NRF2 signaling cascade in amyotrophic lateral sclerosis: bridging the gap between promise and reality.

Amyotrophic lateral sclerosis is a very disabling disease due to the degeneration of motor neurons. Symptoms include muscle weakness and atrophy, spasticity, and progressive paralysis. Currently, there is no treatment to reverse damage to motor neurons and cure amyotrophic lateral sclerosis.

Neural network algorithm for detection of erosions and ankylosis on CT of the sacroiliac joints: multicentre development and validation of diagnostic accuracy.

Objectives: To evaluate the feasibility and diagnostic accuracy of a deep learning network for detection of structural lesions of sacroiliitis on multicentre pelvic CT scans.

Methods: Pelvic CT scans of 145 patients (81 female, 121 Ghent University/24 Alberta University, 18-87 years old, mean 40 ± 13 years, 2005-2021) with a clinical suspicion of sacroiliitis were retrospectively included. After manual sacroiliac joint (SIJ) segmentation and structural lesion annotation, a U-Net for SIJ segmentation and two separate convolutional neural networks (CNN) for erosion and ankylosis detection were trained.

Sigma-1 receptor agonist PRE-084 confers protection against TAR DNA-binding protein-43 toxicity through NRF2 signalling.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and lower motor neurons. As a consequence, ALS patients display a locomotor disorder related to muscle weakness and progressive paralysis. Pathological mechanisms that participate in ALS involve deficient unfolded protein response, mitochondrial dysfunction and oxidative stress, among others.

Morphological, behavioral and cellular analyses revealed different phenotypes in Wolfram syndrome wfs1a and wfs1b zebrafish mutant lines.

Wolfram syndrome (WS) is a rare genetic disease characterized by diabetes, optic atrophy and deafness. Patients die at 35 years of age, mainly from respiratory failure or dysphagia. Unfortunately, there is no treatment to block the progression of symptoms and there is an urgent need for adequate research models.

Activation of the sigma-1 receptor chaperone alleviates symptoms of Wolfram syndrome in preclinical models.

The Wolfram syndrome is a rare autosomal recessive disease affecting many organs with life-threatening consequences; currently, no treatment is available. The disease is caused by mutations in the gene, coding for the protein wolframin, an endoplasmic reticulum (ER) transmembrane protein involved in contacts between ER and mitochondria termed as mitochondria-associated ER membranes (MAMs). Inherited mutations usually reduce the protein's stability, altering its homeostasis and ultimately reducing ER to mitochondria calcium ion transfer, leading to mitochondrial dysfunction and cell death.

Sigma-1 receptor chaperones rescue nucleocytoplasmic transport deficit seen in cellular and Drosophila ALS/FTD models.

In a subgroup of patients with amyotrophic lateral sclerosis (ALS)/Frontotemporal dementia (FTD), the (G4C2)-RNA repeat expansion from C9orf72 chromosome binds to the Ran-activating protein (RanGAP) at the nuclear pore, resulting in nucleocytoplasmic transport deficit and accumulation of Ran in the cytosol. Here, we found that the sigma-1 receptor (Sig-1R), a molecular chaperone, reverses the pathological effects of (G4C2)-RNA repeats in cell lines and in Drosophila. The Sig-1R colocalizes with RanGAP and nuclear pore proteins (Nups) and stabilizes the latter.

Divorce in Turkish and Moroccan Communities in Belgium.

This paper focuses on divorce amongst Turkish and Moroccan Belgians, with a specific focus on the effect of partner-choice patterns. Divorce patterns of marriages established between 01 January 2001 and either 31 December 2003 (descriptive part), or 31 December 2005 (event-history analyses) are analysed and compared to marriages established between 01 January 1988 and 31 December 1990. We distinguish three marriage types: transnational marriages (i.

Sigma-1 receptor is a key genetic modulator in amyotrophic lateral sclerosis.

