bluuebunny/crossref_metadata_2025 huggingface dataset:
Redox-Coupled Crystal Structural Changes in Bovine Heart Cytochrome c Oxidase
Authors: Yoshikawa Shinya , Shinzawa-Itoh Kyoko , Nakashima Ryosuke , Yaono Rieko , Yamashita Eiki , Inoue Noriko , Yao Min , Fei Ming Jie , Libeu Clare Peters , Mizushima Tsunehiro , Yamaguchi Hiroshi , Tomizaki Takashi , Tsukihara Tomitake
Published: July 2002

Crystal structures of bovine heart cytochrome c oxidase in the fully oxidized, fully reduced, azide-bound, and carbon monoxide–bound states were determined at 2.30, 2.35, 2.9, and 2.8 angstrom resolution, respectively. An aspartate residue apart from the O
2
reduction site exchanges its effective accessibility to the matrix aqueous phase for one to the cytosolic phase concomitantly with a significant decrease in the pK of its carboxyl group, on reduction of the metal sites. The movement indicates the aspartate as the proton pumping site. A tyrosine acidified by a covalently linked imidazole nitrogen is a possible proton donor for the O
2
reduction by the enzyme.
The Ubiquitin-Related Protein RUB1 and Auxin Response in
Arabidopsis
Authors: Pozo J. C. del , Timpte C. , Tan S. , Callis J. , Estelle M.
Published: July 2002

The AXR1 (auxin-resistant) protein, which has features of the ubiquitin-activating enzyme E1, is required for normal response to the plant hormone auxin in
Arabidopsis thaliana
. ECR1 functions together with AXR1 to activate members of the RUB/NEDD8 family of ubiquitin-related proteins. Extracts from mutant seedlings lacking AXR1 did not promote formation of the RUB-ECR1 thiolester, indicating that AXR1 is the major activity in this tissue. AXR1 was localized primarily to the nucleus of dividing and elongating cells, suggesting that the targets of RUB modification are nuclear. These results indicate that auxin response depends on RUB modification of one or more nuclear proteins.
A Conserved HIV gp120 Glycoprotein Structure Involved in Chemokine Receptor Binding
Authors: Rizzuto Carlo D. , Wyatt Richard , Hernández-Ramos Nivia , Sun Ying , Kwong Peter D. , Hendrickson Wayne A. , Sodroski Joseph
Published: July 2002

The entry of primate immunodeficiency viruses into target cells depends on a sequential interaction of the gp120 envelope glycoprotein with the cellular receptors, CD4 and members of the chemokine receptor family. The gp120 third variable (V3) loop has been implicated in chemokine receptor binding, but the use of the CCR5 chemokine receptor by diverse primate immunodeficiency viruses suggests the involvement of an additional, conserved gp120 element. Through the use of gp120 mutants, a highly conserved gp120 structure was shown to be critical for CCR5 binding. This structure is located adjacent to the V3 loop and contains neutralization epitopes induced by CD4 binding. This conserved element may be a useful target for pharmacologic or prophylactic intervention in human immunodeficiency virus (HIV) infections.
Molecular Coproscopy: Dung and Diet of the Extinct Ground Sloth
Nothrotheriops shastensis
Authors: Poinar Hendrik N. , Hofreiter Michael , Spaulding W. Geoffrey , Martin Paul S. , Stankiewicz B. Artur , Bland Helen , Evershed Richard P. , Possnert Göran , Pääbo Svante
Published: July 2002

DNA from excrements can be amplified by means of the polymerase chain reaction. However, this has not been possible with ancient feces. Cross-links between reducing sugars and amino groups were shown to exist in a Pleistocene coprolite from Gypsum Cave, Nevada. A chemical agent,
N
-phenacylthiazolium bromide, that cleaves such cross-links made it possible to amplify DNA sequences. Analyses of these DNA sequences showed that the coprolite is derived from an extinct sloth, presumably the Shasta ground sloth
Nothrotheriops shastensis
. Plant DNA sequences from seven groups of plants were identified in the coprolite. The plant assemblage that formed part of the sloth's diet exists today at elevations about 800 meters higher than the cave.
Mass-Independent Oxygen Isotope Fractionation in Atmospheric CO as a Result of the Reaction CO + OH
Authors: Röckmann T. , Brenninkmeijer C. A. M. , Saueressig G. , Bergamaschi P. , Crowley J. N. , Fischer H. , Crutzen P. J.
Published: July 2002

Atmospheric carbon monoxide (CO) exhibits mass-independent fractionation in the oxygen isotopes. An
17
O excess up to 7.5 per mil was observed in summer at high northern latitudes. The major source of this puzzling fractionation in this important trace gas is its dominant atmospheric removal reaction, CO + OH → CO
2
+ H, in which the surviving CO gains excess
17
O. The occurrence of mass-independent fractionation in the reaction of CO with OH raises fundamental questions about kinetic processes. At the same time the effect is a useful marker for the degree to which CO in the atmosphere has been reacting with OH.
Are We Selfish, Are we Nice, or Are We Nice Because We Are Selfish?
Authors: Nunney Leonard
Published: July 2002

Unto Others
The Evolution and Psychology of Unselfish Behavior. Elliott Sober and David Sloan Wilson. Harvard University Press, Cambridge, MA, 1998. 406 pp. $29.95. ISBN 0-674-93046-0.

