bluuebunny/crossref_metadata_2025 huggingface dataset:
Strongyloides ratti:transplantation of adults recovered from the small intestine at different days after infection into the colon of naive and infection-primed Wistar rats, and the effect of antioxidant treatment on large intestinal parasitism
Authors: SHINTOKU Y. , TAKAGI H. , KADOSAKA T. , NAGAOKA F. , KONDO S. , ITOH M. , HONDA S. , KIMURA E.
Published: June 2011

Strongyloides ratti(Nagoya strain) is unique in that a portion of adults parasitizing the small intestine withstands ‘worm expulsion’, which starts at around day 8 post-infection (p.i.) by host immunity, and establishes in the large intestine after day 19 p.i. To investigate the mechanism, adults obtained from the small intestine at day 7 or 19 p.i. were transplanted into the colon of infection-primed immune rats. Adults obtained at day 7 p.i. were rejected quickly, whereas those obtained at day 19 p.i. could establish infection. Moreover, the body length and the number of intrauterine eggs increased in the large intestine. In a separate experiment, large intestinal parasitism was abolished by the treatment of host rats with an anti-oxidant, butylated hydroxyanisole. These results indicate that small intestinal adults between days 7 and 19 p.i. acquired the ability to parasitize the large intestine of immune rats, and that free radicals produced by the host may have played a significant role in the process.
Dynamics of Sept4 expression in fibrotic livers of mice infected with Schistosoma japonicum
Authors: DUAN Y. N. , QIAN H. Y. , QIN Y. W. , ZHU D. D. , HE X. X. , ZHOU Q. , YANG Y. N. , BAO J. , FENG J. R. , SUN W. , CHEN J. L.
Published: June 2011

In order to investigate the dynamics of Septin4 (Sept4) expression and its function in the formation of fibrotic livers in mice infected with Schistosoma japonicum, we constructed the mouse model of S. japonicum egg-induced liver fibrosis for 24 weeks. Immunohistochemical staining, qRT-PCR and Western blot were used to detect the expression of Sept4 and α-smooth muscle actin (α-SMA). We found Sept4 localized in the perisinusoidal space where hepatic stellate cells (HSCs) distribute in the periphery of circumoval granulomas and the portal venule. The expression of Sept4 and α-SMA had a similar significant tendency of an up-regulation to a peak at 12 weeks post-infection (p.i.) followed by a down-regulation. At 24 weeks p.i. both were at a low level. These results suggest that Sept4 and α-SMA may interact together in HSCs. Based on this evidence, we hypothesize that Sept4 seems to be involved in the formation of inflammatory granulomata and subsequent liver fibrosis by regulating HSCs activation.
Rational Feelings and Moral Agency
Authors: Geiger Ido
Published: June 2011

Kant's conception of moral agency is often charged with attributing no role to feelings. I suggest that respect is the effective force driving moral action. I then argue that four additional types of rational feelings are necessary conditions of moral agency: (1) The affective inner life of moral agents deliberating how to act and reflecting on their deeds is rich and complex (conscience). To act morally we must turn our affective moral perception towards the ends of moral action: (2) the welfare of others (love of others); and (3) our own moral being (self-respect). (4) Feelings shape our particular moral acts (moral feeling). I tentatively suggest that the diversity of moral feelings might be as great as the range of our duties.
Quest for the descent of the Escherichia coli outbreak strain TY2482 – out of Germany?
Authors: Avasthi Tiruvayipati , Kumar Narender , Baddam Ramani , Ahmed Niyaz
Published: June 2011

The recent outbreak of the Escherichia coli infection in north Germany reportedly has killed 35 people and sickened about 4000. Infections were reported in 2001 and 2002 in Germany and Central Africa respectively. In order to dissect all possible connections among the three infection/outbreak strains and to extract the most virulent genes responsible for the augmented pathogenicity of the present German strain (2011), whole genome sequence data of the two isolates (E. coli TY_2482 & LB226692) were analyzed. We report that the German outbreak strain isolated in 2011 is a seasoned clone of the 2002 isolate sequenced from Central Africa (55989) and perhaps a direct descendent of the German EAEC strain reported in 2001 infection cases.
Birth Weight and Subsequent Adiposity Gain in Swedish Children and Adolescents: A 6‐Year Follow‐Up Study
Authors: Labayen Idoia , Ortega Francisco B. , Ruiz Jonatan R. , Sjostrom Michael
Published: June 2011

We examined whether birth weight (BW) predicts changes in body composition over a 6‐year period in Swedish children and adolescents. For this purpose, a total of 247 children (55.5% girls) and 162 adolescents (60.5% girls) were included in the study and were followed up 6 years later. BW was obtained from parental records. We measured weight, height, waist circumference, and the bicep, tricep, subscapular, suprailiac, and medial calf skinfolds, and we calculated BMI, fat‐free mass (FFM), and the sum of five skinfolds. Physical activity was assessed by accelerometry. Changes in pubertal status and baseline anthropometric estimates were used as confounders in all analysis. In the children cohort, we observed that BW was inversely associated with changes in BMI (β = −0.736, P = 0.002) and the sum of five skinfolds (β = −6.381, P = 0.009) regardless of confounders and physical activity, only in girls. We did not find any significant association between BW and adiposity gain estimates in the adolescent cohort. These findings give further support to the concept that low BW may have a programming effect of subsequent adiposity gain from childhood to adolescence. We also confirm the sex‐related differences in the programming effect of body composition.
Attentional Bias to Food Images Associated With Elevated Weight and Future Weight Gain: An fMRI Study
Authors: Yokum Sonja , Ng Janet , Stice Eric
Published: June 2011

