bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Observations at Io with the Galileo Spacecraft
Authors: Frank L. A. , Paterson W. R. , Ackerson K. L. , Vasyliunas V. M. , Coroniti F. V. , Bolton S. J.
Published: July 2002

Plasma measurements made during the flyby of Io on 7 December 1995 with the Galileo spacecraft plasma analyzers reveal that the spacecraft unexpectedly passed directly through the ionosphere of Io. The ionosphere is identified by a dense plasma that is at rest with respect to Io. This plasma is cool relative to those encountered outside the ionosphere. The composition of the ionospheric plasmas includes O
++
, O
+
and S
++
, S
+
, and SO
2
+
ions. The plasma conditions at Io appear to account for the decrease in the magnetic field, without the need to assume that Io has a magnetized interior.
Linker Histones, DNA's Protein Custodians, Gain New Respect
Authors: Pennisi Elizabeth
Published: July 2002

The cell nucleus is like an overcrowded archives, with DNA and proteins wound and twisted into dense packages, called chromatin. Now a series of experimental results, including one reported in this issue (
p. 614
), is sketching a new picture of this archive and how a protein called the linker histone helps to manage it, by either granting or denying the cell's gene-regulating proteins access to particular sequences.
Interlayer Tunneling Models of Cuprate Superconductivity: Implications of a Recent Experiment
Authors: Leggett A. J.
Published: July 2002

It is shown that, given a few generic assumptions, any theory of high-temperature superconductivity that attributes a substantial fraction of the condensation energy to the saving of
c
-axis kinetic energy must predict an inequality relating the
c
-axis penetration depth λ
⊥
(0) to the zero-temperature superconducting-normal energy difference and the fluctuations of the
c
-axis kinetic energy around its mean value. Application of this formula to Tl
2
Ba
2
CuO
6
implies that if λ
⊥
(0) is greater than 10 micrometers, as suggested by a recent experiment, these fluctuations must have an unusual form.
Identification of an Asymmetrically Localized Sensor Histidine Kinase Responsible for Temporally and Spatially Regulated Transcription
Authors: Wingrove James A. , Gober James W.
Published: July 2002

Caulobacter crescentus
undergoes asymmetric cell division, resulting in a stalked cell and a motile swarmer cell. The genes encoding external components of the flagellum are expressed in the swarmer compartment of the predivisional cell through the localized activation of the transcription factor FlbD. The mechanisms responsible for the temporal and spatial activation of FlbD were determined through identification of FlbE, a histidine kinase required for FlbD activity. FlbE is asymmetrically distributed in the predivisional cell. It is located at the pole of the stalked compartment and at the site of cell division in the swarmer compartment. These findings suggest that FlbE and FlbD are activated in response to a morphological change in the cell resulting from cell division events.
Life-Death Balance Within the Cell
Authors: Barinaga Marcia
Published: July 2002

Three separate research groups report in this issue of Science (
pages. 782
,
784
, andp.
787
) that a cellular protein called nuclear factor kappa B (NF-κ B)blocks the programmed form of cell suicide known as apoptosis in several cell types. This finding has led to the suggestion that blocking NF-κ B in tumor cells might make them more vulnerable to drugs or radiation.
A Wave in the Earth
Authors: Johnston Arch C.
Published: July 2002

As the great ice sheets of the last ice age melted and retreated, their weight was lifted from the underlying earth. This unloading and resulting crustal stress may have induced postglacial faulting and earthquakes. In his Perspective, Johnston discusses results reported in the same issue by Arvidsson (
p. 744
), which indicate evidence of very large postglacial earthquakes along the Pärvie fault of northern Sweden.
Fraud Strikes Top Genome Lab
Authors: Marshall Eliot
Published: July 2002

Francis Collins, head of the National Institutes of Health's Human Genome Project, has informed colleagues that a junior researcher in his lab faked data in five papers Collins co-authored. Many of Collins's peers think he handled the incident well once the fraud came to light, confronting the alleged wrongdoer swiftly and retracting all or part of the tainted papers.
Government Gives Green Light to Four New Facilities
Authors: Mervis Jeffrey
Published: July 2002

The Chinese government has approved funding for four big-science projects: a 4-meter wide-field telescope for sky surveys at an observatory northeast of Beijing, a new synchrotron x-ray source on the outskirts of Shanghai, the upgrading of an existing synchrotron in Hefei, and a national seismographic network to monitor crustal movements at major faults. The $55 million investment is part of a government promise to triple spending on science and technology by 2000.
Mg/Ca Thermometry in Coral Skeletons
Authors: Mitsuguchi Takehiro , Matsumoto Eiji , Abe Osamu , Uchida Tetsuo , Isdale Peter J.
Published: July 2002

The magnesium-to-calcium (Mg/Ca) ratio of coral skeletons from Ishigaki Island, Ryukyu Islands, Japan, closely tracked sea surface temperature (SST) over an 8-year period. Measurements were made with the fast technique of inductively coupled plasma-atomic emission spectrometry. The variation of the coral Mg/Ca ratio with SST change is about four times that of the current, widely used coral strontium-to-calcium ratio. The temporal and geographic variation of the seawater Mg
2+
/Ca
2+
ratio probably has little influence on coral Mg/Ca variation. Results indicate that the coral Mg/Ca ratio has the potential to provide fast, precise, high-resolution proxies for past tropical SSTs.
One of Nature's Macromolecular Machines Demystified
Authors: Stubbe JoAnne
Published: July 2002

