bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclease escape elements protect messenger RNA against cleavage by multiple viral endonucleases
Authors: Muller Mandy , Glaunsinger Britt A. 
Published: June 2017

ABSTRACTDuring lytic Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, the viral endonu-clease SOX promotes widespread degradation of cytoplasmic messenger RNA (mRNA). However, select mRNAs, including the transcript encoding interleukin-6 (IL-6), escape SOX-induced cleavage. IL-6 escape is mediated through a 3’ UTR RNA regulatory element that overrides the SOX targeting mechanism. Here, we reveal that this protective RNA element functions to broadly restrict cleavage by a range of homologous and non-homologous viral endonucleases. However, it does not impede cleavage by cellular endonucleases. The IL-6 protective sequence may be representative of a larger class of nuclease escape elements, as we identified a similar protective element in the GADD45B mRNA. The IL-6 and GADD45B-derived elements display similarities in their sequence, putative structure, and several associated RNA binding proteins. However, the overall composition of their ribonucleoprotein complexes appears distinct, leading to differences in the breadth of nucleases restricted. These findings highlight how RNA elements can selectively control transcript abundance in the background of widespread virus-induced mRNA degradation.AUTHOR SUMMARYThe ability of viruses to control the host gene expression environment is crucial to promote viral infection. Many viruses express factors that reduce host gene expression through widespread mRNA decay. However, some mRNAs escape this fate, like the transcript encoding the immunoregulatory cytokine IL-6 during KSHV infection. IL-6 escape relies on an RNA regulatory element located in its 3’UTR and involves the recruitment of a protective protein complex. Here, we show that this escape extends beyond KSHV to a variety of related and unrelated viral endonucleases. However, the IL-6 element does not protect against cellular endonucleases, revealing for the first time a virus-specific nuclease escape element. We identified a related escape element in the GADD45B mRNA, which displays several similarities with the IL-6 element. However, these elements assemble a largely distinct complex of proteins, leading to differences in the breadth of their protective capacity. Collectively, these findings reveal how a putative new class of RNA elements function to control RNA fate in the background of widespread mRNA degradation by viral endonucleases.
Chromatin accessibility dynamics of myogenesis at single cell resolution
Authors: Pliner Hannah A. , Packer Jonathan , McFaline-Figueroa José L. , Cusanovich Darren A. , Daza Riza , Srivatsan Sanjay , Qiu Xiaojie , Jackson Dana , Minkina Anna , Adey Andrew , Steemers Frank J. , Shendure Jay , Trapnell Cole 
Published: June 2017

AbstractOver a million DNA regulatory elements have been cataloged in the human genome, but linking these elements to the genes that they regulate remains challenging. We introduce Cicero, a statistical method that connects regulatory elements to target genes using single cell chromatin accessibility data. We apply Cicero to investigate how thousands of dynamically accessible elements orchestrate gene regulation in differentiating myoblasts. Groups of co-accessible regulatory elements linked by Cicero meet criteria of “chromatin hubs”, in that they are physically proximal, interact with a common set of transcription factors, and undergo coordinated changes in histone marks that are predictive of gene expression. Pseudotemporal analysis revealed a subset of elements bound by MYOD in myoblasts that exhibit early opening, potentially serving as the initial sites of recruitment of chromatin remodeling and histone-modifying enzymes. The methodological framework described here constitutes a powerful new approach for elucidating the architecture, grammar and mechanisms ofcis-regulation on a genome-wide basis.
Wakefulness fluctuations elicit behavioural and neural reconfiguration of awareness
Authors: Noreika Valdas , Canales-Johnson Andrés , Johnson Amy , Arnatkevičiūtė Aurina , Koh Justin , Chennu Srivas , Bekinschtein Tristan A. 
Published: June 2017

