bluuebunny/crossref_metadata_2025 huggingface dataset:
Photoemission Evidence for a Remnant Fermi Surface and a
d-
Wave-Like Dispersion in Insulating Ca
2
CuO
2
Cl
2
Authors: Ronning F. , Kim C. , Feng D. L. , Marshall D. S. , Loeser A. G. , Miller L. L. , Eckstein J. N. , Bozovic I. , Shen Z.-X.
Published: July 2002

An angle-resolved photoemission study is reported on Ca
2
CuO
2
Cl
2
, a parent compound of high-
T
c
superconductors. Analysis of the electron occupation probability, n(
k
), from the spectra shows a steep drop in spectral intensity across a contour that is close to the Fermi surface predicted by the band calculation. This analysis reveals a Fermi surface remnant, even though Ca
2
CuO
2
Cl
2
is a Mott insulator. The lowest energy peak exhibits a dispersion with approximately the |cos

k
x
a

– cos

k
y
a

| form along this remnant Fermi surface. Together with the data from Dy-doped Bi
2
Sr
2
CaCu
2
O
8+δ
, these results suggest that this
d
-wave–like dispersion of the insulator is the underlying reason for the pseudo gap in the underdoped regime.
Statistical Buddy
Authors: Shmaefsky Brian R.
Published: July 2002

Data Desk 6.0
Data Description Inc. Ithaca, NY. $650; $795 (with ActivStats). (607) 257-1000 .
www.datadesk.com

In this review, Shmaefsky evaluates Data Desk, a useful tool for statistical analysis that works on moderate-sized data sets and produces simple graphical presentations. Its strengths are its simple design and its rapid data analysis.
A Semiconductor-Based Photonic Memory Cell
Authors: Zimmermann S. , Wixforth A. , Kotthaus J. P. , Wegscheider W. , Bichler M.
Published: July 2002

Photonic signals were efficiently stored in a semiconductor-based memory cell. The incident photons were converted to electron-hole pairs that were locally stored in a quantum well that was laterally modulated by a field-effect tunable electrostatic superlattice. At large superlattice potential amplitudes, these pairs were stored for a time that was at least five orders of magnitude longer than their natural lifetime. At an arbitrarily chosen time, they were released in a short and intense flash of incoherent light, which was triggered by flattening the superlattice amplitude.
Structure of the VHL-ElonginC-ElonginB Complex: Implications for VHL Tumor Suppressor Function
Authors: Stebbins Charles E. , Kaelin William G. , Pavletich Nikola P.
Published: July 2002

Mutation of the VHL tumor suppressor is associated with the inherited von Hippel–Lindau (VHL) cancer syndrome and the majority of kidney cancers. VHL binds the ElonginC-ElonginB complex and regulates levels of hypoxia-inducible proteins. The structure of the ternary complex at 2.7 angstrom resolution shows two interfaces, one between VHL and ElonginC and another between ElonginC and ElonginB. Tumorigenic mutations frequently occur in a 35-residue domain of VHL responsible for ElonginC binding. A mutational patch on a separate domain of VHL indicates a second macromolecular binding site. The structure extends the similarities to the SCF (Skp1-Cul1–F-box protein) complex that targets proteins for degradation, supporting the hypothesis that VHL may function in an analogous pathway.
The View Through the Rocks
Authors: Sloan Lisa Cirbus
Published: July 2002

Interpreting Pre-Quaternary Climate from the Geologic Record
. Judith Totman Parrish. Columbia University Press, New York, 1999. 354 pp. $95, £76. ISBN 0-231-10206-2.

Parrish offers a geological perspective on reconstructing climates of Earth's past, emphasizing the interpretation of data from rocks and fossils.
Discovery of a Small Molecule Insulin Mimetic with Antidiabetic Activity in Mice
Authors: Zhang Bei , Salituro Gino , Szalkowski Deborah , Li Zhihua , Zhang Yan , Royo Inmaculada , Vilella Dolores , Dı́ez Maria Teresa , Pelaez Fernando , Ruby Caroline , Kendall Richard L. , Mao Xianzhi , Griffin Patrick , Calaycay Jimmy , Zierath Juleen R. , Heck James V. , Smith Roy G. , Moller David E.
Published: July 2002

Insulin elicits a spectrum of biological responses by binding to its cell surface receptor. In a screen for small molecules that activate the human insulin receptor tyrosine kinase, a nonpeptidyl fungal metabolite (L-783,281) was identified that acted as an insulin mimetic in several biochemical and cellular assays. The compound was selective for insulin receptor versus insulin-like growth factor I (IGFI) receptor and other receptor tyrosine kinases. Oral administration of L-783,281 to two mouse models of diabetes resulted in significant lowering in blood glucose levels. These results demonstrate the feasibility of discovering novel insulin receptor activators that may lead to new therapies for diabetes.
A Younger Age for the Universe
Authors: Lineweaver Charles H.
Published: July 2002

The age of the universe in the Big Bang model can be calculated from three parameters: Hubble's constant,
h
; the mass density of the universe, Ω
m
; and the cosmological constant, Ω
Λ
. Recent observations of the cosmic microwave background and six other cosmological measurements reduce the uncertainty in these three parameters, yielding an age for the universe of 13.4 ± 1.6 billion years, which is a billion years younger than other recent age estimates. A different standard Big Bang model, which includes cold dark matter with a cosmological constant, provides a consistent and absolutely time-calibrated evolutionary sequence for the universe.
Nota Bene: To Read and Enjoy
Authors: Ahern Kevin
Published: July 2002

Digital facsimiles of several significant historical scientific books, including Galileo Galilei's
Sidereus Nuncius
and Nicolaus Coperincus'
De Revolutionibus Orbium Coelestium
are now available on CD-ROM.
Themes of Thought and Thinking
Authors: Gallistel C. R.
Published: July 2002

The Nature of Cognition
. Robert J. Sternberg, Ed. MIT Press, Cambridge, MA, 1999. 746 pp. $60. ISBN 0-262-19405-8. Paper, $35. ISBN 0-262-69212-0.

