bluuebunny/crossref_metadata_2025 huggingface dataset:
Steady axisymmetric flow in an open cylindrical container with a partially rotating bottom wall
Authors: Piva M. , Meiburg E.
Published: June 2005

The steady motion of a viscous fluid in a cylindrical container with a partially rotating bottom wall and a free surface is investigated by means of axisymmetric Navier–Stokes simulations. The flow above the spinning disk at the center of the bottom wall is dominated by an Ekman boundary layer that drives the fluid radially outward. In contrast, an inward flow ensues along the outer, stationary part of the bottom wall, where the radially increasing pressure distribution set up by the rotating fluid motion near the free surface is not balanced by a corresponding centrifugal force. As a result, flow separation occurs at an intermediate radial location close to the outer edge of the rotating disk. Thus a flow configuration results that is dominated by a meridional vortex above the spinning disk, and a counterrotating vortex above the stationary part of the bottom wall. Simulations are conducted for various aspect ratios and Reynolds numbers, in order to evaluate the resulting changes in the vortex breakdown configurations. As the ratio of container radius to disk radius increases above a value of about 2.3, the influence of the lateral container wall on the features of the central flow in the neighborhood of the spinning disk becomes insignificant. By means of a simplified model problem, it is demonstrated that this rapid loss of influence is due to the exponential decay of the azimuthal surface velocity beyond the edge of the disk. This exponential decay is confirmed by the numerical data, and it reflects the fact that as the lateral wall moves outward, the stationary part of the end wall becomes the main sink for the azimuthal momentum of the fluid.
Tuning the morphology of InP self-assembled quantum structures grown on InAlP surfaces by metalorganic chemical vapor deposition
Authors: Zhang X. B. , Ryou J. H. , Dupuis R. D. , Walter G. , Holonyak N.
Published: June 2005

We describe the growth of InP quantum structures on In0.5Al0.5P lattice-matched matrices deposited on (001) GaAs substrates using metalorganic chemical vapor deposition. We find that the deposited InP initially forms quantum wires, about 50 nm in width and a few nanometers in height. Further deposition of InP leads to the formation of quantum dots (QDs) on top of these wires. By varying the matrix growth conditions, the morphology of the InP quantum structures can be tuned. We demonstrate that the density of the wires and the QDs can be tuned by controlling the diffusion kinetics, i.e., changing the growth rate or growth temperature, during the growth of the In0.5Al0.5P matrix. Linear chains of self-assembled InP QDs can be achieved using optimized matrix layers.
Analysis of octadecyltrichlorosilane treatment of organic thin-film transistors using soft x-ray fluorescence spectroscopy
Authors: Kang S. J. , Yi Y. , Kim C. Y. , Whang C. N. , Callcott T. A. , Krochak K. , Moewes A. , Chang G. S.
Published: June 2005

The effect of octadecyltrichlorosilane (OTS) treatment on the electronic properties of organic thin-film transistors is investigated using soft x-ray absorption and emission spectroscopy. Analysis of Carbon Kα x-ray emission spectra reveals that treating the SiO2 layer with OTS prior to pentacene deposition increases the number of π-bonding states in the active pentacene layer, which is strongly correlated with the conduction of charge carriers. The role of the increased π-bonding states is verified by measuring the current-voltage characteristics of pentacene thin-film transistors with and without OTS treatment. Drain current and field-effect mobility of OTS-treated samples are significantly enhanced as anticipated from the spectroscopic analysis.
Domain-wall displacement triggered by an ac current below threshold
Authors: Tatara Gen , Saitoh Eiji , Ichimura Masahiko , Kohno Hiroshi
Published: June 2005

It is theoretically demonstrated that a displacement of a pinned domain wall, typically of order of μm, can be driven by use of an ac current which is below threshold value. The point here is that finite motion around the pinning center by a low current is enhanced significantly by the resonance if the frequency is tuned close to the pinning frequency as demonstrated by recent experiment.
Night-vision brain area in migratory songbirds
Authors: Mouritsen Henrik , Feenders Gesa , Liedvogel Miriam , Wada Kazuhiro , Jarvis Erich D.
Published: June 2005

Twice each year, millions of night-migratory songbirds migrate thousands of kilometers. To find their way, they must process and integrate spatiotemporal information from a variety of cues including the Earth's magnetic field and the night-time starry sky. By using sensory-driven gene expression, we discovered that night-migratory songbirds possess a tight cluster of brain regions highly active only during night vision. This cluster, here named “cluster N,” is located at the dorsal surface of the brain and is adjacent to a known visual pathway. In contrast, neuronal activation of cluster N was not increased in nonmigratory birds during the night, and it disappeared in migrants when both eyes were covered. We suggest that in night-migratory songbirds cluster N is involved in enhanced night vision, and that it could be integrating vision-mediated magnetic and/or star compass information for night-time navigation. Our findings thus represent an anatomical and functional demonstration of a specific night-vision brain area.
A heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly
Authors: Stray Stephen J. , Bourne Christina R. , Punna Sreenivas , Lewis Warren G. , Finn M. G. , Zlotnick Adam
Published: June 2005

