Deacidification of endolysosomes by neuronal aging drives synapse loss.

Previously, we found that age-dependent accumulation of beta-amyloid is not sufficient to cause synaptic decline. Late-endocytic organelles (LEOs) may be driving synaptic decline as lysosomes (Lys) are a target of cellular aging and relevant for synapses. We found that LAMP1-positive LEOs increased in size and number and accumulated near synapses in aged neurons and brains. LEOs' distal accumulation might relate to the increased anterograde movement in aged neurons. Dissecting the LEOs, we found that late-endosomes accumulated while there are fewer terminal Lys in aged neurites, but not in the cell body. The most abundant LEOs were degradative Lys or endolysosomes (ELys), especially in neurites. ELys activity was reduced because of acidification defects, supported by the reduction in v-ATPase subunit V0a1 with aging. Increasing the acidification of aged ELys recovered degradation and reverted synaptic decline, while alkalinization or v-ATPase inhibition, mimicked age-dependent Lys and synapse dysfunction. We identify ELys deacidification as a neuronal mechanism of age-dependent synapse loss. Our findings suggest that future therapeutic strategies to address endolysosomal defects might be able to delay age-related synaptic decline.

Structure modeling hints at a granular organization of the Golgi ribbon.

BACKGROUND: In vertebrate cells, the Golgi functional subunits, mini-stacks, are linked into a tri-dimensional network. How this "ribbon" architecture relates to Golgi functions remains unclear. Are all connections between mini-stacks equal? Is the local structure of the ribbon of functional importance? These are difficult questions to address, without a quantifiable readout of the output of ribbon-embedded mini-stacks. Endothelial cells produce secretory granules, the Weibel-Palade bodies (WPB), whose von Willebrand Factor (VWF) cargo is central to hemostasis. The Golgi apparatus controls WPB size at both mini-stack and ribbon levels. Mini-stack dimensions delimit the size of VWF "boluses" whilst the ribbon architecture allows their linear co-packaging, thereby generating WPBs of different lengths. This Golgi/WPB size relationship suits mathematical analysis. RESULTS: WPB lengths were quantized as multiples of the bolus size and mathematical modeling simulated the effects of different Golgi ribbon organizations on WPB size, to be compared with the ground truth of experimental data. An initial simple model, with the Golgi as a single long ribbon composed of linearly interlinked mini-stacks, was refined to a collection of mini-ribbons and then to a mixture of mini-stack dimers plus long ribbon segments. Complementing these models with cell culture experiments led to novel findings. Firstly, one-bolus sized WPBs are secreted faster than larger secretory granules. Secondly, microtubule depolymerization unlinks the Golgi into equal proportions of mini-stack monomers and dimers. Kinetics of binding/unbinding of mini-stack monomers underpinning the presence of stable dimers was then simulated. Assuming that stable mini-stack dimers and monomers persist within the ribbon resulted in a final model that predicts a "breathing" arrangement of the Golgi, where monomer and dimer mini-stacks within longer structures undergo continuous linking/unlinking, consistent with experimentally observed WPB size distributions. CONCLUSIONS: Hypothetical Golgi organizations were validated against a quantifiable secretory output. The best-fitting Golgi model, accounting for stable mini-stack dimers, is consistent with a highly dynamic ribbon structure, capable of rapid rearrangement. Our modeling exercise therefore predicts that at the fine-grained level the Golgi ribbon is more complex than generally thought. Future experiments will confirm whether such a ribbon organization is endothelial-specific or a general feature of vertebrate cells.

Melanin processing by keratinocytes: A non-microbial type of host-pathogen interaction?

The mechanisms that regulate skin pigmentation have been the subject of intense research in recent decades. In contrast with melanin biogenesis and transport within melanocytes, little is known about how melanin is transferred and processed within keratinocytes. Several models have been proposed for how melanin is transferred, with strong evidence supporting coupled exo/endocytosis. Recently, two reports suggest that upon internalization, melanin is stored within keratinocytes in an arrested compartment, allowing the pigment to persist for long periods. In this commentary, we identify a striking parallelism between melanin processing within keratinocytes and the host-pathogen interaction with Plasmodium, opening new avenues to understand the complex molecular mechanisms that ensure skin pigmentation and photoprotection.

