bluuebunny/crossref_metadata_2025 huggingface dataset:
New Routes in the Preparation of Mechanically Hard Films
Authors: Sproul William D.
Published: October 2006

Superhard nitride superlattice coatings with nanometer-scale multilayers have hardnesses exceeding 50 gigapascals, making these films highly resistant to abrasion. The nitride superlattice films can be deposited economically by reactive sputtering in production-size equipment on a variety of substrates. A model for the superlattice strength enhancement has been developed that accurately predicts which materials can be used together to produce the enhanced hardness. Advancements in sputtering technology—specifically, pulsed dc power and reactive-gas partial-pressure control—make it possible to reactively deposit nonconducting oxide films at high deposition rates. This technology is being used along with the superlattice strength model in the development of oxide superlattice films.
Search for Past Life on Mars: Possible Relic Biogenic Activity in Martian Meteorite ALH84001
Authors: McKay David S. , Gibson Everett K. , Thomas-Keprta Kathie L. , Vali Hojatollah , Romanek Christopher S. , Clemett Simon J. , Chillier Xavier D. F. , Maechling Claude R. , Zare Richard N.
Published: October 2006

Fresh fracture surfaces of the martian meteorite ALH84001 contain abundant polycyclic aromatic hydrocarbons (PAHs). These fresh fracture surfaces also display carbonate globules. Contamination studies suggest that the PAHs are indigenous to the meteorite. High-resolution scanning and transmission electron microscopy study of surface textures and internal structures of selected carbonate globules show that the globules contain fine-grained, secondary phases of single-domain magnetite and iron sulfides. The carbonate globules are similar in texture and size to some terrestrial bacterially induced carbonate precipitates. Although inorganic formation is possible, formation of the globules by biogenic processes could explain many of the observed features, including the PAHs. The PAHs, the carbonate globules, and their associated secondary mineral phases and textures could thus be fossil remains of a past martian biota.
Spectral Properties of Near-Earth Asteroids: Evidence for Sources of Ordinary Chondrite Meteorites
Authors: Binzel Richard P. , Bus Schelte J. , Burbine Thomas H. , Sunshine Jessica M.
Published: October 2006

Although ordinary chondrite (OC) meteorites dominate observed falls, the identification of near-Earth and main-belt asteroid sources has remained elusive. Telescopic measurements of 35 near-Earth asteroids (∼3 kilometers in diameter) revealed six that have visible wavelength spectra similar to laboratory spectra of OC meteorites. Near-Earth asteroids were found to have spectral properties that span the range between the previously separated domains of OC meteorites and the most common (S class) asteroids, suggesting a link. This range of spectral properties could arise through a diversity of mineralogies and regolith particle sizes, as well as through a time-dependent surface weathering process.
Arabidopsis AUX1

Gene: A Permease-Like Regulator of Root Gravitropism
Authors: Bennett Malcolm J. , Marchant Alan , Green Haydn G. , May Sean T. , Ward Sally P. , Millner Paul A. , Walker Amanda R. , Schulz Burkhard , Feldmann Kenneth A.
Published: October 2006

The plant hormone auxin regulates various developmental processes including root formation, vascular development, and gravitropism. Mutations within the
AUX1
gene confer an auxin-resistant root growth phenotype and abolish root gravitropic curvature. Polypeptide sequence similarity to amino acid permeases suggests that
AUX1
mediates the transport of an amino acid-like signaling molecule. Indole-3-acetic acid, the major form of auxin in higher plants, is structurally similar to tryptophan and is a likely substrate for the
AUX1
gene product. The cloned
AUX1
gene can restore the auxin-responsiveness of transgenic
aux1
roots. Spatially,
AUX1
is expressed in root apical tissues that regulate root gravitropic curvature.
Regulation of Cardiac Na
+
,Ca
2+
Exchange and K
ATP
Potassium Channels by PIP
2
Authors: Hilgemann Donald W. , Ball Rebecca
Published: October 2006

Cardiac Na
+
,Ca
2+
exchange is activated by a mechanism that requires hydrolysis of adenosine triphosphate (ATP) but is not mediated by protein kinases. In giant cardiac membrane patches, ATP acted to generate phosphatidylinositol-4,5-bisphosphate (PIP
2
) from phosphatidylinositol (PI). The action of ATP was abolished by a PI-specific phospholipase C (PLC) and recovered after addition of exogenous PI; it was reversed by a PIP
2
-specific PLC; and it was mimicked by exogenous PIP
2
. High concentrations of free Ca
2+
(5 to 20 μM) accelerated reversal of the ATP effect, and PLC activity in myocyte membranes was activated with a similar Ca
2+
dependence. Aluminum reversed the ATP effect by binding with high affinity to PIP
2
. ATP-inhibited potassium channels (K
ATP
) were also sensitive to PIP
2
, whereas Na
+
,K
+
pumps and Na
+
channels were not. Thus, PIP
2
may be an important regulator of both ion transporters and channels.
Control of MHC Restriction by TCR V
α
CDR1 and CDR2
Authors: Sim Bee-Cheng , Zerva Loukia , Greene Mark I. , Gascoigne Nicholas R. J.
Published: October 2006

