bluuebunny/crossref_metadata_2025 huggingface dataset:
Death Receptors: Signaling and Modulation
Authors: Ashkenazi Avi , Dixit Vishva M.
Published: July 2002

REVIEW

Apoptosis is a cell suicide mechanism that enables metazoans to control cell number in tissues and to eliminate individual cells that threaten the animal's survival. Certain cells have unique sensors, termed death receptors, on their surface. Death receptors detect the presence of extracellular death signals and, in response, they rapidly ignite the cell's intrinsic apoptosis machinery.
A Neoproterozoic Snowball Earth
Authors: Hoffman Paul F. , Kaufman Alan J. , Halverson Galen P. , Schrag Daniel P.
Published: July 2002

Negative carbon isotope anomalies in carbonate rocks bracketing Neoproterozoic glacial deposits in Namibia, combined with estimates of thermal subsidence history, suggest that biological productivity in the surface ocean collapsed for millions of years. This collapse can be explained by a global glaciation (that is, a snowball Earth), which ended abruptly when subaerial volcanic outgassing raised atmospheric carbon dioxide to about 350 times the modern level. The rapid termination would have resulted in a warming of the snowball Earth to extreme greenhouse conditions. The transfer of atmospheric carbon dioxide to the ocean would result in the rapid precipitation of calcium carbonate in warm surface waters, producing the cap carbonate rocks observed globally.
Identification of c-
MYC
as a Target of the APC Pathway
Authors: He Tong-Chuan , Sparks Andrew B. , Rago Carlo , Hermeking Heiko , Zawel Leigh , da Costa Luis T. , Morin Patrice J. , Vogelstein Bert , Kinzler Kenneth W.
Published: July 2002

The adenomatous polyposis coli gene (
APC
) is a tumor suppressor gene that is inactivated in most colorectal cancers. Mutations of
APC
cause aberrant accumulation of β-catenin, which then binds T cell factor–4 (Tcf-4), causing increased transcriptional activation of unknown genes. Here, the c-
MYC
oncogene is identified as a target gene in this signaling pathway. Expression of c-
MYC
was shown to be repressed by wild-type APC and activated by β-catenin, and these effects were mediated through Tcf-4 binding sites in the c-
MYC
promoter. These results provide a molecular framework for understanding the previously enigmatic overexpression of c-MYC in colorectal cancers.
Turbulent Transport Reduction by Zonal Flows: Massively Parallel Simulations
Authors: Lin Z. , Hahm T. S. , Lee W. W. , Tang W. M. , White R. B.
Published: July 2002

Three-dimensional gyrokinetic simulations of microturbulence in magnetically confined toroidal plasmas with massively parallel computers showed that, with linear flow damping, an asymptotic residual flow develops in agreement with analytic calculations. Nonlinear global simulations of instabilities driven by temperature gradients in the ion component of the plasma support the view that turbulence-driven fluctuating zonal flows can substantially reduce turbulent transport. Finally, the outstanding differences in the flow dynamics observed in global and local simulations are found to be due to profile variations.
Why Sex and Recombination?
Authors: Barton N. H. , Charlesworth B.
Published: July 2002

REVIEW

Most higher organisms reproduce sexually, despite the automatic reproductive advantage experienced by asexual variants. This implies the operation of selective forces that confer an advantage to sexuality and genetic recombination, at either the population or individual level. The effect of sex and recombination in breaking down negative correlations between favorable variants at different genetic loci, which increases the efficiency of natural selection, is likely to be a major factor favoring their evolution and maintenance. Various processes that can cause such an effect have been studied theoretically. It has, however, so far proved hard to discriminate among them empirically.
Solution Properties of Single-Walled Carbon Nanotubes
Authors: Chen Jian , Hamon Mark A. , Hu Hui , Chen Yongsheng , Rao Apparao M. , Eklund Peter C. , Haddon Robert C.
Published: July 2002

Naked metallic and semiconducting single-walled carbon nanotubes (SWNTs) were dissolved in organic solutions by derivatization with thionychloride and octadecylamine. Both ionic (charge transfer) and covalent solution-phase chemistry with concomitant modulation of the SWNT band structure were demonstrated. Solution-phase near-infrared spectroscopy was used to study the effects of chemical modifications on the band gaps of the SWNTs. Reaction of soluble SWNTs with dichlorocarbene led to functionalization of the nanotube walls.
Promotion of Trophoblast Stem Cell Proliferation by FGF4
Authors: Tanaka Satoshi , Kunath Tilo , Hadjantonakis Anna-Katerina , Nagy Andras , Rossant Janet
Published: July 2002

The trophoblast cell lineage is essential for the survival of the mammalian embryo in utero. This lineage is specified before implantation into the uterus and is restricted to form the fetal portion of the placenta. A culture of mouse blastocysts or early postimplantation trophoblasts in the presence of fibroblast growth factor 4 (FGF4) permitted the isolation of permanent trophoblast stem cell lines. These cell lines differentiated to other trophoblast subtypes in vitro in the absence of FGF4 and exclusively contributed to the trophoblast lineage in vivo in chimeras.
Evidence for Extreme Climatic Warmth from Late Cretaceous Arctic Vertebrates
Authors: Tarduno J. A. , Brinkman D. B. , Renne P. R. , Cottrell R. D. , Scher H. , Castillo P.
Published: July 2002

