bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renoprotective and haemodynamic effects of adiponectin and peroxisome proliferator-activated receptor agonist, pioglitazone, in renal vasculature of diabetic Spontaneously hypertensive rats
Authors: Afzal Sheryar , Sattar Munavvar Abdul , Johns Edward James , Eseyin Olorunfemi. A. 
Published: February 2020

AbstractPioglitazone, a therapeutic drug for diabetes, possesses full PPAR-γ agonist activity and increase circulating adiponectin plasma concentration. Plasma adiponectin concentration decreases in hypertensive patients with renal dysfunctions. Present study investigated the reno-protective, altered excretory functions and renal haemodynamic responses to adrenergic agonists and ANG II following separate and combined therapy with pioglitazone in diabetic model of hypertensive rats. Pioglitazone was given orally [10mg/kg/day] for 28 days and adiponectin intraperitoneally [2.5µg/kg/day] for last 7 days. Groups of SHR received either pioglitazone or adiponectin in combination. A group of Wistar Kyoto rats [WKY] served as normotensive controls, whereas streptozotocin administered SHRs served as diabetic hypertensive rats. Metabolic data and plasma samples were taken on day 0, 8, 21 and 28. In acute studies, the renal vasoconstrictor actions of Angiotensin II [ANGII], noradrenaline [NA], phenylephrine [PE] and methoxamine [ME] were determined. Diabetic SHRs control had a higher basal mean arterial blood pressure than the WKY, lower RCBP and plasma adiponectin, higher creatinine clearance and urinary sodium excretion compared to WKY [all P<0.05] which were normalized by the individual drug treatments and to greater degree following combined treatment. Responses to intra-renal administration of NA, PE, ME and ANGII were larger in diabetic SHR than WKY and SHRs [P<0.05]. Adiponectin significantly blunted responses to NA, PE, ME and ANG II in diabetic treated SHRs by 40%, whereas the pioglitazone combined therapy with adiponectin further attenuated the responses to adrenergic agonists by 65%. [all P <0.05]. These findings suggest that adiponectin possesses renoprotective effects and improves renal haemodynamics through adiponectin receptors and PPAR-γ in diabetic SHRs, suggesting that synergism exists between adiponectin and pioglitazone. A cross-talk relationship also supposed to exists between adiponectin receptors, PPAR-γ and alpha adrenoceptors in renal vasculature of diabetic SHRs.
High-throughput discovery of trafficking-deficient variants in the cardiac potassium channelKCNH2: Deep mutational scan ofKCNH2trafficking
Authors: Kozek Krystian A. , Glazer Andrew M. , Ng Chai-Ann , Blackwell Daniel , Egly Christian L. , Vanags Loren R. , Blair Marcia , Mitchell Devyn , Matreyek Kenneth A. , Fowler Douglas M. , Knollmann Bjorn C. , Vandenberg Jamie , Roden Dan M. , Kroncke Brett M. 
Published: February 2020

ABSTRACTBackgroundKCHN2encodes the KV11.1 potassium channel responsible forIKr, a major repolarization current during the cardiomyocyte action potential. Variants inKCNH2that decreaseIKrcan cause Type 2 Long QT syndrome, usually due to mistrafficking to the cell surface. Accurately discriminating between variants with normal and abnormal trafficking would help clinicians identify and treat individuals at risk of a major cardiac event. The volume of reported non-synonymousKCNH2variants preclude the use of conventional electrophysiologic methods for functional study.ObjectiveTo report a high-throughput, multiplexed screening method forKCNH2genetic variants capable of measuring the cell surface abundance of hundreds of missense variants inKCNH2.MethodsWe develop a method to quantitateKCNH2variant trafficking on a pilot region of 11 residues in the S5 helix, and generate trafficking scores for 220/231 missense variants in this region.ResultsFor 5/5 variants, high-throughput trafficking scores validated when tested in single variant flow cytometry and confocal microscopy experiments. We additionally compare our results with planar patch electrophysiology and find that loss-of-trafficking variants do not produceIKr, but that some variants which traffic normally may still be functionally compromised.ConclusionsHere, we describe a new method for detecting trafficking-deficient variants inKCNH2in a multiplexed assay. This new method accurately generates trafficking data for variants inKCNH2and can be readily extended to all residues in Kv11.1 and to other cell surface proteins.CLINICAL IMPLICATIONSHundreds ofKCNH2variants have been observed to date, and thousands more will be found as clinical and population sequencing efforts become increasingly widespread. The major mechanism of KV11.1 loss of function is misfolding and failure to traffic to the cell surface. Deep mutational scanning ofKCNH2trafficking is a scalable, high-throughput method that can help identify new loss of function variants and decipher the large number ofKCNH2variants being found in the population.
Microfluidic platform for live cell imaging of 3D cultures with clone retrieval
Authors: Mulas Carla , Hodgson Andrew C , Kohler Timo N , Agley Chibeza C , Hollfelder Florian , Smith Austin , Chalut Kevin 
Published: February 2020