Opuntia ficus-indica (L.) Mill.: A Multi-Benefit Potential to Be Exploited.

Consumer interest in foods with enhanced nutritional quality has increased in recent years. The nutritional and bioactive characterization of fruits and their byproducts, as well as their use in the formulation of new food products, is advisable, contributing to decrease the global concerns related to food waste and food security. Moreover, the compounds present in these raw materials and the study of their biological properties can promote health and help to prevent some chronic diseases. Opuntia ficus-indica (L.) Mill. (prickly pear) is a plant that grows wild in the arid and semi-arid regions of the world, being a food source for ones and a potential for others, but not properly valued. This paper carries out an exhaustive review of the scientific literature on the nutritional composition and bioactive compounds of prickly pear and its constituents, as well as its main biological activities and applications. It is a good source of dietary fiber, vitamins and bioactive compounds. Many of its natural compounds have interesting biological activities such as anti-inflammatory, hypoglycemic and antimicrobial. The antioxidant power of prickly pear makes it a good candidate as an ingredient of new food products with fascinating properties for health promotion and/or to be used as natural extracts for food, pharmaceutic or cosmetic applications. In addition, it could be a key player in food security in many arid and semi-arid regions of the world, where there are often no more plants.

Weibel-Palade bodies at a glance.

The vascular environment can rapidly alter, and the speed with which responses to both physiological and pathological changes are required necessitates the existence of a highly responsive system. The endothelium can quickly deliver bioactive molecules by regulated exocytosis of its secretory granules, the Weibel-Palade bodies (WPBs). WPBs include proteins that initiate both haemostasis and inflammation, as well those that modulate blood pressure and angiogenesis. WPB formation is driven by von Willebrand factor, their most abundant protein, which controls both shape and size of WPBs. WPB are generated in a range of sizes, with the largest granules over ten times the size of the smallest. In this Cell Science at a Glance and the accompanying poster, we discuss the emerging mechanisms by which WPB size is controlled and how this affects the ability of this organelle to modulate haemostasis. We will also outline the different modes of exocytosis and their polarity that are currently being explored, and illustrate that these large secretory organelles provide a model for how elements of secretory granule biogenesis and exocytosis cooperate to support a complex and diverse set of functions.

Type II PI4-kinases control Weibel-Palade body biogenesis and von Willebrand factor structure in human endothelial cells.

Weibel-Palade bodies (WPBs) are endothelial storage organelles that mediate the release of molecules involved in thrombosis, inflammation and angiogenesis, including the pro-thrombotic glycoprotein von Willebrand factor (VWF). Although many protein components required for WPB formation and function have been identified, the role of lipids is almost unknown. We examined two key phosphatidylinositol kinases that control phosphatidylinositol 4-phosphate levels at the trans-Golgi network, the site of WPB biogenesis. RNA interference of the type II phosphatidylinositol 4-kinases PI4KIIα and PI4KIIß in primary human endothelial cells leads to formation of an increased proportion of short WPB with perturbed packing of VWF, as exemplified by increased exposure of antibody-binding sites. When stimulated with histamine, these cells release normal levels of VWF yet, under flow, form very few platelet-catching VWF strings. In PI4KIIα-deficient mice, immuno-microscopy revealed that VWF packaging is also perturbed and these mice exhibit increased blood loss after tail cut compared to controls. This is the first demonstration that lipid kinases can control the biosynthesis of VWF and the formation of WPBs that are capable of full haemostatic function.

von Willebrand factor multimerization and the polarity of secretory pathways in endothelial cells.

