bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunoglobulin E Production in the Absence of Interleukin-4-Secreting CD1-Dependent Cells
Authors: Smiley Stephen T. , Kaplan Mark H. , Grusby Michael J.
Published: July 2002

A lymphocyte population that expresses surface markers found on T cells and natural killer (NK) cells secretes large amounts of interleukin-4 (IL-4) immediately after T cell receptor ligation. These NK-like T cells are thus thought to be important for the initiation of type 2 T helper cell (T
H
2) responses. CD1-deficient mice were found to lack this lymphocyte subset, but they could nevertheless mount a protypical T
H
2 response; after immunization with antibody to immunoglobulin D (IgD), CD1-deficient mice produced IgE. Thus, although dependent on CD1 for their development, IL-4-secreting NK-like T cells are not required for T
H
2 responses.
Modulation of Ras and a-Factor Function by Carboxyl-Terminal Proteolysis
Authors: Boyartchuk Victor L. , Ashby Matthew N. , Rine Jasper
Published: July 2002

Prenylated proteins contain a covalently linked cholesterol intermediate near their carboxyl-termini. Maturation of most prenylated proteins involves proteolytic removal of the last three amino acids. Two genes in
Saccharomyces cerevisiae
,
RCE1
and
AFC1
, were identified that appear to be responsible for this processing. The Afc1 protein is a zinc protease that participates in the processing of yeast
a
-factor mating pheromone. The Rce1 protein contributes to the processing of both Ras protein and
a
-factor. Deletion of both
AFC1
and
RCE1
resulted in the loss of proteolytic processing of prenylated proteins. Disruption of
RCE1
led to defects in Ras localization and signaling and suppressed the activated phenotype associated with the allele

RAS2
val19

.
A Hominoid Genus from the Early Miocene of Uganda
Authors: Gebo Daniel L. , MacLatchy Laura , Kityo Robert , Deino Alan , Kingston John , Pilbeam David
Published: July 2002

Fossils from a large-bodied hominoid from early Miocene sediments of Uganda, along with material recovered in the 1960s, show features of the shoulder and vertebral column that are significantly similar to those of living apes and humans. The large-bodied hominoid from Uganda dates to at least 20.6 million years ago and thus represents the oldest known hominoid sharing these derived characters with living apes and humans.
Microbial Pathogenesis: Genomics and Beyond
Authors: Strauss Evelyn J. , Falkow Stanley
Published: July 2002

The growing number of complete microbial genome sequences provides a powerful tool for studying the biology of microorganisms. In combination with assays for function, genomic-based approaches can facilitate efficient and directed research strategies to elucidate mechanisms of bacterial pathogenicity. As genomic information accrues, the challenge remains to construct a picture of the biology that accurately reflects how individual genes collaborate to create the complex world of microbial specialization.
Trans-kingdom Transposition of the
Drosophila
Element
mariner
Within the Protozoan
Leishmania
Authors: Gueiros-Filho Frederico J. , Beverley Stephen M.
Published: July 2002

Transposable elements of the
mariner
/Tc1 family are postulated to have spread by horizontal transfer and be relatively independent of host-specific factors. This was tested by introducing the
Drosophila mauritiana
element
mariner
into the human parasite
Leishmania major
, a trypanosomatid protozoan belonging to one of the most ancient eukaryotic lineages. Transposition in
Leishmania
was efficient, occurring in more than 20 percent of random transfectants, and proceeded by the same mechanism as in
Drosophila
. Insertional inactivation of a specific gene was obtained, and a modified
mariner
element was used to select for gene fusions, establishing
mariner
as a powerful genetic tool for
Leishmania
and other organisms. These experiments demonstrate the evolutionary range of
mariner
transposition in vivo and underscore the ability of this ubiquitous DNA to parasitize the eukaryotic genome.
Dynamical Lifetimes of Objects Injected into Asteroid Belt Resonances
Authors: Gladman Brett J. , Migliorini Fabbio , Morbidelli Alessandro , Zappalà Vincenzo , Michel Patrick , Cellino Alberto , Froeschlé Christiane , Levison Harold F. , Bailey Mark , Duncan Martin
Published: July 2002

Numerical simulations of particles placed in orbital resonances in the main asteroid belt show that the typical dynamical lifetimes of objects that could become near-Earth asteroids or meteorites are only a few million years, with the majority destroyed by being transferred to Jupiter-crossing orbits or being driven into the sun. Particles that fortuitously migrate to the terrestrial planet region may be pushed to high-inclination orbits by resonances but are still dynamically eliminated on time scales of ∼10 million years. These shorter lifetimes may require a reassessment of our qualitative understanding about near-Earth asteroids and meteorite delivery.
Mitosis in Living Budding Yeast: Anaphase A But No Metaphase Plate
Authors: Straight Aaron F. , Marshall Wallace F. , Sedat John W. , Murray Andrew W.
Published: July 2002

Chromosome movements and spindle dynamics were visualized in living cells of the budding yeast
Saccharomyces cerevisiae
. Individual chromosomal loci were detected by expression of a protein fusion between green fluorescent protein (GFP) and the Lac repressor, which bound to an array of Lac operator binding sites integrated into the chromosome. Spindle microtubules were detected by expression of a protein fusion between GFP and Tub1, the major alpha tubulin. Spindle elongation and chromosome separation exhibited biphasic kinetics, and centromeres separated before telomeres. Budding yeast did not exhibit a conventional metaphase chromosome alignment but did show anaphase A, movement of the chromosomes to the poles.
Evidence for Interacting Gas Flows and an Extended Volatile Source Distribution in the Coma of Comet C/1996 B2 (Hyakutake)
Authors: Harris Walter M. , Combi Michael R. , Honeycutt R. Kent , Mueller Béatrice E. A. , Scherb Frank
Published: July 2002

