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Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by amyloid beta (Aβ) and hyperphosphorylated tau accumulation in the brain. Recent studies indicated that memory retrieval, rather than memory formation, was impaired in the early stage of AD. Our previous study reported that pharmacological activation of hippocampal Epac2 promoted memory retrieval in C57BL/6J mice. A recent study suggested that pharmacological inhibition of Epac2 prevented synaptic potentiation mediated by GluA3-containing AMPARs. In this study, we aimed to investigate proteins associated with Epac2-mediated memory in hippocampal postmortem samples of AD patients and healthy controls compared with the experimental AD model J20 and wild-type mice. Epac2 and phospho-Akt were downregulated in AD patients and J20 mice, while Epac1 and phospho-ERK1/2 were not altered. GluA3 was reduced in J20 mice and tended to decrease in AD patients. PSD95 tended to decrease in AD patients and J20. Interestingly, AKAP5 was increased in AD patients but not in J20 mice, implicating its role in tau phosphorylation. Our study points to the downregulation of hippocampal expression of proteins associated with Epac2 in AD.

The paper presents a mechatronic system for heart rate monitoring. The electrocardiogram acquisitioned with the sensor module will be displayed on the mobile phone using a human–machine interface. The connection between the phone and the sensor module will be established using the Bluetooth technology.

Alzheimer’s disease (AD), the most common form of dementia, currently affects 40–50 million people worldwide. Despite the extensive research into amyloid β (Aβ) deposition and tau protein hyperphosphorylation (p-tau), an effective treatment to stop or slow down the progression of neurodegeneration is missing. Emerging evidence suggests that ferroptosis, an iron-dependent and lipid peroxidation-driven type of programmed cell death, contributes to neurodegeneration in AD. Therefore, how to intervene against ferroptosis in the context of AD has become one of the questions addressed by studies aiming to develop novel therapeutic strategies. However, the underlying molecular mechanism of ferroptosis in AD, when ferroptosis occurs in the disease course, and which ferroptosis-related genes are differentially expressed in AD remains to be established. In this review, we summarize the current knowledge on cell mechanisms involved in ferroptosis, we discuss how these processes relate to AD, and we analyze which ferroptosis-related genes are differentially expressed in AD brain dependant on cell type, disease progression and gender. In addition, we point out the existing targets for therapeutic options to prevent ferroptosis in AD. Future studies should focus on developing new tools able to demonstrate where and when cells undergo ferroptosis in AD brain and build more translatable AD models for identifying anti-ferroptotic agents able to slow down neurodegeneration.

The essay proposes to realize theoretical and experimental research in the field of three-dimensional scans, as well as in the field of reverse engineering to 3D printing. The idea of the theme has left the engineer responsible for different types of electrical / electronic equipment and has to recreate / rebuild CAD models for a number of parts of the equipment configuration, parts that fail after a certain operating time.

A wire harness is a support for transferring signals or electricity. Commonly used in various branches of mechanical engineering, wiring offers more advantages than free cords and cables, that is why its rate in the automobile industry is more than 30% of the total production of cables. The paper deals with the current and future aspects regarding the manufacturing of harnesses for the automotive industry.

Parkinson’s Disease (PD) is the second most common neurodegenerative disease world-wide. Mutations in the multidomain protein Leucine Rich Repeat Kinase 2 (LRRK2) are the most frequent cause of hereditary PD. Furthermore, recent data suggest that independent of mutations, increased kinase activity of LRRK2 plays an essential role in PD pathogenesis. Isolated mitochondria of tissue samples from PD patients carrying LRRK2 mutations display a significant impairment of mitochondrial function. However, due to the complexity of the mitochondrial signaling network, the role of LRRK2 in mitochondrial metabolism is still not well understood. Previously we have shown that D. discoideum Roco4 is a suitable model to study the activation mechanism of LRRK2 in vivo. To get more insight in the LRRK2 pathways regulating mitochondrial activity we used this Roco4 model system in combination with murine RAW macrophages. Here we show that both Dictyostelium roco4 knockout and cells expressing PD-mutants show behavioral and developmental phenotypes that are characteristic for mitochondrial impairment. Mitochondrial activity measured by Seahorse technology revealed that the basal respiration of D. discoideum roco4- cells is significantly increased compared to the WT strain, while the basal and maximal respiration values of cells overexpressing Roco4 are reduced compared to the WT strain. Consistently, LRRK2 KO RAW 264.7 cells exhibit higher maximal mitochondrial respiration activity compared to the LRRK2 parental RAW264.7 cells. Measurement on isolated mitochondria from LRRK2 KO and parental RAW 264.7 cells revealed no difference in activity compared to the parental cells. Furthermore, neither D. discoideum roco4- nor LRRK2 KO RAW 264.7 showed a difference in either the number or the morphology of mitochondria compared to their respective parental strains. This suggests that the observed effects on the mitochondrial respiratory in cells are indirect and that LRRK2/Roco proteins most likely require other cytosolic cofactors to elicit mitochondrial effects.