ABSTRACTCombining live imaging with the ability to retrieve individual cells of interest remains a technical challenge. These combined methods are of particular interest when studying highly dynamic or transient, asynchronous or heterogeneous cell biological and developmental processes. Here we present a method to encapsulate live cells in a 3D hydrogel matrix, via droplet compartmentalisation. Using a small-scale screen, we optimised matrix conditions for the culture and multilineage differentiation of mouse embryonic stem (ES) cells. Moreover, we designed a custom microfluidic platform that is compatible with live imaging. With this platform we are able to retain or extract individual bead/droplets by media flow only, obviating the need for enzymatic cell removal from the platform. We show that we can differentiate mES cells, monitor reporter expression by live imaging, and retrieve individual droplets for functional assays, correlating reporter expression with functional response. Overall, we present a highly flexible 3D cell encapsulation and microfluidic platform that enables both monitoring of cellular dynamics and retrieval for molecular and functional assays.
Fast qualitYconTrol meThod foRderIved diffUsionMetrics (YTTRIUM) in big data analysis: UK Biobank 18608 example
Authors: Maximov Ivan I. , van der Meer Dennis , de Lange Ann-Marie , Kaufmann Tobias , Shadrin Alexey , Frei Oleksandr , Wolfers Thomas , Westlye Lars T. 
Published: February 2020

AbstractDeriving reliable information about the structural and functional architecture of the brainin vivois critical for the clinical and basic neurosciences. In the new era of large population-based datasets, when multiple brain imaging modalities and contrasts are combined in order to reveal latent brain structural patterns and associations with genetic, demographic and clinical information, automated and stringent quality control (QC) procedures are important. Diffusion magnetic resonance imaging (dMRI) is a fertile imaging technique for probing and visualising brain tissue microstructurein vivo,and has been included in most standard imaging protocols in large-scale studies. Due to its sensitivity to subject motion and technical artefacts, automated QC procedures prior to statistical analyses of dMRI data are required to minimise the influence of noise and artefacts. Here, we introduce Fast qualitY conTrol meThod foR derIved diffUsion Metrics (YTTRIUM), a computationally efficient QC method utilising structural similarity to evaluate image quality and mean diffusion metrics. As an example, we applied YTTRIUM in the context of tract-based spatial statistics to assess associations between age and kurtosis imaging and white matter tract integrity in UK Biobank data (n = 18,608). In order to assess the influence of outliers on results obtained using machine learning approaches, we tested the effects of applying YTTRIUM on brain age prediction. We demonstrated that the proposed QC pipeline represents an efficient approach for identifying poor quality datasets and artifacts and increase the accuracy of machine learning based brain age prediction.
Vps54 regulatesDrosophilaneuromuscular junction development and controls postsynaptic density composition via a Rab7-dependent mechanism
Authors: Patel Prajal H. , Wilkinson Emily C. , Starke Emily L. , McGimsey Malea R. , Blankenship J. Todd , Barbee Scott A. 
Published: February 2020

