bluuebunny/crossref_metadata_2025 huggingface dataset:
Symbol Comprehension in Patients With Alzheimer Disease Dementia, Mild Cognitive Impairment, and Major Depressive Disorder
Authors: Boedeker Sebastian , Schulz Philipp , Beblo Thomas , Lenz Eva , Sammer Gebhard , Kreisel Stefan , Driessen Martin , Toepper Max
Published: September 2019

Introduction:

Previous research suggests that specific symbol features attenuate symbol comprehension deficits in seniors suffering from Alzheimer disease dementia (ADD). However, it remains unclear whether these findings also apply to other disorders associated with cognitive dysfunctions.

Methods:

Ninety healthy controls, 30 patients with major depressive disorder (MDD), 35 patients with mild cognitive impairment (MCI), and 55 patients with ADD performed a Symbol Processing Task with 4 different symbol categories. Nonparametric between×within subjects analyses were conducted to examine the impact of different symbol categories on performance accuracy in all experimental groups.

Results:

Analyses revealed a higher symbol comprehension accuracy in healthy seniors than in MDD, MCI, and ADD patients, with the lowest accuracy rates shown by ADD patients. Although the type of symbol hardly affected performance accuracy in healthy seniors and MDD patients, different symbol categories influenced the performance of MCI and ADD patients significantly.

Conclusions:

Our findings indicate that symbols with distracting features impede symbol comprehension in ADD and MCI. Symbols with visual cues, by contrast, facilitate symbol comprehension in ADD and may even be advantageous over standardized symbols used in public life.
Impact of banning smoking in cars with children on exposure to second-hand smoke: a natural experiment in England and Scotland
Authors: Laverty Anthony A , Hone Thomas , Anyanwu Philip E. , Robinson David Taylor , de Vocht Frank , Millett Christopher , Hopkinson Nicholas S
Published: September 2019

A ban on smoking in cars with children was implemented in April 2015 in England and December 2016 in Scotland. With survey data from both countries (NEngland=3,483-6,920 and NScotland=232-319), we used this natural experiment to assess the impact of the ban using a difference-in-differences approach. We conducted logistic regression analyses within a Difference-in-Difference framework and adjusted for age, sex, a marker of deprivation and survey weighting for non-response. Among children aged 13-15 years, self-reported levels of regular exposure to smoke in cars were 3.4% in 2012, 2.2% in 2014 and 1.3% in 2016 for Scotland and 6.3%, 5.9% and 1.6% in England. The ban was associated with a 73% reduction (95%CI -59%, -81%) in self-reported exposure to tobacco smoke among children.
Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer’s disease
Authors: Singleton Ellen H. , Pijnenburg Yolande A. L. , Sudre Carole H. , Groot Colin , Kochova Elena , Barkhof Frederik , Joie Renaud La , Rosen Howard J. , Seeley William W. , Miller Bruce , Cardoso M. Jorge , Papma Janne , Scheltens Philip , Rabinovici Gil D. , Ossenkoppele Rik
Published: September 2019

Objective

We previously found temporoparietal “Alzheimer-typical” atrophy in patients with the behavioral variant of Alzheimer’s disease (bvAD) with relative sparing of frontal regions. Here, we aimed to understand the pathophysiological mechanisms of bvAD based on alternative neuroimaging markers.

Methods

We retrospectively included 150 participants at the University of California San Francisco and University of Berkeley, including 29 bvAD, 28 “typical” amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other groups on glucose metabolism and metabolic connectivity on [18F]FDG-PET, and subcortical gray matter volumes and white matter hyperintensity volumes (WMHV) on MRI. A receiver-operating-characteristic-analysis was performed to determine the measures yielding the highest contrast between groups.

Results

bvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD compared to tAD, partially overlapping with bvFTD. Metabolic connectivity analyses indicated greater anterior default mode network (DMN) involvement in bvAD compared to tAD, mimicking bvFTD. Analyses of subcortical volume and WMHV showed no relevant group differences. The top-3 discriminative measures for bvAD vs. bvFTD were: metabolism in posterior (bvADbvFTD) and parietal cortex (bvAD<bvFTD; AUC: 0.80-0.91, p<0.01), while the top-3 discriminators for bvAD vs. tAD were amygdalar volume (bvAD>tAD), anterior DMN (bvAD<tAD) and salience network metabolism (bvAD<tAD; AUC: 0.66-0.75, p<0.05).

Conclusion

Subtle frontoinsular hypometabolism and anterior DMN involvement may underlie the prominent behavioral phenotype in bvAD.
Life out of water: Genomic and physiological mechanisms underlying skin phenotypic plasticity
Authors: Dong Yun-wei , Blanchard Tessa S. , Noll Angela , Vasquez Picasso , Schmitz Juergen , Kelly Scott P. , Wright Patricia A. , Whitehead Andrew
Published: September 2019