Individual T cell receptor (TCR) V
α
elements are expressed preferentially in CD4 or CD8 peripheral T cell subsets. The closely related V
α
3.1 and V
α
3.2 elements show reciprocal selection into CD4 and CD8 subsets, respectively. Transgenic mice expressing site-directed mutants of a V
α
3.1 gene were used to show that individual residues in either the complementarity-determining region 1 (CDR1) or CDR2 were sufficient to change selection from the CD4 subset to the CD8 subset. Thus, the germline-encoded V
α
elements are a major influence on major histocompatibility class complex (MHC) restriction, most likely by a preferential interaction with one or the other class of MHC molecule.
Auditory Neurophysiologic Responses and Discrimination Deficits in Children with Learning Problems
Authors: Kraus Nina , McGee Therese J. , Carrell Thomas D. , Zecker Steven G. , Nicol Trent G. , Koch Dawn B.
Published: October 2006

Children with learning problems often cannot discriminate rapid acoustic changes that occur in speech. In this study of normal children and children with learning problems, impaired behavioral discrimination of a rapid speech change (/dα/versus/gα/) was correlated with diminished magnitude of an electrophysiologic measure that is not dependent on attention or a voluntary response. The ability of children with learning problems to discriminate another rapid speech change (/bα/versus/wα/) also was reflected in the neurophysiology. These results indicate that some children's discrimination deficits originate in the auditory pathway before conscious perception and have implications for differential diagnosis and targeted therapeutic strategies for children with learning disabilities and attention disorders.
Exploring Biodiversity's Benefits
Authors: Culotta Elizabeth
Published: October 2006

Providence, Rhode Island—In a puzzle dating back to the time of Darwin, ecologists have wondered about diversity's effect on an ecosystem's health. Does it make ecosystems more productive and stable, as some think, or are less diverse ecosystems better off? Recently, however, results produced both in field studies and in mathematical models have been tilting the balance toward the former view. The findings have implications for the management of forests, grazing lands, and other ecosystems.
Protein Builds Second Skeleton
Authors: Roush Wade
Published: October 2006

The villain in a rare inherited disease that relentlessly converts the body's soft connective tissues into bone lurks within the victims' own immune systems, researchers have found. In the disease, called fibrodysplasia ossificans progressiva, the slightest injury to ligaments, tendons, or muscles ultimately causes new bone to appear at the site of the injury. The reason: The white blood cells that invade the tissue in response to injury erroneously manufacture bone morphogenic protein-4 (BMP-4), a powerful signaling protein that ordinarily helps build the skeleton of the developing embryo.
Trypanosome RNA Editing: Resolved
Authors: Sollner-Webb Barbara
Published: October 2006

In trypanosomes, mitochondrial RNAs are modified after their synthesis. Uridylate residues are inserted into the RNA transcript or, less often, deleted. In a research article in this week's issue, Kable
et al
. (
p. 1189
) describe the mechanism whereby uridylate residues are inserted into these RNAs. Sollner-Webb discusses the discoveries and ideas that led to this breakthrough and the questions remaining for the field.
Postseismic Rebound in Fault Step-Overs Caused by Pore Fluid Flow
Authors: Peltzer Gilles , Rosen Paul , Rogez Francois , Hudnut Ken
Published: October 2006

Near-field strain induced by large crustal earthquakes results in changes in pore fluid pressure that dissipate with time and produce surface deformation. Synthetic aperture radar (SAR) interferometry revealed several centimeters of postseismic uplift in pull-apart structures and subsidence in a compressive jog along the Landers, California, 1992 earthquake surface rupture, with a relaxation time of 270 ± 45 days. Such a postseismic rebound may be explained by the transition of the Poisson's ratio of the deformed volumes of rock from undrained to drained conditions as pore fluid flow allows pore pressure to return to hydrostatic equilibrium.
Flux Line Lattice Melting Transition in YBa
2
Cu
3
O
6.94
Observed in Specific Heat Experiments
Authors: Roulin Marlyse , Junod Alain , Walker Eric
Published: October 2006

When a magnetic field penetrates a type II superconductor, it forms a lattice of thin quantized filaments called magnetic vortices. Resistance, magnetization, and neutron diffraction experiments have shown that the vortex lattice of high-temperature superconductors can melt along a line in the field-temperature plane. The calorimetric signature of melting on this line was observed in a high-accuracy adiabatic specific heat experiment performed on YBa
2
Cu
3
O
6.94
. The specific heat of the vortex liquid was greater than that of the vortex solid.
Allelic Diversity and Gene Genealogy at the Self-Incompatibility Locus in the Solanaceae
Authors: Richman Adam D. , Uyenoyama Marcy K. , Kohn Joshua R.
Published: October 2006

The self-incompatibility (
S
) locus of flowering plants offers an example of extreme polymorphism maintained by balancing selection. Estimates of recent and long-term effective population size (
N
e
) were determined for two solanaceous species by examination of
S
-allele diversity. Estimates of recent
N
e
in two solanaceous species differed by an order of magnitude, consistent with differences in the species' ecology. In one species, the evidence was consistent with historical population restriction despite a large recent
N
e
. In the other, no severe bottleneck was indicated over millions of years. Bottlenecks are integral to founder-event speciation, and loci that are subject to balancing selection can be used to evaluate the frequency of this mode of speciation.
Luteinizing Hormone Deficiency and Female Infertility in Mice Lacking the Transcription Factor NGFI-A (Egr-1)
Authors: Lee Stephen L. , Sadovsky Yoel , Swirnoff Alexander H. , Polish Jeffrey A. , Goda Pam , Gavrilina Galina , Milbrandt Jeffrey
Published: October 2006