Heteroaryldihydropyrimidines (HAPs) are a new class of antivirals inhibiting production of hepatitis B virus (HBV) virions in tissue culture. Here, we examine the effect of a representative HAP molecule, methyl 4-(2-chloro-4-fluorophenyl)-6-methyl-2-(pyridin-2-yl)-1,4-dihydropyrimidine-5-carboxylate (HAP-1), on the
in vitro
assembly of HBV capsid protein (Cp). HAP-1 enhances the rate and extent of Cp assembly over a broad concentration range. Aberrant particles, dominated by hexagonal arrays of Cp, were observed from assembly reactions with high HAP-1 concentrations. HAP-1 also led to dissociation of metastable HBV capsids, overcoming a kinetic barrier to dissociation by scavenging Cp and redirecting its assembly into hexamer-rich structures. Thus, HAP drugs act as allosteric effectors that induce an assembly-active state and, at high concentration, preferentially stabilize noncapsid polymers of Cp. HAP compounds may have multiple effects
in vivo
stemming from inappropriate assembly of Cp. These results show that activating and deregulating virus assembly may be a powerful general approach for antiviral therapeutics.
A chemical waveform synthesizer
Authors: Olofsson Jessica , Bridle Helen , Sinclair Jon , Granfeldt Daniel , Sahlin Eskil , Orwar Owe
Published: June 2005

Algorithms and methods were developed to synthesize complex chemical waveforms in open volumes by using a scanning-probe microfluidic platform. Time-dependent variations and oscillations of one or several chemical species around the scanning probe, such as formation of sine waves, damped oscillations, and generation of more complex patterns, are demonstrated. Furthermore, we show that intricate bursting and chaotic calcium oscillations found in biological microdomains can be reproduced and that a biological cell can be used as a probe to study receptor functionalities as a function of exposure to time-dependent variations of receptor activators and inhibitors. Thus, the method allows for studies of biologically important oscillatory reactions. More generally, the system allows for detailed studies of complex time-varying chemical and physical phenomena in solution or at solution/surface interfaces.
Nucleosome assembly protein-1 is a linker histone chaperone in
Xenopus
eggs
Authors: Shintomi Keishi , Iwabuchi Mari , Saeki Hideaki , Ura Kiyoe , Kishimoto Takeo , Ohsumi Keita
Published: June 2005

In eukaryotic cells, genomic DNA is primarily packaged into nucleosomes through sequential ordered binding of the core and linker histone proteins. The acidic proteins termed histone chaperones are known to bind to core histones to neutralize their positive charges, thereby facilitating their proper deposition onto DNA to assemble the core of nucleosomes. For linker histones, however, little has been known about the regulatory mechanism for deposition of linker histones onto the linker DNA. Here we report that, in
Xenopus
eggs, the linker histone is associated with the
Xenopus
homologue of nucleosome assembly protein-1 (NAP-1), which is known to be a chaperone for the core histones H2A and H2B in
Drosophila
and mammalian cells [Ito, T., Bulger, M., Kobayashi, R. & Kadonaga, J. T. (1996)
Mol. Cell Biol.
16, 3112–3124; Chang, L., Loranger, S. S., Mizzen, C., Ernst, S. G., Allis, C. D. & Annunziato, A. T. (1997)
Biochemistry
36, 469–480]. We show that NAP-1 acts as the chaperone for the linker histone in both sperm chromatin remodeling into nucleosomes and linker histone binding to nucleosome core dimers. In the presence of NAP-1, the linker histone is properly deposited onto linker DNA at physiological ionic strength, without formation of nonspecific aggregates. These results strongly suggest that NAP-1 functions as a chaperone for the linker histone in
Xenopus
eggs.
Cell and plastid division are coordinated through the prereplication factor AtCDT1
Authors: Raynaud Cécile , Perennes Claudette , Reuzeau Christophe , Catrice Olivier , Brown Spencer , Bergounioux Catherine
Published: June 2005

The cell division cycle involves nuclear and cytoplasmic events, namely organelle multiplication and distribution between the daughter cells. Until now, plastid and plant cell division have been considered as independent processes because they can be uncoupled. Here, down-regulation of AtCDT1a and AtCDT1b, members of the prereplication complex, is shown to alter both nuclear DNA replication and plastid division in
Arabidopsis thaliana
. These data constitute molecular evidence for relationships between the cell-cycle and plastid division. Moreover, the severe developmental defects observed in AtCDT1-RNA interference (RNAi) plants underline the importance of coordinated cell and organelle division for plant growth and morphogenesis.
Genomic analysis of
Drosophila
chromosome underreplication reveals a link between replication control and transcriptional territories
Authors: Belyakin Stepan N. , Christophides George K. , Alekseyenko Artyom A. , Kriventseva Evgenia V. , Belyaeva Elena S. , Nanayev Roman A. , Makunin Igor V. ,   Heidelberg Fly Array Consortium§, Kafatos Fotis C. , Zhimulev Igor F.
Published: June 2005