The authors of
Unto Others
present an evolutionary argument for unselfish behavior as the product of group selection, coupled with a "completely different" section on psychological altruism. They stress a pluralistic approach to altruism, and to levels of selection. The reviewer finds the book more focused on the debates than on the science.
High-Resolution Protein Design with Backbone Freedom
Authors: Harbury Pehr B. , Plecs Joseph J. , Tidor Bruce , Alber Tom , Kim Peter S.
Published: July 2002

Recent advances in computational techniques have allowed the design of precise side-chain packing in proteins with predetermined, naturally occurring backbone structures. Because these methods do not model protein main-chain flexibility, they lack the breadth to explore novel backbone conformations. Here the de novo design of a family of α-helical bundle proteins with a right-handed superhelical twist is described. In the design, the overall protein fold was specified by hydrophobic-polar residue patterning, whereas the bundle oligomerization state, detailed main-chain conformation, and interior side-chain rotamers were engineered by computational enumerations of packing in alternate backbone structures. Main-chain flexibility was incorporated through an algebraic parameterization of the backbone. The designed peptides form α-helical dimers, trimers, and tetramers in accord with the design goals. The crystal structure of the tetramer matches the designed structure in atomic detail.
Exploiting the Basis of Proline Recognition by SH3 and WW Domains: Design of N-Substituted Inhibitors
Authors: Nguyen Jack T. , Turck Christoph W. , Cohen Fred E. , Zuckermann Ronald N. , Lim Wendell A.
Published: July 2002

Src homology 3 (SH3) and WW protein interaction domains bind specific proline-rich sequences. However, instead of recognizing critical prolines on the basis of side chain shape or rigidity, these domains broadly accepted amide N-substituted residues. Proline is apparently specifically selected in vivo, despite low complementarity, because it is the only endogenous N-substituted amino acid. This discriminatory mechanism explains how these domains achieve specific but low-affinity recognition, a property that is necessary for transient signaling interactions. The mechanism can be exploited: screening a series of ligands in which key prolines were replaced by nonnatural N-substituted residues yielded a ligand that selectively bound the Grb2 SH3 domain with 100 times greater affinity.
The Percolation Phase Transition in Sea Ice
Authors: Golden K. M. , Ackley S. F. , Lytle V. I.
Published: July 2002

Sea ice exhibits a marked transition in its fluid transport properties at a critical brine volume fraction
p
c
of about 5 percent, or temperature
T
c
of about –5°C for salinity of 5 parts per thousand. For temperatures warmer than
T
c
, brine carrying heat and nutrients can move through the ice, whereas for colder temperatures the ice is impermeable. This transition plays a key role in the geophysics, biology, and remote sensing of sea ice. Percolation theory can be used to understand this critical behavior of transport in sea ice. The similarity of sea ice microstructure to compressed powders is used to theoretically predict
p
c
of about 5 percent.
Ozone Isotope Enrichment: Isotopomer-Specific Rate Coefficients
Authors: Mauersberger K. , Erbacher B. , Krankowsky D. , Günther J. , Nickel R.
Published: July 2002

Six rate coefficients of relative ozone formation contradict the role of molecular symmetry in the process that results in the enrichment of heavy ozone isotopomers. The results show that collisions between light atoms, such as
16
O, and heavy molecules, such as
34
O
2
and
36
O
2
, have a rate coefficient advantage of about 25 and 50 percent, respectively, over collisions involving heavy atoms and light molecules. These results suggest that the observed isotope effect for each isotopomer may be caused by the preponderance of a single reaction channel and not through molecular symmetry selection.
Asymmetric Scattering of Polarized Electrons by Organized Organic Films of Chiral Molecules
Authors: Ray K. , Ananthavel S. P. , Waldeck D. H. , Naaman R.
Published: July 2002

Electron transmission experiments demonstrate a large asymmetry in the scattering probability of polarized electrons by thin organized films of chiral molecules. This large asymmetry results from the interaction of the electron's wavefunction with many scatterers (molecules) in the organized monolayer structure and represents a manifestation of quantum interference on the scale of supramolecular lengths.
The Origin of Chaos in the Outer Solar System
Authors: Murray N. , Holman M.
Published: July 2002

Classical analytic theories of the solar system indicate that it is stable, but numerical integrations suggest that it is chaotic. This disagreement is resolved by a new analytic theory. The theory shows that the chaos among the jovian planets results from the overlap of the components of a mean motion resonance among Jupiter, Saturn, and Uranus, and provides rough estimates of the Lyapunov time (10
7
years) and the dynamical lifetime of Uranus (10
18
years). The jovian planets must have entered the resonance after all the gas and most of the planetesimals in the protoplanetary disk were removed.
Apaf-1 and Caspase-9 in p53-Dependent Apoptosis and Tumor Inhibition
Authors: Soengas M. S. , Alarcón R. M. , Yoshida H. , J. A. , Giaccia  , Hakem R. , Mak T. W. , Lowe S. W.
Published: July 2002

The ability of p53 to promote apoptosis in response to mitogenic oncogenes appears to be critical for its tumor suppressor function. Caspase-9 and its cofactor Apaf-1 were found to be essential downstream components of p53 in Myc-induced apoptosis. Like p53 null cells, mouse embryo fibroblast cells deficient in Apaf-1 and caspase-9, and expressing c-
Myc
, were resistant to apoptotic stimuli that mimic conditions in developing tumors. Inactivation of Apaf-1 or caspase-9 substituted for p53 loss in promoting the oncogenic transformation of
Myc
-expressing cells. These results imply a role for Apaf-1 and caspase-9 in controlling tumor development.
Dense Populations of a Giant Sulfur Bacterium in Namibian Shelf Sediments
Authors: Schulz H. N. , Brinkhoff T. , Ferdelman T. G. , Mariné M. Hernández , Teske A. , Jørgensen B. B.
Published: July 2002

