bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunosuppressive properties of human umbilical cord‐derived mesenchymal stem cells: role of B7‐H1 and IDO
Authors: Tipnis Shabari , Viswanathan Chandra , Majumdar Anish S
Published: April 2010

Umbilical cord is a rich source of mesenchymal stromal or stem cells (MSCs) that can be used for developing allogeneic cell therapy to treat intractable diseases. In this report, we present evidence that umbilical cord‐derived MSCs (UCMSCs) possess important immunomodulatory properties that may enable them to survive in an allogeneic environment. UCMSCs do not express human leukocyte antigen (HLA)‐DR and co‐stimulatory molecules CD80 and CD86 that are required for T‐cell activation. More importantly, UCMSCs constitutively express a negative regulator of T‐cell activation, B7‐H1, and its expression is increased after interferon‐γ (IFN‐γ) treatment. In addition, IFN‐γ treatment induced indoleamine 2,3‐dioxygenase (IDO) and HLA‐DR expression in UCMSCs. Neither control nor IFN‐γ‐treated UCMSCs stimulated allogeneic T‐cell proliferation, and both cell populations inhibited third‐party dendritic cell (DC)‐mediated allostimulatory activity. Addition of a B7‐H1‐specific blocking antibody or an IDO inhibitor, 1 methyl tryptophan (1‐MT) abrogated the T‐cell immunosuppressive activity of these cells. Furthermore, UCMSCs prevented the differentiation and maturation of peripheral blood monocyte‐derived DCs, and augmented the generation of regulatory T cells (Tregs) in culture. The immunosuppressive effects of UCMSCs are largely mediated by cell‐to‐cell contact, although some inhibitory activity was observed with cell‐free supernatant. Our study suggests that these immunomodulatory properties of UCMSCs could potentially improve the outcome of allogeneic stem cell therapy.
Women directors' contribution to board decision‐making and strategic involvement: The role of equality perception
Authors: Nielsen Sabina , Huse Morten
Published: April 2010

Abstract In times of vivid debates about the role of women on corporate boards, this article investigates the contribution of women directors to board decision‐making and strategic involvement. Based on survey data from multiple respondents in 120 Norwegian firms, we find that women directors influence board strategic involvement through their contribution to board decision‐making, which in turn depends on women directors' professional experiences and the different values they bring along. Drawing upon stereotype threat theory, we further find that perception of women as unequal board members may limit their potential contribution to board decision‐making.
Toward a theory of public entrepreneurship
Authors: Klein Peter G. , Mahoney Joseph T. , McGahan Anita M. , Pitelis Christos N.
Published: April 2010

AbstractThis paper explores innovation, experimentation, and creativity in the public domain and in the public interest. Researchers in various disciplines have studiedpublic entrepreneurship, but there is little work in management and economics on the nature, incentives, constraints, and boundaries of entrepreneurship directed to public ends. We identify a framework for analyzing public entrepreneurship and its relationship to private entrepreneurial behavior. We submit that public and private entrepreneurship share essential features but differ critically regarding the definition and measurement of objectives, the nature of the selection environment, and the opportunities for rent seeking. We describe four levels of analysis for studying public entrepreneurship, provide examples, and suggest new research directions.
Photoemission study of the SiO2 conversion mechanism to magnesium silicate
Authors: Casey Patrick , Hughes Greg
Published: April 2010

The objective of this work is to investigate interface chemistries which minimize the interfacial silicon oxide transition region at Si/high-k dielectric interfaces. We report on the mechanism by which a silicon native oxide layer is converted into magnesium silicate. The deposition of metal Mg onto a SiO2 native oxide surface resulted in the formation of a magnesium silicide in addition to substochiometric silicon oxides and a significant decrease in the oxidised silicon signal. Annealing to 300 °C resulted in the decomposition of the magnesium silicide, oxidation of the Mg, and the desorption of excess metallic Mg. Subsequent annealing to 500 °C resulted in converting the SiO2 into magnesium silicate. The results suggest that the decomposition of the Mg silicide in the presence of the residual native oxide facilitates silicate formation at 500 °C. Due to the reported thermal stability of Mg silicate it is suggested that this process may be beneficial in modifying the interface characteristics of the Si/high-k dielectric interface which has potentially significant implications for future semiconductor device generations.
Deep levels in GaAs(001)/InAs/InGaAs/GaAs self-assembled quantum dot structures and their effect on quantum dot devices
Authors: Asano Tetsuya , Fang Zhaoqiang , Madhukar Anupam
Published: April 2010

Currently lattice mismatch strain-driven three-dimensional coherent island based quantum dots, dubbed self-assembled quantum dots (SAQDs), constitute the most developed class of quantum dots with successful applications to lasers and considerable potential for infrared detectors in the 1–12 μm regime. This is in no small part a consequence of the extensive studies on the formation and control of the islands and on their capping by appropriate overlayer materials under optimal growth conditions. By contrast, surprisingly few studies have been reported on the presence and nature of the deep levels in SAQD structures, much less direct studies of the impact of deep levels on SAQD based device characteristics. The latter is of particular significance to devices such as detectors that require large numbers of SAQD layers [i.e., multiple quantum dot (MQD) structures] and are thus increasingly prone to accumulating strain-induced defect formation with increasing numbers of quantum dot layers. In this paper, we report the results of a study of the density, energy profile, and spatial profile of deep levels in different regions of GaAs(001)/InAs/InGaAs/GaAs SAQD structures in which the InGaAs/GaAs capping layers have been grown at different growth conditions. Different types of deep levels are found in different regions and, as expected, their densities are found to increase in the presence of the SAQDs. The study shows that it is the density of deep levels in the GaAs capping layer, forced to be grown at the low temperature of ∼500 °C to suppress In outdiffusion, which has a significant adverse impact on quantum dot device characteristics. Their density can be reduced by growth conditions such as migration enhanced epitaxy that permit high quality overgrowths at temperatures as low as ∼350 °C. Nevertheless, the ultimate performance limitation of thick MQD based devices resides in the ability to realize low density of the deep levels relative to the density of SAQDs.
Development of high-speed polarizing imaging system for operation in high pulsed magnetic field
Authors: Katakura I. , Tokunaga M. , Matsuo A. , Kawaguchi K. , Kindo K. , Hitomi M. , Akahoshi D. , Kuwahara H.
Published: April 2010