Behavioral studies reveal that obese vs. lean individuals show attentional bias to food stimuli. Yet research has not investigated this relation using objective brain imaging or tested whether attentional bias to food stimuli predicts future weight gain, which are important aims given the prominence of food cues in the environment. We used functional magnetic resonance imaging (fMRI) to examine attentional bias in 35 adolescent girls ranging from lean to obese using an attention network task involving food and neutral stimuli. BMI correlated positively with speed of behavioral response to both appetizing food stimuli and unappetizing food stimuli, but not to neutral stimuli. BMI correlated positively with activation in brain regions related to attention and food reward, including the anterior insula/frontal operculum, lateral orbitofrontal cortex (OFC), ventrolateral prefrontal cortex (vlPFC), and superior parietal lobe, during initial orientation to food cues. BMI also correlated with greater activation in the anterior insula/frontal operculum during reallocation of attention to appetizing food images and with weaker activation in the medial OFC and ventral pallidum during reallocation of attention to unappetizing food images. Greater lateral OFC activation during initial orientation to appetizing food cues predicted future increases in BMI. Results indicate that overweight is related to greater attentional bias to food cues and that youth who show elevated reward circuitry responsivity during food cue exposure are at increased risk for weight gain.
Lifestyle Factors and 5‐Year Abdominal Fat Accumulation in a Minority Cohort: The IRAS Family Study
Authors: Hairston Kristen G. , Vitolins Mara Z. , Norris Jill M. , Anderson Andrea M. , Hanley Anthony J. , Wagenknecht Lynne E.
Published: June 2011

The objective of this study was to examine whether lifestyle factors were associated with 5‐year change in abdominal fat measured by computed tomography (CT) in the Insulin Resistance and Atherosclerosis (IRAS) Family Study. We obtained abdominal CT scans at baseline and at 5 years, from African Americans (AA) (N = 339) and Hispanic Americans (N = 775), aged 18–81 years. Visceral (VAT) and subcutaneous (SAT) adipose tissue was measured at the L4/L5 vertebral level. Physical activity was documented by self‐report of vigorous activity and a 1‐year recall instrument. Dietary intake was assessed at follow‐up using a semi‐quantitative food frequency questionnaire referencing the previous year. Generalized linear models, accounting for family structure, were used to assess the associations between percent change in fat accumulation and smoking, physical activity, total calories, polyunsaturated, monounsaturated, protein, and saturated fat intake, percent of calories from sweets, and soluble and insoluble fiber. Soluble fiber intake and participation in vigorous activity were inversely related to change in VAT, independent of change in BMI. For each 10 g increase in soluble fiber, rate of VAT accumulation decreased by 3.7% (P = 0.01). Soluble fiber was not associated with change in SAT (0.2%, P = 0.82). Moderately active participants had a 7.4% decrease in rate of VAT accumulation and a 3.6% decrease in rate of SAT accumulation versus less active participants (P = 0.003 and P = 0.01, respectively). Total energy expenditure was also inversely associated with accumulation of VAT. Soluble fiber intake and increased physical activity were related to decreased VAT accumulation over 5 years.
Terahertz response of field-effect transistors in saturation regime
Authors: Elkhatib T. A. , Kachorovskii V. Yu. , Stillman W. J. , Rumyantsev S. , Zhang X.-C. , Shur M. S.
Published: June 2011

We report on the broadband terahertz response of InGaAs/GaAs high electron mobility transistors operating at 1.63 THz and room temperature deep in the saturation regime. We demonstrate that responses show linear increase with drain-to-source voltage (or drain-bias current) and might reach very high values up to 170 V/W. We also develop a phenomenological theory valid both in the Ohmic and in the saturation regimes.
Synchronization transitions in coupled time-delay electronic circuits with a threshold nonlinearity
Authors: Srinivasan K. , Senthilkumar D. V. , Murali K. , Lakshmanan M. , Kurths J.
Published: June 2011

Experimental observations of typical kinds of synchronization transitions are reported in unidirectionally coupled time-delay electronic circuits with a threshold nonlinearity and two time delays, namely feedback delay τ1 and coupling delay τ2. We have observed transitions from anticipatory to lag via complete synchronization and their inverse counterparts with excitatory and inhibitory couplings, respectively, as a function of the coupling delay τ2. The anticipating and lag times depend on the difference between the feedback and the coupling delays. A single stability condition for all the different types of synchronization is found to be valid as the stability condition is independent of both the delays. Further, the existence of different kinds of synchronizations observed experimentally is corroborated by numerical simulations and from the changes in the Lyapunov exponents of the coupled time-delay systems.
Parameteric studies of nonlinear oblique magnetosonic waves in two-ion-species plasmas
Authors: Toida Mieko , Kondo Yuichi
Published: June 2011

