bluuebunny/crossref_metadata_2025 huggingface dataset:
Affinity-Driven Peptide Selection of an NFAT Inhibitor More Selective Than Cyclosporin A
Authors: Aramburu José , Yaffe Michael B. , López-Rodrı́guez Cristina , Cantley Lewis C. , Hogan Patrick G. , Rao Anjana
Published: July 2002

The flow of information from calcium-mobilizing receptors to nuclear factor of activated T cells (NFAT)–dependent genes is critically dependent on interaction between the phosphatase calcineurin and the transcription factor NFAT. A high-affinity calcineurin-binding peptide was selected from combinatorial peptide libraries based on the calcineurin docking motif of NFAT. This peptide potently inhibited NFAT activation and NFAT-dependent expression of endogenous cytokine genes in T cells, without affecting the expression of other cytokines that require calcineurin but not NFAT. Substitution of the optimized peptide sequence into the natural calcineurin docking site increased the calcineurin responsiveness of NFAT. Compounds that interfere selectively with the calcineurin-NFAT interaction without affecting calcineurin phosphatase activity may be useful as therapeutic agents that are less toxic than current drugs.
A Species of Small Antisense RNA in Posttranscriptional Gene Silencing in Plants
Authors: Hamilton Andrew J. , Baulcombe David C.
Published: July 2002

Posttranscriptional gene silencing (PTGS) is a nucleotide sequence–specific defense mechanism that can target both cellular and viral mRNAs. Here, three types of transgene-induced PTGS and one example of virus-induced PTGS were analyzed in plants. In each case, antisense RNA complementary to the targeted mRNA was detected. These RNA molecules were of a uniform length, estimated at 25 nucleotides, and their accumulation required either transgene sense transcription or RNA virus replication. Thus, the 25-nucleotide antisense RNA is likely synthesized from an RNA template and may represent the specificity determinant of PTGS.
The Source and Fate of Massive Carbon Input During the Latest Paleocene Thermal Maximum
Authors: Katz Miriam E. , Pak Dorothy K. , Dickens Gerald R. , Miller Kenneth G.
Published: July 2002

Lithologic, faunal, seismic, and isotopic evidence from the Blake Nose (subtropical western North Atlantic) links a massive release of biogenic methane ∼55.5 million years ago to a warming of deep-ocean and high-latitude surface waters, a large perturbation in the combined ocean-atmosphere carbon cycle (the largest of the past 90 million years), a mass extinction event in benthic faunas, and a radiation of mammalian orders. The deposition of a mud clast interval and seismic evidence for slope disturbance are associated with intermediate water warming, massive carbon input to the global exogenic carbon cycle, pelagic carbonate dissolution, a decrease in dissolved oxygen, and a benthic foraminiferal extinction event. These events provide evidence to confirm the gas hydrate dissociation hypothesis and identify the Blake Nose as a site of methane release.
Arthritis Provoked by Linked T and B Cell Recognition of a Glycolytic Enzyme
Authors: Matsumoto Isao , Staub Adrien , Benoist Christophe , Mathis Diane
Published: July 2002

The hallmark of rheumatoid arthritis (RA) is specific destruction of the synovial joints. In a mouse line that spontaneously develops a disorder with many of the features of human RA, disease is initiated by T cell recognition of a ubiquitously expressed self-antigen; once initiated, pathology is driven almost entirely by immunoglobulins. In this study, the target of both the initiating T cells and pathogenic immunoglobulins was identified as glucose-6-phosphate isomerase, a glycolytic enzyme. Thus, some forms of RA or related arthritides may develop by a mechanism fundamentally different from the currently popular paradigm of a joint-specific T cell response.
A Lower Mantle Source for Central European Volcanism
Authors: Goes Saskia , Spakman Wim , Bijwaard Harmen
Published: July 2002

Cenozoic rifting and volcanism in Europe have been associated with either passive or active mantle upwellings. Tomographic images show a low velocity structure between 660- and 2000-kilometer depth, which we propose to represent a lower mantle upwelling under central Europe that may feed smaller upper-mantle plumes. The position of the rift zones in the foreland of the Alpine belts and the relatively weak volcanism compared to other regions with plume-associated volcanism are probably the result of the past and present subduction under southern Europe.
Rad6-Dependent Ubiquitination of Histone H2B in Yeast
Authors: Robzyk Kenneth , Recht Judith , Osley Mary Ann
Published: July 2002

Although ubiquitinated histones are present in substantial levels in vertebrate cells, the roles they play in specific biological processes and the cellular factors that regulate this modification are not well characterized. Ubiquitinated H2B (uH2B) has been identified in the yeast
Saccharomyces cerevisiae
, and mutation of the conserved ubiquitination site is shown to confer defects in mitotic cell growth and meiosis. uH2B was not detected in
rad6
mutants, which are defective for the ubiquitin-conjugating enzyme Ubc2, thus identifying Rad6 as the major cellular activity that ubiquitinates H2B in yeast.
Eta-1 (Osteopontin): An Early Component of Type-1 (Cell-Mediated) Immunity
Authors: Ashkar Samy , Weber Georg F. , Panoutsakopoulou Vassiliki , Sanchirico Marie E. , Jansson Marianne , Zawaideh Samer , Rittling Susan R. , Denhardt David T. , Glimcher Melvin J. , Cantor Harvey
Published: July 2002

