bluuebunny/crossref_metadata_2025 huggingface dataset:
New Tumor Suppressor Found--Twice
Authors: Pennisi Elizabeth
Published: July 2002

Two teams, one of which reports its results on (
page 1943
) and the other in the April issue of Nature Genetics, have ended in a near dead heat in their race to find what appears to be a particularly important tumor suppressor. The gene, located on chromosome 10, may be involved in several kinds of cancers, including gliomas, a deadly brain cancer, and prostate, breast, and kidney cancer. It encodes a protein, the amino acid sequence of which indicates that it is a tyrosine phosphatase, an enzyme that removes phosphate groups from the amino acid tyrosine. Cancer researchers had long suspected that such phosphatases might be tumor suppressors because they directly counteract the actions of another set of enzymes that play a key role in cell's growth-stimulating pathways. This is the first direct proof of that suspicion.
Prepaper Publicity Ignites Race to Publish
Authors: Pennisi Elizabeth
Published: July 2002

In late January, the biotech firm Myriad Genetics put out a press release announcing the discovery of a new tumor suppressor. The company took the step to forestall possible charges of insider trading by company employees, but it also had another effect: triggering an intense effort by a competing group to get its own discovery of the gene into print.
Predator-Free Guppies Take an Evolutionary Leap Forward
Authors: Morell Virginia
Published: July 2002

It's a rare biologist who manages to catch a glimpse of evolution happening in the wild, but on (
page 1934
)page 1934 of this issue, researchers report just such a case in Trinidadian guppies. When moved to predator-free pools, the fish grew larger and reached sexual maturity later, all in the space of 4 to 7 years—showing that evolution can sometimes move at top speed.
DNA on the Big Screen
Authors: Stokstad Erik
Published: July 2002

An atomic force microscope has made the first movie of an enzyme at work on a DNA molecule. By tapping an ultrafine probe across the sample, the microscope followed an RNA polymerase molecule as it ratcheted down the DNA strand, linking nucleotide bases to create an RNA template for a protein.
Ground-Based Thermal Infrared Observations of Comet Hale-Bopp (C/1995 O1) During 1996
Authors: Hayward T. L. , Hanner M. S.
Published: July 2002

Thermal infrared (IR) imaging and spectroscopy of comet Hale-Bopp (C/1995 O1) during June, August, and September 1996 traced the development of the dust coma several months before perihelion. Images revealed nightly variations in the brightness of the inner coma from 1 to 12 June that were correlated with the appearance of a northward-pointing jet. The central IR flux increased by a factor of 8 between 1 June and 30 September, and the September data showed IR jets that corresponded to similar structures that were visible in reflected sunlight at shorter wavelengths. At all epochs, 8- to 13-micrometer spectra of the central coma revealed a strong silicate emission feature, including an 11.2-micrometer feature indicative of crystalline olivine, even when the comet was at a heliocentric distance of 4.1 astronomical units.
Signaling by Phosphoinositide-3,4,5-Trisphosphate Through Proteins Containing Pleckstrin and Sec7 Homology Domains
Authors: Klarlund Jes K. , Guilherme Adilson , Holik John J. , Virbasius Joseph V. , Chawla Anil , Czech Michael P.
Published: July 2002

Signal transmission by many cell surface receptors results in the activation of phosphoinositide (PI) 3-kinases that phosphorylate the 3′ position of polyphosphoinositides. From a screen for mouse proteins that bind phosphoinositides, the protein GRP1 was identified. GRP1 binds phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P
3
] through a pleckstrin homology (PH) domain and displays a region of high sequence similarity to the yeast Sec7 protein. The PH domain of the closely related protein cytohesin-1, which, through its Sec7 homology domain, regulates integrin β2 and catalyzes guanine nucleotide exchange of the small guanine nucleotide-binding protein ARF1, was also found to specifically bind PtdIns(3,4,5)P
3
. GRP1 and cytohesin-1 appear to connect receptor-activated PI 3-kinase signaling pathways with proteins that mediate biological responses such as cell adhesion and membrane trafficking.
Martian ‘Microbes’ Cover Their Tracks
Authors: Kerr Richard A.
Published: July 2002

HOUSTON
--Scientists studying putative microbes in a martian meteorite are finding it surprisingly hard to prove or deny the idea that life once existed on the Red Planet. Researchers at the recent Lunar and Planetary Science Conference dueled to a stalemate on such questions as the temperature of formation of carbonate in the meteorite and whether grains of magnetite might be masquerading as “nanobacteria.” But they also suggested how new studies may settle the question in coming months.
Crystals That Came in from the Cold
Authors: Hemley Russell J.
Published: July 2002

Physics of Cryocrystals.
VADIM G. MANZHELII and YURI A. FREIMAN, Eds. English-language version edited by Michael L. Klein and Alexei A. Maradudin. AIP Press, Woodbury, NY, 1996. xx, 691 pp., illus. $135 or £99. ISBN 1-56396-537-2.
Macrophages as a Source of HIV During Opportunistic Infections
Authors: Orenstein Jan M. , Fox Cecil , Wahl Sharon M.
Published: July 2002

The source of increasing viremia that characterizes the latter stages of human immunodeficiency virus (HIV) disease has remained a paradox because it occurs at a time when lymphoid tissue is quantitatively and qualitatively impaired, and the patients' CD4 T lymphocytes are steadily declining. Here, macrophages, both infected and uninfected with common opportunistic pathogens of HIV disease such as
Mycobacterium avium
complex and
Pneumocystis carinii
, were identified as highly productive sources of HIV in coinfected lymph nodes. These observations indicate that tissue macrophages are not only infected with HIV, but that common pathogens of HIV disease can dramatically increase their production of virus. Thus, prevention or successful treatment of opportunistic coinfections, or both, potentially benefits the patient twofold by limiting the pathology caused by opportunistic infection and by controlling induction of HIV replication.
X-ray and Molecular Emission from the Nearest Region of Recent Star Formation
Authors: Kastner J. H. , Zuckerman B. , Weintraub D. A. , Forveille T.
Published: July 2002

