bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cre-mediated deletion of SMARCA5 disrupts pluripotency in mouse embryonic stem cells
Authors: Cook David P. , Vanderhyden Barbara C. 
Published: April 2020

AbstractIn embryonic stem cells (ESCs), the SWI/SNF, CHD, and INO80 families of ATP-dependent chromatin remodellers have been implicated in maintaining pluripotency-associated gene expression. At the time of this study, the importance of ISWI family remodellers had yet to be defined, and we had sought to assess their involvement. During this time, Barisicet al. (Nature, 2019) elegantly demonstrated that the ISWI homologue SNF2H (Smarca5) is important for nucleosomal periodicity, the binding of select transcription factors, and proper differentiation of mouse ESCs. While we do not dispute their findings to any extent, our experiments have led to slightly different conclusions, and we have chosen to use this platform to share our results.Here, we explore the importance of SNF2H by deriving a conditional knockout mouse ESC line and observing the consequences of SNF2H depletion on the pluripotent state. Cre-mediated deletion ofSnf2hdisrupts hallmark characteristics of pluripotency, resulting in distinct morphological changes; reduced expression of the master transcription factorsOct4,Sox2, andNanog; and reduced alkaline phosphatase activity. To understand the mechanisms of SNF2H-mediated regulation, we mapped SNF2H-bound nucleosomes genome-wide. SNF2H is broadly distributed across the genome but is preferentially enriched at active regulatory regions and transcription factor binding sites.
In vivoselection for formate dehydrogenases with high efficiency and specificity towards NADP+
Authors: Ramirez Liliana Calzadiaz , Calvó-Tusell Carla , Stoffel Gabriele M. M. , Lindner Steffen N. , Osuna Sílvia , Erb Tobias J. , Garcia-Borràs Marc , Bar-Even Arren , Acevedo-Rocha Carlos G. 
Published: April 2020

AbstractEfficient regeneration of cofactors is vital for the establishment of continuous biocatalytic processes. Formate is an ideal electron donor for cofactor regeneration due to its general availability, low reduction potential, and benign byproduct (CO2). However, formate dehydrogenases (FDHs) are usual specific to NAD+, such that NADPH regeneration with formate is challenging. Previous studies reported naturally occurring FDHs or engineered FDHs that accept NADP+, but these enzymes show low kinetic efficiencies and specificities. Here, we harness the power of natural selection to engineer FDH variants to simultaneously optimize three properties: kinetic efficiency with NADP+, specificity towards NADP+, and affinity towards formate. By simultaneously mutating multiple residues of FDH fromPseudomonas sp.101, which exhibits no initial activity towards NADP+, we generate a library of >106variants. We introduce this library into anE. colistrain that cannot produce NADPH. By selecting for growth with formate as sole NADPH source, we isolate several enzyme variants that support efficient NADPH regeneration. We find that the kinetically superior enzyme variant, harboring five mutations, has 5-fold higher efficiency and 13-fold higher specificity than the best enzyme previously engineered, while retaining high affinity towards formate. By using molecular dynamics simulations, we reveal the contribution of each mutation to the superior kinetics of this variant. We further determine how non-additive epistatic effects improve multiple parameters simultaneously. Our work demonstrates the capacity ofin vivoselection to identify superior enzyme variants carrying multiple mutations which would be almost impossible to find using conventional screening methods.
Conserved and Divergent Modulation of Calcification in Atherosclerosis and Aortic Valve Disease by Tissue Extracellular Vesicles
Authors: Blaser Mark C. , Buffolo Fabrizio , Halu Arda , Schlotter Florian , Higashi Hideyuki , Pantano Lorena , Saddic Louis A. , Atkins Samantha K. , Rogers Maximillian A. , Pham Tan , Shvartz Eugenia , Sukhova Galina K , Monticone Silvia , Camussi Giovanni , Body Simon C. , Muehlschlegel Jochen D. , Singh Sasha A. , Aikawa Masanori , Aikawa Elena 
Published: April 2020