ABSTRACTMapping the reports of awareness and its neural underpinnings is instrumental to understand the limits of human perception. The capacity to become aware of objects in the world may be studied by suppressing faint target stimuli with strong masking stimuli, or – alternatively – by manipulating the level of wakefulness from full alertness to mild drowsiness. By combining these two approaches, we studied how perceptual awareness is modulated by decreasing wakefulness. We found dynamic changes in behavioural and neural signatures of conscious access in humans between awake and drowsy states. Behaviourally, we show a decrease in the steepness of the psychophysical function for conscious access in drowsy trials. Neural mapping showed delayed processing of target-mask interaction as the consciousness transition progressed, suggesting that the brain resolution of conscious access shifts from early sensory/perceptual to decision-making stages of processing. Once the goal to report the awareness of a target is set, the system behaviourally adapts to rapid changes in wakefulness, revealing the flexibility of the neural signatures of conscious access, and its suppression, to maintain performance.Significance statementMaintaining full alertness for long periods of time in attentionally demanding situations is challenging and may lead to a decrease in performance. We show the effect of wakefulness fluctuations on behaviour and brain dynamics that humans use to maintain performance. We reveal the neural strategies we have to cope with drowsiness by shifting the weights to more flexible brain processes and relaxing the precision of the decisions we take.
Modelling of the Cardiopulmonary Responses to Maximal Aerobic Exercise in Patients with Cystic Fibrosis
Authors: Williams Craig A. , Wedgwood Kyle C. A. , Mohammadi Hossein , Tomlinson Owen W. , Tsaneva-Atanasova Krasimira 
Published: June 2017

ABSTRACTCystic fibrosis (CF) is a debilitating chronic condition, which requires complex and expensive disease management. Exercise has now been recognised as a critical factor in improving health and quality of life in patients with CF. Hence, cardiopulmonary exercise testing (CPET) is used to determine aerobic fitness of young patients as part of the clinical management of CF. However, at present there is a lack of conclusive evidence for one limiting system of aerobic fitness for CF patients at an individual patient level.Here, we perform detailed data analysis that allows us to identify important systems-level factors that affect aerobic fitness. We use patients’ data and principal component analysis to confirm the dependence of CPET performance on variables associated with ventilation and metabolic rates of oxygen consumption. We find that the time at which participants cross the anaerobic threshold (AT) is well correlated with their overall performance. Furthermore, we propose a predictive modelling framework that captures the relationship between ventilatory dynamics, lung capacity and function and performance in CPET within a group of children and adolescents with CF. Specifically, we show that using Gaussian processes (GP) we can predict AT at the individual patient level with reasonable accuracy given the small sample size of the available group of patients. We conclude by presenting future perspectives for improving and extending the proposed framework.Our modelling and analysis have the potential to pave the way to designing personalised exercise programmes that are tailored to specific individual needs relative to patient’s treatment therapies.
Metabarcoding for the parallel identification of several hundred predators and their preys: application to bat species diet analysis
Authors: Galan Maxime , Pons Jean-Baptiste , Tournayre Orianne , Pierre Éric , Leuchtmann Maxime , Pontier Dominique , Charbonnel Nathalie 
Published: June 2017

AbstractAssessing diet variability is of main importance to better understand the biology of bats and design conservation strategies. Although the advent of metabarcoding has facilitated such analyses, this approach does not come without challenges. Biases may occur throughout the whole experiment, from fieldwork to biostatistics, resulting in the detection of false negatives, false positives or low taxonomic resolution. We detail a rigorous metabarcoding approach based on a short COI minibarcode and two-step PCR protocol enabling the ‘all at once’ taxonomic identification of bats and their arthropod preys for several hundreds of samples. Our study includes faecal pellets collected in France from 357 bats representing 16 species, as well as insect mock communities that mimic bat meals of known composition, negative and positive controls. All samples were analysed using three replicates. We compare the efficiency of DNA extraction methods and we evaluate the effectiveness of our protocol using identification success, taxonomic resolution, sensitivity, and amplification biases. Our parallel identification strategy of predators and preys reduces the risk of mis-assigning preys to wrong predators and decreases the number of molecular steps. Controls and replicates enable to filter the data and limit the risk of false positives, hence guaranteeing high confidence results for both prey occurrence and bat species identification. We validate 551 COI variants from arthropod including 18 orders, 117 family, 282 genus and 290 species. Our method therefore provides a rapid, resolutive and cost-effective screening tool for addressing evolutionary ecological issues or developing ‘chirosurveillance’ and conservation strategies.
A zebrafish model of developmental joint dysplasia: Manipulating the larval mechanical environment to drive the malformation and recovery of joint shape
Authors: Roddy Karen A , Skinner Roddy EH , Brunt Lucy H , Kague Erika , Cross Stephen , Rayfield Emily J , Hammond Chrissy L 
Published: June 2017