The study of the effects of ion composition on perpendicular magnetosonic waves in two-ion-species plasmas [M. Toida, H. Higashino, and Y. Ohsawa, J. Phys. Soc. Jpn. 76, 104052 (2007)] is extended to include oblique waves. First, the conditions necessary for KdV equations for low- and high-frequency modes to be valid are analytically obtained. The upper limit of the amplitude of the low-frequency-mode pulse is expressed as a function of the propagation angle θ, density ratio, and cyclotron frequency ratio of the two ion species. Next, with electromagnetic particle simulations, the nonlinear evolution of a long-wavelength low-frequency-mode disturbance is examined for various θs in two plasmas with different ion densities and cyclotron frequency ratios, and the theory for the low-frequency-mode pulse is confirmed. It is also shown that if the pulse amplitude exceeds the theoretical value of the upper limit of the amplitude, then shorter-wavelength low- and high-frequency-mode waves are generated.
Organic photovoltaics incorporating electron conducting exciton blocking layers
Authors: Lassiter Brian E. , Wei Guodan , Wang Siyi , Zimmerman Jeramy D. , Diev Viacheslav V. , Thompson Mark E. , Forrest Stephen R.
Published: June 2011

We demonstrate that 3,4,9,10 perylenetetracarboxylic bisbenzimidazole (PTCBI) and 1,4,5,8-napthalene-tetracarboxylic-dianhydride (NTCDA) can function as electron conducting and exciton blocking layers when interposed between the acceptor layer and cathode. A low-resistance contact is provided by PTCBI, while NTCDA acts as an exciton blocking layer and optical spacer. Both materials serve as efficient electron conductors, leading to a fill factor as high as 0.70. By using an NTCDA/PTCBI compound blocking layer structure in a functionalized-squaraine/C60-based device, we obtain a spectrally corrected power conversion efficiency of 5.1±0.1% under 1 sun, AM 1.5G simulated solar illumination, an improvement of >25% compared to an analogous device using a conventional bathocuproine layer that has previously been shown to conduct electrons via damage-induced midgap states.
Semiclassical initial value representation study of internal conversion rates
Authors: Ianconescu Reuven , Pollak Eli
Published: June 2011

Internal conversion is an inherently quantum mechanical process. To date, “on the fly” computation of internal conversion rates is limited to harmonic approximations, which would seem to be especially unsuitable, given that the typical transition to the ground electronic state occurs at energies which are far from the harmonic limit. It is thus of interest to study the applicability of the semiclassial initial value representation (SCIVR) approach which is in principle amenable to on the fly studies even with “many” degrees of freedom. In this paper we study the applicability of the Herman-Kluk (HK) SCIVR to a model system with two coupled and anharmonic degrees of freedom. We find that (a) the HK SCIVR is a good approximation to the exact quantum dynamics; (b) computation of the first order correction to the HK-SCIVR approximation corroborates the accuracy; (c) by studying a large parameter range, we find that the harmonic approximation is mostly unsatisfactory; and (d) for the specific model used, the coupling between the modes was found to be relatively unimportant. These results imply that the HK-SCIVR methodology is a good candidate for on the fly studies of internal conversion processes of “large” molecules.
Efficient electro-optic switching in a photonic liquid crystal fiber
Authors: Lorenz Alexander , Kitzerow Heinz-S.
Published: June 2011

Results on the attenuation properties of a band gap guiding microstructured fiber filled with a nematic liquid crystal are presented. The fiber shows broad transmission bands and moderate attenuation in the visible wavelength range. By electric addressing, the fiber can be utilized either as switchable linear polarizer or as a polarization-independent shutter. In the former case, the plane of polarization can be controlled by adjusting the electric field utilizing a four-electrode setup.
Experimental realization of broadband tunable resonators based on anisotropic metafluids
Authors: Spiousas Ignacio , Torrent Daniel , Sánchez-Dehesa José
Published: June 2011

This letter demonstrates the mechanical tuning of modes confined in two-dimensional acoustic cavities based on anisotropic metafluids. The employed metafluids have been designed with effective parameters such that the radial component of the sound speed tensor keeps constant and the acoustic impedance remains finite along the tuning. It is shown that mode frequencies can be mechanically down shifted to extremely low values. Experiments confirm the model predictions and let us to conclude that this type of resonators can be employed for the miniaturization of standard resonators based on isotropic fluids such as air.
Correlation between boson peak and anomalous elastic behavior in GeO2 glass: An in situ Raman scattering study under high-pressure
Authors: Deschamps T. , Martinet C. , de Ligny D. , Bruneel J. L. , Champagnon B.
Published: June 2011

We present low-frequency Raman scattering of pure GeO2 glass under pressure up to 4 GPa, corresponding to an elastic transformation. Intensity variation and frequency shift of the boson peak are analysed and compared to the Debye model. The decrease of the boson peak intensity scaled by the Debye energy is correlated to the elastic anomalous properties under pressure up to 1.5 GPa, and interpreted as an elastic homogenisation process at the local scale. We emphasize similarities between a-GeO2 and a-SiO2 behavior under pressure, and compare our results to other experiments, numerical studies, and predictions of several models concerning amorphous systems.
Mixing thermodynamics of TM1−xGdxN (TM=Ti,Zr,Hf) from first principles
Authors: Alling B. , Höglund C. , Hall-Wilton R. , Hultman L.
Published: June 2011

