bluuebunny/crossref_metadata_2025 huggingface dataset:
A Tobacco Syntaxin with a Role in Hormonal Control of Guard Cell Ion Channels
Authors: Leyman Barbara , Geelen Danny , Quintero Francisco J. , Blatt Michael R.
Published: July 2002

The plant hormone abscisic acid (ABA) regulates potassium and chloride ion channels at the plasma membrane of guard cells, leading to stomatal closure that reduces transpirational water loss from the leaf. The tobacco
Nt-SYR1
gene encodes a syntaxin that is associated with the plasma membrane. Syntaxins and related SNARE proteins aid intracellular vesicle trafficking, fusion, and secretion. Disrupting Nt-Syr1 function by cleavage with
Clostridium botulinum
type C toxin or competition with a soluble fragment of Nt-Syr1 prevents potassium and chloride ion channel response to ABA in guard cells and implicates Nt-Syr1 in an ABA-signaling cascade.
A View from Switzerland
Authors: Desplan Claude
Published: July 2002

Master Control Genes in Development and Evolution
The Homeobox Story. Walter J. Gehring. Yale University Press, New Haven, CT, 1999. 254 pp. $35. ISBN 0-300-07409-3.

In this combination of historical perspective and textbook, Gehring gives a precise personal view of his intellectual lineage and a more detailed (and difficult) survey of different modes of development in animals ranging from worms to mice.
Heart-Making Details
Authors: Wolpert Lewis
Published: July 2002

Heart Development
. Richard P. Harvey and Nadia Rosenthal, Eds. Academic, San Diego, 1999. 550 pp. $159.95. ISBN 0-12-329860-1.

Results from modern molecular and classical embryological analyses of model vertebrate species are used to document our current understanding of the complex processes that shape normal and aberrant hearts.
A Kuroko-Type Polymetallic Sulfide Deposit in a Submarine Silicic Caldera
Authors: Iizasa K. , Fiske R. S. , Ishizuka O. , Yuasa M. , Hashimoto J. , Ishibashi J. , Naka J. , Horii Y. , Fujiwara Y. , Imai A. , Koyama S.
Published: July 2002

Manned submersible studies have delineated a large and actively growing Kuroko-type volcanogenic massive sulfide deposit 400 kilometers south of Tokyo in Myojin Knoll submarine caldera. The sulfide body is located on the caldera floor at a depth of 1210 to 1360 meters, has an area of 400 by 400 by 30 meters, and is notably rich in gold and silver. The discovery of a large Kuroko-type polymetallic sulfide deposit in this arc-front caldera raises the possibility that the numerous unexplored submarine silicic calderas elsewhere might have similar deposits.
Quantum-Well States as Fabry-Pérot Modes in a Thin-Film Electron Interferometer
Authors: Paggel J. J. , Miller T. , Chiang T.-C.
Published: July 2002

Angle-resolved photoemission from atomically uniform silver films on iron (100) shows quantum-well states for absolutely determined film thicknesses ranging from 1 to ∼100 monolayers. These states can be understood in terms of Fabry-Pérot modes in an electron interferometer. A quantitative line shape analysis over the entire two orders of magnitude of thickness range yields an accurate measurement of the band structure, quasiparticle lifetime, electron reflectivity, and phase shift. Effects of confinement energy gap, reflection loss, and surface scattering caused by controlled roughness are demonstrated.
Truncated RanGAP Encoded by the
Segregation Distorter
Locus of
Drosophila
Authors: Merrill Cynthia , Bayraktaroglu Leyla , Kusano Ayumi , Ganetzky Barry
Published: July 2002

Segregation Distorter
(
SD
) in
Drosophila melanogaster
is a naturally occurring meiotic drive system in which the
SD
chromosome is transmitted from
SD/SD
+
males in vast excess over its homolog owing to the induced dysfunction of
SD
+
-bearing spermatids. The
Sd
locus is the key distorting gene responsible for this phenotype. A genomic fragment from the
Sd
region conferred full distorting activity when introduced into the appropriate genetic background by germline transformation. The only functional product encoded by this fragment is a truncated version of the RanGAP nuclear transport protein. These results demonstrate that this mutant RanGAP is the functional
Sd
product.
Streamlined Complexity
Authors: Hanski Ilkka
Published: July 2002

Untangling Ecological Complexity
The Macroscopic Perspective. Brian A. Maurer. University of Chicago Press, Chicago, 1999. 261 pp. $50, £39.95. ISBN 0-226-51132-4. Paper, $18, £14.50. ISBN 0-226-51133-2.

Focusing on testable, quantitative models, Maurer provides a framework for linking population, community, and ecosystem ecology with biogeography and evolutionary biology. He offers an approach for applying wider spatial and temporal perspectives to problems in ecology and conservation biology (such as the impact of global climate changes on biodiversity).
Undetectable Intracellular Free Copper: The Requirement of a Copper Chaperone for Superoxide Dismutase
Authors: Rae T. D. , Schmidt P. J. , Pufahl R. A. , Culotta V. C. , V. O'Halloran T.
Published: July 2002

The copper chaperone for the superoxide dismutase (CCS) gene is necessary for expression of an active, copper-bound form of superoxide dismutase (SOD1) in vivo in spite of the high affinity of SOD1 for copper (dissociation constant = 6 fM) and the high intracellular concentrations of both SOD1 (10 μM in yeast) and copper (70 μM in yeast). In vitro studies demonstrated that purified Cu(I)-yCCS protein is sufficient for direct copper activation of apo-ySOD1 but is necessary only when the concentration of free copper ions ([Cu]
free
) is strictly limited. Moreover, the physiological requirement for yCCS in vivo was readily bypassed by elevated copper concentrations and abrogation of intracellular copper-scavenging systems such as the metallothioneins. This metallochaperone protein activates the target enzyme through direct insertion of the copper cofactor and apparently functions to protect the metal ion from binding to intracellular copper scavengers. These results indicate that intracellular [Cu]
free
is limited to less than one free copper ion per cell and suggest that a pool of free copper ions is not used in physiological activation of metalloenzymes.
Distinct Pathogenic Sequela in Rhesus Macaques Infected with CCR5 or CXCR4 Utilizing SHIVs
Authors: Harouse Janet M. , Gettie Agegnehu , Tan Rei Chin How , Blanchard James , Cheng-Mayer Cecilia
Published: July 2002