Organisms in nature use sophisticated molecular machinery to synthesize polypeptides with useful medicinal properties. In her Perspective, Stubbe discusses work by Li
et al
., published in the same issue (
p. 1188
), in which the components involved in the synthesis of microcin B17 by
Escherichia coli
are purified. Understanding the details of how such posttranslationally modified peptides are made may lead to the development of other novel molecules with antibiotic and antitumor properties.
Protein Folding Monitored at Individual Residues During a Two-Dimensional NMR Experiment
Authors: Balbach Jochen , Forge Vincent , Lau Wai Shun , van Nuland Nico A. J. , Brew Keith , Dobson Christopher M.
Published: July 2002

An approach is described to monitor directly at the level of individual residues the formation of structure during protein folding. A two-dimensional heteronuclear nuclear magnetic resonance (NMR) spectrum was recorded after the rapid initiation of the refolding of a protein labeled with nitrogen-15. The intensities and line shapes of the cross peaks in the spectrum reflected the kinetic time course of the folding events that occurred during the spectral accumulation. The method was used to demonstrate the cooperative nature of the acquisition of the native main chain fold of apo bovine α-lactalbumin. The general approach, however, should be applicable to the investigation of a wide range of chemical reactions.
Asia and Europe Top in World, But Reasons Are Hard to Find
Authors: Vogel Gretchen
Published: July 2002

A new international assessment of student achievement in science and mathematics puts Asia and Eastern Europe at the head of the class. Discounting the importance of such measures as hours spent watching television, classroom size, and level of technology, it leaves unanswered the question of what works in the classroom.
New Way to Read the Record Suggests Abrupt Extinction
Authors: Kerr Richard A.
Published: July 2002

Everyone has heard that an asteroid or comet slammed into Earth 65 million years ago, but did this impact really kill off thousands of species, including the dinosaurs? For many species, the record suggests gradual, not catastrophic, extinction, so paleontologists have been skeptical. But on
page 1360
, researchers using statistical analyses of the fossil record suggest that at least one type of sea creature, the ammonites, was indeed snuffed out quickly at the time of the impact.
Stability of Perovskite (MgSiO
3
) in the Earth's Mantle
Authors: Saxena Surendra K. , Dubrovinsky Leonid S. , Lazor Peter , Cerenius Yngve , Häggkvist Patrik , Hanfland Michael , Hu Jingzhu
Published: July 2002

Available thermodynamic data and seismic models favor perovskite (MgSiO
3
) as the stable phase in the mantle. MgSiO
3
was heated at temperatures from 1900 to 3200 kelvin with a Nd-YAG laser in diamond-anvil cells to study the phase relations at pressures from 45 to 100 gigapascals. The quenched products were studied with synchrotron x-ray radiation. The results show that MgSiO
3
broke down to a mixture of MgO (periclase) and SiO
2
(stishovite or an unquenchable polymorph) at pressures from 58 to 85 gigapascals. These results imply that perovskite may not be stable in the lower mantle and that it might be necessary to reconsider the compositional and density models of the mantle.
Sizing Up Evolutionary Radiations
Authors: Morell Virginia
Published: July 2002

By gauging life 's diversity with differences in size and shape rather than numbers of species, paleontologists are gleaning surprising new insights into evolutionary radiations. For example, on p
page 1492
, an analysis of the ancient marine crinoids or sea lilies raises the heretical notion that competition from other organisms doesn't impede such bursts of evolution. And on
page 1489
, a great radiation of hoofed mammals 25 million years ago is ultimately linked to climate change.
The End of the Message—Another Link Between Yeast and Mammals
Authors: Manley James L. , Takagaki Yoshio
Published: July 2002

Three reports in this week's issue (
p. 1511
,
p. 1514
, and
p. 1517
) demonstrate that subunits of a protein factor that controls addition of the polyadenylated 3
'
tail to messenger RNA are conserved between yeast and mammals. In his Perspective, Manley describes what we know of the conservation of sequence signals for polyadenylation as well as of protein factors between yeast and mammals.
Dependence of Yeast Pre-mRNA 3′-End Processing on CFT1: A Sequence Homolog of the Mammalian AAUAAA Binding Factor
Authors: Stumpf Gabi , Domdey Horst
Published: July 2002

3′-End formation of pre-mRNA in yeast and mammals follows a similar but distinct pathway. In
Saccharomyces cerevisiae
, the cleavage reaction can be reconstituted by two activities called cleavage factor I and II (CFI and CFII). A CFII component, designated CFT1 (cleavage factor two) was identified by its sequence similarity to the AAUAAA-binding subunit of the mammalian cleavage and polyadenylation specificity factor (CPSF), even though the AAUAAA signal sequence appears to play no role in yeast pre-mRNA 3′ processing. Depletion of a yeast whole-cell extract with antibodies to CFT1 protein abolished cleavage and polyadenylation of pre-mRNAs. Addition of CFII restored cleavage activity, but not polyadenylation. Polyadenylation required the further addition of poly(A) polymerase and polyadenylation factor I, suggesting a close but not necessarily direct association of these two factors with the CFT1 protein.
Protein Structure: Nanosecond Crystallographic Snapshots of Protein Structural Changes
Authors: Eaton William A. , Henry Eric R. , Hofrichter James
Published: July 2002

In this issue of
Science
, Srajer
et al.
(
p. 1726
) present nanosecond-long snapshots of carbon monoxide dissociating from myoglobin, the first glimpse of a protein at work. In his Perspective, Eaton
et al
. discuss why this is such a landmark feat and how it was made possible.
INDEPTH Wide-Angle Reflection Observation of
P
-Wave-to-
S
-Wave Conversion from Crustal Bright Spots in Tibet
Authors: Makovsky Yizhaq , Klemperer Simon L. , Ratschbacher Lothar , Brown Larry D. , Li Ming , Zhao Wenjin , Meng Fanle
Published: July 2002

