bluuebunny/crossref_metadata_2025 huggingface dataset:
Limitations of multispacecraft data techniques in measuring wave number spectra of space plasma turbulence
Authors: Sahraoui F. , Belmont G. , Goldstein M. L. , Rezeau L.
Published: April 2010

Unambiguous determination of spatial properties of space plasma turbulence from temporal measurements has been one of the major goals of the Cluster mission. For that purpose, techniques, such as the k filtering, have been developed. Such multipoint measurement techniques combine several time series recorded simultaneously at different points in space to estimate the corresponding energy density in wave number space. Here we present results of such an analysis, including a detailed discussion of the errors and limitations that arise due to the separation of the spacecraft and the quality of the tetrahedral configuration. Specifically, we answer the following questions: (1) What are the minimum and maximum scales that can be accurately measured given a specific distance between the satellites? (2) How important is the geometry of the tetrahedron, and what is the relationship of that geometry to spatial aliasing? (3) How should one perform a proper integration of the angular frequencies to infer wave number spectra, and what role does the Doppler shift play when the magnetofluid is rapidly convecting past the spacecraft? We illustrate the results with analyses with both simulated and Cluster magnetometer data recorded in the solar wind. We also discuss the potential impact on future multispacecraft missions, such as Magnetospheric MultiScale and Cross‐Scale.
Separation of longwave climate feedbacks from spectral observations
Authors: Huang Yi , Leroy Stephen , Gero P. Jonathan , Dykema John , Anderson James
Published: April 2010

We conduct a theoretical investigation into whether changes in the outgoing longwave radiation (OLR) spectrum can be used to constrain longwave greenhouse‐gas forcing and climate feedbacks, with a focus on isolating and quantifying their contributions to the total OLR change in all‐sky conditions. First, we numerically compute the spectral signals of CO2 forcing and feedbacks of temperature, water vapor, and cloud. Then, we investigate whether we can separate these signals from the total change in the OLR spectrum through an optimal detection method. Uncertainty in optimal detection arises from the uncertainty in the shape of the spectral fingerprints, the natural variability of the OLR spectrum, and a nonlinearity effect due to the cross‐correlation of different climate responses. We find that the uncertainties in optimally detected greenhouse‐gas forcing, water vapor, and temperature feedbacks are substantially less than their overall magnitudes in a double‐CO2 experiment, and thus the detection results are robust. The accuracy in surface temperature and cloud feedbacks, however, is limited by the ambiguity in their fingerprints. Combining ambiguous feedback signals reduces the uncertainty in the combined signal. Auxiliary data are required to fully resolve the difficulty.
Ultrathin nucleoporin phenylalanine–glycine repeat films and their interaction with nuclear transport receptors
Authors: Eisele Nico B , Frey Steffen , Piehler Jacob , Görlich Dirk , Richter Ralf P
Published: April 2010

Nuclear pore complexes (NPCs) are highly selective gates that mediate the exchange of all proteins and nucleic acids between the cytoplasm and the nucleus. Their selectivity relies on a supramolecular assembly of natively unfolded nucleoporin domains containing phenylalanine–glycine (FG)‐rich repeats (FG repeat domains), in a way that is at present poorly understood. We have developed ultrathin FG domain films that reproduce the mode of attachment and the density of FG repeats in NPCs, and that exhibit a thickness that corresponds to the nanoscopic dimensions of the native permeability barrier. By using a combination of biophysical characterization techniques, we quantified the binding of nuclear transport receptors (NTRs) to such FG domain films and analysed how this binding affects the swelling behaviour and mechanical properties of the films. The results extend our understanding of the interaction of FG domain assemblies with NTRs and contribute important information to refine the model of transport across the permeability barrier.
Scarface, a secreted serine protease‐like protein, regulates polarized localization of laminin A at the basement membrane of the Drosophila embryo
Authors: Sorrosal Georgina , Pérez Lidia , Herranz Héctor , Milán Marco
Published: April 2010

Cell–matrix interactions brought about by the activity of integrins and laminins maintain the polarized architecture of epithelia and mediate morphogenetic interactions between apposing tissues. Although the polarized localization of laminins at the basement membrane is a crucial step in these processes, little is known about how this polarized distribution is achieved. Here, in Drosophila, we analyse the role of the secreted serine protease‐like protein Scarface in germ‐band retraction and dorsal closure—morphogenetic processes that rely on the activity of integrins and laminins. We present evidence that scarface is regulated by c‐Jun amino‐terminal kinase and that scarface mutant embryos show defects in these morphogenetic processes. Anomalous accumulation of laminin A on the apical surface of epithelial cells was observed in these embryos before a loss of epithelial polarity was induced. We propose that Scarface has a key role in regulating the polarized localization of laminin A in this developmental context.
Induced pluripotent stem cells and senescence: learning the biology to improve the technology
Authors: Banito Ana , Gil Jesús
Published: April 2010

