bluuebunny/crossref_metadata_2025 huggingface dataset:
Maximum and Minimum Temperature Trends for the Globe
Authors: Easterling David R. , Horton Briony , Jones Philip D. , Peterson Thomas C. , Karl Thomas R. , Parker David E. , Salinger M. James , Razuvayev Vyacheslav , Plummer Neil , Jamason Paul , Folland Christopher K.
Published: July 2002

Analysis of the global mean surface air temperature has shown that its increase is due, at least in part, to differential changes in daily maximum and minimum temperatures, resulting in a narrowing of the diurnal temperature range (DTR). The analysis, using station metadata and improved areal coverage for much of the Southern Hemisphere landmass, indicates that the DTR is continuing to decrease in most parts of the world, that urban effects on globally and hemispherically averaged time series are negligible, and that circulation variations in parts of the Northern Hemisphere appear to be related to the DTR. Atmospheric aerosol loading in the Southern Hemisphere is much less than that in the Northern Hemisphere, suggesting that there are likely a number of factors, such as increases in cloudiness, contributing to the decreases in DTR.
Sensitization to Morphine Induced by Viral-Mediated Gene Transfer
Authors: Carlezon William A. , Boundy Virginia A. , Haile Colin N. , Lane Sarah B. , Kalb Robert G. , Neve Rachael L. , Nestler Eric J.
Published: July 2002

Repeated administration of morphine sensitizes animals to the stimulant and rewarding properties of the drug. It also selectively increases expression of GluR1 (an AMPA glutamate receptor subunit) in the ventral tegmental area, a midbrain region implicated in morphine action. By viral-mediated gene transfer, a causal relation is shown between these behavioral and biochemical adaptations: Morphine's stimulant and rewarding properties are intensified after microinjections of a viral vector expressing GluR1 into the ventral tegmental area. These results confirm the importance of AMPA receptors in morphine action and demonstrate specific locomotor and motivational adaptations resulting from altered expression of a single localized gene product.
A Developmental Question
Authors: Tompkins Robert
Published: July 2002

Genomic Potential of Differentiated Cells.
MARIE A. DI BERARDINO. Columbia University Press, New York, 1997. xvi, 386 pp., illus., + plates. $65 or £52. ISBN 0-231-06986-3.
Catalyst for a Cultural Dialogue
Authors: Lewes Kenneth
Published: July 2002

Alfred C. Kinsey
. A Public/Private Life. JAMES H. JONES. Norton, New York, 1997. xx, 937 pp., + plates. Paper, $39.95 or C$49.99. ISBN 0-393-04086-0.
The Nature of Matter
Authors: Perl Martin L.
Published: July 2002

Image and Logic.
A Material Culture of Microphysics. PETER GALISON. University of Chicago Press, Chicago, 1997. xxvi, 955 pp., illus. $90 or £71.95, ISBN 0-226-27916-2; paper, $34.95 or £27.95, ISBN 0-226-27917-0.
Quantum Devices
Authors: Kouwenhoven Leo
Published: July 2002

Transport in Nanostructures.
DAVID K. FERRY and STEPHEN M. GOODNICK. Cambridge University Press, New York, 1997. xii, 512 pp., illus. $100. ISBN 0-521-46141-3. Cambridge Studies in Semiconductor Physics and Microelectronic Engineering, 6.
Laser Control of Chemical Reactions
Authors: Zare Richard N.
Published: July 2002

Experiments show how product pathways can be controlled by irradiation with one or more laser beams during individual bimolecular collisions or during unimolecular decompositions. For bimolecular collisions, control has been achieved by selective excitation of reagent vibrational modes, by control of reagent approach geometry, and by control of orbital alignment. For unimolecular reactions, control has been achieved by quantum interference between different reaction pathways connecting the same initial and final states and by adjusting the temporal shape and spectral content of ultrashort, chirped pulses of radiation. These collision-control experiments deeply enrich the understanding of how chemical reactions occur.
The Quantum-Classical Metal
Authors: Clarke David G. , Strong S. P. , Chaikin P. M. , Chashechkina E. I.
Published: July 2002

In a normal Fermi liquid, Landau's theory precludes the loss of single-fermion quantum coherence in the low-energy, low-temperature limit. For highly anisotropic, strongly correlated metals, there is no proof that this remains the case, and quantum coherence for transport in some directions may be lost intrinsically. This loss of coherence should stabilize an unusual, qualitatively anisotropic non-Fermi liquid, separated by a zero-temperature quantum phase transition from the Fermi liquid state and categorized by the unobservability of certain interference effects. There is compelling experimental evidence for this transition as a function of magnetic field in the metallic phase of the organic conductor (TMTSF)
2
PF
6
(where TMTSF is tetramethyltetraselenafulvalene).
Coupling Termination of Transcription to Messenger RNA Maturation in Yeast
Authors: Birse Charles E. , Minvielle-Sebastia Lionel , Lee Barbara A. , Keller Walter , Proudfoot Nick J.
Published: July 2002

The direct association between messenger RNA (mRNA) 3′-end processing and the termination of transcription was established for the
CYC1
gene of
Saccharomyces cerevisiae
. The mutation of factors involved in the initial cleavage of the primary transcript at the poly(A) site (
RNA14
,
RNA15
, and
PCF11
) disrupted transcription termination at the 3′ end of the
CYC1
gene. In contrast, the mutation of factors involved in the subsequent polyadenylation step (
PAP1
,
FIP1
, and
YTH1
) had little effect. Thus, cleavage factors link transcription termination of RNA polymerase II with pre-mRNA 3′-end processing.
The Civic Importance of Chemistry
Authors: Finlay Mark R.
Published: July 2002