The immediate-early transcription factor NGFI-A (also called Egr-1, zif/268, or Krox-24) is thought to couple extracellular signals to changes in gene expression. Although activins and inhibins regulate follicle-stimulating hormone (FSH) synthesis, no factor has been identified that exclusively regulates luteinizing hormone (LH) synthesis. An analysis of NGFI-A-deficient mice derived from embryonic stem cells demonstrated female infertility that was secondary to LH-β deficiency. Ovariectomy led to increased amounts of FSH-β but not LH-β messenger RNA, which suggested a pituitary defect. A conserved, canonical NGFI-A site in the LH-β promoter was required for synergistic activation by NGFI-A and steroidogenic factor-1 (SF-1). NGFI-A apparently influences female reproductive capacity through its regulation of LH-β transcription.
KUZ, a Conserved Metalloprotease-Disintegrin Protein with Two Roles in

Drosophila

Neurogenesis
Authors: Rooke Jenny , Pan Duojia , Xu Tian , Rubin Gerald M.
Published: October 2006

During neurogenesis in
Drosophila
both neurons and nonneuronal cells are produced from a population of initially equivalent cells. The
kuzbanian
(
kuz
) gene described here is essential for the partitioning of neural and nonneuronal cells during development of both the central and peripheral nervous systems in
Drosophila
. Mosaic analyses indicated that
kuz
is required for cells to receive signals inhibiting the neural fate. These analyses further revealed that the development of a neuron requires a
kuz
-mediated positive signal from neighboring cells. The
kuz
gene encodes a metalloprotease-disintegrin protein with a highly conserved bovine homolog, raising the possibility that
kuz
homologs may act in similar processes during mammalian neurogenesis.
A Protein Farnesyl Transferase Involved in Abscisic Acid Signal Transduction in

Arabidopsis
Authors: Cutler Sean , Ghassemian Majid , Bonetta Dario , Cooney Sarah , McCourt Peter
Published: October 2006

The hormone abscisic acid (ABA) modulates a variety of developmental processes and responses to environmental stress in higher plants. A collection of mutations, designated
era
, in
Arabidopsis thaliana
that confer an enhanced response to exogenous ABA includes mutations in the
Era1
gene, which encodes the β subunit of a protein farnesyl transferase. In yeast and mammalian systems, farnesyl transferases modify several signal transduction proteins for membrane localization. The
era1
mutants suggest that a negative regulator of ABA sensitivity must be acted on by a farnesyl transferase to function.
Superstructure Control in the Crystal Growth and Ordering of Urea Inclusion Compounds
Authors: Hollingsworth M. D. , Brown M. E. , Hillier A. C. , Santarsiero B. D. , Chaney J. D.
Published: October 2006

A template-directed mechanism of crystal growth is demonstrated for urea inclusion compounds (UICs). For UICs containing
n
-alkanone or α+1,ω−1-alkanedione guests, x-ray diffraction revealed superstructure relations between host and guest repeats along the channel axis for guests containing 8 to 14 carbons. For a favorable structural match between host and guest, UICs typically grow as flat hexagonal plates, and atomic force microscopy of {001} surfaces revealed molecularly smooth terraces differing in height by multiples of the guest repeat. If the match is poor, protrusion of guests from the {001} surfaces nucleates growth along the channel axis to form hexagonal needles.
Mantle Viscosity and Ice-Age Ice Sheet Topography
Authors: Peltier W. Richard
Published: October 2006

Ice-age paleotopography and mantle viscosity can both be inferred from observations of Earth's response to the most recent deglaciation event of the current ice age. This procedure requires iterative application of a theoretical model of the global process of glacial isostatic adjustment. Results demonstrate that the iterative inversion procedure converges to a paleotopography that is extremely close to that from the ICE-4G model. The accompanying mantle viscosity profile is furthermore shown to reconcile the requirements of aspherical geoid anomalies related to the mantle convection process, thus resolving a fundamental issue concerning mantle rheology. The combined model also explains postglacial sea level histories for the east coast of the United States.
Radiocarbon in Hydrologic Systems Containing Dissolved Magmatic Carbon Dioxide
Authors: Rose Timothy P. , Davisson M. Lee
Published: October 2006

In regions of active volcanism, the presence of magmatic carbon dioxide (CO
2
) in regional hydrologic systems provides a radiocarbon-depleted tracer for delineating ground-water transport and mixing processes and provides a means of assessing regional magmatic carbon fluxes. Variations in the stable carbon isotopic composition (δ
13
C) and carbon-14 values of springs and surface waters from the southern Cascade Range show consistent patterns of carbon isotopic mixing between magmatic, biogenic, and atmospheric CO
2
reservoirs. Radiocarbon measurements of waters from the Lassen region in northern California were used to construct a ground-water carbon-14 contour map, revealing principal subsurface flow paths and a broad region of diffuse magmatic CO
2
flux.
Purification and Molecular Cloning of Plx1, a Cdc25-Regulatory Kinase from

Xenopus

Egg Extracts
Authors: Kumagai Akiko , Dunphy William G.
Published: October 2006

Cdc2, the cyclin-dependent kinase that controls mitosis, is negatively regulated by phosphorylation on its threonine-14 and tyrosine-15 residues. Cdc25, the phosphatase that dephosphorylates both of these residues, undergoes activation and phosphorylation by multiple kinases at mitosis. Plx1, a kinase that associates with and phosphorylates the amino-terminal domain of Cdc25, was purified extensively from
Xenopus
egg extracts. Cloning of its complementary DNA revealed that Plx1 is related to the Polo family of protein kinases. Recombinant Plx1 phosphorylated Cdc25 and stimulated its activity in a purified system. Cdc25 phosphorylated by Plx1 reacted strongly with MPM-2, a monoclonal antibody to mitotic phosphoproteins. These studies indicate that Plx1 may participate in control of mitotic progression.
Correction of the Mutation Responsible for Sickle Cell Anemia by an RNA-DNA Oligonucleotide
Authors: Cole-Strauss Allyson , Yoon Kyonggeun , Xiang Yufei , Byrne Bruce C. , Rice Michael C. , Gryn Jeff , Holloman William K. , Kmiec Eric B.
Published: October 2006

