bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal Gene Expression in the Waking State: A Role for the Locus Coeruleus
Authors: Cirelli Chiara , Pompeiano Maria , Tononi Giulio
Published: July 2002

Several transcription factors are expressed at higher levels in the waking than in the sleeping brain. In experiments with rats, the locus coeruleus, a noradrenergic nucleus with diffuse projections, was found to regulate such expression. In brain regions depleted of noradrenergic innervation, amounts of c-Fos and nerve growth factor-induced A after waking were as low as after sleep. Phosphorylation of cyclic adenosine monophosphate response element-binding protein was also reduced. In contrast, electroencephalographic activity was unchanged. The reduced activity of locus coeruleus neurons may explain why the induction of certain transcription factors, with potential effects on plasticity and learning, does not occur during sleep.
Scientists With Clout
Authors: Balter Michael
Published: July 2002

London and Manchester, U.K.—Britain's Wellcome Trust is a funding agency run by researchers. It made a killing on the stock market and is now the world's wealthiest biomedical research charity. Its annual grant total nearly eclipses the U.K. government's own biomedical funding agency, and this powerful position is making the country's funding scene increasingly complex.
Mechanism of the Zonal Displacements of the Pacific Warm Pool: Implications for ENSO
Authors: Picaut J. , Ioualalen M. , Menkes C. , Delcroix T. , McPhaden M. J.
Published: July 2002

The western equatorial Pacific warm pool is subject to strong east-west migrations on interannual time scales in phase with the Southern Oscillation Index. The dominance of surface zonal advection in this migration is demonstrated with four different current data sets and three ocean models. The eastward advection of warm and less saline water from the western Pacific together with the westward advection of cold and more saline water from the central-eastern Pacific induces a convergence of water masses at the eastern edge of the warm pool and a well-defined salinity front. The location of this convergence is zonally displaced in association with El Niño-La Niña wind-driven surface current variations. These advective processes and water-mass convergences have significant implications for understanding and simulating coupled ocean-atmosphere interactions associated with El Niño-Southern Oscillation (ENSO).
Stabilizing Lead-Salt Diode Lasers: Understanding and Controlling Chaotic Frequency Emission
Authors: Chin Gordon , Senesac Larry R. , Blass William E. , Hillman John J.
Published: July 2002

Lead-salt tunable diode lasers (TDLs) are the only devices currently available that can generate tunable monochromatic radiation at arbitrary wavelengths between 3 and 30 micrometers and are particularly useful for high-resolution spectroscopy over a wide range of spectral regimes. Detailed observations of TDLs show that the observed instrumental linewidth is actually a temporal average of many narrow (less than 0.5 megahertz) emission “modes.” The time scale characteristic of these “modes,” which appear to be of relatively constant intensity, is of the order of a microsecond. The laser's behavior is highly suggestive of a chaotic process, that is, seemingly random excursions of a dynamic variable (frequency) within a bounded range. This report shows experimentally that TDL emissions are indeed chaotic. Furthermore, in a simple and robust fashion, this chaotic behavior has been successfully controlled with the use of recent techniques that take advantage of chaos to produce a narrow band laser output.
Essential Yeast Protein with Unexpected Similarity to Subunits of Mammalian Cleavage and Polyadenylation Specificity Factor (CPSF)
Authors: Chanfreau Guillaume , Noble Suzanne M. , Guthrie Christine
Published: July 2002

The 3′ ends of most eukaryotic messenger RNAs are generated by internal cleavage and polyadenylation. In mammals, there is a strict dependence of both reactions on the sequence AAUAAA, which occurs upstream of polyadenylation [poly(A)] sites and which is recognized by CPSF. In contrast, cis-acting signals for yeast 3′-end generation are highly divergent from those of mammals, suggesting that trans-acting factors other than poly(A) polymerase would not be conserved. The essential yeast protein Brr5/Ysh1 shows sequence similarity to subunits of mammalian CPSF and is required for 3′-end processing in vivo and in vitro. These results demonstrate a structural and functional conservation of the yeast and mammalian 3′-end processing machineries despite a lack of conservation of the cis sequences.
CRNF, a Molluscan Neurotrophic Factor That Interacts with the p75 Neurotrophin Receptor
Authors: Fainzilber M. , Smit A. B. , Syed N. I. , Wildering W. C. , Hermann P. M. , van der Schors R. C. , Jiménez C. , Li K. W. , van Minnen J. , Bulloch A. G. M. , Ibáñez C. F. , Geraerts W. P. M.
Published: July 2002

A 13.1-kilodalton protein, cysteine-rich neurotrophic factor (CRNF), was purified from the mollusk
Lymnaea stagnalis
by use of a binding assay on the p75 neurotrophin receptor. CRNF bound to p75 with nanomolar affinity but was not similar in sequence to neurotrophins or any other known gene product. CRNF messenger RNA expression was highest in adult foot subepithelial cells; in the central nervous system, expression was regulated by lesion. The factor evoked neurite outgrowth and modulated calcium currents in pedal motor neurons. Thus, CRNF may be involved in target-derived trophic support for motor neurons and could represent the prototype of another family of p75 ligands.
T Cell Telomere Length in HIV-1 Infection: No Evidence for Increased CD4
+
T Cell Turnover
Authors: Wolthers Katja C. , Bea G. , Wisman A. , Otto Sigrid A. , de Roda Husman Ana-Maria , Schaft Niels , de Wolf Frank , Goudsmit Jaap , Coutinho Roel A. , van der Zee Ate G. J. , Meyaard Linde , Miedema Frank
Published: July 2002