AbstractDevelopmental dysplasia of the hip (DDH), a malformation of the acetabulum, is a frequent cause of early onset osteoarthritis. The disease encompasses a spectrum of severities, some of which are more amenable to treatment. Embryonic immobilisation significantly impairs the development of joint shape however the impact of this malformation to the function and growth of the joint in the short to medium term is unclear. We developed a novel model of developmental joint dysplasia using the zebrafish jaw joint to identify the mechanisms regulating cellular plasticity and ability to recover joint shape and function. Larval zebrafish were immobilised either pharmacologically or using targeted ablation of jaw muscles to induce an altered joint shape. Following restoration of muscle activity we dynamically monitored the joint shape and function in individuals at cellular resolution impossible in other vertebrate species. Reflecting the variability of the human condition we found a proportion of joints will recover both their shape and function, while others will not; despite coming from a genetically homogenous population. This allowed us to study what controls likelihood of recovery; we identified a number of cellular changes that predict likelihood of functional recovery, including position of precursor cells, and specific patterns of proliferation, migration and differentiation in joints and associated connective tissues. These factors together predict recovery better than severity of malformation alone. Using Finite Element Analysis we studied the mechanics of joints representative of ones that recover and those that fail to identify differences in patterns of strain that could explain the cellular behaviours that underpin likelihood of recovery. Thus, this model would enable the study of the short to long term impact of altered joint shape on function and could help to identify the changes that render an individual more receptive to treatment and therefore may potentially be indicative of long term joint health.
Delineating the macroscale areal organization of the macaque cortex in vivo
Authors: Xu Ting , Falchier Arnaud , Sullivan Elinor L. , Linn Gary , Ramirez Julian , Ross Deborah , Feczko Eric , Opitz Alexander , Bagley Jennifer , Sturgeon Darrick , Earl Eric , Miranda-Domínguez Oscar , Perrone Anders , Craddock R. Cameron , Schroeder Charles , Colcombe Stan , Fair Damien , Milham Michael P. 
Published: June 2017

SUMMARYComplementing longstanding traditions centered around histology, fMRI approaches are rapidly maturing in delineating brain areal organization at the macroscale. The non-human primate (NHP) provides the opportunity to overcome critical barriers in translational research. Here, we establish the data and scanning conditions for achieving reproducible, stable and internally valid areal parcellations in individuals. We demonstrate that these functional boundaries serve as a functional fingerprint of the individual animals, and can be achieved under anesthesia or awake conditions (rest, naturalistic viewing), though differences between awake and anesthetized states precluded the detection of individual differences across states. Comparison of awake and anesthetized states suggested a more nuanced picture of changes in connectivity for higher order association areas, as well as visual and motor cortex. These results establish feasibility and data requirements for the generation of reproducible individual-specific parcellations in NHP, as well as provide insights into the impact of scan state and motivate efforts toward harmonizing protocols.
An insula-central amygdala circuit for behavioral inhibition
Authors: Schiff Hillary , Bouhuis Anna Lien , Yu Kai , Penzo Mario A. , Li Haohong , He Miao , Li Bo 
Published: June 2017

