bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Combination of Two Human Monoclonal Antibodies Limits Fetal Damage by Zika Virus in Macaques
Authors: Van Rompay Koen K.A. , Coffey Lark L. , Kapoor Tania , Gazumyan Anna , Keesler Rebekah I. , Jurado Andrea , Peace Avery , Agudelo Marianna , Watanabe Jennifer , Usachenko Jodie , Singapuri Anil , Immareddy Ramya , Ardeshir Amir , Stuart Jackson B. , Bournazos Stylianos , Ravetch Jeffrey V. , Balderes Paul J. , Lorenz Ivo C. , Esswein Shannon R. , Keeffe Jennifer , Bjorkman Pamela J. , Wang Qiao , Rice Charles M. , MacDonald Margaret R. , Nussenzweig Michel C. , Robbiani Davide F. 
Published: February 2020

ABSTRACTHuman infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancementin vitro(ADE) and extend their half-lives. Here we report on prophylactic co-administration of the Fc-modified antibodies to pregnant rhesus macaques challenged 3 times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV.Significance statementZika virus (ZIKV) infection during pregnancy can cause fetal abnormalities. Vaccines against ZIKV are under development, but because of potential safety concerns due to disease enhancing antibodies, and the time required by active immunization to induce protective antibodies, there is a need to explore alternative strategies. Recombinant monoclonal antibodies can be modified to prevent enhancement of infection, and thus could be an efficacious and safe alternative to vaccines to confer rapid protection. We show that prophylactic administration of two engineered antibodies, Z004 and Z021, to pregnant macaques partially protects against fetal neurologic damage and limits vertical transmission of ZIKV.
ADAR1 editing dependency in triple-negative breast cancer
Authors: Kung Che-Pei , Cottrell Kyle A. , Ryu Sua , Bramel Emily R. , Kladney Raleigh D. , Bross Emily A. , Maggi Leonard , Weber Jason D. 
Published: February 2020

SummaryTriple-negative breast cancer (TNBC) is the deadliest form of breast cancer. Unlike other types of breast cancer that can be effectively treated by targeted therapies, no such targeted therapy exists for all TNBC patients. The ADAR1 enzyme carries out A-to-I editing of RNA to prevent sensing of cellular double-stranded RNAs (dsRNA). ADAR1 is highly expressed in breast cancer including TNBC. Here, we demonstrate that ADAR1 expression and editing activity is required in TNBC cell lines but not in ER+ and/or Her2+ cells. In TNBC cells, knockdown of ADAR1 attenuates proliferation and tumorigenesis. PKR expression is elevated in TNBC and its activity is induced upon ADAR1-knockdown, which correlates with a decrease in translation. ADAR1-dependent TNBC cell lines also exhibit elevated IFN stimulated gene expression. IFNAR1 reduction significantly rescues the proliferative defects of ADAR1 loss. These findings establish ADAR1 as a novel therapeutic target for TNBC tumors.
Phylogenomic resolution of sea spider diversification through integration of multiple data classes
Authors: Ballesteros Jesús A. , Setton Emily V.W. , Santibáñez López Carlos E. , Arango Claudia P. , Brenneis Georg , Brix Saskia , Cano-Sánchez Esperanza , Dandouch Merai , Dilly Geoffrey F. , Eleaume Marc P. , Gainett Guilherme , Gallut Cyril , McAtee Sean , McIntyre Lauren , Moran Amy L. , Moran Randy , López-González Pablo J. , Scholtz Gerhard , Williamson Clay , Woods H. Arthur , Wheeler Ward C. , Sharma Prashant P. 
Published: February 2020

AbstractDespite significant advances in invertebrate phylogenomics over the past decade, the higher-level phylogeny of Pycnogonida (sea spiders) remains elusive. Due to the inaccessibility of some small-bodied lineages, few phylogenetic studies have sampled all sea spider families. Previous efforts based on a handful of genes have yielded unstable tree topologies. Here, we inferred the relationships of 89 sea spider species using targeted capture of the mitochondrial genome, 56 conserved exons, 101 ultraconserved elements, and three nuclear ribosomal genes. We inferred molecular divergence times by integrating morphological data for fossil species to calibrate 15 nodes in the arthropod tree of life. This integration of data classes resolved the basal topology of sea spiders with high support. The enigmatic family Austrodecidae was resolved as the sister group to the remaining Pycnogonida and the small-bodied family Rhynchothoracidae as the sister group of the robust-bodied family Pycnogonidae. Molecular divergence time estimation recovered a basal divergence of crown group sea spiders in the Ordovician. Comparison of diversification dynamics with other marine invertebrate taxa that originated in the Paleozoic suggests that sea spiders and some crustacean groups exhibit resilience to mass extinction episodes, relative to mollusk and echinoderm lineages.
Glial type specific regulation of CNS angiogenesis by HIFα-activated different signaling pathways
Authors: Zhang Sheng , Kim Bokyung , Zhu Xiaoqing , Gui Xuehong , Wang Yan , Lan Zhaohui , Prabhu Preeti , Fond Kenneth , Wang Aijun , Guo Fuzheng 
Published: February 2020

