bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicogenomic identification of repositioned therapy for a monogenic disease
Authors: Kort Eric J. , Sayed Nazish , Liu Chun , Wu Sean M. , Wu Joseph C. , Jovinge Stefan
Published: September 2019

The cost of drug development from initial concept to FDA approval has been estimated to be about 2.6 billion USD.1 This cost precludes development of targeted therapies for rare diseases such as monogenetic cardiomyopathies. As part of the Library of Integrated Network-based Cellular Signatures (LINCS) program funded by the NIH, the Broad Institute of MIT has publicly released transcriptional profiles quantifying the effects of more than 25,000 perturbagens on the expression of 978 genes in up to 77 cell lines.2 Transcriptomics has been shown to be a powerful tool in repurposing drugs3,4 and this dataset affords us the unique opportunity to systematically identify small molecule mimics or inhibitors of specific genes, thereby identifying novel treatments for genetic disorders. In this report, we take this approach to identify a novel drug therapy for a monogenic form of familial dilated cardiomyopathy with the transcriptional profile of FDA approved drugs. This approach could potentially be replicated for a wide range of monogenic diseases.
Food supplementation affects gut microbiota and immunological resistance to parasites in a wild bird species
Authors: Knutie Sarah A.
Published: September 2019

Supplemental feeding can increase the overall health of animals but also can have varying consequences for animals dealing with parasites. Furthermore, the mechanism mediating the effect of food supplementation on host-parasite interactions remains poorly understood.

The goal of the study was to determine the effect of food supplementation on host defenses against parasitic nest flies and whether host gut microbiota, which can affect immunity, potentially mediates these relationships. In a fully crossed design, I experimentally manipulated the abundance of parasitic nest flies (Protocalliphora sialia) and food availability then characterized the gut microbiota, immune responses, and nest parasite abundance of nestling eastern bluebirds (Sialia sialis).

Food supplemented birds had 75% fewer parasites than unsupplemented birds. Parasite abundance decreased throughout the breeding season for unsupplemented birds, but abundance did not change throughout the season for supplemented birds. Food supplementation increased overall fledging success. Parasitism had a sublethal effects on blood loss, but food supplementation mitigated these effects by increasing parasite resistance via the nestling IgY antibody response.

Food supplementation increased the gut bacterial diversity in nestlings, which was negatively related to parasite abundance. Food supplementation also increased the relative abundance ofClostridiumspp. in nestlings, which was positively related to their antibody response and negatively related to parasite abundance.

Synthesis and applications. Overall, these results suggest that food supplementation, especially early in the breeding season, increases resistance to parasitism during the early life stage of the host, which could be mediated by the effect of supplementation on the gut microbiota. Wildlife food supplementation is a common pastime for humans worldwide and therefore it is important to determine the consequences of this activity on animal health. Furthermore, supplemental feeding could induce resistance to detrimental parasites (e.g. invasive parasites) in hosts when management of the parasite is not immediately possible.
High-resolution Expression Profiling of Selected Gene Sets during Plant Immune Activation
Authors: Ding Pingtao , Ngou Bruno Pok Man , Furzer Oliver J. , Sakai Toshiyuki , Shrestha Ram Krishna , MacLean Dan , Jones Jonathan D. G.
Published: September 2019

Sequence capture followed by next-generation sequencing has broad applications in cost-effective exploration of biological processes at high resolution [1, 2]. Genome-wide RNA sequencing (RNA-seq) over a time course can reveal the dynamics of differential gene expression. However, in many cases, only a limited set of genes are of interest, and are repeatedly used as markers for certain biological processes. Sequence capture can help generate high-resolution quantitative datasets to assess changes in abundance of selected genes. We previously used sequence capture to accelerate Resistance gene cloning [1, 3, 4], investigate immune receptor gene diversity [5] and investigate pathogen diversity and evolution [6, 7].

The plant immune system involves detection of pathogens via both cell-surface and intracellular receptors. Both receptor classes can induce transcriptional reprogramming that elevates disease resistance [8]. To assess differential gene expression during plant immunity, we developed and deployed quantitative sequence capture (CAP-I). We designed and synthesized biotinylated single-strand RNA bait libraries targeted to a subset of defense genes, and generated sequence capture data from 99 RNA-seq libraries. We built a data processing pipeline to quantify the RNA-CAP-I-seq data, and visualize differential gene expression. Sequence capture in combination with quantitative RNA-seq enabled cost-effective assessment of the expression profile of a specified subset of genes. Quantitative sequence capture is not limited to RNA-seq or any specific organism and can potentially be incorporated into automated platforms for high-throughput sequencing.
scClassify: hierarchical classification of cells
Authors: Lin Yingxin , Cao Yue , Kim Hani J , Salim Agus , Speed Terence P. , Lin Dave , Yang Pengyi , Yang Jean Yee Hwa
Published: September 2019