In
Drosophila
polytene chromosomes, most late-replicating regions remain underreplicated. A loss-of-function mutant of the suppressor of underreplication [
Su(UR)
] gene suppresses underreplication (UR), whereas extra copies of this gene enhance the level and number of regions showing UR. By combining DNA microarray analysis with manipulation of the number of
Su(UR)
gene copies, we achieved genomic-scale molecular identification of 1,036 genes that are arranged in clusters located in 52 UR chromosomal regions. These regions overlap extensively (96%) but are not completely identical with late-replicating regions of mitotically dividing Kc cells in culture. Reanalysis of published gene expression profiles revealed that genomic regions defined by replication properties include clusters of coordinately expressed genes. Genomic regions that are UR in polytene chromosomes and late replicated in Kc cell chromosomes show a particularly common association with transcriptional territories that are expressed in testis/males but not ovary/females or embryos. An attractive hypothesis for future testing is that factors involved in replication control, such as SU(UR), may interact physically with those involved in epigenetic silencing of transcription territories.
The coordinate regulation of the p53 and mTOR pathways in cells
Authors: Feng Zhaohui , Zhang Haiyan , Levine Arnold J. , Jin Shengkan
Published: June 2005

Cell growth and proliferation requires an intricate coordination between the stimulatory signals arising from nutrients and growth factors and the inhibitory signals arising from intracellular and extracellular stresses. Alteration of the coordination often causes cancer. In mammals, the mTOR (mammalian target of rapamycin) protein kinase is the central node in nutrient and growth factor signaling, and p53 plays a critical role in sensing genotoxic and other stresses. The results presented here demonstrate that activation of p53 inhibits mTOR activity and regulates its downstream targets, including autophagy, a tumor suppression process. Moreover, the mechanisms by which p53 regulates mTOR involves AMP kinase activation and requires the tuberous sclerosis (TSC) 1/TSC2 complex, both of which respond to energy deprivation in cells. In addition, glucose starvation not only signals to shut down mTOR, but also results in the transient phosphorylation of the p53 protein. Thus, p53 and mTOR signaling machineries can cross-talk and coordinately regulate cell growth, proliferation, and death.
Influence of
in vivo
growth on human glioma cell line gene expression: Convergent profiles under orthotopic conditions
Authors: Camphausen Kevin , Purow Benjamin , Sproull Mary , Scott Tamalee , Ozawa Tomoko , Deen Dennis F. , Tofilon Philip J.
Published: June 2005

Defining the molecules that regulate tumor cell survival is an essential prerequisite for the development of targeted approaches to cancer treatment. Whereas many studies aimed at identifying such targets use human tumor cells grown
in vitro
or as s.c. xenografts, it is unclear whether such experimental models replicate the phenotype of the
in situ
tumor cell. To begin addressing this issue, we have used microarray analysis to define the gene expression profile of two human glioma cell lines (U251 and U87) when grown
in vitro
and
in vivo
as s.c. or as intracerebral (i.c.) xenografts. For each cell line, the gene expression profile generated from tissue culture was significantly different from that generated from the s.c. tumor, which was significantly different from those grown i.c. The disparity between the i.c gene expression profiles and those generated from s.c. xenografts suggests that whereas an
in vivo
growth environment modulates gene expression, orthotopic growth conditions induce a different set of modifications. In this study the U251 and U87 gene expression profiles generated under the three growth conditions were also compared. As expected, the profiles of the two glioma cell lines were significantly different when grown as monolayer cultures. However, the glioma cell lines had similar gene expression profiles when grown i.c. These results suggest that tumor cell gene expression, and thus phenotype, as defined
in vitro
is affected not only by
in vivo
growth but also by orthotopic growth, which may have implications regarding the identification of relevant targets for cancer therapy.
Foliage shedding in deciduous forests lifts up long-distance seed dispersal by wind
Authors: Nathan Ran , Katul Gabriel G.
Published: June 2005

Seed terminal velocity and release height are recognized as key biotic determinants of long-distance dispersal (LDD) of seeds by wind. Yet, potential determinants at the ecosystem level, such as seasonal dynamics in foliage density characterizing many deciduous forests, have received much less attention. We integrated detailed field observations and experiments with a mechanistic wind dispersal model to assess how seasonal variation in foliage density, estimated by leaf-area index (LAI), affects LDD in deciduous forests. We found that the model, previously shown to accurately predict seed dispersal by wind, also reliably describes the effects of LAI variation on wind statistics for a wide range of canopy types. Sparser canopies are characterized by more organized vertical eddy motion that promotes LDD by uplifting seeds to higher elevations where winds are stronger. Yet, sparser canopies are also characterized by reduced mean windspeed aloft. We showed that former effect more than compensates for the latter, i.e., conditions of low LAI are favorable for LDD. This may account for the tendency of many temperate tree species to restrict seed release to either early spring or late fall, when LAI is relatively low. Sensitivity analysis reveals that the typical seasonal variation in LAI can be more important to LDD of seeds by wind than the natural variation in seed terminal velocity. Because our model accurately describes the effects of LAI variation for distinctly different sites, species, and life forms, we suggest that its results reflect a general association between LDD and foliage density dynamics.
The telomerase reverse transcriptase regulates chromatin state and DNA damage responses
Authors: Masutomi Kenkichi , Possemato Richard , Wong Judy M. Y. , Currier Jennifer L. , Tothova Zuzana , Manola Judith B. , Ganesan Shridar , Lansdorp Peter M. , Collins Kathleen , Hahn William C.
Published: June 2005

