bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the relationship between interphase gene positioning, transcriptional regulation and the nuclear matrix
Authors: Elcock Lauren S. , Bridger Joanna M.
Published: January 2010

Since the advent of FISH (fluorescence in situ hybridization), there have been major advances in our understanding of how the genome is organized in interphase nuclei. Indeed, this organization is found to be non-random and individual chromosomes occupy discrete regions known as territories. Determining the factors that drive the spatial positioning of these territories within nuclei has caused much debate; however, in proliferating cells, there is evidently a correlation between radial positioning and gene density. Indeed, gene-poor chromosomes tend to be located towards the nuclear edge, while those that are more gene-rich are positioned more internally. These observations pose a number of questions: first, what is the function of this global organization and, secondly, is it representative of that occurring at a more local scale? During the course of this review, these questions will be considered, in light of the current literature regarding the role of transcription factories and the nuclear matrix in interphase genome organization.
Nuclear envelope influences on genome organization
Authors: Malik Poonam , Zuleger Nikolaj , Schirmer Eric C.
Published: January 2010

The nuclear periphery is a specialized environment in the nucleus that contributes to genome organization and correspondingly to gene regulation. Mammalian chromosomes and certain genes occupy defined positions within the nucleus that are heritable and tissue specific. Genes located at the nuclear periphery tend to be inactive and this negative regulation can be reversed when they are released from the periphery in certain differentiation systems. Recent work using specially designed systems has shown that genes can be artificially tethered to the nuclear periphery by an affinity mechanism. The next important step will be to identify the endogenous NE (nuclear envelope) and chromatin proteins that participate in affinity-driven NE tethering and determine how they are regulated.
Nesprin isoforms: are they inside or outside the nucleus?
Authors: Morris Glenn E. , Randles K. Natalie
Published: January 2010

The giant isoforms of nesprins 1 and 2 are emerging as important players in cellular organization, particularly in the positioning of nuclei, and possibly other organelles, within the cytoplasm. The experimental evidence suggests that nesprins also occur at the inner nuclear membrane, where they interact with the nuclear lamina. In this paper, we consider whether this is consistent with current ideas about nesprin anchorage and about mechanisms for nuclear import of membrane proteins.
Graded photonic crystal terahertz quantum cascade lasers
Authors: Chassagneux Y. , Colombelli R. , Maineult W. , Barbieri S. , Khanna S. P. , Linfield E. H. , Davies A. G.
Published: January 2010

The use of integrated photonic structures to tailor the behavior of light is extremely promising for optimizing performance and for introducing advanced functionalities into optoelectronic devices. We demonstrate a powerful method based on photonic-band engineering which allows the optimization of the resonator quality factors of devices operating on band-edge photonic-crystal states. We also show that carefully designed π-shifts in two-dimensional photonic-resonators give enhanced beam properties. The application of these general techniques to terahertz quantum cascade lasers yields improved maximum operating temperatures, and angularly narrow, single-lobed surface emission of ≈12°×8°. The devices operate at ≈2.8/2.9 THz, with peak output powers of 5 mW at 78 K.
Probing thin-film morphology of conjugated polymers by Raman spectroscopy
Authors: Winfield Jessica M. , Donley Carrie L. , Friend Richard H. , Kim Ji-Seon
Published: January 2010

We use Raman spectroscopy to investigate the thin-film morphology of conjugated polymers [poly(9,9-di-n-octylfluorene-alt-benzothiadiazole (F8BT)] in terms of the polymer chain conformation at interfaces with quartz, a crosslinked benzocyclobutene derivative, polyvinylphenol, and poly(3,4-ethylenedioxythiophene):poly(styrenesulphonate). The polymer chains near the substrate interface adopt a more planar conformation (lower torsion angle between fluorene and benzothiadiazole units) than chains in the bulk of the film for all substrates studied. On annealing, polymer chains both near the interface and in the bulk of the film adopt more planar conformations than in their pristine states but to a different degree. The influence of F8BT molecular weight on polymer chain conformation near the substrate interface is also examined. These results are confirmed by additional absorption and photoluminescence measurements.
Development of a new rectangular NaI(Tl) scintillator and spectroscopy of low-energy charged particles
Authors: Nakamura Hidehito , Kitamura Hisashi , Hazama Ryuta
Published: January 2010

Standard NaI(Tl) scintillators have only one optical window and are housed in airtight protective enclosures to protect against hygroscopicity from moisture in the air. For these reasons, NaI(Tl) scintillators are unsuitable for the collection of scintillation photons or for the detection of low-energy (<1 MeV) charged particles. To overcome these disadvantages, a rectangular NaI(Tl) scintillator has been newly developed. In this paper, we estimate the photon response of this new scintillator. The energy resolution was ΔE (Full Width at Half Maximum)=7.5±0.2% for 662 keV gamma rays from a C137s standard source. The number of photoelectrons was 3,686 for the photoelectric peak. Good energy resolution and photon collection were therefore confirmed for this specialized form of NaI(Tl) scintillator. The ability of this scintillator to detect low-energy particles was confirmed by successful measurement of low-energy charged particles (250–700 keV region) from a C137s thin film radioisotope source.
Theoretical and experimental evidence of enhanced ferromagnetism in Ba and Mn cosubstituted BiFeO3
Authors: Jayakumar O. D. , Achary S. N. , Girija K. G. , Tyagi A. K. , Sudakar C. , Lawes G. , Naik R. , Nisar J. , Peng X. , Ahuja R.
Published: January 2010

