bluuebunny/crossref_metadata_2025_split huggingface dataset:
BioISO: an objective-oriented application for assisting the curation of genome-scale metabolic models
Authors: Cruz Fernando , Capela João , Ferreira Eugénio C. , Rocha Miguel , Dias Oscar 
Published: March 2021

AbstractAs the reconstruction of Genome-Scale Metabolic Models becomes standard practice in systems biology, the number of organisms having at least one metabolic model at the genome-scale is peaking at an unprecedented scale. The automation of several laborious tasks, such as gap-finding and gap-filling, allowed to develop GSMMs for poorly described organisms. However, such models’ quality can be compromised by the automation of several steps, which may lead to erroneous phenotype simulations.The Biological networks constraint-basedIn SilicoOptimization (BioISO) is a computational tool aimed at accelerating the reconstruction of Genome-Scale Metabolic Models. This tool facilitates the manual curation steps by reducing the large search spaces often met when debuggingin silicobiological models.BioISOuses a recursive relation-like algorithm and Flux Balance Analysis to evaluate and guide debugging ofin silicophenotype simulations. The potential ofBioISOto guide the debugging of model reconstructions was showcased using GSMMs available in literature and compared with the results of two other state-of-the-art gap-filling tools (MenecoandfastGapFill). Furthermore,BioISOwas used asMeneco’s gap-finding algorithm to reduce the number of proposed solutions (reaction sets) for filling the gaps.BioISOwas implemented as a webserver available athttps://bioiso.bio.di.uminho.pt; and integrated intomerlinas a plugin.BioISO’simplementation as a Python™ package can also be retrieved fromhttps://github.com/BioSystemsUM/BioISO.
Development and pre-clinical evaluation of Newcastle disease virus-vectored SARS-CoV-2 intranasal vaccine candidate
Authors: Díaz Manolo Fernandez , Calderon Katherine , Rojas-Neyra Aldo , Vakharia Vikram N. , Choque-Guevara Ricardo , Montalvan Angela , Poma-Acevedo Astrid , Rios-Matos Dora , Agurto-Arteaga Andres , Cauti-Mendoza María de Grecia , Perez-Martinez Norma , Isasi-Rivas Gisela , Tataje-Lavanda Luis , Palomino Miryam , Bailón Henri , Sernaque-Aguilar Yacory , Ygnacio-Aguirre Freddy , Criollo-Orozco Manuel , Huaccachi-Gonzalez Edison , Delgado-Ccancce Elmer , Villanueva-Pérez Doris , Montesinos-Millan Ricardo , Gutiérrez-Manchay Kristel , Pauyac-Antezana Katherine , Ramirez-Ortiz Ingrid , Quiñones-Garcia Stefany , Cauna-Orocollo Yudith , Vallejos-Sánchez Katherine , Rios-Angulo Angela A. , Núñez-Fernández Dennis , Salguedo-Bohorquez Mario I. , Ticona Julio , Sánchez Manolo Fernández , García Paquita , Icochea Eliana , Guevara Luis , Zimic Mirko ,   for the COVID-19 Working Group in Perú
Published: March 2021

ABSTRACTThe COVID-19 pandemic has claimed the lives of millions of people worldwide and threatens to become an endemic problem, therefore the need for as many types of vaccines as possible is of high importance.Because of the millions of doses required, it is desirable that vaccines are not only safe and effective, but also easy to administer, store, and inexpensive to produce.Newcastle Disease Virus (NDV) is responsible for a respiratory disease in chickens. It has no pathogenic homologue in humans. NDV is recognized as an oncolytic virus, and its use in humans for oncological treatment is being evaluated.In the present work, we have developed two types of NDV-vectored candidate vaccines, which carry the surface-exposed RBD and S1 antigens of SARS-CoV-2, respectively. These vaccine candidates were produced in specific-pathogen-free embryonating chicken eggs, and purified from allantoic fluid before lyophilization. These vaccines were administered intranasally to three different animal models: mice, rats and hamsters, and evaluated for safety, toxicity, immunogenicity, stability and efficacy. Efficacy was evaluated in a challenge assay against active SARS-CoV-2 virus in the Golden Syrian hamster model.The NDV-vectored vaccine based on the S1 antigen was shown to be safe and highly immunogenic, with the ability to neutralize SARS-CoV-2 in-vitro, even with an extreme dilution of 1/640. Our results reveal that this vaccine candidate protects the lungs of the animals, preventing cellular damage in this tissue. In addition, this vaccine reduces the viral load in the lungs, suggesting that it may significantly reduce the likelihood of transmission. Being lyophilized, this vaccine candidate is very stable and can be stored for several months at 4-8⁰C.In conclusion, our NDV-based vaccine candidate has shown a very favorable performance in the pre-clinical study, serving as evidence for a future evaluation in a Phase-I human clinical trial. This candidate represents a promising tool in the fight against COVID-19.
Dissecting Transition Cells from Single-cell Transcriptome Data through Multiscale Stochastic Dynamics
Authors: Zhou Peijie , Wang Shuxiong , Li Tiejun , Nie Qing 
Published: March 2021

