bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological distribution and population physiology defined by proteomics in a natural microbial community
Authors: Mueller Ryan S , Denef Vincent J , Kalnejais Linda H , Suttle K Blake , Thomas Brian C , Wilmes Paul , Smith Richard L , Nordstrom D Kirk , McCleskey R Blaine , Shah Manesh B , VerBerkmoes Nathan C , Hettich Robert L , Banfield Jillian F
Published: June 2010

An important challenge in microbial ecology is developing methods that simultaneously examine the physiology of organisms at the molecular level and their ecosystem level interactions in complex natural systems. We integrated extensive proteomic, geochemical, and biological information from 28 microbial communities collected from an acid mine drainage environment and representing a range of biofilm development stages and geochemical conditions to evaluate how the physiologies of the dominant and less abundant organisms change along environmental gradients. The initial colonist dominates across all environments, but its proteome changes between two stable states as communities diversify, implying that interspecies interactions affect this organism's metabolism. Its overall physiology is robust to abiotic environmental factors, but strong correlations exist between these factors and certain subsets of proteins, possibly accounting for its wide environmental distribution. Lower abundance populations are patchier in their distribution, and proteomic data indicate that their environmental niches may be constrained by specific sets of abiotic environmental factors. This research establishes an effective strategy to investigate ecological relationships between microbial physiology and the environment for whole communities in situ.
A human B‐cell interactome identifies MYB and FOXM1 as master regulators of proliferation in germinal centers
Authors: Lefebvre Celine , Rajbhandari Presha , Alvarez Mariano J , Bandaru Pradeep , Lim Wei Keat , Sato Mai , Wang Kai , Sumazin Pavel , Kustagi Manjunath , Bisikirska Brygida C , Basso Katia , Beltrao Pedro , Krogan Nevan , Gautier Jean , Dalla‐Favera Riccardo , Califano Andrea
Published: June 2010

Assembly of a transcriptional and post‐translational molecular interaction network in B cells, the human B‐cell interactome (HBCI), reveals a hierarchical, transcriptional control module, where MYB and FOXM1 act as synergistic master regulators of proliferation in the germinal center (GC). Eighty percent of genes jointly regulated by these transcription factors are activated in the GC, including those encoding proteins in a complex regulating DNA pre‐replication, replication, and mitosis. These results indicate that the HBCI analysis can be used for the identification of determinants of major human cell phenotypes and provides a paradigm of general applicability to normal and pathologic tissues.
A novel experimental system of high stability and lifetime for the laser-desorption of biomolecules
Authors: Taherkhani Mehran , Riese Mikko , BenYezzar Mohammed , Müller-Dethlefs Klaus
Published: June 2010

A novel laser desorption system, with improved signal stability and extraordinary long lifetime, is presented for the study of jet-cooled biomolecules in the gas phase using vibrationally resolved photoionization spectroscopy. As a test substance tryptophane is used to characterize this desorption source. A usable lifetime of above 1 month (for a laser desorption repetition rate of 20 Hz) has been observed by optimizing the pellets (graphite/tryptophane, 3 mm diameter and 6 mm length) from which the substance is laser-desorbed. Additionally, the stability and signal-to-noise ratio has been improved by averaging the signal over the entire sample pellet by synchronizing the data acquisition with the rotation of the sample rod. The results demonstrate how a combination of the above helps to produce stable and conclusive spectra of tryptophane using one-color and two-color resonant two-photon ionization studies.
Separability of N-particle fermionic states for arbitrary partitions
Authors: Ichikawa Tsubasa , Sasaki Toshihiko , Tsutsui Izumi
Published: June 2010

We present a criterion of separability for arbitrary s partitions of N-particle fermionic pure states. We show that, despite the superficial nonfactorizability due to the antisymmetry required by the indistinguishability of the particles, the states which meet our criterion have factorizable correlations for a class of observables which are specified consistently with the states. The separable states and the associated class of observables share an orthogonal structure, whose nonuniqueness is found to be intrinsic to the multipartite separability and leads to the nontransitivity in the factorizability, in general. Our result generalizes the previous result obtained by Ghirardi et al. [J. Stat. Phys. 108, 49 (2002)] for the s=2 and s=N case.
Interdiffusion effects and line broadening of hole intersubband absorption in complex GaAs/AlGaAs quantum well structures
Authors: Ikonić Zoran , Malis Oana , Pfeiffer Loren N. , West Kenneth W. , Harrison Paul
Published: June 2010

Detailed modeling of intersubband absorption in p-doped GaAs quantum wells embedded in GaAs/AlAs superlattice barriers is performed. It is shown that a careful analysis of measurements provides valuable information on the structure details, like the extent of interdiffusion and different sources of line broadening, which can be useful for further design of emitters and detectors based on this and other material systems.
X-ray irradiation-induced ionization of CdS1−xSex nanocrystals embedded in borosilicate glass
Authors: Azhniuk Yu. M. , Prymak M. V. , Lopushansky V. V. , Solomon A. M. , Hutych Yu. I. , Gomonnai A. V. , Zahn D. R. T.
Published: June 2010

