bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virulence strategies of an insect herbivore and oomycete plant pathogen converge on a host E3 SUMO ligase
Authors: Liu S. , Lenoir C.J.G. , Amaro T.M.M.M. , Rodriguez P.A. , Huitema E. , Bos J.I.B. 
Published: June 2020

AbstractPathogens and pests secrete proteins (effectors) to interfere with plant immunity through modification of host target functions and disruption of immune signalling networks. Importantly, molecular virulence strategies of distinct pathogens converge on a small set of regulators with central roles in plant immunity. The extent of convergence between pathogen and herbivorous insect virulence strategies is largely unexplored. We found that effectors from the oomycete pathogen, Phytophthora capsici, and the major aphid pest, Myzus persicae target the host immune regulator SIZ1, an E3 SUMO ligase. We show that the oomycete and aphid effector, which both contribute to virulence, feature different activities towards SIZ1. While M. persicae effector Mp64 increases SIZ1 protein levels, P. capsici effector CRN83_152 enhances SIZ1-E3 SUMO ligase activity in vivo. Loss of SIZ1 in host plants leads to reduced host susceptibility to aphids and an oomycete pathogen. Our results suggest convergence of distinct pathogen and pest virulence strategies on an E3 SUMO ligase to enhance host susceptibility.
A Peptide of the Amino-Terminus of GRK2 Induces Hypertrophy and Yet Elicits Cardioprotection after Pressure Overload
Authors: Schumacher Sarah M. , Bledzka Kamila M. , Grondolsky Jessica , Roy Rajika , Gao Erhe , Chuprun J. Kurt , Koch Walter J. 
Published: June 2020

AbstractG protein-coupled receptor (GPCR) kinase 2 (GRK2) expression and activity are elevated early on in response to several forms of cardiovascular stress and are a hallmark of heart failure. Interestingly, though, in addition to its well-characterized role in regulating GPCRs, mounting evidence suggests a GRK2 “interactome” that underlies a great diversity in its functional roles. Several such GRK2 interacting partners are important for adaptive and maladaptive myocyte growth; therefore, an understanding of domain-specific interactions with signaling and regulatory molecules could lead to novel targets for heart failure therapy. While elevated cardiac levels and activity of GRK2 contribute to adverse heart remodeling and contractile dysfunction, inhibition of GRK2 via overexpression of a carboxyl-terminal peptide, βARKct, or its amino-terminal domain Regulator of G protein Signaling (RGS) homology domain (βARKrgs) can enhance cardiac function and can prevent heart failure development via Gβγor Gαq sequestration, respectively. Previously, our lab investigated cardiac-specific transgenic expression of a fragment of this RGS domain (βARKnt) (residues 50-145). In contrast to βARKrgs this fragment did not alter acute hypertrophy after pressure overload or demonstrate RGS activityin vivoagainst Gq-mediated signaling. Herein, we subjected these transgenic mice to pressure overload and found that unlike their littermate controls or previous GRK2 fragments, they exhibited an increased left ventricular wall thickness and mass prior to cardiac stress that underwent proportional hypertrophic growth to controls after acute pressure overload. Importantly, despite this enlarged heart, βARKnt mice did not undergo the expected transition to heart failure observed in controls. Further, βARKnt expression limited adverse left ventricular remodeling and increased cell survival signaling. These data support the idea that the βARKnt peptide embodies a distinct functional interaction and novel means of cardioprotection during pressure-overload induced heart failure.
Divergent SARS-CoV-2-specific T and B cell responses in severe but not mild COVID-19
Authors: Oja Anna E. , Saris Anno , Ghandour Cherien A. , Kragten Natasja A.M. , Hogema Boris M. , Nossent Esther J. , Heunks Leo M.A. , Cuvalay Susan , Slot Ed , Swaneveld Francis H. , Vrielink Hans , Rispens Theo , van der Schoot Ellen , van Lier René A.W. , Brinke Anja Ten , Hombrink Pleun 
Published: June 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. Understanding both the immunological processes providing specific immunity and potential immunopathology underlying the pathogenesis of this disease may provide valuable insights for potential therapeutic interventions. Here, we quantified SARS-CoV-2 specific immune responses in patients with different clinical courses. Compared to individuals with a mild clinical presentation, CD4+ T cell responses were qualitatively impaired in critically ill patients. Strikingly, however, in these patients the specific IgG antibody response was remarkably strong. The observed disparate T and B cell responses could be indicative of a deregulated immune response in critically ill COVID-19 patients.
Inferring Tumor Progression in Large Datasets
Authors: Neyshabouri Mohammadreza Mohaghegh , Jun Seong-Hwan , Lagergren Jens 
Published: June 2020