Images of comet C/1996 B2 (Hyakutake) taken during its close approach to Earth show differences in the distribution of gas and dust in the inner coma and reveal two arc-shaped molecular resonant emission features. The morphology of these features, as well as the apparent decoupling gas from dust in the inner coma, suggest that an extended region of icy grains surrounds the nucleus of Hyakutake and contributes substantially to the production of volatiles. Model simulations suggest the same conclusion and indicate that the brighter arc is explainable by the presence of a trailing condensation of ice-bearing granules with a rate of volatile production approximately 23 percent of that of the nucleus.
Incommensurate Spin Fluctuations in High-Transition Temperature Superconductors
Authors: Wells B. O. , Lee Y. S. , Kastner M. A. , Christianson R. J. , Birgeneau R. J. , Yamada K. , Endoh Y. , Shirane G.
Published: July 2002

Neutron scattering experiments have revealed a fascinating interplay between the hole doping, the spin fluctuations, and the superconductivity of the cuprate superconductors. Recently, electrochemical techniques have been used to produce large single crystals of La
2
CuO
4+

y

, which has mobile oxygen dopants. Staging behavior of the excess oxygen has been demonstrated, and the low-energy spin fluctuations in stage 6 La
2
CuO
4+

y

have been measured. The spin fluctuations are incommensurate with the lattice and have spatial, energy, and temperature dependencies very much like those in La
2−

x

Sr

x

CuO
4
, with similar high transition temperature. This establishes the universality of the incommensurate spin fluctuations among the La
2
CuO
4
-based superconductors.
Ferric Iron Content of Mineral Inclusions in Diamonds from São Luiz: A View into the Lower Mantle
Authors: McCammon Catherine , Hutchison Mark , Harris Jeff
Published: July 2002

Mössbauer spectroscopy on inclusions in diamonds from São Luiz, Brazil, show that (Mg,Fe)O inclusions contain little Fe
3+
(Fe
3+
/ΣFe ≤ 7%), whereas inclusions with pyroxene composition (believed to have been originally in the perovskite structure) and tetragonal almandine-pyrope phase (TAPP) inclusions contain high relative amounts of Fe
3+
(Fe
3+
/ΣFe = 20 to 75%). These observations are consistent with high-pressure experiments on synthetic samples and support the idea that the inclusions originated in the lower mantle. Fe-Mg partitioning data for co-existing (Mg,Fe,Al)(Si,Al)O
3
– (Mg,Fe)O pairs also indicate that the phases were in equilibrium at the time of diamond formation in the lower mantle.
Amidation of Bioactive Peptides: The Structure of Peptidylglycine α-Hydroxylating Monooxygenase
Authors: Prigge Sean T. , Kolhekar Aparna S. , Eipper Betty A. , Mains Richard E. , Amzel L. Mario
Published: July 2002

Many neuropeptides and peptide hormones require amidation at the carboxyl terminus for activity. Peptidylglycine α-amidating monooxygenase (PAM) catalyzes the amidation of these diverse physiological regulators. The amino-terminal domain of the bifunctional PAM protein is a peptidylglycine α-hydroxylating monooxygenase (PHM) with two coppers that cycle through cupric and cuprous oxidation states. The anomalous signal of the endogenous coppers was used to determine the structure of the catalytic core of oxidized rat PHM with and without bound peptide substrate. These structures strongly suggest that the PHM reaction proceeds via activation of substrate by a copper-bound oxygen species. The mechanistic and structural insight gained from the PHM structures can be directly extended to dopamine β-monooxygenase.
Mediation of Sonic Hedgehog-Induced Expression of COUP-TFII by a Protein Phosphatase
Authors: Krishnan Venkatesh , Pereira Fred A. , Qiu Yuhong , Chen Chien-Huan , Beachy Philip A. , Tsai Sophia Y. , Tsai Ming-Jer
Published: July 2002

A Sonic hedgehog (Shh) response element was identified in the chicken ovalbumin upstream promoter–transcription factor II (COUP-TFII) promoter that binds to a factor distinct from
Gli
, a gene known to mediate Shh signaling. Although this binding activity is specifically stimulated by Shh-N (amino-terminal signaling domain), it can also be unmasked with protein phosphatase treatment in the mouse cell line P19, and induction by Shh-N can be blocked by phosphatase inhibitors. Thus, Shh-N signaling may result in dephosphorylation of a target factor that is required for activation of COUP-TFII–, Islet1-, and Gli response element–dependent gene expression. This finding identifies another step in the Shh-N signaling pathway.
The Origin of Chondrules at Jovian Resonances
Authors: Weidenschilling S. J. , Marzari F. , Hood L. L.
Published: July 2002

Isotopic dating indicates that chondrules were produced a few million years after the solar nebula formed. This timing is incompatible with dynamical lifetimes of small particles in the nebula and short time scales for the formation of planetesimals. Temporal and dynamical constraints can be reconciled if chondrules were produced by heating of debris from disrupted first-generation planetesimals. Jovian resonances can excite planetesimal eccentricities enough to cause collisional disruption and melting of dust by bow shocks in the nebular gas. The ages of chondrules may indicate the times of Jupiter's formation and dissipation of gas from the asteroidal region.
Transcriptional and Posttranscriptional Plant Gene Silencing in Response to a Pathogen
Authors: Al-Kaff Nadia S. , Covey Simon N. , Kreike Maria M. , Page Anthony M. , Pinder Rachel , Dale Philip J.
Published: July 2002