Justus von Liebig.
The Chemical Gatekeeper. WILLIAM H. BROCK. Cambridge University Press, Cambridge, 1997. xiv, 374 pp., illus. $79.95. ISBN 0-521-56224-4.
The Lost Colony and Jamestown Droughts
Authors: Stahle David W. , Cleaveland Malcolm K. , Blanton Dennis B. , Therrell Matthew D. , Gay David A.
Published: July 2002

Tree-ring data from Virginia indicate that the Lost Colony of Roanoke Island disappeared during the most extreme drought in 800 years (1587–1589) and that the alarming mortality and the near abandonment of Jamestown Colony occurred during the driest 7-year episode in 770 years (1606–1612). These extraordinary droughts can now be implicated in the fate of the Lost Colony and in the appalling death rate during the early occupations at Jamestown, the first permanent English settlement in America.
Get A Life
Authors: Lenski Richard E.
Published: July 2002

Introduction to Artificial Life
. CHRISTOPH ADAMI. Telos (Springer), New York, 1998. xviii, 374 pp., + CD-ROM disc. $59.95. ISBN 0-387-94646-2.
Requirement for Atm in Ionizing Radiation-Induced Cell Death in the Developing Central Nervous System
Authors: Herzog Karl-Heinz , Chong Miriam J. , Kapsetaki Manuela , Morgan James I. , McKinnon Peter J.
Published: July 2002

Ataxia telangiectasia (AT) is characterized by progressive neurodegeneration that results from mutation of the
ATM
gene. However, neither the normal function of ATM in the nervous system nor the biological basis of the degeneration in AT is known. Resistance to apoptosis in the developing central nervous system (CNS) of

Atm
−/−

mice was observed after ionizing radiation. This lack of death occurred in diverse regions of the CNS, including the cerebellum, which is markedly affected in AT. In wild-type, but not

Atm
−/−

mice, up-regulation of p53 coincided with cell death, suggesting that Atm-dependent apoptosis in the CNS is mediated by p53. Further, p53 null mice showed a similar lack of radiation-induced cell death in the developing nervous system. Atm may function at a developmental survival checkpoint that serves to eliminate neurons with excessive DNA damage.
7500 Years of Prehistoric Footwear from Arnold Research Cave, Missouri
Authors: Kuttruff Jenna T. , DeHart S. Gail , O'Brien Michael J.
Published: July 2002

Accelerator mass spectrometer dating of an assemblage of fibrous and leather footwear from Arnold Research Cave in central Missouri documents a long sequence of shoe construction by prehistoric Midwestern peoples, beginning perhaps as early as 8300 calendar years before the present (cal years B.P.). An earlier fibrous sandal form dates from 8325 to 7675 cal years B.P., and later fibrous or leather slip-ons span the period from 5575 to 1070 cal years B.P. The assemblage adds to a growing picture of the highly varied nature of prehistoric footwear production in the United States throughout the Holocene.
Atomic Philosophies
Authors: Barkan Diana
Published: July 2002

The Atom in the History of Human Thought
.
By Bernard Pullman. Translated by Axel Reisinger
. Oxford University Press, New York, 1998. 414 pp. $30, £25. ISBN 0-19-511447-7.

A history of concepts of the atom, traced primarily through the works of philosophers and other intellectual critics rather than those of scientists. Beginning with the notion of an indivisible fundamental constituent of matter first formulated by the pre-Socratic Greek thinkers, Pullam follows ideas that have and have not survived from the ancients and the pre-moderns into our own contemporary conceptions.
The World Between Crust and Core
Authors: Stevenson David J.
Published: July 2002

The Earth's Mantle
Composition, Structure, and Evolution. Ian Jackson, Ed. Cambridge University Press, New York, 1998. 592 pp. $130, £80. ISBN 0-521-56344-5.

The Earth's Mantle
is a comprehensive overview by members of the Canberra school that considers both matters of consensus and continuing controversy. It provides perspectives from cosmochemistry, isotope geochemistry, fluid dynamics, petrology, seismology, geodynamics, and mineral and rock physics, and is dedicated to the memory of Ted Ringwood.
Expression of a Gene Cluster
kaiABC
as a Circadian Feedback Process in Cyanobacteria
Authors: Ishiura Masahiro , Kutsuna Shinsuke , Aoki Setsuyuki , Iwasaki Hideo , Andersson Carol R. , Tanabe Akio , Golden Susan S. , Johnson Carl H. , Kondo Takao
Published: July 2002

Cyanobacteria are the simplest organisms known to have a circadian clock. A circadian clock gene cluster
kaiABC
was cloned from the cyanobacterium
Synechococcus.
Nineteen clock mutations were mapped to the three
kai
genes. Promoter activities upstream of the
kaiA
and
kaiB
genes showed circadian rhythms of expression, and both
kaiA
and
kaiBC
messenger RNAs displayed circadian cycling. Inactivation of any single
kai
gene abolished these rhythms and reduced
kaiBC
-promoter activity. Continuous
kaiC
overexpression repressed the
kaiBC
promoter, whereas
kaiA
overexpression enhanced it. Temporal
kaiC
overexpression reset the phase of the rhythms. Thus, a negative feedback control of
kaiC
expression by KaiC generates a circadian oscillation in cyanobacteria, and KaiA sustains the oscillation by enhancing
kaiC
expression.
Making Multimedia
Authors: Ghanadan Hamid
Published: July 2002

The author describes the latest software abilities and limitations in producing multimedia presentations for the Web or CD-Rom.
Science and Civics, Still Immiscible
Authors: Lee Kai N.
Published: July 2002

Science in Public
Communication, Culture, and Credibility. Jane Gregory and Steve Miller. Plenum Trade, New York, 1998. 304 pp. $29.95, C$41.95. ISBN 0-306-45860-8.

