bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental Consequences of Trauma on Brain Circuits
Authors: Opendak Maya , Sullivan Regina 
Published: April 2018

Abstract
Traumatic experiences can be challenging at any age, but recent evidence has highlighted the trauma experienced from an attachment figure as particularly detrimental. Fear, or threat, conditioning is a major experimental paradigm that has uncovered the neurobiology of trauma processing. This controlled paradigm has enabled us to understand the changing neurobiology of trauma processing as well as the developmental importance of caregiver presence during trauma. Maternal presence buffers the infant during brief trauma exposure, although repeated trauma in her presence programs the enduring trauma effects on the neurobiology of cognition and emotion. We review the data on innate and learned fear responses across development and describe the interaction between trauma and attachment in early life when threatening cues are processed by the attachment circuitry, rather than fear circuitry, within the brain. This approach can provide insight into age-specific treatments and interventions following infant trauma in the presence of a caregiver.
Large Conductance Potassium Channels in the Nervous System
Authors: Carrasquel-Ursulaez Willy , Lorenzo Yenisleidy , Echeverria Felipe , Latorre Ramon 
Published: April 2018

Abstract
The Slowpoke (Slo) family of large conductance K+ channels comprises four structurally and functionally related members (Slo1, Slo2.1, Slo2.2, and Slo3). With the exception of Slo3, all Slo channels are expressed in neurons, where their diverse functions include influencing the shape, frequency, and propagation of action potentials, as well as neurotransmitter release. The Slo1 channel (KCa1.1; KCNMA1, BK) is Ca2+- and voltage-activated, while the two Slo2 channels, Slo2.1 (KNa1.2, KCNT2, Slick) and Slo2.2 (KNa1.1, KCNT1, Slack), are activated by internal Na+. The functional diversity of the Slo family is greatly increased through alternative splicing, metabolic regulation, and the formation of heterotetramers (Slo2 channels). Co-expression of the pore-forming α subunit of Slo1 with its accessory subunits β and γ further increases channel diversity. This chapter focuses on the role of the Slo channel family in neurons under both physiological and pathological conditions.
Material Evidence
Authors: Morris Sarah P. 
Published: April 2018

Abstract
Unlike in the study of Roman slavery (Joshel and Peterson 2014), the analysis of archaeological evidence for Greek slavery is far more challenging (I. Morris 2011), if we hope to be able to identify slaves, their labour, and their living spaces, in the ancient material record. Rather than trying to identify figures in Greek art as unfree in status, locating their place of work and living quarters in excavated structures, or distinguishing slave burials in ancient Greek necropoleis, this essay proposes that we should look rather for the wider effects of their labour on changes in health, wealth, settlement and landscapes.
Liturgy
Authors: Tucker Karen B. Westerfield 
Published: April 2018

Abstract
From their emergence early in the twentieth century, the liturgical movement and the ecumenical movement, the latter particularly represented by the deliberations of the Faith and Order Commission of the World Council of Churches, both called for and shaped ecumenical discourse on the nature of worship, the content and shape (ordo) of liturgy, sacraments and sacramentality, the practices of worship, and liturgical leadership and participation. This chapter highlights the history and contributions of both of these movements and notes the confluence of the two streams in the recognition of the centrality of worship for Christian life and mission. Attention also focuses on the ecumenical sharing of liturgical music, common liturgical texts, and lectionaries, and the ongoing question of ecumenical worship.
The Unity We Seek
Authors: Bordeianu Radu 
Published: April 2018

Abstract
Orthodox theologians such as Bulgakov, Florovsky, Afanasiev, Staniloae, and Zizioulas consider eucharistic communion to be the sign of ecclesial unity, but their understandings of the boundaries of the church and unity in love, teaching, episcopacy, and Eucharist (including intercommunion) are varied. This chapter analyses Orthodox understandings of the relationship between the Orthodox Church and the Una Sancta of the creed, considers the ecclesial status of other Christians, and assesses various models of unity, such as ‘all in each place’ (New Delhi, 1961). Unity is conditioned theologically: Christians need to confess the same faith, though uniformity is not the goal. Churches should enjoy unity in love, common service at the altar of the poor (in ‘the liturgy after the liturgy’), synodal decision-making, and communion among local churches represented by their bishops. These forms of unity do not represent successive stages, but they mutually condition each other.
Creativity
Authors: Baer John 
Published: April 2018

