bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for allocentric boundary and goal direction information in the human entorhinal cortex and subiculum
Authors: Shine J. P. , Valdés-Herrera J. P. , Tempelmann C. , Wolbers T.
Published: November 2018

In rodents, cells in the medial entorhinal cortex (EC) and subiculum code for the allocentric direction to environment boundaries, which is an important prerequisite for accurate positional coding. Although in humans boundary-related signals have been reported, there is no evidence that they contain allocentric direction information. Furthermore, it has not been possible to separate boundary versus goal direction signals in the EC/subiculum. To address these important questions, participants learned a virtual environment containing four unique boundaries, after which they underwent fMRI scanning where they made judgments about the allocentric direction of a cue object. Using multivariate decoding, we found information regarding allocentric boundary direction in posterior EC and subiculum, whereas in anterior EC and subiculum we could decode allocentric goal direction. These data provide the first evidence of allocentric boundary coding in humans, and are consistent with recent conceptualisations of a division of labour within the EC.
Contextual interference effect is independent of retroactive inhibition but variable practice is not always beneficial
Authors: Thürer Benjamin , Gedemer Sarah , Focke Anne , Stein Thorsten
Published: November 2018

Positive effects of variable practice conditions on subsequent motor memory consolidation and generalization are widely accepted and described as the contextual interference effect (CIE). However, the general benefits of CIE are low and these benefits might even depend on decreased retest performances in the blocked-practicing control group, caused by retroactive inhibition. The aim of this study was to investigate if CIE represents a true learning phenomenon or possibly reflects confounding effects of retroactive inhibition. We tested 48 healthy human participants adapting their reaching movements to three different force field magnitudes. Subjects practiced the force fields in either a Blocked (B), Random (R), or Constant (C) schedule. In addition, subjects of the Blocked group performed either a retest schedule that did (Blocked-Matched; BM) or did not (Blocked-Unmatched; BU) control for retroactive inhibition. Results showed that retroactive inhibition did not affect the results of the BU group much and that the Random group showed a better consolidation performance compared to both Blocked groups. However, compared to the Constant group, the Random group showed only slight benefits in its memory consolidation of the mean performance across all force field magnitudes and no benefits in absolute performance values. This indicates that CIE reflects a true motor learning phenomenon, which is independent of retroactive inhibition. However, random practice is not always beneficial over constant practice.
Multiple Duration Priors Within and Across the Senses
Authors: Rhodes Darren , Seth Anil K. , Roseboom Warrick
Published: November 2018

Perception can be understood as an active process in which sensory samples are combined with prior expectations to shape perceptual content. A prominent example of the influence of priors on perception is that manually reproduced temporal durations are biased towards the mean of previously experienced durations. However, little is known about how prior expectations are acquired and maintained in environments in which multiple competing cues may indicate whether a given prior should be applied in that specific context. We tested whether human participants could acquire and maintain multiple priors for duration, dependent on the sensory signal in which the duration was presented. Human participants were presented with visual flashes or auditory tones, high or low pitch tones, or white noise versus pure tone audio. In each case, the presented duration on a given trial was drawn from a distribution that was, on average, shorter for tones than for flashes, or vice versa. Our participants’ timing reports were consistent with having acquired distinct duration priors dependent on the sensory signal in which the duration was presented (e.g. auditory or visual). Moreover, this was true whether signals differed across, or within, sensory modality. We account for our findings within a Bayesian framework in which duration priors are iteratively updated depending on determination of a common or distinct origin between successive events. Overall, these results show that the human brain can acquire and maintain multiple perceptual priors based on differences in stimulus properties both within and across the senses.
Human Dental Pulp Stem Cells Grown in Neurogenic Media Differentiate into Endothelial Cells and Promote Neovasculogenesis in the Mouse Brain
Authors: Luzuriaga J. , Pastor-Alonso O. , Encinas J.M. , Unda F. , Ibarretxe G. , Pineda JR.
Published: November 2018

Dental Pulp Stem Cells (DPSCs) have a demonstrated capacity to acquire neuronal-like phenotypes, suggesting their use in brain cell therapies. In the present work, we wanted to address the phenotypic fate of adult DPSCs cultured in Neurocult media (Stem Cell Technologies), a cell culture medium without serum routinely used for the expansion of adult neural stem cells (NSCs). Our results showed for the first time, that non-genetically modified adult DPSCs cultured with Neurocult generated neurosphere-like dentospheres expressing the NSC markers Nestin and GFAP, but also the vascular endothelial cell marker CD31. One month post-intracranial graft into athymic nude mice, human CD31+ or Nestin+ DPSC-derived cells were found tightly associated with brain blood vessels increasing their laminin staining. These results suggest that DPSCs integrated and contributed to an increased generation of neovasculature within brain tissue and that Neurocult medium constituted a fast and efficient way to obtain endothelial cells from human DPSCs.
Ensemble projections of global ocean animal biomass with climate change
Authors: Lotze Heike K. , Tittensor Derek P. , Bryndum-Buchholz Andrea , Eddy Tyler D. , Cheung William W. L. , Galbraith Eric D. , Barange Manuel , Barrier Nicolas , Bianchi Daniele , Blanchard Julia L. , Bopp Laurent , Büchner Matthias , Bulman Catherine , Carozza David A. , Christensen Villy , Coll Marta , Dunne John , Fulton Elizabeth A. , Jennings Simon , Jones Miranda , Mackinson Steve , Maury Olivier , Niiranen Susa , OliverosRamos Ricardo , Roy Tilla , Fernandes José A. , Schewe Jacob , Shin Yunne-Jai , Silva Tiago A. M. , Steenbeek Jeroen , Stock Charles A. , Verley Philippe , Volkholz Jan , Walker Nicola D.
Published: November 2018