A Late Cretaceous (92 to 86 million years ago) vertebrate assemblage from the high Canadian Arctic (Axel Heiberg Island) implies that polar climates were warm (mean annual temperature exceeding 14°C) rather than near freezing. The assemblage includes large (2.4 meters long) champsosaurs, which are extinct crocodilelike reptiles. Magmatism at six large igneous provinces at this time suggests that volcanic carbon dioxide emissions helped cause the global warmth.
Role of NADH Shuttle System in Glucose-Induced Activation of Mitochondrial Metabolism and Insulin Secretion
Authors: Eto Kazuhiro , Tsubamoto Yoshiharu , Terauchi Yasuo , Sugiyama Takuya , Kishimoto Takuya , Takahashi Noriko , Yamauchi Naoko , Kubota Naoto , Murayama Shigeo , Aizawa Toru , Akanuma Yasuo , Aizawa Shinichi , Kasai Haruo , Yazaki Yoshio , Kadowaki Takashi
Published: July 2002

Glucose metabolism in glycolysis and in mitochondria is pivotal to glucose-induced insulin secretion from pancreatic β cells. One or more factors derived from glycolysis other than pyruvate appear to be required for the generation of mitochondrial signals that lead to insulin secretion. The electrons of the glycolysis-derived reduced form of nicotinamide adenine dinucleotide (NADH) are transferred to mitochondria through the NADH shuttle system. By abolishing the NADH shuttle function, glucose-induced increases in NADH autofluorescence, mitochondrial membrane potential, and adenosine triphosphate content were reduced and glucose-induced insulin secretion was abrogated. The NADH shuttle evidently couples glycolysis with activation of mitochondrial energy metabolism to trigger insulin secretion.
Seismic Evidence for a Detached Indian Lithospheric Mantle Beneath Tibet
Authors: Kosarev G. , Kind R. , Sobolev S. V. , Yuan X. , Hanka W. , Oreshin S.
Published: July 2002

P
-to-
S
converted teleseismic waves recorded by temporary broadband networks across Tibet show a north-dipping interface that begins 50 kilometers north of the Zangbo suture at the depth of the Moho (80 kilometers) and extends to a depth of 200 kilometers beneath the Bangong suture. Under northern Tibet a segmented south-dipping structure was imaged. These observations suggest a different form of detachment of the Indian and Asian lithospheric mantles caused by differences in their composition and buoyancy.
A Well-Collimated Quasi-Continuous Atom Laser
Authors: Hagley E. W. , Deng L. , Kozuma M. , Wen J. , Helmerson K. , Rolston S. L. , Phillips W. D.
Published: July 2002

Extraction of sodium atoms from a trapped Bose-Einstein condensate (BEC) by a coherent, stimulated Raman process is demonstrated. Optical Raman pulses drive transitions between trapped and untrapped magnetic sublevels, giving the output-coupled BEC fraction a well-defined momentum. The pulsed output coupling can be run at such a rate that the extracted atomic wave packets strongly overlap, forming a highly directional, quasi-continuous matter wave.
Compositional Stratification in the Deep Mantle
Authors: Kellogg Louise H. , Hager Bradford H. , van der Hilst Rob D.
Published: July 2002

A boundary between compositionally distinct regions at a depth of about 1600 kilometers may explain the seismological observations pertaining to Earth's lower mantle, produce the isotopic signatures of mid-ocean ridge basalts and oceanic island basalts, and reconcile the discrepancy between the observed heat flux and the heat production of the mid-ocean ridge basalt source region. Numerical models of thermochemical convection imply that a layer of material that is intrinsically about 4 percent more dense than the overlying mantle is dynamically stable. Because the deep layer is hot, its net density is only slightly greater than adiabatic and its surface develops substantial topography.
Complexity in Natural Landform Patterns
Authors: Werner B. T.
Published: July 2002

Patterns in nature, such as meandering rivers and sand dunes, display complex behavior seemingly at odds with their simplicity of form. Existing approaches to modeling natural landform patterns, reductionism and universality, are incompatible with the nonlinear, open nature of natural systems. An alternative modeling methodology based on the tendency of natural systems to self-organize in temporal hierarchies is described.
ROUGH SHEATH2: A Myb Protein That Represses
knox
Homeobox Genes in Maize Lateral Organ Primordia
Authors: P. Marja C. , Timmermans  , Hudson Andrew , Becraft Philip W. , Nelson Timothy
Published: July 2002

The regulation of members of the
knotted1
-like homeobox (
knox
) gene family is required for the normal initiation and development of lateral organs. The maize
rough sheath2
(
rs2
) gene, which encodes a Myb-domain protein, is expressed in lateral organ primordia and their initials. Mutations in the
rs2
gene permit ectopic expression of
knox
genes in leaf and floral primordia, causing a variety of developmental defects. Ectopic KNOX protein accumulation in
rs2
mutants occurs in a subset of the normal
rs2
-expressing cells. This variegated accumulation of KNOX proteins in
rs2
mutants suggests that
rs2
represses
knox
expression through epigenetic means.
Global Warming and Marine Carbon Cycle Feedbacks on Future Atmospheric CO
2
Authors: Joos Fortunat , Plattner Gian-Kasper , Stocker Thomas F. , Marchal Olivier , Schmittner Andreas
Published: July 2002

A low-order physical-biogeochemical climate model was used to project atmospheric carbon dioxide and global warming for scenarios developed by the Intergovernmental Panel on Climate Change. The North Atlantic thermohaline circulation weakens in all global warming simulations and collapses at high levels of carbon dioxide. Projected changes in the marine carbon cycle have a modest impact on atmospheric carbon dioxide. Compared with the control, atmospheric carbon dioxide increased by 4 percent at year 2100 and 20 percent at year 2500. The reduction in ocean carbon uptake can be mainly explained by sea surface warming. The projected changes of the marine biological cycle compensate the reduction in downward mixing of anthropogenic carbon, except when the North Atlantic thermohaline circulation collapses.
Environment and Behavior of 2.5-Million-Year-Old Bouri Hominids
Authors: Heinzelin Jean de , Clark J. Desmond , White Tim , Hart William , Renne Paul , WoldeGabriel Giday , Beyene Yonas , Vrba Elisabeth
Published: July 2002

