bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurotrophins, Cytokines, and Pain
Authors: Sikandar Shafaq , Sommer Claudia 
Published: April 2019

Abstract
The neurotrophin and cytokine families of proteins regulate neuronal functions that affect survival, growth, and differentiation. Because of their extensive expression throughout the nervous system, some neurotrophins and cytokines are widely accepted to modulate synaptic plasticity and nociceptive processing. Among the neurotrophin family are nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3), which all bind to the tyrosine receptor kinases. The potential for BDNF as a therapeutic target is supported by a large body of evidence demonstrating its role in driving plastic changes in nociceptive pathways to initiate and maintain chronic pain. On the other hand, NGF has already proved fruitful as an analgesic target, with efficacy shown for NGF-neutralizing antibodies for pain relief in rheumatic diseases. The cytokine family includes the interleukins, tumor necrosis factors (TNFs), chemokines, interferons (IFNs), and transforming growth factor ß (TGF-ß) family. These bind, often promiscuously, to the heterogeneous group of cytokine receptors, and this cytokine signaling is essential for normal responses of the innate and adaptive immune systems. In pathophysiological states, chronic inflammation enhances the expression of pro-inflammatory cytokines, and many studies support a modulatory role of cytokines in nociceptive processes. At the forefront of anticytokine therapy for analgesia are TNF and IL6 monoclonal antibodies, which are licensed treatments for pain relief in rheumatoid arthritis. This article reviews the pro- and antinociceptive roles of key members of the neurotrophin and cytokine families in the context of chronic pain mechanisms and therapeutic approaches.
Time and the Separation of Powers
Authors: Scheuerman William E. 
Published: April 2019

Abstract
This chapter explores the temporal presuppositions of both early modern and contemporary models of the separation of powers, one of the intellectual and institutional pillars of modern liberal democracy. The separation of powers’ original conceptual renditions and their justifications are explored, with special attention paid to the idea of a tripartite functional separation of government bodies, checks and balances, and the dispersal of state authority as a necessary presupposition of personal and legal freedom. After exploring the separation of powers’ multifaceted temporal premises, the chapter considers how processes of social acceleration tend to impact them in potentially troublesome ways. Social acceleration throws a wrench into the separation of powers’ finely tuned “clockwork.”
Skilled Anticipation in Sport
Authors: Williams A. Mark , Fawver Bradley , Broadbent David P. , Murphy Colm P. , Ward Paul 
Published: April 2019

Abstract
This chapter We provides a historical overview of research focusing on the topic of anticipation, with a particular focus on its importance in various high-performance domains, including sport. The first half of the chapter will review more than five decades of research which has highlighted some of the key perceptual–cognitive skills underpinning anticipation and how these interact and vary in importance from one situation to another. In the second half, suggestions for future research in this field will be presented, highlighting the need for methodological improvements and identifying ways in which conceptual understanding may be enhanced. While acknowledging the large body of literature that exists focusing on the importance of perceiving kinematic information from opponents during anticipation (i.e., postural cues), the authors bemoan the relative paucity of research focusing on how non-kinematic information related to situational context impacts on anticipation. Implications for research design and the development of conceptual frameworks are highlighted.
Love and Enhancement Technology
Authors: Earp Brian D. 
Published: April 2019

Abstract
Chemical and other interventions into the biological dimensions of love are currently possible and will likely become more powerful in years to come. This chapter explores some of the conceptual issues surrounding what it would mean to change love with biochemical agents, and presents a handful of case studies of individuals and couples who might desire to use such agents as a way of enhancing their love and relationships. The chapter then discusses a number of ethical and other worries that would likely be raised by the development or use of such biotechnologies and offers some tentative responses. Ultimately, it is argued that love-enhancing biotechnology is not just a conceptual possibility, but may already be practically feasible, and is likely in some cases to be morally desirable.
What does a good night’s sleep mean? Nonlinear relations between sleep and children’s cognitive functioning and mental health
Authors: El-Sheikh Mona , Philbrook Lauren E , Kelly Ryan J , Hinnant J Benjamin , Buckhalt Joseph A 
Published: April 2019

Abstract

Study Objectives
We attempted to identify the duration and quality of sleep associated with the optimal child outcomes in key developmental domains including cognitive functioning, academic performance, and mental health. In doing so, we examined nonlinear associations between the sleep and developmental variables. Based on racial/ethnic disparities in children’s sleep, we assessed this variable as a moderator of examined relations.