Ba and Mn doped BiFeO3 prepared through the pyrolysis of xerogel precursors are characterized by powder x-ray diffraction, high resolution transmission electron microscopy, superconducting quantum interference device magnetometry, and polarization measurements. Structural studies by x-ray diffraction and transmission electron microscopy show a tetragonal lattice for Ba substituted BiFeO3 and a rhombohedral lattice for Mn substituted BiFeO3. A large ferromagnetic hysteresis loop is observed for Ba doped BiFeO3. Coexistence of distorted rhombohedral and tetragonal phases is observed in Ba and Mn codoped BiFeO3, where enhanced ferroelectric and ferromagnetic properties are produced by the internal strain. Density functional calculations are used to substantiate the results.
A new streaming potential chamber for zeta potential measurements of particulates
Authors: Guzelsu N. , Wienstien C. , Kotha S. P.
Published: January 2010

A novel streaming potential measurement device has been validated by determining the average electrokinetic (zeta) potential of densely packed particulate such as human erythrocytes and ground bovine cortical bone. The new streaming potential device used in this study is easy to construct in the laboratory, designed to allow dense packing of particles, and determines zeta potentials for a broad range of particle sizes. The streaming potential device consists of four Plexiglas parts: (i) an upper and (ii) a lower chamber, which act as reservoirs for fluid; (iii) a midchamber which connects the upper and lower chambers and holds the sample holder, and (iv) a sample holder. Pressurization of fluid in the top chamber generates a pressure gradient that induces movement of fluid through the stationary sample and into the bottom chamber. Pressure induced flow through the interconnected pores of the densely packed particulate generates a potential difference across the sample that is measured using electrodes housed in the top and bottom chambers. The measured potential difference is then converted to zeta potentials. The advantage of this chamber is its ability to handle densely packed particulates exhibiting a broad distribution of sizes. Dense packing of particulate is achieved by compacting samples at the bottom of the sample holder under centrifugal forces before the device is assembled. This approach allowed us to determine average zeta potentials of densely packed particulate made of soft and hard materials.
Polymer functionalized n-type single wall carbon nanotube photovoltaic devices
Authors: Li Zhongrui , Saini Viney , Dervishi Enkeleda , Kunets Vasyl P. , Zhang Jianhui , Xu Yang , Biris Alexandru R. , Salamo Gregory J. , Biris Alexandru S.
Published: January 2010

Photovoltaic conversion was achieved from high-density p-n heterojunctions formed between polymer functionalized n-type single wall carbon nanotubes (SWNTs) and underlying p-type Si substrate. Functionalization of SWNTs by amine-rich polymers results in the evolution of tubes from p-type to n-type, and the polyethylene imine (PEI) functionalized SWNT film can serve as both photogeneration sites and a charge carrier collecting/transport layer. Photoremoval of oxygen adsorbed on the nanotubes prior to PEI functionalization can increase the conversion efficiency of the polymer functionalized n-type SWNT photovoltaic devices.
Molecular applications of analytical gradient approach for the improved virtual orbital-complete active space configuration interaction method
Authors: Chaudhuri Rajat K. , Chattopadhyay Sudip , Mahapatra Uttam Sinha , Freed Karl F.
Published: January 2010

The improved virtual orbital-complete active space configuration interaction (IVO-CASCI) method is extended to determine the geometry and vibrational frequencies for ground and excited electronic states using an analytical total energy gradient scheme involving both first and second order analytical derivatives. Illustrative applications consider the ground state geometries of the benzene (C6H6), biphenyl (C12H10), and alanine dipeptide (CH3CONHCHCH3CONHCH3) molecules. In addition, the IVO-CASCI geometry optimization has been performed for the first excited singlet (B12u) and triplet states (B31u) of benzene to assess its applicability for excited and open-shell systems. The D6h symmetry benzene triplet optimization produces a saddle point, and a descent along the unstable mode produces the stable minimum. Comparisons with Hartree–Fock, second order Möller–Plesset perturbation theory, complete active space self-consistent field (CASSCF), and density functional theory demonstrate that the IVO-CASCI approach generally fares comparable to or better for all systems studied. The vibrational frequencies of the benzene and biphenyl molecules computed with the analytical gradient based IVO-CASCI method agree with the experiment and with other accurate theoretical estimates. Satisfactory agreement between our results, other benchmark calculations, and available experiment demonstrates the efficacy and potential of the method. The close similarity between CASSCF and IVO-CASCI optimized geometries and the greater computational efficiency of the IVO-CASCI method suggests the replacement of CASSCF treatments by the IVO-CASCI approach, which is free from the convergence problems that often plague CASSCF treatments.
Anomalously enhanced Raman scattering from longitudinal optical phonons on Ag-nanoparticle-covered GaN and ZnO
Authors: Liu C. Y. , Dvoynenko M. M. , Lai M. Y. , Chan T. H. , Lee Y. R. , Wang J.-K. , Wang Y. L.
Published: January 2010

The authors report experimental studies of surface-enhanced Raman scattering (SERS) of wurtzite-type GaN and ZnO crystalline samples covered with Ag-nanoparticles. The longitudinal optical phonons consistently exhibit unusually intense Raman enhancement in comparison with other phonons. The anomaly is interpreted by a proposed model based on a resonant Raman scattering process assisted by metal-induced gap states at the Ag/GaN and Ag/ZnO interfaces. This study suggests that SERS of lattice vibrations in inorganic semiconductors is sensitive to their propagation nature, providing a progressive perspective view on electron-mediated enhanced Raman scattering.
Electrical properties of C-doped p-type GaP and GaPN grown by molecular beam epitaxy
Authors: Liu Zhengxin , Kawanami Hitoshi , Sakata Isao
Published: January 2010