A previously unknown giant sulfur bacterium is abundant in sediments underlying the oxygen minimum zone of the Benguela Current upwelling system. The bacterium has a spherical cell that exceeds by up to 100-fold the biovolume of the largest known prokaryotes. On the basis of 16
S
ribosomal DNA sequence data, these bacteria are closely related to the marine filamentous sulfur bacteria
Thioploca
, abundant in the upwelling area off Chile and Peru. Similar to
Thioploca
, the giant bacteria oxidize sulfide with nitrate that is accumulated to ≤800 millimolar in a central vacuole.
SPA1, a WD-Repeat Protein Specific to Phytochrome A Signal Transduction
Authors: Hoecker Ute , Tepperman James M. , Quail Peter H.
Published: July 2002

The five members of the phytochrome photoreceptor family of
Arabidopsis thaliana
control morphogenesis differentially in response to light. Genetic analysis has identified a signaling pathway that is specifically activated by phytochrome A. A component in this pathway, SPA1 (for “suppressor of phyA-105”), functions in repression of photomorphogenesis and is required for normal photosensory specificity of phytochrome A. Molecular cloning of the
SPA1
gene indicates that SPA1 is a WD (tryptophan–aspartic acid)-repeat protein that also shares sequence similarity with protein kinases. SPA1 can localize to the nucleus, suggesting a possible function in phytochrome A–specific regulation of gene expression.
Mercury in a Spanish Peat Bog: Archive of Climate Change and Atmospheric Metal Deposition
Authors: Martı́nez-Cortizas A. , Pontevedra-Pombal X. , Garcı́a-Rodeja E. , Nóvoa-Muñoz J. C. , Shotyk W.
Published: July 2002

A peat core from a bog in northwest Spain provides a record of the net accumulation of atmospheric mercury since 4000 radiocarbon years before the present. It was found that cold climates promoted an enhanced accumulation and the preservation of mercury with low thermal stability, and warm climates were characterized by a lower accumulation and the predominance of mercury with moderate to high thermal stability. This record can be separated into natural and anthropogenic components. The substantial anthropogenic mercury component began ∼2500 radiocarbon years before the present, which is near the time of the onset of mercury mining in Spain. Anthropogenic mercury has dominated the deposition record since the Islamic period (8th to 11th centuries A.D.). The results shown here have implications for the global mercury cycle and also imply that the thermal lability of the accumulated mercury can be used not only to quantify the effects of human activity, but also as a new tool for quantitative paleotemperature reconstruction.
Positive Selection of Natural Autoreactive B Cells
Authors: Hayakawa Kyoko , Asano Masanao , Shinton Susan A. , Gui Ming , Allman David , Stewart Colin L. , Silver Jack , Hardy Richard R.
Published: July 2002

Lymphocyte development is critically influenced by self-antigens. T cells are subject to both positive and negative selection, depending on their degree of self-reactivity. Although B cells are subject to negative selection, it has been difficult to test whether self-antigen plays any positive role in B cell development. A murine model system of naturally generated autoreactive B cells with a germ line gene–encoded specificity for the Thy-1 (CD90) glycoprotein was developed, in which the presence of self-antigen promotes B cell accumulation and serum autoantibody secretion. Thus, B cells can be subject to positive selection, generated, and maintained on the basis of their autoreactivity.
High H
2
Uptake by Alkali-Doped Carbon Nanotubes Under Ambient Pressure and Moderate Temperatures
Authors: Chen P. , Wu X. , Lin J. , Tan K. L.
Published: July 2002

Lithium- or potassium-doped carbon nanotubes can absorb ∼20 or ∼14 weight percent of hydrogen at moderate (200° to 400°C) or room temperatures, respectively, under ambient pressure. These values are greater than those of metal hydride and cryoadsorption systems. The hydrogen stored in the lithium- or potassium-doped carbon nanotubes can be released at higher temperatures, and the sorption-desorption cycle can be repeated with little decrease in the sorption capacity. The high hydrogen-uptake capacity of these systems may be derived from the special open-edged, layered structure of the carbon nanotubes made from methane, as well as the catalytic effect of alkali metals.
A Phospholipase C-Dependent Inositol Polyphosphate Kinase Pathway Required for Efficient Messenger RNA Export
Authors: York John D. , Odom Audrey R. , Murphy Robert , Ives Eric B. , Wente Susan R.
Published: July 2002

In order to identify additional factors required for nuclear export of messenger RNA, a genetic screen was conducted with a yeast mutant deficient in a factor Gle1p, which associates with the nuclear pore complex (NPC). The three genes identified encode phospholipase C and two potential inositol polyphosphate kinases. Together, these constitute a signaling pathway from phosphatidylinositol 4,5-bisphosphate to inositol hexakisphosphate (IP
6
). The common downstream effects of mutations in each component were deficiencies in IP
6
synthesis and messenger RNA export, indicating a role for IP
6
in
GLE1
function and messenger RNA export.
Pacemaking the Ice Ages by Frequency Modulation of Earth's Orbital Eccentricity
Authors: Rial J. A.
Published: July 2002

Evidence from power spectra of deep-sea oxygen isotope time series suggests that the climate system of Earth responds nonlinearly to astronomical forcing by frequency modulating eccentricity-related variations in insolation. With the help of a simple model, it is shown that frequency modulation of the approximate 100,000-year eccentricity cycles by the 413,000-year component accounts for the variable duration of the ice ages, the multiple-peak character of the time series spectra, and the notorious absence of significant spectral amplitude at the 413,000-year period. The observed spectra are consistent with the classic Milankovitch theories of insolation, so that climate forcing by 100,000-year variations in orbital inclination that cause periodic dust accretion appear unnecessary.
Underinvestment: The Energy Technology and R&D Policy Challenge
Authors: Margolis Robert M. , Kammen Daniel M.
Published: July 2002

