University of Luxembourg

About: University of Luxembourg is a education organization based out in Luxembourg, Luxembourg. It is known for research contribution in the topics: Context (language use) & Computer science. The organization has 4744 authors who have published 22175 publications receiving 381824 citations.

Familial parkinsonism with synuclein pathology Clinical and PET studies of A30P mutation carriers

Abstract: Background: The authors identified the second known mutation in the α-synuclein(SNCA) gene, an alanine-to-proline exchange in amino acid position 30 (A30P), that cosegregates with the disease in one German family with autosomal dominantly inherited parkinsonism (ADP). The authors studied carriers of the A30P mutation to compare the phenotype of this mutation with idiopathic PD (IPD) and to assess nigrostriatal dopaminergic function in symptomatic and preclinical mutation carriers. Methods: The pedigree of the A30P family spans five generations with five affected individuals. The authors performed detailed neurologic examinations followed by mutation analysis in 11 living individuals. In three mutation carriers, two individuals with definite PD and one person at risk for PD, they used l-[18]F-fluoro-3,4-dihydroxyphenylalanine (F-DOPA), [11]C-raclopride (RAC), and [18]F-fluorodeoxyglucose (FDG) PET to investigate presynaptic dopaminergic function, dopamine D2 receptors, and cerebral energy metabolism. The authors studied the cognitive functions of carriers of the A30P mutation using neuropsychological screening. Results: PET studies revealed striatal presynaptic dopaminergic alterations consistent with sporadic IPD in two affected family members and no evidence for nigrostriatal dopaminergic dysfunction in one presymptomatic mutation carrier. Neuropsychological testing in four mutation carriers provided evidence for cognitive impairment as a frequent and early symptom of the A30P mutation; this is also supported by regional cerebral energy metabolism alterations in the clinically presymptomatic subject. Conclusions: The phenotype of the A30P mutation in the SNCA gene is similar to that of sporadic IPD, including a high variability of the age at disease onset, ranging from 54 to 76 years. The follow-up of presymptomatic carriers of the A30P mutation may give insight into preclinical disease stages and early manifestations of PD.

Looking Beyond Chronological Age: Current Knowledge and Future Directions in the Study of Subjective Age

Abstract: The notion of the heterogeneity of aging goes along with the awareness that every person experiences aging differently. Over the past years, scholars have emphasized that the assessment of these subjective experiences of aging contributes to our understanding of a range of psychological and physiological processes and outcomes among older adults. One construct frequently used in this context is subjective age, that is, how old or young a person feels. Subjective age has been shown to be an important correlate as well as a predictor of markers of successful aging such as well-being, health, and longevity. However, less is known about the antecedents of subjective age and the mechanisms underlying the relationship between feeling younger and positive developmental outcomes. This article briefly summarizes and critically evaluates the empirical evidence on this topic and makes suggestions on how to address and potentially overcome currently existing theoretical, methodological, and psychometric challenges. Based on the discussion of these challenges, the paper provides directions for future research by outlining underexplored topics such as intraindividual variability and determinants of subjective age, the match between objective age indicators and subjective age, and how subjective age maps on behavior and functioning.

Targeting autophagy inhibits melanoma growth by enhancing NK cells infiltration in a CCL5-dependent manner

Abstract: While blocking tumor growth by targeting autophagy is well established, its role on the infiltration of natural killer (NK) cells into tumors remains unknown. Here, we investigate the impact of targeting autophagy gene Beclin1 (BECN1) on the infiltration of NK cells into melanomas. We show that, in addition to inhibiting tumor growth, targeting BECN1 increased the infiltration of functional NK cells into melanoma tumors. We provide evidence that driving NK cells to the tumor bed relied on the ability of autophagy-defective tumors to transcriptionally overexpress the chemokine gene CCL5 Such infiltration and tumor regression were abrogated by silencing CCL5 in BECN1-defective tumors. Mechanistically, we show that the up-regulated expression of CCL5 occurred through the activation of its transcription factor c-Jun by a mechanism involving the impairment of phosphatase PP2A catalytic activity and the subsequent activation of JNK. Similar to BECN1, targeting other autophagy genes, such as ATG5, p62/SQSTM1, or inhibiting autophagy pharmacologically by chloroquine, also induced the expression of CCL5 in melanoma cells. Clinically, a positive correlation between CCL5 and NK cell marker NKp46 expression was found in melanoma patients, and a high expression level of CCL5 was correlated with a significant improvement of melanoma patients' survival. We believe that this study highlights the impact of targeting autophagy on the tumor infiltration by NK cells and its benefit as a novel therapeutic approach to improve NK-based immunotherapy.

Semi-stable semantics

Abstract: In this article, we examine an argument-based semantics called semi-stable semantics Semi-stable semantics is quite close to traditional stable semantics in the sense that every stable extension is also a semi-stable extension One of the advantages of semi-stable semantics is that for finite argumentation frameworks there always exists at least one semi-stable extension Furthermore, if there also exists at least one stable extension, then the semi-stable extensions coincide with the stable extensions Semi-stable semantics can be seen as a general approach that can be applied to abstract argumentation, as well as to fields like default logic and answer set programming, yielding an interpretation with properties very similar to those of paraconsistent logic, including the properties of crash resistance and backward compatibility