The electrical properties of C-doped p-type GaP and GaPN epilayers grown by molecular beam epitaxy using CBr4 as a doping source have been investigated. C is shown to be a relatively shallow acceptor both in GaP and GaPN, with the activation energy in the regions of 16–33 and 18–35 meV, respectively. GaP demonstrates ordinary conduction characteristics, whereas GaPN has a typical mixed conduction effect and the impurity conduction becomes dominant at low temperatures. It is conjectured that impurity conduction and ionized impurity scattering mechanisms in GaPN may be related to the inactivated C and N radicals.
Spectral modulation of ultraviolet femtosecond laser pulse by molecular alignment of CO2, O2, and N2
Authors: Wang Yongdong , Dai Xiaomin , Wu Jian , Ding Liang’en , Zeng Heping
Published: January 2010

We demonstrate efficient third harmonic generation of a near infrared femtosecond pulse through cascaded frequency doubling and sum-frequency generation processes, where the group velocity mismatching between the involved fundamental and generated second harmonic pulses, before they are sent to frequency mixing, are precompensated with a properly inserted nonlinear crystal. The spectrum of the generated third harmonic pulse with energy of 1.1 mJ is further modulated by using impulsive molecular alignments of CO2, O2, and N2, where significantly broadened spectrum in the ultraviolet spectral region is observed due to the additional cross-focusing effect from the parallel aligned molecules and the consequently enhanced self-phase modulation.
Improved version of a local contracted configuration interaction of singles and doubles with partial inclusion of triples and quadruples
Authors: Zhang Hongjiang , Malrieu Jean-Paul , Reinhardt Peter , Ma Jing
Published: January 2010

A local contracted single and double configuration interaction (LC-CISD) method, which introduces contracted singly and doubly excited vectors within the framework of bond functions, has been recently proposed [P. Reinhardt et al., J. Chem. Phys. 129, 164106 (2008)]. The present work improves this method by introducing a coupled-electron pair approximation (CEPA-3) dressing and by incorporating the leading part of linked effects of triples (T) and quadruples (Q) through a series of local four-electron full CI calculations. Two different ways have been adopted to incorporate this linked TQ effect. One consists of dressing the first column/line of the whole LC-CISD matrix. The other one introduces an additional contracted wave function responsible for the linked effect for each bond pair. The present LC-CEPA-3+TQ treatments have been applied to the evaluation of equilibrium bond lengths and harmonic frequencies of diatomic molecules (HF, BF, CuH, N2, F2, and Cl2) and single bond breaking in HF, CH4, ClCH3, ClSiH3, n-butane, and F2 molecules, symmetrical stretching of the two OH bonds in a water molecule, and symmetrical expansion of a triangular Be3 cluster. The results show that the performance of the LC-CEPA-3+TQs compares favorably with coupled-cluster singles and doubles (CCSD) and CCSD(T) methods, presenting similar behaviors around equilibrium and better ones for stretched geometries. The LC-CEPA-3 method is strictly separable, and the size consistency error of our treatment of triples and quadruples is extremely small. The strict separability can be further achieved by dressing the doubly excited bond functions with the linked TQ effect. The efficiency of truncations on the bielectronic integrals has also been tested.
The type III effector HopF2

Pto

targets
Arabidopsis
RIN4 protein to promote
Pseudomonas syringae
virulence
Authors: Wilton Mike , Subramaniam Rajagopal , Elmore James , Felsensteiner Corinna , Coaker Gitta , Desveaux Darrell
Published: January 2010

Plant immunity can be induced by two major classes of pathogen-associated molecules. Pathogen- or microbe-associated molecular patterns (PAMPs or MAMPs) are conserved molecular components of microbes that serve as “non-self” features to induce PAMP-triggered immunity (PTI). Pathogen effector proteins used to promote virulence can also be recognized as “non-self” features or induce a “modified-self” state that can induce effector-triggered immunity (ETI). The
Arabidopsis
protein RIN4 plays an important role in both branches of plant immunity. Three unrelated type III secretion effector (TTSE) proteins from the phytopathogen
Pseudomonas syringae
, AvrRpm1, AvrRpt2, and AvrB, target RIN4, resulting in ETI that effectively restricts pathogen growth. However, no pathogenic advantage has been demonstrated for RIN4 manipulation by these TTSEs. Here, we show that the TTSE HopF2

Pto

also targets
Arabidopsis
RIN4. Transgenic plants conditionally expressing HopF2

Pto

were compromised for AvrRpt2-induced RIN4 modification and associated ETI. HopF2

Pto

interfered with AvrRpt2-induced RIN4 modification in vitro but not with AvrRpt2 activation, suggestive of RIN4 targeting by HopF2

Pto

. In support of this hypothesis, HopF2

Pto

interacted with RIN4 in vitro and in vivo. Unlike AvrRpm1, AvrRpt2, and AvrB, HopF2

Pto

did not induce ETI and instead promoted
P. syringae
growth in
Arabidopsis
. This virulence activity was not observed in plants genetically lacking RIN4. These data provide evidence that RIN4 is a major virulence target of HopF2

