bluuebunny/crossref_metadata_2025 huggingface dataset:
Symmetry of unoccupied electronic states in the high-Tc superconductor Sr2CuO2+δCl2−y studied by electron energy-loss spectroscopy
Authors: Yang H. , Liu Q. Q. , Li F. Y. , Jin C. Q. , Yu R. C.
Published: February 2006

The symmetry of unoccupied electronic states at the O and Cu sites in the high-Tc superconductor Sr2CuO2+δCl2−y has been studied by measuring O1s and Cu2p3∕2 absorption edges using orientation-dependent high-energy electron energy-loss spectroscopy. Unlike many conventional superconductors, this superconducting material is found to have considerable O2p holes at the apical oxygen sites (about 40% O2p holes). About 60% O2p holes are found to have px,y symmetry in the CuO2 planes. The unoccupied states on the Cu sites have predominantly in-plane 3dx2−y2 symmetry, probably with an admixture of about 14% 3d3z2−r2 symmetry. The Cu2p3∕2 absorption edge exhibits clearly divalent Cu(2) states, indicating that the doped holes would reside predominantly on O2p orbitals.
Electrostatic separation of superconducting particles from a mixture
Authors: Tao R. , Xu X. , Khilnaney-Chhabria Deepika
Published: February 2006

The newly discovered phenomenon, electric-field-induced formation of superconducting balls, is effective in separating superconducting particles from a mixture with nonsuperconducting particles. In a suitable strong electric field, superconducting particles cling to the electrodes, while normal conducting particles bounce between the electrodes. The superconducting particles could then be collected from the electrodes. To separate superconducting particles from insulating ones, a moderate electric field is applied to force insulating particles to the electrodes to form short chains while keeping the superconducting particles in the middle of capacitor. This technology will be very useful in the fabrication of superconducting materials.
Spin-polarized transport in a lateral two-dimensional diluted magnetic semiconductor electron gas
Authors: Yang W. , Chang Kai , Wu X. G. , Zheng H. Z.
Published: February 2006

The transport property of a lateral two-dimensional paramagnetic diluted magnetic semiconductor electron gas under a spatially periodic magnetic field is investigated theoretically. We find that the electron Fermi velocity along the modulation direction is highly spin dependent even if the spin polarization of the carrier population is negligibly small. It turns out that this spin-polarized Fermi velocity alone can lead to a strong spin polarization of the current, which is still robust against the energy broadening effect induced by the impurity scattering.
Capacitance thermometer made of oxygen isotope-exchanged strontium titanate perovskite
Authors: Takashima Hiroshi , Wang Ruiping , Shirakawa Naoki , Prijamboedi Bambang , Okano Makoto , Shoji Akira , Itoh Mitsuru
Published: February 2006

A thermometer comprising a parallel capacitor made from a single crystal of oxygen isotope-exchanged SrTi(Ox18O1−x16)3 showed a dimensionless temperature sensitivity Sd exceeding 0.123 at 2K in the quantum ferroelectric region. On the other hand, the value of Sd in the quantum paraelectric region was 0.022 at 2K. The thermometric properties of the capacitance sensor were significantly improved by the O18 oxygen isotope exchange. A capacitance thermometer made of O18 oxygen isotope-exchanged SrTi(Ox18O1−x16)3 is a candidate element for accurate monitoring of cryogenic temperatures.
Infrared modulated interlevel spectroscopy of 1.3μm self-assembled quantum dot lasers using a free electron laser
Authors: Sellers I. R. , Mowbray D. J. , Badcock T. J. , Wells J.-P. R. , Phillips P. J. , Carder D. A. , Liu H. Y. , Groom K. M. , Hopkinson M.
Published: February 2006

A modulated far-IR technique is applied to determine the separations of the confined electron and hole states in a 1.3μm emitting self-assembled quantum-dot laser. By utilizing the unusual temperature behavior of the threshold current density, which exhibits a minimum at ∼200K, it is possible to eliminate heating effects associated with the far-IR pulses. In addition, the intense monochromatic laser output results in a relatively strong modulated signal strength. Electron and hole quantization energies of 46.7±0.2 and 13±1meV, respectively, are determined.
Investigation of Eu3+ luminescence intensification in Al2O3 powders codoped with Tb3+ and prepared by low-temperature direct combustion synthesis
Authors: Rakov Nikifor , Maciel Glauco S. , Lozano Whualkuer B. , de Araújo Cid B.
Published: February 2006

The luminescence properties of Eu3+:Tb3+:Al2O3 powders prepared by low-temperature direct combustion synthesis was investigated. It was observed that the presence of Tb3+ (1.0mol%) modifies the dynamics of the radiative transition D05→F27 of Eu3+ (1.0mol%) and produces an enhancement of the luminescence intensity by one order of magnitude.
Electron field emission from composite electrodes of carbon nanotubes-boron-doped diamond and carbon felts
Authors: Rosolen J. Mauricio , Tronto Simone , Marchesin Marcel S. , Almeida Erica C. , Ferreira Neidenei G. , Patrick Poá C. H. , Silva S. Ravi P.
Published: February 2006

The electron field emission of carbon nanotube (CNT)/boron-doped diamond (BDD)/carbon felt electrodes (CNT/BDD/felt) have been investigated. The composite electrode was initially prepared with the growth of BDD on carbon felt and the subsequent growth of CNT by chemical decomposition of methanol. The composite electrodes were characterised using scanning electron microscopy and transmission electron microscopy. For the CNT/BDD/felt samples, the electron field emission was observed at macroscopic fields as low as 1.1Vμm−1. The emission current versus time plot shows significant potential for future field emission applications.
Nanomaterial transfer using hot embossing for flexible electronic devices
Authors: Allen Ashante’ C. , Sunden Erik , Cannon Andrew , Graham Samuel , King William
Published: February 2006