Methods
Two hundred eighty-two children participated (Mage = 9.4 years, SD = .72; 52% boys; 65% white/European American, 35% black/African American). Sleep was examined with actigraphy for seven consecutive nights and with self-reports. Actigraphy-based sleep duration (minutes) and quality (efficiency), as well as self-reported sleep quality were derived. Children reported on their mental health and were administered cognitive performance tests. Mothers and teachers reported on children’s mental health; teachers also reported on academic functioning. Schools provided academic achievement data.

Results
Sleep duration had an accelerating nonlinear negative association with externalizing behaviors. Nonlinear associations were also detected between both actigraphy-derived and subjective reports of sleep quality and multiple developmental domains including academic functioning and mental health and the best functioning corresponded with the highest levels of sleep quality. Emphasizing the importance of individual differences, several examined associations were moderated by race/ethnicity.

Conclusions
Sleep duration and quality emerged as nonlinear predictors of multiple domains of child development. Findings illustrate that the benefits of longer and better-quality sleep did not taper off and that assessments of nonlinear relations may enhance understanding of the nature of associations between sleep and child functioning.
Barriers to hypertension and diabetes management in primary health care in Argentina: qualitative research based on a behavioral economics approach
Authors: Belizan Maria , Alonso Juan P , Nejamis Analía , Caporale Joaquín , Copo Mariano G , Sánchez Mario , Rubinstein Adolfo , Irazola Vilma 
Published: April 2019

AbstractDespite efforts to improve detection and treatment of adults with hypertension and diabetes in Argentina, many public healthcare system users remain undiagnosed or face barriers in managing these diseases. The purpose of this study is to identify health system, provider, and user-related factors that may hinder detection and treatment of hypertension and diabetes using a traditional and behavioral economics approach. We did qualitative research using in-depth semistructured interviews and focus groups with healthcare providers and adult users of Public Primary Care Clinics. Health system barriers included inadequate care accessibility; poor integration between primary care clinics and local hospitals; lack of resources; and gender bias and neglect of adult chronic disease. Healthcare provider–related barriers were inadequate training; lack of availability or reluctance to adopt Clinical Practice Guidelines; and lack of counseling prioritization. From a behavioral economics perspective, bottlenecks were related to inertia and a status quo, overconfidence, and optimism biases. User-related barriers for treatment adherence included lack of accurate information; resistance to adopt lifelong treatment; affordability; and medical advice mistrust. From a behavioral economics perspective, the most significant bottlenecks were overconfidence and optimism, limited attention, and present biases. Based on these findings, new interventions that aim to improve prevention and control of chronic conditions can be proposed. The study provides empirical evidence regarding the barriers and bottlenecks in managing chronic conditions in primary healthcare settings. Results may contribute to the design of behavioral interventions targeted towards healthcare provision for the affected population.
Retropharyngeal Tuberculous Abscess: A Rare Cause of Upper Airway Obstruction and Obstructive Sleep Apnea in Children: A Case Report
Authors: Weldetsadik Abate Yeshidinber , Bedane Alemayehu , Riedel Frank 
Published: April 2019

Abstract
Retropharyngeal tuberculous abscess (RPTBA) is a rare manifestation of tuberculosis (TB) even in high TB burden areas. It rarely manifests as a cause of upper airway obstruction and obstructive sleep apnea (OSA) in children with few case reports in the literature. We report a 22 months old toddler who presented with upper airway obstruction and OSA and was diagnosed with RPTBA. The child recovered completely and growing normally after intra-oral aspiration and 6 months of anti-tuberculosis treatment.
Deep learning based brain age prediction uncovers associated sequence variants
Authors: Jonsson B.A. , Bjornsdottir G. , Thorgeirsson T.E. , Ellingsen L.M. , Bragi Walters G. , Gudbjartsson D.F. , Stefansson H. , Stefansson K. , Ulfarsson M.O. 
Published: April 2019

