bluuebunny/crossref_metadata_2025 huggingface dataset:
Hierarchical structure of ecological and non-ecological processes of differentiation shaped ongoing gastropod radiation in the Malawi Basin
Authors: Van Bocxlaer Bert
Published: September 2017

Ecological processes, non-ecological processes or a combination of both may cause reproductive isolation and speciation, but their specific roles and potentially complex interactions in evolutionary radiations remain poorly understood, which defines a central knowledge gap at the interface of microevolution and macroevolution. Here I examine genome scans in combination with phenotypic and environmental data to disentangle how ecological and non-ecological processes contributed to population differentiation and speciation in an ongoing radiation ofLanistesgastropods from the Malawi Basin. I found a remarkable hierarchical structure of differentiation mechanisms in space and time: neutral and mutation-order processes are older and occur mainly between regions, whereas more recent adaptive processes are the main driver of genetic differentiation and reproductive isolation within regions. The strongest differentiation occurs between habitats and between regions, i.e. when ecological and non-ecological processes act synergistically. The structured occurrence of these processes based on the specific geographical setting and ecological opportunities strongly influenced the potential for evolutionary radiation. The results highlight the importance of interactions between various mechanisms of differentiation in evolutionary radiations, and suggest that non-ecological processes are important in adaptive radiations, including those of cichlids. Insight into such interactions is critical to understanding large-scale patterns of organismal diversity.
Interactive Visual Analysis of Mass Cytometry Data by Hierarchical Stochastic Neighbor Embedding Reveals Rare Cell Types
Authors: van Unen Vincent , Höllt Thomas , Pezzotti Nicola , Li Na , Reinders Marcel J. T. , Eisemann Elmar , Koning Frits , Vilanova Anna , Lelieveldt Boudewijn P. F.
Published: September 2017

Mass cytometry allows high-resolution dissection of the cellular composition of the immune system. However, the high-dimensionality, large size, and non-linear structure of the data poses considerable challenges for data analysis. In particular, dimensionality reduction-based techniques like t-SNE offer single-cell resolution but are limited in the number of cells that can be analysed. Here we introduce Hierarchical Stochastic Neighbor Embedding (HSNE) for the analysis of mass cytometry datasets. HSNE constructs a hierarchy of non-linear similarities that can be interactively explored with a stepwise increase in detail up to the single-cell level. We applied HSNE to a study on gastrointestinal disorders and three other available mass cytometry datasets. We found that HSNE efficiently replicates previous observations and identifies rare cell populations that were previously missed due to downsampling. Thus, HSNE removes the scalability limit of conventional t-SNE analysis, a feature that makes it highly suitable for the analysis of massive high-dimensional datasets.
Effects of G2 checkpoint dynamics on the low-dose hyper-radiosensitivity
Authors: Olobatuyi Oluwole , de Vries Gerda , Hillen Thomas
Published: September 2017

We develop and analyze a system of differential equations to investigate the effects of G2 checkpoint dynamics on the low-dose hyper-radiosensitivity. In experimental studies, it has been found that certain cell lines are more sensitive to low-dose radiation than would be expected from the classical Linear Quadratic model (LQ model). In fact, it is frequently observed that cells incur more damage at a low dose (say 0.3 Gy) than at higher dose (say 1 Gy). This effect has been termed hyper-radiosensitivity (HRS). The HRS is followed by a period of relative radioresistance (per unit dose) of cell kill over the dose range of ~ 0.5 - 1 Gy. This latter phenomenon is termed increased radioresistance (IRR). These effects depend on the type of cells and on their phase in the cell cycle. Here we focus on the HRS phenomenon by fitting a model for the cell cycle that includes G2-checkpoint dynamics and radiation treatment to surviving fraction data for different cell lines including glioma cells, prostate cancer cells, as well as to cell populations that are enriched in certain phases of the cell cycle. The HRS effect is measured in the literature through, the ratio of slopeαs, of the surviving fraction curve at zero dose to slopeαof the corresponding LQ model. We derive an explicit formula for this ratio and we show that it corresponds very closely to experimental observations. Finally, we can identify the dependence of this ratio on the surviving fraction at 2 Gy. It was speculated in the literature that such a relation exists. Our theoretical analysis will help to more systematically identify the HRS in cell lines and opens doors to analyze its use in cancer treatment.

PACS and mathematical subject classification numbers as needed.
A core signaling mechanism at the origin of animal nociception
Authors: Arenas Oscar M. , Zaharieva Emanuela E. , Para Alessia , Vásquez-Doorman Constanza , Petersen Christian P. , Gallio Marco
Published: September 2017

All animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is not well understood. Here, we show that a remarkably conserved signaling mechanism mediates the detection of noxious stimuli in animals as diverse as flatworms and humans. Planarian flatworms are amongst the simplest bilateral animals with a centralized nervous system, and capable of directed behavior. We demonstrate that noxious heat and irritant chemicals elicit robust escape behaviors in the planarianSchmidtea mediterranea, and that the conserved ion channel TRPA1 is required for these responses. TRPA1 mutant fruit flies (Drosophila) are also defective in the avoidance of noxious heat1-3. Unexpectedly, we find that either the planarian or the human TRPA1 can restore noxious heat avoidance to TRPA1 mutantDrosophila, even though neither is directly activated by heat. Instead, our data suggest that TRPA1 activation is mediated by H2O2/Reactive Oxygen Species, early markers of tissue damage rapidly produced as a result of heat exposure. Together, our data reveal a core function for TRPA1 in noxious heat transduction, demonstrate its conservation from planarians to humans, and imply that human nociceptive systems may share a common ancestry with those of most extant animals, tracing back their origin to a progenitor that lived more than 500 million years ago.
SHAMAN: bin-free randomization, normalization and screening of Hi-C matrices
Authors: Mendelson Cohen Netta , Olivares-Chauvet Pedro , Lubling Yaniv , Baran Yael , Lifshitz Aviezer , Hoichman Michael , Tanay Amos
Published: September 2017

Genome wide chromosome conformation capture (Hi-C) is used to interrogate contact frequencies among genomic elements at multiple scales and intensities, ranging from high frequency interactions among proximal regulatory elements, through specific long-range loops between insulator binding sites and up to rare and transient cis‐ and trans-chromosomal contacts. Visualization and statistical analysis of Hi-C data is made difficult by the extreme variation in the background frequencies of chromosomal contacts between elements at short and long genomic distances. Here we introduce SHAMAN for performing Hi-C analysis at dynamic scales, without predefined resolution, and while minimizing biases over very large datasets. Algorithmically, we devise a Markov Chain Monte Carlo-like procedure for randomizing contact matrices such that coverage and contact distance distributions are preserved. We combine this strategy with bin-free assessment of contact enrichment using a K-nearest neighbor approach. We show how to use the new method for visualizing contact hotspots and for quantifying differential contacts in matching Hi-C maps. We demonstrate how contact preferences among regulatory elements, including promoters, enhancers and insulators can be assessed with minimal bias by comparing pooled empirical and randomized matrices. Full support for our methods is available in a new software package that is freely available.
Porcupine: a visual pipeline tool for neuroimaging analysis
Authors: van Mourik Tim , Snoek Lukas , Knapen Tomas , Norris David
Published: September 2017

The field of neuroimaging is rapidly adopting a more reproducible approach to data acquisition and analysis. Data structures and formats are being standardised and data analyses are getting more automated. However, as data analysis becomes more complicated, researchers often have to write longer analysis scripts, spanning different tools across multiple programming languages. This makes it more difficult to share or recreate code, reducing the reproducibility of the analysis. We present a tool, Porcupine, that constructs one’s analysis visually and automatically produces analysis code. The graphical representation improves understanding of the performed analysis, while retaining the flexibility of modifying the produced code manually to custom needs. Not only does Porcupine produce the analysis code, it also creates a shareable environment for running the code, in the form of a Docker image. Together, this forms a reproducible way of constructing, visualising and sharing one’s analysis. Currently, Porcupine links to Nipype functionalities, which in turn accesses most standard neuroimaging analysis tools. With Porcupine, we bridge the gap between a conceptual and an implementational level of analysis and thus create reproducible and shareable science. We give the researcher a better oversight of their pipeline, both while developing and communicating their work. This will reduce the threshold at which less expert users can generate reusable pipelines. We provide a wide range of examples and documentation, as well as installer files for all platforms on our website: https://timvanmourik.github.io/Porcupine. Porcupine is free, open source, andreleased under the GNU General Public License v3.0.

Author Summary

The neuroimaging community is fervently debating that its reproducibility and transparency should be improved, but it is a challenging problem as to how to accomplish this. We here propose a tool, Porcupine, to aid in this process by more easily creating shareable workflows for analysing neuroimaging data. The conceptual understanding of a pipeline is improved by means of the graphical interface, and it automatically produces the code to perform the analysis and to create a sharing environment. This retains full flexibility to modify the script afterwards but in principle produces readily executable code for an end-to-end analysis. Porcupine currently links to all Nipype functionality, but is designed to be extendable to other workflow packages in neuroimaging and beyond. Porcupine is free and is released under the GNU General Public License.
A Genome Scan for Genes Underlying Adult Body Size Differences between Central African Pygmies and their Non-Pygmy Neighbors
Authors: Pemberton Trevor J. , Verdu Paul , Becker Noémie S. , Willer Cristen J. , Hewlett Barry S. , Le Bomin Sylvie , Froment Alain , Rosenberg Noah A. , Heyer Evelyne
Published: September 2017

Background

Central African hunter-gatherer Pygmy populations have reduced body size compared with their often much larger agricultural non-Pygmy neighbors, potentially reflecting adaptation to the anatomical and physiological constraints of their lifestyle in tropical rainforests. Earlier studies investigating the genetics of the pygmy phenotype have focused on standing height, one aspect of this complex phenotype that is itself a composite of skeletal components with different growth patterns. Here, we extend the investigations of standing height to the variability and genetic architecture of sitting height and subischial leg length as well as body mass index (BMI) in a sample of 406 unrelated West Central African Pygmies and non-Pygmies.