Plants are able to respond to pathogen attack to restrain development of a systemic infection. The response of
Brassica napus
(oilseed rape) to systemic infection with the DNA virus cauliflower mosaic virus was shown to result in enhancement and subsequent suppression of viral gene expression in parallel with changes in symptom expression. Transgenes with homology to viral sequences were also affected. This phenomenon, which was shown to be mediated by both transcriptional and posttranscriptional mechanisms, might be related to regulation of highly expressed genetic elements.
Monoallelic Expression of the Interleukin-2 Locus
Authors: Holländer Georg A. , Zuklys Saulius , Morel Corinne , Mizoguchi Emiko , Mobisson Kathrine , Simpson Stephen , Terhorst Cox , Wishart William , Golan David E. , Bhan Atul K. , Burakoff Steven J.
Published: July 2002

The lymphokine interleukin-2 (IL-2) is responsible for autocrine cell cycle progression and regulation of immune responses. Uncontrolled secretion of IL-2 results in adverse reactions ranging from anergy, to aberrant T cell activation, to autoimmunity. With the use of fluorescent in situ hybridization and single-cell polymerase chain reaction in cells with different IL-2 alleles, IL-2 expression in mature thymocytes and T cells was found to be tightly controlled by monoallelic expression. Because IL-2 is encoded at a nonimprinted autosomal locus, this result represents an unusual regulatory mode for controlling the precise expression of a single gene.
Severe Mycobacterial and
Salmonella
Infections in Interleukin-12 Receptor-Deficient Patients
Authors: Jong Rolien de , Altare Frédéric , Haagen Inez-Anne , Elferink Diënne G. , Boer Tjitske de , van Breda Vriesman Peter J. C. , Kabel Peter J. , Draaisma Johannes M. T. , van Dissel Jaap T. , Kroon Frank P. , Casanova Jean-Laurent , Ottenhoff Tom H. M.
Published: July 2002

Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell (T
H
1) responses and interferon-γ (IFN-γ) production. IL-12 binds to high-affinity β1/β2 heterodimeric IL-12 receptor (IL-12R) complexes on T cell and natural killer cells. Three unrelated individuals with severe, idiopathic mycobacterial and S
almonella
infections were found to lack IL-12Rβ1 chain expression. Their cells were deficient in IL-12R signaling and IFN-γ production, and their remaining T cell responses were independent of endogenous IL-12. IL-12Rβ1 sequence analysis revealed genetic mutations that resulted in premature stop codons in the extracellular domain. The lack of IL-12Rβ1 expression results in a human immunodeficiency and shows the essential role of IL-12 in resistance to infections due to intracellular bacteria.
The CO
2
Balance of Unproductive Aquatic Ecosystems
Authors: Duarte Carlos M. , Agustı́ Susana
Published: July 2002

Community respiration (
R
) rates are scaled as the two-thirds power of the gross primary production (
P
) rates of aquatic ecosystems, indicating that the role of aquatic biota as carbon dioxide sources or sinks depends on its productivity. Unproductive aquatic ecosystems support a disproportionately higher respiration rate than that of productive aquatic ecosystems, tend to be heterotrophic (
R > P
), and act as carbon dioxide sources. The average
P
required for aquatic ecosystems to become autotrophic (
P > R
) is over an order of magnitude greater for marshes than for the open sea. Although four-fifths of the upper ocean is expected to be net heterotrophic, this carbon demand can be balanced by the excess production over the remaining one-fifth of the ocean.
Cell Cycle Arrest by Vpr in HIV-1 Virions and Insensitivity to Antiretroviral Agents
Authors: Poon Betty , Grovit-Ferbas Kathie , Stewart Sheila A. , Chen Irvin S. Y.
Published: July 2002

Expression of human immunodeficiency virus–type 1 (HIV-1) Vpr after productive infection of T cells induces cell cycle arrest in the G
2
phase of the cell cycle. In the absence of de novo expression, HIV-1 Vpr packaged into virions still induced cell cycle arrest. Naturally noninfectious virus or virus rendered defective for infection by reverse transcriptase or protease inhibitors were capable of inducing Vpr-mediated cell cycle arrest. These results suggest a model whereby both infectious and noninfectious virions in vivo, such as those surrounding follicular dendritic cells, participate in immune suppression.
Particle Nucleation in the Tropical Boundary Layer and Its Coupling to Marine Sulfur Sources
Authors: Clarke A. D. , Davis D. , Kapustin V. N. , Eisele F. , Chen G. , Paluch I. , Lenschow D. , Bandy A. R. , Thornton D. , Moore K. , Mauldin L. , Tanner D. , Litchy M. , Carroll M. A. , Collins J. , Albercook G.
Published: July 2002

New particle formation in a tropical marine boundary layer setting was characterized during NASA's Pacific Exploratory Mission–Tropics A program. It represents the clearest demonstration to date of aerosol nucleation and growth being linked to the natural marine sulfur cycle. This conclusion was based on real-time observations of dimethylsulfide, sulfur dioxide, sulfuric acid (gas), hydroxide, ozone, temperature, relative humidity, aerosol size and number distribution, and total aerosol surface area. Classic binary nucleation theory predicts no nucleation under the observed marine boundary layer conditions.
Experimental Evolution of Parasites
Authors: Ebert Dieter
Published: July 2002

Serial passage experiments are a form of experimental evolution that is frequently used in applied sciences; for example, in vaccine development. During these experiments, molecular and phenotypic evolution can be monitored in real time, providing insights into the causes and consequences of parasite evolution. Within-host competition generally drives an increase in a parasite's virulence in a new host, whereas the parasite becomes avirulent to its former host, indicating a trade-off between parasite fitnesses on different hosts. Understanding why parasite virulence seldom escalates similarly in natural populations could help us to manage virulence and deal with emerging diseases.
A Nonhyperthermophilic Common Ancestor to Extant Life Forms
Authors: Galtier Nicolas , Tourasse Nicolas , Gouy Manolo
Published: July 2002