We demonstrate hot embossing to pattern carbon nanotubes (CNTs) on flexible substrates. Patterns of CNTs grown on both microtextured and flat silicon templates were transferred into polymer substrates, with good replication of both the CNT patterns and surface relief features. The transferred CNTs formed a highly entangled network with electrical resistance of 1kΩ–9MΩ, depending on growth and embossing conditions. The electrical properties showed a strong sensitivity to both light and temperature. This dry transfer process shows promise for high throughput manufacturing of nanomaterial-based flexible electronic devices.
Nanowave devices for terahertz acoustic phonons
Authors: Lanzillotti-Kimura N. D. , Fainstein A. , Lemaître A. , Jusserand B.
Published: February 2006

The emergence of the area of nanophononics requires the development of terahertz (THz) acoustic devices with tailored properties. We describe nonperiodic planar nanostructures with specific THz phononic response and superior performance. We show that improved devices based on GaAs and AlAs layers can be designed using an optimization Nelder-Mead simplex method, and grown with state-of-the-art molecular beam epitaxy. We also demonstrate that high-resolution Raman scattering provides a powerful tool to characterize these devices. We illustrate the concept with results on acoustic THz edge and color filters.
Low critical current for spin transfer in magnetic tunnel junctions
Authors: Meng Hao , Wang Jianguo , Wang Jian-Ping
Published: February 2006

We report a novel approach to reduce the critical current density for spin transfer in nanoscale magnetic tunnel junction (MTJ) structures. By integrating a spin valve and a MTJ structure with antiparallel pinned layers, the dc critical switching current density is reduced by one order of magnitude (2×106A∕cm2) at room temperature. The magnetoresistive (MR) properties of the MTJ + spin-valve device are dominated by the MTJ layers. The MR ratio is 15.8% with resistance area product of 4.5Ωμm2. This demonstration opens a window for high-density magnetic random access memory design.
Characterization of a differential radio-frequency single-electron transistor
Authors: Schneiderman J. F. , Delsing P. , Shaw M. D. , Bozler H. M. , Echternach P. M.
Published: February 2006

We have fabricated and characterized an electrometer that couples two parallel single-electron transistors (SETs) to a single radio-frequency (RF) tank circuit for use as a differential RF-SET. We demonstrate operation of this device in summing, differential, and single-SET operation modes, and use it to measure a Coulomb staircase from a differential single Cooper-pair box. In differential mode, the device acts to screen out correlated input signals while being sensitive to anticorrelated signals.
Bark anatomy of three indigenous conifers from southern South America
Authors: Castro M. A. , Apóstolo N. M. , Navarro L. E.
Published: February 2006

This paper describes the bark anatomy of three native conifers from southern South America, Podocarpus nubigena Lindl., Saxegothaea conspicua Lindl. (Podocarpaceae) and Araucaria araucana (Mol.) K.Koch. (Araucariaceae). The bark colours of these three conifers are greyish-brown, reddish-brown and true brown, respectively. Morphologically, the bark of S. conspicua is scaly whereas it is fissured in A. araucana and P. nubigena. Fissures are relatively shallow in P. nubigena and relatively deep in A. araucana. The latter two species have elongated stripes and polygonal to irregular plates, respectively. Anatomically, P. nubigena shows a gradual transition between non-collapsed and collapsed phloem. This species shows secondary phloem cells regularly arranged in continuous tangential bands composed of alternating sieve cells, axial parenchyma and fibres. In A. araucana the ordered pattern observed in the non-collapsed secondary phloem is lost in the collapsed phloem. All three species show homocellular and uniseriate rays exhibiting a sinuous trajectory in the collapsed phloem and into the rhytidome. Fibres in P. nubigena are arranged in narrow, tangentially uniseriate lines. Sclereids are observed in S. conspicua whereas ramified sclereids and fibres are present in A. araucana. Minute cell-wall crystals in the fibres are exhibited in all species. The persistent rhytidome occupies a variable proportion of the bark. A. araucana shows thick periderms and rhytidome, with indistinct rays in dead phloem. Starch, tannins and resins are frequent in parenchyma. Secretory canals are present only in A. araucana. In summary, the external morphology, arrangement of axial parenchyma, type of the sclerenchymatous tissue, presence of secretory canals and cell-wall crystals are the most important features that can be used for identification when other diagnostic plant parts are missing.
Reproductive ecology of invasive Ochna serrulata (Ochnaceae) in south-eastern Queensland
Authors: Gosper Carl R. , Vivian-Smith Gabrielle , Hoad Kate
Published: February 2006

We investigated aspects of the reproductive ecology of Ochna serrulata (Hochst.) Walp., an invasive plant in eastern Australia. O. serrulata drupes were similar in size to fleshy fruits of other local invasive plants, but showed some distinct differences in quality, with a very high pulp lipid content (32.8% of dry weight), and little sugar and water. Seeds were dispersed by figbirds, Sphecotheres viridis Vieillot, a locally abundant frugivore, and comprised between 10 and 50% of all non-Ficus spp. fruit consumed during October and November. The rate of removal of O. serrulata drupes was greater in bushland than suburban habitats, indicating that control in bushland habitats should be a priority, but also that suburban habitats are likely to act as significant seed sources for reinvasion of bushland. Germination occurred under all seed-processing treatments (with and without pulp, and figbird gut passage), suggesting that although frugivores are important for dispersal, they are not essential for germination. Recruitment of buried and surface-sown seed differed between greenhouse and field experiments, with minimal recruitment of surface-sown seed in the field. Seed persistence was low, particularly under field conditions, with 0.75% seed viability after 6 months and 0% at 12 months. This provides an opportunity to target control efforts in south-eastern Queensland in spring before fruit set, when there is predicted to be few viable seeds in the soil.
Congruence between phylogeographic patterns in cpDNA variation in Eucalyptus marginata (Myrtaceae) and geomorphology of the Darling Plateau, south-west of Western Australia
Authors: Wheeler M. A. , Byrne M.
Published: February 2006

