bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor expressed CD95 causes suppression of anti-tumor activity of NK cells in a model of triple negative breast cancer
Authors: Qadir Abdul S. , Guégan Jean Philippe , Ginestier Christophe , Chaibi Assia , Bessede Alban , Charafe-Jauffret Emmanuelle , Macario Manon , Lavoué Vincent , de la Motte Rouge Thibault , Law Calvin , Vilker Jacob , Wang Hongbin , Stroup Emily , Schipma Matthew J. , Bridgeman Bryan , Murmann Andrea E. , Ji Zhe , Legembre Patrick , Peter Marcus E. 
Published: February 2021

AbstractThe apoptosis inducing receptor CD95/Fas has multiple tumorigenic activities. Stimulation by its cognate ligand CD95L on many cancer cells increases their growth, motility, ability to invade and/or their cancer stemness. Using genetically engineered mouse models of ovarian and liver cancer, we previously reported that deletion of CD95 in the tumor cells strongly reduced their ability to growin vivo[1, 2]. Using a combination of immune-deficient and immune-competent mouse models, we now establish that loss of CD95 in metastatic triple negative breast cancer cells prevents tumor growth by modulating the immune landscape. CD95 deficient but not wild-type tumors barely grow in an immune-competent environment and show an increase in immune infiltrates into the tumor. This growth reduction is caused by NK cells and does not involve CD8+T cells. On the other hand, in immune compromised mice CD95 k.o. cells are not growth inhibited, but they fail to form metastases. In summary, we demonstrate that in addition to its tumor and metastasis promoting activities, CD95 expression by tumor cells can exert immune suppressive activities providing a new target for immune therapy.
HaVoC, a bioinformatic pipeline for reference-based consensus assembly and lineage assignment for SARS-CoV-2 sequences
Authors: Nguyen Phuoc Truong , Plyusnin Ilya , Sironen Tarja , Vapalahti Olli , Kant Ravi , Smura Teemu 
Published: February 2021

AbstractBackgroundSARS-CoV-2 related research has increased in importance worldwide since December 2019. Several new variants of SARS-CoV-2 have emerged globally, of which the most notable and concerning currently are the UK variant B.1.1.7, the South African variant B1.351 and the Brazilian variant P.1. Detecting and monitoring novel variants is essential in SARS-CoV-2 surveillance. While there are several tools for assembling virus genomes and performing lineage analyses to investigate SARS-CoV-2, each is limited to performing singular or a few functions separately.ResultsDue to the lack of publicly available pipelines, which could perform fast reference-based assemblies on raw SARS-CoV-2 sequences in addition to identifying lineages to detect variants of concern, we have developed an open source bioinformatic pipeline calledHaVoC(Helsinki university Analyzer for Variants Of Concern).HaVoCcan reference assemble raw sequence reads and assign the corresponding lineages to SARS-CoV-2 sequences.ConclusionsHaVoCis a pipeline utilizing several bioinformatic tools to perform multiple necessary analyses for investigating genetic variance among SARS-CoV-2 samples. The pipeline is particularly useful for those who need a more accessible and fast tool to detect and monitor the spread of SARS-CoV-2 variants of concern during local outbreaks.HaVoCis currently being used in Finland for monitoring the spread of SARS-CoV-2 variants.HaVoCuser manual and source code are available athttps://www.helsinki.fi/en/projects/havocandhttps://bitbucket.org/auto_cov_pipeline/havoc, respectively.
AnadAmutation confers nicotinic acid auxotrophy in pro-carcinogenic intestinalEscherichia coliNC101
Authors: Lopez Lacey R. , Barlogio Cassandra J. , Broberg Christopher A. , Wang Jeremy , Arthur Janelle C. 
Published: February 2021