The isolated, young, sunlike star TW Hya and four other young stars in its vicinity are strong x-ray sources. Their similar x-ray and optical properties indicate that the stars make up a physical association that is on the order of 20 million years old and that lies between about 40 and 60 parsecs (between about 130 and 200 light years) from Earth. TW Hya itself displays circumstellar CO, HCN, CN, and HCO
+
emission. These molecules probably orbit the star in a solar-system–sized disk viewed more or less face-on, whereas the star is likely viewed pole-on. Being at least three times closer to Earth than any well-studied region of star formation, the TW Hya Association serves as a test-bed for the study of x-ray emission from young stars and the formation of planetary systems around sunlike stars.
Glacial Cycles and Astronomical Forcing
Authors: Muller Richard A. , MacDonald Gordon J.
Published: July 2002

Narrow spectral features in ocean sediment records offer strong evidence that the cycles of glaciation were driven by astronomical forces. Two million years ago, the cycles match the 41,000-year period of Earth's obliquity. This supports the Croll/Milankovitch theory, which attributes the cycles to variations in insolation. But for the past million years, the spectrum is dominated by a single 100,000-year feature and is a poor match to the predictions of insolation models. The spectrum can be accounted for by a theory that derives the cycles of glaciation from variations in the inclination of Earth's orbital plane.
Peer Review: The Appropriate GPRA Metric for Research
Authors: Kostoff Ronald N.
Published: July 2002

The implementation of the Government Performance and Results Act, whose aim is to improve the accountability of government-funded programs in the United States, could have far-reaching effects on scientific research. Concerns that the ability to do revolutionary research may be compromised by the increased emphasis on short-term measurable goals are discussed. An alternative strategy that could safeguard the open-ended needs of research and allow appropriate oversight is presented.
Power in Palo Alto
Authors: Servos John W.
Published: July 2002

Creating the Cold War University.
The Transformation of Stanford. REBECCA S. LOWEN. University of California Press, Berkeley, 1997. xii, 316 pp. $45 or £35. ISBN 0-520-20541-3.
Close Encounters
Authors: Hoeveler J. David
Published: July 2002

Redeeming Culture.
American Religion in an Age of Science. JAMES GILBERT. University of Chicago Press, Chicago, 1997. x, 407 pp., illus. $28.95 or £23.25. ISBN 0-226-29320-3.
Regulation of Distinct Stages of Skeletal Muscle Differentiation by Mitogen-Activated Protein Kinases
Authors: Bennett Anton M. , Tonks Nicholas K.
Published: July 2002

The signal transduction pathway or pathways linking extracellular signals to myogenesis are poorly defined. Upon mitogen withdrawal from C2C12 myoblasts, the mitogen-activated protein kinase (MAPK) p42Erk2 is inactivated concomitant with up-regulation of muscle-specific genes. Overexpression of MAPK phosphatase-1 (MKP-1) inhibited p42Erk2 activity and was sufficient to relieve the inhibitory effects of mitogens on muscle-specific gene expression. Later during myogenesis, endogenous expression of MKP-1 decreased. MKP-1 overexpression during differentiation prevented myotube formation despite appropriate expression of myosin heavy chain. This indicates that muscle-specific gene expression is necessary but not sufficient to commit differentiated myocytes to myotubes and suggests a function for the MAPKs during the early and late stages of skeletal muscle differentiation.
Mass Spectrometric Analysis of the Anaphase-Promoting Complex from Yeast: Identification of a Subunit Related to Cullins
Authors: Zachariae Wolfgang , Shevchenko Andrej , Andrews Paul D. , Ciosk Rafael , Galova Marta , Stark Michael J. R. , Mann Matthias , Nasmyth Kim
Published: July 2002

Entry into anaphase and exit from mitosis depend on a ubiquitin–protein ligase complex called the anaphase-promoting complex (APC) or cyclosome. At least 12 different subunits were detected in the purified particle from budding yeast, including the previously identified proteins Apc1p, Cdc16p, Cdc23p, Cdc26p, and Cdc27p. Five additional subunits purified in low nanogram amounts were identified by tandem mass spectrometric sequencing. Apc2p, Apc5p, and the RING-finger protein Apc11p are conserved from yeast to humans. Apc2p is similar to the cullin Cdc53p, which is a subunit of the ubiquitin–protein ligase complex SCF
Cdc4
required for the initiation of DNA replication.
Redesigning Enzyme Topology by Directed Evolution
Authors: MacBeath Gavin , Kast Peter , Hilvert Donald
Published: July 2002

Genetic selection was exploited in combination with structure-based design to transform an intimately entwined, dimeric chorismate mutase into a monomeric, four-helix–bundle protein with near native activity. Successful reengineering depended on choosing a thermostable starting protein, introducing point mutations that preferentially destabilize the wild-type dimer, and using directed evolution to optimize an inserted interhelical turn. Contrary to expectations based on studies of other four-helix–bundle proteins, only a small fraction of possible turn sequences (fewer than 0.05 percent) yielded well-behaved, monomeric, and highly active enzymes. Selection for catalytic function thus provides an efficient yet stringent method for rapidly assessing correctly folded polypeptides and may prove generally useful for protein design.
Tales of Terrible Toxins
Authors: Young Michael
Published: July 2002

The Clostridia: Molecular Biology and Pathogenesis
. JULIAN I. ROOD et al., Eds. Academic Press, San Diego, 1997. xviii, 533 pp., illus., + plates. $80. ISBN 0-12-595020-9.
RasGRP, a Ras Guanyl Nucleotide- Releasing Protein with Calcium- and Diacylglycerol-Binding Motifs
Authors: Ebinu Julius O. , Bottorff Drell A. , Chan Edmond Y. W. , Stang Stacey L. , Dunn Robert J. , Stone James C.
Published: July 2002