AbstractBackgroundFewer than 50% of patients develop calcification of both atherosclerotic plaques and aortic valves, implying differential pathogenesis. While circulating extracellular vesicles (EVs) act as biomarkers of cardiovascular diseases, tissue-entrapped EVs associate with early mineralization, but their contents, function, and contributions to disease remain unknown.ResultsGlobal proteomics of human carotid artery endarterectomies and calcified aortic valves from a total of 27 donors/patients revealed significant over-representation of proteins with vesicle-associated pathways/ontologies common to both diseases. We exploited enzymatic digestion, serial (ultra)centrifugation and OptiPrep density-gradient separation to isolate EV populations from diseased arteries and valves. Mass spectrometry found 22 EV marker proteins to be highly enriched in the four least-dense OptiPrep fractions while extracellular matrix proteins predominated in denser fractions, as confirmed by CD63 immunogold electron microscopy and nanoparticle tracking analysis. Proteomics and miRNA-sequencing of OptiPrep-enriched tissue EVs quantified 1,104 proteins and 123 miR cargoes linked to 5,182 target genes. Pathway networks of proteins and miR targets common to artery and valve tissue EVs revealed a shared regulation of Rho GTPase and MAPK intracellular signaling cascades. 179 proteins and 5 miRs were significantly altered between artery and valve EVs; multi-omics integration determined that EVs differentially modulated cellular contraction and p53-mediated transcriptional regulation in diseased vascular vs. valvular tissue.ConclusionsOur findings delineate a strategy to isolate, purify, and study protein and RNA cargoes from EVs entrapped in fibrocalcific tissues. Multi-omics and network approaches implicated tissue-resident EVs in human cardiovascular disease.
Chromatin dynamics during hematopoiesis reveal discrete regulatory modules instructing differentiation
Authors: Georgolopoulos Grigorios , Psatha Nikoletta , Iwata Mineo , Nishida Andrew , Som Tannishtha , Yiangou Minas , Stamatoyannopoulos John A. , Vierstra Jeff 
Published: April 2020

AbstractLineage commitment and differentiation is driven by the concerted action of master transcriptional regulators at their target chromatin sites. Multiple efforts have characterized the key transcription factors (TFs) that determine the various hematopoietic lineages. However, the temporal interactions between individual TFs and their chromatin targets during differentiation and how these interactions dictate lineage commitment remains poorly understood. We performed dense, daily, temporal profiling of chromatin accessibility (DNase I-seq) and gene expression changes (total RNA-seq) alongex vivohuman erythropoiesis to comprehensively define developmentally regulated DNase I hypersensitive sites (DHSs) and transcripts. We link both distal DHSs to their target gene promoters and individual TFs to their target DHSs, revealing that the regulatory landscape is organized in distinct sequential regulatory modules that regulate lineage restriction and maturation. Finally, direct comparison of transcriptional dynamics (bulk and single-cell) and lineage potential between erythropoiesis and megakaryopoiesis uncovers differential fate commitment dynamics between the two lineages as they exit pluripotency. Collectively, these data provide novel insights into the global regulatory landscape during hematopoiesis.
Computational analysis of lamin isoform interactions with nuclear pore complexes
Authors: Kittisopikul Mark , Shimi Takeshi , Tatli Meltem , Tran Joseph R. , Zheng Yixian , Medalia Ohad , Jaqaman Khuloud , Adam Stephen A. , Goldman Robert D. 
Published: April 2020

AbstractNuclear lamin isoforms form fibrous meshworks associated with nuclear pore complexes (NPCs). Using data sets prepared from sub-pixel and segmentation analyses of 3D-Structured Illumination Microscopy images of WT and lamin isoform knockout mouse embryo fibroblasts, we determined with high precision the spatial association of NPCs with specific lamin isoform fibers. These relationships are retained in the enlarged lamin meshworks ofLmna-/-andLmnb1-/-fibroblast nuclei. Cryo-ET observations reveal that the lamin filaments composing the fibers contact the nucleoplasmic ring of NPCs. Knockdown of the ring-associated nucleoporin ELYS induces NPC clusters that exclude lamin A/C fibers, but include LB1 and LB2 fibers. Knockdown of the nucleoporins TPR or NUP153 alter the arrangement of lamin fibers and NPCs. Evidence that the number of NPCs is regulated by specific lamin isoforms is presented. Overall the results demonstrate that lamin isoforms and nucleoporins act together to maintain the normal organization of lamin meshworks and NPCs within the nuclear envelope.
Size-dependent eco-evolutionary feedbacks in fisheries
Authors: Eric Edeline , Nicolas Loeuille 
Published: April 2020