Optical absorption spectra of x-ray irradiated CdS1−xSex nanocrystals embedded in a borosilicate glass matrix are studied. The observed transformation of the confinement-related features in the spectra is related to the x-ray-induced negative ionization of the nanocrystals with charge transfer across the nanocrystal/matrix interface. The radiation-induced changes and their relaxation upon postirradiation storage as a function of nanocrystal size and composition are discussed.
A quantum cascade laser cw cavity ringdown spectrometer coupled to a supersonic expansion source
Authors: Brumfield Brian E. , Stewart Jacob T. , Widicus Weaver Susanna L. , Escarra Matthew D. , Howard Scott S. , Gmachl Claire F. , McCall Benjamin J.
Published: June 2010

A new instrument has been constructed that couples a supersonic expansion source to a continuous wave cavity ringdown spectrometer using a Fabry–Perot quantum cascade laser (QCL). The purpose of the instrument is to enable the acquisition of a cold, rotationally resolved gas phase spectrum of buckminsterfullerene (C60). As a first test of the system, high resolution spectra of the ν8 vibrational band of CH2Br2 have been acquired at ∼1197 cm−1. To our knowledge, this is the first time that a vibrational band not previously recorded with rotational resolution has been acquired with a QCL-based ringdown spectrometer. 62 transitions of the three isotopologues of CH2Br2 were assigned and fit to effective Hamiltonians with a standard deviation of 14 MHz, which is smaller than the laser frequency step size. The spectra have a noise equivalent absorption coefficient of 1.4×10−8 cm−1. Spectral simulations of the band indicate that the supersonic source produces rotationally cold (∼7 K) molecules.
Statistical temperature molecular dynamics simulations applied to phase transitions in liquid crystalline systems
Authors: Lintuvuori Juho S. , Wilson Mark R.
Published: June 2010

The recently developed statistical temperature molecular dynamics (STMD) method [Kim et al., Phys. Rev. Lett. 97, 050601 (2006)] is applied to the simulation of liquid crystalline soft matter systems. Results are presented demonstrating how, in combination with anisotropic soft core potentials, STMD simulation is able to sample efficiently across a large temperature window; and thus bridge across isotropic-liquid crystal phase transitions. Data is presented for two separate systems, namely, a single-site interaction model and an AB rod-coil block copolymer. The results are in excellent agreement with phase diagrams calculated by a series of traditional canonical molecular dynamics simulations bridging similar temperature/energy windows. In addition to the usual energetic and structural information, the STMD technique provides the temperature dependence of the entropy, free energy and heat capacity of the system as by-products of the single simulation. The combined soft-core/STMD strategy is presented as an effective means of scanning the phase diagram of a simple molecular interaction model to understand the relationship between molecular structure and phase behavior.
Coriolis coupling as a source of non-RRKM effects in triatomic near-symmetric top molecules: Diffusive intramolecular energy exchange between rotational and vibrational degrees of freedom
Authors: Kryvohuz M. , Marcus R. A.
Published: June 2010

A classical theory is proposed to describe the non-RRKM effects in activated asymmetric top triatomic molecules observed numerically in classical molecular dynamics simulations of ozone. The Coriolis coupling is shown to result in an effective diffusive energy exchange between the rotational and vibrational degrees of freedom. A stochastic differential equation is obtained for the K-component of the rotational angular momentum that governs the diffusion.
Coriolis coupling as a source of non-RRKM effects in ozone molecule: Lifetime statistics of vibrationally excited ozone molecules
Authors: Kryvohuz M. , Marcus R. A.
Published: June 2010

A theory that describes the non-RRKM (non-Rice-Ramsperger-Kassel-Marcus) effects in the lifetime statistics of activated ozone molecules is derived. The non-RRKM effects are shown to originate due to the diffusive energy exchange between vibrational and rotational degrees of freedom in ozone molecule. The lifetime statistics is found to be intramolecular diffusion controlled at long times. The theoretical results are in good agreement with the direct MD simulations of lifetime statistics.
Study of defect-induced ferromagnetism in hydrogenated anatase TiO2:Co
Authors: Singhal R. K. , Samariya Arvind , Kumar Sudhish , Xing Y. T. , Jain D. C. , Dolia S. N. , Deshpande U. P. , Shripathi T. , Saitovitch Elisa B.
Published: June 2010

Electronic and magnetic properties of Co-doped TiO2 polycrystalline pellets (Ti0.95Co0.05O2) have been investigated using x-ray diffraction, x-ray photoemission, magnetization, and resistance measurements. The as-synthesized and hydrogenated specimens crystallize in the anatase type tetragonal structure containing very small (∼4.4%) rutile phase. The dopant ions of Co are found to be divalent and well incorporated into TiO2 lattice, substituting the Ti site within the anatase phase, with no evidence of metallic Co or any other oxides of Co. The Co doping induces a weak ferromagnetic ordering in the diamagnetic TiO2 host matrix. Interestingly, when the Co-doped TiO2 is annealed in hydrogen atmosphere, it shows a giant enhancement in magnetization. However, an extended reheating in air causes this H-induced magnetization to vanish and the sample regains the as-prepared status. Our findings indicate that ferromagnetism originates from the doped matrix rather than any magnetic clusters and strongly correlated with oxygen vacancies in the doped TiO2. The induced ferromagnetic ordering is found to be a reversible process with regard to oxygen vacancy defects that could be induced or removed, respectively, upon introduction or removal of these defects.
The functionalization of graphene using electron-beam generated plasmas
Authors: Baraket M. , Walton S. G. , Lock E. H. , Robinson J. T. , Perkins F. K.
Published: June 2010

