bluuebunny/crossref_metadata_2025 huggingface dataset:
Fission Yeast Slp1: An Effector of the Mad2-Dependent Spindle Checkpoint
Authors: Kim Sang Hoon , Lin Diana P. , Matsumoto Sanae , Kitazono Ana , Matsumoto Tomohiro
Published: July 2002

Mad2 is a component of the spindle checkpoint, which delays the onset of anaphase until all chromosomes are attached to the spindle. Mad2 formed a complex with Slp1, a WD (tryptophan–aspartic acid)–repeat protein essential for the onset of anaphase. When the physical interaction between the two proteins was disrupted, the spindle checkpoint was no longer functional. Post-anaphase events such as chromosome decondensation and the next round of DNA replication were not delayed even when the spindle assembly was incomplete. This relief of dependence appears to be a result of deregulation of ubiquitin-dependent proteolysis mediated by the anaphase-promoting complex.
Single-Grain
40
Ar-
39
Ar Ages of Glauconies: Implications for the Geologic Time Scale and Global Sea Level Variations
Authors: Smith Patrick E. , Evensen Norman M. , York Derek , Odin Gilles S.
Published: July 2002

The mineral series glaucony supplies 40% of the absolute-age database for the geologic time scale of the last 250 million years. However, glauconies have long been suspected of giving young potassium-argon ages on bulk samples. Laser-probe argon-argon dating shows that glaucony populations comprise grains with a wide range of ages, suggesting a period of genesis several times longer (∼5 million years) than previously thought. An estimate of the age of their enclosing sediments (and therefore of time scale boundaries) is given by the oldest nonrelict grains in the glaucony populations, whereas the formation times of the younger grains appear to be modulated by global sea level.
A Screen for Genes Induced in the Suprachiasmatic Nucleus by Light
Authors: Morris Mary E. , Viswanathan N. , Kuhlman Sandra , Davis Fred C. , Weitz Charles J.
Published: July 2002

The mechanism by which mammalian circadian clocks are entrained to light-dark cycles is unknown. The clock that drives behavioral rhythms is located in the suprachiasmatic nucleus (SCN) of the brain, and entrainment is thought to require induction of genes in the SCN by light. A complementary DNA subtraction method based on genomic representational difference analysis was developed to identify such genes without making assumptions about their nature. Four clones corresponded to genes induced specifically in the SCN by light, all of which showed gating of induction by the circadian clock. Among these genes are c-
fos
and
nur77
, two of the five early-response genes known to be induced in the SCN by light, and
egr-3
, a zinc finger transcription factor not previously identified in the SCN. In contrast to known examples,
egr-3
induction by light is restricted to the ventral SCN, a structure implicated in entrainment.
Formation of Carbonates in the Tatahouine Meteorite
Authors: Barrat J. A. , Gillet Ph. , Lécuyer C. , Sheppard S. M. F. , Lesourd M.
Published: July 2002

The Tatahouine meteorite, in southern Tunisia, shows terrestrial contamination that developed during 63 years of exposure on Earth's surface. Samples collected on the day of the fall in 1931 contained fractures, with no secondary minerals, whereas samples collected in 1994 contain calcite aggregates (70 to 150 micrometers) and rod-shaped forms (100 to 600 nanometers in length and 70 to 80 nanometers in diameter) on the fractures. Carbon isotope analysis of the carbonates within the Tatahouine meteorite [δ
13
C = −2.0 per mil Pee Dee belemnite standard (PDB)] and the underlying ground (δ
13
C = −3.2 per mil PDB) confirm their terrestrial origin.
Activation of the Protein Kinase p38 in the Spindle Assembly Checkpoint and Mitotic Arrest
Authors: Takenaka Katsuya , Moriguchi Tetsuo , Nishida Eisuke
Published: July 2002

The mitogen-activated protein kinase (MAPK) superfamily comprises classical MAPK (also called ERK), c-Jun amino-terminal or stress-activated protein kinase (JNK or SAPK), and p38. Although MAPK is essential for meiotic processes in
Xenopus
oocytes and the spindle assembly checkpoint in
Xenopus
egg extracts, the role of members of the MAPK superfamily in M phase or the spindle assembly checkpoint during somatic cell cycles has not been elucidated. The kinase p38, but not MAPK or JNK, was activated in mammalian cultured cells when the cells were arrested in M phase by disruption of the spindle with nocodazole. Addition of activated recombinant p38 to
Xenopus
cell-free extracts caused arrest of the extracts in M phase, and injection of activated p38 into cleaving embryos induced mitotic arrest. Treatment of NIH 3T3 cells with a specific inhibitor of p38 suppressed activation of the checkpoint by nocodazole. Thus, p38 functions as a component of the spindle assembly checkpoint in somatic cell cycles.
Effect of Substrate Strain on Adsorption
Authors: Gsell M. , Jakob P. , Menzel D.
Published: July 2002

Direct evidence for the effect of local strain at a surface on the bonding strength for adsorbates is presented. Scanning tunneling microscopy revealed that adsorbed oxygen atoms on Ru(0001) surfaces are located preferentially on top of nanometer-size protrusions above subsurface argon bubbles, where tensile strain prevails, and are depleted around their rim in regions of compression, relative to the flat surface. Such effects can be considered as the reverse of adsorbate-induced strain, and their direct local demonstration can be used to test theoretical predictions.
Reductive Dechlorination of DDE to DDMU in Marine Sediment Microcosms
Authors: Quensen John F. , Mueller Sherry A. , Jain Mahendra K. , Tiedje James M.
Published: July 2002