RasGRP, a guanyl nucleotide–releasing protein for the small guanosine triphosphatase Ras, was characterized. Besides the catalytic domain, RasGRP has an atypical pair of “EF hands” that bind calcium and a diacylglycerol (DAG)-binding domain. RasGRP activated Ras and caused transformation in fibroblasts. A DAG analog caused sustained activation of Ras-Erk signaling and changes in cell morphology. Signaling was associated with partitioning of RasGRP protein into the membrane fraction. Sustained ligand-induced signaling and membrane partitioning were absent when the DAG-binding domain was deleted. RasGRP is expressed in the nervous system, where it may couple changes in DAG and possibly calcium concentrations to Ras activation.
Mantle Discontinuity Structure Beneath the Southern East Pacific Rise from
P
-to-
S
Converted Phases
Authors: Shen Yang , Sheehan Anne F. , Dueker Kenneth G. , de Groot–Hedlin Catherine , Gilbert Hersh
Published: July 2002

Receiver functions derived from teleseismic body waves recorded by ocean-bottom seismometers on the southern East Pacific Rise reveal shear waves converted from compressional waves at the mantle discontinuities near 410- and 660-kilometer depth. The thickness of the mantle transition zone between the two discontinuities is normal relative to the global average and indicates that upwelling beneath the southern East Pacific Rise is not associated with an excess temperature in the mantle transition zone.
Also Noteworthy
Authors: Suter Sherman
Published: July 2002

The Code of Kings.
The Language of Seven Sacred Maya Temples and Tombs. Linda Schele and Peter Mathews. Scribner, New York, 1998. 432 pp., illus., $40. ISBN 0-684-80106-X.
A Piece of Your Mind
Authors: Konner Melvin
Published: July 2002

How the Mind Works
. Steven Pinker. Norton, New York, 1997. 672 pp. $29.95, C$39.99. ISBN 0-393-04535-8.
Beyond the Null Hypothesis
Authors: Miller Thomas E. , LeBuhn Gretchen
Published: July 2002

The Ecological Detective
Confronting Models with Data. Ray Hilborn and Marc Mangel. Princeton University Press, Princeton, NJ, 1997. 334 pp., $39.50, £30. ISBN 0-691-03496-6. Paper, $19.95, £16.95. ISBN 0-691-03497-4.

How do we find congruence among field, laboratory, and model? Hilborn and Mangel present an approach to investigating the complex (ecology, in this case) by trying different hypotheses until a coherent picture emerges. The authors make extensive use of computer programming for the generation of hypotheses, exploration of data, and comparison of different models.
Lack of Attention from Loss of Time
Authors: Gold Philip W.
Published: July 2002

ADHD and the Nature of Self Control
. Russell A. Barkley. Guilford, New York, 1997. 432 pp. $40. ISBN 1-57230-250-x.

Barkley presents a working model of attention deficit hyperactivity disorder (ADHD) that locates the underlying neuroanatomical defect in the prefrontal cortex. Thus the attention breakdown is not the central problem, but only one aspect of a tragic impairment of the individual's ability to integrate information and behavior over time.
Conversion of Neuronal Growth Cone Responses from Repulsion to Attraction by Cyclic Nucleotides
Authors: Song Hong-jun , Ming Guo-li , He Zhigang , Lehmann Maxime , McKerracher Lisa , Tessier-Lavigne Marc , Poo Mu-ming
Published: July 2002

Nerve growth is regulated by attractive and repulsive factors in the nervous system. Microscopic gradients of Collapsin-1/Semaphorin III/D (Sema III) and myelin-associated glycoprotein trigger repulsive turning responses by growth cones of cultured
Xenopus
spinal neurons; the repulsion can be converted to attraction by pharmacological activation of the guanosine 3′,5′-monophosphate (cGMP) and adenosine 3′,5′-monophosphate signaling pathways, respectively. Sema III also causes the collapse of cultured rat sensory growth cones, which can be inhibited by activation of the cGMP pathway. Thus cyclic nucleotides can regulate growth cone behaviors and may be targets for designing treatments to alleviate the inhibition of nerve regeneration by repulsive factors.
Detection and Modeling of Nontidal Oceanic Effects on Earth's Rotation Rate
Authors: Marcus Steven L. , Chao Yi , Dickey Jean O. , Gegout Pascal
Published: July 2002

Subdecadal changes in Earth's rotation rate, and hence in the length of day (LOD), are largely controlled by variations in atmospheric angular momentum. Results from two oceanic general circulation models (OGCMs), forced by observed wind stress and heat flux for the years 1992 through 1994, show that ocean current and mass distribution changes also induce detectable LOD variations. The close similarity of axial oceanic angular momentum (OAM) results from two independent OGCMs, and their coherence with LOD, demonstrate that global ocean models can successfully capture the large-scale circulation changes that drive OAM variability on seasonal and shorter time scales.
Beyond Expert Advice
Authors: Daley Larry S. , Ahern Kevin
Published: July 2002

HyperNMR 2.0
. Hypercube Inc. Gainesville, FL. $495. [HyperChem Pro: $995]. Phone: 800-960-1871
www.hyper.com
.

Daley and Ahern review Hyper NMR, computer software that allows prediction of the NMR spectrum of a test molecule. They compare its characteristics to expert systems, also used to predict NMR spectra, and explain how to apply it in the laboratory.
Arabidopsis
NPH1: A Flavoprotein with the Properties of a Photoreceptor for Phototropism
Authors: Christie John M. , Reymond Philippe , Powell Gary K. , Bernasconi Paul , Raibekas Andrei A. , Liscum Emmanuel , Briggs Winslow R.
Published: July 2002

The
NPH1
gene of
Arabidopsis thaliana
encodes a 120-kilodalton serine-threonine protein kinase hypothesized to function as a photoreceptor for phototropism. When expressed in insect cells, the NPH1 protein is phosphorylated in response to blue light irradiation. The biochemical and photochemical properties of the photosensitive protein reflect those of the native protein in microsomal membranes. Recombinant NPH1 noncovalently binds flavin mononucleotide, a likely chromophore for light-dependent autophosphorylation. The fluorescence excitation spectrum of the recombinant protein is similar to the action spectrum for phototropism, consistent with the conclusion that NPH1 is an autophosphorylating flavoprotein photoreceptor mediating phototropic responses in higher plants.
Immortal Time: Circadian Clock Properties of Rat Suprachiasmatic Cell Lines
Authors: Earnest David J. , Liang Fong-Qi , Ratcliff Matt , Cassone Vincent M.
Published: July 2002