Pto

and that a pathogenic advantage can be conveyed by TTSEs that target RIN4.
Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130
Authors: Hegan Denise Campisi , Lu Yuhong , Stachelek Gregory C. , Crosby Meredith E. , Bindra Ranjit S. , Glazer Peter M.
Published: January 2010

Inhibitors of poly(ADP-ribose) polymerase (PARP) are in clinical trials for cancer therapy, on the basis of the role of PARP in recruitment of base excision repair (BER) factors to sites of DNA damage. Here we show that PARP inhibition to block BER is toxic to hypoxic cancer cells, in which homology-dependent repair (HDR) is known to be down-regulated. However, we also report the unexpected finding that disruption of PARP, itself, either via chemical PARP inhibitors or siRNAs targeted to PARP-1, can inhibit HDR by suppressing expression of
BRCA1
and
RAD51
, key factors in HDR of DNA breaks. Mechanistically, PARP inhibition was found to cause increased occupancy of the
BRCA1
and
RAD51
promoters by repressive E2F4/p130 complexes, a pathway prevented by expression of HPV E7, which disrupts p130 activity, or by siRNAs to knock down p130 expression. Functionally, disruption of p130 by E7 expression or by siRNA knockdown also reverses the cytotoxicity and radiosensitivity associated with PARP inhibition, suggesting that the down-regulation of BRCA1 and RAD51 is central to these effects. Direct measurement of HDR using a GFP-based assay demonstrates reduced HDR in cells treated with PARP inhibitors. This work identifies a mechanism by which PARP regulates DNA repair and suggests new strategies for combination cancer therapies.
Distinct forms of G
q
-receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress
Authors: McElligott Zoé A. , Klug Jason R. , Nobis William P. , Patel Sachin , Grueter Brad A. , Kash Thomas L. , Winder Danny G.
Published: January 2010

Long-term depression (LTD) is an important synaptic mechanism for limiting excitatory influence over circuits subserving cognitive and emotional behavior. A major means of LTD induction is through the recruitment of signaling via G
q
-linked receptors activated by norepinephrine (NE), acetylcholine, and glutamate. Receptors from these transmitter families have been proposed to converge on a common postsynaptic LTD maintenance mechanism, such that hetero- and homosynaptic induction produce similar alterations in glutamate synapse efficacy. We report that in the dorsolateral and ventrolateral bed nucleus of the stria terminalis (BNST), recruitment of G
q
-linked receptors by glutamate or NE initiates mechanistically distinct forms of postsynaptically maintained LTD and these LTDs are differentially regulated by stress exposure. In particular, we show that although both mGluR5- and α
1
-adrenergic receptor (AR)-dependent LTDs involve postsynaptic endocytosis, the α
1
-AR-initiated LTD exclusively involves modulation of signaling through calcium-permeable AMPA receptors. Further, α
1
-AR- but not mGluR5- dependent LTD is disrupted by restraint stress. α
1
-AR LTD is also impaired in mice chronically exposed to ethanol. These data thus suggest that in the BNST, NE- and glutamate-activated G
q
-linked signaling pathways differentially tune glutamate synapse efficacy in response to stress.
An end-joining repair mechanism in
Escherichia coli
Authors: Chayot Romain , Montagne Benjamin , Mazel Didier , Ricchetti Miria
Published: January 2010

Bridging broken DNA ends via nonhomologous end-joining (NHEJ) contributes to the evolution and stability of eukaryote genomes. Although some bacteria possess a simplified NHEJ mechanism, the human commensal
Escherichia coli
is thought to rely exclusively on homology-directed mechanisms to repair DNA double-strand breaks (DSBs). We show here that laboratory and pathogenic
E. coli
strains possess a distinct end-joining activity that repairs DSBs and generates genome rearrangements. This mechanism, named alternative end-joining (A-EJ), does not rely on the key NHEJ proteins Ku and Ligase-D which are absent in
E. coli
. Differently from classical NHEJ, A-EJ is characterized by extensive end-resection largely due to RecBCD, by overwhelming usage of microhomology and extremely rare DNA synthesis. We also show that A-EJ is dependent on the essential Ligase-A and independent on Ligase-B. Importantly, mutagenic repair requires a functional Ligase-A. Although generally mutagenic, accurate A-EJ also occurs and is frequent in some pathogenic bacteria. Furthermore, we show the acquisition of an antibiotic-resistance gene via A-EJ, refuting the notion that bacteria gain exogenous sequences only by recombination-dependent mechanisms. This finding demonstrates that
E. coli
can integrate unrelated, nonhomologous exogenous sequences by end-joining and it provides an alternative strategy for horizontal gene transfer in the bacterial genome. Thus, A-EJ contributes to bacterial genome evolution and adaptation to environmental challenges. Interestingly, the key features of A-EJ also appear in A-NHEJ, an alternative end-joining mechanism implicated in chromosomal translocations associated with human malignancies, and we propose that this mutagenic repair might have originated in bacteria.
T7 phage protein Gp2 inhibits the
Escherichia coli
RNA polymerase by antagonizing stable DNA strand separation near the transcription start site
Authors: Cámara Beatriz , Liu Minhao , Reynolds Jonathan , Shadrin Andrey , Liu Bing , Kwok King , Simpson Peter , Weinzierl Robert , Severinov Konstantin , Cota Ernesto , Matthews Steve , Wigneshweraraj Siva R.
Published: January 2010