Phylogeographic patterns in the cp genome of Eucalyptus marginata Don ex Sm., a species common in the mesic region of south-western Australia, were investigated by using RFLP analysis. The chloroplast diversity was structured into two geographically distinct lineages and nested clade analysis inferred historical fragmentation as the major influence on the phylogeographic pattern. The lineages were separated along the geomorphological boundary of the Darling Scarp, which separates the Coastal Plain from the Darling Plateau. The divergence between the lineages is consistent with uplifting of the Darling Plateau in the late Neogene. Further geographic structuring in haplotype distributions was evident in the forest lineage on the Darling Plateau, where one sublineage was present in the central forest region and another was restricted to the south-eastern region. The level of divergence between these sublineages was similar to that between divergent lineages that have been identified in comparative phylogeographic studies of cpDNA variation in three species widespread throughout south-western Australia. In these species, divergence was attributed to the influence of significant changes in climatic oscillations across the semi-arid region during the mid-Pleistocene. The divergence identified in this study indicates that the influence of climatic change was widespread throughout south-western Australia, including the mesic, higher-rainfall region.
Equation of state of the postperovskite phase synthesized from a natural (Mg,Fe)SiO
3
orthopyroxene
Authors: Shieh Sean R. , Duffy Thomas S. , Kubo Atsushi , Shen Guoyin , Prakapenka Vitali B. , Sata Nagayoshi , Hirose Kei , Ohishi Yasuo
Published: February 2006

Using the laser-heated diamond anvil cell, we investigate the stability and equation of state of the postperovskite (ppv, CaIrO
3
-type) phase synthesized from a natural pyroxene composition with 9 mol.% FeSiO
3
. Our measured pressure-volume data from 12–106 GPa for the ppv phase yield a bulk modulus of 219(
5
) GPa and a zero-pressure volume of 164.9(
6
) Å
3
when
K
′
0
= 4. The bulk modulus of ppv is 575(
15
) GPa at a pressure of 100 GPa. The transition pressure is lowered by the presence of Fe. Our x-ray diffraction data indicate the ppv phase can be formed at
P
> 109(
4
) GPa and 2,400(400) K, corresponding to ≈400–550 km above the core-mantle boundary. Direct comparison of volumes of coexisting perovskite and CaIrO
3
-type phases at 80–106 GPa demonstrates that the ppv phase has a smaller volume than perovskite by 1.1(
2
)%. Using measured volumes together with the bulk modulus calculated from equation of state fits, we find that the bulk sound velocity decreases by 2.3(2.1)% across this transition at 120 GPa. Upon decompression without further heating, it was found that the ppv phase could still be observed at pressures as low at 12 GPa, and evidence for at least partial persistence to ambient conditions is also reported.
Directly reactivated, but not indirectly reactivated, memories undergo reconsolidation in the amygdala
Authors: Deębiec Jacek , Doyère Valérie , Nader Karim , LeDoux Joseph E.
Published: February 2006

Memory consolidation refers to a process by which newly learned information is made resistant to disruption. Traditionally, consolidation has been viewed as an event that occurs once in the life of a memory. However, considerable evidence now indicates that consolidated memories, when reactivated through retrieval, become labile (susceptible to disruption) again and undergo reconsolidation. Because memories are often interrelated in complex associative networks rather than stored in isolation, a key question is whether reactivation of one memory makes associated memories labile in a way that requires reconsolidation. We tested this in rats by creating interlinked associative memories using a second-order fear-conditioning task. We found that directly reactivated memories become labile, but indirectly reactivated (i.e., associated) memories do not. This suggests that memory reactivation produces content-limited rather than wholesale changes in a memory and its associations and explains why each time a memory is retrieved and updated, the entire associative structure of the memory is not grossly altered.
Inhibition of a background potassium channel by Gq protein α-subunits
Authors: Chen Xiangdong , Talley Edmund M. , Patel Nitin , Gomis Ana , McIntire William E. , Dong Biwei , Viana Félix , Garrison James C. , Bayliss Douglas A.
Published: February 2006

Two-pore-domain K
+
channels provide neuronal background currents that establish resting membrane potential and input resistance; their modulation provides a prevalent mechanism for regulating cellular excitability. The so-called TASK channel subunits (TASK-1 and TASK-3) are widely expressed, and they are robustly inhibited by receptors that signal through Gαq family proteins. Here, we manipulated G protein expression and membrane phosphatidylinositol 4,5-bisphosphate (PIP
2
) levels in intact and cell-free systems to provide electrophysiological and biochemical evidence that inhibition of TASK channels by Gαq-linked receptors proceeds unabated in the absence of phospholipase C (PLC) activity, and instead involves association of activated Gαq subunits with the channels. Receptor-mediated inhibition of TASK channels was faster and less sensitive to a PLCβ1-ct minigene construct than inhibition of PIP
2
-sensitive Kir3.4(S143T) homomeric channels that is known to be dependent on PLC. TASK channels were strongly inhibited by constitutively active Gαq, even by a mutated version that is deficient in PLC activation. Receptor-mediated TASK channel inhibition required exogenous Gαq expression in fibroblasts derived from Gαq/11 knockout mice, but proceeded unabated in a cell line in which PIP
2
levels were reduced by regulated overexpression of a lipid phosphatase. Direct application of activated Gαq, but not other G protein subunits, inhibited TASK channels in excised patches, and constitutively active Gαq subunits were selectively coimmunoprecipitated with TASK channels. These data indicate that receptor-mediated TASK channel inhibition is independent of PIP
2
depletion, and they suggest a mechanism whereby channel modulation by Gαq occurs through direct interaction with the ion channel or a closely associated intermediary.
The multisensory representation of number in infancy
Authors: Jordan Kerry E. , Brannon Elizabeth M.
Published: February 2006