The discovery that adult somatic cells can be reprogrammed into pluripotent cells by expressing a combination of factors associated with pluripotency holds immense promise for a wide range of biotechnological and therapeutic applications. However, some hurdles—such as improving the low reprogramming efficiencies and ensuring the pluripotent potential, genomic integrity and safety of the resulting cells—must be overcome before induced pluripotent stem cells (iPSCs) can be used for clinical purposes. Several groups have recently shown that key tumour suppressors—such as members of the p53 and p16INK4a/retinoblastoma networks—control the efficiency of iPSC generation by activating cell‐intrinsic programmes such as senescence. Here, we discuss the implications of these discoveries for improving the safety and efficiency of iPSC generation, and for increasing our understanding of different aspects of basic biology—such as the control of pluripotency or the mechanisms involved in the generation of cancer stem cells.
Laying the foundation for epithelia: insights into polarized basement membrane deposition
Authors: Eastburn Dennis J , Mostov Keith E
Published: April 2010

Epithelial tissues are essential for the function of almost all major organs and altering their polarized architecture leads to a variety of diseases. The directed deposition of basement membrane proteins is a crucial but poorly understood process, important to maintain epithelial structure. In this issue of EMBO reports, the Drosophila gene Scarface is shown to regulate it.
Three-dimensional structure of recombinant type 1 inositol 1,4,5-trisphosphate receptor
Authors: Wolfram Francis , Morris Edward , Taylor Colin W.
Published: April 2010

IP3Rs (inositol 1,4,5-trisphosphate receptors) are the intracellular channels that mediate release of Ca2+ from the endoplasmic reticulum in response to the many stimuli that evoke Ins(1,4,5)P3 formation. We characterized and purified type 1 IP3R heterologously expressed in Sf9 insect cells, and used the purified IP3R1 to determine its three-dimensional structure by electron microscopy and single-particle analysis. Recombinant IP3R1 has 4-fold symmetry with overall dimensions of approx. 19.5 nm×19.5 nm×17.5 nm. It comprises a small domain, which is likely to include the pore, linked by slender bridges to a large cytoplasmic domain with four petal-like regions. Our structures of recombinant IP3R1 and native cerebellar IP3R have similar appearances and dimensions. The only notable difference is the absence of a central stigma-like domain from the cytoplasmic region of recombinant IP3R1. The first structure of a recombinant IP3R is an important step towards developing three-dimensional structures of IP3R that better contribute to our understanding of the structural basis of IP3R activation.
AAC Use by Young Children at Home
Authors: Hidecker Mary Jo Cooley
Published: April 2010

This study describes AAC availability and use in 55 young children in the United States.

The children, aged 15 to 75 months, had not yet started kindergarten, had used their latest AAC system for 6 to 24 months, and had a variety of developmental disorders resulting in a severe communication disorder. The primary caregivers, all mothers, completed an 81-question case history about demographics, child's age at diagnosis and AAC receipt, and current AAC availability and use at home. They reported that the children waited an average of 6 months between a diagnosis and acquisition of their first AAC system. Forty children (73%) had received a different AAC system since acquiring their first AAC system. Most had multimodal AAC systems, which included both aided and unaided components, although 11 had used only the unaided AAC system of sign language. More than half of the AAC systems included voice output components. Sign language was the most frequently used AAC within the children's homes. The primary caregivers reported satisfaction with their children's AAC systems. Additional research is needed to describe current AAC practices with young children. These practices should then be evaluated for their effectiveness on both short- and long-term outcomes.
Reframing Europe and the Global: Conceptualizing the Border in Cultural Encounters
Authors: Rovisco Maria
Published: April 2010

In this paper I explore the inadequacy of the representation of the border, which is underpinned by Manichean distinctions of friend and foe, superior and inferior, inside and outside, to analyze the cultural encounter between Europeans and their others. I argue that a great deal of scholarship interest in this cultural encounter is trapped into a border imaginary that loses sight of those cultural phenomena, such as hybridity, transnational identities, and cosmopolitan affiliations, which challenge established political and cultural borders and foster ‘from below’ new imaginations of the European space. By analyzing a complex set of cultural productions—the creative combination of European modes of thought, texts, and styles in the visual and performative arts, with indigenous local artistic styles and mindsets—I show that, as seen as early as the 16th-century, the rise of a global imagination is the result of complex relations of connectivity between Europe and other parts of the world. I propose a new border imaginary, which is underpinned by a cosmopolitan grammar of difference, to account better for the changing nature of the European space within the dynamics of globalization.
Everyday Spaces of Mental Distress: The Spatial Habituation of Home
Authors: Tucker Ian
Published: April 2010

Theorising psychological activity as a spatial product appears a logical extension of moves in social theory to emphasise the role of space and place in the consideration of experience. Catalysed by turns in social and human geographies to highlight the role of space and location in constituting psychological activity, various forms of the ‘spatialisation of experience’ have emerged. In this paper I will follow this theoretical direction in relation to the underlying destabilisation of everyday life that emerges as a product of theoretical formations that emphasise the fluidity of space. More specifically, I will take the example of the home as a central space in the ongoing activity of people with enduring mental distress. Forging a theoretical line that takes in geographies of mental health, the home, and finally, Gilles Deleuze's work on ‘repetition’ and ‘habit’, I will analyse the role of home spaces in everyday life. Key here is a concern regarding the impact of theoretical emphases on continuity, mobility, and instability on understandings of the everyday lives of mental health service users. This includes addressing conceptualisations of the home space alongside the activities of the people who occupy, and hence co-make, such spaces. The article concludes by framing ‘spatial habituation’ of the everyday as central to creating a perceivable stability, analysis of which can aid understanding of the challenges facing people suffering with mental distress.
Crystal Engineering Studies on Ionic Crystals of Pyridine and Carboxylic Acid Derivatives Containing Amide Functional Groups
Authors: Rajput Lalit , Santra Ramkinkar , Biradha Kumar
Published: April 2010