Abstract
This article reviews research and theory dealing with the psychology of creativity. It begins with a discussion of the most influential and widely known theory of creativity, which is based on the structure of the intellect model. It then considers four aspects of divergent thinking that are frequently mentioned in the literature, along with two models for classifying creativity: the “four P” model and the four C model. The article describes other theories of creativity, including the chance configuration theory, the propulsion model, and the five-factor theory of personality. Finally, it examines other important issues in creativity research, such as mental illness, gender differences, birth order, and IQ. It also looks at some of the approaches used in the assessment of creativity, including the Torrance Tests of Creative Thinking and the consensual assessment technique. Finally, it explores the issue of teaching creativity.
Cannabis for the treatment of paediatric epilepsy? An update for Canadian paediatricians
Authors: Huntsman Richard James , Tang-Wai Richard , Acton Bryan , Alcorn Jane , Lyon Andrew William , Mousseau Darrell David , Seifert Blair , Laprairie Robert , Prosser-Loose Erin , Hanuš Lumir Ondrej 
Published: April 2018

Abstract
The plant Cannabis sativa produces over 140 known cannabinoids. These chemicals generate considerable interest in the medical research community for their possible application to several intractable disease conditions. Recent reports have prompted parents to strongly consider Cannabis products to treat their children with drug resistant epilepsy. Physicians, though, are reluctant to prescribe Cannabis products due to confusion about their regulatory status and limited clinical data supporting their use. We provide the general paediatrician with a brief review of cannabinoid biology, the literature regarding their use in children with drug resistant epilepsy, the current Health Canada and Canadian Paediatric Society recommendations and also the regulations from the physician regulatory bodies for each province and territory. Given the complexities of conducting research on Cannabis products for children with epilepsy, we also discuss outstanding research objectives that must be addressed to support Cannabis products as an accepted treatment option for children with refractory epilepsy.
Spontaneous activity emerging from an inferred network model captures complex spatio-temporal dynamics of spike data
Authors: Capone Cristiano , Gigante Guido , Giudice Paolo De 
Published: April 2018

ABSTRACTInference methods are widely used to recover effective models from observed data. However, few studies attempted to investigate the dynamics of inferred models in neuroscience, and none, to our knowledge, at the network level. We introduce a principled modification of a widely used generalized linear model (GLM), and learn its structural and dynamic parameters from in-vitro spike data. The spontaneous activity of the new model captures prominent features of the non-stationary and non-linear dynamics displayed by the biological network, where the reference GLM largely fails, and also reflects fine-grained spatio-temporal dynamical features. Two ingredients were key for success. The first is a saturating transfer function: beyond its biological plausibility, it limits the neurons information transfer, improving robustness against endogenous and external noise. The second is a super-Poisson spikes generative mechanism; it accounts for the undersampling of the network, and allows the model neuron to flexibly incorporate the observed activity fluctuations.
Accurate functional classification of thousands of BRCA1 variants with saturation genome editing
Authors: Findlay Gregory M. , Daza Riza M. , Martin Beth , Zhang Melissa D. , Leith Anh P. , Gasperini Molly , Janizek Joseph D. , Huang Xingfan , Starita Lea M. , Shendure Jay 
Published: April 2018