Cell type identification is a key computational challenge in single-cell RNA-sequencing (scRNA-seq) data. To capitalize on the large collections of well-annotated scRNA-seq datasets, we present scClassify, a hierarchical classification framework based on ensemble learning. scClassify can identify cells from published scRNA-seq datasets more accurately and more finely than in the original publications. We also estimate the cell number needed for accurate classification anywhere in a cell type hierarchy.
Natural Epiallelic Variation is Associated with Quantitative Resistance to the PathogenPlasmodiophora Brassicae
Authors: Liégard Benjamin , Gravot Antoine , Quadrana Leandro , Aigu Yoann , Bénéjam Juliette , Lariagon Christine , Lemoine Jocelyne , Colot Vincent , Manzanares-Dauleux Maria J. , Jubault Mélanie
Published: September 2019

Clubroot caused by the protistPlasmodiophora brassicaeis a major disease affecting cultivatedBrassicaceae. Here, we uncover the existence of a natural epigenetic variation that is associated with partial resistance to clubroot inArabidopsis,by using QTL fine mapping followed by extensive DNA sequence and methylation analyses. We show that at QTLPb-At5.2, DNA methylation variation is extensive across accessions and strictly correlates with expression variation of the two neighboring genes At5g47260 and At5g47280, which encode NLR-immune receptors. Moreover, these natural variants are stably inherited and are not consistently associated with any nucleotide variation. These findings suggest a direct role for epigenetic variation in quantitative resistance of plants to pathogen attacks.
Monotherapy efficacy of BBB-permeable small molecule activators of PP2A in glioblastoma
Authors: Merisaari Joni , Denisova Oxana V. , Doroszko Milena , Le Joncour Vadim , Johansson Patrik , Leenders William P.J. , Kastrinsky David B. , Zaware Nilesh , Narla Goutham , Laakkonen Pirjo , Nelander Sven , Ohlmeyer Michael , Westermarck Jukka
Published: September 2019

Glioblastoma (GB) is a fatal disease in which most targeted therapies have clinically failed. However, pharmacological reactivation of tumor suppressors has not been thoroughly studied as yet as a GB therapeutic strategy. Tumor suppressor Protein Phosphatase 2A (PP2A), is inhibited by non-genetic mechanisms in GB, and thus it would be potentially amendable for therapeutic reactivation. Here we demonstrate, that small molecule activators of PP2A (SMAPs), NZ-8-061 and DBK-1154, effectively cross the in vitro model of blood-brain barrier (BBB), and in vivo partition to mouse brain tissue after oral dosing. In vitro, SMAPs exhibit robust cell killing activity against five established GB cell lines, and nine patient-derived primary glioma cell lines. Collectively these cell lines have heterogenous genetic background, kinase inhibitor resistance profile, and stemness properties; and they represent different clinical GB subtypes. Oral dosing of either of the SMAPs significantly reduced growth of infiltrative intracranial GB tumors. DBK-1154, with both higher degree of brain/blood distribution, and more potent in vitro activity against all tested GB cell lines, also significantly increased survival of mice bearing orthotopic GB xenografts. In summary, this report presents a proof-of-principle data for BBB-permeable tumor suppressor reactivation therapy for glioblastoma cells of heterogenous molecular background.
FOCAL3D: A 3-dimensional clustering package for single-molecule localization microscopy
Authors: Nino D. , Djayakarsana D. , Milstein J. N.
Published: September 2019

Single-molecule localization microscopy (SMLM) yields an image resolution 1-2 orders of magnitude below that of conventional light microscopy, resolving fine details on intracellular structure and macromolecular organization. The massive pointillistic data sets generated by SMLM require the development of new and highly efficient quantification tools. Density based clustering algorithms, such as DBSCAN, can provide spatial statistics on protein/nucleic acid aggregation or dispersion while explicitly identifying macromolecular clusters. The performance of DBSCAN, however, is typically dependent upon an arbitrary, or at least highly subjective, parametric tuning of the algorithm. Moreover, DBSCAN can be computationally expensive, which makes it arduous to evaluate on large image stacks. This is all the more important in 3-dimensions where there exist limited alternatives for quantifying clustering in SMLM data, and where a 2-dimensional analysis of true 3-dimensional data may give rise to image artefacts. We have developed an open-source software package in Python for both identifying and quantifying spatial clustering in 3-dimensional SMLM datasets. FOCAL3D is an extension of our previously developed, 2-dimensional, grid based clustering algorithm FOCAL. FOCAL3D provides a highly efficient way to spatially cluster SMLM datasets, scaling linearly with the number of localizations, and the algorithmic parameters may be systematically optimized so that the resulting analysis is insensitive to variation over a range of parameter choices. We initially validate the performance and parametric insensitivity of FOCAL3D on simulated datasets, then apply the algorithm to 3-dimensional, astigmatic dSTORM images of the nuclear pore complex in human osteosarcoma cells.