AbstractInflammatory bowel diseases and inflammation-associated colorectal cancer are linked to blooms of adherent-invasiveEscherichia coli(AIEC) in the intestinal microbiota. AIEC are functionally defined by their ability to adhere/invade epithelial cells and survive/replicate within macrophages. Changes in micronutrient availability can alter AIEC physiology and interactions with host cells. Thus, culturing AIEC for mechanistic investigations often involves precise nutrient formulation. We observed that the pro-inflammatory and pro-carcinogenic AIEC strain NC101 failed to grow in minimal media (MM). We hypothesized that NC101 was unable to synthesize a vital micronutrient normally found in the host gut. Through nutrient supplementation studies, we identified that NC101 is a nicotinic acid (NA) auxotroph. NA auxotrophy was not observed in the other non-toxigenicE. colior AIEC strains we tested. Sequencing revealed NC101 has a missense mutation innadA, a gene encoding quinolinate synthase A that is important forde novoNAD biosynthesis. Correcting the identifiednadApoint mutation restored NC101 prototrophy without impacting AIEC function, including motility and AIEC-defining survival in macrophages. Our findings, along with the generation of a prototrophic NC101 strain, will greatly enhance the ability to performin vitrofunctional studies that are needed for mechanistic investigations on the role of intestinalE. coliin digestive disease.ImportanceInflammatory bowel diseases (IBD) and colorectal cancer (CRC) are significant global health concerns that are influenced by gut resident microbes, like adherent-invasiveEscherichia coli(AIEC). Nutrient availability influences specialized metabolite production, AIEC-defining functional attributes, and AIEC:host interactions. NC101 is a pro-inflammatory and pro-carcinogenic AIEC strain commonly used for studies on IBD and CRC. We identified that NC101 growthin vitrorequires a micronutrient found in the host gut. By correcting an identified mutation, we generated an NC101 strain that no longer has micronutrient restrictions. Our findings will facilitate future research that necessitates precise nutrient manipulation, enhancing AIEC functional studies and investigations on other auxotrophic intestinal microbiota members. Broadly, this will improve the study of bacterial:host interactions impacting health and disease.
A bacteriophage cocktail significantly reducesListeria monocytogeneswithout deleterious impact on the commensal gut microbiota under simulated gastro-intestinal conditions
Authors: Jakobsen Rasmus Riemer , Trinh Jimmy T. , Bomholtz Louise , Brok-Lauridsen Signe Kristine , Sulakvelidze Alexander , Nielsen Dennis Sandris 
Published: February 2021

AbstractIn this study, we examined the effect of a bacteriophage cocktail (tentatively designated FOP, for Foodborne Outbreak Pill) on the levels ofListeria monocytogenesin simulated small intestine, large intestine, and Caco-2 model systems. We found that FOP survival during simulated passage of the upper gastrointestinal was dependent on stomach pH, and that FOP robustly inhibitedL. monocytogeneslevels with effectiveness comparable to antibiotic treatment (ampicillin) under simulated ilium and colon conditions. FOP did not inhibit the commensal bacteria, whereas ampicillin treatment led to dysbiosis-like conditions. FOP was also more effective than antibiotic in protecting Caco-2 cells from adhesion and invasion byL. monocytogenes, while not triggering an inflammatory response. Our data suggest that FOP may provide a robust protection againstL. monocytogenesshould the bacterium enter the human gastrointestinal tract (e.g., by consumption of contaminated food), without deleterious impact on the commensal bacteria.
Bereavement care for ethnic minority communities: A systematic review of access to, models of, outcomes from, and satisfaction with, service provision
Authors: Mayland Catriona Rachel , Powell Richard A. , Clarke Gemma , Ebenso Bassey , Allsop Matthew J 
Published: February 2021

