bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designing and interpreting 4D tumour spheroid experiments
Authors: Murphy Ryan J. , Browning Alexander P. , Gunasingh Gency , Haass Nikolas K. , Simpson Matthew J. 
Published: August 2021

AbstractTumour spheroid experiments are routinely used to study cancer progression and treatment. Various and inconsistent experimental designs are used, leading to challenges in interpretation and reproducibility. Using multiple experimental designs, live-dead cell staining, and real-time cell cycle imaging, we measure necrotic and proliferation-inhibited regions in over 1000 4D tumour spheroids (3D space plus cell cycle status). By intentionally varying the initial spheroid size and temporal sampling frequencies across multiple cell lines, we collect an abundance of measurements of internal spheroid structure. These data are difficult to compare and interpret. However, using an objective mathematical modelling framework and statistical identifiability analysis we quantitatively compare experimental designs and identify design choices that produce reliable biological insight. Measurements of internal spheroid structure provide the most insight, whereas varying initial spheroid size and temporal measurement frequency is less important. Our general framework applies to spheroids grown in different conditions and with different cell types.
Development of an in vitro model for animal species susceptibility to SARS-CoV-2 replication based on expression of ACE2 and TMPRSS2 in avian cells
Authors: Kapczynski Darrell R. , Sweeney Ryan , Suarez David L. , Spackman Erica , Pantin-Jackwood Mary 
Published: August 2021

ABSTRACTThe SARS-CoV-2 (SC2) virus has caused a worldwide pandemic because of the virus’s ability to transmit efficiently human-to-human. A key determinant of infection is the attachment of the viral spike protein to the host receptor angiotensin-converting enzyme 2 (ACE2). Because of the presumed zoonotic origin of SC2, there is no practical way to assess every species susceptibility to SC2 by direct challenge studies. In an effort to have a better predictive model of animal host susceptibility to SC2, we expressed the ACE2 and/or transmembrane serine protease 2 (TMPRSS2) genes from humans and other animal species in the avian fibroblast cell line, DF1, that is not permissive to infection. We demonstrated that expression of both human ACE2 and TMPRSS2 genes is necessary to support SC2 infection and replication in DF1 and a non-permissive sub-lineage of MDCK cells. Titers of SC2 in these cell lines were comparable to those observed in control Vero cells. To further test the model, we developed seven additional transgenic cell lines expressing the ACE2 and TMPRSS2 derived from Felis (cat), Equus (horse), Sus (pig), Capra (goat), Mesocricetus (Golden hamster), Myotis lucifugus (Little Brown bat) and Hipposideros armiger (Great Roundleaf bat) in DF1 cells. Results demonstrate permissive replication of SC2 in cat, Golden hamster, and goat species, but not pig or horse, which correlated with the results of reported challenge studies. The development of this cell culture model allows for more efficient testing of the potential susceptibility of many different animal species for SC2 and emerging variant viruses.IMPORTANCESARS-CoV-2 (SC2) is believed to have originated in animal species and jumped into humans where it has produced the greatest viral pandemic of our time. Identification of animal species susceptible to SC2 infection would provide information on potential zoonotic reservoirs, and transmission potential at the human-animal interface. Our work provides a model system to test the ability of the virus to replicate in an otherwise non-permissive cell line by transgenic insertion of the ACE2 and TMPRSS2 genes from human and other animal species. The results from our in vitro model positively correlate with animal infection studies enhancing the predicative capability of the model. Importantly, we demonstrate that both proteins are required for successful virus replication. These findings establish a framework to test other animal species for susceptibility to infection that may be critical zoonotic reservoirs for transmission, as well as to test variant viruses that arise over time.
Selection against admixture and gene regulatory divergence in a long-term primate field study
Authors: Vilgalys Tauras P. , Fogel Arielle S. , Mututua Raphael S. , Kinyua Warutere J. , Siodi Long’ida , Anderson Jordan A. , Kim Sang Yoon , Voyles Tawni N. , Robinson Jacqueline A. , Wall Jeffrey D. , Archie Elizabeth A. , Alberts Susan C. , Tung Jenny 
Published: August 2021