A plasmas-based, reversible functionalization of graphene is discussed. Using electron-beam produced plasmas, oxygen and fluorine functionalities have been added by changing the processing gas mixtures from Ar/O2 to Ar/SF6, respectively. The reversibility of the functionalization was investigated by annealing the samples. The chemical composition and structural changes were studied by x-ray photoelectron spectroscopy and Raman spectroscopy.
High-temperature spin polarization of high-mobility charge carriers in hybrid metal-semiconductor structures
Authors: Meilikhov E. Z. , Farzetdinova R. M.
Published: June 2010

We consider magnetic properties of the planar structure consisting of a ferromagnetic metal, diluted magnetic semiconductor, and the quantum well [by the example of the hybrid heterostructure Fe–Ga(Mn)As–InGaAs]. In the framework of the mean-field theory, there is the significant amplification of the ferromagnetism induced by the ferromagnetic metal (Fe) in the system of magnetic impurities (Mn) due to their indirect interaction via the conductivity channel in the quantum well. In the discussed structure, high-temperature ferromagnetism leads to a high spin polarization of the charge carriers (holes, localized in the quantum well), while preserving their high mobility.
Photoelectron imaging of NCCCN−: The triplet ground state and the singlet-triplet splitting of dicyanocarbene
Authors: Goebbert Daniel J. , Pichugin Kostyantyn , Khuseynov Dmitry , Wenthold Paul G. , Sanov Andrei
Published: June 2010

The photoelectron spectra of NCCCN− have been measured at 355 and 266 nm by means of photoelectron imaging. The spectra show two distinct features, corresponding to the ground and first excited states of dycianocarbene. With support from theoretical calculations using the spin-flip coupled-cluster methods, the ground electronic state of HCCCN is assigned as a triplet state, while the first excited state is a closed-shell singlet. The photoelectron band corresponding to the triplet is broad and congested, indicating a large geometry change between the anion and neutral. A single sharp feature of the singlet band suggests that the geometry of the excited neutral is similar to that of the anion. In agreement with these observations, theoretical calculations show that the neutral triplet state is either linear or quasilinear (X̃ B31 or Σ3g−), while the closed-shell singlet (ã A11) geometry is strongly bent, similar to the anion structure. The adiabatic electron binding energy of the closed-shell singlet is measured to be 3.72±0.02 eV. The best estimate of the origin of the triplet band gives an experimental upper bound of the adiabatic electron affinity of NCCCN, EA≤3.25±0.05 eV, while the Franck–Condon modeling yields an estimate of EA(NCCCN)=3.20±0.05 eV. From these results, the singlet-triplet splitting is estimated to be ΔEST(X̃ B31/Σ3g−−ã A11)=0.52±0.05 eV (12.0±1.2 kcal/mol).
Enhancing the performance of quantum dots sensitized solar cell by SiO2 surface coating
Authors: Liu Zhifu , Miyauchi Masahiro , Uemura Yu , Cui Yan , Hara Kohjiro , Zhao Zhigang , Sunahara Kenji , Furube Akihiro
Published: June 2010

This letter reports enhanced performance of quantum dots sensitized solar cells by selectively deposition an insulating SiO2 layer over the quantum dots (QDs) sensitized mesoporous TiO2 photoanode. The incident photon to current conversion efficiency of the CdS/CdSe QDs cosensitized solar cell with SiO2 coating can reach 83%. A power conversion efficiency of 2.05% was obtained.
Retardation of electromigration-induced Ni(P) consumption by an electroless Pd insertion layer
Authors: Lu C. T. , Tseng H. W. , Chang C. H. , Huang T. S. , Liu C. Y.
Published: June 2010

In this study, Ni(P) bond pads joined with Sn solder bumps were stressed with a high current density of 104 A/cm2. Serious electromigration-induced Ni(P) consumption and unusual EM-enhanced diffusion of the interfacial Ni3Sn4 compound layer are observed. However the observed EM-induced Ni(P) consumption and EM-enhanced diffusion of the interfacial Ni3Sn4 compound layer can be effectively retarded by introducing an additional electroless Pd layer on the Ni(P) layer. The improvement in EM resistance due to the Pd layer can be attributed to PdSn4 formation and Pd solutes in the interfacial Ni3Sn4 layer.
Electrically reconfigurable nanophotonic hybrid grating lens array
Authors: Rajasekharan Ranjith , Bay Christoph , Dai Qing , Freeman Jon , Wilkinson Timothy D.
Published: June 2010

We demonstrate a switchable hybrid grating lens array using a nanophotonic device fabricated from multiwall carbon nanotubes and liquid crystals which combines diffraction, lensing, and dispersion. Diffraction experiments and computer simulations both show clear and well defined diffraction orders in two dimensions with voltage dependent diffraction efficiency. These characteristics enable the device to be used in the fabrication of miniaturized spectrometers and integrated optics.
Small gap semiconducting organic charge-transfer interfaces
Authors: Nakano M. , Alves H. , Molinari A. S. , Ono S. , Minder N. , Morpurgo A. F.
Published: June 2010

