bluuebunny/crossref_metadata_2025_split huggingface dataset:
Red blood cell-derived extracellular vesicles mediate intercellular communication in ischemic heart failure
Authors: Das Avash , Valkov Nedyalka , Salvador Ane M. , Kur Ivan , Ziegler Olivia , Yeri Ashish , Garcia Fernando Camacho , Lu Shulin , Khamesra Aushee , Xiao Chunyang , Rodosthenous Rodosthenis , Li Guoping , Srinivasan Srimeenakshi , Toxavidis Vasilis , Tigges John , Laurent Louise C. , Momma Stefan , Ghiran Ionita , Das Saumya 
Published: May 2019

SummaryExtracellular vesicles (EV) mediate intercellular signaling by transferring their cargo to recipient cells. Red blood cell (RBC)-derived EVs constitute a significant proportion of circulating EVs and have been implicated in regulating immune responses. Here, we describe a transgenic mouse model for fluorescent-based mapping of RBC-EV target cells based on the functional transfer of EV-contained Cre-recombinase to target cells. In a murine model of ischemic heart failure, we detect an increase in RBC-EV-targeted cardiomyocytes in the hearts and microglial cells in the brains. Cells targeted by RBC-EVs present an enrichment of genes implicated in cell proliferation and metabolism pathways compared to non-recombined (non-targeted) cells. Cardiomyocytes targeted by RBC-EVs are more likely to demonstrate cellular markers of DNA synthesis and proliferation, suggesting functional significance of EV-mediated signaling. In conclusion, we leverage our mouse model for mapping of RBC-EV targets in murine ischemic heart failure to demonstrate quantitative and qualitative changes in RBC-EV recipients.
Efficient and robust NK-Cell transduction with Baboon Envelope pseudotyped lentivector: a major tool for immunotherapy
Authors: Colamartino Aurelien B.L. , Lemieux William , Bifsha Panojot , Nicoletti Simon , Chakravarti Nitin , Remon Joaquin Sanz , Roméro Hugo , Selleri Silvia , Béland Kathie , Guiot Mélanie , Tremblay-Laganière Camille , Dicaire Renée , Barreiro Luis , Lee Dean A. , Verhoeyen Els , Haddad Elie 
Published: May 2019

ABSTRACTNK-cell resistance to transduction is a major technical hurdle for developing NK-cell immunotherapy. By using Baboon envelope pseudotyped lentiviral vectors (BaEV-LVs) encoding eGFP, we obtained a transduction rate of 23.0±6.6% in freshly-isolated NK-cells (FI-NK) and 83.4±10.1% in NK-cells obtained from the NK-cell Activation and Expansion System (NKAES), even at low MOI, with a sustained transgene expression for at least 21 days. BaEV-LVs outperformed Vesicular Stomatitis Virus type-G (VSV-G)-, RD114-and Measles Virus (MV)-pseudotyped LVs (p<0.001). mRNA expression of both BaEV receptors, ASCT1 and ASCT2, was detected in FI-NK and NKAES, with much higher expression in NKAES. Transduction with BaEV-LVs encoding for CAR-CD22 resulted in robust CAR-expression on 44.2%±14.2% of NKAES cells, which allowed the specific killing of the NK-resistant pre-B-ALL-RS4;11 cell line. Using a larger vector, encoding a dual CD19/CD22-CAR separated by T2A, we were able to transduce and re-expand dual-CAR-expressing NKAES, even with low viral titer. These dual-CAR-NK efficiently and specifically killed both CD19KO-and CD22KO-RS4;11 cells, which may overcome antigen-loss escape in the clinical setting. Our results suggest that BaEV-LVs may efficiently enable NK-cell biological studies and translation of NK-cell-based immunotherapy to the clinic.
Linker dependence of avidity in multivalent interactions between disordered proteins
Authors: Sørensen Charlotte S. , Jendroszek Agnieszka , Kjaergaard Magnus 
Published: May 2019

AbstractMultidomain proteins often interact through several independent binding sites connected by disordered linkers. The architecture of such linkers affect avidity by modulating the effective concentration of intra-molecular binding. The linker dependence of avidity has been estimated theoretically using simple physical models, but such models have not been tested experimentally since the effective concentrations could not be measured directly. We have developed a model system for bivalent protein interactions connected by disordered linkers, where the effective concentration can be measured using a competition experiment. We characterized the bivalent protein interactions kinetically and thermodynamically for a variety of linker lengths and interaction strengths. In total, this allowed us to critically assess the existing theoretical models of avidity in disordered, multivalent interactions. As expected, the onset of avidity occurs when the effective concentration reached the dissociation constant of the weakest interaction. Avidity decreased monotonously with linker length, but only by a third of what is predicted by theoretical models. We suggest that the length dependence of avidity is attenuated by compensating mechanisms such as linker interactions or entanglement. The direct role of linkers in avidity suggest they provide a generic mechanism for allosteric regulation of disordered, multivalent proteins.
All-FIT: Allele-Frequency-based Imputation of Tumor Purity from High-Depth Sequencing Data
Authors: Loh Jui Wan , Guccione Caitlin , Di Clemente Frances , Riedlinger Gregory , Ganesan Shridar , Khiabanian Hossein 
Published: May 2019