AbstractObjectivesTo review and synthesize the existing evidence on bereavement care, within the United Kingdom (UK), for ethnic minority communities in terms of barriers and facilitators to access; models of care; outcomes from, and satisfaction with, service provision.DesignA systematic review adopting a framework synthesis approach was conducted. An electronic search of the literature was undertaken in MEDLINE, Embase, PsycINFO, Social Work Abstract and CINAHL via EBSCO, Global Health, Cochrane library, the Trip database and ProQuest between 2000 and 2020. Search terms included bereavement care, ethnic minority populations and the UK setting.ResultsFrom 3,185 initial records, following screening for eligibility, and full-text review of 164 articles, seven studies were identified. There was no research literature outlining the role of family, friends and existing networks; and a real absence of evidence about outcomes and levels of satisfaction for those from an ethnic minority background who receive bereavement care. From the limited literature, the overarching theme for barriers to bereavement care was ‘unfamiliarity and irregularities’. Four identified subthemes were ‘lack of awareness’; ‘variability in support’; ‘type and format of support’; and ‘culturally specific beliefs’. The overarching theme for facilitators for bereavement care was ‘accessibility’ with the two subthemes being ‘readily available information’ and ‘inclusive approaches’. Three studies reported on examples of different models of care provision.ConclusionsThis review reveals a stark lack of evidence about bereavement care for ethnic minority populations. In particular, understanding more about the role of family, friends and existing support systems, alongside outcomes and satisfaction will begin to develop the evidence base underpinning current provision. Direct user-representation through proactive engagement and co-design approaches may begin to determine the most appropriate models and format of bereavement care for ethnic minority communities to inform service design and delivery.
Computational validation of clonal and subclonal copy number alterations from bulk tumour sequencing
Authors: Antonello Alice , Bergamin Riccardo , Calonaci Nicola , Househam Jacob , Milite Salvatore , Williams Marc J , Anselmi Fabio , d’Onofrio Alberto , Sundaram Vasavi , Sosinsky Alona , Cross William CH , Caravagna Giulio 
Published: February 2021

AbstractThe identification of chromosome number alterations is now widespread in cancer research, but three features of genomic data hinder copy number calling and downstream analyses: the purity of the tumour sample, intra-tumour heterogeneity, and the ploidy of the tumour. To assess these features, consensus methods are often utilised, though these become onerous in projects that involve thousands of genomes. To facilitate the validation of clonal and subclonal copy number variants we present CNAqc, an evolution-inspired toolset that leverages the known quantitative relationships of purity, ploidy and heterogeneity. We validate the algorithms in CNAqc using low-pass single-cell data, as well as extensive simulations. Its application is demonstrated using over 4000 whole genomes and exomes from TCGA, and PCAWG. A real world application of CNAqc in the analysis of clinical tumour samples, has been demonstrated by its incorporation into the validation of clinically accredited bioinformatics pipeline at Genomics England. Our approach is compatible with most bioinformatic pipelines and designed to augment algorithms with automated quality control procedures for data validation.
Comprehensive metabolic engineering for fermenting glycerol efficiently inSaccharomyces cerevisiae
Authors: Khattab Sadat M. R. , Watanabe Takashi 
Published: February 2021