Infection of macaques with chimeric simian–human immunodeficiency virus (SHIV) provides an excellent in vivo model for examining the influence of envelope on HIV-1 pathogenesis. Infection with a pathogenic CCR5 (R5)–specific enveloped virus, SHIV
SF162P
, was compared with infection with the CXCR4 (X4)–specific SHIV
SF33A.2
. Despite comparable levels of viral replication, animals infected with the R5 and X4 SHIV had distinct pathogenic outcomes. SHIV
SF162P
caused a dramatic loss of CD4
+
intestinal T cells followed by a gradual depletion in peripheral CD4
+
T cells, whereas infection with SHIV
SF33A.2
caused a profound loss in peripheral T cells that was not paralleled in the intestine. These results suggest a critical role of co-receptor utilization in viral pathogenesis and provide a reliable in vivo model for preclinical examination of HIV-1 vaccines and therapeutic agents in the context of the HIV-1 envelope protein.
Cloning Genes Encoding MHC Class II-Restricted Antigens: Mutated CDC27 as a Tumor Antigen
Authors: Wang Rong-Fu , Wang Xiang , Atwood Alicia C. , Topalian Suzanne L. , Rosenberg Steven A.
Published: July 2002

In an effort to identify tumor-specific antigens recognized by CD4
+
T cells, an approach was developed that allows the screening of an invariant chain–complementary DNA fusion library in a genetically engineered cell line expressing the essential components of the major histocompatibility complex (MHC) class II processing and presentation pathway. This led to the identification of a mutated form of human CDC27, which gave rise to an HLA-DR4–restricted melanoma antigen. A mutated form of triosephosphate isomerase, isolated by a biochemical method, was also identified as an HLA-DR1–restricted antigen. Thus, this approach may be generally applicable to the identification of antigens recognized by CD4
+
T cells, which could aid the development of strategies for the treatment of patients with cancer, autoimmune diseases, or infectious diseases.
The Nature of the Principal Type 1 Interferon-Producing Cells in Human Blood
Authors: Siegal Frederick P. , Kadowaki Norimitsu , Shodell Michael , Fitzgerald-Bocarsly Patricia A. , Shah Kokila , Ho Stephen , Antonenko Svetlana , Liu Yong-Jun
Published: July 2002

Interferons (IFNs) are the most important cytokines in antiviral immune responses. “Natural IFN-producing cells” (IPCs) in human blood express CD4 and major histocompatibility complex class II proteins, but have not been isolated and further characterized because of their rarity, rapid apoptosis, and lack of lineage markers. Purified IPCs are here shown to be the CD4
+
CD11c
−
type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge. pDC2s are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.
Xyloglucan Fucosyltransferase, an Enzyme Involved in Plant Cell Wall Biosynthesis
Authors: Perrin Robyn M. , DeRocher Amy E. , Bar-Peled Maor , Zeng Weiqing , Norambuena Lorena , Orellana Ariel , Raikhel Natasha V. , Keegstra Kenneth
Published: July 2002

Cell walls are crucial for development, signal transduction, and disease resistance in plants. Cell walls are made of cellulose, hemicelluloses, and pectins. Xyloglucan (XG), the principal load-bearing hemicellulose of dicotyledonous plants, has a terminal fucosyl residue. A 60-kilodalton fucosyltransferase (FTase) that adds this residue was purified from pea epicotyls. Peptide sequence information from the pea FTase allowed the cloning of a homologous gene,
AtFT1
, from
Arabidopsis
. Antibodies raised against recombinant AtFTase immunoprecipitate FTase enzyme activity from solubilized
Arabidopsis
membrane proteins, and
AtFT1
expressed in mammalian COS cells results in the presence of XG FTase activity in these cells.
Climate and Satellite Indicators to Forecast Rift Valley Fever Epidemics in Kenya
Authors: Linthicum Kenneth J. , Anyamba Assaf , Tucker Compton J. , Kelley Patrick W. , Myers Monica F. , Peters Clarence J.
Published: July 2002

All known Rift Valley fever virus outbreaks in East Africa from 1950 to May 1998, and probably earlier, followed periods of abnormally high rainfall. Analysis of this record and Pacific and Indian Ocean sea surface temperature anomalies, coupled with satellite normalized difference vegetation index data, shows that prediction of Rift Valley fever outbreaks may be made up to 5 months in advance of outbreaks in East Africa. Concurrent near–real-time monitoring with satellite normalized difference vegetation data may identify actual affected areas.
An Activating Immunoreceptor Complex Formed by NKG2D and DAP10
Authors: Wu Jun , Song Yaoli , Bakker Alexander B. H. , Bauer Stefan , Spies Thomas , Lanier Lewis L. , Phillips Joseph H.
Published: July 2002