The G+C nucleotide content of ribosomal RNA (rRNA) sequences is strongly correlated with the optimal growth temperature of prokaryotes. This property allows inference of the environmental temperature of the common ancestor to all life forms from knowledge of the G+C content of its rRNA sequences. A model of sequence evolution, assuming varying G+C content among lineages and unequal substitution rates among sites, was devised to estimate ancestral base compositions. This method was applied to rRNA sequences of various species representing the major lineages of life. The inferred G+C content of the common ancestor to extant life forms appears incompatible with survival at high temperature. This finding challenges a widely accepted hypothesis about the origin of life.
Tropospheric Aerosol Climate Forcing in Clear-Sky Satellite Observations over the Oceans
Authors: Haywood J. M. , Ramaswamy V. , Soden B. J.
Published: July 2002

Tropospheric aerosols affect the radiative forcing of Earth's climate, but their variable concentrations complicate an understanding of their global influence. Model-based estimates of aerosol distributions helped reveal spatial patterns indicative of the presence of tropospheric aerosols in the satellite-observed clear-sky solar radiation budget over the world's oceans. The results show that, although geographical signatures due to both natural and anthropogenic aerosols are manifest in the satellite observations, the naturally occurring sea-salt is the leading aerosol contributor to the global-mean clear-sky radiation balance over oceans.
A Simple Predictive Model for the Structure of the Oceanic Pycnocline
Authors: Gnanadesikan Anand
Published: July 2002

A simple theory for the large-scale oceanic circulation is developed, relating pycnocline depth, Northern Hemisphere sinking, and low-latitude upwelling to pycnocline diffusivity and Southern Ocean winds and eddies. The results show that Southern Ocean processes help maintain the global ocean structure and that pycnocline diffusion controls low-latitude upwelling.
The Pex16p Homolog SSE1 and Storage Organelle Formation in
Arabidopsis
Seeds
Authors: Lin Yun , Sun Lin , Nguyen Long V. , Rachubinski Richard A. , Goodman Howard M.
Published: July 2002

Mature
Arabidopsis
seeds are enriched in storage proteins and lipids, but lack starch. In the
shrunken seed 1
(
sse1
) mutant, however, starch is favored over proteins and lipids as the major storage compound. SSE1 has 26 percent identity with Pex16p in
Yarrowia lipolytica
and complements
pex16
mutants defective in the formation of peroxisomes and the transportation of plasma membrane– and cell wall–associated proteins. In
Arabidopsis
maturing seeds, SSE1 is required for protein and oil body biogenesis, both of which are endoplasmic reticulum–dependent. Starch accumulation in
sse1
suggests that starch formation is a default storage deposition pathway.
Odor Response Properties of Rat Olfactory Receptor Neurons
Authors: Duchamp-Viret P. , Chaput M. A. , Duchamp A.
Published: July 2002

Molecular biology studies of olfaction have identified a multigene family of molecular receptors that are likely to be involved in odor transduction mechanisms. However, because previous functional data on peripheral coding were mainly collected from inferior vertebrates, it has been difficult to document the degree of specificity of odor interaction mechanisms. As a matter of fact, studies of the functional expression of olfactory receptors have not demonstrated the low or high specificity of olfactory receptors. In this study, the selectivity of olfactory receptor neurons was investigated in the rat at the cellular level under physiological conditions by unitary extracellular recordings. Individual olfactory receptor neurons were broadly responsive to qualitatively distinct odor compounds. We conclude that peripheral coding is based on activated arrays of olfactory receptor cells with overlapping tuning profiles.
Reach Plans in Eye-Centered Coordinates
Authors: Batista Aaron P. , Buneo Christopher A. , Snyder Lawrence H. , Andersen Richard A.
Published: July 2002

The neural events associated with visually guided reaching begin with an image on the retina and end with impulses to the muscles. In between, a reaching plan is formed. This plan could be in the coordinates of the arm, specifying the direction and amplitude of the movement, or it could be in the coordinates of the eye because visual information is initially gathered in this reference frame. In a reach-planning area of the posterior parietal cortex, neural activity was found to be more consistent with an eye-centered than an arm-centered coding of reach targets. Coding of arm movements in an eye-centered reference frame is advantageous because obstacles that affect planning as well as errors in reaching are registered in this reference frame. Also, eye movements are planned in eye coordinates, and the use of similar coordinates for reaching may facilitate hand-eye coordination.
GTP Binding by Class II Transactivator: Role in Nuclear Import
Authors: Harton Jonathan A. , Cressman Drew E. , Chin Keh-Chuang , Der Channing J. , -Y. Ting Jenny P.
Published: July 2002

Class II transactivator (CIITA) is a global transcriptional coactivator of human leukocyte antigen–D (HLA-D) genes. CIITA contains motifs similar to guanosine triphosphate (GTP)–binding proteins. This report shows that CIITA binds GTP, and mutations in these motifs decrease its GTP-binding and transactivation activity. Substitution of these motifs with analogous sequences from Ras restores CIITA function. CIITA exhibits little GTPase activity, yet mutations in CIITA that confer GTPase activity reduce transcriptional activity. GTP binding by CIITA correlates with nuclear import. Thus, unlike other GTP-binding proteins, CIITA is involved in transcriptional activation that uses GTP binding to facilitate its own nuclear import.
Experimental Determination of the Antiaromaticity of Cyclobutadiene
Authors: Deniz Ashok A. , Peters Kevin S. , Snyder Gary J.
Published: July 2002