We investigated transport properties of organic heterointerfaces formed by single-crystals of two organic donor-acceptor molecules, tetramethyltetraselenafulvalene and 7,7,8,8-tetracyanoquinodimethane (TCNQ). Whereas the individual crystals have unmeasurably high resistance, the interface exhibits a resistivity of few tens of megohm with a temperature dependence characteristic of a small gap semiconductor. We analyze the transport properties based on a simple band diagram that naturally accounts for our observations in terms of charge transfer between two crystals. Together with the recently discovered tetrathiafulvalene–TCNQ interfaces, these results indicate that single-crystal organic heterostructures create functional electronic systems with properties relevant to both fundamental and applied fields.
Decentralisation and Devolution in Canadian Social Housing Policy
Authors: Leone Roberto , Carroll Barbara W
Published: June 2010

Beginning in 1945 Canada had a relatively successful housing policy meeting the needs of returning veterans, baby-boom parents, and, later, baby boomers themselves in addition to those less advantaged through a number of income-support housing programs. The reasons for this success are well documented and largely relied upon the dominance of the federal government in this policy space. This was achieved despite housing being constitutionally primarily a provincial responsibility due to a process known as ‘cooperative federalism’. This success ended in the mid-1990s and Canada has not had a national housing policy, nor successful provincial policies, since that time. Much of the demise of housing policy can be attributed to what at the time was considered to be a unique Canadian federal phenomenon called ‘province building’. We look at the institutional arrangements which made for a successful housing policy for nearly fifty years and the institutional failings which led to its demise. In particular, we analyse why the unique position of municipalities in Canada vis-à-vis other federal states made it more difficult to deal particularly with planning and social housing problems in Canada. The lessons of Canada are apt for other federal states trying to trade off regional and ethnic interests versus national priorities.
Negotiating Local Development: The Italian Experience of ‘Territorial Pacts’
Authors: Ramella Francesco
Published: June 2010

This study deals with a new policy for disadvantaged areas that has been introduced in Italy since the second half of the 1990s. This policy aims to promote local development based on partnerships between public and private actors. I present research carried out on thirty ‘Territorial Pacts’, analysing their impact at the local level. In some cases the results of the new policy were positive; in others they were very disappointing. Three key factors explain these different results. The first relates to the form of social interaction between local actors (the concertation factor). The second involves the presence or absence of policy entrepreneurs—namely, actors and institutions that ensured a strong and effective process management (the leadership factor). The third involves the political and organisational choices made in both the start-up and implementation phases of the pacts (the continuity factor).
The Use and Usefulness of Financial Assistance to UK SMEs
Authors: Han Liang , Benson Alan
Published: June 2010

Existing literature has paid considerable attention to the effects of supporting programmes on the survival and performance of small and medium-sized enterprises (SMEs), but it lacks a deep understanding of the benefits of the use of such assistance and the factors influencing the evaluation of such services from the perspective of SMEs. We examine the factors affecting the propensity to use assistance when SMEs make financial decisions and the usefulness perceived by the users. We examine 2500 UK SMEs and find that the use of assistance and the usefulness of such services, as perceived by SMEs, are much related to: the characteristics of the entrepreneur, the nature of the business, and the financial products used by the business. These empirical results imply that support and advice on financial decision making, available for SMEs, are important for them to better manage and to access finance. Assistance and advice are also very valuable for SMEs and entrepreneurs to compensate for their lack of human capital and thus facilitate overcoming possible problems in managing their businesses.
A potential role for initiator-tRNA in pre-mRNA splicing regulation
Authors: Kamhi Eyal , Raitskin Oleg , Sperling Ruth , Sperling Joseph
Published: June 2010

The translation initiator-tRNA plays a crucial role in the initiation of protein synthesis in both prokaryotic and eukaryotic cells, by employing specific base pairing between its anticodon triplet CAU and the general initiation codon AUG in the mRNA. Here we show that the initiator-tRNA may also act, in a manner that is independent of its role in protein translation, as a pre-mRNA splicing regulator. Specifically, we show that alternative splicing events that are induced by mutations in the translation initiation AUG codon can be suppressed by expressing initiator-tRNA constructs carrying anticodon mutations that compensate for the AUG mutations. These mutated initiator-tRNAs appeared to be uncharged with an amino acid. Our results imply that recognition of the initiation AUG sequence by the anticodon triplet of initiator-tRNA in its unloaded state plays a role in quality control of splicing in the cell nucleus by a yet unresolved mechanism. Identifying the initiator-tRNA as a transacting splicing regulator suggests a novel involvement of this molecule in splicing regulation and provides a critical step toward deciphering this intriguing mechanism.
A kinesin signaling complex mediates the ability of GSK-3β to affect mood-associated behaviors
Authors: Du Jing , Wei Yanling , Liu Lidong , Wang Yun , Khairova Rushaniya , Blumenthal Rayah , Tragon Tyson , Hunsberger Joshua G. , Machado-Vieira Rodrigo , Drevets Wayne , Wang Yu Tian , Manji Husseini K.
Published: June 2010