Progression to acquired immunodeficiency syndrome (AIDS) has been related to exhaustion of the regenerative capacity of the immune system resulting from high T cell turnover. Analysis of telomeric terminal restriction fragment (TRF) length, a marker for cellular replicative history, showed that CD8
+
T cell TRF length decreased but CD4
+
T cell TRF length was stable during the course of human immunodeficiency virus type-1 (HIV-1) infection, which was not explained by differential telomerase activity. This observation provides evidence that turnover in the course of HIV-1 infection can be increased considerably in CD8
+
T cells, but not in CD4
+
T cells. These results are compatible with CD4
+
T cell decline in HIV-1 infection caused by interference with cell renewal.
Molecular Biology: Promiscuous Chromosomal Proteins: Complexes About Sex
Authors: Kuroda Mitzi I. , Villeneuve Anne M.
Published: July 2002

In the phenomenon of dosage compensation, the expression of genes from the entire X chromosome is adjusted to be equivalent between the two sexes. This is necessary because one sex usually has two X chromosomes, while the other has only one. In the Perspective, Kuroda and Villeneuve explain the findings in two reports in this issue of
Science
from Meyer and co-workers (
p. 1732
and
p. 1736
), in which subunits of a protein complex critical for dosage compensation are shown to be also used in the process of chromosome segregation during meiosis, suggesting that both occur by the regulated condensation of chromosomes.
Gibbons Warns of Decline in R&D
Authors: Lawler Andrew
Published: July 2002

This year's budget message from the White House to science agencies, delivered just before Thanksgiving, was a real turkey: Expect less in the 1998 fiscal year, which begins next October, than Congress appropriated this year. And the future holds more of the same, says Science Adviser Jack Gibbons.
Crossing the Hydrophobic Barrier--Insertion of Membrane Proteins
Authors: Engelman Donald M.
Published: July 2002

In this issue of
Science
, Song
et al
. (
p. 1859
) provide the first high-resolution x-ray view of a transmembrane protein that spontaneously inserts into the lipid bilayer. In his Perspective, Engelman discusses what these results mean for our understanding of protein insertion into membranes.
Plasticity of a Different Feather?
Authors: Doupe Allison J.
Published: July 2002

Neurons in the brains of birds change their responses as the birds hear a birdsong over and over again. This “learning” persists and is then forgotten, but in a surprising report by Chew
et al
. (
p. 1909
) in this week's issue of
Science
, it is shown to disappear not in a gradual way over time but in a series of quantized steps. In her Perspective, Doupe comments on the implications of this result.
Requirement of CDC42 for
Salmonella
-Induced Cytoskeletal and Nuclear Responses
Authors: Chen Li-Mei , Hobbie Silke , Galán Jorge E.
Published: July 2002

The bacterial pathogen
Salmonella typhimurium
triggers host cell signaling pathways that lead to cytoskeletal and nuclear responses required for pathogenesis. Here, the role of the small guanosine triphosphate (GTP)-binding protein CDC42Hs in these responses was examined. Expression of a dominant interfering mutant of CDC42 (CDC42HsN17) prevented
S. typhimurium
-induced cytoskeletal reorganization and subsequent macropinocytosis and bacterial internalization into host cells. Cells expressing constitutively active CDC42 (CDC42HsV12) internalized an
S. typhimurium
mutant unable to trigger host cell responses. Furthermore, expression of CDC42HsN17 prevented
S. typhimurium
-induced JNK kinase activation. These results indicate that CDC42 is required for bacterial invasion and induction of nuclear responses in host cells.
Microscopic Growth Mechanisms for Carbon Nanotubes
Authors: Charlier Jean-Christophe , De Vita Alessandro , Blase Xavier , Car Roberto
Published: July 2002

The uncatalyzed edge growth of carbon nanotubes was investigated by first-principles molecular dynamics simulations. At experimental temperatures the open end of single-walled nanotubes closed spontaneously into a graphitic dome, which may explain why these nanotubes do not grow in the absence of transition metal catalysts. On the other hand, chemical bonding between the edges of adjacent coaxial tubes (“lip-lip” interactions) trapped the end of a double-walled nanotube in a metastable energy minimum, thus preventing dome closure. These calculations show that this end geometry exhibits a high degree of chemical activity and easily accommodates incoming carbon fragments, supporting a model of growth by chemisorption from the vapor phase.
The Spectrum of Comet Hale-Bopp (C/1995 O1) Observed with the Infrared Space Observatory at 2.9 Astronomical Units from the Sun
Authors: Crovisier Jacques , Leech Kieron , Bockelée-Morvan Dominique , Brooke Timothy Y. , Hanner Martha S. , Altieri Bruno , Keller H. Uwe , Lellouch Emmanuel
Published: July 2002

Comet Hale-Bopp (C/1995 O1) was observed at wavelengths from 2.4 to 195 micrometers with the Infrared Space Observatory when the comet was about 2.9 astronomical units (AU) from the sun. The main observed volatiles that sublimated from the nucleus ices were water, carbon monoxide, and carbon dioxide in a ratio (by number) of 10:6:2. These species are also the main observed constituents of ices in dense interstellar molecular clouds; this observation strengthens the links between cometary and interstellar material. Several broad emission features observed in the 7- to 45-micrometer region suggest the presence of silicates, particularly magnesium-rich crystalline olivine. These features are similar to those observed in the dust envelopes of Vega-type stars.
Consumption: Challenge to Sustainable Development …
Authors: Myers Norman
Published: July 2002

Consumption cannot persist in its present patterns and forms. This is apparent with respect to, for example, the many consumer products dependent on artificially cheap fossil-fuel energy, which is the single largest source of global warming. There are many ways to shift consumption toward less resource-intensive and polluting types, hence to constrain it rather than restrain it. Moreover, this will often lead to increased quality of life. The way ahead can be illuminated by a clearer scientific understanding of what drives consumption.
Repression of c-
myc
Transcription by Blimp-1, an Inducer of Terminal B Cell Differentiation
Authors: Lin Yi , Wong Kwok-kin , Calame Kathryn
Published: July 2002

