bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large-scale genomic study reveals robust activation of the immune system following advanced Inner Engineering meditation retreat
Authors: Chandran Vijayendran , Bermúdez Mei-Ling , Koka Mert , Chandran Brindha , Pawale Dhanashri , Vishnubhotla Ramana , Alankar Suresh , Maturi Raj , Subramaniam Balachundhar , Sadhasivam Senthilkumar 
Published: May 2021

AbstractThe positive impact of meditation on human wellbeing is well documented, yet its molecular mechanisms are incompletely understood. We applied a comprehensive systems biology approach starting with whole blood gene expression profiling combined with multi-level bioinformatic analyses to characterize the co-expression, transcriptional, and protein-protein interaction networks to identify meditation-specific core network after an advanced 8-day Inner Engineering retreat program. We found the response to oxidative stress, detoxification, and cell cycle regulation pathways were downregulated after meditation. Strikingly, 220 genes directly associated with immune response, including 68 genes related to interferon (IFN) signaling were upregulated, with no significant expression changes in the inflammatory genes. This robust meditation-specific immune response network is significantly dysregulated in multiple sclerosis and severe COVID-19 patients. The work provides a foundation for understanding the effect of meditation and potential implications to voluntarily and non-pharmacologically improve the immune response before immunotherapy for many conditions, including multiple sclerosis and COVID-19 vaccination.
Implications Derived from S-Protein Variants of SARS-CoV-2 from Six Continents
Authors: Hassan Sk. Sarif , Lundstrom Kenneth , Choudhury Pabitra Pal , Palu Giorgio , Uhal Bruce D. , Kandimalla Ramesh , Seyran Murat , Lal Amos , Sherchan Samendra P. , Azad Gajendra Kumar , Aljabali Alaa A. A. , Brufsky Adam M. , Serrano-Aroca Ángel , Adadi Parise , Abd El-Aziz Tarek Mohamed , Redwan Elrashdy M. , Takayama Kazuo , Barh Debmalya , Rezaei Nima , Tambuwala Murtaza , Uversky Vladimir N. 
Published: May 2021

AbstractSpike (S) proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are critical determinants of the infectivity and antigenicity of the virus. Several mutations in the spike protein of SARS-CoV-2 have already been detected, and their effect in immune system evasion and enhanced transmission as a cause of increased morbidity and mortality are being investigated. From pathogenic and epidemiological perspectives, spike proteins are of prime interest to researchers. This study focused on the unique variants of S proteins from six continents Asia, Africa, Europe, Oceania, South America, and North America. In comparison to the other five continents, Africa (29.065%) had the highest percentage of unique S proteins. Notably, only North America had 87% (14046) of the total (16143) specific S proteins available in the NCBI database(across all continents). Based on the amino acid frequency distributions in the S protein variants from all the continents, the phylogenetic relationship implies that unique S proteins from North America were significantly different from those of the other five continents. Overtime, the unique variants originating from North America are most likely to spread to the other geographic locations through international travel or naturally by emerging mutations. Hence it is suggested that restriction of international travel should be considered, and massive vaccination as an utmost measure to combat the spread of COVID-19 pandemic. It is also further suggested that the efficacy of existing vaccines and future vaccine development must be reviewed with careful scrutiny, and if needed, further re-engineered based on requirements dictated by new emerging S protein variants.
Phenotypic and Kinetic Changes of Myeloid Lineage Cells in Innate Response to Chikungunya Infection in Cynomolgus Macaques
Authors: Beddingfield Brandon J. , Sugimoto Chie , Kuroda Marcelo J. , Wang Eryu , Weaver Scott C. , Russell-Lodrigue Kasi E. , Killeen Stephanie Z. , Roy Chad J. 
Published: May 2021