Lithium has been the gold standard in the treatment of bipolar disorder (BPD) for 60 y. Like lithium, glycogen synthase kinase 3 (GSK-3) inhibitors display both antimanic-like and antidepressant-like effects in some animal models. However, the molecular mechanisms of both lithium and GSK-3 inhibitors remain unclear. Here we show that the GSK-3 inhibitor AR-A014418 regulated α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA)-induced GluR1 and GluR2 internalization via phosphorylation of kinesin light chain 2 (KLC2), the key molecule of the kinesin cargo delivery system. Specifically, AMPA stimulation triggered serine phosphorylation of KLC2 and, subsequently, the dissociation of the GluR1/KLC2 protein complex. This suggests that GSK-3 phosphorylation of KLC2 led to the dissociation of AMPA-containing vesicles from the kinesin cargo system. The peptide TAT-KLCpCDK, a specific inhibitor for KLC2 phosphorylation by GSK-3β, reduced the formation of long-term depression. Furthermore, the TAT-KLCpCDK peptide showed antimanic-like effects similar to lithium's on amphetamine-induced hyperactivity, a frequently used animal model of mania. It also induced antidepressant-like effects in the tail suspension and forced swim tests, two commonly used animal models of depression. Taken together, the results demonstrated that KLC2 is a cellular target of GSK-3β capable of regulating synaptic plasticity, particularly AMPA receptor trafficking, as well as mood-associated behaviors in animal models. The kinesin cargo system may provide valuable novel targets for the development of new therapeutics for mood disorders.
Direct regulation of phytoene synthase gene expression and carotenoid biosynthesis by phytochrome-interacting factors
Authors: Toledo-Ortiz Gabriela , Huq Enamul , Rodríguez-Concepción Manuel
Published: June 2010

Carotenoids are key for plants to optimize carbon fixing using the energy of sunlight. They contribute to light harvesting but also channel energy away from chlorophylls to protect the photosynthetic apparatus from excess light. Phytochrome-mediated light signals are major cues regulating carotenoid biosynthesis in plants, but we still lack fundamental knowledge on the components of this signaling pathway. Here we show that phytochrome-interacting factor 1 (PIF1) and other transcription factors of the phytochrome-interacting factor (PIF) family down-regulate the accumulation of carotenoids by specifically repressing the gene encoding phytoene synthase (PSY), the main rate-determining enzyme of the pathway. Both in vitro and in vivo evidence demonstrate that PIF1 directly binds to the promoter of the
PSY
gene, and that this binding results in repression of
PSY
expression. Light-triggered degradation of PIFs after interaction with photoactivated phytochromes during deetiolation results in a rapid derepression of
PSY
gene expression and a burst in the production of carotenoids in coordination with chlorophyll biosynthesis and chloroplast development for an optimal transition to photosynthetic metabolism. Our results also suggest a role for PIF1 and other PIFs in transducing light signals to regulate
PSY
gene expression and carotenoid accumulation during daily cycles of light and dark in mature plants.
Unprecedented acetoacetyl-coenzyme A synthesizing enzyme of the thiolase superfamily involved in the mevalonate pathway
Authors: Okamura Eiji , Tomita Takeo , Sawa Ryuichi , Nishiyama Makoto , Kuzuyama Tomohisa
Published: June 2010

Acetoacetyl-CoA is the precursor of 3-hydroxy-3-methylglutaryl (HMG)-CoA in the mevalonate pathway, which is essential for terpenoid backbone biosynthesis. Acetoacetyl-CoA is also the precursor of poly-β-hydroxybutyrate, a polymer belonging to the polyester class produced by microorganisms. The de novo synthesis of acetoacetyl-CoA is usually catalyzed by acetoacetyl-CoA thiolase
via
a thioester-dependent Claisen condensation reaction between two molecules of acetyl-CoA. Here, we report that
nphT7
, found in the mevalonate pathway gene cluster from a soil-isolated
Streptomyces
sp. strain, encodes an unusual acetoacetyl-CoA synthesizing enzyme. The recombinant enzyme overexpressed in
Escherichia coli
catalyzes a single condensation of acetyl-CoA and malonyl-CoA to give acetoacetyl-CoA and CoA. Replacement of malonyl-CoA with malonyl-(acyl carrier protein) resulted in loss of the condensation activity. No acetoacetyl-CoA synthesizing activity was detected through the condensation of two molecules of acetyl-CoA. Based on these properties of NphT7, we propose to name this unusual enzyme of the thiolase superfamily acetoacetyl-CoA synthase. Coexpression of
nphT7
with the HMG-CoA synthase gene and the HMG-CoA reductase gene in a heterologous host allowed 3.5-fold higher production of mevalonate than when only the HMG-CoA synthase and HMG-CoA reductase genes were expressed. This result suggests that
nphT7
can be used to significantly increase the concentration of acetoacetyl-CoA in cells, eventually leading to the production of useful terpenoids and poly-β-hydroxybutyrate.
RNA polymerase complexes cooperate to relieve the nucleosomal barrier and evict histones
Authors: Kulaeva Olga I. , Hsieh Fu-Kai , Studitsky Vasily M.
Published: June 2010

