bluuebunny/crossref_metadata_2025 huggingface dataset:
Predatory Behavior is Primary Predictor of Movement of Wildland-Urban Cougars
Authors: Buderman Frances E. , Hooten Mevin B. , Alldredge Mat W. , Hanks Ephraim M. , Ivan Jacob S.
Published: February 2018

While many species have suffered from the detrimental impacts of increasing human population growth, some species, such as cougars (Puma concolor), have been observed using human-modified landscapes. However, human-modified habitat can be a source of both increased risk and increased food availability, particularly for large carnivores. Assessing preferential use of the landscape is important for managing wildlife and can be particularly useful in transitional habitats, such as at the wildland-urban interface. Preferential use is often evaluated using resource selection functions (RSFs), but RSFs do not adequately account for the habitat available to an individual at a given time and may mask conflict or avoidance behavior. Contemporary approaches to incorporate landscape availability into the assessment of habitat preference include spatio-temporal point process models, step-selection functions, and continuous-time Markov chain (CTMC) models; in contrast with the other methods, the CTMC model allows for explicit inference on animal movement. We used the CTMC framework to model speed and directionality of movement by a population of cougars inhabiting the Front Range of Colorado, U.S.A., an area exhibiting rapid population growth and increased recreational use, as a function of individual variation and time-varying responses to landscape covariates. The time-varying framework allowed us to detect temporal variability that would be masked in a generalized linear model. We found evidence for individual- and daily temporal-variability in cougar response to landscape characteristics. Distance to nearest kill site emerged as the most important driver of movement at a population-level. We also detected seasonal differences in average response to elevation, heat loading, and distance to roads. Motility was also a function of amount of development, with cougars moving faster in developed areas than in undeveloped areas.
Motor Cortex Encodes A Temporal Difference Reinforcement Learning Process
Authors: Tarigoppula Venkata S Aditya , Choi John S , Hessburg John P , McNiel David B , Marsh Brandi T , Francis Joseph T
Published: February 2018

Temporal difference reinforcement learning (TDRL) accurately models associative learning observed in animals, where they learn to associate outcome predicting environmental states, termed conditioned stimuli (CS), with the value of outcomes, such as rewards, termed unconditioned stimuli (US). A component of TDRL is the value function, which captures the expected cumulative future reward from a given state. The value function can be modified by changes in the animal’s knowledge, such as by the predictability of its environment. Here we show that primary motor cortical (M1) neurodynamics reflect a TD learning process, encoding a state value function and reward prediction error in line with TDRL. M1 responds to the delivery of reward, and shifts its value related response earlier in a trial, becoming predictive of an expected reward, when reward is predictable due to a CS. This is observed in tasks performed manually or observed passively, as well as in tasks without an explicit CS predicting reward, but simply with a predictable temporal structure, that is a predictable environment. M1 also encodes the expected reward value associated with a set of CS in a multiple reward level CS-US task. Here we extend the Microstimulus TDRL model, reported to accurately capture RL related dopaminergic activity, to account for M1 reward related neural activity in a multitude of tasks.

Significance statement

There is a great deal of agreement between aspects of temporal difference reinforcement learning (TDRL) models and neural activity in dopaminergic brain centers. Dopamine is know to be necessary for sensorimotor learning induced synaptic plasticity in the motor cortex (M1), and thus one might expect to see the hallmarks of TDRL in M1, which we show here in the form of a state value function and reward prediction error during. We see these hallmarks even when a conditioned stimulus is not available, but the environment is predictable, during manual tasks with agency, as well as observational tasks without agency. This information has implications towards autonomously updating brain machine interfaces as others and we have proposed and published on.
Big data and single cell transcriptomics: implications for ontological representation
Authors: Aevermann Brian D. , Novotny Mark , Bakken Trygve , Miller Jeremy A. , Diehl Alexander D. , Osumi-Sutherland David , Lasken Roger S. , Lein Ed S. , Scheuermann Richard H.
Published: February 2018

