Regulation of cancer cell lipid metabolism and oxidative phosphorylation by microenvironmental acidosis.

The expansion of cancer cell mass in solid tumors generates a harsh environment characterized by dynamically varying levels of acidosis, hypoxia, and nutrient deprivation. Because acidosis inhibits glycolytic metabolism and hypoxia inhibits oxidative phosphorylation, cancer cells that survive and grow in these environments must rewire their metabolism and develop a high degree of metabolic plasticity to meet their energetic and biosynthetic demands. Cancer cells frequently upregulate pathways enabling the uptake and utilization of lipids and other nutrients derived from dead or recruited stromal cells, and in particular lipid uptake is strongly enhanced in acidic microenvironments.

MicroRNAs targeting TGF-β signaling exacerbate central nervous system autoimmunity by disrupting regulatory T cell development and function.

Transforming growth factor beta (TGF-β) signaling is essential for a balanced immune response by mediating the development and function of regulatory T cells (Tregs) and suppressing autoreactive T cells. Disruption of this balance can result in autoimmune diseases, including multiple sclerosis (MS). MicroRNAs (miRNAs) targeting TGF-β signaling have been shown to be upregulated in naïve CD4 T cells in MS patients, resulting in a limited in vitro generation of human Tregs.

Lactate receptor GPR81 drives breast cancer growth and invasiveness through regulation of ECM properties and Notch ligand DLL4.

Background: The lactate receptor GPR81 contributes to cancer development through unclear mechanisms. Here, we investigate the roles of GPR81 in three-dimensional (3D) and in vivo growth of breast cancer cells and study the molecular mechanisms involved.

Methods: GPR81 was stably knocked down (KD) in MCF-7 human breast cancer cells which were subjected to RNA-seq analysis, 3D growth, in situ- and immunofluorescence analyses, and cell viability- and motility assays, combined with KD of key GPR81-regulated genes.

Impact of the citizen science project COLLECT on ocean literacy and well-being within a north/west African and south-east Asian context.

Plastic pollution is both a societal and environmental problem and citizen science has shown to be a useful tool to engage both the public and professionals in addressing it. However, knowledge on the educational and behavioral impacts of citizen science projects focusing on marine litter remains limited. Our preregistered study investigates the impact of the citizen science project (COLLECT) on the participants' ocean literacy, pro-environmental intentions and attitudes, well-being, and nature connectedness, using a pretest-posttest design.

Dynamic localization of the Na+-HCO3- co-transporter NBCn1 to the plasma membrane, centrosomes, spindle and primary cilia.

Finely tuned regulation of transport protein localization is vital for epithelial function. The Na+-HCO3- co-transporter NBCn1 (also known as SLC4A7) is a key contributor to epithelial pH homeostasis, yet the regulation of its subcellular localization is not understood. Here, we show that a predicted N-terminal β-sheet and short C-terminal α-helical motif are essential for NBCn1 plasma membrane localization in epithelial cells.

LZER0: A Cost-Effective Multi-Purpose GNSS Platform.

Recent advances in Global Navigation Satellite System (GNSS) technology have made low-cost sensors available to the mass market, opening up new opportunities for real-time ground deformation and structure monitoring. In this paper, we present a new product developed in this framework by the National Institute of Oceanography and Applied Geophysics-OGS in collaboration with a private company (SoluTOP SAS): a cost-effective, multi-purpose GNSS platform called LZER0, suitable not only for surveying measurements, but also for monitoring tasks. The LZER0 platform is a complete system that includes the GNSS equipment (M8T single-frequency model produced by u-blox) and the web portal where the results are displayed.

A Qualitative Study on Emotions Experienced at the Coast and Their Influence on Well-Being.

Coastal environments are increasingly shown to have a positive effect on our health and well-being. Various mechanisms have been suggested to explain this effect. However, so far little focus has been devoted to emotions that might be relevant in this context, especially for people who are directly or indirectly exposed to the coast on a daily basis.

