bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct Mechanism for Antidepressant Activity by Blockade of Central Substance P Receptors
Authors: Kramer Mark S. , Cutler Neal , Feighner John , Shrivastava Ram , Carman John , Sramek John J. , Reines Scott A. , Liu Guanghan , Snavely Duane , Wyatt-Knowles Edwina , Hale Jeffrey J. , Mills Sander G. , MacCoss Malcolm , Swain Christopher J. , Harrison Timothy , Hill Raymond G. , Hefti Franz , Scolnick Edward M. , Cascieri Margaret A. , Chicchi Gary G. , Sadowski Sharon , Williams Angela R. , Hewson Louise , Smith David , Carlson Emma J. , Hargreaves Richard J. , Rupniak Nadia M. J.
Published: July 2002

The localization of substance P in brain regions that coordinate stress responses and receive convergent monoaminergic innervation suggested that substance P antagonists might have psychotherapeutic properties. Like clinically used antidepressant and anxiolytic drugs, substance P antagonists suppressed isolation-induced vocalizations in guinea pigs. In a placebo-controlled trial in patients with moderate to severe major depression, robust antidepressant effects of the substance P antagonist MK-869 were consistently observed. In preclinical studies, substance P antagonists did not interact with monoamine systems in the manner seen with established antidepressant drugs. These findings suggest that substance P may play an important role in psychiatric disorders.
Ammonia Synthesis at Atmospheric Pressure
Authors: Marnellos George , Stoukides Michael
Published: July 2002

Ammonia was synthesized from its elements at atmospheric pressure in a solid state proton (H
+
)–conducting cell-reactor. Hydrogen was flowing over the anode and was converted into protons that were transported through the solid electrolyte and reached the cathode (palladium) over which nitrogen was passing. At 570°C and atmospheric pressure, greater than 78 percent of the electrochemically supplied hydrogen was converted into ammonia. The thermodynamic requirement for a high-pressure process is eliminated.
North Atlantic Oscillation Dynamics Recorded in Greenland Ice Cores
Authors: Appenzeller C. , Stocker T. F. , Anklin M.
Published: July 2002

Carefully selected ice core data from Greenland can be used to reconstruct an annual proxy North Atlantic oscillation (NAO) index. This index for the past 350 years indicates that the NAO is an intermittent climate oscillation with temporally active (coherent) and passive (incoherent) phases. No indication for a single, persistent, multiannual NAO frequency is found. In active phases, most of the energy is located in the frequency band with periods less than about 15 years. In addition, variability on time scales of 80 to 90 years has been observed since the mid-19th century.
Control of Chemical Reactions by Feedback-Optimized Phase-Shaped Femtosecond Laser Pulses
Authors: Assion A. , Baumert T. , Bergt M. , Brixner T. , Kiefer B. , Seyfried V. , Strehle M. , Gerber G.
Published: July 2002

Tailored femtosecond laser pulses from a computer-controlled pulse shaper were used to optimize the branching ratios of different organometallic photodissociation reaction channels. The optimization procedure is based on the feedback from reaction product quantities in a learning evolutionary algorithm that iteratively improves the phase of the applied femtosecond laser pulse. In the case of CpFe(CO)
2
Cl, it is shown that two different bond-cleaving reactions can be selected, resulting in chemically different products. At least in this case, the method works automatically and finds optimal solutions without previous knowledge of the molecular system and the experimental environment.
Isotopic Mass and Lattice Constant: X-ray Standing Wave Measurements
Authors: Kazimirov Alexander , Zegenhagen Jörg , Cardona Manuel
Published: July 2002

The molecular volume of crystals depends on their isotopic masses. This influence originates from the zero-point motion and the resulting small differences in lattice constants. This effect was measured with high precision by using an x-ray standing wave. The standing wave is generated during Bragg reflection and thus is in phase with the planes of the substrate crystal, which is covered with a homoepitaxial film that has a different isotopic composition than the substrate. The positions of the surface planes of the film with respect to the substrate planes are revealed by the photoelectrons excited by the maxima of the standing wave. For germanium-76 on natural germanium(111), a difference in lattice constant of −1.1 × 10
−5
and −2.5 × 10
−5
at 300 and 54 kelvin, respectively, was found. The results are in good agreement with theoretical predictions.
Comprehensive Sequence Analysis
Authors: Calvet James P.
Published: July 2002

OMIGA 1.1
. Oxford Molecular Group Inc. Oxford, UK. Industry $1995; academic/government $1495. Phone: (800) 876-9994.
products@oxmol.com

In this review, Calvet assesses the comprehensive DNA and protein sequence analysis program OMIGA 1.1 and finds it powerful and easy to use.
Isolated and Companion Young Brown Dwarfs in the Taurus and Chamaeleon Molecular Clouds
Authors: Tamura Motohide , Itoh Yoichi , Oasa Yumiko , Nakajima Tadashi
Published: July 2002

Infrared imaging observations have detected a dozen faint young stellar objects (YSOs) in the Taurus and Chamaeleon molecular clouds whose near-infrared colors are similar to those of classical T Tauri stars (TTS). They are around four magnitudes fainter than low-luminosity YSOs in Taurus detected in earlier surveys and as much as eight magnitudes fainter than typical TTS. The extreme faintness of the objects and their lower luminosity relative to previously identified brown dwarfs in the Pleiades indicate that these faint YSOs are very young brown dwarfs on the order of 1 million years old.
Terrible Lizards--Impure Science?
Authors: Dodson Peter
Published: July 2002

The Last Dinosaur Book
The Life and Times of a Cultural Icon. W. J. T. Mitchell. University of Chicago Press, Chicago, 1998. 333 pp. $35. ISBN 0-226-53204-6.

This is not another book about dinosaurs, but an examination of dinosaurs in popular culture, past and present. Mitchell's enthusiastic, though sometimes superficial, study touches on dinosaur appearances in settings ranging from books to business, movies to museums, and television to toy stores.
Organizing Pelagic Ecosystems
Authors: Smith Sharon L.
Published: July 2002

Ecological Geography of the Sea
. Alan Longhurst. Academic, San Diego, 1998. 412 pp. $79.95. ISBN 0-12-455558-6.

