bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct generation of 20 W peak power picosecond optical pulses from an external-cavity mode-locked GaInN laser diode incorporating a flared waveguide
Authors: Oki Tomoyuki , Koda Rintaro , Kono Shunsuke , Miyajima Takao , Watanabe Hideki , Kuramoto Masaru , Ikeda Masao , Yokoyama Hiroyuki
Published: September 2011

We directly generated 1.6-ps optical pulses with a peak power of 20 W at a repetition of 1 GHz using a blue-violet GaInN mode-locked laser diode incorporating a flared waveguide operating in single transverse mode. The flared waveguide enabled optical pulses to be generated with peak powers of over six times higher than those produced using a straight waveguide while preserving the pulse duration.
Functional characterization of bacterial sRNAs using a network biology approach
Authors: Modi Sheetal R. , Camacho Diogo M. , Kohanski Michael A. , Walker Graham C. , Collins James J.
Published: August 2011

Small RNAs (sRNAs) are important components of posttranscriptional regulation. These molecules are prevalent in bacterial and eukaryotic organisms, and involved in a variety of responses to environmental stresses. The functional characterization of sRNAs is challenging and requires highly focused and extensive experimental procedures. Here, using a network biology approach and a compendium of gene expression profiles, we predict functional roles and regulatory interactions for sRNAs in
Escherichia coli
. We experimentally validate predictions for three sRNAs in our inferred network: IsrA, GlmZ, and GcvB. Specifically, we validate a predicted role for IsrA and GlmZ in the SOS response, and we expand on current knowledge of the GcvB sRNA, demonstrating its broad role in the regulation of amino acid metabolism and transport. We also show, using the inferred network coupled with experiments, that GcvB and Lrp, a transcription factor, repress each other in a mutually inhibitory network. This work shows that a network-based approach can be used to identify the cellular function of sRNAs and characterize the relationship between sRNAs and transcription factors.
Relaxed selection is a precursor to the evolution of phenotypic plasticity
Authors: Hunt Brendan G. , Ometto Lino , Wurm Yannick , Shoemaker DeWayne , Yi Soojin V. , Keller Laurent , Goodisman Michael A. D.
Published: September 2011

Phenotypic plasticity allows organisms to produce alternative phenotypes under different conditions and represents one of the most important ways by which organisms adaptively respond to the environment. However, the relationship between phenotypic plasticity and molecular evolution remains poorly understood. We addressed this issue by investigating the evolution of genes associated with phenotypically plastic castes, sexes, and developmental stages of the fire ant
Solenopsis invicta
. We first determined if genes associated with phenotypic plasticity in
S. invicta
evolved at a rapid rate, as predicted under theoretical models. We found that genes differentially expressed between
S. invicta
castes, sexes, and developmental stages all exhibited elevated rates of evolution compared with ubiquitously expressed genes. We next investigated the evolutionary history of genes associated with the production of castes. Surprisingly, we found that orthologs of caste-biased genes in
S. invicta
and the social bee
Apis mellifera
evolved rapidly in lineages without castes. Thus, in contrast to some theoretical predictions, our results suggest that rapid rates of molecular evolution may not arise primarily as a consequence of phenotypic plasticity. Instead, genes evolving under relaxed purifying selection may more readily adopt new forms of biased expression during the evolution of alternate phenotypes. These results suggest that relaxed selective constraint on protein-coding genes is an important and underappreciated element in the evolutionary origin of phenotypic plasticity.
Radiocarbon-dated archaeological record of early first millennium B.C. mounted pastoralists in the Kunlun Mountains, China
Authors: Wagner Mayke , Wu Xinhua , Tarasov Pavel , Aisha Ailijiang , Ramsey Christopher Bronk , Schultz Michael , Schmidt-Schultz Tyede , Gresky Julia
Published: September 2011

Pastoral nomadism, as a successful economic and social system drawing on mobile herding, long-distance trade, and cavalry warfare, affected all polities of the Eurasian continent. The role that arid Inner Asia, particularly the areas of northwestern China, Kazakhstan, and Mongolia, played in the emergence of this phenomenon remains a fundamental and still challenging question in prehistoric archaeology of the Eurasian steppes. The cemetery of Liushiu (Xinjiang, China) reveals burial features, bronze bridle bits, weaponry, adornment, horse skulls, and sheep/goat bones, which, together with paleopathological changes in human skeletons, indicate the presence of mobile pastoralists and their flocks at summer pastures in the Kunlun Mountains, ∼2,850 m above sea level. Radiocarbon dates place the onset of the burial activity between 1108 and 893 B.C. (95% probability range) or most likely between 1017 and 926 B.C. (68%). These data from the Kunlun Mountains show a wider frontier within the diversity of mobile pastoral economies of Inner Asia and support the concept of multiregional transitions toward Iron Age complex pastoralism and mounted warfare.
Identification and mechanism of regulation of the zebrafish dorsal determinant
Authors: Lu Fu-I , Thisse Christine , Thisse Bernard
Published: September 2011