Many immune receptors are composed of separate ligand-binding and signal-transducing subunits. In natural killer (NK) and T cells, DAP10 was identified as a cell surface adaptor protein in an activating receptor complex with NKG2D, a receptor for the stress-inducible and tumor-associated major histocompatibility complex molecule MICA. Within the DAP10 cytoplasmic domain, an Src homology 2 (SH2) domain–binding site was capable of recruiting the p85 subunit of the phosphatidylinositol 3-kinase (PI 3-kinase), providing for NKG2D-dependent signal transduction. Thus, NKG2D-DAP10 receptor complexes may activate NK and T cell responses against MICA-bearing tumors.
The Promise of Comparative Genomics in Mammals
Authors: O'Brien Stephen J. , Menotti-Raymond Marilyn , Murphy William J. , Nash William G. , Wienberg Johannes , Stanyon Roscoe , Copeland Neal G. , Jenkins Nancy A. , Womack James E. , Marshall Graves Jennifer A.
Published: July 2002

Dense genetic maps of human, mouse, and rat genomes that are based on coding genes and on microsatellite and single-nucleotide polymorphism markers have been complemented by precise gene homolog alignment with moderate-resolution maps of livestock, companion animals, and additional mammal species. Comparative genetic assessment expands the utility of these maps in gene discovery, in functional genomics, and in tracking the evolutionary forces that sculpted the genome organization of modern mammalian species.
Negative Feedback Regulation of TGF-β Signaling by the SnoN Oncoprotein
Authors: Stroschein Shannon L. , Wang Wei , Zhou Sharleen , Zhou Qiang , Luo Kunxin
Published: July 2002

Smad proteins mediate transforming growth factor–β (TGF-β) signaling to regulate cell growth and differentiation. The SnoN oncoprotein was found to interact with Smad2 and Smad4 and to repress their abilities to activate transcription through recruitment of the transcriptional corepressor N-CoR. Immediately after TGF-β stimulation, SnoN is rapidly degraded by the nuclear accumulation of Smad3, allowing the activation of TGF-β target genes. By 2 hours, TGF-β induces a marked increase in SnoN expression, resulting in termination of Smad-mediated transactivation. Thus, SnoN maintains the repressed state of TGF-β–responsive genes in the absence of ligand and participates in negative feedback regulation of TGF-β signaling.
Cell Survival Promoted by the Ras-MAPK Signaling Pathway by Transcription-Dependent and -Independent Mechanisms
Authors: Bonni Azad , Brunet Anne , West Anne E. , Datta Sandeep Robert , Takasu Mari A. , Greenberg Michael E.
Published: July 2002

A mechanism by which the Ras–mitogen-activated protein kinase (MAPK) signaling pathway mediates growth factor–dependent cell survival was characterized. The MAPK-activated kinases, the Rsks, catalyzed the phosphorylation of the pro-apoptotic protein BAD at serine 112 both in vitro and in vivo. The Rsk-induced phosphorylation of BAD at serine 112 suppressed BAD-mediated apoptosis in neurons. Rsks also are known to phosphorylate the transcription factor CREB (cAMP response element–binding protein) at serine 133. Activated CREB promoted cell survival, and inhibition of CREB phosphorylation at serine 133 triggered apoptosis. These findings suggest that the MAPK signaling pathway promotes cell survival by a dual mechanism comprising the posttranslational modification and inactivation of a component of the cell death machinery and the increased transcription of pro-survival genes.
Single-Bond Formation and Characterization with a Scanning Tunneling Microscope
Authors: Lee H. J. , Ho W.
Published: July 2002

A scanning tunneling microscope (STM) was used to manipulate the bonding of a carbon monoxide (CO) molecule and to analyze the structure and vibrational properties of individual products. Individual iron (Fe) atoms were evaporated and coadsorbed with CO molecules on a silver (110) surface at 13 kelvin. A CO molecule was transferred from the surface to the STM tip and bonded with an Fe atom to form Fe(CO). A second CO molecule was similarly transferred and bonded with Fe(CO) to form Fe(CO)
2
. Controlled bond formation and characterization at the single-bond level probe chemistry at the spatial limit.
Microarray Analysis of
Drosophila
Development During Metamorphosis
Authors: White Kevin P. , Rifkin Scott A. , Hurban Patrick , Hogness David S.
Published: July 2002

Metamorphosis is an integrated set of developmental processes controlled by a transcriptional hierarchy that coordinates the action of hundreds of genes. In order to identify and analyze the expression of these genes, high-density DNA microarrays containing several thousand
Drosophila melanogaster
gene sequences were constructed. Many differentially expressed genes can be assigned to developmental pathways known to be active during metamorphosis, whereas others can be assigned to pathways not previously associated with metamorphosis. Additionally, many genes of unknown function were identified that may be involved in the control and execution of metamorphosis. The utility of this genome-based approach is demonstrated for studying a set of complex biological processes in a multicellular organism.
Induction of Nitric Oxide -- Dependent Apoptosis in Motor Neurons by Zinc-Deficient Superoxide Dismutase
Authors: Estévez Alvaro G. , Crow John P. , Sampson Jacinda B. , Reiter Christopher , Zhuang Yingxin , Richardson Gloria J. , Tarpey Margaret M. , Barbeito Luis , Beckman Joseph S.
Published: July 2002

Mutations in copper, zinc superoxide dismutase (SOD) have been implicated in the selective death of motor neurons in 2 percent of amyotrophic lateral sclerosis (ALS) patients. The loss of zinc from either wild-type or ALS-mutant SODs was sufficient to induce apoptosis in cultured motor neurons. Toxicity required that copper be bound to SOD and depended on endogenous production of nitric oxide. When replete with zinc, neither ALS-mutant nor wild-type copper, zinc SODs were toxic, and both protected motor neurons from trophic factor withdrawal. Thus, zinc-deficient SOD may participate in both sporadic and familial ALS by an oxidative mechanism involving nitric oxide.
Requirement of CD9 on the Egg Plasma Membrane for Fertilization
Authors: Miyado Kenji , Yamada Gen , Yamada Shuichi , Hasuwa Hidetoshi , Nakamura Yasuhiro , Ryu Fuminori , Suzuki Kentaro , Kosai Kenichiro , Inoue Kimiko , Ogura Atsuo , Okabe Masaru , Mekada Eisuke
Published: July 2002