A high-speed polarizing microscope system combined with a 37 T pulse magnet has been developed. This system was applied to successfully visualize the field-induced collapse of charge-orbital ordering in a layered manganite La1/2Sr3/2MnO4. Quantitative analyses of the obtained polarizing microscope images provided clear evidence of this transition in contrast to rather moderate changes in magnetization and magnetoresistance. The ability of this system to carry out quantitative analysis was further tested through the observation of Faraday rotation in a Tb3Ga5O12 crystal. The Verdet constant determined from the polarizing images is in reasonable agreement with that in literature. Local intensity analyses of the images indicate that we can investigate magneto-optical signals within an accuracy of 0.85% in an area of 9.6×9.6 μm2.
Transient formation of internal potentials in solid electrolytes
Authors: Martin Bjoern , Kliem Herbert
Published: April 2010

Electrode effects can play an important role in ion-conducting polymers in which a space charge polarization of mobile internal ions prevails. The ions are shifted in an external field and they are attracted to the electrodes due to Coulomb forces caused by their own image charges. These image charges influence the static and dynamic charge distribution. This can be proved experimentally by measurements of the transient surface potential with the scanning Kelvin probe using polyethylene oxide doped with lithium perchlorate (PEO-LiClO4). Simulations performed with a three-dimensional hopping model coincide with the experimental results qualitatively.
An alternative construction of the positive inner product for pseudo-Hermitian Hamiltonians: Examples
Authors: Das Ashok , Greenwood L.
Published: April 2010

In this paper, we build on our earlier proposal for the construction of a positive inner product for pseudo-Hermitian Hamiltonians and present examples to clarify the procedure. We focus on two detailed calculations where the method is used, namely, a simple (generalized 2×2 matrix) pseudo-Hermitian Hamiltonian, which can be diagonalized, and a second system where the Hamiltonian cannot be diagonalized, but can be described as a perturbation of the harmonic oscillator. When the quantum mechanical system cannot be diagonalized exactly, our construction can be carried out perturbatively and we develop the general formalism for such a perturbative calculation systematically (for real eigenvalues).
An optimization-based “phase field” model for polycrystalline ferroelectrics
Authors: Li F. X. , Zhou X. L. , Soh A. K.
Published: April 2010

An optimization-based computational model is proposed to study domain evolution in polycrystalline ferroelectrics composed of numerous grains, each of which consists of multiple domains. Domain switching is realized by an optimization process to minimize the free energy of each grain. Similar to phase field modeling, no priori domain-switching criterion is imposed in the proposed model. Moreover, by focusing on the volume fractions of domains only, the computational complexity of this model becomes much smaller and the domain textures evolution can be captured. Simulation results on both tetragonal and rhombohedral lead titanate zirconate ceramics illustrate the efficiency of this model.
Nonlinear electrophoretic motion of dielectric microparticles in nematic liquid crystals
Authors: Ryzhkova A. V. , Podgornov F. V. , Haase W.
Published: April 2010

The motion of dielectric microparticles induced by external ac electric field, E, was investigated in the cell with in-plane stripe electrodes and filled with homeotropically aligned nematic liquid crystal. It was demonstrated that the average velocity of the microparticles depended on the third power of the electric field strength (v=μ(3)E3). The experimental results were explained by the induced charge electrophoresis.
High stability of amorphous hafnium-indium-zinc-oxide thin film transistor
Authors: Chong Eugene , Jo Kyoung Chul , Lee Sang Yeol
Published: April 2010

Time dependence of the threshold voltage (Vth) shift in amorphous hafnium-indium-zinc oxide (a-HIZO) thin film transistor has been reported under on-current bias temperature stress measured at 60 °C. X-ray photoelectron spectroscopy results show the decrease in oxygen vacancies by Hf metal cations in a-HIZO systems after annealing process. High stability of a-HIZO systems has been observed due to low charge injection from the channel layer. Hf metal cations have been effectively incorporated into the IZO thin films as a suppressor against both the oxygen deficiencies and the carrier generation.
Multiferroic properties and surface potential behaviors in cobalt-doped BiFeO3 film
Authors: Zhang Q. , Kim C. H. , Jang Y. H. , Hwang H. J. , Cho J. H.
Published: April 2010