AbstractAdmixture has profoundly influenced evolution across the tree of life, including in humans and other primates1,2. However, we have limited insight into the genetic and phenotypic consequences of admixture in primates, especially during its key early stages. Here, we address this gap by combining 50 years of field observations with population and functional genomic data from yellow (Papio cynocephalus) and anubis (P. anubis) baboons in Kenya, in a longitudinally studied population that has experienced both historical and recent admixture3. We use whole-genome sequencing to characterize the extent of the hybrid zone, estimate local ancestry for 442 known individuals, and predict the landscape of introgression across the genome. Despite no major fitness costs to hybrids, we identify signatures of selection against introgression that are strikingly similar to those described for archaic hominins4–6. These signatures are strongest near loci with large ancestry effects on gene expression, supporting the importance of gene regulation in primate evolution and the idea that selection targeted large regulatory effects following archaic hominin admixture7,8. Our results show that genomic data and field observations of hybrids are important and mutually informative. They therefore demonstrate the value of other primates as living models for phenomena that we cannot observe in our own lineage.
MEKK3-TGFβ crosstalk regulates inward arterial remodeling
Authors: Deng Hanqiang , Xu Yanying , Hu Xiaoyue , Zhuang Zhen W. , Chang Yuzhou , Wang Yewei , Ntokou Aglaia , Schwartz Martin A. , Su Bing , Simons Michael 
Published: August 2021

AbstractArterial remodeling is an important adaptive mechanism that maintains normal fluid shear stress in a variety of physiologic and pathologic conditions. Inward remodeling, a process that leads to reduction in arterial diameter, plays a critical role in progression of such common diseases as hypertension and atherosclerosis. Yet despite its pathogenic importance, molecular mechanisms controlling inward remodeling remain undefined. Mitogen-activated protein kinases (MAPKs) perform a number of functions ranging from control of proliferation to migration and cell fate transitions. While the MAPK ERK1/2 signaling pathway has been extensively examined in the endothelium, less is known about the role of the MEKK3/ERK5 pathway in vascular remodeling. To better define the role played by this signaling cascade, we studied the effect of endothelial-specific deletion of its key upstream MAP3K, MEKK3, in adult mice. The gene’s deletion resulted in a gradual inward remodeling of both pulmonary and systematic arteries leading to spontaneous hypertension in both vascular circuits and accelerated progression of atherosclerosis in hyperlipidemic mice. Molecular analysis revealed activation of TGFβ signaling both in vitro and in vivo. Endothelial-specific TGFβR1 knockout prevented inward arterial remodeling in MEKK3 endothelial knockout mice. These data point to the unexpected participation of endothelial MEKK3 in regulation of TGFβR1-Smad2/3 signaling and inward arterial remodeling in artery diseases.SignificanceInward remodeling of arteries to reduce lumen diameter is a major factor in disease progression and morbidity in multiple vascular diseases, including hypertension and atherosclerosis. However, molecular mechanisms controlling inward arterial remodeling remain largely undefined. In this study, we identify endothelial MEKK3 as an unexpected regulator of inward remodeling via inhibition of TGFβ-Smad2/3 signaling. Genetic deletion of MEKK3 in adult endothelium results in induction of TGFβ-Smad2/3 signaling, endothelial-to-mesenchymal transition and inward remodeling in both pulmonary and arterial circuits. The latter process results in pulmonary and systemic hypertension and accelerates atherosclerosis. These results provide a new basis for understanding the inward artery remodeling that leads to reduced blood flow to affected tissues and exacerbates hypertension in vascular disease.
Characterising the Photoplethysmography Pulse Waveform for Use in Human Neuroscience: The Hybrid Excess and Decay (HED) Model
Authors: Williamson Simon , Daniel-Watanabe Lucie , Finnemann Johanna , Powell Craig , Teed Adam , Allen Micah , Paulus Martin , Khalsa Sahib S. , Fletcher Paul C. 
Published: August 2021