Longhurst offers an inclusive overview of oceanic ecology, based on the inseparability of the physical environment and the biological communities. Successfully integrating ideas from terrestrial ecology, his synthesis will prove useful to laymen, teachers, graduate students, and research scientists.
Choosing to Favor Animals
Authors: Morrison Adrian R.
Published: July 2002

The Human Use of Animals
Case Studies in Ethical Choices. F. Barbara Orlans, Tom L. Beauchamp, Rebecca Dresser, David B. Morton, John P. Gluck. Oxford University Press, New York, 1998. 342 pp. $55. ISBN 0-19-511907-X. Paper, $26. ISBN 0-19-511908-8.

This collection of papers is offered as an examination of how far it is ethically justifiable to harm animals in order to benefit humans. The reviewer finds the examination is not balanced, with many of the authors believing that such use of animals is morally wrong.
Role of Serotonin in the Paradoxical Calming Effect of Psychostimulants on Hyperactivity
Authors: Gainetdinov Raul R. , Wetsel William C. , Jones Sara R. , Levin Edward D. , Jaber Mohamed , Caron Marc G.
Published: July 2002

The mechanism by which psychostimulants act as calming agents in humans with attention-deficit hyperactivity disorder (ADHD) or hyperkinetic disorder is currently unknown. Mice lacking the gene encoding the plasma membrane dopamine transporter (DAT) have elevated dopaminergic tone and are hyperactive. This activity was exacerbated by exposure to a novel environment. Additionally, these mice were impaired in spatial cognitive function, and they showed a decrease in locomotion in response to psychostimulants. This paradoxical calming effect of psychostimulants depended on serotonergic neurotransmission. The parallels between the DAT knockout mice and individuals with ADHD suggest that common mechanisms may underlie some of their behaviors and responses to psychostimulants.
Shifting the Spotlight from Center Stage
Authors: Shapiro Jill
Published: July 2002

Women's Science
Learning and Succeeding from the Margins. Margaret A. Eisenhart and Elizabeth Finkel. University of Chicago Press, Chicago, 1998. 290 pp. $45, £35.95. ISBN 0-226-19544-9. Paper, $15, £11.95. ISBN 0-226-19545-7.

Using findings from case studies of four settings marked by higher-than-usual female participation, Eisenhart and Finkel examine aspects of the learning and practice of science and engineering by women.
Uncle Sam Wants You
Authors: Hull David L.
Published: July 2002

Mystery of Mysteries
Is Evolution a Social Construction?. Michael Ruse. Harvard University Press, Cambridge, MA, 1999. 320 pp. $27.50, £16.95. ISBN 0-674-46706-X.

Through studies of 11 evolutionary biologists, Ruse examines the relative importance of data, beliefs about science, and cultural factors in deciding the course of their discipline from the late 18th century to today.
Control of Hippocampal Morphogenesis and Neuronal Differentiation by the LIM Homeobox Gene
Lhx5
Authors: Zhao Yangu , Sheng Hui Z. , Amini Reshad , Grinberg Alexander , Lee Eric , Huang SingPing , Taira Masanori , Westphal Heiner
Published: July 2002

The mammalian hippocampus contains the neural circuitry that is crucial for cognitive functions such as learning and memory. The development of such circuitry is dependent on the generation and correct placement of the appropriate number and types of neurons. Mice lacking function of the LIM homeobox gene
Lhx5
showed a defect in hippocampus development. Hippocampal neural precursor cells were specified and proliferated, but many of them failed to either exit the cell cycle or to differentiate and migrate properly.
Lhx5
is therefore essential for the regulation of precursor cell proliferation and the control of neuronal differentiation and migration during hippocampal development.
Infectious Avenues to Cancer
Authors: Ganem Don
Published: July 2002

Microbes and Malignancy
Infection as a Cause of Human Cancers. Julie Parsonnet, Ed. Oxford University Press, New York, 1999. 477 pp. $79.95, £59.50. ISBN 0-19-510401-3.

The contributors explore epidemiologic, clinical, and molecular aspects of the links between infectious microorganisms and several cancers.
Structural Catholicism
Authors: Wiltzius Pierre
Published: July 2002

The Structure of Materials
. Samuel M. Allen and Edwin L. Thomas. Wiley, New York, 1999. 463 pp. $102.95. ISBN 0-471-00082-5.

Adopting a perspective that reflects modern materials research and development, Allen and Thomas organize their textbook around structural descriptions of three states of condensed matter: glasses, crystals, and liquid crystals.
It's in the Genes
Authors: Stent Gunther S.
Published: July 2002

Time, Love, Memory
A Great Biologist and His Quest for the Origins of Behavior.
By Jonathan Weiner
. Knopf, New York, 1999. 314 pp. $27.50, C$36.95. ISBN 0-679-44435-1.

The Pulitzer Prize-wining author of
The Beak of the Finch
provides an enjoyable yet realistic portrayal of the research of Seymour Benzer and his colleagues into the connections between genes and behavior.
What It's All About
Authors: Allen Barry
Published: July 2002

The Social Construction of What?
. Ian Hacking. Harvard University Press, Cambridge, MA, 1999. 271 pp. $29.95, £18.50. ISBN 0-674-81200-X.

Hacking's examination of philosophical sticking points between social constructionists and their critics is not intended to decide the science wars but to clearly explain what is at stake.
Representing the World in a Computer
Authors: Sleeman Brian
Published: July 2002

The Nature of Mathematical Modeling
. Neil Gershenfeld. Cambridge University Press, Cambridge, 1999. 356 pp. $39.95, £24.95. ISBN 0-521-57095-6.

