bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering the postsynaptic calcium-mediated energy homeostasis through mitochondria-endoplasmic reticulum contact sites using systems modeling
Authors: Leung A. , Ohadi D. , Pekkurnaz G. , Rangamani P. 
Published: September 2020

AbstractSpatiotemporal compartmentation of calcium dynamics is critical for neuronal function, particularly in post-synaptic spines. This exquisite level of Ca2+compartmentalization is achieved through the storage and release of Ca2+from various intracellular organelles particularly the endoplasmic reticulum (ER) and the mitochondria. Mitochondria and ER are established storage organelles controlling Ca2+dynamics in neurons. Mitochondria also generate a majority of energy used within postsynaptic spines to support the downstream events associated with neuronal stimulus. Recently, high resolution microscopy has unveiled direct contact sites between the ER and the mitochondria, which directly channel Ca2+release from the ER into the mitochondrial membrane. In this study, we develop a computational 3D reaction-diffusion model to investigate the role of MERCs in regulating Ca2+and ATP dynamics. This spatiotemporal model accounts for Ca2+oscillations initiated by glutamate stimulus of metabotropic and ionotropic glutamate receptors and Ca2+changes in four different compartments: cytosol, ER, mitochondria, and the MERC microdomain. Our simulations predict that the organization of these organelles and differential distribution of key Ca2+channels such as IP3receptor and ryanodine receptor modulate Ca2+dynamics in response to different stimuli. We further show that the crosstalk between geometry (mitochondria and MERC) and metabolic parameters (cytosolic ATP hydrolysis, ATP generation) influences the cellular energy state. Our findings shed light on the importance of organelle interactions in predicting Ca2+dynamics in synaptic signaling. Overall, our model predicts that a combination of MERC linkage and mitochondria size is necessary for optimal ATP production in the cytosol.
Fine interaction profiling of VemP and mechanisms responsible for its translocation-coupled arrest-cancelation
Authors: Miyazaki Ryoji , Akiyama Yoshinori , Mori Hiroyuki 
Published: September 2020

AbstractBacterial cells utilize monitoring substrates, which undergo force-sensitive translation elongation arrest, to feedback-regulate a Sec-related gene.Vibrio alginolyticusVemP controls the expression of SecD/F that stimulates a late step of translocation by undergoing export-regulated elongation arrest. Here, we attempted at delineating the pathway of the VemP nascent-chain interaction with Sec-related factors, and identified the signal recognition particle (SRP) and PpiD (a membrane-anchored periplasmic chaperone) in addition to other translocon components and a ribosomal protein as interacting partners. Our results showed that SRP is required for the membrane-targeting of VemP, whereas PpiD acts cooperatively with SecD/F in the VemP arrest-cancelation. We also identified the conserved Arg-85 residue in VemP as an essential element for the regulated arrest-cancelation of VemP. We propose a scheme of the arrest-cancelation processes of VemP, which likely monitors late steps in the protein translocation pathway.
Single-Cell Transcriptomic Attributes and Unbiased Computational Modeling for the Prediction of Immunomodulatory Potency of Mesenchymal Stromal Cells
Authors: Pradhan Pallab , Chatterjee Paramita , Stevens Hazel Y. , Glen Chad , Medrano-Trochez Camila , Jimenez Angela , Kippner Linda , Seeto Wen Jun , Li Ye , Gibson Greg , Kurtzberg Joanne , Kontanchek Theresa , Yeago Carolyn , Roy Krishnendu 
Published: September 2020