The data and software package are available at: http://www.utm.utoronto.ca/milsteinlab/software/
Coordinated multiplexing of information about separate objects in visual cortex
Authors: Jun Na Young , Ruff Douglas A. , Kramer Lily E. , Bowes Brittany , Tokdar Surya T , Cohen Marlene R , Groh Jennifer M
Published: September 2019

Sensory receptive fields are large enough that they can contain more than one perceptible stimulus. How, then, can the brain encode information abouteachof the stimuli that may be present at a given moment? We recently showed that when more than one stimulus is present, single neurons can fluctuate between coding one vs. the other(s) across some time period, suggesting a form of neural multiplexing of different stimuli (Caruso et al., 2018). Here we investigate (a) whether such coding fluctuations occur in early visual cortical areas; (b) how coding fluctuations are coordinated across the neural population; and (c) how coordinated coding fluctuations depend on the parsing of stimuli into separate vs. fused objects. We found coding fluctuations do occur in macaque V1 but only when the two stimuli form separate objects. Such separate objects evoked a novel pattern of V1 spike count (“noise”) correlations involving distinct distributions of positive and negative values. This bimodal correlation pattern was most pronounced among pairs of neurons showing the strongest evidence for coding fluctuations or multiplexing. Whether a given pair of neurons exhibited positive or negative correlations depended on whether the two neurons both responded better to the same object or had different object preferences. Distinct distributions of spike count correlations based on stimulus preferences were also seen in V4 for separate objects but not when two stimuli fused to form one object. These findings suggest multiple objects evoke different response dynamics than those evoked by single stimuli, lending support to the multiplexing hypothesis and suggesting a means by which information about multiple objects can be preserved despite the apparent coarseness of sensory coding.

Significance Statement

How the brain separates information about multiple objects despite overlap in the neurons responsive to each item is not well understood. Here we show that some neurons in V1 exhibit coding fluctuations in response to two objects, and that these coding fluctuations are coordinated at the population level in ways that are not observed for single objects. Broadly similar results were obtained in V4. These response dynamics lend support to the hypothesis that information about individual objects may be multiplexed across the neural population, preserving information about each item despite the coarseness of sensory coding.
A spatial genomic approach identifies time lags and historic barriers to gene flow in a rapidly fragmenting Appalachian landscape
Authors: Maigret Thomas A. , Cox John J. , Weisrock David W.
Published: September 2019

The resolution offered by genomic data sets coupled with recently developed spatially informed analyses are allowing researchers to quantify population structure at increasingly fine temporal and spatial scales. However, uncertainties regarding data set size and quality thresholds and the time scale at which barriers to gene flow become detectable have limited both empirical research and conservation measures. Here, we used restriction site associated DNA sequencing to generate a large SNP data set for the copperhead snake (Agkistrodon contortrix) and address the population genomic impacts of recent and widespread landscape modification across an approximately 1000 km2 region of eastern Kentucky. Nonspatial population-based assignment and clustering methods supported little to no population structure. However, using individual-based spatial autocorrelation approaches we found evidence for genetic structuring which closely follows the path of a historic highway which experienced high traffic volumes from ca. 1920 to 1970. We found no similar spatial genomic signatures associated with more recently constructed highways or surface mining activity, though a time lag effect may be responsible for the lack of any emergent spatial genetic patterns. Subsampling of our SNP data set suggested that similar results could be obtained with as few as 250 SNPs, and thresholds for missing data exhibited limited impacts on the spatial patterns we detected outside of very strict or permissive extremes. Our findings highlight the importance of temporal factors in landscape genetics approaches, and suggest the potential advantages of large genomic data sets and fine-scale, spatially-informed approaches for quantifying subtle genetic patterns in temporally complex landscapes.
The Panama Canal after a century of human impacts
Authors: Salgado Jorge , Vélez María I. , González-Arango Catalina , Rose Neil L. , Yang Handong , Huguet Carme , Camacho Juan , O’Dea Aaron
Published: September 2019

Large tropical river dam projects are set to accelerate over the forthcoming decades to satisfy growing demand for energy, irrigation and flood control. When tropical rivers are dammed, the immediate impacts are well studied, but the long-term (decades-centuries) consequences of impoundment remain poorly known. Here, we gather historical and paleoecological data from Gatun Lake, formed by the building of the Gatun Dam (Panama Canal, Panamá) over 100 years ago, to reconstruct the limnological evolution of the system in response to individual and linked stressors (river damming, forest flooding, deforestation, invasive species, pollution and hydro-climate). We found that after a century of dam construction parallels associated with the natural hydrological functioning of river floodplains persist. Hence, hydrology remains the most important temporal structural factor positively stimulating primary productivity, deposition of new minerals, and reduction of water transparency during wet periods. During dry periods, clear water and aerobic conditions prevail and nutrients transform into available forms in the detrital-rich reductive sediments. We highlight the importance of climate change as an ultimate rather than proximate anthropogenic factor for sustainable management options of tropical dams.
Studying Spatial Memory in Augmented and Virtual reality
Authors: Maidenbaum Shachar , Patel Ansh , Garlin Isaiah , Jacobs Josh
Published: September 2019

Spatial memory is a crucial part of our lives. Spatial memory research and rehabilitation in humans is typically performed either in real environments, which is challenging practically, or in Virtual Reality (VR), which has limited realism. Here we explored the use of Augmented Reality (AR) for studying spatial cognition. AR combines the best features of real and VR paradigms by allowing subjects to learn spatial information in a flexible fashion while walking through a real-world environment. To compare these methods, we had subjects perform the same spatial memory task in VR and AR settings. Although subjects showed good performance in both, subjects reported that the AR task version was significantly easier, more immersive, and more fun than VR. Importantly, memory performance was significantly better in AR compared to VR. Our findings validate that integrating AR can lead to improved techniques for spatial memory research and suggest their potential for rehabilitation.