In vertebrates, the animal–vegetal axis is determined during oogenesis and at ovulation, the egg is radially symmetric. In anamniotes, following fertilization, a microtubule-dependent movement leads to the displacement of maternal dorsal determinants from the vegetal pole to the future dorsal side of the embryo, providing the initial breaking of radial symmetry [Weaver C, Kimelman D (2004)
Development
131:3491–3499]. These dorsal determinants induce β-catenin nuclear translocation in dorsal cells of the blastula. Previous work in amphibians has shown that secreted Wnt11/5a complexes, regulated by the Wnt antagonist Dkk-1, are required for the initiation of embryonic axis formation [Cha et al. (2009)
Curr Biol
29:1573–1580]. In the current study, we determined that the vegetal maternal dorsal determinant in fish is not the Wnt11/5a complex but the canonical Wnt, Wnt8a. Translation of this mRNA and secretion of the Wnt8a protein result in a dorsal-to-ventral gradient of Wnt stimulation, extending across the entire embryo. This gradient is counterbalanced by two Wnt inhibitors, Sfrp1a and Frzb. These proteins are essential to restrict the activation of the canonical Wnt pathway to the dorsal marginal blastomeres by defining the domain where the Wnt8a activity gradient is above the threshold value necessary for triggering the canonical β-catenin pathway. In summary, this study establishes that the zebrafish maternal dorsal determinant, Wnt8a, is required to localize the primary dorsal center, and that the extent of this domain is defined by the activity of two maternally provided Wnt antagonists, Sfrp1a and Frzb.
Chemical modulation of memory formation in larval zebrafish
Authors: Wolman Marc A. , Jain Roshan A. , Liss Laura , Granato Michael
Published: August 2011

Whole organism–based small-molecule screens have proven powerful in identifying novel therapeutic chemicals, yet this approach has not been exploited to identify new cognitive enhancers. Here we present an automated high-throughput system for measuring nonassociative learning behaviors in larval zebrafish. Using this system, we report that spaced training blocks of repetitive visual stimuli elicit protein synthesis–dependent long-term habituation in larval zebrafish, lasting up to 24 h. Moreover, repetitive acoustic stimulation induces robust short-term habituation that can be modulated by stimulation frequency and instantaneously dishabituated through cross-modal stimulation. To characterize the neurochemical pathways underlying short-term habituation, we screened 1,760 bioactive compounds with known targets. Although we found extensive functional conservation of short-term learning between larval zebrafish and mammalian models, we also discovered several compounds with previously unknown roles in learning. These compounds included a myristic acid analog known to interact with Src family kinases and an inhibitor of cyclin dependent kinase 2, demonstrating that high-throughput chemical screens combined with high-resolution behavioral assays provide a powerful approach for the discovery of novel cognitive modulators.
Forced expression of laminin β1 in podocytes prevents nephrotic syndrome in mice lacking laminin β2, a model for Pierson syndrome
Authors: Suh Jung Hee , Jarad George , VanDeVoorde Rene G. , Miner Jeffrey H.
Published: August 2011

Pierson syndrome is a congenital nephrotic syndrome with ocular and neurological defects caused by mutations in
LAMB2
, the gene encoding the basement membrane protein laminin β2 (Lamβ2). It is the kidney glomerular basement membrane (GBM) that is defective in Pierson syndrome, as Lamβ2 is a component of laminin-521 (LM-521; α5β2γ1), the major laminin in the mature GBM. In both Pierson syndrome and the

Lamb2
−/−

mouse model for this disease, laminin β1 (Lamβ1), a structurally similar homolog of Lamβ2, is marginally increased in the GBM, but it fails to fully compensate for the loss of Lamβ2, leading to the filtration barrier defects and nephrotic syndrome. Here we generated several lines of Lamβ1 transgenic mice and used them to show that podocyte-specific Lamβ1 expression in
Lamb2
−/−
mice abrogates the development of nephrotic syndrome, correlating with a greatly extended lifespan. In addition, the more Lamβ1 was expressed, the less urinary albumin was excreted. Transgenic Lamβ1 expression increased the level of Lamα5 in the GBM of rescued mice, consistent with the desired increased deposition of laminin-511 (α5β1γ1) trimers. Ultrastructural analysis revealed occasional knob-like subepithelial GBM thickening but intact podocyte foot processes in aged rescued mice. These results suggest the possibility that up-regulation of
LAMB1
in podocytes, should it become achievable, would likely lessen the severity of nephrotic syndrome in patients carrying
LAMB2
mutations.
Mapping the receptor site for α-scorpion toxins on a Na
+
channel voltage sensor
Authors: Wang Jinti , Yarov-Yarovoy Vladimir , Kahn Roy , Gordon Dalia , Gurevitz Michael , Scheuer Todd , Catterall William A.
Published: August 2011

The α-scorpions toxins bind to the resting state of Na
+
channels and inhibit fast inactivation by interaction with a receptor site formed by domains I and IV. Mutants T1560A, F1610A, and E1613A in domain IV had lower affinities for
Leiurus quinquestriatus hebraeus
toxin II (LqhII), and mutant E1613R had ∼73-fold lower affinity. Toxin dissociation was accelerated by depolarization and increased by these mutations, whereas association rates at negative membrane potentials were not changed. These results indicate that Thr1560 in the S1-S2 loop, Phe1610 in the S3 segment, and Glu1613 in the S3-S4 loop in domain IV participate in toxin binding. T393A in the SS2-S6 loop in domain I also had lower affinity for LqhII, indicating that this extracellular loop may form a secondary component of the receptor site. Analysis with the Rosetta-Membrane algorithm resulted in a model of LqhII binding to the voltage sensor in a resting state, in which amino acid residues in an extracellular cleft formed by the S1-S2 and S3-S4 loops in domain IV interact with two faces of the wedge-shaped LqhII molecule. The conserved gating charges in the S4 segment are in an inward position and form ion pairs with negatively charged amino acid residues in the S2 and S3 segments of the voltage sensor. This model defines the structure of the resting state of a voltage sensor of Na
+
channels and reveals its mode of interaction with a gating modifier toxin.
Dynamics and control of state-dependent networks for probing genomic organization
Authors: Rajapakse Indika , Groudine Mark , Mesbahi Mehran
Published: September 2011

