scholarly journals Cdc42 and Par6–PKCζ regulate the spatially localized association of Dlg1 and APC to control cell polarization

2005 ◽  
Vol 170 (6) ◽  
pp. 895-901 ◽  
Author(s):  
Sandrine Etienne-Manneville ◽  
Jean-Baptiste Manneville ◽  
Sarah Nicholls ◽  
Michael A. Ferenczi ◽  
Alan Hall
Keyword(s):  
Total Internal Reflection ◽  
Biochemical Analysis ◽  
Control Cell ◽  
Leading Edge ◽  
Cell Polarization ◽  
Physical Interaction ◽  
Biological Processes ◽  
Polyposis Coli ◽  
Tumor Suppressor Proteins ◽  
Wide Range

Cell polarization is essential in a wide range of biological processes such as morphogenesis, asymmetric division, and directed migration. In this study, we show that two tumor suppressor proteins, adenomatous polyposis coli (APC) and Dlg1-SAP97, are required for the polarization of migrating astrocytes. Activation of the Par6–PKCζ complex by Cdc42 at the leading edge of migrating cells promotes both the localized association of APC with microtubule plus ends and the assembly of Dlg-containing puncta in the plasma membrane. Biochemical analysis and total internal reflection fluorescence microscopy reveal that the subsequent physical interaction between APC and Dlg1 is required for polarization of the microtubule cytoskeleton.

scholarly journals ROLE OF CXCR3 CHEMOKINE RECEPTOR AND ITS LIGANDS IN CERTAIN DISEASES

2019 ◽  
Vol 21 (4) ◽  
pp. 617-632 ◽  
Author(s):  
N. A. Arsentieva ◽  
A. V. Semenov ◽  
D. A. Zhebrun ◽  
E. V. Vasilyeva ◽  
Areg A. Totolian
Keyword(s):  
Immune Responses ◽  
Chemokine Receptor ◽  
Wide Spectrum ◽  
Control Cell ◽  
Autoimmune Disorders ◽  
Cell Polarization ◽  
Main Function ◽  
Activated T Cells ◽  
Wide Range

Chemokines are a special family of cytokines whose main function is to control cell migration; they are key players in the innate and adaptive immune responses. Directed chemotaxis of specific leukocyte subpopulations is necessary not only to maintain homeostasis, but also in development of some immunopathological conditions such as cancer, inflammation, infection, allergies and autoimmune disorders. Chemokines are pleiotropic molecules that are involved in physiological and pathophysiological processes. For example, the CXCR3 chemokine receptor is expressed on various cells: activated T and B lymphocytes, natural killers, eosinophils and neutrophils, dendritic cells, fibroblasts, endothelial and epithelial cells. Hence, CXCR3 and its ligands have a wide range of functional activity. CXCR3 ligands are the IFNγ-induced chemokines: CXCL9, CXCL10, CXCL11, and platelet-derived chemokines: CXCL4, CXCL4L1. All the CXCR3 ligands share common angiostatic properties due to lack of the Glu-Leu-Arg (ELR) motif. IFNγ-induced ligands of the CXCR3 are proinflammatory chemokines, they mainly recruit activated T cells and exert an effect on T cell polarization. Due to wide spectrum of biological activity, the ligands of CXCR3 receptor are involved in pathogenesis of various disorders, such as inflammation, infection, cancer, allergies and autoimmune disorders. In this review, we discuss the role of CXCR3 ligands in immunopathogenesis of various diseases, including the results of our studies in chronic hepatitis C, rheumatoid arthritis and pulmonary tuberculosis. Moreover, we have also discussed the potential laboratory diagnostic applicability of the chemokines in various diseases. This review illustrates a universal role of IFNγ-induced chemokines as mediators of immune responses in various diseases. The studies of CXCR3 ligands, their isoforms and receptors, interactions between themselves and with their receptors can provide a significant contribution to our understanding of the chemokine network. Understanding the system of IFNγ-dependent chemokines may have clinical implications, both for diagnostic tasks, and for therapeutic purposes.

iTSP-PseAAC: Identify Tumor Suppressor Proteins by Using Fully Connected Neural Network and PseAAC