CD9 is an integral membrane protein associated with integrins and other membrane proteins. Mice lacking CD9 were produced by homologous recombination. Both male and female CD9
−/−
mice were born healthy and grew normally. However, the litter size from CD9
−/−
females was less than 2% of that of the wild type. In vitro fertilization experiments indicated that the cause of this infertility was due to the failure of sperm-egg fusion. When sperm were injected into oocytes with assisted microfertilization techniques, however, the fertilized eggs developed to term. These results indicate that CD9 has a crucial role in sperm-egg fusion.
Single-File Diffusion of Colloids in One-Dimensional Channels
Authors: Wei Q.-H. , Bechinger C. , Leiderer P.
Published: July 2002

Single-file diffusion, prevalent in many processes, refers to the restricted motion of interacting particles in narrow micropores with the mutual passage excluded. A single-filing system was developed by confining colloidal spheres in one-dimensional circular channels of micrometer scale. Optical video microscopy study shows evidence that the particle self-diffusion is non-Fickian for long periods of time. In particular, the distribution of particle displacement is a Gaussian function.
Honeybee Navigation: Nature and Calibration of the "Odometer"
Authors: Srinivasan Mandyan V. , Zhang Shaowu , Altwein Monika , Tautz Jürgen
Published: July 2002

There are two theories about how honeybees estimate the distance to food sources. One theory proposes that distance flown is estimated in terms of energy consumption
.
The other suggests that the cue is visual, and is derived from the extent to which the image of the world has moved on the eye during the trip. Here the two theories are tested by observing dances of bees that have flown through a short, narrow tunnel to collect a food reward. The results show that the honeybee's “odometer” is visually driven. They also provide a calibration of the dance and the odometer in visual terms.
Secular Variation of Iron Isotopes in North Atlantic Deep Water
Authors: Zhu Xiang-Kun , O'Nions R. Keith , Guo Yueling , Reynolds Ben C.
Published: July 2002

A high-precision iron isotope time series for a ferromanganese crust demonstrates that the iron isotope composition in North Atlantic Deep Water has changed substantially over the past 6 million years and that iron isotope variations in the crust are closely correlated to those of lead isotopes. The close correlation between the two isotope series indicates that the observed iron isotope variations predominantly reflect those of iron input from terrigenous sources and provides no evidence for biologically induced mass fractionation within North Atlantic Deep Water.
Identification of a Coordinate Regulator of Interleukins 4, 13, and 5 by Cross-Species Sequence Comparisons
Authors: Loots G. G. , Locksley R. M. , Blankespoor C. M. , Wang Z. E. , Miller W. , Rubin E. M. , Frazer K. A.
Published: July 2002

Long-range regulatory elements are difficult to discover experimentally; however, they tend to be conserved among mammals, suggesting that cross-species sequence comparisons should identify them. To search for regulatory sequences, we examined about 1 megabase of orthologous human and mouse sequences for conserved noncoding elements with greater than or equal to 70% identity over at least 100 base pairs. Ninety noncoding sequences meeting these criteria were discovered, and the analysis of 15 of these elements found that about 70% were conserved across mammals. Characterization of the largest element in yeast artificial chromosome transgenic mice revealed it to be a coordinate regulator of three genes,
interleukin-4
,
interleukin-13
, and
interleukin-5
, spread over 120 kilobases.
Specialized Fatty Acid Synthesis in African Trypanosomes: Myristate for GPI Anchors
Authors: Morita Yasu S. , Paul Kimberly S. , Englund Paul T.
Published: July 2002

African trypanosomes, the cause of sleeping sickness, need massive amounts of myristate to remodel glycosyl phosphatidylinositol (GPI) anchors on their surface glycoproteins. However, it has been believed that the parasite is unable to synthesize any fatty acids, and myristate is not abundant in the hosts' bloodstreams. Thus, it has been unclear how trypanosomes meet their myristate requirement. Here we found that they could indeed synthesize fatty acids. The synthetic pathway was unique in that the major product, myristate, was preferentially incorporated into GPIs and not into other lipids. The antibiotic thiolactomycin inhibited myristate synthesis and killed the parasite, making this pathway a potential chemotherapeutic target.
Ubiquitin Protein Ligase Activity of IAPs and Their Degradation in Proteasomes in Response to Apoptotic Stimuli
Authors: Yang Yili , Fang Shengyun , Jensen Jane P. , Weissman Allan M. , Ashwell Jonathan D.
Published: July 2002

To determine why proteasome inhibitors prevent thymocyte death, we examined whether proteasomes degrade anti-apoptotic molecules in cells induced to undergo apoptosis. The c-IAP1 and XIAP inhibitors of apoptosis were selectively lost in glucocorticoid- or etoposide-treated thymocytes in a proteasome-dependent manner before death. IAPs catalyzed their own ubiquitination in vitro, an activity requiring the RING domain. Overexpressed wild-type c-IAP1, but not a RING domain mutant, was spontaneously ubiquitinated and degraded, and stably expressed XIAP lacking the RING domain was relatively resistant to apoptosis-induced degradation and, correspondingly, more effective at preventing apoptosis than wild-type XIAP. Autoubiquitination and degradation of IAPs may be a key event in the apoptotic program.
The Nature of Pristine Noble Gases in Mantle Plumes
Authors: Trieloff Mario , Kunz Joachim , Clague David A. , Harrison Darrell , Allègre Claude J.
Published: July 2002