AbstractThe mechanisms by which oligodendroglia modulate CNS angiogenesis remain elusive. Previousin vitrodata suggest that oligodendroglia regulate CNS endothelial cell proliferation and blood vessel formation through hypoxia inducible factor alpha (HIFα)-activated Wnt (but not VEGF) signaling. Usingin vivogenetic models, we show that HIFα in oligodendroglia is necessary and sufficient for angiogenesis independent of CNS regions. At the molecular level, HIFα stabilization in oligodendroglia does not perturb Wnt signaling but remarkably activates VEGF. At the functional level, genetically blocking oligodendroglia-derived VEGF but not Wnt significantly decreases oligodendroglial HIFα-regulated CNS angiogenesis. Interestingly, blocking astroglia-derived Wnt signaling reduces astroglial HIFα-regulated CNS angiogenesis. Together, ourin vivodata clearly demonstrate that oligodendroglial HIFα regulates CNS angiogenesis through Wnt-independent and VEGF-dependent signaling. Our findings represent an alternative mechanistic understanding of CNS angiogenesis by postnatal glial cells and unveil a glial cell type-dependent HIFα-Wnt axis in regulating CNS vessel formation.
Molecular Modeling Evaluation of the Binding Effect of Ritonavir, Lopinavir and Darunavir to Severe Acute Respiratory Syndrome Coronavirus 2 Proteases
Authors: Lin Shen , Shen Runnan , He Jingdong , Li Xinhao , Guo Xushun 
Published: February 2020

AbstractThree anti-HIV drugs, ritonavir, lopinavir and darunavir, might have therapeutic effect on coronavirus disease 2019 (COVID-19). In this study, the structure models of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteases, coronavirus endopeptidase C30 (CEP_C30) and papain like viral protease (PLVP), were built by homology modeling. Ritonavir, lopinavir and darunavir were then docked to the models, respectively, followed by energy minimization of the protease-drug complexes. In the simulations, ritonavir can bind to CEP_C30 most suitably, and induce significant conformation changes of CEP_C30; lopinavir can also bind to CEP_C30 suitably, and induce significant conformation changes of CEP_C30; darunavir can bind to PLVP suitably with slight conformation changes of PLVP. It is suggested that the therapeutic effect of ritonavir and lopinavir on COVID-19 may be mainly due to their inhibitory effect on CEP_C30, while ritonavir may have stronger efficacy; the inhibitory effect of darunavir on SARS-CoV-2 and its potential therapeutic effect may be mainly due to its inhibitory effect on PLVP.
Generation of Xylose-inducible promoter tools forPseudomonasspecies and their use in implicating a role for the Type II secretion system protein XcpQ in inhibition of corneal epithelial wound closure
Authors: Callaghan Jake D. , Stella Nicholas A. , Lehner Kara M. , Treat Benjamin R. , Brothers Kimberly M. , St. Leger Anthony J. , Shanks Robert M. Q. 
Published: February 2020

ABSTRACTTunable control of gene expression is an invaluable tool for biological experiments. In this study, we describe a new xylose-inducible promoter system and evaluate it in bothPseudomonas aeruginosaandP. fluorescens. ThePxutpromoter derived from theP. flurorescens xutoperon was incorporated into a broad host-range pBBR1-based plasmid and compared to theEscherichia coli-derivedPBADpromoter usinggfpas a reporter. GFP-fluorescence from thePxutpromoter was inducible in bothPseudomonasspecies, but not inE. coli,which may facilitate cloning of toxic genes usingE. colito generate plasmids. ThePxutpromoter was expressed at a lower inducer concentration thanPBADinP. fluorescensand highergfplevels were achieved usingPxut. Flow cytometry analysis indicated thatPxutwas more leaky thanPBADin the testedPseudomonasspecies, but was expressed in a higher proportion of cells when induced. D-xylose did not support growth ofP. aeruginosaorP. fluorescensas a sole carbon source and is less expensive than many other commonly used inducers which could facilitate large scale applications. The efficacy of this system aided in demonstrating a role for theP. aeruginosatype II secretion system gene fromxcpQin bacterial inhibition of corneal epithelial cell wound closure. This study introduces a new inducible promoter system for gene expression for use inPseudomonasspecies.ImportancePseudomonasspecies are enormously important in human infections, biotechnology, and as a model system for interrogating basic science questions. In this study we have developed a xylose-inducible promoter system and evaluated it inP. aeruginosaandP. fluorescensand found it to be suitable for the strong induction of gene expression. Furthermore, we have demonstrated its efficacy in controlled gene expression to show that a type 2 secretion system protein fromP. aeruginosa, XcpQ, is important for host-pathogen interactions in a corneal wound closure model.
Relative contribution of non-structural protein 1 in dengue pathogenesis
Authors: Lee Pei Xuan , Ting Donald Heng Rong , Boey Clement Peng Hee , Tan Eunice Tze Xin , Chia Janice Zuo Hui , Ong Li Ching , Chua Yen Leong , Hapuarachchi Chanditha , Ng Lee Ching , Alonso Sylvie 
Published: February 2020

