bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving replicability in single-cell RNA-Seq cell type discovery with Dune
Authors: de Bézieux Hector Roux , Street Kelly , Fischer Stephan , Van den Berge Koen , Chance Rebecca , Risso Davide , Gillis Jesse , Ngai John , Purdom Elizabeth , Dudoit Sandrine
Published: March 2020

Single-cell transcriptome sequencing (scRNA-Seq) has allowed many new types of investigations at unprecedented and unique levels of resolution. Among the primary goals of scRNA-Seq is the classification of cells into potentially novel cell types. Many approaches build on the existing clustering literature to develop tools specific to single-cell applications. However, almost all of these methods rely on heuristics or user-supplied parameters to control the number of clusters identified. This affects both the resolution of the clusters within the original dataset as well as their replicability across datasets. While many recommendations exist to select these tuning parameters, most of them are quite ad hoc. In general, there is little assurance that any given set of parameters will represent an optimal choice in the ever-present trade-off between cluster resolution and replicability. For instance, it may be the case that another set of parameters will result in more clusters that are also more replicable, or in fewer clusters that are also less replicable.

Here, we propose a new method calledDunefor optimizing the trade-off between the resolution of the clusters and their replicability across datasets. Our method takes as input a set of clustering results on a single dataset, derived from any set of clustering algorithms and associated tuning parameters, and iteratively merges clusters within partitions in order to maximize their concordance between partitions. As demonstrated on a variety of scRNA-Seq datasets from different platforms,Duneoutperforms existing techniques, that rely on hierarchical merging for reducing the number of clusters, in terms of replicability of the resultant merged clusters. It provides an objective approach for identifying replicable consensus clusters most likely to represent common biological features across multiple datasets.
Two new genetically modified mouse alleles labeling distinct phases of retinal ganglion cell development by fluorescent proteins
Authors: Ge Yichen , Wu Fuguo , Cheng Mobin , Mu Xiuqian
Published: March 2020

During development, retinal progenitor cells (RPCs) take on different trajectories for distinct cell fates. Previous studies have identified key regulators involved in two key steps of retinal ganglion cell (RGC) genesis; Atoh7 functions in a subpopulation of RPCs to render them competent for the RGC fate, whereas Pou4f2 and Isl1 function to specify the RGC fate and promote RGC differentiation. Extensive research has been performed on the roles of these transcription factors in RGC development, but properties of these two phases they represent and the cellular context in which these two factors function have not been thoroughly investigated, largely due to the cellular heterogeneity of developing retina. In this paper, we describe two novel knock-in mouse alleles,Atoh7zsGreenCreERT2andPou4f2FlagtdTomato, which enabled us to label retinal cells in the two phases of RGC development by fluorescent proteins. In addition, theAtoh7zsGreenCreERT2allele also allowed for indirect labeling of RGCs and other cell types upon tamoxifen induction in a dose-dependent manner. Further, these alleles could be used to purify retinal cells of these different phases by fluorescence assisted cell sorting (FACS). Thus, these two alleles can serve as very useful tools for studying the molecular and genetic mechanisms underlying RGC formation.
Hippo signaling promotes Ets21c-dependent apical cell extrusion in theDrosophilawing disc
Authors: Ai Xianlong , Wang Dan , Zhang Junzheng , Shen Jie
Published: March 2020

Cell extrusion is a crucial regulator of epithelial tissue development and homeostasis. Epithelial cells undergoing apoptosis, bearing pathological mutations, and possessing developmental defects are actively extruded toward elimination. However, the molecular mechanisms ofDrosophilaepithelial cell extrusion are not fully understood. Here, we report that activation of the conserved Hippo (Hpo) signaling pathway induces both apical and basal cell extrusion in theDrosophilawing disc epithelia. We show that canonical Yorki targets Diap1, and that dMyc and Cyclin E are not required for either apical or basal cell extrusion induced by activation of this pathway. Another target gene,bantam, is only involved in basal cell extrusion, suggesting novel Hpo-regulated apical cell extrusion mechanisms. Using RNA-Seq analysis, we found that JNK signaling is activated in the extruding cells. We provide genetic evidence that JNK signaling activation is both sufficient and necessary for Hpo-regulated cell extrusion. Furthermore, we demonstrate that the ETS-domain transcription factor Ets21c, an ortholog of proto-oncogenesFLI1andERG, acts downstream of JNK signaling to mediate apical cell extrusion. Our findings reveal a novel molecular link between Hpo signaling and cell extrusion.