Human infants can discriminate visual and auditory stimuli solely on the basis of number, suggesting a developmental foundation for the nonverbal number representations of adult humans. Recent studies suggest that these language-independent number representations are multisensory in both adult humans and nonhuman animals. Surprisingly, however, previous studies have yielded mixed evidence concerning whether nonverbal numerical representations independent of sensory modality are present early in human development. In this article, we use a paradigm that avoids stimulus confounds present in previous studies of cross-modal numerical mapping in infants. We show that 7-month-old infants preferentially attend to visual displays of adult humans that numerically match the number of adult humans they hear speaking. These data provide evidence that by 7 months of age, infants connect numerical representations across different sensory modalities when presented with human faces and voices. Results support the possibility of a shared system between preverbal infants and nonverbal animals for representing number.
Lamprey type II collagen and
Sox9
reveal an ancient origin of the vertebrate collagenous skeleton
Authors: Zhang GuangJun , Miyamoto Michael M. , Cohn Martin J.
Published: February 2006

Type II collagen is the major cartilage matrix protein in the jawed vertebrate skeleton. Lampreys and hagfishes, by contrast, are thought to have noncollagenous cartilage. This difference in skeletal structure has led to the hypothesis that the vertebrate common ancestor had a noncollagenous skeleton, with type II collagen becoming the predominant cartilage matrix protein after the divergence of jawless fish from the jawed vertebrates ≈500 million years ago. Here we report that lampreys have two type II collagen (
Col2α1
) genes that are expressed during development of the cartilaginous skeleton. We also demonstrate that the adult lamprey skeleton is rich in Col2α1 protein. Furthermore, we have isolated a lamprey orthologue of
Sox9
, a direct transcriptional regulator of
Col2α1
in jawed vertebrates, and show that it is coexpressed with both
Col2α1
genes during skeletal development. These results reveal that the genetic pathway for chondrogenesis in lampreys and gnathostomes is conserved through the activation of cartilage matrix molecules and suggest that a collagenous skeleton evolved surprisingly early in vertebrate evolution.
Synergistic roles of Mdm2 and Mdm4 for p53 inhibition in central nervous system development
Authors: Xiong Shunbin , Van Pelt Carolyn S. , Elizondo-Fraire Ana C. , Liu Geng , Lozano Guillermina
Published: February 2006

Loss of
Mdm2
or
Mdm4
leads to embryo lethal phenotypes that are p53-dependent. To determine whether Mdm2 and Mdm4 inhibit p53 function redundantly in a more restricted cell type, conditional alleles were crossed to a neuronal specific Cre transgene to delete
Mdm2
and
Mdm4
in the CNS. Mice lacking
Mdm2
in the CNS developed hydranencephaly at embryonic day 12.5 due to apoptosis, whereas
Mdm4
deletion showed a proencephaly phenotype at embryonic day 17.5 because of cell cycle arrest and apoptosis. The deletion of both genes, strikingly, contributed to an even earlier and more severe CNS phenotype. Additionally,
Mdm2
and
Mdm4
had a gene dosage effect, because loss of three of the four
Mdm
alleles also showed a more accelerated CNS phenotype than deletion of either gene alone. All phenotypes were rescued by deletion of
p53
. Thus, these
in vivo
data demonstrate the importance of Mdm4 independent of Mdm2 in inhibition of p53.
Magnetic superlattices and their nanoscale phase transition effects
Authors: Cheon Jinwoo , Park Jong-Il , Choi Jin-sil , Jun Young-wook , Kim Sehun , Kim Min Gyu , Kim Young-Min , Kim Youn Joong
Published: February 2006

The systematic assembly of nanoscale constituents into highly ordered superlattices is of significant interest because of the potential of their multifunctionalities and the discovery of new collective properties. However, successful observations of such superlattice-associated nanoscale phenomena are still elusive. Here, we present magnetic superlattices of Co and Fe
3
O
4
nanoparticles with multidimensional symmetry of either AB (NaCl) or AB
2
(AlB
2
). The discovery of significant enhancement (≈25 times) of ferrimagnetism is further revealed by forming previously undescribed superlattices of magnetically soft–hard Fe
3
O
4
@CoFe
2
O
4
through the confined geometrical effect of thermally driven intrasuperlattice phase transition between the nanoparticulate components.
Cytokine receptor-mediated trafficking of preformed IL-4 in eosinophils identifies an innate immune mechanism of cytokine secretion
Authors: Spencer Lisa A. , Melo Rossana C. N. , Perez Sandra A. C. , Bafford Staci P. , Dvorak Ann M. , Weller Peter F.
Published: February 2006