A state-dependent dynamic network is a collection of elements that interact through a network, whose geometry evolves as the state of the elements changes over time. The genome is an intriguing example of a state-dependent network, where chromosomal geometry directly relates to genomic activity, which in turn strongly correlates with geometry. Here we examine various aspects of a genomic state-dependent dynamic network. In particular, we elaborate on one of the important ramifications of viewing genomic networks as being state-dependent, namely, their controllability during processes of genomic reorganization such as in cell differentiation.
Expanded functions for a family of plant intracellular immune receptors beyond specific recognition of pathogen effectors
Authors: Bonardi Vera , Tang Saijun , Stallmann Anna , Roberts Melinda , Cherkis Karen , Dangl Jeffery L.
Published: September 2011

Plants and animals deploy intracellular immune receptors that perceive specific pathogen effector proteins and microbial products delivered into the host cell. We demonstrate that the ADR1 family of
Arabidopsis
nucleotide-binding leucine-rich repeat (NB-LRR) receptors regulates accumulation of the defense hormone salicylic acid during three different types of immune response: (
i
) ADRs are required as “helper NB-LRRs” to transduce signals downstream of specific NB-LRR receptor activation during effector-triggered immunity; (
ii
) ADRs are required for basal defense against virulent pathogens; and (
iii
) ADRs regulate microbial-associated molecular pattern-dependent salicylic acid accumulation induced by infection with a disarmed pathogen. Remarkably, these functions do not require an intact P-loop motif for at least one ADR1 family member. Our results suggest that some NB-LRR proteins can serve additional functions beyond canonical, P-loop–dependent activation by specific virulence effectors, extending analogies between intracellular innate immune receptor function from plants and animals.
CENP-C recruits M18BP1 to centromeres to promote CENP-A chromatin assembly
Authors: Moree Ben , Meyer Corey B. , Fuller Colin J. , Straight Aaron F.
Published: September 2011

Eukaryotic chromosomes segregate by attaching to microtubules of the mitotic spindle through a chromosomal microtubule binding site called the kinetochore. Kinetochores assemble on a specialized chromosomal locus termed the centromere, which is characterized by the replacement of histone H3 in centromeric nucleosomes with the essential histone H3 variant CENP-A (centromere protein A). Understanding how CENP-A chromatin is assembled and maintained is central to understanding chromosome segregation mechanisms. CENP-A nucleosome assembly requires the Mis18 complex and the CENP-A chaperone HJURP. These factors localize to centromeres in telophase/G1, when new CENP-A chromatin is assembled. The mechanisms that control their targeting are unknown. In this paper, we identify a mechanism for recruiting the Mis18 complex protein M18BP1 to centromeres. We show that depletion of CENP-C prevents M18BP1 targeting to metaphase centromeres and inhibits CENP-A chromatin assembly. We find that M18BP1 directly binds CENP-C through conserved domains in the CENP-C protein. Thus, CENP-C provides a link between existing CENP-A chromatin and the proteins required for new CENP-A nucleosome assembly.
SPREAD: spatial phylogenetic reconstruction of evolutionary dynamics
Authors: Bielejec Filip , Rambaut Andrew , Suchard Marc A. , Lemey Philippe
Published: September 2011

Summary: SPREAD is a user-friendly, cross-platform application to analyze and visualize Bayesian phylogeographic reconstructions incorporating spatial–temporal diffusion. The software maps phylogenies annotated with both discrete and continuous spatial information and can export high-dimensional posterior summaries to keyhole markup language (KML) for animation of the spatial diffusion through time in virtual globe software. In addition, SPREAD implements Bayes factor calculation to evaluate the support for hypotheses of historical diffusion among pairs of discrete locations based on Bayesian stochastic search variable selection estimates. SPREAD takes advantage of multicore architectures to process large joint posterior distributions of phylogenies and their spatial diffusion and produces visualizations as compelling and interpretable statistical summaries for the different spatial projections.

Availability: SPREAD is licensed under the GNU Lesser GPL and its source code is freely available as a GitHub repository: https://github.com/phylogeography/SPREAD

Contact:  filip.bielejec@rega.kuleuven.be
Impact of activated vitamin D on insulin resistance in nondiabetic chronic kidney disease patients
Authors: Friedman David J. , Bhatt Nisha , Hayman Najwah S. , Nichols Brendan J. , Herman Mark , Nikolaev Nikolay , Danziger John
Published: September 2011

Background

Although vitamin D deficiency has been associated with increased insulin resistance, a causal link has not been established. Interpreting the relationship has been confounded by a close correlation between vitamin D deficiency and obesity. The current clinical approach of assessing endogenous 25‐hydroxyvitamin D (25(OH)D) concentrations in patients with chronic kidney disease (CKD), and independently administering activated vitamin D (AD), allows a unique opportunity to clarify cause and effect in the relationship of vitamin D, obesity and insulin resistance.

Methods  We assessed how 25(OH)D and body mass index (BMI) related to fasting insulin concentrations in 120 nondiabetic patients with CKD. In addition, we described how treatment with AD modified these relationships.

