bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV-1 Langerhans' Cell Tropism Associated with Heterosexual Transmission of HIV
Authors: Soto-Ramirez Luis E. , Renjifo Boris , McLane Mary F. , Marlink Richard , O'Hara Carl , Sutthent Ruengpung , Wasi Chantapong , Vithayasai Prakong , Vithayasai Vicharn , Apichartpiyakul Chatchawann , Auewarakul Prasert , Cruz Victor Peña , Chui Dao-Shan , Osathanondh Rapin , Mayer Kenneth , Lee Tun-Hou , Essex Max
Published: October 2006

Heterosexual transmission by vaginal intercourse accounts for most transmission of human immunodeficiency virus-type 1 (HIV-1) in Africa and Asia but is less important in the HIV-1 epidemics of the United States and Western Europe. Epithelial Langerhans' cells (LCs) represent a possible source of initial cell contact for vaginal infection. Fifteen primary isolates of HIV-1 from U.S. homosexuals and 18 HIV-1 isolates from Thailand heterosexuals were evaluated for growth in LCs of U.S. origin. All the viruses from the Thai heterosexuals, which were subtype E, grew more efficiently in the LCs than any of the viruses from the U.S. homosexuals, which are subtype B. These results suggest that LC tropism is associated with the efficiency of heterosexual transmission of HIV.
Intermittently Flowing Rivers of Magnetic Flux
Authors: Nori Franco
Published: October 2006

The behavior of magnetic fields inside superconductors has implications for both technology and fundamental condensed matter physics. In his Perspective, Nori discusses results published in the same issue by Matsuda
et al.
(
p. 1393
) on the motion of magnetic flux lines in a high transition temperature superconductor. Video sequences show how the flux lines move around and are sometimes trapped by defects in the material.
Global Patterns of Linkage Disequilibrium at the CD4 Locus and Modern Human Origins
Authors: Tishkoff S. A. , Dietzsch E. , Speed W. , Pakstis A. J. , Kidd J. R. , Cheung K. , Bonné-Tamir B. , Santachiara-Benerecetti A. S. , Moral P. , Krings M. , Pääbo S. , Watson E. , Risch N. , Jenkins T. , Kidd K. K.
Published: October 2006

Haplotypes consisting of alleles at a short tandem repeat polymorphism (STRP) and an Alu deletion polymorphism at the CD4 locus on chromosome 12 were analyzed in more than 1600 individuals sampled from 42 geographically dispersed populations (13 African, 2 Middle Eastern, 7 European, 9 Asian, 3 Pacific, and 8 Amerindian). Sub-Saharan African populations had more haplotypes and exhibited more variability in frequencies of haplotypes than the Northeast African or non-African populations. The Alu deletion was nearly always associated with a single STRP allele in non-African and Northeast African populations but was associated with a wide range of STRP alleles in the sub-Saharan African populations. This global pattern of haplotype variation and linkage disequilibrium suggests a common and recent African origin for all non-African human populations.
Observation of Dynamic Interaction of Vortices with Pinning Centers by Lorentz Microscopy
Authors: Matsuda Tsuyoshi , Harada Ken , Kasai Hiroto , Kamimura Osamu , Tonomura Akira
Published: October 2006

When a magnetic field penetrates a superconductor, it forms lattices of thin filaments called magnetic vortices. If a current is applied, these vortices move if not pinned down, destroying the superconductivity. The spatiotemporal behavior of the vortices was observed in a niobium film with a square lattice of defects made by ion irradiation. The vortices formed a domain of lattices. When the intensity of the applied magnetic field was decreased, the vortices were driven out of the film across its edges; when the intensity was increased, the vortices were driven into the film. The lattice exhibited brief and intermittent flow in “rivers” along domain boundaries. The rivers did not always flow along the same paths because new lattice domain configurations emerged whenever the flow stopped.
Reversible Cleavage and Formation of the Dioxygen O-O Bond Within a Dicopper Complex
Authors: Halfen Jason A. , Mahapatra Samiran , Wilkinson Elizabeth C. , Kaderli Susan , Young Victor G. , Que Lawrence , Zuberbühler Andreas D. , Tolman William B.
Published: October 2006

A key step in dioxygen evolution during photosynthesis is the oxidative generation of the O-O bond from water by a manganese cluster consisting of M
2
(μ-O)
2
units (where M is manganese). The reverse reaction, reductive cleavage of the dioxygen O-O bond, is performed at a variety of dicopper and di-iron active sites in enzymes that catalyze important organic oxidations. Both processes can be envisioned to involve the interconversion of dimetal-dioxygen adducts, M
2
(O
2
), and isomers having M
2
(μ-O)
2
cores. The viability of this notion has been demonstrated by the identification of an equilibrium between synthetic complexes having [Cu
2
(μ-η
2
:η
2
-O
2
)]
2+
and [Cu
2
(μ-O)
2
]
2+
cores through kinetic, spectroscopic, and crystallographic studies.
Egr-1-Induced Endothelial Gene Expression: A Common Theme in Vascular Injury
Authors: Khachigian Levon M. , Lindner Volkhard , Williams Amy J. , Collins Tucker
Published: October 2006