Photoacoustic calorimetry was used to quantify the antiaromaticity of 1,3-cyclobutadiene (CBD) by measuring the heat release accompanying its formation via photofragmentation of a polycyclic precursor. In combination with quantum yield measurements and thermochemical calculations, this measurement provides an enthalpy of formation for CBD of 114 ± 11 (2σ) kilocalories per mole (kcal/mol). The extraordinary reactivity of this prototypical antiaromatic hydrocarbon had previously made its heat of formation inaccessible except by theoretical calculations. Relative to a hypothetical strainless, conjugated diene reference, CBD is destabilized by a total of 87 kcal/mol, 32 kcal/mol of which can be attributed to ring strain and 55 kcal/mol to antiaromaticity (compared with 21 kcal/mol for the aromatic stabilization of benzene). Relative to a reference with isolated double bonds, CBD's antiaromaticity is 48 kcal/mol (compared with 32 kcal/mol for the aromaticity of benzene).
The Gelation of CO
2
: A Sustainable Route to the Creation of Microcellular Materials
Authors: Shi C. , Huang Z. , Kilic S. , Xu J. , Enick R. M. , Beckman E. J. , Carr A. J. , Melendez R. E. , Hamilton A. D.
Published: July 2002

Compounds with strong thermodynamic affinity for carbon dioxide (CO
2
) have been designed and synthesized that dissolve in CO
2
, then associate to form gels. Upon removal of the CO
2
, these gels produced free-standing foams with cells with an average diameter smaller than 1 micrometer and a bulk density reduction of 97 percent relative to the parent material.
Feedback Connections to the Lateral Geniculate Nucleus and Cortical Response Properties
Authors: Murphy Penelope C. , Duckett Simon G. , Sillito Adam M.
Published: July 2002

The cerebral cortex receives sensory input from the periphery by means of thalamic relay nuclei, but the flow of information goes both ways. Each cortical area sends a reciprocal projection back to the thalamus. In the visual system, the synaptic relations that govern the influence of thalamic afferents on orientation selectivity in the cortex have been studied extensively. It now appears that the connectivity of the corticofugal feedback pathway is also fundamentally linked to the orientation preference of the cortical cells involved.
Surfactant-Mediated Two-Dimensional Crystallization of Colloidal Crystals
Authors: Ramos Laurence , Lubensky T. C. , Dan Nily , Nelson Philip , Weitz D. A.
Published: July 2002

Colloidal particles can form unexpected two-dimensional ordered colloidal crystals when they interact with surfactants of the opposite charge. Coulomb interactions lead to self-limited adsorption of the particles on the surface of vesicles formed by the surfactants. The adsorbed particles form ordered but fluid rafts on the vesicle surfaces, and these ultimately form robust two-dimensional crystals. This use of attractive Coulomb interaction between colloidal particles and surfactant structures offers a potential new route to self-assembly of ordered colloidal structures.
Transgenic Mouse Model of Stunned Myocardium
Authors: Murphy Anne M. , Kögler Harald , Georgakopoulos Dimitrios , McDonough Jason L. , Kass David A. , Van Eyk Jennifer E. , Marbán Eduardo
Published: July 2002

Stunned myocardium is a syndrome of reversible contractile failure that frequently complicates coronary artery disease. Cardiac excitation is uncoupled from contraction at the level of the myofilaments. Selective proteolysis of the thin filament protein troponin I has been correlated with stunned myocardium. Here, transgenic mice expressing the major degradation product of troponin I (TnI
1–193
) in the heart were found to develop ventricular dilatation, diminished contractility, and reduced myofilament calcium responsiveness, recapitulating the phenotype of stunned myocardium. Proteolysis of troponin I also occurs in ischemic human cardiac muscle. Thus, troponin I proteolysis underlies the pathogenesis of a common acquired form of heart failure.
Voltage- and Tension-Dependent Lipid Mobility in the Outer Hair Cell Plasma Membrane
Authors: Oghalai John S. , Zhao Hong-Bo , Kutz J. Walter , Brownell William E.
Published: July 2002

The mechanism responsible for electromotility of outer hair cells in the ear is unknown but is thought to reside within the plasma membrane. Lipid lateral diffusion in the outer hair cell plasma membrane is a sigmoidal function of transmembrane potential and bathing media osmolality. Cell depolarization or hyposmotic challenge shorten the cell and reduce membrane fluidity by half. Changing the membrane tension with amphipathic drugs results in similar reductions. These dynamic changes in membrane fluidity represent the modulation of membrane tension by lipid-protein interactions. The voltage dependence may be associated with the force-generating motors that contribute to the exquisite sensitivity of mammalian hearing.
A Monoclinic Post-Stishovite Polymorph of Silica in the Shergotty Meteorite
Authors: Goresy Ahmed El , Dubrovinsky Leonid , Sharp Thomas G. , Saxena Surendra K. , Chen Ming
Published: July 2002

A post-stishovite phase of silica was identified in the Shergotty meteorite by x-ray diffraction and field emission scanning electron microscopy. The diffraction pattern revealed a monoclinic lattice, similar to the baddeleyite-structured polymorph with the cell parameters
a
= 4.375(1) angstroms,
b
= 4.584(1) angstroms,
c
= 4.708(1) angstroms, β= 99.97(3), ρ = 4.30(2) grams per cubic centimeter, where the numbers in parentheses are the maximum deviations. Transmission electron microscopy investigations indicate the presence of the α-lead dioxide–like polymorph, stishovite, and secondary cristobalite in the same silica grain. The mixture of high-density polymorphs suggests that several post-stishovite phases were formed during the shock event on the Shergotty parent body.
Microrobots for Micrometer-Size Objects in Aqueous Media: Potential Tools for Single-Cell Manipulation
Authors: Jager Edwin W. H. , Inganäs Olle , Lundström Ingemar
Published: July 2002

