bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic analysis reveals a functional role for myocardial trabeculae in adults
Authors: Meyer Hannah V , Dawes Timothy JW , Serrani Marta , Bai Wenjia , Tokarczuk Paweł , Cai Jiashen , de Marvao Antonio , Rueckert Daniel , Matthews Paul M , Costantino Maria L , Birney Ewan , Cook Stuart A , O’Regan Declan P 
Published: February 2019

ABSTRACTSince being first described by Leonardo da Vinci in 1513 it has remained an enigma why the endocardial surfaces of the adult heart retain a complex network of muscular trabeculae – with their persistence thought to be a vestige of embryonic development. For causative physiological inference we harness population genomics, image-based intermediate phenotyping andin silicomodelling to determine the effect of this complex cardiovascular trait on function. Using deep learning-based image analysis we identified genetic associations with trabecular complexity in 18,097 UK Biobank participants which were replicated in an independently measured cohort of 1,129 healthy adults. Genes in these associated regions are enriched for expression in the fetal heart or vasculature and implicate loci associated with haemodynamic phenotypes and developmental pathways. A causal relationship between increasing trabecular complexity and both ventricular performance and electrical activity are supported by complementary biomechanical simulations and Mendelian randomisation studies. These findings show that myocardial trabeculae are a previously-unrecognised determinant of cardiovascular physiology in adult humans.
Rift Valley fever virus minigenome system for investigating the role of L protein residues in viral transcription and replication
Authors: Jérôme Hanna , Rudolf Martin , Lelke Michaela , Pahlmann Meike , Busch Carola , Bockholt Sabrina , Wurr Stephanie , Günther Stephan , Rosenthal Maria , Kerber Romy 
Published: February 2019

AbstractReplicon systems are important molecular tools for investigating the function of virus proteins and regulatory elements involved in viral RNA synthesis. We developed an ambisense minigenome system for Rift Valley fever virus (RVFV) to dissect the effects of L gene mutations on viral transcription versus replication. The S RNA segment with regulatory elements for ambisense gene expression served as backbone for the minigenome. Expression of the luciferase reporter gene allowed the overall activity of the RVFV replication complex to be assessed, while northern blot analysis enabled differentiation between synthesis of viral mRNA and replication intermediates. The functionality of the system was demonstrated by probing residues predictably involved in the active site of the cap-snatching endonuclease in the N-terminus of the L protein. Corresponding mutations led to a selective defect in the viral mRNA synthesis as described for other viruses of theBunyaviralesorder. The analysis of further L gene mutants revealed an essential and specific role of a C-terminal region in the RVFV L protein in viral transcription. In summary, the established minigenome system is suitable for functional testing of the relevance of residues for viral transcription and replication. It may be used to validate hypotheses arising from structural or biochemical investigations of the RVFV replication complex.
Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling
Authors: Liu Yong , Li Yujiao , Eyo Ukpong B. , Chen Tingjun , Umpierre Anthony D. , Zhu Jia , Bosco Dale B. , Dong Hailong , Wu Long-Jun 
Published: February 2019

AbstractMicroglia are resident immune cells that dynamically survey the brain parenchyma, interacting with neurons in both health and disease. However, it is still unclear how neuronal network activity drives microglial dynamics. Utilizing in vivo two-photon imaging of microglia in awake mice, we found that inhibition of neuronal activity under general anesthesia dramatically increased microglial process surveillance. Accordingly, both sensory deprivation and optogenetic inhibition of local neuronal network activity in awake mice resulted in similar increases in microglial process surveillance. We further determined that reduced norepinephrine signaling is responsible for the observed increase in microglial process surveillance. Our results demonstrate that microglial process dynamics are directly influenced by neural activities through norepinephrine signaling in awake animals and indicate the importance of awake imaging for studying microglia-neuron interactions.
Galectin-3 inhibits Paracoccidioides brasiliensis growth and impacts paracoccidioidomycosis through multiple mechanisms
Authors: Hatanaka Otavio , Rezende Caroline Patini , Moreno Pedro , Fernandes Fabrício Freitas , Oliveira Brito Patrícia Kellen Martins , Martinez Roberto , Coelho Carolina , Roque-Barreira Maria Cristina , Casadevall Arturo , Almeida Fausto 
Published: February 2019

