bluuebunny/crossref_metadata_2025_split huggingface dataset:
Energy deficit-independent stress response in the Frataxin-depleted heart: evidence that Integrated Stress Response can predominate over mTORC1 activation
Authors: Vásquez-Trincado César , Patel Monika , Sivaramakrishnan Aishwarya , Bekeová Carmen , Anderson-Pullinger Lauren , Wang Nadan , Tang Hsin-Yao , Seifert Erin L. 
Published: June 2020

ABSTRACTFriedreich’s ataxia (FRDA) is an inherited disorder caused by depletion of frataxin (FXN), a mitochondrial protein required for iron-sulfur cluster (ISC) biogenesis. Cardiac dysfunction is the main cause of death. Yet pathogenesis, and, more generally, how the heart adapts to FXN loss, remain poorly understood, though are expected to be linked to an energy deficit. We modified a transgenic (TG) mouse model of inducible FXN depletion that permits phenotypic evaluation of the heart at FXN levels < 20% of normal, without heart failure. We investigated substrate-specific bioenergetics and nutrient and stress signaling in the heart, to evaluate how this model responds to FXN depletion. After > 8 weeks with FXN levels < 20% of normal, TG hearts did not display overt hypertrophy and were in fact smaller; global protein translation was lower, while protein degradative pathways were unaltered. Cardiac contractility was maintained, likely due to preserved β-oxidation, though oxidative phosphorylation capacity for pyruvate was lower. Bioenergetics alterations matched mitochondrial proteomics changes, including a non-uniform decrease in abundance of ISC-containing proteins. In parallel, both mTORC1 signaling and the integrated stress response (ISR) were activated. The lack of overt cardiac hypertrophy, consistent with lower global protein translation, suggests that ISR predominated over mTORC1 activation. Suppression of a major ATP demanding process could benefit the FXN-depleted heart, at least short term. Thus, the FXN-depleted heart may enter a protective state, not necessarily linked to a major energy deficit. Finally, we propose the model used here as a pre-clinical model of cardiomyopathy in FRDA.
Prediction of non-canonical routes for SARS-CoV-2 infection in human placenta cells
Authors: Constantino F. B. , Cury S. S. , Nogueira C. R. , Carvalho R. F. , Justulin L. A. 
Published: June 2020

AbstractThe SARS-CoV-2 is the causative agent of the COVID-19 pandemic. The data available about COVID-19 during pregnancy have demonstrated placental infection; however, the intrauterine transmission of SARS-CoV-2 is still debated. Intriguingly, while canonical SARS-CoV-2 cell entry mediators are expressed at low levels in placental cells, the receptors for viruses that cause congenital infections such as the cytomegalovirus and Zika virus are highly expressed in these cells. Here we analyzed the transcriptional profile (microarray and single-cell RNA-Seq) of proteins potentially interacting with coronaviruses to identify non-canonical mediators of SARS-CoV-2 infection and replication in the placenta. We show that, despite low levels of the canonical cell entry mediatorsACE2andTMPRSS2, cells of the syncytiotrophoblast, villous cytotrophoblast, and extravillous trophoblast co-express high levels of the potential non-canonical cell-entry mediatorsDPP4andCTSL. We also found changes in the expression ofDAAM1andPAICSgenes during pregnancy, which are translated into proteins also predicted to interact with coronaviruses proteins. These results provide new insight into the interaction between SARS-CoV-2 and host proteins that may act as non-canonical routes for SARS-CoV-2 infection and replication in the placenta cells.
Autoencoder based local T cell repertoire density can be used to classify samples and T cell receptors
Authors: Dvorkin Shirit , Levi Reut , Louzoun Yoram 
Published: June 2020

AbstractRecent advances in T cell repertoire (TCR) sequencing allow for characterization of repertoire properties, as well as the frequency and sharing of specific TCR. However, there is no efficient measure for the local density of a given TCR. TCRs are often described either through their Complementary Determining region 3 (CDR3) sequences, or theirV/J usage or their clone size. We here show that the local repertoire density can be estimated using a combined representation of these components through distance conserving autoencoders and Kernel Density Estimates (KDE).We present ELATE – an Encoder based LocAl Tcr dEnsity and show that the resulting density of a sample can be used as a novel measure to study repertoire properties. The cross-density between two samples can be used as a similarity matrix to fully characterize samples from the same host. Finally, the same projection in combination with machine learning algorithms can be used to predict TCR-peptide binding through the local density of known TCRs binding a specific target.Code availability-https://github.com/louzounlab/Autoencoder
Application of Good Agricultural Practices (GAP) by the Banana Farmers of Chitwan, Nepal
Authors: Joshi Arati , Kalauni Dharmendra , Tiwari Ujjal 
Published: June 2020