Constitutive expression of telomerase prevents senescence and crisis by maintaining telomere homeostasis. However, recent evidence suggests that telomerase is dynamically regulated in normal cells and also contributes to transformation independently of net telomere elongation. Here, we show that suppression of the telomerase catalytic subunit [human telomerase reverse transcriptase (hTERT)] expression abrogates the cellular response to DNA double strand breaks. Loss of hTERT does not alter short-term telomere integrity but instead affects the overall configuration of chromatin. Cells lacking hTERT exhibit increased radiosensitivity, diminished capacity for DNA repair, and fragmented chromosomes, demonstrating that loss of hTERT impairs the DNA damage response.
Use of DNA barcodes to identify flowering plants
Authors: Kress W. John , Wurdack Kenneth J. , Zimmer Elizabeth A. , Weigt Lee A. , Janzen Daniel H.
Published: June 2005

Methods for identifying species by using short orthologous DNA sequences, known as “DNA barcodes,” have been proposed and initiated to facilitate biodiversity studies, identify juveniles, associate sexes, and enhance forensic analyses. The cytochrome
c
oxidase 1 sequence, which has been found to be widely applicable in animal barcoding, is not appropriate for most species of plants because of a much slower rate of cytochrome
c
oxidase 1 gene evolution in higher plants than in animals. We therefore propose the nuclear internal transcribed spacer region and the plastid
trnH-psbA
intergenic spacer as potentially usable DNA regions for applying barcoding to flowering plants. The internal transcribed spacer is the most commonly sequenced locus used in plant phylogenetic investigations at the species level and shows high levels of interspecific divergence. The
trnH-psbA
spacer, although short (≈450-bp), is the most variable plastid region in angiosperms and is easily amplified across a broad range of land plants. Comparison of the total plastid genomes of tobacco and deadly nightshade enhanced with trials on widely divergent angiosperm taxa, including closely related species in seven plant families and a group of species sampled from a local flora encompassing 50 plant families (for a total of 99 species, 80 genera, and 53 families), suggest that the sequences in this pair of loci have the potential to discriminate among the largest number of plant species for barcoding purposes.
Building a human kinase gene repository: Bioinformatics, molecular cloning, and functional validation
Authors: Park Jaehong , Hu Yanhui , Murthy T. V. S. , Vannberg Fredrik , Shen Binghua , Rolfs Andreas , Hutti Jessica E. , Cantley Lewis C. , LaBaer Joshua , Harlow Ed , Brizuela Leonardo
Published: June 2005

Kinases catalyze the phosphorylation of proteins, lipids, sugars, nucleosides, and other important cellular metabolites and play key regulatory roles in all aspects of eukaryotic cell physiology. Here, we describe the mining of public databases to collect the sequence information of all identified human kinase genes and the cloning of the corresponding ORFs. We identified 663 genes, 511 encoding protein kinases, and 152 encoding nonprotein kinases. We describe the successful cloning and sequence verification of 270 of these genes. Subcloning of this gene set in mammalian expression vectors and their use in high-throughput cell-based screens allowed the validation of the clones at the level of expression and the identification of previously uncharacterized modulators of the survivin promoter. Moreover, expressions of the kinase genes in bacteria, followed by autophosphorylation assays, identified 21 protein kinases that showed autocatalytic activity. The work described here will facilitate the functional assaying of this important gene family in phenotypic screens and their use in biochemical and structural studies.
Genome-wide requirements for
Mycobacterium tuberculosis
adaptation and survival in macrophages
Authors: Rengarajan Jyothi , Bloom Barry R. , Rubin Eric J.
Published: June 2005

Macrophages are central to host defense against microbes, but intracellular pathogens have evolved to evade their antimicrobial functions.
Mycobacterium tuberculosis
(MTB) has successfully exploited macrophages as its primary niche
in vivo
, but the bacterial genome-wide requirements that promote its intracellular survival remain undefined. Here we comprehensively identify the MTB genes required for survival by screening for transposon mutants that fail to grow within primary macrophages. We identify mutants showing decreased growth in macrophage environments that model stages of the host immune response. By systematically analyzing several biologically relevant data sets, we have been able to identify putative pathways that could not be predicted by genome organization alone. In one example, phosphate transport, requiring physically unlinked genes, was found to be critical for MTB growth in macrophages and important for establishing persistent infection in lungs. Remarkably, the majority of MTB genes found by this analysis to be required for survival are constitutively expressed rather than regulated by macrophages, revealing the host-adapted lifestyle of an evolutionarily selected intracellular pathogen.
Cytokine-driven cell cycling is mediated through Cdc25A
Authors: Khaled Annette R. , Bulavin Dmitry V. , Kittipatarin Christina , Li Wen Qing , Alvarez Michelle , Kim Kyungjae , Young Howard A. , Fornace Albert J. , Durum Scott K.
Published: June 2005

Lymphocytes are the central mediators of the immune response, requiring cytokines for survival and proliferation. Survival signaling targets the Bcl-2 family of apoptotic mediators, however, the pathway for the cytokine-driven proliferation of lymphocytes is poorly understood. Here we show that cytokine-induced cell cycle progression is not solely dependent on the synthesis of cyclin-dependent kinases (Cdks) or cyclins. Rather, we observe that in lymphocyte cell lines dependent on interleukin-3 or interleukin-7, or primary lymphocytes dependent on interleukin 7, the phosphatase Cdc25A is the critical mediator of proliferation. Withdrawal of IL-7 or IL-3 from dependent lymphocytes activates the stress kinase, p38 MAPK, which phosphorylates Cdc25A, inducing its degradation. As a result, Cdk/cyclin complexes remain phosphorylated and inactive and cells arrest before the induction of apoptosis. Inhibiting p38 MAPK or expressing a mutant Cdc25A, in which the two p38 MAPK target sites, S75 and S123, are altered, renders cells resistant to cytokine withdrawal, restoring the activity of Cdk/cyclin complexes and driving the cell cycle independent of a growth stimulus.
Real-time analysis of the role of Ca2+ in flagellar movement and motility in single sea urchin sperm
Authors: Wood Christopher D. , Nishigaki Takuya , Furuta Toshiaki , Baba Shoji A. , Darszon Alberto
Published: June 2005