Maintenance of the chromatin states and histone modification patterns during transcription is essential for proper gene regulation and cell survival. Histone octamer survives moderate transcription, but is evicted during intense transcription in vivo by RNA polymerase II (Pol II). Previously we have shown that nucleosomes can survive transcription by single Pol II complexes in vitro. To study the mechanism of histone displacement from DNA, the encounter between multiple complexes of RNA polymerase and a nucleosome was analyzed in vitro. Multiple transcribing Pol II complexes can efficiently overcome the high nucleosomal barrier and displace the entire histone octamer, matching the observations in vivo. DNA-bound histone hexamer left behind the first complex of transcribing enzyme is evicted by the next Pol II complex. Thus transcription by single Pol II complexes allows survival of the original H3/H4 histones, while multiple, closely spaced complexes of transcribing Pol II can induce displacement of all core histones along the gene.
How desert ants use a visual landmark for guidance along a habitual route
Authors: Collett Matthew
Published: June 2010

Many animals learn to follow habitual routes between important locations, but how they encode their routes is still largely unknown. Desert ants traveling between their nest and a food site develop stable, visually guided routes that can wind through desert scrub without the use of trail pheromones. Their route memories are sufficiently robust that if a nest-bound ant is caught at the end of its route and replaced somewhere earlier along it, the ant will recapitulate the route from the release site. Insects appear to use panoramas to recognize when they are on a familiar route. I examine here the cues then used for their guidance. Several mechanisms are known for straight segments of a route; but how does an ant encode a curved route along which both the views it sees, and the directions it takes, are constantly changing? The results here suggest that when an ant travels past a landmark on a familiar route, it uses the gradually changing direction of the landmark to trigger a set of associated learned heading directions. A route through a complex 2D environment could thus be encoded and followed economically if it is divided into panorama-defined segments, with each segment controlled by such a 1D mapping. The solution proposed for the ants would be simple to implement in an autonomous robot.
Restricted Arp3 expression in the testis prevents blood–testis barrier disruption during junction restructuring at spermatogenesis
Authors: Lie Pearl P. Y. , Chan Apple Y. N. , Mruk Dolores D. , Lee Will M. , Cheng C. Yan
Published: June 2010

In epithelia, a primary damage of tight junctions (TJ) always leads to a secondary disruption of adherens junction (AJ), and vice versa. This response, if occurring in the testis, would disrupt spermatogenesis because the blood–testis barrier (BTB) must remain intact during the transit of spermatids in the seminiferous epithelium, which is associated with extensive apical ectoplasmic specialization (apical ES, a testis-specific AJ type) restructuring. As such, apical ES restructuring accompanied with the transit of developing spermatids during spermiogenesis must be segregated from the BTB to avoid an immunological barrier breakdown in all stages of the seminiferous epithelial cycle, except at stage VIII when spermiation and BTB restructuring take place concurrently. We report herein a mechanism involving restricted spatial and temporal expression of Arp2/3 complex and N-WASP, whose actin branching activity associated with apical ES and BTB restructuring in the seminiferous epithelium. High expression of Arp3 at the apical ES was shown to correlate with spermatid movement and proper spermatid orientation. Likewise, high Arp3 level at the BTB associated with its restructuring to accommodate the transit of preleptotene spermatocytes at stage VIII of the epithelial cycle. These findings were validated by in vitro and in vivo studies using wiskostatin, an inhibitor that blocks N-WASP from activating Arp2/3 complex to elicit actin branching. Inhibition of actin branching caused a failure of spermatid transit plus a loss of proper orientation in the epithelium, and a “tightened” Sertoli cell TJ permeability barrier, supporting the role of Arp2/3 complex in segregating the events of AJ and BTB restructuring.
Characterization and reversal of synaptic defects in the amygdala in a mouse model of fragile X syndrome
Authors: Suvrathan Aparna , Hoeffer Charles A. , Wong Helen , Klann Eric , Chattarji Sumantra
Published: June 2010

Fragile X syndrome (FXS), a common inherited form of mental impairment and autism, is caused by transcriptional silencing of the fragile X mental retardation 1 (
FMR1
) gene. Earlier studies have identified a role for aberrant synaptic plasticity mediated by the metabotropic glutamate receptors (mGluRs) in FXS. However, many of these observations are derived primarily from studies in the hippocampus. The strong emotional symptoms of FXS, on the other hand, are likely to involve the amygdala. Unfortunately, little is known about how exactly FXS affects synaptic function in the amygdala. Here, using whole-cell recordings in brain slices from adult
Fmr1
knockout mice, we find mGluR-dependent long-term potentiation to be impaired at thalamic inputs to principal neurons in the lateral amygdala. Consistent with this long-term potentiation deficit, surface expression of the AMPA receptor subunit, GluR1, is reduced in the lateral amygdala of knockout mice. In addition to these postsynaptic deficits, lower presynaptic release was manifested by a decrease in the frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs), increased paired-pulse ratio, and slower use-dependent block of NMDA receptor currents. Strikingly, pharmacological inactivation of mGluR5 with 2-methyl-6-phenylethynyl-pyridine (MPEP) fails to rescue either the deficit in long-term potentiation or surface GluR1. However, the same acute MPEP treatment reverses the decrease in mEPSC frequency, a finding of potential therapeutic relevance. Therefore, our results suggest that synaptic defects in the amygdala of knockout mice are still amenable to pharmacological interventions against mGluR5, albeit in a manner not envisioned in the original hippocampal framework.
Polyketide synthase chemistry does not direct biosynthetic divergence between 9- and 10-membered enediynes
Authors: Horsman Geoff P. , Chen Yihua , Thorson Jon S. , Shen Ben
Published: June 2010

