bluuebunny/crossref_metadata_2025 huggingface dataset:
Chain Migration of Neuronal Precursors
Authors: Lois Carlos , García-Verdugo Jose-Manuel , Alvarez-Buylla Arturo
Published: October 2006

In the brain of adult mice, cells that divide in the subventricular zone of the lateral ventricle migrate up to 5 millimeters to the olfactory bulb where they differentiate into neurons. These migrating cells were found to move as chains through a well-defined pathway, the rostral migratory stream. Electron microscopic analysis of serial sections showed that these chains contained only closely apposed, elongated neuroblasts connected by membrane specializations. A second cell type, which contained glial fibrillary acidic protein, ensheathed the chains of migrating neuroblasts. Thus, during chain migration, neural precursors moved associated with each other and were not guided by radial glial or axonal fibers.
Role of Rho in Chemoattractant-Activated Leukocyte Adhesion Through Integrins
Authors: Laudanna Carlo , Campbell James J. , Butcher Eugene C.
Published: October 2006

Heterotrimeric guanine nucleotide binding protein (G protein)-linked receptors of the chemoattractant subfamily can trigger adhesion through leukocyte integrins, and in this role they are thought to regulate immune cell-cell interactions and trafficking. In lymphoid cells transfected with formyl peptide or interleukin-8 receptors, agonist stimulation activated nucleotide exchange on the small guanosine triphosphate-binding protein RhoA in seconds. Inactivation of Rho by C3 transferase exoenzyme blocked agonist-induced lymphocyte α4β1 adhesion to vascular cell adhesion molecule-1 and neutrophil β2 integrin adhesion to fibrinogen. These findings suggest that Rho participates in signaling from chemoattractant receptors to trigger rapid adhesion in leukocytes.
Role of a Peptide Tagging System in Degradation of Proteins Synthesized from Damaged Messenger RNA
Authors: Keiler Kenneth C. , Waller Patrick R. H. , Sauer Robert T.
Published: October 2006

Variants of λ repressor and cytochrome b
562
translated from messenger RNAs without stop codons were modified by carboxyl terminal addition of an
ssrA
-encoded peptide tag and subsequently degraded by carboxyl terminal-specific proteases present in both the cytoplasm and periplasm of
Escherichia coli
. The tag appears to be added to the carboxyl terminus of the nascent polypeptide chain by cotranslational switching of the ribosome from the damaged messenger RNA to
ssrA
RNA.
Phenotypes of Mouse
diabetes
and Rat
fatty
Due to Mutations in the OB (Leptin) Receptor
Authors: Chua Streamson C. , Chung Wendy K. , Wu-Peng X. Sharon , Zhang Yiying , Liu Shun-Mei , Tartaglia Louis , Leibel Rudolph L.
Published: October 2006

Mice harboring mutations in the
obese
(
ob
) and
diabetes
(
db
) genes display similar phenotypes, and it has been proposed that these genes encode the ligand and receptor, respectively, for a physiologic pathway that regulates body weight. The cloning of
ob
, and the demonstration that it encodes a secreted protein (leptin) that binds specifically to a receptor (OB-R) in the brain, have validated critical aspects of this hypothesis. Here it is shown by genetic mapping and genomic analysis that mouse
db
, rat
fatty
(a homolog of
db
), and the gene encoding the OB-R are the same gene.
Ligand Binding: Molecular Mechanics Calculation of the Streptavidin-Biotin Rupture Force
Authors: Grubmüller Helmut , Heymann Berthold , Tavan Paul
Published: October 2006

The force required to rupture the streptavidin-biotin complex was calculated here by computer simulations. The computed force agrees well with that obtained by recent single molecule atomic force microscope experiments. These simulations suggest a detailed multiple-pathway rupture mechanism involving five major unbinding steps. Binding forces and specificity are attributed to a hydrogen bond network between the biotin ligand and residues within the binding pocket of streptavidin. During rupture, additional water bridges substantially enhance the stability of the complex and even dominate the binding interactions. In contrast, steric restraints do not appear to contribute to the binding forces, although conformational motions were observed.
Researchers, Book Your Flights
Authors: Normile Dennis
Published: October 2006

A growing number of researchers, lured in part by Japan's world-class facilities, are learning that working in Japan can be fun—as well as scientifically profitable.
MIT Torn by Bitter Dispute Over Missile
Authors: Friedly Jock
Published: October 2006

Five years after the Gulf War, academics at the Massachusetts Institute of Technology (MIT) are still locked in a struggle over the Patriot's record in shooting down Iraqi Scud missiles. Ted Postol, a professor who specializes in arms control and national security, concluded that the Patriot was a near-total failure. But the debate at MIT now centers on Postol's claims that Patriot's manufacturer, Raytheon Corp., improperly stated that MIT engineering Professor Shaoul Ezekiel had debunked Postol's analyses. Ezekiel had never challenged Postol's analyses directly. Postol has accused Ezekiel of unethical conduct by not publicly refuting Raytheon's claim, but two MIT investigations have cleared Ezekiel of misconduct.
Funding Crisis Provokes Street Protests
Authors: Allakhverdov Andrey
Published: October 2006

Moscow—Researchers and technicians from the Russian Academy of Sciences took to the streets last week to protest the government's failure to turn over promised funding to the academy. The nonpayments have provoked a funding crisis that has shut down most research at academy institutes.
Putting Stiffness in Earth's Mantle
Authors: Kerr Richard A.
Published: October 2006