Cell-mediated (type-1) immunity is necessary for immune protection against most intracellular pathogens and, when excessive, can mediate organ-specific autoimmune destruction. Mice deficient in Eta-1 (also called osteopontin) gene expression have severely impaired type-1 immunity to viral infection [herpes simplex virus–type 1 (KOS strain)] and bacterial infection (
Listeria monocytogenes
) and do not develop sarcoid-type granulomas. Interleukin-12 (IL-12) and interferon-γ production is diminished, and IL-10 production is increased. A phosphorylation-dependent interaction between the amino-terminal portion of Eta-1 and its integrin receptor stimulated IL-12 expression, whereas a phosphorylation-independent interaction with CD44 inhibited IL-10 expression. These findings identify Eta-1 as a key cytokine that sets the stage for efficient type-1 immune responses through differential regulation of macrophage IL-12 and IL-10 cytokine expression.
Suppression of Rain and Snow by Urban and Industrial Air Pollution
Authors: Rosenfeld Daniel
Published: July 2002

Direct evidence demonstrates that urban and industrial air pollution can completely shut off precipitation from clouds that have temperatures at their tops of about –10°C over large areas. Satellite data reveal plumes of reduced cloud particle size and suppressed precipitation originating from major urban areas and from industrial facilities such as power plants. Measurements obtained by the Tropical Rainfall Measuring Mission satellite reveal that both cloud droplet coalescence and ice precipitation formation are inhibited in polluted clouds.
Candidate Taste Receptors in
Drosophila
Authors: Clyne Peter J. , Warr Coral G. , Carlson John R.
Published: July 2002

Little is known about the molecular mechanisms of taste perception in animals, particularly the initial events of taste signaling. A large and diverse family of seven transmembrane domain proteins was identified from the
Drosophila
genome database with a computer algorithm that identifies proteins on the basis of structure. Eighteen of 19 genes examined were expressed in the
Drosophila
labellum, a gustatory organ of the proboscis. Expression was not detected in a variety of other tissues. The genes were not expressed in the labellum of a
Drosophila
mutant,

pox-neuro
70

, in which taste neurons are eliminated. Tissue specificity of expression of these genes, along with their structural similarity, supports the possibility that the family encodes a large and divergent family of taste receptors.
Correlates of Sleep and Waking in
Drosophila melanogaster
Authors: Shaw Paul J. , Cirelli Chiara , Greenspan Ralph J. , Tononi Giulio
Published: July 2002

Drosophila
exhibits a circadian rest-activity cycle, but it is not known whether fly rest constitutes sleep or is mere inactivity. It is shown here that, like mammalian sleep, rest in
Drosophila
is characterized by an increased arousal threshold and is homeostatically regulated independently of the circadian clock. As in mammals, rest is abundant in young flies, is reduced in older flies, and is modulated by stimulants and hypnotics. Several molecular markers modulated by sleep and waking in mammals are modulated by rest and activity in
Drosophila
, including cytochrome oxidase C, the endoplasmic reticulum chaperone protein BiP, and enzymes implicated in the catabolism of monoamines. Flies lacking one such enzyme, arylalkylamine
N
-acetyltransferase, show increased rest after rest deprivation. These results implicate the catabolism of monoamines in the regulation of sleep and waking in the fly and suggest that
Drosophila
may serve as a model system for the genetic dissection of sleep.
Cell Surface Engineering by a Modified Staudinger Reaction
Authors: Saxon Eliana , Bertozzi Carolyn R.
Published: July 2002

Selective chemical reactions enacted within a cellular environment can be powerful tools for elucidating biological processes or engineering novel interactions. A chemical transformation that permits the selective formation of covalent adducts among richly functionalized biopolymers within a cellular context is presented. A ligation modeled after the Staudinger reaction forms an amide bond by coupling of an azide and a specifically engineered triarylphosphine. Both reactive partners are abiotic and chemically orthogonal to native cellular components. Azides installed within cell surface glycoconjugates by metabolism of a synthetic azidosugar were reacted with a biotinylated triarylphosphine to produce stable cell-surface adducts. The tremendous selectivity of the transformation should permit its execution within a cell's interior, offering new possibilities for probing intracellular interactions.
Reversal of Antipsychotic-Induced Working Memory Deficits by Short-Term Dopamine D1 Receptor Stimulation
Authors: Castner Stacy A. , Williams Graham V. , Goldman-Rakic Patricia S.
Published: July 2002

Chronic blockade of dopamine D2 receptors, a common mechanism of action for antipsychotic drugs, down-regulates D1 receptors in the prefrontal cortex and, as shown here, produces severe impairments in working memory. These deficits were reversed in monkeys by short-term coadministration of a D1 agonist, ABT 431, and this improvement was sustained for more than a year after cessation of D1 treatment. These findings indicate that pharmacological modulation of the D1 signaling pathway can produce long-lasting changes in functional circuits underlying working memory. Resetting this pathway by brief exposure to the agonist may provide a valuable strategy for therapeutic intervention in schizophrenia and other dopamine dysfunctional states.
The Initial Domestication of Goats (
Capra hircus
) in the Zagros Mountains 10,000 Years Ago
Authors: Zeder Melinda A. , Hesse Brian
Published: July 2002

Initial goat domestication is documented in the highlands of western Iran at 10,000 calibrated calendar years ago. Metrical analyses of patterns of sexual dimorphism in modern wild goat skeletons (
Capra hircus aegagrus
) allow sex-specific age curves to be computed for archaeofaunal assemblages. A distinct shift to selective harvesting of subadult males marks initial human management and the transition from hunting to herding of the species. Direct accelerator mass spectrometry radiocarbon dates on skeletal elements provide a tight temporal context for the transition.
Hot and Dry Deep Crustal Xenoliths from Tibet
Authors: Hacker Bradley R. , Gnos Edwin , Ratschbacher Lothar , Grove Marty , McWilliams Michael , Sobolev Stephen V. , Wan Jiang , Zhenhan Wu
Published: July 2002