The authors examine debates on the nature and roles of popular science, the public understanding of science, and the presentation of science in the mass media. Among the topics they touch upon are science in museums and the public perception of risks of alar on apples, bovine spongiform encephalopathy, and collisions with comets.
Changes in the Carbon Balance of Tropical Forests: Evidence from Long-Term Plots
Authors: Phillips Oliver L. , Malhi Yadvinder , Higuchi Niro , Laurance William F. , Núñez Percy V. , Vásquez Rodolfo M. , Laurance Susan G. , Ferreira Leandro V. , Stern Margaret , Brown Sandra , Grace John
Published: July 2002

The role of the world's forests as a “sink” for atmospheric carbon dioxide is the subject of active debate. Long-term monitoring of plots in mature humid tropical forests concentrated in South America revealed that biomass gain by tree growth exceeded losses from tree death in 38 of 50 Neotropical sites. These forest plots have accumulated 0.71 ton, plus or minus 0.34 ton, of carbon per hectare per year in recent decades. The data suggest that Neotropical forests may be a significant carbon sink, reducing the rate of increase in atmospheric carbon dioxide.
Confirming Antiquity in the Americas
Authors: Grayson Donald K.
Published: July 2002

Monte Verde
A Late Pleistocene Settlement in Chile, Vol. 2: The Archaeological Context and Interpretation. Tom D. Dillehay. Smithsonian Institution Press, Washington, DC, 1997. 1071 pp. $155. ISBN 1-56098-680-8.

Dillehay and his co-workers present a comprehensive description and analysis of the evidence for a pre-Clovis human presence at a site 16,000 kilometers south of the Bering Land Bridge some 12,500 years before the present. Among the topics the contributors consider are Monte Verde's setting and stratigraphy, radiocarbon data, artifacts, and possible structures.
A Family of cAMP-Binding Proteins That Directly Activate Rap1
Authors: Kawasaki Hiroaki , Springett Gregory M. , Mochizuki Naoki , Toki Shinichiro , Nakaya Mie , Matsuda Michiyuki , Housman David E. , Graybiel Ann M.
Published: July 2002

cAMP (3′,5′ cyclic adenosine monophosphate) is a second messenger that in eukaryotic cells induces physiological responses ranging from growth, differentiation, and gene expression to secretion and neurotransmission. Most of these effects have been attributed to the binding of cAMP to cAMP-dependent protein kinase A (PKA). Here, a family of cAMP-binding proteins that are differentially distributed in the mammalian brain and body organs and that exhibit both cAMP-binding and guanine nucleotide exchange factor (GEF) domains is reported. These cAMP-regulated GEFs (cAMP-GEFs) bind cAMP and selectively activate the Ras superfamily guanine nucleotide binding protein Rap1A in a cAMP-dependent but PKA-independent manner. Our findings suggest the need to reformulate concepts of cAMP-mediated signaling to include direct coupling to Ras superfamily signaling.
The Fascination of Fungi
Authors: Kohn Linda M.
Published: July 2002

Magical Mushrooms, Mischievous Molds
. George W. Hudler. Princeton University Press, Princeton, NJ, 1998. 264 pp. $29.95, £22.95. ISBN 0-691-02873-7.

Hudler, a plant pathologist, offers an engaging collection of fascinating tales about the biology of fungi, with particular emphasis on their interactions with and importance to humans.
Reduced Immunotoxicity and Preservation of Antibacterial Activity in a Releasable Side-Chain Carbapenem Antibiotic
Authors: Rosen Hugh , Hajdu Richard , Silver Lynn , Kropp Helmut , Dorso Karen , Kohler Joyce , Sundelof Jon G. , Huber Joann , Hammond Gail G. , Jackson Jesse J. , Gill Charles J. , Thompson Randall , Pelak Barbara A. , Epstein-Toney Jeffrey H. , Lankas George , Wilkening Robert R. , Wildonger Kenneth J. , Blizzard Timothy A. , DiNinno Frank P. , Ratcliffe Ronald W. , Heck James V. , Kozarich John W. , Hammond Milton L.
Published: July 2002

A carbapenem antibiotic, L-786,392, was designed so that the side chain that provides high-affinity binding to the penicillin-binding proteins responsible for bacterial resistance was also the structural basis for ameliorating immunopathology. Expulsion of the side chain upon opening of the beta-lactam ring retained antibacterial activity while safely expelling the immunodominant epitope. L-786,392 was well tolerated in animal safety studies and had significant in vitro and in vivo activities against methicillin- and vancomycin-resistant Staphylococci and vancomycin-resistant Enterococci.
Regulation of Keystone Predation by Small Changes in Ocean Temperature
Authors: Sanford Eric
Published: July 2002

Key species interactions that are sensitive to temperature may act as leverage points through which small changes in climate could generate large changes in natural communities. Field and laboratory experiments showed that a slight decrease in water temperature dramatically reduced the effects of a keystone predator, the sea star
Pisaster ochraceus
, on its principal prey. Ongoing changes in patterns of cold water upwelling, associated with El Niño events and longer term geophysical changes, may thus have far-reaching impacts on the composition and diversity of these rocky intertidal communities.
Control of Autoimmune Diabetes in NOD Mice by GAD Expression or Suppression in β Cells
Authors: Yoon Ji-Won , Yoon Chang-Soon , Lim Hye-Won , Huang Qi Quan , Kang Yup , Pyun Kwang Ho , Hirasawa Kensuke , Sherwin Robert S. , Jun Hee-Sook
Published: July 2002

