scholarly journals The SCF/KIT pathway implements self-organised epithelial patterning by cell movement

2020 ◽  
Author(s):  
Alexandre Chuyen ◽  
Charlotte Rulquin ◽  
Virginie Thomé ◽  
Raphaël Clément ◽  
Laurent Kodjabachian ◽  
...  
Keyword(s):  
Outer Layer ◽  
Large Scale ◽  
Cell Movement ◽  
Intercellular Junctions ◽  
Tyrosine Kinase Receptor ◽  
Random Pattern ◽  
List Type ◽  
Multiciliated Cells ◽  
Actin Remodelling ◽  
Pattern Emergence

SUMMARYHow individual cell behaviours lead to the emergence of global patterns is poorly understood. In the Xenopus embryonic epidermis, multiciliated cells (MCCs) are born in a random pattern within an inner mesenchymal layer, and subsequently intercalate at regular intervals into an outer epithelial layer. Using both experiments and mathematical modelling, we show that this transition from chaotic to ordered distribution relies on mutual repulsion among motile immature MCCs, and affinity towards outer-layer intercellular junctions. Consistently, ARP2/3-mediated actin remodelling is required for MCC pattern emergence. Using multiple functional approaches, we show that the Kit tyrosine kinase receptor, expressed in MCCs, and its ligand Scf, expressed in outer-layer cells, are both required for regular MCC distribution. While Scf behaves as a potent adhesive cue for MCCs, Kit expression is sufficient to confer order to a disordered heterologous cell population. Our work reveals how a single signalling system can implement self-organised large-scale patterning.Highlights- Immature multiciliated cells transit from a disordered to an ordered pattern- The transition is a self-organising process based on repulsive and affinity movements- ARP2/3-dependent actin remodelling is required for pattern emergence- The SCF/KIT pathway promotes both repulsion and affinity movementseTOC blurbIn developing Xenopus epidermis, immature multiciliated cells (MCCs), initially chaotically distributed within an inner layer, emerge in an orderly pattern among cells of the outer layer. This process involves MCC mutual repulsion and affinity towards outer-layer intercellular junctions. The SCF/KIT signalling pathway promotes both properties to allow regular MCC distribution.

scholarly journals Disease Risk, Spatial Patterns, and Incidence-Severity Relationships of Fusarium Head Blight in No-till Spring Wheat Following Maize or Soybean

Plant Disease ◽  
2015 ◽  
Vol 99 (10) ◽  
pp. 1360-1366 ◽  
Author(s):  
Pierri Spolti ◽  
Denis A. Shah ◽  
José Maurício C. Fernandes ◽  
Gary C. Bergstrom ◽  
Emerson M. Del Ponte
Keyword(s):  
Fusarium Head Blight ◽  
Large Scale ◽  
Disease Risk ◽  
Random Pattern ◽  
Southern Brazil ◽  
Head Blight ◽  
Previous Crop ◽  
Regional Sources ◽  
Epidemiological Surveys ◽  
The Relationship

The first large-scale survey of Fusarium head blight (FHB) in commercial wheat fields in southern Brazil was conducted over three years (2009 to 2011). The objectives were to: (i) evaluate whether increased FHB risk is associated with within-field maize residue; (ii) determine the spatial pattern of FHB incidence; and (iii) quantify the relationship between FHB incidence and severity. FHB was assessed in a total of 160 fields between early milk and dough. Incidence ranged from 1.0 to 89.9% (median = 25%) and severity from 0.02 to 18.6% (median = 1.3%). FHB risk was neither lower nor higher in wheat following maize than in wheat following soybean. Only 18% of fields were classified as having aggregated patterns of FHB-symptomatic spikes. A binary power law description of the variances was consistent with an overall random pattern of the disease. These results conform with the hypothesis that FHB epidemics in southern Brazil are driven by sufficient atmospherically-transported inoculum from regional sources. The incidence-severity relationship was coherent across growing season, growth stage, and previous crop; one common fitted curve described the relationship across all observations. Estimating severity from incidence may be useful in reducing the workload in epidemiological surveys.