AbstractAdvances of single-cell technologies allow scrutinizing of heterogeneous cell states, however, analyzing transitions from snap-shot single-cell transcriptome data remains challenging. To investigate cells with transient properties or mixed identities, we present MuTrans, a method based on multiscale reduction technique for the underlying stochastic dynamical systems that prescribes cell-fate transitions. By iteratively unifying transition dynamics across multiple scales, MuTrans constructs the cell-fate dynamical manifold that depicts progression of cell-state transition, and distinguishes meta-stable and transition cells. In addition, MuTrans quantifies the likelihood of all possible transition trajectories between cell states using the coarse-grained transition path theory. Downstream analysis identifies distinct genes that mark the transient states or drive the transitions. Mathematical analysis reveals consistency of the method with the well-established Langevin equation and transition rate theory. Applying MuTrans to datasets collected from five different single-cell experimental platforms and benchmarking with seven existing tools, we show its capability and scalability to robustly unravel complex cell fate dynamics induced by transition cells in systems such as tumor EMT, iPSC differentiation and blood cell differentiation. Overall, our method bridges data-driven and model-based approaches on cell-fate transitions at single-cell resolution.
A network regularized linear model to infer spatial expression pattern for single cells
Authors: Gu Chaohao , Liu Zhandong 
Published: March 2021

AbstractSpatial gene-expression is a crucial determinant of cell fate and behavior. Recent imaging and sequencing-technology advancements have enabled scientists to develop new tools that use spatial information to measure gene-expression at close to single-cell levels. Yet, while Fluorescence In-situ Hybridization (FISH) can quantify transcript numbers at single-cell resolution, it is limited to a small number of genes. Similarly, slide-seq was designed to measure spatial-expression profiles at the single-cell level but has a relatively low gene-capture rate. And although single-cell RNA-seq enables deep cellular gene-expression profiling, it loses spatial information during sample-collection. These major limitations have stymied these methods’ broader application in the field. To overcome spatio-omics technology’s limitations and better understand spatial patterns at single-cell resolution, we designed a computation algorithm that uses glmSMA to predict cell locations by integrating scRNA-seq data with a spatialomics reference atlas. We treated cell-mapping as a convex optimization problem by minimizing the differences between cellular-expression profiles and location-expression profiles with a L1 regularization and graph Laplacian based L2 regularization to ensure a sparse and smooth mapping. We validated the mapping results by reconstructing spatial-expression patterns of well-known marker genes in complex tissues, like the mouse cerebellum and hippocampus. We used the biological literature to verify that the reconstructed patterns can recapitulate cell-type and anatomy structures. Our work thus far shows that, together, we can use glmSMA to accurately assign single cells to their original reference-atlas locations.
MicroRNA binding site variation is enriched in psychiatric disorders
Authors: Geaghan Michael P. , Reay William R. , Cairns Murray J. 
Published: March 2021