Cells are fundamental functional units of multicellular organisms, with different cell types playing distinct physiological roles in the body. The recent advent of single cell transcriptional profiling using RNA sequencing is producing “big data”, enabling the identification of novel human cell types at an unprecedented rate. In this review, we summarize recent work characterizing cell types in the human central nervous and immune systems using single cell and single nuclei RNA sequencing, and discuss the implications that these discoveries are having on the representation of cell types in the reference Cell Ontology (CL). We propose a method based on random forest machine learning for identifying sets of necessary and sufficient marker genes that can be used to assemble consistent and reproducible cell type definitions for incorporation into the CL. The representation of defined cell type classes and their relationships in the CL using this strategy will make the cell type classes findable, accessible, interoperable, and reusable (FAIR), allowing the CL to serve as a reference knowledgebase of information about the role that distinct cellular phenotypes play in human health and disease.
GEOMetaCuration: A web-based application for accurate manual curation of Gene Expression Omnibus metadata
Authors: Li Zhao , Li Jin , Yu Peng
Published: February 2018

Metadata curation has become increasingly important for biological discovery and biomedical research because a large amount of heterogeneous biological data is currently freely available. To facilitate efficient metadata curation, we developed an easy-to-use web-based curation application, GEOMetaCuration, for curating the metadata of Gene Expression Omnibus datasets. It can eliminate mechanical operations that consume precious curation time and can help coordinate curation efforts among multiple curators. It improves the curation process by introducing various features that are critical to metadata curation, such as a back-end curation management system and a curator-friendly front-end. The application is based on a commonly used web development framework of Python/Django and is open-sourced under the GNU General Public License V3. GEOMetaCuration is expected to benefit the biocuration community and to contribute to computational generation of biological insights using large-scale biological data. An example use case can be found at the demo website: http://geometacuration.yubiolab.org. Source code URL: https://bitbucket.com/yubiolab/GEOMetaCuration
Reproducible model development in the Cardiac Electrophysiology Web Lab
Authors: Daly Aidan C. , Clerx Michael , Beattie Kylie A. , Cooper Jonathan , Gavaghan David J. , Mirams Gary R.
Published: February 2018

The modelling of the electrophysiology of cardiac cells is one of the most mature areas of systems biology. This extended concentration of research effort brings with it new challenges, foremost among which is that of choosing which of these models is most suitable for addressing a particular scientific question. In a previous paper, we presented our initial work in developing an online resource for the characterisation and comparison of electrophysiological cell models in a wide range of experimental scenarios. In that work, we described how we had developed a novel protocol language that allowed us to separate the details of the mathematical model (the majority of cardiac cell models take the form of ordinary differential equations) from the experimental protocol being simulated. We developed a fully-open online repository (which we termed the Cardiac Electrophysiology Web Lab) which allows users to store and compare the results of applying the same experimental protocol to competing models. In the current paper we describe the most recent and planned extensions of this work, focused on supporting the process of model building from experimental data. We outline the necessary work to develop a machine-readable language to describe the process of inferring parameters from wet lab datasets, and illustrate our approach through a detailed example of fitting a model of the hERG channel using experimental data. We conclude by discussing the future challenges in making further progress in this domain towards our goal of facilitating a fully reproducible approach to the development of cardiac cell models.
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

The 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

The 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

To 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 Statement

Distinct 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

Proteins, 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 implementation

mol2sphere 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

Motivation

Accurate 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.

Results

PopPhy-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.

Conclusion

PopPhy-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.

Contact

yagndai@uic.edu

Availability

Source code is publicly available athttps://github.com/derekreiman/PopPhy-CNN

Supplementary information

Supplementary 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

Basal 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

It 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

Concepts 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.
Biased competition in the absence of input bias: predictions from corticostriatal computation
Authors: Ardid Salva , Sherfey Jason S. , McCarthy Michelle M. , Hass Joachim , Pittman-Polletta Benjamin R. , Kopell Nancy
Published: February 2018

