scholarly journals Exploiting teeth as a model to study basic features of signaling pathways

2020 ◽  
Vol 48 (6) ◽  
pp. 2729-2742
Author(s):  
Pierfrancesco Pagella ◽  
Cristina Porcheri ◽  
Thimios A. Mitsiadis
Keyword(s):  
Signaling Pathways ◽  
Classical Model ◽  
Experimental Models ◽  
Dental Tissues ◽  
Complex Interactions ◽  
Experimental Approaches ◽  
The Many ◽  
Basic Features ◽  
Embryonic Organ ◽  
Excellent Tool

Teeth constitute a classical model for the study of signaling pathways and their roles in mediating interactions between cells and tissues in organ development, homeostasis and regeneration. Rodent teeth are mostly used as experimental models. Rodent molars have proved fundamental in the study of epithelial–mesenchymal interactions and embryonic organ morphogenesis, as well as to faithfully model human diseases affecting dental tissues. The continuously growing rodent incisor is an excellent tool for the investigation of the mechanisms regulating stem cells dynamics in homeostasis and regeneration. In this review, we discuss the use of teeth as a model to investigate signaling pathways, providing an overview of the many unique experimental approaches offered by this organ. We discuss how complex networks of signaling pathways modulate the various aspects of tooth biology, and the models used to obtain this knowledge. Finally, we introduce new experimental approaches that allow the study of more complex interactions, such as the crosstalk between dental tissues, innervation and vascularization.

scholarly journals Estimation of Damage Induced by Single-Hole Rock Blasting: A Review on Analytical, Numerical, and Experimental Solutions

Energies ◽  
2020 ◽  
Vol 14 (1) ◽  
pp. 29
Author(s):  
Mahdi Shadabfar ◽  
Cagri Gokdemir ◽  
Mingliang Zhou ◽  
Hadi Kordestani ◽  
Edmond V. Muho
Keyword(s):  
Structural Reliability ◽  
Numerical Models ◽  
Experimental Models ◽  
Rock Blasting ◽  
Discussion Section ◽  
Reliability Models ◽  
Fine Grain ◽  
Experimental Approaches ◽  
Engineering Projects

This paper presents a review of the existing models for the estimation of explosion-induced crushed and cracked zones. The control of these zones is of utmost importance in the rock explosion design, since it aims at optimizing the fragmentation and, as a result, minimizing the fine grain production and recovery cycle. Moreover, this optimization can reduce the damage beyond the set border and align the excavation plan with the geometric design. The models are categorized into three groups based on the approach, i.e., analytical, numerical, and experimental approaches, and for each group, the relevant studies are classified and presented in a comprehensive manner. More specifically, in the analytical methods, the assumptions and results are described and discussed in order to provide a useful reference to judge the applicability of each model. Considering the numerical models, all commonly-used algorithms along with the simulation details and the influential parameters are reported and discussed. Finally, considering the experimental models, the emphasis is given here on presenting the most practical and widely employed laboratory models. The empirical equations derived from the models and their applications are examined in detail. In the Discussion section, the most common methods are selected and used to estimate the damage size of 13 case study problems. The results are then utilized to compare the accuracy and applicability of each selected method. Furthermore, the probabilistic analysis of the explosion-induced failure is reviewed using several structural reliability models. The selection, classification, and discussion of the models presented in this paper can be used as a reference in real engineering projects.

scholarly journals How to Get Component Maps for Aircraft Gas Turbine Performance Calculations

1996 ◽  
Author(s):  
Joachim Kurzke
Keyword(s):  
Gas Turbine ◽  
High Speed ◽  
Measured Data ◽  
Turbine Performance ◽  
The Many ◽  
Map Data ◽  
Performance Calculation ◽  
Excellent Tool ◽  
Very High ◽  
Drawing Program

Precise simulations of gas turbine performance cannot be done without component maps. In the early days of a new project one often has to use scaled maps of similar machines. Alternatively one can calculate the component partload characteristics provided that the many details needed for such an exercise are available. In a later stage often rig tests will be done to get detailed information about the behavior of the compressors respectively turbines. Performance calculation programs usually require the map data in a specific format. To produce this format needs some preprocessing. Measured data cannot be used directly because they show a scatter and they are not evenly distributed over the range of interest. Due to limitations in the test equipment often there is lack of data for very low and very high speed. With the help of a specialized drawing program available on a PC one can easily eliminate the scatter in the data and also inter- and extrapolate additional lines of constant corrected speed. Many graphs showing both the measured data and the lines passing through the data as a function of physically meaningful parameters allow to check whether the result makes sense or not. The extrapolation of compressor maps toward very low speed, as required for the calculation of starting, idle and windmilling performance calculations, is discussed in some detail. Instead of true measured data one can use data read from maps published in open literature. The program is also an excellent tool for checking and extending component maps one has derived from sparse information about a gas turbine to be simulated.

