bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microfluidics for Electrophysiology, Imaging, and Behavioral Analysis ofHydra
Authors: Badhiwala Krishna N. , Gonzales Daniel L. , Vercosa Daniel G. , Avants Benjamin W. , Robinson Jacob T. 
Published: February 2018

ABSTRACTThe cnidarianHydra vulgarisprovides an exciting opportunity to discover the relationship between animal behavior and the activity of every neuron in highly plastic, diffuse network of spiking cells. However,Hydra’sdeformable and contractile body makes it difficult to manipulate the local environment while recording neural activity. Here, we present a suite of microfluidic technologies capable of simultaneous electrical, chemical, and optical interrogation of these soft, deformable organisms. Specifically, we demonstrate devices that can immobilizeHydrafor hours-long simultaneous electrical and optical recording, and chemical stimulation of behaviors revealing neural activity during muscle contraction. We further demonstrate quantitative locomotive and behavioral tracking made possible by confining the animal to quasi-two-dimensional micro-arenas. Together, these proof-of-concept devices show that microfluidics provide a platform for scalable, quantitative cnidarian neurobiology. The experiments enabled by this technology may help reveal how highly plastic networks of neurons provide robust control of animal behavior.
Pcdh18a-positive tip cells instruct notochord formation in zebrafish
Authors: Bosze Bernadett , Mattes Benjamin , Sinner Claude , Stricker Kathrin , Gourain Victor , Thumberger Thomas , Tlili Sham , Weber Sabrina , Wittbrodt Joachim , Saunders Timothy E. , Strähle Uwe , Schug Alexander , Scholpp Steffen 
Published: February 2018

AbstractThe notochord defines the axial structure of all vertebrates during development. Notogenesis is a result of major cell reorganization in the mesoderm, the convergence and the extension of the axial cells. However, it is currently not known how these processes act together in a coordinated way during notochord formation. Analysing the tissue flow, we determined the displacement of the axial mesoderm and identified, relative to the ectoderm, an actively-migrating notochord tip cell population and a group of trailing notochordal plate cells. Molecularly, these tip cells express Protocadherin18a, a member of the cadherin superfamily. We show that Pcdh18a-mediated recycling of E-cadherin adhesion complexes transforms these tip cells into a cohesive and fast migrating cell group. In turn, these tip cells subsequently instruct the trailing mesoderm. We simulated cell migration during early mesoderm formation using a lattice-based mathematical framework, and predicted that the requirement for an anterior, local motile cell cluster could guide the intercalation of the posterior, axial cells. Indeed, grafting experiments validated the predictions and induced ectopic notochord-like rods. Our findings indicate that the tip cells influence the trailing mesodermal cell sheet by inducing the formation of the notochord.
Pregnancy associated plasma protein-aa (Pappaa) regulates photoreceptor synaptic development to mediate visually guided behavior
Authors: Miller Andrew H. , Howe Hollis B. , Krause Bryan M. , Friedle Scott A. , Banks Matthew I. , Perkins Brian D. , Wolman Marc A. 
Published: February 2018

AbstractTo guide behavior, sensory systems detect the onset and offset of stimuli and process these distinct inputs via parallel pathways. In the retina, this strategy is implemented by splitting neural signals for light onset and offset via synapses connecting photoreceptors to ON and OFF bipolar cells, respectively. It remains poorly understood which molecular cues establish the architecture of this synaptic configuration to split light onset and offset signals. A mutant with reduced synapses between photoreceptors and one bipolar cell type, but not the other, could reveal a critical cue. From this approach, we report a novel synaptic role pregnancy associated plasma protein aa (pappaa) in promoting the structure and function of cone synapses that transmit light offset information. Electrophysiological and behavioral analyses indicated pappaa mutant zebrafish have dysfunctional cone to OFF bipolar cell synapses and impaired responses to light offset, but intact cone to ON bipolar cell synapses and light onset responses. Ultrastructural analyses of pappaa mutant cones showed a lack of presynaptic domains at synapses with OFF bipolar cells. pappaa is expressed postsynaptically to the cones during retinal synaptogenesis and encodes a secreted metalloprotease known to stimulate insulin-like growth factor 1 (IGF1) signaling. Induction of dominant negative IGF1 receptor expression during synaptogenesis reduced light offset responses. Conversely, stimulating IGF1 signaling at this time improved pappaa mutants’ light offset responses and cone presynaptic structures. Together, our results indicate Pappaa-regulated IGF1 signaling as a novel pathway that establishes how cone synapses convey light offset signals to guide behavior.Significance StatementDistinct sensory inputs, like stimulus onset and offset, are often split at distinct synapses into parallel circuits for processing. In the retina, photoreceptors and ON and OFF bipolar cells form discrete synapses to split neural signals coding light onset and offset, respectively. The molecular cues that establish this synaptic configuration to specifically convey light onset or offset remain unclear. Our work reveals a novel cue: pregnancy associated plasma protein aa (pappaa), which regulates photoreceptor synaptic structure and function to specifically transmit light offset information. Pappaa is a metalloprotease that stimulates local insulin-like growth factor 1 (IGF1) signaling. IGF1 promotes various aspects of synaptic development and function and is broadly expressed; thus requiring local regulators, like Pappaa, to govern its specificity.
mol2sphere: Spherical Decomposition of Multi-Domain Molecules for Visualization and Coarse Grained Spatial Modeling
Authors: Masison Joseph , Michalski Paul J. , Loew Leslie M. , Schuyler Adam D. 
Published: February 2018