The Hata Member of the Bouri Formation is defined for Pliocene sedimentary outcrops in the Middle Awash Valley, Ethiopia. The Hata Member is dated to 2.5 million years ago and has produced a new species of
Australopithecus
and hominid postcranial remains not currently assigned to species. Spatially associated zooarchaeological remains show that hominids acquired meat and marrow by 2.5 million years ago and that they are the near contemporary of Oldowan artifacts at nearby Gona. The combined evidence suggests that behavioral changes associated with lithic technology and enhanced carnivory may have been coincident with the emergence of the
Homo
clade from
Australopithecus afarensis
in eastern Africa.
Fas-Induced Caspase Denitrosylation
Authors: Mannick Joan B. , Hausladen Alfred , Liu Limin , Hess Douglas T. , Zeng Ming , Miao Qian X. , Kane Laurie S. , Gow Andrew J. , Stamler Jonathan S.
Published: July 2002

Only a few intracellular S-nitrosylated proteins have been identified, and it is unknown if protein S-nitrosylation/denitrosylation is a component of signal transduction cascades. Caspase-3 zymogens were found to be S-nitrosylated on their catalytic-site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway. Decreased caspase-3 S-nitrosylation was associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active-site thiol. Protein S-nitrosylation/denitrosylation can thus serve as a regulatory process in signal transduction pathways.
Polymersomes: Tough Vesicles Made from Diblock Copolymers
Authors: Discher Bohdana M. , Won You-Yeon , Ege David S. , Lee James C-M. , Bates Frank S. , Discher Dennis E. , Hammer Daniel A.
Published: July 2002

Vesicles were made from amphiphilic diblock copolymers and characterized by micromanipulation. The average molecular weight of the specific polymer studied, polyethyleneoxide-polyethylethylene (EO
40
-EE
37
), is several times greater than that of typical phospholipids in natural membranes. Both the membrane bending and area expansion moduli of electroformed polymersomes (polymer-based liposomes) fell within the range of lipid membrane measurements, but the giant polymersomes proved to be almost an order of magnitude tougher and sustained far greater areal strain before rupture. The polymersome membrane was also at least 10 times less permeable to water than common phospholipid bilayers. The results suggest a new class of synthetic thin-shelled capsules based on block copolymer chemistry.
The Global Topography of Mars and Implications for Surface Evolution
Authors: Smith David E. , Zuber Maria T. , Solomon Sean C. , Phillips Roger J. , Head James W. , Garvin James B. , Banerdt W. Bruce , Muhleman Duane O. , Pettengill Gordon H. , Neumann Gregory A. , Lemoine Frank G. , Abshire James B. , Aharonson Oded , David C. , Brown  , Hauck Steven A. , Ivanov Anton B. , McGovern Patrick J. , Zwally H. Jay , Duxbury Thomas C.
Published: July 2002

Elevations measured by the Mars Orbiter Laser Altimeter have yielded a high-accuracy global map of the topography of Mars. Dominant features include the low northern hemisphere, the Tharsis province, and the Hellas impact basin. The northern hemisphere depression is primarily a long-wavelength effect that has been shaped by an internal mechanism. The topography of Tharsis consists of two broad rises. Material excavated from Hellas contributes to the high elevation of the southern hemisphere and to the scarp along the hemispheric boundary. The present topography has three major drainage centers, with the northern lowlands being the largest. The two polar cap volumes yield an upper limit of the present surface water inventory of 3.2 to 4.7 million cubic kilometers.
Thermoelectric Cooling and Power Generation
Authors: DiSalvo Francis J.
Published: July 2002

In a typical thermoelectric device, a junction is formed from two different conducting materials, one containing positive charge carriers (holes) and the other negative charge carriers (electrons). When an electric current is passed in the appropriate direction through the junction, both types of charge carriers move away from the junction and convey heat away, thus cooling the junction. Similarly, a heat source at the junction causes carriers to flow away from the junction, making an electrical generator. Such devices have the advantage of containing no moving parts, but low efficiencies have limited their use to specialty applications, such as cooling laser diodes. The principles of thermoelectric devices are reviewed and strategies for increasing the efficiency of novel materials are explored. Improved materials would not only help to cool advanced electronics but could also provide energy benefits in refrigeration and when using waste heat to generate electrical power.
A Diamond Trilogy: Superplumes, Supercontinents, and Supernovae
Authors: Haggerty Stephen E.
Published: July 2002

Diamond is a remarkable mineral and has been long recognized for its unusual physical and chemical properties: robust and widespread in industry, yet regally adorned. This diversity is even greater than formally appreciated because diamond is recognized as an extraordinary recorder of astrophysical and geodynamic events that extend from the far reaches of space to Earth's deep interior. Many diamonds are natural antiques that formed in presolar supernovae by carbon vapor deposition, in asteroidal impacts and meteorite craters by shock metamorphism, and in Earth's mantle 1 to 2 billion years after planetary accretion from fluids and melts. The carbon in diamond is primordial, but there are unexplained isotopic fractionations and uncertainties in heterogeneity.
Normal-Mode and Free-Air Gravity Constraints on Lateral Variations in Velocity and Density of Earth's Mantle
Authors: Ishii Miaki , Tromp Jeroen
Published: July 2002