Gershenfeld provides a concise and accessible compendium of techniques for developing simulations and quantitative descriptions of complex phenomena.
Incubating Bioweapons
Authors: Haseltine William A.
Published: July 2002

Biohazard
The Chilling True Story of the Largest Covert Biological Weapons Program in the World--Told from the Inside by the Man Who Ran It. Ken Alibek, with Stephen Handelman. Random House, New York, 1999. 335 pp. $24.95, C$37.95. ISBN 0-375-50231-9.

Alibek offers a fact-filled description of Soviet programs to cultivate biological agents and adapt them for use in weapons programs that he helped run until his 1992 defection.
Reacting to History
Authors: Labinger Jay
Published: July 2002

Chemical Creativity
Ideas from the Work of Woodward, Hückel, Meerwein, and Others. Jerome A. Berson. Wiley-VCH, Weinheim, Germany, 1999. 207 pp. Paper, $54.95. ISBN 3-527-29754-5.

Through a series of essays on specific research problems, Berson examines the origination and development of ideas in chemistry.
Complex Facets of a Strong Interactor
Authors: Gaillard Mary K.
Published: July 2002

Strange Beauty
Murray Gell-Mann and the Revolution in Twentieth-Century Physics. George Johnson. Knopf, New York, 1999. 446 pp. $30. ISBN 0-679-43764-9.

Johnson illuminates the complexities of the life and science of the Nobel Prize-winner whose contributions to physics include the quark and the Eightfold Way.
Detection of Nonthermal Melting by Ultrafast X-ray Diffraction
Authors: Siders C. W. , Cavalleri A. , Sokolowski-Tinten K. , Tóth Cs. , Guo T. , Kammler M. , Hoegen M. Horn von , Wilson K. R. , Linde D. von der , Barty C. P. J.
Published: July 2002

Using ultrafast, time-resolved, 1.54 angstrom x-ray diffraction, thermal and ultrafast nonthermal melting of germanium, involving passage through nonequilibrium extreme states of matter, was observed. Such ultrafast, optical-pump, x-ray diffraction probe measurements provide a way to study many other transient processes in physics, chemistry, and biology, including direct observation of the atomic motion by which many solid-state processes and chemical and biochemical reactions take place.
Three-Dimensional Structure of the Human TFIID-IIA-IIB Complex
Authors: Andel Frank , Ladurner Andreas G. , Inouye Carla , Tjian Robert , Nogales Eva
Published: July 2002

The multisubunit transcription factor IID (TFIID) is an essential component of the eukaryotic RNA polymerase II machinery that works in concert with TFIIA (IIA) and TFIIB (IIB) to assemble initiation complexes at core eukaryotic promoters. Here the structures of human TFIID and the TFIID-IIA-IIB complex that were obtained by electron microscopy and image analysis to 35 angstrom resolution are presented. TFIID is a trilobed, horseshoe-shaped structure, with TFIIA and TFIIB bound on opposite lobes and flanking a central cavity. Antibody studies locate the TATA-binding protein (TBP) between TFIIA and TFIIB at the top of the cavity that most likely encompasses the TATA DNA binding region of the supramolecular complex.
Solving the Sverdlovsk Mystery
Authors: Tucker Jonathan B.
Published: July 2002

Anthrax
The Investigation of a Deadly Outbreak. Jeanne Guillemin. University of California Press, Berkeley, 1999. 339 pp. $27.50. ISBN 0-520-22204-0.

Guillemin blends epidemiology, Russian history, and the scientific method in her account of the 1992 investigation by U.S. scientists (in which she played a major role) into the cause of the anthrax epidemic that struck Sverdlovsk in 1979.
Dreams of Arctic Tea Plantations
Authors: Schiebinger Londa
Published: July 2002

Linnaeus
Nature and Nation. Lisbet Koerner. Harvard University Press, Cambridge, MA, 1999. 308 pp. $39.95. ISBN 0-674-09745-9.

Drawing on her own research and excellent Swedish scholarship, Koerner presents a Linnaeus who saw his taxonomic innovations as secondary to an unsuccessful program to make Sweden economically self-sufficient through the science of natural history.
Hematopoietic Stem Cell Quiescence Maintained by p21
cip1/waf1
Authors: Cheng Tao , Rodrigues Neil , Shen Hongmei , Yang Yong-guang , Dombkowski David , Sykes Megan , Scadden David T.
Published: July 2002

Relative quiescence is a defining characteristic of hematopoietic stem cells, while their progeny have dramatic proliferative ability and inexorably move toward terminal differentiation. The quiescence of stem cells has been conjectured to be of critical biologic importance in protecting the stem cell compartment, which we directly assessed using mice engineered to be deficient in the G
1
checkpoint regulator, cyclin-dependent kinase inhibitor, p21
cip1/waf1
(p21). In the absence of p21, hematopoietic stem cell proliferation and absolute number were increased under normal homeostatic conditions. Exposing the animals to cell cycle–specific myelotoxic injury resulted in premature death due to hematopoietic cell depletion. Further, self-renewal of primitive cells was impaired in serially transplanted bone marrow from p21
−/−
mice, leading to hematopoietic failure. Therefore, p21 is the molecular switch governing the entry of stem cells into the cell cycle, and in its absence, increased cell cycling leads to stem cell exhaustion. Under conditions of stress, restricted cell cycling is crucial to prevent premature stem cell depletion and hematopoietic death.
Spontaneous Ordering of Oxide Nanostructures
Authors: Aggarwal S. , Monga A. P. , Perusse S. R. , Ramesh R. , Ballarotto V. , Williams E. D. , Chalamala B. R. , Wei Y. , Reuss R. H.
Published: July 2002

