bluuebunny/crossref_metadata_2025 huggingface dataset:
Local Cerebral Glucose Utilization in Chronic Middle Cerebral Artery Occlusion in the Cat
Authors: Komatsumoto Saturo , Greenberg Joel H. , Hickey William F. , Reivich Martin
Published: April 2011

This study examines the correlation between local CMRglc (LCMRglc) alterations and clinicopathological changes in a chronic middle cerebral artery (MCA) occlusion model in the cat. The left MCA was occluded for a period of 2 h. The animals were grouped into mild, moderate, and severe ischemia based on the depression of the EEG 30 min after the MCA occlusion. Following release of the clip, the animals were allowed to recover for a week during which time daily neurological examinations were performed. On the seventh day [14C]2-deoxyglucose was injected for the determination of LCMRglc. Alternative blocks were processed for histological evaluation in which both neuronal and phagocytic changes were graded into four categories (0 = normal to 3 = severe). LCMRglc (μmol/100 g/min) in the ischemic hemisphere (all histological grades) was significantly lower than the metabolic rate in comparable regions of the sham MCA occlusion group. Regions with significant phagocytosis (grade 2 and 3) invariably exhibited activated glucose metabolism (57.4 ± 8.4 and 105.9 ± 6.8 μmol/100 g/min, respectively), which was significantly higher than in regions without phagocytosis (30.4 ± 0.8 μmol/100 g/min). There was a significant gradient of metabolism in the central, peripheral, and boundary zone and the non-MCA territory in the animals with severe ischemic lesions. LCMRglc in the central MCA territory was well correlated with the EEG amplitude changes ( r = 0.82, p < 0.05) and the morphological score ( r = –0.89, p < 0.05). The metabolic rate was significantly depressed in both the ipsilateral and the contralateral central MCA territories in comparison with the sham occlusion animals. The depression in LCMRglc in the contralateral hemisphere correlated well with the concomitant depression in the contralateral EEG amplitude. These studies demonstrate that local heterogeneous metabolic alterations and contralateral cortical diaschisis exist chronically following temporary MCA occlusion and that the increases in local cerebral glucose metabolism seen in chronic stroke may be due to phagocytotic activity.
Inverse Agonism at α2A Adrenoceptors Augments the Hypophagic Effect of Sibutramine in Rats
Authors: Janhunen Sanna K. , van der Zwaal Esther M. , La Fleur Susanne E. , Adan Roger A.H.
Published: April 2011

Because the use of monoamine reuptake inhibitors as weight‐reducing agents is limited by adverse effects, novel antiobesity drugs are needed. We studied acute effects of the noradrenaline (NA) and serotonin (5‐HT) reuptake inhibitor sibutramine (SIB), alone and after pretreatment with α1‐ and α2‐adrenoceptor (AR), and 5‐HT1/2/7, 5‐HT1B and 5‐HT2C receptor antagonists in order to determine which ARs and 5‐HT receptors act downstream of SIB on feeding and locomotion. Acute effects on caloric and water intake, meal microstructure and locomotion were assessed, using an automated weighing system and telemetry in male rats with restricted 18‐h access to Western style diet. SIB 3 mg/kg reduced meal size and frequency, which suggests enhanced within‐ and postmeal satiety. Imiloxan (α2B‐AR), WB4101 (α1‐AR), SB‐224289 (5‐HT1B), and modestly BRL 44408 (α2A/D‐AR) attenuated SIB's effect on meal size, suggesting that α2B‐ and α1‐ARs and 5‐HT1B receptors mediate within‐meal satiety, with a modest role for α2A/D‐ARs. Only prazosin (α1/2B/2C‐AR) counteracted SIB's effect on meal frequency. At 3 mg/kg, SIB modestly increased locomotion. This effect was blocked by metergoline (5‐HT1/2/7), WB4101 (α1‐AR), and RX821002 (α2‐AR). Interestingly, the α2‐AR antagonists atipamezole and RX821002 enhanced SIB's effect on caloric intake, probably due to inverse agonistic actions at α2A‐autoreceptors that further enhanced release of NA that regulates caloric intake. Thus, an inverse agonist of presynaptic α2A‐ARs might beneficially enhance SIB's weight‐reducing effect and offer novel treatment for obesity. All in all, the present data supports the ARs and 5‐HT receptors involved in the effects of SIB on different aspects of caloric intake and locomotion.
Inhibiting Food Reward: Delay Discounting, Food Reward Sensitivity, and Palatable Food Intake in Overweight and Obese Women
Authors: Appelhans Bradley M. , Woolf Kathleen , Pagoto Sherry L. , Schneider Kristin L. , Whited Matthew C. , Liebman Rebecca
Published: April 2011