Conducting polymers are excellent materials for actuators that are operated in aqueous media. Microactuators based on polypyrrole-gold bilayers enable large movement of structures attached to these actuators and are of particular interest for the manipulation of biological objects, such as single cells. A fabrication method for creating individually addressable and controllable polypyrrole-gold microactuators was developed. With these individually controlled microactuators, a micrometer-size manipulator, or microrobotic arm, was fabricated. This microrobotic arm can pick up, lift, move, and place micrometer-size objects within an area of about 250 micrometers by 100 micrometers, making the microrobot an excellent tool for single-cell manipulation.
Interdigital Regulation of Digit Identity and Homeotic Transformation by Modulated BMP Signaling
Authors: Dahn Randall D. , Fallon John F.
Published: July 2002

The developmental mechanisms specifying digital identity have attracted 30 years of intense interest, but still remain poorly understood. Here, through experiments on chick foot development, we show digital identity is not a fixed property of digital primordia. Rather, digital identity is specified by the interdigital mesoderm, demonstrating a patterning function for this tissue before its regression. More posterior interdigits specify more posterior digital identities, and each primordium will develop in accordance with the most posterior cues received. Furthermore, inhibition of interdigital bone morphogenetic protein (BMP) signaling can transform digit identity, suggesting a role for BMPs in this process.
Element-Selective Single Atom Imaging
Authors: Suenaga K. , Tencé M. , Mory C. , Colliex C. , Kato H. , Okazaki T. , Shinohara H. , Hirahara K. , Bandow S. , Iijima S.
Published: July 2002

Electron energy-loss spectroscopy (EELS) is widely used to identify elemental compositions of materials studied by microscopy. We demonstrate that the sensitivity and spatial resolution of EELS can be extended to the single-atom limit. A chemical map for gadolinium (Gd) clearly reveals the distribution of Gd atoms inside a single chain of metallofullerene molecules (Gd@C
82
) generated within a single-wall carbon nanotube. This characterization technique thus provides the “eyes” to see and identify individual atoms in nanostructures. It is likely to find broad application in nanoscale science and technology research.
TCR-Induced Transmembrane Signaling by Peptide/MHC Class II Via Associated Ig-α/β Dimers
Authors: Lang Paul , Stolpa John C. , Freiberg Benjamin A. , Crawford Frances , Kappler John , Kupfer Abraham , Cambier John C.
Published: July 2002

Previous findings suggest that during cognate T cell–B cell interactions, major histocompatability complex (MHC) class II molecules transduce signals, leading to Src-family kinase activation, Ca
2+
mobilization, and proliferation. Here, we show that antigen stimulation of resting B cells induces MHC class II molecules to associate with Immunoglobulin (Ig)-α/Ig-β (CD79a/CD79b) heterodimers, which function as signal transducers upon MHC class II aggregation by the T cell receptor (TCR). The B cell receptor (BCR) and MHC class II/Ig-α/Ig-β are distinct complexes, yet class II–associated Ig-α/β appears to be derived from BCR. Hence, Ig-α/β are used in a sequential fashion for transduction of antigen and cognate T cell help signals.
Physical Structure and Inversion Charge at a Semiconductor Interface with a Crystalline Oxide
Authors: McKee R. A. , Walker F. J. , Chisholm M. F.
Published: July 2002

We show that the physical and electrical structure and hence the inversion charge for crystalline oxides on semiconductors can be understood and systematically manipulated at the atomic level. Heterojunction band offset and alignment are adjusted by atomic-level structural and chemical changes, resulting in the demonstration of an electrical interface between a polar oxide and a semiconductor free of interface charge. In a broader sense, we take the metal oxide semiconductor device to a new and prominent position in the solid-state electronics timeline. It can now be extensively developed using an entirely new physical system: the crystalline oxides–on–semiconductors interface.
In Vitro Antimicrobial Properties of Recombinant ASABF, an Antimicrobial Peptide Isolated from the Nematode
Ascaris suum
Authors: Zhang Hong , Yoshida Shigenobu , Aizawa Tomoyasu , Murakami Ritsuko , Suzuki Masato , Koganezawa Nozomu , Matsuura Atsushi , Miyazawa Mitsuhiro , Kawano Keiichi , Nitta Katsutoshi , Kato Yusuke
Published: July 2002

ASABF is a CSαβ-type antimicrobial peptide that contains four intramolecular disulfide bridges (Y. Kato and S. Komatsu, J. Biol. Chem. 271:30493–30498, 1996). In the present study, a recombinant ASABF was produced by using a yeast expression system, and its antimicrobial activity was characterized in detail. The recombinant ASABF was active against all gram-positive bacteria tested (7 of 7; minimum bactericidal concentration [MBC], 0.03 to 1 μg/ml) except
Leuconostoc mesenteroides
, some gram-negative bacteria (8 of 14; MBC, >0.5 μg/ml), and some yeasts (3 of 9; MBC >3 μg/ml). Slight hemolytic activity (4.2% at 100 μg/ml) against human erythrocytes was observed only under low-ionic-strength conditions. Less than 1 min of contact was enough to kill
Staphylococcus aureus
ATCC 6538P. The bactericidal activity against
S. aureus
was inhibited by salts.
Prediction of Quinolone Activity against
Mycobacterium avium
by Molecular Topology and Virtual Computational Screening
Authors: Gozalbes Rafael , Brun-Pascaud Monique , García-Domenech Ramon , Gálvez Jorge , Girard Pierre-Marie , Doucet Jean-Pierre , Derouin Francis
Published: July 2002