Results

In addition to their significantly reduced standing height compared with non-Pygmies, we find Pygmies to have significantly shorter sitting heights and subischial leg lengths as well as higher sitting/standing height ratios than non-Pygmies. However, while male Pygmies had significantly lower BMI compared with male non-Pygmies, the BMI of females were instead similar. Consistent with prior observations with standing height, sitting height and subischial leg length were strongly correlated with inferred levels of non-Pygmy genetic admixture while BMI was instead weakly correlated, likely reflecting the greater contribution of non-genetic factors to the determination of body weight compared with height. Using 196,725 SNPs on the Illumina Cardio-MetaboChip with genotypes on 358 Pygmy and 169 non-Pygmy individuals together with single-and multi-marker association approaches, we identified a single genomic region and seven genes associated with Pygmy/non-Pygmy categorization as well as 9, 10, 9, and 10 genes associated with standing and sitting height, sitting/standing height ratio, and subischial leg length, respectively. Many of the genes identified have putative functions consistent with a role in determining their associated trait as well as the complex Central African pygmy phenotype.

Conclusions

These findings highlight the potential of modestly sized datasets of Pygmies and non-Pygmies to detect biologically meaningful associations with traits contributing to the Central African pygmy phenotype. Moreover, they provide new insights into the phenotypic and genetic bases of the complex pygmy phenotype and offer new opportunities to facilitate our understanding of its complex evolutionary origins.
Precision genome-editing with CRISPR/Cas9 in human induced pluripotent stem cells
Authors: Budde John P. , Martinez Rita , Hsu Simon , Wen Natalie , Chen Jason A. , Coppola Giovanni , Goate Alison M. , Cruchaga Carlos , Karch Celeste M.
Published: September 2017

Genome engineering in human induced pluripotent stem cells (iPSCs) represent an opportunity to examine the contribution of pathogenic and disease modifying alleles to molecular and cellular phenotypes. However, the practical application of genome-editing approaches in human iPSCs has been challenging. We have developed a precise and efficient genome-editing platform that relies on allele-specific guideRNAs (gRNAs) paired with a robust method for culturing and screening the modified iPSC clones. By applying an allele-specific gRNA design strategy, we have demonstrated greatly improved editing efficiency without the introduction of additional modifications of unknown consequence in the genome. Using this approach, we have modified nine independent iPSC lines at five loci associated with neurodegeneration. This genome-editing platform allows for efficient and precise production of isogenic cell lines for disease modeling. Because the impact of CRISPR/Cas9 on off-target sites remains poorly understood, we went on to perform thorough off-target profiling by comparing the mutational burden in edited iPSC lines using whole genome sequencing. The bioinformatically predicted off-target sites were unmodified in all edited iPSC lines. We also found that the numbers ofde novogenetic variants detected in the edited and unedited iPSC lines were similar. Thus, our CRISPR/Cas9 strategy does not specifically increase the mutational burden. Furthermore, our analyses of thede novogenetic variants that occur during iPSC culture and genome-editing indicate an enrichment ofde novovariants at sites identified in dbSNP. Taken together, we propose that this enrichment represents regions of the genome more susceptible to mutation. Herein, we present an efficient and precise method for allele-specific genome-editing in iPSC and an analyses pipeline to distinguish off-target events fromde novomutations occurring with culture.
Whole genome sequence-based haplotypes reveal single origin of the sickle allele during the Holocene Wet Phase
Authors: Shriner Daniel , Rotimi Charles N.
Published: September 2017

Five classical designations of sickle haplotypes are based on the presence/absence of restriction sites and named after ethnic groups or geographic regions from which patients originated. Each haplotype is thought to represent an independent occurrence of the sickle mutation. We investigated the origins of the sickle mutation using whole genome sequence data. We identified 156 carriers from the 1000 Genomes Project, the African Genome Variation Project, and Qatar. We defined a new haplotypic classification using 27 polymorphisms in linkage disequilibrium with rs334. Network analysis revealed a common haplotype that differed from the ancestral haplotype only by the derived sickle mutation at rs334 and correlated collectively with the Central African Republic/Bantu, Cameroon, and Arabian/Indian designations. Other haplotypes were derived from this haplotype and fell into two clusters, one comprised of haplotypes correlated with the Senegal designation and the other comprised of haplotypes correlated with both the Benin and Senegal designations. The near-exclusive presence of the original sickle haplotype in the Central African Republic, Kenya, Uganda, and South Africa is consistent with this haplotype predating the Bantu Expansion. Modeling of balancing selection indicated that the heterozygote advantage was 15.2%, an equilibrium frequency of 12.0% was reached after 87 generations, and the selective environment predated the mutation. The posterior distribution of the ancestral recombination graph yielded an age of the sickle mutation of 259 generations, corresponding to 7,300 years and the Holocene Wet Phase. These results clarify the origin of the sickle allele and improve and simplify the classification of sickle haplotypes.
FRONTAL EYE FIELD INACTIVATION DIMINISHES SUPERIOR COLLICULUS ACTIVITY, BUT DELAYED SACCADIC ACCUMULATION GOVERNS REACTION TIME INCREASES
Authors: Peel Tyler R. , Dash Suryadeep , Lomber Stephen G. , Corneil Brian D.
Published: September 2017

Stochastic accumulator models provide a comprehensive framework for how neural activity could produce behavior. Neural activity within the frontal eye fields (FEF) and intermediate layers of the superior colliculus (iSC) support such models for saccade initiation, by relating variations in saccade reaction time (SRT) to variations in parameters such as baseline, rate of accumulation of activity, or threshold. Here, by recording iSC activity during reversible cryogenic inactivation of the FEF in non-human primates, we causally test which parameter(s) best explains concomitant increases in SRT. While FEF inactivation decreased all aspects of ipsilesional iSC activity, decreases in accumulation rate and threshold poorly predicted accompanying increases in SRT. Instead, SRT increases best correlated with delays in the onset of saccade-related accumulation. We conclude that FEF signals govern the onset of saccade-related accumulation within the iSC, and that the onset of accumulation is a relevant parameter for stochastic accumulation models of saccade initiation.