ABSTRACTVps54 is a subunit of the Golgi-associated retrograde protein (GARP) complex, which is involved in tethering endosome-derived vesicles to thetrans-Golgi network (TGN). In the wobbler mouse, a model for human motor neuron (MN) disease, reduction in the levels of Vps54 causes neurodegeneration. However, it is unclear how disruption of GARP-mediated vesicle transport leads to MN dysfunction and ultimately neurodegeneration. To better understand the role of Vps54 in MNs, we have disrupted expression of theVps54ortholog inDrosophilaand examined the impact on the larval neuromuscular junction (NMJ). Here, we show that both null mutants and MN-specific knockdown ofVps54leads to NMJ overgrowth. Reduction ofVps54partially disrupts localization of the t-SNARE, Syntaxin-16, to the TGN but has no impact on endosomal pools. Presynaptic knockdown ofVps54in MNs combined with overexpression of the small GTPases Rab5, Rab7, or Rab11 suppresses theVps54NMJ phenotype. Conversely, knockdown ofVps54combined with overexpression of dominant negative Rab7 causes axonal and behavioral abnormalities including a decrease in postysynaptic Dlg and GluRIIB levels without any effect on GluRIIA. Taken together, these data suggest thatVps54controls larval MN axon development and postsynaptic density composition by modulating Rab7-mediated endosomal trafficking.
Synaptomic analysis of dopaminergic inputs reveal hub synapses in the mouse striatum
Authors: Paget-Blanc Vincent , Pfeffer Marlene E. , Pronot Marie , Lapios Paul , Angelo Maria-Florencia , Walle Roman , Cordelières Fabrice P. , Levet Florian , Claverol Stéphane , Lacomme Sabrina , Petrel Melina , Martin Christelle , Pitard Vincent , Desmedt-Peyrusse Véronique , Biederer Thomas , Perrais David , Trifilieff Pierre , Herzog Etienne 
Published: February 2020

SUMMARYDopamine is a monoamine involved in reward processing and motor control. Volume transmission is thought to be the mechanism by which monoamines modulate effector systems at glutamate and GABA synapses. Hence, dopamine synapses are scarcely described. We applied fluorescence activated synaptosome sorting to explore the features of the dopaminergic synaptome. We provide the proteome of striatal dopaminergic synapses with 57 proteins specifically enriched. Beyond canonical markers of dopamine neurotransmission (Th, Slc6a3/DAT, Slc18a2/VMAT2), we validated 6 proteins belonging to pre- and postsynaptic sides (Cpne7, Apba1/Mint1, Cadps2, Cadm2/SynCAM 2, Stx4 and Mgll). Moreover, dopaminergic varicosities adhere to both a post-synapse with cognate receptors and glutamatergic, GABAergic or cholinergic synapses in structures we named dopaminergic “hub synapses”. Markers of presynaptic vesicles and active zone, post-synaptic density and spine apparatus, are significantly increased upon association with dopamine inputs in hubs. Thus neuromodulation frequently operates from hub synapses affecting associated synapses and is not solely dependent on volume transmission. Finally, FASS provides a new framework for the exploration of dopaminergic synapses and more generally for discrete synapse populations ex-vivo.HighlightsA first proteome of dopaminergic synapses in the striatumStriatal dopaminergic synaptosomes display post-synaptic cognate receptorsDopaminergic projections build hub synapses with excitatory, inhibitory, and cholinergic projections.Cortico-striatal synaptic scaffolds are strengthened upon association in hub synapses.
G protein-Coupled Receptor Distribution Impacts the Effectiveness of Signal Transmission
Authors: Zhou Ming-Yi , Hu Ya-Yu , Chuang Huai-Hu 
Published: February 2020

AbstractNumbers of activated receptor dictate efficacy of neurotransmitter stimulation. Many PLC coupled receptors activated by ligands elicit canonical downstream Gq/11 pathway to induce endogenous Ca2+gated chloride channels. The coupling from receptors to effectors was analyzed inXenopusoocytes expressing genetically modified angiotensin receptor type 1 receptor (AT1R). The latency between ATII binding and Ca2+-induced Cl−current surge was inversely correlated. AT1R activation triggered a chain of chemical reactions, of which the products were playing messengers for subsequent events. Messenger accumulation must rate-limit the agonism. For accurate quantification the speed of ATII triggered theiCl−. The T-form AT1R-IRK1 fusion exhibits faster induction compared to the M-form. The latency of the recorded none vanishediCl−, marking the lowest genuine calcium activation, took place at earlier time point by the timer time. The evokediCl−however reached similar maximal amplitudes. This kinetic effect raises the possibility to use temporal coding to complement amplitude coding (analogous to FM versus AM radio transmission) for receptor-agonist pairs.
Inhibitory neurons are a Central Controlling regulator in the effective cortical microconnectome
Authors: Kajiwara Motoki , Nomura Ritsuki , Goetze Felix , Akutsu Tatsuya , Shimono Masanori 
Published: February 2020