The Devonian radiation of vertebrates from aquatic into terrestrial habitats required behavioral, physiological, and morphological adaptations. Changes to skin structure and function were likely crucial, but adaptations were needed to resolve contrasting demands of maintaining a mechanical and physiological barrier while also facilitating ion and gas transport. Little is known of the mechanisms that underlie skin plasticity and adaptation between water and air. We performed experiments using two isogenic lineages of an amphibious killifish (Kryptolebias marmoratusfrom brackish and freshwater habitats) and used transcriptional and morphological data to reveal mechanisms recruited to resolve the dual challenges of skin providing both a barrier and an exchange interface during terrestrial acclimation. Transcriptional regulators of skin morphogenesis were quickly activated upon emersion. Regulation of cell-cell adhesion complexes, coupled with pathways homologous with those that regulate stratum corneum formation, was consistent with barrier function and mechanical reinforcement. Cutaneous respiration was associated with regulation of angiogenesis pathways and with blood vessel architecture that facilitated extremely short diffusion distances and direct delivery to ionocyotes. Evolutionary analyses revealed directional selection operating on proteins involved in barrier and respiratory functions, reinforcing the importance of these mechanisms for enabling the amphibious lifestyle ofK. marmoratus. Fish from brackish niches were more resilient to emersion and also differed from freshwater fish in ionoregulatory responses to emersion. We conclude that plasticity of barrier, respiratory, and ionoregulatory functions in skin evolved to support the amphibious lifestyle ofK. marmoratus; similar processes may have facilitated the terrestrial radiation of ancient fishes.

Significance statement

The transition of vertebrate life from water to land coincided with solving multiple physiological challenges including avoiding drying out while also exchanging gases and ions with the environment. Though changes in the skin were likely important, little is known of the mechanisms that underlie skin flexibility and adaptation between water and air. We performed air exposure experiments with an amphibious killifish; gene expression profiling, microscopy, and evolutionary analysis of proteins revealed cell structures, proteins, and molecular pathways that support skin flexibility and adaptations during air exposure, and ion regulation contributed to differences in killifish abilities to adjust to air. Amphibious killifish are useful models to help us understand changes that enable water to air transitions in contemporary and ancient fishes.
Machine Learning Analysis of Motor Evoked Potential Time Series to Predict Disability Progression in Multiple Sclerosis
Authors: Yperman Jan , Becker Thijs , Valkenborg Dirk , Popescu Veronica , Hellings Niels , Wijmeersch Bart Van , Peeters Liesbet M
Published: September 2019

Background

Evoked potentials (EPs) are a measure of the conductivity of the central nervous system. They are used to monitor disease progression of multiple sclerosis patients. Previous studies only extracted a few variables from the EPs, which are often further condensed into a single variable: the EP score. We perform a machine learning analysis of motor EP that uses the whole time series, instead of a few variables, to predict disability progression after two years. Obtaining realistic performance estimates of this task has been difficult because of small data set sizes. We recently extracted a dataset of EPs from the Rehabiliation & MS Center in Overpelt, Belgium. Our data set is large enough to obtain, for the first time, a performance estimate on an independent test set containing different patients.

Methods

We extracted a large number of time series features from the motor EPs with the highly comparative time series analysis software package. Mutual information with the target and the Boruta method are used to find features which contain information not included in the features studied in the literature. We use random forests (RF) and logistic regression (LR) classifiers to predict disability progression after two years. Statistical significance of the performance increase when adding extra features is checked with the DeLong hypothesis test.

Results

Including extra time series features in motor EPs leads to a statistically significant improvement compared to using only the known features, although the effect is limited in magnitude (∆AUC = 0.02 for RF and ∆AUC = 0.05 for LR). RF with extra time series features obtains the best performance (AUC = 0.75 ± 0.07), which is good considering the limited number of biomarkers in the model. RF (a nonlinear classifier) outperforms LR (a linear classifier).

Conclusions

Using machine learning methods on EPs shows promising predictive performance. Using additional EP time series features beyond those already in use leads to a modest increase in performance. Larger datasets, preferably multi-center, are needed for further research. Given a large enough dataset, these models may be used to support clinicians in their decision making process regarding future treatment.
Compartmentalization of intestinal bacteria by hepatic ILC3s prevents infections after surgery
Authors: Jakob Manuel O. , Sanchez-Taltavull Daniel , Yilmaz Bahtiyar , Malinka Thomas , Mooser Catherine , Daniel Spari , Salm Lilian A. , Freiburghaus Katrin , Pereyra David , Hapfelmeier Siegfried , Masoodi Mojgan , Starlinger Patrick , Stroka Deborah , Tschan Franziska , Candinas Daniel , de Agüero Mercedes Gomez , Beldi Guido
Published: September 2019

Infections after surgical interventions are assumed to be caused by contamination. We show by analyzing multicentric data of 6561 patients that surgical infections as well as sepsis had a predominantly enteric microbial signature irrespective of the type of surgery, suggesting failure of intestinal bacterial compartmentalization. In mice, we reveal that hepatic surgery induced dysregulation of intestinal and hepatic type 3 innate lymphoid cells (ILC3s) and intestinal leakage resulting in enteric bacterial translocation via lymphatic vessels. In the absence of hepatic ILC3s, inflammasome activation and the induction of antimicrobial peptide encoding genes, bacteria colonized remote systemic organs and impaired surgical outcomes. Conversely, mammalian-microbial commensalism is required for the education of host immunity to ensure optimal hepatic healing responses. In fact, microbial-derived products were sufficient for the induction of proliferative transcriptional networks in the mouse liver, as illustrated by serum transfer experiments, mass spectrometry and RNA expression analysis, indicating that the balanced exposure of the host to commensals is essential for recovery. This study reveals the intestinal origin of microbes causing complications after surgical interventions and highlights host protective mechanisms of controlled commensalism that prevent infections.

