bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tfap2b specifies an embryonic melanocyte stem cell that retains adult multi-fate potential
Authors: Brombin Alessandro , Simpson Daniel J. , Travnickova Jana , Brunsdon Hannah , Zeng Zhiqiang , Lu Yuting , Young Adelaide I.J. , Chandra Tamir , Patton E. Elizabeth 
Published: June 2021

SummaryMelanocytes, our pigment producing cells, are replenished from multiple stem cell niches in adult tissues. Although pigmentation traits are known risk-factors for melanoma, we know little about melanocyte stem cell (McSC) populations other than hair follicle McSCs, and lack key lineage markers with which to identify McSCs and study their function. Here, we discover that Tfap2b, and a select set of its target genes, specifies an McSC population at the dorsal root ganglia in zebrafish. Functionally, Tfap2b is required for only a few late-stage embryonic melanocytes, and instead is essential for McSC-dependent melanocyte regeneration. Fate- mapping data reveal that tfap2b-expressing McSCs have multi-fate potential, and are the cell-of- origin for large patches of adult melanocytes, and two other pigment cell types, iridophores and xanthophores. Hence, Tfap2b confers McSC identity in early development, thereby distinguishing McSCs from other neural crest and pigment cell lineages, and retains multi-fate potential in the adult zebrafish.HighlightsTfap2b and its target genes specify McSCs with mixed pigment cell identitiesFunctional dependence on Tfap2b for melanocyte regeneration from the McSCtfap2b specifies ErbB-dependent McSCs at the stem cell nicheFate mapping reveals Tfap2b-McSCs have multi-fate potential for adult pigment cells
Multiplexed bioluminescence microscopy via phasor analysis
Authors: Yao Zi , Brennan Caroline K. , Scipioni Lorenzo , Chen Hongtao , Ng Kevin , Digman Michelle A. , Prescher Jennifer A. 
Published: June 2021

ABSTRACTMicroscopic bioluminescence imaging has been historically challenging due to a lack of detection methods and easily resolved probes. Here we combine bioluminescence with phasor analysis, an optical method commonly used to distinguish spectrally similar fluorophores. Bioluminescent phasor enabled rapid differentiation of multiple luciferase reporters and resonance energy transfer processes. The merger of bioluminescence and phasor analysis provides a platform for routine, time-lapse imaging of collections of cellular features.
Single-cell RNA sequencing-based characterization of resident lung mesenchymal stromal cells in bronchopulmonary dysplasia
Authors: Mižíková I. , Lesage F. , Cyr-Depauw C. , Cook D. P. , Hurskainen M. , Hänninen S.M. , Vadivel A. , Bardin P. , Zhong S. , Carpen O. , Vanderhyden B. C. , Thébaud B. 
Published: June 2021

ABSTRACTLate lung development is a period of alveolar and microvascular formation, which is pivotal in ensuring sufficient and effective gas exchange. Defects in late lung development manifest in premature infants as a chronic lung disease named bronchopulmonary dysplasia (BPD). Numerous studies demonstrated the therapeutic properties of exogenous bone marrow and umbilical cord-derived mesenchymal stromal cells (MSCs) in experimental BPD. However, very little is known regarding the regenerative capacity of resident lung MSCs (L-MSCs) during normal development and in BPD. In this study we aimed to characterize the L-MSC population in homeostasis and upon injury. We used single-cell RNA sequencing (scRNA-seq) to profile in situ Ly6a+ L-MSCs in the lungs of normal and O2-exposed neonatal mice (a well-established model to mimic BPD) at three developmental timepoints (postnatal days 3, 7 and 14). Hyperoxia exposure increased the number, and altered the expression profile of L-MSCs, particularly by increasing the expression of multiple pro-inflammatory, pro-fibrotic, and anti-angiogenic genes. In order to identify potential changes induced in the L-MSCs transcriptome by storage and culture, we profiled 15,000 Ly6a+ L-MSCs after in vitro culture. We observed great differences in expression profiles of in situ and cultured L-MSCs, particularly those derived from healthy lungs. Additionally, we have identified the location of L-MSCs in the developing lung and propose Serpinf1 as a novel, culture-stable marker of L-MSCs. Finally, cell communication analysis suggests inflammatory signals from immune and endothelial cells as main drivers of hyperoxia-induced changes in L-MSCs transcriptome.
A new approach to measure forces at junction vertices in an epithelium
Authors: Villeneuve Clémentine , Mathieu Samuel , Lagoutte Emilie , Goud Bruno , Chavrier Philippe , Manneville Jean-Baptiste , Rossé Carine 
Published: June 2021