AbstractHarvesting may drive body downsizing along with population declines and decreased harvesting yields. These changes are commonly construed as consequences of direct harvest selection, where small-bodied, early-reproducing individuals are immediately favoured. However, together with directly selecting against a large body size, harvesting and body downsizing alter many ecological features, such as competitive and trophic interactions, and thus also indirectly reshape natural selection acting back on body sizes through eco-evolutionary feedback loops (EEFLs). We sketch plausible scenarios of simple EEFLs in which one-dimensional, density-dependent natural selection acts either antagonistically or synergistically with direct harvest selection on body size. Antagonistic feedbacks favour body-size stasis but erode genetic variability and associated body-size evolvability, and may ultimately impair population persistence and recovery. In contrast, synergistic feedbacks drive fast evolution towards smaller body sizes and favour population resilience, but may have far-reaching bottom-up or top-down effects. We illustrate the further complexities resulting from multiple environmental feedbacks using a co-evolving predator-prey pair, in which case outcomes from EEFLs depend not only on population densities, but also on whether prey sit above or below the optimal predator/prey body-size ratio, and whether prey are more or less evolvable than their predators. EEFLs improve our ability to understand and predict nature’s response to harvesting, but their integration into the research agenda will require a full consideration of the effects and dynamics of natural selection.
Interpersonal brain synchronization with instructor compensates for learner’s sleep deprivation in interactive learning
Authors: Pan Yafeng , Guyon Camille , Borragán Guillermo , Hu Yi , Peigneux Philippe 
Published: April 2020

AbstractRecent advances shifted the focus on single-brain functioning toward two-brain communication during learning interactions, following the demonstration that interpersonal brain synchronization (IBS) can track instructor-learner information exchange. Here, we investigated (i) whether sleep deprivation (SD) that potentially impacts both social interactions and learning abilities modulates IBS, and (ii) conversely whether and to what extent IBS might compensate for SD-related learning deficits. Instructors (always with regular sleep, RS) were asked to teach numerical reasoning strategies to learners (either SD or RS), during which the activity of both brains was simultaneously recorded using functional near-infrared spectroscopy (fNIRS). SD learners initially performed below their baseline level, worse than RS learners, but learning improvement was comparable between RS and SD conditions after learning with the instructor. IBS within the instructor-learner dyads was higher in the SD (vs. RS) condition in the left inferior frontal cortex. In addition, clustered IBS (estimated by nonnegative matrix factorization) was correlated with performance improvement. Finally, Granger Causality analyses revealed biased causality with higher instructor-to-learner than learner-to-instructor directionality in brain signal processing. Together, these results indicate that SD-related learning deficits can to some extent be compensated via interactions with an instructor, as reflected by increased IBS and preserved learning ability. It suggests an essential role of the instructor in driving synchrony between teaching and SD learning brains during interactions.
Enabling Fast Annotation Process With Table2Annotation Tool
Authors: Larmande Pierre , Jibril Kazim Muhammed 
Published: April 2020

AbstractSemantic annotation is the process in which semantic concepts are linked to natural language. It helps in boosting the search and access of resources and can be used in information retrieval systems to increase the queries from the user. In this paper, we are interested in identifying ontological concepts in scientific text contained in spreadsheet. We developed a tool which is able to handle various types of spreadsheet. Furthermore, we used the benefits of NCBO Annotator API provided by BioPortal to enhance the semantic annotation functionalities covering spreadsheet data. Table2Annotation developed strengths in certain criteria like speed, error handling and complex concept matching.AvailabilityGitHub :https://github.com/pierrelarmande/ontology-project
Estrogen exacerbates mammary involution through neutrophil dependent and independent mechanism
Authors: Lim Chew Leng , Or Yu Zuan , Ong Zoe , Chung Hwa Hwa , Hayashi Hirohito , Shrestha Smeeta , Chiba Shunsuke , Feng Lin , Lin Valerie CL 
Published: April 2020

