Different Role of Platelet Glycoprotein GP Ia/IIa in Platelet Contact and Activation Induced by Type I and Type III Collagens

Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis (type III). It is a multifaceted phenomenon governed by the activation of genes associated with cell migration, extracellular matrix degradation, DNA repair, and angiogenesis. The cancer cells employ EMT to acquire the ability to migrate, resist therapeutic agents and escape immunity. One of the key biomarkers of EMT is vimentin, a type III intermediate filament that is normally expressed in mesenchymal cells but is upregulated during cancer metastasis. This review highlights the pivotal role of vimentin in the key events during EMT and explains its role as a downstream as well as an upstream regulator in this highly complex process. This review also highlights the areas that require further research in exploring the role of vimentin in EMT. As a cytoskeletal protein, vimentin filaments support mechanical integrity of the migratory machinery, generation of directional force, focal adhesion modulation and extracellular attachment. As a viscoelastic scaffold, it gives stress-bearing ability and flexible support to the cell and its organelles. However, during EMT it modulates genes for EMT inducers such as Snail, Slug, Twist and ZEB1/2, as well as the key epigenetic factors. In addition, it suppresses cellular differentiation and upregulates their pluripotent potential by inducing genes associated with self-renewability, thus increasing the stemness of cancer stem cells, facilitating the tumour spread and making them more resistant to treatments. Several missense and frameshift mutations reported in vimentin in human cancers may also contribute towards the metastatic spread. Therefore, we propose that vimentin should be a therapeutic target using molecular technologies that will curb cancer growth and spread with reduced mortality and morbidity.

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Evidence of corticosteroid action along the nephron

AJP Renal Physiology ◽

10.1152/ajprenal.1984.246.2.f111 ◽

1984 ◽

Vol 246 (2) ◽

pp. F111-F123 ◽

Cited By ~ 3

Author(s):

D. Marver

Keyword(s):

Collecting Duct ◽

Type I ◽

Type Ii ◽

Cortical Collecting Duct ◽

Distal Nephron ◽

Type Iii ◽

Collecting Ducts ◽

Collecting Tubule ◽

Cortical Collecting Tubule

The kidney contains three classes of corticosteroid-binding proteins receptors. They include a mineralocorticoid-specific (Type I), a glucocorticoid-specific (Type II), and a corticosterone-specific (Type III) site. The Type I and Type III sites roughly parallel each other along the nephron, with maximal binding occurring in the late distal convoluted or connecting segment and the cortical and medullary collecting ducts. Type II sites occur throughout the nephron, with maximal concentrations appearing in the proximal tubule and the late distal convoluted-cortical collecting duct region. The function of the Type I sites in the connecting segment is unclear since chronic mineralocorticoid therapy does not influence the potential difference in this segment as it does in the cortical collecting tubule. Furthermore, the specific role of Type II versus Type III sites in the distal nephron is unknown. Finally, the possible influence of sodium on both latent and steroid-induced renal cortical and medullary Na-K-ATPase is discussed.

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The role of mixotrophy in plankton bloom dynamics, and the consequences for productivity

ICES Journal of Marine Science ◽

10.1016/j.icesjms.2005.03.001 ◽

2005 ◽

Vol 62 (5) ◽

pp. 833-840 ◽

Cited By ~ 32

Author(s):

Astrid C. Hammer ◽

Jonathan W. Pitchford

Keyword(s):

Phytoplankton Bloom ◽

Equilibrium Structure ◽

Structure Stability ◽

Type I ◽

Single Individual ◽

Predator Prey ◽

Type Iii ◽

Predator Prey Model ◽

Plankton Bloom

Abstract Mixotrophy (=heterotrophy and photosynthesis by a single individual) is a common phenomenon in aquatic ecosystems, in particular under light- or nutrient-limitation. However, it is not usually considered in mathematical models of biological populations. This paper shows how different types of mixotrophy might be usefully incorporated into a general predator–prey model, and explores the consequences for plankton bloom dynamics and productivity. It is demonstrated, analytically and numerically, that even small levels of type III mixotrophy (a small fraction of the zooplankton also being involved in primary production) have significant effects on a system's equilibrium structure, stability, and short-term dynamics. Type III mixotrophy has a stabilizing effect on the system by reducing its excitability, i.e. its propensity to exhibit blooms. Compared with the non-mixotrophic benchmark, for a phytoplankton bloom to be triggered in a system with type III mixotrophy, a much larger perturbation is necessary. Type II mixotrophy (a small fraction of algae engage in phagotrophy) and type I mixotrophy (equal phagotrophy and phototrophy) are briefly discussed. The potential consequences for productivity are also studied. Our results indicate that the phytoplankton–zooplankton system becomes more productive in the presence of type III mixotrophy.

