bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Src Tyrosine Kinase with a Human Potassium Channel Mediated by SH3 Domain
Authors: Holmes Todd C. , Fadool Debra A. , Ren Ruibao , Levitan Irwin B.
Published: July 2002

The human Kv1.5 potassium channel (hKv1.5) contains proline-rich sequences identical to those that bind to Src homology 3 (SH3) domains. Direct association of the Src tyrosine kinase with cloned hKv1.5 and native hKv1.5 in human myocardium was observed. This interaction was mediated by the proline-rich motif of hKv1.5 and the SH3 domain of Src. Furthermore, hKv1.5 was tyrosine phosphorylated, and the channel current was suppressed, in cells coexpressing v-Src. These results provide direct biochemical evidence for a signaling complex composed of a potassium channel and a protein tyrosine kinase.
NMDA Channel Regulation by Channel-Associated Protein Tyrosine Kinase Src
Authors: Yu Xian-Min , Askalan Rand , Keil Gary J. , Salter Michael W.
Published: July 2002

The
N
-methyl-D-aspartate (NMDA) receptor mediates synaptic transmission and plasticity in the central nervous system (CNS) and is regulated by tyrosine phosphorylation. In membrane patches excised from mammalian central neurons, the endogenous tyrosine kinase Src was shown to regulate the activity of NMDA channels. The action of Src required a sequence [Src(40–58)] within the noncatalytic, unique domain of Src. In addition, Src coprecipitated with NMDA receptor proteins. Finally, endogenous Src regulated the function of NMDA receptors at synapses. Thus, NMDA receptor regulation by Src may be important in development, plasticity, and pathology in the CNS.
Obesity Sheds Its Secrets
Authors: Gura Trisha
Published: July 2002

The fat-busting hormone leptin no longer looks to be the quick route to a svelte figure that early reports suggested. But while leptin itself may not pan out as an obesity treatment, in the past year, researchers have learned much more about how and where the hormone works in the body and how it interacts with other molecules—information that may help them design drugs that can trim body fat.
Positional Cloning of a Gene for Nematode Resistance in Sugar Beet
Authors: Cai Daguang , Kleine Michael , Kifle Sirak , Harloff Hans-Joachim , Sandal Niels N. , Marcker Kjeld A. , Klein-Lankhorst René M. , Salentijn Elma M. J. , Lange Wouter , Stiekema Willem J. , Wyss Urs , Grundler Florian M. W. , Jung Christian
Published: July 2002

The

Hs1
pro-1

locus confers resistance to the beet cyst nematode (
Heterodera schachtii
Schmidt), a major pest in the cultivation of sugar beet (
Beta vulgaris
L.). The

Hs1
pro-1

gene was cloned with the use of genome-specific satellite markers and chromosomal break-point analysis. Expression of the corresponding complementary DNA in a susceptible sugar beet conferred resistance to infection with the beet cyst nematode. The native

Hs1
pro-1

gene, expressed in roots, encodes a 282-amino acid protein with imperfect leucine-rich repeats and a putative membrane-spanning segment, features similar to those of disease resistance genes previously cloned from higher plants.
Isolation of Putative Progenitor Endothelial Cells for Angiogenesis
Authors: Asahara Takayuki , Murohara Toyoaki , Sullivan Alison , Silver Marcy , van der Zee Rien , Li Tong , Witzenbichler Bernhard , Schatteman Gina , Isner Jeffrey M.
Published: July 2002

Putative endothelial cell (EC) progenitors or angioblasts were isolated from human peripheral blood by magnetic bead selection on the basis of cell surface antigen expression. In vitro, these cells differentiated into ECs. In animal models of ischemia, heterologous, homologous, and autologous EC progenitors incorporated into sites of active angiogenesis. These findings suggest that EC progenitors may be useful for augmenting collateral vessel growth to ischemic tissues (therapeutic angiogenesis) and for delivering anti- or pro-angiogenic agents, respectively, to sites of pathologic or utilitarian angiogenesis.
Deciding Advantageously Before Knowing the Advantageous Strategy
Authors: Bechara Antoine , Damasio Hanna , Tranel Daniel , Damasio Antonio R.
Published: July 2002

Deciding advantageously in a complex situation is thought to require overt reasoning on declarative knowledge, namely, on facts pertaining to premises, options for action, and outcomes of actions that embody the pertinent previous experience. An alternative possibility was investigated: that overt reasoning is preceded by a nonconscious biasing step that uses neural systems other than those that support declarative knowledge. Normal participants and patients with prefrontal damage and decision-making defects performed a gambling task in which behavioral, psychophysiological, and self-account measures were obtained in parallel. Normals began to choose advantageously before they realized which strategy worked best, whereas prefrontal patients continued to choose disadvantageously even after they knew the correct strategy. Moreover, normals began to generate anticipatory skin conductance responses (SCRs) whenever they pondered a choice that turned out to be risky, before they knew explicitly that it was a risky choice, whereas patients never developed anticipatory SCRs, although some eventually realized which choices were risky. The results suggest that, in normal individuals, nonconscious biases guide behavior before conscious knowledge does. Without the help of such biases, overt knowledge may be insufficient to ensure advantageous behavior.
Earthquakes Cannot Be Predicted
Authors: Geller Robert J. , Jackson David D. , Kagan Yan Y. , Mulargia Francesco
Published: July 2002