AbstractThe mechanical properties of cell-cell junctions are critical for the stability of an epithelium. Cell-cell junction ablation experiments are classically used as a readout for junctional mechanics. However, without the knowledge of the viscoelastic properties of the microenvironment of the ablated junction, tensile junctional forces cannot be measured. Here we combine laser ablation with intracellular microrheology and develop a model to measure tensile forces exerted on cell-cell junctions. We show that the overexpression of the proto-oncogene atypical Protein Kinase C iota (aPKCi) in a single cell within a normal epithelium induces a gradient of junctional tension with neighbouring cells. Our method allows us to demonstrate that junctions contacting the aPKCi-overexpressing cell display a mechanical asymmetry which correlates with the levels of E-cadherin and P-MLC2. Measuring intracellular viscoelasticity is crucial for accurate measurements of cell-cell junction mechanics in the context of development or cancer research.TeaserWe combine cytoplasmic and junctional mechanics to detect asymmetry in forces exerted on cell-cell junctions.
Alpha peak frequency is linked to episodic memory impairment in pathological aging
Authors: Puttaert Delphine , Wens Vincent , Fery Patrick , Rovai Antonin , Trotta Nicola , Coquelet Nicolas , De Breucker Sandra , Sadeghi Niloufar , Coolen Tim , Goldman Serge , Peigneux Philippe , Bier Jean-Christophe , De Tiège Xavier 
Published: June 2021

AbstractThe Free and Cued Selective Reminding Test (FCSRT) is a largely validated neuropsychological test for the identification of amnestic syndrome from the early stage of Alzheimer’s disease (AD). Previous electrophysiological data suggested a slowing down of the alpha rhythm in the AD-continuum as well as a key role of this rhythmic brain activity for episodic memory processes. This study therefore investigates the link between alpha brain activity and alterations in episodic memory as assessed by the FCSRT. For that purpose, 37 patients with altered FCSRT performance underwent a comprehensive neuropsychological assessment, supplemented by 18F-fluorodeoxyglucose positron emission tomography/structural magnetic resonance imaging (18FDG-PET/MR), and 10 minutes of resting-state magnetoencephalography (MEG). The individual alpha peak frequency (APF) in MEG resting-state data was positively correlated with patients’ encoding efficiency as well as with the efficacy of semantic cues in facilitating patients’ retrieval of previous stored word. The APF also correlated positively with patients’ hippocampal volume and their regional glucose consumption in the posterior cingulate cortex. Overall, this study demonstrates that alterations in the ability to learn and store new information for a relatively short-term period are related to a slowing down of alpha rhythmic activity, possibly due to altered interactions in the extended mnemonic system. As such, a decreased APF may be considered as an electrophysiological correlate of short-term episodic memory dysfunction accompanying pathological aging.
Binding of phosphatidylserine-positive microparticles by PBMCs classifies disease severity in COVID-19 patients
Authors: Rausch Lisa , Lutz Konstantin , Schifferer Martina , Winheim Elena , Gruber Rudi , Rinke Linus , Hellmuth Johannes C. , Scherer Clemens , Muenchhoff Maximilian , Mandel Christopher , Bergwelt-Baildon Michael , Simons Mikael , Straub Tobias , Krug Anne B. , Kranich Jan , Brocker Thomas 
Published: June 2021

