bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetics and identities of extracellular peptidases in subsurface sediments of the White Oak River Estuary, NC
Authors: Steen Andrew D. , Kevorkian Richard T. , Bird Jordan T. , Dombrowski Nina , Baker Brett J. , Hagen Shane M. , Mulligan Katherine H. , Schmidt Jenna M. , Webber Austen T. , Royalty Taylor , Alperin Marc J.
Published: October 2016

Anoxic subsurface sediments contain communities of heterotrophic microorganisms that metabolize organic carbon at extraordinarily slow rates. In order to assess the mechanisms by which subsurface microorganisms access detrital sedimentary organic matter, we measured kinetics of a range of extracellular peptidases in anoxic sediments of the White Oak River estuary, NC. Nine distinct peptidase substrates were enzymatically hydrolyzed at all depths. Potential peptidase activities (Vmax) decreased with increasing sediment depth, althoughVmaxexpressed on a per cell basis was approximately the same at all depths. Half-saturation constants (Km) decreased with depth, indicating peptidases that functioned more efficiently at low substrate concentrations. Potential activities of extracellular peptidases acting on molecules that are enriched in degraded organic matter (D-phenylalanine and L-ornithine) increased relative to enzymes that act on L-phenylalanine, further suggesting microbial community adaptation to access degraded organic matter. Nineteen classes of predicted, exported peptidases were identified in genomic data from the same site, of which genes for class C25 (gingipain-like) peptidases represented more than 40% at each depth. Methionine aminopeptidases, zinc carboxypeptidases, and class S24-like peptidases, which are involved in single-stranded DNA repair, were also abundant. These results suggest a subsurface heterotrophic microbial community that primarily accesses low-quality detrital organic matter via a diverse suite of well-adapted extracellular enzymes.

Importance

Burial of organic carbon in marine and estuarine sediments represents a long-term sink for atmospheric carbon dioxide. Globally, ∼40% of organic carbon burial occurs in anoxic estuaries and deltaic systems. However, the ultimate controls on the amount of organic matter that is buried in sediments, versus oxidized into CO2, are poorly constrained. Here we used a combination of enzyme assays and metagenomic analysis to identify how subsurface microbial communities catalyze the first step of proteinaceous organic carbon degradation. Our results show that microbial communities in deeper sediments are adapted to access molecules characteristic of degraded organic matter, suggesting that those heterotrophs are adapted to life in the subsurface.
Linking structure and activity in nonlinear spiking networks
Authors: Ocker Gabriel Koch , Josić Krešimir , Shea-Brown Eric , Buice Michael A.
Published: October 2016

Recent experimental advances are producing an avalanche of data on both neural connectivity and neural activity. To take full advantage of these two emerging datasets we need a framework that links them, revealing how collective neural activity arises from the structure of neural connectivity and intrinsic neural dynamics. This problem ofstructure-driven activityhas drawn major interest in computational neuroscience. Existing methods for relating activity and architecture in spiking networks rely on linearizing activity around a central operating point and thus fail to capture the nonlinear responses of individual neurons that are the hallmark of neural information processing. Here, we overcome this limitation and present a new relationship between connectivity and activity in networks of nonlinear spiking neurons by developing a diagrammatic fluctuation expansion based on statistical field theory. We explicitly show how recurrent network structure produces pairwise and higher-order correlated activity, and how nonlinearities impact the networks' spiking activity. Our findings open new avenues to investigating how single-neuron nonlinearities—including those of different cell types—combine with connectivity to shape population activity and function.
Degenerate time-dependent network dynamics anticipate seizures in human epileptic brain
Authors: Tauste Campo Adrià , Principe Alessandro , Ley Miguel , Rocamora Rodrigo , Deco Gustavo
Published: October 2016

Epileptic seizures are known to follow specific changes in brain dynamics. While some algorithms can nowadays robustly detect these changes, a clear understanding of the mechanism by which these alterations occur and generate seizures is still lacking. Here, we provide cross-validated evidence that such changes are initiated by an alteration of physiological network state dynamics. Specifically, our analysis of long intracranial EEG recordings from a group of 10 patients identifies a critical phase of a few hours in which time-dependent network states become less variable (“degenerate”) and is followed by a global functional connectivity reduction before seizure onset. This critical phase is characterized by an abnormal occurrence of highly correlated network instances and is shown to particularly affect the activity of resection regions in patients with validated postsurgical outcome. Our approach characterizes pre-seizure networks dynamics as a cascade of two sequential events providing new insights into seizure prediction and control.
SIRVs: Spike-In RNA Variants as External Isoform Controls in RNA-Sequencing
Authors: Paul Lukas , Kubala Petra , Horner Gudrun , Ante Michael , Holländer Igor , Alexander Seitz , Reda Torsten
Published: October 2016