ABSTRACTThe study was conducted to identify the cultivation practices followed by the banana growers and compares it with the framework of Good Agricultural Practices as recommended by the World Banana Forum. Both qualitative and quantitative approach was used for data collection. The scheduled interview was carried out from 103 banana growers, two focused group discussion was carried out with the banana growers, and two key informant interview was carried out; one with the President of Banana Growers Association, Chitwan and another with Executive Director of Chamber of Commerce and Industry, Chitwan. The findings revealed that GAP related to soil management and fertilization (87.4%) and harvesting and on-farm processing (94.2%) is adopted at a low level. Only 36% of farmers apply an appropriate dose of chemical fertilizer, 28% follow crop rotation and 7.8% perform mulching/ intercropping. About 38% of the respondents do not have any source of irrigation. About 98% of the farmers do not perform any processing, cleaning, storing, and packaging of banana. Further, 55% of farmers do not use appropriate personal protective equipment while applying pesticides. The results showed that there is low awareness regarding GAP among the banana farmers in the Chitwan district. Therefore, the conduction of awareness programs and training related to GAP is recommended. By far, no study has been carried out to analyze the good agricultural practices applied by banana growers in Nepal. This study identified the prevailing gap in farmer’s practices and good agricultural practices.
A systematic review of European farmer and non-farmer attitudes towards landscapes, ecosystem services, and agricultural management practices: Implications for permanent grassland management
Authors: Tindale Sophie J. , Elliott John , Elings Marjolein , Gallardo-Cobos Rosa , Hunter Erik , Lieberherr Eva , Miškolci Simona , Price Paul Newell , Quatrini Simone , Sánchez-Zamora Pedro , Schlueter Hannah , Frewer Lynn J. 
Published: June 2020

AbstractPermanent grassland (PG) is an important agricultural land use for the delivery of multiple ecosystem services (ES), including carbon sequestration, water quality protection, food production, habitat provision, and cultural activities. However, PG environments are threatened by sub-optimal management, cultivation, and abandonment that are influenced by context, land manager’s attitudes and societal demand for ES. Therefore, the perceptions and attitudes of key decision-makers (farmers) and other stakeholders (non-farmers, including citizens and consumers of the products of permanent grasslands, and ES) need to be understood to ensure the sustainability of PGs and the ES they provide. A systematic review of the literature identified 135 scholarly articles. Application of thematic analysis, allowed the organization, and synthesis of current research related to (different) stakeholder attitudes, and how these influence PG management and the delivery of ES. The results suggest that different stakeholders hold different views towards permanent grassland, with farmers in particular having to balance economic with other (potentially conflicting) drivers. The types of knowledge held by different groups of stakeholders, access to sources of information, as well as the influence of knowledge on behaviour; and environmental values (for example in relation to aesthetics or conservation of biodiversity) explained why certain motivations for attitudes and behaviours are held. A major gap, however, was identified in relation to PG as opposed to other types of landscape.
Microtubules regulate pancreatic beta cell heterogeneity via spatiotemporal control of insulin secretion hot spots
Authors: Trogden Kathryn P. , McKinney Hudson , Zhu Xiaodong , Arpag Goker , Folland Thomas G. , Osipovich Anna B. , Magnuson Mark A , Zanic Marija , Gu Guoqiang , Holmes William R. , Kaverina Irina 
Published: June 2020

