bluuebunny/crossref_metadata_2025 huggingface dataset:
Closing In on a Stomach-Sparing Aspirin Substitute
Authors: Service Robert F.
Published: October 2006

Chronic use of aspirin and other so-called nonsteroidal anti-inflammatory drugs (NSAIDs) can cause stomach bleeding, kidney failure, or worse. The problem is that the compounds not only subdue a key enzyme involved in triggering inflammation and pain; they also stifle a nearly identical enzyme that helps maintain tissues such as the stomach lining. Now researchers at a number of drug companies are making progress toward “superaspirins”—compounds capable of discriminating between the twin enzymes, which would enable them to fight pain without causing dangerous side effects.
Visualizing the Logic Behind RNA Self-Assembly
Authors: Michel François , Westhof Eric
Published: October 2006

The crystal structure of the
Tetrahymena
intron, the first RNA shown to have catalytic activity, has been solved [see the two papers by Cate
et al
. in this week's issue (
p. 1678
and
p. 1696
)]. Michel and Westhof discuss, in their Perspective, the new structural features that emerge from this new view of RNA.
Dynamic Control and Amplification of Molecular Chirality by Circular Polarized Light
Authors: Huck Nina P. M. , Jager Wolter F. , de Lange Ben , Feringa Ben L.
Published: October 2006

The enantiomers of a racemic photoresponsive material represent two distinct states that can be modulated with irradiation at a single wavelength by changing the handedness of the light. Dynamic control over molecular chirality was obtained by the interconversion of enantiomers of helically shaped molecules with either left or right circular polarized light (CPL). Photoresolution of the bistable compound as a dopant in a nematic liquid crystalline phase by CPL irradiation led to a chiral mesoscopic phase. The chiral information inherent to CPL is therefore transmitted to the bistable molecule, followed by amplification and macroscopic expression of the chirality.
A Revised Chronology for Mississippi River Subdeltas
Authors: Törnqvist Torbjörn E. , Kidder Tristram R. , Autin Whitney J. , van der Borg Klaas , de Jong Arie F. M. , Klerks Cornelis J. W. , Snijders Els M. A. , Storms Joep E. A. , van Dam Remke L. , Wiemann Michael C.
Published: October 2006

Radiocarbon measurements by accelerator mass spectrometry relating to three of the four late Holocene Mississippi River subdeltas yielded consistent results and were found to differ by up to 2000 carbon-14 years from previously inferred ages. These geological data are in agreement with archaeological carbon-14 data and stratigraphic ages based on ceramic seriation and were used to develop a revised chronologic framework, which has implications for prehistoric human settlement patterns, coastal evolution and wetland loss, and sequence-stratigraphic interpretations.
A Plea to Protect Threatened Collections
Authors: Williams Nigel
Published: October 2006

Cambridge, U.K.—As species after species slide into extinction around the globe, natural history museums, with their vast repositories of specimens, provide an increasingly important record of past biodiversity and a source of data for future studies. But the central message from the Second World Congress on the Preservation and Conservation of Natural History Collections last month is that the museums themselves are a threatened species. Many collections, particularly in developing countries, may even become extinct withouta concerted effort to preserve them.
In Boston, a Revolutionary Experience
Authors: Roush Wade
Published: October 2006

Boston—Science policy-makers in Washington have been urging professors to focus more on science literacy for the vast majority of students who won't themselves become researchers. A new program at Northeastern University in Boston does just that by integrating science and the humanities. Geology professors are working on their students' writing skills, while music professors incorporate the physics of sound in their classes.
Quick Work Draws Scientific Praise, Colleagues' Complaints
Authors: Cohen Jon
Published: October 2006

When Stephen O'Brien quickly put together a powerful analysis of the link between genetic mutations and susceptibility to HIV infection, he set off a flap among some colleagues and competitors. O'Brien analyzed DNA from cell lines he had established from large numbers of blood samples provided by other investigators, some of whom say they were not aware of the study until a draft manuscript was circulated. Others complained that his readyaccess to the cell lines gave him an unfair advantage. O'Brien, who included as co-authors those who provided samples, says the work was covered by collaborative agreements. Theflap highlights an issue that is becoming increasingly important in biomedical research: Who should control research on scarce samples?
A Parallel Spliceosome
Authors: Nilsen Timothy W.
Published: October 2006

In this issue of
Science
, Tarn and Steitz (
p. 1824
) report the identification of two new RNAs that reside in the special spliceosome that acts on the rare AT-AC class of introns. In his Perspective, Nilsen describes why the now complete description of the RNA components of this spliceosome has larger implications for splicing mechanisms in general.
Noble Gases and Earth's Accretion
Authors: Harper Charles L. , Jacobsen Stein B.
Published: October 2006

Earth probably accreted in two stages corresponding to conditions before and after the removal of gas from the nebular disk. Helium and neon in the mantle primarily record a solarlike component likely incorporated during the first stage by solution into a magma ocean blanketed under a massive protoatmosphere of molecular hydrogen and helium. The heavier noble gases primarily reflect a meteoritic (planetary) component trapped in accreted planetesimals. This model provides a possible explanation for the reduced and oxidized accretion stages inferred from siderophile elements and may explain why the present mantle appears to be too oxidized to be in equilibrium with the core.
Copper Sources, Metal Production, and Metals Trade in Late Postclassic Mesoamerica
Authors: Hosler Dorothy , Macfarlane Andrew
Published: October 2006