2021 ◽  
Vol 15 ◽  
Author(s):  
Muhammad Awais ◽  
Waqar Hussain ◽  
Nouman Rasool ◽  
Yaser Daanial Khan
Keyword(s):  
Tumor Suppressor ◽  
Cross Validation ◽  
Control Cell ◽  
Normal Function ◽  
In Vivo Studies ◽  
Tumor Suppressor Proteins ◽  
Proposed Model ◽  
Self Consistency

Background: The uncontrolled growth due to accumulation of genetic and epigenetic changes as a result of loss or reduction in the normal function of Tumor Suppressor Genes (TSGs) and Pro-oncogenes is known as cancer. TSGs control cell division and growth by repairing of DNA mistakes during replication and restrict the unwanted proliferation of a cell or activities, those are the part of tumor production. Objectives: This study aims to propose a novel, accurate, user-friendly model to predict tumor suppressor proteins, which would be freely available to experimental molecular biologists to assist them using in vitro and in vivo studies. Methods: The predictor model has used the input feature vector (IFV) calculated from the physicochemical properties of proteins based on FCNN to compute the accuracy, sensitivity, specificity, and MCC. The proposed model was validated against different exhaustive validation techniques i.e. self-consistency and cross-validation. Results: Using self-consistency, the accuracy is 99%, for cross-validation and independent testing has 99.80% and 100% accuracy respectively. The overall accuracy of the proposed model is 99%, sensitivity value 98% and specificity 99% and F1-score was 0.99. Conclusion: It concludes, the proposed model for prediction of the tumor suppressor proteins can predict the tumor suppressor proteins efficiently, but it still has space for improvements in computational ways as the protein sequences may rapidly increase, day by day.

scholarly journals Energetics of mesoscale cell turbulence in two-dimensional monolayers

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Shao-Zhen Lin ◽  
Wu-Yang Zhang ◽  
Dapeng Bi ◽  
Bo Li ◽  
Xi-Qiao Feng
Keyword(s):  
Kinetic Energy ◽  
Tumor Metastasis ◽  
Cell Types ◽  
Boltzmann Distribution ◽  
Scaling Exponent ◽  
Biological Processes ◽  
Two Dimensional ◽  
Cell Monolayers ◽  
Wide Range ◽  
Epithelial Cell Monolayers

AbstractInvestigation of energy mechanisms at the collective cell scale is a challenge for understanding various biological processes, such as embryonic development and tumor metastasis. Here we investigate the energetics of self-sustained mesoscale turbulence in confluent two-dimensional (2D) cell monolayers. We find that the kinetic energy and enstrophy of collective cell flows in both epithelial and non-epithelial cell monolayers collapse to a family of probability density functions, which follow the q-Gaussian distribution rather than the Maxwell–Boltzmann distribution. The enstrophy scales linearly with the kinetic energy as the monolayer matures. The energy spectra exhibit a power-decaying law at large wavenumbers, with a scaling exponent markedly different from that in the classical 2D Kolmogorov–Kraichnan turbulence. These energetic features are demonstrated to be common for all cell types on various substrates with a wide range of stiffness. This study provides unique clues to understand active natures of cell population and tissues.

Experimental Studies of Leading Edge Contouring Influence on Secondary Losses in Transonic Turbines

2012 ◽  
Author(s):  
Ranjan Saha ◽  
Jens Fridh ◽  
Torsten Fransson ◽  
Boris I. Mamaev ◽  
Mats Annerfeldt
Keyword(s):  
Gas Turbine ◽  
Guide Vane ◽  
Experimental Studies ◽  
Three Dimensional ◽  
Leading Edge ◽  
Secondary Flows ◽  
Noticeable Effect ◽  
Flow Angle ◽  
Wide Range ◽  
Contour Plots

An experimental study of the hub leading edge contouring using fillets is performed in an annular sector cascade to observe the influence of secondary flows and aerodynamic losses. The investigated vane is a three dimensional gas turbine guide vane (geometrically similar) with a mid-span aspect ratio of 0.46. The measurements are carried out on the leading edge fillet and baseline cases using pneumatic probes. Significant precautions have been taken to increase the accuracy of the measurements. The investigations are performed for a wide range of operating exit Mach numbers from 0.5 to 0.9 at a design inlet flow angle of 90°. Data presented include the loading, fields of total pressures, exit flow angles, radial flow angles, as well as profile and secondary losses. The vane has a small profile loss of approximately 2.5% and secondary loss of about 1.1%. Contour plots of vorticity distributions and velocity vectors indicate there is a small influence of the vortex-structure in endwall regions when the leading edge fillet is used. Compared to the baseline case the loss for the filleted case is lower up to 13% of span and higher from 13% to 20% of the span for a reference condition with Mach no. of 0.9. For the filleted case, there is a small increase of turning up to 15% of the span and then a small decrease up to 35% of the span. Hence, there are no significant influences on the losses and turning for the filleted case. Results lead to the conclusion that one cannot expect a noticeable effect of leading edge contouring on the aerodynamic efficiency for the investigated 1st stage vane of a modern gas turbine.