AbstractIdentification of mutations of the genes that give cancer a selective advantage is an important step towards research and clinical objectives. As such, there has been a growing interest in developing methods for identification of driver genes and their temporal order within a single patient (intra-tumor) as well as across a cohort of patients (inter-tumor). In this paper, we develop a probabilistic model for tumor progression, in which the driver genes are clustered into several ordered driver pathways. We develop an efficient inference algorithm that exhibits favorable scalability to the number of genes and samples compared to a previously introduced ILP-based method. Adopting a probabilistic approach also allows principled approaches to model selection and uncertainty quantification. Using a large set of experiments on synthetic datasets, we demonstrate our superior performance compared to the ILP-based method. We also analyze two biological datasets of colorectal and glioblastoma cancers. We emphasize that while the ILP-based method puts many seemingly passenger genes in the driver pathways, our algorithm keeps focused on truly driver genes and outputs more accurate models for cancer progression.Author summaryCancer is a disease caused by the accumulation of somatic mutations in the genome. This process is mainly driven by mutations in certain genes that give the harboring cells some selective advantage. The rather few driver genes are usually masked amongst an abundance of so-called passenger mutations. Identification of the driver genes and the temporal order in which the mutations occur is of great importance towards research and clinical objectives. In this paper, we introduce a probabilistic model for cancer progression and devise an efficient inference algorithm to train the model. We show that our method scales favorably to large datasets and provides superior performance compared to an ILP-based counterpart on a wide set of synthetic data simulations. Our Bayesian approach also allows for systematic model selection and confidence quantification procedures in contrast to the previous non-probabilistic progression models. We also study two large datasets on colorectal and glioblastoma cancers and validate our inferred model in comparison to the ILP-based method.
Structure of the complete, membrane-assembled COPII coat reveals a complex interaction network
Authors: Hutchings Joshua , Stancheva Viktoriya G. , Brown Nick R. , Cheung Alan C.M. , Miller Elizabeth A. , Zanetti Giulia 
Published: June 2020

AbstractThe COPII coat mediates Endoplasmic Reticulum (ER) to Golgi trafficking for thousands of proteins. Five essential coat proteins assemble at the ER into a characteristic two-layer architecture, which recruits cargo proteins whilst sculpting membrane carriers with diverse morphologies. How coat architecture drives membrane curvature whilst ensuring morphological plasticity is largely unknown, yet is central to understanding mechanisms of carrier formation. Here, we use an established reconstitution system to visualise the complete, membrane-assembled COPII coat with unprecedented detail by cryo-electron tomography and subtomogram averaging. We discover a network of interactions within and between coat layers, including multiple interfaces that were previously unknown. We reveal the physiological importance of these interactions using genetic and biochemical approaches. A newly resolved Sec31 C-terminal domain provides order to the coat and is essential to drive membrane curvature in cells. Moreover, a novel outer coat assembly mode provides a basis for coat adaptability to varying membrane curvatures. Furthermore, a newly resolved region of Sec23, which we term the L-loop, imparts coat stability and in part dictates membrane shape. Our results suggest these interactions collectively contribute to coat organisation and membrane curvature, providing a structural framework to understand regulatory mechanisms of COPII trafficking and secretion.
Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol
Authors: Wang Hao , Kulas Joshua A. , Ferris Heather A. , Hansen Scott B. 
Published: June 2020