Results  In the full cohort, fasting insulin concentrations varied inversely with both 25(OH)D (r = −0·22, P = 0·02) and BMI (r = −0·36, P < 0·0001). The administration of AD altered these relationships. In individuals treated with AD, there was no association between 25(OH)D and fasting insulin, and the mean fasting insulin concentrations were significantly lower than in those not receiving AD (40·5 ± 22·0 vs 54·1 ± 30·9 pm, P = 0·01). In a multivariate analysis, both AD treatment and BMI were independent predictors of fasting insulin. Furthermore, obese patients treated with AD had insulin concentrations similar to nonobese patients (46·1 ± 24·9 vs 40·2 ± 21·5 pm), whereas untreated obese patients had markedly higher fasting insulin concentrations (74·4 ± 33·4 pm, P = 0·003).

Conclusion  25(OH)D deficiency is associated with insulin resistance in CKD. Replacement with pharmacologic doses of AD is associated with lower fasting insulin concentrations, especially in obese patients.
Intron retention regulates the expression of pectin methyl esterase inhibitor (Pmei) genes during wheat growth and development
Authors: Rocchi V. , Janni M. , Bellincampi D. , Giardina T. , D’Ovidio R.
Published: September 2011

Pectin is an important component of the plant cell wall and its remodelling occurs during normal plant growth or following stress responses. Pectin is secreted into the cell wall in a highly methyl‐esterified form and subsequently de‐methyl‐esterified by pectin methyl esterase (PME), whose activity is controlled by the pectin methyl esterase inhibitor protein (PMEI). Cereal cell wall contains a low amount of pectin; nonetheless the level and pattern of pectin methyl esterification play a primary role during development or pathogen infection. Since few data are available on the role of PMEI in plant development and defence of cereal species, we isolated and characterised three Pmei genes (Tdpmei2.1, Tdpmei2.2 and Tdpmei3) and their encoded products in wheat. Sequence comparisons showed a low level of intra‐ and inter‐specific sequence conservation of PMEIs. Tdpmei2.1 and Tdpmei2.2 share 94% identity at protein level, but only 20% identity with the product of Tdpmei3. All three Tdpmei genes code for functional inhibitors of plant PMEs and do not inhibit microbial PMEs or a plant invertase. RT‐PCR analyses demonstrated, for the first time to our knowledge, that Pmei genes are regulated by intron retention. Processed and unprocessed transcripts of Tdpmei2.1 and Tdpmei2.2 accumulated in several organs, but anthers contained only mature transcripts. Tdpmei3 lacks introns and its transcript accumulated mainly in stem internodes. These findings suggest that products encoded by these Tdpmei genes control organ‐ or tissue‐specific activity of specific PME isoforms in wheat.
Rapid identification of fungal pathogens by rolling circle amplification using Fonsecaea as a model
Authors: Najafzadeh M. J. , Sun J. , Vicente V. A. , de Hoog G. S.
Published: September 2011

We aimed to describe a rapid and sensitive assay for identification of pathogenic fungi without sequencing. The method of rolling circle amplification (RCA) is presented with species of Fonsecaea, agents of human chromoblastomycosis, as a model. The internal transcribed spacer (ITS) rDNA region of 103 Fonsecaea strains was sequenced and aligned in view of designing three specific padlock probes to be used for the detection of single nucleotide polymorphisms in three Fonsecaea species. The 38 strains included for testing the specificity of RCA comprised 17 isolates of Fonsecaea pedrosoi, 13 of Fonsecaea monophora and eight of Fonsecaea nubica. The assay successfully amplified DNA of the target fungi at the level of species, while no cross reactivity was observed. The amplification product was visualised on a 1% agarose gel to verify the specificity of probe–template binding. Amounts of reagents were minimised to avoid the generation of false‐positive results. The simplicity, sensitivity, robustness and low costs provide RCA a distinct position among isothermal techniques for DNA diagnostics as a very practical identification method.
Mucins in inflammatory bowel diseases and colorectal cancer
Authors: Sheng Yong H , Hasnain Sumaira Z , Florin Timothy H J , McGuckin Michael A
Published: September 2011

The gastrointestinal tract is protected by a mucus barrier with both secreted and cell‐surface mucins contributing to the exclusion of luminal microbes and toxins. Alterations in the structure and/or quantity of mucins alter the barrier function of mucus and could play roles in initiating and maintaining mucosal inflammation in inflammatory bowel diseases (IBD), and in driving cancer development in the intestine. The aim of this review is to focus on the roles of the mucins in IBD. The polymorphisms of mucin genes that have been associated with susceptibility to IBD, and alterations in mucin expression as well as factors that regulate production of the mucins in IBD, are summarized. Data from animal models of intestinal inflammation, which support the importance of mucins in IBD and cancer development, are also discussed.
Optimal conservation investment for a biodiversity‐rich agricultural landscape*
Authors: White Ben , Sadler Rohan
Published: September 2011

This study develops a theoretical and empirical framework for optimal conservation planning using satellite land cover data and economic data from a farm survey. A case study is presented for a region within the South‐west Australia Biodiversity Hotspot (Nature403, 853). This Biodiversity Hotspot is a focus for conservation investment as it combines a relatively high level of biodiversity with severe threat to the biodiversity from agriculture. The conservation planning model developed determines the optimal set of bush fragments for conservation. This model can also be used to assess the trade‐off between the budget and a vegetation species metric. Results from the case study show that, without an effective conservation scheme that at least fences fragments, significant plant biodiversity losses will occur in the North East Wheatbelt Regional Organisation of Councils region of the WA wheatbelt over a 10‐year period. A perfect price discriminating auction scheme could reduce the costs of conservation by around 17 per cent relative to a fixed‐payment scheme; however, a fixed payment on outcome (measured as change in the species metric) scheme represents a viable second‐best alternative, to a conservation auction, where conservation spending is spatially targeted.
MANAGING CITIZENS' EXPECTATIONS OF PUBLIC SERVICE PERFORMANCE: EVIDENCE FROM OBSERVATION AND EXPERIMENTATION IN LOCAL GOVERNMENT
Authors: JAMES OLIVER
Published: September 2011