AbstractPsychiatric disorders and other complex traits have a polygenic architecture, often associated with dozens or even hundreds of independent genomic loci. As each of these have a relatively small influence on the trait, the dissection of their biological components is a non-trivial task. For psychiatric disorders in particular, the majority of associated loci lie within non-coding regions of the genome, suggesting that most of the genetic risk for disease originates from the disruption of regulatory sequences. While previously exploration of the heritability of these sequences has focused on variants that modify DNA elements, those that altercis-acting RNA sequences, such as miRNA binding sites, are also likely to have a significant impact in these disorders. MiRNA have already been shown to be dysregulated in these disorders through both genetic and environmental influence, so it is reasonable to suspect their target genes may also be affected by common variation. In this study, we investigated the distribution of miRNA binding site variants (MBSVs) predicted to alter miRNA binding affinity in psychiatric disorders and observed significant enrichment in schizophrenia, depression, bipolar disorder, and anorexia nervosa. We also observed significant enrichment of MBSVs in genes targeted by several miRNA families, including miR-335-5p, miR-21-5p/590-5p, miR-361-5p, and miR-557 in both schizophrenia and depression, and nominally significant enrichment of MBSV for miR-323b-3p in schizophrenia. We also identified a significant association between MBSVs in gene sets involved in regulation of the synapse and synaptic depression in schizophrenia. While these observations support the role of miRNA in the pathophysiology of psychiatric disorders, we also observed significant association of MBSVs in other complex traits suggesting that MBSVs are an important class of regulatory variants that have functional implications for many disorders.
Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients
Authors: Martin-Vicente María , Almansa Raquel , Martínez Isidoro , Tedim Ana P. , Bustamante Elena , Tamayo Luis , Aldecoa César , Gómez José Manuel , Renedo Gloria , Berezo Jose Ángel , Cedeño Jamil Antonio , Mamolar Nuria , Olivares Pablo García , Herrán Rubén , Cicuendez Ramón , Enríquez Pedro , Ortega Alicia , Jorge Noelia , de la Fuente Amanda , Bustamante-Munguira Juan , Muñoz-Gómez María José , González-Rivera Milagros , Puertas Carolina , Más Vicente , Vázquez Mónica , Pérez-García Felipe , Rico-Feijoo Jesús , Martín Silvia , Motos Anna , Fernandez-Barat Laia , Eiros Jose María , Dominguez-Gil Marta , Ferrer Ricard , Barbé Ferrán , Kelvin David J , Bermejo-Martin Jesús F , Resino Salvador , Torres Antoni 
Published: March 2021

AbstractPurposeto evaluate the association between anti-SARS-CoV-2 S IgM and IgG antibodies with viral RNA load in plasma, the frequency of antigenemia and with the risk of mortality in critically ill patients with COVID-19.Methodsanti-SARS-CoV-2 S antibodies levels, viral RNA load and antigenemia were profiled in plasma of 92 adult patients in the first 24 hours following ICU admission. The impact of these variables on 30-day mortality was assessed by using Kaplan-Meier curves and multivariate Cox regression analysis.Resultsnon survivors showed more frequently absence of anti-SARS-CoV-2 S IgG and IgM antibodies than survivors (26.3% vs 5.6% for IgM and 18.4% vs 5.6% for IgG), and a higher frequency of antigenemia (47.4% vs 22.2%) (p <0.05). Non survivors showed lower concentrations of anti-S IgG and IgM and higher viral RNA loads in plasma, which were associated to increased 30-day mortality and decreased survival mean time. [Adjusted HR (CI95%), p]: [S IgM (AUC ≥60): 0.48 (0.24; 0.97), 0.040]; [S IgG (AUC ≥237): 0.47 (0.23; 0.97), 0.042]; [Antigenemia (+): 2.45 (1.27; 4.71), 0.007]; [N1 viral load (≥ 2.156 copies/mL): 2.21 (1.11; 4.39),0.024]; [N2 viral load (≥ 3.035 copies/mL): 2.32 (1.16; 4.63), 0.017]. Frequency of antigenemia was >2.5-fold higher in patients with absence of antibodies. Levels of anti-SARS-CoV-2 S antibodies correlated inversely with viral RNA load.Conclusionabsence / insufficient levels of anti-SARS-CoV-2 S antibodies following ICU admission is associated to poor viral control, evidenced by increased viral RNA loads in plasma, higher frequency of antigenemia, and also to increased 30-day mortality.Take-home messageabsent or low levels of antibodies against the S protein of SARS-CoV- 2 at ICU admission is associated to an increased risk of mortality, higher frequency of antigenemia and higher viral RNA loads in plasma. Profiling anti-SARS-CoV-2 s antibodies at ICU admission could help to predict outcome and to better identify those patients potentially deserving replacement treatment with monoclonal or polyclonal antibodies.
Microfluidic Live-Imaging technology to perform research activities in 3D models
Authors: Martino Capuzzo Arnaud , Vigo Daniele 
Published: March 2021