The contributors present a series of essays that approach cognition in terms of conceptual themes in such aspects as the variety of kinds of cognition and alternative methods of studying it.
The Powers of Flowers
Authors: Endress Peter K.
Published: July 2002

The Rose's Kiss
A Natural History of Flowers. Peter Bernhardt. Island Press, Washington, DC 1999. 277 pp. $24.95. ISBN I-55963-564-9.

Supplementing science with links to poetry, culture, and mythology, Bernhardt offers an entertaining and informative introduction to the biology of flowers.
Personal Planetaria
Authors: Marvel Kevin B.
Published: July 2002

Starry Night Pro
. Sienna Software Inc. Toronto, Ontario, Canada. $149, C$199. 416-410-0259.
www.siennasoft.com

This electronic star chart and desktop planetarium allows the user to view the heavens from anyplace in or near the solar system and to create electronic movies of celestial events.
Snails and Tails or Sugar and Spice
Authors: Hall Kira
Published: July 2002

The Two Sexes
Growing Up Apart, Coming Together. Eleanor E. Maccoby. Harvard University Press, Cambridge, MA, 1998. 384 pp. $39.95, £25.95. ISBN 0-674-91481-3.

Maccoby examines how human development from infancy into adulthood is affected by gender. She finds childhood experiences in same-sex groups particularly important in shaping subsequent relations between males and females.
A Capacitance Standard Based on Counting Electrons
Authors: Keller Mark W. , Eichenberger Ali L. , Martinis John M. , Zimmerman Neil M.
Published: July 2002

A capacitance standard based directly on the definition of capacitance was built. Single-electron tunneling devices were used to place
N
electrons of charge
e
onto a cryogenic capacitor
C
, and the resulting voltage change Δ
V
was measured. Repeated measurements of
C
=
Ne
/Δ
V
with this method have a relative standard deviation of 0.3 × 10
–6
. This standard offers a natural basis for capacitance analogous to the Josephson effect for voltage and the quantum Hall effect for resistance.
Balancing Research and Teaching
Authors: Chalupa Leo M.
Published: July 2002

Gone for Good
Tales of University Life After the Golden Age. Stuart Rojstaczer. Oxford University Press, New York, 1999. 299 pp. $22. ISBN 0-19-512682-3.

Using his experiences at Duke, Rojstacer offers a chatty, personal assessment of the current status of the American research university. He would prefer to shift the existing arrangements so that there is more emphasis on undergraduate education.
What Makes One Tic?
Authors: Licinio Julio
Published: July 2002

A Cursing Brain?
The Histories of Tourette Syndrome. Howard I. Kushner. Harvard University Press, Cambridge, MA, 1999. 319 pp. $29.95. ISBN 0-674-18022-4.

Kushner blends a detailed description of Tourette's syndrome with an insightful account of how changes in medical (and cultural) views have altered the characterization and treatment of the illness.
The Gravity Field of Mars: Results from Mars Global Surveyor
Authors: Smith David E. , Sjogren William L. , Tyler G. Leonard , Balmino Georges , Lemoine Frank G. , Konopliv Alex S.
Published: July 2002

Observations of the gravity field of Mars reveal a planet that has responded differently in its northern and southern hemispheres to major impacts and volcanic processes. The rough, elevated southern hemisphere has a relatively featureless gravitational signature indicating a state of near-isostatic compensation, whereas the smooth, low northern plains display a wider range of gravitational anomalies that indicates a thinner but stronger surface layer than in the south. The northern hemisphere shows evidence for buried impact basins, although none large enough to explain the hemispheric elevation difference. The gravitational potential signature of Tharsis is approximately axisymmetric and contains the Tharsis Montes but not the Olympus Mons or Alba Patera volcanoes. The gravity signature of Valles Marineris extends into Chryse and provides an estimate of material removed by early fluvial activity.
A Bright View, Too Focused
Authors: Faiman David
Published: July 2002

From Space to Earth
The Story of Solar Electricity. John Perlin. Aatec, Ann Arbor, MI, 1999. 240 pp. $32. ISBN 0-937948-14-4.

Using a series of fascinating and well-written accounts of individuals who have developed, advocated, and employed solar cells, Perlin describes the evolution of photovoltaics. Our reviewer objected to the partisan attitude, sales-talk style, and general neglect of other solar power technologies.
Ion Penetration of the Water-Oil Interface
Authors: Wu Kai , Iedema Martin J. , Cowin James P.
Published: July 2002

Ions typically pass with difficulty from water into organic phases because of water's superior solvation power. This inhibits such processes as ion transport in batteries or in lipid bilayers of cells. Ion penetration across such an interface was studied with unusual structural control. Hydronium ions were soft-landed at 1 electron volt on cold films of 3-methylpentane (“oil”) on a metal substrate. The field produced by these ions drove them through the films when warmed. Coadsorption of water (0.14 to 35 bilayers) inhibited the ion penetration by creating a solvation energy trap. A Born solvation model successfully predicted the trapping energies (0 to 38 kilojoules per mole).
Two Views of a Star's Life
Authors: Chapman Clark R.
Published: July 2002

Carl Sagan
A Life in the Cosmos. William Poundstone. Henry Holt, New York, 1999. 491 pp. $30, C$45. ISBN 0-8050-5766-8.

Carl Sagan
A Life. Keay Davidson. John Wiley, New York, 1999. 560 pp. $30, C$41.95. ISBN 0-471-25286-7.

In their examination of the life and science of Carl Sagan, the biographies by Keay Davidson and William Poundstone pay particular attention to the causes and consequences of his celebrity status.
Reef Processes in the Long View
Authors: Veron J.E. N.
Published: July 2002

Reef Evolution
. Rachel Wood. Oxford University Press, Oxford, 1999. 426 pp. $100, £55. ISBN 0-19-854999-7. Paper, $37.50, £22.50. ISBN 0-19-857784-2.

Wood's overview of reef processes, primarily from a geological perspective, provides an admirable synthesis that will have a substantial impact on all who study reefs, biologists and geologists alike.
Big Synapse Stories
Authors: Augustine George J.
Published: July 2002

The Squid Giant Synapse
A Model for Chemical Transmission. Rodolfo R. Llinás. Oxford University Press, New York, 1999. 332 pp. + CD-ROM. $85, £49.95. ISBN 0-19-511652-6.