Citizens' expectations of public service performance influence their attitudes and behaviour towards services, including satisfaction, choice of service and political voice about them. However, there has been little research on what sets expectations. This paper assesses the effects of prior service performance and information about prior performance on two forms of citizen expectations, positive expectations of what performance will be and normative expectations of what performance should be. In an observational study, prior performance is positively related to expectations of what performance will be. Prior performance is positively related to high normative expectations but is unrelated to low normative expectations. The resilience of normative expectations suggests that poor performance will trigger dissatisfaction and citizen response rather than lowering expectations creating passive acceptance. In a field experiment, performance information effects are found for positive but not normative expectations. Providing information about excellent performance raises positive expectations and providing information about poor performance lowers positive expectations; negativity bias is evident with information about poor performance having a larger effect. Performance information that is credible to citizens can be used to manage citizens' positive expectations but their normative expectations are less amenable to influence by this route.
Agentic or Communal? Associations between Interpersonal Goals, Popularity, and Bullying in Middle Childhood and Early Adolescence
Authors: Caravita Simona C. S. , Cillessen Antonius H. N.
Published: September 2011

This study investigated whether perceived popularity mediates and/or moderates the association between agentic goals and bullying, and whether sociometric popularity mediates and/or moderates the association between communal goals and bullying. Age and gender differences were also examined. Participants were 276 fourth and fifth graders (middle childhood sample) and 196 seventh and eighth graders (early adolescence sample). Peer status and bullying were assessed with sociometric measures, interpersonal goals with self‐reports. The theoretical model included both mediation and moderation effects. An age‐related reversal was found in how status mediated the associations between goals and bullying. Sociometric popularity mediated the association of agentic goals with bullying in middle childhood but of communal goals with bullying in early adolescence. Perceived popularity mediated the association of communal goals with bullying in middle childhood but of agentic goals with bullying in early adolescence. In middle childhood, perceived popularity also moderated the effect of agentic goals on bullying. The results were discussed in terms of the role of bullying as a means to enhance status in early adolescence.
Effects of atorvastatin metabolites on induction of drug‐metabolizing enzymes and membrane transporters through human pregnane X receptor
Authors: Hoffart E , Ghebreghiorghis L , Nussler AK , Thasler WE , Weiss TS , Schwab M , Burk O
Published: September 2011

BACKGROUND AND PURPOSE Atorvastatin metabolites differ in their potential for drug interaction because of differential inhibition of drug‐metabolizing enzymes and transporters. We here investigate whether they exert differential effects on the induction of these genes via activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR).

EXPERIMENTAL APPROACH Ligand binding to PXR or CAR was analysed by mammalian two‐hybrid assembly and promoter/reporter gene assays. Additionally, surface plasmon resonance was used to analyse ligand binding to CAR. Primary human hepatocytes were treated with atorvastatin metabolites, and mRNA and protein expression of PXR‐regulated genes was measured. Two‐hybrid co‐activator interaction and co‐repressor release assays were utilized to elucidate the molecular mechanism of PXR activation.

KEY RESULTS All atorvastatin metabolites induced the assembly of PXR and activated CYP3A4 promoter activity. Ligand binding to CAR could not be proven. In primary human hepatocytes, the para‐hydroxy metabolite markedly reduced or abolished induction of cytochrome P450 and transporter genes. While significant differences in co‐activator recruitment were not observed, para‐hydroxy atorvastatin demonstrated only 50% release of co‐repressors.

CONCLUSIONS AND IMPLICATIONS Atorvastatin metabolites are ligands of PXR but not of CAR. Atorvastatin metabolites demonstrate differential induction of PXR target genes, which results from impaired release of co‐repressors. Consequently, the properties of drug metabolites have to be taken into account when analysing PXR‐dependent induction of drug metabolism and transport. The drug interaction potential of the active metabolite, para‐hydroxy atorvastatin, might be lower than that of the parent compound.
Roflumilast inhibits the release of chemokines and TNF‐α from human lung macrophages stimulated with lipopolysaccharide
Authors: Buenestado A , Grassin‐Delyle S , Guitard F , Naline E , Faisy C , Israël‐Biet D , Sage E , Bellamy JF , Tenor H , Devillier P
Published: September 2011

BACKGROUND AND PURPOSE Lung macrophages are critically involved in respiratory diseases. This study assessed the effects of the PDE4 inhibitor roflumilast and its active metabolite, roflumilast N‐oxide on the release of a range of chemokines (CCL2, 3, 4, CXCL1, 8, 10) and of TNF‐α, from human lung macrophages, stimulated with bacterial lipopolysaccharide LPS.

EXPERIMENTAL APPROACH Lung macrophages isolated from resected human lungs were incubated with roflumilast, roflumilast N‐oxide, PGE2, the COX inhibitor indomethacin, the COX‐2 inhibitor NS‐398 or vehicle and stimulated with LPS (24 h). Chemokines, TNF‐α, PGE2 and 6‐keto PGF1α were measured in culture supernatants by immunoassay. COX‐2 mRNA expression was assessed with RT‐qPCR. PDE activities were determined in macrophage homogenates.