We report the spontaneous formation of uniformly distributed arrays of “tips” (tall conical hillocks) upon oxidation of palladium (Pd) thin films. The formation of the palladium oxide tips depended on the thickness and granularity of the Pd film and on annealing and oxidation conditions. As the Pd film thickness increased from 40 to 200 nanometers, the average height of the tips increased from 0.5 to 1.2 micrometers, their height distribution became broader, and their density decreased from 55 × 10
6
to 12 × 10
6
per square centimeter. Enhanced photoelectron emission from locations corresponding to the tips suggests their possible use in field emission applications.
A Map of Babel
Authors: Robbins Trevor W.
Published: July 2002

n01se
A Series of Exhibitions About Information and Transformation. Adam Lowe and Simon Schaffer, Curators. Kettle's Yard, Whipple Museum of the History of Science, Cambridge University Museum of Archaeology and Anthropology, Cambridge, 22 January to 26 March 2000. Fitzwilliam Museum, Cambridge, 18 January to 16 April. The Wellcome Trust's Two10 Gallery, London, 27 January to 19 May.

n01se
Universal Language, Pattern Recognition, Data Synaesthetics. Adam Lowe and Simon Schaffer, Eds. Kettle's Yard, Cambridge, 2000. Unpaged, £9.95. ISBN 0-90-7074-78-2.

The artist Lowe and the historian of science Schaffer devised a multi-modal, and multi-nodal, exhibition of art and science organized around the themes of perception and communication. They also edited the book from the show, which combines images and pictures of objects with short essays by an eclectic group of contributors including Umberto Eco, Peter Galison, Lisa Jardine, Bruno Latour, and Malcolm Longair.
Windows Through the Dusty Disks Surrounding the Youngest Low-Mass Protostellar Objects
Authors: Cernicharo J. , Noriega-Crespo A. , Cesarsky D. , Lefloch B. , González-Alfonso E. , Najarro F. , Dartois E. , Cabrit S.
Published: July 2002

The formation and evolution of young low-mass stars are characterized by important processes of mass loss and accretion occurring in the innermost regions of their placentary circumstellar disks. Because of the large obscuration of these disks at optical and infrared wavelengths in the early protostellar stages (class 0 sources), they were previously detected only at radio wavelengths using interferometric techniques. We have detected with the Infrared Space Observatory the mid-infrared (mid-IR) emission associated with the class 0 protostar VLA1 in the HH1-HH2 region located in the Orion nebula. The emission arises in three wavelength windows (at 5.3, 6.6, and 7.5 micrometers) where the absorption due to ices and silicates has a local minimum that exposes the central part of the young protostellar system to mid-IR investigations. The mid-IR emission arises from a central source with a diameter of 4 astronomical units at an averaged temperature of ∼700 K, deeply embedded in a dense region with a visual extinction of 80 to 100 magnitudes.
Role of 4.5
S
RNA in Assembly of the Bacterial Signal Recognition Particle with Its Receptor
Authors: Peluso Paul , Herschlag Daniel , Nock Silke , Freymann Douglas M. , Johnson Arthur E. , Walter Peter
Published: July 2002

The mechanism by which a signal recognition particle (SRP) and its receptor mediate protein targeting to the endoplasmic reticulum or to the bacterial plasma membrane is evolutionarily conserved. In
Escherichia coli
, this reaction is mediated by the Ffh/4.5
S
RNA ribonucleoprotein complex (Ffh/4.5
S
RNP; the SRP) and the FtsY protein (the SRP receptor). We have quantified the effects of 4.5
S
RNA on Ffh-FtsY complex formation by monitoring changes in tryptophan fluorescence. Surprisingly, 4.5
S
RNA facilitates both assembly and disassembly of the Ffh-FtsY complex to a similar extent. These results provide an example of an RNA molecule facilitating protein-protein interactions in a catalytic fashion.
Learning from the Dead
Authors: Flessa Karl W.
Published: July 2002

Taphonomy
A Process Approach. Ronald E. Martin. Cambridge University Press, New York, 1999. 524 pp. $100. ISBN 0-521-59171-6. Paper, $44.95. ISBN 0-521-59833-8.

Martin's review of the study of incompleteness and bias in the fossil record pulls together case studies from marine microfossils, marine invertebrates, vertebrates, plants, and pollen.
Hallowed Halls for Nature
Authors: Winsor Mary P.
Published: July 2002

Nature's Museums
Victorian Science and the Architecture of Display. Carla Yanni. Johns Hopkins University Press, Baltimore, MD, 2000. 215 pp. $49.95. ISBN 0-8018-6326-0.

Yanni provides an extensively illustrated account of changing and conflicted roles of the central institutions of Victorian science museums built to house and display the diverse natural world.
Ensuring Enough to Eat
Authors: Clarke Adrienne E.
Published: July 2002

Feeding the World
A Challenge for the Twenty-First Century. Vaclav Smil. MIT Press, Cambridge, MA, 2000. 388 pp. $32.95. ISBN 0-262-19432-5.

Smil presents a cautiously optimistic case that we will be able to feed a great part of the world's population without irreversible damage to the biosphere.
Remember Marcellus's Warning
Authors: Levy Thomas E.
Published: July 2002

The Mythic Past
Biblical Archaeology and the Myth of Israel. Thomas L. Thompson. Basic (Perseus), New York, 1999. 432 pp. $30, C$44.95, £18.50. ISBN 0-465-00622-1. Paper, $17.50, C$25.95, £10.95. ISBN 0-465-00649-3.

From his survey of recent decades of studies on archaeological, agricultural, economic, and linguistic aspects of early Palestine history, Thompson concludes that the Old Testament provides no historical evidence for the early history of Israel. Our reviewer strongly disagrees.
Facets of Faces
Authors: Fortune Brandon Brame
Published: July 2002

Defining Features
Scientific and Medical Portraits 1660-2000. Ludmilla Jordanova, Curator. National Portrait Gallery, London, 14 April to 17 September 2000.

Defining Features
Scientific and Medical Portraits 1660-2000. Ludmilla Jordanova. Reaktion Books, London, in association with the National Portrait Gallery, London, 2000. Paper, 192 pp. $24.95, £14.95. ISBN 1-86189-059-1.