A number of pathophysiologically relevant genes, including platelet-derived growth factor B-chain (PDGF-B), are induced in the vasculature after acute mechanical injury. In rat aorta, the activated expression of these genes was preceded by a marked increase in the amount of the early-growth-response gene product Egr-1 at the endothelial wound edge. Egr-1 interacts with a novel element in the proximal PDGF-B promoter, as well as with consensus elements in the promoters of other genes induced by endothelial injury. This interaction is crucial for injury-induced PDGF-B promoter-dependent expression. Sp1, whose binding site in the PDGF-B promoter overlaps that of Egr-1, occupies this element in unstimulated cells and is displaced by increasing amounts of Egr-1. These findings implicate Egr-1 in the up-regulated expression of PDGF-B and other potent mediators in mechanically injured arterial endothelial cells.
Iron Metabolism in Eukaryotes—Mars and Venus at It Again
Authors: Kaplan Jerry , O'Halloran Thomas V.
Published: October 2006

Iron and copper are cofactors for many enzymes and are stored, transported, and sequestered by cells, but the complexities of their metabolism are not completely understood. Two new papers, one in this week's
Science
and one in the
Journal of Biological Inorganic Chemistry
(vol. 1, no. 1, p. 15), push our understanding of iron metabolism forward on two fronts. Stearman
et al.
(
p. 1552
) have described a protein in yeast that transports iron across cell membranes, and Zaitseva and co-workers present the structure of the ferroxidase ceruloplasmin. In their Perspective, Kaplan and O'Halloran discuss iron metabolism and how these results advance the field.
Coat Proteins and Vesicle Budding
Authors: Schekman Randy , Orci Lelio
Published: October 2006

The trafficking of proteins within eukaryotic cells is achieved by the capture of cargo and targeting molecules into vesicles that bud from a donor membrane and deliver their contents to a receiving compartment. This process is bidirectional and may involve multiple organelles within a cell. Distinct coat proteins mediate each budding event, serving both to shape the transport vesicle and to select by direct or indirect interaction the desired set of cargo molecules. Secretion, which has been viewed as a default pathway, may require sorting and packaging signals on transported molecules to ensure their rapid delivery to the cell surface.
Phosphoinositides as Regulators in Membrane Traffic
Authors: De Camilli Pietro , Emr Scott D. , McPherson Peter S. , Novick Peter
Published: October 2006

Phosphorylated products of phosphatidylinositol play critical roles in the regulation of membrane traffic, in addition to their classical roles as second messengers in signal transduction at the cell surface. Growing evidence suggests that phosphorylation-dephosphorylation of the polar heads of phosphoinositides (polyphosphorylated inositol lipids) in specific intracellular locations signals either the recruitment or the activation of proteins essential for vesicular transport. Cross talk between phosphatidylinositol metabolites and guanosine triphosphatases is an important feature of these regulatory mechanisms.
Microsecond Catalytic Partial Oxidation of Alkanes
Authors: Goetsch Duane A. , Schmidt Lanny D.
Published: October 2006

A single layer of woven platinum-10 percent rhodium gauze was used as a catalyst for the partial oxidation of ethane, propane,
n
-butane, and isobutane. This configuration produced oxygen conversions of equal to or greater than 90 percent and had high selectivity to olefins and oxygenated hydrocarbons at contact times as short as 10 microseconds at atmospheric pressure. This reactor operates by rapid chemical heating (∼5 microseconds) followed by rapid quenching to avoid homogeneous reactions, which decompose products. Mixing of the cold unreacted gas passing between the gauze wires with the hot product gas results in rapid quenching (∼200 microseconds) of the products from ∼800° to ∼400°C. The rapid quenching avoids successive homogeneous decomposition reactions of unstable products such as olefins and aldehydes but still allows homogeneous chain reactions that produce these species. The strong variations in products with the feed alkane showed that the reaction pathways operating at ∼10
−5
seconds are quite different than those operating at longer residence times. These results could have a significant effect on the direct conversion of alkanes to oxygenates such as formaldehyde.
Structure and Evolution of Lithospheric Slab Beneath the Sunda Arc, Indonesia
Authors: Widiyantoro Sri , van der Hilst Rob
Published: October 2006

Tomographic imaging reveals seismic anomalies beneath the Sunda island arc, Indonesia, that suggest that the lithospheric slab penetrates to a depth of at least 1500 kilometers. The Sunda slab forms the eastern end of a deep anomaly associated with the past subduction of the plate underlying the Mesozoic Tethys Ocean. In accord with previous studies, the lithospheric slab was imaged as a continuous feature from the surface to the lower mantle below Java, with a local deflection where the slab continues into the lower mantle. The deep slab seems to be detached from the upper mantle slab beneath Sumatra. This complex slab structure is related to the Tertiary evolution of southeastern Asia and the Indian Ocean region.
The Majorite-Pyrope + Magnesiowüstite Assemblage: Constraints on the History of Shock Veins in Chondrites
Authors: Chen Ming , Sharp Thomas G. , Goresy Ahmed El , Wopenka Brigitte , Xie Xiande
Published: October 2006

Shock veins in the Sixiangkou (L6) chondrite contain two high-pressure assemblages: (i) majorite-pyrope solid solution plus magnesiowüstite that crystallized at high pressures and temperatures from a shock-induced silicate melt of bulk Sixiangkou composition and (ii) ringwoodite plus low-calcium majorite that were produced by solid-state transformation of olivine and low-calcium pyroxene. The morphology and chemistry of the majorite-pyrope garnet and the size of the magnesiowüstite crystals indicate a longer duration at high pressure and temperature than predicted by impact scenarios. This pressure-temperature regime is constrained by the olivine-ringwoodite and orthopyroxene-majorite phase transformations, fusion of the meteorite constituents, and crystallization of majorite-pyrope solid solution plus magnesiowüstite from that melt under high pressure.
Opposite Modulation of Cocaine-Seeking Behavior by D
1
- and D
2
-Like Dopamine Receptor Agonists
Authors: Self David W. , Barnhart William J. , Lehman David A. , Nestler Eric J.
Published: October 2006