The von Willebrand factor (VWF) synthesized and secreted by endothelial cells is central to hemostasis and thrombosis, providing a multifunctional adhesive platform that brings together components needed for these processes. VWF secretion can occur from both apical and basolateral sides of endothelial cells, and from constitutive, basal, and regulated secretory pathways, the latter two via Weibel-Palade bodies (WPB). Although the amount and structure of VWF is crucial to its function, the extent of VWF release, multimerization, and polarity of the 3 secretory pathways have only been addressed separately, and with conflicting results. We set out to clarify these relationships using polarized human umbilical vein endothelial cells (HUVECs) grown on Transwell membranes. We found that regulated secretion of ultra-large (UL)-molecular-weight VWF predominantly occurred apically, consistent with a role in localized platelet capture in the vessel lumen. We found that constitutive secretion of low-molecular-weight (LMW) VWF is targeted basolaterally, toward the subendothelial matrix, using the adaptor protein complex 1 (AP-1), where it may provide the bulk of collagen-bound subendothelial VWF. We also found that basally-secreted VWF is composed of UL-VWF, released continuously from WPBs in the absence of stimuli, and occurs predominantly apically, suggesting this could be the main source of circulating plasma VWF. Together, we provide a unified dataset reporting the amount and multimeric state of VWF secreted from the constitutive, basal, and regulated pathways in polarized HUVECs, and have established a new role for AP-1 in the basolateral constitutive secretion of VWF.

Host cell autophagy contributes to Plasmodium liver development.

Autophagy plays an important role in the defence against intracellular pathogens. However, some microorganisms can manipulate this host cell pathway to their advantage. In this study, we addressed the role of host cell autophagy during Plasmodium berghei liver infection. We show that vesicles containing the autophagic marker LC3 surround parasites from early time-points after invasion and throughout infection and colocalize with the parasitophorous vacuole membrane. Moreover, we show that the LC3-positive vesicles that surround Plasmodium parasites are amphisomes that converge from the endocytic and autophagic pathways, because they contain markers of both pathways. When the host autophagic pathway was inhibited by silencing several of its key regulators such as LC3, Beclin1, Vps34 or Atg5, we observed a reduction in parasite size. We also found that LC3 surrounds parasites in vivo and that parasite load is diminished in a mouse model deficient for autophagy. Together, these results show the importance of the host autophagic pathway for parasite development during the liver stage of Plasmodium infection.

Host PI(3,5)P2 activity is required for Plasmodium berghei growth during liver stage infection.

Malaria parasites go through an obligatory liver stage before they infect erythrocytes and cause disease symptoms. In the host hepatocytes, the parasite is enclosed by a parasitophorous vacuole membrane (PVM). Here, we dissected the interaction between the Plasmodium parasite and the host cell late endocytic pathway and show that parasite growth is dependent on the phosphoinositide 5-kinase (PIKfyve) that converts phosphatidylinositol 3-phosphate [PI(3)P] into phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2 ] in the endosomal system. We found that inhibition of PIKfyve by either pharmacological or non-pharmacological means causes a delay in parasite growth. Moreover, we show that the PI(3,5)P2 effector protein TRPML1 that is involved in late endocytic membrane fusion, is present in vesicles closely contacting the PVM and is necessary for parasite growth. Thus, our studies suggest that the parasite PVM is able to fuse with host late endocytic vesicles in a PI(3,5)P2 -dependent manner, allowing the exchange of material between the host and the parasite, which is essential for successful infection.

The host endocytic pathway is essential for Plasmodium berghei late liver stage development.

The obligate intracellular liver stage of the Plasmodium parasite represents a bottleneck in the parasite life cycle and remains a promising target for therapeutic intervention. During this stage, parasites undergo dramatic morphological changes and achieve one of the fastest replication rates among eukaryotic species. Nevertheless, relatively little is known about the parasite interactions with the host hepatocyte. Using immunofluorescence, live cell imaging and electron microscopy, we show that Plasmodium berghei parasites are surrounded by vesicles from the host late endocytic pathway. We found that these vesicles are acidic and contain the membrane markers Rab7a, CD63 and LAMP1. When host cell vesicle acidification was disrupted using ammonium chloride or Concanamycin A during the late liver stage of infection, parasite survival was not affected, but schizont size was significantly decreased. Furthermore, when the host cell endocytic pathway was loaded with BSA-gold, gold particles were found within the parasite cytoplasm, showing the transport of material from the host endocytic pathway toward the parasite interior. These observations reveal a novel Plasmodium-host interaction and suggest that vesicles from the host endolysosomal pathway could represent an important source of nutrients exploited by the fast-growing late liver stage parasites.

