Reporting of adverse events in muscle strengthening interventions in youth: A systematic review

To document the extent to which AEs, resulting from intervention studies targeting muscle-strengthening training (MST) in youth, are reported by researchers

Fatty acid-related modulations of membrane fluidity in cells: detection and implications

Metabolic homeostasis of fatty acids is complex and well-regulated in all organisms. The biosynthesis of saturated fatty acids (SFA) in mammals provides substrates for ?-oxidation and ATP production. Monounsaturated fatty acids (MUFA) are products of desaturases that introduce a methylene group in cis geometry in SFA. Polyunsaturated fatty acids (n-6 and n-3 PUFA) are products of elongation and desaturation of the essential linoleic acid and ?-linolenic acid, respectively. The liver processes dietary fatty acids and exports them in lipoproteins for distribution and storage in peripheral tissues. The three types of fatty acids are integrated in membrane phospholipids and determine their biophysical properties and functions. This study was aimed at investigating effects of fatty acids on membrane biophysical properties under varying nutritional and pathological conditions, by integrating lipidomic analysis of membrane phospholipids with functional two-photon microscopy (fTPM) of cellular membranes. This approach was applied to two case studies: first, pancreatic beta-cells, to investigate hormetic and detrimental effects of lipids. Second, red blood cells extracted from a genetic mouse model defective in lipoproteins, to understand the role of lipids in hepatic diseases and metabolic syndrome and their effect on circulating cells

A large-scale test of the link between intergroup contact and support for social change

Guided by the early findings of social scientists, practitioners have long advocated for greater contact between groups to reduce prejudice and increase social cohesion. Recent work, however, suggests that intergroup contact can undermine support for social change towards greater equality, especially among disadvantaged group members. Using a large and heterogeneous dataset (12,997 individuals from 69 countries), we demonstrate that intergroup contact and support for social change towards greater equality are positively associated among members of advantaged groups (ethnic majorities and cis-heterosexuals) but negatively associated among disadvantaged groups (ethnic minorities and sexual and gender minorities). Specification-curve analysis revealed important variation in the size—and at times, direction—of correlations, depending on how contact and support for social change were measured. This allowed us to identify one type of support for change—willingness to work in solidarity— that is positively associated with intergroup contact among both advantaged and disadvantaged group members

Need satisfaction in intergroup contact:A multinational study of pathways toward social change