SUMMARY STATEMENT

Activation of Hippo signaling induces cell extrusion in theDrosophilawing epithelia, in whichbantammediates basal cell extrusion and Ets21c mediates apical cell extrusion.
Vitamin D regulation of a SOD1-to-SOD2 antioxidative switch to prevent osteosarcoma transformation
Authors: Lisse Thomas S.
Published: March 2020

Superoxide, a form of reactive oxygen species (ROS), is catabolized by superoxide dismutase (SOD) and contributes to carcinogenesis via the oxidative damage it inflicts on cells. The aim of this research was to analyze the potential vitamin D-mediated regulation of the antioxidative “SOD1-to-SOD2 switch” within the human MG-63 osteosarcoma model. For this study, real-time PCR analysis was performed using MG-63 cells exposed to metabolically active 1,25(OH)2D3. Frist, a sustained statistically significant >2-fold suppression of proliferating cell nuclear antigen (PCNA) transcripts was observed after 10nM but not at 100nM of 1,25(OH)2D3treatment, suggesting a cytostatic effect. In order to assess regulators of mitochondrial oxidative phosphorylation, gene expression ofCOX2andCOX4l1of the mitochondrial complex IV and antioxidative enzymes (SOD1, SOD2andCatalase(CAT)) were monitored. For COX2 and COX4l1, no changes in gene expression were observed. However, a concomitant decrease in CAT and SOD1 mRNA, and increase in SOD2 mRNA after 24 hours of 10nM 1,25(OH)2D3treatment were observed. A ~8-fold increase in SOD2 mRNA was apparent after 48 hours. The significant increase in SOD2 activity in the presence of vitamin D indicates an antioxidant potential and sensitization of vitamin D during osteosarcoma transformation and mitochondrial detoxification over time.
Chemokine receptor 2-targeted molecular imaging in pulmonary fibrosis
Authors: Brody Steven L. , Gunsten Sean P. , Luehmann Hannah P. , Sultan Debbie H. , Hoelscher Michelle , Heo Gyu Seong , Pan Jiehong , Koenitzer Jeffrey R. , Lee Ethan C. , Huang Tao , Mpoy Cedric , Guo Shuchi , Laforest Richard , Salter Amber , Russell Tonya D. , Shifren Adrian , Combadiere Christophe , Lavine Kory J. , Kreisel Daniel , Humphreys Benjamin D. , Rogers Buck E. , Gierada David S. , Byers Derek E. , Gropler Robert J. , Chen Delphine L. , Atkinson Jeffrey J. , Liu Yongjian
Published: March 2020

Idiopathic pulmonary fibrosis (IPF) is a progressive, inflammatory lung disease that is monitored clinically by measures of lung function, without effective molecular markers of disease activity or therapeutic efficacy. Lung immune cells active in the pro-fibrotic process include inflammatory monocyte and interstitial macrophages that express the C-C motif chemokine receptor 2 (CCR2). CCR2+monocyte lung influx is essential for disease phenotypes in models of fibrosis and identified in lungs from subjects with IPF. Here, we show that our peptide-based radiotracer64Cu-DOTA-ECL1i identifies CCR2+inflammatory monocytes and interstitial macrophages in multiple preclinical mouse models of lung fibrosis, using positron emission tomography (PET) imaging. Mice with bleomycin-induced fibrosis treated with blocking antibodies to interleukin-1β, a mediator of fibrosis associated with CCR2+cell inflammation, or with pirfenidone, an approved anti-fibrotic agent, demonstrated decreased CCR2-dependent interstitial macrophage accumulation and reduced64Cu-DOTA-ECL1i PET uptake, compared to controls. Lung tissues from patients with fibrotic lung disease demonstrated abundant CCR2+cells surrounding regions of fibrosis, and an ex vivo tissue-binding assay showed correlation between radiotracer localization and CCR2+cells. In a phase 0/1 clinical study of64Cu-DOTA-ECL1i PET, healthy volunteers showed little lung uptake, while subjects with pulmonary fibrosis exhibited increased uptake, notably in zones of subpleural fibrosis, reflecting the distribution of CCR2+cells in the profibrotic niche. These findings support a pathologic role of inflammatory lung monocytes/macrophages in fibrotic lung disease and the translational use of64Cu-DOTA-ECL1i PET to track CCR2-specific inflammation for image-guided therapy.

One Sentence Summary

PET imaging of CCR2+cells in lung fibrosis identifies a therapeutic response in mouse models and displays a perifibrotic signal in subjects with IPF.
Quantitative proteomics links the LRRC59 interactome to mRNA translation on the ER membrane
Authors: Hannigan Molly M. , Hoffman Alyson M. , Thompson J. Will , Zheng Tianli , Nicchitta Christopher V.
Published: March 2020

Protein synthesis on the endoplasmic reticulum (ER) requires the dynamic coordination of resident membrane proteins and cytoplasmic translation factors. While ER membrane proteins functioning in ribosome association, mRNA anchoring, and protein translocation, have been identified, little is known regarding the higher order organization of ER-localized translation. Here we utilized proximity proteomics to identify neighboring protein networks for the ribosome interactors SEC61β, RPN1, SEC62, and LRRC59. Whereas the SEC61β and RPN1 BioID reporters revealed translocon-associated networks, the SEC62 and LRRC59 reporters identified divergent interactome networks of previously unexplored functions. Notably, the SEC62 interactome is enriched in redox-linked proteins and ER luminal chaperones, whereas the LRRC59 interactome is enriched in SRP pathway components, translation factors, and ER-localized RNA-binding proteins. Analysis of the LRRC59 interactome by native immunoprecipitation identified similar protein and functional enrichments. Combined, these data reveal a functional domain organization for the ER and suggest a key role for LRRC59 in the organization of mRNA translation on the ER.