This Viewpoint examines data on international trends in energy research and development (R&D) funding, patterns of U.S. energy technology patents and R&D funding, and U.S. R&D intensities across selected sectors. The data present a disturbing picture: (i) Energy technology funding levels have declined significantly during the past two decades throughout the industrial world; (ii) U.S. R&D spending and patents, both overall and in the energy sector, have been highly correlated during the past two decades; and (iii) the R&D intensity of the U.S. energy sector is extremely low. It is argued that recent cutbacks in energy R&D are likely to reduce the capacity of the energy sector to innovate. The trends are particularly troubling given the need for increased international capacity to respond to emerging risks such as global climate change.
Chemical "Double Slits": Dynamical Interference of Photodissociation Pathways in Water
Authors: Dixon R. N. , Hwang D. W. , Yang X. F. , Harich S. , Lin J. J. , Yang X.
Published: July 2002

Photodissociation of water at a wavelength of 121.6 nanometers has been investigated by using the H-atom Rydberg tagging technique. A striking even-odd intensity oscillation was observed in the OH(X) product rotational distribution. Model calculations attribute this oscillation to an unusual dynamical interference brought about by two dissociation pathways that pass through dissimilar conical intersections of potential energy surfaces, but result in the same products. The interference pattern and the OH product rotational distribution are sensitive to the positions and energies of the conical intersections, one with the atoms collinear as H–OH and the other as H–HO. An accurate simulation of the observations would provide a detailed test of global H
2
O potential energy surfaces for the three (X̃/Ã/B̃) contributing states. The interference observed from the two conical intersection pathways provides a chemical analog of Young's well-known double-slit experiment.
Altered Cochlear Fibrocytes in a Mouse Model of DFN3 Nonsyndromic Deafness
Authors: Minowa O. , Ikeda K. , Sugitani Y. , Oshima T. , Nakai S. , Katori Y. , Suzuki M. , Furukawa M. , Kawase T. , Zheng Y. , Ogura M. , Asada Y. , Watanabe K. , Yamanaka H. , Gotoh S. , Nishi-Takeshima M. , Sugimoto T. , Kikuchi T. , Takasaka T. , Noda T.
Published: July 2002

DFN3, an X chromosome-linked nonsyndromic mixed deafness, is caused by mutations in the
BRN-4
gene, which encodes a POU transcription factor. Brn-4-deficient mice were created and found to exhibit profound deafness. No gross morphological changes were observed in the conductive ossicles or cochlea, although there was a dramatic reduction in endocochlear potential. Electron microscopy revealed severe ultrastructural alterations in cochlear spiral ligament fibrocytes. The findings suggest that these fibrocytes, which are mesenchymal in origin and for which a role in potassium ion homeostasis has been postulated, may play a critical role in auditory function.
Inhibitors of the Nonmevalonate Pathway of Isoprenoid Biosynthesis as Antimalarial Drugs
Authors: Jomaa Hassan , Wiesner Jochen , Sanderbrand Silke , Altincicek Boran , Weidemeyer Claus , Hintz Martin , Türbachova Ivana , Eberl Matthias , Zeidler Johannes , Lichtenthaler Hartmut K. , Soldati Dominique , Beck Ewald
Published: July 2002

A mevalonate-independent pathway of isoprenoid biosynthesis present in
Plasmodium falciparum
was shown to represent an effective target for chemotherapy of malaria. This pathway includes 1-deoxy-
d
-xylulose 5-phosphate (DOXP) as a key metabolite. The presence of two genes encoding the enzymes DOXP synthase and DOXP reductoisomerase suggests that isoprenoid biosynthesis in
P. falciparum
depends on the DOXP pathway. This pathway is probably located in the apicoplast. The recombinant
P. falciparum
DOXP reductoisomerase was inhibited by fosmidomycin and its derivative, FR-900098. Both drugs suppressed the in vitro growth of multidrug-resistant
P. falciparum
strains. After therapy with these drugs, mice infected with the rodent malaria parasite
P. vinckei
were cured.
Muscle and Movement Representations in the Primary Motor Cortex
Authors: Kakei Shinji , Hoffman Donna S. , Strick Peter L.
Published: July 2002

What aspects of movement are represented in the primary motor cortex (M1): relatively low-level parameters like muscle force, or more abstract parameters like handpath? To examine this issue, the activity of neurons in M1 was recorded in a monkey trained to perform a task that dissociates three major variables of wrist movement: muscle activity, direction of movement at the wrist joint, and direction of movement in space. A substantial group of neurons in M1 (28 out of 88) displayed changes in activity that were muscle-like. Unexpectedly, an even larger group of neurons in M1 (44 out of 88) displayed changes in activity that were related to the direction of wrist movement in space independent of the pattern of muscle activity that generated the movement. Thus, both “muscles” and “movements” appear to be strongly represented in M1.
Regulation of Intestinal α-Defensin Activation by the Metalloproteinase Matrilysin in Innate Host Defense
Authors: Wilson Carole L. , Ouellette Andre J. , Satchell Donald P. , Ayabe Tokiyoshi , López-Boado Yolanda S. , Stratman Jennifer L. , Hultgren Scott J. , Matrisian Lynn M. , Parks William C.
Published: July 2002

Precursors of α-defensin peptides require activation for bactericidal activity. In mouse small intestine, matrilysin colocalized with α-defensins (cryptdins) in Paneth cell granules, and in vitro it cleaved the pro segment from cryptdin precursors. Matrilysin-deficient (MAT
−/−
) mice lacked mature cryptdins and accumulated precursor molecules. Intestinal peptide preparations from MAT
−/−
mice had decreased antimicrobial activity. Orally administered bacteria survived in greater numbers and were more virulent in MAT
−/−
mice than in MAT
+/+
mice. Thus, matrilysin functions in intestinal mucosal defense by regulating the activity of defensins, which may be a common role for this metalloproteinase in its numerous epithelial sites of expression.
Osmium Isotope Constraints on Ore Metal Recycling in Subduction Zones
Authors: McInnes Brent I. A. , McBride Jannene S. , Evans Noreen J. , Lambert David D. , Andrew Anita S.
Published: July 2002