Cell lines derived from the rat suprachiasmatic nucleus (SCN) were screened for circadian clock properties distinctive of the SCN in situ. Immortalized SCN cells generated robust rhythms in uptake of the metabolic marker 2-deoxyglucose and in their content of neurotrophins. The phase relationship between these rhythms in vitro was identical to that exhibited by the SCN in vivo. Transplantation of SCN cell lines, but not mesencephalic or fibroblast lines, restored the circadian activity rhythm in arrhythmic, SCN-lesioned rats. Thus, distinctive oscillator, pacemaker, and clock properties of the SCN are not only retained but also maintained in an appropriate circadian phase relationship by immortalized SCN progenitors.
Whale Origins--Conquering the Seas
Authors: Heyning John E.
Published: July 2002

The Emergence of Whales
Evolutionary Patterns in the Origin of Cetacea. J. G. M. Thewissen, Ed. Plenum, New York, 1998. 491 pp. $115. ISBN 0-306-45853-5.

The contributors to this data-rich volume marshal a wide range of evidence (including molecular genetics, functional morphology, isotopic signatures, and paleoecology) to track the transformation of four-footed terrestrial mammals into fully aquatic cetaceans.
Erythropoietin Receptor Activation by a Ligand-Induced Conformation Change
Authors: Remy Ingrid , Wilson Ian A. , Michnick Stephen W.
Published: July 2002

Erythropoietin and other cytokine receptors are thought to be activated through hormone-induced dimerization and autophosphorylation of JAK kinases associated with the receptor intracellular domains. An in vivo protein fragment complementation assay was used to obtain evidence for an alternative mechanism in which unliganded erythropoietin receptor dimers exist in a conformation that prevents activation of JAK2 but then undergo a ligand-induced conformation change that allows JAK2 to be activated. These results are consistent with crystallographic evidence of distinct dimeric configurations for unliganded and ligand-bound forms of the erythropoietin receptor.
A High Point for Evolution
Authors: Sejnowski Terrence J.
Published: July 2002

Evolving Brains
. John Morgan Allman. Scientific American Library, New York, 1999. 238 pp. $34.95. ISBN 0-7167-5076-7.

Allman integrates recent findings from molecular genetics, behavior, and paleontology into an interesting evolutionary narrative, based on large-brained animals' needs for dependable, high-quality food supplies.
Infinitesimal Steps
Authors: Dauben Joseph W.
Published: July 2002

Reasoning with the Infinite
From the Closed World to the Mathematical Universe. Michel Blay. University of Chicago Press, Chicago, 1998. 226 pp. $30, £25.95. ISBN 0-226-05834-4.

The French historian Blay's examination of the emergence of a mathematical physics (the analysis of nature in terms of quantitative laws that allow predictions based on mathematical reason) focuses on lesser known figures (Fontenelle, Wronski) rather than on the more successful efforts of more influential practitioners (Euler, Lagrange, Laplace, Cauchy).
Enough Remains to Work With
Authors: Baumiller Tomasz K.
Published: July 2002

The Adequacy of the Fossil Record
. Stephen K. Donovan and Christopher R. C. Paul, Eds. Wiley, Chichester, UK, 1998. 322 pp. $125, £50. ISBN 0-471-96988-5.

The contributors discuss theoretical issues, quantitative approaches, and case studies demonstrating that the incomplete fossil record provides data adequate for examining a wide range of evolutionary questions.
Electrochemical Defect-Mediated Thin-Film Growth
Authors: Sieradzki K. , R. S. , Brankovic  , Dimitrov N.
Published: July 2002

An electrodeposition technique is described that produces atomically flat epitaxial metal overlayers of quality similar to that obtained by ultrahigh vacuum techniques at elevated temperature. In this approach, a metal of interest such as silver is co-deposited with a reversibly deposited mediator metal. The mediator is periodically deposited and stripped from the surface, and this serves to significantly increase the density of two-dimensional islands of silver atoms, promoting a layer-by-layer thin-film growth mode. In situ scanning tunneling microscopy was used to demonstrate the growth process for the heteroepitaxial system silver/gold (111) with either lead or copper as the mediator.
Thermal Equation of State of Aluminum-Enriched Silicate Perovskite
Authors: Zhang Jianzhong , Weidner Donald J.
Published: July 2002

Inferences of the chemical homogeneity of Earth's mantle depend on comparing laboratory-derived equations of state of mantle phases with seismically determined properties of the material in situ. A uniform chemical composition of the entire mantle has been found to be consistent with measurements, to date, of these properties for the end-member MgSiO
3
perovskite phase. New pressure-volume-temperature data for silicate perovskite containing 5 mole percent Al
2
O
3
has yielded different values of the equation of state parameters, with the bulk modulus being significantly smaller at lower mantle conditions than for aluminum-free perovskite, thus requiring adjustments in other components to match seismic observations.
Temperature Dependence of the Half-Integer Magnetic Flux Quantum
Authors: Kirtley J. R. , Tsuei C. C. , Moler K. A.
Published: July 2002

The temperature dependence of the half-integer magnetic flux quantum effect in thin-film tricrystal samples of the high-critical-temperature cuprate superconductor YBa
2
Cu
3
O
7–δ
was measured and found to persist from a temperature of 0.5 kelvin through a critical temperature of about 90 kelvin, with no change in total flux. This result implies that
d
-wave symmetry pairing predominates in this cuprate, with a small component of time-reversal symmetry breaking, if any, over the entire temperature range.
Coincident Induction of Long-Term Facilitation in
Aplysia
: Cooperativity Between Cell Bodies and Remote Synapses
Authors: Sherff Carolyn M. , Carew Thomas J.
Published: July 2002

Induction of long-term synaptic changes at one synapse can facilitate the induction of long-term plasticity at another synapse. Evidence is presented here that if
Aplysia
sensory neuron somata and their remote motor neuron synapses are simultaneously exposed to serotonin pulses insufficient to induce long-term facilitation (LTF) at either site alone, processes activated at these sites interact to induce LTF. This coincident induction of LTF requires that (i) the synaptic pulse occur within a brief temporal window of the somatic pulse, and (ii) local protein synthesis occur immediately at the synapse, followed by delayed protein synthesis at the soma.
Precise Timing
Authors: Ekstrom Christopher R.
Published: July 2002

The Quantum Beat
The Physical Principles of Atomic Clocks. Fouad G. Major. Springer, New York, 1998. 489 pp. $49.95. ISBN 0-387-98301-5.