AbstractDengue is a major public health concern in the tropical and sub-tropical world with no effective treatment. The controversial live attenuated virus vaccine Dengvaxia has boosted the pursuit of sub-unit vaccine approaches, and the non-structural protein 1 (NS1) has recently emerged as a promising candidate. However, we found that NS1 immunization or passive transfer of NS1 antibodies failed to confer protection in symptomatic dengue mouse models using two non mouse-adapted DENV2 strains from the Cosmopolitan genotype that currently circulates in South-East Asia. Furthermore, exogenous administration of purified NS1 did not worsenin vivovascular leakage in sub-lethally infected mice, thereby supporting that NS1 does not play a critical role in the pathogenesis of these DENV2 strains. Virus chimerization approaches indicated that the prME structural region, but not NS1, plays a critical role in drivingin vivofitness and virulence of the virus, through induction of key pro-inflammatory cytokines. This work highlights that the pathogenic role of NS1 is DENV strain-dependent, which warrants re-evaluation of NS1 as a universal dengue vaccine candidate.
Sorting liposomes of distinct sizes by DNA-brick assisted centrifugation
Authors: Yang Yang , Wu Zhenyong , Wang Laurie , Zhou Kaifeng , Xia Kai , Xiong Qiancheng , Xiong Yong , Melia Thomas J , Karatekin Erdem , Gu Hongzhou , Lin Chenxiang 
Published: February 2020

AbstractThe “tiny bubbles of fluid” wrapped by lipid-bilayer membranes, termed vesicles, are abundant in cells and extracellular space, performing critical tasks including nutrient uptake, cargo transport, and waste confinement. Vesicles on different missions and transport routes are often distinct both in size and in chemical composition, which confers specificity to their interactions with other membranous compartments. Therefore, to accurately recapitulate the vesicles’ structure and behavior, it is important to use homogeneous liposomes (vesicles made of synthetic components) with precisely defined attributes as model membranes. Although existing methods can generate liposomes of selected sizes with reasonable homogeneity, the scalable production of uniformly-sized liposomes across a wide range of dimensions and compositions remains challenging. Here we report a streamlined, high-throughput sorting technique that uses cholesterol-modified “nanobricks” made of a few DNA oligonucleotides to differentiate hetero-sized liposomes by their buoyant densities. After DNA-brick coating, milligrams of liposomes of different origins (e.g., produced via extrusion or sonication, and reconstituted with membrane proteins) can be separated by centrifugation into six to eight homogeneous populations with mean diameters from 30 to 130 nm. In proof of concept experiments, we show that these uniform, leak-free liposomes are ideal substrates to study, with an unprecedented resolution, how membrane curvature influences the activity of peripheral (ATG3) and integral (SNARE) membrane proteins. We anticipate that our sorting technique will facilitate the quantitative understanding of membrane curvature in vesicular transport. Furthermore, adding a facile and standardized separation step to the conventional liposome preparation pipeline may benefit the formulation and prototyping of liposomal drug-carrying vehicles.
Gut lymph purification regulates monocyte activity in rats with ischemia-reperfusion injury-induced sepsis
Authors: Zhang Wei , Chen Jie , Jin Can , Zhang Shuncheng , Gu Juan , Shi Meimei 
Published: February 2020

ABSTRACTObjectiveTo confirm that gut lymph purification (GLP) based on oXiris regulates monocyte activity by targeting the removal of ischemia-reperfusion injury (IRI)-induced intestinal toxic substances (ITSs) in rats.MethodsSepsis was induced by intestinal IRI in 24 adult male Sprague-Dawley rats that were randomly divided into the control, intestinal IRI, and IRI+GLP groups. The gut lymph fluid (GLF) was drained for 180 minutes. The ITSs levels and the proliferation, apoptosis and positive expression rates of MHC-II molecules of monocytes coincubated with the GLF were detected.ResultsEndotoxin, TNF-α, IL-4, IL-6 and IL-10 levels in the lymph and plasma of the IRI group were significantly higher than those of the control group (p< 0.01). Compared with the IRI group, GLP treatment significantly decreased the ITS levels (p< 0.05). Monocyte proliferation and the positive expression rate of MHC-□ molecules were significantly reduced after co-culturing with GLF upon IRI (p< 0.01), and the apoptotic rate was significantly increased (p< 0.01). However, culturing monocytes with GLP significantly enhanced the monocyte proliferation, increased the positive expression rate of MHC-□ monocytes (p< 0.01), and reduced the apoptotic rate (p< 0.01).ConclusionsGLP therapy based on oXiris effectively removed ITSs from the GLF after IRI, thereby blocking the main process of multiple organ dysfunction syndrome by regulating monocyte activity.
Uncovering the impact of food sharing platform business models: a theory of change approach
Authors: Michelini Laura , Grieco Cecilia , Ciulli Francesca , Di Leo Alessio 
Published: February 2020