AbstractMotivationClinical sequencing aims to identify somatic mutations in cancer cells for accurate diagnosis and treatment. However, most widely used clinical assays lack patient-matched control DNA and additional analysis is needed to distinguish somatic and unfiltered germline variants. Such computational analyses require accurate assessment of tumor cell content in individual specimens. Histological estimates often do not corroborate with results from computational methods that are primarily designed for normal-tumor matched data and can be confounded by genomic heterogeneity and presence of sub-clonal mutations.MethodsAll-FIT is an iterative weighted least square method to estimate specimen tumor purity based on the allele frequencies of variants detected in high-depth, targeted, clinical sequencing data.ResultsUsing simulated and clinical data, we demonstrate All-FIT’s accuracy and improved performance against leading computational approaches, highlighting the importance of interpreting purity estimates based on expected biology of tumors.Availability and ImplementationFreely available at http://software.khiabanian-lab.org.
Deleting a UBE3A substrate rescues impaired hippocampal physiology and learning in Angelman syndrome mice
Authors: Sell Gabrielle L. , Xin Wendy , Cook Emily K. , Zbinden Mark A. , Schaffer Thomas B. , O’Meally Robert N. , Cole Robert N. , Bonci Antonello , Margolis Seth S. 
Published: May 2019

ABSTRACTIn humans, loss-of-function mutations in the UBE3A gene lead to the neurodevelopmental disorder Angelman syndrome (AS). AS patients have severe impairments in speech, learning and memory, and motor coordination, for which there is currently no treatment. In addition, UBE3A is duplicated in >1-2% of patients with autism spectrum disorders – a further indication of the significant role it plays in brain development. Altered expression of UBE3A, an E3 ubiquitin ligase, is hypothesized to lead to impaired levels of its target proteins, but identifying the contribution of individual UBE3A targets to UBE3A-dependent deficits remains of critical importance. Ephexin5 is a putative UBE3A substrate that has restricted expression early in development, regulates synapse formation during hippocampal development, and is abnormally elevated in AS mice, modeled by maternally-derived Ube3a gene deletion. Here, we report that Ephexin5 is a direct substrate of UBE3A ubiquitin ligase activity. Furthermore, removing Ephexin5 from AS mice specifically rescued hippocampus-dependent behaviors, CA1 physiology, and deficits in dendritic spine number. Our findings identify Ephexin5 as a key driver of hippocampal dysfunction and related behavioral deficits in AS mouse models. These results demonstrate the exciting potential of targeting Ephexin5, and possibly other UBE3A substrates, to improve symptoms of AS and other UBE3A-related developmental disorders.
CAIX forms a transport metabolon with monocarboxylate transporters in human breast cancer cells
Authors: Ames Samantha , Andring Jacob T. , McKenna Robert , Becker Holger M. 
Published: May 2019

AbstractTumor cells rely on glycolysis to meet their elevated demand for energy. Thereby they produce significant amounts of lactate and protons, which are exported via monocarboxylate transporters (MCTs), supporting the formation of an acidic microenvironment. The present study demonstrates that carbonic anhydrase IX (CAIX), one of the major acid/base regulators in cancer cells, forms a protein complex with MCT1 and MCT4 in tissue samples from human breast cancer patients, but not healthy breast tissue. Formation of this transport metabolon requires binding of CAIX to the Ig1 domain of the MCT1/4 chaperon CD147 and is required for CAIX-mediated facilitation of MCT1/4 activity. Application of an antibody, directed against the CD147-Ig1 domain, displaces CAIX from the transporter and suppresses CAIX-mediated facilitation of proton-coupled lactate transport. In cancer cells, this “metabolon disruption” results in a decrease in lactate transport, reduced glycolysis and ultimately reduced cell proliferation. Taken together, the study shows that carbonic anhydrases form transport metabolons with acid/base transporters in human tumor tissue and that these interactions can be exploited to interfere with tumor metabolism and proliferation.
SAMbinder: A web server for predicting SAM binding residues of a protein from its amino acid sequence
Authors: Agrawal Piyush , Mishra Gaurav , Raghava Gajendra P. S. 
Published: May 2019