Spike-In RNA variants (SIRVs) enable for the first time the validation of RNA sequencing workflows using external isoform transcript controls. 69 transcripts, derived from seven human model genes, cover the eukaryotic transcriptome complexity of start- and end-site variations, alternative splicing, overlapping genes, and antisense transcription in a condensed format. Reference RNA samples were spiked with SIRV mixes, sequenced, and exemplarily four data evaluation pipelines were challenged to account for biases introduced by the RNA-Seq workflow. The deviations of the respective isoform quantifications from the known inputs allow to determine the comparability of sequencing experiments and to extrapolate to which degree alterations in an RNA-Seq workflow affect gene expression measurements. The SIRVs as external isoform controls are an important gauge for inter-experimental comparability and a modular spike-in contribution to clear the way for diagnostic RNA-Seq applications.
An improved assembly and annotation of the allohexaploid wheat genome identifies complete families of agronomic genes and provides genomic evidence for chromosomal translocations
Authors: Clavijo Bernardo J. , Venturini Luca , Schudoma Christian , Accinelli Gonzalo Garcia , Kaithakottil Gemy , Wright Jonathan , Borrill Philippa , Kettleborough George , Heavens Darren , Chapman Helen , Lipscombe James , Barker Tom , Lu Fu-Hao , McKenzie Neil , Raats Dina , Ramirez-Gonzalez Ricardo H. , Coince Aurore , Peel Ned , Percival-Alwyn Lawrence , Duncan Owen , Trösch Josua , Yu Guotai , Bolser Dan , Namaati Guy , Kerhornou Arnaud , Spannagl Manuel , Gundlach Heidrun , Haberer Georg , Davey Robert P. , Fosker Christine , Di Palma Federica , Phillips Andrew , Millar A. Harvey , Kersey Paul J. , Uauy Cristobal , Krasileva Ksenia V. , Swarbreck David , Bevan Michael W. , Clark Matthew D.
Published: October 2016

Advances in genome sequencing and assembly technologies are generating many high quality genome sequences, but assemblies of large, repeat-rich polyploid genomes, such as that of bread wheat, remain fragmented and incomplete. We have generated a new wheat whole-genome shotgun sequence assembly using a combination of optimised data types and an assembly algorithm designed to deal with large and complex genomes. The new assembly represents more than 78% of the genome with a scaffold N50 of 88.8kbp that has a high fidelity to the input data. Our new annotation combines strand-specific Illumina RNAseq and PacBio full-length cDNAs to identify 104,091 high confidence protein-coding genes and 10,156 non-coding RNA genes. We confirmed three known and identified one novel genome rearrangements. Our approach enables the rapid and scalable assembly of wheat genomes, the identification of structural variants, and the definition of complete gene models, all powerful resources for trait analysis and breeding of this key global crop. [Supplemental material is available for this article.]
Condensin II mutation causes T-cell lymphoma through tissue-specific genome instability
Authors: Woodward Jessica , Taylor Gillian C. , Soares Dinesh C. , Boyle Shelagh , Sie Daoud , Read David , Chathoth Keerthi , Vukovic Milica , Tarrats Nuria , Jamieson David , Campbell Kirsteen J. , Blyth Karen , Acosta Juan Carlos , Ylstra Bauke , Arends Mark J. , Kranc Kamil R. , Jackson Andrew P. , Bickmore Wendy A. , Wood Andrew J.
Published: October 2016

Chromosomal instability is a hallmark of cancer, but mitotic regulators are rarely mutated in tumors. Mutations in the condensin complexes, which restructure chromosomes to facilitate segregation during mitosis, are significantly enriched in cancer genomes, but experimental evidence implicating condensin dysfunction in tumorigenesis is lacking. We report that mice inheriting missense mutations in a condensin II subunit (Caph2nes) develop T-cell lymphoma. Before tumors develop, we found that the same Caph2 mutation impairs ploidy maintenance to a different extent in different hematopoietic cell types, with ploidy most severely perturbed at the CD4+CD8+ T-cell stage from which tumors initiate. Premalignant CD4+CD8+ T cells show persistent catenations during chromosome segregation, triggering DNA damage in diploid daughter cells and elevated ploidy. Genome sequencing revealed that Caph2 single-mutant tumors are near diploid but carry deletions spanning tumor suppressor genes, whereas P53 inactivation allowed Caph2 mutant cells with whole-chromosome gains and structural rearrangements to form highly aggressive disease. Together, our data challenge the view that mitotic chromosome formation is an invariant process during development and provide evidence that defective mitotic chromosome structure can promote tumorigenesis.
Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis
Authors: Martin Carol-Anne , Murray Jennie E. , Carroll Paula , Leitch Andrea , Mackenzie Karen J. , Halachev Mihail , Fetit Ahmed E. , Keith Charlotte , Bicknell Louise S. , Fluteau Adeline , Gautier Philippe , Hall Emma A. , Joss Shelagh , Soares Gabriela , Silva João , Bober Michael B. , Duker Angela , Wise Carol A. , Quigley Alan J. , Phadke Shubha R. ,   The Deciphering Developmental Disorders Study, Wood Andrew J. , Vagnarelli Paola , Jackson Andrew P.
Published: October 2016

Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish “condensinopathies” as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size.
Whole-genome analysis of the methylome and hydroxymethylome in normal and malignant lung and liver
Authors: Li Xin , Liu Yun , Salz Tal , Hansen Kasper D. , Feinberg Andrew
Published: October 2016