AbstractVariants of uncertain significance (VUS) fundamentally limit the utility of genetic information in a clinical setting. The challenge of VUS is epitomized by BRCA1, a tumor suppressor gene integral to DNA repair and genomic stability. Germline BRCA1 loss-of-function (LOF) variants predispose women to early-onset breast and ovarian cancers. Although BRCA1 has been sequenced in millions of women, the risk associated with most newly observed variants cannot be definitively assigned. Data sharing attenuates this problem but it is unlikely to solve it, as most newly observed variants are exceedingly rare. In lieu of genetic evidence, experimental approaches can be used to functionally characterize VUS. However, to date, functional studies of BRCA1 VUS have been conducted in a post hoc, piecemeal fashion. Here we employ saturation genome editing to assay 96.5% of all possible single nucleotide variants (SNVs) in 13 exons that encode functionally critical domains of BRCA1. Our assay measures cellular fitness in a haploid human cell line whose survival is dependent on intact BRCA1 function. The resulting function scores for nearly 4,000 SNVs are bimodally distributed and almost perfectly concordant with established assessments of pathogenicity. Sequence-function maps enhanced by parallel measurements of variant effects on mRNA levels reveal mechanisms by which loss-of-function SNVs arise. Hundreds of missense SNVs critical for protein function are identified, as well as dozens of exonic and intronic SNVs that compromise BRCA1 function by disrupting splicing or transcript stability. We predict that these function scores will be directly useful for the clinical interpretation of cancer risk based on BRCA1 sequencing. Furthermore, we propose that this paradigm can be extended to overcome the challenge of VUS in other genes in which genetic variation is clinically actionable.
Population dynamics of Escherichia coli in the gastrointestinal tracts of Tanzanian children
Authors: Richter Taylor K. S. , Hazen Tracy H. , Lam Diana , Coles Christian L. , Seidman Jessica C. , You Yaqi , Silbergeld Ellen K. , Fraser Claire M. , Rasko David A. 
Published: April 2018

AbstractThe stability of the Escherichia coli populations in the human gastrointestinal tract are not fully appreciated, and represent a significant knowledge gap regarding gastrointestinal community structure, as well as resistance to incoming pathogenic bacterial species and antibiotic treatment. The current study examines the genomic content of 240 Escherichia coli isolates from children 2 to 35 months old in Tanzania. The E. coli strains were isolated from three time points spanning a six month time period, with or without antibiotic treatment. The resulting isolates were sequenced, and the genomes compared. The findings in this study highlight the transient nature of E. coli strains in the gastrointestinal tract of children, as during a six-month interval, no one individual contained phylogenomically related isolates at all three time points. While the majority of the isolates at any one time point were phylogenomically similar, most individuals did not contain phylogenomically similar isolates at more than two time points. Examination of global genome content, canonical E. coli virulence factors, multilocus sequence type, serotype, and antimicrobial resistance genes identified diversity even among phylogenomically similar strains. There was no apparent increase in the antimicrobial resistance gene content after antibiotic treatment. The examination of the E. coli from longitudinal samples from multiple children in Tanzania provides insight into the genomic diversity and population variability of resident E. coli within the rapidly changing environment of the gastrointestinal tract.ImportanceThis study increases the number of resident Escherichia coli genome sequences, and explores E. coli diversity through longitudinal sampling. We investigate the genomes of E. coli isolated from human gastrointestinal tracts as part of an antibiotic treatment program among rural Tanzanian children. Phylogenomics demonstrates that resident E. coli are diverse, even within a single host. Though the E. coli isolates of the gastrointestinal community tend to be phylogenomically similar at a given time, they differed across the interrogated time points, demonstrating the variability of the members of the E. coli community. Exposure to antibiotic treatment did not have an apparent impact on the E. coli community or the presence of resistance and virulence genes within E. coli genomes. The findings of this study highlight the variable nature of bacterial members of the human gastrointestinal tract.
Adaptive periodicity in the infectivity of malaria gametocytes to mosquitoes
Authors: Schneider Petra , Rund Samuel S. C. , Smith Natasha L. , Prior Kimberley F. , O’Donnell Aidan J. , Reece Sarah E. 
Published: April 2018