Copper ore sources exploited during the Late Postclassic Period (1300 to 1521 A.D.) were located by means of lead isotope analyses of copper ores from 15 deposits in West Mexico, Oaxaca, and Veracruz and of 171 copper artifacts from nine Mesoamerican archaeological sites in West Mexico and in southern, central, and northeastern Mesoamerica. West Mexican ores provided copper metal for most artifacts from the west Mexican settlements of Atoyac and Urichu, as well as for some artifacts from Aztec towns, Huastec centers, a Maya site, and settlements in Oaxaca and Chiapas. West Mexico was not marginal to Mesoamerican events but played the primary role in the production and distribution of copper and bronze artifacts, one of Mesoamerica's key exotic goods.
Methane Hydrate and Free Gas on the Blake Ridge from Vertical Seismic Profiling
Authors: Holbrook W. Steven , Hoskins Hartley , Wood Warren T. , Stephen Ralph A. , Lizarralde Daniel
Published: October 2006

Seismic velocities measured in three drill holes through a gas hydrate deposit on the Blake Ridge, offshore South Carolina, indicate that substantial free gas exists to at least 250 meters beneath the bottom-simulating reflection (BSR). Both methane hydrate and free gas exist even where a clear BSR is absent. The low reflectance, or blanking, above the BSR is caused by lithologic homogeneity of the sediments rather than by hydrate cementation. The average methane hydrate saturation above the BSR is relatively low (5 to 7 percent of porosity), which suggests that earlier global estimates of methane in hydrates may be too high by as much as a factor of 3.
Initiation of Runaway Cell Death in an
Arabidopsis
Mutant by Extracellular Superoxide
Authors: Jabs Thorsten , Dietrich Robert A. , Dangl Jeffery L.
Published: October 2006

Reactive oxygen intermediates (ROIs) regulate apoptosis during normal development and disease in animals. ROIs are also implicated in hypersensitive resistance responses of plants against pathogens.
Arabidopsis
lsd1
mutants exhibited impaired control of cell death in the absence of pathogen and could not control the spread of cell death once it was initiated. Superoxide was necessary and sufficient to initiate lesion formation; it accumulated before the onset of cell death and subsequently in live cells adjacent to spreading
lsd1
lesions. Thus, runaway cell death seen in
lsd1
plants reflected abnormal accumulation of superoxide and lack of responsiveness to signals derived from it.
Genetic Restriction of HIV-1 Infection and Progression to AIDS by a Deletion Allele of the
CKR5
Structural Gene
Authors: Dean Michael , Carrington Mary , Winkler Cheryl , Huttley Gavin A. , Smith Michael W. , Allikmets Rando , Goedert James J. , Buchbinder Susan P. , Vittinghoff Eric , Gomperts Edward , Donfield Sharyne , Vlahov David , Kaslow Richard , Saah Alfred , Rinaldo Charles , Detels Roger , O'Brien Stephen J.
Published: October 2006

The chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4
+
T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). The
CKR5
structural gene was mapped to human chromosome 3p21, and a 32-base pair deletion allele (
CKR5Δ32
) was identified that is present at a frequency of ∼0.10 in the Caucasian population of the United States. An examination of 1955 patients included among six well-characterized acquired immunodeficiency syndrome (AIDS) cohort studies revealed that 17 deletion homozygotes occurred exclusively among 612 exposed HIV-1 antibody-negative individuals (2.8 percent) and not at all in 1343 HIV-1-infected individuals. The frequency of
CKR5
deletion heterozygotes was significantly elevated in groups of individuals that had survived HIV-1 infection for more than 10 years, and, in some risk groups, twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in
CKR5
deletion heterozygotes than in individuals homozygous for the normal
CKR5
gene. The
CKR5Δ32
deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.
Mechanism of Inhibition of HIV-1 Reverse Transcriptase by Nonnucleoside Inhibitors
Authors: Spence Rebecca A. , Kati Warren M. , Anderson Karen S. , Johnson Kenneth A.
Published: October 2006

The mechanism of inhibition of HIV-1 reverse transcriptase by three nonnucleoside inhibitors is described. Nevirapine, O-TIBO, and CI-TIBO each bind to a hydrophobic pocket in the enzyme-DNA complex close to the active site catalytic residues. Pre-steady-state kinetic analysis was used to establish the mechanism of inhibition by these noncompetitive inhibitors. Analysis of the pre-steady-state burst of DNA polymerization indicated that inhibitors blocked the chemical reaction, but did not interfere with nucleotide binding or the nucleotide-induced conformational change. Rather, in the presence of saturating concentrations of the inhibitors, the nucleoside triphosphate bound tightly (
K
d
, 100 nM), but nonproductively. The data suggest that an inhibitor combining the functionalities of a nonnucleoside inhibitor and a nucleotide analog could bind very tightly and specifically to reverse transcriptase and could be effective in the treatment of AIDS.
Involvement of CRAF1, a relative of TRAF, in CD40 signaling
Authors: Cheng Genhong , Cleary Aileen M. , Ye Zheng-sheng , Hong David I. , Lederman Seth , Baltimore David
Published: October 2006

CD40 is a receptor on the surface of B lymphocytes, the activation of which leads to B cell survival, growth, and differentiation. A yeast two-hybrid screen identified a gene,
CRAF1
, encoding a protein that interacts directly with the CD40 cytoplasmic tail through a region of similarity to the tumor necrosis factor-α (TNF-α) receptor-associated factors. Overexpression of a truncated
CRAF1
gene inhibited CD40-mediated up-regulation of CD23. A region of
CRAF1
was similar to the TNF-α receptor-associated factors TRAF1 and TRAF2 and so defined a shared TRAF-C domain that was necessary and sufficient for CD40 binding and homodimerization. The CRAF1 sequence also predicted a long amphipathic helix, a pattern of five zinc fingers, and a zinc ring finger. It is likely that other members of the TNF receptor superfamily use
CRAF
-related proteins in their signal transduction processes.
Altered Cytokine Export and Apoptosis in Mice Deficient in Interleukin-1β Converting Enzyme
Authors: Kuida Keisuke , Lippke Judith A. , Ku George , Harding Matthew W. , Livingston David J. , Su Michael S.-S. , Flavell Richard A.
Published: October 2006