Anhydrous metasedimentary and mafic xenoliths entrained in 3-million-year-old shoshonitic lavas of the central Tibetan Plateau record a thermal gradient reaching about 800° to 1000°C at a depth of 30 to 50 kilometers; just before extraction, these same xenoliths were heated as much as 200°C. Although these rocks show that the central Tibetan crust is hot enough to cause even dehydration melting of mica, the absence of hydrous minerals, and the match of our calculated
P
-wave speeds and Poisson's ratios with seismological observations, argue against the presence of widespread crustal melting.
Nonbiological Fractionation of Iron Isotopes
Authors: Anbar A. D. , Roe J. E. , Barling J. , Nealson K. H.
Published: July 2002

Laboratory experiments demonstrate that iron isotopes can be chemically fractionated in the absence of biology. Isotopic variations comparable to those seen during microbially mediated reduction of ferrihydrite are observed. Fractionation may occur in aqueous solution during equilibration between inorganic iron complexes. These findings provide insight into the mechanisms of iron isotope fractionation and suggest that nonbiological processes may contribute to iron isotope variations observed in sediments.
Nipah Virus: A Recently Emergent Deadly Paramyxovirus
Authors: Chua K. B. , Bellini W. J. , Rota P. A. , Harcourt B. H. , Tamin A. , Lam S. K. , Ksiazek T. G. , Rollin P. E. , Zaki S. R. , Shieh W.-J. , Goldsmith C. S. , Gubler D. J. , Roehrig J. T. , Eaton B. , Gould A. R. , Olson J. , Field H. , Daniels P. , Ling A. E. , Peters C. J. , Anderson L. J. , Mahy B. W. J.
Published: July 2002

A paramyxovirus virus termed Nipah virus has been identified as the etiologic agent of an outbreak of severe encephalitis in people with close contact exposure to pigs in Malaysia and Singapore. The outbreak was first noted in late September 1998 and by mid-June 1999, more than 265 encephalitis cases, including 105 deaths, had been reported in Malaysia, and 11 cases of encephalitis or respiratory illness with one death had been reported in Singapore. Electron microscopic, serologic, and genetic studies indicate that this virus belongs to the family
Paramyxoviridae
and is most closely related to the recently discovered Hendra virus. We suggest that these two viruses are representative of a new genus within the family
Paramyxoviridae
. Like Hendra virus, Nipah virus is unusual among the paramyxoviruses in its ability to infect and cause potentially fatal disease in a number of host species, including humans.
The Prefrontal Cortex: Response Selection or Maintenance Within Working Memory?
Authors: Rowe James B. , Toni Ivan , Josephs Oliver , Frackowiak Richard S. J. , Passingham Richard E.
Published: July 2002

It is controversial whether the dorsolateral prefrontal cortex is involved in the maintenance of items in working memory or in the selection of responses. We used event-related functional magnetic resonance imaging to study the performance of a spatial working memory task by humans. We distinguished the maintenance of spatial items from the selection of an item from memory to guide a response. Selection, but not maintenance, was associated with activation of prefrontal area 46 of the dorsal lateral prefrontal cortex. In contrast, maintenance was associated with activation of prefrontal area 8 and the intraparietal cortex. The results support a role for the dorsal prefrontal cortex in the selection of representations. This accounts for the fact that this area is activated both when subjects select between items on working memory tasks and when they freely select between movements on tasks of willed action.
A Primitive T Cell-Independent Mechanism of Intestinal Mucosal IgA Responses to Commensal Bacteria
Authors: Macpherson Andrew J. , Gatto Dominique , Sainsbury Elizabeth , Harriman Gregory R. , Hengartner Hans , Zinkernagel Rolf M.
Published: July 2002

The immunoglobulin A (IgA) is produced to defend mucosal surfaces from environmental organisms, but host defenses against the very heavy load of intestinal commensal microorganisms are poorly understood. The IgA against intestinal commensal bacterial antigens was analyzed; it was not simply “natural antibody” but was specifically induced and responded to antigenic changes within an established gut flora. In contrast to IgA responses against exotoxins, a significant proportion of this specific anti-commensal IgA induction was through a pathway that was independent of T cell help and of follicular lymphoid tissue organization, which may reflect an evolutionarily primitive form of specific immune defense.
Impaired Cued and Contextual Memory in NPAS2-Deficient Mice
Authors: Garcia Joseph A. , Zhang Di , Estill Sandi Jo , Michnoff Carolyn , Rutter Jared , Reick Martin , Scott Kristin , Diaz-Arrastia Ramon , McKnight Steven L.
Published: July 2002

Neuronal PAS domain protein 2 (NPAS2) is a basic helix-loop-helix (bHLH) PAS domain transcription factor expressed in multiple regions of the vertebrate brain. Targeted insertion of a β-galactosidase reporter gene (lacZ) resulted in the production of an NPAS2-lacZ fusion protein and an altered form of NPAS2 lacking the bHLH domain. The neuroanatomical expression pattern of NPAS2-lacZ was temporally and spatially coincident with formation of the mature frontal association/limbic forebrain pathway. NPAS2-deficient mice were subjected to a series of behavioral tests and were found to exhibit deficits in the long-term memory arm of the cued and contextual fear task. Thus, NPAS2 may serve a dedicated regulatory role in the acquisition of specific types of memory.
Evidence for Recent Groundwater Seepage and Surface Runoff on Mars
Authors: Malin Michael C. , Edgett Kenneth S.
Published: July 2002