The mixing thermodynamics of GdN with TiN, ZrN, and HfN is studied using first-principles methods. We find that while Ti1−xGdxN has a strong preference for phase separation due to the large lattice mismatch, Zr1−xGdxN and Hf1−xGdxN readily mix, possibly in the form of ordered compounds. In particular, ZrGdN2 is predicted to order in a rocksalt counterpart to the L11 structure at temperatures below 1020 K. These mixed nitrides are promising candidates as neutron absorbing, thermally and chemically stable, thin film materials.
Unusual magnetoresistance in a topological insulator with a single ferromagnetic barrier
Authors: Kong B. D. , Semenov Y. G. , Krowne C. M. , Kim K. W.
Published: June 2011

Tunneling surface current through a thin ferromagnetic barrier on a three-dimensional topological insulator is shown to possess an extraordinary response to the orientation of barrier magnetization. In contrast to conventional magnetoresistance devices that are sensitive to the relative alignment of two magnetic layers, a drastic change in the transmission current is achieved by a single layer when its magnetization rotates by 90°. Numerical estimations predict a giant magnetoresistance as large as 800% at room temperature with the proximate exchange energy of 40 meV at the barrier interface. When coupled with electrical control of magnetization direction, this phenomenon may be used to enhance the gating function with potentially sharp turn-on/off for low power applications.
Lasing in localized modes of a slow light photonic crystal waveguide
Authors: Yang Jin-Kyu , Noh Heeso , Rooks Michael J. , Solomon Glenn S. , Vollmer Frank , Cao Hui
Published: June 2011

We demonstrate lasing in GaAs photonic crystal waveguides with InAs quantum dots as gain medium. Structural disorder is present due to fabrication imperfection and causes multiple scattering of light and localization of light. Lasing modes with varying spatial extend are observed at random locations along the guide. Lasing frequencies are determined by the local structure and occur within a narrow frequency band which coincides with the slow light regime of the waveguide mode. The three-dimensional numerical simulation reveals that the main loss channel for lasing modes located away from the waveguide end is out-of-plane scattering by structural disorder.
Strong absorption and selective thermal emission from a midinfrared metamaterial
Authors: Mason J. A. , Smith S. , Wasserman D.
Published: June 2011

We demonstrate thin-film metamaterials with resonances in the midinfrared (mid-IR) wavelength range. Our structures are numerically modeled and experimentally characterized by reflection and angularly resolved thermal emission spectroscopy. We demonstrate strong and controllable absorption resonances across the mid-IR wavelength range. In addition, the polarized thermal emission from these samples is shown to be highly selective and largely independent of emission angles from normal to 45°. Experimental results are compared to numerical models with excellent agreement. Such structures hold promise for large-area, low-cost metamaterial coatings for control of gray- or black-body thermal signatures, as well as for possible mid-IR sensing applications.
Note: High-pressure generation using nano-polycrystalline diamonds as anvil materials
Authors: Nakamoto Y. , Sakata M. , Sumiya H. , Shimizu K. , Irifune T. , Matsuoka T. , Ohishi Y.
Published: June 2011

Nano-polycrystalline diamonds (NPDs) consist of nanosized diamond grains oriented in random directions. They have high toughness and isotropic mechanical properties. A NPD has neither the cleavage feature nor the anisotropy of hardness peculiar to single-crystal diamonds. Therefore, it is thought to be useful as a diamond anvil. We previously reported the usefulness of a NPD as an anvil for high-pressure development. In this study, some additional high-pressure generating tests using diamond anvils of various shapes prepared from NPDs were conducted to investigate the advantage of using NPDs for anvil applications. The results revealed that the achievable pressure value of a NPD anvil with a culet size of more than 300 μm is about 1.5 to 2 times higher than that of single-crystal diamond anvils, indicating that NPD anvils have considerable potential for large-volume diamond anvils with large culet sizes.
Properties of a plasma-based laser-triggered micro-lens
Authors: Toncian T. , Amin M. , Borghesi M. , Cecchetti C. A. , Clarke R. J. , Fuchs J. , Jung R. , Kudyakov T. , Notley M. , Pipahl A. C. , Wilson P. A. , Willi O.
Published: June 2011

This paper investigates the characteristic properties of a laser triggered micro-lens for focusing and energy selection of laser generated MeV proton and ion beams. Both experimental and computational studies that have been carried out leading to the understanding of the physical processes driving the micro-lens. After a one side irradiation of a hollow metallic cylinder a radial electric field develops inside the cylinder. Hot electrons generated by the interaction between laser pulse and cylinder wall spread inside the cylinder generating a plasma at the wall. This plasma expands into vacuum and sustains an electric field that acts as a collecting lens for proton or ion beams propagating axially through the cylinder. Various measurements including the reduction of the intrinsic beam divergence, the focusing quality, the energy selection and temporal response were carried out which contribute to the understanding of the lens properties. In addition, proton imaging was employed to study the electron transport inside the cylinder, revealing a transport along the wall surface. Each aspect studied experimentally is interpreted using 2D PIC and ray tracing simulations. A very good consistency between experimental and computational data was found.
Involvement of the Rho–mDia1 pathway in the regulation of Golgi complex architecture and dynamics
Authors: Zilberman Yuliya , Alieva Naila O. , Miserey-Lenkei Stéphanie , Lichtenstein Alexandra , Kam Zvi , Sabanay Helena , Bershadsky Alexander
Published: June 2011