Transcription of c-
myc
in plasma cells, which are terminally differentiated B cells, is repressed by plasmacytoma repressor factor. This factor was identified as Blimp-1, known for its ability to induce B cell differentiation. Blimp-1 repressed c-
myc
promoter activity in a binding site–dependent manner. Treatment of BCL
1
lymphoma cells with interleukin-2 (IL-2) plus IL-5 induced Blimp-1 and caused a subsequent decline in c-Myc protein. Ectopic expression of Blimp-1 in Abelson-transformed precursor B cells repressed endogenous c-Myc and caused apoptosis; Blimp-1–induced death was partially overcome by ectopic expression of c-Myc. Thus, repression of c-
myc
is a component of the Blimp-1 program of terminal B cell differentiation.
Prevention of Mucosal
Escherichia coli
Infection by FimH-Adhesin-Based Systemic Vaccination
Authors: Langermann Solomon , Palaszynski Susan , Barnhart Michelle , Auguste Gale , Pinkner Jerome S. , Burlein Jeanne , Barren Philip , Koenig Scott , Leath Simon , Jones C. Hal , Hultgren Scott J.
Published: July 2002

Virtually all uropathogenic strains of
Escherichia coli
, the primary cause of cystitis, assemble adhesive surface organelles called type 1 pili that contain the FimH adhesin. Sera from animals vaccinated with candidate FimH vaccines inhibited uropathogenic
E. coli
from binding to human bladder cells in vitro. Immunization with FimH reduced in vivo colonization of the bladder mucosa by more than 99 percent in a murine cystitis model, and immunoglobulin G to FimH was detected in urinary samples from protected mice. Furthermore, passive systemic administration of immune sera to FimH also resulted in reduced bladder colonization by uropathogenic
E. coli
. This approach may represent a means of preventing recurrent and acute infections of the urogenital mucosa.
Protein Localization and Cell Fate in Bacteria
Authors: Shapiro Lucy , Losick Richard
Published: July 2002

A major breakthrough in understanding the bacterial cell is the discovery that the cell is highly organized at the level of protein localization. Proteins are positioned at particular sites in bacteria, including the cell pole, the incipient division plane, and the septum. Differential protein localization can control DNA replication, chromosome segregation, and cytokinesis and is responsible for generating daughter cells with different fates upon cell division. Recent discoveries have revealed that progression through the cell cycle and communication between cellular compartments are mediated by two-component signal transduction systems and signaling pathways involving transcription factor activation by proteolytic processing. Asymmetric cell division in
Caulobacter crescentus
and sporulation in
Bacillus subtilis
are used as paradigms for the control of the cell cycle and cellular morphogenesis in bacterial cells.
Signaling in Plant-Microbe Interactions
Authors: Baker Barbara , Zambryski Patricia , Staskawicz Brian , Dinesh-Kumar S. P.
Published: July 2002

Analysis of viral and bacterial pathogenesis has revealed common themes in the ways in which plants and animals respond to pathogenic agents. Pathogenic bacteria use macromolecule delivery systems (types III and IV) to deliver microbial avirulence proteins and transfer DNA-protein complexes directly into plant cells. The molecular events that constitute critical steps of plant-pathogen interactions seem to involve ligand-receptor mechanisms for pathogen recognition and the induction of signal transduction pathways in the plant that lead to defense responses. Unraveling the molecular basis of disease resistance pathways has laid a foundation for the rational design of crop protection strategies.
Folding-Unfolding Transitions in Single Titin Molecules Characterized with Laser Tweezers
Authors: Kellermayer Miklós S. Z. , Smith Steven B. , Granzier Henk L. , Bustamante Carlos
Published: July 2002

Titin, a giant filamentous polypeptide, is believed to play a fundamental role in maintaining sarcomeric structural integrity and developing what is known as passive force in muscle. Measurements of the force required to stretch a single molecule revealed that titin behaves as a highly nonlinear entropic spring. The molecule unfolds in a high-force transition beginning at 20 to 30 piconewtons and refolds in a low-force transition at ∼2.5 piconewtons. A fraction of the molecule (5 to 40 percent) remains permanently unfolded, behaving as a wormlike chain with a persistence length (a measure of the chain’s bending rigidity) of 20 angstroms. Force hysteresis arises from a difference between the unfolding and refolding kinetics of the molecule relative to the stretch and release rates in the experiments, respectively. Scaling the molecular data up to sarcomeric dimensions reproduced many features of the passive force versus extension curve of muscle fibers.
Cellular Differentiation Regulated by Gibberellin in the
Arabidopsis thaliana pickle
Mutant
Authors: Ogas Joe , Cheng Jin-Chen , Sung Z. Renee , Somerville Chris
Published: July 2002

The plant growth regulator gibberellin (GA) has a profound effect on shoot development and promotes developmental transitions such as flowering. Little is known about any analogous effect GA might have on root development. In a screen for mutants,
Arabidopsis
plants carrying a mutation designated
pickle
(
pkl
) were isolated in which the primary root meristem retained characteristics of embryonic tissue. Expression of this aberrant differentiation state was suppressed by GA. Root tissue from plants carrying the
pkl
mutation spontaneously regenerated new embryos and plants.
Functional Genomics: It's All How You Read It
Authors: Hieter Philip , Boguski Mark
Published: July 2002