Relatively young landforms on Mars, seen in high-resolution images acquired by the Mars Global Surveyor Mars Orbiter Camera since March 1999, suggest the presence of sources of liquid water at shallow depths beneath the martian surface. Found at middle and high martian latitudes (particularly in the southern hemisphere), gullies within the walls of a very small number of impact craters, south polar pits, and two of the larger martian valleys display geomorphic features that can be explained by processes associated with groundwater seepage and surface runoff. The relative youth of the landforms is indicated by the superposition of the gullies on otherwise geologically young surfaces and by the absence of superimposed landforms or cross-cutting features, including impact craters, small polygons, and eolian dunes. The limited size and geographic distribution of the features argue for constrained source reservoirs.
Global Water Resources: Vulnerability from Climate Change and Population Growth
Authors: Vörösmarty Charles J. , Green Pamela , Salisbury Joseph , Lammers Richard B.
Published: July 2002

The future adequacy of freshwater resources is difficult to assess, owing to a complex and rapidly changing geography of water supply and use. Numerical experiments combining climate model outputs, water budgets, and socioeconomic information along digitized river networks demonstrate that (i) a large proportion of the world's population is currently experiencing water stress and (ii) rising water demands greatly outweigh greenhouse warming in defining the state of global water systems to 2025. Consideration of direct human impacts on global water supply remains a poorly articulated but potentially important facet of the larger global change question.
Cell-Cell Signaling and Movement by the Floral Transcription Factors LEAFY and APETALA1
Authors: Sessions Allen , Yanofsky Martin F. , Weigel Detlef
Published: July 2002

LEAFY (
LFY
) and
APETALA1
(
AP1
) encode unrelated transcription factors that activate overlapping sets of homeotic genes in
Arabidopsis
flowers. Sector analysis and targeted expression in transgenic plants were used to study whether
LFY
and
AP1
can participate in cell-cell signaling between and within different layers of the floral meristem.
LFY
signaled equally well from all layers and had substantial long-range action within layers. Nonautonomous action of
LFY
was accompanied by movement of the protein to adjacent cells, where it directly activated homeotic target genes. In contrast,
AP1
had only limited nonautonomous effects, apparently mediated by downstream genes because activation of early target genes by
AP1
was cell-autonomous.
High-Gain Harmonic-Generation Free-Electron Laser
Authors: Yu L.-H. , Babzien M. , Ben-Zvi I. , DiMauro L. F. , Doyuran A. , Graves W. , Johnson E. , Krinsky S. , Malone R. , Pogorelsky I. , Skaritka J. , Rakowsky G. , Solomon L. , Wang X. J. , Woodle M. , Yakimenko V. , Biedron S. G. , Galayda J. N. , Gluskin E. , Jagger J. , Sajaev V. , Vasserman I.
Published: July 2002

A high-gain harmonic-generation free-electron laser is demonstrated. Our approach uses a laser-seeded free-electron laser to produce amplified, longitudinally coherent, Fourier transform–limited output at a harmonic of the seed laser. A seed carbon dioxide laser at a wavelength of 10.6 micrometers produced saturated, amplified free-electron laser output at the second-harmonic wavelength, 5.3 micrometers. The experiment verifies the theoretical foundation for the technique and prepares the way for the application of this technique in the vacuum ultraviolet region of the spectrum, with the ultimate goal of extending the approach to provide an intense, highly coherent source of hard x-rays.
A 22,000-Year Record of Monsoonal Precipitation from Northern Chile's Atacama Desert
Authors: Betancourt J. L. , Latorre C. , Rech J. A. , Quade J. , Rylander K. A.
Published: July 2002

Fossil rodent middens and wetland deposits from the central Atacama Desert (22° to 24°S) indicate increasing summer precipitation, grass cover, and groundwater levels from 16.2 to 10.5 calendar kiloyears before present (ky B.P.). Higher elevation shrubs and summer-flowering grasses expanded downslope across what is now the edge of Absolute Desert, a broad expanse now largely devoid of rainfall and vegetation. Paradoxically, this pluvial period coincided with the summer insolation minimum and reduced adiabatic heating over the central Andes. Summer precipitation over the central Andes and central Atacama may depend on remote teleconnections between seasonal insolation forcing in both hemispheres, the Asian monsoon, and Pacific sea surface temperature gradients. A less pronounced episode of higher groundwater levels in the central Atacama from 8 to 3 ky B.P. conflicts with an extreme lowstand of Lake Titicaca, indicating either different climatic forcing or different response times and sensitivities to climatic change.
Climate Extremes: Observations, Modeling, and Impacts
Authors: Easterling David R. , Meehl Gerald A. , Parmesan Camille , Changnon Stanley A. , Karl Thomas R. , Mearns Linda O.
Published: July 2002

One of the major concerns with a potential change in climate is that an increase in extreme events will occur. Results of observational studies suggest that in many areas that have been analyzed, changes in total precipitation are amplified at the tails, and changes in some temperature extremes have been observed. Model output has been analyzed that shows changes in extreme events for future climates, such as increases in extreme high temperatures, decreases in extreme low temperatures, and increases in intense precipitation events. In addition, the societal infrastructure is becoming more sensitive to weather and climate extremes, which would be exacerbated by climate change. In wild plants and animals, climate-induced extinctions, distributional and phenological changes, and species' range shifts are being documented at an increasing rate. Several apparently gradual biological changes are linked to responses to extreme weather and climate events.
Molecular and Neuronal Substrate for the Selective Attenuation of Anxiety
Authors: Löw Karin , Crestani Florence , Keist Ruth , Benke Dietmar , Brünig Ina , Benson Jack A. , Fritschy Jean-Marc , Rülicke Thomas , Bluethmann Horst , Möhler Hanns , Rudolph Uwe
Published: July 2002