scholarly journals Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Munemasa Mori ◽  
Renin Hazan ◽  
Paul S. Danielian ◽  
John E. Mahoney ◽  
Huijun Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Large Scale ◽  
Abnormal Development ◽  
Basal Bodies ◽  
Transcriptional Program ◽  
Mutant Proteins ◽  
Multiprotein Complexes ◽  
Airway Diseases ◽  
Multiciliated Cells ◽  
Cytoplasmic Structures

Abstract Abnormal development of multiciliated cells is a hallmark of a variety of human conditions associated with chronic airway diseases, hydrocephalus and infertility. Multiciliogenesis requires both activation of a specialized transcriptional program and assembly of cytoplasmic structures for large-scale centriole amplification that generates basal bodies. It remains unclear, however, what mechanism initiates formation of these multiprotein complexes in epithelial progenitors. Here we show that this is triggered by nucleocytoplasmic translocation of the transcription factor E2f4. After inducing a transcriptional program of centriole biogenesis, E2f4 forms apical cytoplasmic organizing centres for assembly and nucleation of deuterosomes. Using genetically altered mice and E2F4 mutant proteins we demonstrate that centriole amplification is crucially dependent on these organizing centres and that, without cytoplasmic E2f4, deuterosomes are not assembled, halting multiciliogenesis. Thus, E2f4 integrates nuclear and previously unsuspected cytoplasmic events of centriole amplification, providing new perspectives for the understanding of normal ciliogenesis, ciliopathies and cancer.

scholarly journals In Vivo CRISPR Screens Identify E3 Ligase Cop1 as a Modulator of Macrophage Infiltration and Cancer Immunotherapy Target

2020 ◽  
Author(s):  
Xiaoqing Wang ◽  
Collin Tokheim ◽  
Binbin Wang ◽  
Shengqing Stan Gu ◽  
Qin Tang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Immunotherapy ◽  
Tumor Immunity ◽  
Large Scale ◽  
Integrated Approach ◽  
Immune Checkpoint Blockade ◽  
Macrophage Infiltration ◽  
List Type

SUMMARYDespite remarkable clinical efficacies of immune checkpoint blockade (ICB) in cancer treatment, ICB benefits in triple-negative breast cancer (TNBC) remain limited. Through pooled in vivo CRISPR knockout (KO) screens in syngeneic TNBC mouse models, we found that inhibition of the E3 ubiquitin ligase Cop1 in cancer cells decreases the secretion of macrophage-associated chemokines, reduces tumor macrophage infiltration, and shows synergy in anti-tumor immunity with ICB. Transcriptomics, epigenomics, and proteomics analyses revealed Cop1 functions through proteasomal degradation of the C/ebpδ protein. Cop1 substrate Trib2 functions as a scaffold linking Cop1 and C/ebpδ, which leads to polyubiquitination of C/ebpδ. Cop1 inhibition stabilizes C/ebpδ to suppress the expression of macrophage chemoattractant genes. Our integrated approach implicates Cop1 as a target for improving cancer immunotherapy efficacy by regulating chemokine secretion and macrophage levels in the TNBC tumor microenvironment.HighlightsLarge-scale in vivo CRISPR screens identify new immune targets regulating the tumor microenvironmentCop1 knockout in cancer cells enhances anti-tumor immunityCop1 modulates chemokine secretion and macrophage infiltration into tumorsCop1 targets C/ebpδ degradation via Trib2 and influences ICB response

scholarly journals Screening and potent applicability analysis of commonly used pesticides against desert locust: an integrative entomo-informatics approach