DNA methylation at the 5-position of cytosine (5mC) is an epigenetic modification that regulates gene expression and cellular plasticity in development and disease. The ten-eleven translocation (TET) gene family oxidizes 5mC to 5-hydroxymethylcytosine (5hmC), providing an active mechanism for DNA demethylation, and it may also provide its own regulatory function. Here we applied oxidative bisulfite sequencing to generate whole-genome DNA methylation and hydroxymethylation maps at single-base resolution in human normal liver and lung as well as paired tumor tissues. We found that 5hmC is significantly enriched in CpG island (CGI) shores while depleted in CGIs themselves, especially in active genes, which exhibit a bimodal distribution of 5hmC around CGI that corresponds to H3K4me1 modifications. Hydroxymethylation on promoters, gene bodies, and transcription termination regions (TTRs) showed strong positive correlation with gene expression within and across tissues, suggesting that 5hmC is a marker of active genes and could play a role in gene expression mediated by DNA demethylation. Comparative analysis of methylomes and hydroxymethylomes revealed that 5hmC is significantly enriched in both tissue-specific DMRs (t-DMRs) and cancer-specific DMRs (c-DMRs), and 5hmC is negatively correlated with methylation changes, especially in non-CGI-associated DMRs. These findings revealed novel reciprocity between epigenetic markers at CGI shores corresponding to differential gene expression in normal tissues and matching tumors. Overall, our study provided a comprehensive analysis of the interplay between the methylome, hydroxymethylome, and histone modifications during tumorigenesis.
A multi-slice simulation algorithm for grazing-incidence small-angle X-ray scattering
Authors: Venkatakrishnan S. V. , Donatelli Jeffrey , Kumar Dinesh , Sarje Abhinav , Sinha Sunil K. , Li Xiaoye S. , Hexemer Alexander
Published: October 2016

Grazing-incidence small-angle X-ray scattering (GISAXS) is an important technique in the characterization of samples at the nanometre scale. A key aspect of GISAXS data analysis is the accurate simulation of samples to match the measurement. The distorted-wave Born approximation (DWBA) is a widely used model for the simulation of GISAXS patterns. For certain classes of sample such as nanostructures embedded in thin films, where the electric field intensity variation is significant relative to the size of the structures, a multi-slice DWBA theory is more accurate than the conventional DWBA method. However, simulating complex structures in the multi-slice setting is challenging and the algorithms typically used are designed on a case-by-case basis depending on the structure to be simulated. In this paper, an accurate algorithm for GISAXS simulations based on the multi-slice DWBA theory is presented. In particular, fundamental properties of the Fourier transform have been utilized to develop an algorithm that accurately computes the average refractive index profile as a function of depth and the Fourier transform of the portion of the sample within a given slice, which are key quantities required for the multi-slice DWBA simulation. The results from this method are compared with the traditionally used approximations, demonstrating that the proposed algorithm can produce more accurate results. Furthermore, this algorithm is general with respect to the sample structure, and does not require any sample-specific approximations to perform the simulations.
Crystal structure of methyl 1-allyl-4-methyl-1H-benzo[c][1,2]thiazine-3-carboxylate 2,2-dioxide
Authors: Azotla-Cruz Liliana , Shishkina Svitlana , Ukrainets Igor , Lijanova Irina , Likhanova Natalya
Published: October 2016

In the title compound, C14H15NO4S, the dihydrothiazine ring adopts a distorted sofa conformation with the S atom displaced from the mean plane through the N and C ring atoms by 0.767 (1) Å. The allyl substituent (C—C=C) is inclined to this mean plane by 78.5 (7)° and the acetate group [C(=O)—O—C] by 66.5 (3)°. In the crystal, molecules are linked by C—H...π interactions forming chains propagating along the a-axis direction.
2,5-Dimethylanilinium 4-hydroxybenzoate–2,5-dimethylaniline–4-hydroxybenzoic acid (1/1/1)
Authors: Mani A. , Rajesh K. , Kumar P. Praveen , Chakkaravarthi G.
Published: October 2016

The asymmetric unit of the title compound, C8H12N+·C7H5O3
−·C8H11N·C7H6O3, contains a 2,5-dimethylanilinium cation, 4-hydroxybenzoate anion and neutral 2,5-dimethylaniline and 4-hydroxybenzoic acid molecules. The components are connected by N—H...O, O—H...O and N—H...N hydrogen bonds, which generate R
2
2(8), R
4
4(20) and R
4
4(24) loops, as part of a three-dimensional network. The crystal structure also features weak C—H...π interactions.
Bryophyte traits explain climate‐warming effects on tree seedling establishment
Authors: Lett Signe , Nilsson Marie‐Charlotte , Wardle David A. , Dorrepaal Ellen
Published: October 2016

Above the alpine tree line, bryophytes cover much of the tundra soil surface in dense, often monospecific carpets. Therefore, when climate warming enables tree seedling establishment above the tree line, interaction with the bryophyte layer is inevitable. Bryophytes are known to modify their environment in various ways. However, little is known about to which extent and by which mechanisms bryophytes affect the response of tree seedlings to climate warming.