Benzodiazepine tranquilizers are used in the treatment of anxiety disorders. To identify the molecular and neuronal target mediating the anxiolytic action of benzodiazepines, we generated and analyzed two mouse lines in which the α2 or α3 GABA
A
(γ-aminobutyric acid type A) receptors, respectively, were rendered insensitive to diazepam by a knock-in point mutation. The anxiolytic action of diazepam was absent in mice with the α2(H101R) point mutation but present in mice with the α3(H126R) point mutation. These findings indicate that the anxiolytic effect of benzodiazepine drugs is mediated by α2 GABA
A
receptors, which are largely expressed in the limbic system, but not by α3 GABA
A
receptors, which predominate in the reticular activating system.
Experimental Verification of Decoherence-Free Subspaces
Authors: Kwiat Paul G. , Berglund Andrew J. , Altepeter Joseph B. , White Andrew G.
Published: July 2002

Using spontaneous parametric down-conversion, we produce polarization-entangled states of two photons and characterize them using two-photon tomography to measure the density matrix. A controllable decoherence is imposed on the states by passing the photons through thick, adjustable birefringent elements. When the system is subject to collective decoherence, one particular entangled state is seen to be decoherence-free, as predicted by theory. Such decoherence-free systems may have an important role for the future of quantum computation and information processing.
Oxidative Damage Linked to Neurodegeneration by Selective α-Synuclein Nitration in Synucleinopathy Lesions
Authors: Giasson Benoit I. , Duda John E. , Murray Ian V. J. , Chen Qiping , Souza José M. , Hurtig Howard I. , Ischiropoulos Harry , Trojanowski John Q. , -Y. Lee Virginia M.
Published: July 2002

Aggregated α-synuclein proteins form brain lesions that are hallmarks of neurodegenerative synucleinopathies, and oxidative stress has been implicated in the pathogenesis of some of these disorders. Using antibodies to specific nitrated tyrosine residues in α-synuclein, we demonstrate extensive and widespread accumulations of nitrated α-synuclein in the signature inclusions of Parkinson's disease, dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease, and multiple system atrophy brains. We also show that nitrated α-synuclein is present in the major filamentous building blocks of these inclusions, as well as in the insoluble fractions of affected brain regions of synucleinopathies. The selective and specific nitration of α-synuclein in these disorders provides evidence to directly link oxidative and nitrative damage to the onset and progression of neurodegenerative synucleinopathies.
Orbital Forcing of the Marine Isotope Stage 9 Interglacial
Authors: Stirling C. H. , Esat T. M. , Lambeck K. , McCulloch M. T. , Blake S. G. , Lee D.-C. , Halliday A. N.
Published: July 2002

Milankovitch orbital forcing theory has been used to assign time scales to many paleoclimate records. However, the validity of this theory remains uncertain, and independent sea-level chronologies used to test its applicability have been restricted largely to the past ∼135,000 years. Here, we report U-series ages for coral reefs formed on Henderson Island during sea-level high-stands occurring at ∼630,000 and ∼330,000 years ago. These data are consistent with the hypothesis that interglacial climates are forced by Northern Hemisphere summer solar insolation centered at 65°N latitude, as predicted by Milankovitch theory.
Role of the ENTH Domain in Phosphatidylinositol-4,5-Bisphosphate Binding and Endocytosis
Authors: Itoh Toshiki , Koshiba Seizo , Kigawa Takanori , Kikuchi Akira , Yokoyama Shigeyuki , Takenawa Tadaomi
Published: July 2002

Endocytic proteins such as epsin, AP180, and Hip1R (Sla2p) share a conserved modular region termed the epsin NH
2
-terminal homology (ENTH) domain, which plays a crucial role in clathrin-mediated endocytosis through an unknown target. Here, we demonstrate a strong affinity of the ENTH domain for phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P
2
]. With nuclear magnetic resonance analysis of the epsin ENTH domain, we determined that a cleft formed with positively charged residues contributed to phosphoinositide binding. Overexpression of a mutant, epsin Lys
76
→ Ala
76
, with an ENTH domain defective in phosphoinositide binding, blocked epidermal growth factor internalization in COS-7 cells. Thus, interaction between the ENTH domain and PtdIns(4,5)P
2
is essential for endocytosis mediated by clathrin-coated pits.
Defensive Function of Herbivore-Induced Plant Volatile Emissions in Nature
Authors: Kessler André , Baldwin Ian T.
Published: July 2002

Herbivore attack is known to increase the emission of volatiles, which attract predators to herbivore-damaged plants in the laboratory and agricultural systems. We quantified volatile emissions from
Nicotiana attenuata
plants growing in natural populations during attack by three species of leaf-feeding herbivores and mimicked the release of five commonly emitted volatiles individually. Three compounds (
cis-3
-hexen-1-ol, linalool, and
cis
-α-bergamotene) increased egg predation rates by a generalist predator; linalool and the complete blend decreased lepidopteran oviposition rates. As a consequence, a plant could reduce the number of herbivores by more than 90% by releasing volatiles. These results confirm that indirect defenses can operate in nature.
Biogenic Carbon Cycling in the Upper Ocean: Effects of Microbial Respiration
Authors: Rivkin Richard B. , Legendre Louis
Published: July 2002