Influence of the Belgian Coast on Well-Being During the COVID-19 Pandemic.

There is increasing evidence that blue spaces, particularly coastal environments, are beneficial for well-being. During the first-wave lockdown of the COVID-19 pandemic in Belgium, access to the coast was restricted due to restraint in circulation. Making use of this unique opportunity, this study investigated whether access and visits to the coast were positively associated with well-being by using a quasi-experimental design.

The Voltage-Gated Sodium Channel Beta4 Subunit Maintains Epithelial Phenotype in Mammary Cells.

The gene, coding for the Naβ4 subunit of voltage-gated sodium channels, was recently found to be expressed in normal epithelial cells and down-regulated in several cancers. However, its function in normal epithelial cells has not been characterized. In this study, we demonstrated that reducing Naβ4 expression in MCF10A non-cancer mammary epithelial cells generated important morphological changes observed both in two-dimensional cultures and in three-dimensional cysts.

Erythropoietin alters the pharmacokinetics of organic anions mainly eliminated by the kidney in rats.

Erythropoietin (EPO) is a cytokine originally used for its effects on the hematopoietic system, and is widely prescribed around the world. In the present study, the effects of EPO administration on -aminohippurate (PAH, a prototype organic anion) pharmacokinetics and on the renal expression of PAH transporters were evaluated. Male Wistar rats were treated with EPO or saline (control group).

Dynamic Na/H exchanger 1 (NHE1) - calmodulin complexes of varying stoichiometry and structure regulate Ca-dependent NHE1 activation.

Calmodulin (CaM) engages in Ca-dependent interactions with numerous proteins, including a still incompletely understood physical and functional interaction with the human Na/H-exchanger NHE1. Using nuclear magnetic resonance (NMR) spectroscopy, isothermal titration calorimetry, and fibroblasts stably expressing wildtype and mutant NHE1, we discovered multiple accessible states of this functionally important complex existing in different NHE1:CaM stoichiometries and structures. We determined the NMR solution structure of a ternary complex in which CaM links two NHE1 cytosolic tails.

Loot box engagement and problem gambling among adolescent gamers: Findings from a national survey.

Loot boxes represent a form of microtransaction in many video games that have some resemblance with gambling. Research on this subject is still in its infancy, and particular there are few studies involving young people. Using cross-sectional survey data from a representative sample of 1,137 participants aged 12-16 years, this study examined loot box engagement patterns and links with problem gambling severity.

3D multicellular models to study the regulation and roles of acid-base transporters in breast cancer.

As a result of elevated metabolic rates and net acid extrusion in the rapidly proliferating cancer cells, solid tumours are characterized by a highly acidic microenvironment, while cancer cell intracellular pH is normal or even alkaline. Two-dimensional (2D) cell monocultures, which have been used extensively in breast cancer research for decades, cannot precisely recapitulate the rich environment and complex processes occurring in tumours in vivo. The use of such models can consequently be misleading or non-predictive for clinical applications.

Time evolution of methotrexate-induced kidney injury: A comparative study between different biomarkers of renal damage in rats.

Methotrexate (MTX) is commonly used in the treatment of malignant diseases and autoimmune and chronic inflammatory disorders. Along with its effective therapeutic power, MTX has adverse effects on the kidneys. Discovery of new biomarkers is required to improve the early detection of renal damage and optimize the effectiveness of treatments.

Time course effects of methotrexate on renal handling of water and electrolytes in rats. Role of aquaporin-2 and Na-K-2Cl-cotransporter.

Methotrexate (MTX) is a derivate of folic acid, commonly used as an anchor drug for the treatment and management of malignant diseases and autoimmune disorders. However, nephrotoxicity is an important drawback of MTX therapy. Unfortunately, there are not enough studies reporting the nature of the renal failure induced by MTX.