Veined peridotite xenoliths from the mantle beneath the giant Ladolam gold deposit on Lihir Island, Papua New Guinea, are 2 to 800 times more enriched in copper, gold, platinum, and palladium than surrounding depleted arc mantle. Gold ores have osmium isotope compositions similar to those of the underlying subduction-modified mantle peridotite source region, indicating that the primary origin of the metals was the mantle. Because the mantle is relatively depleted in gold, copper, and palladium, tectonic processes that enhance the advective transport and concentration of these fluid soluble metals may be a prerequisite for generating porphyry-epithermal copper-gold deposits.
Neurogenesis in the Neocortex of Adult Primates
Authors: Gould Elizabeth , Reeves Alison J. , Graziano Michael S. A. , Gross Charles G.
Published: July 2002

In primates, prefrontal, inferior temporal, and posterior parietal cortex are important for cognitive function. It is shown that in adult macaques, new neurons are added to these three neocortical association areas, but not to a primary sensory area (striate cortex). The new neurons appeared to originate in the subventricular zone and to migrate through the white matter to the neocortex, where they extended axons. These new neurons, which are continually added in adulthood, may play a role in the functions of association neocortex.
Interlocked Feedback Loops Within the
Drosophila
Circadian Oscillator
Authors: Glossop Nick R. J. , Lyons Lisa C. , Hardin Paul E.
Published: July 2002

Drosophila Clock
(
dClk
) is rhythmically expressed, with peaks in mRNA and protein (dCLK) abundance early in the morning.
dClk
mRNA cycling is shown here to be regulated by PERIOD-TIMELESS (PER-TIM)–mediated release of dCLK- and CYCLE (CYC)–dependent repression. Lack of both PER-TIM derepression and dCLK-CYC repression results in high levels of
dClk
mRNA, which implies that a separate
dClk
activator is present. These results demonstrate that the
Drosophila
circadian feedback loop is composed of two interlocked negative feedback loops: a
per-tim
loop, which is activated by dCLK-CYC and repressed by PER-TIM, and a
dClk
loop, which is repressed by dCLK-CYC and derepressed by PER-TIM.
An Essential Role for BLNK in Human B Cell Development
Authors: Minegishi Yoshiyuki , Rohrer Jurg , Coustan-Smith Elaine , Lederman Howard M. , Pappu Rajita , Campana Dario , Chan Andrew C. , Conley Mary Ellen
Published: July 2002

The signal transduction events that control the progenitor B cell (pro-B cell) to precursor B cell (pre-B cell) transition have not been well delineated. In evaluating patients with absent B cells, a male with a homozygous splice defect in the cytoplasmic adapter protein BLNK (B cell linker protein) was identified. Although this patient had normal numbers of pro-B cells, he had no pre-B cells or mature B cells, indicating that BLNK plays a critical role in orchestrating the pro-B cell to pre-B cell transition. The immune system and overall growth and development were otherwise normal in this patient, suggesting that BLNK function is highly specific.
Collisional Breakup in a Quantum System of Three Charged Particles
Authors: Rescigno T. N. , Baertschy M. , Isaacs W. A. , McCurdy C. W.
Published: July 2002

Since the invention of quantum mechanics, even the simplest example of the collisional breakup of a system of charged particles, e
−
+ H → H
+
+ e
−
+ e
−
(where e
−
is an electron and H is hydrogen), has resisted solution and is now one of the last unsolved fundamental problems in atomic physics. A complete solution requires calculation of the energies and directions for a final state in which all three particles are moving away from each other. Even with supercomputers, the correct mathematical description of this state has proved difficult to apply. A framework for solving ionization problems in many areas of chemistry and physics is finally provided by a mathematical transformation of the Schrödinger equation that makes the final state tractable, providing the key to a numerical solution of this problem that reveals its full dynamics.
Enhanced Morphine Analgesia in Mice Lacking β-Arrestin 2
Authors: Bohn Laura M. , Lefkowitz Robert J. , Gainetdinov Raul R. , Peppel Karsten , Caron Marc G. , Lin Fang-Tsyr
Published: July 2002

The ability of morphine to alleviate pain is mediated through a heterotrimeric guanine nucleotide binding protein (G protein)–coupled heptahelical receptor (GPCR), the μ opioid receptor (μOR). The efficiency of GPCR signaling is tightly regulated and ultimately limited by the coordinated phosphorylation of the receptors by specific GPCR kinases and the subsequent interaction of the phosphorylated receptors with β-arrestin 1 and β-arrestin 2. Functional deletion of the β-arrestin 2 gene in mice resulted in remarkable potentiation and prolongation of the analgesic effect of morphine, suggesting that μOR desensitization was impaired. These results provide evidence in vivo for the physiological importance of β-arrestin 2 in regulating the function of a specific GPCR, the μOR. Moreover, they suggest that inhibition of β-arrestin 2 function might lead to enhanced analgesic effectiveness of morphine and provide potential new avenues for the study and treatment of pain, narcotic tolerance, and dependence.
Connectivity of Marine Populations: Open or Closed?
Authors: Cowen Robert K. , Lwiza Kamazima M. M. , Sponaugle Su , Paris Claire B. , Olson Donald B.
Published: July 2002