AbstractPredicting which substances are suitable for consumption during foraging is critical for animals to survive. While food-seeking behavior is extensively studied, the neural circuit mechanisms underlying avoidance of potentially poisonous substances remain poorly understood. Here we examined the role of the insular cortex (IC) to central amygdala (CeA) circuit in the establishment of such avoidance behavior. Using anatomic tracing approaches combined with optogenetics-assisted circuit mapping, we found that the gustatory region of the IC sends direct excitatory projections to the lateral division of the CeA (CeL), making monosynaptic excitatory connections with distinct populations of CeL neurons. Specific inhibition of neurotransmitter release from the CeL-projecting IC neurons prevented mice from acquiring the “no-go” response, while leaving the “go” response largely unaffected in a tastant (sucrose/quinine)-reinforced “go/no-go” task. Furthermore, selective activation of the IC-CeL pathway with optogenetics drove unconditioned lick suppression in thirsty animals, induced aversive responses, and was sufficient to instruct conditioned action suppression in response to a cue predicting the optogenetic activation. These results indicate that activity in the IC-CeL circuit is necessary for establishing anticipatory avoidance responses to an aversive tastant, and is also sufficient to drive learning of such anticipatory avoidance. This function of the IC-CeL circuit is likely important for guiding avoidance of substances with unpleasant tastes during foraging in order to minimize the chance of being poisoned.Significance StatementThe ability to predict which substances are suitable for consumption is critical for survival. Here we found that activity in the insular cortex (IC) to central amygdala (CeA) circuit is necessary for establishing avoidance responses to an unpleasant tastant, and is also sufficient to drive learning of such avoidance responses. These results suggest that the IC-CeA circuit is critical for behavioral inhibition in anticipation of potentially poisonous substances during foraging.
Global DNA methylation, as estimated in blood samples, does not correlate with variations of body condition, anatomical features and hematological parameters in American bullfrogs(Lithobates catesbeianus)kept captive under distinct environmental conditions
Authors: García Braulio Ayala , Fuentes-Farías Alma L. , Ospina Gabriel Gutiérrez 
Published: June 2017

AbstractDifferent levels of Global DNA Methylation (GDM) could have facilitated the emergence of new species, without relying on gene mutations, through promoting ontogenetic phenotypic plasticity. If this assertion was correct, one could expect individuals of the same species living under distinct environmental conditions to be genetically similar, but having different GDM levels and being phenotypically divergent. We tested this presumption by studying the relationship between variability of functional morphological traits and GDM levels in American bullfrog(Lithobates catesbeianus), in green houses located in two geographical sites. Our analyses revealed that body linear morphometry, skull geometry, scaled mass index, packed cell volume and neutrophil counts differed significantly among males and females within and between localities. GDM, nonetheless, was rather similar among sex and locality groups. These results show that levels of GDM, at least under our experimental contexts, does not correlate with functional morphological trait variability.
Workplace happiness: work engagement, career satisfaction, and subjective well-being
Authors: Joo Baek-Kyoo , Lee Insuk 
Published: June 2017