Significance Statement

The superior colliculus (SC) and frontal eye fields (FEF) are two of the best-studied areas in the primate brain. Surprisingly, little is known about what happens in the SC when the FEF is temporarily inactivated. Here, we show that temporary FEF inactivation decreases all aspects of functionally-related activity in the SC. This combination of techniques also allowed us to relate changes in SC activity to concomitant increases in saccadic reaction time (SRT). Although stochastic accumulator models relate SRT increases to reduced rates of accumulation or increases in threshold, such changes were not observed in the SC. Instead, FEF inactivation delayed the onset of saccade-related accumulation, emphasizing the importance of this parameter in biologically-plausible models of saccade initiation.
EPAC1 regulates endothelial Annexin A2 cell surface translocation and plasminogen activation
Authors: Yang Wenli , Mei Fang C. , Cheng Xiaodong
Published: September 2017

Annexins, a family of highly conserved calcium-and phospholipid-binding proteins, play important roles in a wide range of physiological functions. Among the twelve known annexins in human, Annexin A2 (AnxA2) is one of the most extensively studied and has been implicated in various human diseases. AnxA2 can exist as a monomer or a heterotetrameric complex with S100A10 (P11) and plays a critical role in many cellular processes including exocytosis/endocytosis and membrane organization. At the endothelial cell surface, (AnxA2•P11)2 tetramer, acting as a coreceptor for plasminogen and tissue plasminogen activator (t-PA), accelerates t-PA dependent activation of the fibrinolytic protease, plasmin, the enzyme responsible for thrombus dissolution and degradation of fibrin. This study shows that exchange proteins directly activated by cAMP isoform 1 (EPAC1) interacts with AnxA2 and regulates its biological functions by modulating its membrane translocation in endothelial cells. Using genetic and pharmacological approaches, it is demonstrated that EPAC1, acting through the PLCε-PKC pathway, inhibits AnxA2 surface translocation and plasminogen activation. These results suggest that EPAC1 plays a role in the regulation of fibrinolysis in endothelial cells and may represent a novel therapeutic target for disorders of fibrinolysis.
The lectin-specific activity ofToxoplasma gondiimicroneme proteins 1 and 4 binds Toll-like receptor 2 and 4 N-glycans to regulate innate immune priming
Authors: Sardinha-Silva Aline , Mendonça-Natividade Flávia C. , Pinzan Camila F. , Lopes Carla D. , Costa Diego L. , Jacot Damien , Fernandes Fabricio F. , Zorzetto-Fernandes André L. V. , Gay Nicholas J. , Sher Alan , Jankovic Dragana , Soldati-Favre Dominique , Grigg Michael E. , Roque-Barreira Maria Cristina
Published: September 2017

Infection of host cells byToxoplasma gondiiis an active process, which is regulated by secretion of microneme (MICs) and rhoptry proteins (ROPs and RONs) from specialized organelles in the apical pole of the parasite. MIC1, MIC4 and MIC6 assemble into an adhesin complex, secreted on the parasite surface and function to promote infection competency. MIC1 and MIC4 are known to bind terminal sialic acid residues and galactose residues, respectively and to induce IL-12 production from splenocytes. Here we show that rMIC1- and rMIC4-stimulated dendritic cells and macrophages to produce proinflammatory cytokines, and they do so by engaging TLR2 and TLR4. This process depends on sugar recognition, since point mutations in the carbohydrate-recognition domains (CRD) of rMIC1 and rMIC4 inhibit innate immune cells activation. HEK cells transfected with TLR2 glycomutants were selectively unresponsive to MICs. Followingin vitroinfection, parasites lacking MIC1 or MIC4, as well as expressing MIC proteins with point mutations in their CRD, failed to induce wild-type (WT) levels of IL-12 secretion by innate immune cells. However, only MIC1 was shown to impact systemic levels of IL-12 and IFN-γin vivo. Together, our data show that MIC1 and MIC4 interact physically with TLR2 and TLR4 N-glycans to trigger IL-12 responses, and MIC1 is playing a significant rolein vivoby alteringT. gondiiinfection competency and murine pathogenesis.