The severity of dry and hot climate extremes and their related impacts on vegetation in Madagascar.

Madagascar is a low-income country, highly vulnerable to natural disasters affecting the small-scale subsistence farming system. Recently, climate change and environmental degradation have contributed to an intensification of food insecurity. We aim to monitor the link between dry and hot extremes on vegetation conditions, separated or concurrently, using satellite data, such as LST, ET, ET0, and FAPAR products from SEVIRI/MSG disseminated by LSASAF-EUMETSAT. The analysis was made for a long record from 2004 to 2021, focusing on the extreme seasons of 2020 and 2021. Results highlight the higher impact of combined dry and hot events when compared with isolated events, with a strong response of vegetation in the southern part of Madagascar. Results point to the added value of using the recent data records from geostationary satellites with high temporal resolution and updated in near real-time, to early detect, monitor, and characterize the impact of climate extremes on vegetation dynamics.

Melon peel flour: utilization as a functional ingredient in bakery products.

Food by-products are a major concern with a direct impact on the economy, society, and environment. The valorisation of these by-products could be an advantageous approach to face the increase in food waste since it can compromise environmental health and food sustainability. On the other hand, this valorisation would allow the development of new food products with health benefits for the population. Cucumis melo L. is a highly consumed fruit all over the world since it has excellent sensory and nutritional qualities, being also a good source of bioactive compounds. However, its peel and seeds are usually discarded. The aim of this study was to evaluate the potential of melon peel flour as a functional ingredient for innovative food products. For that, two different formulations containing melon peel flour were developed (a biscuit and a muffin) by replacing a conventional flour (wheat flour) in different percentages (50% and 100%, respectively). The nutritional composition, total phenolic content, and antioxidant potential of the developed products were studied, showing a high content of fibre, high levels of phenolic compounds and good sensory acceptability. These results show that it is possible to enrich different foods with melon peel flour in order to improve their nutritional properties, contributing to improving public health, simultaneously valorising a usually rejected by-product, reducing food waste and the environmental impact.

Pre- and Postharvest Strategies for Pleurotus ostreatus Mushroom in a Circular Economy Approach.

Mushroom cultivation presents a viable solution for utilizing agro-industrial byproducts as substrates for growth. This process enables the transformation of low-economic-value waste into nutritional foods. Enhancing the yield and quality of preharvest edible mushrooms, along with effectively preserving postharvest mushrooms, stands as a significant challenge in advancing the industry. Implementing pre- and postharvest strategies for Pleurotus ostreatus (Jacq.) P. Kumm (oyster mushroom) within a circular economy framework involves optimizing resource use, minimizing waste, and creating a sustainable and environmentally friendly production system. This review aimed to analyze the development and innovation of the different themes and trends by bibliometric analysis with a critical literature review. Furthermore, this review outlines the cultivation techniques for Pleurotus ostreatus, encompassing preharvest steps such as spawn production, substrate preparation, and the entire mushroom growth process, which includes substrate colonization, fruiting, harvesting, and, finally, the postharvest. While novel methodologies are being explored for maintaining quality and extending shelf-life, the evaluation of the environmental impact of the entire mushroom production to identify areas for improvement is needed. By integrating this knowledge, strategies can be developed for a more sustainable and circular approach to Pleurotus ostreatus mushroom cultivation, promoting environmental stewardship and long-term viability in this industry.

Challenges of the Application of In Vitro Digestion for Nanomaterials Safety Assessment.

Considering the increase in the production and use of nanomaterials (NM) in food/feed and food contact materials, novel strategies for efficient and sustainable hazard characterization, especially in the early stages of NM development, have been proposed. Some of these strategies encompass the utilization of in vitro simulated digestion prior to cytotoxic and genotoxic assessment. This entails exposing NM to fluids that replicate the three successive phases of digestion: oral, gastric, and intestinal. Subsequently, the resulting digestion products are added to models of intestinal cells to conduct toxicological assays, analyzing multiple endpoints. Nonetheless, exposure of intestinal cells to the digested products may induce cytotoxicity effects, thereby posing a challenge to this strategy. The aim of this work was to describe the challenges encountered with the in vitro digestion INFOGEST 2.0 protocol when using the digestion product in toxicological studies of NM, and the adjustments implemented to enable its use in subsequent in vitro biological assays with intestinal cell models. The adaptation of the digestion fluids, in particular the reduction of the final bile concentration, resulted in a reduced toxic impact of digestion products.