AbstractThere is strong evidence that the pro-inflammatory microenvironment during post-partum mammary involution promotes parity-associated breast cancer. Estrogen exposure during mammary involution drives tumour growth through the activity of neutrophils. However, how estrogen and neutrophils influence mammary involution are unknown. Combined analysis of transcriptomic, protein, and immunohistochemical data in Balb/c mice with and without neutrophil depletion showed that estrogen promotes involution by exacerbating inflammation, cell death and adipocytes repopulation through neutrophil-dependent and neutrophil-independent mechanisms. Remarkably, 88% of estrogen-regulated genes in mammary tissue were mediated through neutrophils, which were recruited through estrogen-induced CXCL2-CXCR2 signalling. While neutrophils mediate estrogen-induced inflammation and adipocytes repopulation, estrogen-induced mammary cell death was mediated by neutrophils-independent upsurges of cathepsins and their lysosomal leakages that are critical for lysosome-mediated cell death. Notably, these multifaceted effects of estrogen are unique to the phase of mammary involution. These findings are important for the development of intervention strategies for parity-associated breast cancer.
Leading in: inclusive leadership, inclusive climates and sexual harassment
Authors: Perry Elissa L. , Block Caryn J. , Noumair Debra A. 
Published: April 2020

PurposeThe purpose of this paper is to present a model that explores the relationship between inclusive leadership, inclusive climates and sexual harassment and other negative work-related outcomes, at the work unit and individual levels.Design/methodology/approachA conceptual model of inclusive work unit leadership, inclusive work unit climate and sexual harassment based on a review of the literature.FindingsLeaders who behave more inclusively are expected to have work units and work unit members who experience more positive outcomes and fewer negative outcomes including sexual harassment and other forms of mistreatment. Leaders impact their work unit and work unit members' outcomes directly as well as indirectly through the more inclusive work unit climates they create.Research limitations/implicationsThe sexual harassment literature has identified climate for sexual harassment as a key predictor of sexually harassing behavior and its attendant negative outcomes. A focus on a broader inclusive climate, and inclusive leadership, may provide a richer understanding of the conditions under which sexual harassment and other forms of mistreatment occur and can be mitigated.Practical implicationsThis model can help identify strategies organizations can employ (e.g. inclusive leadership development programs) to combat sexual harassment.Social implicationsThis model may improve understanding of the systemic, organizational causes of sexual harassment reducing sexual harassment victims' potential self-blame and helping policymakers craft more effective sexual harassment interventions.Originality/valueThe paper conceives of work climates that contribute to sexual harassment more broadly than generally has been the case in the sexual harassment literature to date. The model highlights the important role that leaders play in shaping inclusive climates. It also contributes to the nascent literature on inclusion and inclusive climates, which has paid relatively little attention to exclusion and mistreatment including sexual harassment that are likely to arise in less inclusive workplaces.
Perils of road freight market deregulation: cabotage in the European Union
Authors: Sternberg Henrik S. , Hofmann Erik , Overstreet Robert E. 
Published: April 2020

PurposeThe purpose of this paper is to examine the impacts of the ongoing freight market deregulation in the European Union (EU). Specifically, this case study focuses on cabotage penetration rates in Germany, the largest logistics market in Europe. In light of the upcoming trade barriers, we intend to move this topic forward by emphasising its interdisciplinary nature.Design/methodology/approachBased on the analysis of Eurostat data, expert interviews and a review of related literature, we elaborate and discuss four propositions related to the factors affecting cabotage penetration, future cabotage levels and the effects on modal split and empty runs.FindingsWe found that cabotage in Germany plays a more important role than officially reported and has increased drastically since 2008. Given our analysis, increased cabotage penetration seems to thwart efforts within the EU to promote a modal shift from road to rail and increased national empty runs are the future outcome of current regulations. In Germany, the cabotage share is likely to reach 16% in the next five years.Research limitations/implicationsThis paper highlights the need for incorporating a more contextual understanding in freight carrier selection theory development in general as well as country-specific investigations in particular.Practical implicationsLogistics managers and policymakers looking at future strategies are advised to take the ongoing deregulation trend into consideration. European freight movement using cabotage operators may represent significant cost savings; however, these cost savings come at an environmental and social sustainability price as the modal shift to rail and fill rates suffer.Originality/valueThis paper represents an empirical and unbiased point of view, in contrast to the reports of the European Commission (pro-deregulation) or the reports of the haulage associations and labour unions (anti-deregulation).
Silence from the brands: message control, brand ambassadorship, and the public interest
Authors: Dahle Dag Yngve , Wæraas Arild 
Published: April 2020