AbstractThe brain is a network system in which excitatory and inhibitory neurons keep the activity balanced in the highly non-uniform connectivity pattern of the microconnectome. It is well known that the relative percentage of inhibitory neurons is much smaller than excitatory neurons. So, in general, how the inhibitory neurons can keep the balance with the surrounding excitatory neurons is an important question.We observed effective networks, reflecting causal interactions, of ~1000 neurons in cortical acute slices. Surprisingly, we found that inhibitory neurons are not only located at more central positions than excitatory neurons but also have stronger controlling ability of other neurons than excitatory neurons. Besides, we found that the precedence in centrality and controlling ability of inhibitory neurons are well observed in deep cortical layers by comparing with distribution of neurons coloured by NeuN immunostaining data. Preceding the observation, we also found that inhibitory neurons show higher firing rate than excitatory neurons, and that their firing rate also closely obey a log-normal distribution as previously known about excitatory neurons. Additionally, their connectivity strengths also obeyed a log-normal distribution.In summary, within the network interaction of huge numbers of neurons, inhibitory neurons seem to produce a central controlling system that sustains the homeostatic behavior of the brain. A similar evaluation in different life stages and in disease statesetc.will not only provide deeper understandings in the homeostasis of the brain, but also will provide a selective and effective way to stimulate individual neurons to modulate neuropsychiatry or neurodegeneration disease states.
Exploring the relationship between ICT, SCM practices and organizational performance in agri-food supply chain
Authors: Kumar Anil , Singh Rohit Kr , Modgil Sachin 
Published: February 2020

PurposeThis paper presents the concerns in agri-food supply chain. Further the research investigates the role of information and communication technology (ICT) in agri-food supply chain and determines the impact of supply chain management (SCM) practices on firm performance.Design/methodology/approachThe theoretical framework was proposed for the study on the basis of existing literature. Data for the study was collected with the help of structured questionnaire from 121 executives and officers of the public food distribution agency. Partial least square (PLS)–structured equation modeling was employed to test the framework and hypotheses.FindingsThe results indicate that ICT and SCM practices (logistics integration and supplier relationships) have a significant relationship. Furthermore, SCM practices (information sharing, supplier relationship and logistics integration) have a significant and positive impact on performance of the organization.Research limitations/implicationsFurther research could be carried out to test the moderation effect of SCM practices between ICT and organizational performance (OP). Extending the research study to the companies operating in other sectors can enhance the external validity of the study and improve the accuracy of parameters examined.Practical implicationsThis study can be of interest to the agri-food industry as well as other industry practitioners interested in improving the performance of the organization from the view of supply chain.Originality/valueThe outcomes of this study have important implications that translate into a series of recommendations for the management of public food distribution as well as other agri-food-based supply chains.
A thematic analysis of the quality audit reports in developing a framework for assessing the achievement of the graduate attributes
Authors: Halibas Alrence Santiago , Mehtab Shameena , Al-Attili Alaa , Alo Benjamin , Cordova Ronald , Cruz Maria Elisa Linda Taeza 
Published: February 2020