Although leukocytes of the innate immune system, including eosinophils, contain within their granules preformed stores of cytokines available for selective and rapid release, little is known about the mechanisms governing the mobilization and secretion of these cytokines. Here we show that a cytokine receptor, the IL-4 receptor α chain, mediates eotaxin-stimulated mobilization of preformed IL-4 from eosinophil granules into secretory vesicles. Eosinophils contain substantial intracellular quantities of several granule- and vesicle-associated cytokine receptors, including IL-4, IL-6, and IL-13 receptors as well as CCR3. Both IL-4 and IL-4 receptor α chain colocalized in eosinophil granules; and after eotaxin-stimulation, IL-4 receptor α chain, bearing bound IL-4, was mobilized into secretory vesicles. These findings indicate that intracellular cytokine receptors within secretory vesicles transport their cognate cytokines requisite for the secretion of cytokines preformed in innate immune leukocytes.
High frequency of centromere inactivation resulting in stable dicentric chromosomes of maize
Authors: Han Fangpu , Lamb Jonathan C. , Birchler James A.
Published: February 2006

Somatic chromosome spreads from maize (
Zea mays
L.) plants containing B-A translocation chromosomes undergoing the chromosome type breakage–fusion–bridge cycle were examined by FISH. The size and type of extra chromosomes varied among cells of the same individual. A collection of minichromosomes derived from the chromosome type breakage–fusion–bridge cycle was examined for the presence of stable dicentric chromosomes. Six of 23 chromosomes in the collection contained two regions with DNA sequences typical of centromeres. Functional analysis and immunolabeling of CENH3, the centromere-specific histone H3 variant, revealed only one functional centromere per chromosome, despite the duplicate centromere sequences. One plant was found with an inactive B centromere that had been translocated to the short arm of chromosome 9. The translocated centromere region appeared identical to that of a normal B chromosome. The inactivation of the centromeres was stable for at least four generations. By using dicentrics from dispensable chromosomes, centromere inactivation was found to be quite common under these circumstances.
Structure-based inhibitor design of AccD5, an essential acyl-CoA carboxylase carboxyltransferase domain of
Mycobacterium tuberculosis
Authors: Lin Ting-Wan , Melgar Melrose M. , Kurth Daniel , Swamidass S. Joshua , Purdon John , Tseng Teresa , Gago Gabriela , Baldi Pierre , Gramajo Hugo , Tsai Shiou-Chuan
Published: February 2006

Mycolic acids and multimethyl-branched fatty acids are found uniquely in the cell envelope of pathogenic mycobacteria. These unusually long fatty acids are essential for the survival, virulence, and antibiotic resistance of
Mycobacterium tuberculosis
. Acyl-CoA carboxylases (ACCases) commit acyl-CoAs to the biosynthesis of these unique fatty acids. Unlike other organisms such as
Escherichia coli
or humans that have only one or two ACCases,
M. tuberculosis
contains six ACCase carboxyltransferase domains, AccD1–6, whose specific roles in the pathogen are not well defined. Previous studies indicate that AccD4, AccD5, and AccD6 are important for cell envelope lipid biosynthesis and that its disruption leads to pathogen death. We have determined the 2.9-Å crystal structure of AccD5, whose sequence, structure, and active site are highly conserved with respect to the carboxyltransferase domain of the
Streptomyces coelicolor
propionyl-CoA carboxylase. Contrary to the previous proposal that AccD4–5 accept long-chain acyl-CoAs as their substrates, both crystal structure and kinetic assay indicate that AccD5 prefers propionyl-CoA as its substrate and produces methylmalonyl-CoA, the substrate for the biosyntheses of multimethyl-branched fatty acids such as mycocerosic, phthioceranic, hydroxyphthioceranic, mycosanoic, and mycolipenic acids. Extensive
in silico
screening of National Cancer Institute compounds and the University of California, Irvine, ChemDB database resulted in the identification of one inhibitor with a
K
i
of 13.1 μM. Our results pave the way toward understanding the biological roles of key ACCases that commit acyl-CoAs to the biosynthesis of cell envelope fatty acids, in addition to providing a target for structure-based development of antituberculosis therapeutics.
Involvement of a tissue-specific autoantibody in skin disorders of murine systemic lupus erythematosus and autoinflammatory diseases
Authors: Nishimura Hiroyuki , Strominger Jack L.
Published: February 2006

Human systemic lupus erythematosus (SLE) and its murine model, MRLlpr/lprmice, are well known to develop a wide range of symptoms, such as glomerulonephritis, dermatitis, and arthritis, as an immune-complex disease. However, the deposition of circulating immune complex does not fully explain the tissue specificity of disease. Tissue-specific autoantigens may also be involved in tissue inflammation. In this study, desmoglein 3 (Dsg3), a major component of epidermal desmosomes, was identified as a skin-specific autoantigen. Several murine models of skin inflammation were found to develop autoantibodies to Dsg3 tightly correlated with disease aggravation, especially in MRLlpr/lprmice. Furthermore, SLE-prone skin disease-free FcγRIIb-deficient mice developed skin inflammation upon immunization with Dsg3. Taken together with histological studies, we concluded that skin-specific Dsg3 serves as an autoantigen in chronic skin inflammatory diseases accompanied by mast cell degranulation, including both murine SLE and other autoinflammatory diseases.
Ligand-specific allosteric regulation of coactivator functions of androgen receptor in prostate cancer cells
Authors: Baek Sung Hee , Ohgi Kenneth A. , Nelson Charles A. , Welsbie Derek , Chen Charlie , Sawyers Charles L. , Rose David W. , Rosenfeld Michael G.
Published: February 2006