Major provides nonspecialists with an informative, technical description of the use of the properties of individual atoms to measure frequencies and time intervals
Use of Chemokine Receptors by Poxviruses
Authors: Lalani Alshad S. , Masters Jennefer , Zeng Wei , Barrett John , Pannu Rajeet , Everett Helen , Arendt Christopher W. , McFadden Grant
Published: July 2002

Chemokine receptors serve as portals of entry for certain intracellular pathogens, most notably human immunodeficiency virus (HIV). Myxoma virus is a member of the poxvirus family that induces a lethal systemic disease in rabbits, but no poxvirus receptor has ever been defined. Rodent fibroblasts (3T3) that cannot be infected with myxoma virus could be made fully permissive for myxoma virus infection by expression of any one of several human chemokine receptors, including CCR1, CCR5, and CXCR4. Conversely, infection of 3T3-CCR5 cells can be inhibited by RANTES, anti-CCR5 polyclonal antibody, or herbimycin A but not by monoclonal antibodies that block HIV-1 infection or by pertussis toxin. These findings suggest that poxviruses, like HIV, are able to use chemokine receptors to infect specific cell subtypes, notably migratory leukocytes, but that their mechanisms of receptor interactions are distinct.
Self-Assembling Amphiphilic Siderophores from Marine Bacteria
Authors: Martinez J. S. , Zhang G. P. , Holt P. D. , Jung H.-T. , Carrano C. J. , Haygood M. G. , Butler Alison
Published: July 2002

Most aerobic bacteria secrete siderophores to facilitate iron acquisition. Two families of siderophores were isolated from strains belonging to two different genera of marine bacteria. The aquachelins, from
Halomonas aquamarina
strain DS40M3, and the marinobactins, from
Marinobacter
sp. strains DS40M6 and DS40M8, each contain a unique peptidic head group that coordinates iron(III) and an appendage of one of a series of fatty acid moieties. These siderophores have low critical micelle concentrations (CMCs). In the absence of iron, the marinobactins are present as micelles at concentrations exceeding their CMC; upon addition of iron(III), the micelles undergo a spontaneous phase change to form vesicles. These observations suggest that unique iron acquisition mechanisms may have evolved in marine bacteria.
Why Stem Cells?
Authors: van der Kooy Derek , Weiss and Samuel
Published: July 2002

Stem cells are viewed from the perspectives of their function, evolution, development, and cause. Counterintuitively, most stem cells may arise late in development, to act principally in tissue renewal, thus ensuring an organism's long-term survival. Surprisingly, recent reports suggest that tissue-specific adult stem cells have the potential to contribute to replenishment of multiple adult tissues.
A Mutation in
PRKAG3
Associated with Excess Glycogen Content in Pig Skeletal Muscle
Authors: Milan Denis , Jeon Jin-Tae , Looft Christian , Amarger Valerie , Robic Annie , Thelander Mattias , Rogel-Gaillard Claire , Paul Sven , Iannuccelli Nathalie , Rask Lars , Ronne Hans , Lundström Kerstin , Reinsch Norbert , Gellin Joel , Kalm Ernst , Roy Pascale Le , Chardon Patrick , Andersson Leif
Published: July 2002

A high proportion of purebred Hampshire pigs carries the dominant
RN
−
mutation, which causes high glycogen content in skeletal muscle. The mutation has beneficial effects on meat content but detrimental effects on processing yield. Here, it is shown that the mutation is a nonconservative substitution (R200Q) in the
PRKAG3
gene, which encodes a muscle-specific isoform of the regulatory γ subunit of adenosine monophosphate–activated protein kinase (AMPK). Loss-of-function mutations in the homologous gene in yeast (
SNF4
) cause defects in glucose metabolism, including glycogen storage. Further analysis of the PRKAG3 signaling pathway may provide insights into muscle physiology as well as the pathogenesis of noninsulin-dependent diabetes mellitus in humans, a metabolic disorder associated with impaired glycogen synthesis.
Impaired Prion Replication in Spleens of Mice Lacking Functional Follicular Dendritic Cells
Authors: Montrasio Fabio , Frigg Rico , Glatzel Markus , Klein Michael A. , Mackay Fabienne , Aguzzi Adriano , Weissmann Charles
Published: July 2002

In scrapie-infected mice, prions are found associated with splenic but not circulating B and T lymphocytes and in the stroma, which contains follicular dendritic cells (FDCs). Formation and maintenance of mature FDCs require the presence of B cells expressing membrane-bound lymphotoxin-α/β. Treatment of mice with soluble lymphotoxin-β receptor results in the disappearance of mature FDCs from the spleen. We show that this treatment abolishes splenic prion accumulation and retards neuroinvasion after intraperitoneal scrapie inoculation. These data provide evidence that FDCs are the principal sites for prion replication in the spleen.
Realm of the Rainbow
Authors: Lazar Thomas
Published: July 2002

Color
A Multidisciplinary Approach. Heinrich Zollinger. Wiley-VCH, Weinheim, and Verlag Helvetica Chimica Acta, Zürich, 1999. 268 pp. $120, £70, DM198, EUR101.24, sFr176. ISBN 3-906390-18-7.