KEY RESULTS Expression of PDE4 in lung macrophages was increased after incubation with LPS. Roflumilast and roflumilast N‐oxide concentration‐dependently reduced the LPS‐stimulated release of CCL2, CCL3, CCL4, CXCL10 and TNF‐α from human lung macrophages, whereas that of CXCL1 or CXCL8 was not altered. This reduction by the PDE4 inhibitors was further accentuated by exogenous PGE2 (10 nM) but abolished in the presence of indomethacin or NS‐398. Conversely, addition of PGE2 (10 nM), in the presence of indomethacin restored inhibition by roflumilast. LPS also increased PGE2 and 6‐keto PGF1α release from lung macrophages which was associated with an up‐regulation of COX‐2 mRNA.

CONCLUSIONS AND IMPLICATIONS Roflumilast and roflumilast N‐oxide reduced LPS‐induced release of CCL2, 3, 4, CXCL10 and TNF‐α in human lung macrophages.
A NEW LOOK AT AN ANCIENT ORDER: GENERIC REVISION OF THE BANGIALES (RHODOPHYTA)1
Authors: Sutherland Judith E. , Lindstrom Sandra C. , Nelson Wendy A. , Brodie Juliet , Lynch Michael D. J. , Hwang Mi Sook , Choi Han‐Gu , Miyata Masahiko , Kikuchi Norio , Oliveira Mariana C. , Farr Tracy , Neefus Chris , Mols‐Mortensen Agnes , Milstein Daniela , Müller Kirsten M.
Published: September 2011

The red algal order Bangiales has been revised as a result of detailed regional studies and the development of expert local knowledge of Bangiales floras, followed by collaborative global analyses based on wide taxon sampling and molecular analyses. Combined analyses of the nuclear SSU rRNA gene and the plastid RUBISCO LSU (rbcL) gene for 157 Bangiales taxa have been conducted. Fifteen genera of Bangiales, seven filamentous and eight foliose, are recognized. This classification includes five newly described and two resurrected genera. This revision constitutes a major change in understanding relationships and evolution in this order. The genus Porphyra is now restricted to five described species and a number of undescribed species. Other foliose taxa previously placed in Porphyra are now recognized to belong to the genera Boreophyllum gen. nov., Clymene gen. nov., Fuscifolium gen. nov., Lysithea gen. nov., Miuraea gen. nov., Pyropia, and Wildemania. Four of the seven filamentous genera recognized in our analyses already have generic names (Bangia, Dione, Minerva, and Pseudobangia), and are all currently monotypic. The unnamed filamentous genera are clearly composed of multiple species, and few of these species have names. Further research is required: the genus to which the marine taxon Bangia fuscopurpurea belongs is not known, and there are also a large number of species previously described as Porphyra for which nuclear SSU ribosomal RNA (nrSSU) or rbcL sequence data should be obtained so that they can be assigned to the appropriate genus.
Categorizing the Effect of Comorbidity: A Qualitative Study of Individuals’ Experiences in a Low‐Vision Rehabilitation Program
Authors: Whitson Heather E. , Steinhauser Karen , Ammarell Natalie , Whitaker Diane , Cousins Scott W. , Ansah Deidra , Sanders Linda L. , Cohen Harvey J.
Published: September 2011

Objectives

To identify generalizable ways that comorbidity affects older adults’ experiences in a health service program directed toward an index condition and to develop a framework to assist clinicians in approaching comorbidity in the design, delivery, and evaluation of such interventions.

Design

A qualitative data content analysis of interview transcripts to identify themes related to comorbidity.

Setting

An outpatient low‐vision rehabilitation program for macular disease.

Participants

In 2007/08, 98 individuals undergoing low‐vision rehabilitation and their companions provided 624 semistructured interviews that elicited perceptions about barriers and facilitators of successful program participation.

Results

The interviews revealed five broad themes about comorbidity: (i) “good days, bad days,” reflecting participants’ fluctuating health status during the program because of concurrent medical problems; (ii) “communication barriers.” which were sometimes due to participant impairments and sometimes situational; (iii) “overwhelmed,” which encompassed pragmatic and emotional concerns of participants and caregivers; (iv) “delays,” which referred to the tendency of comorbidities to delay progress in the program and to confer added inconvenience during lengthy appointments; and (v) value of companion involvement in overcoming some barriers imposed by comorbid conditions.

Conclusion

This study provides a taxonomy and conceptual framework for understanding consequences of comorbidity in the experience of individuals receiving a health service. If confirmed in individuals receiving interventions for other index diseases, the framework suggests actionable items to improve care and facilitate research involving older adults.
Mechanical Esophageal Displacement During Catheter Ablation for Atrial Fibrillation
Authors: KORUTH JACOB S. , REDDY VIVEK Y. , MILLER MARC A. , PATEL KALPESH K. , COFFEY JAMES O. , FISCHER AVI , GOMES J. ANTHONY , DUKKIPATI SRINIVAS , D’AVILA ANDRE , MITTNACHT ALEXANDER
Published: September 2011

Esophageal Deviation in AF Ablation.Objective:To determine the feasibility and safety of esophageal displacement during atrial fibrillation (AF) ablation, to prevent thermal injury.

Background:Patients undergoing AF ablation are at risk of esophageal thermal injury, which ranges from superficial ulceration, to gastroparesis, to the rare but catastrophic atrioesophageal fistula. A common approach to avoid damage is luminal esophageal temperature (LET) monitoring; however, (1) temperature rises mandate interruptions in energy delivery that interrupt workflow and potentially decrease procedural efficacy, and (2) esophageal fistulas have been reported even with LET monitoring.