DDT is reductively dechlorinated to DDD and dehydrochlorinated to DDE; it has been thought that DDE is not degraded further in the environment. Laboratory experiments with DDE-containing marine sediments showed that DDE is dechlorinated to DDMU in both methanogenic and sulfidogenic microcosms and that DDD is dehydrochlorinated to DDMU three orders of magnitude more slowly. Thus, DDD does not appear to be an important precursor of the DDMU found in these sediments. These results imply that remediation decisions and risk assessments based on the recalcitrance of DDE in marine and estuarine sediments should be reevaluated.
Percolation of Core Melts at Lower Mantle Conditions
Authors: Shannon M. C. , Agee C. B.
Published: July 2002

Experiments at high pressure and temperature to determine the dihedral angle of core melts in lower mantle phases yielded a value of ∼71° for perovskite-dominated matrices. This angle, although greater than the 60° required for completely efficient percolation, is considerably less than the angles observed in mineral matrices at upper mantle pressure-temperature conditions in experiments. In other words, molten iron alloy can flow much more easily in lower mantle mineralogies than in upper mantle mineralogies. Accordingly, although segregation of core material by melt percolation is probably not feasible in the upper mantle, core formation by percolation may be possible in the lower mantle.
Silacalix-[
n
]-phosphaarenes: Macrocyclic Ligands Based on Dicoordinate Phosphorus Centers
Authors: Avarvari Narcis , Mézailles Nicolas , Ricard Louis , Floch Pascal Le , Mathey François
Published: July 2002

The synthesis of polyphosphinine macrocycles, which consist of a 16-membered ring with four phosphorus atoms (P
4
) and a 12-membered ring with three phosphorus atoms (P
3
), is described. Their high coordination ability is demonstrated by the quantitative synthesis of the rhodium and iridium cation complexes of the P
4
macrocycle and by quantitative synthesis of the W(CO)
3
complex of the P
3
compound. Unlike the other available macrocyclic ligands bearing oxygen, sulfur, di- or tricoordinate nitrogen, and even tricoordinate phosphorus as ligating atoms, which are all essentially σ donors, these dicoordinate phosphorus-based macrocycles have strong π-acceptor properties. Their use can be envisaged for the stabilization of negative oxidation states of transition metals or in reductive catalysis.
Endocranial Capacity in an Early Hominid Cranium from Sterkfontein, South Africa
Authors: Conroy Glenn C. , Weber Gerhard W. , Seidler Horst , Tobias Phillip V. , Kane Alex , Brunsden Barry
Published: July 2002

Two- and three-dimensional computer imaging shows that endocranial capacity in an ∼2.8- to 2.6-million-year-old early hominid cranium (Stw 505) from Sterkfontein, South Africa, tentatively assigned to
Australopithecus africanus
, is ∼515 cubic centimeters. Although this is the largest endocranial capacity recorded for this species, it is still markedly less than anecdotal reports of endocranial capacity exceeding 600 cubic centimeters. No australopithecine has an endocranial capacity approaching, let alone exceeding, 600 cubic centimeters. Some currently accepted estimates of early hominid endocranial capacity may be inflated, suggesting that the tempo and mode of early hominid brain evolution may need reevaluation.
Combinatorial Electrochemistry: A Highly Parallel, Optical Screening Method for Discovery of Better Electrocatalysts
Authors: Reddington Erik , Sapienza Anthony , Gurau Bogdan , Viswanathan Rameshkrishnan , Sarangapani S. , Smotkin Eugene S. , Mallouk Thomas E.
Published: July 2002

Combinatorial screening of electrochemical catalysts by current-voltage methods can be unwieldy for large sample sizes. By converting the ions generated in an electrochemical half-cell reaction to a fluorescence signal, the most active compositions in a large electrode array have been identified. A fluorescent acid-base indicator was used to image high concentrations of hydrogen ions, which were generated in the electrooxidation of methanol. A 645-member electrode array containing five elements (platinum, ruthenium, osmium, iridium, and rhodium), 80 binary, 280 ternary, and 280 quaternary combinations was screened to identify the most active regions of phase space. Subsequent “zoom” screens pinpointed several very active compositions, some in ternary and quaternary regions that were bounded by rather inactive binaries. The best catalyst, platinum(44)/ruthenium(41)/osmium(10)/iridium(5) (numbers in parentheses are atomic percent), was significantly more active than platinum(50)/ruthenium(50) in a direct methanol fuel cell operating at 60°C, even though the latter catalyst had about twice the surface area of the former.
Progress in the Development of an HIV-1 Vaccine
Authors: Letvin Norman L.
Published: July 2002

Containment of the acquired immunodeficiency syndrome (AIDS) epidemic will require an effective human immunodeficiency virus type 1 (HIV-1) vaccine. Accumulating evidence suggests that such a vaccine must efficiently elicit an HIV-1–specific cytotoxic T lymphocyte (CTL) response. Nonhuman primate models will continue to provide an important tool for assessing the extent of protective immunity induced by various immunization strategies. Although replication-competent AIDS viruses attenuated for pathogenicity by selective gene deletions have provided protective immunity in nonhuman primate models, the long-term safety of such vaccines in human populations is suspect. Inactivated virus and subunit vaccines have elicited neither CTLs nor antibodies capable of neutralizing a wide array of patient HIV-1 isolates. Considerable effort is now being focused on evaluating live vector-based vaccine and plasmid DNA vaccine approaches for preventing HIV-1 infection both in animal model and human studies. Our growing understanding of the biology of HIV-1 and immune responses to this virus will continue to suggest improved vaccination approaches for exploration.
Black Carbon in Deep-Sea Sediments
Authors: Masiello C. A. , Druffel E. R. M.
Published: July 2002