Eggs of many marine and mammalian species attract sperm by releasing chemoattractants that modify the bending properties of flagella to redirect sperm paths toward the egg. This process, called chemotaxis, is dependent on extracellular Ca2+. We used stroboscopic fluorescence imaging to measure intracellular Ca2+ concentration ([Ca2+]i) in the flagella of swimming sea urchin sperm. Uncaging of cyclic GMP induced Ca2+ entry via at least two distinct pathways, and we identified a nimodipine-sensitive pathway, compartmentalized in the flagella, as a key regulator of flagellar bending and directed motility changes. We found that, contrary to current models, the degree of flagellar bending does not vary in proportion to the overall [Ca2+]i. Instead we propose a new model whereby flagella bending is increased by Ca2+ flux through the nimodipine-sensitive pathway, and is unaffected by [Ca2+]i increases through alternative pathways.
Essential roles of Gα12/13 signaling in distinct cell behaviors driving zebrafish convergence and extension gastrulation movements
Authors: Lin Fang , Sepich Diane S. , Chen Songhai , Topczewski Jacek , Yin Chunyue , Solnica-Krezel Lilianna , Hamm Heidi
Published: June 2005

Gα12/13 have been implicated in numerous cellular processes, however, their roles in vertebrate gastrulation are largely unknown. Here, we show that during zebrafish gastrulation, suppression of both Gα12 and Gα13 signaling by overexpressing dominant negative proteins and application of antisense morpholino-modified oligonucleotide translation interference disrupted convergence and extension without changing embryonic patterning. Analyses of mesodermal cell behaviors revealed that Gα12/13 are required for cell elongation and efficient dorsalward migration during convergence independent of noncanonical Wnt signaling. Furthermore, Gα12/13 function cell-autonomously to mediate mediolateral cell elongation underlying intercalation during notochord extension, likely acting in parallel to noncanonical Wnt signaling. These findings provide the first evidence that Gα12 and Gα13 have overlapping and essential roles in distinct cell behaviors that drive vertebrate gastrulation.
Inp1p is a peroxisomal membrane protein required for peroxisome inheritance inSaccharomyces cerevisiae
Authors: Fagarasanu Monica , Fagarasanu Andrei , Tam Yuen Yi C. , Aitchison John D. , Rachubinski Richard A.
Published: June 2005

Cells have evolved molecular mechanisms for the efficient transmission of organelles during cell division. Little is known about how peroxisomes are inherited. Inp1p is a peripheral membrane protein of peroxisomes of Saccharomyces cerevisiae that affects both the morphology of peroxisomes and their partitioning during cell division. In vivo 4-dimensional video microscopy showed an inability of mother cells to retain a subset of peroxisomes in dividing cells lacking the INP1 gene, whereas cells overexpressing INP1 exhibited immobilized peroxisomes that failed to be partitioned to the bud. Overproduced Inp1p localized to both peroxisomes and the cell cortex, supporting an interaction of Inp1p with specific structures lining the cell periphery. The levels of Inp1p vary with the cell cycle. Inp1p binds Pex25p, Pex30p, and Vps1p, which have been implicated in controlling peroxisome division. Our findings are consistent with Inp1p acting as a factor that retains peroxisomes in cells and controls peroxisome division. Inp1p is the first peroxisomal protein directly implicated in peroxisome inheritance.
Histone deacetylase activity is essential for the expression of HoxA9 and for endothelial commitment of progenitor cells
Authors: Rössig Lothar , Urbich Carmen , Brühl Thomas , Dernbach Elisabeth , Heeschen Christopher , Chavakis Emmanouil , Sasaki Ken-ichiro , Aicher Diana , Diehl Florian , Seeger Florian , Potente Michael , Aicher Alexandra , Zanetta Lucia , Dejana Elisabetta , Zeiher Andreas M. , Dimmeler Stefanie
Published: June 2005

The regulation of acetylation is central for the epigenetic control of lineage-specific gene expression and determines cell fate decisions. We provide evidence that the inhibition of histone deacetylases (HDACs) blocks the endothelial differentiation of adult progenitor cells. To define the mechanisms by which HDAC inhibition prevents endothelial differentiation, we determined the expression of homeobox transcription factors and demonstrated that HoxA9 expression is down-regulated by HDAC inhibitors. The causal involvement of HoxA9 in the endothelial differentiation of adult progenitor cells is supported by the finding that HoxA9 overexpression partially rescued the endothelial differentiation blockade induced by HDAC inhibitors. Knockdown and overexpression studies revealed that HoxA9 acts as a master switch to regulate the expression of prototypical endothelial-committed genes such as endothelial nitric oxide synthase, VEGF-R2, and VE-cadherin, and mediates the shear stress–induced maturation of endothelial cells. Consistently, HoxA9-deficient mice exhibited lower numbers of endothelial progenitor cells and showed an impaired postnatal neovascularization capacity after the induction of ischemia. Thus, HoxA9 is regulated by HDACs and is critical for postnatal neovascularization.
Recruitment of Gr-1+ monocytes is essential for control of acute toxoplasmosis
Authors: Robben Paul M. , LaRegina Marie , Kuziel William A. , Sibley L. David
Published: June 2005