We aimed to assess and understand the importance of bryophyte species identity and traits for tree seedling performance at tree line temperatures and their response to warmer conditions. Seedlings of two common, tree line‐forming tree species (Betula pubescensandPinus sylvestris) were planted into intact cushions of eight common tundra bryophyte species and bryophyte‐free soil and grown for 18 weeks at current (7·0 °C) and near‐future (30–50 years; 9·2 °C) tree line average growing‐season temperatures. Seedling performance (biomass increase and N‐uptake) was measured and related to bryophyte species identity and traits indicative of their impact on the environment.

Tree seedlings performed equally well or better in the presence of bryophytes than in bryophyte‐free soil, which contrasts to their usually negative effects in milder climates. In addition, seedling performance and their response to higher temperatures depended on bryophyte species and seedlings of both species grew largest in the pan‐boreal and subarctic bryophyteHylocomium splendens. However,B. pubescensseedlings showed much stronger responses to higher temperatures when grown in bryophytes than in bryophyte‐free soil, while the opposite was true forP. sylvestrisseedlings. ForB. pubescens, but not forP. sylvestris, available organic nitrogen of the bryophyte species was the trait that best predicted seedling responses to higher temperatures, likely because these seedlings had increased N‐demands.

Synthesis. Climatically driven changes in bryophyte species distribution may not only have knock‐on effects on vascular plant establishment, but temperature effects on seedling performance are themselves moderated by bryophytes in a species‐specific way. Bryophyte traits can serve as a useful tool for understanding and predicting these complex interactions.
Rapid transgenerational effects in Knautia arvensis in response to plant community diversity
Authors: Rottstock Tanja , Kummer Volker , Fischer Markus , Joshi Jasmin
Published: October 2016

Plant species persistence in natural communities requires coping with biotic and abiotic challenges. These challenges also depend on plant community composition and diversity. Over time, biodiversity effects have been shown to be strengthened via increasing species complementarity in mixtures. Little is known, however, whether differences in community diversity and composition induce rapid transgenerational phenotypic adaptive differentiation during community assembly. We expect altered plant–plant and other biotic interactions (mutualists or antagonists) in high vs. low diverse communities to affect immediate within‐ and between‐species trait differentiations due to competition for light and nutrients.

Three years after the initiation of a large‐scale, long‐term biodiversity experiment in Jena, Germany, we tested for effects of varying experimental plant community diversity (1–60 plant species; one to four plant functional groups) and composition (with or without legumes and/or grasses) on phenotypic differentiation and variation of the tall herb Knautia arvensis. We measured reproduction at different diversity levels in the Jena Experiment (residents hereafter) and, in an additional common garden experiment without competition, recorded subsequent offspring performance (i.e. growth, reproductive success and susceptibility to powdery mildew) to test for differentiation in phenotypic expression and variability.

We observed phenotypic differences among diversity levels with reduced fecundity of K. arvensis residents in more diverse communities. In the next generation grown under common garden conditions, offspring from high‐diversity plots showed reduced growth (i.e. height) and lower reproduction (i.e. fewer infructescences), but increased phenotypic trait variability (e.g. in leaf width and powdery mildew presence) and also tended to be less susceptible to powdery mildew infection.

Community composition also affected Knautia parents and offspring. In the presence of legumes, resident plants produced more seeds (increased fecundity); however, germination rate of those seeds was reduced at an early seedling stage (reduced fertility).

Synthesis. We conclude that rapid transgenerational effects of community diversity and composition on both mean and variation of phenotypic traits among offspring exist. In addition to heritable variation, environmentally induced epigenetic and/or maternal processes matter for early plant community assembly and may also determine future species coexistence and community stability.
Templates and exclusions: victim centrism in Canada's Truth and Reconciliation Commission on Indian residential schools
Authors: Niezen Ronald
Published: October 2016

In this article I use an ethnographic approach to consider the causes and consequences of a focus on ‘survivor’ experience in Canada's Truth and Reconciliation Commission (TRC) on Indian residential schools. In this Truth Commission, the interconnected concepts of ‘survivor’, ‘cultural genocide’, ‘trauma’, and ‘healing’ became reference points for much of the testimony that was presented and the ways the schools were represented. Canada's Truth Commission thus offers an example of the consequences of ‘victim centrism’, including the ways that ‘truth‐telling’ can be influenced by the affirmation of particular survivor experiences and the wider goal of reforming the dominant historical narrative of the state through public education. Canada's TRC was limited by its mandate to a particular kind of institution and scope of collective harm. It was at the same time active in its creation of narrative templates, which guided the expression of traumatic personal experience and affirmed the category of residential school ‘survivor’ as the focal point for understanding policy‐driven loss of language, tradition, and political integrity.
On contrastive perception and ineffability: assessing sensory experience without colour terms in an Amazonian society
Authors: Surrallés Alexandre
Published: October 2016

Based on ethnographic material relating to the Candoshi, an indigenous people from the Upper Amazon, this article explores how they evaluate sensory experiences pertaining to colours without one of the main descriptive tools used for this purpose: colour names. After a review of the research concerning ineffability and colour naming, the article shows that the Candoshi do not have any terms for colours in their language. It then describes how, through a range of practices referred to as ‘contrastive perception’, they manage to communicate sensory experience, including that relating to colours, with accuracy. The last section concludes by discussing some of the theoretical implications of these findings in the light of previous research into the issue.
Acts of Solidarity: Crossing and Reiterating Israeli–Palestinian Frontiers
Authors: Koensler Alexander
Published: October 2016