AbstractMachine learning algorithms trained to recognize age-related structural changes in magnetic resonance images (MRIs) of healthy individuals can be used to predict biological brain age in independent samples. The difference between predicted and chronological age, predicted age difference (PAD), is a phenotype holding promise for the study of normal brain ageing and brain diseases, and genetic discoveryviagenome-wide association studies (GWASs). Here, we present a new deep learning approach to predict brain age from a T1-weighted MRI. The method was trained on a dataset of healthy Icelanders (N= 1264) and tested on two datasets, the IXI (N= 544) and UK Biobank (N= 12395) datasets, utilizing transfer learning to improve accuracy on new sites. A GWAS of PAD in the UK Biobank data (discovery set: N=12395, replication set: N=4453) yielded two sequence variants, rs1452628-T (β=-0.08,P= 1.15 · 10−9) and rs2435204-G (β=0.102,P= 9.73 · 10−12). The former is nearKCNK2and correlates with reduced sulcal width, whereas the latter correlates with reduced white matter surface area and tags a well-known inversion at 17q21.31 (H2). The genetic association analysis was also confined to variants known to associate with brain structure, yielding three additional sequence variants associating with PAD.
AVibrio choleraeBolA-like protein is required for proper cell shape and cell envelope integrity
Authors: Fleurie Aurore , Zoued Abdelrahim , Alvarez Laura , Hines Kelly M. , Cava Felipe , Xu Libin , Davis Brigid M. , Waldor Matthew K. 
Published: April 2019

AbstractBolA family proteins are conserved in gram-negative bacteria and many eukaryotes. While diverse cellular phenotypes have been linked to this protein family, the molecular pathways through which these proteins mediate their effects are not well-described. Here, we investigated the role of BolA family proteins inVibrio cholerae, the cholera pathogen. LikeEscherichia coli,V. choleraeencodes two BolA proteins, BolA and IbaG. However, in marked contrast toE. coli, wherebolAis linked to cell shape andibaGis not, inV. cholerae, bolAmutants lack morphological defects, whereasibaGproved critical for the generation and/or maintenance of the pathogen’s morphology. Notably, the bizarre-shaped, multi-polar, elongated and wide cells that predominated in exponential phase ΔibaG V. choleraecultures were not observed in stationary phase cultures. TheV. choleraeΔibaGmutant exhibited increased sensitivity to cell envelope stressors, including cell wall acting antibiotics and bile, and was defective in intestinal colonization. ΔibaG V. choleraehad reduced peptidoglycan and lipid II and altered outer membrane lipids, likely contributing to the mutant’s morphological defects and sensitivity to envelope stressors. Transposon-insertion sequencing analysis ofibaG’s genetic interactions suggested thatibaGis involved in several processes involved in the generation and homeostasis of the cell envelope. Furthermore, co-purification studies revealed that IbaG interacts with proteins containing iron-sulfur clusters or involved in their assembly. Collectively, our findings suggest thatV. choleraeIbaG controls cell morphology and cell envelope integrity through its role in biogenesis or trafficking of iron-sulfur cluster proteins.ImportanceBolA-like proteins are conserved across prokaryotes and eukaryotes. These proteins have been linked to a variety of phenotypes, but the pathways and mechanisms through which they act have not been extensively characterized. Here, we unraveled the role of the BolA-like protein IbaG in the cholera pathogenVibrio cholerae. The absence of IbaG was associated with dramatic changes in cell morphology, sensitivity to envelope stressors, and intestinal colonization defects. IbaG was found to be required for biogenesis of several components of theV. choleraecell envelope and to interact with numerous iron-sulfur cluster containing proteins and factors involved in their assembly. Thus, our findings suggest that IbaG governsV. choleraecell shape and cell envelope homeostasis through its effects on iron-sulfur proteins and associated pathways. The diversity of processes involving iron-sulfur containing proteins is likely a factor underlying the range of phenotypes associated with BolA family proteins.
Disease-associated mutations hyperactivate KIF1A motility and anterograde axonal transport of synaptic vesicle precursors
Authors: Chiba Kyoko , Min Chen , Arai Shogo , Hashimoto Koichi , McKenney Richard J. , Niwa Shinsuke 
Published: April 2019