Three-component wide-angle seismic data acquired in southern Tibet during Project INDEPTH show strong
P
-to-
S
converted reflections from reflectors that are aligned at a depth of "∼15 kilometers beneath the northern Yadong-Gulu rift. These converted reflections are locally higher in amplitude than the corresponding
P
-wave reflections. Modeling of reflection mode conversion as a function of incidence angle indicates that this condition obtains for a reflector that is a solid over fluid interface; it is not typical of a solid-solid interface. The likely candidates for a fluid trapped within the crystalline crust of southern Tibet are granitic magma and water (brine).
Dynamical Signature of the Mott-Hubbard Transition in Ni(S,Se)
2
Authors: Husmann A. , Jin D. S. , Zastavker Y. V. , Rosenbaum T. F. , Yao X. , Honig J. M.
Published: July 2002

The transition metal chalcogenide Ni(S,Se)
2
is one of the few highly correlated, Mott-Hubbard systems without a strong first-order structural distortion that normally cuts off the critical behavior at the metal-insulator transition. The zero-temperature (
T
) transition was tuned with pressure, and significant deviations were found near the quantum critical point from the usual

T
1/2

behavior of the conductivity characteristic of electron-electron interactions in the presence of disorder. The transport data for pressure and temperature below 1 kelvin could be collapsed onto a universal scaling curve.
Ethylene as a Signal Mediating the Wound Response of Tomato Plants
Authors: O'Donnell P. J. , Calvert C. , Atzorn R. , Wasternack C. , Leyser H. M. O. , Bowles D. J.
Published: July 2002

Plants respond to physical injury, such as that caused by foraging insects, by synthesizing proteins that function in general defense and tissue repair. In tomato plants, one class of wound-responsive genes encodes proteinase inhibitor (pin) proteins shown to block insect feeding. Application of many different factors will induce or inhibit
pin
gene expression. Ethylene is required in the transduction pathway leading from injury, and ethylene and jasmonates act together to regulate
pin
gene expression during the wound response.
Smiles and Status Quo at NSF
Authors: Mervis Jeffrey
Published: July 2002

A low-key manner and a commitment to the agency's traditional missions have helped Neal Lane keep the National Science Foundation afloat in rough waters. But is nice what NSF needs?
Ironing Out the Wrinkles in the Prion Strain Problem
Authors: Grady Denise
Published: July 2002

One of the biggest stumbling blocks to accepting the prion hypothesis—the notion that naked protein particles can cause neurodegenerative diseases like Creutzfeldt-Jakob disease of humans and mad cow disease—has been the existence of multiple prion strains with different, and apparently inheritable, characteristics. New work, reported on
page 2079
, now provides compelling evidence for the idea that the different strains consist of the same protein misfolded in different ways, with each able to impose its brand of misfolding on the normal prion protein by simple contact, thereby transmitting disease with unique strain characteristics. (See also the Special News Report, “Putting Prions to the Test,”
Science
, 12 July 1996,
p. 184
.)
Molecular Basis of Gene-for-Gene Specificity in Bacterial Speck Disease of Tomato
Authors: Scofield Steven R. , Tobias Christian M. , Rathjen John P. , Chang Jeff H. , Lavelle Daniel T. , Michelmore Richard W. , Staskawicz Brian J.
Published: July 2002

Transient expression of the
Pseudomonas syringae
avirulence gene
avrPto
in plant cells resulted in a
Pto
-dependent necrosis. The AvrPto avirulence protein was observed to interact directly with the Pto resistance protein in the yeast two-hybrid system. Mutations in the
Pto
and
avrPto
genes which reduce in vivo activity had parallel effects on association in the two-hybrid assay. These data suggest that during infection the pathogen delivers AvrPto into the plant host cell and that resistance is specified by direct interaction of Pto with AvrPto.
Cognitive Neuroscience: Getting a Grasp on Working Memory
Authors: Wickelgren Ingrid
Published: July 2002

Without it, you couldn't understand this sentence, add up a restaurant tab in your head, or even find your way home. The “it” is working memory, an erasable mental blackboard that allows you to hold briefly in your mind the information essential for comprehension, reasoning, and planning. Now, neurobiologists are beginning to identify the neural machinery underlying this critical ability. They have found that working memory relies on cooperation among scattered areas of the brain, with the prefrontal cortex apparently working as the orchestrator that coordinates the activity of these various regions.
Large Enhancement of Magnetoresistance in Tl
2
Mn
2
O
7
: Pyrochlore Versus Perovskite
Authors: Ramirez A. P. , Subramanian M. A.
Published: July 2002

The synthesis of and magneto-transport in the “colossal magnetoresistance” (CMR) pyrochlore-structure compounds Tl
2
−

x

Sc

x

Mn
2
O
7
for 0 ≤
x
≤ 0.5 are reported. The maximum resistivity (ρ) increases by 10
5
while the Curie temperature (
T
c
) decreases by only 25% between
x
= 0 and 0.4. For
x
= 0.2 to 0.3, the magnetoresistance at both high field (6 tesla) and low field (<0.05 tesla) are significantly enhanced over the undoped (
x
= 0) compound. Structural analysis indicates that all of the manganese ions are near the +4 oxidation state. The behavior of ρ and
T
c
suggests that scandium substitution affects mainly electronic conduction on the thallium-oxygen sublattice while leaving the magnetism essentially unchanged. These results demonstrate a distinct way of manipulating magneto-transport properties in CMR materials.
Lake Baikal Record of Continental Climate Response to Orbital Insolation During the Past 5 Million Years
Authors: Williams D. F. , Peck J. , Karabanov E. B. , Prokopenko A. A. , Kravchinsky V. , King J. , Kuzmin M. I.
Published: July 2002