ABSTRACTOne of the most surprising differences observed when comparing cell cultures in 2D and 3D is morphological dissimilarity and their evolution over time. Cells grown in a monolayer tend to flatten in the lower part of the plate adhering to and spreading in the horizontal plane without expanding in the vertical dimension. The result is that cells grown in 2D have a forced apex-basal polarity. 3D cultures support co-cultivation and crosstalking between multiple cell types, which regulate development and formation in the in vivo counterpart. 3D models culture, with or without a scaffold matrix, can exhibit morein vivo-likemorphology and physiology. 3D cultures recapitulate relevant physiological cellular processes, transforming into unique platforms for drug screening. To support and guarantee the functional maintenance of a 3D structure, one must consider the structures and dynamics of regulatory networks, increasingly studied with live-imaging microscopy. However, commercially available technologies that can be used for current laboratory needs are limited, although there is a need to facilitate the acquisition of cellular kinetics with a high spatial and temporal resolution, to elevate visual performance and consequently that of experimentation. The CELLviewer is a newly conceived and developed multi-technology instrumentation, combining and synchronizing the work of different scientific disciplines. This work aims to test the system with two models: the first model is a singleJurkatcell while the second is anMCF-7spheroid. After having grown both models, the two models used are loaded into the microfluidic cartridge for each experiment and recorded in time-lapse for a total of 4 hours. After adaptive autofocus, when sliding inside the cartridge chamber, the samples used are tracked under the action of the optics and the 3D rotation was experimentally successfully obtained. A cell viability assessment was then used using the MitoGreen dye, a fluorescence marker selectively permeable to live cells. The ImageJ software was used to: calculate the model diameter, create fluorescence intensity graphs along a straight line passing through the cell, visualize the spatial fluorescence intensity distribution in 3D.
The developmental hourglass model is applicable to the spinal cord
Authors: Mukaigasa Katsuki , Sakuma Chie , Yaginuma Hiroyuki 
Published: March 2021

SummaryThe developmental hourglass model predicts that embryonic morphology is most conserved at the mid-embryonic stage and diverges at the early and late stages. This model is generally considered by whole embryonic level. Here, we demonstrate that the hourglass model is also applicable to a reduced element, the spinal cord. In the middle of spinal cord development, dorsoventrally arrayed neuronal progenitor domains are established, which are conserved among vertebrates. We found that, by comparing the single-cell transcriptomes between mice and zebrafish, V3 interneurons, a subpopulation of the post-mitotic spinal neurons, display divergent molecular profiles. We also found non-conservation ofcis-regulatory elements located around the progenitor fate determinants, indicating the rewiring of the upstream gene regulatory network. These results demonstrate that, despite the conservation of the progenitor domains, processes before and after the progenitor domain specification diverged. This study may help understand the molecular basis of the developmental hourglass model.
Co-culture of type I and type II pneumocytes as a model of alveolar epithelium
Authors: Brookes Oliver , Boland Sonja , Kuen René Lai , Baeza-Squiban Armelle 
Published: March 2021