Activation of the mesolimbic dopamine system is known to trigger relapse in animal models of cocaine-seeking behavior. We found that this “priming” effect was selectively induced by D
2
-like, and not by D
1
-like, dopamine receptor agonists in rats. Moreover, D
1
-like receptor agonists prevented cocaine-seeking behavior induced by cocaine itself, whereas D
2
-like receptor agonists enhanced this behavior. These results demonstrate an important dissociation between D
1
- and D
2
-like receptor processes in cocaine-seeking behavior and support further evaluation of D
1
-like receptor agonists as a possible pharmacotherapy for cocaine addiction.
Coordination of Three Signaling Enzymes by AKAP79, a Mammalian Scaffold Protein
Authors: Klauck Theresa M. , Faux Maree C. , Labudda Kirstin , Langeberg Lorene K. , Jaken Susan , Scott John D.
Published: October 2006

Multivalent binding proteins, such as the yeast scaffold protein Sterile-5, coordinate the location of kinases by serving as platforms for the assembly of signaling units. Similarly, in mammalian cells the cyclic adenosine 3′,5′-monophosphate-dependent protein kinase (PKA) and phosphatase 2B [calcineurin (CaN)] are complexed by an A kinase anchoring protein, AKAP79. Deletion analysis and binding studies demonstrate that a third enzyme, protein kinase C (PKC), binds AKAP79 at a site distinct from those bound by PKA or CaN. The subcellular distributions of PKC and AKAP79 were similar in neurons. Thus, AKAP79 appears to function as a scaffold protein for three multifunctional enzymes.
Control of the Gene
optomotor-blind
in
Drosophila
Wing Development by
decapentaplegic
and
wingless
Authors: Grimm Stefan , Pflugfelder Gert O.
Published: October 2006

Diffusible factors of several protein families control appendage outgrowth and patterning in both insects and vertebrates. In
Drosophila
wing development, the gene
decapentaplegic
(
dpp
) is expressed along the anteroposterior compartment boundary. Early
wingless
(
wg
) expression is involved in setting up the dorsoventral boundary. Interaction between
dpp
- and
wg-
expressing cells promotes appendage outgrowth. Here, it is shown that
optomotor-blind
(
omb
) expression is required for distal wing development and is controlled by both
dpp
and
wg
. Ectopic
omb
expression can lead to the growth of additional wings. Thus,
omb
is essential for wing development and is controlled by two signaling pathways.
River Meandering as a Self-Organization Process
Authors: Stølum Hans-Henrik
Published: October 2006

Simulations of freely meandering rivers and empirical data show that the meandering process self-organizes the river morphology, or planform, into a critical state characterized by fractal geometry. The meandering process oscillates in space and time between a state in which the river planform is ordered and one in which it is chaotic. Clusters of river cutoffs tend to cause a transition between these two states and to force the system into stationary fluctuations around the critical state.
Requirement for cAMP-PKA Pathway Activation by M Phase-Promoting Factor in the Transition from Mitosis to Interphase
Authors: Grieco Domenico , Porcellini Antonio , Avvedimento Enrico V. , Gottesman Max E.
Published: October 2006

Cell cycle progression in cycling
Xenopus
egg extracts is accompanied by fluctuations in the concentration of adenosine 3′,5′-monophosphate (cAMP) and in the activity of the cAMP-dependent protein kinase (PKA). The concentration of cAMP and the activity of PKA decrease at the onset of mitosis and increase at the transition between mitosis and interphase. Blocking the activation of PKA at metaphase prevented the transition into interphase; the activity of M phase-promoting factor (MPF; the cyclin B-p34
cdc2
complex) remained high, and mitotic cyclins were not degraded. The arrest in mitosis was reversed by the reactivation of PKA. The inhibition of protein synthesis prevented the accumulation of cyclin and the oscillations of MPF, PKA, and cAMP. Addition of recombinant nondegradable cyclin B activated p34
cdc2
and PKA and induced the degradation of full-length cyclin B. Addition of cyclin A activated p34
cdc2
but not PKA, nor did it induce the degradation of full-length cyclin B. These findings suggest that cyclin degradation and exit from mitosis require MPF-dependent activation of the cAMP-PKA pathway.
Mutations in the Gene Encoding Cystatin B in Progressive Myoclonus Epilepsy (EPM1)
Authors: Pennacchio Len A. , Lehesjoki Anna-Elina , Stone Nancy E. , Willour Virginia L. , Virtaneva Kimmo , Miao Jinmin , D'Amato Elena , Ramirez Lucia , Faham Malek , Koskiniemi Marjaleena , Warrington Janet A. , Norio Reijo , de la Chapelle Albert , Cox David R. , Myers Richard M.
Published: October 2006

Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is an autosomal recessive inherited form of epilepsy, previously linked to human chromosome 21q22.3. The gene encoding cystatin B was shown to be localized to this region, and levels of messenger RNA encoded by this gene were found to be decreased in cells from affected individuals. Two mutations, a 3′ splice site mutation and a stop codon mutation, were identified in the gene encoding cystatin B in EPM1 patients but were not present in unaffected individuals. These results provide evidence that mutations in the gene encoding cystatin B are responsible for the primary defect in patients with EPM1.
Resetting the
Drosophila
Clock by Photic Regulation of PER and a PER-TIM Complex
Authors: Lee Choogon , Parikh Vaishali , Itsukaichi Tomoko , Bae Kiho , Edery Isaac
Published: October 2006