One Sentence Summary

Intestinal bacteria cause surgical infections
Club cell TRPV4 as a damage sensor driving lung allergic inflammation
Authors: Wiesner Darin L. , Merkhofer Richard M. , Ober Carole , Kujoth Greg C. , Gern James E. , Schneider Rebeca Brockman , Evans Michael D. , Jackson Daniel J. , Warner Thomas , Jarjour Nizar N. , Esnault Stephane J. , Feldman Michael B. , Freeman Matthew , Mou Hongmei , Vyas Jatin M. , Klein Bruce S.
Published: September 2019

Airway epithelium is the first body surface to contact inhaled irritants and report danger. We studied how epithelial cells recognize and respond to protease, which is a critical component of many allergens that provoke asthma. In a murine model, the aeroallergen alkaline protease 1 (Alp1) of Aspergillus sp. elicited helper T (Th) cell-dependent lung eosinophilia. Bronchiolar club cells responded rapidly to Alp1 by coordinating the accumulation of allergic immune cells in the lung. Alp1 degraded bronchiolar cell junctions, and club cells within the bronchioles propagated this signal via calcium and calcineurin to incite inflammation. In two human cohorts, we linked fungal sensitization and asthma with SNP/protein expression of the mechanosensitive calcium channel, TRPV4. TRPV4 was also necessary and sufficient for club cells to sensitize mice to Alp1. Thus, club cells detect junction damage as mechanical stress, which signals danger via TRPV4, calcium and calcineurin to initiate Th cell sensitization.

Graphical Abstract
Gravity-based microfiltration reveals unexpected prevalence of circulating tumor cell clusters in ovarian and colorectal cancer
Authors: Meunier Anne , Hernández-Castro Javier Alejandro , Chahley Nicholas , Communal Laudine , Kheireddine Sara , Koushki Newsha , Davoudvandi Nadia , Al Habyan Sara , Péant Benjamin , Lazaris Anthoula , Ng Andy , Veres Teodor , McCaffrey Luke , Provencher Diane , Metrakos Peter , Mes-Masson Anne-Marie , Juncker David
Published: September 2019

Circulating tumor cells (CTCs) are rare (few cells per milliliter of blood) and mostly isolated as single cell CTCs (scCTCs). CTC clusters (cCTCs), even rarer, are of growing interest, notably because of their higher metastatic potential, but very difficult to isolate. Here, we introduce gravity-based microfiltration (GµF) for facile isolation of cCTCs while minimizing unwanted cluster disaggregation, with ∼85% capture efficiency. GµF from orthotopic ovarian cancer mouse models, from 17 epithelial ovarian cancer (EOC) with either localized or metastatic disease, and from 13 metastatic colorectal cancer liver metastasis (CRCLM) patients uncovered cCTCs in every case, with between 2-100+ cells. cCTCs represented between 5-30% of all CTC capture events, and 10-80% of CTCs were clustered; remarkably, in 10 patients, most CTCs were circulating not as scCTCs, but as cCTCs. GµF uncovered the unexpected prevalence and frequency of cCTCs including sometimes very large ones in EOC patients, and motivates additional studies to uncover their properties and role in disease progression.
Identification of gut microbiome markers for schizophrenia delineates a potential role of Streptococcus
Authors: Zhu Feng , Ju Yanmei , Wang Wei , Wang Qi , Guo Ruijin , Ma Qingyan , Sun Qiang , Fan Yajuan , Xie Yuying , Yang Zai , Jie Zhuye , Zhao Binbin , Xiao Liang , Yang Lin , Zhang Tao , Feng Junqin , Guo Liyang , He Xiaoyan , Chen Yunchun , Chen Ce , Gao Chengge , Xu Xun , Yang Huanming , Wang Jian , Dang Yonghui , Madsen Lise , Brix Susanne , Kristiansen Karsten , Jia Huijue , Ma Xiancang
Published: September 2019

Emerging evidence has linked the gut microbiota to schizophrenia. However, the functional changes in the gut microbiota and the biological role of individual bacterial species in schizophrenia have not been explored systematically. Here, we characterized the gut microbiota in schizophrenia using shotgun metagenomic sequencing of feces from a discovery cohort of 90 drug-free patients and 81 controls, as well as a validation cohort of 45 patients taking antipsychotics and 45 controls. We screened 83 schizophrenia-associated bacterial species and constructed a classifier comprising 26 microbial biomarkers that distinguished patients from controls with a 0.896 area under the receiver operating characteristics curve (AUC) in the discovery cohort and 0.765 AUC in the validation cohort. Our analysis of fecal metagenomes revealed that schizophrenia-associated gut–brain modules included short-chain fatty acids synthesis, tryptophan metabolism, and synthesis/degradation of neurotransmitters including glutamate, γ-aminobutyric acid, and nitric oxide. The schizophrenia-enriched gut bacterial species include several oral cavity-resident microbes, such as Streptococcus vestibularis. We transplanted Streptococcus vestibularis into the gut of the mice with antibiotic-induced microbiota depletion to explore its functional role. We observed that this microbe transiently inhabited the mouse gut and this was followed by hyperactivity and deficit in social behaviors, accompanied with altered neurotransmitter levels in peripheral tissues. In conclusion, our study identified 26 schizophrenia-associated bacterial species representing potential microbial targets for future treatment, as well as gut–brain modules, some of which may give rise to new microbial metabolites involved in the development of schizophrenia.
Neuronal population dynamics during motor plan cancellation in non-human primates
Authors: Pani Pierpaolo , Giamundo Margherita , Giarrocco Franco , Mione Valentina , Brunamonti Emiliano , Mattia Maurizio , Ferraina Stefano
Published: September 2019