scholarly journals CaM kinase IIδ2-dependent regulation of vascular smooth muscle cell polarization and migration

2008 ◽  
Vol 294 (6) ◽  
pp. C1465-C1475 ◽  
Author(s):  
Melissa Z. Mercure ◽  
Roman Ginnan ◽  
Harold A. Singer
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Vascular Smooth Muscle ◽  
Cell Monolayer ◽  
Leading Edge ◽  
Cell Polarization ◽  
Loss Of Function ◽  
Downstream Signaling ◽  
Transient Activation ◽  
And Migration

Previous studies indicate involvement of the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) in vascular smooth muscle (VSM) cell migration. In the present study, molecular loss-of-function studies were used specifically to assess the role of the predominant CaMKIIδ2 isoform on VSM cell migration using a scratch wound healing assay. Targeted CaMKIIδ2 knockdown using siRNA or inhibition of activity by overexpressing a kinase-negative mutant resulted in attenuation of VSM cell migration. Temporal and spatial assessments of kinase autophosphorylation indicated rapid and transient activation in response to wounding, in addition to a sustained activation in the leading edge of migrating and spreading cells. Furthermore, siRNA-mediated suppression of CaMKIIδ2 resulted in the inhibition of wound-induced Rac activation and Golgi reorganization, and disruption of leading edge morphology, indicating an important function for CaMKIIδ2 in regulating VSM cell polarization. Numerous previous reports link activation of CaMKII to ERK1/2 signaling in VSM. Wound-induced ERK1/2 activation was also found to be dependent on CaMKII; however, ERK activity did not account for effects of CaMKII in regulating Golgi polarization, indicating alternative mechanisms by which CaMKII affects the complex events involved in cell migration. Wounding a VSM cell monolayer results in CaMKIIδ2 activation, which positively regulates VSM cell polarization and downstream signaling, including Rac and ERK1/2 activation, leading to cell migration.

scholarly journals Reversing resistance: different routes and common themes across pathogens

2017 ◽  
Vol 284 (1863) ◽  
pp. 20171619 ◽  
Author(s):  
Richard C. Allen ◽  
Jan Engelstädter ◽  
Sebastian Bonhoeffer ◽  
Bruce A. McDonald ◽  
Alex R. Hall
Keyword(s):  
Fitness Cost ◽  
Biological Processes ◽  
Short Supply ◽  
Compensatory Evolution ◽  
Wide Range ◽  
Different Types ◽  
Cost Of Resistance

Resistance spreads rapidly in pathogen or pest populations exposed to biocides, such as fungicides and antibiotics, and in many cases new biocides are in short supply. How can resistance be reversed in order to prolong the effectiveness of available treatments? Some key parameters affecting reversion of resistance are well known, such as the fitness cost of resistance. However, the population biological processes that actually cause resistance to persist or decline remain poorly characterized, and consequently our ability to manage reversion of resistance is limited. Where do susceptible genotypes that replace resistant lineages come from? What is the epidemiological scale of reversion? What information do we need to predict the mechanisms or likelihood of reversion? Here, we define some of the population biological processes that can drive reversion, using examples from a wide range of taxa and biocides. These processes differ primarily in the origin of revertant genotypes, but also in their sensitivity to factors such as coselection and compensatory evolution that can alter the rate of reversion, and the likelihood that resistance will re-emerge upon re-exposure to biocides. We therefore argue that discriminating among different types of reversion allows for better prediction of where resistance is most likely to persist.

scholarly journals The RhoA-ROCK pathway in the regulation of T and B cell responses

