bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk-Stratification of Children Presenting to Ambulatory Paediatrics with First-Onset Seizures: Should We Order an Urgent CT Brain?
Authors: Brugman Jaanri , Solomons Regan Shane , Lombard Carl , Redfern Andrew , Du Plessis Anne-Marie 
Published: October 2019

Abstract

Introduction
A computed tomography (CT) brain scan is an often-utilised emergency department imaging modality to detect emergent intra-cranial pathology in a child with a first seizure. Identifying children at low risk of having a clinically significant intra-cranial abnormality could prevent unnecessary radiation exposure and contrast/sedation-related risks.

Objectives
To identify clinical variables which could predict clinically significant CT brain abnormalities and use recursive partitioning analysis to define a low-risk group of children in whom emergent CT brain can be deferred.

Methods
Retrospective cross-sectional review of 468 children who underwent emergent CT brain after presenting to a low- and middle-income paediatric emergency department following first seizure.

Results
In total 133/468 (28.4%) of CT brain scans had clinically significant abnormalities. Failure to return to neurological baseline and focal neurological deficit persisting &gt;36 h had statistical significance in a multiple regression analysis. Recursive partitioning analysis, applied to a subgroup without suspected tuberculous meningitis (n = 414), classified 153 children aged between 6 months and 5 years, who had a normal neurological baseline, had returned to baseline post-seizure, and were not in status epilepticus, as non-clinically significant scans and 98% were correctly classified.

Conclusion
Our study re-inforces the American Academy of Neurology recommendation that children with persistent post-ictal abnormal neurological status and/or post-ictal focal deficit be prioritised for emergent CT brain. Having excluded children with suspected tuberculous meningitis, the remaining subgroup aged 6 months to 5 years presenting with a non-status first seizure, normal neurological baseline and return to baseline post-seizure, are at very low risk of having a clinically significant CT brain abnormality.
Reduction in Perinatal Mortality after Implementation of HBB Training at a District Hospital in Mali
Authors: Innerdal M , Simaga I , Diall H , Eielsen M , Niermeyer S , Eielsen O , Saugstad O D 
Published: October 2019

Abstract

Background
Mali has a high neonatal mortality rate of 38/1000 live births; in addition the fresh stillbirth rate (FSR) is 23/1000 births and of these one-third are caused by intrapartum events.

Objectives
The aims are to evaluate the effect of helping babies breathe (HBB) on mortality rate at a district hospital in Kati district, Mali.

Methods
HBB first edition was implemented in April 2016. One year later the birth attendants were trained in HBB second edition and started frequent repetition training. This is a before and after study comparing the perinatal mortality during the period before HBB training with the period after HBB training, the period after HBB first edition and the period after HBB second edition. Perinatal mortality is defined as FSR plus neonatal deaths in the first 24 h of life.

Results
There was a significant reduction in perinatal mortality rate (PMR) between the period before and after HBB training, from 21.7/1000 births to 6.0/1000 live births; RR 0.27, (95% CI 0.19–0.41; p &lt; 0.0001). Very early neonatal mortality rate (24 h) decreased significantly from 6.3/1000 to 0.8/1000 live births; RR 0.12 (95% CI 0.05–0.33; p = 0.0006). FSR decreased from 15.7/1000 to 5.3/1000, RR 0.33 (95% CI 0.22–0.52; p &lt; 0.0001). No further reduction occurred after introducing the HBB second edition.

Conclusion
HBB may be effective in a local first-level referral hospital in Mali.
Identification of functionally connected multi-omic biomarkers for Alzheimer’s Disease using modularity-constrained Lasso
Authors: Xie Linhui , Varathan Pradeep , Nho Kwangsik , Saykin Andrew J. , Salama Paul , Yan Jingwen 
Published: October 2019