With the use of a large collection of free-oscillation data and additional constraints imposed by the free-air gravity anomaly, lateral variations in shear velocity, compressional velocity, and density within the mantle; dynamic topography on the free surface; and topography on the 660-km discontinuity and the core-mantle boundary were determined. The velocity models are consistent with existing models based on travel-time and waveform inversions. In the lowermost mantle, near the core-mantle boundary, denser than average material is found beneath regions of upwellings centered on the Pacific Ocean and Africa that are characterized by slow shear velocities. These anomalies suggest the existence of compositional heterogeneity near the core-mantle boundary.
Increased Summertime UV Radiation in New Zealand in Response to Ozone Loss
Authors: McKenzie Richard , Connor Brian , Bodeker Greg
Published: July 2002

Long-term decreases in summertime ozone over Lauder, New Zealand (45°S), are shown to have led to substantial increases in peak ultraviolet (UV) radiation intensities. In the summer of 1998–99, the peak sunburning UV radiation was about 12 percent more than in the first years of the decade. Larger increases were seen for DNA-damaging UV radiation and plant-damaging UV radiation, whereas UV-A (315 to 400 nanometers) radiation, which is insensitive to ozone, showed no increase, in agreement with model calculations. These results provide strong evidence of human-induced increases in UV radiation, in a region where baseline levels of UV radiation were already relatively high.
Recognition of the Codon-Anticodon Helix by Ribosomal RNA
Authors: Yoshizawa Satoko , Fourmy Dominique , Puglisi Joseph D.
Published: July 2002

Translational fidelity is established by ribosomal recognition of the codon-anticodon interaction within the aminoacyl–transfer RNA (tRNA) site (A site) of the ribosome. Experiments are presented that reveal possible contacts between 16
S
ribosomal RNA and the codon-anticodon complex. N1 methylation of adenine at position 1492 (A1492) and A1493 interfered with A-site tRNA binding. Mutation of A1492 and A1493 to guanine or cytosine also impaired A-site tRNA binding. The deleterious effects of A1492G or A1493G (or both) mutations were compensated by 2′fluorine substitutions in the mRNA codon. The results suggest that the ribosome recognizes the codon-anticodon complex by adenine contacts to the messenger RNA backbone and provide a mechanism for molecular discrimination of correct versus incorrect codon-anticodon pairs.
Long-Term Potentiation--A Decade of Progress?
Authors: Malenka Robert C. , Nicoll and Roger A.
Published: July 2002

Long-term potentiation of synaptic transmission in the hippocampus is the leading experimental model for the synaptic changes that may underlie learning and memory. This review presents a current understanding of the molecular mechanisms of this long-lasting increase in synaptic strength and describes a simple model that unifies much of the data that previously were viewed as contradictory.
Iron Isotope Biosignatures
Authors: Beard Brian L. , Johnson Clark M. , Cox Lea , Sun Henry , Nealson Kenneth H. , Aguilar Carmen
Published: July 2002

The
56
Fe/
54
Fe of Fe-bearing phases precipitated in sedimentary environments varies by 2.5 per mil (δ
56
Fe values of +0.9 to −1.6 per mil). In contrast, the
56
Fe/
54
Fe of Fe-bearing phases in igneous rocks from Earth and the moon does not vary measurably (δ
56
Fe = 0.0 ± 0.3 per mil). Experiments with dissimilatory Fe-reducing bacteria of the genus
Shewanella algae
grown on a ferrihydrite substrate indicate that the δ
56
Fe of ferrous Fe in solution is isotopically lighter than the ferrihydrite substrate by 1.3 per mil. Therefore, the range in δ
56
Fe values of sedimentary rocks may reflect biogenic fractionation, and the isotopic composition of Fe may be used to trace the distribution of microorganisms in modern and ancient Earth.
Interiors of Giant Planets Inside and Outside the Solar System
Authors: Guillot Tristan
Published: July 2002

An understanding of the structure and composition of the giant planets is rapidly evolving because of (i) high-pressure experiments with the ability to study metallic hydrogen and define the properties of its equation of state and (ii) spectroscopic and in situ measurements made by telescopes and satellites that allow an accurate determination of the chemical composition of the deep atmospheres of the giant planets. However, the total amount of heavy elements that Jupiter, Saturn, Uranus, and Neptune contain remains poorly constrained. The discovery of extrasolar giant planets with masses ranging from that of Saturn to a few times the mass of Jupiter opens up new possibilities for understanding planet composition and formation. Evolutionary models predict that gaseous extrasolar giant planets should have a variety of atmospheric temperatures and chemical compositions, but the radii are estimated to be close to that of Jupiter (between 0.9 and 1.7 Jupiter radii), provided that they contain mostly hydrogen and helium.
Genomic Views of Human History
Authors: Owens Kelly , King Mary-Claire
Published: July 2002

New tools of genomic analysis shed light on historical puzzles. Migrations of ancient peoples, differences in migration patterns of males and females, historical demography of cultures with ancient roots, and patterns of human genetic diversity are increasingly the focus of integrated analysis by historians, anthropologists, and geneticists.
Four Evolutionary Strata on the Human X Chromosome
Authors: Lahn Bruce T. , Page David C.
Published: July 2002