Overeating is believed to result when the appetitive motivation to consume palatable food exceeds an individual's capacity for inhibitory control of eating. This hypothesis was supported in recent studies involving predominantly normal weight women, but has not been tested in obese populations. The current study tested the interaction between food reward sensitivity and inhibitory control in predicting palatable food intake among energy‐replete overweight and obese women (N = 62). Sensitivity to palatable food reward was measured with the Power of Food Scale. Inhibitory control was assessed with a computerized choice task that captures the tendency to discount large delayed rewards relative to smaller immediate rewards. Participants completed an eating in the absence of hunger protocol in which homeostatic energy needs were eliminated with a bland preload of plain oatmeal, followed by a bogus laboratory taste test of palatable and bland snacks. The interaction between food reward sensitivity and inhibitory control was a significant predictor of palatable food intake in regression analyses controlling for BMI and the amount of preload consumed. Probing this interaction indicated that higher food reward sensitivity predicted greater palatable food intake at low levels of inhibitory control, but was not associated with intake at high levels of inhibitory control. As expected, no associations were found in a similar regression analysis predicting intake of bland foods. Findings support a neurobehavioral model of eating behavior in which sensitivity to palatable food reward drives overeating only when accompanied by insufficient inhibitory control. Strengthening inhibitory control could enhance weight management programs.
Infusion of Glucose and Lipids at Physiological Rates Causes Acute Endoplasmic Reticulum Stress in Rat Liver
Authors: Boden Guenther , Song Weiwei , Duan Xunbao , Cheung Peter , Kresge Karen , Barrero Carlos , Merali Salim
Published: April 2011

Endoplasmic reticulum (ER) stress has recently been implicated as a cause for obesity‐related insulin resistance; however, what causes ER stress in obesity has remained uncertain. Here, we have tested the hypothesis that macronutrients can cause acute (ER) stress in rat liver. Examined were the effects of intravenously infused glucose and/or lipids on proximal ER stress sensor activation (PERK, eIF2‐α, ATF4, Xbox protein 1 (XBP1s)), unfolded protein response (UPR) proteins (GRP78, calnexin, calreticulin, protein disulphide isomerase (PDI), stress kinases (JNK, p38 MAPK) and insulin signaling (insulin/receptor substrate (IRS) 1/2 associated phosphoinositol‐3‐kinase (PI3K)) in rat liver. Glucose and/or lipid infusions, ranging from 23.8 to 69.5 kJ/4 h (equivalent to between ∼17% and ∼50% of normal daily energy intake), activated the proximal ER stress sensor PERK and ATF6 increased the protein abundance of calnexin, calreticulin and PDI and increased two GRP78 isoforms. Glucose and glucose plus lipid infusions induced comparable degrees of ER stress, but only infusions containing lipid activated stress kinases (JNK and p38 MAPK) and inhibited insulin signaling (PI3K). In summary, physiologic amounts of both glucose and lipids acutely increased ER stress in livers 12‐h fasted rats and dependent on the presence of fat, caused insulin resistance. We conclude that this type of acute ER stress is likely to occur during normal daily nutrient intake.
Palladium-catalyzed C–H bond functionalization of C6-arylpurines
Authors: Guo Hai-Ming , Rao Wei-Hao , Niu Hong-Ying , Jiang Li-Li , Meng Ge , Jin Jia-Jia , Yang Xi-Ning , Qu Gui-Rong
Published: April 2011

A highly regioselective Pd-catalyzed CAr–H bond activation method was developed for the modification of purines (nucleosides) with different functional groups by using purine as a directing group. This approach provides a new access to a variety of functionalized purines (nucleosides).
Octanuclear gold(i) alkynyl-diphosphine clusters showing thermochromic luminescence
Authors: Koshevoy Igor O. , Lin Chia-Li , Karttunen Antti J. , Haukka Matti , Shih Chun-Wei , Chou Pi-Tai , Tunik Sergey P. , Pakkanen Tapani A.
Published: April 2011

The unprecedented Au(i) alkynyl-diphosphine clusters demonstrate intense phosphorescence in solution and thermally dependent emission in the crystalline form.
Saving Space, Sharing Time: Integrated Infrastructures of Daily Life in Cohousing
Authors: Jarvis Helen
Published: April 2011

This paper explores the concept of collective housing, notably the North American model of purpose-built cohousing, to understand better the functions of space and time at the neglected scale of collective (colocated) interhousehold collaboration. The defining features of this form of intentional community typically include the clustering of smaller-than-average private residences to maximise shared open spaces for social interaction; common facilities for shared daily use; and consensus-based collective self-governance. This paper critically examines the infrastructures of daily life which evolve from, and ease, collective activity and the shared occupation of space. Discussion draws on observations from eight communities in the UK and USA, using selected ethnographic vignettes to illustrate a variety of alternative temporalities which coincide with a shifting and blurring of privatised dwelling. The resulting analysis exposes multiple temporal scales and innovative uses and meanings of time and space. The paper concludes by speculating on the contemporary significance of collective living arrangements and the role this might play in future sustainability.
Elite Knowledges: Framing Risk and the Geographies of Credit
Authors: Wainwright Thomas
Published: April 2011

This paper examines the history of credit scoring in Britain, and how this technology was imported from the US and adapted by the British retail banking sector. It seeks to highlight the elites who develop the social codes embedded within credit scoring software, to offer insight into the complex techno-economic networks that produce the geographies of financial inclusion, exclusion, and differential risk pricing. It is argued that the scientific status of these systems is questionable, due to the social interactions involved within the statistical modelling. Finally, the paper suggests that the spaces of credit are fluid, based upon the frequent social recalibrations of these models.
Fit for Purpose? Welfare Reform and Challenges for Health and Labour Market Policy in the UK
Authors: Lindsay Colin , Houston Donald
Published: April 2011