In this multifaceted account, Zollinger views the color spectrum from the perspectives of physics, chemistry, biology, and culture. He covers topics ranging from the quantum chemistry of light emission, through the neurophysiology of the visual cortex, psychology, and linguistics, to the aesthetics of color in the history of art.
Counter-Revolutionary Kuhn?
Authors: Rouse Joseph
Published: July 2002

Thomas Kuhn
A Philosophical History for Our Times. Steve Fuller. University of Chicago Press, Chicago, 2000. 490 pp. $35, £24.50. ISBN 0-226-26894-2.

In this detailed and provocative account, Fuller argues that--despite the dramatic shift in the image of science and scientific progress that followed
The Structure of Scientific Revolutions
--Kuhn held very conservative views of science and how it ought to be studied.
mGluR1 in Cerebellar Purkinje Cells Essential for Long-Term Depression, Synapse Elimination, and Motor Coordination
Authors: Ichise Taeko , Kano Masanobu , Hashimoto Kouichi , Yanagihara Dai , Nakao Kazuki , Shigemoto Ryuichi , Katsuki Motoya , Aiba Atsu
Published: July 2002

Targeted deletion of metabotropic glutamate receptor–subtype 1 (mGluR1) gene can cause defects in development and function in the cerebellum. We introduced the mGluR1α transgene into mGluR1-null mutant [mGluR1 (–/–)] mice with a Purkinje cell (PC)–specific promoter. mGluR1-rescue mice showed normal cerebellar long-term depression and regression of multiple climbing fiber innervation, events significantly impaired in mGluR1 (–/–) mice. The impaired motor coordination was rescued by this transgene, in a dose-dependent manner. We propose that mGluR1 in PCs is a key molecule for normal synapse formation, synaptic plasticity, and motor control in the cerebellum.
Mass Balance of the Greenland Ice Sheet at High Elevations
Authors: Thomas R. , Akins T. , Csatho B. , Fahnestock M. , Gogineni P. , Kim C. , Sonntag J.
Published: July 2002

Comparison of ice discharge from higher elevation areas of the entire Greenland Ice Sheet with total snow accumulation gives estimates of ice thickening rates over the past few decades. On average, the region has been in balance, but with thickening of 21 centimeters per year in the southwest and thinning of 30 centimeters per year in the southeast. The north of the ice sheet shows less variability, with average thickening of 2 centimeters per year in the northeast and thinning of about 5 centimeters per year in the northwest. These results agree well with those from repeated altimeter surveys, except in the extreme south, where we find substantially higher rates of both thickening and thinning.
Greenland Ice Sheet: High-Elevation Balance and Peripheral Thinning
Authors: Krabill W. , Abdalati W. , Frederick E. , Manizade S. , Martin C. , Sonntag J. , Swift R. , Thomas R. , Wright W. , Yungel J.
Published: July 2002

Aircraft laser-altimeter surveys over northern Greenland in 1994 and 1999 have been coupled with previously reported data from southern Greenland to analyze the recent mass-balance of the Greenland Ice Sheet. Above 2000 meters elevation, the ice sheet is in balance on average but has some regions of local thickening or thinning. Thinning predominates at lower elevations, with rates exceeding 1 meter per year close to the coast. Interpolation of our results between flight lines indicates a net loss of about 51 cubic kilometers of ice per year from the entire ice sheet, sufficient to raise sea level by 0.13 millimeter per year—approximately 7% of the observed rise.
A Potent Greenhouse Gas Identified in the Atmosphere: SF
5
CF
3
Authors: Sturges W. T. , Wallington T. J. , Hurley M. D. , Shine K. P. , Sihra K. , Engel A. , Oram D. E. , Penkett S. A. , Mulvaney R. , Brenninkmeijer C. A. M.
Published: July 2002

We detected a compound previously unreported in the atmosphere, trifluoromethyl sulfur pentafluoride (SF
5
CF
3
). Measurements of its infrared absorption cross section show SF
5
CF
3
to have a radiative forcing of 0.57 watt per square meter per parts per billion. This is the largest radiative forcing, on a per molecule basis, of any gas found in the atmosphere to date. Antarctic firn measurements show it to have grown from near zero in the late 1960s to about 0.12 part per trillion in 1999. It is presently growing by about 0.008 part per trillion per year, or 6% per year. Stratospheric profiles of SF
5
CF
3
suggest that it is long-lived in the atmosphere (on the order of 1000 years).
Asef, a Link Between the Tumor Suppressor APC and G-Protein Signaling
Authors: Kawasaki Yoshihiro , Senda Takao , Ishidate Takao , Koyama Ryo , Morishita Tsuyoshi , Iwayama Yoriko , Higuchi Osamu , Akiyama Tetsu
Published: July 2002

The
adenomatous polyposis coli
gene (
APC
) is mutated in familial adenomatous polyposis and in sporadic colorectal tumors. Here the APC gene product is shown to bind through its armadillo repeat domain to a Rac-specific guanine nucleotide exchange factor (GEF), termed Asef. Endogenous APC colocalized with Asef in mouse colon epithelial cells and neuronal cells. Furthermore, APC enhanced the GEF activity of Asef and stimulated Asef-mediated cell flattening, membrane ruffling, and lamellipodia formation in MDCK cells. These results suggest that the APC-Asef complex may regulate the actin cytoskeletal network, cell morphology and migration, and neuronal function.
Antiphase Oscillation of the Left and Right Suprachiasmatic Nuclei
Authors: de la Horacio O. , Iglesia  , Meyer Jennifer , Carpino Alan , Schwartz William J.
Published: July 2002

An unusual property of the circadian timekeeping systems of animals is rhythm “splitting,” in which a single daily period of physical activity (usually measured as wheel running) dissociates into two stably coupled components about 12 hours apart; this behavior has been ascribed to a clock composed of two circadian oscillators cycling in antiphase. We analyzed gene expression in the hypothalamic circadian clock, the suprachiasmatic nucleus (SCN), of behaviorally “split” hamsters housed in constant light. The results show that the two oscillators underlying the split condition correspond to the left and right sides of the bilaterally paired SCN.
Varied Fates from Similar States
Authors: Austad Steven
Published: July 2002

Chance, Development, and Aging
. Caleb E. Finch and Thomas B. L. Kirkwood. Oxford University Press, New York, 2000. 288 pp. $35, £24.95. ISBN 0-19-513361-7.