Food-web processes are important controls of oceanic biogenic carbon flux and ocean-atmosphere carbon dioxide exchange. Two key controlling parameters are the growth efficiencies of the principal trophic components and the rate of carbon remineralization. We report that bacterial growth efficiency is an inverse function of temperature. This relationship permits bacterial respiration in the euphotic zone to be computed from temperature and bacterial production. Using the temperature-growth efficiency relationship, we show that bacterial respiration generally accounts for most community respiration. This implies that a larger fraction of assimilated carbon is respired at low than at high latitudes, so a greater proportion of production can be exported in polar than in tropical regions. Because bacterial production is also a function of temperature, it should be possible to compute euphotic zone heterotrophic respiration at large scales using remotely sensed information.
Integrated Genomic and Proteomic Analyses of a Systematically Perturbed Metabolic Network
Authors: Ideker Trey , Thorsson Vesteinn , Ranish Jeffrey A. , Christmas Rowan , Buhler Jeremy , Eng Jimmy K. , Bumgarner Roger , Goodlett David R. , Aebersold Ruedi , Hood Leroy
Published: July 2002

We demonstrate an integrated approach to build, test, and refine a model of a cellular pathway, in which perturbations to critical pathway components are analyzed using DNA microarrays, quantitative proteomics, and databases of known physical interactions. Using this approach, we identify 997 messenger RNAs responding to 20 systematic perturbations of the yeast galactose-utilization pathway, provide evidence that approximately 15 of 289 detected proteins are regulated posttranscriptionally, and identify explicit physical interactions governing the cellular response to each perturbation. We refine the model through further iterations of perturbation and global measurements, suggesting hypotheses about the regulation of galactose utilization and physical interactions between this and a variety of other metabolic pathways.
Humans as the World's Greatest Evolutionary Force
Authors: Palumbi Stephen R.
Published: July 2002

In addition to altering global ecology, technology and human population growth also affect evolutionary trajectories, dramatically accelerating evolutionary change in other species, especially in commercially important, pest, and disease organisms. Such changes are apparent in antibiotic and human immunodeficiency virus (HIV) resistance to drugs, plant and insect resistance to pesticides, rapid changes in invasive species, life-history change in commercial fisheries, and pest adaptation to biological engineering products. This accelerated evolution costs at least $33 billion to $50 billion a year in the United States. Slowing and controlling arms races in disease and pest management have been successful in diverse ecological and economic systems, illustrating how applied evolutionary principles can help reduce the impact of humankind on evolution.
Prostaglandins and Leukotrienes: Advances in Eicosanoid Biology
Authors: Funk Colin D.
Published: July 2002

Prostaglandins and leukotrienes are potent eicosanoid lipid mediators derived from phospholipase-released arachidonic acid that are involved in numerous homeostatic biological functions and inflammation. They are generated by cyclooxygenase isozymes and 5-lipoxygenase, respectively, and their biosynthesis and actions are blocked by clinically relevant nonsteroidal anti-inflammatory drugs, the newer generation coxibs (selective inhibitors of cyclooxygenase-2), and leukotriene modifiers. The prime mode of prostaglandin and leukotriene action is through specific G protein–coupled receptors, many of which have been cloned recently, thus enabling specific receptor agonist and antagonist development. Important insights into the mechanisms of inflammatory responses, pain, and fever have been gleaned from our current understanding of eicosanoid biology.
The Phosphoinositide 3-Kinase Pathway
Authors: Cantley Lewis C.
Published: July 2002

Phosphorylated lipids are produced at cellular membranes during signaling events and contribute to the recruitment and activation of various signaling components. The role of phosphoinositide 3-kinase (PI3K), which catalyzes the production of phosphatidylinositol-3,4,5-trisphosphate, in cell survival pathways; the regulation of gene expression and cell metabolism; and cytoskeletal rearrangements are highlighted. The PI3K pathway is implicated in human diseases including diabetes and cancer, and understanding the intricacies of this pathway may provide new avenues for therapuetic intervention.
Antibiotic Susceptibility Pattern of
Mycobacterium marinum
Authors: Aubry Alexandra , Jarlier Vincent , Escolano Sylvie , Truffot-Pernot Chantal , Cambau Emmanuelle
Published: July 2002

In vitro activities of 17 antibiotics against 53 clinical strains of
Mycobacterium marinum
, an atypical mycobacterium responsible for cutaneous infections, were determined using the reference agar dilution method. Rifampin and rifabutin were the most active drugs (MICs at which 90% of the isolates tested were inhibited [MIC
90
s], 0.5 and 0.6 μg/ml, respectively). MICs of minocycline (MIC
90
, 4 μg/ml), doxycycline (MIC
90
, 16 μg/ml), clarithromycin (MIC
90
, 4 μg/ml), sparfloxacin (MIC
90
, 2 μg/ml), moxifloxacin (MIC
90
, 1 μg/ml), imipenem (MIC
90
, 8 μg/ml), sulfamethoxazole (MIC
90
, 8 μg/ml) and amikacin (MIC
90
, 4 μg/ml) were close to the susceptibility breakpoints. MICs of isoniazid, ethambutol, trimethoprim, azithromycin, ciprofloxacin, ofloxacin, and levofloxacin were above the concentrations usually obtained in vivo. For each drug, the MIC
50
, geometric mean MIC, and modal MIC were very close, showing that all the strains had a similar susceptibility pattern. Percent agreement (within ±1 log
2
dilution) between MICs yielded by the Etest method and by the agar dilution method used as reference were 83, 59, 43, and 24% for minocycline, rifampin, clarithromycin, and sparfloxacin, respectively. Reproducibility with the Etest was low, in contrast to that with the agar dilution method. In conclusion,
M. marinum
is a naturally multidrug-resistant species for which the agar dilution method is more accurate than the Etest for antibiotic susceptibility testing.
Efficacy of Ravuconazole in Treatment of Mucosal Candidosis in SCID Mice
Authors: Clemons Karl V. , Stevens David A.
Published: July 2002