Seven crystal structures of pyromellitic acid or trimesic acid salts of molecules that contain pyridine and amide functionalities were determined and their structures were analyzed in detail in terms of various intermolecular interactions. The presence of multiple functionalities (acid, pyridine, amide, and hydroxy groups) in these structures resulted in diversified supramolecular architectures. Amide-to-amide hydrogen bonds are not observed in any of these structures because of interference by the anions, water molecules, or pyridinium cations. The symmetry of the components was found to be important in determining the resultant supramolecular synthon and, therefore, the overall architecture. The pyromellitate anions exhibited four types of geometries which, differ in valencies and intramolecular hydrogen bonding, and these anions also exhibit self stacks when they have planar geometries.
Understanding Supramolecular Interactions Provides Clues for Building Molecules into Minerals and Materials: a Retrosynthetic Analysis of Copper-Based Solids
Authors: Singh Monika , Thomas Jency , Ramanan Arunachalam
Published: April 2010

The influence of non-covalent interactions on the crystal packing of molecules is well documented in the literature. Unlike molecular solids, crystal engineering of non-molecular solids is difficult to interpret as aggregation is complicated by the presence of neutral as well as ionic species and a range of forces operating, from weak hydrogen bonding to strong covalent interactions. In this perspective, we demonstrate for the first time the role of non-bonding interactions in the occurrence of oxide, hydroxide, or chloride linkages in oxides, hydroxychlorides, and chlorides of copper-based minerals and coordination polymers in terms of a mechanistic approach based on supramolecular retrosynthesis. The model proposed here visualizes the crystal nucleus as a supramolecular analogue of a transition state wherein appropriate tectons (chemically reasonable molecules) aggregate through non-bonding forces that can be perceived through well-known supramolecular synthons. The mechanistic approach provides chemical insights into the occurrence of different topologies and solid-state phenomena like polymorphism.
Giant Polytungstoarsenate Clusters Derived from New [As4W19O68(H2O)]14 - Building Blocks
Authors: Chang Song , Zhang Zhiming , Li Yangguang , Yao Shuang , Wang Enbo
Published: April 2010

A new compound K8Na4[As4W19O69]·19.5H2O (1), which can be described as an extended structure of [As2W19O67(H2O)]14–, was synthesized and used as building blocks to construct the high nuclear polytungstoarsenate cluster K10Na8[(W13O28)(H2O)6(OH)4(AsW9O33)4]·56H2O (2). Polyoxoanion 2 is composed of four trivacant Keggin B-α-type [AsW9O33] units encapsulating a unique polytungstate cluster W13O32(OH)4(H2O)6, which has never observed in the polyoxometalate chemistry. Electrocatalytic studies indicate that compound 2 displays electrocatalytic activity toward the reduction of nitrate.
Pb···π Aryl Interactions as Supramolecular Synthons
Authors: Tiekink Edward R. T. , Zukerman-Schpector Julio
Published: April 2010

A survey of lead (Pb) structures containing Pb···π aryl interactions has been conducted. Such contacts usually lead to zero- or one-dimensional aggregates with rare examples of two- and three-dimensional architectures. The Pb···π aryl interactions are found only in crystal structures containing lead(ii) centres and arise as a result of electron donation of the lead-bound lone pair of electrons to the lowest unoccupied molecular orbital of the accepting aryl ring. The prevalence of Pb···π interactions as a supramolecular synthon is relatively low, occurring in ~3% of all structures containing lead and at least one aryl ring, but these are more likely to form compared with Sn···π interactions.
Solid-State Synthesis of Coordination Polymers for [2+2] Photoreactions by Grinding
Authors: Nagarathinam Mangayarkarasi , Vittal Jagadese J.
Published: April 2010

The feasibility of molecular solid-state reactions by grinding for the synthesis of coordination polymers with aligned trans-1,2-bis(4-pyridyl)ethene ligands suitable for [2+2] photoreaction has been investigated. The results provide an insight into the reactivity of the precursors in the absence of solvents.
Supramolecular Polymers Based on Cyclodextrins and Their Derivatives
Authors: Harada Akira , Hashidzume Akihito
Published: April 2010

Since Lehn introduced the concept in the 1990s, supramolecular polymers have been developed rapidly by several research groups. Supramolecular polymers should be key materials for establishment of a sustainable society. This short review describes briefly hydrogen-bonded and coordination supramolecular polymers, and then reviews our research on cyclodextrin-based supramolecular polymers.
Breaking Down the Supramolecular Ensemble: Single-Molecule Studies of the Concentration Dependence of Main-Chain Supramolecular Polymer Molecular Weight Distributions on Surfaces
Authors: Serpe Michael J. , Whitehead Jason R. , Craig Stephen L.
Published: April 2010

Single molecule atomic force microscopy (AFM) studies of oligonucleotide-based supramolecular polymers on surfaces are used to examine the molecular weight distribution of the polymers formed between a functionalized surface and an AFM tip as a function of monomer concentration. For the concentrations examined here, excellent agreement with a multi-stage open association model of polymerization is obtained, without the need to invoke additional contributions from secondary steric interactions at the surface.
Solid-State Photoreversible Polymerization of n-Alkyl-Linked Bis-Thymines using Non-Covalent Polymer-Templating
Authors: Johnston Priscilla , Hearn Milton T.W. , Saito Kei
Published: April 2010