AbstractThat periodicity in the biting activity of mosquito vectors explains why malaria parasites have evolved rhythms in cycles of asexual replication in the host’s blood was proposed almost 50 years ago. Yet, tests of this hypothesis have proved inconclusive. Using the rodent malaria Plasmodium chabaudi, we examine rhythms in the density and infectivity of transmission forms (gametocytes) in the host’s blood, parasite development inside mosquitoes, and onwards transmission.Moreover, we control for the confounding effects of rhythms in mosquito susceptibility. We reveal that at night, gametocytes are twice as infective to mosquitoes, despite being less numerous in the blood. This enhanced infectiousness at night interacts with mosquito rhythms to increase sporozoite burdens by almost four-fold when mosquitoes feed during their day. Thus, daytime blood-feeding (e.g. driven by the use of bed nets) may render gametocytes less infective, but this is compensated for by the greater susceptibility of mosquitoes.
Benchmarking optimization methods for parameter estimation in large kinetic models
Authors: Villaverde Alejandro F. , Fröhlich Fabian , Weindl Daniel , Hasenauer Jan , Banga Julio R. 
Published: April 2018

AbstractMotivationMechanistic kinetic models usually contain unknown parameters, which need to be estimated by optimizing the fit of the model to experimental data. This task can be computationally challenging due to the presence of local optima and ill-conditioning. While a variety of optimization methods have been suggested to surmount these issues, it is not obvious how to choose the best one for a given problem a priori, since many factors can influence their performance. A systematic comparison of methods that are suited to parameter estimation problems of sizes ranging from tens to hundreds of optimization variables is currently missing, and smaller studies indeed provided contradictory findings.ResultsHere, we use a collection of benchmark problems to evaluate the performance of two families of optimization methods: (i) a multi-start of deterministic local searches; and (ii) a hybrid metaheuristic combining stochastic global search with deterministic local searches. A fair comparison is ensured through a collaborative evaluation, involving researchers applying each method on a daily basis, and a consideration of multiple performance metrics capturing the trade-off between computational efficiency and robustness. Our results show that, thanks to recent advances in the calculation of parametric sensitivities, a multi-start of gradient-based local methods is often a successful strategy, but a better performance can be obtained with a hybrid metaheuristic. The best performer is a combination of a global scatter search metaheuristic with an interior point local method, provided with gradients estimated with adjoint-based sensitivities. We provide an implementation of this novel method in an open-source software toolbox to render it available to the scientific community.Availability and ImplementationThe code to reproduce the results is available at Zenodo https://doi.org/10.5281/zenodo.1160343Contactjan.hasenauer@helmholtz-muenchen.de, julio@iim.csic.es
Spatial Self-Organization Resolves Conflicts Between Individuality and Collective Migration
Authors: Fu X. , Kato S. , Long J. , Mattingly H.H. , He C. , Vural D.C. , Zucker S.W. , Emonet T. 
Published: April 2018

AbstractCollective behavior can spontaneously emerge when individuals follow common rules of interaction. However, the behavior of each individual will differ due to existing genetic and non-genetic variation within the population. It remains unclear how this individuality is managed to achieve collective behavior. We quantified individuality in bands of clonalEscherichia colicells that migrate collectively along a channel by following a self-generated gradient of attractant. We discovered that despite substantial differences in individual chemotactic abilities, the cells are able to migrate as a coherent group by spontaneously sorting themselves within the moving band. This sorting mechanism ensures that differences between individual chemotactic abilities are compensated by differences in the local steepness of the traveling gradient each individual must navigate, and determines the minimum performance required to travel with the band. By resolving conflicts between individuality and collective migration, this mechanism enables populations to maintain advantageous diversity while on the move.
Cdt1 variants reveal unanticipated aspects of interactions with Cyclin/CDK and MCM important for normal genome replication
Authors: Pozo Pedro N. , Matson Jacob P. , Cole Yasemin , Kedziora Katarzyna M. , Grant Gavin D. , Temple Brenda , Cook Jeanette Gowen 
Published: April 2018