AbstractChikungunya is an emerging threat, spreading across multiple continents. The immune response to infection can lead to protection and convalescence, or result in long term sequelae such as arthritis. Early innate immune events during acute infection have been characterized for some cell types, but more must be elucidated with respect to cellular responses of monocytes and other myeloid lineage cells. In addition to their roles in protection and inflammation resolution, monocytes and macrophages are sites for viral replication and reservoirs for the virus. They are also found in joints post-infection, possibly playing a role in long term CHIKV-induced pathology. We examined kinetic and phenotypic changes in myeloid lineage cells, including monocytes, in cynomolgus macaques early after infection with CHIKV. We found increased turnover of monocytes and mDCs early during infection, with an accompanying decreases in both cell types, as well as a simultaneous increase in pDC number. An increase in CD16 and CD14 was seen along with a decrease in monocyte HLA-DR expression within 3 days of infection, potentially indicating monocyte deactivation. A transient decrease in T cells, B cells and NK cells correlates with lymphocytopenia observed during human infections with CHIKV. CD4+ T cell turnover decreased in blood, indicating relocation of cells to effector sites. This data indicates CHIKV influences turnover rates and kinetics of myeloid lineage cells early during infection, and may prove useful in development of therapeutics and evaluation of infection-induced pathogenesis.
3’HS1 CTCF binding site in human β-globin locus regulates fetal hemoglobin expression
Authors: Himadewi Pamela , David Wang Xue Qing , Feng Fan , Gore Haley , Liu Yushuai , Yu Lei , Liu Jie , Kurita Ryo , Nakamura Yukio , Pfeifer Gerd , Zhang Xiaotian 
Published: May 2021

SummaryMutations in the adult β-globin gene can lead to a variety of hemoglobinopathies, including sickle cell disease and β-thalassemia. An increase in fetal hemoglobin expression throughout adulthood, a condition named Hereditary Persistence of Fetal Hemoglobin (HPFH), has been found to ameliorate hemoglobinopathies. Deletional HPFH occurs through the excision of a significant portion of the 3’ end of the β-globin locus, including a CTCF binding site termed 3’HS1. Here, we show that the deletion of this CTCF site alone induces fetal hemoglobin expression in both adult CD34+ hematopoietic stem and progenitor cells and HUDEP-2 erythroid progenitor cells. This induction is driven by the ectopic access of a previously postulated distal enhancer located in the OR52A1 gene downstream of the locus, which can also be insulated by the inversion of the 3’HS1 CTCF site. This suggests that genetic editing of this binding site can have therapeutic implications to treat hemoglobinopathies.
Functional and structural modifications of influenza antibodies during pregnancy
Authors: Jennewein Madeleine F. , Kosikova Martina , Noelette Francesca J. , Radvak Peter , Boudreau Carolyn M. , Campbell James D. , Chen Wilbur H. , Xie Hang , Alter Galit , Pasetti Marcela F. 
Published: May 2021

SUMMARYPregnancy represents a unique tolerogenic immune state which may alter susceptibility to infection and vaccine-response. Here we characterized humoral immunity to seasonal influenza vaccine strains in pregnant and non-pregnant women. Pregnant women had reduced hemagglutinin subtype-1 (H1)-IgG, IgG1, and IgG2, hemagglutination inhibition and group 1 and 2 stem IgG. However, H1-specific avidity and FcγR1 binding increased. Influenza-antibodies in pregnancy had distinct Fc and Fab glycans characterized by di-galactosylation and di-sialylation. In contrast, agalactosylation and bisection were prominent outside of pregnancy. H1-specific Fc-functionality was moderately reduced in pregnancy, although likely compensated by stronger binding to cognate antigen and FcR. Multivariate analysis revealed distinct populations characterized by FcγR1 binding, H1-IgG levels, and glycosylation. Pooled sera from pregnant women exhibited longer retention in vivo. Our results demonstrate structural and functional modulation of humoral immunity during pregnancy in an antigen-specific manner towards reduced inflammation, increased retention in circulation, and efficient placental transport.
Hypertrophic Chondrocytes Serve as a Reservoir for Marrow Associated Skeletal Stem and Progenitor Cells, Osteoblasts, and Adipocytes During Skeletal Development
Authors: Long Jason T. , Leinroth Abigail , Liao Yihan , Ren Yinshi , Mirando Anthony J. , Nguyen Tuyet , Guo Wendi , Sharma Deepika , Rouse Douglas , Wu Colleen , Cheah Kathryn Song Eng , Karner Courtney M. , Hilton Matthew J. 
Published: May 2021