Whether or not the Earth's mantle gets stiffer at great depths is an issue that has bitterly divided geophysicists. If it does, the lower mantle may be sealed off from the upper mantle, as the composition of some surface rocks implies; if not, the mantle may mix from top to bottom, as other indicators suggest. A new study settles the issue, showing to most geophysicists' satisfaction that the mantle does stiffen drastically with depth. But this very stiff lower mantle is allowing theorists to find a middle ground between whole-mantle and layered mixing.
Middle to Late Paleozoic Atmospheric CO
2
Levels from Soil Carbonate and Organic Matter
Authors: Mora Claudia I. , Driese Steven G. , Colarusso Lee Ann
Published: October 2006

The stable carbon isotope compositions of ancient soil carbonate and coexisting soil organic matter indicate that atmospheric CO
2
levels decreased by a factor of 10 during the middle to late Paleozoic era. Proxy measurements of CO
2
were made by application of a soil carbonate CO
2
paleobarometer to a suite of paleosols that share key physical and chemical characteristics. The estimates agree with theoretical models that imply that a decrease in Paleozoic atmospheric CO
2
levels was associated with afforestation of the land surface by terrestrial plants and with global climate change leading to the extensive Permo-Carboniferous glaciation.
Imitation of
Escherichia coli
Aspartate Receptor Signaling in Engineered Dimers of the Cytoplasmic Domain
Authors: Cochran Andrea G. , Kim Peter S.
Published: October 2006

Transmembrane signaling by bacterial chemotaxis receptors appears to require a conformational change within a receptor dimer. Dimers were engineered of the cytoplasmic domain of the
Escherichia coli
aspartate receptor that stimulated the kinase CheA in vitro. The folding free energy of the leucine-zipper dimerization domain was harnessed to twist the dimer interface of the receptor, which markedly affected the extent of CheA activation. Response to this twist was attenuated by modification of receptor regulatory sites, in the same manner as adaptation resets sensitivity to ligand in vivo. These results suggest that the normal allosteric activation of the chemotaxis receptor has been mimicked in a system that lacks both ligand-binding and transmembrane domains. The most stimulatory receptor dimer formed a species of tetrameric size.
Model Estimations Biased by Truncated Expansions: Possible Artifacts in Seismic Tomography
Authors: Trampert Jeannot , Snieder Roel
Published: October 2006

In most linear imaging problems, where the model to be sought is expanded in a set of basis functions, it is common practice to truncate the set at a certain (arbitrary) level. The solution then depends on the chosen parameterization, and neglected basis functions may leak into the solution to produce artifacts in the retrieved model. An unbiased estimate of the coefficients of the true model may be obtained in the chosen finite basis set; here, a method to suppress leakage is illustrated on an example of global seismic tomography.
Radiation-Induced Diamond Formation in Uranium-Rich Carbonaceous Materials
Authors: Daulton Tyrone L. , Ozima Minoru
Published: October 2006

Nanometer-sized diamonds were identified by transmission electron microscopy in a uranium-rich, coal-like carbonaceous assemblage of Precambrian age. This observation, together with estimates of formation efficiencies, supports the hypothesis that diamond can form in carbonaceous material irradiated by the radioactive decay products of uranium. The results also suggest that the formation of carbonados cannot be sufficiently explained by a radiation mechanism alone.
Biomimetic Templating of Porous Lamellar Silicas by Vesicular Surfactant Assemblies
Authors: Tanev Peter T. , Pinnavaia Thomas J.
Published: October 2006

A biomimetic templating approach to the synthesis of lamellar silicas is demonstrated. The procedure is based on the hydrolysis and cross-linking of a neutral silicon alkoxide precursor in the interlayered regions of multilamellar vesicles formed from a neutral diamine bola-amphiphile. Unlike earlier surfactant-templating approaches, this method produces porous lamellar silicas (designated MSU-V) with vesicular particle morphology, exceptional thermal stability, a high degree of framework cross-linking, unusually high specific surface area and pore volume, and sorption properties that are typical of pillared lamellar materials. This approach circumvents the need for a separate pillaring step in building porosity into a lamellar host structure and offers new opportunities for the direct fabrication of adsorbents, catalysts, and nanoscale devices.
Enhanced Fidelity of 3TC-Selected Mutant HIV-1 Reverse Transcriptase
Authors: Wainberg Mark A. , Drosopoulos William C. , Salomon Horacio , Hsu Mayla , Borkow Gadi , Parniak Michael A. , Gu Zhengxian , Song Qingbin , Manne Jayanthi , Islam Sabina , Castriota Gino , Prasad Vinayaka R.
Published: October 2006

Monotherapy with (−)2′,3′-dideoxy-3′-thiacytidine (3TC) leads to the appearance of a drug-resistant variant of human immunodeficiency virus-type 1 (HIV-1) with the methionine-184 → valine (M184V) substitution in the reverse transcriptase (RT). Despite resulting drug resistance, treatment for more than 48 weeks is associated with a lower plasma viral burden than that at baseline. Studies to investigate this apparent contradiction revealed the following. (i) Titers of HIV-neutralizing antibodies remained stable in 3TC-treated individuals in contrast to rapid declines in those treated with azidothymidine (AZT). (ii) Unlike wild-type HIV, growth of M184V HIV in cell culture in the presence of d4T, AZT, Nevirapine, Delavirdine, or Saquinavir did not select for variants displaying drug resistance. (iii) There was an increase in fidelity of nucleotide insertion by the M184V mutant compared with wild-type enzyme.
High-Pressure Compounds in Methane-Hydrogen Mixtures
Authors: Somayazulu M. S. , Finger L. W. , Hemley R. J. , Mao H. K.
Published: October 2006