2020 ◽  
Author(s):  
Anik Banik ◽  
Md. Fuad Mondal ◽  
Md. Mostafigur Rahman Khan ◽  
Sheikh Rashel Ahmed ◽  
Md. Mehedi Hasan
Keyword(s):  
Binding Affinity ◽  
Large Scale ◽  
Schistocerca Gregaria ◽  
Indian Subcontinent ◽  
Locusta Migratoria ◽  
Field Trials ◽  
The Other ◽  
List Type ◽  
Agricultural Pesticides ◽  
Global Threat

AbstractThe locust problem is a global threat for food security. Locusts can fly and migrate overseas within a zip and creating a large-scale devastation to the diversified agro-ecosystem. GIS based analysis showed the recent movement of locusts, among them Schistocerca gregaria and Locusta migratoria are predominant in Indian subcontinent and are found more notorious and devastating one. This devastation needs to be stopped to save human race from food deprivation. In our study, we screened some commonly used agricultural pesticides and strongly recommended three of them viz. biphenthrin, diafenthiuron and silafluofen which might be potential to control the desert locusts based on their binding affinity towards the locust’s survival proteins. Our phylogenetic analysis reveals that these three recommended pesticides might also show potency to the other locust species as well as they are also way safer than the other commercially available pesticides. These proposed pesticide’s bioactive analogs from fungus and bacteria may also show efficacy as next generation controlling measures of locust as well as different kind of pests. These recommended pesticides are expected to be highly effective against locusts and needs to bring forward by the entomologists’ by performing experimental field trials.HighlightsGIS map unmasked the 2020 migratory pattern of locusts which now predominant towards Indian subcontinent.Biphenthrin, diafenthiuron and silafluofen showed maximum binding affinity.Biphenthrin and diafenthiuron were relatively safer than silafluofen.Bioactive analogs from fungus and bacteria could be an alternative to control locusts.Pesticides inhibition hotspots for desert locusts were unrevealed.

scholarly journals ComplexBrowser: a tool for identification and quantification of protein complexes in large scale proteomics datasets

2019 ◽  
Author(s):  
Wojciech Michalak ◽  
Vasileios Tsiamis ◽  
Veit Schwämmle ◽  
Adelina Rogowska-Wrzesińska
Keyword(s):  
T Cell Activation ◽  
Protein Complex ◽  
Quantitative Proteomics ◽  
Large Scale ◽  
Protein Complexes ◽  
Quantitative Measure ◽  
Exploratory Analysis ◽  
List Type ◽  
Link Type ◽  
Complex Components

AbstractWe have developed ComplexBrowser, an open source, online platform for supervised analysis of quantitative proteomics data that focuses on protein complexes. The software uses information from CORUM and Complex Portal databases to identify protein complex components. Based on the expression changes of individual complex subunits across the proteomics experiment it calculates Complex Fold Change (CFC) factor that characterises the overall protein complex expression trend and the level of subunit co-regulation. Thus up- and down-regulated complexes can be identified. It provides interactive visualisation of protein complexes composition and expression for exploratory analysis. It also incorporates a quality control step that includes normalisation and statistical analysis based on Limma test. ComplexBrowser performance was tested on two previously published proteomics studies identifying changes in protein expression in human adenocarcinoma tissue and during activation of mouse T-cells. The analysis revealed 1519 and 332 protein complexes, of which 233 and 41 were found co-ordinately regulated in the respective studies. The adopted approach provided evidence for a shift to glucose-based metabolism and high proliferation in adenocarcinoma tissues and identification of chromatin remodelling complexes involved in mouse T-cell activation. The results correlate with the original interpretation of the experiments and also provide novel biological details about protein complexes affected. ComplexBrowser is, to our knowledge, the first tool to automate quantitative protein complex analysis for high-throughput studies, providing insights into protein complex regulation within minutes of analysis.A fully functional demo version of ComplexBrowser v1.0 is available online via http://computproteomics.bmb.sdu.dk/Apps/ComplexBrowser/The source code can be downloaded from: https://bitbucket.org/michalakw/complexbrowserHighlightsAutomated analysis of protein complexes in proteomics experimentsQuantitative measure of the coordinated changes in protein complex componentsInteractive visualisations for exploratory analysis of proteomics resultsIn briefComplexBrowser is capable of identifying protein complexes in datasets obtained from large scale quantitative proteomics experiments. It provides, in the form of the CFC factor, a quantitative measure of the coordinated changes in complex components. This facilitates assessing the overall trends in the processes governed by the identified protein complexes providing a new and complementary way of interpreting proteomics experiments.