none43siFinanziamenti esterni a vari co-autoriWhat role does intergroup contact play in promoting support for social change toward greater social equality? Drawing on the needs-based model of reconciliation, we theorized that when inequality between groups is perceived as illegitimate, disadvantaged group members will experience a need for empowerment and advantaged group members a need for acceptance. When intergroup contact satisfies each group's needs, it should result in more mutual support for social change. Using four sets of survey data collected through the Zurich Intergroup Project in 23 countries, we tested several preregistered predictions, derived from the above reasoning, across a large variety of operationalizations. Two studies of disadvantaged groups (Ns = 689 ethnic minority members in Study 1 and 3,382 sexual/gender minorities in Study 2) support the hypothesis that, after accounting for the effects of intergroup contact and perceived illegitimacy, satisfying the need for empowerment (but not acceptance) during contact is positively related to support for social change. Two studies with advantaged groups (Ns = 2,937 ethnic majority members in Study 3 and 4,203 cis-heterosexual individuals in Study 4) showed that, after accounting for illegitimacy and intergroup contact, satisfying the need for acceptance (but also empowerment) is positively related to support for social change. Overall, findings suggest that intergroup contact is compatible with efforts to promote social change when group-specific needs are met. Thus, to encourage support for social change among both disadvantaged and advantaged group members, it is essential that, besides promoting mutual acceptance, intergroup contact interventions also give voice to and empower members of disadvantaged groups.mixedHässler, Tabea; Ullrich, Johannes; Sebben, Simone; Shnabel, Nurit; Bernardino, Michelle; Valdenegro, Daniel; Van Laar, Colette; González, Roberto; Visintin, Emilio Paolo; Tropp, Linda R; Ditlmann, Ruth K; Abrams, Dominic; Aydin, Anna Lisa; Pereira, Adrienne; Selvanathan, Hema Preya; von Zimmermann, Jorina; Lantos, Nóra Anna; Sainz, Mario; Glenz, Andreas; Kende, Anna; Oberpfalzerová, Hana; Bilewicz, Michal; Branković, Marija; Noor, Masi; Pasek, Michael H; Wright, Stephen C; Žeželj, Iris; Kuzawinska, Olga; Maloku, Edona; Otten, Sabine; Gul, Pelin; Bareket, Orly; Corkalo Biruski, Dinka; Mugnol-Ugarte, Luiza; Osin, Evgeny; Baiocco, Roberto; Cook, Jonathan E; Dawood, Maneeza; Droogendyk, Lisa; Loyo, Angélica Herrera; Jelić, Margareta; Kelmendi, Kaltrina; Pistella, JessicaHässler, Tabea; Ullrich, Johannes; Sebben, Simone; Shnabel, Nurit; Bernardino, Michelle; Valdenegro, Daniel; Van Laar, Colette; González, Roberto; Visintin, Emilio Paolo; Tropp, Linda R; Ditlmann, Ruth K; Abrams, Dominic; Aydin, Anna Lisa; Pereira, Adrienne; Selvanathan, Hema Preya; von Zimmermann, Jorina; Lantos, Nóra Anna; Sainz, Mario; Glenz, Andreas; Kende, Anna; Oberpfalzerová, Hana; Bilewicz, Michal; Branković, Marija; Noor, Masi; Pasek, Michael H; Wright, Stephen C; Žeželj, Iris; Kuzawinska, Olga; Maloku, Edona; Otten, Sabine; Gul, Pelin; Bareket, Orly; Corkalo Biruski, Dinka; Mugnol-Ugarte, Luiza; Osin, Evgeny; Baiocco, Roberto; Cook, Jonathan E; Dawood, Maneeza; Droogendyk, Lisa; Loyo, Angélica Herrera; Jelić, Margareta; Kelmendi, Kaltrina; Pistella, Jessic

Hormetic and regulatory effects of lipid peroxidation mediators in pancreatic beta cells

Nutrient sensing mechanisms of carbohydrates, amino acids and lipids operate distinct pathways that are essential for the adaptation to varying metabolic conditions. The role of nutrient-induced biosynthesis of hormones is paramount for attaining metabolic homeostasis in the organism. Nutrient overload attenuate key metabolic cellular functions and interfere with hormonal-regulated inter- and intra-organ communication, which may ultimately lead to metabolic derangements. Hyperglycemia and high levels of saturated free fatty acids induce excessive production of oxygen free radicals in tissues and cells. This phenomenon, which is accentuated in both type-1 and type-2 diabetic patients, has been associated with the development of impaired glucose tolerance and the etiology of peripheral complications. However, low levels of the same free radicals also induce hormetic responses that protect cells against deleterious effects of the same radicals. Of interest is the role of hydroxyl radicals in initiating peroxidation of polyunsaturated fatty acids (PUFA) and generation of α,β-unsaturated reactive 4-hydroxyalkenals that avidly form covalent adducts with nucleophilic moieties in proteins, phospholipids and nucleic acids. Numerous studies have linked the lipid peroxidation product 4-hydroxy-2E-nonenal (4-HNE) to different pathological and cytotoxic processes. Similarly, two other members of the family, 4-hydroxyl-2E-hexenal (4-HHE) and 4-hydroxy-2E,6Z-dodecadienal (4-HDDE), have also been identified as potential cytotoxic agents. It has been suggested that 4-HNE-induced modifications in macromolecules in cells may alter their cellular functions and modify signaling properties. Yet, it has also been acknowledged that these bioactive aldehydes also function as signaling molecules that directly modify cell functions in a hormetic fashion to enable cells adapt to various stressful stimuli. Recent studies have shown that 4-HNE and 4-HDDE, which activate peroxisome proliferator-activated receptor δ (PPARδ) in vascular endothelial cells and insulin secreting beta cells, promote such adaptive responses to ameliorate detrimental effects of high glucose and diabetes-like conditions. In addition, due to the electrophilic nature of these reactive aldehydes they form covalent adducts with electronegative moieties in proteins, phosphatidylethanolamine and nucleotides. Normally these non-enzymatic modifications are maintained below the cytotoxic range due to efficient cellular neutralization processes of 4-hydroxyalkenals. The major neutralizing enzymes include fatty aldehyde dehydrogenase (FALDH), aldose reductase (AR) and alcohol dehydrogenase (ADH), which transform the aldehyde to the corresponding carboxylic acid or alcohols, respectively, or by biding to the thiol group in glutathione (GSH) by the action of glutathione-S-transferase (GST). This review describes the hormetic and cytotoxic roles of oxygen free radicals and 4-hydroxyalkenals in beta cells exposed to nutritional challenges and the cellular mechanisms they employ to maintain their level at functional range below the cytotoxic threshold