Most marine populations are thought to be well connected via long-distance dispersal of larval stages. Eulerian and Lagrangian flow models, coupled with linear mortality estimates, were used to examine this assumption. The findings show that when simple advection models are used, larval exchange rates may be overestimated; such simplistic models fail to account for a decrease of up to nine orders of magnitude in larval concentrations resulting from diffusion and mortality. The alternative process of larval retention near local populations is shown to exist and may be of great importance in the maintenance of marine population structure and management of coastal marine resources.
An Oral Vaccine Against NMDAR1 with Efficacy in Experimental Stroke and Epilepsy
Authors: During Matthew J. , Symes Charles W. , Lawlor Patricia A. , Lin John , Dunning Jane , Fitzsimons Helen L. , Poulsen David , Leone Paola , Xu Ruian , Dicker Bridget L. , Lipski Janusz , Young Deborah
Published: July 2002

The brain is generally considered immunoprivileged, although increasing examples of immunological responses to brain antigens, neuronal expression of major histocompatibility class I genes, and neurological autoimmunity have been recognized. An adeno-associated virus (AAV) vaccine generated autoantibodies that targeted a specific brain protein, the NR1 subunit of the
N
-methyl-
d
-aspartate (NMDA) receptor. After peroral administration of the AAV vaccine, transgene expression persisted for at least 5 months and was associated with a robust humoral response in the absence of a significant cell-mediated response. This single-dose vaccine was associated with strong anti-epileptic and neuroprotective activity in rats for both a kainate-induced seizure model and also a middle cerebral artery occlusion stroke model at 1 to 5 months following vaccination. Thus, a vaccination strategy targeting brain proteins is feasible and may have therapeutic potential for neurological disorders.
Salmonella
Pathogenicity Island 2-Dependent Evasion of the Phagocyte NADPH Oxidase
Authors: Vazquez-Torres Andrés , Xu Yisheng , Jones-Carson Jessica , Holden David W. , Lucia Scott M. , Dinauer Mary C. , Mastroeni Pietro , Fang Ferric C.
Published: July 2002

A type III protein secretion system encoded by
Salmonella
pathogenicity island 2 (SPI2) has been found to be required for virulence and survival within macrophages. Here, SPI2 was shown to allow
Salmonella typhimurium
to avoid NADPH oxidase–dependent killing by macrophages. The ability of SPI2-mutant bacteria to survive in macrophages and to cause lethal infection in mice was restored by abrogation of the NADPH oxidase–dependent respiratory burst. Ultrastructural and immunofluorescence microscopy demonstrated efficient localization of the NADPH oxidase in the proximity of vacuoles containing SPI2-mutant but not wild-type bacteria, suggesting that SPI2 interferes with trafficking of oxidase-containing vesicles to the phagosome.
Nonrandom Extinction and the Loss of Evolutionary History
Authors: Purvis Andy , Agapow Paul-Michael , Gittleman John L. , Mace Georgina M.
Published: July 2002

The hierarchical nature of phylogenies means that random extinction of species affects a smaller fraction of higher taxa, and so the total amount of evolutionary history lost may be comparatively slight. However, current extinction risk is not phylogenetically random. We show the potentially severe implications of the clumped nature of threat for the loss of biodiversity. An additional 120 avian and mammalian genera are at risk compared with the number predicted under random extinction. We estimate that the prospective extra loss of mammalian evolutionary history alone would be equivalent to losing a monotypic phylum.
Carrier-Envelope Phase Control of Femtosecond Mode-Locked Lasers and Direct Optical Frequency Synthesis
Authors: Jones David J. , Diddams Scott A. , Ranka Jinendra K. , Stentz Andrew , Windeler Robert S. , Hall John L. , Cundiff Steven T.
Published: July 2002

We stabilized the carrier-envelope phase of the pulses emitted by a femtosecond mode-locked laser by using the powerful tools of frequency-domain laser stabilization. We confirmed control of the pulse-to-pulse carrier-envelope phase using temporal cross correlation. This phase stabilization locks the absolute frequencies emitted by the laser, which we used to perform absolute optical frequency measurements that were directly referenced to a stable microwave clock.
Species Diversity and Biological Invasions: Relating Local Process to Community Pattern
Authors: Levine Jonathan M.
Published: July 2002

In a California riparian system, the most diverse natural assemblages are the most invaded by exotic plants. A direct in situ manipulation of local diversity and a seed addition experiment showed that these patterns emerge despite the intrinsic negative effects of diversity on invasions. The results suggest that species loss at small scales may reduce invasion resistance. At community-wide scales, the overwhelming effects of ecological factors spatially covarying with diversity, such as propagule supply, make the most diverse communities most likely to be invaded.
Subducted Seamount Imaged in the Rupture Zone of the 1946 Nankaido Earthquake
Authors: Kodaira Shuichi , Takahashi Narumi , Nakanishi Ayako , Miura Seiichi , Kaneda Yoshiyuki
Published: July 2002

The Nankai Trough is a vigorous subduction zone where large earthquakes have been recorded since the seventh century, with a recurrence time of 100 to 200 years. The 1946 Nankaido earthquake was unusual, with a rupture zone estimated from long-period geodetic data that was more than twice as large as that derived from shorter period seismic data. In the center of this earthquake rupture zone, we used densely deployed ocean bottom seismographs to detect a subducted seamount 13 kilometers thick by 50 kilometers wide at a depth of 10 kilometers. We propose that this seamount might work as a barrier inhibiting brittle seismogenic rupture.
Involvement of Cellular Caveolae in Bacterial Entry into Mast Cells
Authors: Shin Jeoung-Sook , Gao Zhimin , Abraham Soman N.
Published: July 2002