To understand the cortical neuronal dynamics behind movement generation and control most studies focused on tasks where actions were planned and then executed, using different instances of visuomotor transformations. However, to fully understand the dynamics related to movement control one must also study how movements are actively inhibited. Inhibition, indeed, represents the first level of control both when different alternatives are available and only one solution could be adopted, and when it is necessary to maintain the current position.
We recorded neuronal activity from a multielectrode array in the dorsal premotor (PMd) cortex of monkeys performing a countermanding reaching task that requires, in a subset of trials, to cancel a planned movement before its onset. In the analysis of the neuronal state-space of PMd we found a subspace in which activities conveying temporal information were confined during active inhibition and position holding. Movement execution required activities to escape from this subspace toward an orthogonal subspace and, furthermore, surpass a threshold associated with the maturation of the motor plan. These results revealed further details in the neuronal dynamics underlying movement control, extending the hypothesis that neuronal computation confined in an -output-null- subspace does not produce movements.
Native seed addition as an effective tool for post-invasion restoration
Authors: Bucharova Anna , Krahulec František
Published: September 2019

Invasive plant species reduce biodiversity, alter ecosystem processes, and cause economic losses. Control of invasive plants is therefore highly desired by land managers and policy makers. However, invasive plant control strategies frequently fail, partly because management often concentrates only on the eradication of invasive plants and not on revegetation with native species that use the available resources and prevent reinvasion. In this study, we focused on the intracontinental invader Rumex alpinus L., which was introduced by humans from the Alps to the lower mountains of Central Europe, where it has spread to semi-natural meadows, suppresses local biodiversity, and reduces the quality of hay used as cattle fodder. The species can be effectively removed using herbicide, but this leaves behind a persistent seed bank. Without further treatment, the invader rapidly regenerates and reinvades the area. We supplemented the herbicide treatment by adding the seeds of native grasses. Addition of native-seed effectively suppressed the regeneration of the invader from the seed bank, reduced its biomass, and consequently, prevented massive reinvasion. While the invader removal was successful, the restored community remained species-poor because the dense sward of native grasses blocked the regeneration of native forbs from the seed bank. Nevertheless, the addition of native seed proved to be an effective tool in preventing reinvasion after the eradication of the invasive plant.
5’ tRNA halves are highly expressed in the primate hippocampus and sequence-specifically regulate gene expression
Authors: Jehn Julia , Treml Jana , Wulsch Svenja , Ottum Benjamin , Erb Verena , Hewel Charlotte , Kooijmans Roxana N. , Wester Laura , Fast Isabel , Rosenkranz David
Published: September 2019

Fragments of mature tRNAs have long been considered as mere degradation products without physiological function. However, recent reports show that tRNA fragments (tRFs) play prominent roles in diverse cellular processes across a wide spectrum of species. Contrasting the situation in other small RNA pathways the mechanisms behind these effects appear more diverse, more complex and are generally less well understood. In addition, surprisingly little is known about the expression profiles of tRFs across different tissues and species. Here, we provide an initial overview of tRF expression in different species and tissues, revealing very high tRF-levels particularly in the primate hippocampus. We further modulated the regulation capacity of selected tRFs in human cells by transfecting synthetic tRF mimics (“overexpression”) or antisense-RNAs (“inhibition”) and identified differentially expressed transcripts based on RNAseq. We then used a novel k-mer mapping approach to dissect the underlying targeting rules, demonstrating that 5’ tRNA halves (5’ tRHs) silence genes in a sequence-specific manner, while the most efficient target sites align to the mid-region of the 5’ tRH and are located within the CDS or 3’ UTR of the target. This amends previous observations that tRFs guide Argonaut proteins to silence their targets via a miRNA-like 5’ seed match and suggests a yet unknown mechanism of regulation. Finally, our data suggests that some 5’ tRHs are also able to sequence-specifically stabilize mRNAs as upregulated mRNAs are also significantly enriched for 5’ tRH target sites.
Loss of Piccolo function in rats induces Pontocerebellar Hypoplasia type 3-like phenotypes
Authors: Falck Joanne , Bruns Christine , Hoffmann Sheila , Straub Isabelle , Plautz Erik J. , Orlando Marta , Munawar Humaira , Rivalan Marion , Winter York , Izsvák Zsuzsanna , Schmitz Dietmar , Hamra F. Kent , Hallermann Stefan , Garner Craig , Ackermann Frauke
Published: September 2019