The interleukin-1β (IL-1β) converting enzyme (ICE) processes the inactive IL-1β precursor to the proinflammatory cytokine. Adherent monocytes from mice harboring a disrupted ICE gene (ICE
-/-
) did not export IL-1β or interleukin-1α (IL-1α) after stimulation with lipopolysaccharide. Export of tumor necrosis factor-α and interleukin-6 (IL-6) from these cells was also diminished. Thymocytes from ICE
-/-
mice were sensitive to apoptosis induced by dexamethasone or ionizing radiation, but were resistant to apoptosis induced by Fas antibody. Despite this defect in apoptosis, ICE
-/-
mice proceed normally through development.
Antigen-Specific Development of Primary and Memory T Cells in Vivo
Authors: McHeyzer-Williams Michael G. , Davis Mark M.
Published: October 2006

The expansion and contraction of specific helper T cells in the draining lymph nodes of normal mice after injection with antigen was followed. T cell receptors from purified primary and memory responder cells had highly restricted junctional regions, indicating antigen-driven selection. Selection for homogeneity in the length of the third complementarity-determining region (CDR3) occurs before selection for some of the characteristic amino acids, indicating the importance of this parameter in T cell receptor recognition. Ultimately, particular T cell receptor sequences come to predominate in the secondary response and others disappear, showing the selective preservation or expansion of specific T cell clones.
Specific DNA-RNA Hybrid Binding by Zinc Finger Proteins
Authors: Shi Yigong , Berg Jeremy M.
Published: October 2006

Zinc finger proteins of the Cys
2
His
2
type represent a large class of proteins that have been assumed to function by means of specific interactions with DNA. Experiments motivated by structural characteristics of zinc finger protein-DNA complexes revealed that certain zinc finger proteins bound DNA-RNA hybrids with affinities comparable to or greater than those for DNA duplexes. The interactions between the zinc finger proteins and the DNA-RNA hybrids were dependent on which strand was RNA and were sequence-specific. Thus, interactions with DNA-RNA hybrids should be considered with regard to the biological roles of zinc finger proteins.
Initiation of Protein Synthesis by the Eukaryotic Translational Apparatus on Circular RNAs
Authors: Chen Chang-you , Sarnow Peter
Published: October 2006

The ribosome scanning model predicts that eukaryotic ribosomal 40
S
subunits enter all messenger RNAs at their 5′ ends. Here, it is reported that eukaryotic ribosomes can initiate translation on circular RNAs, but only if the RNAs contain internal ribosome entry site elements. Long-repeating polypeptide chains were synthesized from RNA circles with continuous open reading frames. These results indicate that ribosomes can translate such RNA circles for multiple consecutive rounds and that the free 5′ end of a messenger RNA is not necessarily the entry point for 40
S
subunits.
Generation of Memory B Cells and Plasma Cells in Vitro
Authors: Arpin Christophe , Déchanet Julie , Van Kooten Cees , Merville Pierre , Grouard Géraldine , Brière Francine , Banchereau Jacques , Liu Yong-Jun
Published: October 2006

After germinal center B cells undergo somatic mutation and antigen selection, they become either memory B cells or plasma cells, but the signal requirements that control entry into either pathway have been unclear. When purified human germinal center cells were cultured with interleukin-2, interleukin-10, and cells expressing CD40 ligand, cells with characteristics of memory B cells were generated. Removal of CD40 ligand from the system resulted in terminal differentiation of germinal center B cells into cells with the characteristics of plasma cells. These results indicate that CD40 ligand directs the differentiation of germinal center B cells toward memory B cells rather than toward plasma cells.
Anharmonic Wave Functions of Proteins: Quantum Self-Consistent Field Calculations of BPTI
Authors: Roitberg Adrian , Gerber R. Benny , Elber Ron , Ratner Mark A.
Published: October 2006

The harmonic approximation for the potential energy of proteins is known to be inadequate for the calculation of many protein properties. To study the effect of anharmonic terms on protein vibrations, the anharmonic wave functions for the ground state and low-lying excited states of the bovine pancreatic trypsin inhibitor (BPTI) were calculated. The results suggest that anharmonic treatments are essential for protein vibrational spectroscopy. The calculation uses the vibrational self-consistent field approximation, which includes anharmonicity and interaction among modes in a mean-field sense. Properties obtained include the quantum coordinate fluctuations, zero-point energies, and the vibrational absorption spectrum.
Mutations in Fas Associated with Human Lymphoproliferative Syndrome and Autoimmunity
Authors: Rieux-Laucat F. , Le Deist F. , Hivroz C. , Roberts I. A. G. , Debatin K. M. , Fischer A. , de Villartay J. P.
Published: October 2006

Fas (also known as Apo1 and CD95) is a cell surface receptor involved in apoptotic cell death. Fas expression and function were analyzed in three children (including two siblings) with a lymphoproliferative syndrome, two of whom also had autoimmune disorders. A large deletion in the gene encoding Fas and no detectable cell surface expression characterized the most affected patient. Clinical manifestations in the two related patients were less severe: Fas-mediated apoptosis was impaired and a deletion within the intracytoplasmic domain was detected. These findings illustrate the crucial regulatory role of Fas and may provide a molecular basis for some autoimmune diseases in humans.
A Role for CD5 in TCR-Mediated Signal Transduction and Thymocyte Selection
Authors: Tarakhovsky Alexander , Kanner Steven B. , Hombach Joachim , Ledbetter Jeffrey A. , Müller Werner , Killeen Nigel , Rajewsky Klaus
Published: October 2006