The effect of pressure on chemical interactions in molecular mixtures is important for problems spanning fundamental chemistry, planetary science, and materials science. Diamond-anvil cell studies reveal pressure-induced chemistry in the CH
4
-H
2
system. The system, which has no known compounds at ambient conditions, formed four molecular compounds, CH
4
(H
2
)
2
, (CH
4
)
2
H
2
, CH
4
(H
2
)
4
, and CH
4
H
2
, at pressures up to 10 gigapascals. These have been characterized by synchrotron single-crystal x-ray diffraction, polycrystalline x-ray diffraction, Raman spectroscopy, and visual observation. Although CH
4
(H
2
)
2
crystallizes in the MgZn
2
-type, hexagonal Laves phase structure, (CH
4
)H
2
has a body-centered tetragonal structure that is similar to that of Al
2
Cu. The 1:1 and 1:2 compounds are stable to at least 30 gigapascals.
Friedreich's Ataxia: Autosomal Recessive Disease Caused by an Intronic GAA Triplet Repeat Expansion
Authors: Campuzano Victoria , Montermini Laura , Moltò Maria Dolores , Pianese Luigi , Cossée Mireille , Cavalcanti Francesca , Monros Eugenia , Rodius François , Duclos Franck , Monticelli Antonella , Zara Federico , Cañizares Joaquin , Koutnikova Hana , Bidichandani Sanjay I. , Gellera Cinzia , Brice Alexis , Trouillas Paul , De Michele Giuseppe , Filla Alessandro , De Frutos Rosa , Palau Francisco , Patel Pragna I. , Di Donato Stefano , Mandel Jean-Louis , Cocozza Sergio , Koenig Michel , Pandolfo Massimo
Published: October 2006

Friedreich's ataxia (FRDA) is an autosomal recessive, degenerative disease that involves the central and peripheral nervous systems and the heart. A gene,
X25
, was identified in the critical region for the FRDA locus on chromosome 9q13. The gene encodes a 210-amino acid protein, frataxin, that has homologs in distant species such as
Caenorhabditis elegans
and yeast. A few FRDA patients were found to have point mutations in
X25
, but the majority were homozygous for an unstable GAA trinucleotide expansion in the first
X25
intron.
New Zealand's Leap Into Gene Therapy
Authors: Marshall Eliot
Published: October 2006

New Zealand's first-ever gene therapy experiment took place last week when researchers at Auckland Medical School treated two children with Canavan disease, the disease that figured in the movie
Lorenzo's Oil
. The test was the first targeted at a neurological disease other than brain cancer, and it used a novel “vector” to insert genes into the target cells. The chances of therapeutic benefit are considered slim, however. The treatment was developed mostly in the United States, where clinical trials of gene therapies must be approved by the Recombinant DNA Advisory Committee. Some RAC members have raised concerns that it may set a precedent for moving clinical tests outside RAC's jurisdiction.
Giant Merger Creates Biotech Power
Authors: Koenig Robert
Published: October 2006

Berlin—The announcement last week that the Swiss drug giants Sandoz and Ciba-Geigy plan to merge is the latest in a series of consolidations that is changing the face of the world's pharmaceutical industry. The two companies last year spent a total of more than $2 billion on R&D. The new joint company, to be called Novartis, is expected to be a force in genome-related research, although some pruning of overlapping research is expected.
Rat Study Sheds Light on Cocaine Craving
Authors: O'Brien Claire
Published: October 2006

To a cocaine addict, a small dose of the drug is bad news: It “primes” the brain's reward system, intensifying the craving for more cocaine. Now a team of researchers at Yale University reports in this issue of Science (
p. 1586
) that in rats, this craving appears to be associated with activation of one class of receptors for the neurotransmitter dopamine, called D
2
-like receptors. Activation of a second class of dopamine receptors, D
1
-like receptors, appears to reduce craving for the drug. If the same effect applied to humans, compounds that selectively activate D
1
-like receptors might be useful in preventing relapse of drug use in cocaine-dependent people.
Molecules on Ice
Authors: Clary David C.
Published: October 2006

Every spring over the Antarctic, an ozone hole forms—a localized region where the ozone concentration in the atmosphere is greatly reduced. The ozone is destroyed by a complex chain of chemical reactions beginning with hydrochloric acid. In his Perspective, Clary describes work published in the same issue by Gertner and Hynes (
p. 1563
) that identifies a new mechanism by which the HCl sticks to ice particles.
Common Principles of Protein Translocation Across Membranes
Authors: Schatz Gottfried , Dobberstein Bernhard
Published: October 2006

Most major systems that transport proteins across a membrane share the following features: an amino-terminal transient signal sequence on the transported protein, a targeting system on the cis side of the membrane, a hetero-oligomeric transmembrane channel that is gated both across and within the plane of the membrane, a peripherally attached protein translocation motor that is powered by the hydrolysis of nucleoside triphosphate, and a protein folding system on the trans side of the membrane. These transport systems are divided into two families: export systems that export proteins out of the cytosol, and import systems that transport proteins into cytosol-like compartments.
Targeting of Motor Proteins
Authors: Vallee Richard B. , Sheetz Michael P.
Published: October 2006

Microtubules are responsible for chromosome segregation and the movement and reorganization of membranous organelles. Many aspects of microtubule-based motility can be attributed to the action of motor proteins, producing force directed toward either end of microtubules. How these proteins are targeted to the appropriate organellar sites within the cell, however, has remained a mystery. Recent work has begun to define the targeting mechanism for two well-studied motor proteins, kinesin and cytoplasmic dynein.
Toward an Astrophysical Theory of Chondrites
Authors: Shu Frank H. , Shang Hsien , Lee Typhoon
Published: October 2006