Highlights

We built matching spatial memory tasks in VR and AR

Subjectively, subjects find the AR easier, more immersive and more fun

Objectively, subjects are significantly more accurate in AR compared to VR

Pointing based tasks did not fully show the same advantages

Only AR walking significantly correlated with SBSoD, suggesting mobile AR better captures more natural spatial performance
Δ9-Tetrahydrocannabinol (THC) impairs visual working memory performance: A randomized crossover trial
Authors: Adam Kirsten C. S. , Doss Manoj K. , Pabon Elisa , Vogel Edward K. , de Wit Harriet
Published: September 2019

With the increasing prevalence of legal cannabis use and availability, there is an urgent need to identify cognitive impairments related to its use. It is widely believed that cannabis, or its main psychoactive component Δ9-tetrahydrocannabinol (THC), impairs working memory, i.e., the ability to temporarily hold information in mind. However, our review of the literature yielded surprisingly little empirical support for an effect of THC or cannabis on working memory. We thus conducted a study with 3 main goals: (1) quantify the effect of THC on visual working memory in a well-powered sample (2) test the potential role of cognitive effects (mind wandering and metacognition) in disrupting working memory, and (3) demonstrate how insufficient sample size and task duration reduce the likelihood of detecting a drug effect. We conducted two double-blind, randomized crossover experiments in which healthy adults (N=23, 23) performed a reliable and validated visual working memory task (the “Discrete Whole-Report task”, 90 trials) after administration of THC (7.5 and/or 15 mg oral) or placebo. We also assessed self-reported ‘mind wandering’ (Exp 1) and metacognitive accuracy about ongoing task performance (Exp 2). THC impaired working memory performance (d = .65), increased mind wandering (Exp 1), and decreased metacognitive accuracy about task performance (Exp 2). Thus, our findings indicate that THC does impair visual working memory, and that this impairment may be related to both increased mind-wandering and decreased monitoring of task performance. Finally, we used a down-sampling procedure to illustrate the effects of task length and sample size on power to detect the acute effect of THC on working memory.
Cell type-specific enhancer-promoter connectivity maps in the human brain and disease risk association
Authors: Nott Alexi , Holtman Inge R. , Coufal Nicole G. , Schlachetzki Johannes C.M. , Yu Miao , Hu Rong , Han Claudia Z. , Pena Monique , Xiao Jiayang , Wu Yin , Keuelen Zahara , Pasillas Martina P. , O’Connor Carolyn , Schafer Simon T. , Shen Zeyang , Rissman Robert A. , Brewer James B. , Gosselin David , Gonda David D. , Levy Michael L. , Rosenfeld Michael G. , McVicker Graham , Gage Fred H. , Ren Bing , Glass Christopher K.
Published: September 2019

Unique cell type-specific patterns of activated enhancers can be leveraged to interpret non-coding genetic variation associated with complex traits and diseases such as neurological and psychiatric disorders. Here, we have defined active promoters and enhancers for major cell types of the human brain. Whereas psychiatric disorders were primarily associated with regulatory regions in neurons, idiopathic Alzheimer’s disease (AD) variants were largely confined to microglia enhancers. Interactome maps connecting GWAS variants in cell type-specific enhancers to gene promoters revealed an extended microglia gene network in AD. Deletion of a microglia-specific enhancer harboring AD-risk variants ablated BIN1 expression in microglia but not in neurons or astrocytes. These findings revise and expand the genes likely to be influenced by non-coding variants in AD and suggest the probable brain cell types in which they function.

One Sentence Summary

Identification of cell type-specific regulatory elements in the human brain enables interpretation of non-coding GWAS risk variants.
Neurobehavioural characterisation and stratification of reinforcement-related behaviour
Authors: Jia Tianye , Ing Alex , Quinlan Erin Burke , Tay Nicole , Luo Qiang , Francesca Biondo , Banaschewski Tobias , Barker Gareth J. , Bokde Arun L.W. , Bromberg Uli , Büchel Christian , Desrivières Sylvane , Feng Jianfeng , Flor Herta , Grigis Antoine , Garavan Hugh , Gowland Penny , Heinz Andreas , Ittermann Bernd , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Nees Frauke , Orfanos Dimitri Papadopoulos , Paus Tomáš , Poustka Luise , Fröhner Juliane H. , Smolka Michael N. , Walter Henrik , Whelan Robert , Schumann Gunter ,   IMAGEN Consortium
Published: September 2019