AbstractIn the past decade, a large number of genetic biomarkers have been discovered through large-scale genome wide association studies (GWASs) in Alzheimer’s disease (AD), such asAPOE, TOMM40andCLU. Despite this significant progress, existing genetic findings are largely passengers not directly involved in the driver events, which presents challenges for replication and translation into targetable mechanisms. In this paper, leveraging the protein interaction network, we proposed a modularity-constrained Lasso model to jointly analyze the genotype, gene expression and protein expression data. With a prior network capturing the functional relationship between SNPs, genes and proteins, the newly introduced penalty term maximizes the global modularity of the subnetwork involving selected markers and encourages the selection of multi-omic markers with dense functional connectivity, instead of individual markers. We applied this new model to the real data in ROS/MAP cohort for discovery of biomarkers related to cognitive performance. A functionally connected subnetwork involving 276 multi-omic biomarkers, including SNPs, genes and proteins, were identified to bear predictive power. Within this subnetwork, multiple trans-omic paths from SNPs to genes and then proteins were observed, suggesting that cognitive performance can be potentially affected by the genetic mutations due to their cascade effect on the expression of downstream genes and proteins.
The RNA export factor Mex67 functions as a mobile nucleoporin
Authors: Derrer Carina Patrizia , Mancini Roberta , Vallotton Pascal , Huet Sébastien , Weis Karsten , Dultz Elisa 
Published: October 2019

AbstractThe RNA export factor Mex67 is essential for the transport of mRNA through the nuclear pore complex (NPC) in yeast, but the molecular mechanism of this export process remains poorly understood. Here, we use quantitative fluorescence micro-scopy techniques in live budding yeast cells to investigate how Mex67 facilitates mRNA export. We show that Mex67 exhibits little interaction with mRNA in the nucleus and localizes to the NPC independently of mRNA, occupying a set of binding sites offered by FG repeats in the NPC. The ATPase Dbp5, which is thought to remove Mex67 from transcripts, does not affect the interaction of Mex67 with the NPC. Strikingly, we find that the essential function of Mex67 is spatially restricted to the NPC since a fusion of Mex67 to the nucleoporin Nup116 rescues a deletion of MEX67. Thus, Mex67 functions as a mobile nuclear pore component, which receives mRNA export substrates in the central channel of the NPC to facilitate their translocation to the cytoplasm.
β-arrestin-dependent ERK signaling positively correlates with reduced anxiety-like and conditioned fear-related behavior in mice
Authors: Ko Mee Jung , Chiang Terrance , Mukadam Arbaaz A. , Mulia Grace E. , Gutridge Anna M. , Lin Angel , Chester Julia A. , van Rijn Richard M. 
Published: October 2019

AbstractExposure to anxiety- or fear-invoking stimuli initiates a convergence of executive actions orchestrated by multiple proteins and neurotransmitters across the brain. Dozens of G protein-coupled receptors (GPCRs) have been linked to regulation of fear and anxiety. GPCR signaling involves canonical G protein pathways but may also engage downstream kinases and effectors through β-arrestin scaffolds. Here, we investigate whether β-arrestin signaling can regulate anxiety-like and fear-related behavior. Using the δ-opioid receptor (δOR) as a model GPCR, we found that β-arrestin 2-dependent activation of extracellular signal–regulated kinases (ERK1/2) in the dorsal hippocampus and the amygdala are critical for δOR agonist-induced anxiolytic-like effects. In contrast, G protein-mediated δOR signaling was associated with decreased ERK1/2 activity and increased fear-related behavior. Our results also indicate unique contributions for β-arrestin isoforms in modulation of anxiety-like and fear-related behavior. Overall, our findings highlight the significance of non-canonical β-arrestin signaling in the regulation of emotions.One sentence summaryUsing pharmacological and genetic strategies, we reveal the importance of non-canonical β-arrestin-mediated G protein-coupled receptor signaling in anxiety-like behaviors.
Antibody-free enzyme-assisted chemical labeling for detection of transcriptome-wideN6-methyladenosine
Authors: Wang Ye , Xiao Yu , Dong Shunqing , Yu Qiong , Jia Guifang 
Published: October 2019