Through this exhibition and its accompanying book, Ludmilla Jordanova provides a concise overview of portraiture and its function within the historical and social world of scientists, doctors, inventors, and their work.
Sex on the Brain
Authors: Marler Catherine
Published: July 2002

The Mating Mind
. How Sexual Choice Shaped the Evolution of Human Nature. Geoffrey F. Miller. Doubleday, New York, 2000. 509 pp. $27.50, C$42.95. ISBN 0-385-49516-1. Heinemann, London, 2000. 528 pp. £20.00. ISBN 0-434-00741-2.

Miller argues that the evolution of the human brain was driven by the same factor responsible for the peacock's tail: the need to attract and win sexual partners
Pushing Buffalo to the Brink
Authors: Sherow James E.
Published: July 2002

The Destruction of the Bison
An Environmental History, 1750-1920. Andrew C. Isenberg. Cambridge University Press, New York, 2000. 218 pp. $24.95. ISBN 0-521-77172-2.

Isenberg argues that the near extinction of the bison was not a simple matter of hunting for commercial profit but reflected complex interactions among Native and Euroamerican societies and the grassland environment of the Great Plains.
Against Triage
Authors: Pimm Stuart L.
Published: July 2002

The California Condor
A Saga of Natural History and Conservation. Noel and Helen Snyder. AP Natural World (Academic Press), San Diego, 2000. 432 pp. $29.95. ISBN 0-12-654005-5.

This account of the biology and conservation of one of the most endangered North American species draws on the authors' extensive experiences in condor research and in the controversies that have attended efforts to assure the birds' future.
Iron in the Soul
Authors: Marshall John C.
Published: July 2002

An Odd Kind of Fame
Stories of Phineas Gage. Malcolm Macmillan. MIT Press, Cambridge, MA, 2000. 576 pp. $39.95, £27.50. ISBN 0-262-13363-6.

Macmillian provides the definitive account of Gage and the stories that have come to be told about him by researchers interested in the higher functions of the human brain.
Plant Biology at Center Stage
Authors: Kende Hans
Published: July 2002

Biochemistry and Molecular Biology of Plants
. Bob B. Buchanan, Wilhelm Gruissem, and Russell L. Jones, Eds. American Society of Plant Physiologists, Rockville, MD, 2000. 1407 pp. $149.95. ISBN 0-943088-37-2. Paper, $99.95. ISBN 0-943088-39-9.

This comprehensive and up-to-date text will serve as an essential reference for researchers in plant biology. Contributions from over 50 authors cover cell biology, reproduction, energy flow, metabolic and developmental integration, and the extension of plant biochemistry to agricultural and environmental problems.
How We Got Here and Where We Are Going
Authors: Ridley Mark
Published: July 2002

Human Natures
Genes, Cultures, and the Human Prospect. Paul R. Ehrlich. Island Press, Washington, DC, 2000. 543 pp. $29.95. ISBN 1-55963-779-X.

Ehrlich presents a narrative of human evolutionary history with the aim of considering what we can learn from it about our values and our future prospects.
Microfabricating Conjugated Polymer Actuators
Authors: Jager Edwin W. H. , Smela Elisabeth , Inganäs Olle
Published: July 2002

Conjugated polymer actuators can be operated in aqueous media, which makes them attractive for laboratories-on-a-chip and applications under physiological conditions. One of the most stable conjugated polymers under these conditions is polypyrrole, which can be patterned by means of standard photolithography. Polypyrrole-gold bilayer actuators that bend out of the plane of the wafer have been microfabricated in our laboratory. These can be used to move and position other microcomponents. Here we review the current status of these microactuators, outlining the methods used to fabricate them. We describe the devices that have been demonstrated as well as some potential future applications.
Synchronous Radiocarbon and Climate Shifts During the Last Deglaciation
Authors: Hughen Konrad A. , Southon John R. , Lehman Scott J. , Overpeck Jonathan T.
Published: July 2002

Radiocarbon data from the Cariaco Basin provide calibration of the carbon-14 time scale across the period of deglaciation (15,000 to 10,000 years ago) with resolution available previously only from Holocene tree rings. Reconstructed changes in atmospheric carbon-14 are larger than previously thought, with the largest change occurring simultaneously with the sudden climatic cooling of the Younger Dryas event. Carbon-14 and published beryllium-10 data together suggest that concurrent climate and carbon-14 changes were predominantly the result of abrupt shifts in deep ocean ventilation.
Origin and Environmental Setting of Ancient Agriculture in the Lowlands of Mesoamerica
Authors: Pope Kevin O. , Pohl Mary E. D. , Jones John G. , Lentz David L. , Nagy Christopher von , Vega Francisco J. , Quitmyer Irvy R.
Published: July 2002

Archaeological research in the Gulf Coast of Tabasco reveals the earliest record of maize cultivation in Mexico. The first farmers settled along beach ridges and lagoons of the Grijalva River delta. Pollen from cultivated
Zea
appears with evidence of forest clearing about 5100 calendar years B.C. (yr B.C.) [6200
14
C years before the present (yr B.P.)]. Large
Zea
sp. pollen, typical of domesticated maize (
Zea mays
), appears about 5000 calendar yr B.C. (6000 yr B.P.). A
Manihot
sp. pollen grain dated to 4600 calendar yr B.C. (5800 yr B.P.) may be from domesticated manioc. About 2500 calendar yr B.C. (4000 yr B.P.), domesticated sunflower seeds and cotton pollen appear as farming expanded.
Persistence ofChlamydia trachomatisIs Induced by Ciprofloxacin and Ofloxacin In Vitro
Authors: Dreses-Werringloer Ute , Padubrin Ingrid , Jürgens-Saathoff Barbara , Hudson Alan P. , Zeidler H. , Köhler L.
Published: July 2002