AbstractPhotoplethysmography (PPG) offers a widely-used, convenient and non-invasive approach to monitoring basic indices of cardiovascular function such as heart rate and blood oxygenation. However, while the pulse waveform, generated by PPG comprises features that are shaped by physiological and psychological factors, it is frequently overlooked in analyses of such data. We suggest that studies could be enriched by exploiting the possibilities afforded by a systematic analysis of PPG waveforms. To do this we initially require a robust and automated means of characterising it, thereby allowing us to examine variations across individuals and between different physiological and psychological contexts. We present a psychophysiologically-relevant model, the Hybrid Excess and Decay (HED) Model, which characterises pulse wave morphology in terms of three underlying pressure waves and a decay function. We show that these parameters capture PPG data with a high degree of precision and, moreover, are sensitive to specific, physiologically-relevant changes within individuals. We present the theoretical and practical basis for the model and demonstrate its performance when applied to a pharmacological dataset of 105 participants receiving intravenous administrations of the sympathomimetic drug isoproterenol (Isoprenaline). We conclude by discussing the possible value in using the HED model to complement standard measures of PPG outputs.
Neuroblast migration along cellular substrates in the developing porcine brain
Authors: Porter Demisha D.L. , Henry Sara N. , Ahmed Sadia , Morton Paul D. 
Published: August 2021

AbstractIn the past decade it has become evident that neuroblasts continue to supply the human cortex with interneurons via unique migratory streams shortly following birth. Due to the size of the human brain, these newborn neurons must migrate long distances through complex cellular landscapes to reach their final locations. This process is poorly understood, largely due to technical difficulties in acquiring and studying neurotypical postmortem human samples along with diverging developmental features of well-studied mouse models. We reasoned that migratory streams of neuroblasts utilize cellular substrates, such as blood vessels, to guide their trek from the subventricular zone to distant cortical targets. Here we evaluate the association between young interneuronal migratory streams and their preferred cellular substrates in gyrencephalic piglets during the developmental equivalent of human birth, infancy, and toddlerhood.
Critical Role for Isoprenoids in Apicoplast Biogenesis by Malaria Parasites
Authors: Okada Megan , Rajaram Krithika , Swift Russell P. , Mixon Amanda , Maschek John Alan , Prigge Sean T. , Sigala Paul A. 
Published: August 2021

ABSTRACTIsopentenyl pyrophosphate (IPP) is an essential metabolic output of the apicoplast organelle inPlasmodium falciparummalaria parasites and is required for prenylation-dependent vesicular trafficking and other cellular processes. We have elucidated a critical and previously uncharacterized role for IPP in apicoplast biogenesis. Inhibiting IPP synthesis blocks apicoplast elongation and inheritance by daughter merozoites, and apicoplast biogenesis is rescued by exogenous IPP and polyprenols. Knockout of the only known isoprenoid-dependent apicoplast pathway, tRNA prenylation by MiaA, has no effect on blood-stage parasites and thus cannot explain apicoplast reliance on IPP. However, we have localized an annotated polyprenyl synthase (PPS) to the apicoplast lumen. PPS knockdown is lethal to parasites, rescued by IPP, and blocks apicoplast biogenesis, thus explaining apicoplast dependence on isoprenoid synthesis. We hypothesize that PPS synthesizes long-chain polyprenols critical for apicoplast membrane fluidity and biogenesis. This work critically expands the paradigm for isoprenoid utilization in malaria parasites and identifies a novel essential branch of apicoplast metabolism suitable for therapeutic targeting.
Methods for recording and imaging spreading depolarizations and seizure-like events in mouse hippocampal slices
Authors: Lu Yi-Ling , Scharfman Helen E. 
Published: August 2021