Glutamic acid decarboxylase (GAD) is a pancreatic β cell autoantigen in humans and nonobese diabetic (NOD) mice. β Cell–specific suppression of GAD expression in two lines of antisense GAD transgenic NOD mice prevented autoimmune diabetes, whereas persistent GAD expression in the β cells in the other four lines of antisense GAD transgenic NOD mice resulted in diabetes, similar to that seen in transgene-negative NOD mice. Complete suppression of β cell GAD expression blocked the generation of diabetogenic T cells and protected islet grafts from autoimmune injury. Thus, β cell–specific GAD expression is required for the development of autoimmune diabetes in NOD mice, and modulation of GAD might, therefore, have therapeutic value in type 1 diabetes.
Genome Sequence of the Radioresistant Bacterium
Deinococcus radiodurans
R1
Authors: White Owen , Eisen Jonathan A. , Heidelberg John F. , Hickey Erin K. , Peterson Jeremy D. , Dodson Robert J. , Haft Daniel H. , Gwinn Michelle L. , Nelson William C. , Richardson Delwood L. , Moffat Kelly S. , Qin Haiying , Jiang Lingxia , Pamphile Wanda , Crosby Marie , Shen Mian , Vamathevan Jessica J. , Lam Peter , McDonald Lisa , Utterback Terry , Zalewski Celeste , Makarova Kira S. , Aravind L. , Daly Michael J. , Minton Kenneth W. , Fleischmann Robert D. , Ketchum Karen A. , Nelson Karen E. , Salzberg Steven , Smith Hamilton O. , Craig J. , Venter  , Fraser Claire M.
Published: July 2002

The complete genome sequence of the radiation-resistant bacterium
Deinococcus radiodurans
R1 is composed of two chromosomes (2,648,638 and 412,348 base pairs), a megaplasmid (177,466 base pairs), and a small plasmid (45,704 base pairs), yielding a total genome of 3,284,156 base pairs. Multiple components distributed on the chromosomes and megaplasmid that contribute to the ability of
D. radiodurans
to survive under conditions of starvation, oxidative stress, and high amounts of DNA damage were identified.
Deinococcus radiodurans
represents an organism in which all systems for DNA repair, DNA damage export, desiccation and starvation recovery, and genetic redundancy are present in one cell.
Complete Genome Sequence of
Neisseria meningitidis
Serogroup B Strain MC58
Authors: Tettelin Hervé , Saunders Nigel J. , Heidelberg John , Jeffries Alex C. , Nelson Karen E. , Eisen Jonathan A. , Ketchum Karen A. , Hood Derek W. , Peden John F. , Dodson Robert J. , Nelson William C. , Gwinn Michelle L. , DeBoy Robert , Peterson Jeremy D. , Hickey Erin K. , Haft Daniel H. , Salzberg Steven L. , White Owen , Fleischmann Robert D. , Dougherty Brian A. , Mason Tanya , Ciecko Anne , Parksey Debbie S. , Blair Eric , Cittone Henry , Clark Emily B. , Cotton Matthew D. , Utterback Terry R. , Khouri Hoda , Qin Haiying , Vamathevan Jessica , Gill John , Scarlato Vincenzo , Masignani Vega , Pizza Mariagrazia , Grandi Guido , Sun Li , Smith Hamilton O. , Fraser Claire M. , Moxon E. Richard , Rappuoli Rino , Venter J. Craig
Published: July 2002

The 2,272,351–base pair genome of
Neisseria meningitidis
strain MC58 (serogroup B), a causative agent of meningitis and septicemia, contains 2158 predicted coding regions, 1158 (53.7%) of which were assigned a biological role. Three major islands of horizontal DNA transfer were identified; two of these contain genes encoding proteins involved in pathogenicity, and the third island contains coding sequences only for hypothetical proteins. Insights into the commensal and virulence behavior of
N. meningitidis
can be gleaned from the genome, in which sequences for structural proteins of the pilus are clustered and several coding regions unique to serogroup B capsular polysaccharide synthesis can be identified. Finally,
N. meningitidis
contains more genes that undergo phase variation than any pathogen studied to date, a mechanism that controls their expression and contributes to the evasion of the host immune system.
Response of Schwann Cells to Action Potentials in Development
Authors: Stevens Beth , Fields R. Douglas
Published: July 2002

Sensory axons become functional late in development when Schwann cells (SC) stop proliferating and differentiate into distinct phenotypes. We report that impulse activity in premyelinated axons can inhibit proliferation and differentiation of SCs. This neuron-glial signaling is mediated by adenosine triphosphate acting through P2 receptors on SCs and intracellular signaling pathways involving Ca
2+
, Ca
2+
/calmodulin kinase, mitogen-activated protein kinase, cyclic adenosine 3′,5′-monophosphate response element binding protein, and expression of c-
fos
and
Krox-24
. Adenosine triphosphate arrests maturation of SCs in an immature morphological stage and prevents expression of O4, myelin basic protein, and the formation of myelin. Through this mechanism, functional activity in the developing nervous system could delay terminal differentiation of SCs until exposure to appropriate axon-derived signals.
Tangled Causes of the Bomb's Creators
Authors: Rhodes Richard
Published: July 2002

In the Shadow of the Bomb
Oppenheimer, Bethe, and the Moral Responsibility of the Scientist. S. S. Schweber. Princeton University Press, Princeton, NJ, 2000. 278 pp. $24.95, £15.95. ISBN 0-691-04989-0.

Schweber, Bethe's authorized biographer, approaches the theme of scientists' moral responsibilities through a comparison of two prominent participants in the development of nuclear weapons. He considers the similarities and differences in their choices and in the consequences of their political involvements.
Generalized Potential of Adult Neural Stem Cells
Authors: Clarke Diana L. , Johansson Clas B. , Wilbertz Johannes , Veress Biborka , Nilsson Erik , Karlström Helena , Lendahl Urban , Frisén Jonas
Published: July 2002

The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation of chimeric chick and mouse embryos and give rise to cells of all germ layers. This demonstrates that an adult neural stem cell has a very broad developmental capacity and may potentially be used to generate a variety of cell types for transplantation in different diseases.
Wandering Genes
Authors: Lahr Marta Mirazón
Published: July 2002

Migration and Colonization in Human Microevolution
. Alan Fix. Cambridge University Press, New York, 1999. 254 pp. $69.95. ISBN 0-521-59206-2.