ABSTRACTThe earliest step in DNA replication is origin licensing which is the DNA loading of MCM helicase complexes. The Cdt1 protein is essential for MCM loading during G1 phase of the cell cycle, yet the mechanism of Cdt1 function is still incompletely understood. We examined a collection of rare Cdt1 variants that cause a form of primordial dwarfism (Meier-Gorlin syndrome) plus one hypomorphicDrosophilaallele to shed light on Cdt1 function. Three hypomorphic variants load MCM less efficiently than WT Cdt1, and their lower activity correlates with impaired MCM binding. A structural homology model of the human Cdt1-MCM complex position the altered Cdt1 residues at two distinct interfaces rather than the previously described single MCM interaction domain. Surprisingly, one dwarfism allele (Cdt1-A66T) is more active than WT Cdt1. This hypermorphic variant binds both Cyclin A and SCFSkp2poorly relative to WT Cdt1. Detailed quantitative live cell imaging analysis demonstrated no change in stability of this variant however. Instead, we propose that Cyclin A/CDK inhibits Cdt1 licensing function independently of the creation of the SCFSkp2phosphodegron. Together, these findings identify key Cdt1 interactions required for both efficient origin licensing and tight Cdt1 regulation to ensure normal cell proliferation and genome stability.
Enhanced super-resolution microscopy by extreme value based emitter recovery
Authors: Ma Hongqiang , Jiang Wei , Xu Jianquan , Liu Yang 
Published: April 2018

ABSTRACTSuper-resolution localization microscopy allows visualization of biological structure at nanoscale resolution. However, the presence of heterogeneous background can degrade the nanoscale resolution by tens of nanometers and introduce significant image artifacts. Here we develop a new approach, referred to as extreme value based emitter recovery (EVER), to accurately recover the distorted fluorescent emitters from heterogeneous background. Through numerical simulation and biological experiments, we demonstrate that EVER significantly improves the accuracy and fidelity of the reconstructed super-resolution image for a wide variety of imaging characteristics. EVER requires no manual adjustment of parameters and is implemented as an easy-to-use ImageJ plugin that can immediately enhance the quality of super-resolution images. Our method paves the way for accurate nanoscale imaging of samples with heterogeneous background fluorescence, such as thicker tissue and cells.
Earthworms and Cadmium - heavy metal resistant gut bacteria as indicators for heavy metal pollution in soils?
Authors: Šrut Maja , Menke Sebastian , Höckner Martina , Sommer Simone 
Published: April 2018

AbstractPreservation of the soil resources stability is of paramount importance for the ecosystem, particularly in the current era of environmental change, which presents a severe pollution burden (e.g. by heavy metals) to soil ecosystems and its fauna. Gut microbiomes are becoming recognized as important players in organism health, with comprehension of their perturbations in the polluted environment offering new insights into the nature and extent of heavy metal effects on the health of soil biota. Our aim was therefore to evaluate the effect of environmentally relevant heavy metal concentrations of cadmium (Cd) on the earthworm gut microbiota. Cd exposure led to perturbations of several heavy metal resistant taxa as well as taxa able to bind heavy metals, revealing the potential of the earthworm-microbiota system in overcoming humancaused heavy metal pollution. An ‘indicator species analysis’ linked bacterial generaPaenibacillusandFlavobacterium, and members of the order Actinomycetales with Cd treatment, suggesting the possible use of these bacterial taxa as biomarkers of exposure for Cd stressed soils. The results of this study will be essential to understanding of the soil fauna health, under anthropogenic disturbance, and will have implications for environmental monitoring and protection of soil resources.ImportanceSoil heavy metal pollution presents a severe burden for soil invertebrates and can have impact on their health, which in turn reflects on the health of the entire ecosystem. Gut microbiome is recognized as a central driver of the host health and its shifts can have severe consequences for the host. In this study we investigated the impact of cadmium (Cd) on earthworm gut microbiota, in a controlled experiment using cutting edge next generation sequencing and state of the art bioinformatics tools. The significance of this study is in identifying the gut bacterial taxa which are indicators for Cd treatment and are potential biomarkers of exposure to Cd. Therefore, this study contributes to develop efficient measures to qualify environmental pollution and to protect fragile soil resources and ultimately human health.