PurposeGraduates are expected to possess the knowledge and right skillset, commonly known as graduate attributes, which they need to become employable and work-ready. This study describes the approaches that were employed by an academic institution in developing an assessment framework for measuring the student achievement of the graduate attributes and learning outcomes.Design/methodology/approachIt used thematic analysis in analyzing the 43 audit reports of higher educational institutions (HEIs) in Oman which have undergone the regional quality audit as well as the outcomes of the institutional standards assessment.FindingsThe analysis exposed the critical issues necessary for embedding graduate attributes and learning outcomes in higher education. Likewise, the study revealed that the assessment of the graduate attributes (GAs) and learning outcomes (LOs) is the area that garnered the most number of comments from the audit panel, and 69 per cent of the HEIs are still problematic in this area. Moreover, most of the HEIs in Oman lack the mechanisms to assess student learning as evidenced in the regional accreditation outcomes. Only 43.8 per cent of the HEIs, which have undergone the institutional accreditation process, have garnered a Met Rating in the Graduate Attributes and Student Learning Outcome criterion. Hence, this study presupposes its high relevance and usefulness to the work in this area, drawing from the experience of an HEI in Oman.Practical implicationsThis study will present the relevant and meaningful content, especially good practices and potential gaps that inform HEIs regarding the current trends, policies, and practices relevant to the assessment of graduate attributes and learning outcomes in higher education.Originality/valueThis study extends the limited literature on the assessment of graduate attributes and learning outcomes, especially among the HEIs in Oman.
An exploration of sensory processing patterns and their association with demographic factors in healthy adults
Authors: Machingura Tawanda , Kaur Gurjeet , Lloyd Chris , Mickan Sharon , Shum David , Rathbone Evelyne , Green Heather 
Published: February 2020

Purpose
Previous research has provided limited evidence on whether and how demographic factors associate with sensory processing patterns (SPP) in adults. This paper aims to examine relationships between SPPs and sociodemographic factors of age, sex, education and ethnicity in healthy adults.

Design/methodology/approach
A cross-sectional study design was used. A total of 71 adult participants was recruited from the community, using convenience sampling. Each participant completed the Adolescent/Adult Sensory Profile (AASP) and the Depression Anxiety Stress Scales – short version (DASS-21). Demographic information on age, sex, education and ethnicity was collected. Results were analysed using descriptive statistics and multivariate analyses of covariance (MANCOVA).

Findings
SPPs, as measured by the AASP, were significantly correlated to demographic factors of age and education after controlling for emotional distress using the DASS-21. A statistically significant multivariate effect was found across the four dependent variables (low registration, seeking, sensitivity and avoiding) for the age category, F = 6.922, p = 0.009,

ηp2 = 0.145, in the presence of a covariate DASS. The education category showed significance only in the seeking domain (p = 0.008,

ηp2 = 0.10) after controlling for DASS. There was no significant correlation between SPPs and gender or ethnicity. Results also indicated that mean scores of participants in this study were “similar to most people” as standardised in the AASP.

Research limitations/implications
This was a cross-sectional study with limitations including that the study used a relatively small sample and was based on self-reported healthy participants.

Practical implications
SPPs may correlate with healthy adults’ age and to a lesser extent education. This suggests that it might be helpful to consider such demographic factors when interpreting SPPs in clinical populations, although further research in larger samples is needed to reach firmer conclusions about possible implications of demographic variables.

Originality/value
The findings in this paper add to the growing evidence that suggest that SPPs vary with sociodemographic factors.
The red thread of information
Authors: Hartel Jenna 
Published: February 2020

PurposeIn The Invisible Substrate of Information Science, a landmark article about the discipline of information science, Marcia J. Bates wrote that “…we are always looking for the red thread of information in the social texture of people's lives” (1999a, p. 1048). To sharpen our understanding of information science and to elaborate Bates' idea, the work at hand answers the question: Just what does the red thread of information entail?Design/methodology/approachThrough a close reading of Bates' oeuvre and by applying concepts from the reference literature of information science, nine composite entities that qualify as the red thread of information are identified, elaborated, and related to existing concepts in the information science literature. In the spirit of a scientist–poet (White, 1999), several playful metaphors related to the color red are employed.FindingsBates' red thread of information entails: terms, genres, literatures, classification systems, scholarly communication, information retrieval, information experience, information institutions, and information policy. This same constellation of phenomena can be found in resonant visions of information science, namely, domain analysis (Hjørland, 2002), ethnography of infrastructure (Star, 1999), and social epistemology (Shera, 1968).Research limitations/implicationsWith the vital vermilion filament in clear view, newcomers can more easily engage the material, conceptual, and social machinery of information science, and specialists are reminded of what constitutes information science as a whole. Future researchers and scientist–poets may wish to supplement the nine composite entities with additional, emergent information phenomena.Originality/valueThough the explication of information science that follows is relatively orthodox and time-bound, the paper offers an imaginative, accessible, yet technically precise way of understanding the field.