Circulating murine monocytes comprise two largely exclusive subpopulations that are responsible for seeding normal tissues (Gr-1−/CCR2−/CX3CR1high) or responding to sites of inflammation (Gr-1+/CCR2+/CX3CR1lo). Gr-1+ monocytes are recruited to the site of infection during the early stages of immune response to the intracellular pathogen Toxoplasma gondii. A murine model of toxoplasmosis was thus used to examine the importance of Gr-1+ monocytes in the control of disseminated parasitic infection in vivo. The recruitment of Gr-1+ monocytes was intimately associated with the ability to suppress early parasite replication at the site of inoculation. Infection of CCR2−/− and MCP-1−/− mice with typically nonlethal, low doses of T. gondii resulted in the abrogated recruitment of Gr-1+ monocytes. The failure to recruit Gr-1+ monocytes resulted in greatly enhanced mortality despite the induction of normal Th1 cell responses leading to high levels of IL-12, TNF-α, and IFN-γ. The profound susceptibility of CCR2−/− mice establishes Gr-1+ monocytes as necessary effector cells in the resistance to acute toxoplasmosis and suggests that the CCR2-dependent recruitment of Gr-1+ monocytes may be an important general mechanism for resistance to intracellular pathogens.
Ethanol Modulates the VR-1 Variant Amiloride-insensitive Salt Taste Receptor. II. Effect on Chorda Tympani Salt Responses
Authors: Lyall Vijay , Heck Gerard L. , Phan Tam-Hao T. , Mummalaneni Shobha , Malik Shahbaz A. , Vinnikova Anna K. , DeSimone John A.
Published: June 2005

The effect of ethanol on the amiloride- and benzamil (Bz)-insensitive salt taste receptor was investigated by direct measurement of intracellular Na+ activity ([Na+]i) using fluorescence imaging in polarized fungiform taste receptor cells (TRCs) and by chorda tympani (CT) taste nerve recordings. CT responses to KCl and NaCl were recorded in Sprague-Dawley rats, and in wild-type (WT) and vanilloid receptor-1 (VR-1) knockout mice (KO). CT responses were monitored in the presence of Bz, a specific blocker of the epithelial Na+ channel (ENaC). CT responses were also recorded in the presence of agonists (resiniferatoxin and elevated temperature) and antagonists (capsazepine and SB-366791) of VR-1 that similarly modulate the Bz-insensitive VR-1 variant salt taste receptor. In the absence of mineral salts, ethanol induced a transient decrease in TRC volume and elicited only transient phasic CT responses. In the presence of mineral salts, ethanol increased the apical cation flux in TRCs without a change in volume, increased transepithelial electrical resistance across the tongue, and elicited CT responses that were similar to salt responses, consisting of both a phasic component and a sustained tonic component. At concentrations <50%, ethanol enhanced responses to KCl and NaCl, while at ethanol concentrations >50%, those CT responses were inhibited. Resiniferatoxin and elevated temperature increased the sensitivity of the CT response to ethanol in salt-containing media, and SB-366791 inhibited the effect of ethanol, resiniferatoxin, and elevated temperature on the CT responses to mineral salts. VR-1 KO mice demonstrated no Bz-insensitive CT response to NaCl and no sensitivity to ethanol. We conclude that ethanol increases salt taste sensitivity by its direct action on the Bz-insensitive VR-1 variant salt taste receptor.
The Limit of Photoreceptor Sensitivity
Authors: Holcman David , Korenbrot Juan I.
Published: June 2005

Detection threshold in cone photoreceptors requires the simultaneous absorption of several photons because single photon photocurrent is small in amplitude and does not exceed intrinsic fluctuations in the outer segment dark current (dark noise). To understand the mechanisms that limit light sensitivity, we characterized the molecular origin of dark noise in intact, isolated bass single cones. Dark noise is caused by continuous fluctuations in the cytoplasmic concentrations of both cGMP and Ca2+ that arise from the activity in darkness of both guanylate cyclase (GC), the enzyme that synthesizes cGMP, and phosphodiesterase (PDE), the enzyme that hydrolyzes it. In cones loaded with high concentration Ca2+ buffering agents, we demonstrate that variation in cGMP levels arise from fluctuations in the mean PDE enzymatic activity. The rates of PDE activation and inactivation determine the quantitative characteristics of the dark noise power density spectrum. We developed a mathematical model based on the dynamics of PDE activity that accurately predicts this power spectrum. Analysis of the experimental data with the theoretical model allows us to determine the rates of PDE activation and deactivation in the intact photoreceptor. In fish cones, the mean lifetime of active PDE at room temperature is ∼55 ms. In nonmammalian rods, in contrast, active PDE lifetime is ∼555 ms. This remarkable difference helps explain why cones are noisier than rods and why cone photocurrents are smaller in peak amplitude and faster in time course than those in rods. Both these features make cones less light sensitive than rods.
Relating Musical Structure and Content to Aesthetic Response: A Model and Analysis of Beethoven's Piano Sonata Op. 110
Authors: Ockelford Adam
Published: June 2005