High-precision noble gas data show that the Hawaiian and Icelandic mantle plume sources contain uniquely primitive neon that is composed of moderately nucleogenic neon-21 and a primordial component indistinguishable from the meteoritic occurrence of solar neon. This suggests that Earth's solar-type rare gas inventory was acquired during accretion from small planetesimals previously irradiated by solar wind from the early sun. However, nonradiogenic argon, krypton, and xenon isotopes derived from the mantle display nonsolar compositions and indicate an atmosphere-like fingerprint that is not due to recent subduction.
Spatial Patterns in the Distribution of Tropical Tree Species
Authors: Condit Richard , Ashton Peter S. , Baker Patrick , Bunyavejchewin Sarayudh , Gunatilleke Savithri , Gunatilleke Nimal , Hubbell Stephen P. , Foster Robin B. , Itoh Akira , LaFrankie James V. , Lee Hua Seng , Losos Elizabeth , Manokaran N. , Sukumar R. , Yamakura Takuo
Published: July 2002

Fully mapped tree census plots of large area, 25 to 52 hectares, have now been completed at six different sites in tropical forests, including dry deciduous to wet evergreen forest on two continents. One of the main goals of these plots has been to evaluate spatial patterns in tropical tree populations. Here the degree of aggregation in the distribution of 1768 tree species is examined based on the average density of conspecific trees in circular neighborhoods around each tree. When all individuals larger than 1 centimeter in stem diameter were included, nearly every species was more aggregated than a random distribution. Considering only larger trees (≥ 10 centimeters in diameter), the pattern persisted, with most species being more aggregated than random. Rare species were more aggregated than common species. All six forests were very similar in all the particulars of these results.
Regulation of B Lymphocyte and Macrophage Development by Graded Expression of PU.1
Authors: DeKoter Rodney P. , Singh Harinder
Published: July 2002

The ets family transcription factor PU.1 is required for the development of multiple lineages of the immune system. Using retroviral transduction of
PU.1
complementary DNA into mutant hematopoietic progenitors, we demonstrate that differing concentrations of the protein regulate the development of B lymphocytes as compared with macrophages. A low concentration of PU.1 protein induces the B cell fate, whereas a high concentration promotes macrophage differentiation and blocks B cell development. Conversely, a transcriptionally weakened mutant protein preferentially induces B cell generation. Our results suggest that graded expression of a transcription factor can be used to specify distinct cell fates in the hematopoietic system.
Lack of a Role for Iron in the Lyme Disease Pathogen
Authors: Posey James E. , Gherardini Frank C.
Published: July 2002

A fundamental tenet of microbial pathogenesis is that bacterial pathogens must overcome host iron limitation to establish a successful infection. Surprisingly, the Lyme disease pathogen
Borrelia burgdorferi
has bypassed this host defense by eliminating the need for iron.
B. burgdorferi
grew normally and did not alter gene expression in the presence of iron chelators. Furthermore, typical bacterial iron-containing proteins were not detected in cell lysates, nor were the genes encoding such proteins identified in the genome sequence. The intracellular concentration of iron in
B. burgdorferi
was estimated to be less than 10 atoms per cell, well below a physiologically relevant concentration.
A Nanoplotter with Both Parallel and Serial Writing Capabilities
Authors: Hong Seunghun , Mirkin Chad A.
Published: July 2002

The development of an eight-pen nanoplotter capable of doing parallel dip-pen nanolithography (DPN) is reported. Because line width and patterning speed in DPN are independent of contact force, only one of the tips in the parallel writing mode (the “imaging” tip) has a feedback system to monitor tip position and to write the pattern; all other tips reproduce what occurs at the imaging tip in a passive fashion. Proof-of-concept experiments that demonstrate eight-pen parallel writing, ink and rinsing wells, and “molecular corralling” via a nanoplotter-generated structure are reported.
Signaling Specificity by Frizzled Receptors in
Drosophila
Authors: Boutros Michael , Mihaly Jozsef , Bouwmeester Tewis , Mlodzik Marek
Published: July 2002

Wnt-Frizzled (Fz) signaling pathways play recurring important roles during the development and homeostasis of vertebrates and invertebrates. Fz receptors can signal through β-catenin–dependent and –independent pathways. In
Drosophila
, Fz and Fz2 are redundant receptors for Wg. In addition, Fz conveys signals through a distinct pathway to organize planar polarization of epithelial structures. We demonstrate that the cytoplasmic sequences of Fz2 and Fz preferentially activate the β-catenin and planar polarity cascade, respectively. Both receptors activate either pathway, but with different efficiencies. Intrinsic differences in signaling efficiency in closely related receptors might be a general mechanism for generating signaling specificity in vivo.
Requirement of Mis6 Centromere Connector for Localizing a CENP-A-Like Protein in Fission Yeast
Authors: Takahashi Kohta , Chen Ee Sin , Yanagida Mitsuhiro
Published: July 2002

Mammalian kinetochores contain the centromere-specific histone H3 variant CENP-A, whose incorporation into limited chromosomal regions may be important for centromere function and chromosome segregation during mitosis. However, regulation of CENP-A localization and its role have not been clear. Here we report that the fission yeast homolog SpCENP-A is essential for establishing centromere chromatin associated with equal chromosome segregation. SpCENP-A binding to the nonrepetitious inner centromeres depended on Mis6, an essential centromere connector protein acting during G
1
-S phase of the cell cycle. Mis6 is likely required for recruiting SpCENP-A to form proper connection of sister centromeres.
An All-Dielectric Coaxial Waveguide
Authors: Ibanescu M. , Fink Y. , Fan S. , Thomas E. L. , Joannopoulos J. D.
Published: July 2002