ABSTRACTGlycerol is an eco-friendly solvent enhancing plant-biomass decomposition through a glycerolysis process in many pretreatment methods. Nonetheless, the lack of efficient conversion of glycerol by naturalSaccharomyces cerevisiaerestrains many of these scenarios. Here we outline the complete strategy for the generation of efficient glycerol fermenting yeast by rewriting the oxidation of cytosolic nicotinamide adenine dinucleotide (NADH) by O2-dependent dynamic shuttle while abolishing both glycerol phosphorylation and biosynthesis pathways. By following a vigorous glycerol oxidative pathway, the engineered strain demonstrated augmentation in conversion efficiency (CE) reach up to 0.49g-ethanol/g-glycerol—98% of theoretical conversion—with production rate >1 g/L-1h-1when supplementing glycerol as a single fed-batch on a rich-medium. Furthermore, the engineered strain showed a new capability toward ferment a mixture of glycerol and glucose with producing >86 g/L of bioethanol with 92.8% of the CE. To our knowledge, this is the highest ever reported titer in this regard. Notably, this strategy flipped our ancestral yeast from non-growth on glycerol, on the minimal medium, to a fermenting strain with productivities 0.25-0.5 g/L-1h-1and 84-78% of CE, respectively and 90% of total conversions to the products. The findings in metabolic engineering here may release the limitations of utilizing glycerol in several eco-friendly biorefinery approaches.IMPORTANCEWith the avenues for achieving efficient lignocellulosic biorefinery scenarios, glycerol gained keen attention as an eco-friendly biomass-derived solvent for enhancing the dissociation of lignin and cell wall polysaccharides during pretreatment process. Co-fermentation of glycerol with the released sugars from biomass after the glycerolysis expands the resource for ethanol production and release from the burden of component separation. Titer productivities are one of the main obstacles for industrial applications of this process. Therefore, the generation of highly efficient glycerol fermenting yeast significantly promotes the applicability of the integrated biorefineries scenario. Besides, the glycerol is an important carbon resource for producing chemicals. Hence, the metabolic flux control of yeast from glycerol contributes to generation of cell factory producing chemicals from glycerol, promoting the association between biodiesel and bioethanol industries. Thus, this study will shed light on solving the problems of global warming and agricultural wastes, leading to establishment of the sustainable society.
Chemical ecology of an apex predator life cycle
Authors: Mucci Nicholas C. , Jones Katarina A. , Cao Mengyi , Wyatt Michael R. , Foye Shane , Kauffman Sarah , Taufer Michela , Chikaraishi Yoshito , Steffan Shawn , Campagna Shawn , Goodrich-Blair Heidi 
Published: February 2021

AbstractMicrobial symbiotic interactions, mediated by small molecule signaling, drive physiological processes of higher order systems. Metabolic analytic technologies advancements provide new avenues to examine how chemical ecology, or conversion of existing biomass to new forms, changes over a symbiotic lifecycle. We examine such processes using the tripartite relationship between nematode hostSteinernema carpocapsae, its obligate mutualist bacterium,Xenorhabdus nematophila, and the insects they infect together. We integrate trophic, metabolomics, and gene regulation analyses to understand insect biomass conversion to nematode or bacterium biomass. Trophic analysis established bacteria as the primary insect consumers, with nematodes at trophic position 4.37, indicating consumption of bacteria and likely other nematodes. Significant, discrete metabolic phases were distinguishable from each other, indicating the insect chemical environment changes reproducibly during bioconversion. Tricarboxylic acid cycle components and amino acids were significantly affected throughout infection. These findings contribute to an ongoing understanding of how symbiont associations shape chemical environments.TeaserEntomopathogenic nematodes act as an apex predator in some ecosystems through altering chemical environments of their prey.
Invadopodia enable cooperative invasion and metastasis of breast cancer cells
Authors: Perrin L. , Belova E. , Bayarmagnai B. , Tüzel E. , Gligorijevic B. 
Published: February 2021

AbstractInvasive and non-invasive cancer cells can invade together during the cooperative invasion. However, the events leading to it, role of EMT and the consequences this may have on metastasis are unknown. In this study, we demonstrate that the isogenic 4T1 and 67NR breast cancer cells sort from each other in 3D spheroids, followed by cooperative invasion. By time-lapse microscopy, we show that the invasive 4T1 cells move more persistently compared to non-invasive 67NR, sorting and accumulating at the spheroid-ECM interface, a process dependent on cell-ECM adhesions and independent from E-cadherin cell-cell adhesions. Elimination of invadopodia in 4T1 cells blocks invasion, demonstrating that invadopodia requirement is limited to leader cells. Importantly, we demonstrate that cells with and without invadopodia can also engage in cooperative metastasis in preclinical mouse models. Altogether, our results suggest that a small number of cells with invadopodia can drive the metastasis of heterogeneous cell clusters.
Innate Immune sensing of Influenza A viral RNA through IFI16 promotes pyroptotic cell death
Authors: Mishra Shalabh , Raj Athira S , Kumar Akhilesh , Rajeevan Ashwathi , Kumari Puja , Kumar Himanshu 
Published: February 2021