The squid giant synapse has provided a model system for investigating how synapses allow communication among nerve cells. Llinás has contributed much to our understanding of the system, and his personal perspective provides a valuable background for synaptic physiologists.
Fishing Stories
Authors: Meyer Axel
Published: July 2002

A Fish Caught in Time
The Search for the Coelacanth. Samantha Weinberg. Fourth Estate, London, 1999. 239 pp. £13.99. ISBN 1-85702-906-2. Harper and Collins, New York, 2000. 240 pp. $24, $C36.50. ISBN 0-06-019495-2.

Weinberg, a British travel writer, offers a history of the discoveries and subsequent studies of the extant coelacanths, "living fossil" crossopterygian fishes. Her breezy account highlights the personalities of the researchers and the conflicts among them.
All Alone After All?
Authors: McKay Christopher P.
Published: July 2002

Rare Earth
Why Complex Life Is Uncommon in the Universe. Peter D. Ward and Donald Brownlee. Copernicus (Springer-Verlag), New York, 2000. 361 pp. ISBN 0-387-98701-0.

The authors, a paleontologist and an astronomer, argue that while life at the level of microbes may be common in the universe, life at the level of even simple animals is likely to be extremely rare.
Roots of the Fact
Authors: Poovey Mary
Published: July 2002

A Culture of Fact
England, 1550-1720. Barbara J. Shapiro. Cornell University Press, Ithaca, NY, 2000. 296 pp. $42.50. ISBN 0-8014-3686-9.

In opposition to previous claims that the concept of fact initially developed in the domain of Baconian natural philosophy, Shapiro argues that the concept originated in the English law court of the 16th century.
Approaches to Studying Sex
Authors: Gomendio Montserrat
Published: July 2002

Reproduction in Context
Social and Environmental Influences on Reproduction. Kim Wallen and Jill E. Schneider, Eds. MIT Press, Cambridge, MA, 2000. 534 pp. $60, £37.50. ISBN 0-262-23204-9.

The contributors to this volume integrate ecology, physiology, and neuroendocrinology in an evolutionary framework to discuss reproduction as one aspect of whole organisms.
Voluminous, Varied, and Vital
Authors: Raikhel Natasha V.
Published: July 2002

Plant Cell Vacuoles
An Introduction. Deepesh N. De. CSIRO, Collingwood, Victoria, Australia, 2000. 304 pp. Paper, $60, £58.95, A$85. ISBN 0-643-06254-8.

De provides an encyclopedic tour through the past quarter century of literature about plant cell vacuoles, multifunctional organelles that are crucial for the regulation and maintenance of plant growth and development.
All Kinds of Bubbles
Authors: Barker G. C.
Published: July 2002

The Physics of Foams
. Denis Weaire and Stefan Hutzler. Clarendon Press, Oxford, 1999. 260 pp. $80, £47.50. ISBN 0-19-850551-5.

Universal Foam
From Cappuccino to the Cosmos. Sidney Perkowitz. Walker and Company, New York, 2000. 206 pp. $24, C$35.95. ISBN 0-8027-1357-2.

These two broad-ranging and enlightening books offer complimentary perspectives on the physics of foam. Writing for a general audience, Perkowitz pursues the topic's alliance of physics and chemistry from the kitchen to the laboratory to the structure of the universe. Weaire and Hutzler's more technical account, which pays considerable attention to the recent progress and future prospects enabled by computer simulations, will benefit researchers at all levels.
Nota Bene: Organizing the Elements
Authors: Uppenbrink Julia
Published: July 2002

Mendeleyev's Dream
The Quest for the Elements.
By Paul Strathern
. Hamish Hamilton, London, 2000. 320 pp. £12.99. ISBN 0-241-14065-X.

Novelist and writer Strathern sketches a history of chemistry that he frames with the story of Mendeleyev's development of the periodic table.
Playing for Keeps
Authors: Sigmund Karl , Nowak Martin A.
Published: July 2002

Game Theory Evolving
A Problem-Centered Introduction to Modeling Strategic Interaction. Herbert Gintis. Princeton University Press, Princeton, NJ, 2000. 567 pp. $55, £35. ISBN 0-691-00942-2. Paper, $29.95, £18.95. ISBN 0-691-00943-0.

Gintis, an economist, offers game theory as a tool kit for exploring behavior in a wide range of social situations. His text shows how the approach has challenged the concept of rationality.
Cinemas of the Wild
Authors: Lovejoy Thomas
Published: July 2002

Reel Nature
America's Romance with Wildlife on Film.
By Gregg Mitman
. Harvard University Press, Cambridge, MA, 1999. 303 pp. $29.95. ISBN 0-674-71571-3.
Wildlife Films
.
By Derek Bousé,
. University of Pennsylvania Press. Philadelphia, 2000. 296 pp. $55. ISBN 0-8122-3555-X. Paper, $22.50. ISBN 0-8122-1728-4.

These books examine the long and rich history of nature films. Mitman focuses on how the interaction of science, cultural values, and motion-picture technologies has shaped American views of wildlife. Bousé, argues that the genre's emphasis on telling stories rather than revealing fact has made it so successful at popularizing science.
Hematin Polymerization Assay as a High-Throughput Screen for Identification of New Antimalarial Pharmacophores
Authors: Kurosawa Yae , Dorn Arnulf , Kitsuji-Shirane Michiko , Shimada Hisao , Satoh Tomoko , Matile Hugues , Hofheinz Werner , Masciadri Raffaello , Kansy Manfred , Ridley Robert G.
Published: July 2002