Sigma-1 receptor (S1R) is an endoplasmic reticulum (ER) chaperone that not only regulates mitochondrial respiration but also controls cellular defense against ER and oxidative stress. This makes S1R a potential therapeutic target in amyotrophic lateral sclerosis (ALS). Especially, as a missense mutation E102Q in S1R has been reported in few familial ALS cases.

Glycolysis upregulation is neuroprotective as a compensatory mechanism in ALS.

Amyotrophic Lateral Sclerosis (ALS), is a fatal neurodegenerative disorder, with TDP-43 inclusions as a major pathological hallmark. Using a model of TDP-43 proteinopathy we found significant alterations in glucose metabolism including increased pyruvate, suggesting that modulating glycolysis may be neuroprotective. Indeed, a high sugar diet improves locomotor and lifespan defects caused by TDP-43 proteinopathy in motor neurons or glia, but not muscle, suggesting that metabolic dysregulation occurs in the nervous system.

Mitochondrial quality control in amyotrophic lateral sclerosis: towards a common pathway?

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by loss of upper and lower motor neurons. Different mechanisms contribute to the disease initiation and progression, including mitochondrial dysfunction which has been proposed to be a central determinant in ALS pathogenesis. Indeed, while mitochondrial defects have been mainly described in ALS-linked SOD1 mutants, it is now well established that mitochondria become also dysfunctional in other ALS conditions.

Enhancing Mitofusin/Marf ameliorates neuromuscular dysfunction in Drosophila models of TDP-43 proteinopathies.

Transactive response DNA-binding protein 43 kDa (TDP-43) is considered a major pathological protein in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The precise mechanisms by which TDP-43 dysregulation leads to toxicity in neurons are not fully understood. Using TDP-43-expressing Drosophila, we examined whether mitochondrial dysfunction is a central determinant in TDP-43 pathogenesis.

Social inequality in adolescents' healthy food intake: the interplay between economic, social and cultural capital.

Background: Current explanations of health inequalities in adolescents focus on behavourial and economic determinants and rarely include more meaningful forms of economic, cultural, and social capital. The aim of the study was to investigate how the interplay between capitals constitutes social inequalities in adolescent healthy food intake.

Methods: Data were collected in the 2013/14 Flemish Health Behavior among School-aged Children (HBSC) survey, which is part of the international WHO HBSC survey.

Gender Differences in the Development of Sexual Excitation and Inhibition Through the Life Course: Preliminary Findings from a Representative Study in Flanders.

The dual control model proposes that there are individual differences in the propensity for sexual excitation and sexual inhibition. Research to date has considered the effect of age on these traits as a simple linear effect, and studies examining gender differences in age effects are lacking. There are, however, indications that the associations of age with excitation and inhibition are nonlinear and that there might be gender differences in these associations.

Enhanced neuronal glucose transporter expression reveals metabolic choice in a HD Drosophila model.

Huntington's disease is a neurodegenerative disorder caused by toxic insertions of polyglutamine residues in the Huntingtin protein and characterized by progressive deterioration of cognitive and motor functions. Altered brain glucose metabolism has long been suggested and a possible link has been proposed in HD. However, the precise function of glucose transporters was not yet determined.

PINK1-induced mitophagy promotes neuroprotection in Huntington's disease.

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by aberrant expansion of CAG repeat in the huntingtin gene. Mutant Huntingtin (mHtt) alters multiple cellular processes, leading to neuronal dysfunction and death. Among those alterations, impaired mitochondrial metabolism seems to have a major role in HD pathogenesis.

The importance of economic, social and cultural capital in understanding health inequalities: using a Bourdieu-based approach in research on physical and mental health perceptions.

In this article we adopt a Bourdieu-based approach to study social inequalities in perceptions of mental and physical health. Most research takes into account the impact of economic or social capital on health inequalities. Bourdieu, however, distinguishes between three forms of capital that can determine peoples' social position: economic, social and cultural capital.

An Exploratory Study of Factors Associated With Sexual Inhibition and Excitation: Findings From a Representative Survey in Flanders.