ABSTRACTAlzheimer’s Disease (AD) is characterized by the presence of β-Amyloid (Aβ) plaques, tau tangles, inflammation, and loss of cognitive function. Genetic variation in a cholesterol transport protein, apolipoprotein E (apoE), is the most common genetic marker for sporadic AD.In vitroevidence suggests apoE links to Aβ production through nanoscale lipid compartments (also called lipid rafts), but its regulationin vivois unclear. Here we use super-resolution imaging in mouse brain to show apoE utilizes astrocyte-derived cholesterol to specifically traffic neuronal amyloid precursor protein (APP) into lipid rafts where it interacts with β- and γ-secretases to generate Aβ-peptide. We find that targeted deletion of astrocyte cholesterol synthesis robustly reduces amyloid and tau burden in a mouse model of AD. Treatment with cholesterol-free apoE or knockdown of cholesterol synthesis in astrocytes decreases cholesterol levels in cultured neurons and causes APP to traffic out of lipid rafts where it interacts with α-secretase and gives rise to soluble APPα (sAPPα), a neuronal protective product of APP. Changes in cellular cholesterol have no effect on α-, β-, and γ-secretase trafficking, suggesting the ratio of Aβ to sAPPα is regulated by the trafficking of the substrate, not the enzymes. Treatment of astrocytes with inflammatory cytokines IL-1β, IL-6 and TNF-α upregulates the synthesis of cholesterol in the astrocytes. We conclude that cholesterol is kept low in neurons to inhibit Aβ formation and enable astrocyte regulation of Aβ formation by cholesterol regulation.HighlightsApoE regulates amyloid precursor protein localization to rafts and its exposure to α-vs. β-secretase.α-, β-, and γ-Secretases are activated by substrate presentation.ApoE specifically transports astrocyte cholesterol to neurons.Astrocyte cholesterol synthesis disruption prevents Alzheimer’s-associated amyloid pathology in mice.
AL-PHA beads: bioplastic-based protease biosensors for global health applications
Authors: Kelwick Richard J. R. , Webb Alexander J. , Wang Yizhou , Heliot Amelie , Allan Fiona , Emery Aidan M. , Templeton Michael R. , Freemont Paul S. 
Published: June 2020

ABSTRACTProteases are multi-functional proteolytic enzymes that have complex roles in human health and disease. Therefore, the development of protease biosensors can be beneficial to global health applications. To this end, we developed Advanced proteoLytic detector PolyHydroxyAlkanoates (AL-PHA) beads – a library of over 20 low-cost, biodegradable, bioplastic-based protease biosensors. Broadly, these biosensors utilise PhaC-reporter fusion proteins that are bound to microbially manufactured polyhydroxyalkanoate beads. In the presence of a specific protease, superfolder green fluorescent reporter proteins are cleaved from the AL-PHA beads - resulting in a loss of bead fluorescence. The Tobacco Etch Virus (TEV) AL-PHA biosensor detected the proteolytic activity of at least 1.85 pM of AcTEV. AL-PHA beads were also engineered to detect cercarial elastase fromSchistosoma mansoni-derived cercarial transformation fluid (SmCTF) samples, as well as cancer-associated metalloproteinases in extracellular vesicle and cell-conditioned media samples. We envision that AL-PHA beads could be further developed for use in resource-limited settings.
Accurate contrast determination for X-ray speckle visibility spectroscopy
Authors: Sun Yanwen , Montana-Lopez Jordi , Fuoss Paul , Sutton Mark , Zhu Diling 
Published: June 2020