AbstractSummaryProteins, especially those involved in signaling pathways are composed of functional modules consisting of long strings of amino acids. These functional “domains” are linked together in geometric arrangements that can be rigid or flexible, depending on the nature of the linker domains. To understand the structure-function relationships in these macromolecules, it would be helpful to visualize the geometric arrangement of domains. Furthermore, accurate spatial representation of domain structure is necessary for coarse-grain models of the multi-molecular interactions that comprise signaling pathways. Here we introduce a new tool, mol2sphere, that transforms the atomistic structure of a macromolecule into a series of linked spheres corresponding to domains. mol2sphere does this with a k-means clustering algorithm. It may be used for visualization or for coarse grain modeling and simulation.Availability and implementationmol2sphere is available as both a plugin for PyMOL and as a new feature within the SpringSaLaD modeling and simulation software. They run on all desktop platforms and are available with documentation at, respectively, https://nmrbox.org/registry/mol2sphere and http://vcell.org/ssalad. Source code is available for the PyMOL (and python) implementations on the NMRbox platform and for the SpringSaLaD implementation at https://github.com/jmasison/SpringSaLaD.
PopPhy-CNN: A Phylogenetic Tree Embedded Architecture for Convolution Neural Networks for Metagenomic Data
Authors: Reiman Derek , Metwally Ahmed A. , Dai Yang 
Published: February 2018

AbstractMotivationAccurate prediction of the host phenotype from a metgenomic sample and identification of the associated bacterial markers are important in metagenomic studies. We introduce PopPhy-CNN, a novel convolutional neural networks (CNN) learning architecture that effectively exploits phylogentic structure in microbial taxa. PopPhy-CNN provides an input format of 2D matrix created by embedding the phylogenetic tree that is populated with the relative abundance of microbial taxa in a metagenomic sample. This conversion empowers CNNs to explore the spatial relationship of the taxonomic annotations on the tree and their quantitative characteristics in metagenomic data.ResultsPopPhy-CNN is evaluated using three metagenomic datasets of moderate size. We show the superior performance of PopPhy-CNN compared to random forest, support vector machines, LASSO and a baseline 1D-CNN model constructed with relative abundance microbial feature vectors. In addition, we design a novel scheme of feature extraction from the learned CNN models and demonstrate the improved performance when the extracted features are used to train support vector machines.ConclusionPopPhy-CNN is a novel deep learning framework for the prediction of host phenotype from metagenomic samples. PopPhy-CNN can efficiently train models and does not require excessive amount of data. PopPhy-CNN facilities not only retrieval of informative microbial taxa from the trained CNN models but also visualization of the taxa on the phynogenetic tree.Contactyagndai@uic.eduAvailabilitySource code is publicly available athttps://github.com/derekreiman/PopPhy-CNNSupplementary informationSupplementary data are available atBioinformaticsonline.
Synaptic release of acetylcholine rapidly suppresses cortical activity by recruiting muscarinic receptors in layer 4
Authors: Dasgupta Rajan , Seibt Frederik , Beierlein Michael 
Published: February 2018

AbstractBasal forebrain (BF) cholinergic projections to neocortex dynamically regulate information processing. However, the underlying synaptic and cellular mechanisms remain poorly understood. While synaptically released acetylcholine (ACh) can recruit nicotinic ACh receptors (nAChRs) expressed in distinct types of interneurons, previous work has not defined a clear role for muscarinic ACh receptors (mAChRs) in the fast cholinergic control of cortical activity. To address this question, we employed a slice model of cortical activity and used optogenetics to selectively activate cholinergic afferents. We found that transient ACh increases led to a rapid and persistent suppression of cortical activity, mediated by mAChRs in layer 4 and by nAChRs in layer 2/3. Furthermore, mAChR-dependent cholinergic control was mediated at least in part by a short-latency and long-lasting inhibition of layer 4 excitatory neurons. Thus, the activation of postsynaptic mAChRs is central to the flexible cholinergic control of cortical activity.
Why multiple infections favour virulent parasites
Authors: Sofonea Mircea T. , Alizon Samuel , Michalakis Yannis 
Published: February 2018