In the UK, as in some other EU states, the focus of recent welfare reforms has switched from those on unemployment benefits to those receiving sickness/incapacity benefits (IBs), reflecting concerns around the large numbers falling into the this last group. The Labour government elected in 1997 introduced a range of measures to activate those on IBs, setting a target of a one million reduction in the number of claimants by the end of 2015. The Conservative Party similarly came to acknowledge that high levels of IB claiming represented a problem of ‘unemployment hidden as sickness’, and in coalition now proposes even more aggressive supply-side strategies. This paper provides an extensive review of the most recent evidence to identify factors driving the rise in the number of people claiming IBs and, in light of this analysis, assesses whether current policy is fit for purpose. An important conclusion is that any national ‘one-size fits all’ supply-side policy response is blind to the distinctive geography of receipt of IBs and the complex combination of factors that leave some people trapped on these benefits.
Quality of Life in Urban-Classified and Rural-Classified English Local Authority Areas
Authors: Campanera Josep M , Higgins Paul
Published: April 2011

This paper presents the results of an analysis of the Audit Commission's local quality-of-life indicators dataset to compare reported outcomes amongst 208 urban-classified and 144 rural-classified English local authority areas. We contextualise the demarcation of the urban and rural by reference to the transformational politics of the previous Labour government and its establishment of the sustainable communities initiative, whose controversial ‘place-based’ revitalisation essence continues to shape local government policy. According to the collectivist sustainability interpretation of the 73 indicators analysed, our results reveal that not only do urban-classified English local authority areas register a significantly lower quality of life than their rural counterparts but that they are also subject to much greater statistical and spatial variation. In addition, we find that the community-related and economy-related indicators serve to distinguish the reported quality-of-life conditions of rural and urban localities most, whereas the scores for transport are uniquely superior for urban areas, especially London. In considering the policy implications of our results, we draw attention to Labour's much-trumpeted justice-based approach to sustainable development, and contemplate the viability of the Conservative–Liberal Democrat coalition government's ‘Big Society’ endeavour.
Structure and assembly of the essential RNA ring component of a viral DNA packaging motor
Authors: Ding Fang , Lu Changrui , Zhao Wei , Rajashankar Kanagalaghatta R. , Anderson Dwight L. , Jardine Paul J. , Grimes Shelley , Ke Ailong
Published: April 2011

Prohead RNA (pRNA) is an essential component in the assembly and operation of the powerful bacteriophage
ϕ
29 DNA packaging motor. The pRNA forms a multimeric ring via intermolecular base-pairing interactions between protomers that serves to guide the assembly of the ring ATPase that drives DNA packaging. Here we report the quaternary structure of this rare multimeric RNA at 3.5 Å resolution, crystallized as tetrameric rings. Strong quaternary interactions and the inherent flexibility helped rationalize how free pRNA is able to adopt multiple oligomerization states in solution. These characteristics also allowed excellent fitting of the crystallographic pRNA protomers into previous prohead/pRNA cryo-EM reconstructions, supporting the presence of a pentameric, but not hexameric, pRNA ring in the context of the DNA packaging motor. The pentameric pRNA ring anchors itself directly to the phage prohead by interacting specifically with the fivefold symmetric capsid structures that surround the head-tail connector portal. From these contacts, five RNA superhelices project from the pRNA ring, where they serve as scaffolds for binding and assembly of the ring ATPase, and possibly mediate communication between motor components. Construction of structure-based designer pRNAs with little sequence similarity to the wild-type pRNA were shown to fully support the packaging of
ϕ
29 DNA.
Aryl-homoserine lactone quorum sensing in stem-nodulating photosynthetic bradyrhizobia
Authors: Ahlgren Nathan A. , Harwood Caroline S. , Schaefer Amy L. , Giraud Eric , Greenberg E. Peter
Published: April 2011

Many
Proteobacteria
possess LuxI-LuxR–type quorum-sensing systems that produce and detect fatty acyl-homoserine lactone (HSL) signals. The photoheterotroph
Rhodopseudomonas palustris
is unusual in that it produces and detects an aryl-HSL,
p
-coumaroyl-HSL, and signal production requires an exogenous source of
p
-coumarate. A photosynthetic stem-nodulating member of the genus
Bradyrhizobium
produces a small molecule signal that elicits an
R. palustris
quorum-sensing response. Here, we show that this signal is cinnamoyl-HSL and that cinnamoyl-HSL is produced by the LuxI homolog BraI and detected by BraR. Cinnamoyl-HSL reaches concentrations on the order of 50 nM in cultures of stem-nodulating bradyrhizobia grown in the presence or absence of cinnamate. Acyl-HSLs often reach concentrations of 0.1–30 μM in bacterial cultures, and generally, LuxR-type receptors respond to signals in a concentration range from 5 to a few hundred nanomolar. Our stem-nodulating
Bradyrhizobium
strain responds to picomolar concentrations of cinnamoyl-HSL and thus, produces cinnamoyl-HSL in excess of the levels required for a signal response without an exogenous source of cinnamate. The ability of
Bradyrhizobium
to produce and respond to cinnamoyl-HSL shows that aryl-HSL production is not unique to
R. palustris
, that the aromatic acid substrate for aryl-HSL synthesis does not have to be supplied exogenously, and that some acyl-HSL quorum-sensing systems may function at very low signal production and response levels.
The 2010 Josephine Waters Bennett Lecture: Albrecht Dürer as Collector*
Authors: Smith Jeffrey Chipps
Published: April 2011