The chondrules, calcium-aluminum-rich inclusions (CAIs), and rims in chondritic meteorites could be formed when solid bodies are lifted by the aerodynamic drag of a magnetocentrifugally driven wind out of the relative cool of a shaded disk close to the star into the heat of direct sunlight. For reasonable self-consistent parameters of the bipolar outflow, the base and peak temperatures reached by solid bodies resemble those needed to melt CAIs and chondrules. The process also yields a natural sorting mechanism that explains the size distribution of CAIs and chondrules, as well as their fine-grained and coarse-grained rims. After reentry at great distances from the original launch radius, the CAIs, chondrules, and their rims would be compacted with the ambient nebular dust comprising the matrices, forming the observed chondritic bodies.
A Permease-Oxidase Complex Involved in High-Affinity Iron Uptake in Yeast
Authors: Stearman Robert , Yuan Daniel S. , Yamaguchi-Iwai Yuko , Klausner Richard D. , Dancis Andrew
Published: October 2006

Iron must cross biological membranes to reach essential intracellular enzymes. Two proteins in the plasma membrane of yeast—a multicopper oxidase, encoded by the
FET3
gene, and a permease, encoded by the
FTR1
gene—were shown to mediate high-affinity iron uptake.
FET3
expression was required for FTR1 protein to be transported to the plasma membrane.
FTR1
expression was required for apo-FET3 protein to be loaded with copper and thus acquire oxidase activity. FTR1 protein also played a direct role in iron transport. Mutations in a conserved sequence motif of FTR1 specifically blocked iron transport.
Protein Folding Triggered by Electron Transfer
Authors: Pascher Torbjörn , Chesick John P. , Winkler Jay R. , Gray Harry B.
Published: October 2006

Rapid photochemical electron injection into unfolded ferricytochrome
c
titrated with 2.3 to 4.6 M guanidine hydrochloride (GuHCl) at pH 7 and 40°C produced unfolded ferrocytochrome, which then converted to the folded protein. Two folding phases were observed: a fast process with a time constant of 40 microseconds (4.6 M GuHCl), and a slower phase with a rate constant of 90 ± 20 per second (2.3 M GuHCl). The activation free energy for the slow step varied linearly with GuHCl concentration; the rate constant, extrapolated to aqueous solution, was 7600 per second. Electron-transfer methods can bridge the nanosecond to millisecond measurement time gap for protein folding.
Molecular Dynamics Simulation of Hydrochloric Acid Ionization at the Surface of Stratospheric Ice
Authors: Gertner Bradley J. , Hynes James T.
Published: October 2006

Molecular dynamics simulations were used to study the acid ionization of hydrochloric acid (HCl) at the basal plane surface of ice at 190 kelvin, as a model for the acid ionization process in Antarctic polar stratospheric clouds (PSCs). Initial conditions for HCl placement within the top bilayer of the ice lattice were selected on the basis of relevant dynamic equilibrium adsorption-desorption conditions. Free energy changes calculated for the first step in the stepwise acid ionization mechanism ranged from −5.8 to −6.7 kilocalories per mole for various likely initial conditions. These results indicate that acid ionization is thermodynamically favorable and that this process has important implications for ozone depletion mechanisms involving PSCs.
Iridium Metal in Chicxulub Impact Melt: Forensic Chemistry on the K-T Smoking Gun
Authors: Schuraytz Benjamin C. , Lindstrom David J. , Marín Luis E. , Martinez René R. , Mittlefehldt David W. , Sharpton Virgil L. , Wentworth Susan J.
Published: October 2006

Iridium concentrations in successively smaller subsplits of melt rock and melt breccia from the Chicxulub impact basin were tracked to isolate and identify iridium carrier phases. Iridium-rich particles were isolated from two samples, and a micrometer-scale, silicate-enclosed aggregate of subhedral iridium metal grains was identified in one, confirming earlier reports of iridium at ground zero of the impact at the Cretaceous-Tertiary (K-T) boundary. The aggregate may be either a phase formed after the collision or a relict of the Chicxulub basin-forming meteorite. In either case, its presence indicates that even among the largest impact structures on Earth, meteoritic components may be preserved within the crater.
Exchange of Carbon Dioxide by a Deciduous Forest: Response to Interannual Climate Variability
Authors: Goulden Michael L. , Munger J. William , Fan Song-Miao , Daube Bruce C. , Wofsy Steven C.
Published: October 2006

The annual net uptake of CO
2
by a deciduous forest in New England varied from 1.4 to 2.8 metric tons of carbon per hectare between 1991 and 1995. Carbon sequestration was higher than average in 1991 because of increased photosynthesis and in 1995 because of decreased respiration. Interannual shifts in photosynthesis were associated with the timing of leaf expansion and senescence. Shifts in annual respiration were associated with anomalies in soil temperature, deep snow in winter, and drought in summer. If this ecosystem is typical of northern biomes, interannual climate variations on seasonal time scales may modify annual CO
2
exchange in the Northern Hemisphere by 1 gigaton of carbon or more each year.
Human Foamy Virus Replication: A Pathway Distinct from That of Retroviruses and Hepadnaviruses
Authors: Yu Shuyuarn F. , Baldwin David N. , Gwynn Samuel R. , Yendapalli Suneetha , Linial Maxine L.
Published: October 2006