Enediynes are potent antitumor antibiotics that are classified as 9- or 10-membered according to the size of the enediyne core structure. However, almost nothing is known about enediyne core biosynthesis, and the determinants of 9- versus 10-membered enediyne core biosynthetic divergence remain elusive. Previous work identified enediyne-specific polyketide synthases (PKSEs) that can be phylogenetically distinguished as being involved in 9- versus 10-membered enediyne biosynthesis, suggesting that biosynthetic divergence might originate from differing PKSE chemistries. Recent in vitro studies have identified several compounds produced by the PKSE and associated thioesterase (TE), but condition-dependent product profiles make it difficult to ascertain a true catalytic difference between 9- and 10-membered PKSE-TE systems. Here we report that PKSE chemistry does not direct 9- versus 10-membered enediyne core biosynthetic divergence as revealed by comparing the products from three 9-membered and two 10-membered PKSE-TE systems under identical conditions using robust in vivo assays. Three independent experiments support a common catalytic function for 9- and 10-membered PKSEs by the production of a heptaene metabolite from: (
i
) all five cognate PKSE-TE pairs in
Escherichia coli
; (
ii
) the C-1027 and calicheamicin cognate PKSE-TEs in
Streptomyces lividans
K4-114; and (
iii
) selected native producers of both 9- and 10-membered enediynes. Furthermore, PKSEs and TEs from different 9- and 10-membered enediyne biosynthetic machineries are freely interchangeable, revealing that 9- versus 10-membered enediyne core biosynthetic divergence occurs beyond the PKSE-TE level. These findings establish a starting point for determining the origins of this biosynthetic divergence.
Systemically dispersed innate IL-13–expressing cells in type 2 immunity
Authors: Price April E. , Liang Hong-Erh , Sullivan Brandon M. , Reinhardt R. Lee , Eisley Chris J. , Erle David J. , Locksley Richard M.
Published: June 2010

Type 2 immunity is a stereotyped host response to allergens and parasitic helminths that is sustained in large part by the cytokines IL-4 and IL-13. Recent advances have called attention to the contributions by innate cells in initiating adaptive immunity, including a novel lineage-negative population of cells that secretes IL-13 and IL-5 in response to the epithelial cytokines IL-25 and IL-33. Here, we use IL-4 and IL-13 reporter mice to track lineage-negative innate cells that arise during type 2 immunity or in response to IL-25 and IL-33 in vivo. Unexpectedly, lineage-negative IL-25 (and IL-33) responsive cells are widely distributed in tissues of the mouse and are particularly prevalent in mesenteric lymph nodes, spleen, and liver. These cells expand robustly in response to exogenous IL-25 or IL-33 and after infection with the helminth
Nippostrongylus brasiliensis
, and they are the major innate IL-13–expressing cells under these conditions. Activation of these cells using IL-25 is sufficient for worm clearance, even in the absence of adaptive immunity. Widely dispersed innate type 2 helper cells, which we designate Ih2 cells, play an integral role in type 2 immune responses.
Chromosome rearrangements and aneuploidy in yeast strains lacking both Tel1p and Mec1p reflect deficiencies in two different mechanisms
Authors: McCulley Jennifer L. , Petes Thomas D.
Published: June 2010

The human ATM and ATR proteins participate in the DNA damage and DNA replication checkpoint pathways and are critical to maintaining genome stability. The
Saccharomyces cerevisiae
homologs of ATM and ATR are Tel1p and Mec1p, respectively. Haploid
tel1 mec1
strains have very short telomeres and very high rates of chromosomal aberrations. Here, we examine genetic stability in
tel1 mec1
diploid cells. In the absence of induced DNA damage, these yeast strains had very high frequencies of aneuploidy (both trisomy and monosomy) in addition to elevated rates of chromosome rearrangements. Although we found the aneuploidy in the
tel1 mec1
diploids mimicked that observed in
bub1
diploids, the
tel1 mec1
diploids had a functional spindle assembly checkpoint. Restoration of wild-type telomere lengths in the
tel1 mec1
strain substantially reduced the rate of chromosome rearrangements but had no effect on the frequency of aneuploidy.
Sialidase enhances recovery from spinal cord contusion injury
Authors: Mountney Andrea , Zahner Matthew R. , Lorenzini Ileana , Oudega Martin , Schramm Lawrence P. , Schnaar Ronald L.
Published: June 2010

Axons fail to regenerate in the injured spinal cord, limiting motor and autonomic recovery and contributing to long-term morbidity. Endogenous inhibitors, including those on residual myelin, contribute to regeneration failure. One inhibitor, myelin-associated glycoprotein (MAG), binds to sialoglycans and other receptors on axons. MAG inhibition of axon outgrowth in some neurons is reversed by treatment with sialidase, an enzyme that hydrolyzes sialic acids and eliminates MAG–sialoglycan binding. We delivered recombinant sialidase intrathecally to rats following a spinal cord contusive injury. Sialidase (or saline solution) was infused to the injury site continuously for 2 wk and then motor behavior, autonomic physiology, and anatomic outcomes were determined 3 wk later. Sialidase treatment significantly enhanced hindlimb motor function, improved bulbospinally mediated autonomic reflexes, and increased axon sprouting. These findings validate sialoglycans as therapeutic targets and sialidase as a candidate therapy for spinal cord injury.
Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function
Authors: Sander Leif E. , Sackett Sara Dutton , Dierssen Uta , Beraza Naiara , Linke Reinhold P. , Müller Michael , Blander J. Magarian , Tacke Frank , Trautwein Christian
Published: June 2010