Albrecht Dürer avidly collected for his professional and personal pleasure. Drawing upon textual and artistic evidence, it is possible to assess what sorts of objects he acquired. Through purchases, bartering, and gifts, Dürer amassed an important library with authors ranging from Euclid to Martin Luther. Among his many dealings with contemporary masters, he exchanged drawings with Raphael, swapped prints with Lucas van Leyden, and bought a Salvator Mundi illuminated by Susanna Horenbout. Dürer was fascinated by objects of natural rarity and of exotic, non-European origins. He also self-collected. Some paintings and drawings, occasionally inscribed with biographical or autobiographical information, were intended primarily for his, his family's, and his close friends’ private consumption. The holdings displayed in his Nuremberg house anticipated the art and wonder chambers that became popular later in the sixteenth century. The collection offers new insights into Dürer's conscious efforts of self-fashioning.
Urban Literary Patronage in the Early Modern Low Countries: Public Festive Culture and Individual Authorship*
Authors: Mareel Samuel
Published: April 2011

This essay deals with the nature, background, and consequences of urban patronage for individual rhetoricians in the fifteenth- and sixteenth-century Low Countries. Although this phenomenon is most likely rooted in courtly practice, it is mainly because of the usefulness of rhetoricians in the context of urban public festivals that some of them received financial rewards from city authorities. My analysis shows how in the Low Countries urban festive culture and the oral dissemination of literary texts played an important, and heretofore largely neglected, role in the professionalization and individualization of authorship during the early modern period.
A multiscale technique for the validation of a numerical code for predicting the pressure field induced by a high-power spark
Authors: Villa A , Malgesini R , Barbieri L
Published: April 2011

A more precise knowledge of the pressure field induced by a high-power spark is essential to estimate the mechanical damage that a lightning strike can induce near the impact point. In this work we propose a multiscale approach to validate a numerical magnetohydro-dynamic model that can predict the pressure field when a very high-power discharge is considered. Two simplified models for the arc resistance are considered and their respective results are compared. A brief analysis regarding the numerical issues involved in the solution of a very high temperature gas is included. The numerical code has been validated against the experimental data of a short-arc discharge using a current waveform prescribed by the aeronautical standards. Our study shows that a strong shock wave is generated in the first power peak and this travels away from the arc column maintaining a relatively high strength a few tens of centimetres away. The pressure in the arc region remains high for the whole discharge period.
Analysis of the Al–PANI interfaces by complex impedance spectroscopy
Authors: Cazati T , Maciel A C , Eiras C , Constantino C J L , da Cunha H N , Bianchi R F
Published: April 2011

This paper describes a new approach to improve the analysis of surface modification of free-standing semiconducting polymer films emerged from the interfacial interaction between aluminium electrode and HCl-doped polyaniline (PANI) films. The Al–PANI–Al structure was prepared by casting PANI/N-methyl-2-pirrolidone onto a glass substrate and then being sandwiched between Al electrodes after immersion in HCl aqueous solutions and then dried. The Al–polymer interface was investigated by means of complex impedance spectroscopy in the frequency domain on HCl-doped PANI films. The dc conductivity of the interfacial layer between the Al and PANI surface exposed to air during the film processing is higher than those obtained with Al and PANI surface exposed to glass. Raman spectroscopy data confirm this evidence. Here, it is speculated that some dissociated chlorine and aluminium-salt-containing species have contributed as ionic carriers increasing the electrical conductivity of the polymer bulk, and by the formation of an Al2O3 thin layer between the Al and PANI films. An equivalent circuit model considering the influence of Al–PANI reactions on the electrical behaviour of the Al–PANI–Al structure was proposed. Additionally, it was demonstrated that the impedance spectroscopy facilitates the identification of interface modification in the Al–PANI–Al films.
Ferroelectricity in ultrathin asymmetric ferroelectric tunnel junctions: vanishing critical thickness
Authors: Lakshminarayana G , Yang Rong , Mao Mengfei , Zhang Yang , Qiu Jianrong
Published: April 2011

Parts of the discussion and conclusion of this article are similar to that published in [1].

The aim of our paper is to discuss the effect of Yb co-doping on the infrared luminescence property of Bi-, Pb-, Pb, Sb-, and Sn-doped germanate glasses based on our previous investigations [2] and the research results published in [1]. In this paper, we have presented complete optical characterization results (absorption, photo-luminescence, NIR luminescence, and lifetime decay curves) on the prepared Bi, Bi/Yb; Pb, Pb/Yb; Sb, Sb/Yb; and Sn, Sn/Yb-doped gadalonium (Gd)-based aluminogermanate glasses. This is principally new and was not published by anybody before. We have presented in total 27 figures including the inset plots in our paper in support of our discussion. The research results we presented in our paper are generally a substantial development of the previously reported results on the near-infrared luminescent materials. Also, we have provided the results on the observed enhancement of near-infrared luminescence with Yb co-doping in table 1 in the manuscript which is a novel result. However, we over-cited the expressions in [1] for discussion and conclusion. The authors sincerely apologise to M Sharonovet aland the publishers for the unnecessary replication.