Human foamy virus (HFV) is the prototype of the
Spumavirus
genus of Retroviridae. In all other retroviruses, the
pol
gene products, including reverse transcriptase, are synthesized as Gag-Pol fusion proteins and are cleaved to functional enzymes during viral budding or release. In contrast, the Pol protein of HFV is translated from a spliced messenger RNA and lacks Gag domains. Infectious HFV particles contain double-stranded DNA similar in size to full-length provirus, suggesting that reverse transcription has taken place in viral particles before new rounds of infection, reminiscent of hepadnaviruses. These data suggest that foamy viruses possess a replication pathway containing features of both retroviruses and hepadnaviruses but distinct from both.
Similarities Between Initiation of V(D)J Recombination and Retroviral Integration
Authors: van Gent Dik C. , Mizuuchi Kiyoshi , Gellert Martin
Published: October 2006

In the first step of V(D)J recombination, the RAG1 and RAG2 proteins cleave DNA between a signal sequence and the adjacent coding sequence, generating a blunt signal end and a coding end with a closed hairpin structure. These hairpins are intermediates leading to the formation of assembled antigen receptor genes. It is shown here that the hairpins are formed by a chemical mechanism of direct trans-esterification, very similar to the early steps of transpositional recombination and retroviral integration. A minor variation in the reaction is sufficient to divert the process from transposition to hairpin formation.
Cell Cycle Regulation of E2F Site Occupation in Vivo
Authors: Zwicker Jörk , Liu Ningshu , Engeland Kurt , Lucibello Frances C. , Müller Rolf
Published: October 2006

DNA-binding E2F complexes have been identified throughout the mammalian cell cycle, including the transcriptionally inactive complexes with pocket proteins, which occur early in the prereplicative G
1
phase of the cycle, and the transactivating free E2F, which increases in late G
1
. Here, a regulatory B-
myb
promoter site was shown to bind with high affinity to free E2F and to E2F-pocket protein complexes in an indistinguishable way in vitro. In contrast, in vivo footprinting with NIH 3T3 cells demonstrated E2F site occupation specifically in early G
1
, when the B-
myb
promoter is inactive. These observations indicate that a novel mechanism governs E2F-DNA interactions during the cell cycle and emphasize the relevance of E2F site-directed transcriptional repression.
Rapid Degradation of the G
1
Cyclin Cln2 Induced by CDK-Dependent Phosphorylation
Authors: Lanker Stefan , Valdivieso M. Henar , Wittenberg Curt
Published: October 2006

Cyclins regulate the major cell cycle transitions in eukaryotes through association with cyclin-dependent protein kinases (CDKs). In yeast, G
1
cyclins are essential, rate-limiting activators of cell cycle initiation. G
1
-specific accumulation of one G
1
cyclin, Cln2, results from periodic gene expression coupled with rapid protein turnover. Site-directed mutagenesis of
CLN2
revealed that its phosphorylation provides a signal that promotes rapid degradation. Cln2 phosphorylation is dependent on the Cdc28 protein kinase, the CDK that it activates. These findings suggest that Cln2 is rendered self-limiting by virtue of its ability to activate its cognate CDK subunit.
Budget Freeze Nips Comet Camera
Authors: Gavaghan Helen
Published: October 2006

Europe's Rosetta spacecraft is scheduled to shadow the comet Wirtanen for 2 years early in the next century, sending back spectacular close-up views—a scientific and public relations bonanza. But there's a catch: Nobody seems willing to pay for a camera to take those close-up shots.
Fermat Prover Points to Next Challenges
Authors: Cipra Barry
Published: October 2006

With the proof of Fermat's Last Theorem now on the books, what's left for number theorists to do? Plenty, says Andrew Wiles, the Princeton University mathematician who knocked off the Last Theorem. In recent lectures, Wiles laid out the next challenges in the theory of elliptic curves—the cubic equations that are ubiquitous in mathematics and were at the heart of his attack on Fermat's problem. The powerful tools he developed for his proof may bring the next step much closer.
Shot Noise in Quantum Conductors
Authors: Kouwenhoven Leo
Published: October 2006

Electronic noise in a device is often an irritating source of interference. In very small quantum devices, however, noise may have interesting physical properties. In his Perspective, Kouwenhoven describes experiments with devices that allow the passage of electrons from one resevoir to another through a small channel. For some conditions, the electrons act more like quantum waves rather than particles and the electronic noise in this structure can be made to vanish completely.
On the Shape of C
6
H
6
+
Authors: Lindner R. , Müller-Dethlefs K. , Wedum E. , Haber K. , Grant E. R.
Published: October 2006

The benzene molecule serves as a benchmark among the aromatic hydrocarbons and has been the subject of numerous experimental and theoretical studies. Despite such intensive investigations, the precise structure of the benzene cation (C
6
H
6
+
) is not known. Now, experiments measuring high-resolution state-to-state threshold photoionization spectra of benzene concretely establish the terms of vibronic levels in the distorted cation that are split by higher order Jahn-Teller coupling between its
2
E
1g
electronic ground state and ν
6
e
2g
in-plane ring-bending vibrational mode. This assignment, in turn, sets the absolute energy phase of the vibronic pseudorotation in this coordinate and thereby offers a definitive experimental determination of the shape of the benzene cation.
Nonlinear Spectroscopy on a Single Quantum System: Two-Photon Absorption of a Single Molecule
Authors: Plakhotnik Taras , Walser Daniel , Pirotta Marco , Renn Alois , Wild Urs P.
Published: October 2006

Two-photon fluorescence excitation spectra of single diphenyloctatetraene molecules trapped in an
n
-tetradecane matrix were measured at cryogenic temperatures. The purely electronic zero-phonon line (transition at 444 nanometers) of these single molecules with a width of about 60 megahertz was excited by a continuous-wave, single-mode laser at 888 nanometers. Even though the two-photon absorption cross section is extremely small, a high photon count rate and low background allowed nonlinear spectroscopy to be extended to the single-molecule level. This experiment also suggests the possibility of two-photon single-molecule scanning microscopy.
Neonatal Tolerance Revisited: Turning on Newborn T Cells with Dendritic Cells
Authors: Ridge John Paul , Fuchs Ephraim J. , Matzinger Polly
Published: October 2006