Classical accounts of biased competition (BC) require an input bias to resolve the competition between neuronal ensembles driving downstream processing. However, flexible and reliable selection of behaviorally-relevant ensembles can occur with unbiased stimulation: striatal D1 and D2 spiny projecting neurons (SPNs) receive balanced cortical input, yet their activity determines the choice between GO and NO-GO pathways in the basal ganglia. We present a corticostriatal model identifying three mechanisms that rely on physiological asymmetries to effect rate- and time-coded BC in the presence of balanced inputs. First, tonic input strength determines which SPN phenotype exhibit higher mean firing rate (FR). Second, low strength oscillatory inputs induce higher FR in D2 SPNs but higher coherence between D1 SPNs. Third, high strength inputs oscillating at distinct frequencies preferentially activate D1 or D2 SPN populations. Of these mechanisms, the latter accommodates observed rhythmic activity supporting rule-based decision making in prefrontal cortex.
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

Gradients 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.
A de novo Ser111Thr variant in aquaporin-4 in a patient with intellectual disability, transient signs of brain ischemia, transient cardiac hypertrophy, and progressive gait disturbance
Authors: Berland Siren , Toft-Bertelsen Trine L. , Aukrust Ingvild , Byska Jan , Vaudel Marc , Bindoff Laurence A. , MacAulay Nanna , Houge Gunnar
Published: February 2018

Aquaporin-4, encoded by AQP4, is the major water channel in the central nervous system and plays an important role in the brain's water balance, including edema formation and clearance. Using genomic copy-number analysis and trio-exome sequencing, we investigated a male patient with intellectual disability, hearing loss, and progressive gait dysfunction and found a de novo missense change Ser111Thr in AQP4 as the only suspicious finding. Perinatally, signs of brain ischemia were detected in relation to acute collapse 2 h after birth that resolved a few days later. At the age of 3 mo, cardiac hypertrophy was detected that persisted through childhood but was completely resolved by age 16. In theory, this neurodevelopmental disorder with transient cardiomyopathy could be caused by a disturbance of cellular water balance. Ser111 is an extremely conserved residue in the short cytoplasmic loop between AQP4 transmembrane helix 2 and 3, present across all AQP isoforms from plants to mammals, and it does not appear to be a phosphorylation site. We found that the Ser111Thr change does not affect water permeability or protein stability, suggesting another and possibly regulatory role. Although causality remains unproven, this case study draws attention to AQP4 as a candidate gene for a unique developmental disorder and to a specific serine as a residue of possibly great functional importance in many AQPs.
Rapid whole-genome sequencing identifies a novel AIRE variant associated with autoimmune polyendocrine syndrome type 1
Authors: Sanford Erica , Watkins Kelly , Nahas Shareef , Gottschalk Michael , Coufal Nicole G. , Farnaes Lauge , Dimmock David , Kingsmore Stephen F. ,   on behalf of the RCIGM Investigators
Published: February 2018

Autoimmune polyendocrine syndrome type 1 (APS-1; OMIM #240300), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare monogenic autoimmune disorder caused by mutations in the autoimmune regulator (AIRE) gene. APS-1 is classically characterized by a triad of chronic mucocutaneous candidiasis, autoimmune hypoparathyroidism, and autoimmune adrenocortical insufficiency. We report a 5-yr-old female who presented with symptoms of tetany due to hypocalcemia and was subsequently found to be secondary to hypoparathyroidism. Rapid trio whole-genome sequencing revealed compound heterozygous variants in AIRE in the proband, with a paternally inherited, pathogenic, frameshift variant (c.1265delC; p.Pro422LeufsTer58) and a novel, likely pathogenic, maternally inherited missense variant (c.268T>C; p.Tyr90His).
Microinjection ofXenopusOocytes
Authors: Aguero Tristan , Newman Karen , King Mary Lou
Published: February 2018