Human sex chromosomes evolved from autosomes. Nineteen ancestral autosomal genes persist as differentiated homologs on the X and Y chromosomes. The ages of individual X-Y gene pairs (measured by nucleotide divergence) and the locations of their X members on the X chromosome were found to be highly correlated. Age decreased in stepwise fashion from the distal long arm to the distal short arm in at least four “evolutionary strata.” Human sex chromosome evolution was probably punctuated by at least four events, each suppressing X-Y recombination in one stratum, without disturbing gene order on the X chromosome. The first event, which marked the beginnings of X-Y differentiation, occurred about 240 to 320 million years ago, shortly after divergence of the mammalian and avian lineages.
Structure of an E6AP-UbcH7 Complex: Insights into Ubiquitination by the E2-E3 Enzyme Cascade
Authors: Huang Lan , Kinnucan Elspeth , Wang Guangli , Beaudenon Sylvie , Howley Peter M. , Huibregtse Jon M. , Pavletich Nikola P.
Published: July 2002

The E6AP ubiquitin-protein ligase (E3) mediates the human papillomavirus-induced degradation of the p53 tumor suppressor in cervical cancer and is mutated in Angelman syndrome, a neurological disorder. The crystal structure of the catalytic hect domain of E6AP reveals a bilobal structure with a broad catalytic cleft at the junction of the two lobes. The cleft consists of conserved residues whose mutation interferes with ubiquitin-thioester bond formation and is the site of Angelman syndrome mutations. The crystal structure of the E6AP hect domain bound to the UbcH7 ubiquitin-conjugating enzyme (E2) reveals the determinants of E2-E3 specificity and provides insights into the transfer of ubiquitin from the E2 to the E3.
Fluid Flow in Chondritic Parent Bodies: Deciphering the Compositions of Planetesimals
Authors: Young Edward D. , Ash Richard D. , England Philip , Rumble Douglas
Published: July 2002

Alteration of the Allende meteorite caused shifts in oxygen isotope ratios along a single mass fractionation line. If alteration was caused by aqueous fluid, the pattern of oxygen isotope fractionation can be explained only by flow of reactive water down a temperature gradient. Down-temperature flow of aqueous fluid within planetesimals is sufficient to explain the mineralogical and oxygen isotopic diversity among CV, CM, and CI carbonaceous chondrites and displacement of the terrestrial planets from the primordial slope 1.00 line on the oxygen three-isotope plot.
Interacting Minds--A Biological Basis
Authors: Frith Chris D. , Frith Uta
Published: July 2002

The ability to “mentalize,” that is to understand and manipulate other people's behavior in terms of their mental states, is a major ingredient in successful social interactions. A rudimentary form of this ability may be seen in great apes, but in humans it is developed to a high level. Specific impairments of mentalizing in both developmental and acquired disorders suggest that this ability depends on a dedicated and circumscribed brain system. Functional imaging studies implicate medial prefrontal cortex and posterior superior temporal sulcus (STS) as components of this system. Clues to the specific function of these components in mentalizing come from single cell recording studies: STS is concerned with representing the actions of others through the detection of biological motion; medial prefrontal regions are concerned with explicit representation of states of the self. These observations suggest that the ability to mentalize has evolved from a system for representing actions.
Domain Movement in Gelsolin: A Calcium-Activated Switch
Authors: Robinson Robert C. , Mejillano Marisan , Le Vincent P. , Burtnick Leslie D. , Yin Helen L. , Choe Senyon
Published: July 2002

The actin-binding protein gelsolin is involved in remodeling the actin cytoskeleton during growth-factor signaling, apoptosis, cytokinesis, and cell movement. Calcium-activated gelsolin severs and caps actin filaments. The 3.4 angstrom x-ray structure of the carboxyl-terminal half of gelsolin (G4–G6) in complex with actin reveals the basis for gelsolin activation. Calcium binding induces a conformational rearrangement in which domain G6 is flipped over and translated by about 40 angstroms relative to G4 and G5. The structural reorganization tears apart the continuous β sheet core of G4 and G6. This exposes the actin-binding site on G4, enabling severing and capping of actin filaments to proceed.
Control of Early Viral and Bacterial Distribution and Disease by Natural Antibodies
Authors: Ochsenbein Adrian F. , Fehr Thomas , Lutz Claudia , Suter Mark , Brombacher Frank , Hengartner Hans , Zinkernagel Rolf M.
Published: July 2002

Natural antibodies are often dismissed from immunological analysis as “background,” but they may play an important role in conferring immunity against infections. In antibody-free mice infected with various viruses or with
Listeria monocytogenes
, viral or bacterial titers in peripheral organs, including the kidney and brain, were 10 to 100 times greater than in antibody-competent mice (and enhanced their susceptibility to some infections), and titers in secondary lymphoid organs were 10 to 100 times lower than in antibody-competent mice. Thus, natural antibodies play a crucial role by preventing pathogen dissemination to vital organs and by improving immunogenicity through enhanced antigen-trapping in secondary lymphoid organs.
Dynamics of the Pacific-North American Plate Boundary in the Western United States
Authors: Flesch Lucy M. , Holt William E. , Haines A. John , Shen-Tu Bingming
Published: July 2002

The vertically averaged deviatoric stress tensor field within the western United States was determined with topographic data, geoid data, recent global positioning system observations, and strain rate magnitudes and styles from Quaternary faults. Gravitational potential energy differences control the large fault-normal compression on the California coast. Deformation in the Basin and Range is driven, in part, by gravitational potential energy differences, but extension directions there are modified by plate interaction stresses. The California shear zone has relatively low vertically averaged viscosity of about 10
21
pascal·seconds, whereas the Basin and Range has a higher vertically averaged viscosity of 10
22
pascal·seconds.
Cool Glacial Temperatures and Changes in Moisture Source Recorded in Oman Groundwaters
Authors: Weyhenmeyer Constanze E. , Burns Stephen J. , Waber H. Niklaus , Aeschbach-Hertig Werner , Kipfer Rolf , Loosli H. Hugo , Matter Albert
Published: July 2002