Climate change is shifting the abundance and distribution of marine species with consequences for ecosystem functioning, seafood supply, management and conservation. Several approaches for future projection exist but these have never been compared systematically to assess their variability. We conducted standardized ensemble projections including 6 global fisheries and marine ecosystem models, forced with 2 Earth-system models and 4 emission scenarios in a fished and unfished ocean, to derive average trends and associated uncertainties. Without fishing, mean global animal biomass decreased by 5% (±4%) under low and 17% (±11%) under high emissions by 2100, primarily driven by increasing temperature and decreasing primary production. These climate-change effects were slightly weaker for larger animals and in a fished ocean. Considerable regional variation ranged from strong biomass increases in high latitudes to strong decreases in mid-low latitudes, with good model agreement on the direction of change but variable magnitude. Uncertainties due to differences among ecosystem or Earth-system models were similar, suggesting equal need for model improvement. Our ensemble projections provide the most comprehensive outlook on potential climate-driven ecological changes in the ocean to date. Realized future trends will largely depend on how fisheries and management adapt to these changes in a changing climate.
Linking Branch Lengths Across Loci Provides the Best Fit for Phylogenetic Inference
Authors: Duchêne David A. , Tong K. Jun , Foster Charles S. P. , Duchêne Sebastián , Lanfear Robert , Ho Simon Y. W.
Published: November 2018

Evolution leaves heterogeneous patterns of nucleotide variation across the genome, with different loci subject to varying degrees of mutation, selection, and drift. Appropriately modelling this heterogeneity is important for reliable phylogenetic inference. One modelling approach in statistical phylogenetics is to apply independent models of molecular evolution to different groups of sites, where the groups are usually defined by locus, codon position, or combinations of the two. The potential impacts of partitioning data for the assignment of substitution models are well appreciated. Meanwhile, the treatment of branch lengths has received far less attention. In this study, we examined the effects of linking and unlinking branch-length parameters across loci. By analysing a range of empirical data sets, we find that the best-fitting model for phylogenetic inference is consistently one in which branch lengths are proportionally linked: gene trees have the same pattern of branch-length variation, but with varying absolute tree lengths. This model provided a substantially better fit than those that either assumed identical branch lengths across gene trees or that allowed each gene tree to have its own distinct set of branch lengths. Using simulations, we show that the fit of the three different models of branch lengths varies with the length of the sequence alignment and with the number of taxa in the data set. Our findings suggest that a model with proportionally linked branch lengths across loci is likely to provide the best fit under the conditions that are most commonly seen in practice. In future work, improvements in fit might be afforded by models with levels of complexity intermediate to proportional and free branch lengths. The results of our study have implications for model selection, computational efficiency, and experimental design in phylogenomics.
Rapid task-dependent tuning of the mouse olfactory bulb
Authors: Koldaeva Anzhelika , Schaefer Andreas T , Fukunaga Izumi
Published: November 2018

Adapting neural representation to rapidly changing behavioural demands is a key challenge for the nervous system. Here, we demonstrate that the output of the primary olfactory area, the mouse olfactory bulb, is already a target of dynamic and reproducible modulation. The modulation depends on the stimulus tuning of a given neuron, making olfactory responses more discriminable through selective amplification in a demand-specific way.
Penaeidins are a novel family of antiviral effectors against WSSV in shrimp
Authors: Xiao Bang , Fu Qihui , Niu Shengwen , Li Haoyang , Lǚ Kai , Wang Sheng , Yin Bin , Weng Shaoping , Li Chaozheng , He Jianguo
Published: November 2018