Caveolae are subcellular structures implicated in the import and transcytosis of macromolecules and in transmembrane signaling. To date, evidence for the existence of caveolae in hematopoietic cells has been ambiguous. Caveolae were detected in the microvilli and intracellular vesicles of cultured mouse bone marrow–derived mast cells (BMMCs). CD48, a receptor for FimH-expressing (type 1 fimbriated)
Escherichia coli
, was specifically localized to plasmalemmal caveolae in BMMCs. The involvement of caveolae in bacterial entry into BMMCs was indicated because caveolae-disrupting and -usurping agents specifically blocked
E. coli
entry, and markers of caveolae were actively recruited to sites of bacterial entry. The formation of bacteria-encapsulating caveolar chambers in BMMCs represents a distinct mechanism of microbial entry into phagocytes.
Earthquake Potential Along the Northern Hayward Fault, California
Authors: Bürgmann Roland , Schmidt D. , Nadeau R. M. , d'Alessio M. , Fielding E. , Manaker D. , McEvilly T. V. , Murray M. H.
Published: July 2002

The Hayward fault slips in large earthquakes and by aseismic creep observed along its surface trace. Dislocation models of the surface deformation adjacent to the Hayward fault measured with the global positioning system and interferometric synthetic aperture radar favor creep at ∼7 millimeters per year to the bottom of the seismogenic zone along a ∼20-kilometer-long northern fault segment. Microearthquakes with the same waveform repeatedly occur at 4- to 10-kilometer depths and indicate deep creep at 5 to 7 millimeters per year. The difference between current creep rates and the long-term slip rate of ∼10 millimeters per year can be reconciled in a mechanical model of a freely slipping northern Hayward fault adjacent to the locked 1868 earthquake rupture, which broke the southern 40 to 50 kilometers of the fault. The potential for a major independent earthquake of the northern Hayward fault might be less than previously thought.
Genes Expressed in Human Tumor Endothelium
Authors: Croix Brad St. , Rago Carlo , Velculescu Victor , Traverso Giovanni , Romans Katharine E. , Montgomery Elizabeth , Lal Anita , Riggins Gregory J. , Lengauer Christoph , Vogelstein Bert , Kinzler Kenneth W.
Published: July 2002

To gain a molecular understanding of tumor angiogenesis, we compared gene expression patterns of endothelial cells derived from blood vessels of normal and malignant colorectal tissues. Of over 170 transcripts predominantly expressed in the endothelium, 79 were differentially expressed, including 46 that were specifically elevated in tumor-associated endothelium. Several of these genes encode extracellular matrix proteins, but most are of unknown function. Most of these tumor endothelial markers were expressed in a wide range of tumor types, as well as in normal vessels associated with wound healing and corpus luteum formation. These studies demonstrate that tumor and normal endothelium are distinct at the molecular level, a finding that may have significant implications for the development of anti-angiogenic therapies.
Discrete Atom Imaging of One-Dimensional Crystals Formed Within Single-Walled Carbon Nanotubes
Authors: Meyer Rüdiger R. , Sloan Jeremy , Dunin-Borkowski Rafal E. , Kirkland Angus I. , Novotny Miles C. , Bailey Sam R. , Hutchison John L. , Green Malcolm L. H.
Published: July 2002

The complete crystallography of a one-dimensional crystal of potassium iodide encapsulated within a 1.6-nanometer-diameter single-walled carbon nanotube has been determined with high-resolution transmission electron microscopy. Individual atoms of potassium and iodine within the crystal were identified from a phase image that was reconstructed with a modified focal series restoration approach. The lattice spacings within the crystal are substantially different from those in bulk potassium iodide. This is attributed to the reduced coordination of the surface atoms of the crystal and the close proximity of the van der Waals surface of the confining nanotube.
A Mechanical Model for Intraplate Earthquakes: Application to the New Madrid Seismic Zone
Authors: Kenner Shelley J. , Segall and Paul
Published: July 2002

We present a time-dependent model for the generation of repeated intraplate earthquakes that incorporates a weak lower crustal zone within an elastic lithosphere. Relaxation of this weak zone after tectonic perturbations transfers stress to the overlying crust, generating a sequence of earthquakes that continues until the zone fully relaxes. Simulations predict large (5 to 10 meters) slip events with recurrence intervals of 250 to 4000 years and cumulative offsets of about 100 meters, depending on material parameters and far-field stress magnitude. Most are consistent with earthquake magnitude, coseismic slip, recurrence intervals, cumulative offset, and surface deformation rates in the New Madrid Seismic Zone. Computed interseismic strain rates may not be detectable with available geodetic data, implying that low observed rates of strain accumulation cannot be used to rule out future damaging earthquakes.
Polyploidy and the Evolution of Gender Dimorphism in Plants
Authors: Miller J. S. , Venable D. L.
Published: July 2002

Gender dimorphism and polyploidy are important evolutionary transitions that have evolved repeatedly in many plant families. We show that gender dimorphism in North American
Lycium
(Solanaceae) has evolved in polyploid, self-compatible taxa whose closest relatives are cosexual, self-incompatible diploids. This has occurred independently in South African
Lycium
. We present additional evidence for this pathway to gender dimorphism from 12 genera involving at least 20 independent evolutionary events. We propose that polyploidy is a trigger of unrecognized importance for the evolution of gender dimorphism, which operates by disrupting self-incompatibility and leading to inbreeding depression. Subsequently, male sterile mutants invade and increase because they are unable to inbreed.
Localized Rac Activation Dynamics Visualized in Living Cells
Authors: Kraynov Vadim S. , Chamberlain Chester , Bokoch Gary M. , Schwartz Martin A. , Slabaugh Sarah , Hahn Klaus M.
Published: July 2002