Microinjection ofXenopusoocytes has proven to be a valuable tool in a broad array of studies that require expression of DNA or RNA into functional protein. These studies are diverse and range from expression cloning to receptor–ligand interaction to nuclear programming. Oocytes offer a number of advantages for such studies, including their large size (∼1.2 mm in diameter), capacity for translation, and enormous nucleus (0.3–0.4 mm). They are cost effective, easily manipulated, and can be injected in large numbers in a short time period. Oocytes have a large maternal stockpile of all the essential components for transcription and translation. Consequently, the investigator needs only to introduce by microinjection the specific DNA or RNA of interest for synthesis. Oocytes translate virtually any exogenous RNA regardless of source, and the translated proteins are folded, modified, and transported to the correct cellular locations. Here we present procedures for the efficient microinjection of oocytes and their subsequent care.
Crystal structure of silver [(propane-1,3-diyldinitrilo-κ2N,N′)tetraacetato-κ4O,O′,O′′,O′′′]chromate(III) from synchrotron X-ray data
Authors: Moon Dohyun , Ryoo Keon Sang , Choi Jong-Ha
Published: February 2018

The asymmetric unit of the title compound, Ag[Cr(C11H14N2O8)]·3H2O, contains one [Cr(1,3-pdta)]−anion [1,3-pdta is (propane-1,3-diyldinitrilo)tetraacetate], one Ag+cation and three water molecules. The Cr3+ion is coordinated to the four O and two N atoms of the 1,3-pdta ligand, displaying a distorted octahedral geometry. The mean Cr—N and Cr—O bond lengths are 2.0727 (17) and 1.9608 (15) Å, respectively. The conformations of the chelate rings were found to be envelope for the glycinates and twist-boat for the six-membered diamine (T) ring. The Ag+cation is surrounded by six O atoms from three non-coordinated carbonyl O atoms of neighbouring 1,3-pdta groups and three water molecules. The crystal structure is stabilized by intermolecular hydrogen bonding involving the water O—H group as donor and the carboxyl O atom as acceptor.
Macromolecular refinement by model morphing using non-atomic parameterizations
Authors: Cowtan Kevin , Agirre Jon
Published: February 2018

Refinement is a critical step in the determination of a model which explains the crystallographic observations and thus best accounts for the missing phase components. The scattering density is usually described in terms of atomic parameters; however, in macromolecular crystallography the resolution of the data is generally insufficient to determine the values of these parameters for individual atoms. Stereochemical and geometric restraints are used to provide additional information, but produce interrelationships between parameters which slow convergence, resulting in longer refinement times. An alternative approach is proposed in which parameters are not attached to atoms, but to regions of the electron-density map. These parameters can move the density or change the local temperature factor to better explain the structure factors. Varying the size of the region which determines the parameters at a particular position in the map allows the method to be applied at different resolutions without the use of restraints. Potential applications include initial refinement of molecular-replacement models with domain motions, and potentially the use of electron density from other sources such as electron cryo-microscopy (cryo-EM) as the refinement model.
An introduction to experimental phasing of macromolecules illustrated bySHELX; new autotracing features
Authors: Usón Isabel , Sheldrick George M.
Published: February 2018

For the purpose of this article, experimental phasing is understood to mean the determination of macromolecular structures by exploiting small intensity differences of Friedel opposites and possibly of reflections measured at different wavelengths or for heavy-atom derivatives, without the use of specific structural models. TheSHELXprograms provide a robust and efficient route for routine structure solution by the SAD, MAD and related methods, but involve a number of simplifying assumptions that may limit their applicability in borderline cases. The substructure atoms (i.e.those with significant anomalous scattering) are first located by direct methods, and the experimental data are then used to estimate phase shifts that are added to the substructure phases to obtain starting phases for the native reflections. These are then improved by density modification and, if the resolution of the data and the type of structure permit, polyalanine tracing. A number of extensions to the tracing algorithm are discussed; these are designed to improve its performance at low resolution. Given native data to 2.5 Å resolution or better, a correlation coefficient greater than 25% between the structure factors calculated from such a trace and the native data is usually a good indication that the structure has been solved.
CCP4i2: the new graphical user interface to theCCP4 program suite
Authors: Potterton Liz , Agirre Jon , Ballard Charles , Cowtan Kevin , Dodson Eleanor , Evans Phil R. , Jenkins Huw T. , Keegan Ronan , Krissinel Eugene , Stevenson Kyle , Lebedev Andrey , McNicholas Stuart J. , Nicholls Robert A. , Noble Martin , Pannu Navraj S. , Roth Christian , Sheldrick George , Skubak Pavol , Turkenburg Johan , Uski Ville , von Delft Frank , Waterman David , Wilson Keith , Winn Martyn , Wojdyr Marcin
Published: February 2018