SUMMARYInfection with SARS-CoV-2 is associated with thromboinflammation, involving thrombotic and inflammatory responses, in many COVID-19 patients. In addition, immune dysfunction occurs in patients characterized by T cell exhaustion and severe lymphopenia. We investigated the distribution of phosphatidylserine (PS), a marker of dying cells, activated platelets, and platelet-derived microparticles (PMP), during the clinical course of COVID-19. We found an unexpectedly high amount of blood cells loaded with PS+ PMPs for weeks after the initial COVID-19 diagnosis. Elevated frequencies of PS+PMP+ PBMCs correlated strongly with increasing disease severity. As a marker, PS outperformed established laboratory markers for inflammation, leucocyte composition, and coagulation, currently used for COVID-19 clinical outcome prognosis. PS+ PMPs preferentially bound to CD8+ T cells with gene expression signatures of proliferating effector rather than memory T cells. As PS+ PMPs carried programmed death-ligand 1 (PD-L1), they may affect T cell expansion or function. Our data provide a novel marker for disease severity and show that PS, which can trigger the blood coagulation cascade, the complement system, and inflammation, resides on activated immune cells. Therefore, PS may serve as a beacon to attract thromboinflammatory processes toward lymphocytes and cause immune dysfunction in COVID-19.
Structure and dynamics of the chromatin remodeler ALC1 bound to a PARylated nucleosome
Authors: Bacic Luka , Gaullier Guillaume , Sabantsev Anton , Lehmann Laura C. , Brackmann Klaus , Dimakou Despoina , Halic Mario , Hewitt Graeme , Boulton Simon J. , Deindl Sebastian 
Published: June 2021

ABSTRACTThe chromatin remodeler ALC1 is recruited to and activated by DNA damage-induced poly(ADP-ribose) (PAR) chains deposited by PARP1/PARP2/HPF1 upon detection of DNA lesions. ALC1 has emerged as a candidate drug target for cancer therapy as its loss confers synthetic lethality in homologous recombination-deficient cells. However, structure-based drug design and molecular analysis of ALC1 have been hindered by the requirement for PARylation and the highly heterogeneous nature of this post-translational modification. Here, we reconstituted an ALC1 and PARylated nucleosome complex modified in vitro using PARP2 and HPF1. This complex was amenable to cryo-EM structure determination without cross-linking, which enabled visualization of several intermediate states of ALC1 from the recognition of the PARylated nucleosome to the tight binding and activation of the remodeler. Functional biochemical assays with PARylated nucleosomes highlight the importance of nucleosomal epitopes for productive remodeling and reveal that ALC1 preferentially slides nucleosomes away from DNA breaks.
A highly efficient reporter system for identifying and characterizing in vitro expanded hematopoietic stem cells
Authors: Che James L.C. , Bode Daniel , Kucinski Iwo , Cull Alyssa H. , Bain Fiona , Barile Melania , Boyd Grace , Belmonte Miriam , Jassinskaja Maria , Rubio-Lara Juan , Shepherd Mairi S. , Clay Anna , Wilkinson Adam C. , Nakauchi Hiromitsu , Yamazaki Satoshi , Göttgens Berthold , Kent David G. 
Published: June 2021

SummaryHematopoietic stem cells (HSCs) cultured outside the body are the fundamental component of a wide range of cellular and gene therapies. Recent efforts have achieved more than 200-fold expansion of functional HSCs, but their molecular characterization has not been possible due to the substantial majority of cells being non-HSCs and single cell-initiated cultures displaying substantial clone-to-clone variability. Using the Fgd5 reporter mouse in combination with the EPCR surface marker, we report exclusive identification of HSCs from non-HSCs in expansion cultures. Linking single clone functional transplantation data with single clone gene expression profiling, we show that the molecular profile of expanded HSCs is similar to actively cycling fetal liver HSCs and shares a gene expression signature with functional HSCs from all sources, including Prdm16, Fstl1 and Palld. This new tool can now be applied to a wide-range of functional screening and molecular experiments previously not possible due to limited HSC numbers.
Functional Redundancy in Ocean Microbiomes Controls Trait Stability
Authors: Royalty Taylor M. , Steen Andrew D. 
Published: June 2021