In academic and public discourse on the Zionist–Palestinian conflict, there still prevails a ‘methodological nationalism’ based on a separatist imagination overshadowing the existence and role of Israeli–Palestinian forms of communality and solidarity. This article analyses micro‐political practices that cross existing frontiers, both within Israel and between the occupied Palestinian territories and Israel. Through recent conceptualizations of ‘acts’, I read these ethnographic episodes in their intentional and performative dimension. What is the role of these ‘acts’? What are their effects, both on participants and the wider public? Through two interconnected cases, different functions of acts are explored. The first case relates to encounters between Israelis and Palestinians in the embattled city of Hebron in the occupied Palestinian territories; the second investigates moments during a Gandhi‐inspired peace march at the ‘internal’ frontier of the Israeli Negev desert. The ethnographic perspective reveals what lies behind and beneath the acts, going beyond the conflict's obvious structures of power. Acts function primarily as a valve of catharsis for the participants themselves, both overcoming and reproducing hegemonic discursive elements of the conflict. Paradoxically, acts of solidarity are often crucial in shaping public knowledge about the conflict in more sectarian terms.
Institutionalization and Depoliticization of the Right to the City: Changing Scenarios for Radical Social Movements
Authors: Belda‐Miquel Sergio , Peris Blanes Jordi , Frediani Alexandre
Published: October 2016

The right to the city, a concept previously associated with radical social movements, has been accepted by several governments and has inspired new public policies. However, some authors see this process of institutionalization as involving a loss of a significant part of the radical origins of the concept. This article approaches this process and the new opportunities and limitations it may entail for social movement organizations with a more radical perspective on the right to the city. We explore the paradigmatic case of Brazil and the action of a particular organization, the Movimento dos Sem Teto da Bahia (MSTB, or Homeless Movement of Bahia) in the city of Salvador. We draw on the discussion of the politics of the right to the city and on an original combination of social movement theories and critical discourse analysis in order to analyse political‐institutional and discursive changes in urban reform in Brazil and Salvador. We then analyse how the MSTB moves within this new context, navigating its tensions and contradictions while advancing a radical project of transformation of urban reality within a reformist context. We also reflect on the relevance of Lefebvrian ideas for understanding and inspiring contemporary struggles for the right to the city.
Effects of Microwave and Ultrasound Assisted Extraction on the Recovery of Soy Proteins for Soy Allergen Detection
Authors: Amponsah Amma , Nayak Balunkeswar
Published: October 2016

The extraction of soy proteins for soy allergen detections is conventionally achieved with PBS buffer for at least 2 h at room temperature or 4 °C. This method has been reported to be inefficient due to time consumption and inadequate protein extraction resulting in false negative allergen detection and mislabeling of foods containing allergenic proteins. This study investigated the application of microwave (MAE) and ultrasound assisted extraction (UAE) techniques to extract and improve recovery of allergens from various soy matrices. Soy proteins were extracted from raw soy flour, soy protein isolate (SPI) and soy milk using MAE at 60, 70, and 100 °C for 5 and 10 min and UAE at 4 and 23 °C for extraction times of 1, 5, and 10 min with PBS, Laemmli and urea buffers. Extracts were analyzed for total proteins, protein profile, and antibody‐based detection (ELISA) of soy proteins. Conventional extraction with each of the buffers was used as controls. Overall, proteins recovered from MAE and UAE samples were higher than recoveries from the controls in all soy matrices. Under all extraction conditions, Laemmli and urea buffer recovered more proteins than PBS. Electrophoresis analysis of protein showed bands around 75, 50, and 33 kDa indicating the presence of soy allergenic proteins β‐conglycinin and glycinin, in all samples. Using sandwich ELISA, control and UAE extracts resulted in high soy protein detection but this reduced in MAE extracts.
skelesim: an extensible, general framework for population genetic simulation in R
Authors: Parobek Christian M. , Archer Frederick I. , DePrenger‐Levin Michelle E. , Hoban Sean M. , Liggins Libby , Strand Allan E.
Published: October 2016

Simulations are a key tool in molecular ecology for inference and forecasting, as well as for evaluating new methods. Due to growing computational power and a diversity of software with different capabilities, simulations are becoming increasingly powerful and useful. However, the widespread use of simulations by geneticists and ecologists is hindered by difficulties in understanding these softwares' complex capabilities, composing code and input files, a daunting bioinformatics barrier and a steep conceptual learning curve. skelesim (an R package) guides users in choosing appropriate simulations, setting parameters, calculating genetic summary statistics and organizing data output, in a reproducible pipeline within the R environment. skelesim is designed to be an extensible framework that can ‘wrap’ around any simulation software (inside or outside the R environment) and be extended to calculate and graph any genetic summary statistics. Currently, skelesim implements coalescent and forward‐time models available in the fastsimcoal2 and rmetasim simulation engines to produce null distributions for multiple population genetic statistics and marker types, under a variety of demographic conditions. skelesim is intended to make simulations easier while still allowing full model complexity to ensure that simulations play a fundamental role in molecular ecology investigations. skelesim can also serve as a teaching tool: demonstrating the outcomes of stochastic population genetic processes; teaching general concepts of simulations; and providing an introduction to the R environment with a user‐friendly graphical user interface (using shiny).
Faster estimation of Bayesian models in ecology using Hamiltonian Monte Carlo
Authors: Monnahan Cole C. , Thorson James T. , Branch Trevor A.
Published: October 2016