Black carbon (BC) enters the ocean through aerosol and river deposition. BC makes up 12 to 31 percent of the sedimentary organic carbon (SOC) at two deep ocean sites, and it is 2400 to 13,900 carbon-14 years older than non-BC SOC deposited concurrently. BC is likely older because it is stored in an intermediate reservoir before sedimentary deposition. Possible intermediate pools are oceanic dissolved organic carbon (DOC) and terrestrial soils. If DOC is the intermediate reservoir, then BC is 4 to 22 percent of the DOC pool. If soils are the intermediate reservoir, then the importance of riverine carbon in the ocean carbon cycle has been underestimated.
Carbon Dioxide Emission from European Estuaries
Authors: Frankignoulle Michel , Abril Gwenaël , Borges Alberto , Bourge Isabelle , Canon Christine , Delille Bruno , Libert Emile , Théate Jean-Marie
Published: July 2002

The partial pressure of carbon dioxide (pCO
2
) in surface waters and related atmospheric exchanges were measured in nine European estuaries. Averaged fluxes over the entire estuaries are usually in the range of 0.1 to 0.5 mole of CO
2
per square meter per day. For wide estuaries, net daily fluxes to the atmosphere amount to several hundred tons of carbon (up to 790 tons of carbon per day in the Scheldt estuary). European estuaries emit between 30 and 60 million tons of carbon per year to the atmosphere, representing 5 to 10% of present anthropogenic CO
2
emissions for Western Europe.
Migration of Fluids Beneath Yellowstone Caldera Inferred from Satellite Radar Interferometry
Authors: Wicks Charles , Thatcher Wayne , Dzurisin Daniel
Published: July 2002

Satellite interferometric synthetic aperture radar is uniquely suited to monitoring year-to-year deformation of the entire Yellowstone caldera (about 3000 square kilometers). Sequential interferograms indicate that subsidence within the caldera migrated from one resurgent dome to the other between August 1992 and August 1995. Between August 1995 and September 1996, the caldera region near the northeast dome began to inflate, and accompanying surface uplift migrated to the southwest dome between September 1996 and June 1997. These deformation data are consistent with hydrothermal or magmatic fluid migration into and out of two sill-like bodies that are about 8 kilometers directly beneath the caldera.
Isotopic Evidence for the Cretaceous-Tertiary Impactor and Its Type
Authors: Shukolyukov A. , Lugmair G. W.
Published: July 2002

High-precision mass spectrometric analysis of chromium in sediment samples from the Cretaceous-Tertiary (K-T) boundary coincident with the extinction of numerous organisms on Earth confirms the cosmic origin of the K-T phenomenon. The isotopic composition of chromium in K-T boundary samples from Stevns Klint, Denmark, and Caravaca, Spain, is different from that of Earth and indicates its extraterrestrial source. The chromium isotopic signature is consistent with a carbonaceous chondrite–type impactor. The observed differences in the chromium isotopic composition among various meteorite classes can serve as a diagnostic tool for deciphering the nature of impactors that have collided with Earth during its history.
Genetic Neurodegenerative Diseases: The Human Illness and Transgenic Models
Authors: Price Donald L. , Sisodia Sangram S. , Borchelt David R.
Published: July 2002

The neurodegenerative disorders, a heterogeneous group of chronic progressive diseases, are among the most puzzling and devastating illnesses in medicine. Some of these disorders, such as Alzheimer's disease, amyotrophic lateral sclerosis, the prion diseases, and Parkinson's disease, can occur sporadically and, in some instances, are caused by inheritance of gene mutations. Huntington's disease is acquired in an entirely genetic manner. Transgenic mice that express disease-causing genes recapitulate many features of these diseases. This review provides an overview of transgenic mouse models of familial amyotrophic lateral sclerosis, familial Alzheimer's disease, and Huntington's disease and the emerging insights relevant to the underlying molecular mechanisms of these diseases.
Large-Scale Sprouting of Cortical Connections After Peripheral Injury in Adult Macaque Monkeys
Authors: Florence Sherre L. , Taub Hilary B. , Kaas Jon H.
Published: July 2002

Distributions of thalamic and cortical connections were investigated in four macaque monkeys with long-standing, accidental trauma to a forelimb, to determine whether the growth of new connections plays a role in the reorganization of somatosensory cortex that occurs after major alterations in peripheral somatosensory inputs. In each monkey, microelectrode recordings of cortical areas 3b and 1 demonstrated massive reorganizations of the cortex related to the affected limb. Injections of tracers in area 1 of these monkeys revealed normal patterns of thalamocortical connections, but markedly expanded lateral connections in areas 3b and 1. Thus, the growth of intracortical but not thalamocortical connections could account for much of the reorganization of the sensory maps in cortex.
Transient Phase-Induced Nucleation
Authors: Sirota E. B. , Herhold A. B.
Published: July 2002

A transient metastable rotator phase occurring on crystallization of hexadecane into its triclinic phase from the supercooled melt was directly observed with time-resolved synchrotron x-ray scattering. In this system, the limit of supercooling (the crystallization temperature) is determined by the thermodynamic stability of the transient phase with respect to the liquid. The crystallization kinetics of the homologous series of n -alkanes was measured and explained in terms of a crossover from stability to “long-lived” metastability to transient metastability. This crossover allowed further confirmation of the nature of the transient phase.
The Dynamics of Zooxanthellae Populations: A Long-Term Study in the Field
Authors: Fagoonee I. , Wilson H. B. , Hassell M. P. , Turner J. R.
Published: July 2002