A model is presented which aims to show how, for listeners familiar with a given style, aesthetic response to music may be related to its ‘structure’ (as defined in relation to ‘zygonic’ theory) and ‘content’ (the particular perceived qualities of sound that pertain to a given musical event). The model combines recent empirical findings from music psychology with other approaches adapted from music theory and philosophy. Intramusical considerations, which form the core of the model, are positioned within a broader socio-cultural, cognitive and physical context. The new framework is used to inform an analysis of Beethoven's Piano Sonata op.110, which examines in particular the notions of teleology in music and narrative metaphor.
The Mechanisms of the Music Trade in Central Germany, 1600–40
Authors: Rose Stephen
Published: June 2005

One of the main challenges facing early printers and publishers of music was how to distribute their products to a dispersed, niche market. At the start of the seventeenth century there were two principal routes of dissemination in German-speaking lands: the general book trade (including the fairs at Frankfurt am Main and Leipzig) and the composer's own initiatives (whether via presentation copies, or via self-publication as pursued by Michael Praetorius, Johann Hermann Schein and Heinrich Schütz). This article traces the transactions by which music was disseminated, examines the range of music available through the book trade, and asks how booksellers and musicians negotiated the market for printed music.
Publishing Music from the Fitzwilliam Museum, Cambridge: The Work of Vincent Novello and Samuel Wesley in the 1820s
Authors: Olleson Philip , Palmer Fiona M.
Published: June 2005

In 1816, Richard Fitzwilliam died, bequeathing his important music collection to the University of Cambridge. In 1824 the University decided to allow selections from it to be published. The most important outcome was Vincent Novello's five-volumeThe Fitzwilliam Music(1825–7), containing Latin church music by Italian composers of the sixteenth to the eighteenth centuries, but there was also an edition by Samuel Wesley of three hymn tunes by Handel to words by his father, and Wesley also projected an edition of motets from Byrd'sGradualiawhich for financial reasons was never published. This article discusses Fitzwilliam's bequest, the involvement of Novello and Wesley, the two publications that resulted in the 1820s, and Wesley's unsuccessful Byrd project.
President, patron, friend and lover: Charles Montagu's significance to the history of science
Authors: Higgitt Rebekah
Published: May 2005

This article examines the legacy of Charles Montagu, Lord Halifax, within the history of science. Although he was President of The Royal Society from 1695 to 1698, Montagu is best known for his political career and as a patron of the arts. As this article shows, Montagu's own scientific interests were limited and his chief significance to the history of science lies in his friendship with a later President, Isaac Newton. It is argued, firstly, that their relationship had important, though indirect, consequences for The Royal Society and, secondly, that its treatment by historians of science has been revealing of changing views of the status of science and its practitioners. Particular attention is given to the approaches of the first generation of Newtonian scholars and biographers in the 19th century.
Transport of neutral solute in articular cartilage: effects of loading and particle size
Authors: Zhang Le , Szeri A.Z
Published: June 2005

We investigate the influence that matrix structure, size of diffusing molecules and type and intensity of mechanical loading have on the transport of neutral solutes in articular cartilage. Although this type of investigation has been performed in the past, earlier researchers assumed a constant diffusion coefficient. By contrast, our diffusion coefficient depends on the local deformation of the matrix, and thus varies both in space and in time during an experiment.

We derive a three-dimensional formulation of the problem based on mixture theory and utilize the commercial finite-element code ABAQUS to study it numerically. We also make use of the Cohen–Turnbull–Yasuda model to correlate the decrease of the diffusion coefficient with the increase in tortuosity, owing to the presence of the matrix. Under appropriate circumstances, the equations derived here reduce to the classical convection/diffusion equation and the equations of the biphasic cartilage model. Even though we chose axisymmetric sample geometry for the present calculations, the model can easily be applied to irregular three-dimensional samples.

Our results reinforce and refine previously published studies. The neutral solute's rate of diffusion is reduced under static compression, due to the strain dependence of the diffusion coefficient; an increase in static compression leads to a decrease in the rate of transport of solutes of all sizes. Dynamic loading, on the other hand, augments solute transport due to convection, depending on particle size. The transport of small molecular size solute is moderately enhanced, but only within the surface layer; however, the rate of transport of large molecule solute is greatly increased, even in the deep layer of the cartilage.
Robustness mechanisms in primate societies: a perturbation study
Authors: Flack Jessica C , Krakauer David C , de Waal Frans B. M
Published: June 2005