CD5 is a transmembrane protein that is expressed on the surface of T cells and a subset of B cells. The absence of CD5 rendered thymocytes hyperresponsive to stimulation through the T cell antigen receptor (TCR) in vitro. Selection of T cells expressing three distinct transgenic TCRs was also abnormal in CD5-deficient mice. These observations indicate that CD5 can influence the fate of developing thymocytes by acting as a negative regulator of TCR-mediated signal transduction.
The RNA Component of Human Telomerase
Authors: Feng Junli , Funk Walter D. , Wang Sy-Shi , Weinrich Scott L. , Avilion Ariel A. , Chiu Choy-Pik , Adams Robert R. , Chang Edwin , Allsopp Richard C. , Yu Jinghua , Le Siyuan , West Michael D. , Harley Calvin B. , Andrews, William H. , Greider Carol W. , Villeponteau Bryant
Published: October 2006

Eukaryotic chromosomes are capped with repetitive telomere sequences that protect the ends from damage and rearrangements. Telomere repeats are synthesized by telomerase, a ribonucleic acid (RNA)-protein complex. Here, the cloning of the RNA component of human telomerase, termed hTR, is described. The template region of hTR encompasses 11 nucleotides (5′-CUAACCCUAAC) complementary to the human telomere sequence (TTAGGG)

n

. Germline tissues and tumor cell lines expressed more hTR than normal somatic cells and tissues, which have no detectable telomerase activity. Human cell lines that expressed hTR mutated in the template region generated the predicted mutant telomerase activity. HeLa cells transfected with an antisense hTR lost telomeric DNA and began to die after 23 to 26 doublings. Thus, human telomerase is a critical enzyme for the long-term proliferation of immortal tumor cells.
Functional Characterization and Developmental Regulation of Mouse Telomerase RNA
Authors: Blasco María A. , Funk Walter , Villeponteau Bryant , Greider Carol W.
Published: October 2006

Telomerase synthesizes telomeric DNA repeats onto chromosome ends de novo. The mouse telomerase RNA component was cloned and contained only 65 percent sequence identity with the human telomerase RNA. Alteration of the template region in vivo generated altered telomerase products. The shorter template regions of the mouse and other rodent telomerase RNAs could account for the shorter distribution of products (processivity) generated by the mouse enzyme relative to the human telomerase. Amounts of telomerase RNA increased in immortal cells derived from primary mouse fibroblasts. RNA was detected in all newborn mouse tissues tested but was decreased during postnatal development.
Ethylene Insensitivity Conferred by
Arabidopsis
ERS Gene
Authors: Hua Jian , Chang Caren , Sun Qi , Meyerowitz Elliot M.
Published: October 2006

ERS
(
ethylene response sensor
), a gene in the
Arabidopsis thaliana
ethylene hormone-response pathway, was uncovered by cross-hybridization with the
Arabidopsis
ETR1
gene. The deduced ERS protein has sequence similarity with the amino-terminal domain and putative histidine protein kinase domain of ETR1, but it does not have a receiver domain as found in ETR1. A missense mutation identical to the dominant
etr1-4
mutation was introduced into the
ERS
gene. The altered
ERS
gene conferred dominant ethylene insensitivity to wild-type
Arabidopsis
. Double-mutant analysis indicates that
ERS
acts upstream of the
CTR1
protein kinase gene in the ethylene-response pathway.
Regulation of Hippocampal Transmitter Release During Development and Long-Term Potentiation
Authors: Bolshakov Vadim Y. , Siegelbaum Steven A.
Published: October 2006

Developmental changes in rat hippocampal transmitter release and synaptic plasticity were investigated. Recordings from pairs of pyramidal neurons in slices showed that an action potential in a CA3 neuron released only a single quantum of transmitter onto a CA1 neuron. Failures of synaptic transmission reflected probabilistic transmitter release. The probability of release (
P
r
) was 0.9 in 4- to 8-day-old rats and decreased to less than 0.5 at 2 to 3 weeks. Long-term potentiation (LTP) in 2- to 3-week-old rats was associated with an increase in
P
r
from a single synaptic site. The high initial
P
r
in 4- to 8-day-old rats normally occludes the expression of LTP at this stage.
Magnetic Resonance Elastography by Direct Visualization of Propagating Acoustic Strain Waves
Authors: Muthupillai R. , Lomas D. J. , Rossman P. J. , Greenleaf J. F. , Manduca A. , Ehman R. L.
Published: October 2006

A nuclear magnetic resonance imaging (MRI) method is presented for quantitatively mapping the physical response of a material to harmonic mechanical excitation. The resulting images allow calculation of regional mechanical properties. Measurements of shear modulus obtained with the MRI technique in gel materials correlate with independent measurements of static shear modulus. The results indicate that displacement patterns corresponding to cyclic displacements smaller than 200 nanometers can be measured. The findings suggest the feasibility of a medical imaging technique for delineating elasticity and other mechanical properties of tissue.
Circadian Oscillations of Cytosolic and Chloroplastic Free Calcium in Plants
Authors: Johnson Carl Hirschie , Knight Marc R. , Kondo Takao , Masson Patrick , Sedbrook John , Haley Ann , Trewavas Anthony
Published: October 2006