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2295 ◽  
Author(s):  
Edd Ricker ◽  
Luvana Chowdhury ◽  
Woelsung Yi ◽  
Alessandra B. Pernis
Keyword(s):  
Immune Responses ◽  
Biological Processes ◽  
Dynamic Interactions ◽  
Cell Responses ◽  
Important Mediator ◽  
Downstream Effectors ◽  
Wide Range ◽  
Response To Stress ◽  
The Impact ◽  
Rho Kinases

Effective immune responses require the precise regulation of dynamic interactions between hematopoietic and non-hematopoietic cells. The Rho subfamily of GTPases, which includes RhoA, is rapidly activated downstream of a diverse array of biochemical and biomechanical signals, and is emerging as an important mediator of this cross-talk. Key downstream effectors of RhoA are the Rho kinases, or ROCKs. The ROCKs are two serine-threonine kinases that can act as global coordinators of a tissue’s response to stress and injury because of their ability to regulate a wide range of biological processes. Although the RhoA-ROCK pathway has been extensively investigated in the non-hematopoietic compartment, its role in the immune system is just now becoming appreciated. In this commentary, we provide a brief overview of recent findings that highlight the contribution of this pathway to lymphocyte development and activation, and the impact that dysregulation in the activation of RhoA and/or the ROCKs may exert on a growing list of autoimmune and lymphoproliferative disorders.

scholarly journals Deep6mA: A deep learning framework for exploring similar patterns in DNA N6-methyladenine sites across different species

2021 ◽  
Vol 17 (2) ◽  
pp. e1008767
Author(s):  
Zutan Li ◽  
Hangjin Jiang ◽  
Lingpeng Kong ◽  
Yuanyuan Chen ◽  
Kun Lang ◽  
...  
Keyword(s):  
Deep Learning ◽  
Prediction Accuracy ◽  
Cross Validation ◽  
Biological Processes ◽  
Biological Functions ◽  
Learning Framework ◽  
Wide Range ◽  
Genomic Scale ◽  
Downstream Gene Expression ◽  
Fold Cross Validation

N6-methyladenine (6mA) is an important DNA modification form associated with a wide range of biological processes. Identifying accurately 6mA sites on a genomic scale is crucial for under-standing of 6mA’s biological functions. However, the existing experimental techniques for detecting 6mA sites are cost-ineffective, which implies the great need of developing new computational methods for this problem. In this paper, we developed, without requiring any prior knowledge of 6mA and manually crafted sequence features, a deep learning framework named Deep6mA to identify DNA 6mA sites, and its performance is superior to other DNA 6mA prediction tools. Specifically, the 5-fold cross-validation on a benchmark dataset of rice gives the sensitivity and specificity of Deep6mA as 92.96% and 95.06%, respectively, and the overall prediction accuracy is 94%. Importantly, we find that the sequences with 6mA sites share similar patterns across different species. The model trained with rice data predicts well the 6mA sites of other three species: Arabidopsis thaliana, Fragaria vesca and Rosa chinensis with a prediction accuracy over 90%. In addition, we find that (1) 6mA tends to occur at GAGG motifs, which means the sequence near the 6mA site may be conservative; (2) 6mA is enriched in the TATA box of the promoter, which may be the main source of its regulating downstream gene expression.

scholarly journals RecRWR: A Recursive Random Walk Method for Improved Identification of Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-7
Author(s):  
Joel Perdiz Arrais ◽  
José Luís Oliveira
Keyword(s):  
Random Walk ◽  
Dna Microarrays ◽  
Physical Interaction ◽  
Biomedical Data ◽  
Biological Processes ◽  
Biological Noise ◽  
Random Walk With Restarts ◽  
Generation Sequencing ◽  
Selection Of ◽  
Best Disease

High-throughput methods such as next-generation sequencing or DNA microarrays lack precision, as they return hundreds of genes for a single disease profile. Several computational methods applied to physical interaction of protein networks have been successfully used in identification of the best disease candidates for each expression profile. An open problem for these methods is the ability to combine and take advantage of the wealth of biomedical data publicly available. We propose an enhanced method to improve selection of the best disease targets for a multilayer biomedical network that integrates PPI data annotated with stable knowledge from OMIM diseases and GO biological processes. We present a comprehensive validation that demonstrates the advantage of the proposed approach, Recursive Random Walk with Restarts (RecRWR). The obtained results outline the superiority of the proposed approach, RecRWR, in identifying disease candidates, especially with high levels of biological noise and benefiting from all data available.

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