Infection of
Escherichia coli
by the T7 phage leads to rapid and selective inhibition of the host RNA polymerase (RNAP)—a multi-subunit enzyme responsible for gene transcription—by a small (∼7 kDa) phage-encoded protein called Gp2. Gp2 is also a potent inhibitor of
E. coli
RNAP in vitro. Here we describe the first atomic resolution structure of Gp2, which reveals a distinct run of surface-exposed negatively charged amino acid residues on one side of the molecule. Our comprehensive mutagenesis data reveal that two conserved arginine residues located on the opposite side of Gp2 are important for binding to and inhibition of RNAP. Based on a structural model of the Gp2-RNAP complex, we propose that inhibition of transcription by Gp2 involves prevention of RNAP-promoter DNA interactions required for stable DNA strand separation and maintenance of the “transcription bubble” near the transcription start site, an obligatory step in the formation of a transcriptionally competent promoter complex.
ISG15 conjugation system targets the viral NS1 protein in influenza A virus–infected cells
Authors: Zhao Chen , Hsiang Tien-Ying , Kuo Rei-Lin , Krug Robert M.
Published: January 2010

ISG15 is an IFN-α/β–induced, ubiquitin-like protein that is conjugated to a wide array of cellular proteins through the sequential action of three conjugation enzymes that are also induced by IFN-α/β. Recent studies showed that ISG15 and/or its conjugates play an important role in protecting cells from infection by several viruses, including influenza A virus. However, the mechanism by which ISG15 modification exerts antiviral activity has not been established. Here we extend the repertoire of ISG15 targets to a viral protein by demonstrating that the NS1 protein of influenza A virus (NS1A protein), an essential, multifunctional protein, is ISG15 modified in virus-infected cells. We demonstrate that the major ISG15 acceptor site in the NS1A protein in infected cells is a critical lysine residue (K41) in the N-terminal RNA-binding domain (RBD). ISG15 modification of K41 disrupts the association of the NS1A RBD domain with importin-α, the protein that mediates nuclear import of the NS1A protein, whereas the RBD retains its double-stranded RNA-binding activity. Most significantly, we show that ISG15 modification of K41 inhibits influenza A virus replication and thus contributes to the antiviral action of IFN-β. We also show that the NS1A protein directly and specifically binds to Herc5, the major E3 ligase for ISG15 conjugation in human cells. These results establish a “loss of function” mechanism for the antiviral activity of the IFN-induced ISG15 conjugation system, namely, that it inhibits viral replication by conjugating ISG15 to a specific viral protein, thereby inhibiting its function.
Rpd3-dependent boundary formation at telomeres by removal of Sir2 substrate
Authors: Ehrentraut Stefan , Weber Jan M. , Dybowski J. Nikolaj , Hoffmann Daniel , Ehrenhofer-Murray Ann E.
Published: January 2010

Boundaries between euchromatic and heterochromatic regions until now have been associated with chromatin-opening activities. Here, we identified an unexpected role for histone deacetylation in this process. Significantly, the histone deacetylase (HDAC) Rpd3 was necessary for boundary formation in
Saccharomyces cerevisiae
.
rpd3
Δ led to silent information regulator (SIR) spreading and repression of subtelomeric genes. In the absence of a known boundary factor, the histone acetyltransferase complex SAS-I,
rpd3
Δ caused inappropriate SIR spreading that was lethal to yeast cells. Notably, Rpd3 was capable of creating a boundary when targeted to heterochromatin. Our data suggest a mechanism for boundary formation whereby histone deacetylation by Rpd3 removes the substrate for the HDAC Sir2, so that Sir2 no longer can produce O-acetyl-ADP ribose (OAADPR) by consumption of NAD
+
in the deacetylation reaction. In essence, OAADPR therefore is unavailable for binding to Sir3, preventing SIR propagation.
Basic mathematical rules are encoded by primate prefrontal cortex neurons
Authors: Bongard Sylvia , Nieder Andreas
Published: January 2010

Mathematics is based on highly abstract principles, or rules, of how to structure, process, and evaluate numerical information. If and how mathematical rules can be represented by single neurons, however, has remained elusive. We therefore recorded the activity of individual prefrontal cortex (PFC) neurons in rhesus monkeys required to switch flexibly between “greater than” and “less than” rules. The monkeys performed this task with different numerical quantities and generalized to set sizes that had not been presented previously, indicating that they had learned an abstract mathematical principle. The most prevalent activity recorded from randomly selected PFC neurons reflected the mathematical rules; purely sensory- and memory-related activity was almost absent. These data show that single PFC neurons have the capacity to represent flexible operations on most abstract numerical quantities. Our findings support PFC network models implementing specific “rule-coding” units that control the flow of information between segregated input, memory, and output layers. We speculate that these neuronal circuits in the monkey lateral PFC could readily have been adopted in the course of primate evolution for syntactic processing of numbers in formalized mathematical systems.
Nuclear location of an endogenously expressed antigen, EBNA1, restricts access to macroautophagy and the range of CD4 epitope display
Authors: Leung Carol S. , Haigh Tracey A. , Mackay Laura K. , Rickinson Alan B. , Taylor Graham S.
Published: January 2010