A chimeric oligonucleotide composed of DNA and modified RNA residues was used to direct correction of the mutation in the hemoglobin β
S
allele. After introduction of the chimeric molecule into lymphoblastoid cells homozygous for the β
S
mutation, there was a detectable level of gene conversion of the mutant allele to the normal sequence. The efficient and specific conversion directed by chimeric molecules may hold promise as a therapeutic method for the treatment of genetic diseases.
Enhanced Protein C Activation and Inhibition of Fibrinogen Cleavage by a Thrombin Modulator
Authors: Berg David T. , Wiley Michael R. , Grinnell Brian W.
Published: October 2006

A modulator of the enzymatic activity of human thrombin, designated LY254603, was identified that enhances the thrombin-catalyzed generation of the anticoagulant factor activated protein C, yet inhibits thrombin-dependent fibrinogen clotting. By means of mutant substrates, it was shown that LY254603 mediates the change in enzymatic substrate specificity through an alteration in thrombin's S3 substrate recognition site, a mechanism that appeared to be independent of allosteric changes induced by either sodium ions or by thrombomodulin. This compound may represent the prototype of a class of agents that specifically modulates the balance between thrombin's procoagulant and anticoagulant functions.
Crystal Structure of the

Aequorea victoria

Green Fluorescent Protein
Authors: Ormö Mats , Cubitt Andrew B. , Kallio Karen , Gross Larry A. , Tsien Roger Y. , Remington S. James
Published: October 2006

The green fluorescent protein (GFP) from the Pacific Northwest jellyfish
Aequorea victoria
has generated intense interest as a marker for gene expression and localization of gene products. The chromophore, resulting from the spontaneous cyclization and oxidation of the sequence -Ser
65
(or Thr
65
)-Tyr
66
-Gly
67
-, requires the native protein fold for both formation and fluorescence emission. The structure of Thr
65
GFP has been determined at 1.9 angstrom resolution. The protein fold consists of an 11-stranded β barrel with a coaxial helix, with the chromophore forming from the central helix. Directed mutagenesis of one residue adjacent to the chromophore, Thr
203
, to Tyr or His results in significantly red-shifted excitation and emission maxima.
Bimodal Interaction of Coatomer with the p24 Family of Putative Cargo Receptors
Authors: Fiedler Klaus , Veit Michael , Stamnes Mark A. , Rothman James E.
Published: October 2006

Cytoplasmic domains of members of the p24 family of putative cargo receptors were shown to bind to coatomer, the coat protein of COPI-coated transport vesicles. Domains that contained dilysine endoplasmic reticulum retrieval signals bound the α-, β′-, and ϵ-COP subunits of coatomer, whereas other p24 domains bound the β-, γ-, and ζ-COP subunits and required a phenylalanine-containing motif. Transit of a CD8-p24 chimera from the endoplasmic reticulum through the Golgi complex was slowed when the phenylalanine motif was mutated, suggesting that this motif may function as an anterograde transport signal. The either-or bimodal binding of coatomer to p24 tails suggests models for how coatomer can potentially package retrograde-directed and anterograde-directed cargo into distinct COPI-coated vesicles.
Judge Dismisses Suit Against Stanford
Authors: Friedly Jock
Published: October 2006

A federal judge in San Jose, California, has dismissed a multimillion-dollar lawsuit against Stanford University, claiming that it had vastly overcharged the federal government for indirect costs, or overheads, on government research grants and contracts. The suit was filed by Paul Biddle, a federal accountant who first raised concerns about Stanford's billing practices in 1989. Its dismissal may be the final chapter in a painful saga in which Stanford admitted inappropriately charging several items to overheads—including a yacht—but was deemed by several investigations to have committed no more than accounting errors.
The Effect of Alumina on Phase Transformations at the 660-Kilometer Discontinuity from Fe-Mg Partitioning Experiments
Authors: Wood B. J. , Rubie D. C.
Published: October 2006

Experimental data on the partitioning of Fe and Mg between coexisting silicate perovskite, magnesiowüstite, and γ-(Mg,Fe)
2
SiO
4
demonstrate that Fe substitution in perovskite is strongly coupled to Al
2
O
3
concentration. In Al
2
O
3
-free compositions, perovskite has a low Fe/(Fe+Mg) ratio: for a bulk Fe/(Fe+Mg) of 0.11, perovskite has a value close to 0.04, whereas magnesiowüstite has a ratio near 0.17. In peridotitic mantle, however, where the perovskite should contain 4 to 5 weight percent Al
2
O
3
, it has essentially the same Fe/(Fe+Mg) ratio as coexisting magnesiowüstite. Under lower mantle conditions, therefore, perovskite and magnesiowüstite should, in peridotite, each have an Fe/(Fe+Mg) ratio close to 0.11.
Organic Optical Limiter with a Strong Nonlinear Absorptive Response
Authors: Perry J. W. , Mansour K. , Lee I.-Y. S. , Wu X.-L. , Bedworth P. V. , Chen C.-T. , Ng D. , Marder S. R. , Miles P. , Wada T. , Tian M. , Sasabe H.
Published: October 2006