In mammalian cells, the Golgi apparatus is a ribbon-like, compact structure composed of multiple membrane stacks connected by tubular bridges. Microtubules are known to be important to Golgi integrity, but the role of the actin cytoskeleton in the maintenance of Golgi architecture remains unclear. Here we show that an increase in Rho activity, either by treatment of cells with lysophosphatidic acid or by expression of constitutively active mutants, resulted in pronounced fragmentation of the Golgi complex into ministacks. Golgi dispersion required the involvement of mDia1 formin, a downstream target of Rho and a potent activator of actin polymerization; moreover, constitutively active mDia1, in and of itself, was sufficient for Golgi dispersion. The dispersion process was accompanied by formation of dynamic F-actin patches in the Golgi area. Experiments with cytoskeletal inhibitors (e.g., latrunculin B, blebbistatin, and Taxol) revealed that actin polymerization, myosin-II–driven contractility, and microtubule-based intracellular movement were all involved in the process of Golgi dispersion induced by Rho–mDia1 activation. Live imaging of Golgi recovery revealed that fusion of the small Golgi stacks into larger compartments was repressed in cells with active mDia1. Furthermore, the formation of Rab6-positive transport vesicles derived from the Golgi complex was enhanced upon activation of the Rho–mDia1 pathway. Transient localization of mDia1 to Rab6-positive vesicles was detected in cells expressing active RhoA. Thus, the Rho–mDia1 pathway is involved in regulation of the Golgi structure, affecting remodeling of Golgi membranes.
Histone H2B ubiquitylation and H3 lysine 4 methylation prevent ectopic silencing of euchromatic loci important for the cellular response to heat
Authors: Leung Amy , Cajigas Ivelisse , Jia Peilin , Ezhkova Elena , Brickner Jason H. , Zhao Zhongming , Geng Fuqiang , Tansey William P.
Published: June 2011

In Saccharomyces cerevisiae, ubiquitylation of histone H2B signals methylation of histone H3 at lysine residues 4 (K4) and 79. These modifications occur at active genes but are believed to stabilize silent chromatin by limiting movement of silencing proteins away from heterochromatin domains. In the course of studying atypical phenotypes associated with loss of H2B ubiquitylation/H3K4 methylation, we discovered that these modifications are also required for cell wall integrity at high temperatures. We identified the silencing protein Sir4 as a dosage suppressor of loss of H2B ubiquitylation, and we showed that elevated Sir4 expression suppresses cell wall integrity defects by inhibiting the function of the Sir silencing complex. Using comparative transcriptome analysis, we identified a set of euchromatic genes—enriched in those required for the cellular response to heat—whose expression is attenuated by loss of H2B ubiquitylation but restored by disruption of Sir function. Finally, using DNA adenine methyltransferase identification, we found that Sir3 and Sir4 associate with genes that are silenced in the absence of H3K4 methylation. Our data reveal that H2B ubiquitylation/H3K4 methylation play an important role in limiting ectopic association of silencing proteins with euchromatic genes important for cell wall integrity and the response to heat.
PhyloCSF: a comparative genomics method to distinguish protein coding and non-coding regions
Authors: Lin Michael F. , Jungreis Irwin , Kellis Manolis
Published: June 2011

Motivation: As high-throughput transcriptome sequencing provides evidence for novel transcripts in many species, there is a renewed need for accurate methods to classify small genomic regions as protein coding or non-coding. We present PhyloCSF, a novel comparative genomics method that analyzes a multispecies nucleotide sequence alignment to determine whether it is likely to represent a conserved protein-coding region, based on a formal statistical comparison of phylogenetic codon models.

Results: We show that PhyloCSF's classification performance in 12-species Drosophila genome alignments exceeds all other methods we compared in a previous study. We anticipate that this method will be widely applicable as the transcriptomes of many additional species, tissues and subcellular compartments are sequenced, particularly in the context of ENCODE and modENCODE, and as interest grows in long non-coding RNAs, often initially recognized by their lack of protein coding potential rather than conserved RNA secondary structures.

Availability and Implementation: The Objective Caml source code and executables for GNU/Linux and Mac OS X are freely available at http://compbio.mit.edu/PhyloCSF

Contact:  mlin@mit.edu; manoli@mit.edu
Tanglegrams for rooted phylogenetic trees and networks
Authors: Scornavacca Celine , Zickmann Franziska , Huson Daniel H.
Published: June 2011

Motivation: In systematic biology, one is often faced with the task of comparing different phylogenetic trees, in particular in multi-gene analysis or cospeciation studies. One approach is to use a tanglegram in which two rooted phylogenetic trees are drawn opposite each other, using auxiliary lines to connect matching taxa. There is an increasing interest in using rooted phylogenetic networks to represent evolutionary history, so as to explicitly represent reticulate events, such as horizontal gene transfer, hybridization or reassortment. Thus, the question arises how to define and compute a tanglegram for such networks.

Results: In this article, we present the first formal definition of a tanglegram for rooted phylogenetic networks and present a heuristic approach for computing one, called the NN-tanglegram method. We compare the performance of our method with existing tree tanglegram algorithms and also show a typical application to real biological datasets. For maximum usability, the algorithm does not require that the trees or networks are bifurcating or bicombining, or that they are on identical taxon sets.

Availability: The algorithm is implemented in our program Dendroscope 3, which is freely available from www.dendroscope.org.