Whereas exogenously acquired proteins are the major source of antigens feeding the MHC class II pathway in antigen-presenting cells, some endogenously expressed antigens also access that pathway but the rules governing such access are poorly understood. Here we address this using Epstein–Barr virus (EBV)-coded nuclear antigen EBNA1, a protein naturally expressed in EBV-infected B lymphoblastoid cell lines (LCLs) and a source of multiple CD4+T cell epitopes. Using CD4+T cell clones against three indicator epitopes, we find that two epitopes are weakly displayed on the LCL surface whereas the third is undetectable, a pattern of limited epitope presentation that is maintained even when nuclear expression of EBNA1 is induced to high supraphysiological levels. Inhibitor and siRNA studies show that, of the two epitopes weakly presented under these conditions, one involves macroautophagy, and the second involves antigen delivery to the MHC II pathway by another endogenous route. In contrast, when EBNA1 is expressed as a cytoplasmic protein, all three CD4 epitopes are processed and presented much more efficiently, and all involve macroautophagy. We conclude that EBNA1’s nuclear location limits its accessibility to the macroautophagy pathway and, in consequence, limits the level and range of EBNA1 CD4 epitopes naturally displayed on the infected cell surface.
PAS domain containing chemoreceptor couples dynamic changes in metabolism with chemotaxis
Authors: Xie Zhihong , Ulrich Luke E. , Zhulin Igor. B. , Alexandre Gladys
Published: January 2010

Chemoreceptors provide sensory specificity and sensitivity that enable motile bacteria to seek optimal positions for growth and metabolism in gradients of various physicochemical cues. Despite the abundance of chemoreceptors, little is known regarding the sensory specificity and the exact contribution of individual chemoreceptors to the lifestyle of bacteria.
Azospirillum brasilense
are motile bacteria that can fix atmospheric nitrogen under microaerophilic conditions. Here, we characterized a chemoreceptor in this organism, named AerC, which functions as a redox sensor that enables the cells to seek microaerophilic conditions that support optimum nitrogen fixation. AerC is a representative of a widespread class of soluble chemoreceptors that monitor changes in the redox status of the electron transport system via the FAD cofactor associated with its PAS domains. In
A. brasilense
, AerC clusters at the cell poles. Its cellular localization and contribution to the behavioral response correlate with its expression pattern and with changes in the overall cellular FAD content under nitrogen-fixing conditions. AerC-mediated energy taxis in
A. brasilense
prevails under conditions of nitrogen fixation, illustrating a strategy by which cells optimize chemosensing to signaling cues that directly affect current metabolic activities and thus revealing a mechanism by which chemotaxis is coordinated with dynamic changes in cell physiology.
Evidence for the role of organics in aerosol particle formation under atmospheric conditions
Authors: Metzger Axel , Verheggen Bart , Dommen Josef , Duplissy Jonathan , Prevot Andre S. H. , Weingartner Ernest , Riipinen Ilona , Kulmala Markku , Spracklen Dominick V. , Carslaw Kenneth S. , Baltensperger Urs
Published: January 2010

New particle formation in the atmosphere is an important parameter in governing the radiative forcing of atmospheric aerosols. However, detailed nucleation mechanisms remain ambiguous, as laboratory data have so far not been successful in explaining atmospheric nucleation. We investigated the formation of new particles in a smog chamber simulating the photochemical formation of H
2
SO
4
and organic condensable species. Nucleation occurs at H
2
SO
4
concentrations similar to those found in the ambient atmosphere during nucleation events. The measured particle formation rates are proportional to the product of the concentrations of H
2
SO
4
and an organic molecule. This suggests that only one H
2
SO
4
molecule and one organic molecule are involved in the rate-limiting step of the observed nucleation process. Parameterizing this process in a global aerosol model results in substantially better agreement with ambient observations compared to control runs.
Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression
Authors: Le Anne , Cooper Charles R. , Gouw Arvin M. , Dinavahi Ramani , Maitra Anirban , Deck Lorraine M. , Royer Robert E. , Vander Jagt David L. , Semenza Gregg L. , Dang Chi V.
Published: January 2010

As the result of genetic alterations and tumor hypoxia, many cancer cells avidly take up glucose and generate lactate through lactate dehydrogenase A (LDHA), which is encoded by a target gene of c-Myc and hypoxia-inducible factor (HIF-1). Previous studies with reduction of LDHA expression indicate that LDHA is involved in tumor initiation, but its role in tumor maintenance and progression has not been established. Furthermore, how reduction of LDHA expression by interference or antisense RNA inhibits tumorigenesis is not well understood. Here, we report that reduction of LDHA by siRNA or its inhibition by a small-molecule inhibitor (FX11 [3-dihydroxy-6-methyl-7-(phenylmethyl)-4-propylnaphthalene-1-carboxylic acid]) reduced ATP levels and induced significant oxidative stress and cell death that could be partially reversed by the antioxidant
N
-acetylcysteine. Furthermore, we document that FX11 inhibited the progression of sizable human lymphoma and pancreatic cancer xenografts. When used in combination with the NAD
+
synthesis inhibitor FK866, FX11 induced lymphoma regression. Hence, inhibition of LDHA with FX11 is an achievable and tolerable treatment for LDHA-dependent tumors. Our studies document a therapeutical approach to the Warburg effect and demonstrate that oxidative stress and metabolic phenotyping of cancers are critical aspects of cancer biology to consider for the therapeutical targeting of cancer energy metabolism.
Spatiotemporal controlled delivery of nanoparticles to injured vasculature
Authors: Chan Juliana M. , Zhang Liangfang , Tong Rong , Ghosh Debuyati , Gao Weiwei , Liao Grace , Yuet Kai P. , Gray David , Rhee June-Wha , Cheng Jianjun , Golomb Gershon , Libby Peter , Langer Robert , Farokhzad Omid C.
Published: January 2010