Finch and Kirkwood draw on research in developmental biology to argue that random variations in cell fate and function modify genetic and external environmental influences to determine the course of aging in individuals.
Birth of the Kaapvaal Tectosphere 3.08 Billion Years Ago
Authors: Moser D. E. , Flowers R. M. , Hart R. J.
Published: July 2002

The crustal remnants of Earth's Archean continents have been shielded from mantle convection by thick roots of ancient mantle lithosphere. The precise time of crust-root coupling (tectosphere birth) is poorly known but is needed to test competing theories of continental plate genesis. Our mapping and geochronology of an impact-generated section through the Mesoarchean crust of the Kaapvaal craton indicates tectosphere birth at 3.08 ± 0.01 billion years ago, roughly 0.12 billion years after crust assembly. Growth of the southern African mantle root by subduction processes occurred within about 0.2 billion years. The assembly of crust before mantle may be common to the tectosphere.
Betrayed by Batteries?
Authors: Reich Leonard S.
Published: July 2002

The Electric Vehicle and the Burden of History
. David A. Kirsch. Rutgers University Press, New Brunswick, NJ, 2000. 307 pp. $52. ISBN 0-8135-2808-9; Paper, $20. ISBN 0-8135-2809-7.

Exploring the early 20th century rise and fall of electric vehicles, Kirsch explains the abandonment of electric vehicles in terms of the business strategies of their manufacturers and electric utilities as well as the expectations and choices of consumers.
Bactericidal Activities of HMR 3647, Moxifloxacin, and Rifapentine against
Mycobacterium leprae
in Mice
Authors: Consigny Sophie , Bentoucha Abdelhalim , Bonnafous Pascale , Grosset Jacques , Ji Baohong
Published: July 2002

Bactericidal activities of HMR 3647 (HMR), moxifloxacin (MXFX), and rifapentine (RPT) against
Mycobacterium leprae
, measured by the proportional bactericidal technique in the mouse footpad system, were compared with those of the established antileprosy drugs clarithromycin (CLARI), ofloxacin (OFLO), and rifampin (RMP). Administered in five daily doses of 100 mg/kg of body weight, HMR appeared slightly more bactericidal than CLARI. In a single dose, MXFX at 150 mg/kg was more active than the same dose of OFLO and displayed exactly the same level of activity as RMP at 10 mg/kg; the combination MXFX-minocycline (MINO) (MM) was more bactericidal than the combination OFLO-MINO (OM); RPT at 10 mg/kg was more bactericidal than the same dose of RMP and even more active than the combination RMP-OFLO-MINO (ROM); the combination RPT-MXFX-MINO (PMM) killed 99.9% of viable
M. leprae
and was slightly more bactericidal than RPT alone, indicating that the combination PMM showed an additive effect against
M. leprae
.
Thrombin-Induced Platelet Microbicidal Protein Susceptibility Phenotype Influences the Outcome of Oxacillin Prophylaxis and Therapy of Experimental
Staphylococcus aureus
Endocarditis
Authors: Dhawan V. K. , Bayer A. S. , Yeaman M. R.
Published: July 2002

We previously showed that in vitro susceptibility profiles of
Staphylococcus aureus
to thrombin-induced platelet microbicidal protein 1 (tPMP-1) impacted the outcome of vancomycin treatment in experimental infective endocarditis. In this same model, treatment with oxacillin (a more rapid staphylocidal agent than vancomycin) enhanced the clearance of both tPMP-1-susceptible and -resistant cells from vegetations. The extent of clearance was greater for tPMP-1-susceptible cells.
Anti-Epstein-Barr Virus (EBV) Activity of β-
l
-5-Iododioxolane Uracil Is Dependent on EBV Thymidine Kinase
Authors: Kira Toshihiko , Grill Susan P. , Dutschman Ginger E. , Lin Ju-Sheng , Qu Fucheng , Choi Yongseok , Chu Chung K. , Cheng Yung-Chi
Published: July 2002

β-
l
-5-Iododioxolane uracil was shown to have potent anti-Epstein-Barr virus (EBV) activity (50% effective concentration = 0.03 μM) with low cytotoxicity (50% cytotoxic concentration = 1,000 μM). It exerts its antiviral activity by suppressing replicative EBV DNA and viral protein synthesis. This compound is phosphorylated in cells where the EBV is replicating but not in cells where the EBV is latent. EBV-specific thymidine kinase could phosphorylate β-
l
-5-iododioxolane uracil to the monophosphate metabolite. The

K
m

of β-
l
-5-iododioxolane uracil with EBV thymidine kinase was estimated to be 5.5 μM, which is similar to that obtained with thymidine but about fivefold higher than that obtained with 2′ fluoro-5-methyl-β-
l
-arabinofuranosyl uracil, the first
l
-nucleoside analogue discovered to have anti-EBV activity. The relative
V
max
is seven times higher than that of thymidine. The anti-EBV activity of β-
l
-5-iododioxolane uracil and its intracellular phosphorylation could be inhibited by 5′-ethynylthymidine, a potent EBV thymidine kinase inhibitor. The present study suggests that β-
l
-5-iododioxolane uracil exerts its action after phosphorylation; therefore, EBV thymidine kinase is critical for the antiviral action of this drug.
Antiretroviral Agents Inhibit Infection of Human Cells by Porcine Endogenous Retroviruses
Authors: Powell S. K. , Gates M. E. , Langford G. , Gu M.-L. , Lockey C. , Long Z. , Otto E.
Published: July 2002