The spatial coexistence of magnetic and ferroelectric domains in multiferroic BiFe0.96Co0.04O3 film is confirmed by multimode scanning probe microscopy. The applied bias dependence of the surface potential in BiFe0.96Co0.04O3 indicates that surface potential is determined by the interplay of polarization and surface charges. It is also shown that multiferroic BiFe0.96Co0.04O3 can more easily trap surface charges than the well-known ferroelectric PbZr0.53Ti0.47O3. The time evolution of surface potential exhibits an exponential decay, which is closely related to the observed spread of surface charges. The study on BiFe0.96Co0.04O3 unveils the origin and evolution behavior of the surface potential in BiFeO3-based multiferroic films.
Phase-locked ring-defect photonic crystal vertical-cavity surface-emitting laser
Authors: Liu Anjin , Chen Wei , Xing Mingxin , Zhou Wenjun , Qu Hongwei , Zheng Wanhua
Published: April 2010

Phase-locked oxide-confined ring-defect photonic crystal vertical-cavity surface-emitting laser is presented. The coupled-mode theory is employed to illustrate the two supermodes of the device, in-phase and out-of-phase supermode. Experimental results verify the two supermodes by the characteristics of the spectra and the far field patterns. At the lower current, only the out-of-phase supermode is excited, whereas under the higher current, the in-phase supermode also appears at the shorter wavelength range. In addition, the measured spectral separation between the two supermodes agrees well with the theoretical result.
Abnormal pressure-induced structural transformations of gallium nitride nanowires
Authors: Dong Zhaohui , Song Yang
Published: April 2010

One-dimensional nanostructured GaN was studied at pressures up to 65 GPa by in situ synchrotron x-ray diffraction. A wurtzite-to-rocksalt transformation was observed at ∼55 GPa, an onset pressure higher than that for bulk GaN, but lower than that for nanocrystalline GaN. Such transformation was found extremely incomplete even at the highest pressure but was facilitated by decompression. In addition, GaN nanowires exhibited drastically different volume responses to compression than did GaN in other forms. These unusual pressure behaviors of GaN nanowires are attributed to the interplay of several factors involving the intrinsic nanoproperties and the compression conditions.
Pre-Columbian agricultural landscapes, ecosystem engineers, and self-organized patchiness in Amazonia
Authors: McKey Doyle , Rostain Stéphen , Iriarte José , Glaser Bruno , Birk Jago Jonathan , Holst Irene , Renard Delphine
Published: April 2010

The scale and nature of pre-Columbian human impacts in Amazonia are currently hotly debated. Whereas pre-Columbian people dramatically changed the distribution and abundance of species and habitats in some parts of Amazonia, their impact in other parts is less clear. Pioneer research asked whether their effects reached even further, changing how ecosystems function, but few in-depth studies have examined mechanisms underpinning the resilience of these modifications. Combining archeology, archeobotany, paleoecology, soil science, ecology, and aerial imagery, we show that pre-Columbian farmers of the Guianas coast constructed large raised-field complexes, growing on them crops including maize, manioc, and squash. Farmers created physical and biogeochemical heterogeneity in flat, marshy environments by constructing raised fields. When these fields were later abandoned, the mosaic of well-drained islands in the flooded matrix set in motion self-organizing processes driven by ecosystem engineers (ants, termites, earthworms, and woody plants) that occur preferentially on abandoned raised fields. Today, feedbacks generated by these ecosystem engineers maintain the human-initiated concentration of resources in these structures. Engineer organisms transport materials to abandoned raised fields and modify the structure and composition of their soils, reducing erodibility. The profound alteration of ecosystem functioning in these landscapes coconstructed by humans and nature has important implications for understanding Amazonian history and biodiversity. Furthermore, these landscapes show how sustainability of food-production systems can be enhanced by engineering into them fallows that maintain ecosystem services and biodiversity. Like anthropogenic dark earths in forested Amazonia, these self-organizing ecosystems illustrate the ecological complexity of the legacy of pre-Columbian land use.
Exotic behavior and crystal structures of calcium under pressure
Authors: Oganov Artem R. , Ma Yanming , Xu Ying , Errea Ion , Bergara Aitor , Lyakhov Andriy O.
Published: April 2010

Experimental studies established that calcium undergoes several counterintuitive transitions under pressure: fcc → bcc → simple cubic → Ca-IV → Ca-V, and becomes a good superconductor in the simple cubic and higher-pressure phases. Here, using ab initio evolutionary simulations, we explore the behavior of Ca under pressure and find a number of new phases. Our structural sequence differs from the traditional picture for Ca, but is similar to that for Sr. The β-tin (
I
4
1
/
amd
) structure, rather than simple cubic, is predicted to be the theoretical ground state at 0 K and 33–71 GPa. This structure can be represented as a large distortion of the simple cubic structure, just as the higher-pressure phases stable between 71 and 134 GPa. The structure of Ca-V, stable above 134 GPa, is a complex host-guest structure. According to our calculations, the predicted phases are superconductors with
Tc
increasing under pressure and reaching approximately 20 K at 120 GPa, in good agreement with experiment.
Unidirectional Brownian motion observed in an
in silico
single molecule experiment of an actomyosin motor
Authors: Takano Mitsunori , Terada Tomoki P. , Sasai Masaki
Published: April 2010

The actomyosin molecular motor, the motor composed of myosin II and actin filament, is responsible for muscle contraction, converting chemical energy into mechanical work. Although recent single molecule and structural studies have shed new light on the energy-converting mechanism, the physical basis of the molecular-level mechanism remains unclear because of the experimental limitations. To provide a clue to resolve the controversy between the lever-arm mechanism and the Brownian ratchet-like mechanism, we here report an
in silico
single molecule experiment of an actomyosin motor. When we placed myosin on an actin filament and allowed myosin to move along the filament, we found that myosin exhibits a unidirectional Brownian motion along the filament. This unidirectionality was found to arise from the combination of a nonequilibrium condition realized by coupling to the ATP hydrolysis and a ratchet-like energy landscape inherent in the actin-myosin interaction along the filament, indicating that a Brownian ratchet-like mechanism contributes substantially to the energy conversion of this molecular motor.
Multifractal network generator
Authors: Palla Gergely , Lovász László , Vicsek Tamás
Published: April 2010