A model of orogastric candidosis in SCID mice, which mimics disease seen in AIDS patients, was used to evaluate ravuconazole in comparison with fluconazole for treatment. Mice were infected orally with
Candida albicans
and received either no treatment or oral treatment once daily for 12 days with 1, 5, or 25 mg of ravuconazole per kg of body weight per day, 5 or 25 mg of fluconazole per kg per day, or diluent (10% dimethyl sulfoxide in 0.5% carboxymethyl cellulose). The numbers of
C. albicans
CFU in the esophagus, stomach, small intestine, and cecum on day 25 in mice given no treatment and diluent were equivalent. Both doses of fluconazole significantly reduced numbers of CFU in all four tissues but were equivalent to each other. Ravuconazole showed dose-responsive improvement of clearance of CFU. Ravuconazole at 25 mg/kg was superior in reduction of numbers of CFU in all tissues to controls or 25 mg of fluconazole per kg and to other regimens in at least three tissues. Fluconazole at 25 mg/kg cured no infection in any tissue, whereas 25 mg of ravuconazole/kg cleared infection in all tissues from 50% of mice. Ravuconazole has good efficacy and the potential to cure mucosal candidosis in the absence of a functional immune response.
In Vitro Activities of Posaconazole, Itraconazole, Voriconazole, Amphotericin B, and Fluconazole against 37 Clinical Isolates of Zygomycetes
Authors: Sun Qiu N. , Fothergill Annette W. , McCarthy Dora I. , Rinaldi Michael G. , Graybill John R.
Published: July 2002

In vitro antifungal susceptibility testing results of a new antifungal triazole, posaconazole (POS), were compared to results with amphotericin B (AMB), itraconazole (ITC), voriconazole (VRC), and fluconazole (FLC) against clinical agents of zygomycosis. The MICs of POS at which 50% and 90% of the isolates were inhibited were 0.25 and 4 μg/ml, respectively. POS was significantly more active than VRC and FLC and slightly more active than ITC. The results suggest that POS has significant potential for clinical development against the zygomycetes.
Quantitative Analysis of Small-Subunit rRNA Genes in Mixed Microbial Populations via 5′-Nuclease Assays
Authors: Suzuki Marcelino T. , Taylor Lance T. , DeLong Edward F.
Published: July 2002

Few techniques are currently available for quantifying specific prokaryotic taxa in environmental samples. Quantification of specific genotypes has relied mainly on oligonucleotide hybridization to extracted rRNA or intact rRNA in whole cells. However, low abundance and cellular rRNA content limit the application of these techniques in aquatic environments. In this study, we applied a newly developed quantitative PCR assay (5′-nuclease assay, also known as TaqMan) to quantify specific small-subunit (SSU) rRNA genes (rDNAs) from uncultivated planktonic prokaryotes in Monterey Bay. Primer and probe combinations for quantification of SSU rDNAs at the domain and group levels were developed and tested for specificity and quantitative reliability. We examined the spatial and temporal variations of SSU rDNAs from
Synechococcus
plus
Prochlorococcus
and marine
Archaea
and compared the results of the quantitative PCR assays to those obtained by alternative methods. The 5′-nuclease assays reliably quantified rDNAs over at least 4 orders of magnitude and accurately measured the proportions of genes in artificial mixtures. The spatial and temporal distributions of planktonic microbial groups measured by the 5′-nuclease assays were similar to the distributions estimated by quantitative oligonucleotide probe hybridization, whole-cell hybridization assays, and flow cytometry.
Heavy Metal Coprecipitation with Hydrozincite [Zn
5
(CO
3
)
2
(OH)
6
] from Mine Waters Caused by Photosynthetic Microorganisms
Authors: Podda Francesca , Zuddas Paola , Minacci Andrea , Pepi Milva , Baldi Franco
Published: July 2002

An iron-poor stream of nearly neutral pH polluted by mine tailings has been investigated for a natural phenomenon responsible for the polishing of heavy metals in mine wastewaters. A white mineralized mat, which was determined to be hydrozincite [Zn
5
(CO
3
)
2
(OH)
6
] by X-ray diffraction analysis, was observed in the stream sediments mainly in spring. The precipitate shows a total organic matter residue of 10% dry weight and contains high concentrations of Pb, Cd, Ni, Cu, and other metals. Scanning electron microscopy analysis suggests that hydrozincite is mainly of biological origin. Dormant photosynthetic microorganisms have been retrieved from 1-year-old dry hydrozincite. The autofluorescent microorganisms were imaged by a scanning confocal laser microscope. A photosynthetic filamentous bacterium, classified as
Scytonema
sp. strain ING-1, was found associated with microalga
Chlorella
sp. strain SA1. This microbial community is responsible for the natural polishing of heavy metals in the water stream by coprecipitation with hydrozincite.
Community Composition of Marine Bacterioplankton Determined by 16S rRNA Gene Clone Libraries and Fluorescence In Situ Hybridization
Authors: Cottrell Matthew T. , Kirchman David L.
Published: July 2002