We conducted a quantitative structure-activity relationship study using a database of 158 quinolones previously tested against
Mycobacterium avium-M. intracellulare
complex in order to develop a model capable of predicting the activity of new quinolones against the
M. avium-M. intracellulare
complex in vitro. Topological indices were used as structural descriptors and were related to anti-
M. avium-M. intracellulare
complex activity by using the linear discriminant analysis (LDA) statistical technique. The discriminant equation thus obtained correctly classified 137 of the 158 quinolones, including 37 of a test group of 44 randomly chosen compounds. This model was then applied to 24 quinolones, including recently developed fluoroquinolones, whose MICs were subsequently determined in vitro by using the Alamar blue microplate assay; the biological results confirmed the model's predictions. The MICs of these 24 quinolones were then treated by multilinear regression (MLR) to establish a model capable of classifying them according to their in vitro activities. Using this model, a good correlation between measured and predicted MICs was found (
r
2
= 0.88;
r
2
cv
[cross-validation correlation] = 0.82). Moxifloxacin, sparfloxacin, and gatifloxacin were the most potent against the
M. avium- M. intracellulare
complex, with MICs of 0.2, 0.4, and 0.9 μg/ml, respectively. Finally, virtual modifications of these three drugs were evaluated in LDA and MLR models in order to determine the importance of different substituents in their activity. We conclude that the combination of molecular-topology methods, LDA, and MLR provides an excellent tool for the design of new quinolone structures with enhanced activity.
Indinavir Pharmacokinetics and Parmacodynamics in Children with Human Immunodeficiency Virus Infection
Authors: Gatti Giorgio , Vigano' Alessandra , Sala Natascia , Vella Stefano , Bassetti Matteo , Bassetti Dante , Principi Nicola
Published: July 2002

The indinavir dosage regimen currently used for human immunodeficiency virus (HIV)-infected children is not based on pharmacokinetic data obtained in the target patient population. The purpose of our study was to characterize indinavir pharmacokinetics and pharmacodynamics in HIV-infected children. Eleven children (age range, 9.0 to 13.6 years; weight range, 21.7 to 56.0 kg) receiving indinavir (500 mg/m
2
every 8 h) in combination with lamivudine and stavudine were studied. The correlation of indinavir pharmacokinetic parameters and demographic parameters was evaluated. Also, the pharmacodynamic relationship between parameters of indinavir exposure and parameters of renal toxicity and immunologic recovery was studied. The area under the indinavir concentration-time curve (AUC) and patient body surface area (BSA) showed a significant negative correlation (
r
= 0.73;
P
= 0.012). Patients with smaller BSA had excessive indinavir AUC compared to adults. On the other hand, the median minimum drug concentration in plasma (
C
min
) was lower than that reported for adults. The maximum indinavir concentration in serum was higher in patients with renal toxicity (5 out of 11 children), but the difference was not statistically significant (15.3 ± 8.2 versus 9.8 ± 4.4 mg/liter;
P
= 0.19). There was a trend toward higher immunologic efficacy in patients with greater indinavir exposure: the time-averaged AUC of the percentage of CD4
+
lymphocytes over the baseline value for patients with indinavir
C
min
> 95% inhibitory concentration (IC
95
) was higher than in patients with
C
min
< IC
95
(
P
= 0.068). Our study suggests that a dose reduction may be appropriate for children with small BSA and that a 6-h dosage regimen may be indicated for a substantial percentage of patients. Due to the low number of patients enrolled in this study, our results should be confirmed by a larger study.
Antimicrobial Activities of Mefloquine and a Series of Related Compounds
Authors: Kunin C. M. , Ellis W. Y.
Published: July 2002

Mefloquine was found to have bactericidal activity against methicillin- and fluoroquinolone-susceptible and -resistant strains of
Staphylococcus aureus
and
Staphylococcus epidermidis
and gentamicin- and vancomycin-resistant strains of
Enterococcus faecalis
and
Enterococcus faecium
. The MICs were 16 μg/ml, and the minimal bactericidal concentrations (MBCs) were 16 to 32 μg/ml. These concentrations cannot be achieved in serum. Mefloquine was active at a more achievable concentration against penicillin-susceptible and -resistant
Streptococcus pneumoniae
, with MICs of 0.2 to 1.5 μg/ml. Mefloquine was not active against gram-negative bacteria and yeasts. In an attempt to find more active derivatives, 400 mefloquine-related compounds were selected from the chemical inventory of The Walter Reed Army Institute of Research. We identified a series of compounds containing a piperidine methanol group attached to pyridine, quinoline, and benzylquinoline ring systems. These had activities similar to that of mefloquine against
S. pneumoniae
but were far more active against other gram-positive bacteria (MICs for staphylococci, 0.8 to 6.3 μg/ml). They had activities similar to that of amphotericin B against
Candida
spp. and
Cryptococcus neoformans
. Combinations of the compounds with gentamicin and vancomycin were additive against staphylococci and pneumococci. The MIC and MBC of gentamicin were decreased by four- to eightfold when this drug was combined with limiting dilutions of the compounds. There was no antagonism with other antimicrobial drugs. The compounds were rapidly bactericidal. They appear to act by disrupting cell membranes. Combinations of the compounds with aminoglycoside antibiotics may have potential for therapeutic use.
Identification and Expression of Genes Involved in Biosynthesis of
l
-Oleandrose and Its Intermediate
l
-Olivose in the Oleandomycin Producer
Streptomyces antibioticus
Authors: Aguirrezabalaga Ignacio , Olano Carlos , Allende Nerea , Rodriguez Leticia , Braña Alfredo F. , Méndez Carmen , Salas José A.
Published: July 2002