scholarly journals Chromatin Dynamics in Intestinal Epithelial Homeostasis: A Paradigm of Cell Fate Determination versus Cell Plasticity

2020 ◽  
Vol 16 (6) ◽  
pp. 1062-1080
Author(s):  
Jérémie Rispal ◽  
Fabrice Escaffit ◽  
Didier Trouche
Keyword(s):  
Signaling Pathways ◽  
Cell Fate ◽  
Chromatin Modification ◽  
Intestinal Cell ◽  
Intestinal Epithelial ◽  
Cell Plasticity ◽  
Chromatin Dynamics ◽  
Irritable Bowel ◽  
The Many

AbstractThe rapid renewal of intestinal epithelium is mediated by a pool of stem cells, located at the bottom of crypts, giving rise to highly proliferative progenitor cells, which in turn differentiate during their migration along the villus. The equilibrium between renewal and differentiation is critical for establishment and maintenance of tissue homeostasis, and is regulated by signaling pathways (Wnt, Notch, Bmp…) and specific transcription factors (TCF4, CDX2…). Such regulation controls intestinal cell identities by modulating the cellular transcriptome. Recently, chromatin modification and dynamics have been identified as major actors linking signaling pathways and transcriptional regulation in the control of intestinal homeostasis. In this review, we synthesize the many facets of chromatin dynamics involved in controlling intestinal cell fate, such as stemness maintenance, progenitor identity, lineage choice and commitment, and terminal differentiation. In addition, we present recent data underlying the fundamental role of chromatin dynamics in intestinal cell plasticity. Indeed, this plasticity, which includes dedifferentiation processes or the response to environmental cues (like microbiota’s presence or food ingestion), is central for the organ’s physiology. Finally, we discuss the role of chromatin dynamics in the appearance and treatment of diseases caused by deficiencies in the aforementioned mechanisms, such as gastrointestinal cancer, inflammatory bowel disease or irritable bowel syndrome.

scholarly journals MicroRNA Analysis of Human Stroke Brain Tissue Resected during Decompressive Craniectomy/Stroke-Ectomy Surgery

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1860
Author(s):  
Andrew P. Carlson ◽  
William McKay ◽  
Jeremy S. Edwards ◽  
Radha Swaminathan ◽  
Karen S. SantaCruz ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Brain Tissue ◽  
Stroke Patient ◽  
Mirna Expression ◽  
Strong Association ◽  
Bioinformatic Analysis ◽  
Experimental Models ◽  
Aberrant Expression ◽  
Tissue Samples ◽  
Human Stroke

Background: Signaling pathways mediated by microRNAs (miRNAs) have been identified as one of the mechanisms that regulate stroke progression and recovery. Recent investigations using stroke patient blood and cerebrospinal fluid (CSF) demonstrated disease-specific alterations in miRNA expression. In this study, for the first time, we investigated miRNA expression signatures in freshly removed human stroke brain tissue. Methods: Human brain samples were obtained during craniectomy and brain tissue resection in severe stroke patients with life-threatening brain swelling. The tissue samples were subjected to histopathological and immunofluorescence microscopy evaluation, next generation miRNA sequencing (NGS), and bioinformatic analysis. Results: miRNA NGS analysis detected 34 miRNAs with significantly aberrant expression in stroke tissue, as compared to non-stroke samples. Of these miRNAs, 19 were previously identified in stroke patient blood and CSF, while dysregulation of 15 miRNAs was newly detected in this study. miRNA direct target gene analysis and bioinformatics approach demonstrated a strong association of the identified miRNAs with stroke-related biological processes and signaling pathways. Conclusions: Dysregulated miRNAs detected in our study could be regarded as potential candidates for biomarkers and/or targets for therapeutic intervention. The results described herein further our understanding of the molecular basis of stroke and provide valuable information for the future functional studies in the experimental models of stroke.

scholarly journals Māori Urban Migrations and Identities, ‘Ko Ngā Iwi Nuku Whenua’: A study of Urbanisation in the Wellington Region during the Twentieth Century