Acute Kidney Injury and Electrolyte Imbalances Caused by Dapagliflozin Short-Term Use.

Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), has shown demonstrated benefits for renal and cardiovascular outcomes in large clinical trials. However, short-term concerns regarding its impact on renal function and electrolyte balance exist. This study aimed to evaluate the short-term effects of dapagliflozin on renal function and electrolyte balance in patients newly prescribed the medication. A retrospective analysis of 246 patients who initiated dapagliflozin therapy was conducted. Serum creatinine, sodium, and potassium levels were measured at baseline (before dapagliflozin) and 5-8 days after initiation (endpoint). A Wilcoxon signed-rank test, Pearson's chi-square test, and Fischer's exact test were used for the data analysis. Glycemia and sodium levels were significantly higher at the baseline compared to the endpoint (p < 0.001). Conversely, creatinine and potassium levels were significantly higher at the endpoint than at the baseline (p < 0.001). The prevalence of hyponatremia and hyperkalemia were increased at the endpoint (17.5% vs. 10.2% and 16.7% vs. 8.9%, respectively). Although not statistically significant, a trend towards increased hyponatremia with the co-administration of furosemide was observed (p = 0.089). No significant association was found between potassium-sparing medications (p > 0.05) and hyperkalemia, except for angiotensin receptor blockers (p = 0.017). The combination of dapagliflozin and furosemide significantly increased the risk of acute kidney injury (AKI) at the endpoint (p = 0.006). Age, gender, and chronic kidney disease status did not significantly influence the occurrence of AKI, hyponatremia, or hyperkalemia (p > 0.05). These findings emphasize the importance of the close monitoring of renal function and electrolyte balance, particularly in the early stages of dapagliflozin therapy, especially in patients receiving diuretics or renin-angiotensin-aldosterone system inhibitors.

Edible Coatings and Future Trends in Active Food Packaging-Fruits' and Traditional Sausages' Shelf Life Increasing.

The global food production industry faces environmental concerns exacerbated by substantial food waste. European countries are striving to reduce food waste towards a circular bioeconomy and sustainable development. To address environmental issues and reduce plastic waste, researchers are developing sustainable active packaging systems, including edible packaging made from industry residues. These innovations aim to increase food safety and quality, extend shelf life, and reduce plastic and food waste. Particularly important in the context of the growing demand for fresh and minimally processed fruits, edible coatings have emerged as a potential solution that offers numerous advantages in maintaining fruit quality. In addition to fruit, edible coatings have also been investigated for animal-based foods to meet the demand for high-quality, chemical-free food and extended shelf life. These products globally consumed can be susceptible to the growth of harmful microorganisms and spoilage. One of the main advantages of using edible coatings is their ability to preserve meat quality and freshness by reducing undesirable physicochemical changes, such as color, texture, and moisture loss. Furthermore, edible coatings also contribute to the development of a circular bioeconomy, promoting sustainability in the food industry. This paper reviews the antimicrobial edible coatings investigated in recent years in minimally processed fruits and traditional sausages. It also approaches bionanocomposites as a recently emerged technology with potential application in food quality and safety.

The Health Effects of Low Glycemic Index and Low Glycemic Load Interventions on Prediabetes and Type 2 Diabetes Mellitus: A Literature Review of RCTs.