Reinforcement-related cognitive processes, such as reward processing, impulsiveness and emotional processing are critical components of externalising and internalising behaviours. It is unclear to what extent each of these processes contributes to individual behavioural symptoms, how their neural substrates give rise to distinct behavioural outcomes, and if neural profiles across different reinforcement-related processes might differentiate individual behaviours. We created a statistical framework that enabled us to directly compare functional brain activation during reward anticipation, motor inhibition and viewing of emotional faces in the European IMAGEN cohort of 2000 14-year-old adolescents. We observe significant correlations and modulation of reward anticipation and motor inhibition networks in hyperactivity, impulsivity, inattention and conduct symptoms, and describe neural signatures across neuroimaging tasks that differentiate these behaviours. We thus characterise shared and distinct functional brain activation patterns that underlie different externalising symptoms and identify neural stratification markers, while accounting for clinically observed co-morbidity.
Characterizing neural coding performance for populations of sensory neurons: comparing a weighted spike distance metrics to other analytical methods
Authors: Marsat G. , Daly K.C. , Drew J.A.
Published: September 2019

The identity of sensory stimuli is encoded in the spatio-temporal patterns of responses of the encoding neural population. For stimuli to be discriminated reliably, differences in population responses must be accurately decoded by downstream networks. Several methods to compare patterns of responses have been used by neurophysiologists to characterize the accuracy of the sensory responses studied. Among the most widely used analysis, we note methods based on Euclidean distances or on spike metric distances. Methods based on artificial neural networks and machine learning that recognize and/or classify specific input patterns have also gained popularity. Here, we first compare these three strategies using datasets from three different model systems: the moth olfactory system, the electrosensory system of gymnotids, and leaky-integrate- and-fire (LIF) model responses. We show that the input-weighting procedure inherent to artificial neural networks allows the efficient extraction of information relevant to stimulus discrimination. To combine the convenience of methods such as spike metric distances but leverage the advantages of weighting the inputs, we propose a measure based on geometric distances where each dimension is weighted proportionally to how informative it is. We show that the result of this Weighted Euclidian Distance (WED) analysis performs as well or better than the artificial neural network we tested and outperforms the more traditional spike distance metrics. We applied information theoretic analysis to LIF responses and compare their encoding accuracy with the discrimination accuracy quantified through this WED analysis. We show a high degree of correlation between discrimination accuracy and information content and that our weighting procedure allowed the efficient use of information present to perform the discrimination task. We argue that our proposed measure provides the flexibility and ease of use sought by neurophysiologists while providing a more powerful way to extract relevant information than more traditional methods.
CSAG1 Maintains the Integrity of the Mitotic Centrosome in Cells with Defective P53
Authors: Sapkota Hem , Wren Jonathan D. , Gorbsky Gary J.
Published: September 2019

Centrosomes focus microtubules to promote mitotic spindle bipolarity, a critical requirement for balanced chromosome segregation. Comprehensive understanding of centrosome function and regulation requires a complete inventory of components. While many centrosome components have been identified, others may yet remain undiscovered. We have used a bioinformatics approach, based on “guilt by association” expression to identify novel mitotic components among the large group of predicted human proteins that have yet to be functionally characterized. Here we identify Chondrosarcoma-Associated Gene 1 (CSAG1) in maintaining centrosome integrity during mitosis. Depletion of CSAG1 disrupts centrosomes and leads to multipolar spindles more effectively in cells with compromised p53 function. Thus, CSAG1 may reflect a class of “mitotic addiction” genes whose expression is more essential in transformed cells.
Modeling Cell-Specific Dynamics and Regulation of the Common Gamma Chain Cytokines
Authors: Farhat Ali M. , Weiner Adam C. , Posner Cori , Kim Zoe S. , Orcutt-Jahns Brian , Carlson Scott M. , Meyer Aaron S.
Published: September 2019

Many receptor families exhibit both pleiotropy and redundancy in their regulation, with multiple ligands, receptors, and responding cell populations. Any intervention, therefore, has multiple effects, confounding intuition about how to precisely manipulate signaling for therapeutic purposes. The common γ-chain cytokine receptor dimerizes with complexes of the cytokines interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21 and their corresponding “private” receptors. These cytokines have existing uses and future potential as immune therapies due to their ability to regulate the abundance and function of specific immune cell populations. However, engineering cell specificity into a therapy is confounded by the complexity of the family across responsive cell types. Here, we build a binding-reaction model for the ligand-receptor interactions of common γ-chain cytokines enabling quantitative predictions of response. We show that accounting for receptor-ligand trafficking is essential to accurately model cell response. This model accurately predicts ligand response across a wide panel of cell types under diverse experimental designs. Further, we can predict the effect and specificity of natural or engineered ligands across cell types. We then show that tensor factorization is a uniquely powerful tool to visualize changes in the input-output behavior of the family across time, cell types, ligands, and concentration. In total, these results present a more accurate model of ligand response validated across a panel of immune cell types, and demonstrate an approach for generating interpretable guidelines to manipulate the cell type-specific targeting of engineered ligands. These techniques will in turn help to study and therapeutically manipulate many other complex receptor-ligand families.