Can the time, location, and magnitude of future earthquakes be predicted reliably and accurately? In their Perspective, Geller
et al
.'s answer is “no.” Citing recent results from the physics of nonlinear systems “chaos theory,” they argue that any small earthquake has some chance of cascading into a large event. According to research cited by the authors, whether or not this happens depends on unmeasurably fine details of conditions in Earth's interior. Earthquakes are therefore inherently unpredictable. Geller
et al
. suggest that controversy over prediction lingers because prediction claims are not stated as objectively testable scientific hypotheses, and due to overly optimistic reports in the mass media.
SBF Cell Cycle Regulator as a Target of the Yeast PKC-MAP Kinase Pathway
Authors: Madden Kevin , Sheu Yi-Jun , Baetz Kristin , Andrews Brenda , Snyder Michael
Published: July 2002

Protein kinase C (PKC) signaling is highly conserved among eukaryotes and has been implicated in the regulation of cellular processes such as cell proliferation and growth. In the budding yeast,
PKC1
functions to activate the
SLT2(MPK1)
mitogen-activated protein (MAP) kinase cascade, which is required for the maintenance of cell integrity during asymmetric cell growth. Genetic studies, coimmunoprecipitation experiments, and analysis of protein phosphorylation in vivo and in vitro indicate that the SBF transcription factor (composed of Swi4p and Swi6p), an important regulator of gene expression at the G
1
to S phase cell cycle transition, is a target of the Slt2p(Mpk1p) MAP kinase. These studies provide evidence for a direct role of the
PKC1
pathway in the regulation of the yeast cell cycle and cell growth and indicate that conserved signaling pathways can act to control key regulators of cell division.
Activation of β-Catenin-Tcf Signaling in Colon Cancer by Mutations in β-Catenin or APC
Authors: Morin Patrice J. , Sparks Andrew B. , Korinek Vladimir , Barker Nick , Clevers Hans , Vogelstein Bert , Kinzler Kenneth W.
Published: July 2002

Inactivation of the adenomatous polyposis coli (
APC
) tumor suppressor gene initiates colorectal neoplasia. One of the biochemical activities associated with the APC protein is down-regulation of transcriptional activation mediated by β-catenin and T cell transcription factor 4 (Tcf-4). The protein products of mutant
APC
genes present in colorectal tumors were found to be defective in this activity. Furthermore, colorectal tumors with intact
APC
genes were found to contain activating mutations of β-catenin that altered functionally significant phosphorylation sites. These results indicate that regulation of β-catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or β-catenin.
Ferroelectric Field Effect Transistor Based on Epitaxial Perovskite Heterostructures
Authors: Mathews S. , Ramesh R. , Venkatesan T. , Benedetto J.
Published: July 2002

Ferroelectric field effect devices offer the possibility of nonvolatile active memory elements. Doped rare-earth manganates, which are usually associated with colossal magnetoresistive properties, have been used as the semiconductor channel material of a prototypical epitaxial field effect device. The carrier concentration of the semiconductor channel can be “tuned” by varying the manganate stochiometry. A device with La
0.7
Ca
0.3
MnO
3
as the semiconductor and PbZr
0.2
Ti
0.8
O
3
as the ferroelectric gate exhibited a modulation in channel conductance of at least a factor of 3 and a retention loss of 3 percent after 45 minutes without power.
Primary Production in Antarctic Sea Ice
Authors: Arrigo Kevin R. , Worthen Denise L. , Lizotte Michael P. , Dixon Paul , Dieckmann Gerhard
Published: July 2002

A numerical model shows that in Antarctic sea ice, increased flooding in regions with thick snow cover enhances primary production in the infiltration (surface) layer. Productivity in the freeboard (sea level) layer is also determined by sea ice porosity, which varies with temperature. Spatial and temporal variation in snow thickness and the proportion of first-year ice thus determine regional differences in sea ice primary production. Model results show that of the 40 teragrams of carbon produced annually in the Antarctic ice pack, 75 percent was associated with first-year ice and nearly 50 percent was produced in the Weddell Sea.
Positional Cloning of the Gene for Multiple Endocrine Neoplasia-Type 1
Authors: Chandrasekharappa Settara C. , Guru Siradanahalli C. , Manickam Pachiappan , Olufemi Shodimu-Emmanuel , Collins Francis S. , Emmert-Buck Michael R. , Debelenko Larisa V. , Zhuang Zhengping , Lubensky Irina A. , Liotta Lance A. , Crabtree Judy S. , Wang Yingping , Roe Bruce A. , Weisemann Jane , Boguski Mark S. , Agarwal Sunita K. , Kester Mary Beth , Kim Young S. , Heppner Christina , Dong Qihan , Spiegel Allen M. , Burns A. Lee , Marx Stephen J.
Published: July 2002

Multiple endocrine neoplasia–type 1 (MEN1) is an autosomal dominant familial cancer syndrome characterized by tumors in parathyroids, enteropancreatic endocrine tissues, and the anterior pituitary. DNA sequencing from a previously identified minimal interval on chromosome 11q13 identified several candidate genes, one of which contained 12 different frameshift, nonsense, missense, and in-frame deletion mutations in 14 probands from 15 families. The
MEN1
gene contains 10 exons and encodes a ubiquitously expressed 2.8-kilobase transcript. The predicted 610–amino acid protein product, termed menin, exhibits no apparent similarities to any previously known proteins. The identification of
MEN1
will enable improved understanding of the mechanism of endocrine tumorigenesis and should facilitate early diagnosis.
U-Th Isotopes in Arc Magmas: Implications for Element Transfer from the Subducted Crust
Authors: Hawkesworth C. J. , Turner S. P. , McDermott F. , Peate D. W. , van Calsteren P.
Published: July 2002