Acute-phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and antiinflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Using a mouse model of polymicrobial sepsis, we show that abrogation of APP production by hepatocyte-specific gp130 deletion, the signaling receptor shared by IL-6 family cytokines, strongly increased mortality despite normal bacterial clearance. Hepatic gp130 signaling through STAT3 was required to control systemic inflammation. Notably, hepatic gp130–STAT3 activation was also essential for mobilization and tissue accumulation of myeloid-derived suppressor cells (MDSCs), a cell population mainly known for antiinflammatory properties in cancer. MDSCs were critical to regulate innate inflammation, and their adoptive transfer efficiently protected gp130-deficient mice from sepsis-associated mortality. The hepatic APPs serum amyloid A and Cxcl1/KC cooperatively promoted MDSC mobilization, accumulation, and survival, and reversed dysregulated inflammation and restored survival of gp130-deficient mice. Thus, gp130-dependent communication between the liver and MDSCs through APPs controls inflammatory responses during infection.
ACNE: a summarization method to estimate allele-specific copy numbers for Affymetrix SNP arrays
Authors: Ortiz-Estevez Maria , Bengtsson Henrik , Rubio Angel
Published: June 2010

Motivation: Current algorithms for estimating DNA copy numbers (CNs) borrow concepts from gene expression analysis methods. However, single nucleotide polymorphism (SNP) arrays have special characteristics that, if taken into account, can improve the overall performance. For example, cross hybridization between alleles occurs in SNP probe pairs. In addition, most of the current CN methods are focused on total CNs, while it has been shown that allele-specific CNs are of paramount importance for some studies. Therefore, we have developed a summarization method that estimates high-quality allele-specific CNs.

Results: The proposed method estimates the allele-specific DNA CNs for all Affymetrix SNP arrays dealing directly with the cross hybridization between probes within SNP probesets. This algorithm outperforms (or at least it performs as well as) other state-of-the-art algorithms for computing DNA CNs. It better discerns an aberration from a normal state and it also gives more precise allele-specific CNs.

Availability: The method is available in the open-source R package ACNE, which also includes an add on to the aroma.affymetrix framework (http://www.aroma-project.org/).

Contact:  arubio@ceit.es

Supplementaruy information:  Supplementary data are available at Bioinformatics online.
Efficient learning of microbial genotype–phenotype association rules
Authors: MacDonald Norman J. , Beiko Robert G.
Published: June 2010

Motivation: Finding biologically causative genotype–phenotype associations from whole-genome data is difficult due to the large gene feature space to mine, the potential for interactions among genes and phylogenetic correlations between genomes. Associations within phylogentically distinct organisms with unusual molecular mechanisms underlying their phenotype may be particularly difficult to assess.

Results: We have developed a new genotype–phenotype association approach that uses Classification based on Predictive Association Rules (CPAR), and compare it with NETCAR, a recently published association algorithm. Our implementation of CPAR gave on average slightly higher classification accuracy, with approximately 100 time faster running times. Given the influence of phylogenetic correlations in the extraction of genotype–phenotype association rules, we furthermore propose a novel measure for downweighting the dependence among samples by modeling shared ancestry using conditional mutual information, and demonstrate its complementary nature to traditional mining approaches.

Availability: Software implemented for this study is available under the Creative Commons Attribution 3.0 license from the author at http://kiwi.cs.dal.ca/Software/PICA

Contact:  beiko@cs.dal.ca

Supplementary information:  Supplementary data are available Bioinformatics online.
Patching gaps in plant genomes results in gene movement and erosion of colinearity
Authors: Wicker Thomas , Buchmann Jan P. , Keller Beat
Published: June 2010

Colinearity of genes in plant genomes generally decreases with increasing evolutionary distance while the actual number of genes remains more or less constant. To characterize the molecular mechanisms of this “gene movement,” we identified non-colinear genes by three-way comparison of the genomes of Brachypodium, rice, and sorghum. We found that genomic fragments of up to 50 kb containing the non-colinear genes are duplicated to acceptor sites elsewhere in the genome. Apparent movement of genes may usually be the result of subsequent deletions of genes in the donor region. Often, the duplicated fragments are precisely bordered by transposable elements (TEs) at the acceptor site. Highly diagnostic sequence motifs at these borders strongly suggest that these gene movements were the result of double-strand break (DSB) repair through synthesis-dependent strand annealing. In these cases, a copy of the foreign DNA fragment is used as filler DNA to repair the DSB linked with the transposition of TEs. Interestingly, most TEs we found associated with gene movement have a very low copy number in the genome and for several we did not find autonomous copies. This suggests that some of these elements spontaneously arose from unspecific interaction with TE proteins that are encoded by autonomous elements. Additionally, we found evidence that gene movements can also be caused when DSBs are repaired after template slippage or unequal crossing-over events. The observed frequency of gene movements can explain the erosion of gene colinearity between plant genomes during evolution.