Molecules with weak ground-state absorption that form strongly absorbing excited states can be used in optical limiters, which can protect sensors or human eyes from optical damage. Phthalocyanine complexes bearing heavy atoms or paramagnetic groups or in solvents containing heavy atoms show optical limiting enhanced by excited triplet-state absorption. A nonhomogeneous distribution of indium tetra(
tert
-butyl)phthalocyanine chloride along the beam path substantially enhances the excited-state absorption, yielding an optical limiter with a linear transmittance of 0.70 that can attenuate 8-nanosecond, 532-nanometer laser pulses by factors of up to 540.
Predicting the Occurrence of Endangered Species in Fragmented Landscapes
Authors: Wahlberg Niklas , Moilanen Atte , Hanski Ilkka
Published: October 2006

Reliable prediction of metapopulation persistence in fragmented landscapes has become a priority in conservation biology, with ongoing destruction of habitat confining increasing numbers of species into networks of small patches. A spatially realistic metapopulation model, which includes the first-order effects of patch area and isolation on extinction and colonization, has been tested. The distribution of an endangered butterfly was successfully predicted on the basis of parameter values estimated for a well-studied congeneric species. This modeling approach can be a practical tool in the study and conservation of species in highly fragmented landscapes.
Mechanisms of Heading Perception in Primate Visual Cortex
Authors: Bradley David C. , Maxwell Marsha , Andersen Richard A. , Banks Martin S. , Shenoy Krishna V.
Published: October 2006

When we move forward while walking or driving, what we see appears to expand. The center or focus of this expansion tells us our direction of self-motion, or heading, as long as our eyes are still. However, if our eyes move, as when tracking a nearby object on the ground, the retinal image is disrupted and the focus is shifted away from the heading. Neurons in primate dorso-medial superior temporal area responded selectively to an expansion focus in a certain part of the visual field, and this selective region shifted during tracking eye movements in a way that compensated for the retinal focus shift. Therefore, these neurons account for the effect of eye movements on what we see as we travel forward through the world.
Ecological Determinants of Species Loss in Remnant Prairies
Authors: Leach Mark K. , Givnish Thomas J.
Published: October 2006

Recensuses of 54 Wisconsin prairie remnants showed that 8 to 60 percent of the original plant species were lost from individual remnants over a 32- to 52-year period. The pattern of species loss was consistent with the proposed effects of fire suppression caused by landscape fragmentation. Short, small-seeded, or nitrogen-fixing plants showed the heaviest losses, as did species growing in the wettest, most productive environments. The interruption of landscape-scale processes (such as wildfire) by fragmentation is an often overlooked mechanism that may be eroding biodiversity in many habitats around the world.
Effects of Disturbance on River Food Webs
Authors: Wootton J. Timothy , Parker Michael S. , Power Mary E.
Published: October 2006

A multitrophic model integrating the effects of flooding disturbance and food web interactions in rivers predicted that removing floods would cause increases of predator-resistant grazing insects, which would divert energy away from the food chain leading to predatory fish. Experimental manipulations of predator-resistant grazers and top predators, and large-scale comparisons of regulated and unregulated rivers, verified the model predictions. Thus, multitrophic models can successfully synthesize a variety of ecological processes, and conservation programs may benefit by taking a food web perspective instead of concentrating on a single species.
Crystal Structure of a Group I Ribozyme Domain: Principles of RNA Packing
Authors: Cate Jamie H. , Gooding Anne R. , Podell Elaine , Zhou Kaihong , Golden Barbara L. , Kundrot Craig E. , Cech Thomas R. , Doudna Jennifer A.
Published: October 2006

Group I self-splicing introns catalyze their own excision from precursor RNAs by way of a two-step transesterification reaction. The catalytic core of these ribozymes is formed by two structural domains. The 2.8-angstrom crystal structure of one of these, the P4-P6 domain of the
Tetrahymena thermophila
intron, is described. In the 160-nucleotide domain, a sharp bend allows stacked helices of the conserved core to pack alongside helices of an adjacent region. Two specific long-range interactions clamp the two halves of the domain together: a two-Mg
2+
-coordinated adenosine-rich corkscrew plugs into the minor groove of a helix, and a GAAA hairpin loop binds to a conserved 11-nucleotide internal loop. Metal- and ribose-mediated backbone contacts further stabilize the close side-by-side helical packing. The structure indicates the extent of RNA packing required for the function of large ribozymes, the spliceosome, and the ribosome.
Identification of the "Active Sites" of a Surface-Catalyzed Reaction
Authors: Zambelli T. , Wintterlin J. , Trost J. , Ertl G.
Published: October 2006

The dissociation of nitric oxide on a ruthenium(0001) surface was studied by scanning tunneling microscopy. The distribution of nitrogen atoms after the dissociation allowed the identification of the "active sites" for this reaction, which are formed by the low-coordinated, top metal atoms of atomic steps. It is proposed that their activity is caused by local changes in the electronic structure. The structure of the steps determines whether they remain active or become deactivated by oxygen atoms. The results demonstrate the complex manner in which the structure of a catalytic surface determines the reactivity of the catalyst and confirm the active sites concept.
RNA Tertiary Structure Mediation by Adenosine Platforms
Authors: Cate Jamie H. , Gooding Anne R. , Podell Elaine , Zhou Kaihong , Golden Barbara L. , Szewczak Alexander A. , Kundrot Craig E. , Cech Thomas R. , Doudna Jennifer A.
Published: October 2006