We introduce a new approach to constructing networks with realistic features. Our method, in spite of its conceptual simplicity (it has only two parameters) is capable of generating a wide variety of network types with prescribed statistical properties, e.g., with degree or clustering coefficient distributions of various, very different forms. In turn, these graphs can be used to test hypotheses or as models of actual data. The method is based on a mapping between suitably chosen singular measures defined on the unit square and sparse infinite networks. Such a mapping has the great potential of allowing for graph theoretical results for a variety of network topologies. The main idea of our approach is to go to the infinite limit of the singular measure and the size of the corresponding graph simultaneously. A very unique feature of this construction is that with the increasing system size the generated graphs become topologically more structured. We present analytic expressions derived from the parameters of the—to be iterated—initial generating measure for such major characteristics of graphs as their degree, clustering coefficient, and assortativity coefficient distributions. The optimal parameters of the generating measure are determined from a simple simulated annealing process. Thus, the present work provides a tool for researchers from a variety of fields (such as biology, computer science, biology, or complex systems) enabling them to create a versatile model of their network data.
Territorial expansion and primary state formation
Authors: Spencer Charles S.
Published: April 2010

A major research problem in anthropology is the origin of the state and its bureaucratic form of governance. Of particular importance for evaluating theories of state origins are cases of primary state formation, whereby a first-generation state evolves without contact with any preexisting states. A general model of this process, the territorial-expansion model, is presented and assessed with archaeological data from six areas where primary states emerged in antiquity: Mesoamerica, Peru, Egypt, Mesopotamia, the Indus Valley, and China. In each case, the evidence shows a close correspondence in time between the first appearance of state institutions and the earliest expansion of the state's political-economic control to regions lying more than a day's round-trip from the capital. Although additional research will add detail and clarity to the empirical record, the results to date are consistent with the territorial-expansion model, which argues that the success of such long-distance expansion not only demanded the bureaucratization of central authority but also helped provide the resources necessary to underwrite this administrative transformation.
Space representation for eye movements is more contralateral in monkeys than in humans
Authors: Kagan Igor , Iyer Asha , Lindner Axel , Andersen Richard A.
Published: April 2010

Contralateral hemispheric representation of sensory inputs (the right visual hemifield in the left hemisphere and vice versa) is a fundamental feature of primate sensorimotor organization, in particular the visuomotor system. However, many higher-order cognitive functions in humans show an asymmetric hemispheric lateralization—e.g., right brain specialization for spatial processing—necessitating a convergence of information from both hemifields. Electrophysiological studies in monkeys and functional imaging in humans have investigated space and action representations at different stages of visuospatial processing, but the transition from contralateral to unified global spatial encoding and the relationship between these encoding schemes and functional lateralization are not fully understood. Moreover, the integration of data across monkeys and humans and elucidation of interspecies homologies is hindered, because divergent findings may reflect actual species differences or arise from discrepancies in techniques and measured signals (electrophysiology vs. imaging). Here, we directly compared spatial cue and memory representations for action planning in monkeys and humans using event-related functional MRI during a working-memory oculomotor task. In monkeys, cue and memory-delay period activity in the frontal, parietal, and temporal regions was strongly contralateral. In putative human functional homologs, the contralaterality was significantly weaker, and the asymmetry between the hemispheres was stronger. These results suggest an inverse relationship between contralaterality and lateralization and elucidate similarities and differences in human and macaque cortical circuits subserving spatial awareness and oculomotor goal-directed actions.
Transient tether between the SRP RNA and SRP receptor ensures efficient cargo delivery during cotranslational protein targeting
Authors: Shen Kuang , Shan Shu-ou
Published: April 2010

Kinetic control of macromolecular interactions plays key roles in biological regulation. An example of such control occurs in cotranslational protein targeting by the signal recognition particle (SRP), during which the SRP RNA and the cargo both accelerate complex assembly between the SRP and SRP receptor FtsY 10
2
-fold. The molecular mechanism underlying these rate accelerations was unclear. Here we show that a highly conserved basic residue, Lys399, on the lateral surface of FtsY provides a novel RNA tetraloop receptor to mediate the SRP RNA- and cargo-induced acceleration of SRP–FtsY complex assembly. We propose that the SRP RNA, by using its tetraloop to interact with FtsY–Lys399, provides a transient tether to stabilize the early stage and transition state of complex formation; this accelerates the assembly of a stable SRP–FtsY complex and allows the loading of cargo to be efficiently coupled to its membrane delivery. The use of a transient tether to increase the lifetime of collisional intermediates and reduce the dimension of diffusional search represents a novel and effective mechanism to accelerate macromolecular interactions.
Tumor-infiltrating NY-ESO-1–specific CD8
+
T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer
Authors: Matsuzaki Junko , Gnjatic Sacha , Mhawech-Fauceglia Paulette , Beck Amy , Miller Austin , Tsuji Takemasa , Eppolito Cheryl , Qian Feng , Lele Shashikant , Shrikant Protul , Old Lloyd J. , Odunsi Kunle
Published: April 2010