Contact:  scornava@informatik.uni-tuebingen.de; huson@informatik.uni-tuebingen.de
Meta-IDBA: a de Novo assembler for metagenomic data
Authors: Peng Yu , Leung Henry C. M. , Yiu S. M. , Chin Francis Y. L.
Published: June 2011

Motivation: Next-generation sequencing techniques allow us to generate reads from a microbial environment in order to analyze the microbial community. However, assembling of a set of mixed reads from different species to form contigs is a bottleneck of metagenomic research. Although there are many assemblers for assembling reads from a single genome, there are no assemblers for assembling reads in metagenomic data without reference genome sequences. Moreover, the performances of these assemblers on metagenomic data are far from satisfactory, because of the existence of common regions in the genomes of subspecies and species, which make the assembly problem much more complicated.

Results: We introduce the Meta-IDBA algorithm for assembling reads in metagenomic data, which contain multiple genomes from different species. There are two core steps in Meta-IDBA. It first tries to partition the de Bruijn graph into isolated components of different species based on an important observation. Then, for each component, it captures the slight variants of the genomes of subspecies from the same species by multiple alignments and represents the genome of one species, using a consensus sequence. Comparison of the performances of Meta-IDBA and existing assemblers, such as Velvet and Abyss for different metagenomic datasets shows that Meta-IDBA can reconstruct longer contigs with similar accuracy.

Availability: Meta-IDBA toolkit is available at our website http://www.cs.hku.hk/~alse/metaidba.

Contact:  chin@cs.hku.hk
A folding algorithm for extended RNA secondary structures
Authors: zu Siederdissen Christian Höner , Bernhart Stephan H. , Stadler Peter F. , Hofacker Ivo L.
Published: June 2011

Motivation: RNA secondary structure contains many non-canonical base pairs of different pair families. Successful prediction of these structural features leads to improved secondary structures with applications in tertiary structure prediction and simultaneous folding and alignment.

Results: We present a theoretical model capturing both RNA pair families and extended secondary structure motifs with shared nucleotides using 2-diagrams. We accompany this model with a number of programs for parameter optimization and structure prediction.

Availability: All sources (optimization routines, RNA folding, RNA evaluation, extended secondary structure visualization) are published under the GPLv3 and available at www.tbi.univie.ac.at/software/rnawolf/.

Contact:  choener@tbi.univie.ac.at
Detecting epistatic effects in association studies at a genomic level based on an ensemble approach
Authors: Li Jing , Horstman Benjamin , Chen Yixuan
Published: June 2011

Motivation: Most complex diseases involve multiple genes and their interactions. Although genome-wide association studies (GWAS) have shown some success for identifying genetic variants underlying complex diseases, most existing studies are based on limited single-locus approaches, which detect single nucleotide polymorphisms (SNPs) essentially based on their marginal associations with phenotypes.

Results: In this article, we propose an ensemble approach based on boosting to study gene–gene interactions. We extend the basic AdaBoost algorithm by incorporating an intuitive importance score based on Gini impurity to select candidate SNPs. Permutation tests are used to control the statistical significance. We have performed extensive simulation studies using three interaction models to evaluate the efficacy of our approach at realistic GWAS sizes, and have compared it with existing epistatic detection algorithms. Our results indicate that our approach is valid, efficient for GWAS and on disease models with epistasis has more power than existing programs.

Contact:  jingli@case.edu
Detection and interpretation of metabolite–transcript coresponses using combined profiling data
Authors: Redestig Henning , Costa Ivan G.
Published: June 2011

Motivation: Studying the interplay between gene expression and metabolite levels can yield important information on the physiology of stress responses and adaptation strategies. Performing transcriptomics and metabolomics in parallel during time-series experiments represents a systematic way to gain such information. Several combined profiling datasets have been added to the public domain and they form a valuable resource for hypothesis generating studies. Unfortunately, detecting coresponses between transcript levels and metabolite abundances is non-trivial: they cannot be assumed to overlap directly with underlying biochemical pathways and they may be subject to time delays and obscured by considerable noise.

Results: Our aim was to predict pathway comemberships between metabolites and genes based on their coresponses to applied stress. We found that in the presence of strong noise and time-shifted responses, a hidden Markov model-based similarity outperforms the simpler Pearson correlation but performs comparably or worse in their absence. Therefore, we propose a supervised method that applies pathway information to summarize similarity statistics to a consensus statistic that is more informative than any of the single measures. Using four combined profiling datasets, we show that comembership between metabolites and genes can be predicted for numerous KEGG pathways; this opens opportunities for the detection of transcriptionally regulated pathways and novel metabolically related genes.

Availability: A command-line software tool is available at http://www.cin.ufpe.br/~igcf/Metabolites.

Contact:  henning@psc.riken.jp; igcf@cin.ufpe.br

Supplementary information:  Supplementary data are available at Bioinformatics online.
StructHDP: automatic inference of number of clusters and population structure from admixed genotype data
Authors: Shringarpure Suyash , Won Daegun , Xing Eric P.
Published: June 2011

Motivation: Clustering of genotype data is an important way of understanding similarities and differences between populations. A summary of populations through clustering allows us to make inferences about the evolutionary history of the populations. Many methods have been proposed to perform clustering on multilocus genotype data. However, most of these methods do not directly address the question of how many clusters the data should be divided into and leave that choice to the user.