The crystal structure of a group I intron domain reveals an unexpected motif that mediates both intra- and intermolecular interactions. At three separate locations in the 160-nucleotide domain, adjacent adenosines in the sequence lie side-by-side and form a pseudo-base pair within a helix. This adenosine platform opens the minor groove for base stacking or base pairing with nucleotides from a noncontiguous RNA strand. The platform motif has a distinctive chemical modification signature that may enable its detection in other structured RNAs. The ability of this motif to facilitate higher order folding provides one explanation for the abundance of adenosine residues in internal loops of many RNAs.
Parallel and Antiparallel (G·GC)
2
Triple Helix Fragments in a Crystal Structure
Authors: Vlieghe Dominique , Van Meervelt Luc , Dautant Alain , Gallois Bernard , Précigoux Gilles , Kennard Olga
Published: October 2006

Nucleic acid triplexes are formed by sequence-specific interactions between single-stranded polynucleotides and the double helix. These triplexes are implicated in genetic recombination in vivo and have application to areas that include genome analysis and antigene therapy. Despite the importance of the triple helix, only limited high-resolution structural information is available. The x-ray crystal structure of the oligonucleotide d(GGCCAATTGG) is described; it was designed to contain the d(G⋅GC)
2
fragment and thus provide the basic repeat unit of a DNA triple helix. Parameters derived from this crystal structure have made it possible to construct models of both parallel and antiparallel triple helices.
Interaction of U2AF
65
RS Region with Pre-mRNA of Branch Point and Promotion Base Pairing with U2 snRNA
Authors: Valcárcel Juan , Gaur Rajesh K. , Singh Ravinder , Green Michael R.
Published: October 2006

The mammalian splicing factor U2AF
65
binds to the polypyrimidine tract adjacent to the 3′ splice site and promotes assembly of U2 small nuclear ribonucleoprotein on the upstream branch point, an interaction that involves base pairing with U2 small nuclear RNA (snRNA). U2AF
65
contains an RNA binding domain, required for interaction with the polypyrimidine tract, and an arginine-serine-rich (RS) region, required for U2 snRNP recruitment and splicing. Here it is reported that binding of U2AF
65
to the polypyrimidine tract directed the RS domain to contact the branch point and promoted U2 snRNA-branch point base pairing even in the absence of other splicing factors. Analysis of RS domain mutants indicated that the ability of U2AF
65
to contact the branch point, to promote the U2 snRNA-branch point interaction, and to support splicing are related activities, requiring only a few basic amino acids. Thus, the U2AF
65
RS domain plays a direct role in modulating spliceosomal RNA-RNA interactions.
Small-Conductance, Calcium-Activated Potassium Channels from Mammalian Brain
Authors: Köhler M. , Hirschberg B. , Bond C. T. , Kinzie J. M. , Marrion N. V. , Maylie J. , Adelman J. P.
Published: October 2006

Members of a previously unidentified family of potassium channel subunits were cloned from rat and human brain. The messenger RNAs encoding these subunits were widely expressed in brain with distinct yet overlapping patterns, as well as in several peripheral tissues. Expression of the messenger RNAs in
Xenopus
oocytes resulted in calcium-activated, voltage-independent potassium channels. The channels that formed from the various subunits displayed differential sensitivity to apamin and tubocurare. The distribution, function, and pharmacology of these channels are consistent with the SK class of small-conductance, calcium-activated potassium channels, which contribute to the afterhyperpolarization in central neurons and other cell types.
A Cyclin-Dependent Kinase-Activating Kinase (CAK) in Budding Yeast Unrelated to Vertebrate CAK
Authors: Espinoza F. Hernan , Farrell Alison , Erdjument-Bromage Hediye , Tempst Paul , Morgan David O.
Published: October 2006

Progress through the cell cycle is governed by the cyclin-dependent kinases (CDKs), the activation of which requires phosphorylation by the CDK-activating kinase (CAK). In vertebrates, CAK is a trimeric enzyme containing CDK7, cyclin H, and MAT1. CAK from the budding yeast
Saccharomyces cerevisiae
was identified as an unusual 44-kilodalton protein kinase, Cak1, that is only distantly related to CDKs. Cak1 accounted for most CAK activity in yeast cell lysates, and its activity was constant throughout the cell cycle. The
CAK1
gene was essential for cell viability. Thus, the major CAK in
S. cerevisiae
is distinct from the vertebrate enzyme, suggesting that budding yeast and vertebrates may have evolved different mechanisms of CDK activation.
Regulation of Interferon-γ-Activated STAT1 by the Ubiquitin-Proteasome Pathway
Authors: Kim Tae Kook , Maniatis Tom
Published: October 2006

STAT proteins (signal transducers and activators of transcription) are latent cytoplasmic transcription factors that are phosphorylated by Janus kinases in response to cytokines. Phosphorylated STAT proteins translocate to the nucleus, where they transiently turn on specific sets of cytokine-inducible genes. The mechanism that controls the amounts of activated STAT proteins is not understood. STAT1 proteins activated by interferon-γ treatment in HeLa cells were shown to be stabilized by a proteasome inhibitor and ubiquitinated in vivo. Thus, the amount of activated STAT1 may be negatively regulated by the ubiquitin-proteasome pathway.
Neurogenic Amplification of Immune Complex Inflammation
Authors: Bozic Carmen R. , Lu Bao , Höpken Uta E. , Gerard Craig , Gerard Norma P.
Published: October 2006

The formation of intrapulmonary immune complexes in mice generates a vigorous inflammatory response characterized by microvascular permeability and polymorphonuclear neutrophil influx. Gene-targeted disruption of the substance P receptor (NK-1R) protected the lung from immune complex injury, as did disruption of the C5a anaphylatoxin receptor. Immunoreactive substance P was measurable in fluids lining the lung at time points before neutrophil influx and may thus be involved in an early step in the inflammatory response to immune complexes in the lung.
ER Degradation of a Misfolded Luminal Protein by the Cytosolic Ubiquitin-Proteasome Pathway
Authors: Hiller Mark M. , Finger Andreas , Schweiger Markus , Wolf Dieter H.
Published: October 2006