There are a number of challenges associated with designing nanoparticles for medical applications. We define two challenges here: (
i
) conventional targeting against up-regulated cell surface antigens is limited by heterogeneity in expression, and (
ii
) previous studies suggest that the optimal size of nanoparticles designed for systemic delivery is approximately 50–150 nm, yet this size range confers a high surface area-to-volume ratio, which results in fast diffusive drug release. Here, we achieve spatial control by biopanning a phage library to discover materials that target abundant vascular antigens exposed in disease. Next, we achieve temporal control by designing 60-nm hybrid nanoparticles with a lipid shell interface surrounding a polymer core, which is loaded with slow-eluting conjugates of paclitaxel for controlled ester hydrolysis and drug release over approximately 12 days. The nanoparticles inhibited human aortic smooth muscle cell proliferation in vitro and showed greater in vivo vascular retention during percutaneous angioplasty over nontargeted controls. This nanoparticle technology may potentially be used toward the treatment of injured vasculature, a clinical problem of primary importance.
The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism
Authors: Clower Cynthia V. , Chatterjee Deblina , Wang Zhenxun , Cantley Lewis C. , Vander Heiden Matthew G. , Krainer Adrian R.
Published: January 2010

Cancer cells preferentially metabolize glucose by aerobic glycolysis, characterized by increased lactate production. This distinctive metabolism involves expression of the embryonic M2 isozyme of pyruvate kinase, in contrast to the M1 isozyme normally expressed in differentiated cells, and it confers a proliferative advantage to tumor cells. The M1 and M2 pyruvate-kinase isozymes are expressed from a single gene through alternative splicing of a pair of mutually exclusive exons. We measured the expression of M1 and M2 mRNA and protein isoforms in mouse tissues, tumor cell lines, and during terminal differentiation of muscle cells, and show that alternative splicing regulation is sufficient to account for the levels of expressed protein isoforms. We further show that the M1-specific exon is actively repressed in cancer-cell lines—although some M1 mRNA is expressed in cell lines derived from brain tumors—and demonstrate that the related splicing repressors hnRNP A1 and A2, as well as the polypyrimidine-tract-binding protein PTB, contribute to this control. Downregulation of these splicing repressors in cancer-cell lines using shRNAs rescues M1 isoform expression and decreases the extent of lactate production. These findings extend the links between alternative splicing and cancer, and begin to define some of the factors responsible for the switch to aerobic glycolysis.
Adolescents’ evaluative beliefs of failure: Explorations in a Chinese Singaporean sample
Authors: Sim Tick N. , Wong Eleanor X.
Published: January 2010

Our study explored evaluative beliefs of failure to see whether positive and negative beliefs of failure are bivariate in nature within three domains of an adolescent's life (academic, social, and athletic) and how such beliefs are differentially linked to the importance of a domain, the frequency of failure in a domain, and the extremity of negative emotions experienced when encountering failure in a domain. A total of 163 Chinese Singaporean students in Secondary 3 and 4 (Grades 9 and 10) from two Singapore schools participated in the study by completing a questionnaire. Results from various analyses converged to demonstrate that evaluative beliefs could be distinguished by both valence (positive and negative) and domain (academic, social, and athletic). The six evaluative beliefs were also distinguished from failure attributions. While there was consensus in what constituted negative beliefs of failure across domains, positive beliefs of failure showed some domain specificity, with unique aspects in particular domains (e.g., the inevitability of failure only in the academic domain). Positive and negative beliefs in the different domains were correlated among themselves, but positive and negative beliefs were uncorrelated within (except for academic) and across domains. Positive and negative beliefs were also differentially linked to domain importance, failure frequency, and extremity of negative emotion. Unexpectedly, domain importance was not linked to negative beliefs but was linked to positive beliefs, while positive and negative beliefs showed domain‐specific links with failure frequency. As expected, however, negative beliefs were (positively) linked to extremity of negative emotions while positive beliefs were not linked to such extremity. The conceptual, substantive, and practical implications of these results are discussed.
Combinational Soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor Proteins VAMP8 and Vti1b Mediate Fusion of Antimicrobial and Canonical Autophagosomes with Lysosomes
Authors: Furuta Nobumichi , Fujita Naonobu , Noda Takeshi , Yoshimori Tamotsu , Amano Atsuo
Published: January 2010

Autophagy plays a crucial role in host defense, termed antimicrobial autophagy (xenophagy), as it functions to degrade intracellular foreign microbial invaders such as group A Streptococcus (GAS). Xenophagosomes undergo a stepwise maturation process consisting of a fusion event with lysosomes, after which the cargoes are degraded. However, the molecular mechanism underlying xenophagosome/lysosome fusion remains unclear. We examined the involvement of endocytic soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) in xenophagosome/lysosome fusion. Confocal microscopic analysis showed that SNAREs, including vesicle-associated membrane protein (VAMP)7, VAMP8, and vesicle transport through interaction with t-SNAREs homologue 1B (Vti1b), colocalized with green fluorescent protein-LC3 in xenophagosomes. Knockdown of Vti1b and VAMP8 with small interfering RNAs disturbed the colocalization of LC3 with lysosomal membrane protein (LAMP)1. The invasive efficiency of GAS into cells was not altered by knockdown of VAMP8 or Vti1b, whereas cellular bactericidal efficiency was significantly diminished, indicating that antimicrobial autophagy was functionally impaired. Knockdown of Vti1b and VAMP8 also disturbed colocalization of LC3 with LAMP1 in canonical autophagy, in which LC3-II proteins were negligibly degraded. In contrast, knockdown of Syntaxin 7 and Syntaxin 8 showed little effect on the autophagic fusion event. These findings strongly suggest that the combinational SNARE proteins VAMP8 and Vti1b mediate the fusion of antimicrobial and canonical autophagosomes with lysosomes, an essential event for autophagic degradation.
The New Music Theater
Authors: Salzman Eric , Desi Thomas
Published: January 2010