An in vitro cell culture model was used to investigate the long-term effect of ciprofloxacin and ofloxacin on infection withChlamydia trachomatis. Standard in vitro susceptibility testing clearly indicated successful suppression of chlamydial growth. To mimic better in vivo infection conditions, extended treatment with the drugs was started after infection in vitro had been well established. Incubation of such established chlamydial cultures with ciprofloxacin and ofloxacin not only failed to eradicate the organism from host cells, but rather induced a state of chlamydial persistence. This state was characterized by the presence of nonculturable, but fully viable, bacteria and the development of aberrant inclusions. In addition chlamydia exhibited altered steady-state levels of key chlamydial antigens, with significantly reduced major outer membrane protein and near constant hsp60 levels. Resumption of overt chlamydial growth occurred after withdrawal of ciprofloxacin, confirming the viability of persisting chlamydia. In vitro ciprofloxacin results are consistent with clinical data, thereby providing an explanation for treatment failures of ciprofloxacin. Parallel in vitro studies with ofloxacin suggest a better correlation between clinical and laboratory-defined efficacy, although the clinical studies on which this assessment is based did not include monitoring of chlamydial persistence. The data presented here clearly demonstrate that under at least some circumstances, standard determination of MICs and minimal bactericidal concentrations forC. trachomatisallows no more than a simple definition of whether an antibiotic has some anti chlamydial activity; however, such testing is not always sufficient to verify that the antibiotic will eliminate the organism in vivo.
Failure of Short-Course Ceftriaxone Chemotherapy for Multidrug-Resistant Typhoid Fever in Children: a Randomized Controlled Trial in Pakistan
Authors: Bhutta Zulfiqar A. , Khan Iqtidar A. , Shadmani Mamoon
Published: July 2002

The precise duration of therapy of multidrug-resistant (MDR) typhoid with broad-spectrum cephalosporins is uncertain. We prospectively randomized 57 children with culture-proven MDR typhoid to receive treatment with intravenous ceftriaxone (CRO) (65 mg/kg of body weight/day) for 7 days (short course;
n
= 29) or 14 days (conventional;
n
= 28). The response to therapy, as evaluated by the serial monitoring of the typhoid morbidity score and bacteriological clearance, was comparable between groups. In contrast to the conventional therapy, 14% of the children receiving CRO for 7 days had a confirmed bacteriological relapse within 4 weeks of stopping therapy.
In Vitro Activities of Methylenecyclopropane Analogues of Nucleosides and Their Phosphoralaninate Prodrugs against Cytomegalovirus and Other Herpesvirus Infections
Authors: Rybak Rachel J. , Hartline Caroll B. , Qiu Yao-Ling , Zemlicka Jiri , Harden Emma , Marshall Gwen , Sommadossi Jean-Pierre , Kern Earl R.
Published: July 2002

Human cytomegalovirus (HCMV) infection does not generally cause problems in the immunocompetent adult but can result in severe clinical disease in the fetus, neonate, and immunocompromised host. Ganciclovir (GCV), the agent currently used to treat most HCMV infections, has resulted in much therapeutic success; however, efficacy remains suboptimal. Therefore, there is still a need to develop new compounds for use against HCMV infections. In the present study, several
Z
- and
E
-series methylenecyclopropane analogues and their phosphoroalaninate prodrugs were tested initially for activity against HCMV, strain AD169, and murine cytomegalovirus (MCMV) in vitro. Many were found to exhibit efficacy comparable to that of GCV against HCMV in plaque assays and were active against MCMV as well. The compounds were also tested for efficacy against herpes simplex virus types 1 and 2, varicella-zoster virus, and Epstein-Barr virus, and some had levels of activity that were comparable to that of acyclovir. In addition, the compounds synguanol (QYL-438) and 2-amino-6-cyclopropylamino analogue (QYL-769) were chosen for further evaluation and were found to be effective against additional laboratory and clinical isolates of HCMV and GCV-resistant isolates. QYL-438 and QYL-769 were found to be nontoxic in human and mouse fibroblasts and were considerably less toxic than GCV in granulocyte macrophage CFUs and erythroid burst-forming units. These results provide evidence for the high activity of some of these methylenecyclopropane analogues against various herpesviruses, particularly HCMV, in tissue culture and suggest that further evaluation is warranted to determine their potential for use in future clinical studies.
Characterization of a
Mycobacterium smegmatis
Mutant That Is Simultaneously Resistant to
d
-Cycloserine and Vancomycin
Authors: Peteroy Marcy , Severin Anatoly , Zhao Frances , Rosner Dalya , Lopatin Uri , Scherman Hataichanouk , Belanger Aimee , Harvey Bohdan , Hatfull Graham F. , Brennan Patrick J. , Connell Nancy D.
Published: July 2002

A mutant of
Mycobacterium smegmatis
has been isolated that is simultaneously resistant to both
d
-cycloserine (
d
-CS) and vancomycin. Genetic complementation with a PBP4 homolog restores sensitivity to both drugs. Resistance to
d
-CS and vancomycin in this mutant is most likely due to a novel mechanism involving peptidoglycan assembly at the cell surface.
Effect of Zidovudine on the Primary Cytolytic T-Lymphocyte Response and T-Cell Effector Function
Authors: Francke Sabine , Orosz Charles G. , Hayes Kathleen A. , Mathes Lawrence E.
Published: July 2002

Azidothymidine (AZT) and other nucleoside analogues, used to treat AIDS, can cause severe clinical side effects and are suspected of suppressing immune cell proliferation and effector immune cell function. The purpose of the present study was to quantitatively measure the effects of AZT on cytotoxic T-lymphocyte (CTL) priming and to determine if the major histocompatibility complex-restricted CTL killing was affected by AZT exposure. For this purpose, we employed a murine alloantigen model and limiting-dilution analysis (LDA) to estimate cytotoxic effector cell frequencies of alloreactive splenocytes treated with drug during antigen sensitization. This noninfectious model was chosen to avoid analysis of a virus-compromised immune system. Exposure of splenocytes to therapeutic concentrations of AZT (2 to 10 μM) caused a two- to threefold dose-dependent reduction in CLT precursor frequency. This reduction was caused by decreased proliferation of alloantigen-specific CTLs rather than loss of function, because full cytolytic function could be restored by adjusting the AZT-treated effector/target cell ratios to that of untreated cells. In addition, when AZT was added to the assay system at various times during antigen sensitization there was a time-related loss of the suppressive effect on the generation of cytolytic effector function, suggesting that functional CTLs are not affected by even high doses of AZT. Taken together, the data indicate that the reduction of CTL function associated with AZT treatment is due to a quantitative decrease of effector cell precursor frequency rather than to direct drug cytotoxicity or interference with mediation of cytolysis. Furthermore, antigen-naive immune cells were most sensitive to this effect during the first few days following antigen encounter.
Effects of Azithromycin and Rifampin onChlamydia trachomatisInfection In Vitro
Authors: Dreses-Werringloer Ute , Padubrin Ingrid , Zeidler Henning , Köhler Lars
Published: July 2002