Concentrations of atmospheric noble gases (neon, argon, krypton, and xenon) dissolved in groundwaters from northern Oman indicate that the average ground temperature during the Late Pleistocene (15,000 to 24,000 years before present) was 6.5° ± 0.6°C lower than that of today. Stable oxygen and hydrogen isotopic groundwater data show that the origin of atmospheric water vapor changed from a primarily southern, Indian Ocean source during the Late Pleistocene to a dominantly northern, Mediterranean source today. The reduced northern water vapor source is consistent with a drier Last Glacial Maximum through much of northern Africa and Arabia.
Synaptic Assembly of the Brain in the Absence of Neurotransmitter Secretion
Authors: Verhage Matthijs , Maia Ascanio S. , Plomp Jaap J. , Brussaard Arjen B. , Heeroma Joost H. , Vermeer Hendrika , Toonen Ruud F. , Hammer Robert E. , van den Timo K. , Berg  , Missler Markus , Geuze Hans J. , Südhof Thomas C.
Published: July 2002

Brain function requires precisely orchestrated connectivity between neurons. Establishment of these connections is believed to require signals secreted from outgrowing axons, followed by synapse formation between selected neurons. Deletion of a single protein, Munc18-1, in mice leads to a complete loss of neurotransmitter secretion from synaptic vesicles throughout development. However, this does not prevent normal brain assembly, including formation of layered structures, fiber pathways, and morphologically defined synapses. After assembly is completed, neurons undergo apoptosis, leading to widespread neurodegeneration. Thus, synaptic connectivity does not depend on neurotransmitter secretion, but its maintenance does. Neurotransmitter secretion probably functions to validate already established synaptic connections.
Central Role for G Protein-Coupled Phosphoinositide 3-Kinase γ in Inflammation
Authors: Hirsch Emilio , Katanaev Vladimir L. , Garlanda Cecilia , Azzolino Ornella , Pirola Luciano , Silengo Lorenzo , Sozzani Silvano , Mantovani Alberto , Altruda Fiorella , Wymann Matthias P.
Published: July 2002

Phosphoinositide 3-kinase (PI3K) activity is crucial for leukocyte function, but the roles of the four receptor-activated isoforms are unclear. Mice lacking heterotrimeric guanine nucleotide-binding protein (G protein)–coupled PI3Kγ were viable and had fully differentiated neutrophils and macrophages. Chemoattractant-stimulated PI3Kγ
−/−
neutrophils did not produce phosphatidylinositol 3,4,5-trisphosphate, did not activate protein kinase B, and displayed impaired respiratory burst and motility. Peritoneal PI3Kγ-null macrophages showed a reduced migration toward a wide range of chemotactic stimuli and a severely defective accumulation in a septic peritonitis model. These results demonstrate that PI3Kγ is a crucial signaling molecule required for macrophage accumulation in inflammation.
The Atom-Cavity Microscope: Single Atoms Bound in Orbit by Single Photons
Authors: Hood C. J. , Lynn T. W. , Doherty A. C. , Parkins A. S. , Kimble H. J.
Published: July 2002

The motion of individual cesium atoms trapped inside an optical resonator is revealed with the atom-cavity microscope (ACM). A single atom moving within the resonator generates large variations in the transmission of a weak probe laser, which are recorded in real time. An inversion algorithm then allows individual atom trajectories to be reconstructed from the record of cavity transmission and reveals single atoms bound in orbit by the mechanical forces associated with single photons. In these initial experiments, the ACM yields 2-micrometer spatial resolution in a 10-microsecond time interval. Over the duration of the observation, the sensitivity is near the standard quantum limit for sensing the motion of a cesium atom.
Control of Thickness and Orientation of Solution-Grown Silicon Nanowires
Authors: Holmes Justin D. , Johnston Keith P. , Doty R. Christopher , Korgel Brian A.
Published: July 2002

Bulk quantities of defect-free silicon (Si) nanowires with nearly uniform diameters ranging from 40 to 50 angstroms were grown to a length of several micrometers with a supercritical fluid solution-phase approach. Alkanethiol-coated gold nanocrystals (25 angstroms in diameter) were used as uniform seeds to direct one-dimensional Si crystallization in a solvent heated and pressurized above its critical point. The orientation of the Si nanowires produced with this method could be controlled with reaction pressure. Visible photoluminescence due to quantum confinement effects was observed, as were discrete optical transitions in the ultraviolet-visible absorbance spectra.
Requirement of the Inositol Trisphosphate Receptor for Activation of Store-Operated Ca
2+
Channels
Authors: Ma Hong-Tao , Patterson Randen L. , van Damian B. , Rossum  , Birnbaumer Lutz , Mikoshiba Katsuhiko , Gill Donald L.
Published: July 2002