AbstractThe epithelial tissues of the distal lung are continuously exposed to inhaled air, and are of research interest in studying respiratory exposure to both hazardous and therapeutic materials. Pharmaco-toxicological research depends on the development of sophisticated models of the alveolar epithelium, which better represent the different cell types present in the native lung and interactions between them.We developed an air-liquid interface (ALI) model of the alveolar epithelium which incorporates cell lines representative of both type I (NCI-H441) and type II (hAELVi) epithelial cells. We compared morphology of single cells and the structure of cell layers of the two lines using light and electron microscopy. Working both in monotypic cultures and cocultures, we measured barrier function by trans-epithelial electrical resistance (TEER), and demonstrated that barrier properties can be maintained for 30 days. We created a mathematical model of TEER development over time based on these data in order to make inferences about the interactions occurring in these culture systems. We assessed expression of a panel of relevant genes that play important roles in barrier function and differentiation.The coculture model was observed to form a stable barrier akin to that seen in hAELVi, while expressing surfactant protein C, and having a profile of expression of claudins and aquaporins appropriate for the distal lung. We described cavities which arise within stratified cell layers in NCI-H441 and cocultured cells, and present evidence that these cavities represent an aberrant apical surface. In summary, our results support the coculture of these two cell lines to produce a model which better represents the breadth of functions seen in native alveolar epithelium.
Institutionalisation of weak conceptions of sustainability in the United Nations Clean Development Mechanism: empirical evidence from Malaysian organisations
Authors: Sidhu Ann Marie , Gibbon Jane 
Published: March 2021

PurposeThe purpose of this study is to examine how accounting for sustainable development (SD) in Malaysian organisations decouples economic growth from ecological consequences. The research analyses the empirical evidence of organisational responses and actions that purport to support SD in a developing country.Design/methodology/approachThis study uses a discursive model of institutional theory to examine the relationship between texts, discourse and action within Clean Development Mechanism (CDM) organisations. This study uses both qualitative content and interpretive textual analysis of Malaysian organisations project design documents (PDDs) and interview transcripts to interpret and determine the “conceptions” of SD.FindingsDocumentation and interviews with Malaysian CDM organisations show that SD conceptions range from “business as usual” to weak ecological modernisation. The key narratives are both economic and technocratic but have little to do with SD concerns about ecological limitations and social equity.Originality/valueThe empirical evidence provides insights into the motivations and challenges of a developing country's commitment to SD. We perform the study in an accountability space other than corporate financial reporting. Unlike external corporate reports, PDDs are closer to the underlying organisational reality as they are internal project documents made publicly accessible through the United Nations Framework Convention on Climate Change, allowing for a more transparent evaluation. The evidence shows how the organisational approach to SD is institutionalised through the mediating role of discourse and texts used by the actors within the CDM.
Accountability and governance in pursuit of Sustainable Development Goals: conceptualising how governments create value
Authors: Abhayawansa Subhash , Adams Carol A. , Neesham Cristina 
Published: March 2021

PurposeDrawing on Adams (2017a) conceptualisation of value creation by organisations published in the Accounting, Auditing and Accountability Journal, the purpose of this paper is to develop a conceptualisation of how national governments can create value for society and the economy through their approach to the UN Sustainable Development Goals (SDGs).Design/methodology/approachAn initial conceptual framework was developed from literature situated at the intersection of accountability, public policy and sustainability/sustainable development. The authors' review of extant research on national policy development on value creation, sustainability and the SDGs identified gaps in (understanding of) approaches to national accountability and national governance (by state and civil society) processes. The subsequent thematic analysis of 164 written submissions made to the Australian Senate inquiry on the SDGs between December 2017 and March 2018, together with transcripts of five public hearings where 49 individuals and organisations appeared as witnesses during the second half of 2018, focussed on addressing these gaps.FindingsInput to the Australian Senate Inquiry on the SDGs overwhelmingly emphasised the importance of transparency and stakeholder participation in accountability systems, commenting on data gathering, measuring and communicating. There was an emphasis on the need to involve all parts of society, including business, investors and civil society, and for strong central co-ordination by the Office of the Prime Minister and Cabinet. These data allowed the authors to refine the conceptualisation of how national governments can enhance social and economic value through a focus on the UN SDGs and their approach to accounting, accountability and governance.Practical implicationsThe findings have implications: for national governments in developing approaches to achieve sustainable development; and, for supranational bodies such as the UN in developing agreements, frameworks and guidance for national governments.Originality/valueBuilding on the extant literature about how global governance should be engaged to improve accountability in achieving the SDGs, the conceptual framework developed through the study shifts focus to national governance and accountability, and provides a blueprint for national governments to create value for the economy and society in the face of global sustainable development issues.