AbstractIt is now a fact that several strains/species (hereafter types) of parasites circulate in natural host populations. Parasite polymorphism can even occur within the same host, where distinct parasite types can interact in various ways. This can affect their transmission and, therefore, their evolution. We still lack general predictions regarding the evolution, in such multiple infection contexts, of virulence – the infection-induced host mortality, essentially because its emanation from within-host growth was often ignored so far. Here, we explicitly investigate within-host interactions, within-host competition outcomes, epidemiological dynamics and evolutionary invasibility using a formalism as general as possible. Focusing on chronic dimorphic infections caused by horizontally-transmitted microparasites, we apply both dynamical systems and probabilistic approaches to this bottom-up sequence of dynamics to explore the evolutionary outcomes. We show that within-host growth traits are under strong selective pressure and when small mutations affect them, most of the surviving mutants are more virulent than their resident. We thus identify a robust and unavoidable selection bias towards higher virulence.
Controlling load-dependent contractility of the heart at the single molecule level
Authors: Liu Chao , Kawana Masataka , Song Dan , Ruppel Kathleen M. , Spudich James A. 
Published: February 2018

AbstractConcepts in molecular tension sensing in biology are growing and have their origins in studies of muscle contraction. In the heart muscle, a key parameter of contractility is the detachment rate from actin of myosin, which determines the time that myosin is bound to actin in a force-producing state and, importantly, depends on the load (force) against which myosin works. Here, we measure the detachment rate of single molecules of human β-cardiac myosin and its load dependence. We find that both can be modulated by both small molecule compounds and cardiomyopathy-causing mutations. Furthermore, effects of mutations can be reversed by introducing appropriate compounds. Our results suggest that activating vs. inhibitory perturbations of cardiac myosin are discriminated by the aggregate result on duty ratio, average force, and ultimately average power output and that cardiac contractility can be controlled by tuning the load-dependent kinetics of single myosin molecules.
SAC1 Degrades its Lipid Substrate PtdIns4Pin the Endoplasmic Reticulum to Maintain a Steep Chemical Gradient with Donor Membranes
Authors: Zewe James P. , Wills Rachel C. , Sangappa Sahana , Goulden Brady D. , Hammond Gerald R. V. 
Published: February 2018

AbstractGradients of PtdIns4Pbetween organelle membranes and the endoplasmic reticulum (ER) are thought to drive counter-transport of other lipids via non-vesicular traffic. This novel pathway requires the SAC1 phosphatase to degrade PtdIns4Pin a “cis” configuration at the ER to maintain the gradient. However, SAC1 has also been proposed to act in “trans” at membrane contact sites, which could oppose lipid traffic. It is therefore crucial to determine which mode SAC1 uses in living cells. We report that acute inhibition of SAC1 causes accumulation of PtdIns4Pin the ER, that SAC1 does not enrich at membrane contact sites, and that SAC1 has little activity in “trans”, unless a linker is added between its ER-anchored and catalytic domains. The data reveal an obligate “cis” activity of SAC1, supporting its role in non-vesicular lipid traffic and implicating lipid traffic more broadly in inositol lipid homeostasis and function.
The role of community engagement in building sustainable health-care delivery interventions for Kenya
Authors: Davis Elise Catherine , Arana Elizabeth T. , Creel John S. , Ibarra Stephanie C. , Lechuga Jesus , Norman Rachel A. , Parks Hannah R. , Qasim Ali , Watkins David Y. , Kash Bita A. 
Published: February 2018

Purpose
The purpose of this article is to provide a general review of the health-care needs in Kenya which focuses on the role of community engagement in facilitating access and diminishing barriers to quality care services. Health-care concerns throughout Kenya and the culture of Kenyan’s health-care practices care are considered.

Design/methodology/approach
A comprehensive review covered studies of community engagement from 2000 till present. Studies are collected using Google Scholar, PubMed, EBSCOhost and JSTOR and from government and nongovernment agency websites. The approach focuses on why various populations seek health care and how they seek health care, and on some current health-care delivery models.

Findings
Suggestions for community engagement, including defining the community, are proposed. A model for improved health-care delivery introduces community health workers (CHWs), mHealth technologies and the use of mobile clinics to engage the community and improve health and quality of care in low-income settings.

Practical implications
The results emphasize the importance of community engagement in building a sustainable health-care delivery model. This model highlights the importance of defining the community, setting goals for the community and integrating CHWs and mobile clinics to improve health status and decrease long-term health-care costs. The implementation of these strategies contributes to an environment that promotes health and wellness for all.