Procedures derived from bioinspired mechanisms are increasingly being used to create novel materials based on the principles of green chemistry. Thymine, a nucleic acid base in DNA, has the propensity to both hydrogen bond and photodimerize. Photodimerization of thymine occurs when irradiated at wavelengths of >270 nm and can be reversed by irradiation at wavelengths of <250 nm. In this investigation, n-alkyl-linked bis-thymines have been supramolecularly aligned with poly(vinyl pyrrolidone) templates by non-covalent hydrogen bonding, and photopolymerized in the solid state. Photo-depolymerization of the products was performed to complete the reversible polymerization.
Interplay Between Cyclization and Polymerization in Ditopic Cavitand Monomers
Authors: Tancini Francesca , Rampazzo Enrico , Dalcanale Enrico
Published: April 2010

Quinoxaline kite velcrands were functionalized with a ureidopyrimidone moiety at the lower rim, in order to combine multiple hydrogen bonding and solvophobic interactions to build dual-coded supramolecular structures. The orthogonality of the selected binding motifs has been demonstrated by NMR studies, as well as the reversible nature of the obtained assemblies. At low concentration, the presence of a ring-chain equilibrium has been established by 1H NMR experiments, and confirmed by static and dynamic light scattering measurements.
Photoresponsive Organogel Based on Supramolecular Assembly of Tris(phenylisoxazolyl)benzene
Authors: Haino Takeharu , Saito Hiroshi
Published: April 2010

Azobenzene-substituted tris(phenylisoxazolyl)benzene 1 was developed as a photoresponsive gelator. A detailed study of the self-assembly of the trans- and cis-isomers in solution revealed that the planar trans-isomer assembled to form molecular stacks along its C
3 axis, whereas the cis-isomer did not owing to steric requirements. Based on diffusion ordered spectroscopy experiments, the size of the aggregates formed from the trans-isomer were roughly four times as large as those of the cis-isomer. The photoinduced gel-to-sol transition was achieved by irradiation with UV light at 360 nm. Solid-state morphologies of the trans- and cis-isomers were quite contrastive; the trans-isomer created fibrous supramolecular networks with a lot of voids in which solvent molecules could be immobilized, whereas the cis-isomer never created such fibrous morphologies. The trans–cis structural change of the azobenzene moieties obviously regulates the gelation ability of 1.
Solidification of Ionic Liquids: Theory and Techniques
Authors: Mudring Anja-Verena
Published: April 2010

Ionic liquids (ILs) have become an important class of solvents and soft materials over the past decades. Despite being salts built by discrete cations and anions, many of them are liquid at room temperature and below. They have been used in a wide variety of applications such as electrochemistry, separation science, chemical synthesis and catalysis, for breaking azeotropes, as thermal fluids, lubricants and additives, for gas storage, for cellulose processing, and photovoltaics. It has been realized that the true advantage of ILs is their modular character. Each specific cation–anion combination is characterized by a unique, characteristic set of chemical and physical properties. Although ILs have been known for roughly a century, they are still a novel class of compounds to exploit due to the vast number of possible ion combinations and one fundamental question remains still inadequately answered: why do certain salts like ILs have such a low melting point and do not crystallize readily? This Review aims to give an insight into the liquid–solid phase transition of ILs from the viewpoint of a solid-state chemist and hopes to contribute to a better understanding of this intriguing class of compounds. It will introduce the fundamental theories of liquid–solid-phase transition and crystallization from melt and solution. Aside form the formation of ideal crystals the development of solid phases with disorder and of lower order like plastic crystals and liquid crystals by ionic liquid compounds are addressed. The formation of ionic liquid glasses is discussed and finally practical techniques, strategies and methods for crystallization of ionic liquids are given.
Dynamers: Dynamic Molecular and Supramolecular Polymers
Authors: Lehn Jean-Marie
Published: April 2010

Dynamers are defined as constitutional dynamic polymers, i.e. polymeric entities whose monomeric components are linked through reversible connections and have therefore the capacity to modify their constitution by exchange and reshuffling of their components. They may be either of supramolecular or molecular nature depending on whether the connections are non-covalent interactions or reversible covalent bonds. They are formed respectively either by polyassociation with interactional recognition or by polycondensation with functional recognition between the connecting subunits. Both types are illustrated by specific examples implementing hydrogen bonding on one hand and formation of imine-type bonds on the other. The dynamic properties confer to dynamers the ability to undergo adaptation and driven evolution under the effect of external chemical or physical triggers. Dynamers thus are constitutional dynamic materials resulting from the application of the principles of constitutional dynamic chemistry to polymer science.
A unique regulator controls the activation threshold of quorum-regulated genes in
Pseudomonas aeruginosa
Authors: Siehnel Richard , Traxler Beth , An Ding Ding , Parsek Matthew R. , Schaefer Amy L. , Singh Pradeep K.
Published: April 2010