AbstractTheory predicts that functional redundancy in microbial communities increases trait stability, meaning that traits or functions are less likely to be lost from the community when species go extinct. However, few experiments have empirically tested this prediction, especially in the context of microbial communities and at the landscape scale. In part, the lack of metrics for functional redundancy in microbial ecosystems has prevented addressing this question. In a companion manuscript we proposed a quantitative metric for functional redundancy called Contribution Evenness (CE) that is optimized to reflect trait stability. Here, we use CE to predict the stability of marine microbial functions to species and transcription loss. Using transcriptomes deposited in the Ocean Microbial Reference Gene Catalog (OM-RGC.v2), a catalog of genes and transcripts sequenced by the TARA Ocean expedition, we quantified the functional redundancy for 4,314 KEGG Orthologs (KOs) across 124 marine sites. Functional redundancy was highly correlated with a latent variable consisting of four ocean physiochemical parameters: oxygen and chlorophyll a concentrations, depth, and salinity. Functional redundancy was higher at the poles than in non-polar regions. Simultaneously, regional β-diversity for individual functions was higher for functions with higher functional redundancy. These observations provide evidence that higher functional redundancy indicates increased stability of microbial ecosystem functions on spatiotemporal scales consistent with surface ocean mixing. We suggest that future changes in ocean physiochemistry could likely influence this stability for functions with lower functional redundancy.ImportanceFunctional redundancy describes the state of multiple species performing the same function. Theory suggests functional redundancy stabilizes microbial community functions from disturbances leading to species loss or other changes to the microbiome. Previous work suggests that functional redundancy is common in ocean microbiomes which implies traits should be more stable among metacommunities. Some laboratory experiments demonstrate this idea, but it is difficult to test in the natural world. In a companion manuscript, we proposed a functional redundancy metric sensitive to trait stability. Here, we used this metric to show that functional redundancy varied substantially among ocean microbiomes and that regions with higher functional redundancy had higher regional trait stability. Last, we noted that variations in functional redundancy strongly correlated to ocean physiochemistry. Thus, changes in ocean physiochemistry via climate change may alter community traits to become more or less resistant to disturbance relative to contemporary conditions.
Disturbed retinoid metabolism upon loss of rlbp1a impairs cone function and leads to subretinal lipid deposits and photoreceptor degeneration in the zebrafish retina
Authors: Schlegel Domino K. , Ramkumar Srinivasagan , Lintig Johannes von , Neuhauss Stephan C. F. 
Published: June 2021

AbstractThe RLBP1 gene encodes the 36 kDa cellular retinaldehyde binding protein, CRALBP, a soluble retinoid carrier, in the visual cycle of the eyes. Mutations in RLBP1 are associated with recessively inherited clinical phenotypes, including Bothnia dystrophy, retinitis pigmentosa, retinitis punctata albescens, fundus albipunctatus, and Newfoundland rod-cone dystrophy. However, the etiology of these retinal disorders is not well understood. Here, we generated homologous zebrafish models to bridge this knowledge gap. Duplication of the rlbp1 gene in zebrafish and cell-specific expression of the paralogs rlbp1a in the retinal pigment epithelium and rlbp1b in Müller glial cells allowed us to create intrinsically cell type-specific knockout fish lines. Using rlbp1a and rlbp1b single and double mutants, we investigated the pathological effects on visual function. Our analyses revealed that rlbp1a was essential for cone photoreceptor function and chromophore metabolism in the fish eyes. rlbp1a mutant fish displayed reduced chromophore levels and attenuated cone photoreceptor responses to light stimuli. They accumulated 11-cis and all-trans-retinyl esters which displayed as enlarged lipid droplets in the RPE reminiscent of the subretinal yellow-white lesions in patients with RLBP1 mutations. During aging, these fish developed retinal thinning and cone and rod photoreceptor dystrophy. In contrast, rlbp1b mutants did not display impaired vision. The double mutant essentially replicated the phenotype of the rlbp1a single mutant. Together, our study showed that the rlbp1a zebrafish mutant recapitulated many features of human blinding diseases caused by RLBP1 mutations and provided novel insights into the pathways for chromophore regeneration of cone photoreceptors.Graphical Abstract
Ambidextrous sustainability, organisational structure and performance in hybrid organisations
Authors: Maine Joshua , Florin Samuelsson Emilia , Uman Timur 
Published: June 2021