AbstractSpreading depolarization (SD) is a sudden and synchronized depolarization of principal cells followed by depression of activity, which slowly propagates across brain regions like cortex or hippocampus. SD is considered to be mechanistically relevant to migraine, epilepsy, and traumatic brain injury. Interestingly, research into SD typically uses SD triggered immediately after a focal stimulus. Here we optimize an in vitro experimental model allowing us to record SD without focal stimulation. This method uses electrophysiological recordings and intrinsic optical imaging in slices. The method is also relatively easy and inexpensive. Acute hippocampal slices from mice or rats were prepared and used for extracellular and whole-cell recordings. Recordings were made in a submerged-style chamber with flow of artificial cerebrospinal fluid (aCSF) above and below the slices. Flow was fast (> 5ml/min), and temperature was 32°C. As soon as slices were placed in the chamber, aCSF containing 0 mM Mg2+ and 5 mM K+ (0 Mg2+/5 K+ aCSF) was used. Two major types of activity were observed: SD and seizure-like events (SLEs). Both occurred after many minutes of recording. Although both mouse and rat slices showed SLEs, only mouse slices developed SD and did so in the first hour of 0 Mg2+/5 K+ aCSF exposure. Intrinsic optical imaging showed that most SDs initiated in CA3 and could propagate into CA1 and dentate gyrus. In dentate gyrus, SD propagated in two separate waves: (1) into the hilus and (2) into granule cell and molecular layers simultaneously. This in vitro model can be used to better understand the mechanisms and relationship between SD and SLEs. It could also be useful in preclinical drug screening.
Thirty years and “I'm still Lovin’ it!”: brand perceptions of McDonald's among generation Y and generation Z consumers in China
Authors: Zhang Bowen , Mulhern Frank J. , Wu Yingying , Xu Margaret , Wang Wenqi , Gao Liang 
Published: August 2021

PurposeRecognizing the differences between generations Y and Z, this exploratory study uses generational cohort theory as a framework to examine the brand perception of McDonald's, an international brand which has grown up with consumers for over 30 years in China. The paper aims to discuss this issue.Design/methodology/approachMeasures of brand perception was built based on Aaker's brand personality model. A total 1,103 valid questionnaires were collected through an online survey platform. Factor analysis is the primary method to analysis the data.FindingsThe findings of this study reveal a favourable brand perception of McDonald's among young Chinese consumers which is consistent with Aaker's brand personality model and support the use of generational cohort theory as a market segmentation tool for brand perception. The differences between the two generational cohorts are not shown to be significant.Originality/valueThe most important contribution of this study is the evaluation of the personality of a major brand in China for Gen Z, a topic with very little existing research. Also, this research suggests future in-depth research into generational cohort theory in a Chinese context by recognizing homogeneity and heterogeneity exist simultaneously between generational cohorts.
The impact of the perceived risk of COVID-19 on consumers' attitude and behavior toward locally produced food
Authors: Palau-Saumell Ramon , Matute Jorge , Derqui Belén , Meyer Jan-Hinrich 
Published: August 2021

PurposeThis study analyzes the impact of the COVID-19 pandemic on the consumption of locally produced food. In particular, it examines an extended model of the theory of planned behavior, with the addition of the perceived risk of becoming infected with the disease, locavorism and internal locus of control.Design/methodology/approachThe study employs data collected from an online panel of consumers from the five largest cities in Spain (n = 1,000). It uses partial least squares structural equation modeling (PLS-SEM) to test and validate the proposed theoretical model.FindingsThe results indicate that the perceived risk of COVID-19 drives consumers to embrace locavorism more and, although locavorism is a strong predictor of attitude, internal locus of control also has a strong impact on attitude and switching intentions. Subjective norm and attitude are strong predictors of switching intentions and purchase intentions, and switching intentions also have a powerful impact on purchase intentions.Originality/valueThis study extends previous research on locally produced food consumption in that it has proposed and tested a new conceptual model with the inclusion of the perceived risk of COVID-19, locavorism, internal locus of control and switching intentions, which were found to have an influence on purchasing behavior.
Impact of the strategic sourcing process on the supply chain response to the COVID-19 effects
Authors: Frederico Guilherme F. , Kumar Vikas , Garza-Reyes Jose Arturo 
Published: August 2021