ABSTRACTHypertrophic chondrocytes give rise to osteoblasts during skeletal development; however, the process by which these non-mitotic cells make this transition is not well understood. Prior studies have also suggested that skeletal stem and progenitor cells (SSPCs) localize to the surrounding periosteum and serve as a major source of marrow associated SSPCs, osteoblasts, osteocytes, and adipocytes during skeletal development. To further understand the cell transition process by which hypertrophic chondrocytes contribute to osteoblasts or other marrow associated cells, we utilized inducible and constitutive hypertrophic chondrocyte lineage tracing and reporter mouse models (Col10a1CreERT2; R26-tdTomatof/+andCol10a1Cre; R26-tdTomatof/+) in combination with aPDGFRa-H2B-GFPtransgenic line, single cell RNA-sequencing, bulk RNA-sequencing, immunofluorescence staining, and cell transplantation assays. Our data demonstrate that hypertrophic chondrocytes undergo a process of dedifferentiation to generate marrow associated SSPCs that serve as a primary source of osteoblasts during skeletal development. These hypertrophic chondrocyte derived SSPCs commit to a CXCL12-abundant reticular (CAR) cell phenotype during skeletal development and demonstrate unique abilities to recruit vasculature and promote bone marrow establishment, while also contributing to the adipogenic lineage.
Spatially distributed infection increases viral load in a computational model of SARS-CoV-2 lung infection
Authors: Moses Melanie E. , Hofmeyr Steven , Cannon Judy L. , Andrews Akil , Gridley Rebekah , Hinga Monica , Leyba Kirtus , Pribisova Abigail , Surjadidjaja Vanessa , Tasnim Humayra , Forrest Stephanie 
Published: May 2021

AbstractA key question in SARS-CoV-2 infection is why viral loads and patient outcomes vary dramatically across individuals. Because spatial-temporal dynamics of viral spread and immune response are challenging to study in vivo, we developed Spatial Immune Model of Coronavirus (SIMCoV), a scalable computational model that simulates hundreds of millions of lung cells, including respiratory epithelial cells and T cells. SIMCoV replicates viral growth dynamics observed in patients and shows how spatially dispersed infections can lead to increased viral loads. The model also shows how the timing and strength of the T cell response can affect viral persistence, oscillations, and control. By incorporating spatial interactions, SIMCoV provides a parsimonious explanation for the dramatically different viral load trajectories among patients by varying only the number of initial sites of infection, and the magnitude and timing of the T cell immune response. When the branching airway structure of the lung is explicitly represented, we find that virus spreads faster than in a 2D layer of epithelial cells, but much more slowly than in an undifferentiated 3D grid or in a well-mixed ODE model. These results illustrate how realistic spatially explicit computational models can improve understanding of within-host dynamics of SARS-CoV-2 infection.SummaryA key question in SARS-CoV-2 infection is why viral loads and patient outcomes are so different across individuals. Because it’s difficult to see how the virus spreads in the lungs of infected people, we developed Spatial Immune Model of Coronavirus (SIMCoV), a computational model that simulates hundreds of millions of cells, including lung cells and immune cells. SIMCoV simulates how virus grows and then declines, and the simulations match data observed in patients. SIMCoV shows that when there are more initial infection sites, the virus grows to a higher peak. The model also shows how the timing of the immune response, particularly the T cell response, can affect how long the virus persists and whether it is ultimately cleared from the lungs. SIMCoV shows that the different viral loads in different patients can be explained by how many different places the virus is initially seeded inside their lungs. We explicitly add the branching airway structure of the lung into the model and show that virus spreads slightly faster than it would in a two-dimensional layer of lung cells, but much slower than traditional mathematical models based on differential equations. These results illustrate how realistic spatial computational models can improve understanding of how SARS-CoV-2 infection spreads in the lung.
Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution
Authors: Amicone Massimo , Borges Vítor , Alves Maria João , Isidro Joana , Zé-Zé Líbia , Duarte Sílvia , Vieira Luís , Guiomar Raquel , Gomes João Paulo , Gordo Isabel 
Published: May 2021