An in vitro cell culture model was used to investigate the long-term effects of azithromycin, rifampin, and the combination of azithromycin and rifampin onChlamydia trachomatisinfection. Although standard in vitro susceptibility testing indicated efficient inhibition by azithromycin, prolonged treatment did not reveal a clear elimination of chlamydia from host cells. Chlamydia were temporarily arrested in a persistent state, characterized by culture-negative, but viable, metabolically active chlamydia, as demonstrated by the presence of short-lived rRNA transcripts. Additionally, azithromycin induced generation of aberrant inclusions and an altered steady-state level of chlamydial antigens, with the predominance of Hsp60 protein compared to the level of the major outer membrane protein. Treatment with azithromycin finally resulted in suppression of rRNA synthesis. Chlamydial lipopolysaccharide and processed, functional rRNA were detectable throughout the entire incubation period. These in vitro data show a good correlation to those from some recent clinical investigations that have reported on the persistence of chlamydia, despite appropriate antibiotic treatment with azithromycin. Rifampin was highly active by in vitro susceptibility testing, but prolonged exposure to rifampin alone for up to 20 days resulted in the emergence of resistance. No development of resistance to rifampin was observed when chlamydia-infected cells were incubated with a combination of azithromycin and rifampin. This combination was shown to be more efficient than azithromycin alone, in that suppression of rRNA synthesis occurred earlier. Thus, such a combination may prove more useful than azithromycin alone.
Ritonavir-Saquinavir Dual Protease Inhibitor Compared to Ritonavir Alone in Human Immunodeficiency Virus-Infected Patients
Authors: Michelet Christian , Ruffault Annick , Sébille Véronique , Arvieux Cedric , Jaccard Philippe , Raffi François , Bazin Claude , Chapplain Jean-Marc , Chauvin Jean-Pierre , Dohin Elisabeth , Cartier François , Bellissant Eric
Published: July 2002

The objective of this study was to evaluate the antiretroviral efficacy and safety of ritonavir (600 mg twice a day [b.i.d.])-saquinavir (400 mg b.i.d.) compared to ritonavir (600 mg b.i.d.) in patients pretreated and receiving continued treatment with two nucleoside analogs. The study was placebo controlled, randomized, and double blind. Inclusion criteria included protease inhibitor naive status and a viral load of >10,000 copies/ml. The main end point was viral load at week 24. Forty-seven patients were included (25 given ritonavir and 22 given ritonavir-saquinavir) and monitored until week 48. At inclusion, 23% had had at least one AIDS-defining event. Previous treatment durations (mean and standard deviation) were 42 ± 25 and 37 ± 23 months, viral loads were 4.75 ± 0.62 and 4.76 ± 0.50 log10copies/ml, and CD4 cell counts were 236 ± 126 and 234 ± 125/mm3in the ritonavir and ritonavir-saquinavir groups, respectively. At week 24, viral loads were 2.81 ± 1.48 and 2.08 ± 1.14 log10copies/ml (P= 0.04) and CD4 cell counts were 330 ± 151 and 364 ± 185/mm3(P= 0.49) in the ritonavir and ritonavir-saquinavir groups, respectively. Similar results were observed at week 48. Moreover, at week 48, 40 and 68% (P= 0.05) and 28 and 59% (P= 0.03) of patients achieved viral suppression at below 200 and 50 copies/ml in the ritonavir and ritonavir-saquinavir groups, respectively. At week 24, six patients in the ritonavir group but only one in the ritonavir-saquinavir group had key mutations conferring resistance to protease inhibitors. Clinical and biological tolerances were similar in both groups. In nucleoside analog-pretreated patients, ritonavir-saquinavir has higher antiretroviral efficacy than and is as well tolerated as ritonavir alone.
Efficacy of Recombinant Gamma Interferon for Treatment of Systemic Cryptococcosis in SCID Mice
Authors: Clemons Karl V. , Lutz Jon E. , Stevens David A.
Published: July 2002

We have previously shown that gamma interferon (IFN-γ) is a useful adjunct to therapy of experimental systemic cryptococcosis in normal mice. To better emulate AIDS patients, SCID mice were infected intravenously withCryptococcus neoformans. Mice received no therapy, 3 mg of amphotericin B (AmB) per kg of body weight, or 105U of IFN-γ alone (prophylactically and therapeutically or only therapeutically) or with AmB. In the first experiment, >75% of the mice survived. Therapy with AmB alone was efficacious compared to no therapy in all organs. Both regimens of IFN-γ alone were efficacious in the brain and lungs, and the combination of AmB and IFN-γ showed significant synergy in the kidneys. AmB alone cured 40% of mice of infection, whereas the combination regimens cured >50% of the mice and 90% of the brain infections. In a second study, IFN-γ again proved efficacious alone, and when given with AmB its efficacy was improved. Therapeutic IFN-γ alone was effective only in the liver compared to no therapy, and the combination regimen, although highly effective, showed no significant synergy. In a third experiment, AmB alone or in combination with IFN-γ prolonged survival compared to no therapy or IFN-γ alone. The combination regimen showed significant synergy over AmB alone in the brain, liver, kidneys, and lungs. AmB alone cured no mice of infections in more than two organs, whereas AmB in combination with IFN-γ cured 55% of infections in three or more organs. These results indicate that IFN-γ has therapeutic efficacy in severely immunodeficient animals, especially in combination with AmB. Significant synergistic activity was noted in all organs except the spleen. Overall, IFN-γ has utility as an adjunctive therapy against systemic cryptococcosis in the severely immunocompromised host.
Antimicrobial Susceptibility of
Ehrlichia phagocytophila
Authors: Horowitz Harold W. , Hsieh T.-C. , Aguero-Rosenfeld Maria E. , Kalantarpour Fatemeh , Chowdhury Ishraq , Wormser Gary P. , Wu Joseph M.
Published: July 2002