AbstractMotivationS-adenosyl-L-methionine (SAM) is one of the important cofactor present in the biological system and play a key role in many diseases. There is a need to develop a method for predicting SAM binding sites in a protein for designing drugs against SAM associated disease. Best of our knowledge, there is no method that can predict the binding site of SAM in a given protein sequence.ResultThis manuscript describes a method SAMbinder, developed for predicting SAM binding sites in a protein from its primary sequence. All models were trained, tested and evaluated on 145 SAM binding protein chains where no two chains have more than 40% sequence similarity. Firstly, models were developed using different machine learning techniques on a balanced dataset contain 2188 SAM interacting and an equal number of non-interacting residues. Our Random Forest based model developed using binary profile feature got maximum MCC 0.42 with AUROC 0.79 on the validation dataset. The performance of our models improved significantly from MCC 0.42 to 0.61, when evolutionary information in the form of PSSM profile is used as a feature. We also developed models on realistic dataset contains 2188 SAM interacting and 40029 non-interacting residues and got maximum MCC 0.61 with AUROC of 0.89. In order to evaluate the performance of our models, we used internal as well as external cross-validation technique.Availability and implementationhttps://webs.iiitd.edu.in/raghava/sambinder/.
Application of extracellular flux analysis for determining mitochondrial function in mammalian oocytes and early embryos
Authors: Muller Bethany , Lewis Niamh , Adeniyi Tope , Leese Henry J , Brison Daniel , Sturmey Roger G 
Published: May 2019

1.AbstractBackgroundMitochondria provide the major source of ATP for mammalian oocyte maturation and early embryo development. Oxygen Consumption Rate (OCR) is an established measure of mitochondrial function. OCR by mammalian oocytes and embryos has generally been restricted to overall uptake and detailed understanding of the components of OCR dedicated to specific molecular events remains lacking.ResultsHere, extracellular flux analysis (EFA) was applied to small groups of bovine, equine, mouse and human oocytes and bovine early embryos to measure OCR. Using EFA, we report the changes in mitochondrial activity during the processes of oocyte maturation, fertilization, and pre-implantation development to blastocyst stage in response to physiological demands in mammalian embryos. Crucially, we describe the real time partitioning of overall OCR to spare capacity, proton leak, non-mitochondrial and coupled respiration – showing that while there are alterations in activity over the course of development to respond to physiological demand, the overall efficiency is unchanged.ConclusionEFA is shown to be able to measure mitochondrial function in small groups of mammalian oocytes and embryos in a manner which is robust, rapid and easy to use. EFA is non-invasive and allows real-time determination of the impact of compounds on OCR, facilitating an assessment of the parameters of mitochondrial activity. This provides proof-of-concept for EFA as an accessible system with which to study oocyte and embryo metabolism.
Matter of opinion
Authors: Puroila Jenni , Mäkelä Hannele 
Published: May 2019

PurposeThe purpose of this paper is to contribute to the socio-political role of materiality assessment in sustainability reporting literature and discuss the potential of materiality assessment to advance more inclusive accounting and reporting practices, in particular critical dialogic accounting.Design/methodology/approachDrawing on literature on the concept of materiality together with insights from stakeholder engagement, commensuration and critical dialogic accounting the paper analyses disclosure on materiality in sustainability reports. Empirically, qualitative content analysis is used to analyse 44 sustainability reports from the leading companies.FindingsThe authors argue that, first, the technic-rational approach to materiality portrays the assessment as a neutral and value-free measurement, and second, the materiality matrix presents the multiple stakeholders as having a unified understanding of what is considered important in corporate sustainability. Thus, the technic-rational approach to the materiality assessment, reinforced with the use of the matrix is a value-laden judgement of what matters in corporate sustainability and narrows down rather than opens up the complexity of the assessment of material sustainability issues, stakeholder engagement and the societal pursuit of sustainable development.Originality/valueThe understandings and implications of the concept of materiality are ambiguous and wide-reaching, as, through constituting the legitimised set of claims and information on corporate sustainable performance, it impacts our understanding of sustainable development at large, and affects the corporate and policy-level transition towards sustainability. Exploring insights from critical dialogic accounting help us to elaborate on the conceptions and practical implications of materiality assessment that enhance stakeholder engagement in a democratic, rather than managerial, spirit.
Reassessing the contents and context of governance in Asia: recognizing achievements
Authors: Huque Ahmed Shafiqul 
Published: May 2019

Purpose
Good governance has been declared as the key target of most Asian governments, but it appears to be an unattainable objective. The purpose of this paper is to explore the potentials for establishing governance across Asian countries. Drawing upon the literature and experience of Asian countries, the study argues that governance represents an unclear state that is rooted more in perception than reality. An extensive review of the indicators of governance reveals the anomaly and unorganized efforts to measure it, and points to the need for recognizing accomplishments in areas that are not directly or indirectly covered in the existing schemes of assessment.