Hannigan et al. characterize the protein interactomes of four ER ribosome-binding proteins, providing evidence that ER-bound ribosomes reside in distinct molecular environments. Their data link SEC62 to ER redox regulation and chaperone trafficking, and suggest a role for LRRC59 in SRP-coupled protein synthesis.
ZFP423 regulates early patterning and multiciliogenesis in the hindbrain choroid plexus
Authors: Casoni Filippo , Croci Laura , Vincenti Francesca , Podini Paola , Massimino Luca , Cremona Ottavio , Consalez G. Giacomo
Published: March 2020

The choroid plexus (ChP) is a secretory tissue that produces cerebrospinal fluid (CSF) and secretes it into the ventricular system. CSF flows from the lateral to the third ventricle, and then to the fourth ventricle through the cerebral aqueduct. Recent studies have uncovered new, active roles for this structure in the regulation of neural stem cell maintenance and differentiation into neurons.Zfp423,encoding a Kruppel-type zinc finger transcription factor essential for cerebellar development and mutated in rare cases of cerebellar vermis hypoplasia / Joubert syndrome and other ciliopathies, is expressed in the hindbrain roof plate (RP), from which the IV ventricle ChP arises, and in mesenchymal cells giving rise to the stroma and leptomeninges.Zfp423mutants display a marked reduction of the hindbrain ChP (hChP), which fails to express key markers of its secretory function and genes implicated in its development and maintenance (Lmx1a, Otx2). The mutant hChP displays a complete lack of multiciliated ependymal cells. A transcriptome analysis conducted at the earliest stages of hChP development and subsequent validations demonstrate that the mutant hChp displays a strong deregulation of pathways involved in early hindbrain patterning and multiciliated cell fate specification. Our results proposeZfp423as a master gene and one of the earliest known determinants of hChP development.
Strong evolutionary convergence of receptor-binding protein spike between COVID-19 and SARS-related coronaviruses
Authors: Wu Yonghua
Published: March 2020

Coronavirus Disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS)-related coronaviruses (e.g., 2019-nCoV and SARS-CoV) are phylogenetically distantly related, but both are capable of infecting human hosts via the same receptor, angiotensin-converting enzyme 2, and cause similar clinical and pathological features, suggesting their phenotypic convergence. Yet, the molecular basis that underlies their phenotypic convergence remains unknown. Here, we used a recently developed molecular phyloecological approach to examine the molecular basis leading to their phenotypic convergence. Our genome-level analyses show that the spike protein, which is responsible for receptor binding, has undergone significant Darwinian selection along the branches related to 2019-nCoV and SARS-CoV. Further examination shows an unusually high proportion of evolutionary convergent amino acid sites in the receptor binding domain (RBD) of the spike protein between COVID-19 and SARS-related CoV clades, leading to the phylogenetic uniting of their RBD protein sequences. In addition to the spike protein, we also find the evolutionary convergence of its partner protein,ORF3a, suggesting their possible co-evolutionary convergence. Our results demonstrate a strong adaptive evolutionary convergence between COVID-19 and SARS-related CoV, possibly facilitating their adaptation to similar or identical receptors. Finally, it should be noted that many observed bat SARS-like CoVs that have an evolutionary convergent RBD sequence with 2019-nCoV and SARS-CoV may be pre-adapted to human host receptor ACE2, and hence would be potential new coronavirus sources to infect humans in the future.
Structural basis underlying strong interactions between ankyrins and spectrins
Authors: Li Jianchao , Chen Keyu , Zhu Ruichi , Zhang Mingjie
Published: March 2020

Ankyrins (encoded byANK1/2/3corresponding to Ankyrin-R/B/G or AnkR/B/G), via binding to spectrins, connect plasma membranes with actin cytoskeleton to maintain mechanical strengths and to modulate excitabilities of diverse cells such as neurons, muscle cells, and erythrocytes. Cellular and genetic evidences suggest that each isoform of ankyrins pairs with a specific β-spectrin in discrete subcellular membrane microdomains for distinct functions, though the molecular mechanisms underlying such ankyrin/β-spectrin pairings are unknown. In this study, we discover that a conserved and short extension N-terminal to the ZU5N-ZU5C-UPA tandem (exZZU) is critical for each ankyrin to bind to β-spectrins with high affinities. Structures of AnkB/G exZZU in complex with spectrin repeats13-15 of β2/β4-spectrins solved here reveal that the extension sequence of exZZU forms an additional β-strand contributing to the structural stability and enhanced affinity of each ZU5N/spectrin repeat interaction. The junction site between the extension and ZU5Nis exactly the position of a splicing-mediated miniexon insertion site of AnkB/G. The complex structures further reveal that the UPA domain of exZZU directly participates in spectrin binding. Formation of the exZZU supramodule juxtaposes the ZU5Nand UPA domains for simultaneous interacting with spectrin repeats 14 and 15. However, our biochemical and structural investigations indicate that the direct and strong interactions between ankyrins and β-spectrins do not appear to determine their pairing specificities. Therefore, there likely exists additional mechanism(s) for modulating functional pairings between ankyrins and β-spectrins in cells.
A global barley panel revealing genomic signatures of breeding in modern cultivars
Authors: Hill Camilla Beate , Angessa Tefera Tolera , Zhang Xiao-Qi , Chen Kefei , Zhou Gaofeng , Tan Cong , Wang Penghao , Westcott Sharon , Li Chengdao
Published: March 2020