NY-ESO-1 is a “cancer-testis” antigen frequently expressed in epithelial ovarian cancer (EOC) and is among the most immunogenic tumor antigens defined to date. In an effort to understand in vivo tolerance mechanisms, we assessed the phenotype and function of NY-ESO-1–specific CD8
+
T cells derived from peripheral blood lymphocytes (PBLs), tumor-infiltrating lymphocytes (TILs), and tumor-associated lymphocytes (TALs) of EOC patients with NY-ESO-1-expressing tumors, with or without humoral immunity to NY-ESO-1. Whereas NY-ESO-1–specific CD8
+
T cells were readily detectable ex vivo with tetramers in TILs and TALs of seropositive patients, they were only detectable in PBLs following in vitro stimulation. Compared with PBLs, tumor-derived NY-ESO-1–specific CD8
+
T cells demonstrated impaired effector function, preferential usage of dominant T-cell receptor, and enriched coexpression of inhibitory molecules LAG-3 and PD-1. Expression of LAG-3 and PD-1 on CD8
+
T cells was up-regulated by IL-10, IL-6 (cytokines found in tumor ascites), and tumor-derived antigen-presenting cells. Functionally, CD8
+
LAG-3
+
PD-1
+
T cells were more impaired in IFN-γ/TNF-α production compared with LAG-3
+
PD-1
−
or LAG-3
−
PD-1
−
subsets. Dual blockade of LAG-3 and PD-1 during T-cell priming efficiently augmented proliferation and cytokine production by NY-ESO-1–specific CD8
+
T cells, indicating that antitumor function of NY-ESO-1-specific CD8
+
T cells could potentially be improved by therapeutic targeting of these inhibitory receptors.
I-BAR protein antagonism of endocytosis mediates directional sensing during guided cell migration
Authors: Quinones Gabriel A. , Jin Janet , Oro Anthony E.
Published: April 2010

Although directed cellular migration facilitates the coordinated movement of cells during development and repair, the mechanisms regulating such migration remain poorly understood. Missing-in-metastasis (MIM) is a defining member of the inverse Bin/Amphiphysin/Rvs domain (I-BAR) subfamily of lipid binding, cytoskeletal regulators whose levels are altered in a number of cancers. Here, we provide the first genetic evidence that an I-BAR protein regulates directed cell migration in vivo. Drosophila MIM (dmim) is involved in Drosophila border cell migration, with loss of dmim function resulting in a lack of directional movement by the border cell cluster. In vivo endocytosis assays combined with genetic analyses demonstrate that the dmim product regulates directed cell movement by inhibiting endocytosis and antagonizing the activities of the CD2-associated protein/cortactin complex in these cells. These studies demonstrate that DMIM antagonizes pro-endocytic components to facilitate polarity and localized guidance cue sensing during directional cell migration.
Class switching and meiotic defects in mice lacking the E3 ubiquitin ligase RNF8
Authors: Santos Margarida Almeida , Huen Michael S.Y. , Jankovic Mila , Chen Hua-Tang , López-Contreras Andrés J. , Klein Isaac A. , Wong Nancy , Barbancho Juan L.R. , Fernandez-Capetillo Oscar , Nussenzweig Michel C. , Chen Junjie , Nussenzweig André
Published: April 2010

53BP1 is a well-known mediator of the cellular response to DNA damage. Two alternative mechanisms have been proposed to explain 53BP1’s interaction with DNA double-strand breaks (DSBs), one by binding to methylated histones and the other via an RNF8 E3 ligase–dependent ubiquitylation pathway. The formation of RNF8 and 53BP1 irradiation-induced foci are both dependent on histone H2AX. To evaluate the contribution of the RNF8-dependent pathway to 53BP1 function, we generated RNF8 knockout mice. We report that RNF8 deficiency results in defective class switch recombination (CSR) and accumulation of unresolved immunoglobulin heavy chain–associated DSBs. The CSR DSB repair defect is milder than that observed in the absence of 53BP1 but similar to that found in H2AX−/− mice. Moreover, similar to H2AX but different from 53BP1 deficiency, RNF8−/− males are sterile, and this is associated with defective ubiquitylation of the XY chromatin. Combined loss of H2AX and RNF8 does not cause further impairment in CSR, demonstrating that the two genes function epistatically. Importantly, although 53BP1 foci formation is RNF8 dependent, its binding to chromatin is preserved in the absence of RNF8. This suggests a two-step mechanism for 53BP1 association with chromatin in which constitutive loading is dependent on interactions with methylated histones, whereas DNA damage–inducible RNF8-dependent ubiquitylation allows its accumulation at damaged chromatin.
The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer
Authors: Allen Irving C. , TeKippe Erin McElvania , Woodford Rita-Marie T. , Uronis Joshua M. , Holl Eda K. , Rogers Arlin B. , Herfarth Hans H. , Jobin Christian , Ting Jenny P.-Y.
Published: April 2010