Circadian clocks can be reset by light stimulation. To investigate the mechanism of this phase shifting, the effects of light pulses on the protein and messenger RNA products of the
Drosophila
clock gene
period
(
per
) were measured. Photic stimuli perturbed the timing of the PER protein and messenger RNA cycles in a manner consistent with the direction and magnitude of the phase shift. In addition, the recently identified clock protein TIM (for
timeless
) interacted with PER in vivo, and this association was rapidly decreased by light. This disruption of the PER-TIM complex in the cytoplasm was accompanied by a delay in PER phosphorylation and nuclear entry and disruption in the nucleus by an advance in PER phosphorylation and disappearance. These results suggest a mechanism for how a unidirectional environmental signal elicits a bidirectional clock response.
Notch and Wingless Signals Collide
Authors: Blair Seth S.
Published: October 2006

Two important signal transduction pathways for developmental pattern formation in Drosophila are triggered by the binding of the Wingless protein to its receptor and the Delta protein's binding to its receptor Notch. In a paper in this issue of
Science
(
p. 1826
), these two pathways are shown to intersect as a result of a physical interaction between Dishevelled, a cytoplasmic protein in the Wingless pathway, and the intracellular COOH-terminus of the Notch protein. In his Perspective, Blair discusses this mutually inhibitory intersection of these two key signaling pathways.
Isolation, Structure, and Electronic Calculations of the Heterofullerene Salt K
6
C
59
N
Authors: Prassides Kosmas , Keshavarz-K. Majid , Hummelen Jan Cornelis , Andreoni Wanda , Giannozzi Paolo , Beer Ernst , Bellavia Cheryl , Cristofolini Luigi , González Rosario , Lappas Alexandros , Murata Yasuo , Malecki Magdalena , Srdanov Vojislav , Wudl Fred
Published: October 2006

An intercalation compound of azafullerene, K
6
C
59
N, was prepared and structurally characterized. It is isostructural with the fullerene compound K
6
C
60
, adopts a body-centered-cubic structure (lattice constant
a
= 11.31 angstroms), and consists of quasi-spherical monomeric (C
59
N)
6−
ions. Density functional calculations of the structural and electronic properties confirm the similarity to K
6
C
60
but also suggest a sizable deformation, principally confined in the vicinity of the nitrogen atom, of both the molecular structure and the electron states. These results show that study of the intercalation chemistry of azafullerene promises to reveal a rich family of both
n
- and
p
-doped systems with novel conducting and magnetic properties, like their fullerene antecedents.
The Elasticity of a Single Supercoiled DNA Molecule
Authors: Strick T. R. , Allemand J.-F. , Bensimon D. , Bensimon A. , Croquette V.
Published: October 2006

Single linear DNA molecules were bound at multiple sites at one extremity to a treated glass cover slip and at the other to a magnetic bead. The DNA was therefore torsionally constrained. A magnetic field was used to rotate the beads and thus to coil and pull the DNA. The stretching force was determined by analysis of the Brownian fluctuations of the bead. Here, the elastic behavior of individual λ DNA molecules over- and underwound by up to 500 turns was studied. A sharp transition was discovered from a low to a high extension state at a force of ∼0.45 piconewtons for underwound molecules and at a force of ∼3 piconewtons for overwound ones. These transitions, probably reflecting the formation of alternative structures in stretched coiled DNA molecules, might be relevant for DNA transcription and replication.
Identification of
d
-Peptide Ligands Through Mirror-Image Phage Display
Authors: Schumacher Ton N. M. , Mayr Lorenz M. , Minor Daniel L. , Milhollen Michael A. , Burgess Michael W. , Kim Peter S.
Published: October 2006

Genetically encoded libraries of peptides and oligonucleotides are well suited for the identification of ligands for many macromolecules. A major drawback of these techniques is that the resultant ligands are subject to degradation by naturally occurring enzymes. Here, a method is described that uses a biologically encoded library for the identification of D-peptide ligands, which should be resistant to proteolytic degradation. In this approach, a protein is synthesized in the D-amino acid configuration and used to select peptides from a phage display library expressing random L-amino acid peptides. For reasons of symmetry, the mirror images of these phage-displayed peptides interact with the target protein of the natural handedness. The value of this approach was demonstrated by the identification of a cyclic D-peptide that interacts with the Src homology 3 domain of c-Src. Nuclear magnetic resonance studies indicate that the binding site for this D-peptide partially overlaps the site for the physiological ligands of this domain.
A Neural Tetraspanin, Encoded by
late bloomer
, That Facilitates Synapse Formation
Authors: Kopczynski Casey C. , Davis Graeme W. , Goodman Corey S.
Published: October 2006

Upon contacting its postsynaptic target, a neuronal growth cone transforms into a presynaptic terminal. A membrane component on the growth cone that facilitates synapse formation was identified by means of a complementary DNA-based screen followed by genetic analysis. The
late bloomer
(
lbl
) gene in
Drosophila
encodes a member of the tetraspanin family of cell surface proteins. LBL protein is transiently expressed on motor axons, growth cones, and terminal arbors. In
lbl
mutant embryos, the growth cone of the RP3 motoneuron contacts its target muscles, but synapse formation is delayed and neighboring motoneurons display an increase in ectopic sprouting.
Failure of the Cystic Fibrosis Transmembrane Conductance Regulator to Conduct ATP
Authors: Reddy M. M. , Quinton P. M. , Haws C. , Wine J. J. , Grygorczyk R. , Tabcharani J. A. , Hanrahan J. W. , Gunderson K. L. , Kopito R. R.
Published: October 2006