ABSTRACTThe thermodimorphic pathogenic fungi Paracoccidioides brasiliensis and Paracoccioidioides lutzii are the etiologic causes of paracoccidioidomycosis (PCM), the most prevalent systemic mycosis in Latin America. Galectin-3 (Gal-3), an animal β-galactoside-binding protein, modulates important roles during microbial infections, such as triggering a Th2-polarized immune response in PCM. Herein, we demonstrate that Gal-3 also plays other important roles in P. brasiliensis infection. We verified Gal-3 levels are upregulated in human and mice infections and establish that Gal-3 inhibits P. brasiliensis growth by inhibiting budding. Furthermore, Gal-3 affects disruption and internalization of extracellular vesicles (EV) from P. brasiliensis by macrophages. Our results suggest important roles for Gal-3 in P. brasiliensis infection, indicating that increased Gal-3 production during P. brasiliensis infection may account for affecting the fungal growth and EV stability, promoting a benefic course of experimental PCM.IMPORTANCEParacoccidiodomycosis (PCM) is the most prevalent systemic mycosis in Latin America. Although the immune mechanisms to control PCM are still not fully understood, several events of the host innate and adaptive immunity are crucial to determine the progress of the infection. Mammalian β-galactoside-binding protein Galectin-3 (Gal-3) plays significant roles during microbial infections, and has been studied for its immunomodulatory roles but it can also have direct antimicrobial effects. We asked whether this protein plays a role in P. brasiliensis. We report herein that Gal-3 indeed has direct effects on fungal pathogen, inhibiting fungal growth and reducing extracellular vesicles stability. Our results suggest a direct role for Gal-3 in P. brasiliensis infection, with beneficial effects for the mammalian host.
Therapeutic Challenges of Multidrug Resistant Acinetobacter baumannii in Eastern Africa: Systematic Review
Authors: Geteneh Alene , Demissew Assalif , Adimas Alemale , Alemu Derbie , Girma Lencho 
Published: February 2019

AbstractAcinetobacter baumannii, an opportunistic gram negative bacterium, is known to emerge as a major health threat in Eastern Africa. Clinical isolates exhibit resistance to carbapenems and most or all available antibiotics. This review is intended to present concerns about resistance and therapeutic challenges of multi drug resistance Acinetobacter baumannii in Eastern Africa. Data was obtained from PubMed and Google scholar, and from free goggle access and web Medline for facts about Acinetobacter baumannii and its resistance pattern. Moreover, Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow chart was used to guide the selection of study materials. Total of 98 articles identified, 13 fit the criteria and were included for the final analysis. In East Africa the overall prevalence of Acinetobacter baumannii was 4.95%, while the overall rate of multi drug resistance, carbapenem and pan resistance was 87.3%, 64.8% and 25.2% respectively. Colistin resurges as potential therapeutic options to overcome the lack of new antibiotic treatment of Acinetobacter baumannii. There needs a collaborative effort in researches targeted for Acinetobacter baumannii treatment and respond for call of “Research and Development of new antibiotics” to control its damning impact.
Mouse navigation strategies for odor source localization
Authors: Liu Annie , Papale Andrew E , Hengenius James , Patel Khusbu , Ermentrout Bard , Urban Nathaniel N 
Published: February 2019