Colitis-associated cancer (CAC) is a major complication of inflammatory bowel diseases. We show that components of the inflammasome are protective during acute and recurring colitis and CAC in the dextran sulfate sodium (DSS) and azoxymethane + DSS models. Mice lacking the inflammasome adaptor protein PYCARD (ASC) and caspase-1 demonstrate increased disease outcome, morbidity, histopathology, and polyp formation. The increased tumor burden is correlated with attenuated levels of IL-1β and IL-18 at the tumor site. To decipher the nucleotide-binding domain, leucine-rich-repeat-containing (NLR) component that is involved in colitis and CAC, we assessed Nlrp3 and Nlrc4 deficient mice. Nlrp3−/− mice showed an increase in acute and recurring colitis and CAC, although the disease outcome was less severe in Nlrp3−/− mice than in Pycard−/− or Casp1−/− animals. No significant differences were observed in disease progression or outcome in Nlrc4−/− mice compared with similarly treated wild-type animals. Bone marrow reconstitution experiments show that Nlrp3 gene expression and function in hematopoietic cells, rather than intestinal epithelial cells or stromal cells, is responsible for protection against increased tumorigenesis. These data suggest that the inflammasome functions as an attenuator of colitis and CAC.
Detection and characterization of novel sequence insertions using paired-end next-generation sequencing
Authors: Hajirasouliha Iman , Hormozdiari Fereydoun , Alkan Can , Kidd Jeffrey M. , Birol Inanc , Eichler Evan E. , Sahinalp S. Cenk
Published: April 2010

Motivation: In the past few years, human genome structural variation discovery has enjoyed increased attention from the genomics research community. Many studies were published to characterize short insertions, deletions, duplications and inversions, and associate copy number variants (CNVs) with disease. Detection of new sequence insertions requires sequence data, however, the ‘detectable’ sequence length with read-pair analysis is limited by the insert size. Thus, longer sequence insertions that contribute to our genetic makeup are not extensively researched.

Results: We present NovelSeq: a computational framework to discover the content and location of long novel sequence insertions using paired-end sequencing data generated by the next-generation sequencing platforms. Our framework can be built as part of a general sequence analysis pipeline to discover multiple types of genetic variation (SNPs, structural variation, etc.), thus it requires significantly less-computational resources than de novo sequence assembly. We apply our methods to detect novel sequence insertions in the genome of an anonymous donor and validate our results by comparing with the insertions discovered in the same genome using various sources of sequence data.

Availability: The implementation of the NovelSeq pipeline is available at http://compbio.cs.sfu.ca/strvar.htm

Contact:  eee@gs.washington.edu; cenk@cs.sfu.ca
Description of Holtermanniella gen. nov., including Holtermanniella
takashimae sp. nov. and four new combinations, and proposal of the order Holtermanniales to accommodate tremellomycetous yeasts of the Holtermannia clade
Authors: Wuczkowski Michael , Passoth Volkmar , Turchetti Benedetta , Andersson Ann-Christin , Olstorpe Matilda , Laitila Arja , Theelen Bart , van Broock María , Buzzini Pietro , Prillinger Hansjörg , Sterflinger Katja , Schnürer Johan , Boekhout Teun , Libkind Diego
Published: April 2010

The novel genus Holtermanniella is proposed here to accommodate four Cryptococcus species closely related to Holtermannia corniformis that are included in the Holtermannia clade (Basidiomycota, Agaricomycotina). Thus, four novel combinations are proposed: Holtermanniella nyarrowii comb. nov., Holtermanniella festucosa comb. nov., Holtermanniella mycelialis comb. nov. and Holtermanniella wattica comb. nov. In addition, a novel anamorphic yeast species was studied with 15 isolates obtained from different habitats around the world. Analysis of the sequences of the D1/D2 region of their large subunit rDNA showed that the novel species is placed phylogenetically within the Holtermannia clade of the Tremellomycetes (Agaricomycotina, Basidiomycota). PCR fingerprinting and sequencing of ITS1–5.8S–ITS2 showed genetic intraspecific variability among the strains: three groups were formed, which did not correlate with geographical origin or substrate. This novel species, designated the type species of Holtermanniella gen. nov., is described as Holtermanniella takashimae sp. nov.; the type strain is CBS 11174T (=HB 982T =DBVPG 8012T). The order Holtermanniales ord. nov. is proposed here to include Holtermannia (the type genus) and Holtermanniella.
Rhizobium tubonense sp. nov., isolated from root nodules of Oxytropis glabra
Authors: Zhang Rong Juan , Hou Bao Chao , Wang En Tao , Li Ying , Zhang Xiao Xia , Chen Wen Xin
Published: April 2010

Four rhizobial strains, designated CCBAU 85046T, CCBAU 85051, CCBAU 85048 and CCBAU 85049, isolated from root nodules ofOxytropis glabragrown in Tibet, China, were previously defined, using amplified 16S rRNA gene restriction analysis, as a novel group within the genusRhizobium. To clarify their taxonomic position, these strains were further analysed and compared with reference strains of related bacteria using a polyphasic approach. The 16S rRNA gene analysis showed that the four isolates formed a distinct phylogenetic lineage in the genusRhizobium. The isolates showed highest sequence similarity (97.8 %) toRhizobium indigoferaeCCBAU 71042T. Phenotypic and physiological tests, DNA–DNA hybridization, phylogenetic analyses of housekeeping genesrecA,atpDandglnIIand fatty acid profiles also indicated that these four strains constitute a novel group distinct from recognized species of the genusRhizobium. Based on this evidence, strains CCBAU 85046T, CCBAU 85051, CCBAU 85048 and CCBAU 85049 represent a novel species in the genusRhizobium, for which the nameRhizobium tubonensesp. nov. is proposed. The type strain is CCBAU 85046T(=LMG 25225T=HAMBI 3066T) and its DNA G+C content is 59.52 mol% (Tm). Strain CCBAU 85046Tcould form effective nodules on plant speciesVigna unguiculataandMedicago sativabut not on its host of originOxytropis glabra.
Erwinia piriflorinigrans sp. nov., a novel pathogen that causes necrosis of pear blossoms
Authors: López María M. , Roselló Montserrat , Llop Pablo , Ferrer Sergi , Christen Richard , Gardan Louis
Published: April 2010