Quorum-sensing (QS) systems allow organisms, such as the pathogen
Pseudomonas aeruginosa
, to link gene expression with their population density and the diffusion and flow characteristics of their environment. The leading hypotheses about QS systems' biological functions necessitate that QS-controlled gene expression be suppressed until a threshold culture density (the quorum) is reached. Despite a detailed understanding of QS in
P. aeruginosa
, known regulatory elements do not fully explain how the quorum threshold for gene activation is produced. Here we investigated the mechanism with a screening approach that used random gene activation. These experiments uncovered a regulator without close homologs in other species that produces the quorum expression threshold. Expression of this regulator (named QteE) reduces LasR protein stability without affecting LasR transcription or translation. QteE also independently reduces RhlR levels. Because QteE can block QS when signal levels are high, it could provide a mechanism for individual cells to exert autonomous control over their QS regulons. This unique regulator governs two central QS control points in
P. aeruginosa
and shapes the expression pattern thought fundamental to the biological functions of QS.
Chandra
enables study of x-ray jets
Authors: Schwartz Daniel
Published: April 2010

The exquisite angular resolution of the
Chandra
x-ray telescope has enabled the detection and study of resolved x-ray jets in a wide variety of astronomical systems.
Chandra
has detected extended jets in our galaxy from protostars, symbiotic binaries, neutron star pulsars, black hole binaries, extragalactic jets in radio sources, and quasars. The x-ray data play an essential role in deducing the emission mechanism of the jets, in revealing the interaction of jets with the intergalactic or intracluster media, and in studying the energy generation budget of black holes.
Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function
Authors: Hu Wenwei , Zhang Cen , Wu Rui , Sun Yvonne , Levine Arnold , Feng Zhaohui
Published: April 2010

Whereas cell cycle arrest, apoptosis, and senescence are traditionally thought of as the major functions of the tumor suppressor p53, recent studies revealed two unique functions for this protein: p53 regulates cellular energy metabolism and antioxidant defense mechanisms. Here, we identify glutaminase 2 (GLS2) as a previously uncharacterized p53 target gene to mediate these two functions of the p53 protein. GLS2 encodes a mitochondrial glutaminase catalyzing the hydrolysis of glutamine to glutamate. p53 increases the GLS2 expression under both nonstressed and stressed conditions. GLS2 regulates cellular energy metabolism by increasing production of glutamate and α-ketoglutarate, which in turn results in enhanced mitochondrial respiration and ATP generation. Furthermore, GLS2 regulates antioxidant defense function in cells by increasing reduced glutathione (GSH) levels and decreasing ROS levels, which in turn protects cells from oxidative stress (e.g., H
2
O
2
)-induced apoptosis. Consistent with these functions of GLS2, the activation of p53 increases the levels of glutamate and α-ketoglutarate, mitochondrial respiration rate, and GSH levels and decreases reactive oxygen species (ROS) levels in cells. Furthermore, GLS2 expression is lost or greatly decreased in hepatocellular carcinomas and the overexpression of GLS2 greatly reduced tumor cell colony formation. These results demonstrated that as a unique p53 target gene, GLS2 is a mediator of p53’s role in energy metabolism and antioxidant defense, which can contribute to its role in tumor suppression.
SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis
Authors: Luthi-Carter Ruth , Taylor David M. , Pallos Judit , Lambert Emmanuel , Amore Allison , Parker Alex , Moffitt Hilary , Smith Donna L. , Runne Heike , Gokce Ozgun , Kuhn Alexandre , Xiang Zhongmin , Maxwell Michele M. , Reeves Steven A. , Bates Gillian P. , Neri Christian , Thompson Leslie M. , Marsh J. Lawrence , Kazantsev Aleksey G.
Published: April 2010

Huntington’s disease (HD), an incurable neurodegenerative disorder, has a complex pathogenesis including protein aggregation and the dysregulation of neuronal transcription and metabolism. Here, we demonstrate that inhibition of sirtuin 2 (SIRT2) achieves neuroprotection in cellular and invertebrate models of HD. Genetic or pharmacologic inhibition of SIRT2 in a striatal neuron model of HD resulted in gene expression changes including significant down-regulation of RNAs responsible for sterol biosynthesis. Whereas mutant huntingtin fragments increased sterols in neuronal cells, SIRT2 inhibition reduced sterol levels via decreased nuclear trafficking of SREBP-2. Importantly, manipulation of sterol biosynthesis at the transcriptional level mimicked SIRT2 inhibition, demonstrating that the metabolic effects of SIRT2 inhibition are sufficient to diminish mutant huntingtin toxicity. These data identify SIRT2 inhibition as a promising avenue for HD therapy and elucidate a unique mechanism of SIRT2-inhibitor-mediated neuroprotection. Furthermore, the ascertainment of SIRT2’s role in regulating cellular metabolism demonstrates a central function shared with other sirtuin proteins.
Updating realistic access
Authors: Rossner Mike
Published: April 2010

Universal public access mandates will reveal the value of biomedical research journals.
Impacts of Ethanol on Planted Acreage in Market Equilibrium
Authors: Feng Hongli , Babcock Bruce A.
Published: April 2010