Coral bleaching characterized by the expulsion of symbiotic algae (zooxanthellae) is an increasing problem worldwide. Global warming has been implicated as one cause, but the phenomenon cannot be fully comprehended without an understanding of the variability of zooxanthellae populations in field conditions. Results from a 6-year field study are presented, providing evidence of density regulation but also of large variability in the zooxanthellae population with regular episodes of very low densities. These bleaching events are likely to be part of a constant variability in zooxanthellae density caused by environmental fluctuations superimposed on a strong seasonal cycle in abundance.
CD3- and CD28-Dependent Induction of PDE7 Required for T Cell Activation
Authors: Li Linsong , Yee Cassian , Beavo Joseph A.
Published: July 2002

Costimulation of both the CD3 and CD28 receptors is essential for T cell activation. Induction of adenosine 3′,5′-monophosphate (cAMP)–specific phosphodiesterase-7 (PDE7) was found to be a consequence of such costimulation. Increased PDE7 in T cells correlated with decreased cAMP, increased interleukin-2 expression, and increased proliferation. Selectively reducing PDE7 expression with a PDE7 antisense oligonucleotide inhibited T cell proliferation; inhibition was reversed by blocking the cAMP signaling pathways that operate through cAMP-dependent protein kinase (PKA). Thus, PDE7 induction and consequent suppression of PKA activity is required for T cell activation, and inhibition of PDE7 could be an approach to treating T cell–dependent disorders.
Defective Angiogenesis in Mice Lacking Endoglin
Authors: Li Dean Y. , Sorensen Lise K. , Brooke Benjamin S. , Urness Lisa D. , Davis Elaine C. , Taylor Douglas G. , Boak Beth B. , Wendel Daniel P.
Published: July 2002

Endoglin is a transforming growth factor–β (TGF-β) binding protein expressed on the surface of endothelial cells. Loss-of-function mutations in the human endoglin gene
ENG
cause hereditary hemorrhagic telangiectasia (HHT1), a disease characterized by vascular malformations. Here it is shown that by gestational day 11.5, mice lacking endoglin die from defective vascular development. However, in contrast to mice lacking TGF-β, vasculogenesis was unaffected. Loss of endoglin caused poor vascular smooth muscle development and arrested endothelial remodeling. These results demonstrate that endoglin is essential for angiogenesis and suggest a pathogenic mechanism for HHT1.
Topography of the Lunar Poles from Radar Interferometry: A Survey of Cold Trap Locations
Authors: Margot J. L. , Campbell D. B. , Jurgens R. F. , Slade M. A.
Published: July 2002

Detailed topographic maps of the lunar poles have been obtained by Earth-based radar interferometry with the 3.5-centimeter wavelength Goldstone Solar System Radar. The interferometer provided maps 300 kilometers by 1000 kilometers of both polar regions at 150-meter spatial resolution and 50-meter height resolution. Using ray tracing, these digital elevation models were used to locate regions that are in permanent shadow from solar illumination and may harbor ice deposits. Estimates of the total extent of shadowed areas poleward of 87.5 degrees latitude are 1030 and 2550 square kilometers for the north and south poles, respectively.
Preventing Neurodegeneration in the
Drosophila
Mutant
bubblegum
Authors: Min Kyung-Tai , Benzer Seymour
Published: July 2002

The
Drosophila melanogaster
recessive mutant
bubblegum
(
bgm
) exhibits adult neurodegeneration, with marked dilation of photoreceptor axons. The
bubblegum
mutant shows elevated levels of very long chain fatty acids (VLCFAs), as seen in the human disease adrenoleukodystrophy (ALD). In ALD, the excess can be lowered by dietary treatment with “Lorenzo's oil,” a mixture of unsaturated fatty acids. Feeding the fly mutant one of the components, glyceryl trioleate oil, blocked the accumulation of excess VLCFAs as well as development of the pathology. Mutant flies thus provide a potential model system for studying mechanisms of neurodegenerative disease and screening drugs for treatment.
Visible Cone-Beam Tomography With a Lensless Interferometric Camera
Authors: Marks Daniel L. , Stack Ronald A. , Brady David J. , Munson David C. , Brady Rachael B.
Published: July 2002

Digital processing of optical coherence functions can reconstruct three-dimensional objects illuminated by incoherent light. It is shown that Fourier analysis of the mutual intensity of the field produces projections that are mathematically identical to the projections of x-ray cone-beam tomography. A lensless interferometric camera that captures planes of mutual intensity data is described and used to reconstruct an incoherently illuminated visible object in three dimensions.
Regulation of NMDA Receptors by an Associated Phosphatase-Kinase Signaling Complex
Authors: Westphal Ryan S. , Tavalin Steven J. , Lin Jerry W. , Alto Neal M. , Fraser Iain D. C. , Langeberg Lorene K. , Sheng Morgan , Scott John D.
Published: July 2002

Regulation of
N
-methyl-
d
-aspartate (NMDA) receptor activity by kinases and phosphatases contributes to the modulation of synaptic transmission. Targeting of these enzymes near the substrate is proposed to enhance phosphorylation-dependent modulation. Yotiao, an NMDA receptor–associated protein, bound the type I protein phosphatase (PP1) and the adenosine 3′,5′-monophosphate (cAMP)–dependent protein kinase (PKA) holoenzyme. Anchored PP1 was active, limiting channel activity, whereas PKA activation overcame constitutive PP1 activity and conferred rapid enhancement of NMDA receptor currents. Hence, yotiao is a scaffold protein that physically attaches PP1 and PKA to NMDA receptors to regulate channel activity.
Biotechnology and Food Security in the 21st Century
Authors: Serageldin Ismail
Published: July 2002