Hematin polymerization is a parasite-specific process that enables the detoxification of heme following its release in the lysosomal digestive vacuole during hemoglobin degradation, and represents both an essential and a unique pharmacological drug target. We have developed a high-throughput in vitro microassay of hematin polymerization based on the detection of
14
C-labeled hematin incorporated into polymeric hemozoin (malaria pigment). The assay uses 96-well filtration microplates and requires 12 h and a Wallac 1450 MicroBeta liquid scintillation counter. The robustness of the assay allowed the rapid screening and evaluation of more than 100,000 compounds. Random screening was complemented by the development of a pharmacophore hypothesis using the “Catalyst” program and a large amount of data available on the inhibitory activity of a large library of 4-aminoquinolines. Using these methods, we identified “hit” compounds belonging to several chemical structural classes that had potential antimalarial activity. Follow-up evaluation of the antimalarial activity of these compounds in culture and in the
Plasmodium berghei
murine model further identified compounds with actual antimalarial activity. Of particular interest was a triarylcarbinol (Ro 06-9075) and a related benzophenone (Ro 22-8014) that showed oral activity in the murine model. These compounds are chemically accessible and could form the basis of a new antimalarial medicinal chemistry program.
Safety, Tolerability, and Pharmacokinetics of Single Oral Doses of BCH-10652 in Healthy Adult Males
Authors: Smith Patrick F. , Forrest Alan , Ballow Charles H. , Martin David E. , Proulx Louise
Published: July 2002

Racemic dOTC (BCH-10652) is a novel nucleoside reverse transcriptase inhibitor consisting of two enantiomers of 2′-deoxy-3′-oxa-4′-thiocytidine, (−)dOTC and (+)dOTC, that have both shown activity against human immunodeficiency virus type 1. The objectives of this study were to characterize the safety, tolerability, and stereospecific pharmacokinetics of single oral doses of racemic dOTC in healthy, nonsmoking adult male volunteers. Subjects received single oral doses of 100, 200, 400, 800, and 1,600 mg of racemic dOTC in a placebo-controlled, dose-rising, incomplete crossover study design, and the pharmacokinetics of both (+)dOTC and (−)dOTC were determined. At least six subjects were studied at each dose level, with each subject studied in three of five periods, receiving two different doses of racemic dOTC and one placebo dose. Plasma and urine drug concentrations were measured for 24 to 48 h after each dose. Pharmacokinetic models were fitted to the plasma concentrations of (+)dOTC and (−)dOTC using maximum likelihood and maximum a posteriori Bayesian procedures. Statistical hypothesis testing was by nonparametric analysis of variance (where possible) and, when tests with dose as a covariate were performed, by linear mixed-effects modeling. The mean terminal elimination half-lives for (+)dOTC and (−)dOTC were 15.3 h (coefficient of variation [CV], 28%) and 11.3 h (CV, 43%), respectively (
P
< 0.05). The mean CV for total oral clearance (liter/h/65 kg) was 17.5 (25%) for (+)dOTC and 21.5 (24%) for (−)dOTC; for oral steady-state volume of distribution (liter/65 kg), values were 61.8 (24%) for (+)dOTC and 34.1 (33%) for (−)dOTC (
P
< 0.05). The mean CV for renal clearance (liter/h/65 kg) of (+)dOTC was 10.4 (19%) and for (−)dOTC was 13.6 (20%) (
P
< 0.05). There was no significant effect of dose size on the pharmacokinetics of racemic dOTC. All doses were well tolerated, and no serious adverse events or laboratory abnormalities were observed.
In Vitro Activities of Rabeprazole, a Novel Proton Pump Inhibitor, and Its Thioether Derivative Alone and in Combination with Other Antimicrobials against Recent Clinical Isolates of
Helicobacter pylori
Authors: Kawakami Yoshiyuki , Akahane Takayuki , Yamaguchi Masaru , Oana Kozue , Takahashi Yuko , Okimura Yukie , Okabe Tadashi , Gotoh Akira , Katsuyama Tsutomu
Published: July 2002

The MICs of rabeprazole sodium (RPZ), a newly developed benzimidazole proton pump inhibitor (PPI), against 133 clinical
Helicobacter pylori
strains revealed a higher degree of activity than the another two PPIs, lansoprazole and omeprazole. Time-kill curve assays of RPZ, when combined with amoxicillin, clarithromycin, or metronidazole, disclosed that synergistic effects were demonstrated in combination with each antibiotic examined. Moreover, no apparent antagonistic effect appeared among all of the strains tested.
In Vivo Activity and Pharmacokinetics of Ziracin (SCH27899), a New Long-Acting Everninomicin Antibiotic, in a Murine Model of Penicillin-Susceptible or Penicillin-Resistant Pneumococcal Pneumonia
Authors: Wang Erjian , Simard Marie , Bergeron Yves , Beauchamp Denis , Bergeron Michel G.
Published: July 2002

The effectiveness of ziracin (SCH27899), a novel everninomicin, was at first investigated against lethal pneumonia caused by a penicillin-susceptible
Streptococcus pneumoniae
strain. A single intravenous injection of ziracin at a dose of 60 mg/kg of body weight given at 18 h postinfection protected 100% mice and led to the complete clearance of bacteria from their lungs. The activity of ziracin was observed to be the same as that of ceftriaxone: the 50% protective doses (PD
50
s) of ziracin and ceftriaxone were 24.8 and 24.6 mg/kg, respectively. Evaluation of this therapy with leukopenic mice showed that a single injection of ziracin protected 75% of these mice. A delay in therapy with ziracin, which was initiated at 48 h postinfection with 30 mg/kg given once daily for 3 days, resulted in an 83% survival rate of immunocompetent mice. The efficacy of ziracin was further compared to that of vancomycin against lethal pneumonia caused by a penicillin-resistant
S. pneumoniae
strain in leukopenic mice. The PD
50
s of ziracin and vancomycin were 40.5 and 44.2 mg/kg, respectively. Treatment with ziracin at 30 mg/kg once daily for 2 days (initiated 18 h postinfection) yielded an 83% survival rate and achieved complete eradication of the bacteria. The results were the same as those obtained with vancomycin administered at 15 mg/kg twice daily for 2 days. It is notable that the high survival rates for mice treated with ziracin were associated with effective eradication of the bacteria and rapid recovery of pulmonary tissues from pneumonia. The pharmacokinetic properties of ziracin, ceftriaxone, and vancomycin were estimated following intravenous administration of a single dose of 30 mg/kg to immunocompetent mice. The half-life of ziracin was observed to be longer than those of ceftriaxone and vancomycin (2.3 h versus 1.0 and 0.36 h in the bloodstream and 3 h versus 1.9 and 0.45 h in lung tissues). The areas under the concentration-time curves (AUCs) in lung tissue for ziracin versus those for ceftriaxone and vancomycin were 36 μg · h/g versus 20 and 9.5 μg · h/g. The prolonged half-life and high AUC for ziracin in tissue contributed to its excellent in vivo activities.
Novel Gene Cassettes and Integrons
Authors: Peters E. D. J. , Leverstein-van Hall M. A. , Box A. T. A. , Verhoef J. , Fluit A. C.
Published: July 2002