The future of plant cultivar improvement lies in the evaluation of genetic resources from currently available germplasm. Recent efforts in plant breeding have been aimed at developing new and improved varieties from poorly adapted crops to suit local environments. However, the impact of these breeding efforts is poorly understood. Here, we assess the contributions of both historical and recent breeding efforts to local adaptation and crop improvement in a global barley panel by analysing the distribution of genetic variants with respect to geographic region or historical breeding category. By tracing the impact breeding had on the genetic diversity of barley released in Australia, where the history of barley production is relatively young, we identify 69 candidate regions within 922 genes that were under selection pressure. We also show that modern Australian barley varieties exhibit 12% higher genetic diversity than historical cultivars. Finally, field-trialling and phenotyping for agriculturally relevant traits across a diverse range of Australian environments suggests that genomic regions under strong breeding selection and their candidate genes are closely associated with key agronomic traits. In conclusion, our combined dataset and germplasm collection provide a rich source of genetic diversity that can be applied to understanding and improving environmental adaptation and enhanced yields.

Author summary

Today’s gene pool of crop genetic diversity has been shaped during domestication and more recently by breeding. Genetic diversity is vital for crop species to be able to adapt to changing environments. There is concern that recent breeding efforts have eroded the genetic diversity of many domesticated crops including barley. The present study assembled a global panel of barley genotypes with a focus on historical and modern Australian varieties.

Genome-wide data was used to detect genes that are thought to have been under selection during crop breeding in Australian barley. The results demonstrate that despite being more extensively bred, modern Australian barley varieties exhibit higher genetic diversity than historical cultivars, countering the common perception that intensive breeding leads to genetic erosion of adaptive diversity in modern cultivars. In addition, some loci (particularly those related to phenology) were subject to selection during the introduction of other barley varieties to Australia – these genes might continue to be important targets in breeding efforts in the face of changing climatic conditions.
Rapid formation of peptide/lipid co-aggregates by the amyloidogenic seminal peptide PAP248-286
Authors: Vane E.W. , He S. , Maibaum L. , Nath A.
Published: March 2020

Protein/lipid co-assembly is an understudied phenomenon that is important to the function of antimicrobial peptides as well as the pathological effects of amyloid. Here we study the co-assembly process of PAP248-286, a seminal peptide that displays both amyloid-forming and antimicrobial activity. PAP248-286is a fragment of prostatic acid phosphatase and has been reported to form amyloid fibrils, known as semen-derived enhancer of viral infection (SEVI), that enhance the viral infectivity of HIV. We find that in addition to forming amyloid, PAP248-286much more readily assembles with lipid vesicles into peptide/lipid co-aggregates that resemble amyloid fibrils in some important ways but are a distinct species. The formation of these co-aggregates, which we term “messicles”, is controlled by the peptide:lipid (P:L) ratio and by the lipid composition. The optimal P:L ratio is around 1:10 and at least 70% anionic lipid is required for co-aggregate formation. Once formed, messicles are not disrupted by subsequent changes in P:L ratio. We propose that messicles form through a polyvalent assembly mechanism, where a critical surface density of PAP248-286on liposomes enables peptide-mediated particle bridging into larger species. Even at ~100-fold lower PAP248-286concentrations, messicles form at least 10-fold faster than amyloid fibrils. It is therefore possible that, some or all of the biological activities assigned to SEVI, the amyloid form of PAP248-286, could instead be attributed to a PAP248-286/lipid co-aggregate. More broadly speaking, this work provides a potential framework for the discovery and characterization of peptide/lipid co-aggregates by other amyloid-forming proteins and antimicrobial peptides.

Statement of Significance

PAP248-286, a fragment of prostatic acid phosphatase, forms amyloid thought to enhances the infectivity of many viruses, including HIV. This amyloid, termed semen-derived enhancer of viral infection (SEVI), has been assigned responsibility for all of PAP248-286’s biological activities, while the monomer is thought to be inactive. However, SEVI formation is quite slow and requires very high concentrations of PAP248-286. Here, we show that PAP248-286can instead assemble much more rapidly with lipid membranes to form another species, mechanistically and morphologically distinct from both monomer and SEVI amyloid. We have characterized this new species, which could play a role in the biological activities currently ascribed to SEVI. Additionally, our proposed mechanism for peptide/lipid co-assembly could apply to other biologically important systems.
Septin Roles and Mechanisms in Organization of Endothelial Cell Junctions
Authors: Kim Joanna , Cooper John A.
Published: March 2020