Summary points

A dynamical model of the γ-chain cytokines accurately models responses to IL-2, IL-15, IL-4, and IL-7.

Receptor trafficking is necessary for capturing ligand response.

Tensor factorization maps responses across cell populations, receptors, cytokines, and dynamics to visualize cytokine specificity.

An activation model coupled with tensor factorization provides design specifications for engineering cell-specific responses.
Kv1 potassium channels control action potential firing of putative GABAergic deep cerebellar nuclear neurons
Authors: Feria Pliego Jessica Abigail , Pedroarena Christine M.
Published: September 2019

The Kv1 voltage-gated potassium channels (kv1.1-1.8) display characteristic low-threshold activation ranges what enables their role in regulating diverse aspects of neuronal function, such as the action potential (AP) threshold and waveform, and thereby influence neuronal excitability or synaptic transmission. Kv1 channels are highly expressed in the cerebellar cortex and nuclei and mutations of human Kv1 genes are associated to episodic forms of ataxia (EAT-1). Besides the well-established role of Kv1 channels in regulating the basket-Purkinje cells inhibitory synapses of cerebellar cortex, cerebellar Kv1 channels regulate the principal deep cerebellar nuclear neurons activity (DCNs). DCNs however, include as well different groups of GABAergic cells that project locally to target principal DCNs, or to the inferior-olive or recurrently to the cerebellar cortex, but whether their function is controlled by Kv1 channels remains unclear. Here, using cerebellar slices from the GAD67-GFP line mice to identify putative GABAergic-DCNs and specific Kv1 channel blockers (dendrotoxins-alpha/I/K (DTXs)) we provide evidence that putative GABAergic-DCNs spontaneous and evoked activity is controlled by Kv1 currents. DTXs shifted in the hyperpolarizing direction the voltage threshold of spontaneous APs in GABAergic-DCNs, increased GABAergic-DCNs spontaneous firing rate and decreased these neurons ability to fire repetitively action potentials at high frequency. Moreover, in spontaneously silent putative nucleo-cortical DCNs, DTXs application induced depolarization and tonic firing. These results strongly suggest that Kv1 channels regulate GABAergic-DCNs activity and thereby can control previously unrecognized aspects of cerebellar function.
An inducible genome editing system for plants
Authors: Wang Xin , Ye Lingling , Ursache Robertas , Mähönen Ari Pekka
Published: September 2019

Conditional manipulation of gene expression is a key approach to investigating the primary function of a gene in a biological process. While conditional and cell-type specific overexpression systems exist for plants, there are currently no systems available to disable a gene completely and conditionally. Here, we present a novel tool with which target genes can be efficiently conditionally knocked out at any developmental stage. The target gene is manipulated using the CRISPR-Cas9 genome editing technology, and conditionality is achieved with the well-established estrogen-inducible XVE system. Target genes can also be knocked-out in a cell-type specific manner. Our tool is easy to construct and will be particularly useful for studying genes which have null-alleles that are non-viable or show strong developmental defects.
Novel regulators of nitric oxide signaling triggered by host perception in a plant pathogen
Authors: Ding Yi , Gardiner Donald M. , Xiao Di , Kazan Kemal
Published: September 2019

The rhizosphere interaction between plant roots or pathogenic microbes is initiated by mutual exchange of signals. However, how soil pathogens sense host signals is largely unknown. Here, we studied early molecular events associated with host recognition in Fusarium graminearum, an economically important fungal pathogen that can infect both roots and heads of cereal crops. We found that host-sensing prior to physical contact with plant roots radically alters the transcriptome and triggers nitric oxide (NO) production in F. graminearum. We identified an ankyrin-repeat domain containing protein (FgANK1) required for host-mediated NO production and virulence in F. graminearum. In the absence of host plant, FgANK1 resides in the cytoplasm. In response to host signals, FgANK1 translocates to the nucleus and interacts with a zinc finger transcription factor (FgZC1), also required for NO production and virulence in F. graminearum. Our results reveal new mechanistic insights into host-recognition strategies employed by soil pathogens.
Automation of (Macro)molecular Properties Using a Bootstrapping Swarm Artificial Neural Network Method: Databases for Machine Learning
Authors: Rahmani Blerta , Kamberaj Hiqmet
Published: September 2019

In this study, we employed a novel method for prediction of (macro)molecular properties using a swarm artificial neural network method as a machine learning approach. In this method, a (macro)molecular structure is represented by a so-calleddescription vector, which then is the input in a so-calledbootstrapping swarm artificial neural network(BSANN) for training the neural network. In this study, we aim to develop an efficient approach for performing the training of an artificial neural network using either experimental or quantum mechanics data. In particular, we aim to create different user-friendly online accessible databases of well-selected experimental (or quantum mechanics) results that can be used as proof of the concepts. Furthermore, with the optimized artificial neural network using the training data served as input for BSANN, we can predict properties and their statistical errors of new molecules using the plugins provided from that web-service. There are four databases accessible using the web-based service. That includes a database of 642 small organic molecules with known experimental hydration free energies, the database of 1475 experimental pKa values of ionizable groups in 192 proteins, the database of 2693 mutants in 14 proteins with given values of experimental values of changes in the Gibbs free energy, and a database of 7101 quantum mechanics heat of formation calculations.