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion channel regulated by protein kinase A and adenosine triphosphate (ATP). Loss of CFTR-mediated chloride ion conductance from the apical plasma membrane of epithelial cells is a primary physiological lesion in cystic fibrosis. CFTR has also been suggested to function as an ATP channel, although the size of the ATP anion is much larger than the estimated size of the CFTR pore. ATP was not conducted through CFTR in intact organs, polarized human lung cell lines, stably transfected mammalian cell lines, or planar lipid bilayers reconstituted with CFTR protein. These findings suggest that ATP permeation through the CFTR is unlikely to contribute to the normal function of CFTR or to the pathogenesis of cystic fibrosis.
Similarity Among the

Drosophila

(6-4)Photolyase, a Human Photolyase Homolog, and the DNA Photolyase-Blue-Light Photoreceptor Family
Authors: Todo Takeshi , Ryo Haruko , Yamamoto Kazuo , Toh Hiroyuki , Inui Taiichiro , Ayaki Hitoshi , Nomura Taisei , Ikenaga Mituo
Published: October 2006

Ultraviolet light (UV)-induced DNA damage can be repaired by DNA photolyase in a light-dependent manner. Two types of photolyase are known, one specific for cyclobutane pyrimidine dimers (CPD photolyase) and another specific for pyrimidine (6-4) pyrimidone photoproducts [(6-4)photolyase]. In contrast to the CPD photolyase, which has been detected in a wide variety of organisms, the (6-4)photolyase has been found only in
Drosophila melanogaster
. In the present study a gene encoding the
Drosophila
(6-4)photolyase was cloned, and the deduced amino acid sequence of the product was found to be similar to the CPD photolyase and to the blue-light photoreceptor of plants. A homolog of the
Drosophila
(6-4)photolyase gene was also cloned from human cells.
Silk Properties Determined by Gland-Specific Expression of a Spider Fibroin Gene Family
Authors: Guerette Paul A. , Ginzinger David G. , Weber Bernhard H. F. , Gosline John M.
Published: October 2006

Spiders produce a variety of silks that range from Lycra-like elastic fibers to Kevlar-like superfibers. A gene family from the spider
Araneus diadematus
was found to encode silk-forming proteins (fibroins) with different proportions of amorphous glycine-rich domains and crystal domains built from poly(alanine) and poly(glycine-alanine) repeat motifs. Spiders produce silks of different composition by gland-specific expression of this gene family, which allows for a range of mechanical properties according to the crystal-forming potential of the constituent fibroins. These principles of fiber property control may be important in the development of genetically engineered structural proteins.
Replication of HIV-1 in Dendritic Cell-Derived Syncytia at the Mucosal Surface of the Adenoid
Authors: Frankel Sarah S. , Wenig Bruce M. , Burke Allen P. , Mannan Poonam , Thompson Lester D. R. , Abbondanzo Susan L. , Nelson Ann M. , Pope Melissa , Steinman Ralph M.
Published: October 2006

Human immunodeficiency virus-type 1 (HIV-1) replicates actively in infected individuals, yet cells with intracellular depots of viral protein are observed only infrequently. Many cells expressing the HIV-1 Gag protein were detected at the surface of the nasopharyngeal tonsil or adenoid. This infected mucosal surface contained T cells and dendritic cells, two cell types that together support HIV-1 replication in culture. The infected cells were multinucleated syncytia and expressed the S100 and p55 dendritic cell markers. Eleven of the 13 specimens analyzed were from donors who did not have symptoms of acquired immunodeficiency syndrome (AIDS). The interaction of dendritic cells and T cells in mucosa may support HIV-1 replication, even in subclinical stages of infection.
Equilibrium-Point Control Hypothesis Examined by Measured Arm Stiffness During Multijoint Movement
Authors: Gomi Hiroaki , Kawato Mitsuo
Published: October 2006

For the last 20 years, it has been hypothesized that well-coordinated, multijoint movements are executed without complex computation by the brain, with the use of springlike muscle properties and peripheral neural feedback loops. However, it has been technically and conceptually difficult to examine this “equilibrium-point control” hypothesis directly in physiological or behavioral experiments. A high-performance manipulandum was developed and used here to measure human arm stiffness, the magnitude of which during multijoint movement is important for this hypothesis. Here, the equilibrium-point trajectory was estimated from the measured stiffness, the actual trajectory, and the generated torque. Its velocity profile differed from that of the actual trajectory. These results argue against the hypothesis that the brain sends as a motor command only an equilibrium-point trajectory similar to the actual trajectory.
Immunological Memory and Protective Immunity: Understanding Their Relation
Authors: Ahmed Rafi , Gray David
Published: October 2006

The immune system can remember, sometimes for a lifetime, the identity of a pathogen. Understanding how this is accomplished has fascinated immunologists and microbiologists for many years, but there is still considerable debate regarding the mechanisms by which long-term immunity is maintained. Some of the controversy stems from a failure to distinguish between effector and memory cells and to define their roles in conferring protection against disease. Here the current understanding of the cellular basis of immune memory is reviewed and the relative contributions made to protective immunity by memory and effector T and B cells are examined.
Autocatalysis During Fullerene Growth
Authors: Eggen B. R. , Heggie M. I. , Jungnickel G. , Latham C. D. , Jones R. , Briddon P. R.
Published: October 2006

Total energy calculations with a local spin density functional have been applied to the Stone-Wales transformation in fullerene (C
60
). In the formation of the almost exclusively observed
I

h

isomer of C
60
with isolated pentagons, the final transformation must be from a
C