Conflict management mechanisms have a direct, critical effect on system robustness because they mitigate conflict intensity and help repair damaged relationships. However, robustness mechanisms can also have indirect effects on system integrity by facilitating interactions among components. We explore the indirect role that conflict management mechanisms play in the maintenance of social system robustness, using a perturbation technique to ‘knockout’ components responsible for effective conflict management. We explore the effects of knockout on pigtailed macaque (
Macaca nemestrina
) social organization, using a captive group of 84 individuals. This system is ideal in addressing this question because there is heterogeneity in performance of conflict management. Consequently, conflict managers can be easily removed without disrupting other control structures. We find that powerful conflict managers are essential in maintaining social order for the benefit of all members of society. We show that knockout of components responsible for conflict management results in system destabilization by significantly increasing mean levels of conflict and aggression, decreasing socio-positive interaction and decreasing the operation of repair mechanisms.
Influence of spatial heterogeneity on an emerging infectious disease: the case of dengue epidemics
Authors: Favier Charly , Schmit Delphine , Müller-Graf Christine D.M , Cazelles Bernard , Degallier Nicolas , Mondet Bernard , Dubois Marc A
Published: June 2005

The importance of spatial heterogeneity and spatial scales (at a village or neighbourhood scale) has been explored with individual-based models. Our reasoning is based on the Chilean Easter Island (EI) case, where a first dengue epidemic occurred in 2002 among the relatively small population localized in one village. Even in this simple situation, the real epidemic is not consistent with homogeneous models. Conversely, including contact heterogeneity on different scales (intra-households, inter-house, inter-areas) allows the recovery of not only the EI epidemiological curve but also the qualitative patterns of Brazilian urban dengue epidemic in more complex situations.
Host specificity of insect herbivores in tropical forests
Authors: Novotny Vojtech , Basset Yves
Published: June 2005

Studies of host specificity in tropical insect herbivores are evolving from a focus on insect distribution data obtained by canopy fogging and other mass collecting methods, to a focus on obtaining data on insect rearing and experimentally verified feeding patterns. We review this transition and identify persisting methodological problems. Replicated quantitative surveys of plant–herbivore food webs, based on sampling efforts of an order of magnitude greater than is customary at present, may be cost-effectively achieved by small research teams supported by local assistants. Survey designs that separate historical and ecological determinants of host specificity by studying herbivores feeding on the same plant species exposed to different environmental or experimental conditions are rare. Further, we advocate the use of host‐specificity measures based on plant phylogeny. Existing data suggest that a minority of species in herbivore communities feed on a single plant species when alternative congeneric hosts are available. Thus, host plant range limits tend to coincide with those of plant genera, rather than species or suprageneric taxa. Host specificity among tropical herbivore guilds decreases in the sequence: granivores>leaf-miners>fructivores>leaf-chewers=sap-suckers>xylophages>root-feeders, thus paralleling patterns observed in temperate forests. Differences in host specificity between temperate and tropical forests are difficult to assess since data on tropical herbivores originate from recent field studies, whereas their temperate counterparts derive from regional host species lists, assembled over many years. No major increase in host specificity from temperate to tropical communities is evident. This conclusion, together with the recent downward revisions of extremely high estimates of tropical species richness, suggest that tropical ecosystems may not be as biodiverse as previously thought.
Dual functions of a melanin-based ornament in the common yellowthroat
Authors: Tarof Scott A , Dunn Peter O , Whittingham Linda A
Published: June 2005

Melanin-based ornaments often function as signals in male–male competition, whereas carotenoid-based ornaments appear to be important in female mate choice. This difference in function is thought to occur because carotenoid pigments are more costly to produce than melanins and are thus more reliable indicators of male quality. We examined the role of melanin- and carotenoid-based ornaments in male–male competition and female choice in the common yellowthroatGeothlypis trichas, a sexually dichromatic passerine. Males display a black facial mask produced by melanin pigmentation and a bright yellow bib (throat, breast and belly) produced by carotenoid pigmentation. In controlled aviary experiments, mask size was the best predictor of both male–male competition and female mate choice, and, therefore, mask size may be regarded as an ornament of dual function. These dual functions may help to maintain the reliability of mask size as an indicator of male quality, despite the potentially low cost of production. The size of the bib was unrelated to male–male competition or female choice, but there was a tendency for females to prefer males with more colourful bibs. We propose that the black mask is important in competition for territories with other males and for attracting females. Our results highlight the need for more studies of the mechanisms of sexual selection in species with ornaments composed of different pigment types.
Differential gene expression in queen–worker caste determination in bumble-bees
Authors: Pereboom Jeffrey J. M , Jordan William C , Sumner Seirian , Hammond Robert L , Bourke Andrew F. G
Published: June 2005

Investigating how differential gene expression underlies caste determination in the social Hymenoptera is central to understanding how variation in gene expression underlies adaptive phenotypic diversity. We investigated for the first time the association between differential gene expression and queen–worker caste determination in the bumble-beeBombus terrestris. Using suppression subtractive hybridization we isolated 12 genes that were differentially expressed in queen- and worker-destined larvae. We found that the sets of genes underlying caste differences in larvae and adults failed to overlap greatly. We also found thatB. terrestrisshares some of the genes whose differential expression is associated with caste determination in the honeybee,Apis mellifera, but their expression patterns were not identical. Instead, we foundB. terrestristo exhibit a novel pattern, whereby most genes upregulated (i.e. showing relatively higher levels of expression) in queen-destined larvae early in development were upregulated in worker-destined larvae late in development. Overall, our results suggest that caste determination inB. terrestrisinvolves a difference not so much in the identity of genes expressed by queen- and worker-destined larvae, but primarily in the relative timing of their expression. This conclusion is of potential importance in the further study of phenotypic diversification via differential gene expression.