Methods: We present StructHDP, which is a method for automatically inferring the number of clusters from genotype data in the presence of admixture. Our method is an extension of two existing methods, Structure and Structurama. Using a Hierarchical Dirichlet Process (HDP), we model the presence of admixture of an unknown number of ancestral populations in a given sample of genotype data. We use a Gibbs sampler to perform inference on the resulting model and infer the ancestry proportions and the number of clusters that best explain the data.

Results: To demonstrate our method, we simulated data from an island model using the neutral coalescent. Comparing the results of StructHDP with Structurama shows the utility of combining HDPs with the Structure model. We used StructHDP to analyze a dataset of 155 Taita thrush, Turdus helleri, which has been previously analyzed using Structure and Structurama. StructHDP correctly picks the optimal number of populations to cluster the data. The clustering based on the inferred ancestry proportions also agrees with that inferred using Structure for the optimal number of populations. We also analyzed data from 1048 individuals from the Human Genome Diversity project from 53 world populations. We found that the clusters obtained correspond with major geographical divisions of the world, which is in agreement with previous analyses of the dataset.

Availability: StructHDP is written in C++. The code will be available for download at http://www.sailing.cs.cmu.edu/structhdp.

Contact:  suyash@cs.cmu.edu; epxing@cs.cmu.edu
An integrative clustering and modeling algorithm for dynamical gene expression data
Authors: Sivriver Julia , Habib Naomi , Friedman Nir
Published: June 2011

Motivation: The precise dynamics of gene expression is often crucial for proper response to stimuli. Time-course gene-expression profiles can provide insights about the dynamics of many cellular responses, but are often noisy and measured at arbitrary intervals, posing a major analysis challenge.

Results: We developed an algorithm that interleaves clustering time-course gene-expression data with estimation of dynamic models of their response by biologically meaningful parameters. In combining these two tasks we overcome obstacles posed in each one. Moreover, our approach provides an easy way to compare between responses to different stimuli at the dynamical level. We use our approach to analyze the dynamical transcriptional responses to inflammation and anti-viral stimuli in mice primary dendritic cells, and extract a concise representation of the different dynamical response types. We analyze the similarities and differences between the two stimuli and identify potential regulators of this complex transcriptional response.

Availability: The code to our method is freely available http://www.compbio.cs.huji.ac.il/DynaMiteC.

Contact:  nir@cs.huji.ac.il
Systematic exploration of error sources in pyrosequencing flowgram data
Authors: Balzer Susanne , Malde Ketil , Jonassen Inge
Published: June 2011

Motivation: 454 pyrosequencing, by Roche Diagnostics, has emerged as an alternative to Sanger sequencing when it comes to read lengths, performance and cost, but shows higher per-base error rates. Although there are several tools available for noise removal, targeting different application fields, data interpretation would benefit from a better understanding of the different error types.

Results: By exploring 454 raw data, we quantify to what extent different factors account for sequencing errors. In addition to the well-known homopolymer length inaccuracies, we have identified errors likely to originate from other stages of the sequencing process. We use our findings to extend the flowsim pipeline with functionalities to simulate these errors, and thus enable a more realistic simulation of 454 pyrosequencing data with flowsim.

Availability: The flowsim pipeline is freely available under the General Public License from http://biohaskell.org/Applications/FlowSim.

Contact:  susanne.balzer@imr.no
Detection and Molecular Characterization of Boscalid-Resistant Botrytis cinerea Isolates from Strawberry
Authors: Veloukas Thomas , Leroch Michaela , Hahn Matthias , Karaoglanidis George S.
Published: June 2011

Botrytis cinerea isolates (n = 122) were collected from strawberry fields located in northern Greece during a 3-year period (2008–10) and tested for their sensitivity to the succinate dehydrogenase inhibitor boscalid. Sensitivity measurements showed three distinct phenotypes consisting of isolates highly sensitive (fungicide concentration causing inhibition of germ tube growth by 50% [EC50 values] of 0.05 to 0.21 μg ml–1), moderately resistant (EC50 values of 1.37 to 7.79 μg ml–1), or highly resistant (EC50 values of >50 μg ml–1) to boscalid. Sequence analysis of the sdhB gene revealed five mutations leading to amino acid substitutions in the SdhB subunit in isolates moderately resistant and highly resistant to boscalid. Three moderately resistant isolates showed a nucleotide change from A to T at codon 230, resulting in an asparagine to isoleucine (N230I) substitution. Several moderately resistant isolates showed a nucleotide change from C to T at codon 272, resulting in a substitution from histidine to arginine (H272R) whereas, in another set of isolates, a nucleotide change from A to G was found at the same codon, leading to a substitution from histidine to tyrosine (H272Y). One highly resistant isolate had a nucleotide change from A to T at codon 272, leading to a substitution from histidine to leucine (H272L), whereas, in three other highly resistant isolates, a double nucleotide change from CC to TT was observed at codon 225, resulting in a substitution from proline to phenylalanine (P225F). To facilitate rapid detection of these mutations associated with resistance to boscalid, a primer-introduced restriction analysis polymerase chain reaction was developed. The method was successfully applied to the moderately and highly resistant subpopulations and showed that the H272R mutation was predominant with relative frequencies of 28.5, 37.5, and 30% during 2008, 2009, and 2010, respectively. In contrast, the H272L mutation was detected at a frequency of 2.5% only in the 2009 population, whereas the P225F mutation was detected at a frequency of 7.5% only in the 2010 population.
A novel FK-506-binding-like protein that lacks peptidyl-prolyl isomerase activity is involved in intracellular infection and in vivo virulence of Burkholderia pseudomallei
Authors: Norville Isobel H. , Breitbach Katrin , Eske-Pogodda Kristin , Harmer Nicholas J. , Sarkar-Tyson Mitali , Titball Richard W. , Steinmetz Ivo
Published: June 2011