Bayesian inference is a powerful tool to better understand ecological processes across varied subfields in ecology, and is often implemented in generic and flexible software packages such as the widely used BUGS family (BUGS, WinBUGS, OpenBUGS and JAGS). However, some models have prohibitively long run times when implemented in BUGS. A relatively new software platform called Stan uses Hamiltonian Monte Carlo (HMC), a family of Markov chain Monte Carlo (MCMC) algorithms which promise improved efficiency and faster inference relative to those used by BUGS. Stan is gaining traction in many fields as an alternative to BUGS, but adoption has been slow in ecology, likely due in part to the complex nature of HMC.

Here, we provide an intuitive illustration of the principles of HMC on a set of simple models. We then compared the relative efficiency of BUGS and Stan using population ecology models that vary in size and complexity. For hierarchical models, we also investigated the effect of an alternative parameterization of random effects, known as non‐centering.

For small, simple models there is little practical difference between the two platforms, but Stan outperforms BUGS as model size and complexity grows. Stan also performs well for hierarchical models, but is more sensitive to model parameterization than BUGS. Stan may also be more robust to biased inference caused by pathologies, because it produces diagnostic warnings where BUGS provides none. Disadvantages of Stan include an inability to use discrete parameters, more complex diagnostics and a greater requirement for hands‐on tuning.

Given these results, Stan is a valuable tool for many ecologists utilizing Bayesian inference, particularly for problems where BUGS is prohibitively slow. As such, Stan can extend the boundaries of feasible models for applied problems, leading to better understanding of ecological processes. Fields that would likely benefit include estimation of individual and population growth rates, meta‐analyses and cross‐system comparisons and spatiotemporal models.
Lidocaine Pretreatment Reduces the Discomfort of Intranasal Midazolam Administration: A Randomized, Double‐blind, Placebo‐controlled Trial
Authors: Smith David , Cheek Hugh , Denson Brenda , Pruitt Christopher M.
Published: October 2016

Objective

Intranasal (IN) midazolam is a commonly prescribed medication for pediatric sedation and anxiolysis. One of its most frequently encountered adverse effects is discomfort with administration. While it has been proposed that premedicating with lidocaine reduces this undesirable consequence, this combination has not been thoroughly researched. The objective of our study was to assess whether topical lidocaine lessens the discomfort associated with IN midazolam administration.

Methods

This was a double‐blind, randomized, placebo‐controlled trial performed in an urban, academic pediatric emergency department. Children 6–12 years of age who were receiving IN midazolam for procedural sedation received either 4% lidocaine or 0.9% saline (placebo) via mucosal atomizer. Subjects were subsequently given IN midazolam in a similar fashion and then rated their discomfort using the Wong‐Baker FACES Pain Rating Scale (WBS). The primary endpoint of WBS score was analyzed with a two‐tailed Mann‐Whitney U‐test, with p < 0.05 considered statistically significant.

Results

Seventy‐seven patients were enrolled over a consecutive 8‐month period. One child was excluded from analysis due to a discrepancy in recording the drug identification number. Study groups were similar in regard to demographic information and indication for sedation. Subjects who received IN lidocaine reported less discomfort with IN midazolam administration (median WBS = 3, interquartile range [IQR] = 0–6) than those who received placebo (median WBS = 8, IQR = 2–9; p = 0.006).

Conclusions

Premedication with topical lidocaine reduces the discomfort associated with administration of IN midazolam (ClinicalTrials.gov, NCT02396537).
Evidence for GABA‐A receptor dysregulation in gambling disorder: correlation with impulsivity
Authors: Mick Inge , Ramos Anna C. , Myers Jim , Stokes Paul R. , Chandrasekera Samantha , Erritzoe David , Mendez Maria A. , Gunn Roger N. , Rabiner Eugenii A. , Searle Graham E. , Galduróz José C. F. , Waldman Adam D. , Bowden‐Jones Henrietta , Clark Luke , Nutt David J. , Lingford‐Hughes Anne R.
Published: October 2016