TheCCP4 (Collaborative Computational Project, Number 4) software suite for macromolecular structure determination by X-ray crystallography groups brings together many programs and libraries that, by means of well established conventions, interoperate effectively without adhering to strict design guidelines. Because of this inherent flexibility, users are often presented with diverse, even divergent, choices for solving every type of problem. Recently, CCP4 introducedCCP4i2, a modern graphical interface designed to help structural biologists to navigate the process of structure determination, with an emphasis on pipelining and the streamlined presentation of results. In addition,CCP4i2 provides a framework for writing structure-solution scripts that can be built up incrementally to create increasingly automatic procedures.
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.
A longitudinal study of heavy time investment in work
Authors: Snir Raphael
Published: February 2018

Purpose

The purpose of this paper is to examine heavy time investment in work from both dispositional and situational perspectives.

Design/methodology/approach

Data were collected twice, at the beginning and at the end of a 12-year period, from the same respondents of the Meaning of Work project in Israel.

Findings

The classification of respondents as heavy work investors (work more than 50 weekly hours) or as ordinary workers is stable over the years, which indirectly supports the dispositional perspective. The situational perspective is generally not supported. Remaining at the same workplace or changing workplaces and a stable or changing classification of a person as a heavy work investor or as an ordinary worker over the years are dependent on each other. However, no relation was found between change in financial needs and a person’s level of time investment in work. Only two out of 14 relevant life events relate positively and significantly to the level of time investment in work over the years: appointment to manage other workers and receiving greater work autonomy.

Practical implications

The effectiveness of policies designed to encourage working long hours on the one hand, or a work-life balance on the other, is questionable. However, a specific intervention which, based on the findings of this study, may encourage time investment in work is expanding the job vertically.

Originality/value

This is an exceptional longitudinal study examining stability (over time) and situational predictors of work hours among the same individuals.
What factors explain the price of top quality wines?
Authors: Ferro Gustavo , Benito Amaro Ignacio
Published: February 2018

Purpose

Given the growing supply of wines and the large number of new consumers with purchasing power but lacking knowledge of the subtleties of high-quality wines, expert opinions are used for consumers as proxies for quality. This study aims to determine the determinants of prices in top-quality wine market. The authors also seek to estimate the role for country of origin, grape, producing region and winery in prices. And, finally, the authors try to show how countries, regions and wineries can help increase their position in international rankings.

Design/methodology/approach

The authors try to answer: What factors explain the price of top-quality wines (defined as best rated in a standardized ranking)? To some extent, in the hands of producers influence prices, which imply long-term decisions or large investments in land and marketing. Other variables that consumer value does affect prices. The authors try also to detect undervalued or overvalued wines, grapes, regions, wineries or producer countries. The authors estimate an econometric model of hedonic prices using a 14-year sample of the Wine Spectator’s 100 top-rated wines for the American market between 2003 and 2016, totaling 1,400 observations. The sample is a great cross-section because each wine is unique.

Findings

The authors’ contribution is twofold: the determination of the price explanatory values and the identification and attribution of price differences by country, grape, region and winery. Also, the authors detected grapes, countries, regions and wineries which are overvalued or undervalued with respect to the average prediction of the model.

Research limitations/implications

The findings are useful to understand the role of price explanatory variables, as well as for making policy and managerial decisions. From the model, collective or managerial actions can be derived to increase particular wines’ positions in international rankings. The proxy for “quality” in the study is not the only possible definition.

Practical implications

In some cases, managerial choices could be conditioned by the policies or history. There is some room for collective action and public policies to improve regions’ and countries’ reputation.

Social implications

There are clear synergies for policies that can raise the prestige of countries and regions and their spillovers on the brand name reputation of individual wineries.

Originality/value

The results, policy and managerial implications are of interest for business, countries interested in improving their position in international rankings and for consumers to make more informed decisions.