A 9.8-kb DNA region from the oleandomycin gene cluster in
Streptomyces antibioticus
was cloned. Sequence analysis revealed the presence of 8 open reading frames encoding different enzyme activities involved in the biosynthesis of one of the two 2,6-deoxysugars attached to the oleandomycin aglycone:
l
-oleandrose (the
oleW
,
oleV
,
oleL
, and
oleU
genes) and
d
-desosamine (the
oleNI
and
oleT
genes), or of both (the
oleS
and
oleE
genes). A
Streptomyces albus
strain harboring the
oleG2
glycosyltransferase gene integrated into the chromosome was constructed. This strain was transformed with two different plasmid constructs (pOLV and pOLE) containing a set of genes proposed to be required for the biosynthesis of dTDP-
l
-olivose and dTDP-
l
-oleandrose, respectively. Incubation of these recombinant strains with the erythromycin aglycon (erythronolide B) gave rise to two new glycosylated compounds, identified as
l
-3-
O
-olivosyl- and
l
-3-
O
-oleandrosyl-erythronolide B, indicating that pOLV and pOLE encode all enzyme activities required for the biosynthesis of these two 2,6-dideoxysugars. A pathway is proposed for the biosynthesis of these two deoxysugars in
S. antibioticus
.
Comparative Killing Rates of Fluoroquinolones and Cell Wall-Active Agents
Authors: Fung-Tomc Joan C. , Gradelski Elizabeth , Valera Lourdes , Kolek Benjamin , Bonner Daniel P.
Published: July 2002

Killing rates of fluoroquinolones, β-lactams, and vancomycin were compared against
Enterobacteriaceae
,
Staphylococcus aureus
, pneumococci, streptococci, and
Enterococcus faecalis
. The times required for fluoroquinolones to decrease viability by 3 log
10
were 1.5 h for
Enterobacteriaceae
, 4 to 6 h for staphylococci, and ≥6 h for streptococci and enterococci. Thus, the rate of killing by fluoroquinolones is organism group dependent; overall, they killed more rapidly than β-lactams and vancomycin.
In Vitro Activity of Telithromycin (HMR3647), a New Ketolide, against Clinical Isolates of
Mycoplasma pneumoniae
in Japan
Authors: Yamaguchi Toshiyuki , Hirakata Yoichi , Izumikawa Koichi , Miyazaki Yoshitsugu , Maesaki Shigefumi , Tomono Kazunori , Yamada Yasuaki , Kamihira Shimeru , Kohno Shigeru
Published: July 2002

The in vitro activity of telithromycin (HMR3647), a new ketolide, against
Mycoplasma pneumoniae
was determined by the broth microdilution test using 41 clinical isolates obtained in Japan, as compared with those of five macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin, and josamycin), minocycline, and levofloxacin. Telithromycin was less potent than azithromycin, but it was more active than four other macrolides, minocycline, and levofloxacin; its MICs at which 50 and 90% of the isolates tested were inhibited were both 0.00097 μg/ml, justifying clinical studies to determine its efficacy for treatment of
M. pneumoniae
.
Evidence for the Existence of a Multidrug Efflux Transporter Distinct from NorA in
Staphylococcus aureus
Authors: Kaatz Glenn W. , Seo Susan M. , O'Brien Louise , Wahiduzzaman Mohammad , Foster Timothy J.
Published: July 2002

A
Staphylococcus aureus norA
disruption mutant was created by allelic replacement. Exposure of this mutant to norfloxacin produced SA K1748, a derivative with raised fluoroquinolone MICs, found to be the result of a
grlA
mutation, and raised organic cation MICs. Ethidium and enoxacin uptake was identical in SA K1748 and its parent, but pre-exposure of SA K1748 to organic cations caused a reduction in ethidium uptake as a result of increased efflux. Altered ethidium uptake and efflux, as well as increased MICs of other organic cations, suggest that SA K1748 possesses a non-NorA multidrug efflux transporter that is inducible by its substrates.
Quinolone Resistance in Enterotoxigenic
Escherichia coli
Causing Diarrhea in Travelers to India in Comparison with Other Geographical Areas
Authors: Vila Jordi , Vargas Martha , Ruiz Joaquim , Corachan Manuel , Jimenez de Anta M. Teresa , Gascon Joaquim
Published: July 2002

Enterotoxigenic
Escherichia coli
isolates were identified as a cause of traveler's diarrhea in 82 of 520 (16%) patients and tested for resistance to seven antimicrobial agents. Thirty patients (36%) needed antimicrobial therapy: 17 (56%) for persistence of symptoms and 13 (44%) for severity of symptoms. Ampicillin, tetracycline, and trimethoprim-sulfamethoxazole resistance was high. Chloramphenicol showed moderate activity, and amoxicillin plus clavulanic acid, nalidixic acid, and ciprofloxacin showed very good activity. Five nalidixic acid-resistant strains were isolated, four from patients visiting India.
Failure of Azithromycin in Treatment of Brill-Zinsser Disease
Authors: Turčinov Drago , Kuzman Ilija , Herendić Boris
Published: July 2002

Two patients suffering from Brill-Zinsser disease were treated with azithromycin, which did not prove effective.
Rickettsia prowazekii
, the agent causing Brill-Zinsser disease, cannot be treated with azithromycin. Both patients had epidemiological features consistent with and a clinical course typical of the disease. The diagnosis of Brill-Zinsser disease was serologically confirmed.