As a behavioural addiction, gambling disorder (GD) provides an opportunity to characterize addictive processes without the potentially confounding effects of chronic excessive drug and alcohol exposure. Impulsivity is an established precursor to such addictive behaviours, and GD is associated with greater impulsivity. There is also evidence of GABAergic dysregulation in substance addiction and in impulsivity. This study therefore investigated GABAA receptor availability in 15 individuals with GD and 19 healthy volunteers (HV) using [11C]Ro15‐4513, a relatively selective α5 benzodiazepine receptor PET tracer and its relationship with impulsivity. We found significantly higher [11C]Ro15‐4513 total distribution volume (VT) in the right hippocampus in the GD group compared with HV. We found higher levels of the ‘Negative Urgency’ construct of impulsivity in GD, and these were positively associated with higher [11C]Ro15‐4513 VT in the amygdala in the GD group; no such significant correlations were evident in the HV group. These results contrast with reduced binding of GABAergic PET ligands described previously in alcohol and opiate addiction and add to growing evidence for distinctions in the neuropharmacology between substance and behavioural addictions. These results provide the first characterization of GABAA receptors in GD with [11C]Ro15‐4513 PET and show greater α5 receptor availability and positive correlations with trait impulsivity. This GABAergic dysregulation is potential target for treatment.
Progressive white matter impairment as a predictor of outcome in a cohort of opioid‐dependent patient's post‐detoxification
Authors: Ivers Jo‐Hanna , Fitzgerald Jacqueline , Whelan Christopher , Sweeney Brion , Keenan Eamon , Fagan Andrew , McMarrow Jason , Meany Jim , Barry Joe , Frodl Thomas
Published: October 2016

White matter impairment is associated with opioid dependence. However, the specific neuropathology related to opioid dependence is still not fully understood. The main aims of this study were to: (1) assess the association between white matter impairment and duration of dependence; (2) examine whether this impairment correlates with treatment outcome measures in opioid‐dependent patients post‐detoxification. Fifty‐eight opioid‐dependent patients participated, 20 females and 38 males, across three groups: less than 10 years use (n = 18), 10–15 years use (n = 26) and 16–25+ years use (n = 14). Diffusion tensor imaging was used to assess white matter impairment; whole brain voxel‐wise analysis of fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were performed by Tract‐Based‐Spatial‐Statistics to pinpoint abnormalities in white matter. The longer the subjects were dependent on opioids, the more widespread and severely the white‐matter integrity was disrupted. A general linear model was used to examine patients who relapsed compared to those who were abstinent at follow‐up. No statistical difference was found between groups (p > 0.05). Partial correlations were performed to investigate the relationship between clinical outcome measures (physical health, psychological well being and quality of life and hope for the future) and white‐matter microstructural differences. Significant correlations were found between AD in the posterior corona radiata (L) and MD in the superior longitudinal fasciculus and a clinical measure for HOPE at 9‐month follow‐up. Nevertheless, it must be noted that the calculation of numerous correlations raises the possibility of a type I error, namely; to incorrectly conclude the occurrence of a significant correlation. The ability to investigate the structure–clinical relationship may improve our understanding of the pathological abnormalities associated with opioid dependence and has promise for use in evaluating future therapeutic outcomes in this population.
HSFY and ZNF280BY show copy number variations within 17 water buffalo populations
Authors: Zhang X. , Han H. , Zhang T. , Sun T. , Xi Y. , Chen N. , Huang Y. , Dang R. , Lan X. , Chen H. , Lei C.
Published: October 2016

Recent transcriptomic analysis of the bovine Y chromosome revealed abundant presence of multi‐copy protein coding gene families on the male‐specific region of the Y chromosome (MSY). Copy number variations (CNVs) of several MSY genes are closely related to semen quality and male reproduction in cattle. However, the CNVs of MSY genes in water buffalo are largely unknown. Therefore, this study aimed to investigate the CNVs of HSFY and ZNF280BY of 298 buffaloes from 17 populations distributed in China, Vietnam and Laos using quantitative PCR. Our results revealed that the median copy numbers of the HSFY and ZNF280BY genes were 47 (ranging from 20 to 145) and 269 (ranging from 73 to 974) respectively. In conclusion, this study indicated that HSFY and ZNF280BY showed abundant CNVs within swamp buffalo populations.
Anti‐inflammatory therapies in atopic dermatitis
Authors: Heratizadeh A. , Werfel T.
Published: October 2016

The pathogenesis of atopic dermatitis (AD) is multifactorial and complex. Consequently, clinical signs and symptoms vary strongly depending on individually relevant trigger factors and the stage of the disease. So far, treatment of AD was commonly limited to topical treatment or, in more severe cases, to systemic drugs mostly approved for other indications than AD. However, emerging data on new anti‐inflammatory agents have been published in the recent years. As these new substances specifically focus on immune responses in AD, these are partially considered as possible ‘breakthrough’ in the treatment of AD. Therapeutic strategies of the future appear to be ‘customized’ for inflammation in AD as they target pro‐inflammatory, highly relevant cytokines and cytokine receptors, such as IL‐4Rα, IL‐13, IL‐31, and IL‐17. Further innovative therapeutic approaches aim to block the function of relevant molecules such as thymic stromal lymphopoietin, chemoattractant‐receptor homologous molecule expressed on Th2 lymphocytes (CRTh2), and phosphodiesterase (PDE)‐4 inhibitors. Recently, anti‐inflammatory effects in AD by antagonizing the histamine (H)‐4 receptor have also been detected. Finally, specific immunotherapy is under further investigation as treatment option for AD patients with clinically relevant sensitization.
Latent class analysis shows that paediatricians' opinions about the advanced resuscitation of extremely preterm infants were diverse and influenced by personal beliefs
Authors: Ambrósio Cristiane Ribeiro , Sanudo Adriana , de Almeida Maria Fernanda Branco , Guinsburg Ruth
Published: October 2016

Aim

The aim of this study was to survey paediatricians, who taught neonatal resuscitation in Brazil, about when they would apply advanced resuscitation in the delivery room for newborn infants born at 23–26 weeks of gestational age.