The androgen receptor not only mediates prostate development but also serves as a key regulator of primary prostatic cancer growth. Although initially responsive to selective androgen receptor modulators (SARMs), which cause recruitment of the nuclear receptor–corepressor (N-CoR) complex, resistance invariably occurs, perhaps in response to inflammatory signals. Here we report that dismissal of nuclear receptor–corepressor complexes by specific signals or androgen receptor overexpression results in recruitment of many of the cohorts of coactivator complexes that permits SARMs and natural ligands to function as agonists. SARM-bound androgen receptors appear to exhibit failure to recruit specific components of the coactivators generally bound by liganded nuclear receptors, including cAMP response element-binding protein (CBP)/p300 or coactivator-associated arginine methyltransferase 1 (CARM1) to the SARM-bound androgen receptor, although still causing transcriptional activation of androgen receptor target genes. SARM-bound androgen receptors use distinct LXXLL (L, leucine; X, any amino acid) helices in the p160 nuclear receptor interaction domains that may impose selective allosteric effects, providing a component of the molecular basis of differential responses to different classes of ligands by androgen receptor.
An optimal brain can be composed of conflicting agents
Authors: Livnat Adi , Pippenger Nicholas
Published: February 2006

Many behaviors have been attributed to internal conflict within the animal and human mind. However, internal conflict has not been reconciled with evolutionary principles, in that it appears maladaptive relative to a seamless decision-making process. We study this problem through a mathematical analysis of decision-making structures. We find that, under natural physiological limitations, an optimal decision-making system can involve “selfish” agents that are in conflict with one another, even though the system is designed for a single purpose. It follows that conflict can emerge within a collective even when natural selection acts on the level of the collective only.
Negative epistasis between natural variants of the
Saccharomyces cerevisiae MLH1
and
PMS1
genes results in a defect in mismatch repair
Authors: Heck Julie Akiko , Argueso Juan Lucas , Gemici Zekeriyya , Reeves Richard Guy , Bernard Ann , Aquadro Charles F. , Alani Eric
Published: February 2006

In budding yeast, the MLH1-PMS1 heterodimer is the major MutL homolog complex that acts to repair mismatches arising during DNA replication. Using a highly sensitive mutator assay, we observed that
Saccharomyces cerevisiae
strains bearing the S288c-strain-derived
MLH1
gene and the SK1-strain-derived
PMS1
gene displayed elevated mutation rates that conferred a long-term fitness cost. Dissection of this negative epistatic interaction using S288c-SK1 chimeras revealed that a single amino acid polymorphism in each gene accounts for this mismatch repair defect. Were these strains to cross in natural populations, segregation of alleles would generate a mutator phenotype that, although potentially transiently adaptive, would ultimately be selected against because of the accumulation of deleterious mutations. Such fitness “incompatibilities” could potentially contribute to reproductive isolation among geographically dispersed yeast. This same segregational mutator phenotype suggests a mechanism to explain some cases of a human cancer susceptibility syndrome known as hereditary nonpolyposis colorectal cancer, as well as some sporadic cancers.
Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling
Authors: Bourquin Jean-Pierre , Subramanian Aravind , Langebrake Claudia , Reinhardt Dirk , Bernard Olivier , Ballerini Paola , Baruchel André , Cavé Hélène , Dastugue Nicole , Hasle Henrik , Kaspers Gertjan L. , Lessard Michel , Michaux Lucienne , Vyas Paresh , van Wering Elisabeth , Zwaan Christian M. , Golub Todd R. , Orkin Stuart H.
Published: February 2006

Individuals with Down syndrome (DS) are predisposed to develop acute megakaryoblastic leukemia (AMKL), characterized by expression of truncated GATA1 transcription factor protein (GATA1s) due to somatic mutation. The treatment outcome for DS-AMKL is more favorable than for AMKL in non-DS patients. To gain insight into gene expression differences in AMKL, we compared 24 DS and 39 non-DS AMKL samples. We found that non-DS-AMKL samples cluster in two groups, characterized by differences in expression of HOX/TALE family members. Both of these groups are distinct from DS-AMKL, independent of chromosome 21 gene expression. To explore alterations of the GATA1 transcriptome, we used cross-species comparison with genes regulated by GATA1 expression in murine erythroid precursors. Genes repressed after GATA1 induction in the murine system, most notably GATA-2, MYC, and KIT, show increased expression in DS-AMKL, suggesting that GATA1s fail to repress this class of genes. Only a subset of genes that are up-regulated upon GATA1 induction in the murine system show increased expression in DS-AMKL, including GATA1 and BACH1, a probable negative regulator of megakaryocytic differentiation located on chromosome 21. Surprisingly, expression of the chromosome 21 gene RUNX1, a known regulator of megakaryopoiesis, was not elevated in DS-AMKL. Our results identify relevant signatures for distinct AMKL entities and provide insight into gene expression changes associated with these related leukemias.
Defining the primary route for lutein synthesis in plants: The role of
Arabidopsis
carotenoid β-ring hydroxylase CYP97A3
Authors: Kim Joonyul , DellaPenna Dean
Published: February 2006