References

[1] Sharonov M Yuet al2008 Spectroscopic study of optical centers formed in Bi-, Pb-, Sb-, Sn-, Te-, and In-doped germanate glassesOpt. Lett.332131

[2] Ruan Jet al2008 Enhanced broadband near-infrared luminescence and optical amplification in Yb–Bi codoped phosphate glassesAppl. Phys. Lett.92101121
Subcellular Golgi localization of stathmin family proteins is promoted by a specific set of DHHC palmitoyl transferases
Authors: Levy Aurore D. , Devignot Véronique , Fukata Yuko , Fukata Masaki , Sobel André , Chauvin Stéphanie
Published: April 2011

Protein palmitoylation is a reversible lipid modification that plays critical roles in protein sorting and targeting to specific cellular compartments. The neuronal microtubule-regulatory phosphoproteins of the stathmin family (SCG10/stathmin 2, SCLIP/stathmin 3, and RB3/stathmin 4) are peripheral proteins that fulfill specific and complementary roles in the formation and maturation of the nervous system. All neuronal stathmins are localized at the Golgi complex and at vesicles along axons and dendrites. Their membrane anchoring results from palmitoylation of two close cysteine residues present within their homologous N-terminal targeting domains. By preventing palmitoylation with 2-bromopalmitate or disrupting the integrity of the Golgi with brefeldin A, we were able to show that palmitoylation of stathmins 2 and 3 likely occurs at the Golgi and is crucial for their specific subcellular localization and trafficking. In addition, this membrane binding is promoted by a specific set of palmitoyl transferases that localize with stathmins 2 and 3 at the Golgi, directly interact with them, and enhance their membrane association. The subcellular membrane–associated microtubule-regulatory activity of stathmins might then be fine-tuned by extracellular stimuli controlling their reversible palmitoylation, which can be viewed as a crucial regulatory process for specific and local functions of stathmins in neurons.
Glucosidase II andN-glycan mannose content regulate the half-lives of monoglucosylated species in vivo
Authors: Stigliano Ivan D. , Alculumbre Solana G. , Labriola Carlos A. , Parodi Armando J. , D'Alessio Cecilia
Published: April 2011

Glucosidase II (GII) sequentially removes the two innermost glucose residues from the glycan (Glc3Man9GlcNAc2) transferred to proteins. GII also participates in cycles involving the lectin/chaperones calnexin (CNX) and calreticulin (CRT) as it removes the single glucose unit added to folding intermediates and misfolded glycoproteins by the UDP-Glc:glycoprotein glucosyltransferase (UGGT). GII is a heterodimer in which the α subunit (GIIα) bears the active site, and the β subunit (GIIβ) modulates GIIα activity through its C-terminal mannose 6-phosphate receptor homologous (MRH) domain. Here we report that, as already described in cell-free assays, in live Schizosaccharomyces pombe cells a decrease in the number of mannoses in the glycan results in decreased GII activity. Contrary to previously reported cell-free experiments, however, no such effect was observed in vivo for UGGT. We propose that endoplasmic reticulum α-mannosidase–mediated N-glycan demannosylation of misfolded/slow-folding glycoproteins may favor their interaction with the lectin/chaperone CNX present in S. pombe by prolonging the half-lives of the monoglucosylated glycans (S. pombe lacks CRT). Moreover, we show that even N-glycans bearing five mannoses may interact in vivo with the GIIβ MRH domain and that the N-terminal GIIβ G2B domain is involved in the GIIα–GIIβ interaction. Finally, we report that protists that transfer glycans with low mannose content to proteins have nevertheless conserved the possibility of displaying relatively long-lived monoglucosylated glycans by expressing GIIβ MRH domains with a higher specificity for glycans with high mannose content.
Multi-platform segmentation for joint detection of copy number variants
Authors: Teo Shu Mei , Pawitan Yudi , Kumar Vikrant , Thalamuthu Anbupalam , Seielstad Mark , Chia Kee Seng , Salim Agus
Published: April 2011

Motivation: With the expansion of whole-genome studies, there is rapid evolution of genotyping platforms. This leads to practical issues such as upgrading of genotyping equipment which often results in research groups having data from different platforms for the same samples. While having more data can potentially yield more accurate copy-number estimates, combining such data is not straightforward as different platforms show different degrees of attenuation of the true copy-number or different noise characteristics and marker panels. Currently, there is still a relative lack of procedures for combining information from different platforms.

Results: We develop a method, called MPSS, based on a correlated random-effect model for the unobserved patterns and extend the robust smooth segmentation approach to the multiple-platform scenario. We also propose an objective criterion for discrete segmentation required for downstream analyses. For each identified segment, the software reports a P-value to indicate the likelihood of the segment being a true CNV. From the analyses of real and simulated data, we show that MPSS has better operating characteristics when compared to single-platform methods, and have substantially higher sensitivity compared to an existing multiplatform method.

Availability: The methods are implemented in an R package MPSS, and the source is available from http://www.meb.ki.se/~yudpaw.