Hieter and Boguski describe the new era of functional genomics that is being entered as the mapping and sequencing (structural genomics) phase of the Human Genome Project draws to a close. Functional genomics involves the development of global experimental approaches for analyzing gene function by utilizing information and reagents provided by structural genomics. Functional genomic data needs to be generated by rigorous experiments to allow a fair evaluation of the emerging technologies. The data should also be made publicly accessible in order for the scientific community to gain maximum benefit.
Enhanced Intergrain Tunneling Magnetoresistance in Half-Metallic CrO
2
Films
Authors: Hwang H. Y. , Cheong S.-W.
Published: July 2002

Low-field tunneling magnetoresistance was observed in films of half-metallic CrO
2
that were grown by high-pressure thermal decomposition of CrO
3
. High-temperature annealing treatments modified the intergrain barriers of the as-grown films through surface decomposition of CrO
2
into insulating Cr
2
O
3
, which led to a threefold enhancement of the low-field magnetoresistance. This enhancement indicates the potential of this simple method to directly control the interface barrier characteristics that determine the magnetotransport properties.
Crystal Structure of the Catalytic Domains of Adenylyl Cyclase in a Complex with G
sα
·GTPγS
Authors: Tesmer John J. G. , Sunahara Roger K. , Gilman Alfred G. , Sprang Stephen R.
Published: July 2002

The crystal structure of a soluble, catalytically active form of adenylyl cyclase in a complex with its stimulatory heterotrimeric G protein α subunit (G
s
α
) and forskolin was determined to a resolution of 2.3 angstroms. When P-site inhibitors were soaked into native crystals of the complex, the active site of adenylyl cyclase was located and structural elements important for substrate recognition and catalysis were identified. On the basis of these and other structures, a molecular mechanism is proposed for the activation of adenylyl cyclase by G
s
α
.
Alignment of Conduits for the Nascent Polypeptide Chain in the Ribosome-Sec61 Complex
Authors: Beckmann Roland , Bubeck Doryen , Grassucci Robert , Penczek Pawel , Verschoor Adriana , Blobel Günter , Frank Joachim
Published: July 2002

An oligomer of the Sec61 trimeric complex is thought to form the protein-conducting channel for protein transport across the endoplasmic reticulum. A purified yeast Sec61 complex bound to monomeric yeast ribosomes as an oligomer in a saturable fashion. Cryo–electron microscopy of the ribosome-Sec61 complex and a three-dimensional reconstruction showed that the Sec61 oligomer is attached to the large ribosomal subunit by a single connection. Moreover, a funnel-shaped pore in the Sec61 oligomer aligned with the exit of a tunnel traversing the large ribosomal subunit, strongly suggesting that both structures function together in the translocation of proteins across the endoplasmic reticulum membrane.
Modification of the NADH of the Isoniazid Target (InhA) from
Mycobacterium tuberculosis
Authors: Rozwarski Denise A. , Grant Gregory A. , Barton Derek H. R. , Jacobs William R. , Sacchettini James C.
Published: July 2002

The preferred antitubercular drug isoniazid specifically targets a long-chain enoyl-acyl carrier protein reductase (InhA), an enzyme essential for mycolic acid biosynthesis in
Mycobacterium tuberculosis
. Despite the widespread use of this drug for more than 40 years, its precise mode of action has remained obscure. Data from x-ray crystallography and mass spectrometry reveal that the mechanism of isoniazid action against InhA is covalent attachment of the activated form of the drug to the nicotinamide ring of nicotinamide adenine dinucleotide bound within the active site of InhA.
Photonic Channels for Quantum Communication
Authors: van Enk S. J. , Cirac J. I. , Zoller P.
Published: July 2002

A general photonic channel for quantum communication is defined. By means of local quantum computing with a few auxiliary atoms, this channel can be reduced to one with effectively less noise. A scheme based on quantum interference is proposed that iteratively improves the fidelity of distant entangled particles.
Cretaceous Vertical Motion of Australia and the AustralianAntarctic Discordance
Authors: Gurnis Michael , Müller R. Dietmar , Moresi Louis
Published: July 2002

A three-dimensional model of mantle convection in which the known history of plate tectonics is imposed predicts the anomalous Cretaceous vertical motion of Australia and the present-day distinctive geochemistry and geophysics of the Australian-Antarctic Discordance. The dynamic models infer that a subducted slab associated with the long-lived Gondwanaland-Pacific converging margin passed beneath Australia during the Cretaceous, partially stagnated in the mantle transition zone, and is presently being drawn up by the Southeast Indian Ridge.
Evolution of a Transfer RNA Gene Through a Point Mutation in the Anticodon
Authors: Saks Margaret E. , Sampson Jeffrey R. , Abelson John
Published: July 2002

The transfer RNA (tRNA) multigene family comprises 20 amino acid–accepting groups, many of which contain isoacceptors. The addition of isoacceptors to the tRNA repertoire was critical to establishing the genetic code, yet the origin of isoacceptors remains largely unexplored. A model of tRNA evolution, termed “tRNA gene recruitment,” was formulated. It proposes that a tRNA gene can be recruited from one isoaccepting group to another by a point mutation that concurrently changes tRNA amino acid identity and messenger RNA coupling capacity. A test of the model showed that an
Escherichia coli
strain, in which the essential tRNA
UGU
Thr
gene was inactivated, was rendered viable when a tRNA
Arg
with a point mutation that changed its anticodon from UCU to UGU (threonine) was expressed. Insertion of threonine at threonine codons by the “recruited” tRNA
Arg
was corroborated by in vitro aminoacylation assays showing that its specificity had been changed from arginine to threonine. Therefore, the recruitment model may account for the evolution of some tRNA genes.
Gas-Phase Ionic Reactions: Dynamics and Mechanism of Nucleophilic Displacements
Authors: Chabinyc Michael L. , Craig Stephen L. , Regan Colleen K. , Brauman John I.
Published: July 2002