Lutein, a dihydroxy derivative of α-carotene (β,ε-carotene), is the most abundant carotenoid in photosynthetic plant tissues where it plays important roles in light-harvesting complex-II structure and function. The synthesis of lutein from lycopene requires at least four distinct enzymatic reactions: β- and ε-ring cyclizations and hydroxylation of each ring at the C-3 position. Three carotenoid hydroxylases have already been identified in
Arabidopsis
, two nonheme diiron β-ring monooxygenases (the
B1
and
B2
loci) that primarily catalyze hydroxylation of the β-ring of β,β-carotenoids and one heme-containing monooxygenase (CYP97C1, the
LUT1
locus) that catalyzes hydroxylation of the ε-ring of β,ε-carotenoids. In this study, we demonstrate that
Arabidopsis
CYP97A3 (the
LUT5
locus) encodes a fourth carotenoid hydroxylase with major
in vivo
activity toward the β-ring of α-carotene (β,ε-carotene) and minor activity on the β-rings of β-carotene (β,β-carotene). A
cyp97a3
-null allele,
lut5-1
, causes an accumulation of α-carotene at a level equivalent to β-carotene in wild type, which is stably incorporated into photosystems, and a 35% reduction in β-carotene-derived xanthophylls. That
lut5-1
still produces 80% of wild-type lutein levels, indicating at least one of the other carotene hydroxylases, can partially compensate for the loss of CYP97A3 activity. From these data, we propose a model for the preferred pathway for lutein synthesis in plants: ring cyclizations to form α-carotene, β-ring hydroxylation of α-carotene by CYP97A3 to produce zeinoxanthin, followed by ε-ring hydroxylation of zeinoxanthin by CYP97C1 to produce lutein.
53BP1 and p53 synergize to suppress genomic instability and lymphomagenesis
Authors: Morales Julio C. , Franco Sonia , Murphy Michael M. , Bassing Craig H. , Mills Kevin D. , Adams Melissa M. , Walsh Nicole C. , Manis John P. , Rassidakis George Z. , Alt Frederick W. , Carpenter Phillip B.
Published: February 2006

p53-binding protein 1 (53BP1) participates in the cellular response to DNA double-stranded breaks where it associates with various DNA repair/cell cycle factors including the H2AX histone variant. Mice deficient for
53BP1
(
53BP1
−/−
) are sensitive to ionizing radiation and immunodeficient because of impaired Ig heavy chain class switch recombination. Here we show that, as compared with
p53
−/−
mice,
53BP1
−/−
/
p53
−/−
animals more rapidly develop tumors, including T cell lymphomas and, at lower frequency, B lineage lymphomas, sarcomas, and teratomas. In addition, T cells from animals deficient for both
53BP1
and
p53
(
53BP1
−/−
/
p53
−/−
) display elevated levels of genomic instability relative to T cells deficient for either
53BP1
or
p53
alone. In contrast to
p53
−/−
T cell lymphomas, which routinely display aneuploidy but not translocations,
53BP1
−/−
/
p53
−/−
thymic lymphomas fall into two distinct cytogenetic categories, with many harboring clonal translocations (40%) and the remainder showing aneuploidy (60%). We propose that 53BP1, in the context of
p53
deficiency, suppresses T cell lymphomagenesis through its roles in both cell-cycle checkpoints and double-stranded break repair.
Homodimeric cross-over structure of the human granulocyte colony-stimulating factor (GCSF) receptor signaling complex
Authors: Tamada Taro , Honjo Eijiro , Maeda Yoshitake , Okamoto Tomoyuki , Ishibashi Matsujiro , Tokunaga Masao , Kuroki Ryota
Published: February 2006

A crystal structure of the signaling complex between human granulocyte colony-stimulating factor (GCSF) and a ligand binding region of GCSF receptor (GCSF-R), has been determined to 2.8 Å resolution. The GCSF:GCSF-R complex formed a 2:2 stoichiometry by means of a cross-over interaction between the Ig-like domains of GCSF-R and GCSF. The conformation of the complex is quite different from that between human GCSF and the cytokine receptor homologous domain of mouse GCSF-R, but similar to that of the IL-6/gp130 signaling complex. The Ig-like domain cross-over structure necessary for GCSF-R activation is consistent with previously reported thermodynamic and mutational analyses.
Theileria parvacandidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes
Authors: Graham Simon P. , Pellé Roger , Honda Yoshikazu , Mwangi Duncan M. , Tonukari Nyerhovwo J. , Yamage Mat , Glew E. Jane , de Villiers Etienne P. , Shah Trushar , Bishop Richard , Abuya Evelyne , Awino Elias , Gachanja James , Luyai Anthony E. , Mbwika Ferdinand , Muthiani Anthony M. , Ndegwa David M. , Njahira Moses , Nyanjui John K. , Onono Fredrick O. , Osaso Julius , Saya Rosemary M. , Wildmann Claude , Fraser Claire M. , Maudlin Ian , Gardner Malcolm J. , Morzaria Subhash P. , Loosmore Sheena , Gilbert Sarah C. , Audonnet Jean-Christophe , van der Bruggen Pierre , Nene Vishvanath , Taracha Evans L. N.
Published: February 2006

East Coast fever, caused by the tick-borne intracellular apicomplexan parasiteTheileria parva, is a highly fatal lymphoproliferative disease of cattle. The pathogenic schizont-induced lymphocyte transformation is a unique cancer-like condition that is reversible with parasite removal. Schizont-infected cell-directed CD8+cytotoxic T lymphocytes (CTL) constitute the dominant protective bovine immune response after a single exposure to infection. However, the schizont antigens targeted byT. parva-specific CTL are undefined. Here we show the identification of five candidate vaccine antigens that are the targets of MHC class I-restricted CD8+CTL from immune cattle. CD8+T cell responses to these antigens were boosted inT. parva-immune cattle resolving a challenge infection and, when used to immunize naïve cattle, induced CTL responses that significantly correlated with survival from a lethal parasite challenge. These data provide a basis for developing a CTL-targeted anti-East Coast fever subunit vaccine. In addition, orthologs of these antigens may be vaccine targets for other apicomplexan parasites.
Combined top-down and bottom-up proteomics identifies a phosphorylation site in stem–loop-binding proteins that contributes to high-affinity RNA binding
Authors: Borchers Christoph H. , Thapar Roopa , Petrotchenko Evgeniy V. , Torres Matthew P. , Speir J. Paul , Easterling Michael , Dominski Zbigniew , Marzluff William F.
Published: February 2006