An increase in multiresistant
Enterobacteriaceae
was observed at one of the departments of the University Medical Center Utrecht. Nine different integrons and 17 gene cassettes were found, including the new gene cassette
aadA8
. This cassette was highly related to
aadA3
and
aadA2
. In addition, an unknown promoter sequence was found for two integrons.
In70 of Plasmid pAX22, a
bla
VIM-1
-Containing Integron Carrying a New Aminoglycoside Phosphotransferase Gene Cassette
Authors: Riccio Maria Letizia , Pallecchi Lucia , Fontana Roberta , Rossolini Gian Maria
Published: July 2002

An
Achromobacter xylosoxydans
strain showing broad-spectrum resistance to β-lactams (including carbapenems) and aminoglycosides was isolated at the University Hospital of Verona (Verona, Italy). This strain was found to produce metallo-β-lactamase activity and to harbor a 30-kb nonconjugative plasmid, named pAX22, carrying a
bla
VIM-1
determinant inserted into a class 1 integron. Characterization of this integron, named In70, revealed an original array of four gene cassettes containing, respectively, the
bla
VIM-1
gene and three different aminoglycoside resistance determinants, including an
aacA4
allele, a new
aph
-like gene named
aphA15
, and an
aadA1
allele. The
aphA15
gene is the first example of an
aph
-like gene carried on a mobile gene cassette, and its product exhibits close similarity to the APH(3′)-IIa aminoglycoside phosphotransferase encoded by Tn
5
(36% amino acid identity) and to an APH(3′)-IIb enzyme from
Pseudomonas aeruginosa
(38% amino acid identity). Expression of the cloned
aphA15
gene in
Escherichia coli
reduced the susceptibility to kanamycin and neomycin as well as (slightly) to amikacin, netilmicin, and streptomycin. Characterization of the 5′ and 3′ conserved segments of In70 and of their flanking regions showed that In70 belongs to the group of class 1 integrons associated with defective transposon derivatives originating from Tn
402
-like elements. The structure of the 3′ conserved segment indicates the closest ancestry with members of the In0-In2 lineage. In70, with its array of cassette-borne resistance genes, can mediate broad-spectrum resistance to most β-lactams and aminoglycosides.
Alkylglycerol Prodrugs of Phosphonoformate Are Potent In Vitro Inhibitors of Nucleoside-Resistant Human Immunodeficiency Virus Type 1 and Select for Resistance Mutations That Suppress Zidovudine Resistance
Authors: Hammond Jennifer L. , Koontz Dianna L. , Bazmi Holly Z. , Beadle James R. , Hostetler Saskia E. , Kini Ganesh D. , Aldern Kathy A. , Richman Douglas D. , Hostetler Karl Y. , Mellors John W.
Published: July 2002

Phosphonoformate (foscarnet; PFA) is a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), but its use for the treatment of HIV-1 infection is limited by toxicity and the lack of an orally bioavailable formulation. Alkylglycerol-conjugated prodrugs of PFA (1-
O
-octadecyl-
sn
-glycero-3-PFA [B-PFA]) having
sn
-2 substituents of hydrogen (deoxybatyl-PFA [DB-PFA]), methyl (MB-PFA), or ethyl (EB-PFA) are more-potent inhibitors of wild-type HIV-1 in vitro than unmodified PFA and are orally bioavailable in mice. We have evaluated the activities of these compounds against a panel of nucleoside-resistant HIV-1 variants and have characterized the resistant variants that emerge following in vitro selection with the prodrugs. Except for an HIV-1 variant encoding the K65R mutation in RT that exhibited 3.3- to 8.2-fold resistance, the nucleoside-resistant viruses included in the panel were sensitive to the PFA prodrugs (<3-fold increase in 50% inhibitory concentration), including multinucleoside-resistant variants encoding the Q151M complex of mutations or the T69S[SA] insert. Viruses resistant to the PFA prodrugs (>10-fold) were selected in vitro after 15 or more serial passages of HIV-1 in MT-2 cells in escalating prodrug concentrations. Mutations detected in the resistant viruses were S117T, F160Y, and L214F (DB-PFA); M164I and L214F (MB-PFA); and W88G and L214F (EB-PFA). The S117T, F160Y, and M164I mutations have not been previously identified. Generation of recombinant viruses encoding the single and double mutations confirmed their roles in prodrug resistance, including 214F, which generally increased the level of resistance. When introduced into a zidovudine (AZT)-resistant background (67N 70R 215F 219Q), the W88G, S117T, F160Y, and M164I mutations reversed AZT resistance. This suppression of AZT resistance is consistent with the effects of other foscarnet resistance mutations that reduce ATP-dependent removal of AZT monophosphate from terminated template primers. The favorable activity and resistance profiles of these PFA prodrugs warrant their further evaluation as clinical candidates.
Intramacrophage Passage of
Mycobacterium tuberculosis
and
M. avium
Complex Alters the Drug Susceptibilities of the Organisms as Determined by Intracellular Susceptibility Testing Using Macrophages and Type II Alveolar Epithelial Cells
Authors: Tomioka Haruaki , Sato Katsumasa , Sano Chiaki , Sano Keisuke , Shimizu Toshiaki
Published: July 2002