AbstractHeterogeneity of glucose-stimulated insulin secretion (GSIS) in pancreatic islets is physiologically important but poorly understood. Here, we utilize whole mouse islets to determine how microtubules affect secretion toward the vascular extracellular matrix. Our data indicate that microtubule stability in the β-cell population is heterogenous, and that cells with more stable microtubules secrete less in response to a stimulus. Consistently, microtubule hyper-stabilization prevents, and microtubule depolymerization promotes β-cell activation. Analysis of spatiotemporal patterns of secretion events shows that microtubule depolymerization activates otherwise dormant β-cells via initiation of secretion clusters (hot spots). Microtubule depolymerization also enhances secretion from individual cells, introducing both additional clusters and scattered events. Interestingly, without microtubules, the timing of clustered secretion is dysregulated, extending the first phase of GSIS. Our findings uncover a novel microtubule function in tuning insulin secretion hot spots, which leads to accurately measured and timed response to glucose stimuli and promotes functional β-cell heterogeneity.
The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity
Authors: Zhang Lizhou , Jackson Cody B , Mou Huihui , Ojha Amrita , Rangarajan Erumbi S , Izard Tina , Farzan Michael , Choe Hyeryun 
Published: June 2020

ABSTRACTSARS coronavirus 2 (SARS-CoV-2) isolates encoding a D614G mutation in the viral spike (S) protein predominate over time in locales where it is found, implying that this change enhances viral transmission. We therefore compared the functional properties of the S proteins with aspartic acid (SD614) and glycine (SG614) at residue 614. We observed that retroviruses pseudotyped with SG614infected ACE2-expressing cells markedly more efficiently than those with SD614. This greater infectivity was correlated with less S1 shedding and greater incorporation of the S protein into the pseudovirion. Similar results were obtained using the virus-like particles produced with SARS-CoV-2 M, N, E, and S proteins. However, SG614did not bind ACE2 more efficiently than SD614, and the pseudoviruses containing these S proteins were neutralized with comparable efficiencies by convalescent plasma. These results show SG614is more stable than SD614, consistent with epidemiological data suggesting that viruses with SG614transmit more efficiently.
APP binds to the EGFR ligands HB-EGF and EGF, acting synergistically with EGF to promote ERK signaling and neuritogenesis
Authors: da Rocha Joana F. , Bastos Luísa , Domingues Sara C. , Bento Ana R. , Konietzko Uwe , da Cruz e Silva Odete A. B. , Vieira Sandra I. 
Published: June 2020

AbstractThe amyloid precursor protein (APP) is a transmembrane glycoprotein central to Alzheimer’s disease (AD) with functions in brain development and plasticity, including in neurogenesis and neurite outgrowth. Epidermal growth factor (EGF) and heparin-binding EGF-like growth factor (HB-EGF) are well described neurotrophic and neuromodulator EGFR ligands, both implicated in neurological disorders like Schizophrenia and AD. Here we show that APP interacts with these two EGFR ligands and characterize the effects of APP-EGF interaction in ERK activation and neuritogenesis. HB-EGF was identified as a novel APP interactor in a yeast two-hybrid screen of a human brain cDNA library. Yeast co-transformation and co-immunoprecipitation assays confirmed APP interaction with HB-EGF. Moreover, co-immunoprecipitation also revealed that APP binds to cellular pro-EGF. Overexpression of HB-EGF in HeLa cells, or exposure of SH-SY5Y cells to EGF, both resulted in increased APP protein levels. EGF and APP were also observed to synergistically activate the ERK signaling pathway, crucial for early neuronal differentiation. Immunofluorescence analysis of cellular neuritogenesis in conditions of APP overexpression and EGF exposure, confirmed a synergistic effect in promoting the number and the mean length of neurite-like processes per cell. Synergistic ERK activation and neuritogenic effects were completely blocked by the EGFR inhibitor PD 168393, implying EGF-induced activation of EGFR as part of the mechanism. This work shows novel APP protein interactors and provides a major insight into the APP-driven mechanisms underlying neurite outgrowth and neuronal differentiation, with potential relevance for AD and for adult neuroregeneration.
Spatiotemporal Dynamics of Sound Representations reveal a Hierarchical Progression of Category Selectivity
Authors: Lowe Matthew X. , Mohsenzadeh Yalda , Lahner Benjamin , Charest Ian , Oliva Aude , Teng Santani 
Published: June 2020