X-ray speckle visibility spectroscopy using X-ray free-electron lasers has long been proposed as a probe of fast dynamics in noncrystalline materials. In this paper, numerical modeling is presented to show how the data interpretation of visibility spectroscopy can be impacted by the nonidealities of real-life X-ray detectors. Using simulated detector data, this work provides a detailed analysis of the systematic errors of several contrast extraction algorithms in the context of low-count-rate X-ray speckle visibility spectroscopy and their origins are discussed. Here, it was found that the finite detector charge cloud and pixel size lead to an unavoidable `degeneracy' in photon position determination, and that the contrasts extracted using different algorithms can all be corrected by a simple linear model. The results suggest that experimental calibration of the correction coefficient at the count rate of interest is possible and essential. This allows computationally lightweight algorithms to be implemented for on-the-fly analysis.
Enablers and barriers to knowledge management in universities: perspectives from South Africa and Mauritius
Authors: Veer Ramjeawon Poonam , Rowley Jennifer 
Published: June 2020

PurposeUniversities need to manage their knowledge assets, and, to work creatively to maximize the enablers and minimize the barriers associated with knowledge management processes. This research offers a comparative perspective on knowledge management in universities in two countries whose university sectors are at different stages of their development, South Africa and Mauritius.Design/methodology/approachSemi-structured interviews were conducted with expert informants from 10 high-ranking universities in Mauritius and South Africa, who held senior roles in research and its management within their respective universitiesFindingsBoth enablers and barriers (eandb) were evident in relation to: strategies and policies, organizational structures, rewards and incentives, culture, technology, leadership, human resources, resources and funding, and university-industry linkages, although the significance of these eandbs varied between the three knowledge processes, knowledge creation, knowledge sharing and knowledge transfer. Overall, Mauritius, with a less developed university sector, faced more challenges in respect of knowledge management than did South Africa.Originality/valueThis study's theoretical contribution is a holistic framework for enabling KM in universities on the basis of a mapping between KM eandb's and KM processes. This comparative country level study, embracing a number of universities, offers insights into national policy, and cultural expectations that influence the extent and nature of barriers and enablers to effective KM. The insights offered by this study will be valuable for Mauritius and South Africa, and also for universities in other countries.
Accuracy of road construction preliminary estimate: examining the influencing factors
Authors: Akinradewo Opeoluwa , Aigbavboa Clinton , Oke Ayodeji 
Published: June 2020

PurposePreparation of preliminary estimate is difficult owing to the lack of full project details in the early phases of the construction project. This paper seeks to assess the estimation techniques used for road projects and the critical factors affecting their accuracy in the Ghanaian construction industry.Design/methodology/approachQuantitative research design was adopted and questionnaire was designed to retrieve data. The target population were engineers and quantity surveyors who were contacted using an e-questionnaire through their professional bodies owing to location constraints. Retrieved data were analysed using descriptive and exploratory factor analysis. In order to compare the opinions of the respondents, the Mann–Whitney U-test was employed.FindingsThe survey revealed that subjective, parametric, comparative and analytical estimations are in use in Ghana. The most critical factors influencing the accuracy of estimation techniques are improper project planning, insufficient preliminary site investigation and usage of shortcuts, among others.Research limitations/implicationsThis study was limited to Accra, Ghana, due to time and distance constraint.Practical implicationsFor accuracy of preliminary estimates to be improved, estimators being the custodian of the estimate are expected to be devoid of errors such as arithmetic calculation errors, inaccurate quantity measurement and error of omission. The usage of estimating software can eliminate these human errors.Originality/valueThe study will assist policymakers and stakeholders in aligning mitigative actions for factors influencing preliminary estimate of road projects with defined clusters rather than basic ranks. With attention focussed on the characteristics of each cluster, accuracy of preliminary estimate can be improved.
An enhanced adaptive butterfly optimization algorithm rigorously verified on engineering problems and implemented to ISAR image motion compensation
Authors: Ustun Deniz 
Published: June 2020

Purpose
This study aims to evolve an enhanced butterfly optimization algorithm (BOA) with respect to convergence and accuracy performance for numerous benchmark functions, rigorous constrained engineering design problems and an inverse synthetic aperture radar (ISAR) image motion compensation.