The sedimentary record of biogenic silica from Lake Baikal in south-central Siberia suggests that this region of central Asia was impacted by two major cooling episodes at 2.8 to 2.6 and 1.8 to 1.6 million years ago. The spectral evolution of this continental interior site parallels the evolutionary frequency spectra for various marine oxygen isotope records. In the Baikal record, the 41,000-year obliquity cycle is particularly strong from 1.8 to 0.8 million years ago; variance in the 100,000-year eccentricity band increases during the past 0.8 million years. The expected precession frequency of 23,000 years is highest during the past 400,000 years. The modulation of the predicted 23,000- and 41,000-year insolation forcing by the 100,000- and 400,000-year eccentricity bands indicates that the transfer of variance from the precession and obliquity frequencies to the eccentricity part of the spectrum occurred in the Eurasian continental interior, as well as in tropical and high-latitude ocean sites.
Thermoregulation in the Mouths of Feeding Gray Whales
Authors: Heyning John E. , Mead James G.
Published: July 2002

Vascular structures for heat conservation in the tongue of the gray whale (
Eschrichtius robustus
) are reported here. Numerous individual countercurrent heat exchangers are found throughout the massive tongue. These converge at the base of the tongue to form a bilateral pair of retia. Temperature measurements from the oral cavity of a live gray whale indicate that more heat may be lost through the blubber layer over the body than through the tongue, despite the fact that the tongue is far more vascularized and has much less insulation. These heat exchangers substantially reduce heat loss when these whales feed in cold waters.
Clams As Recorders of Ocean Ridge Volcanism and Hydrothermal Vent Field Activity
Authors: Hart Stanley R. , Blusztajn Jerzy
Published: July 2002

The clam
Calyptogena magnifica
lives at abyssal depths in association with hydrothermal venting on midocean ridges. Analysis of strontium/calcium ratios in
C. magnifica
shells provides a temperature proxy with submonthly time resolution. A 21-year strontium/calcium record of two clams from 9°50′N on the East Pacific Rise captures the known 1991 and 1992 eruptive events, documents several additional events between 1992 and 1996, and demonstrates the absence of major hydrothermal episodes during the period 1974 to 1991. These clam archives can increase our understanding of the thermal and chemical history of midocean ridge hydrothermal and volcanic activity on decadal time scales.
Sexual Selection, Receiver Biases, and the Evolution of Sex Differences
Authors: Ryan Michael J.
Published: July 2002

REVIEW

Recent approaches to analyzing the evolution of female mating preferences emphasize how historical influences on female receiver systems can bias the evolution of male traits that females find attractive. These studies combine animal behavior, sensory biology, phylogenetics, and artificial neural network models. They attempt to understand why specific phenotypes involved in sexual selection have evolved, rather than merely determining whether such traits and preferences are adaptive. It is now clear that traits and preferences often do not coevolve via genetic correlations, that female mating preferences for a given male trait are influenced by adaptations and constraints outside of the context of female responses to that particular trait, and that receiver biases can explain much of the diversity in male signaling phenotypes. It also appears that an understanding of historical effects will prove valuable in investigating why neural and cognitive systems respond to sensory stimuli as they do.
A Role for DNA-PK in Retroviral DNA Integration
Authors: Daniel René , Katz Richard A. , Skalka Anna Marie
Published: July 2002

Retroviral DNA integration is catalyzed by the viral protein integrase. Here, it is shown that DNA-dependent protein kinase (DNA-PK), a host cell protein, also participates in the reaction. DNA-PK-deficient murine
scid
cells infected with three different retroviruses showed a substantial reduction in retroviral DNA integration and died by apoptosis.
Scid
cell killing was not observed after infection with an integrase-defective virus, suggesting that abortive integration is the trigger for death in these DNA repair–deficient cells. These results suggest that the initial events in retroviral integration are detected as DNA damage by the host cell and that completion of the integration process requires the DNA-PK–mediated repair pathway.
Structural Rearrangements Underlying K
+
-Channel Activation Gating
Authors: Perozo Eduardo , Marien D. , Cortes  , Cuello Luis G.
Published: July 2002

The intramembrane molecular events underlying activation gating in the
Streptomyces
K
+
channel were investigated by site-directed spin-labeling methods and electron paramagnetic resonance spectroscopy. A comparison of the closed and open conformations of the channel revealed periodic changes in spin-label mobility and intersubunit spin-spin interaction consistent with rigid-body movements of the two transmembrane helices TM1 and TM2. These changes involve translations and counterclockwise rotations of both helices relative to the center of symmetry of the channel. The movement of TM2 increases the diameter of the permeation pathway along the point of convergence of the four subunits, thus opening the pore. Although the extracellular residues flanking the selectivity filter remained immobile during gating, small movements were detected at the C-terminal end of the pore helix, with possible implications to the gating mechanism.
A Nucleoside Transporter from
Trypanosoma brucei
Involved in Drug Resistance
Authors: Mäser Pascal , Sütterlin Christine , Kralli Anastasia , Kaminsky Ronald
Published: July 2002