AbstractProgrammed cell death pathways are triggered by various stresses or stimuli, including viral infections. The mechanism underlying the regulation of these pathways upon Influenza A virus IAV infection is not well characterized. We report that a cytosolic DNA sensor IFI16 is essential for the activation of programmed cell death pathways in IAV infected cells. We have identified that IFI16 functions as an RNA sensor for influenza A virus by binding to genomic RNA. The activation of IFI16 triggers the production of type I, III interferons, and also other pro-inflammatory cytokines via the STING-TBK1 and Pro-caspase-1 signaling axis, thereby promoting cell death (apoptosis and pyroptosis in IAV infected cells). Whereas, IFI16 knockdown cells showed reduced inflammatory responses and also prevented cell mortality during IAV infection. These results demonstrate the pivotal role of IFI16-mediated IAV sensing and its essential role in activating programmed cell death pathways.
Recognizing nonmonotonicity of exogenous determinants in a stochastic profit efficiency framework: have banks overinvested in IT capital?
Authors: Prakash Navendu , Singh Shveta , Sharma Seema 
Published: February 2021

PurposeThe purpose of this study is to explore and evaluate potential nonmonotonicity in the determinants of profit efficiency, specifically IT and R&D investments in the Indian commercial banking sector.Design/methodology/approachThe study employs an alternative stochastic profit efficiency framework and introduces nonmonotonic effects by parameterizing the location and scale parameters of the inefficiency component on an unbalanced panel data set of 72 commercial banks in the 2008–2019 period. Marginal effects across quartiles are calculated using a bias-corrected and accelerated bootstrap procedure of 500 simulations. The study disaggregates across ownership and size for gauging the impact of structure on the associations between determinants of profit efficiency.FindingsThe study partially rejects the productivity paradox as it discovers a negative association of IT and R&D with profit inefficiency. However, the observed nonmonotonicity of IT is of significance for bank managers, as the study concludes that overinvestment in IT is detrimental to a bank’s profit-maximizing interests. Further, bank size, loan default and credit risk depict a nonmonotonic relationship across the sample with large banks, high NPAs and high credit risk associated with reducing profit efficiency. In addition, higher margins and greater diversification are related positively to efficiency, and banks with cost-heavy structures or having high liquidity risk associated negatively with efficiency.Originality/valueTo the best knowledge of the authors, the study is perhaps the first to acknowledge and incorporate nonmonotonic associations of IT investments amidst other exogenous determinants under a stochastic profit efficiency framework.
Measuring national intellectual capital: a novel approach
Authors: Vo Duc Hong , Tran Ngoc Phu 
Published: February 2021

PurposeA very few studies have been conducted to measure a degree of national intellectual capital for selected groups of countries. This paper is conducted to construct a new index of national intellectual capital (INIC) which is simple, quantifiable, relevant and comparable for countries around the globe.Design/methodology/approachThe styudy’s new INIC uses various indicators which are proxies for fundamental aspects of intellectual capital, including (1) human capital, (2) structural capital and (3) relational capital. These indicators are publicly available for many countries. The principal component analysis is utilized to derive the INIC. Various tests have also been conducted to ensure that the new index is appropriate and fit for purpose.FindingsFindings from this paper confirm that the new INIC has a strong correlation of 0.80 with an index developed by Lin et al. (2014) (the LECB index), an advanced INIC to date. The LECB index has been infrequently updated and covered selected countries due to data and information unavailability. In addition, the study’s tests indicate that a high correlation of 0.75 is observed between the study’s index and GDP per capita. The new INIC represents an advancement in relation to its simplicity, quantification, relevance and international comparison across nations.Practical implicationsThe estimates of national intellectual capital using the approach in this study will open a new strand of theoretical and empirical studies in relation to national intellectual capital and other economic and social issues of interests. This novel and innovative approach will provide policymakers with a valuable framework to formulate and implement relevant policies to enhance and improve national intellectual capital.Originality/valueTo the best knowledge of the authors, this is the first study of its type, which is conducted to measure national intellectual capital based on publicly available data. Required data cover an extended period of years and a majority of countries. As such, an INIC will enhance transparency and feasibility for international comparison across countries.