The magnitude of land conversion caused by biofuels expansion largely determines whether biofuels reduce net greenhouse gas emissions. To examine this issue, we model how equilibrium changes in input use and land allocation decisions respond to market‐ and policy‐induced increases in corn ethanol demand. We demonstrate why total cropland area unambiguously increases with increased ethanol demand. The impact of ethanol price subsidies and consumption mandates are examined in the context of technical change. If ethanol demand is elastic enough, an exogenous increase in corn yields leads to cropland expansion with price subsidies. Yield increases under consumption mandates reduce land use.
Should Farmers Follow the Recommendations of Market Advisory Services? A Hierarchical Bayesian Approach to Estimation of Expected Performance
Authors: Cabrini Silvina M. , Irwin Scott H. , Good Darrel L.
Published: April 2010

A Bayesian hierarchical approach is employed to estimate individual expected performance of agricultural market advisory services. Skeptical beliefs based on market efficiency are incorporated as prior information. For a skeptical decision maker who is willing to follow an advisory program only if it is expected to increase price received by more than 1%, one of the corn programs, most of the soybean programs, and a few wheat programs may be valuable marketing alternatives. The expectation under this model from following the single top‐ranked program are price increases of 1%, 4%, and 3% for corn, soybeans, and wheat, respectively.
How Do Agricultural Policy Restrictions on Global Trade and Welfare Differ Across Commodities?
Authors: Croser Johanna L. , Lloyd Peter J. , Anderson Kym
Published: April 2010

For decades the world's agricultural markets have been highly distorted by government policies, but differently for different commodities such that a ranking of weighted average nominal rates of assistance across countries can be misleading as an indicator of the trade or welfare effects of policies affecting global markets. This article develops two theory‐based indicators, drawing on the recent literature on trade restrictiveness indexes. It estimates those indicators for each of 28 key agricultural commodities from 1960 to 2004, based on a sample of 75 countries that together account for more than three‐quarters of the world's production of those agricultural commodities.
A CROC stronger than ROC: measuring, visualizing and optimizing early retrieval
Authors: Swamidass S. Joshua , Azencott Chloé-Agathe , Daily Kenny , Baldi Pierre
Published: April 2010

Motivation: The performance of classifiers is often assessed using Receiver Operating Characteristic ROC [or (AC) accumulation curve or enrichment curve] curves and the corresponding areas under the curves (AUCs). However, in many fundamental problems ranging from information retrieval to drug discovery, only the very top of the ranked list of predictions is of any interest and ROCs and AUCs are not very useful. New metrics, visualizations and optimization tools are needed to address this ‘early retrieval’ problem.

Results: To address the early retrieval problem, we develop the general concentrated ROC (CROC) framework. In this framework, any relevant portion of the ROC (or AC) curve is magnified smoothly by an appropriate continuous transformation of the coordinates with a corresponding magnification factor. Appropriate families of magnification functions confined to the unit square are derived and their properties are analyzed together with the resulting CROC curves. The area under the CROC curve (AUC[CROC]) can be used to assess early retrieval. The general framework is demonstrated on a drug discovery problem and used to discriminate more accurately the early retrieval performance of five different predictors. From this framework, we propose a novel metric and visualization—the CROC(exp), an exponential transform of the ROC curve—as an alternative to other methods. The CROC(exp) provides a principled, flexible and effective way for measuring and visualizing early retrieval performance with excellent statistical power. Corresponding methods for optimizing early retrieval are also described in the Appendix.

Availability: Datasets are publicly available. Python code and command-line utilities implementing CROC curves and metrics are available at http://pypi.python.org/pypi/CROC/

Contact:  pfbaldi@ics.uci.edu
Small RNAs in angiosperms: sequence characteristics, distribution and generation
Authors: Chen Dijun , Meng Yijun , Ma Xiaoxia , Mao Chuanzao , Bai Youhuang , Cao Junjie , Gu Haibin , Wu Ping , Chen Ming
Published: April 2010

High-throughput sequencing (HTS) has opened up a new era for small RNA (sRNA) exploration. Using HTS data for a global survey of sRNAs in 26 angiosperms, elevated GC contents were detected in the monocots, whereas the 5′-terminal compositions were quite uniform among the angiosperms. Chromosome-wide distribution patterns of sRNAs were investigated by using scrolling-window analysis. We performed de novo natural antisense transcript (NAT) prediction, and found that the overlapping regions of trans-NATs, but not cis-NATs, were hotspots for sRNA generation. One cis-NAT generates phased natural antisense short interfering RNAs (nat-siRNAs) specifically from flowers in Arabidopsis, while one in rice produces phased nat-siRNAs from grains, suggesting their organ-specific regulatory roles.

Contact:  clspwu@zju.edu.cn; mchen@zju.edu.cn

Supplementary information:  Supplementary data are available at Bioinformatics online.
Correction of sequencing errors in a mixed set of reads
Authors: Salmela Leena
Published: April 2010

Motivation: High-throughput sequencing technologies produce large sets of short reads that may contain errors. These sequencing errors make de novo assembly challenging. Error correction aims to reduce the error rate prior assembly. Many de novo sequencing projects use reads from several sequencing technologies to get the benefits of all used technologies and to alleviate their shortcomings. However, combining such a mixed set of reads is problematic as many tools are specific to one sequencing platform. The SOLiD sequencing platform is especially problematic in this regard because of the two base color coding of the reads. Therefore, new tools for working with mixed read sets are needed.