PurposeDrawing on paradox theory, this study explores how ambidextrous sustainability relates to organisational performance in hybrid organisations represented by Swedish municipal housing corporations, and how this relationship is contingent on the organisational structure of these organisations.Design/methodology/approachThe study relies on the data collected from Swedish municipal housing corporations. These data sources consist of a survey sent to the management team members in Swedish municipal housing corporations, financial and non-financial archival data on these corporations, interviews with the management team and board members, and observations of meetings involving the management team and board of directors at a Swedish municipal housing corporation. Quantitative data of the study were analysed using descriptive statistics, correlation analysis and linear multiple regression analysis. Qualitative data were analysed employing deductive thematic analysis and were used to illustrate and discuss the results of the quantitative analysis.FindingsThe quantitative findings show that ambidextrous sustainability, i.e. the alignment between an explorative orientation and an exploitative orientation towards sustainability, has a weakly positive relationship with financial performance and a positive relationship with social performance in hybrid organisations represented by Swedish municipal housing corporations. The study further shows that a high level of the structural element “connectedness” weakened the relationship between the ambidextrous sustainability and financial performance of the organisation in the study. In contrast, a lower level of connectedness reinforced and strengthened this relationship. Our qualitative material illustrates how the quantitative findings could be explained by the interaction between the board of directors and the management team of these hybrid organisations.Originality/valueThe study shows how ambidextrous sustainability, employed for conceptualisation of the sustainability strategy in hybrid organisations, represented by Swedish municipal housing corporations, can impact on facets of performance (i.e. financial, social and environmental) differently. The study further highlights the importance of organisational structures in these relationships in a hybrid context.
A multivariate regression approach toward prioritizing BIM adoption barriers in the Ethiopian construction industry
Authors: Alemayehu Shihunegn , Nejat Ali , Ghebrab Tewodros , Ghosh Souparno 
Published: June 2021

PurposeBuilding information modeling (BIM) is a process of creating an intelligent virtual model integrating project data from design to construction and operation. BIM models enhance the process of communicating the progress of construction to stakeholders and facilitate integrated project delivery, coordination and clash detection. However, barriers within the construction industry in Ethiopia has led to slow BIM adoption in the country. The aim of this paper is to identify perceived BIM barriers, provide a platform to quantify their importance and develop a regression model to link individual's personal/professional attributes to their perception of BIM barrier.Design/methodology/approachTo address the objectives of this research, an online survey was developed to collect feedback from construction professionals in Ethiopia on 20 major adoption barriers extracted from a thorough review of literature. Relative importance index and strength of consensus metric were employed to identify the significance of barriers. This was then succeeded by performing exploratory factor analysis to determine the major constructs of BIM barriers which was then used to develop a multivariate regression model linking respondents' personal attributes to their perception of BIM barrier.FindingsResults revealed the importance of project complexity and BIM maturity level in prioritizing barriers that are more relevant under various contexts. More specifically, results indicated the following study highlights: Project complexity led to higher perceived weights for lack of appropriate physical/cloud infrastructures, and a BIM standard. Higher levels of BIM maturity signified the importance of BIM internal issues such as liability, licensing and maintenance issues among other adoption barriers. Female participants tended not to consider intangibility of BIM benefits as a major barrier towards BIM adoption compared to male participants. Age of the participants turned out to be the least important factor in their prioritization of BIM perceived adoption barriers.Originality/valueWhile many research studies have explored BIM adoption barriers in various countries around the world, none to the best of the authors' knowledge have attempted to develop a model to highlight the impact of individuals' personal/professional attributes on their perception of adoption barriers within their community which can help with prioritizing the barriers that are deemed to be more important given the characteristics of the community under study. Our result indicated the importance of BIM maturity level and project complexity in prioritizing barriers associated with BIM adoption within Ethiopia's construction industry.