Mycobacterium tuberculosis
and
M. avium
complex strains given intramacrophage passage (I-type) were compared with those cultured in a liquid medium (E-type) for their drug susceptibilities when they were replicating in Mono-Mac-6 macrophages or A-549 cells. Their intracellular susceptibilities to rifalazil, clarithromycin, and levofloxacin were decreased more in I-type organisms than in E-type organisms, except that their rifalazil susceptibility inside A-549 cells was markedly increased in I-type organisms.
Chromosomal System for Studying AmpC-Mediated β-Lactam Resistance Mutation in
Escherichia coli
Authors: Petrosino Joseph F. , Pendleton Amanda R. , Weiner Joel H. , Rosenberg Susan M.
Published: July 2002

In some enterobacterial pathogens, but not in
Escherichia coli
, loss-of-function mutations in the
ampD
gene are a common route to β-lactam antibiotic resistance. We constructed an assay system for studying mechanism(s) of enterobacterial
ampD
mutation using the well-developed genetics of
E. coli
. We integrated the
Enterobacter ampRC
genes into the
E. coli
chromosome. These cells acquire spontaneous recombination- and SOS response-independent β-lactam resistance mutations in
ampD
. This chromosomal system is useful for studying mutation mechanisms that promote antibiotic resistance.
TEM-71, a Novel Plasmid-Encoded, Extended-Spectrum β-Lactamase Produced by a Clinical Isolate of
Klebsiella pneumoniae
Authors: Rasheed J. Kamile , Anderson Gregory J. , Queenan Anne Marie , Biddle James W. , Oliver Antonio , Jacoby George A. , Bush Karen , Tenover Fred C.
Published: July 2002

TEM-71, a novel extended-spectrum β-lactamase from a
Klebsiella pneumoniae
clinical isolate, had an isoelectric point of 6.0 and a substrate profile showing preferential hydrolysis of cefotaxime over ceftazidime. It differed from TEM-1 by two substitutions, Gly238Ser and Glu240Lys, and was under the control of the strong
P4
promoter.
Efficacy of β-Lactams for Treating Experimentally Induced Pneumonia Due to a Carbapenem-Hydrolyzing Metallo-β-Lactamase-Producing Strain of
Pseudomonas aeruginosa
Authors: Bellais Samuel , Mimoz Olivier , Léotard Sophie , Jacolot Anne , Petitjean Olivier , Nordmann Patrice
Published: July 2002

A rat pneumonia model was established with a
Pseudomonas aeruginosa
strain that produced the plasmid-encoded metallocarbapenemase VIM-2. A significant decrease in lung bacterial titers was observed when imipenem, cefepime, ceftazidime, and piperacillin-tazobactam were given at the highest doses recommended for humans, despite their high MICs. Aztreonam at high doses produced a similar decrease in bacterial titers.
Osmotic Stress-Induced Genetic Rearrangements in
Escherichia coli
H10407 Detected by Randomly Amplified Polymorphic DNA Analysis
Authors: Jolivet-Gougeon Anne , David-Jobert Sandrine , Tamanai-Shacoori Zohreh , Ménard Christian , Cormier Michel
Published: July 2002

Randomly amplified polymorphic DNA (RAPD) analysis is a DNA polymorphism assay commonly used for fingerprinting genomes. After optimizing the reaction conditions, samples of
Escherichia coli
H10407 DNA were assayed to determine the influence of osmotic and/or oligotrophic stress on variations in RAPD banding patterns. Genetic rearrangements or DNA topology variations could be detected as changes in agarose gel electrophoresis banding profiles. A new amplicon generated using DNA extracted from bacteria prestarved by an osmotic stress and resuscitated in rich medium was observed. Enrichment improved recovery of mutator cells and allowed them to be detected in samples, suggesting that DNA modifications, such as stress-induced alterations and supercoiling phenomena, should be taken into consideration before beginning RAPD analyses.
Utilization of Dimethyl Sulfide as a Sulfur Source with the Aid of Light by
Marinobacterium
sp. Strain DMS-S1
Authors: Fuse Hiroyuki , Takimura Osamu , Murakami Katsuji , Yamaoka Yukiho , Omori Toshio
Published: July 2002

Strain DMS-S1 isolated from seawater was able to utilize dimethyl sulfide (DMS) as a sulfur source only in the presence of light in a sulfur-lacking medium. Phylogenetic analysis based on 16S ribosomal DNA genes indicated that the strain was closely related to
Marinobacterium georgiense
. The strain produced dimethyl sulfoxide (DMSO), which was a main metabolite, and small amounts of formate and formaldehyde when grown on DMS as the sole sulfur source. The cells of the strain grown with succinate as a carbon source were able to use methyl mercaptan or methanesulfonate besides DMS but not DMSO or dimethyl sulfone as a sole sulfur source. DMS was transformed to DMSO primarily at wavelengths between 380 and 480 nm by heat-stable photosensitizers released by the strain. DMS was also degraded to formaldehyde in the presence of light by unidentified heat-stable factors released by the strain, and it appeared that strain DMS-S1 used the degradation products, which should be sulfite, sulfate, or methanesulfonate, as sulfur sources.
Effect of Copper Speciation on Whole-Cell Soluble Methane Monooxygenase Activity inMethylosinus trichosporiumOB3b
Authors: Morton John D. , Hayes Kim F. , Semrau Jeremy D.
Published: July 2002

Soluble methane monooxygenase (sMMO) activity inMethylosinus trichosporiumOB3b was found to be more strongly affected as copper-to-biomass ratios changed in a newly developed medium, M2M, which uses pyrophosphate for metal chelation, than in nitrate mineral salts (NMS), which uses EDTA. When M2M medium was amended with EDTA, sMMO activity was similar to that in NMS medium, indicating that EDTA-bound copper had lower bioavailability than pyrophosphate-bound copper. EDTA did not limit the association of copper with the cells; rather, copper was sequestered in a form which did not affect sMMO activity.
Application of Rapid Dot Blot Immunoassay for Detection of
Salmonella enterica
Serovar Enteritidis in Eggs, Poultry, and Other Foods
Authors: Yoshimasu Mark Akira , Zawistowski Jerzy
Published: July 2002