The coupling mechanism between endoplasmic reticulum (ER) calcium ion (Ca
2+
) stores and plasma membrane (PM) store-operated channels (SOCs) is crucial to Ca
2+
signaling but has eluded detection. SOCs may be functionally related to the TRP family of receptor-operated channels. Direct comparison of endogenous SOCs with stably expressed TRP3 channels in human embryonic kidney (HEK293) cells revealed that TRP3 channels differ in being store independent. However, condensed cortical F-actin prevented activation of both SOC and TRP3 channels, which suggests that ER-PM interactions underlie coupling of both channels. A cell-permeant inhibitor of inositol trisphosphate receptor (InsP
3
R) function, 2-aminoethoxydiphenyl borate, prevented both receptor-induced TRP3 activation and store-induced SOC activation. It is concluded that InsP
3
Rs mediate both SOC and TRP channel opening and that the InsP
3
R is essential for maintaining coupling between store emptying and physiological activation of SOCs.
Target-Oriented and Diversity-Oriented Organic Synthesis in Drug Discovery
Authors: Schreiber Stuart L.
Published: July 2002

Modern drug discovery often involves screening small molecules for their ability to bind to a preselected protein target. Target-oriented syntheses of these small molecules, individually or as collections (focused libraries), can be planned effectively with retrosynthetic analysis. Drug discovery can also involve screening small molecules for their ability to modulate a biological pathway in cells or organisms, without regard for any particular protein target. This process is likely to benefit in the future from an evolving forward analysis of synthetic pathways, used in diversity-oriented synthesis, that leads to structurally complex and diverse small molecules. One goal of diversity-oriented syntheses is to synthesize efficiently a collection of small molecules capable of perturbing any disease-related biological pathway, leading eventually to the identification of therapeutic protein targets capable of being modulated by small molecules. Several synthetic planning principles for diversity-oriented synthesis and their role in the drug discovery process are presented in this review.
Dilational Processes Accompanying Earthquakes in the Long Valley Caldera
Authors: Dreger Douglas S. , Tkalčić Hrvoje , Johnston Malcolm
Published: July 2002

Regional distance seismic moment tensor determinations and broadband waveforms of moment magnitude 4.6 to 4.9 earthquakes from a November 1997 Long Valley Caldera swarm, during an inflation episode, display evidence of anomalous seismic radiation characterized by non–double couple (NDC) moment tensors with significant volumetric components. Observed coseismic dilation suggests that hydrothermal or magmatic processes are directly triggering some of the seismicity in the region. Similarity in the NDC solutions implies a common source process, and the anomalous events may have been triggered by net fault-normal stress reduction due to high-pressure fluid injection or pressurization of fluid-saturated faults due to magmatic heating.
Impaired Nociception and Pain Sensation in Mice Lacking the Capsaicin Receptor
Authors: Caterina M. J. , Leffler A. , Malmberg A. B. , Martin W. J. , Trafton J. , Petersen-Zeitz K. R. , Koltzenburg M. , Basbaum A. I. , Julius D.
Published: July 2002

The capsaicin (vanilloid) receptor VR1 is a cation channel expressed by primary sensory neurons of the “pain” pathway. Heterologously expressed VR1 can be activated by vanilloid compounds, protons, or heat (>43°C), but whether this channel contributes to chemical or thermal sensitivity in vivo is not known. Here, we demonstrate that sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli. VR1
−/−
mice showed normal responses to noxious mechanical stimuli but exhibited no vanilloid-evoked pain behavior, were impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation. Thus, VR1 is essential for selective modalities of pain sensation and for tissue injury–induced thermal hyperalgesia.
Control of Homeostasis of CD8
+
Memory T Cells by Opposing Cytokines
Authors: Ku Chia Chi , Murakami Masaaki , Sakamoto Akemi , Kappler John , Marrack Philippa
Published: July 2002

Memory T cells maintain their numbers for long periods after antigen exposure. Here we show that CD8
+
T cells of memory phenotype divide slowly in animals. This division requires interleukin-15 and is markedly increased by inhibition of interleukin-2 (IL-2). Therefore, the numbers of CD8
+
memory T cells in animals are controlled by a balance between IL-15 and IL-2.
Separation of Long DNA Molecules in a Microfabricated Entropic Trap Array
Authors: Han J. , Craighead H. G.
Published: July 2002

A nanofluidic channel device, consisting of many entropic traps, was designed and fabricated for the separation of long DNA molecules. The channel comprises narrow constrictions and wider regions that cause size-dependent trapping of DNA at the onset of a constriction. This process creates electrophoretic mobility differences, thus enabling efficient separation without the use of a gel matrix or pulsed electric fields. Samples of long DNA molecules (5000 to ∼160,000 base pairs) were efficiently separated into bands in 15-millimeter-long channels. Multiple-channel devices operating in parallel were demonstrated. The efficiency, compactness, and ease of fabrication of the device suggest the possibility of more practical integrated DNA analysis systems.
How Soft Is a Protein? A Protein Dynamics Force Constant Measured by Neutron Scattering
Authors: Zaccai Giuseppe
Published: July 2002

An effective environmental force constant is introduced to quantify the molecular resilience (or its opposite, “softness”) of a protein structure and relate it to biological function and activity. Specific resilience-function relations were found in neutron-scattering experiments on purple membranes containing bacteriorhodopsin, the light-activated proton pump of halobacteria; the connection between resilience and stability is illustrated by a study of myoglobin in different environments. Important advantages of the neutron method are that it can characterize the dynamics of any type of biological sample—which need not be crystalline or monodisperse—and that it enables researchers to focus on the dynamics of specific parts of a complex structure with deuterium labeling.
Gone with the Wind: The Origin of S0 Galaxies in Clusters
Authors: Quilis Vicent , Moore Ben , Bower Richard
Published: July 2002