The dual control model of sexual response was developed to account for individual differences in sexual excitation and inhibition. According to this model, the balance between excitation and inhibition is of crucial importance in determining an individual's sexual response to a stimulus. In this study, we aimed to contribute to the existing literature on sexual excitation and inhibition in two ways.

Cultural capital and attitudes toward homosexuals: exploring the relation between lifestyles and homonegativity.

This article explores the potential of cultural capital as explanatory factor in understanding homonegativity. Building on recent findings suggesting the need for a cultural component in understanding homonegativity, this article explores the relation between lifestyles (the measurable expression of cultural capital) and homonegativity. Using the "Social-Cultural Changes in Flanders 2006" survey (a population-wide survey in Flanders, the northern part of Belgium), we observed that homonegativity is lowest in lifestyle clusters where cultural capital is higher.

Direct analysis of phthalate ester biomarkers in urine without preconcentration: method validation and monitoring.

Phthalates, which are ubiquitous in the environment, are readily metabolized in human bodies to their respective monoesters. These phthalate monoesters are non-persistent with short half-lives, which make them the ideal biomarkers of human exposure to phthalates. In this study a direct analysis method without preconcentration was developed and validated for the following phthalate ester metabolites in urine: mono-(2-ethylhexyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl)phthalate, monobenzyl phthalate, mono-isobutylphthalate, mono-n-butyl phthalate and monoethyl phthalate.

The Drosophila inner-membrane protein PMI controls crista biogenesis and mitochondrial diameter.

Cristae are mitochondrial inner-membrane structures that concentrate respiratory chain complexes and hence regulate ATP production. Mechanisms controlling crista morphogenesis are poorly understood and few crista determinants have been identified. Among them are the Mitofilins that are required to establish crista junctions and ATP-synthase subunits that bend the membrane at the tips of the cristae.

Reducing canonical Wingless/Wnt signaling pathway confers protection against mutant Huntingtin toxicity in Drosophila.

Huntington's disease (HD) is a genetic neurodegenerative disease characterized by movement disorders, cognitive decline and neuropsychiatric symptoms. HD is caused by expanded CAG tract within the coding region of Huntingtin protein. Despite major insights into the molecular mechanisms leading to HD, no effective cure is yet available.

Partner selection and divorce in ethnic minorities: distinguishing between two types of ethnic homogamous marriages.

This article compares divorce risks according to marriage type. The common dichotomy between ethnic homogamous and ethnic heterogamous marriages is further elaborated by differentiating a third marriage type; ethnic homogamous marriages between individuals from an ethnic minority group and a partner from the country of origin. Based on the analysis of data concerning the Turkish and Moroccan minorities in Belgium, it has been confirmed that the divorce risk associated with these marriages is higher than that of other ethnic homogamous marriages.

Increased energy metabolism rescues glia-induced pathology in a Drosophila model of Huntington's disease.

Huntington's disease (HD) is a polyglutamine (polyQ) disease caused by an expanded CAG tract within the coding region of Huntingtin protein. Mutant Huntingtin (mHtt) is ubiquitously expressed, abundantly in neurons but also significantly in glial cells. Neuron-intrinsic mechanism and alterations in glia-to-neuron communication both contribute to the neuronal dysfunction and death in HD pathology.

Hepatocyte-specific ABCA1 transfer increases HDL cholesterol but impairs HDL function and accelerates atherosclerosis.

Aims: The ATP-binding cassette transporter A1 (ABCA1) lipidates apolipoprotein (apo) A-I. The hypothesis that hepatocyte-specific ABCA1 overexpression results in high-density lipoprotein (HDL) dysfunction was evaluated by comparing the effects of murine ABCA1 (AdABCA1) and human apo A-I (AdA-I) transfer on lipoprotein profile, HDL function, and progression of atherosclerosis.

Methods And Results: Gene transfer in male and female C57BL/6 apo E(-/-) mice was performed at the age of 3 months with E1E3E4-deleted adenoviral vectors containing hepatocyte-specific expression cassettes.