Septins play an important role in regulating the barrier function of the endothelial monolayer of the microvasculature. Depletion of septin 2 protein alters the organization of vascular endothelial (VE)-cadherin at cell-cell adherens junctions as well as the dynamics of membrane protrusions at endothelial cell-cell contact sites. Here, we report the discovery that localization of septin 2 at endothelial cell junctions is important for the distribution of a number of other junctional molecules. We also found that treatment of microvascular endothelial cells with the inflammatory mediator TNF-α led to sequestration of septin 2 away from cell junctions and into the cytoplasm, without an effect on the overall level of septin 2 protein. Interestingly, TNF-α treatment of endothelial monolayers produced effects similar to those of depletion of septin 2 on various molecular components of adherens junctions (AJs) and tight junctions (TJs). Immunofluorescence staining revealed disruption of the integrity of AJs and TJs at cell-cell junctions without significant changes in protein expression except for VE-cadherin and nectin-2. To investigate the mechanism of junctional localization of septin 2, we mutated the polybasic motif of septin 2, which is proposed to interact with PIP2in the plasma membrane. Overexpression of PIP2-binding mutant (PIP2BM) septin 2 led to loss of septin 2 from cell junctions with accumulation in the cytoplasm. This redistribution of septin 2 away from the membrane led to effects on cell junction molecules similar to those observed for depletion of septin 2. We conclude that septin localization to the membrane is essential for function and that septins support the localization of multiple cell junction molecules in endothelial cells.
Chemogenetic activation of mesoaccumbal Gamma-Aminobutyric Acid projections selectively tunes responses to predictive cues when reward value is abruptly decreased
Authors: Wakabayashi Ken T. , Feja Malte , Leigh Martin P.K. , Baindur Ajay N. , Suarez Mauricio , Meyer Paul J. , Bass Caroline E.
Published: March 2020

Background

Mesolimbic circuits regulate the attribution of motivational significance to incentive cues that predict reward, yet this network also plays a key role in adapting reward-seeking behavior when the contingencies linked to a cue unexpectedly change. Here we asked whether mesoaccumbal gamma-aminobutyric acid (GABA) projections enhance adaptive responding to incentive cues of abruptly altered reward value, and whether these effects were distinct from global activation of all ventral tegmental area (VTA) GABA circuits.

Methods

We used a viral targeting system to chemogenetically activate mesoaccumbal GABA projections in male rats during a novel cue-dependent operant Value Shifting (VS) task, in which the volume of a sucrose reward associated with a predictive cue is suddenly altered, from the beginning and throughout the session. We compared the results with global activation of VTA GABA neurons, which will activate local inhibitory circuits and long loop projections.

Results

We found that activation of mesoaccumbal GABA projections decreases responding to incentive cues associated with smaller-than-expected rewards. This tuning of behavioral responses was specific to cues associated with smaller-than-expected rewards, but did not impact measures related to consuming the reward. In marked contrast, activating all VTA(GABA)neurons resulted in a uniform decrease in responding to incentive cues irrespective of changes in the size of the reward.

Conclusions

Targeted activation of mesoaccumbal GABA neurons facilitate adaptation in reward-seeking behaviors. This suggests that these projections may play a very specific role in associative learning processes.
TranslocatingMycobacterium ulcerans: an experimental model
Authors: Hammoudi N , Fellag M , Militello M , Bouam A , Drancourt M
Published: March 2020

Mycobacterium ulceransis a non-tuberculous environmental mycobacterium responsible for extensive cutaneous and subcutaneous ulcers in mammals, named Buruli ulcer in patients.M. ulceranshas been seldom detected in the feces of mammals but not in patients, nevertheless the detection and isolation ofM. ulceransin animal feces does not feet with the current epidemiological schemes for the disease. Here using an experimental model in which rats were fed with 109colony-forming units ofM. ulcerans, we detectedM. ulceransin feces of challenged rats for two weeks and along their digestive tract for 10 days.M. ulceranswas further detected in the lymphatic system including cervical and axillary lymph nodes and the spleen, but not in any other tissue including the healthy and breached skin, 10 days post-challenge. These observations indicate that in some herbivorous mammals,M. ulceranscontamination by the digestive route may precede translocation and limited infection of the lymphatic tissues without systemic infection. These herbivorous mammals may be sources ofM. ulceransfor exposed populations but are unlikely reservoirs for the pathogen.
Cathepsin K maintains the number of lymphocytesin vivo
Authors: Hausinger Renate , Hackl Marianne , Jardon-Alvarez Ana , Kehr Miriam , Marquez Sandra Romero , Hettler Franziska , Kehr Christian , Grziwok Sandra , Schreck Christina , Peschel Christian , Istvanffy Rouzanna , Oostendorp Robert A.J.
Published: March 2020

In this study, we investigated the influence of the loss of Cathepsin K (Ctsk)gene on the hematopoietic systemin vitroandin vivo. We found that cultures with Lineage-SCA1+KIT+(LSK) cells onCtskdeficient stromal cells display reduced colony formation and proliferation, with increased differentiation, giving rise to repopulating cells with reduced ability to repopulate the donor LSK and T cell compartments in the bone marrow. Subsequentin vivoexperiments showed impairment of lymphocyte numbers, but, gross effects on early hematopoiesis or myelopoiesis were not found. Most consistently inin vivoexperimental settings, we found a significant reduction of (donor) T cell numbers in the bone marrow. Lymphocyte deregulation is also found in transplantation experiments, which revealed thatCtskis required for optimal regeneration not only of T cells, but also of B cells. Interestingly, cell non-autonomousCtskregulates both B- and T cell numbers, but T cell numbers in the bone marrow require an additional autonomousCtsk-dependent process. Thus, we show thatCtskis required for the maintenance of hematopoietic stem cellsin vitro, butin vivo, Ctskdeficiency most strongly affects lymphocyte homeostasis, particularly of T cells in the bone marrow.
C-Eci: A Cubic-Eci Combined Clearing Method For 3D Follicular Content Analysis In The Fish Ovary
Authors: Lesage Manon , Thomas Manon , Bugeon Jérôme , Branthonne Adèle , Gay Stéphanie , Cardona Emilie , Bobe Julien , Thermes Violette
Published: March 2020