AUTHOR SUMMARY

Toxoplasmosis is caused by the protozoanToxoplasma gondii, belonging to the Apicomplexa phylum. This phylum comprises important parasites able to infect a broad diversity of animals, including humans. A particularity ofT. gondiiis its ability to invade virtually any nucleated cell of all warm-blooded animals through an active process, which depends on the secretion of adhesin proteins. These proteins are discharged by specialized organelles localized in the parasite apical region, and termed micronemes and rhoptries. We show in this study that two microneme proteins fromT. gondiiutilize their adhesion activity to stimulate innate immunity. These microneme proteins, denoted MIC1 and MIC4, recognize specific sugars on receptors expressed on the surface of mammalian immune cells. This binding activates these innate immune cells to secrete cytokines, which promotes efficient host defense mechanisms against the parasite and regulate their pathogenesis. This activity promotes a chronic infection by controlling parasite replication during acute infection.
Mobile nucleosomes and the accessibility of transcription factors to DNA: a modified dynamic equilibrium model
Authors: Khamis Hadeel , Rudnizky Sergei , Kaplan Ariel
Published: September 2017

Nucleosomes, the basic building block of chromatin, regulate the accessibility of the transcription machinery to DNA. Recent studies have revealed that the nucleosome's spontaneous, thermally driven positional dynamics are modulated by different factors, and exploited by the cell as a regulatory mechanism. In particular, enrichment of mobile nucleosomes at the promoters of genes suggests that the mobility of nucleosomes may affect the ability of transcription factors to bind DNA. However, a quantitative model describing the effect nucleosome mobility on the effective affinity of transcription factors is lacking. We present here a simple equilibrium model that captures the essence of the effect, and show that modulation of the nucleosome's mobility can be a potent and versatile regulator of transcription factor binding.
A note on the analysis of two-stage task results: how changes in task structure affect what model-free and model-based strategies predict about the effects of reward and transition on the stay probability
Authors: da Silva Carolina Feher , Hare Todd A.
Published: September 2017

Many studies that aim to detect model-free and model-based influences on behavior employ two-stage behavioral tasks of the type pioneered by Daw and colleagues in 2011. Such studies commonly modify existing two-stage decision paradigms in order to better address a given hypothesis, which is an important means of scientific progress. It is, however, critical to fully appreciate the impact of any modified or novel experimental design features on the expected results. Here, we use two concrete examples to demonstrate that relatively small changes in the two-stage task design can substantially change the pattern of actions taken by model-free and model-based agents as a function of the reward outcomes and transitions on previous trials. In the first, we show that, under specific conditions, purely model-free agents will produce the reward by transition interactions typically thought to characterize model-based behavior on a two-stage task. The second example shows that model-based agents’ behavior is driven by a main effect of transition-type in addition to the canonical reward by transition interaction whenever the reward probabilities of the final states do not sum to one. Together, these examples emphasize the task-dependence of model-free and model-based behavior and highlight the benefits of using computer simulations to determine what pattern of results to expect from both model-free and model-based agents performing a given two-stage decision task in order to design choice paradigms and analysis strategies best suited to the current question.
An ensemble code in medial prefrontal cortex links prior events to outcomes during learning
Authors: Maggi Silvia , Peyrache Adrien , Humphries Mark D.
Published: September 2017

The prefrontal cortex is implicated in learning the rules of an environment through trial and error. But it is unclear how such learning is related to the prefrontal cortex’s role in short-term memory. Here we ask if the encoding of short-term memory in prefrontal cortex is used by rats learning decision rules in a Y-maze task. We find that a similar pattern of neural ensemble activity is selectively recalled after reinforcement for a correct decision. This reinforcement-selective recall only reliably occurs immediately before the abrupt behavioural transitions indicating successful learning of the current rule, and fades quickly thereafter. We could simultaneously decode multiple, retrospective task events from the ensemble activity, suggesting the recalled ensemble activity has multiplexed encoding of prior events. Our results suggest that successful trial-and-error learning is dependent on reinforcement tagging the relevant features of the environment to maintain in prefrontal cortex short-term memory.
Predictive model identifies strategies to enhance TSP1-mediated apoptosis signaling
Authors: Wu Qianhui , Finley Stacey D.
Published: September 2017

This study explores strategies to enhance thrombospondin-1 (TSP1) induced apoptosis in endothelial cells, an important function that contributes to TSP1’s anti-angiogenic effect. We established a mathematical model of TSP1-mediated intracellular signaling via the CD36 receptor. This model was used to investigate the effects of several approaches to perturb the TSP1-CD36 signaling network. Model simulations predict the population-based response to strategies to enhance TSP1-mediated apoptosis, such as downregulating the apoptosis inhibitor XIAP and inhibiting phosphatase activity. The model also postulates a new mechanism of low dosage doxorubicin treatment in combination with TSP1 stimulation. Using computational analysis, we predict which cells will undergo apoptosis, based on the initial intracellular concentrations of particular signaling species. Overall, the modeling framework predicts molecular strategies that increase TSP1-mediated apoptosis, which is useful in many disease settings.
Dynamic contrast enhancement and flexible odor codes
Authors: Nizampatnam Srinath , Saha Debajit , Chandak Rishabh , Raman Baranidharan
Published: September 2017