Ferroptosis is a form of regulated cell death that can be modulated by small molecules and has the potential for the development of therapeutics for oncology. Although excessive lipid peroxidation is the defining hallmark of ferroptosis, DNA damage may also play a significant role. In this study, a potential mechanistic role for MIF in homologous recombination (HR) DNA repair is identified. The inhibition or genetic depletion of MIF or other HR proteins, such as breast cancer type 1 susceptibility protein (BRCA1), is demonstrated to significantly enhance the sensitivity of cells to ferroptosis. The interference with HR results in the translocation of the tumor suppressor protein p53 to the mitochondria, which in turn stimulates the production of reactive oxygen species. Taken together, the findings demonstrate that MIF‐directed small molecules enhance ferroptosis via a putative MIF‐BRCA1‐RAD51 axis in HR, which causes resistance to ferroptosis. This suggests a potential novel druggable route to enhance ferroptosis by targeted anticancer therapeutics in the future. [ABSTRACT FROM AUTHOR]

Introduction: Air pollution from diesel combustion is linked in part to the generation of diesel exhaust particles (DEP). DEP exposure induces various processes, including inflammation and oxidative stress, which ultimately contribute to a decline in lung function. Cyclic AMP (cAMP) signaling is critical for lung homeostasis. The impact of DEP on cAMP signaling is largely unknown. Methods: We exposed human bronchial epithelial (BEAS-2B) cells to DEP for 24-72 h and evaluated mitochondrial bioenergetics, markers of oxidative stress and inflammation and the components of cAMP signaling. Mitochondrial bioenergetics was measured at 72 h to capture the potential and accumulative effects of prolonged DEP exposure on mitochondrial function. Results: DEP profoundly altered mitochondrial morphology and network integrity, reduced both basal and ATP-linked respiration as well as the glycolytic capacity of mitochondria. DEP exposure increased gene expression of oxidative stress and inflammation markers such as interleukin-8 and interleukin-6. DEP significantly affected mRNA levels of exchange protein directly activated by cAMP-1 and -2 (Epac1, Epac2), appeared to increase Epac1 protein, but left phospho-PKA levels unhanged. DEP exposure increased A-kinase anchoring protein 1, β2-adrenoceptor and prostanoid E receptor subtype 4 mRNA levels. Interestingly, DEP decreased mRNA levels of adenylyl cyclase 9 and reduced cAMP levels stimulated by forskolin (AC activator), fenoterol (β2-AR agonist) or PGE2 (EPR agonist). Discussion: Our findings suggest that DEP induces mitochondrial dysfunction, a process accompanied by oxidative stress and inflammation, and broadly dampens cAMP signaling. These epithelial responses may contribute to lung dysfunction induced by air pollution exposure. [ABSTRACT FROM AUTHOR]

Respiratory diseases are among the leading causes of morbidity and mortality worldwide, representing a major unmet medical need. New chemical entities rarely make it into the clinic to treat respiratory diseases, which is partially due to a lack of adequate predictive disease models and the limited availability of human lung tissues to model respiratory disease. Human pluripotent stem cells (hPSCs) may help fill this gap by serving as a scalable human in vitro model. In addition, human in vitro models of rare genetic mutations can be generated using hPSCs. hPSC-derived epithelial cells and organoids have already shown great potential for the understanding of disease mechanisms, for finding new potential targets by using high-throughput screening platforms, and for personalised treatments. These potentials can also be applied to other hPSC-derived lung cell types in the future. In this review, we will discuss how hPSCs have brought, and may continue to bring, major changes to the field of respiratory diseases by understanding the molecular mechanisms of the pathology and by finding efficient therapeutics.