2
v

isomer with two pentagon pairs. It was found that the energy barrier for this rearrangement was substantially reduced in the presence of an extra carbon atom. Such atoms were found to bind loosely, preferentially to regions in which there were paired pentagons. Pentagon rearrangements, which are necessary steps in the growth of fullerenes, may therefore result from autocatalysis by carbon.
Arousal--Revisiting the Reticular Activating System
Authors: Steriade Mircea
Published: October 2006

An area deep within the brain has been implicated in control of arousal or mental alertness. Two papers in this week's issue of
Science
[Munk
et al.
(
p. 271
) and Castro-Alamancos and Connors (
p. 274
)] show how signals from this area, the midbrain reticular formation, change the physiology of the cortex, the part of the brain that governs higher functions. In his Perspective, Steriade traces the history of this field and discusses the significance of these results.
Role of Reticular Activation in the Modulation of Intracortical Synchronization
Authors: Munk Matthias H. J. , Roelfsema Pieter R. , König Peter , Engel Andreas K. , Singer Wolf
Published: October 2006

During aroused states of the brain, electroencephalographic activity is characterized by fast, irregular fluctuations of low amplitude, which are thought to reflect desynchronization of neuronal activity. This phenomenon seems at odds with the proposal that synchronization of cortical responses may play an important role in the processing of sensory signals. Here, activation of the mesencephalic reticular formation (MRF), an effective way to “desynchronize the electroencephalogram,” was shown to facilitate oscillatory activity in the gamma frequency range and to enhance the stimulus-specific synchronization of neuronal spike responses in the visual cortex of cats.
Deliberate Flood Renews Habitats
Authors: Wuethrich Bernice
Published: October 2006

For a full week last month, the Colorado River surged through the Grand Canyon at nearly triple its average flow—a torrent not seen since Glen Canyon Dam was completed more than 30 years ago. The flood was a $1.5 million ecological experiment designed to test the idea that controlled floods are a means of rejuvenation for riverbank ecosystems. And early results are positive: The flood stirred up sediments and rebuilt beaches and sandbars, creating new habitats for the Grand Canyon's native fishes.
Giant Magnetoresistance in Transition Metal Oxides
Authors: Rao C. N. R. , Cheetham A. K.
Published: October 2006

Some materials exhibit large changes in electrical resistance in the presence of a magnetic field, and this change can be used in applications from sensor technology to magnetic data storage. In their Perspective, Rao and Cheetham discuss magnetoresistance in perovskite manganates, where the effect is unusually strong. Much has been learned about these materials, and this understanding is driving the search for new materials with even more impressive properties.
Histone Deacetylase: A Regulator of Transcription
Authors: Wolffe Alan P.
Published: October 2006

Histones are DNA binding proteins that bind without regard to the sequence of the DNA and help determine the three-dimensional organization of the chromatin into chromosomes. A paper in this week's issue (Taunton
et al
.,
p. 408
) reports the cloning of histone deacetylase, an ezyme that modifies histones by removing an acetyl group. In his Perspective, Wolffe explains how the action of this enzyme can lead to the regulation of the transcription of certain genes.
Spatiotemporal Chaos in Electroconvection
Authors: Dennin Michael , Ahlers Guenter , Cannell David S.
Published: October 2006

Spatiotemporal chaos (STC) near the onset of electroconvection in a nematic liquid crystal is reported. In samples with conductivities greater than 1 × 10
−8
per ohm per meter, STC was found to evolve by means of a supercritical Hopf bifurcation from the uniform conduction state. Because this example of STC resulted from nonlinear interactions between only four modes, it provides a realistic opportunity to understand the observed phenomena in terms of a weakly nonlinear theory in the form of four coupled complex Ginzburg-Landau equations derived from the full equations of motion of the system. For smaller conductivities, the pattern immediately above onset consisted of localized pulses of convection that coexisted with the conduction state. The pulses had a unique width in the direction perpendicular to the director (the axis parallel to the average orientation) and had much larger and varying lengths parallel to the director.
Continental Crust, Crustal Underplating, and Low-

Q

Upper Mantle Beneath an Oceanic Island Arc
Authors: Suyehiro Kiyoshi , Takahashi Narumi , Ariie Yoshiro , Yokoi Yasutaka , Hino Ryota , Shinohara Masanao , Kanazawa Toshihiko , Hirata Naoshi , Tokuyama Hidekazu , Taira Asahiko
Published: October 2006

A detailed structural model of the crust, subducting slab, and underlying upper mantle across the northern Izu-Ogasawara (Bonin) island arc system is derived from a marine seismic reflection and ocean bottom seismographic refraction survey and subsequent forward modeling combined with tomographic inversion. The model indicates that the crust is thickest beneath the presently active rift zone and a granitic crust may have formed in the mid-crust. A highly attenuative mantle (that is, one with low quality
Q
) seems to be confined mainly beneath the presently active rift zone. In contrast, high
P
-wave velocity persists in the lower crust between the forearc and eastern margin of the back arc basin, suggesting a large-scale magma input responsible for the arc formation.
Rapid Exchange Between Soil Carbon and Atmospheric Carbon Dioxide Driven by Temperature Change
Authors: Trumbore Susan E. , Chadwick Oliver A. , Amundson Ronald
Published: October 2006

Comparison of
14
C (carbon-14) in archived (pre-1963) and contemporary soils taken along an elevation gradient in the Sierra Nevada, California, demonstrates rapid (7 to 65 years) turnover for 50 to 90 percent of carbon in the upper 20 centimeters of soil (A horizon soil carbon). Carbon turnover times increased with elevation (decreasing temperature) along the Sierra transect. This trend was consistent with results from other locations, which indicates that temperature is a dominant control of soil carbon dynamics. When extrapolated to large regions, the observed relation between carbon turnover and temperature suggests that soils should act as significant sources or sinks of atmospheric carbon dioxide in response to global temperature changes.
Homocysteine Antagonism of Nitric Oxide-Related Cytostasis in