Biotechnology can contribute to future food security if it benefits sustainable small-farm agriculture in developing countries. Presently, agrobiotechnology research cites ethical, safety, and intellectual property rights issues. Protection of intellectual property rights encourages private sector investment in agrobiotechnology, but in developing countries the needs of smallholder farmers and environmental conservation are unlikely to attract private funds. Public investment will be needed, and new and imaginative public-private collaboration can make the gene revolution beneficial to developing countries. This is crucial for the well-being of today's hungry people and future generations.
Formation of Ordered Nanoscale Semiconductor Dots by Ion Sputtering
Authors: Facsko S. , Dekorsy T. , Koerdt C. , Trappe C. , Kurz H. , Vogt A. , Hartnagel H. L.
Published: July 2002

A formation process for semiconductor quantum dots based on a surface instability induced by ion sputtering under normal incidence is presented. Crystalline dots 35 nanometers in diameter and arranged in a regular hexagonal lattice were produced on gallium antimonide surfaces. The formation mechanism relies on a natural self-organization mechanism that occurs during the erosion of surfaces, which is based on the interplay between roughening induced by ion sputtering and smoothing due to surface diffusion.
Control of Circadian Rhythms and Photoperiodic Flowering by the
Arabidopsis GIGANTEA
Gene
Authors: Park Deok Hoon , Somers David E. , Kim Yang Suk , Choy Yoon Hi , Lim Hee Kyun , Soh Moon Soo , Kim Hyo Jung , Kay Steve A. , Nam Hong Gil
Published: July 2002

Photoperiodic responses in plants include flowering that is day-length–dependent. Mutations in the
Arabidopsis thaliana GIGANTEA
(
GI
) gene cause photoperiod-insensitive flowering and alteration of circadian rhythms. The
GI
gene encodes a protein containing six putative transmembrane domains. Circadian expression patterns of the
GI
gene and the clock-associated genes,
LHY
and
CCA1
, are altered in
gi
mutants, showing that GI is required for maintaining circadian amplitude and appropriate period length of these genes. The
gi-1
mutation also affects light signaling to the clock, which suggests that GI participates in a feedback loop of the plant circadian system.
Prospects for in Utero Human Gene Therapy
Authors: Zanjani Esmail D. , Anderson W. French
Published: July 2002

Gene therapy for the treatment of disease in children and adults is being actively pursued at many medical centers. However, a number of genetic disorders result in irreversible damage to the fetus before birth. In these cases, as well as for those with genetic diseases who may benefit from therapy before symptoms are manifested, in utero gene therapy (IUGT) could be beneficial. Although some successes with in utero gene transfer have been reported in animals, significant questions remain to be answered before IUGT clinical trials would be acceptable. This review analyzes the state of the art and delineates the studies that still need to be performed before it would be appropriate to consider human IUGT.
Impaired Fas Response and Autoimmunity in
Pten
+/−
Mice
Authors: Cristofano Antonio Di , Kotsi Paraskevi , Peng Yu Feng , Cordon-Cardo Carlos , Elkon Keith B. , Pandolfi Pier Paolo
Published: July 2002

Inactivating mutations in the
PTEN
tumor suppressor gene, encoding a phosphatase, occur in three related human autosomal dominant disorders characterized by tumor susceptibility. Here it is shown that
Pten
heterozygous (
Pten
+/−
) mutants develop a lethal polyclonal autoimmune disorder with features reminiscent of those observed in Fas-deficient mutants. Fas-mediated apoptosis was impaired in
Pten
+/−
mice, and T lymphocytes from these mice show reduced activation-induced cell death and increased proliferation upon activation. Phosphatidylinositol (PI) 3-kinase inhibitors restored Fas responsiveness in
Pten
+/−
cells. These results indicate that
Pten
is an essential mediator of the Fas response and a repressor of autoimmunity and thus implicate the PI 3-kinase/Akt pathway in Fas-mediated apoptosis.
Stability and Variability in Competitive Communities
Authors: Ives A. R. , Gross K. , Klug J. L.
Published: July 2002

Long-term variability in the abundance of populations depends on the sensitivity of species to environmental fluctuations and the amplification of environmental fluctuations by interactions among species. Although competitive interactions and species number may have diverse effects on variability measured at the individual species level, a combination of theoretical analyses shows that these factors have no effect on variability measured at the community level. Therefore, biodiversity may increase community stability by promoting diversity among species in their responses to environmental fluctuations, but increasing the number and strength of competitive interactions has little effect.
Requirement for B Cell Linker Protein (BLNK) in B Cell Development
Authors: Pappu Rajita , Cheng Alec M. , Li Bin , Gong Qian , Chiu Chris , Griffin Nancy , White Mike , Sleckman Barry P. , Chan Andrew C.
Published: July 2002

Linker proteins function as molecular scaffolds to localize enzymes with substrates. In B cells, B cell linker protein (BLNK) links the B cell receptor (BCR)–activated Syk kinase to the phosphoinositide and mitogen-activated kinase pathways. To examine the in vivo role of BLNK, mice deficient in
BLNK
were generated. B cell development in
BLNK
−/−
mice was blocked at the transition from B220
+
CD43
+
progenitor B to B220
+
CD43
−
precursor B cells. Only a small percentage of immunoglobulin M
++
(IgM
++
), but not mature IgM
lo
IgD
hi
, B cells were detected in the periphery. Hence, BLNK is an essential component of BCR signaling pathways and is required to promote B cell development.
Deflection of the Local Interstellar Dust Flow by Solar Radiation Pressure
Authors: Landgraf M. , Augustsson K. , Grün E. , Gustafson B. Å. S.
Published: July 2002