Sensory stimuli evoke spiking activities patterned across neurons and time that are hypothesized to encode information about their identity. Since the same stimulus can be encountered in a multitude of ways, how stable or flexible are these stimulus-evoked responses? Here, we examined this issue in the locust olfactory system. In the antennal lobe, we found that both spatial and temporal features of odor-evoked responses varied in a stimulus-history dependent manner. The response variations were not random, but allowed the antennal lobe circuit to enhance the uniqueness of the current stimulus. Nevertheless, information about the odorant identity became confounded due to this contrast-enhancement computation. Notably, a linear logical classifier (OR-of-ANDs) that can decode information distributed in flexible subsets of neurons generated predictions that matched results from our behavioral experiments. In sum, our results reveal a simple computational logic for achieving the stability vs. flexibility tradeoff in sensory coding.
Evolution of the α-BaMg(CO3)2low-temperature superstructure and the tricritical nature of its α–β phase transition
Authors: Ende Martin , Effenberger Herta , Miletich Ronald
Published: September 2017

The crystal structure of the synthetic double carbonate norsethite [BaMg(CO3)2] has been reinvestigated using X-ray diffraction data within the temperature range 100–500 K using a high-sensitivity PILATUS pixel detector. The previously assumed positional shift of the crystallographically unique oxygen atom is confirmed. The shift is associated with a coupled rotation of symmetry-equivalent carbonate groups. It was possible to follow the shift using high-accuracy experiments under varying temperature conditions between 100 K and the critical transition temperature occurring atTc= 363 ± 3 K. The transition of the α-form (space groupR{\bar 3}c; belowTc), which represents a superstructure of the β-form (space groupR{\bar 3}m, withc′ =c/2; aboveTc) was studied in detail. The tricritical order character of this displacive phase transition was verified by tracking the intensities of the recorded superstructure reflections (l= 2n+ 1) from single-crystal diffraction and using high-precision lattice parameters obtained from powder diffraction in transmission geometry. Thermodynamic properties suggest both rotation of the CO3group and a coordination change of the BaO12coordination polyhedra as the order parameters driving the temperature-dependent α–β phase transition. Nevertheless, a detailed structural analysis reveals the coordination change of the barium atoms to be the main driving force for the observed transformation.
Domestic abuse and older people: factors influencing help-seeking
Authors: Wydall Sarah , Zerk Rebecca
Published: September 2017

Purpose

The purpose of this paper is to explore professionals’ perceptions of the barriers to help-seeking for victim-survivors of domestic abuse aged 60 years and over. Help-seeking as defined by Anderson and Saunders (2003) is not a single act or decision, but a complex and continuous process, victims engage in when seeking support.

Design/methodology/approach

A total of 50 qualitative semi-structured interviews were conducted with statutory practitioners and managers from 21 out of 22 local authorities in Wales. The research team worked collaboratively to produce a coding scheme which was subjected to a systematic coding exercise using the software package NVivo.

Findings

Professionals believed that older people’s “interconnectedness” with family, social embeddedness in the community and “meanings of the home” influenced help-seeking. The research suggests that for older victim-survivors of domestic abuse, age discrimination by practitioners, compounds older people’s experiences of help-seeking, restricting the range, quality and type of support provided. The paper demonstrates that a significant shift is required in practice to ensure that older people are in a position to make informed choices and their wishes are central in the decision-making process.

Research limitations/implications

Further qualitative research is needed to explore what older people themselves believe are the factors that impact on statutory service engagement.

Originality/value

This study is the first in the UK to conduct Pan-Wales research on professionals’ views on help-seeking behaviours of older people. One of the key findings from the study is that professionals from the statutory sector feel that connections to the home and social networks strongly influence help-seeking for older victim-survivors of domestic abuse.
10,000 Voices: service users’ experiences of adult safeguarding
Authors: Montgomery Lorna , Hanlon Deborah , Armstrong Christine
Published: September 2017

Purpose

The purpose of this paper is to describe a small scale pilot study undertaken in Northern Ireland to gather service user feedback from individuals who have been subject to adult safeguarding procedures.

Design/methodology/approach

The aims, methods and findings of the “Adult Safeguarding: 10,000 Voices” pilot project are presented.

Findings

The pilot project highlighted how an initiative which captures the experiences of patients, service users, carers and staff in the health and social care sector (10,000 Voices) could be successfully adapted for use in adult safeguarding, facilitating the collation of complex experiences and enabling insights to be gleaned and shared.

Research limitations/implications

The pilot study is limited by the small number of participants. The findings are preliminary.

Practical implications

For the first time in Northern Ireland the 10,000 Voices model was utilised in the context of a non-health related service, namely, adult safeguarding.

Social implications

This outline of the model and methodology for obtaining service user feedback can inform user involvement in other contexts.

Originality/value

This paper provides an accessible overview of an innovative approach to engaging service users in adult safeguarding, such approaches, to date have been limited.
Job demands, job control, psychological climate, and job satisfaction
Authors: Karanika-Murray Maria , Michaelides George , Wood Stephen J.
Published: September 2017

Purpose

Research into job design and employee outcomes has tended to examine job design in isolation of the wider organizational context, leading to calls to attend to the context in which work is embedded. The purpose of this paper is to examine the effects of the interaction between job design and psychological climate on job satisfaction.

Design/methodology/approach

Cognitive dissonance theory was used to explore the nature of this relationship and its effect on job satisfaction. The authors hypothesized that psychological climate (autonomy, competence, relatedness dimensions) augments favorable perceptions of job demands and control when there is consistency between them (augmentation effect) and compensates for unfavorable perceptions when they are inconsistent (compensation effect).