Nucleophilic displacement reactions (the S
N
2 reaction) of ions in the gas phase are a prototypical reaction system that allows a study of dynamics, mechanisms, and structure-energy relations. This article reviews aspects of the kinetics (especially the applicability of statistical reaction rate theory), the relation of structure and reactivity, and the effects of small numbers of solvent molecules on the reaction and compares the behavior of the ionic reaction in the gas phase with that in solution.
X-ray Crystal Structure of C3d: A C3 Fragment and Ligand for Complement Receptor 2
Authors: Nagar Bhushan , Jones Russell G. , Diefenbach Russell J. , Isenman David E. , Rini James M.
Published: July 2002

Activation and covalent attachment of complement component C3 to pathogens is the key step in complement-mediated host defense. Additionally, the antigen-bound C3d fragment interacts with complement receptor 2 (CR2; also known as CD21) on B cells and thereby contributes to the initiation of an acquired humoral response. The x-ray crystal structure of human C3d solved at 2.0 angstroms resolution reveals an α-α barrel with the residues responsible for thioester formation and covalent attachment at one end and an acidic pocket at the other. The structure supports a model whereby the transition of native C3 to its functionally active state involves the disruption of a complementary domain interface and provides insight into the basis for the interaction between C3d and CR2.
Role of the CLOCK Protein in the Mammalian Circadian Mechanism
Authors: Gekakis Nicholas , Staknis David , Nguyen Hubert B. , Davis Fred C. , Wilsbacher Lisa D. , King David P. , Takahashi Joseph S. , Weitz Charles J.
Published: July 2002

The mouse
Clock
gene encodes a bHLH-PAS protein that regulates circadian rhythms and is related to transcription factors that act as heterodimers. Potential partners of CLOCK were isolated in a two-hybrid screen, and one, BMAL1, was coexpressed with CLOCK and PER1 at known circadian clock sites in brain and retina. CLOCK-BMAL1 heterodimers activated transcription from E-box elements, a type of transcription factor–binding site, found adjacent to the mouse
per1
gene and from an identical E-box known to be important for
per
gene expression in
Drosophila.
Mutant CLOCK from the dominant-negative
Clock
allele and BMAL1 formed heterodimers that bound DNA but failed to activate transcription. Thus, CLOCK-BMAL1 heterodimers appear to drive the positive component of
per
transcriptional oscillations, which are thought to underlie circadian rhythmicity.
Ribozyme-Mediated Repair of Sickle β-Globin mRNAs in Erythrocyte Precursors
Authors: Lan Ning , Howrey Richard P. , Lee Seong-Wook , Smith Clayton A. , Sullenger Bruce A.
Published: July 2002

Sickle cell anemia is the most common heritable hematological disease, yet no curative treatment exists for this disorder. Moreover, the intricacies of globin gene expression have made the development of treatments for hemoglobinopathies based on gene therapy difficult. An alternative genetic approach to sickle cell therapy is based on RNA repair. A trans-splicing group I ribozyme was used to alter mutant β-globin transcripts in erythrocyte precursors derived from peripheral blood from individuals with sickle cell disease. Sickle β-globin transcripts were converted into messenger RNAs encoding the anti-sickling protein γ-globin. These results suggest that RNA repair may become a useful approach in the treatment of genetic disorders.
Post-Cambrian Trilobite Diversity and Evolutionary Faunas
Authors: Adrain Jonathan M. , Fortey Richard A. , Westrop Stephen R.
Published: July 2002

A cluster analysis of the stratigraphic distribution of all Ordovician trilobite families, based on a comprehensive taxonomic database, identified two major faunas with disjunct temporal diversity trends. The Ibex Fauna behaved as a cohort, declining through the Ordovician and disappearing at the end-Ordovician mass extinction. In contrast, the Whiterock Fauna radiated rapidly during the Middle Ordovician and gave rise to all post-Ordovician trilobite diversity. Its pattern of diversification matches that of the Paleozoic Evolutionary Fauna; hence, trilobites were active participants in the great Ordovician radiations. Extinction patterns at the end of the Ordovician are related to clade size: Surviving trilobite families show higher genus diversity than extinguished families.
Gold Nanoelectrodes of Varied Size: Transition to Molecule-Like Charging
Authors: Chen Shaowei , Ingram Roychelle S. , Hostetler Michael J. , Pietron Jeremy J. , Murray Royce W. , Schaaff T. Gregory , Khoury Joseph T. , Alvarez Marcos M. , Whetten Robert L.
Published: July 2002

A transition from metal-like double-layer capacitive charging to redox-like charging was observed in electrochemical ensemble Coulomb staircase experiments on solutions of gold nanoparticles of varied core size. The monodisperse gold nanoparticles are stabilized by short-chain alkanethiolate monolayers and have 8 to 38 kilodaltons core mass (1.1 to 1.9 nanometers in diameter). Larger cores display Coulomb staircase responses consistent with double-layer charging of metal-electrolyte interfaces, whereas smaller core nanoparticles exhibit redox chemical character, including a large central gap. The change in behavior is consistent with new near-infrared spectroscopic data showing an emerging gap between the highest occupied and lowest unoccupied orbitals of 0.4 to 0.9 electron volt.
Interaction of Human Arp2/3 Complex and the
Listeria monocytogenes
ActA Protein in Actin Filament Nucleation
Authors: Welch Matthew D. , Rosenblatt Jody , Skoble Justin , Portnoy Daniel A. , Mitchison Timothy J.
Published: July 2002