Signaling proteins are thought to be tightly regulated spatially and temporally in order to generate specific and localized effects. For Rac and other small guanosine triphosphatases, binding to guanosine triphosphate leads to interaction with downstream targets and regulates subcellular localization. A method called FLAIR (fluorescence activation indicator for Rho proteins) was developed to quantify the spatio-temporal dynamics of the Rac1 nucleotide state in living cells. FLAIR revealed precise spatial control of growth factor–induced Rac activation, in membrane ruffles and in a gradient of activation at the leading edge of motile cells. FLAIR exemplifies a generally applicable approach for examining spatio-temporal control of protein activity.
A PEST-Like Sequence in Listeriolysin O Essential for
Listeria monocytogenes
Pathogenicity
Authors: Decatur Amy L. , Portnoy Daniel A.
Published: July 2002

Establishment and maintenance of an intracellular niche are critical to the success of an intracellular pathogen. Here, the pore-forming protein listeriolysin O (LLO), secreted by
Listeria monocytogenes
, was shown to contain a PEST-like sequence (P, Pro; E, Glu; S, Ser; T, Thr) that is essential for the virulence and intracellular compartmentalization of this pathogen. Mutants lacking the PEST-like sequence entered the host cytosol but subsequently permeabilized and killed the host cell. LLO lacking the PEST-like sequence accumulated in the host-cell cytosol, suggesting that this sequence targets LLO for degradation. Transfer of the sequence to perfringolysin O transformed this toxic cytolysin into a nontoxic derivative that facilitated intracellular growth.
The Role of Mg
2+
as an Impurity in Calcite Growth
Authors: Davis Kevin J. , Dove Patricia M. , De Yoreo James J.
Published: July 2002

Magnesium is a key determinant in CaCO
3
mineralization; however, macroscopic observations have failed to provide a clear physical understanding of how magnesium modifies carbonate growth. Atomic force microscopy was used to resolve the mechanism of calcite inhibition by magnesium through molecular-scale determination of the thermodynamic and kinetic controls of magnesium on calcite formation. Comparison of directly measured step velocities to standard impurity models demonstrated that enhanced mineral solubility through magnesium incorporation inhibited calcite growth. Terrace width measurements on calcite growth spirals were consistent with a decrease in effective supersaturation due to magnesium incorporation. Ca

1−
x

Mg

x

CO
3
solubilities determined from microscopic observations of step dynamics can thus be linked to macroscopic measurements.
Efficient Initiation of HCV RNA Replication in Cell Culture
Authors: Blight Keril J. , Kolykhalov Alexander A. , Rice Charles M.
Published: July 2002

Hepatitis C virus (HCV) infection is a global health problem affecting an estimated 170 million individuals worldwide. We report the identification of multiple independent adaptive mutations that cluster in the HCV nonstructural protein NS5A and confer increased replicative ability in vitro. Among these adaptive mutations were a single amino acid substitution that allowed HCV RNA replication in 10% of transfected hepatoma cells and a deletion of 47 amino acids encompassing the interferon (IFN) sensitivity determining region (ISDR). Independent of the ISDR, IFN-α rapidly inhibited HCV RNA replication in vitro. This work establishes a robust, cell-based system for genetic and functional analyses of HCV replication.
A Short Duration of the Cretaceous-Tertiary Boundary Event: Evidence from Extraterrestrial Helium-3
Authors: Mukhopadhyay S. , Farley K. A. , Montanari A.
Published: July 2002

Analyses of marine carbonates through the interval 63.9 to 65.4 million years ago indicate a near-constant flux of extraterrestrial helium-3, a tracer of the accretion rate of interplanetary dust to Earth. This observation indicates that the bolide associated with the Cretaceous-Tertiary (K-T) extinction event was not accompanied by enhanced solar system dustiness and so could not have been a member of a comet shower. The use of helium-3 as a constant-flux proxy of sedimentation rate implies deposition of the K-T boundary clay in (10 ± 2) × 10
3
years, precluding the possibility of a long hiatus at the boundary and requiring extremely rapid faunal turnover.
(Amino)(Aryl)Carbenes: Stable Singlet Carbenes Featuring a Spectator Substituent
Authors: Solé Stéphane , Gornitzka Heinz , Schoeller Wolfgang W. , Bourissou Didier , Bertrand Guy
Published: July 2002

Several (amino)(aryl)carbenes have been shown to be stable at room temperature in solution and in the solid state. Electroneutrality of the carbene center is ensured by the amino group, which has both π-donor and σ-acceptor electronic character. The aryl group remains a spectator substituent, as shown by single-crystal x-ray analysis and by its chemical behavior. Because only one electron-active substituent is needed, numerous stable carbenes will become accessible, which will open the way for new synthetic developments and applications in various fields.
Regulation of Wnt Signaling and Embryo Patterning by an Extracellular Sulfatase
Authors: Dhoot Gurtej K. , Gustafsson Marcus K. , Ai Xingbin , Sun Weitao , Standiford David M. , Emerson Charles P.
Published: July 2002

The developmental signaling functions of cell surface heparan sulfate proteoglycans (HSPGs) are dependent on their sulfation states. Here, we report the identification of QSulf1, the avian ortholog of an evolutionarily conserved protein family related to heparan-specific
N
-acetyl glucosamine sulfatases. QSulf1 expression is induced by Sonic hedgehog in myogenic somite progenitors in quail embryos and is required for the activation of
MyoD
, a Wnt-induced regulator of muscle specification. QSulf1 is localized on the cell surface and regulates heparan-dependent Wnt signaling in C2C12 myogenic progenitor cells through a mechanism that requires its catalytic activity, providing evidence that QSulf1 regulates Wnt signaling through desulfation of cell surface HSPGs.