Penaeidins are members of a family of key effectors with broad anti-bacterial activities in penaeid shrimp. However, the function of penaeidins in antiviral immunity is rarely reported and remains largely unknown. Herein, we uncovered that penaeidins are a novel family of antiviral effectors against white spot syndrome virus (WSSV). Firstly, RNAi in vivo mediated knockdown of each penaeidin from four identified penaeidins from Litopenaeus vannamei resulted in elevated viral loads and rendered shrimp more susceptible to WSSV, whilst the phenotype of survival rate in penaeidin-silenced shrimp can be rescued via the injection of recombinant penaeidin proteins. Moreover, pull-down assays demonstrated the conserved PEN domain of penaeidin was able to interact with WSSV structural proteins. Furthermore, we observed that colloidal gold-labeled penaeidins were located on the outer surface of the WSSV virion. By infection-blocking assay, we observed that hemocytes had lower viral infection rates in the group of WSSV preincubated with penaeidins than those of control group. Phagocytic activity analysis further showed that penaeidins were able to inhibit phagocytic activity of hemocytes against WSSV Taken together, these results suggest that penaeidins specifically binds to WSSV virion by interacting with its structural proteins, thus preventing viral infection that confers host against WSSV. In addition, dual-luciferase assay and EMSA assay demonstrated that penaeidins were regulated by Dorsal and Relish, two transcription factors of the canonical Toll and IMD pathway, respectively. To our best knowledge, this is the first report on uncovering the antiviral function of penaeidins in the innate immune system of shrimp.

Importances

White spot syndrome, caused by white spot syndrome virus (WSSV), is the most serious disease in shrimp aquaculture, which has long been a scourge of cultured shrimp industry. Herein, we provided some substantial evidences to indicate that penaeidins are a novel family of effectors with antiviral activity against WSSV in shrimp. Penaeidins such as BigPEN, PEN2 and PEN3 were able to interact with the outer surface of WSSV virion via binding to viral structural proteins, and thus preventing viral entry host cells. In addition, we demonstrated that the Toll and IMD signaling pathways can regulate the transcriptional expression of penaeidins, which may suggest an important role of the conserved innate signaling pathways in antiviral immunity. This is the first report of the antiviral mechanism of penaeidins in shrimp, which may provide some new insights into strategies to control WSSV infection in shrimp farms.
Evolutionary dynamics of carbapenem-resistant Acinetobacter baumannii circulating in Chilean hospitals
Authors: Opazo-Capurro Andrés , Martín Iván San , Quezada-Aguiluz Mario , Morales Felipe , Domínguez-Yévenes Mariana , Lima Celia A. , Esposito Fernanda , Cerdeira Louise , Bello-Toledo Helia , Lincopan Nilton , González-Rocha Gerardo
Published: November 2018

We analyze the evolutionary dynamics of ninety carbapenem-resistant Acinetobacter baumannii (CRAB) isolates collected between 1990 and 2015 in Chile. CRAB were identified at first in an isolate collected in 2005, which harbored the ISAba1-blaOXA-69 arrangement. Later, OXA-58- and OXA-23-producing A. baumannii strains emerged in 2007 and 2009, respectively. This phenomenon was associated with variations in the epidemiology of OXA-type carbapenemases, linked to nosocomial lineages belonging to ST109 (CC1), ST162 (CC79), ST15 (CC15) and ST318 (CC15).
Reevaluation of the Role of ERK3 in Perinatal Survival and Post-Natal Growth Using New Genetically-Engineered Mouse Models
Authors: Soulez Mathilde , Saba-El-Leil Marc K. , Turgeon Benjamin , Mathien Simon , Coulombe Philippe , Klinger Sonia , Rousseau Justine , Lévesque Kim , Meloche Sylvain
Published: November 2018

The physiological functions of the atypical MAP kinase ERK3 remain poorly characterized. Previous analysis of mice with a targeted insertion of the lacZ reporter in the Mapk6 locus (Mapk6lacZ) showed that inactivation of ERK3 in Mapk6lacZ mice leads to perinatal lethality associated with intrauterine growth restriction, defective lung maturation, and neuromuscular anomalies. To further explore the role of ERK3 in physiology and disease, we generated novel mouse models expressing a catalytically-inactive (Mapk6KD) or conditional (Mapk6Δ) allele of ERK3. Surprisingly, we found that mice devoid of ERK3 kinase activity or expression survive the perinatal period without any observable lung or neuromuscular phenotype. ERK3 mutant mice reached adulthood, were fertile and showed no apparent health problem. However, analysis of growth curves revealed that ERK3 kinase activity is ncessary for optimal post-natal growth. To gain insight into the genetic basis underlying the discrepancy in phenotypes of different Mapk6 mutant mouse models, we analyzed the regulation of genes flanking the Mapk6 locus by quantitative PCR. We found that expression of several Mapk6 neighboring genes is deregulated in Mapk6lacZ mice, but not in Mapk6KD or Mapk6Δ mutant mice. Our genetic analysis suggests that off-target effects of the targeting construct on local gene expression are likely to be responsible for the perinatal lethality phenotype of Mapk6lacZ mutant mice.
Population genetic structure of the bank vole Myodes glareolus within its glacial refugium in peninsular Italy
Authors: Chiocchio Andrea , Colangelo Paolo , Aloise Gaetano , Amori Gianni , Bertolino Sandro , Bisconti Roberta , Castiglia Riccardo , Canestrelli Daniele
Published: November 2018