Uranium-thorium isotope results from island arc volcanic rocks were used to investigate the rates of transfer of fluids and sediments from the downgoing slab. Uranium, but not thorium, is readily mobilized in the fluid. A negative array between thorium/cerium and neodymium-143/neodymium-144 indicates that significant amounts of the thorium in arc rocks are derived from subducted sediments, although perhaps only about 30 percent of the thorium in subducted sediments is returned to the crust in this way. The transfer times for fluid through the mantle wedge are about 30,000 to 120,000 years, whereas those for sediment melts may be several million years. The low average uranium/thorium ratios of bulk crust primarily reflect different crustal generation processes in the Archaean.
Antarctic Tectonics: Constraints From an ERS-1 Satellite Marine Gravity Field
Authors: McAdoo David , Laxon Seymour
Published: July 2002

A high-resolution gravity field of poorly charted and ice-covered ocean near West Antarctica, from the Ross Sea east to the Weddell Sea, has been derived with the use of satellite altimetry, including ERS-1 geodetic phase, wave-form data. This gravity field reveals regional tectonic fabric, such as gravity lineations, which are the expression of fracture zones left by early (65 to 83 million years ago) Pacific-Antarctic sea-floor spreading that separated the Campbell Plateau and New Zealand continent from West Antarctica. These lineations constrain plate motion history and confirm the hypothesis that Antarctica behaved as two distinct plates, separated from each other by an extensional Bellingshausen plate boundary active in the Amundsen Sea before about 61 million years ago.
A Molecular View of Microbial Diversity and the Biosphere
Authors: Pace Norman R.
Published: July 2002

Over three decades of molecular-phylogenetic studies, researchers have compiled an increasingly robust map of evolutionary diversification showing that the main diversity of life is microbial, distributed among three primary relatedness groups or domains: Archaea, Bacteria, and Eucarya. The general properties of representatives of the three domains indicate that the earliest life was based on inorganic nutrition and that photosynthesis and use of organic compounds for carbon and energy metabolism came comparatively later. The application of molecular-phylogenetic methods to study natural microbial ecosystems without the traditional requirement for cultivation has resulted in the discovery of many unexpected evolutionary lineages; members of some of these lineages are only distantly related to known organisms but are sufficiently abundant that they are likely to have impact on the chemistry of the biosphere.
Effect of Low Glacial Atmospheric CO
2
on Tropical African Montane Vegetation
Authors: Jolly Dominique , Haxeltine Alex
Published: July 2002

Estimates of glacial-interglacial climate change in tropical Africa have varied widely. Results from a process-based vegetation model show how montane vegetation in East Africa shifts with changes in both carbon dioxide concentration and climate. For the last glacial maximum, the change in atmospheric carbon dioxide concentration alone could explain the observed replacement of tropical montane forest by a scrub biome. This result implies that estimates of the last glacial maximum tropical cooling based on tree- line shifts must be revised.
Atmospheric Aerosols: Biogeochemical Sources and Role in Atmospheric Chemistry
Authors: Andreae Meinrat O. , Crutzen Paul J.
Published: July 2002

Atmospheric aerosols play important roles in climate and atmospheric chemistry: They scatter sunlight, provide condensation nuclei for cloud droplets, and participate in heterogeneous chemical reactions. Two important aerosol species, sulfate and organic particles, have large natural biogenic sources that depend in a highly complex fashion on environmental and ecological parameters and therefore are prone to influence by global change. Reactions in and on sea-salt aerosol particles may have a strong influence on oxidation processes in the marine boundary layer through the production of halogen radicals, and reactions on mineral aerosols may significantly affect the cycles of nitrogen, sulfur, and atmospheric oxidants.
Preservation of Chitin in 25-Million-Year-Old Fossils
Authors: Stankiewicz B. Artur , Briggs Derek E. G. , Evershed Richard P. , Flannery Matthew B. , Wuttke Michael
Published: July 2002

Chitin is present in fossil insects from the Oligocene (24.7 million years ago) lacustrine shales of Enspel, Germany. This result, which was obtained by analytical pyrolysis, extends by nearly 25 million years the length of time that chemically detectable remains of this biomolecule are known to survive. The embedding sediment is dominated by diatoms, which reflect high productivity in the paleolake. The primary control on the preservation of chitin is thus not time; it may persist in older sediments where suitable paleoenvironmental conditions prevailed.
Large Porous Particles for Pulmonary Drug Delivery
Authors: Edwards David A. , Hanes Justin , Caponetti Giovanni , Hrkach Jeffrey , Ben-Jebria Abdelaziz , Eskew Mary Lou , Mintzes Jeffrey , Deaver Daniel , Lotan Noah , Langer Robert
Published: July 2002

A new type of inhalation aerosol, characterized by particles of small mass density and large size, permitted the highly efficient delivery of inhaled therapeutics into the systemic circulation. Particles with mass densities less than 0.4 gram per cubic centimeter and mean diameters exceeding 5 micrometers were inspired deep into the lungs and escaped the lungs' natural clearance mechanisms until the inhaled particles delivered their therapeutic payload. Inhalation of large porous insulin particles resulted in elevated systemic levels of insulin and suppressed systemic glucose levels for 96 hours, whereas small nonporous insulin particles had this effect for only 4 hours. High systemic bioavailability of testosterone was also achieved by inhalation delivery of porous particles with a mean diameter (20 micrometers) approximately 10 times that of conventional inhaled therapeutic particles.
Single Polymer Dynamics in an Elongational Flow
Authors: Perkins Thomas T. , Smith Douglas E. , Chu Steven
Published: July 2002