PurposeEmployee happiness or well-being is an emerging topic in management as well as in psychology. The purpose of this paper is to investigate the effects of perceived organizational support (POS) and psychological capital (PsyCap) on happiness in employees’ work (i.e. work engagement), careers (i.e. career satisfaction), and lives (i.e. subjective well-being (SWB)).Design/methodology/approachData were collected from 550 employees in a conglomerate in South Korea. For statistical analysis, we conducted confirmatory factor analysis, reliability and correlation analysis, and structural equation modeling analyses.FindingsEmployees were highly engaged in their work, satisfied with their careers, and felt a greater sense of well-being in their lives when they had higher POS and PsyCap. Work engagement fully mediated the relationship between PsyCap and career satisfaction. POS had an indirect effect on SWB through career satisfaction. With regards to the relationships among the three outcome variables, career satisfaction turned out to fully mediate the relationship between work engagement and SWB. In addition, the direct effect of PsyCap on SWB was also found to be significant.Research limitations/implicationsThis study focused on knowledge workers in South Korean for-profit firms. The participants were mostly male, junior or middle managers. Using a cross-sectional survey method, this empirical study leaves room for speculation about the causality among the variables. As the results of exploratory and confirmatory factor analyses indicate, however, common method variance was found to not be of great concern.Practical implicationsThe mission of human resources (HR) and organization development (OD) professionals in organizations is to improve individual and organizational performance and to enhance employees’ well-being. HR/OD professionals can enhance employees’ happiness not only in their work and careers but also in their lives by improving POS (e.g. growth opportunity, performance management, and compensation system) and developing PsyCap (e.g. staffing, training, and development, etc.).Originality/valueThis study linked the emerging constructs in positive psychology in general, in HR/OB in particular. To date, no study has empirically investigated the effects of PsyCap and POS on the three workplace happiness constructs: work engagement, career satisfaction, and SWB. This is the first study that found the relationship between POS and PsyCap. Last, while South Koreans are more collectivistic and less satisfied with their lives than the Organisation for Economic Co-operation and Development average, the respondents in this study, working for highly reputable firms, perceived high level of happiness in their work and career, and eventually in their lives. Thus, organizational features had a stronger effect on workplace happiness than national culture.
Trashy bags: sustainability crisis of a sustainable business
Authors: Tsamenyi Mathew , Yaa Antwi-Gyamfi Nana 
Published: June 2017

Subject area
Entrepreneurship, Business Strategy, Leadership, Marketing and Decision-making in business.

Study level/applicability
This case is suitable for graduate-level programmes in business management as well as executive education programmes.

Case overview
Stuart Gold, CEO of Trashy Bags is at a crossroads with respect to the future of his business. With deficits estimated at about GHS 120,000 annually, Gold is considering switching from the made-to-stock production model to a made-to-order model. Although the latter may tap into an available market and thus boost revenue, it would likely result in the displacement of the social enterprise’s loyal following and disenfranchisement of its employees’ creativity; not to mention the possibility of neglecting its mandate of repurposing plastic waste. Gold wonders if there is a case for maintaining the current made-to-stock model by driving up sales and reducing costs to eliminate the deficit.

Expected learning outcomes
Students should be able to: appreciate the exigencies of managing social enterprises in a largely profit-oriented economic domain; understand the interplay of choice and trade-offs in business management and apply theory-driven frameworks in making optimal choices and analytically assess instances of tension between the art (e.g. passion, emotional stakes, psychological and other influences on business management philosophies) and science (e.g. the need for business skills, use of effective models and the quest for production efficiency) of business management.

Supplementary materials
Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 3: Entrepreneurship.
Scanning and design thinking: organizational roles for innovation
Authors: Furue Nanami , Washida Yuichi 
Published: June 2017

Purpose
The purpose of this paper is to first suggest scanning focal areas in new product development (NPD) by comparing with design thinking and, second, to uncover what people in different occupations expect of NPD based on future scenarios.

Design/methodology/approach
Authors place scanning and design thinking into a matrix of product-market strategies. In addition, this study adopts several open-end-type questionnaire surveys of employees at Japanese companies who have taken part in idea generation workshops that take a medium- to long-term perspective.

Findings
Authors found that innovations generated through scanning can cover the most difficult and uncertain areas in practice compared with design thinking. This manuscript also reveals occupational categories can be divided into two groups according to different expectations of NPD: the rapid-fire NPD expectation group and late-bloomer NPD expectation group. The former group which consists of marketing and engineering experts tends to expect that NPD is simply a response to existing needs and that profit will be gained expeditiously through NPD, while the latter, which comprising design and research experts, tends to expect that NPD will realize future innovations.

Originality/value
This study shows some common and different points between scanning and design thinking by using a theoretical framework of product-market strategies. Also, this study reveals who will lead innovation based on foresight in business.