Drug resistance of pathogens is an increasing problem whose underlying mechanisms are not fully understood. Cellular uptake of the major drugs against
Trypanosoma brucei
spp., the causative agents of sleeping sickness, is thought to occur through an unusual, so far unidentified adenosine transporter.
Saccharomyces cerevisiae
was used in a functional screen to clone a gene (
TbAT1
) from
Trypanosoma brucei brucei
that encodes a nucleoside transporter. When expressed in yeast,
TbAT1
enabled adenosine uptake and conferred susceptibility to melaminophenyl arsenicals. Drug-resistant trypanosomes harbor a defective
TbAT1
variant. The molecular identification of the entry route of trypanocides opens the way to approaches for diagnosis and treatment of drug-resistant sleeping sickness.
Josephson Persistent-Current Qubit
Authors: Mooij J. E. , Orlando T. P. , Levitov L. , Tian Lin , van der Wal Caspar H. , Lloyd Seth
Published: July 2002

A qubit was designed that can be fabricated with conventional electron beam lithography and is suited for integration into a large quantum computer. The qubit consists of a micrometer-sized loop with three or four Josephson junctions; the two qubit states have persistent currents of opposite direction. Quantum superpositions of these states are obtained by pulsed microwave modulation of the enclosed magnetic flux by currents in control lines. A superconducting flux transporter allows for controlled transfer between qubits of the flux that is generated by the persistent currents, leading to entanglement of qubit information.
Est1 and Cdc13 as Comediators of Telomerase Access
Authors: Evans Sara K. , Lundblad Victoria
Published: July 2002

Cdc13 and Est1 are single-strand telomeric DNA binding proteins that contribute to telomere replication in the yeast
Saccharomyces cerevisiae
. Here it is shown that fusion of Cdc13 to the telomerase-associated Est1 protein results in greatly elongated telomeres. Fusion proteins consisting of mutant versions of Cdc13 or Est1 confer similar telomere elongation, indicating that close physical proximity can bypass telomerase-defective mutations in either protein. Fusing Cdc13 directly to the catalytic core of telomerase allows stable telomere maintenance in the absence of Est1, consistent with a role for Est1 in mediating telomerase access. Telomere length homeostasis therefore is maintained in part by restricting access of telomerase to chromosome termini, but this limiting situation can be overcome by directly tethering telomerase to the telomere.
Microtubule Disassembly by ATP-Dependent Oligomerization of the AAA Enzyme Katanin
Authors: Hartman James J. , Vale Ronald D.
Published: July 2002

Katanin, a member of the AAA adenosine triphosphatase (ATPase) superfamily, uses nucleotide hydrolysis energy to sever and disassemble microtubules. Many AAA enzymes disassemble stable protein-protein complexes, but their mechanisms are not well understood. A fluorescence resonance energy transfer assay demonstrated that the p60 subunit of katanin oligomerized in an adenosine triphosphate (ATP)– and microtubule-dependent manner. Oligomerization increased the affinity of katanin for microtubules and stimulated its ATPase activity. After hydrolysis of ATP, microtubule-bound katanin oligomers disassembled microtubules and then dissociated into free katanin monomers. Coupling a nucleotide-dependent oligomerization cycle to the disassembly of a target protein complex may be a general feature of ATP-hydrolyzing AAA domains.
A Genetic Map and Recombination Parameters of the Human Malaria Parasite
Plasmodium falciparum
Authors: Su Xin-zhuan , Ferdig Michael T. , Huang Yaming , Huynh Chuong Q. , Liu Anna , You Jingtao , Wootton John C. , Wellems Thomas E.
Published: July 2002

Genetic investigations of malaria require a genome-wide, high-resolution linkage map of
Plasmodium falciparum
. A genetic cross was used to construct such a map from 901 markers that fall into 14 inferred linkage groups corresponding to the 14 nuclear chromosomes. Meiotic crossover activity in the genome proved high (17 kilobases per centimorgan) and notably uniform over chromosome length. Gene conversion events and spontaneous microsatellite length changes were evident in the inheritance data. The markers, map, and recombination parameters are facilitating genome sequence assembly, localization of determinants for such traits as virulence and drug resistance, and genetic studies of parasite field populations.
Transition States Between Pyramids and Domes During Ge/Si Island Growth
Authors: Ross F. M. , Tromp R. M. , Reuter M. C.
Published: July 2002

Real-time observations were made of the shape change from pyramids to domes during the growth of germanium-silicon islands on silicon (001). Small islands are pyramidal in shape, whereas larger islands are dome-shaped. During growth, the transition from pyramids to domes occurs through a series of asymmetric transition states with increasing numbers of highly inclined facets. Postgrowth annealing of pyramids results in a similar shape change process. The transition shapes are temperature dependent and transform reversibly to the final dome shape during cooling. These results are consistent with an anomalous coarsening model for island growth.
Timing the Radiations of Leaf Beetles: Hispines on Gingers from Latest Cretaceous to Recent
Authors: Wilf Peter , Labandeira Conrad C. , Kress W. John , Staines Charles L. , Windsor Donald M. , Allen Ashley L. , Johnson Kirk R.
Published: July 2002

Stereotyped feeding damage attributable solely to rolled-leaf hispine beetles is documented on latest Cretaceous and early Eocene ginger leaves from North Dakota and Wyoming. Hispine beetles (6000 extant species) therefore evolved at least 20 million years earlier than suggested by insect body fossils, and their specialized associations with gingers and ginger relatives are ancient and phylogenetically conservative. The latest Cretaceous presence of these relatively derived members of the hyperdiverse leaf-beetle clade (Chrysomelidae, more than 38,000 species) implies that many of the adaptive radiations that account for the present diversity of leaf beetles occurred during the Late Cretaceous, contemporaneously with the ongoing rapid evolution of their angiosperm hosts.
Reinterpreting Space, Time Lags, and Functional Responses in Ecological Models
Authors: Keeling Matt J. , Wilson Howard B. , Pacala Steve W.
Published: July 2002