Actin filament assembly at the cell surface of the pathogenic bacterium
Listeria monocytogenes
requires the bacterial ActA surface protein and the host cell Arp2/3 complex. Purified Arp2/3 complex accelerated the nucleation of actin polymerization in vitro, but pure ActA had no effect. However, when combined, the Arp2/3 complex and ActA synergistically stimulated the nucleation of actin filaments. This mechanism of activating the host Arp2/3 complex at the
L. monocytogenes
surface may be similar to the strategy used by cells to control Arp2/3 complex activity and hence the spatial and temporal distribution of actin polymerization.
A Viral Mechanism for Inhibition of the Cellular Phosphatase Calcineurin
Authors: Miskin James E. , Abrams Charles C. , Goatley Lynnette C. , Dixon Linda K.
Published: July 2002

The transcription factor NFAT (nuclear factor of activated T cells) controls the expression of many immunomodulatory proteins. African swine fever virus inhibits proinflammatory cytokine expression in infected macrophages, and a viral protein A238L was found to display the activity of the immunosuppressive drug cyclosporin A by inhibiting NFAT-regulated gene transcription in vivo. This it does by binding the catalytic subunit of calcineurin and inhibiting calcineurin phosphatase activity.
How Temperature Changes Reset a Circadian Oscillator
Authors: Liu Yi , Merrow Martha , Loros Jennifer J. , Dunlap Jay C.
Published: July 2002

Circadian rhythms control many physiological activities. The environmental entrainment of rhythms involves the immediate responses of clock components. Levels of the clock protein FRQ were measured in
Neurospora
at various temperatures; at higher temperatures, the amount of FRQ oscillated around higher levels. Absolute FRQ amounts thus identified different times at different temperatures, so temperature shifts corresponded to shifts in clock time without immediate synthesis or turnover of components. Moderate temperature changes could dominate light-to-dark shifts in the influence of circadian timing. Temperature regulation of clock components could explain temperature resetting of rhythms and how single transitions can initiate rhythmicity from characteristic circadian phases.
Neural Crest Specification Regulated by the Helix-Loop-Helix Repressor Id2
Authors: Martinsen Brad J. , Bronner-Fraser Marianne
Published: July 2002

Vertebrate neural crest cells, derived from the neural folds, generate a variety of tissues, such as cartilage, ganglia, and cranial (intramembranous) bone. The chick homolog of the helix-loop-helix transcriptional regulator Id2 is expressed in cranial but not trunk neural folds and subsequently in some migrating cranial neural crest cells. Ectopic expression of Id2 with recombinant retroviruses converted ectodermal cells to a neural crest fate, demonstrating that proper regulation of Id2 is important for sustaining epidermal traits. In addition, overexpression of Id2 resulted in overgrowth and premature neurogenesis of the dorsal neural tube. These results suggest that Id2 may allocate ectodermal precursors into neural rather than epidermal lineages.
Quebrada Jaguay: Early South American Maritime Adaptations
Authors: Sandweiss Daniel H. , McInnis Heather , Burger Richard L. , Cano Asunción , Ojeda Bernardino , Paredes Rolando , Sandweiss Marı́a del Carmen , Glascock Michael D.
Published: July 2002

Excavations at Quebrada Jaguay 280 (QJ-280) (16°30′S) in south coastal Peru demonstrated that Paleoindian-age people of the Terminal Pleistocene (about 11,100 to 10,000 carbon-14 years before the present or about 13,000 to 11,000 calibrated years before the present) in South America relied on marine resources while resident on the coast, which extends the South American record of maritime exploitation by a millennium. This site supports recent evidence that Paleoindian-age people had diverse subsistence systems. The presence of obsidian at QJ-280 shows that the inhabitants had contact with the adjacent Andean highlands during the Terminal Pleistocene.
Early Maritime Economy and El Niño Events at Quebrada Tacahuay, Peru
Authors: Keefer David K. , deFrance Susan D. , Moseley Michael E. , Richardson James B. , Satterlee Dennis R. , Day-Lewis Amy
Published: July 2002

The archaeological site of Quebrada Tacahuay, Peru, dates to 12,700 to 12,500 calibrated years before the present (10,770 to 10,530 carbon-14 years before the present). It contains some of the oldest evidence of maritime-based economic activity in the New World. Recovered materials include a hearth, lithic cutting tools and flakes, and abundant processed marine fauna, primarily seabirds and fish. Sediments below and above the occupation layer were probably generated by El Niño events, indicating that El Niño was active during the Pleistocene as well as during the early and middle Holocene.
Regulation of Meiotic S Phase by Ime2 and a Clb5,6-Associated Kinase in
Saccharomyces cerevisiae
Authors: Dirick Léon , Goetsch Loretta , Ammerer Gustav , Byers Breck
Published: July 2002

Cyclin-dependent kinase (Cdk) mutations that prevent entry into the mitotic cell cycle of budding yeast fail to block meiotic DNA replication, suggesting there may be fundamental differences between these pathways. However, S phase in meiosis was found to depend on the same B-type cyclins (Clb5 and Clb6) as it does in mitosis. Meiosis differs instead in the mechanism that controls removal of the Cdk inhibitor Sic1. Destruction of Sic1 and activation of a Clb5-dependent kinase in meiotic cells required the action of the meiosis-specific protein kinase Ime2, thereby coupling early meiotic gene expression to control of DNA replication for meiosis.
The Evolution of Agriculture in Ants
Authors: Mueller Ulrich G. , Rehner Stephen A. , Schultz Ted R.
Published: July 2002