2021 ◽  
Author(s):  
◽  
Erin Keenan
Keyword(s):  
Twentieth Century ◽  
Urban Areas ◽  
Urban Migration ◽  
World War ◽  
Historical Sources ◽  
The Past ◽  
Complex Interactions ◽  
The Subject ◽  
The Many ◽  
Migration Experiences

<p>Māori urbanisation and urban migrations have been the subject of much discussion and research, especially following World War Two when Māori individuals, whānau and communities increasingly became residents of towns and cities that were overwhelmingly Pākehā populated. However, Māori urbanisation experiences and urban migrations are difficult topics to address because kaumātua are reluctant to discuss ‘urban Māori’, especially considering its implications for Māori identities. The original contribution this thesis makes to histories of Māori urban migrations is that it explores these and other understandings of urbanisations to discover some of their historical influences. By discussing urbanisations directly with kaumātua and exploring historical sources of Māori living in, and moving to, the urban spaces of Wellington and the Hutt Valley through the twentieth century, this thesis is a ‘meeting place’ for a range of perspectives on the meanings of urbanisations from the past and the present. Although urbanisation was an incredible time of material change for the individuals and whānau who chose to move into cities such as Wellington, the histories of urban migration experiences exist within a scope of Māori and iwi worldviews that gave rise to multiple experiences and understandings of urbanisations. The Wellington region is used to show that Māori in towns and cities used Māori social and cultural forms in urban areas so that they could, through the many challenges of becoming urban-dwelling, ensure the persistence of their Māoritanga. Urbanisations also allowed Māori to both use traditional identities in urban areas, as well as develop new relationships modelled on kinship. The Ngāti Pōneke community is used as an example of the complex interactions between these identities and how many Māori became active residents in but not conceptually ‘of’ cities. As a result, the multiple and layered Māori identities that permeate throughout Māori experiences of the present and the past are important considerations in approaching and discussing urbanisations. Urban Māori communities have emphasised the significance of varied and layered Māori identities, and this became particularly pronounced through the Māori urban migrations of the twentieth century.</p>

scholarly journals Characterisation of the Semliki Forest Virus-host cell interactome reveals the viral capsid protein as an inhibitor of nonsense-mediated mRNA decay

2020 ◽  
Author(s):  
Lara Contu ◽  
Giuseppe Balistreri ◽  
Michal Domanski ◽  
Anne-Christine Uldry ◽  
Oliver Mühlemann
Keyword(s):  
Host Cell ◽  
Capsid Protein ◽  
Mrna Decay ◽  
Semliki Forest Virus ◽  
Protein Protein Interaction ◽  
Host Cell Proteins ◽  
Complex Interactions ◽  
Nonsense Mediated Mrna Decay ◽  
Interaction Map ◽  
The Many

AbstractThe positive-sense, single-stranded RNA alphaviruses pose a potential epidemic threat. Understanding the complex interactions between the viral and the host cell proteins is crucial for elucidating the mechanisms underlying successful virus replication strategies and for developing specific antiviral interventions. Here we present the first comprehensive protein-protein interaction map between the proteins of Semliki Forest Virus (SFV), a mosquito-borne member of the alphaviruses, and host cell proteins. Among the many identified cellular interactors of SFV proteins, the enrichment of factors involved in translation and nonsense-mediated mRNA decay (NMD) was striking, reflecting the virus’ hijacking of the translation machinery and indicating viral countermeasures for escaping NMD by inhibiting NMD at later time points during the infectious cycle. In addition to observing a general inhibition of NMD about 4 hours post infection, we also demonstrate that transient expression of the SFV capsid protein is sufficient to inhibit NMD in cells, suggesting that the massive production of capsid protein during the SFV reproduction cycle is responsible for NMD inhibition.

New insights in the interaction of FGF/FGFR and steroid receptor signaling in breast cancer

Endocrinology ◽  
2022 ◽  
Author(s):  
Cecilia Pérez Piñero ◽  
Sebastián Giulianelli ◽  
Caroline A Lamb ◽  
Claudia Lanari
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Endocrine Resistance ◽  
Short Review ◽  
Experimental Models ◽  
Luminal Breast Cancer ◽  
Tumor Subtypes ◽  
Stromal Tissue ◽  
The Many