AbstractThe inert chemical property of RNA modificationN6-methyladenosine (m6A) makes it very challenging to detect, and all of the transcriptome-wide m6A detection methods rely on m6A-antibody immunoprecipitation. However, their results are dependent on the quality and specificity of antibodies. Although the endoribonuclease-based single-base m6A sequencing is antibody-free, it maps only 16~25% sites. Here, we present an antibody-free, FTO-assisted chemical labeling method termed m6A-SEAL for m6A detection. We applied m6A-SEAL to profile m6A landscapes in human and plant, which had good overlaps with antibody-based results and displayed the known m6A distribution features in transcriptome. Comparison with all available m6A sequencing methods and specific m6A sites validation by SELECT, we demonstrated that m6A-SEAL has good sensitivity, specificity, and reliability for transcriptome-wide detection of m6A. Given its tagging ability and FTO’s oxidation property, m6A-SEAL enables many applications like enrichment, imaging, and sequencing techniques to drive future functional studies of m6A and other modifications.
Different preference functions act in unison: mate choice and risk-taking behaviour in the Atlantic molly (Poecilia mexicana)
Authors: Sommer-Trembo Carolin , Schreier Michael , Plath Martin 
Published: October 2019

AbstractConsistent individual differences in behaviour (animal personality) are widespread throughout the Animal Kingdom. This includes variation in risk-taking versus risk-averse behavioural tendencies. Variation in several personality dimensions is associated with distinct fitness consequences and thus, may become a target of natural and/or sexual selection. However, the link between animal personality and mate choice—as a major component of sexual selection—remains understudied. We asked (1) whether females and males of the livebearing fish Poecilia mexicana prefer risk-taking mating partners (directional mating preference), (2) or if their preferences are dependent on the choosing individual’s own personality type (assortative mating). We characterized each test subject for its risk-taking behaviour, assessed as the time to emerge from shelter and enter an unknown area. In dichotomous association preference tests, we offered two potential mating partners that differed in risk-taking behaviour but were matched for other phenotypic traits (body size, shape, and colouration). Females, but not males, exhibited a strong directional preference for risk-taking over risk-averse mating partners. At the same time, the strength of females’ preferences correlated positively with their own risk-taking scores. Our study is the first to demonstrate that a strong overall preference for risk-taking mating partners does not preclude effects of choosing individuals’ own personality type on (subtle) individual variation in mating preferences. More generally, two different preferences functions appear to interact to determine the outcome of individual mate choice decisions.
LAMBDR: Long-range amplification and Nanopore sequencing of theMycobacterium bovis direct-repeat region. A novel method for in-silico spoligotyping ofM. bovisdirectly from badger faeces
Authors: James R.S. , Travis E.R. , Millard A. D. , Hewlett P.C. , Kravar-Garde L. , Wellington E.M. 
Published: October 2019

AbstractThe environment is an overlooked source ofMycobacterium bovis, the causative agent of bovine TB. Long read, end to end sequencing of variable repeat regions across theM. bovisgenome was evaluated as a method of acquiring rapid strain level resolution directly from environmental samples. Eight samples ofM. bovis, two BCG strains (Danish and Pasteur), and a singleM. tuberculosistype culture (NCTC 13144) were used to generate data for this method. Long range PCR amplification of the direct repeat region was used to synthesize ∼5kb template DNA for onward sequence analysis. This has permitted culture independent identification ofM. bovisspoligotypes present in the environment. Sequence level analysis of the direct repeat region showed that spoligotyping may underestimate strain diversity due to the inability to identify both SNPs and primer binding mutations using a biotinylated hybridisation approach.
Molecular and Behavioral Effects of Infant Maltreatment across Generations in Rhesus Monkeys
Authors: Klengel Torsten , Morin Elyse L. , Howell Brittany R. , Bramlett Sara , Guzman Dora , Meyer Jerrold S. , Ressler Kerry J. , Sanchez M. Mar 
Published: October 2019