Deciphering mechanisms of oocyte development in female fishes still remains challenging and a comprehensive overview of this process at the level of the organ is still needed. The recent development optical tissue clearing methods have tremendously boosted the 3D imaging of large size biological samples that are naturally opaque. However, no attempt of clearing on fish ovary that accumulates extremely high concentration of lipids within oocytes has been reported to date. To face with this ovarian-specific challenge, we combined two existing clearing methods, the non-toxic solvent-based Eci method for efficient clearing and the CUBIC method to enhance lipid removal and reduce non-specific staining. The methyl green fluorescent dye was used to stain nuclei and delineate follicles. Using this procedure (named C-Eci), ovaries of both medaka and trout could be imaged in 3D and all follicles analyzed. To our knowledge this is the first procedure elaborated for clearing and imaging fish ovary in 3D. The C-Eci methods thus provides an interesting tool for getting precise quantitative data on follicular content in fish ovary and promises to be useful for further morphological studies.

A modified ethyl-cinnamate-based clearing method allows solving fish ovary-specific challenges for 3D imaging, including high lipid-contents, and analyzing the ovarian follicular content in medaka and trout.
Isotopy classes for 3-periodic net embeddings
Authors: Power Stephen C. , Baburin Igor A. , Proserpio Davide M.
Published: March 2020

Entangled embedded periodic nets and crystal frameworks are defined, along with their dimension type, homogeneity type, adjacency depth and periodic isotopy type. Periodic isotopy classifications are obtained for various families of embedded nets with small quotient graphs. The 25 periodic isotopy classes of depth-1 embedded nets with a single-vertex quotient graph are enumerated. Additionally, a classification is given of embeddings ofn-fold copies ofpcuwith all connected components in a parallel orientation andnvertices in a repeat unit, as well as demonstrations of their maximal symmetry periodic isotopes. The methodology of linear graph knots on the flat 3-torus [0,1)3is introduced. These graph knots, with linear edges, are spatial embeddings of the labelled quotient graphs of an embedded net which are associated with its periodicity bases.
Crystal structures of the recreational drug N-(4-methoxyphenyl)piperazine (MeOPP) and three of its salts
Authors: Kiran Kumar Haruvegowda , Yathirajan Hemmige S. , Harish Chinthal Chayanna , Foro Sabine , Glidewell Christopher
Published: March 2020

Crystal structures are reported for N-(4-methoxyphenyl)piperazine (MeOPP), (I), and for its 3,5-dinitrobenzoate, 2,4,6-trinitrophenolate (picrate) and 4-aminobenzoate salts, (II)–(IV), the last of which crystallizes as a monohydrate. In MeOPP, C11H16N2O, (I), the 4-methoxyphenyl group is nearly planar and it occupies an equatorial site on the piperazine ring: the molecules are linked into simple C(10) chains by N—H...O hydrogen bonds. In each of the salts, i.e., C11H17N2O+·C7H3N2O6
−, (II), C11H17N2O+·C6H2N3O7
−, (III), and C11H17N2O+·C7H6NO2
−·H2O, (IV), the effectively planar 4-methoxyphenyl substituent again occupies an equatorial site on the piperazine ring. In (II), two of the nitro groups are disordered over two sets of atomic sites and the bond distances in the anion indicate considerable delocalization of the negative charge over the C atoms of the ring. The ions in (II) are linked by two N—H...O hydrogen bonds to form a cyclic, centrosymmetric four-ion aggregate; those in (III) are linked by a combination of N—H...O and C—H...π(arene) hydrogen bonds to form sheets; and the components of (IV) are linked by N—H...O, O—H...O and C—H...π(arene) hydrogen bonds to form a three-dimensional framework structure. Comparisons are made with the structures of some related compounds.
Crystal structure and photoluminescent properties of bis(4′-chloro-2,2′:6′,2′′-terpyridyl)cobalt(II) dichloride tetrahydrate
Authors: Thippeswamy B. , Suchetan P. A. , Mahadevan K. M. , Nagabhushana H. , Vijayakumar G. R.
Published: March 2020

In the title hydrated complex, [Co(C15H10ClN3)2]Cl2·4H2O, the complete dication is generated by \overline{4} symmetry. The CoN6 moiety shows distortion from regular octahedral geometry with the trans bond angles of two N—Co—N units being 160.62 (9)°. In the crystal, O—H...Cl and C—H...O interactions link the components into (001) sheets. The title compound exhibits blue-light emission, as indicated by photoluminescence data, and a HOMO–LUMO energy separation of 2.23 eV was obtained from its diffuse reflectance spectrum.
The impact of external pressures (gaiatsu) and internal pressures (naiatsu) on Japan's accounting reforms since the late 1990s
Authors: Tsunogaya Noriyuki , Patel Chris
Published: March 2020

Purpose

The paper extends the literature by examining the impact of politics, conflicts and compromises resulting from external pressures (gaiatsu, 外圧) and internal pressures (naiatsu, 内圧) on the convergence and globalization of accounting and accountability in Japan.