Design/methodology/approach
Adaptive BOA (ABOA) is thus developed by incorporating spatial dispersal strategy to the global search and inserting the fittest solution to the local search, and hence its exploration and exploitation abilities are improved.

Findings
The accuracy and convergence performance of ABOA are well verified via exhaustive comparisons with BOA and its existing variants such as improved BOA (IBOA), modified BOA (MBOA) and BOA with Levy flight (BOAL) in terms of various precise metrics through 15 classical and 12 conference on evolutionary computation (CEC)-2017 benchmark functions. ABOA has outstanding accuracy and stability performance better than BOA, IBOA, MBOA and BOAL for most of the benchmarks. The design optimization performance of ABOA is also evaluated for three constrained engineering problems such as welded beam design, spring design and gear train design and the results are compared with those of BOA, MBOA and BOA with chaos. ABOA, therefore, optimizes engineering designs with the most optimal variables. Furthermore, a validation is performed through translational motion compensation (TMC) of the ISAR image for an aircraft, which includes blurriness. In TMC, the motion parameters such as velocity and acceleration of target are optimally predicted by the optimization algorithms. The TMC results are elaborately compared with BOA, IBOA, MBOA and BOAL between each other in view of images, motion parameter and numerical image measuring metrics.

Originality/value
The outperforming results reflect the optimization and design successes of ABOA which is enhanced by establishing better global and local search abilities over BOA and its existing variants.
The role of norms in information security policy compliance
Authors: Wiafe Isaac , Koranteng Felix Nti , Wiafe Abigail , Obeng Emmanuel Nyarko , Yaokumah Winfred 
Published: June 2020

PurposeThe purpose of this paper is to determine which factors influence information system security policy compliance. It examines how different norms influence compliance intention.Design/methodology/approachBased on relevant literature on information system security policy compliance, a research model was developed and validated. An online questionnaire was used to gather data from respondents and partial least square structural equation modelling (PLS-SEM) was used to analyse 432 responses received.FindingsThe results indicated that attitude towards information security compliance mediates the effects of personal norms on compliance intention. In addition, descriptive and subjective norms are significant predictors of personal norms.Originality/valueThough advancement in technology has reached significant heights, it is still inadequate to guaranteed information systems’ security. Researchers have identified humans to be central in ensuring information security. To this effect, this study provides empirical evidence of the role of norms in influence information security behaviour.
Proposing a new model for long-term learning among mid-level school leaders: toward enhancing organizational learning via simulation training
Authors: Shapira-Lishchinsky Orly 
Published: June 2020

PurposeThe purpose of this paper is to propose a new theory promoting long-term learning among mid-level leaders in schools via simulation training.Design/methodology/approachThe proposed model is derived from the socioecological model, a model that takes into account the multifaceted effects of different disciplines. The proposed interdisciplinary model may be assimilated by considering the ethical-social context of mid-level leaders undergoing simulation training.FindingsA new interdisciplinary model emerges from the original socioecological model. The model's interdisciplinary approach, crossing disciplines such as leadership, management and learning, enables this model to serve as a platform for research that enhances long-term learning among mid-level leaders in schools.Practical implicationsThe elicited model, which can be assimilated via simulation training, may enhance long-term learning among mid-level leaders in schools and help to shape educational policy, improve learning and impact the exchange of knowledge between countries.Originality/valueThe emergent interdisciplinary model is expected to foster thinking beyond the traditional boundaries of each discipline and to enhance long-term learning in an ethical context among mid-level school leaders. The model's interdisciplinary approach, which creates new emergent dimensions suited to the challenges of the 21st century, makes this model a unique platform for research and simulation training that enhances long-term learning.