The stretching of individual polymers in a spatially homogeneous velocity gradient was observed through use of fluorescently labeled DNA molecules. The probability distribution of molecular extension was determined as a function of time and strain rate. Although some molecules reached steady state, the average extension did not, even after a ∼300-fold distortion of the underlying fluid element. At the highest strain rates, distinct conformational shapes with differing dynamics were observed. There was considerable variation in the onset of stretching, and chains with a dumbbell shape stretched more rapidly than folded ones. As the strain rate was increased, chains did not deform with the fluid element. The steady-state extension can be described by a model consisting of two beads connected by a spring representing the entropic elasticity of a worm-like chain, but the average dynamics cannot.
A Di-Acidic Signal Required for Selective Export from the Endoplasmic Reticulum
Authors: Nishimura Noriyuki , Balch William E.
Published: July 2002

Transport of membrane proteins between intracellular compartments requires specific sequences in the protein cytoplasmic domain to direct packaging into vesicle shuttles. A sequence that mediates export from the endoplasmic reticulum (ER) has proved elusive. A di-acidic signal (Asp-X-Glu, where X represents any amino acid) on the cytoplasmic tail of vesicular stomatitis virus glycoprotein (VSV-G) and other cargo molecules was required for efficient recruitment to vesicles mediating export from the ER in baby hamster kidney cells. The existence of such a signal provides evidence that export from the ER occurs through a selective mechanism.
Telomerase Catalytic Subunit Homologs from Fission Yeast and Human
Authors: Nakamura Toru M. , Morin Gregg B. , Chapman Karen B. , Weinrich Scott L. , Andrews William H. , Lingner Joachim , Harley Calvin B. , Cech Thomas R.
Published: July 2002

Catalytic protein subunits of telomerase from the ciliate
Euplotes aediculatus
and the yeast
Saccharomyces cerevisiae
contain reverse transcriptase motifs. Here the homologous genes from the fission yeast
Schizosaccharomyces pombe
and human are identified. Disruption of the
S. pombe
gene resulted in telomere shortening and senescence, and expression of mRNA from the human gene correlated with telomerase activity in cell lines. Sequence comparisons placed the telomerase proteins in the reverse transcriptase family but revealed hallmarks that distinguish them from retroviral and retrotransposon relatives. Thus, the proposed telomerase catalytic subunits are phylogenetically conserved and represent a deep branch in the evolution of reverse transcriptases.
Selective Colorimetric Detection of Polynucleotides Based on the Distance-Dependent Optical Properties of Gold Nanoparticles
Authors: Elghanian Robert , Storhoff James J. , Mucic Robert C. , Letsinger Robert L. , Mirkin Chad A.
Published: July 2002

A highly selective, colorimetric polynucleotide detection method based on mercaptoalkyloligonucleotide-modified gold nanoparticle probes is reported. Introduction of a single-stranded target oligonucleotide (30 bases) into a solution containing the appropriate probes resulted in the formation of a polymeric network of nanoparticles with a concomitant red-to-pinkish/purple color change. Hybridization was facilitated by freezing and thawing of the solutions, and the denaturation of these hybrid materials showed transition temperatures over a narrow range that allowed differentiation of a variety of imperfect targets. Transfer of the hybridization mixture to a reverse-phase silica plate resulted in a blue color upon drying that could be detected visually. The unoptimized system can detect about 10 femtomoles of an oligonucleotide.
The Complete Genome Sequence of
Escherichia coli
K-12
Authors: Blattner Frederick R. , Plunkett Guy , Bloch Craig A. , Perna Nicole T. , Burland Valerie , Riley Monica , Collado-Vides Julio , Glasner Jeremy D. , Rode Christopher K. , Mayhew George F. , Gregor Jason , Davis Nelson Wayne , Kirkpatrick Heather A. , Goeden Michael A. , Rose Debra J. , Mau Bob , Shao Ying
Published: July 2002

The 4,639,221–base pair sequence of
Escherichia coli
K-12 is presented. Of 4288 protein-coding genes annotated, 38 percent have no attributed function. Comparison with five other sequenced microbes reveals ubiquitous as well as narrowly distributed gene families; many families of similar genes within
E. coli
are also evident. The largest family of paralogous proteins contains 80 ABC transporters. The genome as a whole is strikingly organized with respect to the local direction of replication; guanines, oligonucleotides possibly related to replication and recombination, and most genes are so oriented. The genome also contains insertion sequence (IS) elements, phage remnants, and many other patches of unusual composition indicating genome plasticity through horizontal transfer.
Structure and Function of a Squalene Cyclase
Authors: Wendt K. Ulrich , Poralla Karl , Schulz Georg E.
Published: July 2002

The crystal structure of squalene-hopene cyclase from
Alicyclobacillus acidocaldarius
was determined at 2.9 angstrom resolution. The mechanism and sequence of this cyclase are closely related to those of 2,3-oxidosqualene cyclases that catalyze the cyclization step in cholesterol biosynthesis. The structure reveals a membrane protein with membrane-binding characteristics similar to those of prostaglandin-H
2
synthase, the only other reported protein of this type. The active site of the enzyme is located in a large central cavity that is of suitable size to bind squalene in its required conformation and that is lined by aromatic residues. The structure supports a mechanism in which the acid starting the reaction by protonating a carbon-carbon double bond is an aspartate that is coupled to a histidine. Numerous surface α helices are connected by characteristic QW-motifs (Q is glutamine and W is tryptophan) that tighten the protein structure, possibly for absorbing the reaction energy without structural damage.
LKLF: A Transcriptional Regulator of Single-Positive T Cell Quiescence and Survival
Authors: Kuo Chay T. , Veselits Margaret L. , Leiden Jeffrey M.
Published: July 2002