Salmonella enterica
serovar Enteritidis was detected in artificially inoculated eggs within 24 h through a rapid monoclonal antibody-based dot blot immunoassay. Detection in poultry and other products required 28 h. Samples were directly enriched in homogenized egg without the need for pre- or postenrichment steps. Serovar Enteritidis was detected in the presence of other bacteria when outcompeted 1:400.
Organization and Transcriptional Analysis of a Six-Gene Cluster around the
rplK-rplA
Operon of
Corynebacterium glutamicum
Encoding the Ribosomal Proteins L11 and L1
Authors: Barreiro Carlos , González-Lavado Eva , Martı́n Juan F.
Published: July 2002

A cluster of six genes, tRNA
Trp
-
secE-nusG-rplK-rplA-pkwR,
was cloned and sequenced from a
Corynebacterium glutamicum
cosmid library and shown to be contiguous in the
C. glutamicum
genome. These genes encode a tryptophanyl tRNA, the protein translocase component SecE, the antiterminator protein NusG, and the ribosomal proteins L11 and L1 in addition to PkwR, a putative regulatory protein of the LacI-GalR family. S1 nuclease mapping analysis revealed that
nusG
and
rplK
are expressed as separate transcriptional units and
rplK
and
rplA
are cotranscribed as a single mRNA. A 19-nucleotide inverted repeat that appears to correspond to a transcriptional terminator was located in the 3′ region downstream from
nusG
. Northern analysis with different probes confirmed the S1 mapping results and showed that the
secE-rplA
four-gene region gives rise to four transcripts.
secE
was transcribed as a 0.5-kb monocistronic mRNA,
nusG
formed two transcripts of 1.4 and 1.0 kb from different initiation sites, and the two ribosomal protein genes
rplK
and
rplA
were cotranscribed as a single mRNA of 1.6 kb. A consensus L1 protein binding sequence was identified in the leader region of the
rplK-rplA
transcript, suggesting that expression of the
rplK-rplA
cluster was regulated by autogenous regulation exerted by the L1 protein at the translation level. The promoters of the
nusG
and
rplK-rplA
genes were subcloned in a novel corynebacterial promoter-probe vector and shown to confer strong expression of the reporter gene.
Molecular Characterization of an Endopolygalacturonase from
Fusarium oxysporum
Expressed during Early Stages of Infection
Authors: Garcı́a-Maceira Fé I. , Di Pietro A. , Huertas-González M. Dolores , Ruiz-Roldán M. Carmen , Roncero M. Isabel G.
Published: July 2002

The tomato vascular wilt pathogen
Fusarium oxysporum
f. sp
. lycopersici
produces an array of pectinolytic enzymes that may contribute to penetration and colonization of the host plant. Here we report the isolation of
pg5
, encoding a novel extracellular endopolygalacturonase (endoPG) that is highly conserved among different formae speciales of
F. oxysporum
. The putative mature
pg5
product has a calculated molecular mass of 35 kDa and a pI of 8.3 and is more closely related to endoPGs from other fungal plant pathogens than to PG1, the major endoPG of
F. oxysporum
. Overexpression of
pg5
in a bacterial heterologous system produced a 35-kDa protein with endoPG activity. Accumulation of
pg5
transcript is induced by citrus pectin and
d
-galacturonic acid and repressed by glucose. As shown by reverse transcription-PCR,
pg5
is expressed by
F. oxysporum
in tomato roots during the initial stages of infection. Targeted inactivation of
pg5
has no detectable effect on virulence toward tomato plants.
Survival of
Campylobacter jejuni
during Stationary Phase: Evidence for the Absence of a Phenotypic Stationary-Phase Response
Authors: Kelly Alison F. , Park Simon F. , Bovill Richard , Mackey Bernard M.
Published: July 2002

When
Campylobacter jejuni
NCTC 11351 was grown microaerobically in rich medium at 39°C, entry into stationary phase was followed by a rapid decline in viable numbers to leave a residual population of 1% of the maximum number or less. Loss of viability was preceded by sublethal injury, which was seen as a loss of the ability to grow on media containing 0.1% sodium deoxycholate or 1% sodium chloride. Resistance of cells to mild heat stress (50°C) or aeration was greatest in exponential phase and declined during early stationary phase. These results show that
C. jejuni
does not mount the normal phenotypic stationary-phase response which results in enhanced stress resistance. This conclusion is consistent with the absence of
rpoS
homologues in the recently reported genome sequence of this species and their probable absence from strain NCTC 11351. During prolonged incubation of
C. jejuni
NCTC 11351 in stationary phase, an unusual pattern of decreasing and increasing heat resistance was observed that coincided with fluctuations in the viable count. During stationary phase of
Campylobacter coli
UA585, nonmotile variants and those with impaired ability to form coccoid cells were isolated at high frequency. Taken together, these observations suggest that stationary-phase cultures of campylobacters are dynamic populations and that this may be a strategy to promote survival in at least some strains. Investigation of two spontaneously arising variants (NM3 and SC4) of
C. coli
UA585 showed that a reduced ability to form coccoid cells did not affect survival under nongrowth conditions.
16S Ribosomal DNA Characterization of Nitrogen-Fixing Bacteria Isolated from Banana (
Musa
spp.) and Pineapple (
Ananas comosus
(L.) Merril)
Authors: Magalhães Cruz Leonardo , Maltempi de Souza Emanuel , Weber Olmar Baler , Baldani José Ivo , Döbereiner Johanna , de Oliveira Pedrosa Fábio
Published: July 2002

Nitrogen-fixing bacteria isolated from banana (
Musa
spp.) and pineapple (
Ananas comosus
(L.) Merril) were characterized by amplified 16S ribosomal DNA restriction analysis and 16S rRNA sequence analysis.
Herbaspirillum seropedicae
,
Herbaspirillum rubrisubalbicans
,
Burkholderia brasilensis,
and
Burkholderia tropicalis
were identified. Eight other types were placed in close proximity to these genera and other alpha and beta
Proteobacteria
.
Comparison of Genotypes and Serotypes of
Campylobacter jejuni
Isolated from Danish Wild Mammals and Birds and from Broiler Flocks and Humans
Authors: Petersen L. , Nielsen E. M. , Engberg J. , On S. L. W. , Dietz H. H.
Published: July 2002

