species.
M. sympodialis
,
M. slooffiae
,
M. globosa
, and
M. obtusa
showed similar susceptibilities to the four agents.
Efficacy of Liposomal Amphotericin B with Prolonged Circulation in Blood in Treatment of Severe Pulmonary Aspergillosis in Leukopenic Rats
Authors: Van Etten Els W. M. , Stearne-Cullen Lorna E. T. , Ten Kate Marian T. , Bakker-Woudenberg Irma A. J. M.
Published: July 2002

The therapeutic efficacy of long-circulating polyethylene glycol-coated liposomal amphotericin B (AMB) (PEG-AMB-LIP) was compared with that of AMB desoxycholate (Fungizone) in a model of severe invasive pulmonary aspergillosis in persistently leukopenic rats as well as in temporarily leukopenic rats. PEG-AMB-LIP treatment (intravenous administration) consisted of a single, or double (every 72 h), or triple (every 72 h) dose of 10 mg of AMB/kg of body weight, a double dose (every 72 h) of 14 mg of AMB/kg, or a 5-day treatment (every 24 h) with 6 mg/kg/dose. AMB desoxycholate was administered for 10 consecutive days at 1 mg of AMB/kg/dose. Treatment was started 30 h after fungal inoculation, at which time mycelial growth was firmly established. Both persistently and temporarily leukopenic rats died between 4 and 9 days after
Aspergillus fumigatus
inoculation when they were left untreated or after treatment with a placebo. In persistently leukopenic rats, a single dose of PEG-AMB-LIP (10 mg/kg) was as effective as the 10-day treatment with AMB desoxycholate (at 1 mg/kg/dose) in significantly prolonging the survival of rats infected with
A. fumigatus
and in reducing the dissemination of
A. fumigatus
to the liver. Prolongation of PEG-AMB-LIP treatment (double or triple dose or 5-day treatment) did not further improve efficacy. For temporarily leukopenic rats no major advances in efficacy were achieved compared to those for persistently leukopenic rats, probably because the leukocyte numbers in blood were restored too late in the course of infection.
Flow Cytometric Monitoring of Antibiotic-Induced Injury in
Escherichia coli
Using Cell-Impermeant Fluorescent Probes
Authors: Mortimer Fiona C. , Mason David J. , Gant Vanya A.
Published: July 2002

Three fluorescent nucleic acid binding dyes—propidium iodide, TO-PRO-1, and SYTOX green—were evaluated, and their abilities to distinguish between bacterial cells with and without an intact cytoplasmic membrane were compared. Each dye was readily able to discriminate between healthy and permeabilized cells of
Escherichia coli
, although SYTOX green showed a greater enhancement in fluorescence intensity on staining-compromised, as opposed to healthy, cells in log-phase growth, than either PI or TO-PRO-1. Flow cytometric analysis of
E. coli
stained with these dyes after exposing them to several antimicrobial agents showed that all three dyes were able to detect antimicrobial action. Notably, however, the intensity of the cell-associated fluorescence was related to the mechanism of action of the antimicrobial agent. Large changes in fluorescence intensity were observed for all the dyes subsequent to β-lactam antibiotic action, but smaller changes (or no change) were seen subsequent to exposure to antimicrobials acting directly or indirectly on nucleic acid synthesis. Furthermore, cell-associated fluorescence did not relate to loss of viability as determined by plate counts. Despite offering much insight into antimicrobial mechanisms of action, these fundamental problems become relevant to the development of rapid antimicrobial susceptibility tests if colony formation is used as the standard.
Pharmacokinetics of an Everninomicin (SCH 27899) in Mice, Rats, Rabbits, and Cynomolgus Monkeys following Intravenous Administration
Authors: Lin C. , Gupta S. , Loebenberg D. , Cayen M. N.
Published: July 2002

The pharmacokinetics of SCH 27899, a novel oligosaccharide compound of the everninomicin class with excellent activity against gram-positive strains, was studied with mice, rats, rabbits, and cynomolgus monkeys following intravenous administration as SCH 27899–
N
-methylglucamine–hydroxypropyl β-cyclodextrin. Concentrations of SCH 27899 in mouse serum, rat plasma, and rabbit serum were determined by a high-pressure liquid chromatography method on a poly(styrene-divinyl benzene) column, and those in monkey plasma were determined by a paired-ion chromatographic method. Plasma and serum concentrations of SCH 27899 exhibited a biexponential decline in all species following intravenous administration. The half-lives at β phase were 3.0 to 7.9 h in mice, rats, and rabbits and 24 h in cynomolgus monkeys. There was a linear relationship between the area under the curve extrapolated to infinity [AUC(I)] in mice and dose. Rabbits also exhibited dose proportionality in AUC(I). However, in rats, increasing the dose from 3 to 60 mg/kg of body weight resulted in a 49-fold increase in AUC(I). When the species was changed from mouse to rat, rabbit, or cynomolgus monkey, AUC(I) increased, whereas clearance (CL) decreased. It was concluded that the pharmacokinetics of SCH 27899 in animals varied with species; CL was the highest in mice and rats, followed by rabbits and cynomolgus monkeys.
Direct Measurement of the Anti-Influenza Agent Zanamivir in the Respiratory Tract following Inhalation
Authors: Peng Amy W. , Milleri Stefano , Stein Daniel S.
Published: July 2002