scholarly journals The Yale Department of Medicine COVID-19 Data Explorer and Repository (DOM-CovX): An Innovative Approach to Promoting Collaborative Scholarship During a Pandemic

2021 ◽  
Author(s):  
Tanima Arora ◽  
Michael Simonov ◽  
Jameel Alausa ◽  
Labeebah Subair ◽  
Brett Gerber ◽  
...  
Keyword(s):  
Clinical Data ◽  
Large Scale ◽  
Innovative Approach ◽  
Academic Productivity ◽  
List Type ◽  
Digital Revolution ◽  
Institutional Climate ◽  
Novel Approach ◽  
Dissemination Of Research ◽  
Academic Faculty

ABSTRACTBackgroundThe COVID-19 pandemic has led to an explosion of research publications spanning epidemiology, basic and clinical science. While a digital revolution has allowed for open access to large datasets enabling real-time tracking of the epidemic, detailed, locally-specific clinical data has been less readily accessible to a broad range of academic faculty and their trainees. This perpetuates the separation of the primary missions of clinically-focused and primary research faculty resulting in lost opportunities for improved understanding of the local epidemic; expansion of the scope of scholarship; limitation of the diversity of the research pool; lack of creation of initiatives for growth and dissemination of research skills needed for the training of the next generation of clinicians and faculty.ObjectivesCreate a common, easily accessible and up-to-date database that would promote access to local COVID-19 clinical data, thereby increasing efficiency, streamlining and democratizing the research enterprise. By providing a robust dataset, a broad range of researchers (faculty, trainees) and clinicians are encouraged to explore and collaborate on novel clinically relevant research questions.MethodsWe constructed a research platform called the Yale Department of Medicine COVID-19 Explorer and Repository (DOM-CovX), to house cleaned, highly granular, de-identified, continually-updated data from over 7,000 patients hospitalized with COVID-19 (1/2020-present) across the Yale New Haven Health System. This included a front-end user interface for simple data visualization of aggregate data and more detailed clinical datasets for researchers after a review board process. The goal is to promote access to local COVID-19 clinical data, thereby increasing efficiency, streamlining and democratizing the research enterprise.Expected OutcomesAccelerate generation of new knowledge and increase scholarly productivity with particular local relevanceImprove the institutional academic climate by:Broadening research scopeExpanding research capability to more diverse group of stakeholders including clinical and research-based faculty and traineesEnhancing interdepartmental collaborationsConclusionsThe DOM-CovX Data Explorer and Repository have great potential to increase academic productivity. By providing an accessible tool for simple data analysis and access to a consistently updated, standardized and large-scale dataset, it overcomes barriers for a wide variety of researchers. Beyond academic productivity, this innovative approach represents an opportunity to improve the institutional climate by fostering collaboration, diversity of scholarly pursuits and expanding medical education. It provides a novel approach that can be expanded to other diseases beyond COVID 19.

scholarly journals Developing linguistic literacy: perspectives from corpus linguistics and multi-dimensional analysis

2002 ◽  
Vol 29 (2) ◽  
pp. 449-488 ◽  
Author(s):  
DOUGLAS BIBER ◽  
RANDI REPPEN ◽  
SUSAN CONRAD
Keyword(s):  
Literacy Development ◽  
Corpus Linguistics ◽  
Large Scale ◽  
List Type ◽  
Linguistic Features ◽  
The Past ◽  
Patterns Of Use ◽  
Special Concern ◽  
Literacy Perspectives ◽  
Research Studies