Contact:  agus_salim@nuhs.edu.sg

Supplementary Information:  Supplementary data are available at Bioinformatics online.
CMView: Interactive contact map visualization and analysis
Authors: Vehlow Corinna , Stehr Henning , Winkelmann Matthias , Duarte José M. , Petzold Lars , Dinse Juliane , Lappe Michael
Published: April 2011

Summary: Contact maps are a valuable visualization tool in structural biology. They are a convenient way to display proteins in two dimensions and to quickly identify structural features such as domain architecture, secondary structure and contact clusters. We developed a tool called CMView which integrates rich contact map analysis with 3D visualization using PyMol. Our tool provides functions for contact map calculation from structure, basic editing, visualization in contact map and 3D space and structural comparison with different built-in alignment methods. A unique feature is the interactive refinement of structural alignments based on user selected substructures.

Availability: CMView is freely available for Linux, Windows and MacOS. The software and a comprehensive manual can be downloaded from http://www.bioinformatics.org/cmview/. The source code is licensed under the GNU General Public License.

Contact:  lappe@molgen.mpg.de, stehr@molgen.mpg.de
Inferring Boolean network structure via correlation
Authors: Maucher Markus , Kracher Barbara , Kühl Michael , Kestler Hans A.
Published: April 2011

Motivation: Accurate, context-specific regulation of gene expression is essential for all organisms. Accordingly, it is very important to understand the complex relations within cellular gene regulatory networks. A tool to describe and analyze the behavior of such networks are Boolean models. The reconstruction of a Boolean network from biological data requires identification of dependencies within the network. This task becomes increasingly computationally demanding with large amounts of data created by recent high-throughput technologies. Thus, we developed a method that is especially suited for network structure reconstruction from large-scale data. In our approach, we took advantage of the fact that a specific transcription factor often will consistently either activate or inhibit a specific target gene, and this kind of regulatory behavior can be modeled using monotone functions.

Results: To detect regulatory dependencies in a network, we examined how the expression of different genes correlates to successive network states. For this purpose, we used Pearson correlation as an elementary correlation measure. Given a Boolean network containing only monotone Boolean functions, we prove that the correlation of successive states can identify the dependencies in the network. This method not only finds dependencies in randomly created artificial networks to very high percentage, but also reconstructed large fractions of both a published Escherichia coli regulatory network from simulated data and a yeast cell cycle network from real microarray data.

Contact:  hans.kestler@uni-ulm.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Correcting errors in short reads by multiple alignments
Authors: Salmela Leena , Schröder Jan
Published: April 2011

Motivation: Current sequencing technologies produce a large number of erroneous reads. The sequencing errors present a major challenge in utilizing the data in de novo sequencing projects as assemblers have difficulties in dealing with errors.

Results: We present Coral which corrects sequencing errors by forming multiple alignments. Unlike previous tools for error correction, Coral can utilize also bases distant from the error in the correction process because the whole read is present in the alignment. Coral is easily adjustable to reads produced by different sequencing technologies like Illumina Genome Analyzer and Roche/454 Life Sciences sequencing platforms because the sequencing error model can be defined by the user. We show that our method is able to reduce the error rate of reads more than previous methods.

Availability: The source code of Coral is freely available at http://www.cs.helsinki.fi/u/lmsalmel/coral/.

Contact:  leena.salmela@cs.helsinki.fi
Alignment-free detection of local similarity among viral and bacterial genomes
Authors: Domazet-Lošo Mirjana , Haubold Bernhard
Published: April 2011

Motivation: Bacterial and viral genomes are often affected by horizontal gene transfer observable as abrupt switching in local homology. In addition to the resulting mosaic genome structure, they frequently contain regions not found in close relatives, which may play a role in virulence mechanisms. Due to this connection to medical microbiology, there are numerous methods available to detect horizontal gene transfer. However, these are usually aimed at individual genes and viral genomes rather than the much larger bacterial genomes. Here, we propose an efficient alignment-free approach to describe the mosaic structure of viral and bacterial genomes, including their unique regions.

Results: Our method is based on the lengths of exact matches between pairs of sequences. Long matches indicate close homology, short matches more distant homology or none at all. These exact match lengths can be looked up efficiently using an enhanced suffix array. Our program implementing this approach, alfy (ALignment-Free local homologY), efficiently and accurately detects the recombination break points in simulated DNA sequences and among recombinant HIV-1 strains. We also apply alfy to Escherichia coli genomes where we detect new evidence for the hypothesis that strains pathogenic in poultry can infect humans.

Availability: alfy is written in standard C and its source code is available under the GNU General Public License from http://guanine.evolbio.mpg.de/alfy/. The software package also includes documentation and example data.

Contact:  haubold@evolbio.mpg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Parallel implementation of the
ab initio
CRYSTAL program: electronic structure calculations for periodic systems
Authors: Bush I. J. , Tomić S. , Searle B. G. , Mallia G. , Bailey C. L. , Montanari B. , Bernasconi L. , Carr J. M. , Harrison N. M.
Published: April 2011

CRYSTAL is an
ab initio
electronic structure program, based on the linear combination of atomic orbitals, for periodic systems. This paper concerns the ability of CRYSTAL to exploit massively parallel computer hardware. A brief review of the theory, numerical implementations and parallel solutions will be given and some of the functionalities and capabilities highlighted. Some features that are unique to CRYSTAL will be described and development plans outlined.
Expansion of mass-flowering crops leads to transient pollinator dilution and reduced wild plant pollination
Authors: Holzschuh Andrea , Dormann Carsten F. , Tscharntke Teja , Steffan-Dewenter Ingolf
Published: April 2011