Methods:A cohort of 20 consecutive patients undergoing radiofrequency (RF) (16 patients) or laser balloon (4 patients) ablation of AF under general anesthesia. After barium instillation, the esophagus was deviated using an endotracheal stylet placed within a thoracic chest tube. LET monitoring was used during catheter ablation. Upper GI endoscopy was performed prior to discharge.

Results:At the pulmonary vein level, leftward deviation measured 2.8 ± 1.6 cm (range: 0.4–5.7) and rightward deviation 2.8 ± 1.8 cm (range: 0.5–4.9). The temperature rose to >38.5 °C in 3/20 (15%) patients. In these 3 patients, there was an average of 2 applications/patient that recorded temperatures >38.5 °C. No patient had a temperature rise > 40 °C. Endoscopy revealed no esophageal ulceration from thermal injury in 18/19 (95%) patients; the sole patient with a thermally mediated ulceration had an unusual esophageal diverticulum fully across the posterior left atrium. Twelve patients (63%) exhibited trauma related to instrumentation with no clinical sequelae.

Conclusions:Mechanical esophageal deviation is feasible and allows for uninterrupted energy delivery along the posterior wall during catheter ablation of AF.J Cardiovasc Electrophysiol, Vol. 23, pp. 147‐154, February 2012)
Accelerating EPI Distortion Correction by Utilizing a Modern GPU‐Based Parallel Computation
Authors: Yang Yao‐Hao , Huang Teng‐Yi , Wang Fu‐Nien , Chuang Tzu‐Chao , Chen Nan‐Kuei
Published: September 2011

BACKGROUND AND PURPOSE

The combination of phase demodulation and field mapping is a practical method to correct echo planar imaging (EPI) geometric distortion. However, since phase dispersion accumulates in each phase‐encoding step, the calculation complexity of phase modulation is Ny‐fold higher than conventional image reconstructions. Thus, correcting EPI images via phase demodulation is generally a time‐consuming task.

METHODS

Parallel computing by employing general‐purpose calculations on graphics processing units (GPU) can accelerate scientific computing if the algorithm is parallelized. This study proposes a method that incorporates the GPU‐based technique into phase demodulation calculations to reduce computation time. The proposed parallel algorithm was applied to a PROPELLER‐EPI diffusion tensor data set.

RESULTS

The GPU‐based phase demodulation method reduced the EPI distortion correctly, and accelerated the computation. The total reconstruction time of the 16‐slice PROPELLER‐EPI diffusion tensor images with matrix size of 128 × 128 was reduced from 1,754 seconds to 101 seconds by utilizing the parallelized 4‐GPU program.

CONCLUSIONS

GPU computing is a promising method to accelerate EPI geometric correction. The resulting reduction in computation time of phase demodulation should accelerate postprocessing for studies performed with EPI, and should effectuate the PROPELLER‐EPI technique for clinical practice.
Sudden oak death disease progression across two forest types and spatial scales
Authors: Ramage Benjamin S. , Forrestel Alison B. , Moritz Max A. , O'Hara Kevin L.
Published: September 2011

Questions

How is sudden oak death disease progression affected by forest type? Which specific factors influence mortality rates and patterns? How do these trends vary across spatial scales?

Location

Point Reyes National Seashore, California,USA.

Methods

Sudden oak death, caused by the exotic pathogenPhytophthora ramorum, is affecting forests throughout coastal California. We investigated disease progression in tanoak (Notholithocarpus densiflorussyn.Lithocarpus densiflorus), the most susceptible species, in two distinct forest types: coast redwood (Sequoia sempervirens) and Douglas‐fir (Pseudotsuga menziesiivar.menziesii). Within each forest type, we used a variant of a split‐plot design to sample proximate areas at two different stages of disease progression (relatively unaffected vs severely impacted), and used generalized linear mixed effects models to analyse these data.

Results

Annual mortality rates were much higher in Douglas‐fir (10.1–26.2%) than in redwood (3.2–8.2%) forest, and data suggested that similarly divergent rates will continue into the future (proportions of surviving trees with disease symptoms remained constant from the beginning to the end of the study period). Across both forest types, survival probabilities were lower for tanoaks with larger diameters and tanoaks in plots (1/20 ha) and neighbourhoods (3‐m radius) with greater basal area of previously killed tanoak. All variables were significant when included in the same model, suggesting that disease spread is occurring simultaneously at two local spatial scales. Several other biotic and abiotic variables were unrelated to tanoak survival probability.

Conclusions

We detected mortality rates that exceed any rates previously associated with sudden oak death, while demonstrating that these rates can vary substantially between adjacent forest types. However, because the Douglas‐fir forests of our study area are adjacent to the ocean, which is somewhat uncommon for this forest type, our findings do not necessarily indicate that all Douglas‐fir forests with a substantial tanoak component are at risk of similar impacts. Our data also suggest that, in both forest types, local patchiness in disease presence/severity is an ephemeral condition resulting primarily from stochastic processes (e.g. long‐distance dispersal events), while intra‐plot spread around infected trees is deterministic and probably inevitable. Our findings should inform scientists and managers throughout the world attempting to understand disease progression in regions recently invaded byP. ramorum(e.g. Europe) and/or affected by other exotic forest pathogens.
Fruit Removal and Natural Seed Dispersal of the Brazil Nut Tree (Bertholletia excelsa) in Central Amazonia, Brazil
Authors: Tuck Haugaasen Joanne M. , Haugaasen Torbjørn , Peres Carlos A. , Gribel Rogerio , Wegge Per
Published: September 2011