For some time it has been thought that antigenic challenge in neonatal life is a tolerogenic rather than immunogenic event. Reexamination of the classic neonatal tolerance experiments of Billingham, Brent, and Medawar showed that tolerance is not an intrinsic property of the newborn immune system, but that the nature of the antigen-presenting cell determines whether the outcome is neonatal tolerance or immunization.
Induction of T
H
1 and T
H
2 Immunity in Neonatal Mice
Authors: Forsthuber Thomas , Yip Hualin C. , Lehmann Paul V.
Published: October 2006

The neonatal period has been thought of as a window in ontogeny, during which the developing immune system is particularly susceptible to tolerization. In the present study, the classic system for induction of neonatal tolerance to protein antigens was reexamined in mice. The presumably tolerogenic protocol was found to trigger a vigorous T helper cell type 2 (T
H
2) immune response. Thus, neonatal “tolerization” induces immune deviation, not tolerance in the immunological sense. Neonates are not immune privileged but generate T
H
2 or T
H
1 responses, depending on the mode of immunization.
Enhancement of Antitumor Immunity by CTLA-4 Blockade
Authors: Leach Dana R. , Krummel Matthew F. , Allison James P.
Published: October 2006

One reason for the poor immunogenicity of many tumors may be that they cannot provide signals for CD28-mediated costimulation necessary to fully activate T cells. It has recently become apparent that CTLA-4, a second counterreceptor for the B7 family of costimulatory molecules, is a negative regulator of T cell activation. Here, in vivo administration of antibodies to CTLA-4 resulted in the rejection of tumors, including preestablished tumors. Furthermore, this rejection resulted in immunity to a secondary exposure to tumor cells. These results suggest that blockade of the inhibitory effects of CTLA-4 can allow for, and potentiate, effective immune responses against tumor cells.
Abnormal Centrosome Amplification in the Absence of p53
Authors: Fukasawa Kenji , Choi Taesaeng , Kuriyama Ryoko , Rulong Shen , Woude George F. Vande
Published: October 2006

The centrosome plays a vital role in mitotic fidelity, ensuring establishment of bipolar spindles and balanced chromosome segregation. Centrosome duplication occurs only once during the cell cycle and is therefore highly regulated. Here, it is shown that in mouse embryonic fibroblasts (MEFs) lacking the p53 tumor suppressor protein, multiple copies of functionally competent centrosomes are generated during a single cell cycle. In contrast, MEFs prepared from normal mice or mice deficient in the retinoblastoma tumor suppressor gene product do not display these abnormalities. The abnormally amplified centrosomes profoundly affect mitotic fidelity, resulting in unequal segregation of chromosomes. These observations implicate p53 in the regulation of centrosome duplication and suggest one possible mechanism by which the loss of p53 may cause genetic instability.
A Piece of the Dinosaur Killer Found?
Authors: Kerr Richard A.
Published: October 2006

Geologists may have found a piece of the rock that killed the dinosaurs. A sample of 65-million-year-old ooze from the North Pacific has yielded what seems to be a fossil meteorite, just millimeters across. It fell into the sediments at the same geologic instant as a 10-kilometer object struck the Yucatán, probably triggering the mass extinction that wiped out the dinosaurs. Assuming the rock is a piece of the shattered impacter, its composition implies that the dinosaur killer was an asteroid, not a comet, as some researchers have speculated.
Interferometer Maps Cosmic Microwaves on the Cheap
Authors: Watson Andrew
Published: October 2006

Cambridge, U.K.—With a relatively cheap prototype ground-based telescope, a British team has created an image of the cosmic microwave background—the faint echo of the big bang—that is many times sharper than those obtained from balloons and satellites. The secret of the instrument's sharp vision is interferometry: combining the signals from separate antennas into a single image. And while the image is largely a proof of principle, it is tantalizing astronomers by showing hot spots—peaks in the density of the primordial universe—that may mark the origins of present-day galaxy clusters.
Warm Climate Surprises
Authors: Overpeck Jonathan T.
Published: October 2006

The present climate, which falls between the last ice age and the next, is relatively stable. New data on past climate change, however, indicates that the climate is capable of undergoing abrupt changes from one mode to another. In his Perspective, Overpeck describes the current research into the history of climate change and how it might influence our thinking about future climate variation.
Cancer Risk of Low-Level Exposure
Authors: Goldman Marvin
Published: October 2006

In his Perspective, Goldman argues that new scientific data on the carcinogenic effects of low-level exposure to radiation indicate that our national policies on allowable limits need to be revised.
Enter
Listeria
, Unruffled
Authors: Gallagher Richard B.
Published: October 2006

Gallagher reports on a new finding, in a recent paper in
Cell
(Mengaud
et al.
, vol. 84, p. 923), on the mechanism by which the Gram-positive bacteria
Listeria
is taken up into the cells of its mammalian host.
Listeria
uses the cell-surface protein E-cadherin as a receptor for entry.
Alpe Arami: A Peridotite Massif from Depths of More Than 300 Kilometers
Authors: Dobrzhinetskaya Larissa , Green Harry W. , Wang Su
Published: October 2006