Interstellar dust grains intercepted by the dust detectors on the Ulysses and Galileo spacecrafts at heliocentric distances from 2 to 4 astronomical units show a deficit of grains with masses from 1 × 10
–17
to 3 × 10
–16
kilograms relative to grains intercepted outside 4 astronomical units. To divert grains out of the 2– to 4–astronomical unit region, the solar radiation pressure must be 1.4 to 1.8 times the force of solar gravity. These figures are consistent with the optical properties of spherical or elongated grains that consist of astronomical silicates or organic refractory material. Pure graphite grains with diameters of 0.2 to 0.4 micrometer experience a solar radiation pressure force as much as twice the force of solar gravity.
Origin of the West Nile Virus Responsible for an Outbreak of Encephalitis in the Northeastern United States
Authors: Lanciotti R. S. , Roehrig J. T. , Deubel V. , Smith J. , Parker M. , Steele K. , Crise B. , Volpe K. E. , Crabtree M. B. , Scherret J. H. , Hall R. A. , MacKenzie J. S. , Cropp C. B. , Panigrahy B. , Ostlund E. , Schmitt B. , Malkinson M. , Banet C. , Weissman J. , Komar N. , Savage H. M. , Stone W. , McNamara T. , Gubler D. J.
Published: July 2002

In late summer 1999, an outbreak of human encephalitis occurred in the northeastern United States that was concurrent with extensive mortality in crows (
Corvus
species) as well as the deaths of several exotic birds at a zoological park in the same area. Complete genome sequencing of a flavivirus isolated from the brain of a dead Chilean flamingo (
Phoenicopterus chilensis
), together with partial sequence analysis of envelope glycoprotein (E-glycoprotein) genes amplified from several other species including mosquitoes and two fatal human cases, revealed that West Nile (WN) virus circulated in natural transmission cycles and was responsible for the human disease. Antigenic mapping with E-glycoprotein–specific monoclonal antibodies and E-glycoprotein phylogenetic analysis confirmed these viruses as WN. This North American WN virus was most closely related to a WN virus isolated from a dead goose in Israel in 1998.
A Delayed Wave of Death from Reproduction in
Drosophila
Authors: Sgrò Carla M. , Partridge Linda
Published: July 2002

Mortality rates typically increase rapidly at the onset of aging but can decelerate at later ages. Reproduction increases the death rate in many organisms. To test the idea that a delayed impact of earlier reproduction contributes to both an increase in death rates and a later deceleration in mortality, the timing of the surplus mortality produced by an increased level of egg production was measured in female
Drosophila
. Reproduction produced a delayed wave of mortality, coincident with the sharp increase in death rates at the onset of aging and the subsequent deceleration of mortality. These results suggest that aging has evolved primarily because of the damaging effects of reproduction earlier in life, rather than because of mutations that have detrimental effects only at late ages.
DNA Topoisomerase IIβ and Neural Development
Authors: Yang Xia , Li Wei , Prescott Elizabeth D. , Burden Steven J. , Wang James C.
Published: July 2002

DNA topoisomerase IIβ is shown to have an unsuspected and critical role in neural development. Neurogenesis was normal in IIβ mutant mice, but motor axons failed to contact skeletal muscles, and sensory axons failed to enter the spinal cord. Despite an absence of innervation, clusters of acetylcholine receptors were concentrated in the central region of skeletal muscles, thereby revealing patterning mechanisms that are autonomous to skeletal muscle. The defects in motor axon growth in IIβ mutant mice resulted in a breathing impairment and death of the pups shortly after birth.
Sainthood Confirmed
Authors: Numbers Ronald L.
Published: July 2002

William Osler
A Life in Medicine. Michael Bliss. Oxford University Press, New York, 1999. 595 pp. $35, £27.50. ISBN 0-19-512346-8.

Bliss's judicious, contextualized retelling of the Osler story presents the case that its subject was a truly great man, in private as well as for his impact on medicine (of his own time and ours).
A Class of Microstructured Particles Through Colloidal Crystallization
Authors: Velev Orlin D. , Lenhoff Abraham M. , Kaler Eric W.
Published: July 2002

Microstructured particles were synthesized by growing colloidal crystals in aqueous droplets suspended on fluorinated oil. The droplets template highly ordered and smooth particle assemblies, which diffract light and have remarkable structural stability. The method allows control of particle size and shape from spheres through ellipsoids to toroids by varying the droplet composition. Cocrystallization in colloidal mixtures yields anisotropic particles of organic and inorganic materials that can, for example, be oriented and turned over by magnetic fields. The results open the way to controllable formation of a wide variety of microstructures.
Homogenization of Fish Faunas Across the United States
Authors: Rahel Frank J.
Published: July 2002

Fish faunas across the continental United States have become more similar through time because of widespread introductions of a group of cosmopolitan species intended to enhance food and sport fisheries. On average, pairs of states have 15.4 more species in common now than before European settlement of North America. The 89 pairs of states that formerly had no species in common now share an average of 25.2 species. Introductions have played a larger role than extirpations in homogenizing fish faunas. Western and New England states have received the most introductions, which is a reflection of the small number of native fishes in these areas considered desirable gamefish by settlers.
Molecular Computation by DNA Hairpin Formation
Authors: Sakamoto Kensaku , Gouzu Hidetaka , Komiya Ken , Kiga Daisuke , Yokoyama Shigeyuki , Yokomori Takashi , Hagiya Masami
Published: July 2002