Salmonella typhimurium
Authors: De Groote Mary Ann , Testerman Traci , Xu Yisheng , Stauffer George , Fang Ferric C.
Published: October 2006

Nitric oxide (NO) is associated with broad-spectrum antimicrobial activity of particular importance in infections caused by intracellular pathogens. An insertion mutation in the
metL
gene of
Salmonella typhimurium
conferred specific hypersusceptibility to
S
-nitrosothiol NO-donor compounds and attenuated virulence of the organism in mice. The
metL
gene product catalyzes two proximal metabolic steps required for homocysteine biosynthesis.
S
-Nitrosothiol resistance was restored by exogenous homocysteine or introduction of the
metL
gene on a plasmid. Measurement of expression of the homocysteine-sensitive
metH
gene indicated that
S
-nitrosothiols may directly deplete intracellular homocysteine. Homocysteine may act as an endogenous NO antagonist in diverse processes including infection, atherosclerosis, and neurologic disease.
The Cerebellum: Movement Coordinator or Much More?
Authors: Barinaga Marcia
Published: October 2006

The cerebellum's main job is supposed to be coordinating movements. But recent work, some of which appears onp
page 545
, suggests that it also participates in many nonmotor brain functions, ranging from the analysis of sensory information, to telling time, to solving puzzles. Not everyone agrees with that idea, however, and even those who do have proposed very different pictures of cerebellar function.
p75
NTR
: A Receptor After All
Authors: Bothwell Mark
Published: October 2006

One of the first growth factor receptors to be cloned, p75
NTR
was supplanted by newer molecules that bind nerve growth factor (NGF). Now in a number of recent papers, including one in this issue of
Science
, p75
NTR
proves to be a receptor for NGF after all, with a specialized function in Schwann's cells. In his Perspective, Bothwell points out that signal transduction by p75
NTR
is in many ways similar to transduction by the tumor necrosis factor receptors, CD40, and Fas, which couple to both apoptotic cell death and the transcription factor NF-kappaB.
Textural Entrapment of Core-Forming Melts
Authors: Minarik William G. , Ryerson Frederick J. , Watson E. Bruce
Published: October 2006

Small volume fractions of metal-rich, iron-nickel-sulfur-oxygen melt do not form an interconnected network in polycrystalline olivine at pressures up to 11 gigapascals. These results suggest that iron-rich melts could not have migrated downward along olivine grain edges to form Earth's core. Core separation at pressures below 11 gigapascals within planetary bodies must have been facilitated by large degrees of partial melting, resulting in either separation of immiscible silicate and metal-sulfide melts or extraction of the silicate melt to concentrate the metallic remainder.
Evaluating Electrostatic Contributions to Binding with the Use of Protein Charge Ladders
Authors: Gao Jinming , Mammen Mathai , Whitesides George M.
Published: October 2006

Electrostatic interactions between charges on ligands and charges on proteins that are remote from the binding interface can influence the free energy of binding (Δ
G
b
). The binding affinities between charged ligands and the members of a charge ladder of bovine carbonic anhydrase (CAII) constructed by random acetylation of the amino groups on its surface were measured by affinity capillary electrophoresis (ACE). The values of Δ
G
b
derived from this analysis correlated approximately linearly with the charge. Opposite charges on the ligand and the members of the charge ladder of CAII were stabilizing; like charges were destabilizing. The combination of ACE and protein charge ladders provides a tool for quantitatively examining the contributions of electrostatics to free energies of molecular recognition in biology.
Adaptive Evolution of Human Immunodeficiency Virus-Type 1 During the Natural Course of Infection
Authors: Wolinsky Steven M. , Korber Bette T. M. , Neumann Avidan U. , Daniels Michael , Kunstman Kevin J. , Whetsell Amy J. , Furtado Manohar R. , Cao Yunzhen , Ho David D. , Safrit Jeffrey T. , Koup Richard A.
Published: October 2006

The rate of progression to disease varies considerably among individuals infected with human immunodeficiency virus-type 1 (HIV-1). Analyses of semiannual blood samples obtained from six infected men showed that a rapid rate of CD4 T cell loss was associated with relative evolutionary stasis of the HIV-1 quasispecies virus population. More moderate rates of CD4 T cell loss correlated with genetic evolution within three of four subjects. Consistent with selection by the immune constraints of these subjects, amino acid changes were apparent within the appropriate epitopes of human leukocyte antigen class I-restricted cytotoxic T lymphocytes. Thus, the evolutionary dynamics exhibited by the HIV-1 quasispecies virus populations under natural selection are compatible with adaptive evolution.
Altered Growth and Branching Patterns in Synpolydactyly Caused by Mutations in HOXD13
Authors: Muragaki Yasuteru , Mundlos Stefan , Upton Joseph , Olsen Bjorn R.
Published: October 2006

Hox
genes regulate patterning during limb development. It is believed that they function in the determination of the timing and extent of local growth rates. Here, it is demonstrated that synpolydactyly, an inherited human abnormality of the hands and feet, is caused by expansions of a polyalanine stretch in the amino-terminal region of HOXD13. The homozygous phenotype includes the transformation of metacarpal and metatarsal bones to short carpal- and tarsal-like bones. The mutations identify the polyalanine stretch outside of the DNA binding domain of HOXD13 as a region necessary for proper protein function.
Interactions Between Electrical Activity and Cortical Microcirculation Revealed by Imaging Spectroscopy: Implications for Functional Brain Mapping
Authors: Malonek Dov , Grinvald Amiram
Published: October 2006