Burkholderia pseudomalleiis a facultative intracellular bacterial pathogen causing melioidosis, an often fatal infectious disease that is endemic in several tropical and subtropical areas around the world. We previously described a Ptk2 cell-based plaque assay screening system ofB. pseudomalleitransposon mutants that led to the identification of several novel virulence determinants. Using this approach we identified a mutant with reduced plaque formation in which theBPSL0918gene was disrupted.BPSL0918encodes a putative FK-506-binding protein (FKBP) representing a family of proteins that typically possess peptidyl-prolyl isomerase (PPIase) activity. AB. pseudomalleiΔBPSL0918mutant showed a severely impaired ability to resist intracellular killing and to replicate within primary macrophages. Complementation of the mutant fully restored its ability to grow intracellularly. Moreover,B. pseudomalleiΔBPSL0918was significantly attenuated in a murine model of infection. Structural modelling confirmed a modified FKBP fold of theBPSL0918-encoded protein but unlike virulence-associated FKBPs from other pathogenic bacteria, recombinant BPSL0918 protein did not possess PPIase activityin vitro. In accordance with this observation BPSL0918 exhibits several mutations in residues that have been proposed to mediate PPIase activity in other FKBPs. To our knowledge thisB. pseudomalleiFKBP represents the first example of this protein family which lacks PPIase activity but is important in intracellular infection of a bacterial pathogen.
Exclusion of synaptotagmin V at the phagocytic cup by Leishmania donovani lipophosphoglycan results in decreased promastigote internalization
Authors: Vinet Adrien F. , Jananji Silvana , Turco Salvatore J. , Fukuda Mitsunori , Descoteaux Albert
Published: June 2011

Regulators of membrane fusion play an important role in phagocytosis, as they regulate the focal delivery of endomembrane that is required for optimal internalization of large particles. During internalization ofLeishmaniapromastigotes, the surface glycolipid lipophosphoglycan (LPG) is transferred to the macrophage membrane and modifies its fusogenic properties. In this study, we investigated the impact of LPG on the recruitment of the exocytosis regulator synaptotagmin V (Syt V) at the area of internalization and on the early steps of phagocytosis. UsingLeishmania donovaniLPG-defective mutants and LPG-coated particles, we established that LPG reduces the phagocytic capacity of macrophages and showed that it causes exclusion of Syt V from the nascent phagosome. Silencing of Syt V inhibited phagocytosis to the same extent as LPG, and these effects were not cumulative, consistent with a Syt V-dependent mechanism for the inhibition of phagocytosis by LPG. Previous work has revealed that LPG-mediated exclusion of Syt V from phagosomes prevents the recruitment of the vacuolar ATPase and acidification. Thus, whereas exclusion of Syt V from phagosomes in the process of formation may be beneficial for the creation of a hospitable intracellular niche, it reduces the phagocytic capacity of macrophages. We propose that the cost associated with a reduced internalization rate may be compensated by increased survival, and could lead to a greater overall parasite fitness.
The effect of an educational programme on attitudes of nurses and medical residents towards the benefits of positive communication and collaboration
Authors: McCaffrey Ruth , Hayes Rose Marie , Cassell Asenath , Miller‐Reyes Sharmin , Donaldson Audeane , Ferrell Cheryl
Published: June 2011

mccaffrey r., hayes r.m., cassell a., miller‐reyes s., donaldson a. & ferrell c. (2012) The effect of an educational programme on attitudes of nurses and medical residents towards the benefits of positive communication and collaboration. Journal of Advanced Nursing 68(2), 293–301.

Aims.  This article is a report of a study to determine the effect of an educational programme and to follow up weekly meetings on nurses and medical resident’s attitudes towards positive communication and collaboration.

Background.  Clear and appropriate communication and interdisciplinary collaboration is critical to the delivery of quality care. Collaborative practice among all healthcare professionals creates a positive work environment, decreases costs, improves job satisfaction among nurses and improves patient care, as well as decreasing patient morbidity and mortality. Poor communication and lack of teamwork or collaboration have been cited as persistent problems in healthcare.

Method.  The study was conducted in 2008 ‐ 2009 at a hospital where a new medical residency programme was beginning and nurses had no prior experience working with medical residents. A quasi‐experimental pre test, post‐test design was used. The Jefferson Scale of Attitudes towards Physician‐Nurse Collaboration and the Communication, Collaboration and Critical Thinking for Quality Patient Outcomes Survey tool measured the attitudes of 68 nurses and 47 medical residents in the areas of positive communication and collaboration.

Results/Findings.  The study demonstrates that a formal educational programme and follow‐up discussions improved the attitudes of both nurses and medical residents on the Jefferson scale (medical residents t = 4·68, P = 0·001, nurses t = 4·37, P = 0·001) and on the communication scale (medical residents t = 4·23, P = 0·001, nurses t = 4·13, P = 0·001).

Conclusion.  Continuing education for nurses, medical residents and other healthcare providers may assist in developing positive communication styles and promote collegiality and team work.