AbstractKIF1A is a kinesin-family motor involved in the axonal transport of synaptic vesicle precursors (SVPs) along microtubules. In humans, more than ten point mutations inKIF1Aare associated with the motor neuron disease, hereditary spastic paraplegia (SPG). However, not all of these mutations appear to inhibit the motility of the KIF1A motor, and thus, a clear molecular explanation for howKIF1Amutations lead to neuropathy is not available. In this study, we establishedin vitromotility assays with purified full-length human KIF1A and found thatKIF1Amutations associated with the pure form of spastic paraplegia hyperactivate motility of the KIF1A motor. Introduction of the corresponding mutations intoCaenorhabditis elegans KIF1Ahomologueunc-104revealed abnormal accumulation of SVPs at the tips of axons and increased anterograde axonal transport of SVPs. Our data reveal that hyper-activation of kinesin motor activity, rather than its loss-of-function, is a novel cause of motor neuron disease in humans.Significance StatementAnterograde axonal transport supplies organelles and protein complexes throughout axonal processes to support neuronal morphology and function. It has been observed that reduced anterograde axonal transport is associated with neuronal diseases. In contrast, here we show that particular disease-associated mutations in KIF1A, an anterograde axonal motor for synaptic vesicle precursors, induce hyperactivation of KIF1A motor activity and increased axonal transport of synaptic vesicle precursors. Our results advance the knowledge of the regulation of motor proteins and axonal transport and cell biology of motor neuron diseases.
Pregnancy-associated plasma protein-aa supports hair cell survival by regulating mitochondrial function
Authors: Alassaf Mroj , Daykin Emily , Mathiaparanam Jaffna , Wolman Marc 
Published: April 2019

AbstractTo support cell survival, mitochondria must balance energy production with oxidative stress. Inner ear hair cells are particularly vulnerable to oxidative stress; thus require tight mitochondrial regulation. We identified a novel molecular regulator of the hair cells’ mitochondria and survival: Pregnancy-associated plasma protein-aa (Pappaa). Hair cells in zebrafish pappaa mutants exhibit mitochondrial defects, including elevated mitochondrial calcium, transmembrane potential, and reactive oxygen species (ROS) production and reduced antioxidant expression. In pappaa mutants, hair cell death is enhanced by stimulation of mitochondrial calcium or ROS production and suppressed by a mitochondrial ROS scavenger. As a secreted metalloprotease, Pappaa stimulates extracellular insulin-like growth factor 1 (IGF1) bioavailability. We found that the pappaa mutants’ enhanced hair cell loss can be suppressed by stimulation of IGF1 availability and that Pappaa-IGF1 signaling acts post-developmentally to support hair cell survival. These results reveal Pappaa as an extracellular regulator of hair cell survival and essential mitochondrial function.
Vireo: Bayesian demultiplexing of pooled single-cell RNA-seq data without genotype reference
Authors: Huang Yuanhua , McCarthy Davis J , Stegle Oliver 
Published: April 2019

AbstractThe joint analysis of multiple samples using single-cell RNA-seq is a promising experimental design, offering both increased throughput while allowing to account for batch variation. To achieve multi-sample designs, genetic variants that segregate between the samples in the pool have been proposed as natural barcodes for cell demultiplexing. Existing demultiplexing strategies rely on access to complete genotype data from the pooled samples, which greatly limits the applicability of such methods, in particular when genetic variation is not the primary object of study. To address this, we here present Vireo, a computationally efficient Bayesian model to demultiplex single-cell data from pooled experimental designs. Uniquely, our model can be applied in settings when only partial or no genotype information is available. Using simulations based on synthetic mixtures and results on real data, we demonstrate the robustness of our model and illustrate the utility of multi-sample experimental designs for common expression analyses.
Discriminating tactile speed in absence of raised texture elements: Role of deformation and vibratory cues
Authors: Moscatelli Alessandro , Ryan Colleen P. , Ciotti Simone , Cosentino Lucia , Ernst Marc O. , Lacquaniti Francesco 
Published: April 2019