Originality/value
This paper evaluates health-care quality and access issues in Kenya and provides sustainable solutions that are linked to effective community engagement. In addition, this paper adds to the limited number of studies that explore health-care quality and access alongside community engagement in low-income settings.
Proposed business and franchising models for primary care in Kenya
Authors: Davis Elise Catherine , Evans Ashley , Uptmore Caroline , Lang Sarah , McElroy Jessica K. , Ellenburg David , Nguyen Tony , Kash Bita A. 
Published: February 2018

Purpose
The purpose of this paper is to present proposed solutions and interventions to some of the major barriers to providing adequate access to healthcare in Kenya. Specific business models are proposed to improve access to quality healthcare in low- and middle-income countries. Finally, strategies are developed for the retail clinic concept (RCC).

Design/methodology/approach
Google Scholar, PubMed and EBSCOhost were among the databases used to collect articles relevant to the purpose in Kenya. Various governmental and news articles were collected from Google searches. Relevant business models from other sectors were considered for potential application to healthcare and the retail clinic concept.

Findings
After a review of current methodologies and approaches to business and franchising models in various settings, the most relevant models are proposed as solutions to improving quality healthcare in Kenya through the RCC. For example, authors reviewed physician recruitment strategies, insurance plans and community engagement. The paper is informed by existing literature and reports as well as key informants.

Research limitations/implications
This paper lacks primary data collection within Kenya and is limited to a brief scoping review of literature. The findings provide effective strategies for various business and franchising models in healthcare.

Originality/value
The assembling of relevant information specific to Kenya and potential business models provides effective means of improving health delivery through business and franchising, focusing on innovative approaches and models that have proven effective in other settings.
The antecedents and dimensionality of knowledge-sharing intention
Authors: Han Seung-hyun 
Published: February 2018

Purpose
This paper aims to focus on the relationships between situational/dispositional variables and an individual’s intention to knowledge sharing, and has theoretical implications for researchers in human resource development and management, as well as implications for practicing managers in organizations. First, this study examines whether an integrative model of knowledge sharing reveals an impact of various antecedents on sharing of knowledge between individuals, which has been rarely explored in a single study. In particular, this study is interested in examining whether the two dimensions improve individual sharing of explicit and tacit knowledge, respectively.

Design/methodology/approach
A quantitative survey design approach is used as the research method for data collection. Initially, a pilot study is conducted to examine the psychometric properties of the measures. A 120-item questionnaire is used to measure personality traits, organizational climate and knowledge-sharing intention. The main study is conducted at the Korean IT companies, which have knowledge management system and actively share knowledge between R&D engineers.

Findings
The results of regression analyses indicate that conscientiousness, openness and extroversion of dispositional variables are positively related to an individual’s intention to share knowledge. Of situational variables, organizational support and identity are positively related to knowledge sharing, and reward is negatively associated with knowledge-sharing intention. Theoretical and practical implications for future research are discussed.

Originality/value
Scholars focused with increasing emphasis over the past 20 years on an organization’s ability to facilitate, utilize and share knowledge as critical components of organizational success. Several scholarly attempts tried to explain the antecedents of knowledge sharing. Despite an increasing demand for a coherent and integrated approach to knowledge sharing, empirical efforts remain largely absent with regard to how knowledge transfer and knowledge-sharing practices among individuals are affected by dispositional and situational variables. Also, individual intention to share knowledge was primarily measured as a unidimensional concept. This is a surprising oversight, given that tacit knowledge and explicit knowledge are critical. Indeed, these may be collectivized successfully for the firm’s driver. To address this gap in our understanding of the personal dynamics involved in knowledge-sharing practices, this study seeks to investigate whether dispositional and situational variables lead to changes in individual’s intention to share tacit and explicit knowledge.
Local institutional adaptation for sustainable water management under increasing climatic variability and change
Authors: Nyamwanza Admire Mutsa 
Published: February 2018

Purpose
The study aims to explore institutional adaptation for sustainable water resources management at the local level in the context of increasing climate-related challenges in Zimbabwe using the case of a semi-arid area in the mid-Zambezi Valley, north of the country.

Design/methodology/approach
Inspired by the critical institutionalism approach, the study uses qualitative methods (i.e. key informant interviews, semi-structured interviews, community workshops and documentary review) to understand the role of different formal and informal water-related institutions vis-à-vis responding to climate-related challenges in the case study area, and how the identified institutions can improve their efforts in the context of national water and environmental policy and regulation frameworks. Thematic analysis was used for data analysis.

Findings
The study found that climatic challenges in the case study area, as in most of rural Africa, have raised the stakes in local water management with respect to regulating access to and balancing competing interests in, and demands for, water. It ultimately argues for the embracing of complexity thinking and flexibility in local water management as well as clear coordination of institutions across scales in the face of increasing climate-related challenges.

Originality/value
The study adds to case studies and evidence-based analyses focused on institutional alternatives for climate adaptation vis-à-vis water resources management in water-stressed rural African communities.