Combining perspectives from biological and social scientists, Fix examines how migration has affected the patterns of genetic variation in human populations. His synthesis uses a diverse set of empirical studies and computer simulations to test and improve models developed by population geneticists.
Decadal Sea Surface Temperature Variability in the Subtropical South Pacific from 1726 to 1997 A.D.
Authors: Linsley Braddock K. , Wellington Gerard M. , Schrag Daniel P.
Published: July 2002

We present a 271-year record of Sr/Ca variability in a coral from Rarotonga in the South Pacific gyre. Calibration with monthly sea surface temperature (SST) from satellite and ship measurements made in a grid measuring 1° by 1° over the period from 1981 to 1997 indicates that this Sr/Ca record is an excellent proxy for SST. Comparison with SST from ship measurements made since 1950 in a grid measuring 5° by 5° also shows that the Sr/Ca data accurately record decadal changes in SST. The entire Sr/Ca record back to 1726 shows a distinct pattern of decadal variability, with repeated decadal and interdecadal SST regime shifts greater than 0.75°C. Comparison with decadal climate variability in the North Pacific, as represented by the Pacific Decadal Oscillation index (1900–1997), indicates that several of the largest decadal-scale SST variations at Rarotonga are coherent with SST regime shifts in the North Pacific. This hemispheric symmetry suggests that tropical forcing may be an important factor in at least some of the decadal variability observed in the Pacific Ocean.
The Essential Anti-Essentialist
Authors: Shweder Richard A.
Published: July 2002

Available Light
Anthropological Reflections on Philosophical Topics. Clifford Geertz. Princeton University Press, Princeton, NJ, 2000. 287 pp. $24.95, £15.95. ISBN 0-691-04974-2.

These 11 essays by the influential and controversial cultural anthropologist Geertz are bound together by the underlying belief in the restricted scope of social science generalizations. The author does not believe there is a universal essence to human nature that strongly determines human behavior.
Rescue of Photoreceptor Degeneration in Rhodopsin-Null
Drosophila
Mutants by Activated Rac1
Authors: Chang Hui-Yun , Ready Donald F.
Published: July 2002

Rhodopsin is essential for photoreceptor morphogenesis; photoreceptors lacking rhodopsin degenerate in humans, mice, and
Drosophila
. Here we report that transgenic expression of a dominant-active
Drosophila
Rho guanosine triphosphatase, Drac1, rescued photoreceptor morphogenesis in rhodopsin-null mutants; expression of dominant-negative Drac1 resulted in a phenotype similar to that seen in rhodopsin-null mutants. Drac1 was localized in a specialization of the photoreceptor cortical actin cytoskeleton, which was lost in rhodopsin-null mutants. Thus, rhodopsin appears to organize the actin cytoskeleton through Drac1, contributing a structural support essential for photoreceptor morphogenesis.
Docosahexaenoic Acid, a Ligand for the Retinoid X Receptor in Mouse Brain
Authors: Urquiza Alexander Mata de , Liu Suya , Sjöberg Maria , Zetterström Rolf H. , Griffiths William , Sjövall Jan , Perlmann Thomas
Published: July 2002

The retinoid X receptor (RXR) is a nuclear receptor that functions as a ligand-activated transcription factor. Little is known about the ligands that activate RXR in vivo. Here, we identified a factor in brain tissue from adult mice that activates RXR in cell-based assays. Purification and analysis of the factor by mass spectrometry revealed that it is docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid that is highly enriched in the adult mammalian brain. Previous work has shown that DHA is essential for brain maturation, and deficiency of DHA in both rodents and humans leads to impaired spatial learning and other abnormalities. These data suggest that DHA may influence neural function through activation of an RXR signaling pathway.
Bakers' Yeast, a Model for Fungal Biofilm Formation
Authors: Reynolds Todd B. , Fink Gerald R.
Published: July 2002

Biofilms are formed by the aggregation of microorganisms into multicellular structures that adhere to surfaces. Here we show that bakers' yeast
Saccharomyces cerevisiae
can initiate biofilm formation. When grown in low-glucose medium, the yeast cells adhered avidly to a number of plastic surfaces. On semi-solid (0.3% agar) medium they formed “mats”: complex multicellular structures composed of yeast-form cells. Both attachment to plastic and mat formation require Flo11p, a member of a large family of fungal cell surface glycoproteins involved in adherence. The ability to study biofilm formation in a tractable genetic system may facilitate the identification of new targets for antifungal therapy.
The Bionic Man: Restoring Mobility
Authors: Craelius William
Published: July 2002

Bionics engineers are making increasingly bold and successful use of their tools to restore mobility to persons with missing or nonfunctional limbs. These tools include the latest materials, minielectronics and megacomputers, advanced robotic mechanisms, and algorithms. With crucial help from their pioneering users, they are learning how and where the residual sensorimotor system can be tapped in order to transmit its intents to replacement or reactivated body parts.
In Vitro Selection of Resistance to Clinafloxacin, Ciprofloxacin, and Trovafloxacin in
Streptococcus pneumoniae
Authors: Nagai Kensuke , Davies Todd A. , Pankuch Glenn A. , Dewasse Bonifacio E. , Jacobs Michael R. , Appelbaum Peter C.
Published: July 2002