It is now well established that Southern European peninsulas have been major glacial refugia for temperate species during Pleistocene climatic oscillations. However, substantial environmental changes occurred also within these peninsulas throughout the Pleistocene, rising questions about the role and interplay of various of micro-evolutionary processes in shaping patterns of intraspecific diversity within these areas. Here, we investigate the patterns of genetic variation in the bank vole Myodes glareolus within the Italian peninsula. By using a panel of 13 microsatellite loci, we found more intra-specific variation than expected based on previous assessments. Indeed, both Bayesian and ordination-based clustering analyses of variation recovered five main geographic/genetic clusters along the peninsula, with three clusters geographically restricted to the southern portion of the study area. This pattern supports the occurrence of multiple sub-refugia for the bank vole in peninsular Italy, likely promoted by the major paleo-environmental changes which affected forested habitats within this area during the Pleistocene. Thus, our results support a scenario whereby the high levels of intraspecific diversity observed within major glacial refugia are better explained by dynamic micro-evolutionary processes occurred within these areas, rather than by long-term demographic stability of refugial population. Finally, the narrow and isolated distribution of some of the identified lineages, suggest the need for future assessments of their conservation and taxonomic status.
Bayesian estimation for stochastic gene expression using multifidelity models
Authors: Vo Huy D. , Fox Zachary , Baetica Ania , Munsky Brian
Published: November 2018

The finite state projection (FSP) approach to solving the chemical master equation has enabled successful inference of discrete stochastic models to predict single-cell gene regulation dynamics. Unfortunately, the FSP approach is highly computationally intensive for all but the simplest models, an issue that is highly problematic when parameter inference and uncertainty quantification takes enormous numbers of parameter evaluations. To address this issue, we propose two new computational methods for the Bayesian inference of stochastic gene expression parameters given single-cell experiments. We formulate and verify an Adaptive Delayed Acceptance Metropolis-Hastings (ADAMH) algorithm to utilize with reduced Krylov-basis projections of the FSP. We then introduce an extension of the ADAMH into a Hybrid scheme that consists of an initial phase to construct a reduced model and a faster second phase to sample from the approximate posterior distribution determined by the constructed model. We test and compare both algorithms to an adaptive Metropolis algorithm with full FSP-based likelihood evaluations on three example models and simulated data to show that the new ADAMH variants achieve substantial speedup in comparison to the full FSP approach. By reducing the computational costs of parameter estimation, we expect the ADAMH approach to enable efficient data-driven estimation for more complex gene regulation models.
Transcriptome responses to reduced dopamine in the Substantia Nigra Pars Compacta reveals a potential protective role for dopamine
Authors: Koltun M. , Cichewicz K. , Gibbs J.T. , Darvas M. , Hirsh J.
Published: November 2018

Parkinson’s Disease (PD), is a neurodegenerative disorder affecting both cognitive and motor functions. It is characterized by decreased brain dopamine (DA) and a selective and progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), whereas dopaminergic neurons in the ventral tegmental area (VTA) show reduced vulnerability. The majority of animal models of PD are genetic lesion or neurotoxin exposure models that lead to death of dopaminergic neurons. Here we use a DAT:TH KO mouse model that by inactivation of the tyrosine hydroxylase (Th) gene in dopamine transporter-expressing neurons, causes selective depletion of striatal dopamine without affecting DA neuron survival. We analyzed transcriptome responses to decreased DA in both pre- and post-synaptic dopaminergic brain regions of DAT:TH KO animals. We detected only few differentially expressed genes in the post-synaptic regions as a function of DA deficiency. This suggests that the broad striatal transcriptional changes in neurodegeneration-based PD models are not direct effects of DA depletion, but are rather a result of DA neuronal death. However, we find a number of dopaminergic genes differentially expressed in SNc, and to a lesser extent in VTA, as a function of DA deficiency, providing evidence for a DA-dependent feedback loop. Of particular interest, expression ofNr4a2, a crucial transcription factor maintaining DA neuron identity, is significantly decreased in SNc, but not VTA, of DAT:TH KO mice, implying a potential protective role for DA in the SNc.
Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits
Authors: Barson D , Hamodi AS , Shen X , Lur G , Constable RT , Cardin JA , Crair MC , Higley MJ
Published: November 2018

Spontaneous and sensory-evoked activity propagates across spatial scales in the mammalian cortex but technical challenges have generally precluded establishing conceptual links between the function of local circuits of neurons and brain-wide network dynamics. To solve this problem, we developed a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake, behaving mice. Our method employs an orthogonal axis design whereby the mesoscopic objective is oriented downward directly above the brain and the two-photon objective is oriented horizontally, with imaging performed through a glass right angle microprism implanted in the skull. In support of this method, we introduce a suite of analysis tools for relating the activity of individual cells to distal cortical areas, as well as a viral method for robust and widespread gene delivery in the juvenile mouse brain. We use these methods to characterize the diversity of associations of individual, genetically-defined neurons with cortex-wide network motifs.
Comparative genomic analysis of the emerging pathogen Streptococcus pseudopneumoniae: novel insights into virulence determinants and identification of a novel species-specific molecular marker
Authors: Garriss Geneviève , Nannapaneni Priyanka , Simões Alexandra S. , Browall Sarah , Sá-Leão Raquel , Goossens Herman , de Lencastre Herminia , Henriques-Normark Birgitta
Published: November 2018