Natural enemy-victim interactions are of major applied importance and of fundamental interest to ecologists. A key question is what stabilizes these interactions, allowing the long-term coexistence of the two species. Three main theoretical explanations have been proposed: behavioral responses, time-dependent factors such as delayed density dependence, and spatial heterogeneity. Here, using the powerful moment-closure technique, we show a fundamental equivalence between these three elements. Limited movement by organisms is a ubiquitous feature of ecological systems, allowing spatial structure to develop; we show that the effects of this can be naturally described in terms of time lags or within-generation functional responses.
A Pharmacokinetic Study of Amphotericin B Lipid Complex Injection (Abelcet) in Patients with Definite or Probable Systemic Fungal Infections
Authors: Adedoyin Adedayo , Swenson Christine E. , Bolcsak Lois E. , Hellmann Andrzej , Radowska Danuta , Horwith Gary , Janoff Andrew S. , Branch Robert A.
Published: July 2002

This study describes a pharmacokinetic evaluation of amphotericin B (AMB) lipid complex injection (ABLC or Abelcet) in 17 patients with systemic fungal infection administered 5 mg/kg of body weight/day by infusion for 10 to 17 days. The results showed that AMB exhibited multiexponential disposition with high clearance, large volume of distribution at steady state, and long apparent elimination half-life but no evidence of accumulation in the blood after multiple daily doses. The results confirm previous observations and further reinforce the suggestion that ABLC may exist as a depot in the tissues from which free AMB is slowly released to limit exposure.
Photoactive Porphyrin Derivative with Broad-Spectrum Activity against Oral Pathogens In Vitro
Authors: Rovaldi C. R. , Pievsky A. , Sole N. A. , Friden P. M. , Rothstein D. M. , Spacciapoli P.
Published: July 2002

Photodynamic therapy (PDT) has historically been used as a means to treat cancerous tumors but has recently been used to kill bacterial cells through the use of targeted photosensitizers. PDT is a potential adjunct to scaling and root planing in the treatment of periodontal disease. However, the effectiveness of porphyrin derivatives against microorganisms has been limited because some gram-negative bacteria are refractory to photodynamic treatment with these agents. We have designed a porphyrin derivative conjugated to a pentalysine moeity that endows the molecule with activity against gram-positive and gram-negative bacteria. Whereas the porphyrin, chlorin e6, showed in vitro activity against a limited spectrum of bacteria, chlorin e6 conjugated to pentalysine showed in vitro activity against all oral microorganisms tested, including
Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Bacteroides forsythus, Campylobacter rectus, Eikenella corrodens, Fusobacterium nucleatum
subsp.
polymorphum, Actinomyces viscosus
, and the streptococci. Potent antimicrobial activity (≥5-log-unit reduction in the numbers of CFU per milliliter) was retained in the presence of up to 25% whole sheep blood. The use of potent, selective agents such as this chlorin e6–pentalysine conjugate to more effectively reduce the pathogenic bacteria in the periodontal pocket may be a significant tool for the treatment of periodontal disease.
pncA
Mutations as a Major Mechanism of Pyrazinamide Resistance in
Mycobacterium tuberculosis
: Spread of a Monoresistant Strain in Quebec, Canada
Authors: Cheng Shao-Ji , Thibert Louise , Sanchez Tracy , Heifets Leonid , Zhang Ying
Published: July 2002

Pyrazinamide (PZA) is an important first-line tuberculosis drug that is part of the currently used short-course tuberculosis chemotherapy. PZA is a prodrug that has to be converted to the active form pyrazinoic acid by pyrazinamidase (PZase) activity, encoded by the
pncA
gene of
Mycobacterium tuberculosis
, and loss of PZase activity is associated with PZA resistance. To further define the genetic basis of PZA resistance and determine the frequency of PZA-resistant strains having
pncA
mutations, we sequenced the
pncA
gene from a panel of 59 PZA-resistant clinical isolates from Canada, the United States, and Korea. Two strains that did not contain
pncA
mutations and had positive PZase turned out to be falsely resistant. Three PZase-negative strains (MIC, >900 μg of PZA per ml) and one PZase-positive strain (strain 9739) (MIC, >300 μg of PZA per ml) did not have
pncA
mutations. The remaining 53 of the 57 PZA-resistant isolates had
pncA
mutations, confirming that
pncA
mutation is the major mechanism of PZA resistance. Various new and diverse mutations were found in the
pncA
gene. Interestingly, 20 PZA-monoresistant strains and 1 multidrug-resistant isolate from Quebec, Canada, all had the same
pncA
mutation profile, consisting of an 8-nucleotide deletion and an amino acid substitution of Arg140→Ser. Strain typing indicated that these strains are highly related and share almost identical IS
6110
patterns. These data strongly suggest the spread of a PZA-monoresistant strain, which has not previously been described.
Actinomycin Production Persists in a Strain of
Streptomyces antibioticus
Lacking Phenoxazinone Synthase
Authors: Jones George H.
Published: July 2002