The stem–loop-binding protein (SLBP) is involved in multiple aspects of histone mRNA metabolism. To characterize the modification status and sites of SLBP, we combined mass spectrometric bottom-up (analysis of peptides) and top-down (analysis of intact proteins) proteomic approaches.
Drosophilia
SLBP is heavily phosphorylated, containing up to seven phosphoryl groups. Accurate
M
r
determination by Fourier transform ion cyclotron resonance (FTICR)-MS and FTICR-MS top-down experiments using a variety of dissociation techniques show there is removal of the initiator methionine and acetylation of the N terminus in the baculovirus-expressed protein, and that T230 is stoichiometrically phosphorylated. T230 is highly conserved; we have determined that this site is also completely phosphorylated in baculovirus-expressed mammalian SLBP and extensively phosphorylated in both
Drosophila
and mammalian cultured cells. Removal of the phosphoryl group from T230 by either dephosphorylation or mutation results in a 7-fold reduction in the affinity of SLBP for the stem–loop RNA.
An efficient rapid system for profiling the cellular activities of molecular libraries
Authors: Melnick Jonathan S. , Janes Jeff , Kim Sungjoon , Chang Jim Y. , Sipes Daniel G. , Gunderson Drew , Jarnes Laura , Matzen Jason T. , Garcia Michael E. , Hood Tami L. , Beigi Ronak , Xia Gang , Harig Richard A. , Asatryan Hayk , Yan S. Frank , Zhou Yingyao , Gu Xiang-Ju , Saadat Alham , Zhou Vicki , King Frederick J. , Shaw Christopher M. , Su Andrew I. , Downs Robert , Gray Nathanael S. , Schultz Peter G. , Warmuth Markus , Caldwell Jeremy S.
Published: February 2006

Rapid quantitative methods for characterizing small molecules, peptides, proteins, or RNAs in a broad array of cellular assays would allow one to discover new biological activities associated with these molecules and also provide a more comprehensive profile of drug candidates early in the drug development process. Here we describe a robotic system, termed the automated compound profiler, capable of both propagating a large number of cell lines in parallel and assaying large collections of molecules simultaneously against a matrix of cellular assays in a highly reproducible manner. To illustrate its utility, we have characterized a set of 1,400 kinase inhibitors in a panel of 35 activated tyrosine-kinase-dependent cellular assays in dose–response format in a single experiment. Analysis of the resulting multidimensional dataset revealed subclusters of both inhibitors and kinases with closely correlated activities. The approach also identified activities for the p38 inhibitor BIRB796 and the dual src/abl inhibitor BMS-354825 and exposed the expected side activities for Glivec/STI571, including cellular inhibition of c-kit and platelet-derived growth factor receptor. This methodology provides a powerful tool for unraveling the cellular biology and molecular pharmacology of both naturally occurring and synthetic chemical diversity.
Tumor endothelial marker 1
(
Tem1
) functions in the growth and progression of abdominal tumors
Authors: Nanda Akash , Karim Baktiar , Peng Zhongsheng , Liu Guosheng , Qiu Weiping , Gan Christine , Vogelstein Bert , St. Croix Brad , Kinzler Kenneth W. , Huso David L.
Published: February 2006

Tumor endothelial marker 1
(
Tem1
;
endosialin
) is the prototypical member of a family of genes expressed in the stroma of tumors. To assess the functional role of
Tem1
, we disrupted the
Tem1
gene in mice by targeted homologous recombination.
Tem1
−/−
mice were healthy, their wound healing was normal, and tumors grew normally when implanted in s.c. sites. However, there was a striking reduction in tumor growth, invasiveness, and metastasis after transplantation of tumors to abdominal sites in mice without functional
Tem1
genes. These data indicate that the stroma can control tumor aggressiveness and that this control varies with anatomic site. Therefore, they have significant implications for the mechanisms underlying tumor invasiveness and for models that evaluate this process.
Evolutionary fate of retroposed gene copies in the human genome
Authors: Vinckenbosch Nicolas , Dupanloup Isabelle , Kaessmann Henrik
Published: February 2006

Given that retroposed copies of genes are presumed to lack the regulatory elements required for their expression, retroposition has long been considered a mechanism without functional relevance. However, through an
in silico
assay for transcriptional activity, we identify here >1,000 transcribed retrocopies in the human genome, of which at least ≈120 have evolved into bona fide genes. Among these, ≈50 retrogenes have evolved functions in testes, more than half of which were recruited as functional autosomal counterparts of X-linked genes during spermatogenesis. Generally, retrogenes emerge “out of the testis,” because they are often initially transcribed in testis and later evolve stronger and sometimes more diverse spatial expression patterns. We find a significant excess of transcribed retrocopies close to other genes or within introns, suggesting that retrocopies can exploit the regulatory elements and/or open chromatin of neighboring genes to become transcribed. In direct support of this hypothesis, we identify 36 retrocopy–host gene fusions, including primate-specific chimeric genes. Strikingly, 27 intergenic retrogenes have acquired untranslated exons
de novo
during evolution to achieve high expression levels. Notably, our screen for highly transcribed retrocopies also uncovered a retrogene linked to a human recessive disorder, gelatinous drop-like corneal dystrophy, a form of blindness. These functional implications for retroposition notwithstanding, we find that the insertion of retrocopies into genes is generally deleterious, because it may interfere with the transcription of host genes. Our results demonstrate that natural selection has been fundamental in shaping the retrocopy repertoire of the human genome.