This study addresses the eventual consequence of cytochrome c oxidase (CytOx) inhibition by ATP at high ATP/ADP ratio in isolated rat heart mitochondria. Earlier, it has been demonstrated that the mechanism of allosteric ATP inhibition of CytOx is one of the key regulations of mitochondrial functions. It is relevant that aiming to maintain a high ATP/ADP ratio for the measurement of CytOx activity effectuating the enzymatic inhibition as well as mitochondrial respiration, optimal concentration of mitochondria is critically important. Likewise, only at this concentration, were the differences in ΔΨm and ROS concentrations measured under various conditions significant. Moreover, when CytOx activity was inhibited in the presence of ATP, mitochondrial respiration and ΔΨm both remained static, while the ROS production was markedly decreased. Consubstantial results were found when the electron transport chain was inhibited by antimycin A, letting only CytOx remain functional to support the energy production. This seems to corroborate that the decrease in mitochondrial ROS production is solely the effect of ATP binding to CytOx which results in static respiration as well as membrane potential.

Nowadays there is a large number of cars in the world, they have overcrowded the cities, therefore the parking places are becoming more and more difficult to find. This reason has led in finding a solution for increasing the number of car parks on a small area. The paper proposes the development, functional description and testing of a smart parking system demonstrator based on elevator principal. The demonstrator can be controlled with the help of an android application which is connected to an Arduino via bluetooth.

Exchange proteins directly activated by cAMP (Epac) proteins are implicated in a wide range of cellular functions including oxidative stress and cell survival. Mitochondrial-dependent oxidative stress has been associated with progressive neuronal death underlying the pathology of many neurodegenerative diseases. The role of Epac modulation in neuronal cells in relation to cell survival and death, as well as its potential effect on mitochondrial function, is not well established. In immortalized hippocampal (HT-22) neuronal cells, we examined mitochondria function in the presence of various Epac pharmacological modulators in response to oxidative stress due to ferroptosis. Our study revealed that selective pharmacological modulation of Epac1 or Epac2 isoforms, exerted differential effects in erastin-induced ferroptosis conditions in HT-22 cells. Epac1 inhibition prevented cell death and loss of mitochondrial integrity induced by ferroptosis, while Epac2 inhibition had limited effects. Our data suggest Epac1 as a plausible therapeutic target for preventing ferroptosis cell death associated with neurodegenerative diseases.

In various neurodegenerative conditions, inflammation plays a significant role in disrupting the blood–brain barrier (BBB), contributing to disease progression. Nitric oxide (NO) emerges as a central regulator of vascular function, with a dual role in inflammation, acting as both a pro- and anti-inflammatory molecule. This study investigates the effects of the NO donor sodium nitroprusside (SNP) in protecting the BBB from lipopolysaccharide (LPS)-induced inflammation, using bEnd.3 endothelial cells as a model system. Additionally, Raw 264.7 macrophages were employed to assess the effects of LPS and SNP on their adhesion to a bEnd.3 cell monolayer. Our results show that LPS treatment induces oxidative stress, activates the JAK2/STAT3 pathway, and increases pro-inflammatory markers. SNP administration effectively mitigates ROS production and IL-6 expression, suggesting a potential anti-inflammatory role. However, SNP did not significantly alter the adhesion of Raw 264.7 cells to bEnd.3 cells induced by LPS, probably because it did not have any effect on ICAM-1 expression, although it reduced VCAM expression. Moreover, SNP did not prevent BBB disruption. This research provides new insights into the role of NO in BBB disruption induced by inflammation. [ABSTRACT FROM AUTHOR]

Huntington's disease is caused by a polyglutamine stretch expansion in the first exon of huntingtin. Here, the authors use infrared spectroscopy and solid-state NMR and show that polymorphic huntingtin exon1 fibres differ in their flanking regions but not their core polyglutamine amyloid structures.