ABSTRACTMesenchymal stromal cells (MSCs) are currently being tested in numerous clinical trials as potential cell therapies for the treatment of various diseases and due to their potential immunomodulatory, pro-angiogenic, and regenerative properties. However, variabilities in tissue sources, donors, and manufacturing processes and the lack of defined critical quality attributes (CQAs) and clinically relevant mechanism of action (MoA) pose significant challenges to identify MSC cell therapy products with a predictable therapeutic outcome. This also hinders regulatory considerations and broad clinical translation of MSCs. MSC products are often administered to the patient immediately after thawing from cryopreserved vials (out-of-thaw). However, the qualifying quality-control assays are either performed before cryopreservation, or after culturing the post-thaw cells for 24-48 hours (culture-rescued), none of which represent the out-of-thaw product administered to patients. In this study, we performed a broad functional characterization of out-of-thaw and culture-rescue MSCs from bone marrow (BM-MSCs) and cord tissue (CT-MSCs) using macrophage activation and T cell proliferation-basedin vitropotency assays and deep phenotypic characterization using single-cell RNA-sequencing. Using this data, we developed unbiased computational models, specifically symbolic regression (SR) and canonical correlation analysis (CCA) models to predict the immunomodulatory potency of MSCs. Overall, our results suggest that manufacturing conditions (OOT vs. CR) have a strong effect on MSC-function on MSC interactions with macrophages and T cells. Furthermore, single-cell RNA-seq analyses of out-of-thaw BM and CT-MSCs indicate a tissue of origin-dependent variability and heterogeneity in the transcriptome profile. Using symbolic regression modeling we identified specific single-cell transcriptomic attributes of MSCs that predict their immunomodulatory potency. In addition, CCA modeling predicted MSC donors with high or low immunomodulatory potency from their transcriptome profiles. Taken together, our results provide a broad framework for identifying predictive CQAs of MSCs that could ultimately help in better understanding of their MOAs and improved reproducibility and manufacturing control of MSCs.
The origin and maintenance of microbial symbionts inDrosophilalarvae
Authors: Guilhot Robin , Lagmairi Auxane , Olazcuaga Laure , Xuéreb Anne , Fellous Simon 
Published: September 2020

AbstractLittle is known on the origin and maintenance of symbionts associated withDrosophilalarvaein natura, which restricts the understanding ofDrosophila-extracellular microorganism symbiosis in the light of evolution. Here, we studied the origin and maintenance of symbionts ofDrosophilalarvae under ecologically realistic conditions, to our knowledge for the first time, using yeast and bacterial isolates and twoDrosophilaspecies: the model organismD. melanogasterand the invasive pestD. suzukii. We discovered thatDrosophilafemales and males both transmit yeast and bacteria symbionts to larvae. In addition, several symbiotic yeasts initially associated with larvae were conserved throughout host life cycle and transmitted to offspring. Our results suggest that stable associations ofDrosophilaflies with bacteria and yeasts may existin naturaand constitute a step forward in the understanding of wildDrosophila-microorganism symbioses.
Designed PKC-targeting bryostatin analogs modulate innate immunity and neuroinflammation
Authors: Abramson Efrat , Hardman Clayton , Shimizu Akira , Hwang Soonmyung , Hester Lynda D. , Snyder Solomon H. , Wender Paul A. , Kim Paul M. , Kornberg Michael D. 
Published: September 2020

SUMMARYNeuroinflammation characterizes multiple neurologic diseases, including primary inflammatory conditions such as multiple sclerosis (MS) and classical neurodegenerative diseases. Aberrant activation of the innate immune system contributes to disease progression in these conditions, but drugs that modulate innate immunity, particularly within the central nervous system (CNS), are lacking. The CNS-pene-trant natural product bryostatin-1 (bryo-1) attenuates neuroinflammation by targeting innate myeloid cells. Supplies of natural bryo-1 are limited but a recent scalable synthesis has enabled access to it and its analogs (termed bryologs), the latter providing a path to more efficacious, better tolerated, and more accessible agents. Here, we show that multiple synthetically accessible bryologs replicate the anti-inflammatory effects of bryo-1 on innate immune cellsin vitro, and a lead bryolog attenuates neuroinflammationin vivo– actions mechanistically dependent on PKC binding. Our findings identify bryologs as promising drug candidates for targeting innate immunity in neuroinflammation and create a platform for evaluation of synthetic PKC modulators in neuroinflammatory diseases such as MS.Graphical Abstract
Quantitative and dynamic cell polarity tracking in plant cells
Authors: Gong Yan , Varnau Rachel , Wallner Eva-Sophie , Bergmann Dominique C. , Cheung Lily S. 
Published: September 2020