Piccolo, a presynaptic active zone protein, is best known for its role in the regulated assembly and function of vertebrate synapses. Genetic studies suggest a further link to several psychiatric disorders as well as Pontocerebellar Hypoplasia type 3 (PCH3), although a causal relationship is lacking. We have characterized recently generated knockout (Pclogt/gt) rats. Analysis revealed a dramatic reduction in brain size compared to wildtype (Pclowt/wt) animals, attributed to a decrease in the size of the cerebral cortical, cerebellar and pontine regions. Analysis of the cerebellum and brainstem revealed a reduced granule cell (GC) layer and a reduction in size of pontine nuclei. Moreover, the maturation of mossy fiber (MF) afferents from pontine neurons and the expression of the α6 GABAA receptor subunit at the MF-GC synapse are perturbed, as well as the innervation of Purkinje cells by cerebellar climbing fibers (CFs). Ultrastructural and functional studies revealed a reduced size of MF boutons, with fewer synaptic vesicles and altered synaptic transmission. These data imply that Piccolo is required for the normal development, maturation and function of neuronal networks formed between the brainstem and cerebellum. Consistently, behavioral studies demonstrated that adult Pclogt/gt rats display impaired motor coordination, despite adequate performance in tasks that reflect muscle strength and locomotion. Together these data suggest that loss of Piccolo function in patients with PCH3 could be causal for many of the observed anatomical and behavioral symptoms, and that the further analysis of these animals could provide fundamental mechanistic insights into this devastating disorder.

Significance Statement

Pontocerebellar Hypoplasia type 3 is a devastating developmental disorder associated with severe developmental delay, progressive microcephaly with brachycephaly, optic atrophy, seizures and hypertonia with hyperreflexia. Recent genetic studies have identified non-sense mutations in the coding region of the Piccolo gene, suggesting a functional link between this disorder and the presynaptic active zone. Our analysis of Piccolo knockout rats supports this hypothesis, formally demonstrating that anatomical and behavioral phenotypes seen in patients with PCH3 are also exhibited by these Piccolo deficient animals.
An agent-based model of molecular aggregation at the cell membrane
Authors: Griffié Juliette , Peters Ruby , Owen Dylan M.
Published: September 2019

Molecular clustering at the plasma membrane has long been identified as a key process and is associated with regulating signalling pathways across cell types. Recent advances in microscopy, in particular the rise of super-resolution, have allowed the experimental observation of nanoscale molecular clusters in the plasma membrane. However, modelling approaches capable of recapitulating these observations are in their infancy, partly because of the extremely complex array of biophysical factors which influence molecular distributions and dynamics in the plasma membrane. We propose here a highly abstracted approach: an agent-based model dedicated to the study of molecular aggregation at the plasma membrane. We show that when molecules are modelled as though they can act (diffuse) in a manner which is influenced by their molecular neighbourhood, many of the distributions observed in cells can be recapitulated, even though such sensing and response is not possible for real membrane molecules. As such, agent-based offers a unique platform which may lead to a new understanding of how molecular clustering in extremely complex molecular environments can be abstracted, simulated and interpreted using simple rules.

Author summary

Molecular aggregation in cell membranes is a key component of cellular machinery, involved across cell types in inter-cellular communication and signalling pathway initiation. As such, understanding the underlying mechanisms and molecule cluster characteristics at a more theoretical level is a pre-requisite. Complete descriptive molecular models have proven impossible to realise due to the overall complexity of the processes involved, highlighting the need for novel approaches. While conceptual models have been shown to be powerful tools and are routinely used in other fields with high level of complexity such as social sciences or economics, they are overall lacking from the literature when it comes to cell studies. We suggest in this work that the same principle applies to cell biology and in particular, the study of molecular clustering. We propose here a general model, independent of cell types or signalling pathways: an agent-based model dedicated to molecular clustering in the plasma membrane. We show we are able to recapitulate molecular aggregation similar to observations in cells while new properties are highlighted by our model, for instance, clustering is a digitised process.
embarcadero: Species distribution modelling with Bayesian additive regression trees in R
Authors: Carlson Colin J.
Published: September 2019

embarcadero is an R package of convenience tools for species distribution modelling with Bayesian additive regression trees (BART), a powerful machine learning approach that has been rarely applied to ecological problems. Like other classification and regression tree methods, BART estimates the probability of a binary outcome based on a set of decision trees. Unlike other methods, BART iteratively generates sets of trees based on a set of priors about tree structure and nodes, and builds a posterior distribution of estimated classification probabilities. So far, BARTs have yet to be applied to species distribution modelling. embarcadero is a workflow wrapper for BART species distribution models, and includes functionality for easy spatial prediction, an automated variable selection procedure, several types of partial dependence visualization, and other tools for ecological application. The embarcadero package is available open source on Github and intended for eventual CRAN release. To show how embarcadero can be used by ecologists, I illustrate a BART workflow for a virtual species distribution model. The supplement includes a more advanced vignette showing how BART can be used for mapping disease transmission risk, using the example of Crimean-Congo haemorrhagic fever in Africa.
GSDMAdrives the most replicated association with asthma in naïve CD4+T cells
Authors: Madore Anne-Marie , Pain Lucile , Boucher-Lafleur Anne-Marie , Meloche Jolyane , Morin Andréanne , Simon Marie-Michelle , Ge Bing , Kwan Tony , Cheung Warren A. , Pastinen Tomi , Laprise Catherine
Published: September 2019

Background

The 17q12-21 locus is the most replicated association with asthma. However, no study had described the genetic mechanisms underlying this association considering all genes of the locus in immune cell samples isolated from asthmatic and non-asthmatic individuals.