An all-dielectric coaxial waveguide that can overcome problems of polarization rotation and pulse broadening in the transmission of optical light is presented here. It consists of a coaxial waveguiding region with a low index of refraction, bounded by two cylindrical, dielectric, multilayer, omnidirectional reflecting mirrors. The waveguide can be designed to support a single mode whose properties are very similar to the unique transverse electromagnetic mode of a traditional metallic coaxial cable. The new mode has radial symmetry and a point of zero dispersion. Moreover, because the light is not confined by total internal reflection, the waveguide can guide light around very sharp corners.
One Sequence, Two Ribozymes: Implications for the Emergence of New Ribozyme Folds
Authors: Schultes Erik A. , Bartel David P.
Published: July 2002

We describe a single RNA sequence that can assume either of two ribozyme folds and catalyze the two respective reactions. The two ribozyme folds share no evolutionary history and are completely different, with no base pairs (and probably no hydrogen bonds) in common. Minor variants of this sequence are highly active for one or the other reaction, and can be accessed from prototype ribozymes through a series of neutral mutations. Thus, in the course of evolution, new RNA folds could arise from preexisting folds, without the need to carry inactive intermediate sequences. This raises the possibility that biological RNAs having no structural or functional similarity might share a common ancestry. Furthermore, functional and structural divergence might, in some cases, precede rather than follow gene duplication.
A [2]Catenane-Based Solid State Electronically Reconfigurable Switch
Authors: Collier Charles P. , Mattersteig Gunter , Wong Eric W. , Luo Yi , Beverly Kristen , Sampaio José , Raymo Françisco M. , Stoddart J. Fraser , Heath James R.
Published: July 2002

A solid state, electronically addressable, bistable [2]catenane-based molecular switching device was fabricated from a single monolayer of the [2]catenane, anchored with phospholipid counterions, and sandwiched between an n-type polycrystalline silicon bottom electrode and a metallic top electrode. The device exhibits hysteretic (bistable) current/voltage characteristics. The switch is opened at +2 volts, closed at −2 volts, and read at ∼0.1 volt and may be recycled many times under ambient conditions. A mechanochemical mechanism for the action of the switch is presented and shown to be consistent with temperature-dependent measurements of the device operation.
Myotonic Dystrophy in Transgenic Mice Expressing an Expanded CUG Repeat
Authors: Mankodi Ami , Logigian Eric , Callahan Linda , McClain Carolyn , White Robert , Henderson Don , Krym Matt , Thornton Charles A.
Published: July 2002

Myotonic dystrophy (DM), the most common form of muscular dystrophy in adult humans, results from expansion of a CTG repeat in the 3′ untranslated region of the
DMPK
gene. The mutant
DMPK
messenger RNA (mRNA) contains an expanded CUG repeat and is retained in the nucleus. We have expressed an untranslated CUG repeat in an unrelated mRNA in transgenic mice. Mice that expressed expanded CUG repeats developed myotonia and myopathy, whereas mice expressing a nonexpanded repeat did not. Thus, transcripts with expanded CUG repeats are sufficient to generate a DM phenotype. This result supports a role for RNA gain of function in disease pathogenesis.
Signal Transduction Through Prion Protein
Authors: Mouillet-Richard S. , Ermonval M. , Chebassier C. , Laplanche J. L. , Lehmann S. , Launay J. M. , Kellermann O.
Published: July 2002

The cellular prion protein PrP
c
is a glycosylphosphatidylinositol-anchored cell-surface protein whose biological function is unclear. We used the murine 1C11 neuronal differentiation model to search for PrP
c
-dependent signal transduction through antibody-mediated cross-linking. A caveolin-1–dependent coupling of PrP
c
to the tyrosine kinase Fyn was observed. Clathrin might also contribute to this coupling. The ability of the 1C11 cell line to trigger PrP
c
-dependent Fyn activation was restricted to its fully differentiated serotonergic or noradrenergic progenies. Moreover, the signaling activity of PrP
c
occurred mainly at neurites. Thus, PrP
c
may be a signal transduction protein.
Dynamics of T Lymphocyte Responses: Intermediates, Effectors, and Memory Cells
Authors: Lanzavecchia Antonio , Sallusto Federica
Published: July 2002

The immune response is initiated in organized lymphoid tissues where antigen-loaded dendritic cells (DCs) encounter antigen-specific T cells. DCs function as packets of information that must be decoded by the T cell before an appropriate immune response can be mounted. We discuss how the dynamics of DC–T cell encounter and the mechanism of T cell differentiation make the decoding of this information stochastic rather than determinate. This results in the generation of both terminally differentiated effector cells and intermediates that play distinctive roles in protection, immunoregulation, and immunological memory.
The Fall, Recovery, Orbit, and Composition of the Tagish Lake Meteorite: A New Type of Carbonaceous Chondrite
Authors: Brown Peter G. , Hildebrand Alan R. , Zolensky Michael E. , Grady Monica , Clayton Robert N. , Mayeda Toshiko K. , Tagliaferri Edward , Spalding Richard , MacRae Neil D. , Hoffman Eric L. , Mittlefehldt David W. , Wacker John F. , Bird J. Andrew , Campbell Margaret D. , Carpenter Robert , Gingerich Heather , Glatiotis Michael , Greiner Erika , Mazur Michael J. , McCausland Phil JA. , Plotkin Howard , Mazur Tina Rubak
Published: July 2002

The preatmospheric mass of the Tagish Lake meteoroid was about 200,000 kilograms. Its calculated orbit indicates affinity to the Apollo asteroids with a semimajor axis in the middle of the asteroid belt, consistent with a linkage to low-albedo C, D, and P type asteroids. The mineralogy, oxygen isotope, and bulk chemical composition of recovered samples of the Tagish Lake meteorite are intermediate between CM and CI meteorites. These data suggest that the Tagish Lake meteorite may be one of the most primitive solar system materials yet studied.
Specific Mutations Induced by Triplex-Forming Oligonucleotides in Mice
Authors: Vasquez Karen M. , Narayanan Latha , Glazer Peter M.
Published: July 2002