AbstractBackground and objectivesTo understand how organisms evolve, it is fundamental to study how mutations emerge and establish. Here, we estimated the rate of mutation accumulation of SARS-CoV-2 in vitro and investigated the repeatability of its evolution when facing a new cell type but no immune or drug pressures.MethodologyWe performed experimental evolution with two strains of SARS-CoV-2, one carrying the originally described spike protein (CoV-2-D) and another carrying the D614G mutation that has spread worldwide (CoV-2-G). After 15 passages in Vero cells and whole genome sequencing, we characterized the spectrum and rate of the emerging mutations and looked for evidences of selection across the genomes of both strains.ResultsFrom the mutations accumulated, and excluding the genes with signals of selection, we estimate a spontaneous mutation rate of 1.25×10-6 nt-1 per infection cycle for both lineages of SARS-CoV-2. We further show that mutation accumulation is heterogeneous along the genome, with the spike gene accumulating mutations at rate five-fold higher than the genomic average. We also observe the emergence of mutators in the CoV-2-G background, likely linked to mutations in the RNA-dependent RNA polymerase and/or in the error-correcting exonuclease protein.Conclusions and implicationsThese results provide valuable information on how spontaneous mutations emerge in SARS-CoV-2 and on how selection can shape its genome towards adaptation to new environments.Lay summaryMutation is the ultimate source of variation. We estimated how the SARS-COV-2 virus—cause of the COVID-19 pandemic—mutates. Upon infecting cells, its genome can change at a rate of 0.04 per replication. We also find that this rate can change and that its spike protein can adapt, even within few replications.
MAP2XANES: a Jupyter interactive notebook for elemental mapping and XANES speciation
Authors: Marini Carlo , Roqué-Rosell Josep , Campeny Marc , Toutounchiavval Shiva , Simonelli Laura 
Published: May 2021

MAP2XANESis an intuitive Jupyter notebook that automatizes the analysis of synchrotron X-ray fluorescence imaging and X-ray absorption spectroscopy for the characterization of complex and heterogeneous samples. The notebook uses basic modules and functions from Numpy, Scipy, Pandas, iPywidgets and Matplotlib libraries for a powerful data reduction process that, in just a few clicks, guides the user through the visualization of elemental maps, space-resolved absorption spectra and their automatized analysis. In particular, by means of linear combination fit of the XANES spectra, the notebook determines the chemical species distribution in the sample under investigation. The direct output of the analysis process is the correlation between the different elemental distributions and the spatial localization of the chemical species detected. An application to mineralogy is thus presented, analyzing the Mn2+, Mn3+and Mn4+distribution in a mineral sample of hausmannite (Mn2+Mn23+O4), courtesy of the Museum of Natural Science of Barcelona.
Intersectionality, vulnerability and resilience: why it is important to review the diversifications within groups at risk to achieve a resilient community
Authors: Chisty Musabber Ali , Dola Syeda Erena Alam , Khan Nesar Ahmed , Rahman Md Mostafizur 
Published: May 2021

PurposeThe objective of this study was to assess the relationship among intersectionality, vulnerability and resilience with evidence. The conceptual framework developed by the study believed that intersectionality and vulnerabilities intersect and reduce the level of disaster resilience.Design/methodology/approachA qualitative approach was followed with relevant support from both primary and secondary data to conduct the study. The study focused on flood as a specific natural hazard to assess the relationship among the indicators of the objective. Focus group discussions (FGDs) were performed in two different flood-prone areas of Bangladesh. FGDs included young men, young women, men and women with disabilities and older people. Also, secondary literature helped to support ground-level data.FindingsIn the face of a flood, results showed that people with intersectional characteristics become more vulnerable within the at-risk groups. There are differences in people's level of vulnerabilities among the people of vulnerable groups. The results support the discussion that intersectionality exaggerates vulnerabilities, thus reducing the level of disaster resilience. The study summarizes that intersectionality needs to be addressed while supporting groups at risk to achieve a resilient community.Research limitations/implicationsThe study is only based on qualitative and secondary data. For more generalized findings and implications, further research is needed. Also, this study will work as a guideline for future studies.Originality/valueThe study is one of the few works related to intersectionality. This study will open a new window to understand the importance of focusing on intersectional conditions while developing plans for disaster risk reduction (DRR).
Developing intrapreneurial self-efficacy through internships? Investigating agency and structure factors
Authors: Deprez Jana , Peeters Ellen R. , Gorgievski Marjan J. 
Published: May 2021