ABSTRACTQuantitative information on the spatiotemporal distribution of polarized proteins is central for understanding cell-fate determination, yet collecting sufficient data for statistical analysis is difficult to accomplish with manual measurements. Here we present POME, a semi-automated pipeline for the quantification of cell polarity, and demonstrate its application to a variety of developmental contexts. POME analysis reveals that during asymmetric cell divisions in theArabidopsis thalianastomatal lineage, polarity proteins BASL and BRXL2 are more asynchronous and less mutually dependent than previously thought. While their interaction is important to maintain their polar localization and recruit other effectors to regulate asymmetric cell divisions, BRXL2 polarization precedes that of BASL and can be initiated in BASL’s absence. Uncoupling of polarization from BASL activity is also seen inBrachypodium distachyon, where we find that the MAPKKK BdYDA1 is segregated and polarized following asymmetric division. Our results demonstrate that POME is a versatile tool, which by itself or combined with tissue-level studies and advanced microscopy techniques can help uncover new mechanisms of cell polarity.
Visualizing the cytosolic delivery of bioconjugated QDs into T cell lymphocytes
Authors: Jing Haoran , Pálmai Marcell , Saed Badeia , George Anne , Snee Preston T. , Hu Ying S. 
Published: September 2020

AbstractThe aggregation state and endosomal trapping of engineered nanocarriers once internalized into cells remain poorly characterized. Here, we visualized the membrane penetrating dynamics of semiconductor quantum dots (QDs) into the cytosol of T cells on a single-cell and single-nanoparticle basis. We water solubilized CdSe/CdZnS QDs with polymer encapsulants functionalized with a cell-penetrating peptide composed of an Asp-Ser-Ser (DSS) repeat sequence. T cells tolerated the 24-h incubation with QDs at concentrations of 5 nM or lower. Single-particle imaging demonstrated that the number of internalized nanoparticles was dependent upon the concentration of the probes for both control (peptide-free) and DSS-QDs. DSS-QDs were mostly distributed as monomers, whereas the control QDs were aggregated into clusters. Single-particle tracking using total internal reflection and highly inclined illumination showed that DSS-QDs were stationary near the activating surface and mobile within the cytosol of the T cell. A correlation exhibited between the mobility and aggregation state of individual QD clusters, with monomeric DSS-QDs showing the highest mobility. In addition, monomeric DSS-QDs displayed much faster diffusion than the endosomes. A small-molecule endosome marker confirmed the absence of colocalization between endosomes and DSS-QDs, indicating their endosomal escape. The ability to deliver and track individual QDs in the cytosol of live T cells creates inroads for the optimization of drug delivery and gene therapy through the use of nanoparticles.
Type II photosynthetic reaction center genes of avocado (Persea americanaMill.) bark microbial communities are dominated by aerobic anoxygenic Alphaproteobacteria
Authors: Aguirre-von-Wobeser Eneas 
Published: September 2020

AbstractThe tree bark environment is an important microbial habitat distributed worldwide on thrillions of trees. However, the microbial communities of tree bark are largely unknown, with most studies on plant aerial surfaces focused on the leaves. Recently, we presented a metagenomic study of bark microbial communities from avocado. In these communities, oxygenic and anoxygenic photosynthesis genes were very abundant, especially when compared to rhizospheric soil from the same trees. In this work, Evolutionary Placement Algorithm analysis was performed on metagenomic reads orthologous to thePufLMgene cluster, encoding for the bacterial type II photosynthetic reaction center. These photosynthetic genes were found affiliated to different groups of bacteria, mostly aerobic anoxygenic photosynthetic Alphaproteobacteria, includingSphingomonas, Methylobacteriumand several Rhodospirillales. These results suggest that anoxygenic photosynthesis in avocado bark microbial communities functions primarily as additional energy source for heterotrophic growth. Together with our previous results, showing a large abundance of cyanobacteria in these communities, a picture emerges of the tree holobiont, where light penetrating the trees canopies and reaching the inner stems, including the trunk, is probably utilized by cyanobacteria for oxygenic photosynthesis, and the far-red light aids the growth of aerobic anoxygenic photosynthetic bacteria.
RWRDC: Predicting Efficacious Drug Combinations in Cancer Based on Random Walk with Restart
Authors: Wang Qi , Yan Guiying 
Published: September 2020