Agricultural land use results in direct biodiversity decline through loss of natural habitat, but may also cause indirect cross-habitat effects on conservation areas. We conducted three landscape-scale field studies on 67 sites to test the hypothesis that mass flowering of oilseed rape (
Brassica napus
) results in a transient dilution of bees in crop fields, and in increased competition between crop plants and grassland plants for pollinators. Abundances of bumble-bees, which are the main pollinators of the grassland plant
Primula veris
, but also pollinate oilseed rape (OSR), decreased with increasing amount of OSR. This landscape-scale dilution affected bumble-bee abundances strongly in OSR fields and marginally in grasslands, where bumble-bee abundances were generally low at the time of
Primula
flowering. Seed set of
Primula veris
, which flowers during OSR bloom, was reduced by 20 per cent when the amount of OSR within 1 km radius increased from 0 to 15 per cent. Hence, the current expansion of bee-attractive biofuel crops results in transient dilution of crop pollinators, which means an increased competition for pollinators between crops and wild plants. In conclusion, mass-flowering crops potentially threaten fitness of concurrently flowering wild plants in conservation areas, despite the fact that, in the long run, mass-flowering crops can enhance abundances of generalist pollinators and their pollination service.
Longer in the tooth, shorter in the record? The evolutionary correlates of hypsodonty in Neogene ruminants
Authors: Raia P. , Carotenuto F. , Eronen J. T. , Fortelius M.
Published: April 2011

The acquisition of hypsodont molars is often regarded as a key innovation in the history of ruminant ungulates. Hypsodont ruminants diversified rapidly during the later Neogene, circa 15–2 Myr ago, and came to dominate the ruminant fossil record in terms of species diversity. Here we show that hypsodont clades had higher speciation and diversification rates than other clades. Hypsodont species had, on average, shorter stratigraphic durations, smaller range size and lower occupancy than non-hypsodont species. Within hypsodont clades, some species were very common and acquired large geographical ranges, whereas others were quite rare and geographically limited. We argue that hypsodont clades diversified in an adaptive radiation-like fashion, with species often splitting cladogenetically while still in the expansive phase of their occupancy history.
The nucleoprotein and matrix protein segments of H5N1 influenza viruses are responsible for dominance in embryonated eggs
Authors: Shimizu Kenta , Li Chengjun , Muramoto Yukiko , Yamada Shinya , Arikawa Jiro , Chen Hualan , Kawaoka Yoshihiro
Published: April 2011

Since their emergence in 1996 in southern China, highly pathogenic H5N1 avian influenza viruses have spread widely and continue to circulate in some countries. Genetic reassortment has created multiple H5N1 virus lineages, some of which are dominant in nature. However, the mechanism by which certain H5N1 influenza virus lineages (or genotypes) become dominant in avian species remains unknown. Here, we used competitive inoculation and genetic analysis of the resultant viruses to show that the nucleoprotein (NP) and matrix protein (M) segments of Fujian-like viruses (clade 2.3.4), which became predominant in southern China in mid-2006, are responsible for viral dominance in embryonated eggs. We further found that specific residues in the NP and M proteins play key roles in conferring this viral dominance; specifically, a glutamic acid at position 66 in M2 was conserved among the Fujian-like viruses. These results suggest roles for these viral proteins in influenza virus dominance.
p38 mitogen-activated protein kinase is crucial for bovine papillomavirus type-1 transformation of equine fibroblasts
Authors: Yuan ZhengQiang , Gault Elizabeth A. , Campo M. Saveria , Nasir Lubna
Published: April 2011

Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by extensive invasion and infiltration of lymphatics, rare regression and high recurrence after surgical intervention. Bovine papillomavirus type-1 (BPV-1) and less commonly BPV-2 are the causative agents of the diseases. It has been demonstrated that BPV-1 viral gene expression is necessary for maintaining the transformation phenotype. However, the underlying mechanism for BPV-1 transformation remains largely unknown, and the cellular factors involved in transformation are not fully understood. Previously mitogen-activated protein kinase (MAPK) signalling pathway has been shown to be important for cellular transformation. This study investigated the role of p38 MAPK (p38) in the transformation of equine fibroblasts by BPV-1. Elevated expression of phosphorylated p38 was observed in BPV-1 expressing fibroblasts due to the expression of BPV-1 E5 and E6. The phosphorylation of the MK2 kinase, a substrate of p38, was also enhanced. Inhibition of p38 activity by its selective inhibitor SB203580 changed cell morphology, reduced the proliferation of sarcoid fibroblasts and inhibited cellular invasiveness, indicating the indispensable role of p38 in BPV-1 transformation of equine fibroblasts. These findings provide new insights into the pathogenesis of equine sarcoids and suggest that p38 could be a potential target for equine sarcoid therapy.
The Unfolded Protein Response Is Triggered by a Plant Viral Movement Protein
Authors: Ye Changming , Dickman Martin B. , Whitham Steven A. , Payton Mark , Verchot Jeanmarie
Published: April 2011