Streptococcus pseudopneumoniae is a close relative of the major human pathogen S. pneumoniae. While initially considered as a commensal species, it has been increasingly associated with lower-respiratory tract infections and high prevalence of antimicrobial resistance (AMR). S. pseudopneumoniae is difficult to identify using traditional typing methods due to similarities with S. pneumoniae and other members of the mitis group (SMG). Using phylogenetic and comparative genomic analyses of SMG genomes, we identified a new molecular marker specific for S. pseudopneumoniae and absent from any other bacterial genome sequenced to date. We found that a large number of known virulence and colonization genes are present in the core S. pseudopneumoniae genome and we reveal the impressive number of known and new surface-exposed proteins encoded by this species. Phylogenetic analyses of S. pseudopneumoniae show that specific clades are associated with allelic variants of core proteins. Resistance to tetracycline and macrolides, the two most common resistances, were encoded by Tn916-like integrating conjugative elements and Mega-2. Overall, we found a tight association of genotypic determinants of AMR as well as phenotypic AMR with a specific lineage of S. pseudopneumoniae. Taken together, our results sheds light on the distribution in S. pseudopneumoniae of genes known to be important during invasive disease and colonization and provide insight into features that could contribute to virulence, colonization and adaptation.

Importance

S. pseudopneumoniae is an overlooked pathogen emerging as the causative agent of lower-respiratory tract infections and associated with chronic obstructive pulmonary disease (COPD) and exacerbation of COPD. However, much remains unknown on its clinical importance and epidemiology, mainly due to the lack of specific means to distinguish it from S. pneumoniae. Here, we provide a new molecular marker entirely specific for S. pseudopneumoniae. Furthermore, our research provides a deep analysis of the presence of virulence and colonization genes, as well as AMR determinants in this species. Our results provide crucial information and pave the way for further studies aiming at understanding the pathogenesis and epidemiology of S. pseudopneumoniae.
Healthy ageing reduces the precision of episodic memory retrieval
Authors: Korkki Saana M. , Richter Franziska R. , Jeyarathnarajah Priyanga , Simons Jon S.
Published: November 2018

Episodic memory declines with older age, but it is unresolved whether this decline reflects reduced probability of successfully retrieving information from memory, or decreased precision of the retrieved information. Here, we used continuous measures of episodic memory retrieval in combination with computational modelling of participants’ retrieval errors to distinguish between these two potential accounts of age-related memory deficits. In three experiments, young and older participants encoded stimuli displays consisting of everyday objects varying along different perceptual features (e.g., location, colour and orientation) in a circular space. At test, participants recreated the features of studied objects using a continuous response dial. Across all three experiments, we observed age-related declines in the precision of episodic memory retrieval, whereas age differences in retrieval success were limited to the most challenging task condition. Reductions in mnemonic precision were evident for retrieval of both item-based and contextual information, and persisted after controlling for age-related decreases in the fidelity of perception and working memory. The findings highlight impoverished precision of memory representations as one factor contributing to age-related episodic memory loss, and suggest that the cognitive and neural changes associated with older age can differentially affect distinct aspects of episodic retrieval.
SpitWorm, an herbivorous robot: Mechanical leaf wounding with simultaneous application of salivary components
Authors: Li Guanjun , Bartram Stefan , Guo Huijuan , Mithöfer Axel , Kunert Maritta , Boland Wilhelm
Published: November 2018

Induction of plant defense against insect herbivory is initiated by a combination of both, mechanical wounding and chemical factors. In order to study both effects independently on plant defense induction, SpitWorm, a computer controlled device which mimics the damage pattern of feeding insect larvae on leaves and can additionally apply oral secretions (OS) or other solutions to the ‘biting site’ during ‘feeding’, was developed and evaluated. The amount of OS left by a Spodoptera littoralis larva during feeding on Phaseolus lunatus (lima bean) leaves was estimated by combining larval foregut volume, biting rate, and quantification of a fluorescent dye injected into the larvae’s foregut prior to feeding. For providing OS amounts by SpitWorm equivalent to larval feeding, dilution and delivery rate were optimized. The effectiveness of SpitWorm was tested by comparing volatile organic compounds (VOC) emissions of P. lunatus leaves treated with either SpitWorm, MecWorm or S. littoralis larvae. Identification and quantification of emitted VOCs revealed that SpitWorm induced a volatile bouquet that is qualitatively and quantitatively similar to herbivory. Additionally, RT-qPCR of four jasmonic acid responsive genes showed that SpitWorm, in contrast to MecWorm, induces the same regulation pattern as insect feeding. Thus, SpitWorm mimics insect herbivory almost identical to real larvae feeding.
Ischemic Preconditioning and Left Ventricular Dysfunction: A Novel Mechanism & Model for Pulseless Electrical Activity
Authors: Patil Kaustubha D , Tunin Richard S , Fink Sarah J , Tao Susumu , Halperin Henry R
Published: November 2018

Background

Pulseless electrical activity (PEA) is a very common rhythm in cardiac arrest and survival is ≈ 5%. Population data suggest coronary ischemia significantly contributes to PEA, but the mechanism is unknown.