Abstract(1)BackgroundCompared with monotherapy, efficacious drug combinations can increase the therapeutic effect, decrease drug resistance of experimental subjects and the side effects of drugs. Therefore, efficacious drug combinations are widely used in the treatment of complex diseases, such as various cancers. However, compared with the mathematical model and computational method, experimental screening efficacious drug combinations is time-consuming, costly, laborious, and inefficient;(2)Methodswe predicted efficacious drug combinations in cancer based on random walk with restart (RWRDC). An efficacious score can be obtained between any two individual drugs by RWRDC;(3)ResultsAs a result, we analyzed the rationality of the efficacious score first. Besides, compared with the other methods by leave-one-out cross-validation, all the Area Under Receiver Operating Characteristic Curves (AUROCs) of RWRDC were higher for data sets of breast cancer, colorectal cancer, and lung cancer. Moreover, the case study of breast cancer showed that RWRDC could discover potential efficacious drug combinations;(4)ConclusionsThese results suggest that RWRDC is a novel way to discover efficacious drug combinations in cancer, which provides new prospects for cancer treatment. Furthermore, RWRDC is a semi-supervised learning framework that can be used to predict combinations of drugs for other complex diseases.
The wounds that do not heal: Black expendability and the traumatizing aftereffects of anti-Black police violence
Authors: Waldron Ingrid R.G. 
Published: September 2020

PurposeThe murders of Black people at the hands of police in 2020 have led to global protests that have called on public officials to defund or abolish the police. What has been drowned out in these conversations, however, is the traumatizing aftereffects of anti-Black police violence as a public health crisis. In this paper, I argue that the racial terrorism of anti-Black police violence is a deeply felt wound in Black communities that extends beyond the individuals who directly experience it and that this type of collective trauma must be understood as an urgent public health crisis.Design/methodology/approachUsing published studies and online commentaries on anti-Black police violence and its mental health impacts in Canada and the United States, this paper examines the mental health impacts of anti-Black police violence at both the individual and community levels.FindingsA public health response to the traumatizing aftereffects of anti-Black police violence and other forms of state violence must highlight important policy imperatives, such as policies of action focused on improving the public health system. It must also encompass a recognition that the public health crisis of anti-Black police violence is not solvable solely by public health agencies alone. Rather, strategic opportunities to address this crisis arise at every level of governmental interaction, including law enforcement, health care, employment, business, education and the media.Originality/valueWhile the impact of anti-Black police violence on the mental health of Black individuals has been emerging in the literature over the last several years, what has been less focused on and what I address in this paper is how the threat of that violence lingers in Black communities long after the protestors have packed up their megaphones, resulting in collective trauma in Black communities.
From “Calling in Black” to “Calling for Antiracism Resources”: the need for systemic resources to address systemic racism
Authors: McCluney Courtney L. , King Danielle D. , Bryant Courtney M. , Ali Abdifatah A. 
Published: September 2020

PurposeThe purpose of this essay is to highlight the urgent need for antiracism resource generation in organizations today.Design/methodology/approachThis essay weaves together popular press articles, academic writings and the authors' lived experiences to summarize, clarify and extend the work needed inside of organizations and academia to dismantle systemic racism.FindingsWe define antiracist resources as personal and material assets that counteract systemic racism through informing and equipping antiracist actions, and identify three resources—adopting a long-term view for learning the history of racism, embracing discomfort to acknowledge racist mistakes and systematically assess how organizational structures maintain white supremacy—for organizations to address systemic racism.Research limitations/implicationsWhile there is a critical need for more antiracism research, there are standards and guidelines that should be followed to conduct that research responsibly with antiracism enacted in research design, methodology decisions and publication practices.Practical implicationsThe authors call for organizations to directly counter-racism via antiracism resources and offer examples for how these resources can inform and equip companies to create equitable workplaces.Originality/valueThis essay offers: (a) an updated, timely perspective on effective responses to systemic racism (e.g. police brutality and COVID-19), (b) a detailed discussion of antiracism resources and (c) specific implications for antiracism work in organizational research.
A worldwide bibliometric and network analysis of work-based learning research
Authors: Bezerra Jacks , Batista Mota Fábio , Waltz Comarú Michele , Amara Maciel Braga Luiza , Fernandes Moutinho Rocha Leonardo , Roberto Carvalho Paulo , Alexandre da Fonseca Tinoca Luís , Matos Lopes Renato 
Published: September 2020