We determined the compositions of bacterioplankton communities in surface waters of coastal California using clone libraries of 16S rRNA genes and fluorescence in situ hybridization (FISH) in order to compare the community structures inferred from these two culture-independent approaches. The compositions of two clone libraries were quite similar to those of clone libraries of marine bacterioplankton examined by previous studies. Clones from γ-proteobacteria comprised ca. 28% of the libraries, while approximately 55% of the clones came from α-proteobacteria, which dominated the clone libraries. The
Cytophaga-Flavobacter
group and three others each comprised 10% or fewer of the clone libraries. The community composition determined by FISH differed substantially from the composition implied by the clone libraries. The
Cytophaga-Flavobacter
group dominated 8 of the 11 communities assayed by FISH, including the two communities assayed using clone libraries. On average only 10% of DAPI (4′,6′-diamidino-2-phenylindole)-stained bacteria were detected by FISH with a probe for α-proteobacteria, but 30% of DAPI-stained bacteria appeared to be in the
Cytophaga-Flavobacter
group as determined by FISH. α-Proteobacteria were greatly overrepresented in clone libraries compared to their relative abundance determined by FISH, while the
Cytophaga-Flavobacter
group was underrepresented in clone libraries. Our data show that the
Cytophaga-Flavobacter
group can be a numerically dominant component of coastal marine bacterioplankton communities.
Biological Role of Xanthomonadin Pigments in
Xanthomonas campestris
pv. Campestris
Authors: Poplawsky A. R. , Urban S. C. , Chun W.
Published: July 2002

Previous studies have indicated that the yellow pigments (xanthomonadins) produced by phytopathogenic
Xanthomonas
bacteria are unimportant during pathogenesis but may be important for protection against photobiological damage. We used a
Xanthomonas campestris
pv. campestris parent strain, single-site transposon insertion mutant strains, and chromosomally restored mutant strains to define the biological role of xanthomonadins. Although xanthomonadin mutant strains were comparable to the parent strain for survival when exposed to UV light; after their exposure to the photosensitizer toluidine blue and visible light, survival was greatly reduced. Chromosomally restored mutant strains were completely restored for survival in these conditions. Likewise, epiphytic survival of a xanthomonadin mutant strain was greatly reduced in conditions of high light intensity, whereas a chromosomally restored mutant strain was comparable to the parent strain for epiphytic survival. These results are discussed with respect to previous results, and a model for epiphytic survival of
X. campestris
pv. campestris is presented.
Naphthalene Degradation and Incorporation of Naphthalene-Derived Carbon into Biomass by the Thermophile
Bacillus thermoleovorans
Authors: Annweiler E. , Richnow H. H. , Antranikian G. , Hebenbrock S. , Garms C. , Franke S. , Francke W. , Michaelis W.
Published: July 2002

The thermophilic aerobic bacterium
Bacillus thermoleovorans
Hamburg 2 grows at 60°C on naphthalene as the sole source of carbon and energy. In batch cultures, an effective substrate degradation was observed. The carbon balance, including naphthalene, metabolites, biomass, and CO
2
, was determined by the application of [1-
13
C]naphthalene. The incorporation of naphthalene-derived carbon into the bulk biomass as well as into specified biomass fractions such as fatty acids and amino acids was confirmed by coupled gas chromatography-mass spectrometry (GC-MS) and isotope analyses. Metabolites were characterized by GC-MS; the established structures allow tracing the degradation pathway under thermophilic conditions. Apart from typical metabolites of naphthalene degradation known from mesophiles, intermediates such as 2,3-dihydroxynaphthalene, 2-carboxycinnamic acid, and phthalic and benzoic acid were identified for the pathway of this bacterium. These compounds indicate that naphthalene degradation by the thermophilic
B. thermoleovorans
differs from the known pathways found for mesophilic bacteria.
Culture-Dependent and Culture-Independent Characterization of Microbial Assemblages Associated with High-Temperature Petroleum Reservoirs
Authors: Orphan V. J. , Taylor L. T. , Hafenbradl D. , Delong E. F.
Published: July 2002

Recent investigations of oil reservoirs in a variety of locales have indicated that these habitats may harbor active thermophilic prokaryotic assemblages. In this study, we used both molecular and culture-based methods to characterize prokaryotic consortia associated with high-temperature, sulfur-rich oil reservoirs in California. Enrichment cultures designed for anaerobic thermophiles, both autotrophic and heterotrophic, were successful at temperatures ranging from 60 to 90°C. Heterotrophic enrichments from all sites yielded sheathed rods (
Thermotogales
), pleomorphic rods resembling
Thermoanaerobacter
, and
Thermococcus
-like isolates. The predominant autotrophic microorganisms recovered from inorganic enrichments using H
2
, acetate, and CO
2
as energy and carbon sources were methanogens, including isolates closely related to
Methanobacterium
,
Methanococcus
, and
Methanoculleus
species. Two 16S rRNA gene (rDNA) libraries were generated from total community DNA collected from production wellheads, using either archaeal or universal oligonucleotide primer sets. Sequence analysis of the universal library indicated that a large percentage of clones were highly similar to known bacterial and archaeal isolates recovered from similar habitats. Represented genera in rDNA clone libraries included
Thermoanaerobacter
,
Thermococcus
,
Desulfothiovibrio
,
Aminobacterium
,
Acidaminococcus
,
Pseudomonas
,
Halomonas
,
Acinetobacter
,
Sphingomonas
,
Methylobacterium
, and
Desulfomicrobium
. The archaeal library was dominated by methanogen-like rDNAs, with a lower percentage of clones belonging to the
Thermococcales
. Our results strongly support the hypothesis that sulfur-utilizing and methane-producing thermophilic microorganisms have a widespread distribution in oil reservoirs and the potential to actively participate in the biogeochemical transformation of carbon, hydrogen, and sulfur in situ.