Triplex-forming oligonucleotides (TFOs) recognize and bind to specific duplex DNA sequences and have been used extensively to modify gene function in cells. Although germ line mutations can be incorporated by means of embryonic stem cell technology, little progress has been made toward introducing mutations in somatic cells of living organisms. Here we demonstrate that TFOs can induce mutations at specific genomic sites in somatic cells of adult mice. Mutation detection was facilitated by the use of transgenic mice bearing chromosomal copies of the
supF
and
cII
reporter genes. Mice treated with a
supF
-targeted TFO displayed about fivefold greater mutation frequencies in the
supF
gene compared with mice treated with a scrambled sequence control oligomer. No mutagenesis was detected in the control gene (
cII
) with either oligonucleotide. These results demonstrate that site-specific, TFO-directed genome modification can be accomplished in intact animals.
Functional Requirement for Class I MHC in CNS Development and Plasticity
Authors: Huh Gene S. , Boulanger Lisa M. , Du Hongping , Riquelme Patricio A. , Brotz Tilmann M. , Shatz Carla J.
Published: July 2002

Class I major histocompatibility complex (class I MHC) molecules, known to be important for immune responses to antigen, are expressed also by neurons that undergo activity-dependent, long-term structural and synaptic modifications. Here, we show that in mice genetically deficient for cell surface class I MHC or for a class I MHC receptor component, CD3ζ, refinement of connections between retina and central targets during development is incomplete. In the hippocampus of adult mutants,
N
-methyl-
d
-aspartate receptor–dependent long-term potentiation (LTP) is enhanced, and long-term depression (LTD) is absent. Specific class I MHC messenger RNAs are expressed by distinct mosaics of neurons, reflecting a potential for diverse neuronal functions. These results demonstrate an important role for these molecules in the activity-dependent remodeling and plasticity of connections in the developing and mature mammalian central nervous system (CNS).
Transgenic Monkeys Produced by Retroviral Gene Transfer into Mature Oocytes
Authors: Chan A. W. S. , Chong K. Y. , Martinovich C. , Simerly C. , Schatten G.
Published: July 2002

Transgenic rhesus monkeys carrying the green fluorescent protein (GFP) gene were produced by injecting pseudotyped replication-defective retroviral vector into the perivitelline space of 224 mature rhesus oocytes, later fertilized by intracytoplasmic sperm injection. Of the three males born from 20 embryo transfers, one was transgenic when accessible tissues were assayed for transgene DNA and messenger RNA. All tissues that were studied from a fraternal set of twins, miscarried at 73 days, carried the transgene, as confirmed by Southern analyses, and the GFP transgene reporter was detected by both direct and indirect fluorescence imaging.
Genetic Correlates of Musical Pitch Recognition in Humans
Authors: Drayna Dennis , Manichaikul Ani , Lange Marlies de , Snieder Harold , Spector Tim
Published: July 2002

We used a twin study to investigate the genetic and environmental contributions to differences in musical pitch perception abilities in humans. We administered a Distorted Tunes Test (DTT), which requires subjects to judge whether simple popular melodies contain notes with incorrect pitch, to 136 monozygotic twin pairs and 148 dizygotic twin pairs. The correlation of DTT scores between twins was estimated at 0.67 for monozygotic pairs and 0.44 for dizygotic pairs. Genetic model-fitting techniques supported an additive genetic model, with heritability estimated at 0.71 to 0.80, depending on how subjects were categorized, and with no effect of shared environment. DTT scores were only weakly correlated with measures of peripheral hearing. This suggests that variation in musical pitch recognition is primarily due to highly heritable differences in auditory functions not tested by conventional audiologic methods.
Delayed Compensation for Missing Keystone Species by Colonization
Authors: Morgan Ernest S. K. , Brown James H.
Published: July 2002

Because individual species can play key roles, the loss of species through extinction or their gain through colonization can cause major changes in ecosystems. For almost 20 years after kangaroo rats were experimentally removed from a Chihuahuan desert ecosystem in the United States, other rodent species were unable to compensate and use the available resources. This changed abruptly in 1995, when an alien species of pocket mouse colonized the ecosystem, used most of the available resources, and compensated almost completely for the missing kangaroo rats. These results demonstrate the importance of individual species and of colonization and extinction events in the structure and dynamics of ecosystems.
Animal and Human Multidrug-Resistant, Cephalosporin-Resistant
Salmonella
Isolates Expressing a Plasmid-Mediated CMY-2 AmpC β-Lactamase
Authors: Winokur P. L. , Brueggemann A. , DeSalvo D. L. , Hoffmann L. , Apley M. D. , Uhlenhopp E. K. , Pfaller M. A. , Doern G. V.
Published: July 2002