Experimental approaches to study seed dispersal of the Brazil nut tree have hitherto relied on exposed seeds deposited on the forest floor. Here we use a new method to study the natural dispersal by large rodents such as agoutis; tracking experimentally manipulated and tagged fruits containing individually marked seeds. Fruit manipulation did not deter agoutis from handling fruits. We found that agoutis usually moved intact fruits away from their original location below the parent tree before either hiding them or gnawing through the pericarp to access the seeds inside. Most fruits were moved to distances of 15–30 m from their original position, but some fruits could be taken as far as 60 m. A large number of seeds extracted from manipulated fruits appeared to be eaten immediately. Only 27 out of 1740 experimental seeds were found buried in shallow caches, generally within 5 m of the opened fruit. Fruit removal distance accounted for a disproportionate amount of total seed movement and seeds in the current study were dispersed significantly farther than in a previous experiment using exposed seeds, suggesting that classic dispersal experiments of this character may severely underestimate seed dispersal distances. We therefore conclude that the new method provides a more realistic and accurate approach to investigate natural seed dispersal of Brazil nuts and that the removal of fruits from underneath parent trees before being opened is the key to the significantly increased distances at which seeds are dispersed.

Abstract in Portuguese is available at http://www.blackwell‐synergy.com/loi/btp.
Debris disc candidates in systems with transiting planets
Authors: Krivov A. V. , Reidemeister M. , Fiedler S. , Löhne T. , Neuhäuser R.
Published: September 2011

Debris discs are known to exist around many planet-host stars, but no debris dust has been found so far in systems with transiting planets. Using publicly available catalogues, we searched for infrared excesses in such systems. In the recently published Wide-field Infrared Survey Explorer catalogue, we found 52 stars with transiting planets. Two systems with one transiting ‘hot Jupiter’ each, TrES-2 and XO-5, exhibit small excesses both at 12 and at 22 μ m at a ≳3σ level. Provided that one or both of these detections are real, the frequency of warm excesses in systems with transiting planets of 2–4 per cent is comparable to that around solar-type stars probed at similar wavelengths with Spitzer’s MIPS and IRS instruments. Modelling suggests that the observed excesses would stem from dust rings with radii of several  au. The inferred amount of dust is close to the maximum expected theoretically from a collisional cascade in asteroid belt analogues. If confirmed, the presence of debris discs in systems with transiting planets may put important constraints on the scenario of formation and migration of hot Jupiters.
Inter‐specific and intra‐specific variability in fruit color preference in two species of Turdus
Authors: LARRINAGA Asier R.
Published: September 2011

One of the main hypotheses proposed to explain the evolution of fruit color deals with a preference of avian frugivores for specific colors, mainly black and red, which are the most common fruit colors in many of the studied habitats. I analyzed fruit color preferences by wild birds belonging to 2 species of the highly frugivorous genus Turdus (Eurasian Blackbird Turdus merula Linnaeus, 1758 and Redwing Turdus iliacus Linnaeus, 1758) by means of captivity experiments with artificial fruits. Despite important within‐individual (i.e. temporal) and among‐individual variability, consistent patterns of species‐specific color preferences emerged. Eurasian Blackbirds tended to prefer red over blue, green and black, whereas Redwings seemed to prefer black over the rest. Green was systematically avoided by both species, suggesting that it might signal unripeness of fruits. Both preferred colors have been previously reported as the most common among fleshy‐fruited plants. The high variability, both within and between individuals, in preferences suggests that they can be subject to changes through experience and learning and, therefore, are not likely to drive the evolution of fruit color. The main differences between both species could be related to the most common fruit color they fed upon during the last months before capture.
The Effect of Using Citric or Acetic Acid on Survival of Listeria monocytogenes during Fish Protein Recovery by Isoelectric Solubilization and Precipitation Process
Authors: Otto R.A. , Beamer S. , Jaczynski J. , Matak K.E.
Published: September 2011

Abstract:  Isoelectric solubilization and precipitation (ISP) is a protein recovery process effective at reducing Listeria innocua, a nonpathogenic bacterium typically used as a surrogate for L. monocytogenes in recovered trout protein. The response of L. monocytogenes to ISP processing was determined and compared to the response of L. innocua. Headed and gutted rainbow trout were inoculated with L. monocytogenes (10.16 log CFU/g), homogenized, and pH‐adjusted with granular citric acid (pH 2.0 and 2.5) or glacial acetic acid (pH 3.0 and 3.5). Proteins were solubilized and centrifugation was used to remove insoluble components (skin, insoluble protein, so on). The supernatant was returned to the protein isoelectric point (pH 5.5) with NaOH and centrifuged to remove precipitated protein. Microbial load was enumerated on both growth and selective media; recovery was not significantly different (P > 0.05). Surviving cells from each component (protein, insoluble, and water) were compared to initial inoculum numbers. Significant reductions were detected at all pH (P < 0.05). The greatest reductions were at pH 3.0 with acetic acid, with a mean log reduction of 3.03 in the combined components, and a 3.53 log reduction in the protein portion. Data were compared to results from a previous study using L. innocua. Significant differences (P < 0.05) in recovery were found between the 2 species at pH 2.0 and 3.0 with greater recovery of L. monocytogenes, regardless of processing pH or acid type. These results demonstrate the variability in resistance between species and indicate that L. innocua is not an appropriate surrogate for L. monocytogenes for ISP processing with organic acids.