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See detailVariants in Miro1 cause alterations of ER-mitochondria contact sites in fibroblasts from Parkinson's disease patients
Berenguer, Clara UL; Grossmann, Dajana; Massart, François UL et al

in Journal of Clinical Medicine (2019)

Background: Although most cases of Parkinson´s disease (PD) are idiopathic with unknown cause, an increasing number of genes and genetic risk factors have been discovered that play a role in PD ... [more ▼]

Background: Although most cases of Parkinson´s disease (PD) are idiopathic with unknown cause, an increasing number of genes and genetic risk factors have been discovered that play a role in PD pathogenesis. Many of the PD‐associated proteins are involved in mitochondrial quality control, e.g., PINK1, Parkin, and LRRK2, which were recently identified as regulators of mitochondrial‐endoplasmic reticulum (ER) contact sites (MERCs) linking mitochondrial homeostasis to intracellular calcium handling. In this context, Miro1 is increasingly recognized to play a role in PD pathology. Recently, we identified the first PD patients carrying mutations in RHOT1, the gene coding for Miro1. Here, we describe two novel RHOT1 mutations identified in two PD patients and the characterization of the cellular phenotypes. Methods: Using whole exome sequencing we identified two PD patients carrying heterozygous mutations leading to the amino acid exchanges T351A and T610A in Miro1. We analyzed calcium homeostasis and MERCs in detail by live cell imaging and immunocytochemistry in patient‐derived fibroblasts. Results: We show that fibroblasts expressing mutant T351A or T610A Miro1 display impaired calcium homeostasis and a reduced amount of MERCs. All fibroblast lines from patients with pathogenic variants in Miro1, revealed alterations of the structure of MERCs. Conclusion: Our data suggest that Miro1 is important for the regulation of the structure and function of MERCs. Moreover, our study supports the role of MERCs in the pathogenesis of PD and further establishes variants in RHOT1 as rare genetic risk factors for neurodegeneration. [less ▲]

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See detailIncreased Circulating VAP-1 Levels Are Associated with Liver Fibrosis in Chronic Hepatitis C Infection.
Kraemer, Marcel; Krawczyk, Marcin; Noor, Fozia UL et al

in Journal of clinical medicine (2019), 8(1),

Vascular adhesion protein-1 (VAP-1) is a multifunction protein. While membrane-bound VAP-1 is an adhesion protein, soluble VAP-1 catalyzes the deamination of primary amines through its semicarbazide ... [more ▼]

Vascular adhesion protein-1 (VAP-1) is a multifunction protein. While membrane-bound VAP-1 is an adhesion protein, soluble VAP-1 catalyzes the deamination of primary amines through its semicarbazide-sensitive amino oxidase (SSAO) activity. VAP-1 supports the transmigration of leukocytes and increases oxidative stress. In chronic liver diseases, it plays a role in leukocyte infiltration and fibrogenesis. Here, we measured VAP-1 plasma concentration and its SSAO activity in 322 patients with chronic hepatitis C infection and evaluated the association of VAP-1 with fibrosis stages. VAP-1 concentration strongly correlated with liver stiffness and was the second strongest influencing variable after gamma-glutamytransferase (GGT) for liver stiffness in regression analysis. The VAP-1 concentration increased with advancing fibrosis stages and the highest concentrations were found in patients with cirrhosis. According to the receiver operating characteristic (ROC) analysis, a VAP-1 cut-off value of 541 ng/mL predicted histologically confirmed cirrhosis (sensitivity 74%; specificity 72%). SSAO activity correlated only moderately with liver stiffness, showing a relatively small increase in advanced fibrosis. To our knowledge, this is the first study on VAP-1 in chronic hepatitis C infection showing its association with progressive fibrosis. In conclusion, VAP-1 plasma concentration, rather than its SSAO activity, may represent a non-invasive biomarker for monitoring fibrogenesis in patients with chronic hepatitis C infection. [less ▲]

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See detailInterference with Processing Negative Stimuli in Problematic Internet Users: Preliminary Evidence from an Emotional Stroop Task.
Schimmenti, Adriano; Starcevic, Vladan; Gervasi, Alessia M. et al

in Journal of clinical medicine (2018), 7(7), 177

Although it has been proposed that problematic Internet use (PIU) may represent a dysfunctional coping strategy in response to negative emotional states, there is a lack of experimental studies that ... [more ▼]

Although it has been proposed that problematic Internet use (PIU) may represent a dysfunctional coping strategy in response to negative emotional states, there is a lack of experimental studies that directly test how individuals with PIU process emotional stimuli. In this study, we used an emotional Stroop task to examine the implicit bias toward positive and negative words in a sample of 100 individuals (54 females) who also completed questionnaires assessing PIU and current affect states. A significant interaction was observed between PIU and emotional Stroop effects (ESEs), with participants who displayed prominent PIU symptoms showing higher ESEs for negative words compared to other participants. No significant differences were found on the ESEs for positive words among participants. These findings suggest that PIU may be linked to a specific emotional interference with processing negative stimuli, thus supporting the view that PIU is a dysfunctional strategy to cope with negative affect. A potential treatment implication for individuals with PIU includes a need to enhance the capacity to process and regulate negative feelings. [less ▲]

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