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The Involvement of Mycobacterium Type III-A CRISPR-Cas System in Oxidative Stress

Frontiers in Microbiology ◽

10.3389/fmicb.2021.774492 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fan Yang ◽

Lingqing Xu ◽

Lujie Liang ◽

Wanfei Liang ◽

Jiachen Li ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Envelope ◽

Reduction Process ◽

Intracellular Survival ◽

Host Immunity ◽

Type I ◽

Type Iii

Type I and type II CRISPR-Cas systems are employed to evade host immunity by targeting interference of bacteria’s own genes. Although Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, possesses integrated type III-A CRISPR-Cas system, its role in mycobacteria remains obscure. Here, we observed that seven cas genes (csm2∼5, cas10, cas6) were upregulated in Mycobacterium bovis BCG under oxidative stress treatment, indicating the role of type III-A CRISPR-Cas system in oxidative stress. To explore the functional role of type III-A CRISPR-Cas system, TCC (Type III-A CRISPR-Cas system, including cas6, cas10, and csm2-6) mutant was generated. Deletion of TCC results in increased sensitivity in response to hydrogen peroxide and reduced cell envelope integrity. Analysis of RNA-seq dataset revealed that TCC impacted on the oxidation-reduction process and the composition of cell wall which is essential for mycobacterial envelop integrity. Moreover, disrupting TCC led to poor intracellular survival in vivo and in vitro. Finally, we showed for the first time that TCC contributed to the regulation of regulatory T cell population, supporting a role of TCC in modulating host immunity. Our finding reveals the important role of TCC in cell envelop homeostasis. Our work also highlights type III-A CRISPR-Cas system as an important factor for intracellular survival and host immunoregulation in mycobacteria, thus may be a potential target for therapy.

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Role of Dynamic Contrast Enhanced MRI in Characterization of Breast Lesions

Nepalese Journal of Radiology ◽

10.3126/njr.v4i1.11366 ◽

2014 ◽

Vol 4 (1) ◽

pp. 23-33

Author(s):

P Issar ◽

SK Issar

Keyword(s):

Benign Lesion ◽

Breast Lesions ◽

Type I ◽

Type Ii ◽

Type Iii ◽

Dynamic Contrast Enhanced ◽

Contrast Enhanced ◽

Malignant Lesions

Purpose: To assess the role of Dynamic contrast enhanced magnetic resonance imaging in characterization of breast lesions and to differentiate benign from malignant lesions on the basis of their morphology and enhancement kinetics. Material and Methods: Sixty patients referred to the department of Radiodiagnosis for breast MRI over a period of twenty months were included. Dynamic contrast enhanced (DCE) Magnetic Resonance Imaging (MRI) was performed to differentiate breast lesions on the basis of morphology and enhancement kinetics. The lesions were classified accordingly into type I (progressive enhancement) Type II (plateau) and Type III (washout) kinetics. Morphology and curves of benign and malignant lesions were compared. Result: fifty one benign lesions were detected in 32 patients and 29 malignant lesions were seen in 22 patients, whereas six patients showed normal MRI. It was found that benign lesion were round or oval in shape with well circumscribed margin and showed homogenous contrast enhancement whereas malignant lesions were irregular with spiculated margin and showed heterogenous contrast enhancement. The distribution curve types of benign lesion were Type I (81.25%-26cases), Type II (18.25%-6cases). For malignant lesions Type I (4.54%-1case), Type II (22.72%-5cases) and Type III (72.72%-16cases). Conclusion: The shape of the time- signal intensity curve were an important criteria in differentiating benign from malignant lesions in dynamic breast MR imaging. A type III time curve is a strong indicator of malignancy and is independent of other criteria. DOI: http://dx.doi.org/10.3126/njr.v4i1.11366 Nepalese Journal of Radiology, Vol.4(1) 2014: 23-33

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Identification of Heparin-Binding Sites in the Fibronectin Type III Domains of the Leukocyte Common Antigen (CD45)

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc20040645 ◽

2004 ◽

Vol 69 (3) ◽

pp. 645-658

Author(s):

Daniel Kavan ◽

Markéta Vančurová ◽

Dana Ulbrichová ◽

Ivana Hladíková ◽

Miloslav Pospíšil ◽

...

Keyword(s):