Secretion of proteins is initiated by their uptake into the endoplasmic reticulum (ER), which possesses a proteolytic system able to degrade misfolded and nonassembled proteins. The ER degradation system was studied with yeast mutants defective in the breakdown of a mutated soluble vacuolar protein, carboxypeptidase yscY (CPY*). The ubiquitin-conjugating enzyme Ubc7p participated in the degradation process, which was mediated by the cytosolic 26
S
proteasome. It is likely that CPY* entered the ER, was glycosylated, and was then transported back out of the ER lumen to the cytoplasmic side of the organelle, where it was conjugated with ubiquitin and degraded.
Sequential Binding of Import Ligands to Distinct Nucleopore Regions During Their Nuclear Import
Authors: Panté Nelly , Aebi Ueli
Published: October 2006

Protein import into nuclei is mediated by the nuclear pore complex (NPC) and by cellular factors. To structurally characterize this process, nuclear import of gold-labeled nucleoplasmin was followed by electron microscopy to identify NPC components interacting with the import ligand complex in vivo. Before translocation into the nucleus, nucleoplasmin sequentially bound to two distinct regions: first to the distal part of the cytoplasmic filaments and then at the cytoplasmic entry to the central gated channel. Evidence that the delivery of the import ligand from the first to the second binding region occurred by bending of the cytoplasmic filaments is presented here.
Plastics May Add New Colors to Lasers' Light Show
Authors: Service Robert F.
Published: October 2006

Lasers are a technological success story, with applications ranging from grocery scanners to compact-disc players. But the semiconductor crystals at the heart of these deviceshave difficulty emitting laser beams in certain colors. Now a new class of materials—plastic polymer thin films—has been coaxed to emit laserlike light in colors across the visible spectrum, as reported on
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Semiconducting Polymers: A New Class of Solid-State Laser Materials
Authors: Hide Fumitomo , Díaz-García María A. , Schwartz Benjamin J. , Andersson Mats R. , Pei Qibing , Heeger Alan J.
Published: October 2006

Gain narrowing in optically pumped thin films, both neat and undiluted, of luminescent conjugated polymers with different molecular structures was demonstrated. These results indicate that the polymers studied have large cross sections for stimulated emission, that population inversion can be achieved at low pump energies, and that the emitted photons travel distances greater than the gain length within the gain medium. The use of simple waveguide structures is sufficient to cause low gain narrowing thresholds in submicrometer-thick films.
Nanorod-Superconductor Composites: A Pathway to Materials with High Critical Current Densities
Authors: Yang Peidong , Lieber Charles M.
Published: October 2006

Most large-scale applications of the high-temperature copper oxide superconductors (HTSCs) require high critical current densities (
J
c
's) at temperatures near the boiling point of liquid nitrogen to be technologically useful, although thermally activated flux flow reduces
J
c
dramatically at these temperatures. This intrinsic limitation can be overcome by introducing nanometer-sized columnar defects into an HTSC. Nanorods of magnesium oxide were grown and incorporated into HTSCs to form nanorod-HTSC composites. In this way, a high density of nanorod columnar defects can be created with orientations perpendicular and parallel to the copper oxide planes. The
J
c
's of the nanorod-HTSC composites are enhanced dramatically at high temperatures and magnetic fields as compared with reference samples; these composites may thus represent a technologically viable strategy for overcoming thermally activated flux flow in large-scale applications.
Peculiarities of Methane Clathrate Hydrate Formation and Solid-State Deformation, Including Possible Superheating of Water Ice
Authors: Stern Laura A. , Kirby Stephen H. , Durham William B.
Published: October 2006

Slow, constant-volume heating of water ice plus methane gas mixtures forms methane clathrate hydrate by a progressive reaction that occurs at the nascent ice/liquid water interface. As this reaction proceeds, the rate of melting of metastable water ice may be suppressed to allow short-lived superheating of ice to at least 276 kelvin. Plastic flow properties measured on clathrate test specimens are significantly different from those of water ice; under nonhydrostatic stress, methane clathrate undergoes extensive strain hardening and a process of solid-state disproportionation or exsolution at conditions well within its conventional hydrostatic stability field.
Rate Constants for Charge Transfer Across Semiconductor-Liquid Interfaces
Authors: Fajardo Arnel M. , Lewis Nathan S.
Published: October 2006

Interfacial charge-transfer rate constants have been measured for
n
-type Si electrodes in contact with a series of viologen-based redox couples in methanol through analyses of the behavior of these junctions with respect to their current density versus potential and differential capacitance versus potential properties. The data allow evaluation of the maximum rate constant (and therefore the electronic coupling) for majority carriers in the solid as well as of the dependence of the rate constant on the driving force for transfer of delocalized electrons from the
n
-Si semiconducting electrode into the localized molecular redox species in the solution phase. The data are in good agreement with existing models of this interfacial electron transfer process and provide insight into the fundamental kinetic events underlying the use of semiconducting photoelectrodes in applications such as solar energy conversion.
The Little Ice Age and Medieval Warm Period in the Sargasso Sea
Authors: Keigwin Lloyd D.
Published: October 2006