Alternatives to grand opera and popular musical go back at least as far as Schoenberg's Pierrot Lunaire, early Stravinsky, and Kurt Weill as well as the Broadway and off-Broadway theater operas of the '30s and '40s, and the modernist experiments of the '60s. Yet this long and continuing history, with its complex ideas and philosophy as well as musical and theatrical achievements, has never been properly sorted out. This book is the first comprehensive attempt in English to cover a still-emerging art form in its widest range. It provides a wealth of examples and descriptions, not only of the works themselves, but of the concepts, ideas, and trends that have gone into the evolution of what may be the most central performance art form of the post-modern world. The first two sections of the book deal with Music in Music Theater (including the many new and various uses of the human voice) and Theater in Music Theater (including culture, text, visual strategies, and the multiple new concepts of space). The third section covers European and American music theaters in their various histories and manifestations, with chapters on the more innovative wing of popular music theater, extended voice, and the influence of new media. The fourth part of the book discusses criticism and analysis, improvisation, the issues surrounding pop and high art, and the crucial questions about the audience for music theater. An appendix includes a music-theater bibliography and information about some of the principal venues for the art form.
Chapter 2 Where the Sound Comes From
Authors: Salzman Eric , Desi Thomas
Published: January 2010

This chapter discusses the evolution of instruments and the orchestra in the theater — onstage, offstage, in the pit, and in the theatrical space — along with issues of musical form in theatrical music. It ends with a discussion of the breakdown of the stage/audience barrier, the use of live electronics, and the introduction of digital technology to transmit, transform, and create sound.
Chapter 3 The Music
Authors: Salzman Eric , Desi Thomas
Published: January 2010

This chapter discusses the following subjects in a music theater context: Verismo to expressionism to musical modernism; the development of neoclassicism, presentational theater and the new chamber opera; cross influences of musical populism and the return of modernism in the form of serialism, anti-theater and electro-acoustics; minimalism and the revival of tonality.
Chapter 5 Text
Authors: Salzman Eric , Desi Thomas
Published: January 2010

This chapter begins by tracing the old and widespread association of music and language through the history of traditional opera to the early 20th century. It then discusses some of the specific uses of words in music: storytelling, the libretto, and musical dramaturgy. Modern treatments include both linear and non-linear storytelling, the dynamics of subject matter often including contemporary news events and personalities as well as social situations. Spoken text with music (“melodrama”) and the issue of whether music itself can tell stories are discussed. The chapter ends with a section on “no sense or nonsense”, or how music theater sometimes moves away from storytelling to found text, and even to abandon words completely.
Chapter 8 The American Eccentrics
Authors: Salzman Eric , Desi Thomas
Published: January 2010

This chapter discusses Harry Partch and “ corporeality”; the music theater of Partch (“Delusion of the Fury”, “Revelation in the Courthouse Park”) and his ideas about tuning, instruments, and voice; Marcel Duchamp and “de-semiotization” in the work and ideas of John Cage (from his early experiments to the late Europeras); the influence of Cage and Cage's circle in America and Europe; theatrical and conceptual work and concepts of Mauricio Kagel, an Argentinian working in Europe; and the conceptual work of Tom Johnson, an American composer living and working in Europe.
Chapter 10 From the Homeland: Teatro Musicale
Authors: Salzman Eric , Desi Thomas
Published: January 2010

This chapter discusses fascism and futurism in Italy; Luigi Dallapiccola; politics, improvisation, post-serialism, the return of the human voice, relationship of opera and music theater; Berio, Nono, Bussotti, Maderna; the 1968 and post-1968 generations; and postmodernism and experimentalism in the work of younger Italian composers.
Chapter 12 Music Theater in Northern Europe
Authors: Salzman Eric , Desi Thomas
Published: January 2010

This chapter discusses the work of British composers including Benjamin Britten, Peter Maxwell Davies, Harrison Birtwistle, Cornelius Cardew, Gavin Bryars, Michael Nyman, Mark-Anthony Turnage, and Andrew Toovey. British performing institutions have included the Pierrot Players and the Almeida Theatre. Also discussed are Louis Andriessen from The Netherlands (and his influence on younger British composers) and Per Nørgård from Denmark. Institutions mentioned are NewOp, Musiktheater Transparant in Antwerp, Die Munt (Théâtre Royal de la Monnaie) in Brussels, and Den Anden Opera in Copenhagen.
Chapter 14 Minimalism and Music Theater
Authors: Salzman Eric , Desi Thomas
Published: January 2010

This chapter discusses the history of minimalism and the work of Philip Glass in music theater and opera, notably his influential Einstein on the Beach with Robert Wilson. It considers the influence of minimalism on opera, particularly in the work of John Adams. Steve Reich's multi-media works with Beryl Korot are discussed along with the spread of minimalism as exemplified by music-theater works of Bang on a Can, Michael Nyman, and other British and European composers influenced by minimalism.