ABSTRACTNavigating an odor landscape is a critical behavior for the survival of many species, including mice. One ethologically relevant mouse behavior is locating food using odor concentration gradients. To model this behavior, we use a naturalistic open field odor-based spot-finding task, examining navigation strategies as mice search for and approach an odor source. Mice were trained to navigate to odor sources paired with food reward. We detected behavioral changes consistent with localization of the odor source when mice were ∼10cm away from the source. These behaviors included both orientation towards the source and increased exploration time. We found that the amplitude of ‘casting,’ lateral back and forth head movement, increased exponentially with proximity to the source. We then created concentration-dependent models to simulate mouse behavior, which provided evidence for a serial-sniffing strategy (sampling concentration, moving in space, then sampling again) and a stereo-sniffing strategy (inter-nostril comparison of concentration in a single sniff). Together, these results elucidate key components of behavioral strategies for odor-based navigation.SUMMARY STATEMENTUse of a naturalistic odor-source localizing task uncovers key strategies underlying successful mouse navigation. Concentration-dependent models successfully recapitulate mouse behavior and reveal important behavioral components.
Rapid, multiplexed, whole genome and plasmid sequencing of foodborne pathogens using long-read nanopore technology
Authors: Taylor Tonya L. , Volkening Jeremy D. , DeJesus Eric , Simmons Mustafa , Dimitrov Kiril M. , Tillman Glenn E. , Suarez David L. , Afonso Claudio L. 
Published: February 2019

AbstractUnited States public health agencies are focusing on next-generation sequencing (NGS) to quickly identify and characterize foodborne pathogens. Here, the MinION nanopore, long-read sequencer was used to simultaneously sequence the entire chromosome and plasmids of Salmonella enterica subsp. enterica serovar Bareilly and Escherichia coli O157:H7. A rapid, random sequencing approach, coupled with de novo genome assembly within a customized data analysis workflow, that can resolve highly-repetitive genomic regions, was developed. In sequencing runs, as short as four hours, using nanopore data alone, full-length genomes were obtained with an average identity of 99.87% for Salmonella Bareilly and 99.89% for E. coli in comparison to the respective MiSeq references. These long-read assemblies provided information on serotype, virulence factors, and antimicrobial resistance genes. Using a custom-developed, SNP-selection workflow, the potential of the nanopore-only assemblies (after only 30 minutes of sequencing) for rapid phylogenetic inference, with identical topology compared to the published dataset, was demonstrated. To achieve maximum quality assemblies, the developed bioinformatics workflow employed additional polishing steps to correct the systematic errors produced by the nanopore-only assemblies. Nanopore sequencing provided a shorter (10 hours library preparation and sequencing) turnaround time compared to other NGS technologies.
Post-decision processing in primate prefrontal cortex influences subsequent choices on an auditory decision-making task
Authors: Tsunada Joji , Cohen Yale E. , Gold Joshua I. 
Published: February 2019

AbstractPerceptual decisions do not occur in isolation but instead reflect ongoing evaluation and adjustment processes that can affect future decisions. However, the neuronal substrates of these across-decision processes are not well understood, particularly for auditory decisions. We measured and manipulated the activity of choice-selective neurons in the ventrolateral prefrontal cortex (vlPFC) while monkeys made decisions about the frequency content of noisy auditory stimuli. As the decision was being formed, vlPFC activity was not modulated strongly by the task. However, after decision commitment, vlPFC population activity encoded the sensory evidence, choice, and outcome of the current trial and predicted subject-specific choice biases on the subsequent trial. Consistent with these patterns of neuronal activity, electrical microstimulation in vlPFC tended to affect the subsequent, but not current, decision. Thus, distributed post-commitment representations of graded decision-related information in prefrontal cortex can play a causal role in evaluating past decisions and biasing subsequent ones.
Loss of function mutation of mouse Snap29 on a mixed genetic background phenocopy abnormalities found in CEDNIK and 22q11.2 Deletion Syndrome patients
Authors: Keser Vafa , Boisclair Lachance Jean-François , Alam Sabrina Shameen , Lim Youngshin , Scarlata Eleonora , Kaur Apinder , Fang Zhang Tian , Lv Shasha , Lachapelle Pierre , O’Flaherty Cristian , Golden Jefferey A. , Jerome-Majewska Loydie A. 
Published: February 2019