Results: We present an error correction tool for correcting substitutions, insertions and deletions in a mixed set of reads produced by various sequencing platforms. We first develop a method for correcting reads from any sequencing technology producing base space reads such as the SOLEXA/Illumina and Roche/454 Life Sciences sequencing platforms. We then further refine the algorithm to correct the color space reads from the Applied Biosystems SOLiD sequencing platform together with normal base space reads. Our new tool is based on the SHREC program that is aimed at correcting SOLEXA/Illumina reads. Our experiments show that we can detect errors with 99% sensitivity and >98% specificity if the combined sequencing coverage of the sets is at least 12. We also show that the error rate of the reads is greatly reduced.

Availability: The JAVA source code is freely available at http://www.cs.helsinki.fi/u/lmsalmel/hybrid-shrec/

Contact:  leena.salmela@cs.helsinki.fi
Structural variation analysis with strobe reads
Authors: Ritz Anna , Bashir Ali , Raphael Benjamin J.
Published: April 2010

Motivation: Structural variation including deletions, duplications and rearrangements of DNA sequence are an important contributor to genome variation in many organisms. In human, many structural variants are found in complex and highly repetitive regions of the genome making their identification difficult. A new sequencing technology called strobe sequencing generates strobe reads containing multiple subreads from a single contiguous fragment of DNA. Strobe reads thus generalize the concept of paired reads, or mate pairs, that have been routinely used for structural variant detection. Strobe sequencing holds promise for unraveling complex variants that have been difficult to characterize with current sequencing technologies.

Results: We introduce an algorithm for identification of structural variants using strobe sequencing data. We consider strobe reads from a test genome that have multiple possible alignments to a reference genome due to sequencing errors and/or repetitive sequences in the reference. We formulate the combinatorial optimization problem of finding the minimum number of structural variants in the test genome that are consistent with these alignments. We solve this problem using an integer linear program. Using simulated strobe sequencing data, we show that our algorithm has better sensitivity and specificity than paired read approaches for structural variation identification.

Contact:  braphael@brown.edu
Incomplete and noisy network data as a percolation process
Authors: Stumpf Michael P. H. , Wiuf Carsten
Published: April 2010

We discuss the ramifications of noisy and incomplete observations of network data on the existence of a giant connected component (GCC). The existence of a GCC in a random graph can be described in terms of a percolation process, and building on general results for classes of random graphs with specified degree distributions we derive percolation thresholds above which GCCs exist. We show that sampling and noise can have a profound effect on the perceived existence of a GCC and find that both processes can destroy it. We also show that the absence of a GCC puts a theoretical upper bound on the false-positive rate and relate our percolation analysis to experimental protein–protein interaction data.
Human intestinal spirochaetosis in northern Japan
Authors: Sato Hajime , Nakamura Shin-ichi , Habano Wataru , Wakabayashi Go , Adachi Yoshikazu
Published: April 2010

A histological diagnosis of human intestinal spirochaetosis (HIS) was made in 114 patients during the period 1994–2007. All patients lived in three prefectures in the northern part of Honshu, Japan. Most patients were elderly and male. Twenty-nine patients complained of abdominal pain, bloody stools, diarrhoea or bowel symptoms, but most patients showed no direct symptoms of bowel disease, and occult faecal blood detected at medical check-up was the main reason for colonoscopic examination. There were no homosexual patients and no immunosuppressed patients. HIS was evenly distributed throughout the whole colorectum. PCR analysis of Brachyspira aalborgi and Brachyspira
pilosicoli revealed that more patients were infected with B. aalborgi. Follow-up PCR studies confirmed that infestation with B. aalborgi could be repeatedly detected over a 6 year period. This study, involving over 100 patients, identified the characteristic features of HIS in northern Japan. The results suggest that these spirochaetes may be harmless commensals that cause no obvious pathological alterations in infected individuals.
‘Neisseria skkuensis’ sp. nov., isolated from the blood of a diabetic patient with a foot ulcer
Authors: Lee Mi Young , Park Eu Gene , Choi Ji Young , Cheong Hae Suk , Chung Doo Ryeon , Peck Kyong Ran , Song Jae-Hoon , Ko Kwan Soo
Published: April 2010

A Gram-negative bacterium was isolated from the blood of a patient with diabetes mellitus. However, it could not be identified by conventional microbiological methods, and so was characterized by phenotypic and genotypic analyses. 16S rRNA gene sequence analysis revealed that the strain belonged to the genus Neisseria. Based on the phenotypic and genotypic characteristics, we propose that strain SMC-A9199T (=KCTC 22696T=JCM 16127T) should be classified as a novel species, ‘Neisseria skkuensis’ sp. nov. The patient was further treated with amoxicillin–clavulanate and ciprofloxacin for 3 weeks.
Role of bacteriocins in mediating interactions of bacterial isolates taken from cystic fibrosis patients
Authors: Bakkal Suphan , Robinson Sandra M. , Ordonez Claudia L. , Waltz David A. , Riley Margaret A.
Published: April 2010