In their conceptual framework for linguistic literacy development, Ravid & Tolchinsky synthesize research studies from several perspectives. One of these is corpus-based research, which has been used for several large-scale research studies of spoken and written registers over the past 20 years. In this approach, a large, principled collection of natural texts (a ‘corpus’) is analysed using computational and interactive techniques, to identify the salient linguistic characteristics of each register or text variety. Three characteristics of corpus-based analysis are particularly important (see Biber, Conrad & Reppen 1998):[bull ] a special concern for the representativeness of the text sample being analysed, and for the generalizability of findings;[bull ] overt recognition of the interactions among linguistic features: the ways in which features co-occur and alternate;[bull ] a focus on register as the most important parameter of linguistic variation: strong patterns of use in one register often represent only weak patterns in other registers.

Turbulent Vorticity Diffusion in the Stronger Wall Jet Managed by a Flat Plate Wing in the Outer Layer

2015 ◽  
Author(s):  
Takuma Katayama ◽  
Shinsuke Mochizuki
Keyword(s):  
Shear Stress ◽  
Flat Plate ◽  
Outer Layer ◽  
Large Scale ◽  
Reynolds Shear Stress ◽  
Three Dimensional ◽  
Quantitative Relationship ◽  
Wall Jet ◽  
Mean Velocity ◽  
The Mean

The present experiment focuses on the vorticity diffusion in a stronger wall jet managed by a three-dimensional flat plate wing in the outer layer. Measurement of the fluctuating velocities and vorticity correlation has been carried out with 4-wire vorticity probe. The turbulent vorticity diffusion due to the large scale eddies in the outer layer is quantitatively examined by using the 4-wire vorticity probe. Quantitative relationship between vortex structure and Reynolds shear stress is revealed by means of directly measured experimental evidence which explains vorticity diffusion process and influence of the manipulating wing. It is expected that the three-dimensional outer layer manipulator contributes to keep convex profile of the mean velocity, namely, suppression of the turbulent diffusion and entrainment.

scholarly journals 4382 All IN for Health: Promoting good health and engaging a health research volunteer community in the Hoosier state

2020 ◽  
Vol 4 (s1) ◽  
pp. 53-53
Author(s):  
Jessica Hall ◽  
Christine Drury ◽  
Carmel Egan
Keyword(s):  
Rural Communities ◽  
Health Research ◽  
Online Community ◽  
Large Scale ◽  
Research Participation ◽  
Good Health ◽  
The State ◽  
List Type ◽  
Research Literacy ◽  
Research Volunteers

OBJECTIVES/GOALS: To improve and expand health and research literacy throughout Indiana by sharing health-focused resources and research outcomes.To encourage and increase health research participation throughout Indiana by promoting health research opportunities, including clinical studies.METHODS/STUDY POPULATION: Discover and understand community concerns and barriers to good health and clinical research participation by providing a platform for individuals and communities to share their voices.Educate Indiana residents on the importance of participating in health research.Engage with the community to meet them where they are (online) and continue to build relationships throughout the state.Promote healthy living for Indiana residents by sharing health education and resources from existing state health organizations and initiatives.Develop and maintain the largest statewide database of research volunteers.RESULTS/ANTICIPATED RESULTS: The anticipated results from this program include engagement of all populations and all communities throughout the state in conversation and education around good health and health research, as well as participation in health research across the CTSI’s partner organizations. Large-scale growth is expected in both the online community and consented volunteer registry is expected to include and engage racially and ethnically diverse populations, as well as special health populations, such as representatives of rural communities, aged, rare disease survivors, and transgender individuals.DISCUSSION/SIGNIFICANCE OF IMPACT: Thorough this work, the Indiana CTSI has developed a unique program, educating the public about health research and opportunities to participate, while simultaneously supporting research departments with marketing promotion of their efforts, and a ready statewide volunteer community.

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