All the data are prepared and optimized in advance using the AMBER force field in CHARMM macromolecular computer simulation program. The BSANN is code for performing the optimization and prediction written in Python computer programming language. The descriptor vectors of the small molecules are based on the Coulomb matrix and sum over bonds properties, and for the macromolecular systems, they take into account the chemical-physical fingerprints of the region in the vicinity of each amino acid.

Graphical TOC Entry
Influence of ortho-substituent on the molecular and crystal structures of 2-(N-arylimino)coumarin-3-carboxamide: isotypic and polymorphic structures
Authors: Shishkina Svitlana V. , Konovalova Irina S. , Kovalenko Sergiy M. , Trostianko Pavlo V. , Geleverya Anna O. , Nikolayeva Lyudmila L. , Bunyatyan Natalya D.
Published: September 2019

During a comprehensive study of a series of 2-(N-arylimino)coumarin-3-carboxamides with the aryl group substituted in the ortho-position by either a halogen atom, a methyl group or a methoxy group, the existence of three groups of isotypic crystal structures has been revealed. The similarity of crystal structures belonging to the same groups was confirmed by the analysis based on the comparison of pairwise interactions energies obtained from quantum chemical calculations. Group I includes unsubstituted, methyl-substituted and polymorphic modification 1 of fluoro-substituted 2-(N-arylimino)coumarin-3-carboxamide. Structures of polymorphic modification 2 of fluoro-substituted derivative, chloro-substituted and polymorphic modification 1 of bromo-substituted 2-(N-arylimino)coumarin-3-carboxamide may represent group II. Group III contains structures of polymorphic modification 2 of bromo-substituted derivative, iodine- and methoxy-substituted 2-(N-arylimino)coumarin-3-carboxamides. Structures of the same type group have extremely close parameters of the unit cell as well as those of molecular and crystal structures. But they are not identical. Polymorphic modifications of fluoro- and bromo-substituted 2-(N-arylimino)coumarin-3-carboxamides belong to different crystal types mainly due to different arrangement of basic structural motifs separated out using quantum chemical calculations.
Crystal structure, vibrational spectroscopy and optical properties of a one-dimensional organic–inorganic hybrid perovskite of [NH3CH2CH(NH3)CH2]BiCl5
Authors: Abdel-Aal Seham K. , Abdel-Rahman Ahmed S. , Gamal Wafia M. , Abdel-Kader Mohamed , Ayoub Hany S. , El-Sherif Ashraf F. , Kandeel M. F. , Bozhko S. , Yakimov E. E. , Yakimov E. B.
Published: September 2019

In this work the crystal structure by single crystal X-ray measurement and optical properties of 1D propane-1,2-diammonium pentachlorobismuthate [NH3CH2CH(NH3)CH3]BiCl5 organic–inorganic hybrid perovskite are presented. It is prepared by mixing ethanolic solution of equimolar ratios (1:1) of its basic components. The title compound crystallized in the noncentrosymmetric orthorhombic space group Pca21 with Z = 8 molecules per unit cell. The unit-cell parameters are a = 19.8403 (7) Å, b = 6.3303 (2) Å, c = 19.0314 (7) Å. The vibrational spectra are studied by Raman and infrared spectroscopy. The optical properties show a strong absorption in the ultraviolet region, the band gap energy E
g is found to be 3.15 eV. Cathodoluminescence measurements are also discussed.
Accommodation providers’ motives in sharing economy: comparison between Turkey and Lithuania
Authors: Urbonavicius Sigitas , Sezer Adil
Published: September 2019

Purpose

The purpose of this paper is to empirically assess and compare motivations and moderating factors that influence intention to provide accommodation in two countries, which are different in terms of their culture and IT infrastructure development.

Design/methodology/approach

Empirical analysis on the basis of 396 valid questionnaires from two countries allowed finding two different models that explain intentions to provide accommodation in the analyzed environments. Subsequent multilevel modeling disclosed differences between influences on intention to provide accommodation in Turkey and Lithuania.

Findings

The results disclosed importance of country contexts in causing diversity between country-specific models and in generating differences of the influences, if the same model for two countries is applied. The most important findings include observed differences in influences of monetary and social motives on intention, as well as in moderations of materialism and mavenism.

Originality/value

Using the self-determination theory as the theoretical background, the study adds to the knowledge on intention to participate in sharing economy from the accommodation providers’ position. Additional value is brought by finding the importance of cultural contexts in the models that describe intentions of accommodation providing in sharing economy.
Exploring the customer experience with Airbnb
Authors: Li Jing , Hudson Simon , So Kevin Kam Fung
Published: September 2019

Purpose

The purpose of this study is to investigate the multi-dimensional structure of the Airbnb customer experience and to examine the influences of this experience on behavioral outcomes.