Objective

This study takes benefit of samples from naïve CD4+T cells and eosinophils isolated from the same 200 individuals to describe specific interactions between genetic variants, gene expression and DNA methylation levels for the 17q12-21 asthma locus.

Methods and Results

After isolation of naïve CD4+T cells and eosinophils from blood samples, next generation sequencing was used to measure DNA methylation levels and gene expression counts. Genetic interactions were then evaluated considering genetic variants from imputed genotype data. In naïve CD4+T cells but not eosinophils, 20 SNPs in the fourth and fifth haplotype blocks modulated bothGSDMAexpression and methylation levels, showing an opposite pattern of allele frequencies and expression counts in asthmatics compared to controls. Moreover, negative correlations have been measured between methylation levels of CpG sites located within the 1.5 kb region from the transcription start site ofGSDMAand its expression counts.

Conclusion

Availability of sequencing data from two key cell types isolated from asthmatic and non-asthmatic individuals allowed identifying a new gene in naïve CD4+T cells that drives the association with the 17q12-21 locus, leading to a better understanding of the genetic mechanisms taking place in it.
Diversity patterns of marine heterotrophic culturable bacteria along vertical and latitudinal gradients
Authors: Sanz-Sáez Isabel , Salazar Guillem , Lara Elena , Royo-Llonch Marta , Vaqué Dolors , Duarte Carlos M. , Gasol Josep M. , Pedrós-Alió Carlos , Sánchez Olga , Acinas Silvia G.
Published: September 2019

Nowadays, there is a significant gap in the knowledge of the diversity and patterns for marine heterotrophic culturable microorganisms. In addition, most of the bacterial isolation efforts have focused on the photic ocean leaving the deep ocean less explored. We have isolated 1561 bacterial strains covering both photic (817) and aphotic layers (744) including isolates from the oxygen minimum zone (362) and the bathypelagic (382) from a variety of oceanographic regions including the North Western Mediterranean Sea, the North and South Atlantic Oceans, the Indian, the Pacific, and the Arctic Oceans. The partial sequencing of the 16S rRNA gene of all isolates revealed that they mainly affiliate with the classesAlphaproteobacteria(35.9%) andGammaproteobacteria(38.6%), as well as, phylumBacteroidetes(16.5%). The generaAlteromonasandErythrobacterwere the most widespread heterotrophic bacteria in the ocean able to grow on solid agar media. When comparing the sequences of all isolates, 37% of them were 100% identical. In fact, we found that 59% of the total aphotic isolates were 100% identical to photic isolates, indicating the ubiquity of some bacterial isolates along the water column. Unweighted UniFrac distances did not show significant differences among stations regardless of their geographic distance or depth, reflecting the wide dispersion of the culturable bacterial assemblage. This isolates collection provides an overview of the distribution patterns of cosmopolitan marine culturable heterotrophic bacteria.
Exercise conditioned plasma dampens inflammation via clusterin and boosts memory
Authors: De Miguel Zurine , Betley Michael J. , Willoughby Drew , Lehallier Benoit , Olsson Niclas , Bonanno Liana , Fairchild Kaci J. , Contrepois Kévin , Elias Joshua E. , Rando Thomas A. , Wyss-Coray Tony
Published: September 2019

Physical exercise seems universally beneficial to human and animal health, slowing cognitive aging and neurodegeneration. Cognitive benefits are tied to increased plasticity and reduced inflammation within the hippocampus, yet little is known about the factors and mechanisms mediating these effects. We discovered “runner” plasma, collected from voluntarily running mice, infused into sedentary mice recapitulates the cellular and functional benefits of exercise on the brain. Importantly, runner plasma reduces baseline neuroinflammatory gene expression and prominently suppresses experimentally induced brain inflammation. Plasma proteomic analysis shows a striking increase in complement cascade inhibitors including clusterin, which is necessary for the anti-inflammatory effects of runner plasma. Cognitively impaired patients participating in structured exercise for 6 months showed higher plasma clusterin levels, which correlated positively with improvements in endurance and aerobic capacity. These findings demonstrate the existence of anti-inflammatory “exercise factors” that are transferrable, benefit the brain, and are present in humans engaging in exercise.
Structural and molecular insight into the pH-induced low-permeability of the voltage-gated potassium channel Kv1.2 through dewetting of the water cavity
Authors: Lee Juhwan , Kang Mooseok , Kim Sangyeol , Chang Iksoo
Published: September 2019

Understanding the gating mechanism of ion channel proteins is key to understanding the regulation of cell signaling through these channels. Channel opening and closing are regulated by diverse environmental factors that include temperature, electrical voltage across the channel, and proton concentration. Low permeability in voltage-gated potassium ion channels (Kv) is intimately correlated with the prolonged action potential duration observed in many acidosis diseases. The Kv channels consist of voltage-sensing domains (S1–S4 helices) and central pore domains (S5–S6 helices) that include a selectivity filter and water-filled cavity. The voltage-sensing domain is responsible for the voltage-gating of Kv channels. While the low permeability of Kv channels to potassium ion is highly correlated with the cellular proton concentration, it is unclear how an intracellular acidic condition drives their closure, which may indicate an additional pH-dependent gating mechanism of the Kv family. Here, we show that two residues E327 and H418 in the proximity of the water cavity of Kv1.2 play crucial roles as a pH switch. In addition, we present a structural and molecular concept of the pH-dependent gating of Kv1.2 in atomic detail, showing that the protonation of E327 and H418 disrupts the electrostatic balance around the S6 helices, which leads to a straightening transition in the shape of their axes and causes dewetting of the water-filled cavity and closure of the channel. Our work offers a conceptual advancement to the regulation of the pH-dependent gating of various voltage-gated ion channels and their related biological functions.