PurposeInternal aspects of public sector branding have received limited attention in existing research. The purpose is to examine, firstly, how public managers experience and handle the tension between empowering employees to be dedicated brand ambassadors while at the same time regulating their voice, and secondly, to outline some implications of aligning employee voice with the organization's brand, especially for the public interest.Design/methodology/approachThe study is based on two sources of data. The first includes official admission statistics for high schools in Oslo, Norway, for 2018/2019. Schools in Oslo, a city which has introduced a competitive secondary education market, fall into three admission levels based on points necessary for entry. The second source is semi-structured interviews with principals in 15 high schools on different admission levels.FindingsMost of the principals were concerned about how marketization of the high schools leads to a skewed distribution of students and an increasing divide between ‘good’ and ‘bad’ schools, but signalled market adaptation through their handling of employee voice. Due to reputation and branding concerns in the competition for students and funding, voice restrictions, not brand ambassadorship, was the preferred strategy to ensure brand alignment. The consequence of this strategy, the paper argues, is public silence at the expense of the public interest.Research limitations/implicationsNot interviewing teachers or middle managers may be seen as a limitation, but principals were chosen as they are the main decision makers and strategists in high schools. Using a qualitative research design may be a limitation, but this design was chosen as it seems appropriate in order to uncover the school executives' perceptions, experiences and thoughts.Practical implicationsSelling the brand to employees and enabling them to further sell it to external stakeholders is an enticing ideal but perhaps less possible to implement in reality for public sector organizations facing strong market mechanisms because the concern for the brand image takes precedence. Public sector managers should exercise care when managing employee voice so as to not negatively influence employees’ commitment to the brand. They should also be aware of the implications of voice restrictions for the public interest. Public silence may cause a less informed public with limited possibilities to make informed school choices and knowing how money is spent.Originality/valueThe present study is among the first to explore internal aspects of public sector branding. Researching the position of employee voice in brand alignment strategies is a novel contribution. The study is unique in its focus on the implications of branding for the public interest.
Performance appraisal, justice and organizational effectiveness: a comparison between two universities
Authors: Kivipõld Kurmet , Türk Kulno , Kivipõld Lea 
Published: April 2020

PurposeThe purpose of this paper is to identify how the design of a performance appraisal system (PAS) affects the perceived justice of academic employees (AE) about their performance appraisal (PA) and how this is associated with organizational effectiveness in terms of organizational leadership (OL).Design/methodology/approachThe study subjects are two economic faculties of two Estonian public universities. The data for the study were collected using the PA Survey with a total of 82 AEs, OL Capability Questionnaire with a total of 72 AEs and the organizations' documents to analyze PAS. Assessment and analysis of the data included: the measurement of PAS design; the measurement of perceived justice from PA; the measurement of organizational leadership capability; analysis of the results gained from studying perceived justice from different PAS designs and organizational effectiveness in terms of OL.FindingsUltimately, the study reveals that PAS design affects academic employees' perception of distributive justice and organizational external effectiveness in terms of OL but does not affect academic employees' perception of procedural justice and organizational internal effectiveness in terms of OL.Research limitations/implicationsThis study suggests that organizational effectiveness depends on perceived justice of employees from the design of PAS. However, the results of this study are valid in the arrangements of academic jobs in universities and in similar or close context of Estonian culture.Originality/valueThis paper demonstrates the role of PAS design in conditions of intellectual job arrangement in universities with its influence on organizational effectiveness in the context of OL.