Pseudomonas aeruginosa (Pa) and Burkholderia cepacia complex (Bcc) lung infections are responsible for much of the mortality in cystic fibrosis (CF). However, little is known about the ecological interactions between these two, often co-infecting, species. This study provides what is believed to be the first report of the intra- and interspecies bacteriocin-like inhibition potential of Pa and Bcc strains recovered from CF patients. A total of 66 strains were screened, and shown to possess bacteriocin-like inhibitory activity (97 % of Pa strains and 68 % of Bcc strains showed inhibitory activity), much of which acted across species boundaries. Further phenotypic and molecular-based assays revealed that the source of this inhibition differs for the two species. In Pa, much of the inhibitory activity is due to the well-known S and RF pyocins. In contrast, Bcc inhibition is due to unknown mechanisms, although RF-like toxins were implicated in some strains. These data suggest that bacteriocin-based inhibition may play a role in governing Pa and Bcc interactions in the CF lung and may, therefore, offer a novel approach to mediating these often fatal infections.
Characterization of the transcriptional regulator Rv3124 of Mycobacterium tuberculosis identifies it as a positive regulator of molybdopterin biosynthesis and defines the functional consequences of a non-synonymous SNP in the Mycobacterium bovis BCG orthologue
Authors: Mendoza Lopez Pablo , Golby Paul , Wooff Esen , Garcia Javier Nunez , Garcia Pelayo M. Carmen , Conlon Kevin , Gema Camacho Ana , Hewinson R. Glyn , Polaina Julio , Suárez García Antonio , Gordon Stephen V.
Published: April 2010

A number of single-nucleotide polymorphisms (SNPs) have been identified in the genome of Mycobacterium bovis BCG Pasteur compared with the sequenced strain M. bovis 2122/97. The functional consequences of many of these mutations remain to be described; however, mutations in genes encoding regulators may be particularly relevant to global phenotypic changes such as loss of virulence, since alteration of a regulator's function will affect the expression of a wide range of genes. One such SNP falls in bcg3145, encoding a member of the AfsR/DnrI/SARP class of global transcriptional regulators, that replaces a highly conserved glutamic acid residue at position 159 (E159G) with glycine in a tetratricopeptide repeat (TPR) located in the bacterial transcriptional activation (BTA) domain of BCG3145. TPR domains are associated with protein–protein interactions, and a conserved core (helices T1–T7) of the BTA domain seems to be required for proper function of SARP-family proteins. Structural modelling predicted that the E159G mutation perturbs the third α-helix of the BTA domain and could therefore have functional consequences. The E159G SNP was found to be present in all BCG strains, but absent from virulent M. bovis and Mycobacterium tuberculosis strains. By overexpressing BCG3145 and Rv3124 in BCG and H37Rv and monitoring transcriptome changes using microarrays, we determined that BCG3145/Rv3124 acts as a positive transcriptional regulator of the molybdopterin biosynthesis moa1 locus, and we suggest that rv3124 be renamed moaR1. The SNP in bcg3145 was found to have a subtle effect on the activity of MoaR1, suggesting that this mutation is not a key event in the attenuation of BCG.
Localization and characterization of Xylella fastidiosa haemagglutinin adhesins
Authors: Voegel Tanja M. , Warren Jeremy G. , Matsumoto Ayumi , Igo Michele M. , Kirkpatrick Bruce C.
Published: April 2010

Xylella fastidiosais a Gram-negative, xylem-inhabiting, plant-pathogenic bacterium responsible for several important diseases including Pierce's disease (PD) of grapevines. The bacteria form biofilms in grapevine xylem that contribute to the occlusion of the xylem vessels.X. fastidiosahaemagglutinin (HA) proteins are large afimbrial adhesins that have been shown to be crucial for biofilm formation. Little is known about the mechanism ofX. fastidiosaHA-mediated cell–cell aggregation or the localization of the adhesins on the cell. We generated anti-HA antibodies and show thatX. fastidiosaHAs are present in the outer membrane and secreted both as soluble proteins and in membrane vesicles. Furthermore, the HA pre-proteins are processed from the predicted molecular mass of 360 kDa to a mature 220 kDa protein. Based on this information, we are evaluating a novel form of potential resistance against PD by generating HA-expressing transgenic grapevines.
Role of vimA in cell surface biogenesis in Porphyromonas gingivalis
Authors: Osbourne Devon O. , Aruni Wilson , Roy Francis , Perry Christopher , Sandberg Lawrence , Muthiah Arun , Fletcher Hansel M.
Published: April 2010

ThePorphyromonas gingivalis vimAgene has been previously shown to play a significant role in the biogenesis of gingipains. Further, inP. gingivalisFLL92, avimA-defective mutant, there was increased auto-aggregation, suggesting alteration in membrane surface proteins. In order to determine the role of the VimA protein in cell surface biogenesis, the surface morphology ofP. gingivalisFLL92 was further characterized. Transmission electron microscopy demonstrated abundant fimbrial appendages and a less well defined and irregular capsule in FLL92 compared with the wild-type. In addition, atomic force microscopy showed that the wild-type had a smoother surface compared with FLL92. Western blot analysis using anti-FimA antibodies showed a 41 kDa immunoreactive protein band inP. gingivalisFLL92 which was missing in the wild-typeP. gingivalisW83 strain. There was increased sensitivity to globomycin and vancomycin in FLL92 compared with the wild-type. Outer membrane fractions from FLL92 had a modified lectin-binding profile. Furthermore, in contrast with the wild-type strain, nine proteins were missing from the outer membrane fraction of FLL92, while 20 proteins present in that fraction from FLL92 were missing in the wild-type strain. Taken together, these results suggest that the VimA protein affects capsular synthesis and fimbrial phenotypic expression, and plays a role in the glycosylation and anchorage of several surface proteins.