AbstractChildhood maltreatment is among the most robust risk factors for subsequent psychiatric and medical disorders, and data in humans and rodents suggest that effects of adverse childhood experiences may be transmitted across generations. Recent indications for biological processes underlying this transfer of experiential effects are intriguing; yet, their relevance in primates is inconclusive due to limitations of current studies. In this study, we bridge research in rodent models and humans with a natural non-human primate model on intergenerational effects of childhood maltreatment. Using a unique, well-controlled, randomized cross-fostering design in rhesus monkeys, we test the influence of ancestral maltreatment on molecular, neuroendocrine and behavioral outcomes in offspring, and show that childhood maltreatment results in transmission of information to the subsequent generation independent of behavioral transmission. We further demonstrate differences in the offspring longitudinal DNA methylation profile of theFKBP5gene, an important regulator of the hypothalamus-pituitary-adrenal axis in offspring of the maltreatment lineage compared to the control lineage. Finally, we show that differences inFKBP5methylation have functional effects on molecular, neuroendocrine and behavioral outcomes in offspring of the maltreatment ancestral line, even if the infants were never exposed to maltreatment nor interacted with their exposed ancestors. Although the molecular mechanism underlying our observations remains unknown, our data point to a potential germline-dependent effect. In summary, our data suggest that history of maltreatment in primates can induce molecular and behavioral changes in a subsequent generation independent of behavioral transmission that may influence risk for mental and physical diseases across generations.
CALX-CBD1 Ca2+-binding cooperativity studied by NMR spectroscopy and ITC with Bayesian statistics
Authors: Cardoso M. V. C. , Rivera J. D. , Vitale P. M. , Degenhardt M. F. S. , Abiko L.A. , Oliveira C. L. P. , Salinas R. K. 
Published: October 2019

ABSTRACTThe Na+/Ca2+ exchanger of Drosophila melanogaster, CALX, is the main Ca2+-extrusion mechanism in olfactory sensory neurons and photoreceptor cells. Na+/Ca2+ exchangers have two Ca2+ sensor domains, CBD1 and CBD2. In contrast to the mammalian homologues, CALX is inhibited by Ca2+-binding to CALX-CBD1, while CALX-CBD2 does not bind Ca2+ at physiological concentrations. CALX-CBD1 consists of a β-sandwich and displays four Ca2+ binding sites at the tip of the domain. In this study, we used NMR spectroscopy and isothermal titration calorimetry (ITC) to investigate the cooperativity of Ca2+-binding to CALX-CBD1. We observed that this domain binds Ca2+ in the slow exchange regime at the NMR chemical shift time scale. Ca2+-binding restricts the dynamics in the Ca2+-binding region. Experiments of 15N CEST and 15N R2 dispersion allowed the determination of Ca2+ dissociation rates (≈ 20 s−1). NMR titration curves of residues in the Ca2+-binding region were sigmoidal due to the contribution of chemical exchange to transverse magnetization relaxation rates, R2. Hence, a novel approach to analyze NMR titration curves was proposed. Ca2+-binding cooperativity was examined assuming two different stoichiometric binding models and using a Bayesian approach for data analysis. Fittings of NMR and ITC binding curves to the Hill model yielded nHill = 2.9 − 3.1, near maximum cooperativity (nHill = 4). By assuming a stepwise model to interpret the ITC data, we found that the probability of binding from 2 up to 4 Ca2+ is at least three orders of magnitude higher than that of binding a single Ca2+. Hence, four Ca2+ ions bind almost simultaneously to CALX-CBD1. Cooperative Ca2+-binding is key to enable this exchanger to efficiently respond to changes in the intracellular Ca2+-concentration in sensory neuronal cells.SIGNIFICANCECALX-CBD1 is the Ca2+-sensor domain of the Na+/Ca2+ exchanger of Drosophila melanogaster. It consists of a β-sandwich, and contains four Ca2+ binding sites at the distal loops. In this study, we examined the cooperative binding of four Ca2+ ions to CALX-CBD1 using NMR spectroscopy and isothermal titration calorimetry (ITC) experiments. NMR and ITC data were analyzed using the framework of the binding polynomial formalism and Bayesian statistics. A novel approach to analyze NMR titration data in the slow exchange regime was proposed. These results support the view that CALX-CBD1 binds four Ca2+ with high cooperativity. The significant ligand binding cooperativity exhibited by this domain is determinant for the efficient allosteric regulation of this exchanger by intracellular Ca2+.
Hunting strategies and the lateral line of Astyanax mexicanus larva
Authors: Yoffe Marina , Patel Kush , Palia Eric , Kolawole Samuel , Streets Amy , Haspel Gal , Soares Daphne 
Published: October 2019