Design/methodology/approach

Using Japan as a case study, it is examined how and why the stimulus for significant accounting reforms arises, how the government manages and reacts to the powerful forces ofgaiatsuand how it balancesnaiatsuamong key stakeholders.

Findings

The ongoing changes in accounting regulations in Japan are neither the result of an unmediated response togaiatsunor the outcome ofnaiatsu. Rather, Japanese accounting changes are the consequence of complex external interactions and internal compromises. Specifically, Japan demonstrates a repetitive pattern of conflict management, which alters the domestic power balance based onnaiatsu, and forces the Japanese government to make compromises to policy changes initiated bygaiatsu.

Research limitations/implications

The findings have implications for the development of accounting and accountability, the globalized business world and international accounting research because they challenge claims made by global standards setters that international standards such as International Financial Reporting Standards are superior, are built on so-called “best practices” and are relevant to all countries.

Originality/value

Invoking the concepts ofgaiatsuandnaiatsuis a critical approach to understanding Japan's convergence toward economic liberalism and Anglo-American models of accounting and accountability.
The study of online reviews and its relationship to online purchase intention for electronic products among the millennials in Malaysia
Authors: Cheong Jian Wei , Muthaly Siva , Kuppusamy Mudiarasan , Han Cheng
Published: March 2020

Purpose

The purpose of this research is to examine the type of online reviews (review timeliness, review quantity, and review valence) and its relationship toward online purchase intention for electronic products among millennials in Malaysia.

Design/methodology/approch

The quantitative approach and simple random sampling methodology were used in this research. Data were gathered through a survey instrument, and the partial least squares structural equation modeling (PLS-SEM) technique was subsequently applied to 215 responses. The model explained 36.3 percent variation of the major constructs in relation to online purchase intention of electronic products amongst Malaysian millennials.

Findings

Review timeliness is the most influential online reviews element towards Malaysian millennials' online purchase intention for electronic products.

Originality/value

This research project has provided the researcher and marketers with more clarity into the area of online purchase intention for electronic products, which is a volatile and dynamic area with continuous uncertainty.
Enhancing consumer engagement in e-commerce live streaming via relational bonds
Authors: Hu Mingyao , Chaudhry Sohail S.
Published: March 2020

Purpose

Enhancing consumer engagement in e-commerce live streaming is critical for e-commerce operators to build relationships and create consumer loyalty. Using the stimulus–organism–response model and theories from relationship marketing, the authors develop and test an integrative conceptual framework that combines various relational bonds, affective commitment, and consumer engagement.

Design/methodology/approach

Using 327 valid responses from consumers of Taobao Live, the authors employed the software Mplus7.0 to evaluate the measurement model and the structural model.

Findings

The results empirically demonstrate that social and structural bonds positively affect consumer engagement directly and indirectly via affective commitment, while financial bonds have only an indirect effect via affective commitment on consumer engagement.

Practical implications

The findings provide useful insights for e-commerce operators, who should invest in establishing relational bonds and stimulating affective commitment to improve consumer engagement.

Originality/value

This study adds to e-commerce research by being one of the first empirical studies on e-commerce live streaming, extends the marketing literature by integrating different relational bonds as antecedents of consumer engagement from the relational perspective, and enriches the affective commitment literature by distinguishing commitment to the online marketplace from commitment to the broadcaster.
Connecting supplier–supplier relationships to achieve supply chain performance of restaurant companies
Authors: Ku Edward C.S. , Hsu Shun-Fa , Wu Wu-Chung
Published: March 2020

Purpose

The goal of this study is to investigate how the development efficiency of restaurant companies' products of their suppliers, supplier–supplier connection, design quality and adaptation affect the supply chain performance (SCP) of restaurant companies.

Design/methodology/approach

We use the stratified random-sampling method for this study. We mailed the research questionnaire to the managers in the cases where they could be identified; a total of 1,063 questionnaires were sent by mail and a useable response of 156 fully completed questionnaires was received.

Findings

When the supplier has good development efficiency of restaurant companies' products, they can comply with the requirements of the budget project, and then, finally adapt to the restaurant companies to strengthen mutual relations of coexistence; suppliers with a good connection can make restaurant companies willing to go along with them.

Research limitations/implications

The limitation of this study was that the different types of suppliers were not compared, and some restaurants without scaled operations may have different effects on the result.

Practical implications

The supplier–supplier connection is established when the suppliers or companies have generated important decisions. The suppliers will cope with the restaurant companies to make the delivery procedure more unhindered and invest in highly specialized equipment in the relationship and finally, improve the SCP.

Originality/value

This study focuses on the restaurant companies in partnership: how to cooperate with the suppliers to make good supply efficiency, and thus enhance the SCP of the restaurant companies. Overall, the results of the study have provided reliable instruments for operationalizing the key effect constructs in the analysis of operational performance.
Joining-the-dots: caring for patients in advanced age
Authors: Miskelly Philippa , Kerse Ngaire , Wiles Janine
Published: March 2020

Purpose

Managing patients in advanced age is complex, especially when it comes to multi-morbidities and polypharmacy. The purpose of this qualitative study is to investigate challenges, opportunities and potential solutions from a primary healthcare provider perspective.