Hairpin formation by single-stranded DNA molecules was exploited in a DNA-based computation in order to explore the feasibility of autonomous molecular computing. An instance of the satisfiability problem, a famous hard combinatorial problem, was solved by using molecular biology techniques. The satisfiability of a given Boolean formula was examined autonomously, on the basis of hairpin formation by the molecules that represent the formula. This computation algorithm can test several clauses in the given formula simultaneously, which could reduce the number of laboratory steps required for computation.
Role of Adenine Nucleotide Translocator 1 in mtDNA Maintenance
Authors: Kaukonen Jyrki , Juselius Jukka K. , Tiranti Valeria , Kyttälä Aija , Zeviani Massimo , Comi Giacomo P. , Keränen Sirkka , Peltonen Leena , Suomalainen Anu
Published: July 2002

Autosomal dominant progressive external ophthalmoplegia is a rare human disease that shows a Mendelian inheritance pattern, but is characterized by large-scale mitochondrial DNA (mtDNA) deletions. We have identified two heterozygous missense mutations in the nuclear gene encoding the heart/skeletal muscle isoform of the adenine nucleotide translocator (
ANT1
) in five families and one sporadic patient. The familial mutation substitutes a proline for a highly conserved alanine at position 114 in the ANT1 protein. The analogous mutation in yeast caused a respiratory defect. These results indicate that ANT has a role in mtDNA maintenance and that a mitochondrial disease can be caused by a dominant mechanism.
Nucleated Conformational Conversion and the Replication of Conformational Information by a Prion Determinant
Authors: Serio Tricia R. , Cashikar Anil G. , Kowal Anthony S. , Sawicki George J. , Moslehi Jahan J. , Serpell Louise , Arnsdorf Morton F. , Lindquist Susan L.
Published: July 2002

Prion proteins can serve as genetic elements by adopting distinct physical and functional states that are self-perpetuating and heritable. The critical region of one prion protein, Sup35, is initially unstructured in solution and then forms self-seeded amyloid fibers. We examined in vitro the mechanism by which this state is attained and replicated. Structurally fluid oligomeric complexes appear to be crucial intermediates in de novo amyloid nucleus formation. Rapid assembly ensues when these complexes conformationally convert upon association with nuclei. This model for replicating protein-based genetic information, nucleated conformational conversion, may be applicable to other protein assembly processes.
92
Nb-
92
Zr and the Early Differentiation History of Planetary Bodies
Authors: Münker C. , Weyer S. , Mezger K. , Rehkämper M. , Wombacher F. , Bischoff A.
Published: July 2002

The niobium-92–zirconium-92 (
92
Nb-
92
Zr) extinct radioactive decay system (half-life of about 36 million years) can place new time constraints on early differentiation processes in the silicate portion of planets and meteorites. Zirconium isotope data show that Earth and the oldest lunar crust have the same relative abundances of
92
Zr as chondrites.
92
Zr deficits in calcium-aluminum–rich inclusions from the Allende meteorite constrain the minimum value for the initial
92
Nb/
93
Nb ratio of the solar system to 0.001. The absence of
92
Zr anomalies in terrestrial and lunar samples indicates that large silicate reservoirs on Earth and the moon (such as a magma ocean residue, a depleted mantle, or a crust) formed more than 50 million years after the oldest meteorites formed.
Optical Gain and Stimulated Emission in Nanocrystal Quantum Dots
Authors: Klimov V. I. , Mikhailovsky A. A. , Xu Su , Malko A. , Hollingsworth J. A. , Leatherdale C. A. , Eisler H.-J. , Bawendi M. G.
Published: July 2002

The development of optical gain in chemically synthesized semiconductor nanoparticles (nanocrystal quantum dots) has been intensely studied as the first step toward nanocrystal quantum dot lasers. We examined the competing dynamical processes involved in optical amplification and lasing in nanocrystal quantum dots and found that, despite a highly efficient intrinsic nonradiative Auger recombination, large optical gain can be developed at the wavelength of the emitting transition for close-packed solids of these dots. Narrowband stimulated emission with a pronounced gain threshold at wavelengths tunable with the size of the nanocrystal was observed, as expected from quantum confinement effects. These results unambiguously demonstrate the feasibility of nanocrystal quantum dot lasers.
Sound Velocities in Iron to 110 Gigapascals
Authors: Fiquet Guillaume , Badro James , Guyot François , Requardt Herwig , Krisch Michael
Published: July 2002

The dispersion of longitudinal acoustic phonons was measured by inelastic x-ray scattering in the hexagonal closed-packed (hcp) structure of iron from 19 to 110 gigapascals. Phonon dispersion curves were recorded on polycrystalline iron compressed in a diamond anvil cell, revealing an increase of the longitudinal wave velocity (
V
P
) from 7000 to 8800 meters per second. We show that hcp iron follows a Birch law for
V
P
, which is used to extrapolate velocities to inner core conditions. Extrapolated longitudinal acoustic wave velocities compared with seismic data suggest an inner core that is 4 to 5% lighter than hcp iron.
Backward Spreading of Memory-Retrieval Signal in the Primate Temporal Cortex
Authors: Naya Yuji , Yoshida Masatoshi , Miyashita Yasushi
Published: July 2002