Tobacco and
Arabidopsis
plants, expressing a transgene for the calcium-sensitive luminescent protein apoaequorin, revealed circadian oscillations in free cytosolic calcium that can be phase-shifted by light-dark signals. When apoaequorin was targeted to the chloroplast, circadian chloroplast calcium rhythms were likewise observed after transfer of the seedlings to constant darkness. Circadian oscillations in free calcium concentrations can be expected to control many calcium-dependent enzymes and processes accounting for circadian outputs. Regulation of calcium flux is therefore fundamental to the organization of circadian systems.
Interaction of Tyrosine-Based Sorting Signals with Clathrin-Associated Proteins
Authors: Ohno Hiroshi , Stewart Jay , Fournier Marie-Christine , Bosshart Herbert , Rhee Ina , Miyatake Shoichiro , Saito Takashi , Gallusser Andreas , Kirchhausen Tomas , Bonifacino Juan S.
Published: October 2006

Tyrosine-based signals within the cytoplasmic domain of integral membrane proteins mediate clathrin-dependent protein sorting in the endocytic and secretory pathways. A yeast two-hybrid system was used to identify proteins that bind to tyrosine-based signals. The medium chains (μ
1
and μ
2
) of two clathrin-associated protein complexes (AP-1 and AP-2, respectively) specifically interacted with tyrosine-based signals of several integral membrane proteins. The interaction was confirmed by in vitro binding assays. Thus, it is likely that the medium chains serve as signal-binding components of the clathrin-dependent sorting machinery.
Inhibition of ICE Family Proteases by Baculovirus Antiapoptotic Protein p35
Authors: Bump Nancy J. , Hackett Maria , Hugunin Margaret , Seshagiri Somasekar , Brady Kenneth , Chen Patrick , Ferenz Catherine , Franklin Simon , Ghayur Tariq , Li Ping , Licari Peter , Mankovich John , Shi Lianfa , Greenberg Arnold H. , Miller Lois K. , Wong Winnie W.
Published: October 2006

The baculovirus antiapoptotic protein p35 inhibited the proteolytic activity of human interleukin-1β converting enzyme (ICE) and three of its homologs in enzymatic assays. Coexpression of p35 prevented the autoproteolytic activation of ICE from its precursor form and blocked ICE-induced apoptosis. Inhibition of enzymatic activity correlated with the cleavage of p35 and the formation of a stable ICE-p35 complex. The ability of p35 to block apoptosis in different pathways and in distantly related organisms suggests a central and conserved role for ICE-like proteases in the induction of apoptosis.
Spatial Memory of Body Linear Displacement: What Is Being Stored?
Authors: Berthoz Alain , Israël Isabelle , Georges-François Pierre , Grasso Renato , Tsuzuku Toshihiro
Published: October 2006

The ability to evaluate traveled distance is common to most animal species. Head trajectory in space is measured on the basis of the converging signals of the visual, vestibular, and somatosensory systems, together with efferent copies of motor commands. Recent evidence from human studies has shown that head trajectory in space can be stored in spatial memory. A fundamental question, however, remains unanswered: How is movement stored? In this study, humans who were asked to reproduce passive linear whole-body displacement distances while blindfolded were also able to reproduce velocity profiles. This finding suggests that a spatiotemporal dynamic pattern of motion is stored and can be retrieved with the use of vestibular and somesthetic cues.
Population Growth and Earth's Human Carrying Capacity
Authors: Cohen Joel E.
Published: October 2006

Earth's capacity to support people is determined both by natural constraints and by human choices concerning economics, environment, culture (including values and politics), and demography. Human carrying capacity is therefore dynamic and uncertain. Human choice is not captured by ecological notions of carrying capacity that are appropriate for nonhuman populations. Simple mathematical models of the relation between human population growth and human carrying capacity can account for faster-than-exponential population growth followed by a slowing population growth rate, as observed in recent human history.
A Synaptic Localization Domain in the Synaptic Cleft Protein Laminin β2 (s-Laminin)
Authors: Martin Paul T. , Ettinger Audrey J. , Sanes Joshua R.
Published: October 2006

The basal lamina that ensheaths skeletal muscle fibers traverses the synaptic cleft at the neuromuscular junction. Synaptic and extrasynaptic portions of the basal lamina contain different laminin β chains: β2 (or s) at synapses and β1 (or B1) extrasynaptically. Laminin β2 is also confined to synapselike patches on myotube surfaces in vitro, whereas β1 is present throughout the extracellular matrix. This differential localization of laminin β chains was analyzed by expression of chimeric β1-β2 molecules in cultured mouse myotubes. A 16-amino acid carboxyl-terminal sequence in β2 was necessary for synaptic localization, and an amino-terminal domain in β1 promoted association with extracellular fibrils. The synaptic targeting sequence of β2 contains a site previously shown to be adhesive for motor neurons.
Sterkfontein Member 2 Foot Bones of the Oldest South African Hominid
Authors: Clarke Ronald J. , Tobias Phillip V.
Published: October 2006

Four articulating hominid foot bones have been recovered from Sterkfontein Member 2, near Johannesburg, South Africa. They have human features in the hindfoot and strikingly apelike traits in the forefoot. While the foot is manifestly adapted for bipedalism, its most remarkable characteristic is that the great toe (hallux) is appreciably medially diverged (varus) and strongly mobile, as in apes. Possibly as old as 3.5 million years, the foot provides the first evidence that bipedal hominids were in southern Africa more than 3.0 million years ago. The bones probably belonged to an early member of
Australopithecus africanus
or another early hominid species.
Recombinant Mouse OB Protein: Evidence for a Peripheral Signal Linking Adiposity and Central Neural Networks
Authors: Campfield L. Arthur , Smith Françoise J. , Guisez Yves , Devos Rene , Burn Paul
Published: October 2006