Findings

Analysis of data from 3,587 individuals partially supported the hypotheses. Compensation effects were observed for job demands under a high autonomy and competence climate and for job control under a low competence climate. Augmentation effects were observed for job demands under a high relatedness climate.

Practical implications

When designing jobs managers should take into account the effects of psychological climate on employee outcomes.

Originality/value

This study has offered a way to bridge the job design and psychological climate fields and demonstrated that the call for more attention to the context in which jobs are embedded is worth heeding.
Long‐term population dynamics: Theory and reality in a peatland ecosystem
Authors: Connor Simon E. , Colombaroli Daniele , Confortini Federico , Gobet Erika , Ilyashuk Boris P. , Ilyashuk Elena A. , van Leeuwen Jacqueline F. N. , Lamentowicz Mariusz , van der Knaap Willem O. , Malysheva Elena , Marchetto Aldo , Margalitadze Nino , Mazei Yuri , Mitchell Edward A. D. , Payne Richard J. , Ammann Brigitta
Published: September 2017

Population dynamics is a field rich in theory and poor in long‐term observational data. Finding sources of long‐term data is critical as ecosystems around the globe continue to change in ways that current theories and models have failed to predict. Here we show how long‐term ecological data can improve our understanding about palaeo‐population change in response to external environmental factors, antecedent conditions and community diversity.

We examined a radiometrically dated sediment core from the Didachara Mire in the mountains of south‐western Georgia (Caucasus) and analysed multiple biological proxies (pollen, fern spores, non‐pollen palynomorphs, charcoal, diatoms, chrysophyte cysts, midges, mites and testate amoebae). Numerical techniques, including multivariate ordination, rarefaction, independent splitting and trait analysis, were used to assess the major drivers of changes in community diversity and population stability. Integrated multi‐proxy analyses are very rare in the Caucasus, making this a unique record of long‐term ecological change in a global biodiversity hotspot.

Synthesis. Population changes in the terrestrial community coincided primarily with external environmental changes, while populations within the peatland community were affected by both internal and external drivers at different times. In general, our observations accord with theoretical predictions that population increases lead to greater stability and declines lead to instability. Random variation and interspecific competition explain population dynamics that diverged from predictions. Population change and diversity trends were positively correlated in all taxonomic groups, suggesting that population‐level instability is greater in more diverse communities, even though diverse communities are themselves more stable. There is a continuing need to confront population theory with long‐term data to test the predictive success of theoretical frameworks, thereby improving their ability to predict future change.
C1q/TNF‐related protein 9 improves the anti‐contractile effects of perivascular adipose tissue via the AMPK‐eNOS pathway in diet‐induced obese mice
Authors: Han Fang , Zhang Yang , Shao Mingxia , Mu Qingjie , Jiao Xiaotong , Hou Ningning , Sun Xiaodong
Published: September 2017

The anti‐contractile property of perivascular adipose tissue (PVAT) is abolished through an endothelium‐dependent pathway in obesity. C1q/tumor necrosis factor‐related protein (CTRP)9 improved endothelial function by promoting endothelium‐dependent vasodilatation. The aims of this study were to investigate whether CTRP9 improves the anti‐contractile effect of PVAT and protects against PVAT dysfunction in obese mice. The mice were treated with a high‐fat diet with or without CTRP9 treatment. Thoracic aortas with or without PVAT (PVAT+ or PVAT−) were prepared, and concentration‐dependent responses to phenylephrine were measured. Obese mice showed a significantly increased contractile response, which was suppressed by CTRP9 treatment both with and without PVAT. PVAT significantly reduced the anti‐contractile effect in obese mice, which was partially restored by CTRP9 treatment. Treatment of the aortic rings (PVAT+) with inhibitors of AMP protein kinase (AMPK), Akt and endothelial nitric oxide synthase (eNOS) attenuated the beneficial effect of CTRP9 on PVAT. Similar results were observed when we pretreated the aortic rings with CTRP9 ex vivo. CTRP9 significantly enhanced the phosphorylation levels of AMPK, Akt and eNOS, and reduced superoxide production and TNF‐α levels in PVAT from obese mice. Our study suggests that CTRP9 enhanced the anti‐contractile effect of PVAT and improved PVAT function by activating the AMPK‐eNOS pathway in obese mice.
Systemic justice and burnout: A multilevel model
Authors: Haines Victor Y. , Patient David L. , Marchand Alain
Published: September 2017

With the aim of extending organisational justice research to embrace significant and enduring aspects of the workplace context, this study examines organisational culture and human resource management (HRM) as constitutive dimensions of systemic justice and relates them to employee health. Bridging organisational justice, HRM, organisational culture, and occupational health research, we advance and test a multilevel model relating systemic justice to burnout. Data collected from 60 organisations; 89 employee groups; and 1,976 employees provide support for the hypothesised relationships between justice‐oriented culture, in terms of organisational values and group culture, and justice‐oriented HRM. In turn, justice‐oriented HRM related directly to employee burnout and indirectly through employee perceived job control and supervisor social support.
The location of projection neurons to the biceps brachii muscle in the telencephalon of the pigeon
Authors: Park J. H. , Ahn J. H. , Choi S. Y. , Cho J. H. , Lee T.‐K. , Kim I. H. , Lee J.‐C. , Choi J. H. , Hwang I. K. , Lee Y. J. , Lee E. , Park S. , Lim J. , Seo K. , Won M.‐H.
Published: September 2017