Infection with Potato virus X (PVX) in Nicotiana benthamiana plants leads to increased transcript levels of several stress-related host genes, including basic-region leucine zipper 60 (bZIP60), SKP1, ER luminal binding protein (BiP), protein disulfide isomerase (PDI), calreticulin (CRT), and calmodulin (CAM). bZIP60 is a key transcription factor that responds to endoplasmic reticulum (ER) stress and induces the expression of ER-resident chaperones (BiP, PDI, CRT, and CAM). SKP1 is a component of SCF (for SKP1-Cullin-F box protein) ubiquitin ligase complexes that target proteins for proteasomal degradation. Expression of PVX TGBp3 from a heterologous vector induces the same set of genes in N. benthamiana and Arabidopsis (Arabidopsis thaliana) leaves. Virus-induced gene silencing was employed to knock down the expression of bZIP60 and SKP1, and the number of infection foci on inoculated leaves was reduced and systemic PVX accumulation was altered. Silencing bZIP60 led to the suppression of BiP and SKP1 transcript levels, suggesting that bZIP60 might be an upstream signal transducer. Overexpression of TGBp3 led to localized necrosis, but coexpression of TGBp3 with BiP abrogated necrosis, demonstrating that the unfolded protein response alleviates ER stress-related cell death. Steady-state levels of PVX replicase and TGBp2 (which reside in the ER) proteins were unaltered by the presence of TGBp3, suggesting that TGBp3 does not contribute to their turnover. Taken together, PVX TGBp3-induced ER stress leads to up-regulation of bZIP60 and unfolded protein response-related gene expression, which may be important to regulate cellular cytotoxicity that could otherwise lead to cell death if viral proteins reach high levels in the ER.
GUN4-Porphyrin Complexes Bind the ChlH/GUN5 Subunit of Mg-Chelatase and Promote Chlorophyll Biosynthesis inArabidopsis
Authors: Adhikari Neil D. , Froehlich John E. , Strand Deserah D. , Buck Stephanie M. , Kramer David M. , Larkin Robert M.
Published: April 2011

The GENOMES UNCOUPLED4 (GUN4) protein stimulates chlorophyll biosynthesis by activating Mg-chelatase, the enzyme that commits protoporphyrin IX to chlorophyll biosynthesis. This stimulation depends on GUN4 binding the ChlH subunit of Mg-chelatase and the porphyrin substrate and product of Mg-chelatase. After binding porphyrins, GUN4 associates more stably with chloroplast membranes and was proposed to promote interactions between ChlH and chloroplast membranes—the site of Mg-chelatase activity. GUN4 was also proposed to attenuate the production of reactive oxygen species (ROS) by binding and shielding light-exposed porphyrins from collisions with O2. To test these proposals, we first engineered Arabidopsis thaliana plants that express only porphyrin binding–deficient forms of GUN4. Using these transgenic plants and particular mutants, we found that the porphyrin binding activity of GUN4 and Mg-chelatase contribute to the accumulation of chlorophyll, GUN4, and Mg-chelatase subunits. Also, we found that the porphyrin binding activity of GUN4 and Mg-chelatase affect the associations of GUN4 and ChlH with chloroplast membranes and have various effects on the expression of ROS-inducible genes. Based on our findings, we conclude that ChlH and GUN4 use distinct mechanisms to associate with chloroplast membranes and that mutant alleles of GUN4 and Mg-chelatase genes cause sensitivity to intense light by a mechanism that is potentially complex.
Effect of doublecortin on self‐renewal and differentiation in brain tumor stem cells
Authors: Santra Manoranjan , Santra Sutapa , Buller Ben , Santra Kastuv , Nallani Ankita , Chopp Michael
Published: April 2011

Analysis of microarray probe data from glioma patient samples, in conjunction with patient Kaplan–Meier survival plots, indicates that expression of a glioma suppressor gene doublecortin (DCX) favors glioma patient survival. From neurosphere formation in culture, time‐lapse microscopic video recording, and tumor xenograft, we show that DCX synthesis significantly reduces self‐renewal of brain tumor stem cells (BTSC) in human primary glioma (YU‐PG, HF66) cells from surgically removed human glioma specimens and U87 cells in vitro and in vivo. Time‐lapse microscopic video recording revealed that double transfection of YU‐PG, HF66, and U87 cells with DCX and neurabin II caused incomplete cell cycle with failure of cytokinesis, that is, endomitosis by dividing into three daughter cells from one mother BTSC. Activation of c‐jun NH2‐terminal kinase 1 (JNK1) after simvastatin (10 nM) treatment of DCX+neurabin II+ BTSC from YU‐PG, HF66, and U87 cells induced terminal differentiation into neuron‐like cells. dUTP nick end labeling data indicated that JNK1 activation also induced apoptosis only in double transfected BTSC with DCX and neurabin II, but not in single transfected BTSC from YU‐PG, HF66, and U87 cells. Western blot analysis showed that procaspase‐3 was induced after DCX transfection and activated after simvastatin treatment in YU‐PG, HF66, and U87 BTSC. Sequential immunoprecipitation and Western blot data revealed that DCX synthesis blocked protein phosphatase‐1 (PP1)/caspase‐3 protein–protein interaction and increased PP1–DCX interaction. These data show that DCX synthesis induces apoptosis in BTSC through a novel JNK1/neurabin II/DCX/PP1/caspase‐3 pathway. (Cancer Sci 2011; 102: 1350–1357)