The recent positional cloning of the mouse
ob
gene and its human homolog has provided the basis to investigate the potential role of the
ob
gene product in body weight regulation. A biologically active form of recombinant mouse OB protein was overexpressed and purified to near homogeneity from a bacterial expression system. Peripheral and central administration of microgram doses of OB protein reduced food intake and body weight of
ob
/
ob
and diet-induced obese mice but not in
db
/
db
obese mice. The behavioral effects after brain administration suggest that OB protein can act directly on neuronal networks that control feeding and energy balance.
Activation of Yeast PBS2 MAPKK by MAPKKKs or by Binding of an SH3-Containing Osmosensor
Authors: Maeda Tatsuya , Takekawa Mutsuhiro , Saito Haruo
Published: October 2006

The role of mitogen-activated protein (MAP) kinase cascades in integrating distinct upstream signals was studied in yeast. Mutants that were not able to activate PBS2 MAP kinase kinase (MAPKK; Pbs2p) at high osmolarity were characterized. Pbs2p was activated by two independent signals that emanated from distinct cell-surface osmosensors. Pbs2p was activated by MAP kinase kinase kinases (MAPKKKs) Ssk2p and Ssk22p that are under the control of the
SLN1-SSK1
two-component osmosensor. Alternatively, Pbs2p was activated by a mechanism that involves the binding of its amino terminal proline-rich motif to the Src homology 3 (SH3) domain of a putative transmembrane osmosensor Sho1p.
Role of the Ubiquitin-Proteasome Pathway in Regulating Abundance of the Cyclin-Dependent Kinase Inhibitor p27
Authors: Pagano Michele , Tam Sun W. , Theodoras Anne M. , Beer-Romero Peggy , Del Sal Giannino , Chau Vincent , Yew P. Renée , Draetta Giulio F. , Rolfe Mark
Published: October 2006

The p27 mammalian cell cycle protein is an inhibitor of cyclin-dependent kinases. Both in vivo and in vitro, p27 was found to be degraded by the ubiquitin-proteasome pathway. The human ubiquitin-conjugating enzymes Ubc2 and Ubc3 were specifically involved in the ubiquitination of p27. Compared with proliferating cells, quiescent cells exhibited a smaller amount of p27 ubiquitinating activity, which accounted for the marked increase of p27 half-life measured in these cells. Thus, the abundance of p27 in cells is regulated by degradation. The specific proteolysis of p27 may represent a mechanism for regulating the activity of cyclin-dependent kinases.
Cloning and Characterization of a G Protein-Activated Human Phosphoinositide-3 Kinase
Authors: Stoyanov Borislav , Volinia Stefano , Hanck Theodor , Rubio Ignacio , Loubtchenkov Michael , Malek Daria , Stoyanova Stefka , Vanhaesebroeck Bart , Dhand Ritu , Nürnberg Bernd , Gierschik Peter , Seedorf Klaus , Hsuan J. Justin , Waterfield Michael D. , Wetzker Reinhard
Published: October 2006

Phosphoinositide-3 kinase activity is implicated in diverse cellular responses triggered by mammalian cell surface receptors and in the regulation of protein sorting in yeast. Receptors with intrinsic and associated tyrosine kinase activity recruit heterodimeric phosphoinositide-3 kinases that consist of p110 catalytic subunits and p85 adaptor molecules containing Src homology 2 (SH2) domains. A phosphoinositide-3 kinase isotype, p110γ, was cloned and characterized. The p110γ enzyme was activated in vitro by both the α and βγ subunits of heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) and did not interact with p85. A potential pleckstrin homology domain is located near its amino terminus. The p110γ isotype may link signaling through G protein-coupled receptors to the generation of phosphoinositide second messengers phosphorylated in the D-3 position.
Mismatch Repair Deficiency in Phenotypically Normal Human Cells
Authors: Parsons Ramon , Li Guo-Min , Longley Matthew , Modrich Paul , Liu Bo , Berk Theresa , Hamilton Stanley R. , Kinzler Kenneth W. , Vogelstein Bert
Published: October 2006

Tumor cells in patients with hereditary nonpolyposis colorectal cancer (HNPCC) are characterized by a genetic hypermutability caused by defects in DNA mismatch repair. A subset of HNPCC patients was found to have widespread mutations not only in their tumors, but also in their non-neoplastic cells. Although these patients had numerous mutations in all tissues examined, they had very few tumors. The hypermutability was associated with a profound defect in mismatch repair at the biochemical level. These results have implications for the relation between mutagenesis and carcinogenesis, and they suggest that mismatch repair deficiency is compatible with normal human development.
Association of Flavin Adenine Dinucleotide with the
Arabidopsis
Blue Light Receptor CRY1
Authors: Lin Chentao , Robertson Dan E. , Ahmad Margaret , Raibekas Andrei A. , Jorns Marilyn Schuman , Dutton P. Leslie , Cashmore Anthony R.
Published: October 2006

The
Arabidopsis thaliana HY4
gene encodes CRY1, a 75-kilodalton flavoprotein mediating blue light-dependent regulation of seedling development. CRY1 is demonstrated here to noncovalently bind stoichiometric amounts of flavin adenine dinucleotide (FAD). The redox properties of FAD bound by CRY1 include an unexpected stability of the neutral radical flavosemiquinone (FADH⋅). The absorption properties of this flavosemiquinone provide a likely explanation for the additional sensitivity exhibited by CRY1-mediated responses in the green region of the visible spectrum. Despite the sequence homology to microbial DNA photolyases, CRY1 was found to have no detectable photolyase activity.
Double Dissociation of Conditioning and Declarative Knowledge Relative to the Amygdala and Hippocampus in Humans
Authors: Bechara Antoine , Tranel Daniel , Damasio Hanna , Adolphs Ralph , Rockland Charles , Damasio Antonio R.
Published: October 2006