Author Summary

The acid sensing ion channels are a biological machinery for maintaining the cell functional under the acidic or basic cellular environment. Understanding the pH-dependent gating mechanism of such channels provides the structural insight to design the molecular strategy in regulating the acidosis. Here, we studied the voltage-gated potassium ion channel Kv1.2 which senses not only the electrical voltage across the channels but also the cellular acidity. We uncovered that two key residues E327 and H418 in the pore domain of Kv1.2 channel play a role as pH-switch in that their protonation control the gating of the pore in Kv1.2 channel. It offered a molecular insight how the acidity reduces the ion permeability in voltage-gated potassium channels.
UMI-Gen: a UMI-based reads simulator for variant calling evaluation in paired-end sequencing NGS libraries
Authors: Sater Vincent , Viailly Pierre-Julien , Lecroq Thierry , Ruminy Philippe , Bérard Caroline , Prieur-Gaston Élise , Jardin Fabrice
Published: September 2019

1

Disclaimer

The author has withdrawn version 2 of this manuscript due to a duplicate posting of manuscript number 027532. Therefore, the author does not wish this work to be cited as reference for the project. 775817v1 is the appropriate submission and the published version of the appropriate preprint can be found in the published article link. If you have any questions, please contact the corresponding author.
Influencing factors of telephone-cardiopulmonary resuscitation in China: a qualitative exploration based on managerial perspectives
Authors: Zhu Xuehua , Gui Li , Chen Ying , Lin Yin
Published: September 2019

Background

Telephone-cardiopulmonary resuscitation(T-CPR) has been proven to systematically improve bystander CPR implementation and thus improve the survival rate of out-of-hospital cardiac arrest (OHCA) patients on a large scale. However, China has a lower proportion of cities that provide T-CPR than other countries.This study aimed to explore the factors affecting the providing of T-CPR based on managerial perspectives and promote the implementation of T-CPR in China to Protect human health.

Methods

This study adopted a descriptive qualitative method.The managers from health bureau and first-aid Center were recruited to participate through purposive sampling. Data were collected using semi-structured interviews and Colaizzi 7-step analysis method was adopted to summarize and conclude the theme.

Results

A total of 10 managers were interviewed.Five main themes were identified: (a) bystander factors, (b) dispatching factors, (c) legal factors, (d) guiding factors, and (e) financial factors.

Conclusion

It is urgent to promote the implementation of T-CPR in China.We can promote it by strengthening the training of bystanders in CPR knowledge and skills, developing T-CPR guidance process suitable for Chines national conditions, building an intelligent prehospital emergency system, promoting the legislation of first aid exemption, and providing financial support from various channels.
Relevance of screening for Chagas and viral hepatitis in Bolivian migrants
Authors: Galván Irene Losada , Gariup Giuseppe , Casellas Aina , Subirà Carme , Almuedo-Riera Alex , Camprubí Daniel , Rodríguez-Valero Natalia , Gascón Joaquim , Muñoz Jose , Pinazo María Jesús
Published: September 2019

Objectives

given the scarcity of data regarding prevalence of various infectious diseases in Latin-American countries, our study aims to assess the burden of T.cruzi, S.stercoralis, HIV and viral hepatitis in Latin-American migrants, with a focus on Bolivian migrants.

Methods

we performed a retrospective observational study of 565 screening evaluations on adults (≥ 18 years) carried out at our referral International Healthcare service in Barcelona. We reviewed structured clinical records and microbiological results of patients attended between February 2012 and April 2015.

Results

the median 35 years old and 74% were women. Bolivian origin accounted for 87% of the screened population. We found a 48% prevalence of T.cruzi, 16% of S.stercoralis, 0.2% of HIV, 92% of HAV, 0.2% HBV and 0.2% HCV.

Conclusions

these results support the relevance of the screening of T. cruzi and S. stercoralis in Bolivian migrants, but challenge the pertinence of systematic screening of HBV in this population.

Author summary

In response to the challenge of detecting diseases not previously present in host countries, screening programs have been implemented for migrants based on the probability of having certain diseases depending on their country of origin and / or migratory route. This increased risk is very clearly established in some cases such as Trypanosoma cruzi infection (the cause of Chagas disease) in people from Latin America; especially from Bolivia. In recent years screening recommendations for Strongyloides stercoralis in this population was proven necessary. Current recommendations regarding systematic screening for hepatitis B establish the relevance of screening based on the probability of the disease in the 2% population of origin. Since there are no reliable and up to date data regarding prevalence of hepatitis B virus in Bolivia, we aimed to analyze data available for migrants from Bolivia in Spain.