Bidirectional signaling between neocortex and limbic cortex has been hypothesized to contribute to the retrieval of long-term memory. We tested this hypothesis by comparing the time courses of perceptual and memory-retrieval signals in two neighboring areas in temporal cortex, area TE (TE) and perirhinal cortex (PRh), while monkeys were performing a visual pair-association task. Perceptual signal reached TE before PRh, confirming its forward propagation. In contrast, memory-retrieval signal appeared earlier in PRh, and TE neurons were then gradually recruited to represent the sought target. A reasonable interpretation of this finding is that the rich backward fiber projections from PRh to TE may underlie the activation of TE neurons that represent a visual object retrieved from long-term memory.
Arabidopsis
NPL1: A Phototropin Homolog Controlling the Chloroplast High-Light Avoidance Response
Authors: Kagawa Takatoshi , Sakai Tatsuya , Suetsugu Noriyuki , Oikawa Kazusato , Ishiguro Sumie , Kato Tomohiko , Tabata Satoshi , Okada Kiyotaka , Wada Masamitsu
Published: July 2002

Chloroplasts relocate their positions in a cell in response to the intensity of incident light, moving to the side wall of the cell to avoid strong light, but gathering at the front face under weak light to maximize light interception. Here,
Arabidopsis thaliana
mutants defective in the avoidance response were isolated, and the mutated gene was identified as
NPL1
(NPH-like 1), a homolog of
NPH1
(nonphototropic hypocotyl 1), a blue light receptor used in phototropism. Hence, NPL1 is likely a blue light receptor regulating the avoidance response under strong light.
UDP-Glucose Dehydrogenase Required for Cardiac Valve Formation in Zebrafish
Authors: Walsh Emily C. , Stainier Didier Y. R.
Published: July 2002

Cardiac valve formation is a complex process that involves cell signaling events between the myocardial and endocardial layers of the heart across an elaborate extracellular matrix. These signals lead to marked morphogenetic movements and transdifferentiation of the endocardial cells at chamber boundaries. Here we identify the genetic defect in zebrafish
jekyll
mutants, which are deficient in the initiation of heart valve formation. The
jekyll
mutation disrupts a homolog of
Drosophila
Sugarless, a uridine 5′-diphosphate (UDP)–glucose dehydrogenase required for heparan sulfate, chondroitin sulfate, and hyaluronic acid production. The atrioventricular border cells do not differentiate from their neighbors in
jekyll
mutants, suggesting that Jekyll is required in a cell signaling event that establishes a boundary between the atrium and ventricle.
Evernimicin (SCH27899) Inhibits a Novel Ribosome Target Site: Analysis of 23S Ribosomal DNA Mutants
Authors: Adrian Peter V. , Mendrick Cara , Loebenberg David , McNicholas Paul , Shaw Karen J. , Klugman Keith P. , Hare Roberta S. , Black Todd A.
Published: July 2002

Spontaneous mutants of susceptible clinical and laboratory isolates of
Streptococcus pneumoniae
exhibiting reduced susceptibility to evernimicin (SCH27899; MIC, 0.5 to 4.0 mg/liter) were selected on plates containing evernimicin. Four isolates that did not harbor mutations in
rplP
(which encodes ribosomal protein L16) were further analyzed. Whole chromosomal DNA or PCR products of the 23S ribosomal DNA (rDNA) operons from these mutants could be used to transform the susceptible
S. pneumoniae
strain R6 to resistance at frequencies of 10
−5
and 10
−4
, respectively, rates 10- to 100-fold lower than that for a single-allele chromosomal marker. The transformants appeared slowly (48 to 72 h) on selective medium, and primary transformants passaged on nonselective medium produced single colonies that displayed heterogeneous susceptibilities to evernimicin. A single passage on selective medium of colonies derived from a single primary transformant homogenized the resistance phenotype. Sequence analysis of the 23S rDNA and rRNA from the resistant mutants revealed single, unique mutations in each isolate at the equivalent
Escherichia coli
positions 2469 (A → C), 2480 (C → T), 2535 (G → A), and 2536 (G → C). The mutations map within two different stems of the peptidyltransferase region of domain V. Because multiple copies of rDNA are present in the chromosome, gene conversion between mutant and wild-type 23S rDNA alleles may be necessary for stable resistance. Additionally, none of the characterized mutants showed cross-resistance to any of a spectrum of protein synthesis inhibitors, suggesting that the target site of evernimicin may be unique.
Mutant Prevention Concentration as a Measure of Fluoroquinolone Potency against Mycobacteria
Authors: Sindelar Georg , Zhao Xilin , Liew Anthony , Dong Yuzhi , Lu Tao , Zhou Jianfeng , Domagala John , Drlica Karl
Published: July 2002

Mutant prevention concentration (MPC) has been proposed as a new measure of antibiotic potency by which the ability to restrict selection of resistant mutants is evaluated. To determine whether MPC provides potency information unavailable from the more customary measurement of the MIC, 18 fluoroquinolones were examined for their ability to block the growth of
Mycobacterium smegmatis
and to select resistant mutants from wild-type populations. Both MPC and MIC were affected by changes in the moiety at the fluoroquinolone C-8 position and in alkyl groups attached to the C-7 piperazinyl ring. When eight resistant mutants, altered in the gyrase A protein, were tested with fluoroquinolones having either a methoxy or a hydrogen at the C-8 position, the MIC for the most resistant mutant correlated better with the MPC than did the MIC for wild-type cells. For C-8-fluorine derivatives, which were generally less active than the C-8-methoxy compounds but which were more active than C-8-hydrogen derivatives, the MICs for both the mutant and the wild type correlated well with the MPCs. Thus, measurement of the MICs for wild-type cells can reflect the ability of a quinolone to restrict the selection of resistance, but often it does not. With the present series of compounds, the most potent contained a C-8-methoxy and a small group attached to the C-7 ring.