The incidence of human infection with
Campylobacter jejuni
is increasing in most developed countries and the reason for this is largely unknown. Although poultry meat is considered to be a major source, it is evident that other reservoirs exist, possibly common to humans and poultry. Environmental sources are believed to be important reservoirs of
Campylobacter
infection in broiler chicken flocks. We investigated the potential importance of wildlife as a source of infection in commercial poultry flocks and in humans by comparing the serotype distributions,
fla
types, and macrorestriction profiles (MRPs) of
C. jejuni
isolates from different sources. The serotype distribution in wildlife was significantly different from the known distributions in broilers and humans. Considerable sero- and genotype diversity was found within the wildlife collection, although two major groups of isolates within serotype O:12 and the O:4 complex were found. Common clonal lines among wildlife, chicken, and/or human isolates were identified within serotype O:2 and the O:4 complex. However, MRPs of O:12 and O:38 strains isolated from wildlife and other sources indicated that some clonal lines propagated in a wide selection of animal species but were not detected in humans or broilers in this study. The applied typing methods successfully identified different clonal groups within a strain collection showing large genomic diversity. However, the relatively low number of wildlife strains with an inferred clonal relationship to human and chicken strains suggests that the importance of wildlife as a reservoir of infection is limited.
Bioremediation (Natural Attenuation and Biostimulation) of Diesel-Oil-Contaminated Soil in an Alpine Glacier Skiing Area
Authors: Margesin R. , Schinner F.
Published: July 2002

We investigated the feasibility of bioremediation as a treatment option for a chronically diesel-oil-polluted soil in an alpine glacier area at an altitude of 2,875 m above sea level. To examine the efficiencies of natural attenuation and biostimulation, we used field-incubated lysimeters (mesocosms) with unfertilized and fertilized (N-P-K) soil. For three summer seasons (July 1997 to September 1999), we monitored changes in hydrocarbon concentrations in soil and soil leachate and the accompanying changes in soil microbial counts and activity. A significant reduction in the diesel oil level could be achieved. At the end of the third summer season (after 780 days), the initial level of contamination (2,612 ± 70 μg of hydrocarbons g [dry weight] of soil
−1
) was reduced by (50 ± 4)% and (70 ± 2)% in the unfertilized and fertilized soil, respectively. Nonetheless, the residual levels of contamination (1,296 ± 110 and 774 ± 52 μg of hydrocarbons g [dry weight] of soil
−1
in the unfertilized and fertilized soil, respectively) were still high. Most of the hydrocarbon loss occurred during the first summer season ([42 ± 6]% loss) in the fertilized soil and during the second summer season ([41 ± 4]% loss) in the unfertilized soil. In the fertilized soil, all biological parameters (microbial numbers, soil respiration, catalase and lipase activities) were significantly enhanced and correlated significantly with each other, as well as with the residual hydrocarbon concentration, pointing to the importance of biodegradation. The effect of biostimulation of the indigenous soil microorganisms declined with time. The microbial activities in the unfertilized soil fluctuated around background levels during the whole study.
Development of a Quantitative Competitive PCR Assay for Detection and Quantification of
Escherichia coli
O157:H7 Cells
Authors: Li Wenli , Drake Mary Anne
Published: July 2002

A quantitative competitive PCR (QC-PCR) assay was developed to detect and quantify
Escherichia coli
O157:H7 cells. From 10
3
to 10
8
CFU of
E. coli
O157:H7 cells/ml was quantified in broth or skim milk, and cell densities predicted by QC-PCR were highly related to viable cell counts (
r
2
= 0.99 and 0.93, respectively). QC-PCR has potential for quantitative detection of pathogenic bacteria in foods.
Antibiotic Resistance in
Salmonella enterica
Serovar Typhimurium Exposed to Microcin-Producing
Escherichia coli
Authors: Carlson Steve A. , Frana Timothy S. , Griffith Ronald W.
Published: July 2002

Microcin 24 is an antimicrobial peptide secreted by uropathogenic
Escherichia coli
. Secretion of microcin 24 provides an antibacterial defense mechanism for
E. coli
. In a plasmid-based system using transformed
Salmonella enterica
, we found that resistance to microcin 24 could be seen in concert with a multiple-antibiotic resistance phenotype. This multidrug-resistant phenotype appeared when
Salmonella
was exposed to an
E. coli
strain expressing microcin 24. Therefore, it appears that multidrug-resistant
Salmonella
can arise as a result of an insult from other pathogenic bacteria.
Purification and Characterization of Thermostable Endo-1,5-α-
l
-Arabinase from a Strain of
Bacillus thermodenitrificans
Authors: Takao Makoto , Akiyama Kana , Sakai Takuo
Published: July 2002

A strain of a thermophilic bacterium, tentatively designated
Bacillus thermodenitrificans
TS-3, with arabinan-degrading activity was isolated. It produced an endo-arabinase (ABN) (EC 3.2.1.99) and two arabinofuranosidases (EC 3.2.1.55) extracellularly when grown at 60°C on a medium containing sugar beet arabinan. The ABN (tentatively called an ABN-TS) was purified 7,417-fold by anion-exchange, hydrophobic, size exclusion, and hydroxyapatite chromatographies. The molecular mass of ABN-TS was 35 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the isoelectric point was pH 4.5. The enzyme was observed to be more thermostable than known ABNs; it had a half-life of 4 h at 75°C. The enzyme had optimal activity at 70°C and pH 6.0. The enzyme had apparent

K
m

values of 8.5 and 45 mg/ml and apparent
V
max
values of 1.6 and 1.1 mmol/min/mg of protein against debranched arabinan (α-1,5-arabinan) and arabinan, respectively. The enzyme had no pectin-releasing activity (protopectinase activity) from sugar beet protopectin, differing from an ABN (protopectinase-C) from mesophilic
Bacillus subtilis
IFO 3134. The pattern of degradation of debranched arabinan by ABN-TS indicated that the enzyme was an endo-acting enzyme and the main end products were arabinobiose and arabinose. The results of preliminary experiments indicated that the culture filtrate of strain TS-3 is suitable for
l
-arabinose production from sugar beet pulp at high temperature.