Mature single-positive (SP) T lymphocytes enter a “resting” state in which they are proliferatively quiescent and relatively resistant to apoptosis. The molecular mechanisms regulating this quiescent phenotype were unknown. Here it was found that the expression of a Kruppel-like zinc finger transcription factor, lung Kruppel-like factor (LKLF), is developmentally induced during the maturation of SP quiescent T cells and rapidly extinguished after SP T cell activation. LKLF-deficient T cells produced by gene targeting had a spontaneously activated phenotype and died in the spleen and lymph nodes from Fas ligand–induced apoptosis. Thus, LKLF is required to program the quiescent state of SP T cells and to maintain their viability in the peripheral lymphoid organs and blood.
Human DNA-(Cytosine-5) Methyltransferase-PCNA Complex as a Target for p21
WAF1
Authors: Chuang Linda S.-H. , Ian Hang-In , Koh Tong-Wey , Ng Huck-Hui , Xu Guoliang , Li Benjamin F. L.
Published: July 2002

DNA–(cytosine-5) methyltransferase (MCMT) methylates newly replicated mammalian DNA, but the factors regulating this activity are unknown. Here, MCMT is shown to bind proliferating cell nuclear antigen (PCNA), an auxiliary factor for DNA replication and repair. Binding of PCNA requires amino acids 163 to 174 of MCMT, occurs in intact cells at foci of newly replicated DNA, and does not alter MCMT activity. A peptide derived from the cell cycle regulator p21
WAF1
can disrupt the MCMT-PCNA interaction, which suggests that p21
WAF1
may regulate methylation by blocking access of MCMT to PCNA. MCMT and p21
WAF1
may be linked in a regulatory pathway, because the extents of their expression are inversely related in both SV40-transformed and nontransformed cells.
Addiction Is a Brain Disease, and It Matters
Authors: Leshner Alan I.
Published: July 2002

Scientific advances over the past 20 years have shown that drug addiction is a chronic, relapsing disease that results from the prolonged effects of drugs on the brain. As with many other brain diseases, addiction has embedded behavioral and social-context aspects that are important parts of the disorder itself. Therefore, the most effective treatment approaches will include biological, behavioral, and social-context components. Recognizing addiction as a chronic, relapsing brain disorder characterized by compulsive drug seeking and use can impact society's overall health and social policy strategies and help diminish the health and social costs associated with drug abuse and addiction.
Direct Visualization of Individual Cylindrical and Spherical Supramolecular Dendrimers
Authors: Hudson S. D. , Jung H.-T. , Percec V. , Cho W.-D. , Johansson G. , Ungar G. , Balagurusamy V. S. K.
Published: July 2002

Electron microscopy methods have been used to visualize individual spherical and cylindrical supramolecular dendrimers, providing definitive confirmation of the structures suggested by previous x-ray diffraction analysis that assumed a microsegregated model. These dendrimers are self-assembled, self-organized, and aligned spontaneously and simultaneously in hexagonal columnar or cubic thermotropic liquid-crystal phases with high uniformity. Homeotropic and planar ordering of the hexagonal columnar liquid crystal was precisely controlled by a variety of surfaces. The stiffness of these cylinders was evaluated by examining their planar texture and its defects.
Knockout-Transgenic Mouse Model of Sickle Cell Disease
Authors: Ryan T. M. , Ciavatta D. J. , Townes T. M.
Published: July 2002

When transgenic mice that expressed human sickle hemoglobin were mated with mice having knockout mutations of the mouse α- and β-globin genes, animals were produced that synthesized only human hemoglobin in adult red blood cells. Similar to many human patients with sickle cell disease, the mice developed a severe hemolytic anemia and extensive organ pathology. Numerous sickled erythrocytes were observed in peripheral blood. Although chronically anemic, most animals survived for 2 to 9 months and were fertile. Drug and genetic therapies can now be tested in this mouse model of sickle cell disease.
Nonsyndromic Deafness DFNA1 Associated with Mutation of a Human Homolog of the
Drosophila
Gene
diaphanous
Authors: Lynch Eric D. , Lee Ming K. , Morrow Jan E. , Welcsh Piri L. , León Pedro E. , King Mary-Claire
Published: July 2002

The gene responsible for autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive hearing loss in a large Costa Rican kindred was previously localized to chromosome 5q31 and named
DFNA1
. Deafness in the family is associated with a protein-truncating mutation in a human homolog of the
Drosophila
gene
diaphanous
. The truncation is caused by a single nucleotide substitution in a splice donor, leading to a four–base pair insertion in messenger RNA and a frameshift. The diaphanous protein is a profilin ligand and target of Rho that regulates polymerization of actin, the major component of the cytoskeleton of hair cells of the inner ear.
Crystal Structure of Methyl-Coenzyme M Reductase: The Key Enzyme of Biological Methane Formation
Authors: Ermler Ulrich , Grabarse Wolfgang , Shima Seigo , Goubeaud Marcel , Thauer Rudolf K.
Published: July 2002

Methyl–coenzyme M reductase (MCR), the enzyme responsible for the microbial formation of methane, is a 300-kilodalton protein organized as a hexamer in an α
2
β
2
γ
2
arrangement. The crystal structure of the enzyme from
Methanobacterium thermoautotrophicum
, determined at 1.45 angstrom resolution for the inactive enzyme state MCR
ox1-silent
, reveals that two molecules of the nickel porphinoid coenzyme F
430
are embedded between the subunits α, α′, β, and γ and α′, α, β′, and γ′, forming two identical active sites. Each site is accessible for the substrate methyl–coenzyme M through a narrow channel locked after binding of the second substrate coenzyme B. Together with a second structurally characterized enzyme state (MCR
silent
) containing the heterodisulfide of coenzymes M and B, a reaction mechanism is proposed that uses a radical intermediate and a nickel organic compound.
CD1d-Restricted and TCR-Mediated Activation of V
α
14 NKT Cells by Glycosylceramides
Authors: Kawano Tetsu , Cui Junqing , Koezuka Yasuhiko , Toura Isao , Kaneko Yoshikatsu , Motoki Kazuhiro , Ueno Hitomi , Nakagawa Ryusuke , Sato Hiroshi , Kondo Eisuke , Koseki Haruhiko , Taniguchi Masaru
Published: July 2002