Design/methodology/approach
The paper is based on a broad review of the literature on governance and political systems in Asian countries. Existing arrangements for assessing governance are critically reviewed to point out the risks in a perception-dependent approach. Secondary sources and insight obtained from relevant research constitute the data analyzed in the paper.

Findings
The paper finds that the target of good governance cannot be fully achieved due to the significant diversity across Asian countries as well as varied perceptions held by assessors. Stakeholders have different perceptions about the requirements and ideal of governance and existing tools for measuring governance are inadequate. Most importantly, assessment frameworks do not recognize contextual dimensions that are relevant to Asian countries. Furthermore, it is important to recognize efforts that are aimed at improving conditions instead of working toward an absolute outcome of governance. Recognition of small successes will contribute to the improvement of circumstances rather than ranking countries on the basis of a limited number of perception-based indicators and listing them on international indices.

Research limitations/implications
The paper does not draw upon primary sources of information and is limited to an assessment of existing arrangements.

Practical implications
The paper will help draw attention to the limitations of existing arrangements of assessing countries and ranking them for the quality of governance. It will also encourage researchers to think about alternative tools for assessing governance and recognizing progress in Asian countries.

Social implications
The paper will encourage governments to identify obstacles to good governance and adopt policies to overcome them.

Originality/value
The paper contributes to the literature presenting a critical view for encouraging alternative approach to governance, incorporating perceptions of diverse stakeholders and highlights the need to recognize progress, however limited, in all areas.
“It put control back onto my family situation”: family experiences of positive behaviour support
Authors: Botterill Sinead , Cottam Susan , Fowke Alex , Theodore Kate 
Published: May 2019

Purpose
Positive behaviour support (PBS) is currently considered best practice for managing challenging behaviour in young people with intellectual and developmental disabilities. A key principle of PBS is that all members of the person’s support network participate in the assessment and intervention. It is, therefore, important to understand what factors act as facilitators or barriers to family engagement; however, research in this area is limited. The purpose of this paper is to conduct a novel piece of qualitative research analysis into experiences of family members of young people who have received family-based PBS.

Design/methodology/approach
Eight parents of a young person with an intellectual or developmental disability who had received PBS were interviewed about their experiences and factors they found helpful and hindering in terms of their engagement. Thematic analysis allowed a detailed and robust interpretation of the qualitative data.

Findings
Five superordinate themes were identified, namely, PBS is more than just strategies, considering the family context, the therapist/family relationship, acknowledging challenges and the ongoing nature of the problem and supporting family member change.

Research limitations/implications
Although research was rigorously conducted, the small sample size mean findings should be considered preliminary.

Originality/value
The literature related to family engagement in PBS is limited and largely based on the opinions of professionals. This study identified factors that parents themselves felt were helpful and hindering in terms of their engagement and offers practical suggestions for services and future research.
Planning of sport and recreational facilities informed by interdisciplinary knowledge
Authors: Hjort Mikkel , Martin W. Mike , Troelsen Jens 
Published: May 2019

PurposeThe purpose of this paper is to develop a design strategy that investigates the systematic use of interdisciplinary knowledge through a transparent decision-making process. The study identifies relevant design parameters that should be considered in the development of this design strategy.Design/methodology/approachThe empirical data were collected through observations of the design process of two new sport facilities, meetings with sport, well-being and aging experts and through semi-structured interviews with end-users. The development of the proposed design strategy is based on a methodology with elements from “Knowledge to Action (KTA),” “Action research” and a “List of value concepts.” The rigid timetable guaranteed systematic progress, where both knowledge from the end-users and experts were incorporated throughout the decision-making process.FindingsThe two case studies documented results involving end-users and experts in a systematic way. In conclusion, it was apparent that the use of interdisciplinary collaboration informed the design outcome.Practical implicationsBased on the two cases, the following advice can be given to the architectural profession: architects should use the KTA model or similar in order to target the search for relevant interdisciplinary knowledge and ensure that relevant evidence is involved in the design process of upcoming projects regarding sport and recreation. Architects should make the design process transparent so that one can see which design decisions have been made through the design process. This must be done to ensure that there is greater coherence between vision and practice.Originality/valueThe study showed how architects could import knowledge, skills and values from other disciplines such as environmental psychology and active living research to improve the decision-making process of future sport and recreation projects. It was also clear that this design decision process could be made more transparent in the effort to allow the various stakeholders to take ownership of the resulting design outcomes.