Preliminary evaluation of the role of ubiquitin-ligase Smurf1 in host resistance to murine coronavirus (MHV) infection

2021 ◽  
Author(s):  
Luiz Pedro de Souza Costa ◽  
Larisse de Souza Barbosa Lacerda ◽  
Jordane Clarisse Pimenta Gaggino ◽  
Celso Queiroz-Junior ◽  
Leticia Soldati silva ◽  
...  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ariadna Recasens ◽  
Sean J. Humphrey ◽  
Michael Ellis ◽  
Monira Hoque ◽  
Ramzi H. Abbassi ◽  
...  

AbstractBoth tumour suppressive and oncogenic functions have been reported for dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Herein, we performed a detailed investigation to delineate the role of DYRK1A in glioblastoma. Our phosphoproteomic and mechanistic studies show that DYRK1A induces degradation of cyclin B by phosphorylating CDC23, which is necessary for the function of the anaphase-promoting complex, a ubiquitin ligase that degrades mitotic proteins. DYRK1A inhibition leads to the accumulation of cyclin B and activation of CDK1. Importantly, we established that the phenotypic response of glioblastoma cells to DYRK1A inhibition depends on both retinoblastoma (RB) expression and the degree of residual DYRK1A activity. Moderate DYRK1A inhibition leads to moderate cyclin B accumulation, CDK1 activation and increased proliferation in RB-deficient cells. In RB-proficient cells, cyclin B/CDK1 activation in response to DYRK1A inhibition is neutralized by the RB pathway, resulting in an unchanged proliferation rate. In contrast, complete DYRK1A inhibition with high doses of inhibitors results in massive cyclin B accumulation, saturation of CDK1 activity and cell cycle arrest, regardless of RB status. These findings provide new insights into the complexity of context-dependent DYRK1A signalling in cancer cells.


Author(s):  
Damiano Caruso ◽  
Francesco Pucciarelli ◽  
Marta Zerunian ◽  
Balaji Ganeshan ◽  
Domenico De Santis ◽  
...  

Abstract Purpose To evaluate the potential role of texture-based radiomics analysis in differentiating Coronavirus Disease-19 (COVID-19) pneumonia from pneumonia of other etiology on Chest CT. Materials and methods One hundred and twenty consecutive patients admitted to Emergency Department, from March 8, 2020, to April 25, 2020, with suspicious of COVID-19 that underwent Chest CT, were retrospectively analyzed. All patients presented CT findings indicative for interstitial pneumonia. Sixty patients with positive COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) and 60 patients with negative COVID-19 RT-PCR were enrolled. CT texture analysis (CTTA) was manually performed using dedicated software by two radiologists in consensus and textural features on filtered and unfiltered images were extracted as follows: mean intensity, standard deviation (SD), entropy, mean of positive pixels (MPP), skewness, and kurtosis. Nonparametric Mann–Whitney test assessed CTTA ability to differentiate positive from negative COVID-19 patients. Diagnostic criteria were obtained from receiver operating characteristic (ROC) curves. Results Unfiltered CTTA showed lower values of mean intensity, MPP, and kurtosis in COVID-19 positive patients compared to negative patients (p = 0.041, 0.004, and 0.002, respectively). On filtered images, fine and medium texture scales were significant differentiators; fine texture scale being most significant where COVID-19 positive patients had lower SD (p = 0.004) and MPP (p = 0.004) compared to COVID-19 negative patients. A combination of the significant texture features could identify the patients with positive COVID-19 from negative COVID-19 with a sensitivity of 60% and specificity of 80% (p = 0.001). Conclusions Preliminary evaluation suggests potential role of CTTA in distinguishing COVID-19 pneumonia from other interstitial pneumonia on Chest CT.


1982 ◽  
Vol 60 (14) ◽  
pp. 752-753
Author(s):  
Daniela N. Männel
Keyword(s):  

2021 ◽  
Vol 331 ◽  
pp. e80
Author(s):  
K.T. Miteva ◽  
F. Burger ◽  
D. Baptista ◽  
A. Roth ◽  
F. Mach ◽  
...  
Keyword(s):  

2017 ◽  
Vol 474 (18) ◽  
pp. 3075-3086 ◽  
Author(s):  
Nikhil Panicker ◽  
Valina L. Dawson ◽  
Ted M. Dawson

Monogenetic, familial forms of Parkinson's disease (PD) only account for 5–10% of the total number of PD cases, but analysis of the genes involved therein is invaluable to understanding PD-associated neurodegenerative signaling. One such gene, parkin, encodes a 465 amino acid E3 ubiquitin ligase. Of late, there has been considerable interest in the role of parkin signaling in PD and in identifying its putative substrates, as well as the elucidation of the mechanisms through which parkin itself is activated. Its dysfunction underlies both inherited and idiopathic PD-associated neurodegeneration. Here, we review recent literature that provides a model of activation of parkin in the setting of mitochondrial damage that involves PINK1 (PTEN-induced kinase-1) and phosphoubiquitin. We note that neuronal parkin is primarily a cytosolic protein (with various non-mitochondrial functions), and discuss potential cytosolic parkin activation mechanisms.


2009 ◽  
Vol 157 (9) ◽  
pp. 552-557 ◽  
Author(s):  
Shyanadrahalli Chandrashekaraiah Vanitha ◽  
Siddapura Ramachandrappa Niranjana ◽  
Sharanaiah Umesha

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