Objectives

We hypothesize ischemic preconditioning (IPC) in the setting of left ventricular (LV) dysfunction can convert ischemia-induced ventricular fibrillation (VF) into ischemia-induced PEA.

Methods

Using percutaneous coronary interventions in anesthetized swine, we studied the effect of IPC prior to ischemia on arrhythmic burden in normal animals and in animals with LV dysfunction. IPC protocol: four cycles of three minutes of coronary occlusion followed by seven minutes of reperfusion. Chronic LV dysfunction protocol: two serial infarcts in two coronary territories, separated by one week of recovery.

Results

In normal animals, IPC prior to ischemia significantly reduced VF incidence (2/8 IPC vs. 7/8 control). In IPC animals with VF, the time to VF was significantly delayed (37.2 ± 7.3 min vs. 20.7 ± 4.9 min, p<0.005). In chronic LV dysfunction animals (EF 15% ± 5%), ischemia caused PEA in all animals (18/18). In non-preconditioned animals, VF followed PEA in all cases (12/12). In preconditioned animals, PEA sustained without VF in 2/6 animals. In 4/6 animals, PEA was prolonged and time to VF was significantly delayed compared to non-preconditioned animals (33.7 ± 7.8 min vs. 12.2 ± 5.0 min, p<0.0001).

Conclusion

IPC delays/prevents VF. IPC with LV dysfunction prior to ischemia produces prolonged PEA. IPC with LV dysfunction prior to ischemia is likely an important mechanism for human PEA arrest. This is the first animal model of ischemic pulseless electrical activity.
Maintenance of spatial gene expression by Polycomb-mediated repression after formation of a vertebrate body plan
Authors: Rougeot Julien , Chrispijn Naomi D. , Aben Marco , Elurbe Dei M. , Andralojc Karolina M. , Murphy Patrick J. , Jansen Pascal W.T.C. , Vermeulen Michiel , Cairns Bradley R. , Kamminga Leonie M.
Published: November 2018

Polycomb group (PcG) proteins are transcriptional repressors that are important regulators of cell fate during embryonic development. Among them, Ezh2 is responsible for catalyzing the epigenetic repressive mark H3K27me3 and is essential for animal development. The ability of zebrafish embryos lacking both maternal and zygoticezh2to form a normal body plan provides a unique model to comprehensively study Ezh2 function during early development in vertebrates. By using a multi-omics approach, we found that Ezh2 is required for the deposition of H3K27me3 and is essential for the recruitment of Polycomb group protein Rnf2. However, and despite the complete absence of PcG-associated epigenetic mark and proteins, only minor changes in H3K4me3 deposition and gene and protein expression occurred. These changes were mainly due to local deregulation of transcription factors outside their normal expression boundaries. Altogether, our results in zebrafish show that Polycomb-mediated gene repression is important right after the body plan is formed to maintain spatially restricted expression profiles of transcription factors and highlight the differences that exist in the timing of PcG protein action between vertebrate species.

Summary statement

Our unique zebrafish model of maternal and zygotic mutant for thePolycombgroup geneezh2reveals major conserved and divergent mechanisms in epigenetic gene repression during vertebrate development.
A Bayesian framework for the analysis of systems biology models of the brain
Authors: Russell-Buckland Joshua , Barnes Chris P. , Tachtsidis Ilias
Published: November 2018

Systems biology models are used to understand complex biological and physiological systems. Interpretation of these models is an important part of developing this understanding. These models are often fit to experimental data in order to understand how the system has produced various phenomena or behaviour that are seen in the data. In this paper, we have outlined a framework that can be used to perform Bayesian analysis of complex systems biology models. In particular, we have focussed on analysing a systems biology of the brain using both simulated and measured data. By using a combination of sensitivity analysis and approximate Bayesian computation, we have shown that it is possible to obtain a more complete understanding of the parameter space as compared to a maximum likelihood estimate based approach. This is done through analysis of simulated and experimental data. NIRS measurements were simulated using the same simulated systemic input data for the model in a ‘healthy’ and ‘impaired’ state. By analysing both of these datasets, we show that different parameter spaces can be distinguished and compared between different physiological states or conditions. Finally, we analyse experimental data using the new Bayesian framework and the previous maximum likelihood estimate approach, showing that the Bayesian approach provides a more complete understanding of the parameter space.