AbstractThe lateral line is the primary modality fish use to create a hydrodynamic image of their environment. These images contribute to a variety of behaviors, from rheotaxis to escape responses. Here we discern the contributions of visual and lateral line modalities in hunting behavior of larvae that have developed under different photic conditions. In particular, cave animals have a hypertrophied sense of mechanosensation, and we studied the common animal model cavefish Astyanax mexicanus and its closest related surface relative. We raised larvae in a diurnal light-dark regimen and in complete darkness. We then examined the distribution of neuromasts in their lateral lines, and their hunting performance in light and dark conditions, with and without the contribution of the lateral line. We report that all larva depend on the lateral line for success in hunting and that surface fish raised in the dark have a greater dependency on the lateral line,
Regulatory Feedbacks on Receptor and Non-receptor Synthesis for Robust Signaling
Authors: Lander A.D. , Nie Q. , Sanchez-Tapia C. , Simonyan A. , Wan F.Y.M. 
Published: October 2019

AbstractElaborate feedback regulatory processes are thought to make biological developments robust, i.e., resistant to changes induced by genetic or environmental perturbations. How this might be done is still not completely understood. Previous numerical simulations on reaction-diffusion models of Dpp gradients in Drosophila wing imaginal disc showed that feedback (of the Hill’s function type) on (signaling) receptors and/or non-(signaling) receptors are of limited effectiveness in promoting robustness. Spatial nonuniformity of the feedback processes is thought to lead to serious shape distortion and a principal cause for ineffectiveness. Through mathematical modeling of a spatially uniform nonlocal feedback mechanism, the present paper provides a theoretical support of these observations. More significantly, the new approach also enables us to uncover in this paper a new, theory-based multi-feedback instrument for broadly effective promotion of robust signaling gradients.
A phage display approach to identify highly selective covalent binders
Authors: Chen Shiyu , Bogyo Matthew 
Published: October 2019

AbstractMolecules that bind macromolecular targets through direct covalent modification have found widespread applications as activity-based probes (ABPs) and as irreversible drugs. Covalent binders can be used to dynamically monitor the activity of enzymes in complex cellular environments, identify targets and induce permanent binding/inhibition of therapeutically important biomolecules. However, the general reactivity of the electrophiles needed for covalent bond formation makes control of selectivity difficult. There is currently no rapid, robust and unbiased screening method to identify new classes of covalent binding ligands from highly diverse pools of candidate molecules. Here we describe the development of a phage display method to screen for highly selective covalent binding ligands. This approach makes use of a reactive linker to form cyclic peptides on the phage surface while simultaneously introducing an electrophilic ‘warhead’ to covalently react with a nucleophile on the target. Using this approach, we identified cyclic peptides that selectively and irreversibly inhibited a cysteine protease with nanomolar potency, exceptional specificity and increased serum stability compared to a linear peptide containing the same electrophile. This approach should enable rapid, unbiased screening to identify new classes of highly selective covalent binding ligands for diverse molecular targets.
Style transfer with variational autoencoders is a promising approach to RNA-Seq data harmonization and analysis
Authors: Russkikh N. , Antonets D. , Shtokalo D. , Makarov A. , Vyatkin Y. , Zakharov A. , Terentyev E. 
Published: October 2019

AbstractMotivationThe transcriptomic data is being frequently used in the research of biomarker genes of different diseases and biological states. The most common tasks there are data harmonization and treatment outcome prediction. Both of them can be addressed via the style transfer approach. Either technical factors or any biological details about the samples which we would like to control (gender, biological state, treatment etc.) can be used as style components.ResultsThe proposed style transfer solution is based on Conditional Variational Autoencoders, Y-Autoencoders and adversarial feature decomposition. In order to quantitatively measure the quality of the style transfer, neural network classifiers which predict the style and semantics after training on real expression were used. Comparison with several existing style-transfer based approaches shows that proposed model has the highest style prediction accuracy on all considered datasets while having comparable or the best semantics prediction accuracy.Availabilityhttps://github.com/NRshka/stvae-sourceContactantonec@novel-soft.comSupplementary informationFigShare.com (https://dx.doi.org/10.6084/m9.figshare.9925115)