The efficacy of antiretroviral drugs against porcine endogenous retroviruses (PERV) that may be harbored in pig organs intended for transplantation was examined in human cells in vitro. The nucleoside analogs zidovudine and dideoxyinosine were found to effectively inhibit PERV replication.
Effects of MS-8209, an Amphotericin B Derivative, on Tumor Necrosis Factor Alpha Synthesis and Human Immunodeficiency Virus Replication in Macrophages
Authors: Clayette Pascal , Martin Marc , Beringue Vincent , Dereuddre-Bosquet Nathalie , Adjou Karim T. , Seman Michel , Dormont Dominique
Published: July 2002

Amphotericin B derivatives, such as MS-8209, have been evaluated as a therapeutic approach to human immunodeficiency virus (HIV) infection. We show that MS-8209, like amphotericin B, increases tumor necrosis factor alpha (TNF-α) mRNA expression and TNF-α production and consequently HIV replication in human macrophages. These effects confirm the pharmacological risk associated with the administration of amphotericin B or its derivatives to HIV-infected patients.
In Vitro Activity of A-192411.29, a Novel Antifungal Lipopeptide
Authors: Nilius Angela M. , Raney Patti M. , Hensey-Rudloff Dena M. , Wang Weibo , Li Qun , Flamm Robert K.
Published: July 2002

A-192411.29 is a novel antifungal agent derived from the structural template of the natural product echinocandin. The in vitro activity of A-192411.29 against common pathogenic yeasts was assessed by National Committee for Clinical Laboratory Standards method M27-A. It demonstrated broad-spectrum, fungicidal activity and was active against the most clinically relevant yeasts, such as
Candida albicans
,
Candida tropicalis
, and
Candida glabrata
, as well as less commonly encountered
Candida
species; in general, its potency on a weight basis was comparable to that of amphotericin B. It maintained potent in vitro activity against
Candida
strains with reduced susceptibilities to fluconazole and amphotericin B. The in vitro activity of A-192411.29 against
Cryptococcus neoformans
was comparable to its activity against
Candida
spp. However, A-192411.29 did not demonstrate complete growth inhibition of
Aspergillus fumigatus
by the broth microdilution method used. A-192411.29 possesses an antifungal profile comparable to or better than those of fluconazole and amphotericin B against pathogenic yeasts, including strains resistant to fluconazole or amphotericin B, suggesting that it may be a therapeutically useful new antifungal drug.
In Vitro Selection of Mutations in the Human Immunodeficiency Virus Type 1 Reverse Transcriptase That Decrease Susceptibility to (−)-β-
d
-Dioxolane-Guanosine and Suppress Resistance to 3′-Azido-3′-Deoxythymidine
Authors: Bazmi Holly Z. , Hammond Jennifer L. , Cavalcanti Socrates C. H. , Chu Chung K. , Schinazi Raymond F. , Mellors John W.
Published: July 2002

Human immunodeficiency virus type 1 (HIV-1) isolates resistant to (−)-β-
d
-dioxolane-guanosine (DXG), a potent and selective nucleoside analog HIV-1 reverse transcriptase (RT) inhibitor, were selected by serial passage of HIV-1
LAI
in increasing drug concentrations (maximum concentration, 30 μM). Two independent selection experiments were performed. Viral isolates for which the DXG median effective concentrations (EC
50
s) increased 7.3- and 12.2-fold were isolated after 13 and 14 passages, respectively. Cloning and DNA sequencing of the RT region from the first resistant isolate identified a K65R mutation (AAA to AGA) in 10 of 10 clones. The role of this mutation in DXG resistance was confirmed by site-specific mutagenesis of HIV-1
LAI
. The K65R mutation also conferred greater than threefold cross-resistance to 2′,3′-dideoxycytidine, 2′,3′-dideoxyinosine, 2′,3′-dideoxy-3′-thiacytidine, 9-(2-phosphonylmethoxyethyl)adenine, 2-amino-6-chloropurine dioxolane, dioxolanyl-5-fluorocytosine, and diaminopurine dioxolane but had only marginal effects on 3′-azido-3′-deoxthymidine (AZT) susceptibility. However, when introduced into a genetic background for AZT resistance (D67N, K70R, T215Y, T219Q), the K65R mutation reversed the AZT resistance. DNA sequencing of RT clones derived from the second resistant isolate identified the L74V mutation, previously reported to cause ddI resistance. The L74V mutation also decreased the AZT resistance when the mutation was introduced into a genetic background for AZT resistance (D67N, K70R, T215Y, T219Q) but to a lesser degree than the K65R mutation did. These findings indicate that DXG and certain 2′,3′-dideoxy compounds (e.g., ddI) can select for the same resistance mutations and thus may not be optimal for use in combination. However, the combination of AZT with DXG or its orally bioavailable prodrug (−)-β-
d
-2,6-diaminopurine-dioxolane should be explored because of the suppressive effects of the K65R and L74V mutations on AZT resistance.
Synergy between Trovafloxacin and Ceftriaxone against Penicillin-Resistant Pneumococci in the Rabbit Meningitis Model and In Vitro
Authors: Cottagnoud Philippe , Acosta Fernando , Cottagnoud Marianne , Neftel Klaus , Täuber Martin G.
Published: July 2002

The bactericidal activities of monotherapy with trovafloxacin (−0.37 ± 0.15 Δlog
10
CFU/ml · h), vancomycin (−0.32 ± 0.12 Δlog
10
CFU/ml · h), and ceftriaxone (−0.36 ± 0.19 Δlog
10
CFU/ml · h) for the treatment of experimental meningitis in rabbits due to a clinical penicillin-resistant pneumococcal strain (MIC, 4 mg/liter) were similar. The combination of ceftriaxone with trovafloxacin considerably improved the killing rates (−0.67 ± 0.16 Δlog
10
CFU/ml · h) and was slightly superior to ceftriaxone with vancomycin (killing rate, −0.53 ± 0.22 Δlog
10
CFU/ml · h), the regimen most commonly used in clinical practice. In vitro, synergy was demonstrated between ceftriaxone and trovafloxacin by the checkerboard method (fractional inhibitory concentration index, 0.5) and by time-killing assays over 8 h.