Human granulocytic ehrlichiosis is a recently described disease caused by an obligate intracellular gram-negative organism recently named
Ehrlichia phagocytophila
. To expand our knowledge of the susceptibility of
E. phagocytophila
, we tested six New York State isolates for susceptibility to 12 antimicrobials using an HL-60 cell culture system. All of the isolates were susceptible to doxycycline (MIC, ≤0.125 μg/ml; minimum bactericidal concentration [MBC], 0.125 to 0.5 μg/ml), rifampin (MIC, ≤0.125 μg/ml; MBC, ≤0.125 μg/ml), ofloxacin (MIC, ≤2 μg/ml; MBC, ≤2 μg/ml), levofloxacin (MIC, ≤1 μg/ml; MBC, ≤1 μg/ml), and trovafloxacin (MIC, ≤0.032 μg/ml; MBC, ≤0.032 μg/ml). Isolates were uniformly resistant to amoxicillin, ceftriaxone, erythromycin, azithromycin, clarithromycin, and amikacin. For one strain, the MBC of chloramphenicol was ≤8 μg/ml. These data suggest that quinolone antibiotics and rifampin may be alternative agents for patients with intolerance to tetracyclines.
Teicoplanin Stress-Selected Mutations Increasing ς
B
Activity in
Staphylococcus aureus
Authors: Bischoff Markus , Berger-Bächi Brigitte
Published: July 2002

A natural
rsbU
mutant of
Staphylococcus aureus,
unable to activate the alternative transcription factor ς
B
via the RsbU pathway and therefore forming unpigmented colonies, produced first-step teicoplanin-resistant mutants upon selection for growth in the presence of teicoplanin, of which the majority were of an intense orange color. By using an
asp23
promoter-luciferase fusion as an indicator, the pigmented mutants were shown to express increased ς
B
activity. Increased ς
B
activity was associated with point mutations in
rsbW,
releasing ς
B
from sequestration by the anti-sigma factor RsbW, or to promoter mutations increasing the ς
B
/RsbW ratio. Genetic manipulations involving the
sigB
operon suggested that the mutations within the operon were associated with the increase in teicoplanin resistance. The upregulation of ς
B
suggests that a ς
B
-controlled gene(s) is directly or indirectly involved in the development of teicoplanin resistance in
S. aureus
. Carotenoids do not contribute to teicoplanin resistance, since inactivation of the dehydrosqualene synthase gene
crtM
abolished pigment formation without affecting teicoplanin resistance. The relevant ς
B
-controlled target genes involved in teicoplanin resistance remain to be identified.
Activities of Faropenem, an Oral β-Lactam, against Recent U.S. Isolates of
Streptococcus pneumoniae
,
Haemophilus influenzae
, and
Moraxella catarrhalis
Authors: Critchley Ian A. , Karlowsky James A. , Draghi Deborah C. , Jones Mark E. , Thornsberry Clyde , Murfitt Kate , Sahm Daniel F.
Published: July 2002

The in vitro activities of faropenem and other antimicrobial agents were determined against 4,725
Streptococcus pneumoniae
isolates, 2,614
Haemophilus influenzae
isolates, and 1,193
Moraxella catarrhalis
isolates collected from 273 U.S. laboratories during 1999. Faropenem MICs at which 90% of isolates are inhibited were 0.008, 0.25, and 1 μg/ml for penicillin-susceptible, -intermediate, and -resistant
S. pneumoniae
strains, respectively; 0.5 and 1 μg/ml for β-lactamase-positive and -negative
H. influenzae
strains, respectively; and 0.12 and 0.5 μg/ml for β-lactamase-negative and -positive
M. catarrhalis
strains, respectively. Faropenem holds promise as an oral therapy for community-acquired respiratory tract infections.
A Missense Mutation in the
fabB
(β-Ketoacyl-Acyl Carrier Protein Synthase I) Gene Confers Thiolactomycin Resistance to
Escherichia coli
Authors: Jackowski Suzanne , Zhang Yong-Mei , Price Allen C. , White Stephen W. , Rock Charles O.
Published: July 2002

Thiolactomycin (TLM) is an antibiotic that inhibits bacterial type II fatty acid synthesis at the condensing enzyme step, and β-ketoacyl-acyl carrier protein synthase I (FabB) is the relevant target in
Escherichia coli
. TLM resistance is associated with the upregulation of efflux pumps. Therefore, a
tolC
knockout mutant (strain ANS1) was constructed to eliminate the contribution of type I secretion systems to TLM resistance. Six independent TLM-resistant clones of strain ANS1 were isolated, and all possessed the same missense mutation in the
fabB
gene (T1168G) that directed the expression of a mutant protein, FabB(F390V). FabB(F390V) was resistant to TLM in vitro. Leucine is the only other amino acid found at position 390 in nature, and the
Staphylococcus aureus
FabF protein, which contains this substitution, was sensitive to TLM. Structural modeling predicted that the CG2 methyl group of the valine side chain interfered with the positioning of the C11 methyl on the isoprenoid side chain of TLM in the binary complex, whereas the absence of a bulky methyl group on the leucine side chain permitted TLM binding. These data illustrate that missense mutations that introduce valine at position 390 confer TLM resistance while maintaining the vital catalytic properties of FabB.