Design/methodology/approach

Fifty-seven participants joined in group discussions on challenges and opportunities of working with advanced age. Participants included general practitioners (GPs), practice nurses, students and administration staff working in ten general practices. A thematic analysis was developed, supported by NVivo software.

Findings

Poor lines of communication and fragmentation of services between differing levels of health care services available for older people were highlighted. This has implications for quality of care and equity of services. Participants also reported challenges in treatment and funding regimes.

Research limitations/implications

The small sample size and regional nature of the study, along with the semi-structured nature of the group discussions and rigorous thematic analysis, indicate that this qualitative data is transferable, dependable, confirmable and credible. Comparing the views of tertiary and community services would be useful.

Practical implications

A range of potential strategies and solutions to the current fragmented services was offered by GPs. For example, adequately funded and staffed community-based health hubs; IT platforms enabling timely flow of patient information between primary and tertiary health providers and creation of medical, nursing and allied health roles aimed at improving synergy between GP and tertiary services.

Originality/value

Obtaining the perspectives of general practice highlights the challenges and complexities of caring for those in advanced age brings. These insights have not been previously been explored in-depth within this setting in New Zealand.
Conceptualising online fashion brand recognition: scale development and validation
Authors: Rahman Muhammad Sabbir , Hossain Md Afnan , Rushan Md Rifayat Islam , Hoque Mohammad Tayeenul , Hassan Hasliza
Published: March 2020

Purpose

This study aims to develop and validate a scale for measuring online fashion brand recognition (OFBR).

Design/methodology/approach

Given the existing literature on brand, multiple stages of studies were conducted as a part of the scale development process. The OFBR scale was validated by a step-by-step process following the scale validation methodology suggested in the specialised literature.

Findings

The results demonstrate the 25 items of five unique factors that form the OFBR construct and confirm the strong validity of the construct. This finding suggests that the five-dimensional approach (online brand familiarity, online visual simplicity, online aesthetic attraction, online brand emotion and online social reputation) plays important role to form OFBR.

Practical implications

A valid and reliable OFBR scale provides a foundation for broadening the understanding on the important constructs that form OFBR, which is essential for online fashion retailing. Knowledge of the crucial antecedents that influence consumers towards online fashion products can enhance marketers’ capability to position their brands towards their target markets.

Originality/value

The relevance of this study lies in validating the scale for measuring OFBR for the first time in the literature on online fashion brand.
Predictions, Pollification, and Pol Profs: the ‘Corbyn Problem’ beyond Corbyn
Authors: Allen Peter , Moon David S.
Published: March 2020

It has been noted that UK political punditry has a ‘Corbyn problem’: an underlying hostility to the Corbyn project and its supporters. As the Corbyn era draws to a close, we take stock and argue that the Corbyn problem was never fully ‘about’ Corbyn. Instead, it was the outward manifestation of a conjunction of tendencies present in contemporary UK politics: the prominence of a relatively small group of ‘intensely involved’ individuals driving dominant political discourse; the inability of traditional purveyors of broadcast media coverage to adapt to contemporary political currents and an unwillingness to self‐reflect on possible biases in their approach; and the ‘pollification’ of election campaign coverage, aided by mainstream political scientists stereotyped in the figure of the ‘Pol Prof’. Combined, these tendencies are hostile to left‐wing political actors and movements. They will not disappear with Corbyn and may even intensify as their structural underpinnings strengthen further.
Atypical endometrial polyps and the incidence of endometrial cancer: a retrospective cohort study
Authors: Jacobs ISM , Tibosch RMG , Geomini PMAJ , Coppus SFPJ , Bongers MY , van Hanegem N
Published: March 2020

Objective

The aim of this study was to evaluate the incidence of endometrial carcinoma, proven after hysterectomy, in patients diagnosed with atypical endometrial hyperplasia confined to a polyp. A secondary aim was to establish factors associated with (pre‐)malignant alterations in a polyp.

Design

A retrospective cohort study.

Setting

Maastricht University Medical Centre (MUMC+) and Máxima Medical Centre in Eindhoven/Veldhoven (Máxima MC).

Population

Women who underwent a hysteroscopic polyp resection between 2008 and 2016.

Methods

Patient characteristics and histopathology results of the polyp and, in the case of a hysterectomy, uterus were collected from patients’ charts.

Results

A total of 1445 complete hysteroscopic polyp resections were included. Of those, 1390 polyps showed benign histopathology results, 39 polyps contained atypical hyperplasia and 16 polyps contained endometrial carcinoma. A hysterectomy was performed in 35 women who were diagnosed with atypical hyperplasia confined to a polyp after hysteroscopic polyp resection. Histopathological assessment showed no additional (pre‐)malignant changes of the endometrium in 12 women (30.8%), atypical hyperplasia in 11 women (28.2%) and endometrial carcinoma in 12 women (30.8%). None of the prognostic factors under consideration were significantly associated with (pre‐)malignant changes in a polyp.

Conclusion

The incidence of endometrial carcinoma in the surrounding endometrium after complete resection of a polyp with atypical hyperplasia is 30.8% in this study. This supports the current advice to perform a hysterectomy and bilateral salpingo‐oophorectomy. No prognostic factor for (pre‐)malignant changes in a polyp was established.

Tweetable abstract

The incidence of endometrial carcinoma after complete resection of a polyp with atypical hyperplasia is high.