Abstract Luminal breast cancer (BrCa) has a favorable prognosis compared to other tumor subtypes. However, with time tumors may evolve and lead to disease progression. Thus, there is a great interest in unraveling the mechanisms that drive tumor metastasis and endocrine resistance. In this review we focused in one of the many pathways that have been involved in tumor progression, the FGF/FGFR axis. We emphasized in data obtained from in vivo experimental models since we believe that in luminal BrCa, tumor growth relies in a crosstalk with the stromal tissue. We revisited the studies that illustrate the interaction between hormone receptors and FGFR. We also highlighted the most frequent alterations found in BrCa cell lines and we provide a short review on the trials that use FGFR inhibitors in combination with endocrine therapies. The analysis of this data suggests that there are many players involved in this pathway that might be also targeted to decrease FGF signaling in addition to specific FGFR inhibitors that may be exploited to increase their efficacy.

scholarly journals Experimental membranous nephropathy redux

2005 ◽  
Vol 289 (4) ◽  
pp. F660-F671 ◽  
Author(s):  
Andrey V. Cybulsky ◽  
Richard J. Quigg ◽  
David J. Salant
Keyword(s):  
Signaling Pathways ◽  
Complement Activation ◽  
Membranous Nephropathy ◽  
Plasma Membranes ◽  
Stress Proteins ◽  
Experimental Models ◽  
Slit Diaphragm ◽  
Glomerular Epithelial Cell ◽  
Substantial Progress ◽  
Key Steps

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Active and passive Heymann nephritis (HN) in rats are valuable experimental models because their features so closely resemble human MN. In HN, subepithelial immune deposits form in situ as a result of circulating antibodies. Complement activation leads to assembly of C5b-9 on glomerular epithelial cell (GEC) plasma membranes and is essential for sublethal GEC injury and the onset of proteinuria. This review revisits HN and focuses on areas of substantial progress in recent years. The response of the GEC to sublethal C5b-9 attack is not simply due to disruption of the plasma membrane but is due to the activation of specific signaling pathways. These include activation of protein kinases, phospholipases, cyclooxygenases, transcription factors, growth factors, NADPH oxidase, stress proteins, proteinases, and others. Ultimately, these signals impact on cell metabolic pathways and the structure/function of lipids and key proteins in the cytoskeleton and slit-diaphragm. Some signals affect GEC adversely. Thus C5b-9 induces partial dissolution of the actin cytoskeleton. There is a decline in nephrin expression, reduction in F-actin-bound nephrin, and loss of slit-diaphragm integrity. Other signals, such as endoplasmic reticulum stress, may limit complement-induced injury, or promote recovery. The extent of complement activation and GEC injury is dependent, in part, on complement-regulatory proteins, which act at early or late steps within the complement cascade. Identification of key steps in complement activation, the cellular signaling pathways, and the targets will facilitate therapeutic intervention in reversing GEC injury in human MN.

scholarly journals Nucleoside Diphosphate Kinase and Flagellin from Pseudomonas aeruginosa Induce Interleukin 1 Expression via the Akt/NF-κB Signaling Pathways

2014 ◽  
Vol 82 (8) ◽  
pp. 3252-3260 ◽  
Author(s):  
Yong-Jae Kim ◽  
Jung-Hoon Lee ◽  
Yeji Lee ◽  
Jingyue Jia ◽  
Se-Hwan Paek ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Proinflammatory Cytokines ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Nucleoside Diphosphate Kinase ◽  
Polymorphonuclear Neutrophils ◽  
Content Type ◽  
The Many

ABSTRACTInflammatory responses are a first line of host defense against a range of invading pathogens, consisting of the release of proinflammatory cytokines followed by attraction of polymorphonuclear neutrophils (PMNs) to the site of inflammation. Among the many virulence factors that contribute to the pathogenesis of infections, nucleoside diphosphate kinase (Ndk) mediates bacterially induced toxicity against eukaryotic cells. However, no study has examined how Ndk affects inflammatory responses. The present study examined the mechanisms by whichPseudomonas aeruginosaactivates inflammatory responses upon infection of cells. The results showed that bacterial Ndk, with the aid of an additional bacterial factor, flagellin, induced expression of the proinflammatory cytokines interleukin-1α (IL-1α) and IL-1β. Cytokine induction appeared to be dependent on the kinase activity of Ndk and was mediated via the NF-κB signaling pathway. Notably, Ndk activated the Akt signaling pathway, which acts upstream of NF-κB, as well as caspase-1, which is a key component of inflammasome. Thus, this study demonstrated thatP. aeruginosa, through the combined effects of Ndk and flagellin, upregulates the expression of proinflammatory cytokines via the Akt/NF-κB signaling pathways.

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