We present three-dimensional, high-resolution hydrodynamical simulations of the interaction between the hot ionized intracluster medium and the cold interstellar medium of spiral galaxies. Ram pressure and turbulent/viscous stripping remove 100% of the atomic hydrogen content of luminous galaxies like the Milky Way within 100 million years. These mechanisms naturally account for the morphology of S0 galaxies and the rapid truncation of star formation implied by spectroscopic observations, as well as a host of observational data on the neutral hydrogen (HI) morphology of galaxies in clusters.
Neuronal Plasticity: Increasing the Gain in Pain
Authors: Woolf Clifford J. , Salter Michael W.
Published: July 2002

We describe those sensations that are unpleasant, intense, or distressing as painful. Pain is not homogeneous, however, and comprises three categories: physiological, inflammatory, and neuropathic pain. Multiple mechanisms contribute, each of which is subject to or an expression of neural plasticity—the capacity of neurons to change their function, chemical profile, or structure. Here, we develop a conceptual framework for the contribution of plasticity in primary sensory and dorsal horn neurons to the pathogenesis of pain, identifying distinct forms of plasticity, which we term activation, modulation, and modification, that by increasing gain, elicit pain hypersensitivity.
Real-Space Imaging of Two-Dimensional Antiferromagnetism on the Atomic Scale
Authors: Heinze S. , Bode M. , Kubetzka A. , Pietzsch O. , Nie X. , Blügel S. , Wiesendanger R.
Published: July 2002

A two-dimensional antiferromagnetic structure within a pseudomorphic monolayer film of chemically identical manganese atoms on tungsten(110) was observed with atomic resolution by spin-polarized scanning tunneling microscopy at 16 kelvin. A magnetic superstructure changes the translational symmetry of the surface lattice with respect to the chemical unit cell. It is shown, with the aid of first-principles calculations, that as a result of this, spin-polarized tunneling electrons give rise to an image corresponding to the magnetic superstructure and not to the chemical unit cell. These investigations demonstrate a powerful technique for the understanding of complicated magnetic configurations of nanomagnets and thin films engineered from ferromagnetic and antiferromagnetic materials used for magnetoelectronics.
Dissociating the Role of the Dorsolateral Prefrontal and Anterior Cingulate Cortex in Cognitive Control
Authors: MacDonald Angus W. , Cohen Jonathan D. , Stenger V. Andrew , Carter Cameron S.
Published: July 2002

Theories of the regulation of cognition suggest a system with two necessary components: one to implement control and another to monitor performance and signal when adjustments in control are needed. Event-related functional magnetic resonance imaging and a task-switching version of the Stroop task were used to examine whether these components of cognitive control have distinct neural bases in the human brain. A double dissociation was found. During task preparation, the left dorsolateral prefrontal cortex (Brodmann's area 9) was more active for color naming than for word reading, consistent with a role in the implementation of control. In contrast, the anterior cingulate cortex (Brodmann's areas 24 and 32) was more active when responding to incongruent stimuli, consistent with a role in performance monitoring.
Aggregation-Based Crystal Growth and Microstructure Development in Natural Iron Oxyhydroxide Biomineralization Products
Authors: Banfield Jillian F. , Welch Susan A. , Zhang Hengzhong , Ebert Tamara Thomsen , Penn R. Lee
Published: July 2002

Crystals are generally considered to grow by attachment of ions to inorganic surfaces or organic templates. High-resolution transmission electron microscopy of biomineralization products of iron-oxidizing bacteria revealed an alternative coarsening mechanism in which adjacent 2- to 3-nanometer particles aggregate and rotate so their structures adopt parallel orientations in three dimensions. Crystal growth is accomplished by eliminating water molecules at interfaces and forming iron-oxygen bonds. Self-assembly occurs at multiple sites, leading to a coarser, polycrystalline material. Point defects (from surface-adsorbed impurities), dislocations, and slabs of structurally distinct material are created as a consequence of this growth mechanism and can dramatically impact subsequent reactivity.
Coseismic and Postseismic Fault Slip for the 17 August 1999, M = 7.5, Izmit, Turkey Earthquake
Authors: Reilinger R. E. , Ergintav S. , Bürgmann R. , McClusky S. , Lenk O. , Barka A. , Gurkan O. , Hearn L. , Feigl K. L. , Cakmak R. , Aktug B. , Ozener H. , Töksoz M. N.
Published: July 2002

We use Global Positioning System (GPS) observations and elastic half-space models to estimate the distribution of coseismic and postseismic slip along the Izmit earthquake rupture. Our results indicate that large coseismic slip (reaching 5.7 meters) is confined to the upper 10 kilometers of the crust, correlates with structurally distinct fault segments, and is relatively low near the hypocenter. Continued surface deformation during the first 75 days after the earthquake indicates an aseismic fault slip of as much as 0.43 meters on and below the coseismic rupture. These observations are consistent with a transition from unstable (episodic large earthquakes) to stable (fault creep) sliding at the base of the seismogenic zone.
Potent Analgesic Effects of GDNF in Neuropathic Pain States
Authors: Boucher Timothy J. , Okuse Kenji , Bennett David L. H. , Munson John B. , Wood John N. , McMahon Stephen B.
Published: July 2002

Neuropathic pain arises as a debilitating consequence of nerve injury. The etiology of such pain is poorly understood, and existing treatment is largely ineffective. We demonstrate here that glial cell line–derived neurotrophic factor (GDNF) both prevented and reversed sensory abnormalities that developed in neuropathic pain models, without affecting pain-related behavior in normal animals. GDNF reduces ectopic discharges within sensory neurons after nerve injury. This may arise as a consequence of the reversal by GDNF of the injury-induced plasticity of several sodium channel subunits. Together these findings provide a rational basis for the use of GDNF as a therapeutic treatment for neuropathic pain states.