Truncated fragments of the phenoxazinone synthase gene,
phsA
, were prepared by the PCR. The resulting fragments were cloned into conjugative plasmid pKC1132 and transferred to
Streptomyces antibioticus
by conjugation from
Escherichia coli
. Two of the resulting constructs were integrated into the
S. antibioticus
chromosome by homologous recombination, and each of the resulting strains, designated 3720/pJSE173 and 3720/pJSE174, contained a disrupted
phsA
gene. Strain 3720/pJSE173 grew poorly, and Southern blotting suggested that genetic changes other than the disruption of the
phsA
gene might have occurred during the construction of that strain. Strain 3720/pJSE174 sporulated well and grew normally on the medium used to prepare inocula for antibiotic production. Strain 3720/pJSE174 also grew as well as the wild-type strain on antibiotic production medium containing either 1 or 5.7 mM phosphate. Strain 3720/pJSE174 was shown to be devoid of phenoxazinone synthase (PHS) activity, and PHS protein was undetectable in this strain by Western blotting. Despite the absence of detectable PHS activity, strain 3720/pJSE174 produced slightly more actinomycin than did the wild-type parent strain in medium containing 1 or 5.7 mM phosphate. The observation that strain 3720/pJSE174, lacking detectable PHS protein or enzyme activity, retained the ability to produce actinomycin supports the conclusion that PHS is not required for actinomycin biosynthesis in
S. antibioticus
.
Phenotypic Characterization of
pncA
Mutants of
Mycobacterium tuberculosis
Authors: Morlock Glenn P. , Crawford Jack T. , Butler W. Ray , Brim Suzanne E. , Sikes David , Mazurek Gerald H. , Woodley Charles L. , Cooksey Robert C.
Published: July 2002

We examined the correlation of mutations in the pyrazinamidase (PZase) gene (
pncA
) with the pyrazinamide (PZA) resistance phenotype with 60
Mycobacterium tuberculosis
isolates. PZase activity was determined by the method of Wayne (L. G. Wayne, Am. Rev. Respir. Dis.
109:
147–151, 1974), and the entire
pncA
nucleotide sequence, including the 74 bp upstream of the start codon, was determined. PZA susceptibility testing was performed by the method of proportions on modified Middlebrook and Cohn 7H10 medium. The PZA MICs were ≥100 μg/ml for 37 isolates, 34 of which had alterations in the
pncA
gene. These mutations included missense substitutions for 24 isolates, nonsense substitutions for 3 isolates, frameshifts by deletion for 4 isolates, a three-codon insertion for 1 isolate, and putative regulatory mutations for 2 isolates. Among 21 isolates for which PZA MICs were <100 μg/ml, 3 had the same mutation (Thr47→Ala) and 18 had the wild-type sequence. For the three Thr47→Ala mutants PZA MICs were 12.5 μg/ml by the method of proportions on 7H10 agar; two of these were resistant to 100 μg of PZA per ml and the third was resistant to 800 μg of PZA per ml by the BACTEC method. In all, 30 different
pncA
mutations were found among the 37
pncA
mutants. No PZase activity was detected in 35 of 37 strains that were resistant to ≥100 μg of PZA per ml or in 34 of 37
pncA
mutants. Reduced PZase activity was found in the three mutants with the Thr47→Ala mutation. This study demonstrates that mutations in the
pncA
gene may serve as a reliable indicator of resistance to ≥100 μg of PZA per ml.
Comparison of Efficacies of RWJ-270201, Zanamivir, and Oseltamivir against H5N1, H9N2, and Other Avian Influenza Viruses
Authors: Govorkova Elena A. , Leneva Irina A. , Goloubeva Olga G. , Bush Karen , Webster Robert G.
Published: July 2002

The orally administered neuraminidase (NA) inhibitor RWJ-270201 was tested in parallel with zanamivir and oseltamivir against a panel of avian influenza viruses for inhibition of NA activity and replication in tissue culture. The agents were then tested for protection of mice against lethal H5N1 and H9N2 virus infection. In vitro, RWJ-270201 was highly effective against all nine NA subtypes. NA inhibition by RWJ-270201 (50% inhibitory concentration, 0.9 to 4.3 nM) was superior to that by zanamivir and oseltamivir carboxylate. RWJ-270201 inhibited the replication of avian influenza viruses of both Eurasian and American lineages in MDCK cells (50% effective concentration, 0.5 to 11.8 μM). Mice given 10 mg of RWJ-270201 per kg of body weight per day were completely protected against lethal challenge with influenza A/Hong Kong/156/97 (H5N1) and A/quail/Hong Kong/G1/97 (H9N2) viruses. Both RWJ-270201 and oseltamivir significantly reduced virus titers in mouse lungs at daily dosages of 1.0 and 10 mg/kg and prevented the spread of virus to the brain. When treatment began 48 h after exposure to H5N1 virus, 10 mg of RWJ-270201/kg/day protected 50% of mice from death. These results suggest that RWJ-270201 is at least as effective as either zanamivir or oseltamivir against avian influenza viruses and may be of potential clinical use for treatment of emerging influenza viruses that may be transmitted from birds to humans.
Metallo-β-Lactamase Producers in Environmental Microbiota: New Molecular Class B Enzyme inJanthinobacterium lividum
Authors: Rossolini Gian Maria , Condemi Maria Adelaide , Pantanella Fabrizio , Docquier Jean-Denis , Amicosante Gianfranco , Thaller Maria Cristina
Published: July 2002