Natural killer T (NKT) lymphocytes express an invariant T cell antigen receptor (TCR) encoded by the V
α
14 and J
α
281 gene segments. A glycosylceramide-containing α-anomeric sugar with a longer fatty acyl chain (C
26
) and sphingosine base (C
18
) was identified as a ligand for this TCR. Glycosylceramide-mediated proliferative responses of V
α
14 NKT cells were abrogated by treatment with chloroquine–concanamycin A or by monoclonal antibodies against CD1d/V
β
8, CD40/CD40L, or B7/CTLA-4/CD28, but not by interference with the function of a transporter-associated protein. Thus, this lymphocyte shares distinct recognition systems with either T or NK cells.
Mechanism of Transcription Through the Nucleosome by Eukaryotic RNA Polymerase
Authors: Studitsky Vasily M. , Kassavetis George A. , Geiduschek E. Peter , Felsenfeld Gary
Published: July 2002

Nucleosomes, the nucleohistone subunits of chromatin, are present on transcribed eukaryotic genes but do not prevent transcription. It is shown here that the large yeast RNA polymerase III transcribes through a single nucleosome. This takes place through a direct internal nucleosome transfer in which histones never leave the DNA template. During this process, the polymerase pauses with a pronounced periodicity of 10 to 11 base pairs, which is consistent with restricted rotation in the DNA loop formed during transfer. Transcription through nucleosomes by the eukaryotic enzyme and by much smaller prokaryotic RNA polymerases thus shares many features, reflecting an important property of nucleosomes.
Chemokines and the Arrest of Lymphocytes Rolling Under Flow Conditions
Authors: Campbell James J. , Hedrick Joseph , Zlotnik Albert , Siani Michael A. , Thompson Darren A. , Butcher Eugene C.
Published: July 2002

Circulating lymphocytes are recruited from the blood to the tissue by rolling along the endothelium until being stopped by a signaling event linked to the G
i
α subunit of a heterotrimeric GTP-binding protein; that event then triggers rapid integrin-dependent adhesion. Four chemokines are now shown to induce such adhesion to intercellular adhesion molecule–1 and to induce arrest of rolling cells within 1 second under flow conditions similar to those of blood. SDF-1 (also called PBSF), 6-C-kine (also called Exodus-2), and MIP-3β (also called ELC or Exodus-3) induced adhesion of most circulating lymphocytes, including most CD4
+
T cells; and MIP-3α (also called LARC or Exodus-1) triggered adhesion of memory, but not naı̈ve, CD4
+
T cells. Thus, chemokines can regulate the arrest of lymphocyte subsets under flowing conditions, which may allow them to control lymphocyte–endothelial cell recognition and lymphocyte recruitment in vivo.
Rare Gas Systematics in Popping Rock: Isotopic and Elemental Compositions in the Upper Mantle
Authors: Moreira Manuel , Kunz Joachim , Allègre Claude
Published: July 2002

New experimental data on the isotopic variations of neon, argon, and xenon in a popping rock imply that the
40
Ar/
36
Ar ratio of the upper mantle is less than 44,000 and that the
129
Xe/
130
Xe ratio is less than 8.2. The elemental abundance pattern of rare gases is chondritic-like and is quite distinct from the solar pattern. These data imply that Earth accreted from planetesimals that probably underwent a transformation of their rare gas budget from solar- to chondritic-like, leaving the isotopic composition unchanged from the solar pattern.
Melatonin Production: Proteasomal Proteolysis in Serotonin
N
-Acetyltransferase Regulation
Authors: Gastel Jonathan A. , Roseboom Patrick H. , Rinaldi Peter A. , Weller Joan L. , Klein David C.
Published: July 2002

The nocturnal increase in circulating melatonin in vertebrates is regulated by 10- to 100-fold increases in pineal serotonin
N
-acetyltransferase (AA-NAT) activity. Changes in the amount of AA-NAT protein were shown to parallel changes in AA-NAT activity. When neural stimulation was switched off by either light exposure or
l
-propranolol–induced β-adrenergic blockade, both AA-NAT activity and protein decreased rapidly. Effects of
l
-propranolol were blocked in vitro by dibutyryl adenosine 3′,5′-monophosphate (cAMP) or inhibitors of proteasomal proteolysis. This result indicates that adrenergic-cAMP regulation of AA-NAT is mediated by rapid reversible control of selective proteasomal proteolysis. Similar proteasome-based mechanisms may function widely as selective molecular switches in vertebrate neural systems.
Early Views of the Martian Surface from the Mars Orbiter Camera of Mars Global Surveyor
Authors: Malin M. C. , Carr M. H. , Danielson G. E. , Davies M. E. , Hartmann W. K. , Ingersoll A. P. , James P. B. , Masursky H. , McEwen A. S. , Soderblom L. A. , Thomas P. , Veverka J. , Caplinger M. A. , Ravine M. A. , Soulanille T. A. , Warren J. L.
Published: July 2002