Eight Erwinia strains, isolated from necrotic pear blossoms in València, Spain, were compared with reference strains of Erwinia amylovora and Erwinia pyrifoliae, both of which are pathogenic to species of pear tree, and to other species of the family Enterobacteriaceae using a polyphasic approach. Phenotypic analyses clustered the novel isolates into one phenon, distinct from other species of the genus Erwinia, showing that the novel isolates constituted a homogeneous phenotypic group. Rep-PCR profiles, PCR products obtained with different pairs of primers and plasmid contents determined by restriction analysis showed differences between the novel strains and reference strains of E. amylovora and E. pyrifoliae. Phylogenetic analysis of 16S rRNA, gpd and recA gene sequences showed that the eight novel strains could not be assigned to any recognized species. On the basis of DNA–DNA hybridization studies, the novel isolates constituted a single group with relatedness values of 87–100 % to the designated type strain of the group, CFBP 5888T. Depending on the method used, strain CFBP 5888T showed DNA–DNA relatedness values of between 22.7 and 50 % to strains of the closely related species E. amylovora and E. tasmaniensis. The DNA G+C contents of two of the novel strains, CFBP 5888T and CFBP 5883, were 51.1 and 50.5 mol%, respectively. On the basis of these and previous results, the novel isolates represent a novel species of the genus Erwinia, for which the name Erwinia piriflorinigrans sp. nov. is proposed. The type strain is CFBP 5888T (=CECT 7348T).
Yaniella fodinae sp. nov., isolated from a coal mine
Authors: Dhanjal Soniya , Ruckmani Arunachalam , Cameotra Swaranjit Singh , Pukall Rüdiger , Klenk Hans-Peter , Mayilraj Shanmugam
Published: April 2010

An orange bacterial strain, designated G5T, was isolated during the study of the bacterial diversity of a coal mine. The cell wall of strain G5Tcontained peptidoglycan type A4α(l-Lys–Gly–l-Glu) and the sugars xylose and mannose. The major menaquinones were MK-8 (45.0 %) and MK-9 (34.0 %) and minor amounts of MK-7 and MK-8(H2) were also found. The major fatty acids were anteiso-C15 : 0(44.9 %) and iso-C15 : 0(44.2 %). The main cellular polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol. 16S rRNA gene sequence analysis showed that strain G5Twas closely related toYaniella halotoleransYIM 70085TandYaniella flavaYIM 70178T(both 96.7 % 16S rRNA gene sequence similarity). The genomic DNA G+C content of strain G5Twas 61.6 mol%. These data and other phenotypic characteristics clearly indicated that strain G5Trepresents a novel species of the genusYaniella, for which the nameYaniella fodinaesp. nov. is proposed. The type strain is G5T(=MTCC 9846T=DSM 22966T).
Paenibacillus rigui sp. nov., isolated from a freshwater wetland
Authors: Baik Keun Sik , Lim Chae Hong , Choe Han Na , Kim Eun Mi , Seong Chi Nam
Published: April 2010

A rod-shaped, endospore-forming, Gram-reaction-variable bacterial strain, designated WPCB173T, was isolated from freshwater collected from the Woopo wetland, Republic of Korea. Based on its phenotypic characteristics and phylogenetic position inferred from 16S rRNA gene sequence analysis, the isolate was identified as being a member of the genus Paenibacillus. Major polar lipids present in strain WPCB173T included phosphatidylethanolamine and several unidentified phospholipids. The diamino acid found in the cell-wall peptidoglycan was meso-diaminopimelic acid. The predominant menaquinone was MK-7. The major cellular fatty acid was anteiso-C15 : 0 (65.2 %). The DNA G+C content was 48.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain WPCB173T clustered with species of the genus Paenibacillus, its closest neighbours being Paenibacillus chinjuensis WN9T (96.7 %) and Paenibacillus soli DCY03T (96.4 %). DNA–DNA hybridization of strain WPCB173T with P. soli DCY03T and P. chinjuensis WN9T showed relatedness values of only 10 and 19 %, respectively. On the basis of the phenotypic and phylogenetic evidence, strain WPCB173T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus rigui sp. nov. is proposed. The type strain of the novel species is WPCB173T (=KCTC 13282T =JCM 16352T).
Phycicoccus ginsenosidimutans sp. nov., isolated from soil of a ginseng field
Authors: Wang Liang , An Dong-Shan , Jin Feng-Xie , Lee Sung-Taik , Im Wan-Taek , Bae Heon-Meen
Published: April 2010

A Gram-positive, non-motile, non-spore-forming, aerobic, coccoid-shaped bacterium, designated BXN5-13T, was isolated from the soil of a ginseng field from Baekdu Mountain in Jilin district, China. Strain BXN5-13T grew optimally at 30 °C and pH 6.5–7.5 with 0–2 % (w/v) NaCl. Strain BXN5-13T had β-glucosidase activity that was connected with ginsenoside-converting ability, so that it was able to convert ginsenoside Rb1 to ginsenoside F2. On the basis of 16S rRNA gene sequence analysis, the closest phylogenetic relatives of strain BXN5-13T were Phycicoccus aerophilus 5516T-20T (98.4 % 16S rRNA gene sequence similarity), P. bigeumensis MSL-03T (98.3 %), P. dokdonensis DS-8T (97.9 %) and P. jejuensis KSW2-15T (96.9 %). Lower sequence similarity (<97.0 %) was found with the type strains of other recognized species of the family Intrasporangiaceae. The predominant quinone was MK-8(H4). The major fatty acids (>10 %) were iso-C15 : 0, C17 : 0, anteiso-C15 : 0 and iso-C16 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol. The cell-wall peptidoglycan contained meso-diaminopimelic acid. The chemotaxonomic data and the high genomic DNA G+C content of strain BXN5-13T (70.8 mol%) supported its affiliation with the genus Phycicoccus. DNA–DNA relatedness between strain BXN5-13T and its closest phylogenetic neighbours was below 16 %. Strain BXN5-13T represents a novel species within the genus Phycicoccus, for which the name Phycicoccus ginsenosidimutans sp. nov. is proposed. The type strain is BXN5-13T (=KCTC 19419T=DSM 21006T=LMG 24462T).
Vibrio marisflavi sp. nov., isolated from seawater
Authors: Wang Hong , Liu Jiwen , Wang Yan , Zhang Xiao-Hua
Published: April 2010