AbstractMotion encoding in touch relies on multiple cues, such as displacements of traceable texture elements, friction-induced vibrations, and gross fingertip deformations by shear force. We evaluated the role of deformation and vibration cues in tactile speed discrimination. To this end, we tested the discrimination of speed of a moving smooth glass plate, and compared the precision of the responses when the same task was performed with a plate having a fine texture. Participants performed the task with and without masking vibrations. Speed discrimination was nearly as precise among the two surface types, as assessed by the steep slope of the psychometric function. Consistent with our previous work, high-frequency vibrations impaired the ability of the participants in discriminating surface speed. Results of the current study showed that it is possible to discriminate motion speed even in absence of a raised texture.HighlightsOn a smooth surface, humans are able to discriminate the speed of a moving surface by frictional motion cuesThe precision of speed discrimination is nearly the same with smooth and fine-textured surface typesHigh frequency vibrations impair the ability to discriminate speed of moving surfaces
The consequences of the heritage experience in brand museums on the consumer–brand relationship
Authors: Pulh Mathilde , Mencarelli Rémi , Chaney Damien 
Published: April 2019

Purpose
This paper aims to investigate the consequences of the heritage experience in brand museums on the consumer–brand relationship. By highlighting its heritage within a museum, the brand proposes a specific experience that deserves attention because it is based on memory and communal identity, thus creating or strengthening a relationship with consumers.

Design/methodology/approach
Ethnographic case studies were conducted through direct observation and extensive interviews with 72 visitors at two brand museums, the Fallot Mustard Mill and the House of the Laughing Cow.

Findings
The results highlight the emergence/strengthening of the relationship between consumers and the brand through the development of intimacy with the brand and the emergence of supportive behaviors toward the brand in the form of commercial support, ambassadorship and volunteering.

Research limitations/implications
By characterizing and articulating the different relational consequences of visiting a brand museum, this research contributes to the literature dedicated to heritage experiences in consumption contexts and to the literature dedicated to consumer–brand relationships in servicescapes.

Practical implications
The study shows the necessity of grounding “heritage” in the physical setting of the brand museum to create a meaningful experience for visitors and, in turn, a deep relationship. Managers should treat brand museums as a relational tool in the marketing strategy of the brand and approach them from the perspective of long-term profitability.

Originality/value
While the literature has examined the spectacular and esthetic experiences brand museums offer, this study is the first to characterize the heritage experience and to document its consequences in terms of the consumer–brand relationship.
A cultural analysis of the secondary housing tourism in Vilcabamba, Ecuador
Authors: Martín Juan Carlos , Bustamante-Sánchez Natalia Soledad 
Published: April 2019

PurposeThis study aims to determine the level of satisfaction of secondary housing tourists in Vilcabamba.Design/methodology/approachThe analysis of satisfaction of this tourism segment in a destination is essential for the different economic agents when evaluating various policies. The analysis is based on the answers provided to 16 items in a questionnaire administered to a representative sample (281 respondents). The authors have used the fuzzy logic to reduce ambiguity in the answers associated to subjective views of human beings who express themselves linguistically. A method based on the degree of similarity to ideal solutions has been used to obtain a classification of relevant satisfaction items.FindingsThe results indicate that the ideal solutions segments are represented by multicultural characteristics of second home tourists and the number of years they have been visiting Vilcabamba. The authors find that foreign tourists are more satisfied than Ecuadorians. Analyzing the most critical factors, it is seen that accessibility to the destination, socio-cultural environment and quality of water achieve a high priority.Research limitations/implicationsSecond home tourists’ satisfaction has been studied with a limited set of 16 attributes, and some attributes also have a multidimensional nature, so a further study analyzing the scale will be needed in the future.Originality/valueThe present study fills an existing gap in the literature of secondary housing tourism where the existing previous research has been mainly focused on retirees’ secondary housing tourism. The study provides interesting insights into local and national authorities, as well as other economic agents, to designing strategies and planning processes of the destinations for secondary housing tourists.