High-resolution images of the martian surface at scales of a few meters show ubiquitous erosional and depositional eolian landforms. Dunes, sandsheets, and drifts are prevalent and exhibit a range of morphology, composition (inferred from albedo), and age (as seen in occurrences of different dune orientations at the same location). Steep walls of topographic depressions such as canyons, valleys, and impact craters show the martian crust to be stratified at scales of a few tens of meters. The south polar layered terrain and superposed permanent ice cap display diverse surface textures that may reflect the complex interplay of volatile and non-volatile components. Low resolution regional views of the planet provide synoptic observations of polar cap retreat, condensate clouds, and the lifecycle of local and regional dust storms.
Electron Transfer: Classical Approaches and New Frontiers
Authors: Tributsch Helmut , Pohlmann Ludwig
Published: July 2002

Electron transfer, under conditions of weak interaction and a medium acting as a passive thermal bath, is very well understood. When electron transfer is accompanied by transient chemical bonding, such as in interfacial coordination electrochemical mechanisms, strong interaction and molecular selectivity are involved. These mechanisms, which take advantage of “passive self-organization,” cannot yet be properly described theoretically, but they show substantial experimental promise for energy conversion and catalysis. The biggest challenge for the future, however, may be dynamic, self-organized electron transfer. As with other energy fluxes, a suitable positive feedback mechanism, through an active molecular environment, can lead to a (transient) decrease of entropy equivalent to an increase of molecular electronic order for the activated complex. A resulting substantial increase in the rate of electron transfer and the possibility of cooperative transfer of several electrons (without intermediates) can be deduced from phenomenological theory. The need to extend our present knowledge may be derived from the observation that chemical syntheses and fuel utilization in industry typically require high temperatures (where catalysis is less relevant), whereas corresponding processes in biological systems are catalyzed at environmental conditions. This article therefore focuses on interfacial or membrane-bound electron transfer and investigates an aspect that nature has developed to a high degree of perfection: self-organization.
Arabidopsis CBF1
Overexpression Induces
COR
Genes and Enhances Freezing Tolerance
Authors: Jaglo-Ottosen Kirsten R. , Gilmour Sarah J. , Zarka Daniel G. , Schabenberger Oliver , Thomashow Michael F.
Published: July 2002

Many plants, including
Arabidopsis
, show increased resistance to freezing after they have been exposed to low nonfreezing temperatures. This response, termed cold acclimation, is associated with the induction of
COR
(cold-regulated) genes mediated by the C-repeat/drought-responsive element (CRT/DRE) DNA regulatory element. Increased expression of
Arabidopsis
CBF1, a transcriptional activator that binds to the CRT/DRE sequence, induced
COR
gene expression and increased the freezing tolerance of nonacclimated
Arabidopsis
plants. We conclude that CBF1 is a likely regulator of the cold acclimation response, controlling the level of
COR
gene expression, which in turn promotes tolerance to freezing.
Visual Input to the Efferent Control System of a Fly's "Gyroscope"
Authors: Chan Wai Pang , Prete Frederick , Dickinson Michael H.
Published: July 2002

Dipterous insects (the true flies) have a sophisticated pair of equilibrium organs called halteres that evolved from hind wings. The halteres are sensitive to Coriolis forces that result from angular rotations of the body and mediate corrective reflexes during flight. Like the aerodynamically functional fore wings, the halteres beat during flight and are equipped with their own set of control muscles. It is shown that motoneurons innervating muscles of the haltere receive strong excitatory input from directionally sensitive visual interneurons. Visually guided flight maneuvers of flies may be mediated in part by efferent modulation of hard-wired equilibrium reflexes.
Is GRO J1744-28 a Strange Star?
Authors: Cheng K. S. , Dai Z. G. , Wei D. M. , Lu T.
Published: July 2002

The unusual hard x-ray burster GRO J1744-28 recently discovered by the Compton Gamma-Ray Observatory can be modeled as a strange star with a dipolar magnetic field of ≤10
11
gauss. According to this model, when the accreted mass of the star exceeds some critical mass, its crust breaks, resulting in the conversion of the accreted matter into strange matter and a release of energy. Subsequently, a fireball forms and expands relativistically outward. The expanding fireball interacts with the surrounding interstellar medium, causing its kinetic energy to be radiated in shock waves and producing a burst of x-ray radiation. The burst energy, duration, interval, and spectrum derived from such a model are consistent with the observations of GRO J1744-28.
Formation of a Preinitiation Complex by S-phase Cyclin CDK-Dependent Loading of Cdc45p onto Chromatin
Authors: Zou Lee , Stillman Bruce
Published: July 2002

Cdc45p, a protein essential for initiation of DNA replication, associates with chromatin after “start” in late G
1
and during the S phase of the cell cycle. Binding of Cdc45p to chromatin depends on Clb-Cdc28 kinase activity as well as functional Cdc6p and Mcm2p, which suggests that Cdc45p associates with the prereplication complex after activation of S-phase cyclin-dependent kinases (CDKs). As indicated by the timing and the CDK dependence, binding of Cdc45p to chromatin is crucial for commitment to initiation of DNA replication. During S phase, Cdc45p physically interacts with minichromosome maintenance (MCM) proteins on chromatin; however, dissociation of Cdc45p from chromatin is slower than that of MCMs, which indicates that the proteins are released by different mechanisms.
Functional Interaction of an Axin Homolog, Conductin, with β-Catenin, APC, and GSK3β
Authors: Behrens Jürgen , Jerchow Boris-Alexander , Würtele Martin , Grimm Jan , Asbrand Christian , Wirtz Ralph , Kühl Michael , Wedlich Doris , Birchmeier Walter
Published: July 2002