Design/methodology/approach

A multi-phase methodology was adopted using a survey questionnaire to explore the dimensions. Data were collected from a sample of 561 Airbnb users in the USA. Exploratory factor analysis and confirmed factor analysis were conducted to evaluate the reliability and validity of the scale.

Findings

First, the results support the hypothesis that the Airbnb customer experience comprises four dimensions: home benefits, personalized services, authenticity and social connection. Second, the study demonstrates that these dimensions significantly influence customers’ behavioral intentions.

Research limitations/implications

The use of a US Airbnb users sample may affect the generalizability of the results.

Practical implications

The findings of this study provide insights for Airbnb hosts and hotel managers. More specifically, this study offers suggestions to Airbnb hosts about how to enhance their services to customers based on the four experience dimensions and to hotels about how they can compete with Airbnb on the four experience dimensions.

Originality/value

This study provides an important theoretical framework for measuring the Airbnb customer experience through an empirical examination.
The medical perspective on mining incidents
Authors: Karlsson Sofia , Saveman Britt-Inger , Gyllencreutz Lina
Published: September 2019

Purpose

The purpose of this paper is to examine emergency medical service (EMS) personnel’s perceptions and experiences of managing underground mining injury incidents.

Design/methodology/approach

In total, 13 EMS personnel were interviewed according to a semi-structured interview guide. The interviews were transcribed verbatim and analyzed using qualitative content analysis.

Findings

An underground mining environment was described as unfamiliar and unsafe and, with no guidelines for operational actions in an extreme environment, such as underground mines, the EMS personnel were uncertain of their role. They therefore became passive and relied on the rescue service and mining company during a major incident. However, the medical care was not considered to be different from any other prehospital care, although a mining environment would make the situation more difficult and it would take longer for the mine workers to be placed under definitive care.

Originality/value

This study complements earlier studies by examining the EMS personnel’s perceptions and experiences of major incidents.
Managerial competencies of 3PL providers
Authors: Sangka Bayu Khresna , Rahman Shams , Yadlapalli Aswini , Jie Ferry
Published: September 2019

Purpose

The purpose of this paper is to identify and prioritise competencies of Indonesian third-party logistics (3PL) managers from the perspective of multinational corporations (MNCs) and local firms.

Design/methodology/approach

Underlined by the theory of action and job performance (competency model), the study proposes a framework that consists of management, logistics, business and information and communication technology competency categories, with 15 competencies. Data are collected from five MNCs and five local 3PL firms operating in Indonesia. The analytic hierarchy process method is used to calculate the priority weights and to prioritise the competencies.

Findings

Results indicate that both the local and MNC 3PL providers emphasise logistics as the “most important” competency category. In the “moderately important” competency group, MNCs prioritise competencies in the management competency category while local firms prioritise competencies in the business competency category.

Research limitations/implications

Results obtained in this study focus on 3PL firms in Indonesian businesses, which may not be applicable to other nations and other industries.

Practical implications

3PL firms, industry peak bodies (e.g. Indonesian Logistics Association) and education providers can benefit from incorporating the findings of this study in developing curricula for higher education and training programmes for certification designed to improve managerial competencies.

Originality/value

By including the perceptions of the MNCs and local 3PL providers, this study advances the literature on 3PL managerial competencies by extending such knowledge to the global environment.
Systems thinking and CMM for continuous improvement in the construction industry
Authors: Omotayo Temitope Seun , Boateng Prince , Osobajo Oluyomi , Oke Adekunle , Obi Loveline Ifeoma
Published: September 2019

Purpose

The purpose of this paper is to present a capability maturity model (CMM) developed to implement continuous improvement in small and medium scale construction companies (SMSCC) in Nigeria.

Design/methodology/approach

A multi-strategy approach involving qualitative studies of SMSCC in Nigeria was conducted. Semi-structured interviews were conducted with purposively selected construction experts in Nigeria to identify variables essential for continuous improvement in SMSCC. Data collected were thematically analysed using NVIVO. Subsequently, a system thinking approach is employed to design and develop the CMM for implementing continuous improvement SMSCC, by exploring possible relationships between the variables established.

Findings

CMM provided a five-level approach for the inclusion of investigated variables such as team performance; culture; structure; post-project reviews, financial risk management, waste management policy and cost control. These variables are factors leading to continuous improvement in SMSCC, implementable within a six to seven and a half years’ timeline.

Practical implications

The system thinking model revealed cogent archetypes in the form of reinforcing loops that can be applied in developing the performance of SMSCC. Continuous improvement is feasible. However, it takes time to implement. Further longitudinal studies on the cost of implementing continuous improvement through CMM a knowledge transfer project can be initiated.

Originality/value

A methodical strategy for enhancing the effectiveness and operations of SMSCC in developing countries can be extracted from the causal loop diagram and the CMM.