Cultivation of fungi for food by fungus-growing ants (Attini: Formicidae) originated about 50 million years ago. The subsequent evolutionary history of this agricultural symbiosis was inferred from phylogenetic and population-genetic patterns of 553 cultivars isolated from gardens of “primitive” fungus-growing ants. These patterns indicate that fungus-growing ants succeeded at domesticating multiple cultivars, that the ants are capable of switching to novel cultivars, that single ant species farm a diversity of cultivars, and that cultivars are shared occasionally between distantly related ant species, probably by lateral transfer between ant colonies.
A Short Circuit in Thermohaline Circulation: A Cause for Northern Hemisphere Glaciation?
Authors: Driscoll N. W. , Haug G. H.
Published: July 2002

The cause of Northern Hemisphere glaciation about 3 million years ago remains uncertain. Closing the Panamanian Isthmus increased thermohaline circulation and enhanced moisture supply to high latitudes, but the accompanying heat would have inhibited ice growth. One possible solution is that enhanced moisture transported to Eurasia also enhanced freshwater delivery to the Arctic via Siberian rivers. Freshwater input to the Arctic would facilitate sea ice formation, increase the albedo, and isolate the high heat capacity of the ocean from the atmosphere. It would also act as a negative feedback on the efficiency of the “conveyor belt” heat pump.
Strong Enhancement of Nonlinear Optical Properties Through Supramolecular Chirality
Authors: Verbiest Thierry , Elshocht Sven Van , Kauranen Martti , Hellemans Louis , Snauwaert Johan , Nuckolls Colin , Katz Thomas J. , Persoons André
Published: July 2002

A new approach to second-order nonlinear optical (NLO) materials is reported, in which chirality and supramolecular organization play key roles. Langmuir-Blodgett films of a chiral helicene are composed of supramolecular arrays of the molecules. The chiral supramolecular organization makes the second-order NLO susceptibility about 30 times larger for the nonracemic material than for the racemic material with the same chemical structure. The susceptibility of the nonracemic films is a respectable 50 picometers per volt, even though the helicene structure lacks features commonly associated with high nonlinearity. Susceptibility components that are allowed only by chirality dominate the second-order NLO response.
Purification and Cloning of a Protein Kinase That Phosphorylates and Activates the Polo-Like Kinase Plx1
Authors: Qian Yue-Wei , Erikson Eleanor , Maller James L.
Published: July 2002

The
Xenopus
polo-like kinase 1 (Plx1) is essential during mitosis for the activation of Cdc25C, for spindle assembly, and for cyclin B degradation. Polo-like kinases from various organisms are activated by phosphorylation by an unidentified protein kinase. A protein kinase, polo-like kinase kinase 1 or xPlkk1, that phosphorylates and activates Plx1 in vitro was purified to near homogeneity and cloned. Phosphopeptide mapping of Plx1 phosphorylated in vitro by recombinant xPlkk1 or in progesterone-treated oocytes indicates that xPlkk1 may activate Plx1 in vivo. The xPlkk1 protein itself was also activated by phosphorylation on serine and threonine residues, and the kinetics of activation of xPlkk1 in vivo closely paralleled the activation of Plx1. Moreover, microinjection of xPlkk1 into
Xenopus
oocytes accelerated the timing of activation of Plx1 and the transition from G
2
to M phase of the cell cycle. These results define a protein kinase cascade that regulates several events of mitosis.
Impaired B Cell Development and Proliferation in Absence of Phosphoinositide 3-Kinase p85α
Authors: Fruman David A. , Snapper Scott B. , Yballe Claudine M. , Davidson Laurie , Yu Jonathan Y. , Alt Frederick W. , Cantley Lewis C.
Published: July 2002

Phosphoinositide 3-kinase (PI3K) activation has been implicated in many cellular responses, including fibroblast growth, transformation, survival, and chemotaxis. Although PI3K is activated by several agents that stimulate T and B cells, the role of PI3K in lymphocyte function is not clear. The mouse gene encoding the PI3K adapter subunit p85α and its splice variants p55α and p50α was disrupted. Most p85α-p55α-p50α
−/−
mice die within days after birth. Lymphocyte development and function was studied with the use of the RAG2-deficient blastocyst complementation system. Chimeric mice had reduced numbers of peripheral mature B cells and decreased serum immunoglobulin. The B cells that developed had diminished proliferative responses to antibody to immunoglobulin M, antibody to CD40, and lipopolysaccharide stimulation and decreased survival after incubation with interleukin-4. In contrast, T cell development and proliferation was normal. This phenotype is similar to defects observed in mice lacking the tyrosine kinase Btk.
Prevention of Constitutive TNF Receptor 1 Signaling by Silencer of Death Domains
Authors: Jiang Yingping , Woronicz John D. , Liu Wei , Goeddel David V.
Published: July 2002

Tumor necrosis factor receptor type 1 (TNF-R1) contains a cytoplasmic death domain that is required for the signaling of TNF activities such as apoptosis and nuclear factor kappa B (NF-κB) activation. Normally, these signals are generated only after TNF-induced receptor aggregation. However, TNF-R1 self-associates and signals independently of ligand when overexpressed. This apparent paradox may be explained by silencer of death domains (SODD), a widely expressed ∼60-kilodalton protein that was found to be associated with the death domain of TNF-R1. TNF treatment released SODD from TNF-R1, permitting the recruitment of proteins such as TRADD and TRAF2 to the active TNF-R1 signaling complex. SODD also interacted with death receptor–3 (DR3), another member of the TNF receptor superfamily. Thus, SODD association may be representative of a general mechanism for preventing spontaneous signaling by death domain–containing receptors.
Oligomeric Structure of the Human EphB2 Receptor SAM Domain
Authors: Thanos Christopher D. , Goodwill Kenneth E. , Bowie James U.
Published: July 2002