PurposeDuring the last few years there has been an increase of interest in work-based learning (WBL), which can be understood as a process of both developing workplace skills and promoting labor force productivity. This paper aims to map the scientific landscape related to WBL research worldwide.Design/methodology/approachcombined bibliometrics and network analysis techniques to analyze data of scientific publications related to WBL indexed at the Web of Science (WoS) Core Collection.Findingsresults show an increase of publications over time: Education & Educational Research as the most frequent research area to which the articles were assigned, the UK and Australia as the main countries and Monash University (Australia) and Middlesex University (England) as the main organizations producing knowledge on WBL.Originality/valueBy offering a global scientific landscape of WBL research published so far, the authors aimed to contribute to future academic debates and studies in this field of knowledge.
State policy in the sphere of protection of cultural heritage in Ukraine
Authors: Malysh Nataliia , Shevchenko Viktoriya , Tkachuk-Miroshnychenko Olena 
Published: September 2020

PurposeThe purpose of this paper is to analyze the efficacy of the state policy of Ukraine in the sphere of protection of tangible and intangible cultural heritage, measures of safeguarding cultural property in the event of armed conflict and to assess how and why the state funding of culture has changed.Design/methodology/approachThe proposal is to investigate this by discussing the national and international policy frameworks through case study by using quantitative and qualitative methods to disclose if state cultural policy initiatives promote public interest in cultural issues and how the political events in the country affect the distribution of the state funding of culture.FindingsUkrainian state cultural policy initiatives appear to be effective in protecting cultural heritage at both central and local levels despite redistribution in the state funding of this sphere. In cooperation with international agencies, Ukraine effectively promotes its intangible cultural heritage properties. Interest of the public in the state cultural policy issues has grown considerably. Problems exist with the protection of Ukrainian cultural sites located in war zones and disputed territories.Originality/valueThese findings demonstrate how the state policies aimed at protecting Ukrainian cultural heritage may be effectively implemented at different levels in cooperation with international agencies; how the political landscape in the country promotes the public interest in cultural policy issues. This case forms an example of steps aimed at protecting cultural properties on disputed territories in cooperation with intermediaries, such as UNESCO.
Liquidity Discount Value of ITM Option
Authors: Son Kyung-Woo , Kim Sang-Su 
Published: September 2020

KOSPI 200 index option market is one of the markets which is perfectly liquid in the world. While ATM options and OTM options are liquid, ITM options are not. This paper derives LDV (liquidity discount value) from the ITM options by using the no-arbitrage condition of synthetic futures considering market friction.
In this paper, we show that theoretically derived LDV is related to trading volume as standard proxy of liquidity measure and LDV in ITM options exhibit a U-shaped pattern across moneyness. Other findings are that the expected returns from the synthetic futures arbitrage trading considering liquidity premium exhibit a U-shaped pattern across moneyness and it depends on the maturity. This means that the longer days remaining to expiration date, the greater the incentive for arbitrage trading.
Sibship size and educational attainment of Canadian baby boomers
Authors: Dilmaghani Maryam 
Published: September 2020

PurposeThe present study assesses how sibship size affects child quality as measured by educational attainment.Design/methodology/approachThe data are from the Canadian General Social Surveys (GSS) of 1986, 1990, 1994 and 1995. The sample is restricted to the individuals born in Canada between 1946 and 1965, that is, the baby-boom generation. In addition to controlling for parental education, the sibship size is instrumented by a non-binary variable created based on the sex composition of the sibship. While most previous studies have pooled both genders, the present paper produces by gender estimatesFindingsThe OLS estimates are statistically significant, negative and moderately large for both male and female baby boomers. When the sibship size is instrumented, the estimates indicate that one additional sibling had reduced the educational attainment of male baby boomers by almost half a year. No causal effect for the sibship size is found for female baby boomers.Originality/valueThis is the first paper on the effects of sibship size on educational attainment, using Canadian data.