Ability of daily sequential subcultures in subinhibitory concentrations of clinafloxacin, ciprofloxacin, and trovafloxacin to select resistant mutants was studied in 10 pneumococci (ciprofloxacin MICs, 1 to 4 μg/ml, and clinafloxacin and trovafloxacin MICs, 0.06 to 0.125 μg/ml [
n
= 9]; ciprofloxacin, clinafloxacin, and trovafloxacin MICs, 32, 0.5, and 2 μg/ml, respectively [
n
= 1]). Subculturing was done 50 times, or until MICs increased fourfold or more. Mutants for which MICs were fourfold (or more) higher than those for parent strains were selected in five strains by clinafloxacin, in six strains by trovafloxacin, and nine strains by ciprofloxacin. Sequence analysis of type II topoisomerase showed that most mutants had mutations in ParC at Ser79 or Asp83 and in GyrA at Ser81, while a few mutants had mutations in ParE or GyrB. In the presence of reserpine, the MICs of ciprofloxacin and clinafloxacin for most mutants were lower (four to eight times lower), but for none of the mutants were trovafloxacin MICs lower, suggesting an efflux mechanism affecting the first two agents but not trovafloxacin. Single-step mutation rates were also determined for eight strains for which the MICs were as follows: 0.06 μg/ml (clinafloxacin), 0.06 to 0.125 μg/ml (trovafloxacin), and 1 μg/ml (ciprofloxacin). Single-step mutation rates with drugs at the MIC were 2.0×10
−9
to <1.1×10
−11
, 5.0×10
−4
to 3.6×10
−9
, and 4.8×10
−4
to 6.7×10
−9
, respectively. For two strains with clinafloxacin MICs of 0.125 to 0.5 μg/ml trovafloxacin MICs of 0.125 to 2 μg/ml, ciprofloxacin MICs of 4 to 32 μg/ml mutation rates with drugs at the MIC were 1.1×10
−8
−9.6×10
−8
, 3.3×10
−6
−6.7×10
−8
, and 2.3×10
−5
−2.4×10
−7
, respectively. Clinafloxacin was bactericidal at four times the MIC after 24 h against three parent and nine mutant strains by time-kill study. This study showed that single and multistep clinafloxacin exposure selected for resistant mutants less frequently than similar exposures to other drugs studied.
Efficacy of a New Cream Formulation of Mupirocin: Comparison with Oral and Topical Agents in Experimental Skin Infections
Authors: Gisby John , Bryant Joanna
Published: July 2002

A new cream formulation of mupirocin developed to improve patient compliance was compared with systemic and topical antibiotics commonly used to treat primary and secondary skin infections. A mouse surgical wound model infected withStaphylococcus aureusorStreptococcus pyogeneswas used. Topical treatment was applied at 4 and 10 h postinfection or oral treatment at a clinically relevant dose was administered 4, 8, and 12 h postinfection; treatments were continued three times daily for a further 3 days. Mupirocin cream was significantly more effective than (P< 0.01; two of eight studies) or not significantly different from (six of eight studies) mupirocin ointment in reducing bacterial numbers. Mupirocin cream was similar in efficacy to oral flucloxacillin but significantly more effective (P< 0.001) than oral erythromycin. It was also similar in efficacy to cephalexin againstS. pyogenesbut superior againstS. aureus(P< 0.01). Mupirocin cream had a similar efficacy to fusidic acid cream againstS. aureusbut was significantly superior againstS. pyogenes(P< 0.01). A hamster impetigo model infected withS. aureuswas also used. Topical or oral treatment was administered at 24 and 30 h postinfection (also 36 h postinfection for oral therapy) and then three times daily for a further 2 days. On day 5, mupirocin cream was significantly more effective than mupirocin ointment in one study (P< 0.01) and of similar efficacy in the other two studies. Mupirocin cream was not significantly different from fusidic acid cream or neomycin-bacitracin cream, but it was significantly superior (P< 0.01) to oral erythromycin and cephalexin. Mupirocin cream was as effective as, or superior to, oral and other topical agents commonly used for skin infections.
Resistance to Macrolides in
Streptococcus pyogenes
in France in Pediatric Patients
Authors: Bingen Edouard , Fitoussi Frederic , Doit Catherine , Cohen Robert , Tanna Asha , George Robert , Loukil Chawki , Brahimi Naima , Le Thomas Isabelle , Deforche Dominique
Published: July 2002

A total of 1,500 recent throat isolates of
Streptococcus pyogenes
collected between 1996 and 1999 from children throughout France were tested for their susceptibility to erythromycin, azithromycin, josamycin, clindamycin, and streptogramin B. The erythromycin-resistant isolates were further studied for their genetic mechanism of resistance, by means of PCR. The clonality of these strains was also investigated by means of serotyping and ribotyping. In all, 6.2% of the strains were erythromycin resistant, and 3.4 and 2.8% expressed the constitutive MLS
B
and M resistance phenotypes and harbored the
ermB
and
mefA
genes, respectively;
ermTR
was recovered from one isolate which also harbored the
ermB
gene. Ten serotypes and 8 ribotypes were identified, but we identified 17 strains by combining serotyping with ribotyping. Among the eight ribotypes, the
mefA
gene was recovered from six clusters, one being predominant, while the
ermB
gene was recovered from four clusters, of which two were predominant.
Single-Dose AmBisome (Liposomal Amphotericin B) as Prophylaxis for Murine Systemic Candidiasis and Histoplasmosis
Authors: Garcia April , Adler-Moore Jill P. , Proffitt Richard T.
Published: July 2002