Our results support the importance of screening for T. cruzi and S.stercoralis in patients from Bolivia. However, our data show a much lower prevalence of this hepatitis B virus (0.2%) than the 2% threshold that would justify systematic screening, so we question the relevance of screening for hepatitis B virus in this population in the absence of other risk factors.
Synaptic and intrinsic mechanisms underlying development of cortical direction selectivity
Authors: Roy Arani , Osik Jason J. , Meschede-Krasa Benyamin , Alford Wesley , Leman Daniel P. , Van Hooser Stephen D.
Published: September 2019

Some neural circuits are constructed through an overproduction of initial connections followed by activity-dependent refinement. Under this paradigm, functional receptive fields would be expected to be narrowed from a diffuse immature condition to a sharper mature condition. Alternatively, neural activity might lead to formation of new connections, leading to expansion of an initially compact receptive field. In the simple cells of the ferret visual cortex undergoing developmental enhancement of direction selectivity, we found evidence for a mixed mechanism: an expansion of the spatiotemporal receptive fields along the temporal dimension combined with a narrowing in space-time through a marked loss of inputs with certain space-time selectivities. Further, the resulting increase in subthreshold direction selectivity was accompanied by increases in near-spike-threshold excitability and input-output gain that resulted in dramatically increased spiking responses. Increases in subthreshold membrane responses and the increased input-output spiking gain were both necessary to explain firing rates in experienced ferrets. These results demonstrate that cortical direction selectivity develops through a combination of plasticity in synaptic and cell-intrinsic properties.
In situdissection of domain boundaries affect genome topology and gene transcription inDrosophila
Authors: Arzate-Mejía Rodrigo G. , Cerecedo-Castillo Angel Josué , Guerrero Georgina , Furlan-Magaril Mayra , Recillas-Targa Félix
Published: September 2019

The molecular mechanisms responsible for Topologically Associated Domains (TADs) formation are not yet fully understood. InDrosophila, it has been proposed that transcription is fundamental for TAD organization while the participation of genetic sequences bound by Architectural Proteins (APs) remains controversial. Here, we investigate the contribution of domain boundaries to TAD organization and the regulation of gene expression at theNotchgene locus inDrosophila. We find that deletion of domain boundaries results in TAD fusion and long-range topological defects that are accompanied by loss of APs and RNA Pol II chromatin binding as well as defects in transcription. Together, our results provide compelling evidence on the contribution of discrete genetic sequences bound by APs and RNA Pol II in the partition of the genome into TADs and in the regulation of gene expression inDrosophila.
Gene-by-environmental modulation of longevity and weight gain in the murine BXD family
Authors: Roy Suheeta , Sleiman Maroun Bou , Jha Pooja , Williams Evan G. , Ingels Jesse F. , Chapman Casey J. , McCarty Melinda S. , Hook Michael , Sun Anna , Zhao Wenyuan , Huang Jinsong , Neuner Sarah M. , Wilmott Lynda A. , Shapaker Thomas M. , Centeno Arthur G. , Mozhui Khyobeni , Mulligan Megan K. , Kaczorowski Catherine C. , Makowski Liza , Lu Lu , Read Robert W. , Sen Saunak , Miller Richard A. , Auwerx Johan , Williams Robert W.
Published: September 2019

Diet and environment profoundly modulate lifespan. We measured longevity as a function of diet and weight gain across a genetically diverse family of mice. We followed 1348 females from two parental strains—C57BL/6J and DBA/2J—and 146 cohorts of BXD isogenic progeny strains (n= 73) across their lifespan on a low fat chow diet (CD, 18% calories from fat) and on a high fat diet (HFD, 60% calories from fat). On average, HFD shortens lifespan by 85 days or 12%, roughly equivalent to an 8–10 year decrease in humans. However, strain variation in the response of diet on longevity is remarkably high, ranging from a longevity loss of 54% in BXD65 to a gain of 37% in BXD8. Baseline weights and early weight gain are both associated with a mean decrease in longevity of ∼4 days/g. By 500 days-of-age, cases fed HFD gained four times as much weight as control on average. However, strain-specific variation was substantial, thus weight gain did not correlate well with lifespan. In summary, high fat had a strong negative effect on longevity, but genetic interactions effects were even stronger. This highlights the unequivocal importance of genetic differences in making dietary recommendations.
Diffraction-based determination of single-crystal elastic constants of polycrystalline titanium alloys
Authors: Heldmann Alexander , Hoelzel Markus , Hofmann Michael , Gan Weimin , Schmahl Wolfgang W. , Griesshaber Erika , Hansen Thomas , Schell Norbert , Petry Winfried
Published: September 2019

Single-crystal elastic constants have been derived by lattice strain measurements using neutron diffraction on polycrystalline Ti-6Al-4V, Ti-6Al-2Sn-4Zr-6Mo and Ti-3Al-8V-6Cr-4Zr-4Mo alloy samples. A variety of model approximations for the grain-to-grain interactions, namely approaches by Voigt, Reuss, Hill, Kroener, de Wit and Matthies, including texture weightings, have been applied and compared. A load-transfer approach for multiphase alloys was also implemented and the results are compared with single-phase data. For the materials under investigation, the results for multiphase alloys agree well with the results for single-phase materials in the corresponding phases. In this respect, all eight elastic constants in the dual-phase Ti-6Al-2Sn-4Zr-6Mo alloy have been derived for the first time.