Author summary

Systems biology models are mathematical representations of biological processes that reproduce the overall behaviour of a biological system. They are comprised by a number of parameters representing biological information. We use them to understand the behaviour of biological systems, such as the brain. We do this by fitting the model’s parameter to observed or simulated data; and by looking at how these values change during the fitting process we investigate the mechanisms controlling the behaviour of our system. We are interested in understanding differences between a healthy and an injured brain. Here we outline a statistical framework that uses a Bayesian approach during the fitting process that can provide us with a distribution of parameters rather than single parameter number. We apply this method when simulating the physiological responses between a healthy and a vascular compromised brain to a drop in oxygenation. We then use experimental data that demonstrates the healthy brain response to an increase in arterial CO2 and fit our brain model predictions to the measurements. In both instances we show that our approach provides more information about the overlap between healthy and unhealthy brain states than a fitting process that provides a single value parameter estimate.
The Bayesian Superorganism: Collective Probability Estimation in Swarm Systems
Authors: Hunt Edmund R. , Franks Nigel R. , Baddeley Roland J.
Published: November 2018

Superorganisms such as social insect colonies are very successful relative to their non-social counterparts. Powerful emergent information processing capabilities would seem to contribute to the abundance of such ‘swarm’ systems, as they effectively explore and exploit their environment collectively. We develop a Bayesian model of collective information processing in a decision-making task: choosing a nest site (a ‘multi-armed bandit’ problem). House-huntingTemnothoraxants are adept at discovering and choosing the best available nest site for their colony: we propose that this is possible via rapid, decentralized estimation of the probability that each choice is best. Viewed this way, their behavioral algorithm can be understood as a statistical method that anticipates recent advances in mathematics. Our nest finding model in-corporates insights from approximate Bayesian computation as a model of colony-level behavior; and particle filtering as a model ofTemnothorax‘tandem running’. Our framework suggests that the mechanisms of complex collective behavior can sometimes be explained as a spatial enactment of Bayesian inference. It facilitates the generation of quantitative hypotheses regarding individual and collective movement behaviors when collective decisions must be made. It also points to the potential for bioinspired statistical techniques. Finally, it suggests simple mechanisms for collective decision-making in engineered systems, such as robot swarms.
Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders
Authors: Andlauer Till F. M. , Guzman-Parra Jose , Streit Fabian , Strohmaier Jana , González Maria José , Flores Susana Gil , Cabaleiro Fabeiro Francisco J. , del Río Noriega Francisco , Perez Fermin Perez , González Jesus Haro , Diaz Guillermo Orozco , de Diego-Otero Yolanda , Moreno-Kuestner Berta , Auburger Georg , Degenhardt Franziska , Heilmann-Heimbach Stefanie , Herms Stefan , Hoffmann Per , Frank Josef , Foo Jerome C. , Treutlein Jens , Witt Stephanie H. , Cichon Sven , Kogevinas Manolis ,   Bipolar Disorder Working Group of the Psychiatric Genomics Consortium,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Rivas Fabio , Mayoral Fermín , Müller-Myhsok Bertram , Forstner Andreas J. , Nöthen Markus M. , Rietschel Marcella
Published: November 2018

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families as well as 438 subjects from an independent, sporadic BD case-control cohort were analysed. Polygenic risk scores (PRS) for BD, schizophrenia, and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had significantly higher PRS for all three psychiatric disorders than the independent controls, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and sporadic BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses, therefore, demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. The PRS explained only part of the observed phenotypic variance and rare variants might have also contributed to disease development.
Structure-factor amplitude reconstruction from serial femtosecond crystallography of two-dimensional membrane-protein crystals
Authors: Casadei Cecilia M. , Nass Karol , Barty Anton , Hunter Mark S. , Padeste Celestino , Tsai Ching-Ju , Boutet Sébastien , Messerschmidt Marc , Sala Leonardo , Williams Garth J. , Ozerov Dmitry , Coleman Matthew , Li Xiao-Dan , Frank Matthias , Pedrini Bill
Published: November 2018

Serial femtosecond crystallography of two-dimensional membrane-protein crystals at X-ray free-electron lasers has the potential to address the dynamics of functionally relevant large-scale motions, which can be sterically hindered in three-dimensional crystals and suppressed in cryocooled samples. In previous work, diffraction data limited to a two-dimensional reciprocal-space slice were evaluated and it was demonstrated that the low intensity of the diffraction signal can be overcome by collecting highly redundant data, thus enhancing the achievable resolution. Here, the application of a newly developed method to analyze diffraction data covering three reciprocal-space dimensions, extracting the reciprocal-space map of the structure-factor amplitudes, is presented. Despite the low resolution and completeness of the data set, it is shown by molecular replacement that the reconstructed amplitudes carry meaningful structural information. Therefore, it appears that these intrinsic limitations in resolution and completeness from two-dimensional crystal diffraction may be overcome by collecting highly redundant data along the three reciprocal-space axes, thus allowing the measurement of large-scale dynamics in pump–probe experiments.
Solvomorphs of tyraminium 5,5-diethylbarbiturate: a rare example of the barbiturateR33(12) hydrogen-bond motif and a crystal structure withZ′ = 4
Authors: Rydz Agnieszka , Gryl Marlena , Stadnicka Katarzyna M.
Published: November 2018