The abundance of FeTiO
3
and chromite precipitates in olivine of the Alpe Arami peridotite massif, Switzerland, requires a much higher solubility for highly charged cations than is found in mantle xenoliths from depths of 250 kilometers. Three previously unknown crystal structures of FeTiO
3
were identified that indicate that the originally exsolved phase was the high-pressure perovskite polymorph of ilmenite, implying a minimum depth of origin of 300 kilometers. These observations, coupled with the unique lattice preferred orientation of olivine, further suggest that the original composition of olivine may reflect that of a precursor phase, perhaps wadsleyite, that is stable only at depths greater than 400 kilometers.
Constraints on Rates of Granitic Magma Transport from Epidote Dissolution Kinetics
Authors: Brandon Alan D. , Creaser Robert A. , Chacko Thomas
Published: October 2006

Epidote is stable only at high pressure in granitic magmas but is found in magmas crystallized at shallow crustal levels. This observation suggests qualitatively that magma transport is sufficiently rapid to prevent complete epidote resorption. Experimental measurements of epidote dissolution showed that the presence of epidote implies that magma transport from the deep crust in these systems was rapid and that the transport was by dikes rather than diapirs.
Caste-Selective Pheromone Biosynthesis in Honeybees
Authors: Plettner Erika , Slessor Keith N. , Winston Mark L. , Oliver James E.
Published: October 2006

Queen and worker honeybees (
Apis mellifera
L.) produce a caste-related blend of functionalized 8- and 10-carbon fatty acids in their mandibular glands. The biological functions of these compounds match the queen's reproductive and the worker's nonreproductive roles in the colony. Studies with deuterated substrates revealed that the biosynthesis of these acids begins with stearic acid, which is hydroxylated at the 17th or 18th position. The 18-carbon hydroxy acid chains are shortened, and the resulting 10-carbon hydroxy acids are oxidized in a caste-selective manner, thereby determining many of the functional differences between queens and workers.
Inhibition of HIV-1 Replication in Lymphocytes by Mutants of the Rev Cofactor eIF-5A
Authors: Bevec Dorian , Jaksche Herbert , Oft Martin , Wöhl Thorsten , Himmelspach Michèle , Pacher Alexandra , Schebesta Michael , Koettnitz Karl , Dobrovnik Marika , Csonga Robert , Lottspeich Friedrich , Hauber Joachim
Published: October 2006

Eukaryotic initiation factor 5A (eIF-5A) is a cellular cofactor required for the function of the human immunodeficiency virus type-1 (HIV-1) Rev trans-activator protein. The majority of a set of eIF-5A mutants did not support growth of yeast cells having an inactivated genomic copy of eIF-5A, indicating that the introduced mutation eliminated eIF-5A activity. Two nonfunctional mutants, eIF-5AM13 and eIF-5AM14, retained their binding capacity for the HIV-1 Rev response element:Rev complex. Both mutants were constitutively expressed in human T cells. When these T cells were infected with replication-competent HIV-1, virus replication was inhibited. The eIF-5AM13 and eIF-5AM14 proteins blocked Rev trans-activation and Rev-mediated nuclear export.
Translational Control of p27
Kip1
Accumulation During the Cell Cycle
Authors: Hengst Ludger , Reed Steven I.
Published: October 2006

Cell cycle phase transitions in eukaryotic cells are driven by regulation of the activity of protein kinases known as cyclin-dependent kinases (Cdks). A broad spectrum Cdk-inhibitory activity associated with a 28-kilodalton protein (p28
Ick1
) was induced in cells treated with the drug lovastatin or upon density-mediated growth arrest and was periodic in the cell cycle, with peak activity in G
1
. The p28
Ick1
protein was shown to be identical to p27
Kip1
, and the periodic or induced inhibitory activity resulted from a periodic accumulation of the protein. Variations in the amount of p27 protein occurred, whereas the abundance of the p27 messenger RNA remained unchanged. In every instance investigated, the posttranscriptional alteration of p27 protein levels was achieved in part by a mechanism of translational control, although in density-arrested fibroblasts and thymidine-arrested HeLa cells the half-life of the protein was also changed.
An RNA Polymerase II Elongation Factor Encoded by the Human
ELL
Gene
Authors: Shilatifard Ali , Lane William S. , Jackson Kenneth W. , Conaway Ronald C. , Conaway Joan W.
Published: October 2006

The human
ELL
gene on chromosome 19 undergoes frequent translocations with the
trithorax
-like
MLL
gene on chromosome 11 in acute myeloid leukemias. Here,
ELL
was shown to encode a previously uncharacterized elongation factor that can increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by polymerase at multiple sites along the DNA. Functionally, ELL resembles Elongin (SIII), a transcription elongation factor regulated by the product of the von Hippel-Lindau (
VHL
) tumor suppressor gene. The discovery of a second elongation factor implicated in oncogenesis provides further support for a close connection between the regulation of transcription elongation and cell growth.
Role of the Nuclear Transport Factor p10 in Nuclear Import
Authors: Nehrbass Ulf , Blobel Günter
Published: October 2006

The nuclear import factor p10 was cloned from
Saccharomyces cerevisiae
and found to be essential. The protein p10 can bind directly to several peptide repeat-containing nucleoporins. It also binds to the guanosine triphosphatase (GTPase) Ran in its guanosine diphosphate (GDP)-bound form and to karyopherin β. Assembly of the karyopherin heterodimer on immobilized nucleoporin yielded cooperative binding of p10 and Ran-GDP. Addition of GTP to this pentameric complex led to dissociation of karyopherin α, presumably via in situ formation of Ran-GTP from Ran-GDP. Thus, p10 appears to coordinate the Ran-dependent association and dissociation reactions underlying nuclear import.
Looking for the Evidence in Medicine
Authors: Taubes Gary
Published: October 2006