Sea surface temperature (SST), salinity, and flux of terrigenous material oscillated on millennial time scales in the Pleistocene North Atlantic, but there are few records of Holocene variability. Because of high rates of sediment accumulation, Holocene oscillations are well documented in the northern Sargasso Sea. Results from a radiocarbon-dated box core show that SST was ∼1°C cooler than today ∼400 years ago (the Little Ice Age) and 1700 years ago, and ∼1°C warmer than today 1000 years ago (the Medieval Warm Period). Thus, at least some of the warming since the Little Ice Age appears to be part of a natural oscillation.
Functional Isolation and Characterization of Human Hematopoietic Stem Cells
Authors: Berardi Anna C. , Wang Anlai , Levine James D. , Lopez Peter , Scadden David T.
Published: October 2006

Hematopoietic cells differentiate in steps marked by the acquisition or loss of specific phenotypic characteristics. Human bone marrow cells that were responsive to the early-acting cytokines Kit ligand and interleukin-3 were forced to a metabolic death. The subfraction remaining represented 1 in 10(5) bone marrow mononuclear cells, was determined to be quiescent by cell cycle analysis, and had a stem cell immunophenotype. The cells were highly enriched for long-term culture-initiating cells, were capable of secondary colony formation, and produced both myeloid and lymphoid progeny. Thus, this technically simple strategy led to the efficient purification of cells with characteristics of hematopoietic stem cells.
Association of Protein Kinase A and Protein Phosphatase 2B with a Common Anchoring Protein
Authors: Coghlan Vincent M. , Perrino Brian A. , Howard Monique , Langeberg Lorene K. , Hicks James B. , Gallatin W. Michael , Scott John D.
Published: October 2006

Specificity of protein kinases and phosphatases may be achieved through compartmentalization with preferred substrates. In neurons, adenosine 3′,5′-monophosphate (cAMP)-dependent protein kinase (PKA) is localized at postsynaptic densities by association of its regulatory subunit with an A kinase anchor protein, AKAP79. Interaction cloning experiments demonstrated that AKAP79 also binds protein phosphatase 2B, or calcineurin (CaN). A ternary complex of PKA, AKAP, and CaN was isolated from bovine brain, and colocalization of the kinase and the phosphatase was established in neurites of cultured hippocampal neurons. The putative CaN-binding domain of AKAP79 is similar to that of the immunophilin FKBP-12, and AKAP79 inhibited CaN phosphatase activity. These results suggest that both PKA and CaN are targeted to subcellular sites by association with a common anchor protein and thereby regulate the phosphorylation state of key neuronal substrates.
A Hot Spot of Binding Energy in a Hormone-Receptor Interface
Authors: Clackson Tim , Wells James A.
Published: October 2006

The x-ray crystal structure of the complex between human growth hormone (hGH) and the extracellular domain of its first bound receptor (hGHbp) shows that about 30 side chains from each protein make contact. Individual replacement of contact residues in the hGHbp with alanine showed that a central hydrophobic region, dominated by two tryptophan residues, accounts for more than three-quarters of the binding free energy. This "functional epitope" is surrounded by less important contact residues that are generally hydrophilic and partially hydrated, so that the interface resembles a cross section through a globular protein. The functionally important residues on the hGHbp directly contact those on hGH. Thus, only a small and complementary set of contact residues maintains binding affinity, a property that may be general to protein-protein interfaces.
Biotherapy of B-cell precursor leukemia by targeting genistein to CD19-associated tyrosine kinases
Authors: Uckun F. M. , Evans W. E. , Forsyth C. J. , Waddick K. G. , Tuel-Ahlgren L. , Chelstrom L. M. , Burkhardt A. , Bolen J. , Myers D. E.
Published: October 2006

B-cell precursor (BCP) leukemia is the most common form of childhood cancer and the second most common form of acute leukemia in adults. Human BCP leukemia was treated in a severe combined immunodeficient mouse model by targeting of the tyrosine kinase inhibitor Genistein (Gen) to the B cell-specific receptor CD19 with the monoclonal antibody B43. The B43-Gen immunoconjugate bound with high affinity to BCP leukemia cells, selectively inhibited CD19-associated tyrosine kinases, and triggered rapid apoptotic cell death. At less than one-tenth the maximum tolerated dose more than 99.999 percent of human BCP leukemia cells were killed, which led to 100 percent long-term event-free survival from an otherwise invariably fatal leukemia. The B43-Gen immunoconjugate might be useful in eliminating leukemia cells in patients who have failed conventional therapy.
The Fas Death Factor
Authors: Nagata Shigekazu , Golstein Pierre
Published: October 2006

Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas-bearing cells. Various cells express Fas, whereas FasL is expressed predominantly in activated T cells. In the immune system, Fas and FasL are involved in down-regulation of immune reactions as well as in T cell-mediated cytotoxicity. Malfunction of the Fas system causes lymphoproliferative disorders and accelerates autoimmune diseases, whereas its exacerbation may cause tissue destruction.
Diverse Effects of the Guanine Nucleotide Exchange Factor RCC1 on RNA Transport
Authors: Cheng Yan , Dahlberg James E. , Lund Elsebet
Published: October 2006

Transport of RNAs within nuclei and through nuclear pore complexes (NPCs) are essential, but poorly understood, steps in gene expression. In experiments with mammalian cells, RCC1, the abundant nuclear guanine nucleotide exchange factor for the guanosine triphosphatase Ran/TC4, was shown to be required for nucleocytoplasmic transport of precursors of spliceosomal small nuclear RNAs (snRNAs), intranuclear transport of U3 snRNA, and processing of ribosomal RNAs, but not for export of transfer RNAs. It is proposed that guanosine triphosphate (GTP)-bound Ran/TC4 associates with ribonucleoprotein particles (RNPs) during intranuclear movement, and that GTP hydrolysis promotes deposition of RNPs at targeted sites such as NPCs or nucleoli.