Binding Sites ◽

Tyrosine Phosphatase ◽

Type I ◽

Heparin Binding ◽

Membrane Glycoproteins ◽

Type Iii ◽

Definitive Evidence ◽

Rich Domain ◽

Fibronectin Domains

Leukocyte common antigens (CD45) are large receptors that are abundantly expressed at the surface of all leukocytes. These receptors are type I membrane glycoproteins possessing two large C-terminal intracellular domains with protein tyrosine phosphatase activity. While the role of these enzyme domains in leukocyte signaling is well documented, the role of the N-terminal extracellular portion of CD45, composed of sequences formed by alternatively spliced exons, the cysteine rich domain, and three type III fibronectin repeats, remains unclear. The presence of fibronectin domains would predict the occurrence of heparin-binding sites, which may account for the documented affinity of CD45 for acid polysaccharides. We addressed this hypothesis using soluble recombinant proteins corresponding to the individual fibronectin domains (FN1 to FN3), and to the entire extracellular portion of CD45 (sCD45). Binding of these proteins to heparin was examined by frontal affinity chromatography. We found that while the sCD45 bound to heparin with Kd of 3.2 × 10-8 mol/l, the binding of FN2 and FN3 was somewhat weaker (Kd was 1.4 and 7.4 × 10-7 mol/l, respectively). The FN1 domain did not interact with heparin. Our results bring definitive evidence for the existence of binding sites for acid polysaccharides in the extracellular domain of CD45. These binding sites may be important for surface interactions of CD45 and for leukocyte signaling.

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Interferon-λ Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation

Viruses ◽

10.3390/v12040405 ◽

2020 ◽

Vol 12 (4) ◽

pp. 405

Author(s):

Yingying Li ◽

Ling Zhao ◽

Zhaochen Luo ◽

Yachun Zhang ◽

Lei Lv ◽

...

Keyword(s):

Rabies Virus ◽

Neuronal Damage ◽

Inflammatory Cells ◽

Inhibitory Effect ◽

Type I ◽

Type Iii ◽

Interferon Stimulated Genes ◽

Viral Spread ◽

Type Iii Ifn

Rabies, caused by rabies virus (RABV), is a fatal neurological disease that still causes more than 59,000 human deaths each year. Type III interferon IFN-λs are cytokines with type I IFN-like antiviral activities. Although IFN-λ can restrict the infection for some viruses, especially intestinal viruses, the inhibitory effect against RABV infection remains undefined. In this study, the function of type III IFN against RABV infection was investigated. Initially, we found that IFN-λ2 and IFN-λ3 could inhibit RABV replication in cells. To characterize the role of IFN-λ in RABV infection in a mouse model, recombinant RABVs expressing murine IFN-λ2 or IFN-λ3, termed as rB2c-IFNλ2 or rB2c-IFNλ3, respectively, were constructed and rescued. It was found that expression of IFN-λ could reduce the pathogenicity of RABV and limit viral spread in the brains by different infection routes. Furthermore, expression of IFN-λ could induce the activation of the JAK-STAT pathway, resulting in the production of interferon-stimulated genes (ISGs). It was also found that rRABVs expressing IFN-λ could reduce the production of inflammatory cytokines in primary astrocytes and microgila cells, restrict the opening of the blood-brain barrier (BBB), and prevent excessive infiltration of inflammatory cells into the brain, which could be responsible for the neuronal damage caused by RABV. Consistently, IFN-λ was found to maintain the integrity of tight junction (TJ) protein ZO-1 of BBB to alleviate neuroinflammation in a transwell model. Our study underscores the role of IFN-λ in inhibiting RABV infection, which potentiates IFN-λ as a possible therapeutic agent for the treatment of RABV infection.

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Signaling Pathways of Type I and Type III Interferons and Targeted Therapies in Systemic Lupus Erythematosus

Cells ◽

10.3390/cells8090963 ◽

2019 ◽

Vol 8 (9) ◽

pp. 963 ◽

Cited By ~ 10

Author(s):

I-Tsu Chyuan ◽

Hong-Tai Tzeng ◽

Ji-Yih Chen

Keyword(s):

Systemic Lupus Erythematosus ◽

Autoimmune Diseases ◽

Signaling Pathways ◽

Lupus Erythematosus ◽

Janus Kinase ◽

Type I ◽

Systemic Lupus ◽

Type Iii ◽

Signature Genes

Type I and type III interferons (IFNs) share several properties in common, including the induction of signaling pathways, the activation of gene transcripts, and immune responses, against viral infection. Recent advances in the understanding of the molecular basis of innate and adaptive immunity have led to the re-examination of the role of these IFNs in autoimmune diseases. To date, a variety of IFN-regulated genes, termed IFN signature genes, have been identified. The expressions of these genes significantly increase in systemic lupus erythematosus (SLE), highlighting the role of type I and type III IFNs in the pathogenesis of SLE. In this review, we first discussed the signaling pathways and the immunoregulatory roles of type I and type III IFNs. Next, we discussed the roles of these IFNs in the pathogenesis of autoimmune diseases, including SLE. In SLE, IFN-stimulated genes induced by IFN signaling contribute to a positive feedback loop of autoimmunity, resulting in perpetual autoimmune inflammation. Based on this, we discussed the use of several specific IFN blocking strategies using anti-IFN-α antibodies, anti-IFN-α receptor antibodies, and IFN-α-kinoid or downstream small molecules, which intervene in Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways, in clinical trials for SLE patients. Hopefully, the development of novel regimens targeting IFN signaling pathways will shed light on promising future therapeutic applications for SLE patients.

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