Renal expression and urinary excretion of Na/dicarboxylate cotransporter 1 (NaDC1) in obstructive nephropathy: a candidate biomarker for this pathology.

Obstructive nephropathy is characterized by alterations in renal function that depends on the degree and type of obstruction. To increase the knowledge about the physiopathological mechanisms involved in the renal damage associated with bilateral ureteral obstruction (BUO), we studied the renal expression and function (as urinary citrate excretion) of sodium-dependent dicarboxylate cotransporter (NaDC1) in rats. In addition, we evaluated the urinary excretion of NaDC1 as a candidate biomarker for this pathology.

Trafficking, localization and degradation of the Na,HCO co-transporter NBCn1 in kidney and breast epithelial cells.

The Na+;HCO3 co-transporter NBCn1 (SLC4A7) is a major regulator of intracellular pH yet its trafficking and turnover are essentially unstudied. Here, we used MDCK-II and MCF-7 cells to investigate these processes in epithelial cells. GFP-NBCn1 membrane localization was abolished by truncation of the full NBCn1 C-terminal tail (C-tail) yet did not require the C-terminal PDZ-binding motif (ETSL).

TGF-β regulation of encephalitogenic and regulatory T cells in multiple sclerosis.

Transforming growth factor beta (TGF-β) is a pleiotropic cytokine that has been shown to influence the differentiation and function of T cells. The role that TGF-β plays in immune-mediated disease, such as multiple sclerosis (MS), has become a major area of investigation since CD4 T cells appear to be a major mediator of autoimmunity. This review provides an analysis of the literature on the role that TGF-β plays in the generation and regulation of encephalitogenic and regulatory T cells (Treg) in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, as well as in T cells of MS patients.

Estrogen-regulated STAT1 activation promotes TLR8 expression to facilitate signaling via microRNA-21 in systemic lupus erythematosus.

Recent studies implicate innate immunity to systemic lupus erythematosus (SLE) pathogenesis. Toll-like receptor (TLR)8 is estrogen-regulated and binds viral ssRNA to stimulate innate immune responses, but recent work indicates that microRNA (miR)-21 within extracellular vesicles (EVs) can also trigger this receptor. Our objective was to examine TLR8 expression/activation to better understand sex-biased responses involving TLR8 in SLE.

Role of Wnt/β-catenin pathway in the nucleus accumbens in long-term cocaine-induced neuroplasticity: a possible novel target for addiction treatment.

Cocaine addiction is a chronic relapsing disorder characterized by the loss of control over drug-seeking and taking, and continued drug use regardless of adverse consequences. Despite years of research, effective treatments for psycho-stimulant addiction have not been identified. Persistent vulnerability to relapse arises from a number of long-lasting adaptations in the reward circuitry that mediate the enduring response to the drug.

Impact of the induced organic anion transporter 1 (Oat1) renal expression by furosemide on the pharmacokinetics of organic anions.

Aim: Furosemide is a loop diuretic. Different authors demonstrated that continuous administration of furosemide modulates the expression of organic anion transporters. This study was undertaken to simultaneously evaluate the effects of furosemide pretreatment on organic anion transporter 1 (Oat1) and multidrug resistance protein 2 (Mrp2) renal expressions, on p-aminohippurate (PAH) pharmacokinetics and on renal and urinary PAH levels in rats.

MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis.

Transforming growth factor beta (TGFβ) signalling is critical for regulatory T cell development and function, and regulatory T cell dysregulation is a common observation in autoimmune diseases, including multiple sclerosis. In a comprehensive miRNA profiling study of patients with multiple sclerosis naïve CD4 T cells, 19 differentially expressed miRNAs predicted to target the TGFβ signalling pathway were identified, leading to the hypothesis that miRNAs may be responsible for the regulatory T cell defect observed in patients with multiple sclerosis. Patients with multiple sclerosis had reduced levels of TGFβ signalling components in their naïve CD4 T cells.