AbstractSynaptosomal-associated protein 29 (SNAP29) is a member of the SNARE family of proteins involved in maintenance of various intracellular protein trafficking pathways. SNAP29 maps to the 22q11.2 region and is deleted in 90% of patients with 22q11.2 deletion syndrome (22q11.2DS). However, the contribution of hemizygosity of SNAP29 to developmental abnormalities in 22q11.2DS remains to be determined. Mutations in SNAP29 are responsible for the developmental syndrome called CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma). On an inbred C57Bl/6J genetic background, only the ichthyotic skin defect associated with CEDNIK was reported. In this study, we show that loss of function mutation of Snap29 on a mixed genetic background not only models skin abnormalities found in CEDNIK, but also phenocopy ophthalmological, neurological, and motor defects found in these patients and a subset of 22q11.2DS patients. Thus, our findings indicate that mouse models of human syndromes should be analyzed on a mixed genetic background. Our work also reveals an unanticipated requirement for Snap29 in male fertility, and support contribution of hemizygosity for SNAP29 to the phenotypic spectrum of abnormalities found in 22q11.2DS patients.
Negative Affect Induces Rapid Learning of Counterfactual Representations: A Model-based Facial Expression Analysis Approach
Authors: Haines Nathaniel , Rass Olga , Shin Yong-Wook , Brown Joshua W. , Ahn Woo-Young 
Published: February 2019

AbstractWhether we are making life-or-death decisions or thinking about the best way to phrase an email, counterfactual emotions including regret and disappointment play an ever-present role in how we make decisions. Functional theories of counterfactual thinking suggest that the experience and future expectation of counterfactual emotions should promote goal-oriented behavioral change. Although many studies find empirical support for such functional theories, the generative cognitive mechanisms through which counterfactual thinking facilitates changes in behavior are underexplored. Here, we develop generative models of risky decision-making that extend regret and disappointment theory to experience-based tasks, which we use to examine how people incorporate counterfactual information into their decisions across time. Further, we use computer-vision to detect positive and negative affect (valence) intensity from participants’ faces in response to feedback, which we use to explore how experienced emotion may correspond to cognitive mechanisms of learning, outcome valuation, or exploration/exploitation—any of which could result in functional changes in behavior. Using hierarchical Bayesian modeling and Bayesian model comparison methods, we found that a model assuming: (1) people learn to explicitly represent and subjectively weight counterfactual outcomes with increasing experience, and (2) people update their counterfactual expectations more rapidly as they experience increasingly intense negative affect best characterized empirical data. Our findings support functional accounts of regret and disappointment and demonstrate the potential for generative modeling and model-based facial expression analysis to enhance our understanding of cognition-emotion interactions.
The intensity of private funding and the results of university? Firm interactions: the case of Brazil
Authors: Rapini Marcia Siqueira , Chiarini Tulio , Bittencourt Pablo , Caliari Thiago 
Published: February 2019

Purpose
The purpose of this paper is to investigate the academic side of university–firm linkages, reporting the results of research (called the “BR Survey”, a primary database) conducted in Brazil with leaders of research groups that interacted with firms. The authors analysed the answers from 662 research groups (from both universities and research institutes) to investigate whether the intensity of private funds affects the results of the interactions. The main intent is to answer the following question: Is there a difference between funding sources and the type of results achieved by research groups when interacting with firms?

Design/methodology/approach
To verify the impact of some variables on the perception of the main results of university–firm interactions, highlighting the impact of funding sources, the authors present a Logit Model defined with binary dependent variables. The null value is categorized as a “scientific result” (new scientific discoveries and research projects; publications, theses and dissertations; human resources’ and students’ education) and the value 1 is classified as an “innovative/technological result” (new products, artefacts and processes; improvement of industrial products and processes; patents, software, design and spin-off firms).