Methods

This cross‐sectional study focused on an electronic questionnaire that was sent to paediatricians who acted as instructors for the Brazilian Neonatal Resuscitation Program from December 2011 to September 2013. The primary outcome was the gestational age at which the respondent would apply advanced resuscitation in the delivery room. Latent class analysis identified the profiles of the instructors, and logistic regression identified the variables associated with belonging to one of the derived classes.

Results

The 560 (82%) instructors who agreed to participate fell into three latent classes: pro‐resuscitation, intermediate and pro‐limitation, with high, intermediate and low probabilities of performing advanced resuscitation in neonates born at 23–26 weeks. In the multivariate model, group membership was associated with the paediatrician's age, years of practice and personal importance of religion and the patient's birthweight, future quality of life and probability of death.

Conclusion

The opinions of paediatricians performing advanced resuscitation on extremely preterm infants in the delivery room were diverse and influenced by personal beliefs.
Striated muscle activator of Rho signalling (STARS) is reduced in ageing human skeletal muscle and targeted by miR‐628‐5p
Authors: Russell A. P. , Wallace M. A. , Kalanon M. , Zacharewicz E. , Della Gatta P. A. , Garnham A. , Lamon S.
Published: October 2016

Aim

The striated muscle activator of Rho signalling (STARS) is a muscle‐specific actin‐binding protein. The STARS signalling pathway is activated by resistance exercise and is anticipated to play a role in signal mechanotransduction. Animal studies have reported a negative regulation of STARS signalling with age, but such regulation has not been investigated in humans.

Methods

Ten young (18–30 years) and 10 older (60–75 years) subjects completed an acute bout of resistance exercise. Gene and protein expression of members of the STARS signalling pathway and miRNA expression of a subset of miRNAs, predicted or known to target members of STARS signalling pathway, were measured in muscle biopsies collected pre‐exercise and 2 h post‐exercise.

Results

For the first time, we report a significant downregulation of the STARS protein in older subjects. However, there was no effect of age on the magnitude of STARS activation in response to an acute bout of exercise. Finally, we established that miR‐628‐5p, a miRNA regulated by age and exercise, binds to the STARS 3’UTR to directly downregulate its transcription.

Conclusion

This study describes for the first time the resistance exercise‐induced regulation of STARS signalling in skeletal muscle from older humans and identifies a new miRNA involved in the transcriptional control of STARS.
Editorial: CAMH – meeting the changing mental health needs of children in the 21st century
Authors: Barlow Jane
Published: October 2016

This is a challenging time for all journals but particularly for those such as CAMH, which must achieve a balance between informing, influencing and transforming the quality and effectiveness of the mental healthcare available to children, young people, their parents and families, while endeavouring to publish high‐quality scientific papers in terms of indicators such as the impact factor (IF). It is also a challenging time more widely in terms of the changing mental health needs of children, and the ability of CAMH services to meet them. This editorial discusses a number of changes that will be made the CAMH journal in 2017 to address these issues.
Chondrodysplasia with multiple dislocations: comprehensive study of a series of 30 cases
Authors: Ranza E. , Huber C. , Levin N. , Baujat G. , Bole‐Feysot C. , Nitschke P. , Masson C. , Alanay Y. , Al‐Gazali L. , Bitoun P. , Boute O. , Campeau P. , Coubes C. , McEntagart M. , Elcioglu N. , Faivre L. , Gezdirici A. , Johnson D. , Mihci E. , Nur B.G. , Perrin L. , Quelin C. , Terhal P. , Tuysuz B. , Cormier‐Daire V.
Published: October 2016

The group of chondrodysplasia with multiple dislocations includes several entities, characterized by short stature, dislocation of large joints, hand and/or vertebral anomalies. Other features, such as epiphyseal or metaphyseal changes, cleft palate, intellectual disability are also often part of the phenotype. In addition, several conditions with overlapping features are related to this group and broaden the spectrum. The majority of these disorders have been linked to pathogenic variants in genes encoding proteins implicated in the synthesis or sulfation of proteoglycans (PG). In a series of 30 patients with multiple dislocations, we have performed exome sequencing and subsequent targeted analysis of 15 genes, implicated in chondrodysplasia with multiple dislocations, and related conditions. We have identified causative pathogenic variants in 60% of patients (18/30); when a clinical diagnosis was suspected, this was molecularly confirmed in 53% of cases. Forty percent of patients remain without molecular etiology. Pathogenic variants in genes implicated in PG synthesis are of major importance in chondrodysplasia with multiple dislocations and related conditions. The combination of hand features, growth failure severity, radiological aspects of long bones and of vertebrae allowed discrimination among the different conditions. We propose key diagnostic clues to the clinician.