Mitochondrial Stress Signalling: HTRA2 and Parkinson's Disease

Mitochondria are cellular energy generators whose activity requires a continuous supply of oxygen. Recent genetic analysis has suggested that defects in mitochondrial quality control may be key factors in the development of Parkinson's disease (PD). Mitochondria have a crucial role in supplying energy to the brain, and their deterioration can affect the function and viability of neurons, contributing to neurodegeneration. These organelles can sow the seeds of their own demise because they generate damaging oxygen-free radicals as a byproduct of their intrinsic physiological functions. Mitochondria have therefore evolved specific molecular quality control mechanisms to compensate for the action of damaging agents such as oxygen-free radicals. PTEN-induced putative kinase 1 (PINK1) and high-temperature-regulated A2 (HTRA2), a mitochondrial protease, have recently been proposed to be key modulators of mitochondrial molecular quality control. Here, we review some of the most recent advances in our understanding of mitochondria stress-control pathways, focusing on how signalling by the p38 stress kinase pathway may regulate mitochondrial stress by modulating the activity of HTRA2 via PINK1 and cyclin-dependent kinase 5 (CDK5). We also propose how defects in this pathway may contribute to PD

Looking at b-learning and online experience in higher education during COVID-19

COVID-19 caused changes in teaching practices at various levels of education, namely in higher education. This study aims to present an analysis of an experience with higher education students in a b-learning pedagogical model, before and during the current pandemic and in different moments of the confinement measures. The curricular unit analyzed started with a blended-learning approach since 2018, considering the importance of innovative pedagogical models in student learning and became an essential resource during the pandemic period. This case study was composed of a sample of 269 students from a Portuguese public University who attended the curricular unit Methods and Study Techniques, as optional, in their 1st year of degree, between February 2018 and March 2021.The data were processed using SPSS v.27, seeking to analyze different moments, according to the different confinement measures decreed by the Portuguese Government. Participants are aged between 17 and 64 years old, 62.5% female and 24.5% worker-students. It was found that regardless of the context of confinement, students showed positive satisfaction with the online course, with its contents, with the platform and with the b-learning pedagogical method, especially during total confinement when classes were in distance learning. The most valued aspects in this modality were the flexibility of teaching the curricular unit and time management. The acquired tools were highly valued by the students, first for the adaptability that gave them, but mainly to face the distance learning challenge in their 1st year of degree, giving them planning and organizing skills for autonomous work. Most students did not point out a disadvantage in this modality, although they expressed the importance of face-to-face classes that were suspended in the context of a pandemic.info:eu-repo/semantics/acceptedVersio

Resonance induced by repulsive interactions in a model of globally-coupled bistable systems

We show the existence of a competition-induced resonance effect for a generic globally coupled bistable system. In particular, we demonstrate that the response of the macroscopic variable to an external signal is optimal for a particular proportion of repulsive links. Furthermore, we show that a resonance also occurs for other system parameters, like the coupling strength and the number of elements. We relate this resonance to the appearance of a multistable region, and we predict the location of the resonance peaks, by a simple spectral analysis of the Laplacian matrix

On requirements engineering for reactive systems: a formal methodology

This paper introduces a rigorous methodology for requirements specification of systems that react to external stimulus and consequently evolve through different operational modes, providing, in each of them, different functionalities. The proposed methodology proceeds in three stages, enriching a simple state- machine with local algebraic specifications. It resorts to an expressive variant of hybrid logic which is latter translated into first-order to allow for ample automatic tool support

Mitochondrial Quality Control and Parkinson’s Disease: A Pathway Unfolds

Recent findings from genetic studies suggest that defective mitochondrial quality control may play an important role in the development of Parkinson's disease (PD). Such defects may result in the impairment of neuronal mitochondria, which leads to both synaptic dysfunction and cell death and results in neurodegeneration. Here, we review state-of-the-art knowledge of how pathways affecting mitochondrial quality control might contribute to PD, with a particular emphasis on the molecular mechanisms employed by PTEN-induced putative kinase 1 (PINK1), HtrA2 and Parkin to regulate mitochondrial quality control

Active learning in the detection of anomalies in cryptocurrency transactions

The cryptocurrency market has grown significantly, and this quick growth has given rise to scams. It is necessary to put fraud detection mechanisms in place. The challenge of inadequate labeling is addressed in this work, which is a barrier to the training of high-performance supervised classifiers. It aims to lessen the necessity for laborious and time-consuming manual labeling. Some unlabeled data points have labels that are more pertinent and informative for the supervised model to learn from. The viability of utilizing unsupervised anomaly detection algorithms and active learning strategies to build an iterative process of acquiring labeled transactions in a cold start scenario, where there are no initial-labeled transactions, is being investigated. Investigating anomaly detection capabilities for a subset of data that maximizes supervised models’ learning potential is the goal. The anomaly detection algorithms under performed, according to the results. The findings underscore the need that anomaly detection algorithms be reserved for situations involving cold starts. As a result, using active learning techniques would produce better outcomes and supervised machine learning model performance.FCT - Fundação para a Ciência e a Tecnologia(UIDB/00319/2020

Parp mutations protect from mitochondrial toxicity in Alzheimer's disease.

Alzheimer's disease is the most common age-related neurodegenerative disorder. Familial forms of Alzheimer's disease associated with the accumulation of a toxic form of amyloid-β (Aβ) peptides are linked to mitochondrial impairment. The coenzyme nicotinamide adenine dinucleotide (NAD+) is essential for both mitochondrial bioenergetics and nuclear DNA repair through NAD+-consuming poly (ADP-ribose) polymerases (PARPs). Here we analysed the metabolomic changes in flies overexpressing Aβ and showed a decrease of metabolites associated with nicotinate and nicotinamide metabolism, which is critical for mitochondrial function in neurons. We show that increasing the bioavailability of NAD+ protects against Aβ toxicity. Pharmacological supplementation using NAM, a form of vitamin B that acts as a precursor for NAD+ or a genetic mutation of PARP rescues mitochondrial defects, protects neurons against degeneration and reduces behavioural impairments in a fly model of Alzheimer's disease. Next, we looked at links between PARP polymorphisms and vitamin B intake in patients with Alzheimer's disease. We show that polymorphisms in the human PARP1 gene or the intake of vitamin B are associated with a decrease in the risk and severity of Alzheimer's disease. We suggest that enhancing the availability of NAD+ by either vitamin B supplements or the inhibition of NAD+-dependent enzymes such as PARPs are potential therapies for Alzheimer's disease

Characterization of edible beeswax-based oleogels aiming at food incorporation

São Paulo School of Advanced Sciences on Reverse Engineering of Processed Foods[Excerpt] Uprising concern and consciousness of consumers, regarding saturated fat consumption, and the consequent demand for healthier food products are well visible in today’s society. Such continuous challenges question the food industry to quickly present solutions. Replace saturated fats in the food processing chain can be accomplished with the incorporation of edible oilbased gels or oleogels, which try to reproduce common fat structural and sensorial characteristics. Oil gelation effectiveness is managed by the gelators’ crystallization behaviour, where beeswax rises as a good candidate. [...]info:eu-repo/semantics/publishedVersio