Few studies regarding the anatomical distribution of motor neurons innervating muscles of the arm have been demonstrated in avian brains. The purpose of this study was to finely determine the localization of cerebral neurons innervating the biceps brachii muscle in the pigeon. The cholera toxin B subunit (CTB) was employed as a retrograde tracer to determine the location of neurons controlling the biceps brachii muscle in the telencephalon following intramuscular injection in male pigeons (n = 7), which were killed 14 days after intramuscular injection with CTB. We found that CTB‐labelled neurons were located contralaterally in the hyperpallium apicale of the rostral telencephalon and that most of the CTB‐labelled neurons were pyramidal in shape. This study shows that CTB is easily taken up by nerve terminals which innervate the biceps brachii muscle of the pigeon and that cerebral motor neurons controlling the biceps brachii muscle are located in the hyperpallium apicale.
Effect of obesity on neonatal hypoglycaemia in mothers with gestational diabetes: A comparative study
Authors: Collins Katherine , Oehmen Raoul , Mehta Shailender
Published: September 2017

Background

Rates of pre‐gestational obesity and gestational diabetes mellitus (GDM) are increasing in Australia. While both are established risk factors for neonatal hypoglycaemia, the additive effect of both risks on neonatal hypoglycaemia is not well understood.

Aims

To determine the influence of obesity on neonatal hypoglycaemia among infants born to GDM mothers. The authors hypothesise the presence of a greater frequency and severity of neonatal hypoglycaemia in infants born to obese GDM women.

Materials and methods

A cohort of 471 singleton GDM pregnancies was retrospectively studied. Women were divided into obese (body mass index (BMI) ≥ 30 kg/m2) and not‐obese (BMI < 30 kg/m2) groups according to self‐reported pre‐pregnancy weight. Perinatal outcomes and details of hypoglycaemic episodes were obtained by reviewing medical records.

Results

Twenty‐five percent (104/410) of the GDM mothers were obese, while 36% (146/410) exceeded pregnancy weight gain recommendations. GDM and obesity resulted in a greater frequency of neonatal hypoglycaemia as compared to women with GDM alone (obese 44%, not obese 34%, P = 0.046). Obesity increased the likelihood of having multiple hypoglycaemic episodes (P = 0.022). Excess weight gain increased the likelihood of the neonate requiring intravenous dextrose (P = 0.0012). No differences were found in the likelihood of nursery admissions or lowest plasma glucose levels.

Conclusions

Pre‐pregnancy obesity and weight gain during pregnancy above the recommended limits increased the likelihood of neonatal hypoglycaemia among infants of GDM mothers. Further studies with larger cohorts are warranted to confirm our findings.
Investigation and management of gastro‐oesophageal reflux in United Kingdom neonatal intensive care units
Authors: Rossor Thomas , Andradi Gwendolyn , Bhat Ravindra , Greenough Anne
Published: September 2017

Aim

In 2004, wide variation in the investigation and management of gastro‐oesophageal reflux (GOR) of infants on UK major neonatal units was demonstrated. Our aim was to resurvey neonatal practitioners to determine current practice and whether it was now evidence based.

Methods

A questionnaire was sent to all 207 UK neonatal units.

Results

Responses were obtained from 84% of units. The most frequent ‘investigation’ was a trial of therapy (83% of units); pH studies were used in 38%, upper GI contrast studies in 19% and multichannel intraluminal impedance (MII)/pH studies in 5%. Only six units suggested a threshold for an abnormal pH study and two units for an abnormal MII study. Infants were commenced on antireflux medication without investigation always in 32% of units, often in 29%, occasionally in 19% and only never in 1%. Gaviscon was used as first line treatment in 60% of units, and other medications included ranitidine in 53%, thickening agents in 27%, proton pump inhibitors in 23%, domperidone in 22% and erythromycin in 6%.

Conclusion

There remains a wide variation in diagnostic and treatment strategies for infants with suspected GOR on neonatal intensive care units, emphasising the need for randomised trials to determine appropriate GOR management.
Primary, congenital neuroaxonal dystrophy with peripheral nerve demyelination in Merino–Border Leicester × Polled Dorset lambs
Authors: Hawes MC , Finnie JW , Jerrett IV , Badman R , Scott M
Published: September 2017

Case report

Clinicopathological features of neuroaxonal dystrophy (NAD) in newborn, Merino–Border Leicester × Polled Dorset lambs are described. The affected lambs were unable to walk at birth and microscopic examination of brainstem and spinal cord sections revealed bilaterally symmetrical accumulations of axonal swellings (spheroids), the histological hallmark of primary NAD. The neurological deficit was also exacerbated by myelin loss and secondary axonal degeneration, particularly in the spinal cord and sciatic nerves, but also, to a more limited extent, in brainstem and spinal nerves.

Conclusions

Although lambs previously diagnosed with NAD have ranged in age from 2 days to 7 months, this is believed to be the first report of congenital NAD in this species. Moreover, the present cases are the only ones in which peripheral nerve demyelination has been found.