A patient with selective bilateral damage to the amygdala did not acquire conditioned autonomic responses to visual or auditory stimuli but did acquire the declarative facts about which visual or auditory stimuli were paired with the unconditioned stimulus. By contrast, a patient with selective bilateral damage to the hippocampus failed to acquire the facts but did acquire the conditioning. Finally, a patient with bilateral damage to both amygdala and hippocampal formation acquired neither the conditioning nor the facts. These findings demonstrate a double dissociation of conditioning and declarative knowledge relative to the human amygdala and hippocampus.
The Earth's Early Evolution
Authors: Bowring Samuel A. , Housh Todd
Published: October 2006

The Archean crust contains direct geochemical information of the Earth's early planetary differentiation. A major outstanding question in the Earth sciences is whether the volume of continental crust today represents nearly all that formed over Earth's history or whether its rates of creation and destruction have been approximately balanced since the Archean. Analysis of neodymium isotopic data from the oldest remnants of Archean crust suggests that crustal recycling is important and that preserved continental crust comprises fragments of crust that escaped recycling. Furthermore, the data suggest that the isotopic evolution of Earth's mantle reflects progressive eradication of primordial heterogeneities related to early differentiation.
A VAMP-Binding Protein from
Aplysia
Required for Neurotransmitter Release
Authors: Skehel Paul A. , Martin Kelsey C. , Kandel Eric R. , Bartsch Dusan
Published: October 2006

Before the fusion of synaptic vesicles with the plasma membrane, a protein complex is thought to form between VAMP—an integral membrane protein of the vesicle—and two proteins associated with the plasma membrane, SNAP-25 and syntaxin. The yeast two-hybrid interaction cloning system has now been used to identify additional proteins from
Aplysia
that interact directly with VAMP. A 33-kilodalton membrane protein, termed VAP-33 (VAMP-associated protein of 33 kilodaltons), was identified whose corresponding messenger RNA was detected only in the central nervous system and the gill of
Aplysia
. Presynaptic injection of antibodies specific for VAP-33 inhibited synaptic transmission, which suggests that VAP-33 is required for the exocytosis of neurotransmitter.
A Constitutively Active Mutant PTH-PTHrP Receptor in Jansen-Type Metaphyseal Chondrodysplasia
Authors: Schipani Ernestina , Kruse Klaus , Jüppner Harald
Published: October 2006

A single heterozygous nucleotide exchange in exon M2 of the gene encoding the parathyroid hormone-parathyroid hormone-related peptide (PTH-PTHrP) receptor was identified in a patient with Jansen-type metaphyseal chondrodysplasia, which changes a strictly conserved histidine residue at position 223 in the receptor's first intracellular loop to arginine. Constitutive, ligand-independent adenosine 3′,5′-monophosphate accumulation was observed in COS-7 cells expressing the mutant PTH-PTHrP receptor but not in cells expressing the wild-type receptor. This finding explains the severe ligand-independent hypercalcemia and hypophosphatemia, and most likely the abnormal formation of endochondral bone, in this rare form of short-limbed dwarfism.
Notch Signaling
Authors: Artavanis-Tsakonas Spyros , Matsuno Kenji , Fortini Mark E.
Published: October 2006

The Notch/Lin-12/Glp-1 receptor family mediates the specification of numerous cell fates during development in
Drosophila
and
Caenorhabditis elegans
. Studies on the expression, mutant phenotypes, and developmental consequences of unregulated receptor activation have implicated these proteins in a general mechanism of local cell signaling, which includes interactions between equivalent cells and between different cell types. Genetic approaches in flies and worms have identified putative components of the signaling cascade, including a conserved family of extracellular ligands and two cellular factors that may associate with the Notch Intracellular domain. One factor, the
Drosophila
Suppressor of Hairless protein, is a DNA-binding protein, which suggests that Notch signaling may involve relatively direct signal transmission from the cell surface to the nucleus. Several vertebrate Notch receptors have also been discovered recently and play important roles in normal development and tumorigenesis.
Activity-Dependent Action Potential Invasion and Calcium Influx into Hippocampal CA1 Dendrites
Authors: Spruston Nelson , Schiller Yitzhak , Stuart Greg , Sakmann Bert
Published: October 2006

The temporal and spatial profile of activity-evoked changes in membrane potential and intracellular calcium concentration in the dendrites of hippocampal CA1 pyramidal neurons was examined with simultaneous somatic and dendritic patch-pipette recording and calcium imaging experiments. Action potentials are initiated close to the soma of these neurons and backpropagate into the dendrites in an activity-dependent manner; those occurring early in a train propagate actively, whereas those occurring later fail to actively invade the distal dendrites. Consistent with this finding, dendritic calcium transients evoked by single action potentials do not significantly attenuate with distance from the soma, whereas those evoked by trains attenuate substantially. Failure of action potential propagation into the distal dendrites often occurs at branch points. Consequently, neighboring regions of the dendritic tree can experience different voltage and calcium signals during repetitive action potential firing. The influence of backpropagating action potentials on synaptic integration and plasticity will therefore depend on both the extent of dendritic branching and the pattern of neuronal activity.
Silver as a Probe of Pore-Forming Residues in a Potassium Channel
Authors: Lü Qiang , Miller Christopher
Published: October 2006