AmBisome is a liposomal formulation of amphotericin B that has broad-spectrum antifungal activity and greatly reduced toxicity compared to the parent drug. In this study, amphotericin B deoxycholate (Fungizone) (1 mg/kg) and AmBisome (1 to 20 mg/kg) were tested as single-dose prophylactic agents in both immunocompetent and immunosuppressed C57BL/6 mice challenged with either
Candida albicans
or
Histoplasma capsulatum
. Prophylactic efficacy was based on survival and fungal burden in the target organ (kidneys or spleen). At 9 to 10 days after histoplasma challenge, 80 to 90% of both immunocompetent and immunosuppressed mice in the control and Fungizone groups had died. All AmBisome-treated mice survived, although in the AmBisome groups given 1 mg/kg, the mice became moribund by day 10 to 12. No spleen CFU were detected in the histoplasma-challenged mice given 10 or 20 mg of AmBisome per kg. By 23 to 24 days after histoplasma challenge, fungal growth and/or death had occurred in all immunosuppressed mice except for four mice receiving 20 mg of AmBisome per kg. There were still no detectable fungi in the spleens of immunocompetent mice given 10 or 20 mg of AmBisome per kg. In the
C. albicans
experiment at 7 days postchallenge, all animals in both untreated and treated groups were alive with culture-positive kidneys. The kidney fungal burdens in AmBisome groups given 5 to 20 mg/kg were at least 1 log unit lower than those in the Fungizone group and significantly lower than those in the untreated control group (
P
< 0.05). There was a trend toward decreasing fungal growth in the kidneys as the dose of AmBisome was increased. In conclusion, these results show that a single high dose of AmBisome (5 to 20 mg/kg) had prophylactic efficacy in immunocompetent and immunosuppressed murine
H. capsulatum
and
C. albicans
models.
Postantibiotic Effects of Antituberculosis Agents Alone and in Combination
Authors: Chan Chiu-Yeung , Au-Yeang Carrie , Yew Wing-Wai , Hui Mamie , Cheng Augustine F. B.
Published: July 2002

The postantibiotic effects (PAEs) of seven antimycobacterial agents, tested at their respective peak concentrations in serum alone and in different combinations, against
Mycobacterium tuberculosis
ATCC 27294 were studied with a radiometric culture system in parallel with the viable count method. Rifampin gave the longest PAE (67.8 h) among the drugs used alone, and combinations of first-line drugs generally gave PAEs longer than 120 h. The data obtained might help provide a better understanding of the scientific basis of intermittently administered antituberculosis chemotherapy.
Effect of Prolonged Treatment with Azithromycin, Clarithromycin, or Levofloxacin onChlamydia pneumoniaein a Continuous-Infection Model
Authors: Kutlin Andrei , Roblin Patricia M. , Hammerschlag Margaret R.
Published: July 2002

Persistent infections withChlamydia pneumoniaehave been implicated in the development of chronic diseases, such as atherosclerosis and asthma. Although azithromycin, clarithromycin, and levofloxacin are frequently used for the treatment of respiratoryC. pneumoniaeinfections, little is known about the dose and duration of therapy needed to treat a putative chronicC. pneumoniaeinfection. In this study, we investigated the effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on the viability ofC. pneumoniaeand cytokine production in an in vitro model of continuous infection. We found that a 30-day treatment with azithromycin, clarithromycin, and levofloxacin at concentrations comparable to those achieved in the pulmonary epithelial lining fluid reduced but did not eliminateC. pneumoniaein continuously infected HEp-2 cells. All three antibiotics decreased levels of interleukin-6 (IL-6) and IL-8 in HEp-2 cells, but this effect appeared to be secondary to the antichlamydial activity, as the cytokine levels correlated with the concentrations of microorganisms. The levels of IL-1β, IL-4, IL-10, tumor necrosis factor alpha, and gamma interferon were too low to assess the effect of antibiotics. These data suggest that the dosage and duration of antibiotic therapy currently being used may not be sufficient to eradicate a putative chronicC. pneumoniaeinfection.
Oral Artesunate Dose-Response Relationship in Acute Falciparum Malaria
Authors: Angus Brian J. , Thaiaporn Itaporn , Chanthapadith Kenechanh , Suputtamongkol Yupin , White Nicholas J.
Published: July 2002

The combination of an oral artemisinin derivative (usually artesunate) and mefloquine has become standard treatment for multidrug-resistant falciparum malaria in several parts of Southeast Asia. The doses of artesunate used in monotherapy and combination treatment have largely been derived empirically. In order to characterize the in vivo dose-response relationship for artesunate and thus rationalize dosing, 47 adult patients with acute uncomplicated falciparum malaria and parasitemia ≥1% were randomized to receive a single oral dose of artesunate varying between 0 and 250 mg together with a curative dose of oral mefloquine. Acceleration of parasite clearance was used as the pharmacodynamic variable. An inhibitory sigmoidal maximum effect (
E
max
) pharmacodynamic model typical of a dose-response curve was fitted to the relationship between dose and shortening of parasite clearance time (PCT). The
E
max
was estimated as 28.6 oral h, and the 50% effective concentration was 1.6 mg/kg of body weight. These results imply that there is no reduction in PCTs with the use of single doses of artesunate higher than 2 mg/kg, and this therefore reflects the average lower limit of the maximally effective dose.
Assessment of Poliovirus Eradication in Japan: Genomic Analysis of Polioviruses Isolated from River Water and Sewage in Toyama Prefecture
Authors: Matsuura Kumiko , Ishikura Mitsuhiro , Yoshida Hiromu , Nakayama Takashi , Hasegawa Sumiyo , Ando Shuji , Horie Hitoshi , Miyamura Tatsuo , Kitamura Takashi
Published: July 2002

Seventy-eight poliovirus strains isolated from river water and sewage in Toyama Prefecture, Japan, during 1993 to 1995 were characterized by the PCR-restriction fragment length polymorphism (RFLP) method and by partially sequencing the VP3 and VP1 regions of the viral genome. Of these isolates, 36 were identified as Sabin vaccine strains, and 42 were identified as vaccine variant strains that had less than 1.4% nucleotide divergence from the Sabin strains, including 7 isolates with patterns different from those of Sabin strains as determined by PCR-RFLP analysis. These findings suggest that wild-type poliovirus was not circulating in Toyama Prefecture.
Medium-Chain Fatty Acids Affect Citrinin Production in the Filamentous Fungus
Monascus ruber
Authors: Hajjaj Hassan , Klaébé Alain , Goma Gérard , Blanc Philippe J. , Barbier Estelle , François Jean
Published: July 2002