The sterile alpha motif (SAM) domain is a protein interaction module that is present in diverse signal-transducing proteins. SAM domains are known to form homo- and hetero-oligomers. The crystal structure of the SAM domain from an Eph receptor tyrosine kinase, EphB2, reveals two large interfaces. In one interface, adjacent monomers exchange amino-terminal peptides that insert into a hydrophobic groove on each neighbor. A second interface is composed of the carboxyl-terminal helix and a nearby loop. A possible oligomer, constructed from a combination of these binding modes, may provide a platform for the formation of larger protein complexes.
Requirement of Cdk2-Cyclin E Activity for Repeated Centrosome Reproduction in
Xenopus
Egg Extracts
Authors: Hinchcliffe Edward H. , Li Chuan , Thompson Elizabeth A. , Maller James L. , Sluder Greenfield
Published: July 2002

The abnormally high number of centrosomes found in many human tumor cells can lead directly to aneuploidy and genomic instability through the formation of multipolar mitotic spindles. To facilitate investigation of the mechanisms that control centrosome reproduction, a frog egg extract arrested in S phase of the cell cycle that supported repeated assembly of daughter centrosomes was developed. Multiple rounds of centrosome reproduction were blocked by selective inactivation of cyclin-dependent kinase 2–cyclin E (Cdk2-E) and were restored by addition of purified Cdk2-E. Confocal immunomicroscopy revealed that cyclin E was localized at the centrosome. These results demonstrate that Cdk2-E activity is required for centrosome duplication during S phase and suggest a mechanism that could coordinate centrosome reproduction with cycles of DNA synthesis and mitosis.
Supertetrahedral Sulfide Crystals with Giant Cavities and Channels
Authors: Li Hailian , Laine Aaron , O'Keeffe M. , Yaghi O. M.
Published: July 2002

Although aluminosilicates and metal phosphates can form porous open-framework materials such as zeolites, sulfide analogs usually form high-density phases because of the relatively small tetrahedral angle at sulfur atoms. One strategy to overcome this limitation is to use tetrahedral clusters as the building blocks to achieve porous sulfide-based networks. The preparation and crystal structures of two indium sulfide open frameworks (ASU-31 and ASU-32) built of supertetrahedral clusters around organic template and water guests are described. ASU-31, based on the sodalite-tetrahedrite network, contains cavities 25.6 angstroms in diameter, and ASU-32, based on the tetragonal CrB
4
network, contains channels with a minimum diameter of 14.7 angstroms. The organic cations can be completely exchanged with sodium ions in aqueous solution at room temperature without degradation of the crystals.
Three-Dimensional Structure of a Recombinant Gap Junction Membrane Channel
Authors: Unger Vinzenz M. , Kumar Nalin M. , Gilula Norton B. , Yeager Mark
Published: July 2002

Gap junction membrane channels mediate electrical and metabolic coupling between adjacent cells. The structure of a recombinant cardiac gap junction channel was determined by electron crystallography at resolutions of 7.5 angstroms in the membrane plane and 21 angstroms in the vertical direction. The dodecameric channel was formed by the end-to-end docking of two hexamers, each of which displayed 24 rods of density in the membrane interior, which is consistent with an α-helical conformation for the four transmembrane domains of each connexin subunit. The transmembrane α-helical rods contrasted with the double-layered appearance of the extracellular domains. Although not indicative for a particular type of secondary structure, the protein density that formed the extracellular vestibule provided a tight seal to exclude the exchange of substances with the extracellular milieu.
A Glycyl Radical Site in the Crystal Structure of a Class III Ribonucleotide Reductase
Authors: Logan Derek T. , Andersson Jessica , Sjöberg Britt-Marie , Nordlund Pär
Published: July 2002

Ribonucleotide reductases catalyze the reduction of ribonucleotides to deoxyribonucleotides. Three classes have been identified, all using free-radical chemistry but based on different cofactors. Classes I and II have been shown to be evolutionarily related, whereas the origin of anaerobic class III has remained elusive. The structure of a class III enzyme suggests a common origin for the three classes but shows differences in the active site that can be understood on the basis of the radical-initiation system and source of reductive electrons, as well as a unique protein glycyl radical site. A possible evolutionary relationship between early deoxyribonucleotide metabolism and primary anaerobic metabolism is suggested.
BRCA1 Inhibition of Estrogen Receptor Signaling in Transfected Cells
Authors: Fan S. , Wang J.-A. , Yuan R. , Ma Y. , Meng Q. , Erdos M. R. , Pestell R. G. , Yuan Fang , Auborn K. J. , Goldberg I. D. , Rosen E. M.
Published: July 2002

Mutations of the breast cancer susceptibility gene
BRCA1
confer increased risk for breast, ovarian, and prostatic cancers, but it is not clear why the mutations are associated with these particular tumor types. In transient transfection assays,
BRCA1
was found to inhibit signaling by the ligand-activated estrogen receptor (ER-α) through the estrogen-responsive enhancer element and to block the transcriptional activation function AF-2 of ER-α. These results raise the possibility that wild-type BRCA1 suppresses estrogen-dependent transcriptional pathways related to mammary epithelial cell proliferation and that loss of this ability contributes to tumorigenesis.
Equivalence in Yield from Marine Reserves and Traditional Fisheries Management
Authors: Hastings Alan , Botsford Louis W.
Published: July 2002

Marine reserves have been proposed as a remedy for overfishing and declining marine biodiversity, but concern that reserves would inherently reduce yields has impeded their implementation. It was found that management of fisheries through reserves and management through effort control produce identical yields under a reasonable set of simplifying assumptions corresponding to a broad range of biological conditions. Indeed, for populations with sedentary adults (invertebrates and reef fishes), reserves have important advantages for sustainability, making marine reserves the preferred management approach.