Medical treatments areThe advent of electronic often dictated by authority, personal experience, and habit, but a 2-year-old collaboration of several thousand doctors and other researchers is working to change that. Known as the Cochrane Collaboration, the British-led effort is literally hand searching the world's literature to find and review all of the randomized control trials ever done—as many as a million of them. Updated regularly, the Cochrane reviews should synthesize the latest knowledge about every therapy or intervention and give its implications for practice and research. The effort could transform the way doctors make treatment decisions, but some experts worry that the reviews will look more definitive than they are, giving rise to a new dogma.
No Women Chemists at Women's College
Authors: Roush Wade
Published: October 2006

Smith College, an elite women's school in Massachusetts, has had no tenured women chemists for the past 38 years, although comparable institutions now have between one and five tenured women chemists apiece. In February, Smith extended its streak, rejecting physical chemist Sharon Palmer's tenure bid, despite unanimous support for her from the department. The rejection—due to what the school says is a poor publication record—has prompted distress both on and off campus. (Also see last week's special issue on “
Maintaining Diversity in Science
.”)
Ceramic Shrinks When the Heat Goes On
Authors: Service Robert F.
Published: October 2006

It's hard to break the laws of physics, but sometimes one can bend the rules. Take the well-founded principle that more heat means more size: Added energy—heat—usually causes atoms to swing around more violently, taking up more space and causing materials to expand. But on page
90
of this issue, a group of researchers describe a ceramic that's found a huge loophole in the rule: It steadily shrinks as the temperature rises over 1000 degrees. The slimming secret, the scientists say, is in the material's zirconium-tungsten-oxygen lattice.
Tilting Against a Major Theory of Movement Control
Authors: Pennisi Elizabeth
Published: October 2006

For years, neuroscientists have thought the brain controls movements, such as those of the arm, by making use of the natural springiness of muscles, combined with reflexes, and not by calculating all the forces needed to get a limb to its final destination. But a new test of that theory, described in a report on page
117
, suggests that's not the case—that the brain is in fact in full control of the muscle contractions that move the arm from one place to another.
No "End of History" for Photolyases
Authors: Sancar Aziz
Published: October 2006

In a process called photoreactivation, blue light reverses the chemical damage done to DNA by ultraviolet light. One mediator of this effect is the enzyme CPD photolyase; a second photolyase, (6-4)photolyase, is now reported from Drosophila in a paper in this week's issue (Todo
et al.
,
p. 109
). In his Perspective, Sancar describes how this discovery defines a family of light-sensitive enzymes that also includes the blue-light receptors of plants and why it represents a reawakening of the photolyase field.
Lymphocyte Homing and Homeostasis
Authors: Butcher Eugene C. , Picker Louis J.
Published: October 2006

The integration and control of systemic immune responses depends on the regulated trafficking of lymphocytes. This lymphocyte “homing” process disperses the immunologic repertoire, directs lymphocyte subsets to the specialized microenvironments that control their differentiation and regulate their survival, and targets immune effector cells to sites of antigenic or microbial invasion. Recent advances reveal that the exquisite specificity of lymphocyte homing is determined by combinatorial “decision processes” involving multistep sequential engagement of adhesion and signaling receptors. These homing-related interactions are seamlessly integrated into the overall interaction of the lymphocyte with its environment and participate directly in the control of lymphocyte function, life-span, and population dynamics. In this article a review of the molecular basis of lymphocyte homing is presented, and mechanisms by which homing physiology regulates the homeostasis of immunologic resources are proposed.
Population Biology of Antigen Presentation by MHC Class I Molecules
Authors: Parham Peter , Ohta Tomoko
Published: October 2006

In principle, the function of major histocompatibility complex (MHC) molecules is simple: to bind a peptide and engage a T cell. In practice, placing this function within the context of the immune response begs questions of population biology: How does the immune response emerge from the interactions among populations of peptides, T cells, and MHC molecules? Within a population of vertebrates, how does MHC polymorphism stamp individuality on the response? Does polymorphism confer differential advantages in responding to parasites? How are the pressures on the MHC reflected in turnover of alleles? The role of mutation, recombination, selection, and drift in the generation and maintenance of MHC class I polymorphism are considered.
Imprint Lithography with 25-Nanometer Resolution
Authors: Chou Stephen Y. , Krauss Peter R. , Renstrom Preston J.
Published: October 2006

A high-throughput lithographic method with 25-nanometer resolution and smooth vertical sidewalls is proposed and demonstrated. The technique uses compression molding to create a thickness contrast pattern in a thin resist film carried on a substrate, followed by anisotropic etching to transfer the pattern through the entire resist thickness. Metal patterns with a feature size of 25 nanometers and a period of 70 nanometers were fabricated with the use of resist templates created by imprint lithography in combination with a lift-off process. With further development, imprint lithography should allow fabrication of sub-10-nanometer structures and may become a commercially viable technique for manufacturing integrated circuits and other nanodevices.
Negative Thermal Expansion from 0.3 to 1050 Kelvin in ZrW
2
O
8
Authors: Mary T. A. , Evans J. S. O. , Vogt T. , Sleight A. W.
Published: October 2006

Negative thermal expansion was found for ZrW
2
O
8
from 0.3 kelvin to its decomposition temperature of about 1050 kelvin. Both neutron and x-ray diffraction data were used to solve and refine the structure of this compound at various temperatures. Cubic symmetry persists for ZrW
2
O
8
over its entire stability range. Thus, the negative thermal expansion behavior is isotropic. Essentially the same behavior was found for isostructural HfW
2
O
8
. No other materials are known to exhibit such behavior over such a broad temperature range. These materials are finding applications as components in composites in order to reduce the composites' overall thermal expansion to near zero.