During submerged culture in the presence of glucose and glutamate, the filamentous fungus
Monascus ruber
produces water-soluble red pigments together with citrinin, a mycotoxin with nephrotoxic and hepatoxic effects on animals. Analysis of the
13
C-pigment molecules from mycelia cultivated with [1-
13
C]-, [2-
13
C]-, or [1,2-
13
C]acetate by
13
C nuclear magnetic resonance indicated that the biosynthesis of the red pigments used both the polyketide pathway, to generate the chromophore structure, and the fatty acid synthesis pathway, to produce a medium-chain fatty acid (octanoic acid) which was then bound to the chromophore by a
trans
-esterification reaction. Hence, to enhance pigment production, we tried to short-circuit the de novo synthesis of medium-chain fatty acids by adding them to the culture broth. Of fatty acids with carbon chains ranging from 6 to 18 carbon atoms, only octanoic acid showed a 30 to 50% stimulation of red pigment production, by a mechanism which, in contrast to expectation, did not involve its direct
trans
-esterification on the chromophore backbone. However, the medium- and long-chain fatty acids tested were readily assimilated by the fungus, and in the case of fatty acids ranging from 8 to 12 carbon atoms, 30 to 40% of their initial amount transiently accumulated in the growth medium in the form of the corresponding methylketone 1 carbon unit shorter. Very interestingly, these fatty acids or their corresponding methylketones caused a strong reduction in, or even a complete inhibition of, citrinin production by
M. ruber
when they were added to the medium. Several data indicated that this effect could be due to the degradation of the newly synthesized citrinin (or an intermediate in the citrinin pathway) by hydrogen peroxide resulting from peroxisome proliferation induced by medium-chain fatty acids or methylketones.
Purification to Homogeneity and Characterization of a Novel
Pseudomonas putida
Chromate Reductase
Authors: Park C. H. , Keyhan M. , Wielinga B. , Fendorf S. , Matin A.
Published: July 2002

Cr(VI) (chromate) is a widespread environmental contaminant. Bacterial chromate reductases can convert soluble and toxic chromate to the insoluble and less toxic Cr(III). Bioremediation can therefore be effective in removing chromate from the environment, especially if the bacterial propensity for such removal is enhanced by genetic and biochemical engineering. To clone the chromate reductase-encoding gene, we purified to homogeneity (>600-fold purification) and characterized a novel soluble chromate reductase from
Pseudomonas putida
, using ammonium sulfate precipitation (55 to 70%), anion-exchange chromatography (DEAE Sepharose CL-6B), chromatofocusing (Polybuffer exchanger 94), and gel filtration (Superose 12 HR 10/30). The enzyme activity was dependent on NADH or NADPH; the temperature and pH optima for chromate reduction were 80°C and 5, respectively; and the

K
m

was 374 μM, with a
V
max
of 1.72 μmol/min/mg of protein. Sulfate inhibited the enzyme activity noncompetitively. The reductase activity remained virtually unaltered after 30 min of exposure to 50°C; even exposure to higher temperatures did not immediately inactivate the enzyme. X-ray absorption near-edge-structure spectra showed quantitative conversion of chromate to Cr(III) during the enzyme reaction.
Microbial Manganese and Sulfate Reduction in Black Sea Shelf Sediments
Authors: Thamdrup Bo , Rosselló-Mora Ramón , Amann Rudolf
Published: July 2002

The microbial ecology of anaerobic carbon oxidation processes was investigated in Black Sea shelf sediments from mid-shelf with well-oxygenated bottom water to the oxic-anoxic chemocline at the shelf-break. At all stations, organic carbon (C
org
) oxidation rates were rapidly attenuated with depth in anoxically incubated sediment. Dissimilatory Mn reduction was the most important terminal electron-accepting process in the active surface layer to a depth of ∼1 cm, while SO
4
2−
reduction accounted for the entire C
org
oxidation below. Manganese reduction was supported by moderately high Mn oxide concentrations. A contribution from microbial Fe reduction could not be discerned, and the process was not stimulated by addition of ferrihydrite. Manganese reduction resulted in carbonate precipitation, which complicated the quantification of C
org
oxidation rates. The relative contribution of Mn reduction to C
org
oxidation in the anaerobic incubations was 25 to 73% at the stations with oxic bottom water. In situ, where Mn reduction must compete with oxygen respiration, the contribution of the process will vary in response to fluctuations in bottom water oxygen concentrations. Total bacterial numbers as well as the detection frequency of bacteria with fluorescent in situ hybridization scaled to the mineralization rates. Most-probable-number enumerations yielded up to 10
5
cells of acetate-oxidizing Mn-reducing bacteria (MnRB) cm
−3
, while counts of Fe reducers were <10
2
cm
−3
. At two stations, organisms affiliated with
Arcobacter
were the only types identified from 16S rRNA clone libraries from the highest positive MPN dilutions for MnRB. At the third station, a clone type affiliated with
Pelobacter
was also observed. Our results delineate a niche for dissimilatory Mn-reducing bacteria in sediments with Mn oxide concentrations greater than ∼10 μmol cm
−3
and indicate that bacteria that are specialized in Mn reduction, rather than known Mn and Fe reducers, are important in this niche.
Lactococcus lactis
as a Cell Factory for High-Level Diacetyl Production
Authors: Hugenholtz Jeroen , Kleerebezem Michiel , Starrenburg Marjo , Delcour Jean , de Vos Willem , Hols Pascal
Published: July 2002

We report the engineering of
Lactococcus lactis
for the efficient conversion of sugar into diacetyl by combining NADH-oxidase overproduction and α-acetolactate decarboxylase inactivation. Eighty percent of the carbon flux was found to be rerouted via α-acetolactate to the production of diacetyl by preloading the cells with NADH-oxidase before their use as a cell factory.