Control of stability of β-catenin is central in the wnt signaling pathway. Here, the protein conductin was found to form a complex with both β-catenin and the tumor suppressor gene product adenomatous polyposis coli (APC). Conductin induced β-catenin degradation, whereas mutants of conductin that were deficient in complex formation stabilized β-catenin. Fragments of APC that contained a conductin-binding domain also blocked β-catenin degradation. Thus, conductin is a component of the multiprotein complex that directs β-catenin to degradation and is located downstream of APC. In
Xenopus
embryos, conductin interfered with wnt-induced axis formation.
Knowing Where and Getting There: A Human Navigation Network
Authors: Maguire Eleanor A. , Burgess Neil , Donnett James G. , Frackowiak Richard S. J. , Frith Christopher D. , O'Keefe John
Published: July 2002

The neural basis of navigation by humans was investigated with functional neuroimaging of brain activity during navigation in a familiar, yet complex virtual reality town. Activation of the right hippocampus was strongly associated with knowing accurately where places were located and navigating accurately between them. Getting to those places quickly was strongly associated with activation of the right caudate nucleus. These two right-side brain structures function in the context of associated activity in right inferior parietal and bilateral medial parietal regions that support egocentric movement through the virtual town, and activity in other left-side regions (hippocampus, frontal cortex) probably involved in nonspatial aspects of navigation. These findings outline a network of brain areas that support navigation in humans and link the functions of these regions to physiological observations in other mammals.
A Calcium Sensor Homolog Required for Plant Salt Tolerance
Authors: Liu Jiping , Zhu Jian-Kang
Published: July 2002

Excessive sodium (Na
+
) in salinized soils inhibits plant growth and development. A mutation in the
SOS3
gene renders
Arabidopsis thaliana
plants hypersensitive to Na
+
-induced growth inhibition.
SOS3
encodes a protein that shares significant sequence similarity with the calcineurin B subunit from yeast and neuronal calcium sensors from animals. The results suggest that intracellular calcium signaling through a calcineurin-like pathway mediates the beneficial effect of calcium on plant salt tolerance.
Biogeochemical Controls and Feedbacks on Ocean Primary Production
Authors: Falkowski Paul G. , Barber Richard T. , Smetacek Victor
Published: July 2002

Changes in oceanic primary production, linked to changes in the network of global biogeochemical cycles, have profoundly influenced the geochemistry of Earth for over 3 billion years. In the contemporary ocean, photosynthetic carbon fixation by marine phytoplankton leads to formation of ∼45 gigatons of organic carbon per annum, of which 16 gigatons are exported to the ocean interior. Changes in the magnitude of total and export production can strongly influence atmospheric CO
2
levels (and hence climate) on geological time scales, as well as set upper bounds for sustainable fisheries harvest. The two fluxes are critically dependent on geophysical processes that determine mixed-layer depth, nutrient fluxes to and within the ocean, and food-web structure. Because the average turnover time of phytoplankton carbon in the ocean is on the order of a week or less, total and export production are extremely sensitive to external forcing and consequently are seldom in steady state. Elucidating the biogeochemical controls and feedbacks on primary production is essential to understanding how oceanic biota responded to and affected natural climatic variability in the geological past, and will respond to anthropogenically influenced changes in coming decades. One of the most crucial feedbacks results from changes in radiative forcing on the hydrological cycle, which influences the aeolian iron flux and, in turn, affects nitrogen fixation and primary production in the oceans.
Reversible Hydrogels from Self-Assembling Artificial Proteins
Authors: Petka Wendy A. , Harden James L. , McGrath Kevin P. , Wirtz Denis , Tirrell David A.
Published: July 2002

Recombinant DNA methods were used to create artificial proteins that undergo reversible gelation in response to changes in pH or temperature. The proteins consist of terminal leucine zipper domains flanking a central, flexible, water-soluble polyelectrolyte segment. Formation of coiled-coil aggregates of the terminal domains in near-neutral aqueous solutions triggers formation of a three-dimensional polymer network, with the polyelectrolyte segment retaining solvent and preventing precipitation of the chain. Dissociation of the coiled-coil aggregates through elevation of pH or temperature causes dissolution of the gel and a return to the viscous behavior that is characteristic of polymer solutions. The mild conditions under which gel formation can be controlled (near-neutral pH and near-ambient temperature) suggest that these materials have potential in bioengineering applications requiring encapsulation or controlled release of molecular and cellular species.
Feedback Inhibition of Macrophage Tumor Necrosis Factor-α Production by Tristetraprolin
Authors: Carballo Ester , Lai Wi S. , Blackshear Perry J.
Published: July 2002

Tumor necrosis factor–α (TNF-α) is a major mediator of both acute and chronic inflammatory responses in many diseases. Tristetraprolin (TTP), the prototype of a class of Cys-Cys-Cys-His (CCCH) zinc finger proteins, inhibited TNF-α production from macrophages by destabilizing its messenger RNA. This effect appeared to result from direct TTP binding to the AU-rich element of the TNF-α messenger RNA. TTP is a cytosolic protein in these cells, and its biosynthesis was induced by the same agents that stimulate TNF-α production, including TNF-α itself. These findings identify TTP as a component of a negative feedback loop that interferes with TNF-α production by destabilizing its messenger RNA. This pathway represents a potential target for anti–TNF-α therapies.
Tetravalent Uranium in Calcite
Authors: Sturchio N. C. , Antonio M. R. , Soderholm L. , Sutton S. R. , Brannon J. C.
Published: July 2002

X-ray absorption spectroscopy and x-ray fluorescence microprobe studies of 35-million-year-old calcite from a Mississippi Valley–type zinc ore deposit indicate substitution of tetravalent uranium for divalent calcium. Thus, tetravalent uranium has a stable location in calcite deposited under reducing conditions. This result validates uranium-series dating methods (including uranium/lead dating) for ancient calcite and shows that calcite provides a sink for uranium in deep groundwater aquifers and anoxic lacustrine and marine basins.