Salmonella
spp. are important food-borne pathogens that are demonstrating increasing antimicrobial resistance rates in isolates obtained from food animals and humans. In this study, 10 multidrug-resistant, cephalosporin-resistant
Salmonella
isolates from bovine, porcine, and human sources from a single geographic region were identified. All isolates demonstrated resistance to cephamycins and extended-spectrum cephalosporins as well as tetracycline, chloramphenicol, streptomycin, and sulfisoxazole. Molecular epidemiological analyses revealed eight distinct chromosomal DNA patterns, suggesting that clonal spread could not entirely explain the distribution of this antimicrobial resistance phenotype. However, all isolates encoded an AmpC-like β-lactamase, CMY-2. Eight isolates contained a large nonconjugative plasmid that could transform
Escherichia coli
. Transformants coexpressed cephalosporin, tetracycline, chloramphenicol, streptomycin, and sulfisoxazole resistances. Plasmid DNA revealed highly related restriction fragments though plasmids appeared to have undergone some evolution over time. Multidrug-resistant, cephalosporin-resistant
Salmonella
spp. present significant therapeutic problems in animal and human health care and raise further questions about the association between antimicrobial resistance, antibiotic use in animals, and transfer of multidrug-resistant
Salmonella
spp. between animals and man.
Protection against Lipopolysaccharide-Induced Death by Fluoroquinolones
Authors: Khan Anis A. , Slifer Teri R. , Araujo Fausto G. , Suzuki Yasuhiro , Remington Jack S.
Published: July 2002

Because fluoroquinolones have an immunomodulatory effect on cytokine production by lipopolysaccharide (LPS)-treated human monocytes, we examined the effect of fluoroquinolones on the survival of mice injected with a lethal dose of LPS. Trovafloxacin (100 mg/kg), ciprofloxacin (250 mg/kg), and tosufloxacin (100 mg/kg) protected 75% (
P
= 0.0001), 25% (
P
= 0.002), and 50% (
P
= 0.002), respectively, of mice against death. The fluoroquinolones significantly reduced serum levels of interleukin-6 and tumor necrosis factor alpha in LPS-treated mice. The protective effects of fluoroquinolones in LPS-induced shock in mice may also occur in humans.
ampR
Gene Mutations That Greatly Increase Class C β-Lactamase Activity in
Enterobacter cloacae
Authors: Kuga Akio , Okamoto Ryoichi , Inoue Matsuhisa
Published: July 2002

The
ampC
and
ampR
genes of
Enterobacter cloacae
GN7471 were cloned into pMW218 to yield pKU403. Four mutant plasmids derived from pKU403 (pKU404, pKU405, pKU406, and pKU407) were isolated in an AmpD mutant of
Escherichia coli
ML4953 by selection with ceftazidime or aztreonam. The β-lactamase activities expressed by pKU404, pKU405, pKU406, and pKU407 were about 450, 75, 160, and 160 times higher, respectively, than that expressed by the original plasmid, pKU403. These mutant plasmids all carried point mutations in the
ampR
gene. In pKU404 and pKU405, Asp-135 was changed to Asn and Val, respectively. In both pKU406 and pKU407, Arg-86 was changed to Cys. The ease of selection of AmpR mutations at a frequency of about 10
−6
in this study strongly suggests that derepressed strains, such as AmpD or AmpR mutants, could frequently emerge in the clinical setting.
Bloodstream Infections Due to
Candida
Species: SENTRY Antimicrobial Surveillance Program in North America and Latin America, 1997-1998
Authors: Pfaller M. A. , Jones R. N. , Doern G. V. , Sader H. S. , Messer S. A. , Houston A. , Coffman S. , Hollis R. J. ,   The SENTRY Participant Group
Published: July 2002

An international program of surveillance of bloodstream infections (BSI) in the United States, Canada, and Latin America detected 306 episodes of candidemia in 34 medical centers (22 in the United States, 6 in Canada, and 6 in Latin America) in 1997 and 328 episodes in 34 medical centers (22 in the United States, 5 in Canada, and 7 in Latin America) in 1998. Of the 634 BSI, 54.3% were due to
Candida albicans
, 16.4% were due to
C. glabrata
, 14.9% were due to
C. parapsilosis
, 8.2% were due to
C. tropicalis
, 1.6% were due to
C. krusei
, and 4.6% were due to other
Candida
spp. The percentage of BSI due to
C. albicans
decreased very slightly in the United States between 1997 and 1998 (56.2 to 54.4%;
P
= 0.68) and increased in both Canada (52.6 to 70.1%;
P
= 0.05) and Latin America (40.5 to 44.6%;
P
= 0.67).
C. glabrata
was the second most common species observed overall, and the percentage of BSI due to
C. glabrata
increased in all three geographic areas between 1997 and 1998.
C. parapsilosis
was the third most prevalent BSI isolate in both Canada and Latin America, accounting for 7.0 and 18.5% of BSI, respectively. Resistance to fluconazole (MIC, ≥64 μg/ml) and itraconazole (MIC, ≥1.0 μg/ml) was observed infrequently in both 1997 (2.3 and 8.5%, respectively) and 1998 (1.5 and 7.6%, respectively). Among the different species of
Candida
, resistance to fluconazole and itraconazole was observed in
C. glabrata
and
C. krusei
, whereas isolates of
C. albicans
,
C. parapsilosis
, and
C. tropicalis
were all highly susceptible to both fluconazole (98.9 to 100% susceptible) and itraconazole (96.4 to 100% susceptible). Isolates from Canada and Latin America were generally more susceptible to both triazoles than U.S. isolates were. Continued surveillance appears necessary to detect these important changes.
Coordinate Suppression of Superantigen-Induced Cytokine Production and T-Cell Proliferation by a Small Nonpeptidic Inhibitor of Class II Major Histocompatibility Complex and CD4 Interaction
Authors: Krakauer Teresa
Published: July 2002

Proinflammatory cytokines mediate the toxic effect of superantigenic staphylococcal exotoxins (SE). TJU103, a small nonpeptidic molecule that blocks the interaction between major histocompatibility complex class II and CD4 molecules inhibited SE-stimulated T-cell proliferation (by 92%) and production of tumor necrosis factor, interleukin 1β, interleukin 6, and gamma interferon (by 66, 56, 76, and 72%, respectively) by human peripheral blood mononuclear cells. These data suggest that TJU103 may be useful for mitigating the pathogenic effects of SE.