Diets with a low glycemic index (GI) and a low glycemic load (GL) can improve glycemic control, blood lipids, blood pressure and BMI in prediabetes and type 2 diabetes (T2DM), but evidence regarding other aspects of cardiometabolic health is limited. We searched the literature for RCTs published from 2013 to 2023 and reviewed the evidence on low-GI/GL diets and their effects on different aspects of health in prediabetes and T2DM, aiming to build a report on all relevant outcomes included in the studies. We included 14 RCTs with 1055 participants, who were mostly middle-aged individuals with T2DM. Interventions were mostly low GI and lasted 1-36 months. Low-GI/GL foods and diets showed benefits in terms of short-term glycemic control, weight and adiposity. Longer-term trials would be necessary to determine whether these benefits persist over time and/or lead to lower CVD risk and mortality. Effects on lipid profile were inconsistent. Some studies also reported positive effects of low-GI/GL interventions on blood pressure, inflammatory biomarkers, renal function and gut microbiota composition. Future trials should focus on some of these novel outcome measures, which may provide important insights into the metabolic effects of low-GI diets on individuals with diabetes.

Influence of Air-Drying Conditions on Quality, Bioactive Composition and Sensorial Attributes of Sweet Potato Chips.

The drying process is an essential thermal process for preserving vegetables and can be used in developing dried products as healthy alternative snacks. The effects of air-drying conditions using a convection dryer with hot air at different temperatures (60°, 65°, 70°, 75°, and 80 °C, in the range 5-200 min, at a fixed air speed of 2.3 m/s) were tested on the quality of slices (2.0 ± 0.1 mm) of dried sweet potato (Bellevue PBR). For each time and temperature, drying condition, physicochemical parameters (moisture content, CIELab color, texture parameters, total phenolic and carotenoid contents) and a sensory evaluation by a panel at the last drying period (200 min) were assessed. Drying time was shown to have a more significant effect than temperature on the quality of dried sweet potato as a snack, except for carotenoid content. Given the raw tuber content, thermal degradation (p < 0.05) of total phenolic compounds (about 70%), regardless of tested conditions, contrasted with the higher stability of total carotenoids (<30%). The dried product, under optimal conditions (≥75 °C for 200 min), achieved a moisture content (≤10%) suitable for preservation, providing a crispy texture with favourable sensory acceptance and providing a carotenoid content similar to the raw product.

Oxalate in Foods: Extraction Conditions, Analytical Methods, Occurrence, and Health Implications.

Oxalate is an antinutrient present in a wide range of foods, with plant products, especially green leafy vegetables, being the main sources of dietary oxalates. This compound has been largely associated with hyperoxaluria, kidney stone formation, and, in more severe cases, systematic oxalosis. Due to its impact on human health, it is extremely important to control the amount of oxalate present in foods, particularly for patients with kidney stone issues. In this review, a summary and discussion of the current knowledge on oxalate analysis, its extraction conditions, specific features of analytical methods, reported occurrence in foods, and its health implications are presented. In addition, a brief conclusion and further perspectives on whether high-oxalate foods are truly problematic and can be seen as health threats are shown.

The Burnout of Nurses in Intensive Care Units and the Impact of the SARS-CoV-2 Pandemic: A Scoping Review.

BACKGROUND: The world's population changed with the emergence of the SARS-CoV-2 pandemic. Burnout arises due to overwork, prolonged work periods, a lack of human and material resources, etc. Several studies have reported the incidence of burnout syndrome in nurses that work in intensive care units (ICUs). The aim was to map the scientific evidence related to nurses' burnout in the ICU, namely the repercussions of SARS-CoV-2 in terms of burnout among nurses. METHODS: A scoping review followed the Joanna Briggs Institute methodology guidelines to search for and synthesise studies published between 2019 and 2022. The databases searched were MEDLINE, CINAHL, LILACS, SCOPUS, PsycINFO and OPEN GREY. A total of fourteen articles were eligible to be included. RESULTS: A content analysis of the selected articles was carried out, and three categories emerged that corresponded to the dimensions of burnout according to Maslach and Leiter: emotional exhaustion, depersonalisation dimension and a lack of personal accomplishment. It was evident that nurses who worked in the ICU during the pandemic showed high levels of burnout. CONCLUSIONS: It is recommended that hospital administrations hire health professionals, namely nurses, as a strategic and operational management strategy to reduce the risk of increased burnout during pandemic outbreaks.