ABSTRACTAs the human brain transforms incoming sounds, it remains unclear whether semantic meaning is assigned via distributed, domain-general architectures or specialized hierarchical streams. Here we show that the spatiotemporal progression from acoustic to semantically dominated representations is consistent with a hierarchical processing scheme. Combining magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) patterns, we found superior temporal responses beginning ~80 ms post-stimulus onset, spreading to extratemporal cortices by ~130 ms. Early acoustically-dominated representations trended systematically toward semantic category dominance over time (after ~200 ms) and space (beyond primary cortex). Semantic category representation was spatially specific: vocalizations were preferentially distinguished in temporal and frontal voice-selective regions and the fusiform face area; scene and object sounds were distinguished in parahippocampal and medial place areas. Our results are consistent with an extended auditory processing hierarchy in which acoustic representations give rise to multiple streams specialized by category, including areas typically considered visual cortex.
Temporal clinical and laboratory response to interleukin-6 receptor blockade with Tocilizumab in 89 hospitalized patients with COVID-19 pneumonia
Authors: Fomina Daria S. , Lysenko Mar’yana A. , Beloglazova Irina P. , Mutovina Zinaida Yu. , Poteshkina Nataliya G. , Samsonova Inna V. , Kruglova Tat’yana S. , Chernov Anton A. , Karaulov Alexander V. , Lederman Michael M. 
Published: June 2020

AbstractBackgroundEmerging evidence links morbidity and mortality of pandemic COVID-19 pneumonia to an inflammatory cytokine storm.MethodsEighty nine patients with COVID-19 pneumonia and heightened systemic inflammation (elevated serum C reactive protein and interleukin-6 levels) were treated with Tocilizumab (TCZ), a human monoclonal IgG1 antibody to the interleukin-6 receptor.ResultsClinical and laboratory improvement was seen comparing baseline and 1-2 day post-infusion indices. Among 72 patients not receiving mechanical ventilation, NEWS2 scores fell from 5 to 2 (p < 0.001) C reactive protein levels fell from 95 to 14 mg/L (p < 0.001) and lymphocyte counts rose from 900 to 1000/uL (p = 0.036). Sixty three of 72 patients were discharged from hospital, one patient died, and 8 remained in hospital at time of writing. Among 17 patients receiving mechanical ventilation, despite a rapid decrease in CRP levels from 89 to 35 mg/L (p = 0.014) and early improvements in NEWS2 scores in 10 of 17, ten patients died and seven remain in hospital at time of writing. Overall, mortality was only seen in patients who had markedly elevated CRP levels (>30 mg/L) and low lymphocyte counts (< 1000/uL) before TCZ administration.ConclusionsInflammation and lymphocytopenia are linked to mortality in COVID-19. Inhibition of IL-6 activity by administration of Tocilizumab, an anti IL-6 receptor antibody is associated with rapid improvement in both CRP and lymphocyte counts and in clinical indices. Controlled clinical trials are needed to confirm the utility of IL-6 blockade in this setting. Additional interventions will be needed for patients requiring mechanical ventilation.
Numerical and experimental study of the laminar separation bubble over SS007 airfoil for micro aerial vehicles
Authors: V. Somashekar , A. Immanuel Selwyn Raj 
Published: June 2020

Purpose
This paper aims to deal with the numerical investigation of laminar separation bubble (LSB) characteristics (length and height of the bubble) of SS007 airfoil at the chord Reynolds number of Rec = 0.68 × 105 to 10.28 × 105.

Design/methodology/approach
The numerical simulations of the flow around SS007 airfoil were carried out by using the commercial fluid dynamics (CFD) software, ANalysis system (ANSYS) 15. To solve the governing equations of the flow, a cell-centred control volume space discretisation approach is used. Wind tunnel experiments were conducted at the chord-based Reynolds number of Rec = 1.6 × 105 to validate the aerodynamic characteristics over SS007 airfoil.

Findings
The numerical results revealed that the LSB characteristics of a SS007 airfoil, and the aerodynamic performances are validated with experimental results. The lift and drag coefficients for both numerical and experimental results show very good correlation at Reynolds number 1.6 × 105. The lift coefficient linearly increases with the increasing angle of attack (AOA) is relatively small. The corresponding drag coefficient was found to be very small. After the formation of LSB which leads to burst to cause airfoil stall, the lift coefficient decreases and increases the drag coefficient.