Modern neuroimaging techniques use signals originating from microcirculation to map brain function. In this study, activity-dependent changes in oxyhemoglobin, deoxyhemoglobin, and light scattering were characterized by an imaging spectroscopy approach that offers high spatial, temporal, and spectral resolution. Sensory stimulation of cortical columns initiates tissue hypoxia and vascular responses that occur within the first 3 seconds and are highly localized to individual cortical columns. However, the later phase of the vascular response is less localized, spreading over distances of 3 to 5 millimeters.
Ocular Dominance Plasticity Under Metabotropic Glutamate Receptor Blockade
Authors: Hensch Takao K. , Stryker Michael P.
Published: October 2006

Occluding vision through one eye during a critical period in early life nearly abolishes responses to that eye in visual cortex. This phenomenon is mimicked by long-term depression of synaptic transmission in vitro, which may require metabotropic glutamate receptors (mGluRs) and is age-dependent. Peaks in mGluR expression and glutamate-stimulated phosphoinositide turnover during visual cortical development have been proposed as biochemical bases for the critical period. Pharmacological blockade of mGluRs specifically prevented synapse weakening in mouse visual cortical slices but did not alter kitten ocular dominance plasticity in vivo. Thus, a heightened mGluR response does not account for the critical period in development.
Molecular Therapies for Vascular Diseases
Authors: Gibbons Gary H. , Dzau Victor J.
Published: October 2006

Vascular disease is the most common cause of death in the industrialized world. Although significant progress has been made in treating these disorders, more therapeutic agents must be developed that effectively prevent, arrest, or reverse this disease. Recent insights into the pathogenesis of vascular disease have opened up a new frontier of molecular therapies that target molecules as diverse as adhesion molecules and transcription factors. The biological rationale for these new therapies and their prospects for success are discussed.
Molecular Electronics Emerges from Molecular Magnetism
Authors: Verdaguer Michel
Published: October 2006

Molecular electronics—the storage and processing of data on individual molecules—may be one path toward increased storage density and speed. In his Perspective, Verdaguer discusses work reported by Sato
et al.
(
p. 704
) in this issue on light-induced changes in the magnetic properties of various preparations of Prussian blue. This leads to switching of the long-range magnetic ordering of the compound and may point the way to molecular information processing.
Direct Measurement of Coupling Between Dendritic Spines and Shafts
Authors: Svoboda Karel , Tank David W. , Denk Winfried
Published: October 2006

Characterization of the diffusional and electrotonic coupling of spines to the dendritic shaft is crucial to understanding neuronal integration and synaptic plasticity. Two-photon photobleaching and photorelease of fluorescein dextran were used to generate concentration gradients between spines and shafts in rat CA1 pyramidal neurons. Diffusional reequilibration was monitored with two-photon fluorescence imaging. The time course of reequilibration was exponential, with time constants in the range of 20 to 100 milliseconds, demonstrating chemical compartmentalization on such time scales. These values imply that electrical spine neck resistances are unlikely to exceed 150 megohms and more likely range from 4 to 50 megohms.
Amelioration of Vascular Dysfunctions in Diabetic Rats by an Oral PKC β Inhibitor
Authors: Ishii Hidehiro , Jirousek Michael R. , Koya Daisuke , Takagi Chikako , Xia Pu , Clermont Allen , Bursell Sven-Erik , Kern Timothy S. , Ballas Lawrence M. , Heath William F. , Stramm Lawrence E. , Feener Edward P. , King George L.
Published: October 2006

The vascular complications of diabetes mellitus have been correlated with enhanced activation of protein kinase C (PKC). LY333531, a specific inhibitor of the β isoform of PKC, was synthesized and was shown to be a competitive reversible inhibitor of PKC β
1
and β
2
, with a half-maximal inhibitory constant of ∼5 nM; this value was one-fiftieth of that for other PKC isoenzymes and one-thousandth of that for non-PKC kinases. When administered orally, LY333531 ameliorated the glomerular filtration rate, albumin excretion rate, and retinal circulation in diabetic rats in a dose-responsive manner, in parallel with its inhibition of PKC activities.
Getting Down to the Core of Homologous Recombination
Authors: Stasiak Andrzej
Published: October 2006

In a paper in this week's issue of
Science
, Voloshin
et al.
(
p. 868
) show that a 20-amino acid peptide from RecA, a bacterial protein that repairs and recombines DNA, can mediate DNA strand exchange—one of the functions of the RecA protein. Stasiak discusses why this result is surprising and what the rest of the RecA protein is for.
Crystal Structure of the Yeast TFIIA/TBP/DNA Complex
Authors: Geiger James H. , Hahn Steve , Lee Sally , Sigler Paul B.
Published: October 2006

The crystal structure of the yeast TFIIA/TBP/TATA promoter complex was solved to 3 angstrom resolution by double-edge multiple wavelength anomalous diffraction from two different species of anomalous scattering elements in the same crystal. The large and small subunits of TFIIA associate intimately to form both domains of a two-domain folding pattern. TFIIA binds as a heterodimer to the side of the TBP/TATA complex opposite to the side that binds TFIIB and does not alter the TBP/DNA interaction. The six-stranded β-sandwich domain interacts with the amino-terminal end of TBP through a stereospecific parallel β-strand interface and with the backbone of the TATA box and the 5′-flanking B-DNA segment. The four-helix-bundle domain projects away from the TBP/TATA complex, thereby presenting a substantial surface for further protein-protein interactions.