PurposeThis research investigates the impact of the strategic sourcing process on the supply chain response to COVID-19. The paper presents practitioners' perspectives (experts in supply chain management, especially involved in the procurement field) on the strategic sourcing process's impact on the supply chain response.Design/methodology/approachThe study follows a survey-based approach for data collection. It uses a descriptive survey methodology where questions related to the impact of the strategic sourcing process on the supply chain response in the face of the coronavirus pandemic were explored by practitioners.FindingsIn total, 130 valid responses were obtained. The results showed that the majority of respondents agreed or strongly agreed that strategic sourcing positively impacts the supply chain response amid the COVID-19 effects. Also, for the five phases of the strategic sourcing process, the majority of respondents considered them as a high and very high impact on the supply chain response.Research limitations/implicationsThis paper provides timely insights for practitioners and academics, especially those involved in the supply chain management area, showing how the strategic sourcing process plays an important role in making supply chains more responsive amid disruption situations.Practical implicationsFindings of this paper clearly shows the impact of the phases of the strategic sourcing process on the responsiveness of the supply chains amid the COVID-19 pandemic. This can encourage supply chain leadership to devote more time to strategic sourcing initiatives to generate improvements on the supply chain performance.Originality/valueThis paper is unique since it brings an unexplored relation in respect to strategic sourcing amid disruption situations, such as the COVID-19 pandemic, from a practitioner's perspective. It also significantly contributes to developing new directions for the supply chain management domain to deal with large-scale disruptions, such as the coronavirus pandemic.
Assessing cognitive, social and teaching presences during emergency remote teaching at a South African university
Authors: Waghid Zayd , Meda Lawrence , Chiroma Jane Adhiambo 
Published: August 2021

PurposeThis study aims to examine how lecturers at a South African university navigated teaching and learning in the current educational landscape obscured by the global pandemic. The authors examine how lecturers employed a community of inquiry (CoI) in their online classrooms within the context of emergency remote teaching (ERT). The study further aims to ascertain students’ feedback concerning current ERT practices at the university toward cultivating a CoI. Doing this would offer more appropriate interventions and support for lecturers and students from, within and for an African context. If not, instructors might risk reproducing and perpetuating the same outdated pedagogies before the pandemic.Design/methodology/approachA mixed-method research design informed by a pragmatist paradigm was used. Primary data were collected from 40 lecturers at the university through online questionnaires of which 10 lecturers responded to e-mail interviews. The original CoI survey was distributed among 150 students in the Faculty of Education at the university.FindingsThe findings revealed that, despite the rushed and trial nature of the use of ERT, there were instances of a CoI among students. The findings further revealed that the majority of the lecturers were not adequately prepared for ERT as a result of limited experience with asynchronous and synchronous online teaching. There was evidence of an absence of a strong active teaching presence that was found to have negatively influenced the development of social and cognitive presences during ERT.Research limitations/implicationsOnly a single faculty at one university was selected in this single case.Practical implicationsThe results of the study have significant implications for faculties and academic staff who are currently teaching online in response to the teaching challenges paused by the COVID-19 pandemic. These findings will assist lecturers in developing appropriate pedagogical intervention strategies to enhance strong and active teaching and social presences necessary for cultivating the cognitive presences among students during ERT.Originality/valueThis is one of the first empirical studies to explore the influence of ERT on the cognitive, social and teaching presences at a university in an African context. The findings and conclusion of the study are novel as they relate to the development of appropriate pedagogical practices and intervention strategies suitable for ERT in response to the current education crisis.