In the past two decades, the solvomorphism phenomenon in organic materials has attracted much attention, especially in the pharmaceutical and materials industries. Cocrystallization with solvent molecules can lead to modified physical and chemical properties of materials. We present here two new solvomorphs (pseudopolymorphs) of tyraminium 5,5-diethylbarbiturate [2-(4-hydroxyphenyl)ethanaminium 5,5-diethyl-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide, C8H12NO+·C8H11N2O3−] with unusual structural features. Pseudopolymorph (I) follows the symmetry of theP21/nspace group and has four tyraminium cations, four barbitalate anions and four molecules of chloroform in the asymmetric unit. Pseudopolymorph (II) crystallizes in the space groupR\overline{3}cwith one tyraminium cation, one barbitalate anion and a small amount of disordered solvent (ethanol and water) located in the cavities. Hirshfeld surface analysis and the Non-Covalent Interaction (NCI) index were used to examine and compare the crystal packing features and intermolecular interactions in (I) and (II). Both materials crystallize with large unit cells and contain nontypical barbitalate ions formed through deprotonation of the barbital N3 position. Pseudopolymorph (I) is an example of a crystal structure with a rarely observed value ofZ′ = 4. Analysis of the hydrogen-bond patterns in (II) showed an unusual arrangement of three barbitalate anions inR33(12) rings, which is the first example of such a hydrogen-bond motif in barbital structures. The mutual arrangement of the ions in the crystal structure of (II) leads to the formation of specific cavities along thecdirection.
Into the light: effects of the presence of cleaning staff on customer experience
Authors: Vos Martijn C. , Sauren Jessica , Knoop Olaf , Galetzka Mirjam , Mobach Mark P. , Pruyn Ad T.H.
Published: November 2018

Purpose

The purpose of this paper is to determine how the presence of cleaning staff affects perceptions and satisfaction of train passengers. Day-time cleaning is becoming increasingly popular in (public) service environments. It is however unknown how the presence of cleaning staff in the service environment affects perceptions and satisfaction of end-users.

Design/methodology/approach

Two experimental field studies were performed. Data for the first study were collected on the trajectory between the train station of Assen and the station of Groningen (N= 506) in the northern part of the Netherlands. Data for the second study were collected on the trajectory between train station “Amsterdam Amstel” and train station “Utrecht Centraal” (N= 1,113) in the central part of the Netherlands. In the experimental condition, two cleaners collected waste and performed minor cleaning activities (i.e. empty trash bins, cleaning doors and tables) during the journey. After the first study, cleaners received hospitality training and corporate uniforms.

Findings

The presence of cleaning staff positively influenced train passengers’ perceptions and satisfaction. Effects were stronger in the second study, after the second consecutive intervention (i.e. hospitality training, corporate uniforms). In both studies, the presence of cleaners positively influenced passengers’ perceptions of staff, cleanliness and comfort. The perception of atmosphere was only significant after the intervention.

Practical implications

The findings of this study allow in-house and corporate facility managers to better understand the possible effects of the presence of their cleaning staff on end-user perceptions and satisfaction.

Originality/value

The study’s value lies in its human centred approach by demonstrating the importance of day-time cleaning. This area of research has been largely neglected in the field of facilities and (public) services management research.
Roles and capacities of Thai family development centres
Authors: Supprasert Warunsicha , Hughes David , Khajornchaikul Piyatida
Published: November 2018

Purpose

The purpose of this paper is to examine Family Development Centre (FDC) staff’s[1] perspectives on their roles and capacity to promote early childhood language learning through good parenting.

Design/methodology/approach

This research employed in-depth interviews with 30 FDC coordinators and volunteer staff, supported by limited field observations.

Findings

Identifying risk, surveillance of at-risk families, building community solidarity and activities to support parenting and children, emerged as key components of FDC work. Volunteers softened their surveillance role by emphasising their social support function and personal links to local communities. Most activities aimed to strengthen family bonding and relationships, with fewer specifically addressing early childhood language deficits. Volunteers found the latter challenging, and generally sought to work in cooperation with education, public health and child care staff where projects involved language development.

Practical implications

Most volunteers said they lacked the capacities to promote early language development effectively and required additional training in such areas as partnerships and collaboration, family and parenting support, and project management. The authors argue that the importance given to partnerships reflects volunteers’ recognition that they need to draw on outside expertise to address children’s language problems. Given resource constraints, volunteers will remain central to family support work for the immediate future. Even with training lay volunteers will not become language experts, and future policy should centre on building a framework of professional support for the community teams.

Originality/value

This study fills a gap in knowledge about FDC volunteer roles and suggests a need for training that focuses on teamwork rather than specialist language expertise.