PurposeThis paper seeks to identify how intrapreneurial self-efficacy (ISE) grows in a group of graduate students during their internship. We investigate which agency and structure factors shape their experience and stabilize or help grow their ISE and how this evolves in the course of their internship.Design/methodology/approachWe conducted group interviews with 49 last year master students of a large Belgian university during their seven-month internship. We focused on those interns with low starter ISE to better understand which factors aid or hinder ISE development.FindingsOur results show that students who did not experience ISE growth were less aware of their own agency factors, lacked supportive colleagues and experienced a misfit with their supervisors. Students who did grow their ISE did so mostly because of an initial experimentation phase, which was structured by their supervisor. This created a positive spiral where they started feeling increasingly better and able to act intrapreneurially.Originality/valueWith this study, we contribute to the extant literature in two main ways. First, we use a graduate employability lens to study the genesis of ISE. As such, we are amongst the first to investigate how education can nurture intrapreneurship and which agency and structure factors are particularly important for this. Second, we take a qualitative process approach, rather than a static and quantitative focus of most entrepreneurial education studies. As such, we gain better knowledge to the drivers of ISE at students first steps and during their internship.
The differentiated impacts of external and internal financing on export: the firm-level evidence
Authors: Meng Xiangyuan , Li Xue , Xiao Wenyan , Li Jie 
Published: May 2021

PurposeThe authors provide firm-level evidence that external financing affects international trade in a way different from internal financing.Design/methodology/approachThe authors separate new entrants from incumbent exporters and investigate the roles of external and internal financing in export market participation and export quantity.FindingsThe authors find that external financing is of particular importance, as well as internal financing, in helping a firm become a new exporter. By contrast, external financing, unlike internal financing, is not significantly important for an incumbent exporter to stay in the international market. Regarding export quantity, a firm's internal financing is positively associated with more export quantity, whereas external financing is not.Originality/valueThe authors’ findings are consistent with the existence of significant fixed cost for entering the export market and external financing is particularly needed to cover such cost. Meanwhile, the financial need for maintaining the export status is much less and can be satisfied via internal financing.
Last-mile logistics in the sharing economy: sustainability paradoxes
Authors: Moncef Btissam , Monnet Dupuy Marlène 
Published: May 2021

PurposeThe purpose of this paper is to explore sustainability paradoxes in sharing economy initiatives by focusing on logistics management in last-mile logistics.Design/methodology/approachIn this exploratory study, a total of 10 case studies were conducted in three categories of companies: anti-waste platforms, food delivery platforms and bicycle delivery companies. Twenty-seven face-to-face interviews with founders and/or managers and contractors (couriers, logistics service providers or volunteers) were the primary source of data collection. The heterogeneity of the sample enabled the authors to build an understanding of sustainability paradoxes in the logistics of sharing economy initiatives.FindingsThe findings indicate how logistics management impacts the sustainability of sharing economy initiatives in last-mile delivery. The authors identify seven paradoxical tensions (five of them social) generated by the contradictions between the organizations' promised environmental and social values and the impacts of their operations.Research limitations/implicationsThis exploratory research is based on a qualitative study of 10 cases and 27 interviews from heterogeneous samples; further empirical research is needed to ensure generalization.Practical implicationsThe paper increases the understanding of environmental and social paradoxical tensions and awareness of logistics challenges.Social implicationsThe paper helps identify ways to reconcile promised values and impacts generated by sharing economy initiatives while managing last-mile delivery.Originality/valueThe results enrich the literature about the paradoxes in sharing economy initiatives by providing illustrations in last-mile logistics and exposing the underlying challenges for sharing economy logistics actors.