In voltage-dependent potassium channels, the molecular determinants of ion selectivity are found in the P (pore) region, a stretch of 21 contiguous residues. Cysteine was introduced at each P region position in a Shaker potassium channel. Residues projecting side chains into the pore were identified by means of channel inhibition by a sulfhydryl-reactive potassium ion analog, silver ion. The pattern of silver ion reactivity contradicts a β barrel architecture of potassium channel pores.
DNA Solution of Hard Computational Problems
Authors: Lipton Richard J.
Published: October 2006

DNA experiments are proposed to solve the famous "SAT" problem of computer science. This is a special case of a more general method that can solve NP-complete problems. The advantage of these results is the huge parallelism inherent in DNA-based computing. It has the potential to yield vast speedups over conventional electronic-based computers for such search problems.
Masking of the CBF1/RBPJ
κ
Transcriptional Repression Domain by Epstein-Barr Virus EBNA2
Authors: Hsieh James J.-D. , Hayward S. Diane
Published: October 2006

Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) is a transcriptional activator that is essential for EBV-driven B cell immortalization. EBNA2 is targeted to responsive promoters through interaction with a cellular DNA binding protein, C promoter binding factor 1 (CBF1). A transcriptional repression domain has been identified within CBF1. This domain also interacts with EBNA2, and repression is masked by EBNA2 binding. Thus, EBNA2 acts by countering transcriptional repression. Mutation at amino acid 233 of CBF1 abolishes repression and correlates with a loss-of-function mutation in the
Drosophila
homolog
Su(H)
.
In Vivo Functional Analysis of the Ras Exchange Factor Son of Sevenless
Authors: Karlovich Chris A. , Bonfini Laura , McCollam Linda , Rogge Ronald D. , Daga Andrea , Czech Michael P. , Banerjee Utpal
Published: October 2006

The Son of sevenless (Sos) protein functions as a guanine nucleotide transfer factor for Ras and interacts with the receptor tyrosine kinase Sevenless through the protein Drk, a homolog of mammalian Grb2. In vivo structure-function analysis revealed that the amino terminus of Sos was essential for its function in flies. A molecule lacking the amino terminus was a potent dominant negative. In contrast, a Sos fragment lacking the Drk binding sites was functional and its activity was dependent on the presence of the Sevenless receptor. Furthermore, membrane localization of Sos was independent of Drk. A possible role for Drk as an activator of Sos is discussed and a Drk-independent interaction between Sos and Sevenless is proposed that is likely mediated by the pleckstrin homology domain within the amino terminus.
Inhibition of Proteasome Activities and Subunit-Specific Amino-Terminal Threonine Modification by Lactacystin
Authors: Fenteany Gabriel , Standaert Robert F. , Lane William S. , Choi Soongyu , Corey E. J. , Schreiber Stuart L.
Published: October 2006

Lactacystin is a
Streptomyces
metabolite that inhibits cell cycle progression and induces neurite outgrowth in a murine neuroblastoma cell line. Tritium-labeled lactacystin was used to identify the 20S proteasome as its specific cellular target. Three distinct peptidase activities of this enzyme complex (trypsin-like, chymotrypsin-like, and peptidylglutamyl-peptide hydrolyzing activities) were inhibited by lactacystin, the first two irreversibly and all at different rates. None of five other proteases were inhibited, and the ability of lactacystin analogs to inhibit cell cycle progression and induce neurite outgrowth correlated with their ability to inhibit the proteasome. Lactacystin appears to modify covalently the highly conserved amino-terminal threonine of the mammalian proteasome subunit X (also called MB1), a close homolog of the LMP7 proteasome subunit encoded by the major histocompatibility complex. This threonine residue may therefore have a catalytic role, and subunit X/MB1 may be a core component of an amino-terminal-threonine protease activity of the proteasome.
Borders of Multiple Visual Areas in Humans Revealed by Functional Magnetic Resonance Imaging
Authors: Sereno M. I. , Dale A. M. , Reppas J. B. , Kwong K. K. , Belliveau J. W. , Brady T. J. , Rosen B. R. , Tootell R. B. H.
Published: October 2006

The borders of human visual areas V1, V2, VP, V3, and V4 were precisely and noninvasively determined. Functional magnetic resonance images were recorded during phase-encoded retinal stimulation. This volume data set was then sampled with a cortical surface reconstruction, making it possible to calculate the local visual field sign (mirror image versus non-mirror image representation). This method automatically and objectively outlines area borders because adjacent areas often have the opposite field sign. Cortical magnification factor curves for striate and extrastriate cortical areas were determined, which showed that human visual areas have a greater emphasis on the center-of-gaze than their counterparts in monkeys. Retinotopically organized visual areas in humans extend anteriorly to overlap several areas previously shown to be activated by written words.
Absence of Polymorphism at the ZFY Locus on the Human Y Chromosome
Authors: Dorit Robert L. , Akashi Hiroshi , Gilbert Walter
Published: October 2006

DNA polymorphism in the Y chromosome, examined at a 729-base pair intron located immediately upstream of the
ZFY
zinc-finger exon, revealed no sequence variation in a worldwide sample of 38 human males. This finding cannot be explained by global constraint on the intron sequence, because interspecific comparisons with other nonhuman primates revealed phylogenetically informative sequence changes. The invariance likely results from either a recent selective sweep, a recent origin for modern
Homo sapiens
, recurrent male population bottlenecks, or historically small effective male population sizes. A coalescence model predicts an expected time to a most recent common ancestral male lineage of 270,000 years (95 percent confidence limits: 0 to 800,000 years).