Findings
The authors found that the modes of interaction (relationship types) and some knowledge transfer channels, besides the number of interactions with firms, have statistically significant coefficients, so their values present different impacts on the results of the interaction. The results suggest that the Brazilian innovation policy towards a more active and entrepreneurial role of universities is fostering innovative/technological results from university–firm interactions.

Originality/value
The originality of the study lies on the results found that given the fact that private funding sources do not affect the conventional mission of Brazilian universities – teaching and research – university research groups should be even more incentivized to search for private funds to carry out their research. This may be a solution to the public fund scarcity and may help in reducing the historical distance between universities and firms in Brazil.
Enhancing customer satisfaction using Kaizen: a case study of Imperial Tobacco Company (ITC)
Authors: Mitra Debnath Roma 
Published: February 2019

Purpose
With rising income and changing lifestyle, increased disposable income along with rapid urbanization is boosting the country’s biscuit market. The purpose of this paper is to represent the implementation of Kaizen in a biscuit-manufacturing unit of Imperial Tobacco Company (ITC). Although the concept of Kaizen is not a standard practice in India, the company chosen for the case study has a prominence in the Indian market.

Design/methodology/approach
The methodologies that have been applied to implement Kaizen in the ITC are discussed. Why-Why techniques, fishbone diagram, failure modes and effects analysis, ABC analysis have been used to study cause and effects.

Findings
It was found that the yield was increased from 88.3 to 92.2 percent, which was a significant change, as far as the product line is concerned. The product complaints were reduced to zero with an added increased product quality rating system to 98.2 from the existing rating of 96.7. The product consistency was also improved as an application of Lean in the manufacturing process.

Research limitations/implications
This case study is restricted to the manufacturing sector, especially in the field of biscuit company.

Practical implications
The paper should assist those practitioners and consultants who have the desire to find a better way of Kaizen implementation in small-scale industries of India. The academia can also use this case study for a better understanding of the difference between the theoretical and application aspects of the concept.

Originality/value
This paper is an original contribution in the existing body of literature. It shows the application of Kaizen in the manufacturing sector in India.
Assessing impacts of implementing low-carbon tourism program for sustainable tourism in a world heritage city
Authors: Thongdejsri Machima , Nitivattananon Vilas 
Published: February 2019

Purpose
This study aims to illustrate the impact-assessment procedure of low-carbon tourism (LCT) program implemented in a world heritage city and to develop specific indicators toward sustainability.

Design/methodology/approach
The impact-assessment framework was indicator-based and designed for creating sustainable tourism (ST) in a case study. A set of indicators in various dimensions was developed and applied, referring to the UNWTO guideline. A mixed method of primary and secondary data collected from different sources included document review, site observation, key informant interview, questionnaire survey and focus-group discussions. Assessment of actual/observed impacts was proceeded based on the data collected from tourists and stakeholders, especially on tourist behaviors and resource consumptions.

Findings
The implementation of LCT program in a world heritage city provided impacts in different dimensions and characters. The observed activities were majorly tourism activities in accommodations and recreational places. The indicator initiation is the first development toward sustainability in a case of tourism study in a city destination. Indicators were developed with participation from key stakeholders and covered sustainability and carbon-emission dimensions. Impact-assessment results show a positive theme in less carbon emission, enhanced local income distribution and community capacity. However, the negative impacts include increased amounts of resource consumption and waste generation in visiting sites. The impact matrix works as the map for decision-makers to maximize benefits and manage the cons of the LCT program toward ST principles.

Research limitations/implications
Research methodology, procedure and results on impact assessment with holistic perspectives imply academic contribution and practical benefits for decision-makers regarding ST development. The number of samples and enterprises was limited because of the program implementation period.

Originality/value
The research illustrates the impact-assessment process for an implemented city-based LCT program toward ST, where stakeholder participation was also functioning. A list of indicators was specially designed and can be practically applied for other LCT programs in city destinations. Applying a sustainability impact-assessment framework to the program can provide a clear presentation on how to develop ST.