PurposeThe purpose of this paper is to explore the potential impact of food sharing platform business models and to identify the limits and barriers in measuring the impact. Using the “theory of change” (ToC) approach, this paper develops a theoretical framework that captures the activities, outputs and outcomes of food sharing platforms and links them to indicators.Design/methodology/approachThe study employs a two-step methodology, which includes a website content analysis followed by two focus groups. The purpose of the website content analysis was to list a set of activities that are performed by food sharing platforms. The focus groups allow to design the ToC and to discuss limits and barriers in measuring the impact of food sharing platforms.FindingsThe study provides an overview of the main areas of impact of food sharing platforms (environmental, social, economic and political) and identifies the related outcomes. Furthermore, the paper highlights the need for the platform to manage the multifaceted tensions of food waste recovery vs prevention and the benefits of food recovery to helping hungry people vs the actual need to eradicate poverty by addressing social injustices and inequalities.Research limitations/implicationsThe selected sample involved in the focus group comprised a wide but not comprehensive set of stakeholders. Indeed, the obtained information cannot be generalized. In addition, the ToC approach requires a certain discretion of the facilitator and introduces the potential for partiality in conducting the analysis.Practical implicationsThe framework helps to unbundle the complex challenge of measuring the impact of food sharing platforms and it provides managers, practitioners and policy makers with a practical tool to direct their activities toward a better impact.Originality/valueFrom a theoretical perspective the study advances the literature on (food) sharing platforms and contributes to research on the sustainability in the food sector. It indicates the impacts a novel actor relying on digital technology can have in the food sector and points out the tensions between food recovery and prevention and the impact on poverty. The proposed framework could be a useful tool to support practitioners in understanding the trade-offs among the outcomes they aim to attain, and to identify the proper strategies to manage them.
Working with addiction: an intercultural-integrative approach to substance dependency during a seven-year delivery of a psychotherapy service in North London
Authors: Sigalas Antony 
Published: February 2020

Purpose
This paper aims to focus on a meta-analysis of an applied integrative model of clinical practice at community level in a third-sector organisation. The psychotherapeutic work was exclusively aimed at those who struggled with their abstinence from their substance use.

Design/methodology/approach
The model adapted to the needs of those who accessed the service, combined culturally sensitive psychoanalytic, systemic and relational frameworks.

Findings
The analysis reflects how such a multi-dimensional approach may be used to address the experience of self-destructiveness in the context of inferiorisation. This paper also presents some statistical information as well as three case vignettes.

Originality/value
The analysis reflects how such a multi-dimensional approach may be used to address the experience of self-destructiveness in the context of inferiorisation.
Engaging university students in an ESL live broadcast
Authors: ChanLin Lih-Juan 
Published: February 2020

Purpose
This study aims to analyze the engagement of community members in an English as a second language (ESL) live broadcast. A platform for encouraging language and culture learning in ESL was planned and implemented. Research purposes were to explore the following aspects for engaging students’ participation: operation-monitoring, planning and implementation, incentives and motives, interactions with multiple formats and challenges.

Design/methodology/approach
The platform used for the ESL live broadcast was Open Broadcaster Software Studio. Through the live videos and instant messages delivered by the network, real-time interactions from different virtual sites were achieved. Observations and operation documentation were recorded. Interviews with the teacher, the library administrator and the students were carried out for collecting data. Inductive analysis was used to analyze the qualitative data from the different sources.

Findings
It was observed that the ESL broadcast reached a great number of users weekly. To engage the ESL broadcast community, efforts to monitor and plan for implementation were made. Students were encouraged by both external incentives and internal motivation. Managing the connectivity problems was essential for guaranteeing the quality of the real-time interactions. From their experiences, the participants were positive about the broadcast approach to learning ESL. More diverse topics and alternatives for oral interactions in the class are suggested in future implementations.

Research limitations/implications
The implementation of the ESL live broadcast provides a model for inviting members within the university community to engage in the language and culture learning. The research is preliminary and is limited to a specific university. Future research on diverse learning settings is needed.

Originality/value
The findings of this study will contribute to the research in streaming media interactions. The case might be applied to other settings and other subject domains.