In a single-center, randomized study, zanamivir (Relenza) concentrations in induced sputum samples and nasal washings of healthy adults following oral inhalation were measured. Concentrations in sputum exceeded the median viral neuraminidase 50% inhibitory concentration at 6, 12, and 24 h, and those in nasal washings did so at 6 and 12 h. There were no zanamivir-related adverse events or laboratory abnormalities.
Characterization of a Fish Antimicrobial Peptide: Gene Expression, Subcellular Localization, and Spectrum of Activity
Authors: Cole Alexander M. , Darouiche Rabih O. , Legarda Diana , Connell Nancy , Diamond Gill
Published: July 2002

Antimicrobial peptides are proposed to act as the first line of mucosal host defense by exerting broad-spectrum microbicidal activity against pathogenic microbes. Pleurocidin, a new 25-residue linear antimicrobial peptide, was recently isolated from the skin secretions of winter flounder (Pleuronectes americanus). The present study identifies the cDNA and gene encoding pleurocidin. The pleurocidin gene comprises four exons. Its upstream region demonstrates consensus binding sequences for transcription factors found in host defense genes in mammals, including sequences identical to the NF-IL6 and alpha and gamma interferon response elements. Pleurocidin is predicted to exist as a 68-residue prepropeptide that undergoes proteolytic cleavage of its amino-terminal signal and carboxy-terminal anionic propiece to form the active, mature peptide. Transmission electron microscopy localized pleurocidin to the mucin granules of skin and intestinal goblet cells. Significant synergy was shown to occur between pleurocidin andd-cycloserine targetingMycobacterium smegmatis. Pleurocidin was functionally active at physiologic concentrations of magnesium and calcium; however, high concentrations of these divalent cations ablated pleurocidin's activity against a standard test strain,Escherichia coliD31. Pleurocidin was tested against bacterial and fungal clinical isolates and showed broad-spectrum antimicrobial activity. Together, these data support the hypothesis that pleurocidin participates in innate mucosal immunity, and it may prove to be a beneficial therapeutic agent.
Enhanced Reduction of
Helicobacter pylori
Load in Precolonized Mice Treated with Combined Famotidine and Urease-Binding Polysaccharides
Authors: Icatlo Faustino C. , Kimura Nobutake , Goshima Hideo , Kodama Yoshikatsu
Published: July 2002

The present study investigated the effect of a model urease-binding polysaccharide in combination with a histamine H
2
receptor antagonist on
Helicobacter pylori
colonization in vivo. Euthymic hairless mice were treated daily with dextran sulfate via drinking water and/or famotidine via intragastric gavage starting at 1 week postchallenge with a CagA
+
VacA
+
(type 1) strain of
H. pylori
. Treatment of precolonized mice for 2 weeks with dextran sulfate combined with famotidine yielded a group mean bacterial load (per 100 mg of gastric tissue) of log
10
1.04 CFU, which was significantly lower than those of the famotidine (log
10
3.35 CFU,
P
< 0.01) and dextran sulfate (log
10
2.45 CFU,
P
< 0.05) monotherapy groups and the infected nontreated group (log
10
3.64 CFU,
P
< 0.01). Eradication was achieved after 2 weeks of treatment in 50% or more of the test mice using drug combinations (1 or 2 weeks of famotidine plus 2 weeks of dextran sulfate) versus none in the monotherapy and positive control groups. The enhanced activity of the drug combination may be related to the daily pattern of transient acid suppression by famotidine inducing periodic bacterial convergence to superficial mucus sites penetrated by dextran sulfate from the lumen. Increased urease-dextran sulfate avidity was observed in vitro in the presence of famotidine and may partly account for the enhanced activity. With potential utility in abbreviating treatment time and eradication of antibiotic-resistant strains, the use of urease-targeted polysaccharides concurrently with a gastric acid inhibitor warrants consideration as an additional component of the standard multidrug chemotherapy of
H. pylori
infection.