Eleven environmental samples from different sources were screened for the presence of metallo-β-lactamase-producing bacteria by using a selective enrichment medium containing a carbapenem antibiotic and subsequently testing each isolate for production of EDTA-inhibitable carbapenemase activity. A total of 15 metallo-β-lactamase-producing isolates, including 10Stenotrophomonas maltophiliaisolates, 3Chryseobacteriumspp., oneAeromonas hydrophilaisolate, and oneJanthinobacterium lividumisolate (a species in which production of metallo-β-lactamase activity was not previously reported), were obtained from 8 samples. In theJ. lividumisolate, named JAC1, production of metallo-β-lactamase activity was elicited upon exposure to β-lactams. Screening of a JAC1 genomic library for clones showing a reduced imipenem susceptibility led to the isolation of a metallo-β-lactamase determinant encoding a new member (named THIN-B) of the highly divergent subclass B3 lineage of metallo-β-lactamases. THIN-B is most closely related (35.6% identical residues) to the L1 enzyme ofS. maltophiliaand more distantly related to the FEZ-1 enzyme ofLegionella gormanii(27.8% identity) and to the GOB-1 enzyme ofChryseobacterium meningosepticum(24.2% identity). Sequences related toblaTHIN-B, and inducible production of metallo-β-lactamase activity, were also detected in theJ. lividumtype strain DSM1522. Expression of theblaTHIN-Bgene inEscherichia coliresulted in decreased susceptibility to several β-lactams, including penicillins, cephalosporins (including cephamycins and oxyimino cephalosporins), and carbapenems, revealing a broad substrate specificity of the enzyme. The results of this study indicated that metallo-β-lactamase-producing bacteria are widespread in the environment and identified a new molecular class B enzyme in the environmental speciesJ. lividum.
Nosocomial Outbreak of Carbapenem-Resistant
Pseudomonas aeruginosa
with a New
bla
IMP
Allele,
bla
IMP-7
Authors: Gibb Alan Patrick , Tribuddharat Chanwit , Moore Richard A. , Louie Thomas J. , Krulicki Wally , Livermore David M. , Palepou Marie-France I. , Woodford Neil
Published: July 2002

Pseudomonas aeruginosa
isolates from an outbreak in Canada were highly resistant to carbapenems and ceftazidime but not piperacillin. They produced a novel integron-associated metallo-β-lactamase, designated IMP-7, with 91% identity to IMP-1.
bla
IMP-7
was not detected with standard
bla
IMP
-specific primers, owing to mismatches in the forward primer.
Mutations Affecting the Rossman Fold of Isoleucyl-tRNA Synthetase Are Correlated with Low-Level Mupirocin Resistance in
Staphylococcus aureus
Authors: Antonio Martin , McFerran Neil , Pallen Mark J.
Published: July 2002

The isoleucyl-tRNA synthetase (
ileS
) gene was sequenced in toto from 9 and in part from 31
Staphylococcus aureus
strains with various degrees of susceptibility to mupirocin. All strains for which the mupirocin MIC was greater than 8 μg/ml contained point mutations affecting the Rossman fold via Val-to-Phe changes at either residue 588 (V588F) or residue 631 (V631F). The importance of the V588F mutation was confirmed by an allele-specific PCR survey of 32 additional strains. Additional mutations of uncertain significance were found in residues clustered on the surface of the IleS protein.
ColE1-Like Plasmid pIP843 of
Klebsiella pneumoniae
Encoding Extended-Spectrum β-Lactamase CTX-M-17
Authors: Cao Van , Lambert Thierry , Courvalin Patrice
Published: July 2002

The resistance of
Klebsiella pneumoniae
BM4493, isolated in Ho Chi Minh City, Vietnam, to cefotaxime and aztreonam was due to production of a novel β-lactamase, CTX-M-17. The
bla
CTX-M-17
gene was borne by 7,086-bp plasmid pIP843, which was entirely sequenced and which was found to belong to the ColE1 family. The 876-bp
bla
CTX-M-17
gene differed from
bla
CTX-M-14
by 2 nucleotides, which led to the single amino acid substitution Glu289→Lys.
bla
CTX-M-17
was flanked upstream by an IS
Ecp1
-like element and downstream by an insertion sequence (IS) IS
903
variant designated IS
903
-C. The transcriptional start site of
bla
CTX-M-17
was located 109 nucleotides upstream from the initiation codon in the IS
Ecp1-
like element, which also provided the promoter sequences. Plasmid pIP843, which was non-self-transferable and nonmobilizable, contained five open reading frames transcribed in the same orientation. Regions homologous to sequences coding for putative RNA II and RNA I transcripts, a
rom
gene, which is involved in initiation of replication, and a
cer
-like gene, which is responsible for the stability of ColE1-like plasmids, were identified. Consensus sequences for putative replication (
oriV
) and transfer (
oriT
) origins were present. Results of primer extension experiments indicated that IS
Ecp1
provides the promoter for expression of
bla
CTX-M-17
and may contribute to dissemination of this gene.
Effect of Telithromycin (HMR 3647) on Polymorphonuclear Neutrophil Killing ofStaphylococcus aureusin Comparison with Roxithromycin
Authors: Vazifeh D. , Abdelghaffar H. , Labro M. T.
Published: July 2002

HMR 3647 (telithromycin), a new ketolide, is active on intracellular pathogens. It was previously demonstrated that it inhibits superoxide anion production in a time- and concentration-dependent manner, at concentrations which inhibit 50% of the control response of about 55 μg/ml (5 min) to 30 μg/ml (30 min); these values are similar to those obtained with roxithromycin, a classical erythromycin A derivative. Here we investigated whether these drugs modified the bactericidal activity of human polymorphonuclear neutrophils (PMN) on four strains ofStaphylococcus aureuswith different profiles of susceptibility to macrolides and ketolides. We found that the main factor involved in killing was the antibacterial potency of the drugs, although combinations of antibiotics with PMN were slightly more active than each component used alone against two of the four strains. In addition, high concentrations of the drugs, which impaired the PMN oxidative burst, did not impair PMN bactericidal activity. Likewise, some cytokines which enhance PMN oxidative metabolism did not modify PMN bactericidal activity in the presence or absence of macrolides or ketolides. These data suggest that oxygen-independent mechanisms contribute to the bactericidal activity of PMN on these strains ofS. aureus. Both live and/or heat-killed bacteria impaired the uptake of telithromycin and roxithromycin (but not that of levofloxacin, a quinolone) in a concentration-dependent manner, owing to a modulation of PMN transductional systems involved in the activation of the macrolide carrier.