A Gram-reaction-negative, facultatively anaerobic bacterial strain, designated WH134T, was isolated from a seawater sample collected at a depth of 10 m near the Yellow Sea Cold Water Mass (YSCWM), 3 ° 59.970′ N 12 ° 0.157′ E, PR China. Cells of strain WH134T were slightly curved rods, motile by means of a polar flagellum and positive for poly-β-hydroxybutyrate (PHB) accumulation. The strain was able to grow in 1–6 % (w/v) NaCl, at pH 5–10 and 16–37 °C but not at 4 or 40 °C. The major cellular fatty acids were summed feature 3 C16
 : 1
ω7c and/or iso-C15 : 0 2-OH, C16 : 0, C18 : 1
ω7c, C18 : 0 and C14 : 0. The DNA G+C content was 42.5 mol%. Phylogenetic analyses based on 16S rRNA, gyrB, topA, recA, ftsZ, mreB, gapA and rpoA gene sequences revealed that strain WH134T belongs to the genus Vibrio and showed gene sequence similarities of 96.6, 75.7, 74.6, 83.6, 78.9, 82.9, 86.0 and 89.4 % , respectively, to Vibrio rumoiensis S-1T. The possession of a flagellum, activity of arginine dihydrolase and lysine decarboxylase and inability to utilize citrate, however, differentiated strain WH134T from V. rumoiensis DSM 19141T. On the basis of the phenotypic, chemotaxonomic and phylogenetic evidence, strain WH134T represents a novel species of the genus Vibrio, for which the name Vibrio marisflavi sp. nov. is proposed. The type strain is WH134T (=CGMCC 1.8994T =LMG 25284T =DSM 23086T).
Nocardioides hungaricus sp. nov., isolated from a drinking water supply system
Authors: Tóth Erika M. , Kéki Zsuzsa , Makk Judit , Homonnay Zalán G. , Márialigeti Károly , Schumann Peter
Published: April 2010

Three Gram-positive, rod-shaped bacterial strains were isolated from the drinking water supply system of the Hungarian capital, Budapest. Phylogenetic analysis on the basis of 16S rRNA gene sequence comparison revealed that the isolates represented a distinct cluster within the clade of the genus Nocardioides and were most closely related to Nocardioides pyridinolyticus OS4T, Nocardioides aquiterrae GW-9T, Nocardioides sediminis MSL-01T and N. hankookensis DS-30T. The peptidoglycan based on ll-2,6-diaminopimelic acid, the major menaquinone MK-8(H4), the cellular fatty acid profile with iso-C16 : 0 and anteiso-C17 : 0 as predominating components and the DNA G+C content of 71.4 mol% (strain 1RaM5-12T) were consistent with the affiliation of the isolates to the genus Nocardioides. Because of differences in physiological characteristics, matrix-assisted laser-desorption/ionization time-of-flight mass spectra of protein extracts, PvuII RiboPrinter patterns and 96.1 % 16S rRNA gene sequence similarity between strain 1RaM5-12T and its closest phylogenetic neighbour, N. pyridinolyticus OS4T, a novel species, Nocardioides hungaricus sp. nov., is proposed. The type strain is 1RaM5-12T (=DSM 21673T =NCAIM 02330T).
Rhizobium vignae sp. nov., a symbiotic bacterium isolated from multiple legume species
Authors: Ren Da Wei , Chen Wen Feng , Sui Xin Hua , Wang En Tao , Chen Wen Xin
Published: April 2010

A group of rhizobial strains isolated from nodules of multiple legume species grown in different geographical regions of China had identical 16S rRNA genes. Phylogenetic analysis based on the 16S rRNA gene sequences showed that the novel strains formed a subclade in the genusRhizobiumtogether withRhizobium galegae,Rhizobium huautlenseandRhizobium alkalisoli, with 99.8 % gene sequence similarity between the strains. The DNA–DNA relatedness values between the representative strain CCBAU 05176TandR. galegaeATCC 43677T,R. huautlenseS02TandR. alkalisoliCCBAU 01393Twere 22.6 %, 8.9 % and 15.9 %, respectively. The novel strains were distinguished from recognized species of the genusRhizobiumby using a polyphasic approach, including PCR-based restriction fragment length polymorphism analysis (RFLP) of the 16S–23S intergenic spacer (IGS), phenotypic and physiological tests, sequence comparisons of housekeeping genes and cellular fatty acid profiles. Therefore, it is suggested that this group of strains represents a novel species for which the nameRhizobium vignaesp. nov. is proposed. The type strain is CCBAU 05176T(=HAMBI 3039T=LMG 25447T).