Practical implications
Low Reynolds number and LSB characteristics concept in aerodynamics is predominant for both civilian and military applications. These include high altitude devices, wind turbines, human powered vehicles, remotely piloted vehicles, sailplanes, unmanned aerial vehicle and micro aerial vehicle. In this paper, the micro aerial vehicle flight conditions considered and investigated the LSB characteristics for different Reynolds number. To have better aerodynamic performances, it is strongly recommended to micro aerial vehicle (MAV) design engineers that the MAV is to fly at 12 m/s (cruise speed).

Social implications
MAVs and unmanned aerial vehicles seem to give some of the technical challenges of nature conservation monitoring and law enforcement a versatile, reliable and inexpensive solution.

Originality/value
The SS007 airfoil delays the flow separation and improves the aerodynamic efficiency by increasing the lift and decreasing the drag. The maximum increase in aerodynamic efficiency is 12.5% at stall angle of attack compared to the reference airfoil at Re = 2 × 105. The results are encouraging and this airfoil could have better aerodynamic performance for the development of MAV.
The revitalization of service orientation: a business services model
Authors: Plugge Albert , Nikou Shahrokh , Bouwman Harry 
Published: June 2020

PurposeDue to the convergence of rapid business developments and digitization challenges, service orientation is back on the research agenda as a concept to improve firms’ business services. Yet, little is known about the type of determinants that are relevant and to what degree they affect a firm’s service-oriented strategy.Design/methodology/approachBuilding on structural equation modeling (SEM) and a unique data set of 131 international firms from different continents, the authors identify and analyze the key determinants in the context of a firm’s service-oriented strategy.FindingsThe findings show that in order to cater for changes, organizations have to manage and adapt the coherence of the determinants’ business services, business processes and knowledge sharing continuously. Moreover, the results show that a service-oriented strategy is not only influenced by business services as such, but business services mediate the relationships between business processes, governance and process-aware information systems to a service-oriented strategy.Research limitations/implicationsA limitation is imposed by the limited sample size and the unbalanced response of participants (executive management). In future research, a more extensive survey among a broader group of participants will help the authors to develop their model further in order to generalize the results, as well as more finely grained research related to geography and size might be pursued. Future empirical research is necessary to identify and test the relationships between other constructs and study their effect on a firm’s service-oriented strategy.Practical implicationsOn a practical level, the authors postulate that an organization’s executive management should pay attention to invest in an organizational entity (department) that manages business services continuously. This organizational entity has to ensure that related processes and knowledge sharing are in place to establish and maintain a service-oriented strategy.Originality/valueThis research contributes to service-oriented literature by operationalizing the implementation of an organization’s service-oriented strategy. The authors’ insights go beyond the findings of Aier et al. (2011). The authors found that a service-oriented strategy influences service-oriented project success positively. The authors extended these findings, based on a unique data set, by studying business services and influencing determinants (i.e. business processes, governance, PAIS and knowledge sharing) within the context of service orientation. The renewed attention to the concept of service orientation provides insights into critical determinants that influence the implementation of a service-oriented strategy.
New cubic B-spline approximation technique for numerical solutions of coupled viscous Burgers equations
Authors: Nazir Tahir , Abbas Muhammad , Iqbal Muhammad Kashif 
Published: June 2020

Purpose
The purpose of this paper is to present a new cubic B-spline (CBS) approximation technique for the numerical treatment of coupled viscous Burgers’ equations arising in the study of fluid dynamics, continuous stochastic processes, acoustic transmissions and aerofoil flow theory.

Design/methodology/approach
The system of partial differential equations is discretized in time direction using the finite difference formulation, and the new CBS approximations have been used to interpolate the solution curves in the spatial direction. The theoretical estimation of stability and uniform convergence of the proposed numerical algorithm has been derived rigorously.

Findings
A different scheme based on the new approximation in CBS functions is proposed which is quite different from the existing methods developed (Mittal and Jiwari, 2012; Mittal and Arora, 2011; Mittal and Tripathi, 2014; Raslan et al., 2017; Shallal et al., 2019). Some numerical examples are presented to validate the performance and accuracy of the proposed technique. The simulation results have guaranteed the superior performance of the presented algorithm over the existing numerical techniques on approximate solutions of coupled viscous Burgers’ equations.

Originality/value
The current approach based on new CBS approximations is novel for the numerical study of coupled Burgers’ equations, and as far as we are aware, it has never been used for this purpose before.