Elaborate cellulosome architecture of Acetivibrio cellulolyticus revealed by selective screening of cohesin–dockerin interactions

Cellulosic waste represents a significant and underutilized carbon source for the biofuel industry. Owing to the recalcitrance of crystalline cellulose to enzymatic degradation, it is necessary to design economical methods of liberating the fermentable sugars required for bioethanol production. One route towards unlocking the potential of cellulosic waste lies in a highly complex class of molecular machines, the cellulosomes. Secreted mainly by anaerobic bacteria, cellulosomes are structurally diverse, cell surface-bound protein assemblies that can contain dozens of catalytic components. The key feature of the cellulosome is its modularity, facilitated by the ultra-high affinity cohesin–dockerin interaction. Due to the enormous number of cohesin and dockerin modules found in a typical cellulolytic organism, a major bottleneck in understanding the biology of cellulosomics is the purification of each cohesin- and dockerin-containing component, prior to analyses of their interaction. As opposed to previous approaches, the present study utilized proteins contained in unpurified whole-cell extracts. This strategy was made possible due to an experimental design that allowed for the relevant proteins to be “purified” via targeted affinity interactions as a function of the binding assay. The approach thus represents a new strategy, appropriate for future medium- to high-throughput screening of whole genomes, to determine the interactions between cohesins and dockerins. We have selected the cellulosome of Acetivibrio cellulolyticus for this work due to its exceptionally complex cellulosome systems and intriguing diversity of its cellulosomal modular components. Containing 41 cohesins and 143 dockerins, A. cellulolyticus has one of the largest number of potential cohesin–dockerin interactions of any organism, and contains unusual and novel cellulosomal features. We have surveyed a representative library of cohesin and dockerin modules spanning the cellulosome’s total cohesin and dockerin sequence diversity, emphasizing the testing of unusual and previously-unknown protein modules. The screen revealed several novel cell-bound cellulosome architectures, thus expanding on those previously known, as well as soluble cellulose systems that are not bound to the bacterial cell surface. This study sets the stage for screening the entire complement of cellulosomal components from A. cellulolyticus and other organisms with large cellulosome systems. The knowledge gained by such efforts brings us closer to understanding the exceptional catalytic abilities of cellulosomes and will allow the use of novel cellulosomal components in artificial assemblies and in enzyme cocktails for sustainable energy-related research programs

Real time quantitative analysis of lipid storage and lipolysis pathways by confocal spectral imaging of intracellular micropolarity

Organisms store fatty acids in triacylglycerols in the form of lipid droplets, or hydrolyze triacylglycerols in response to energetic demands via activation of lipolytic or storage pathways. These pathways are complex sets of sequential reactions that are finely regulated in different cell types. Here we present a high spatial and temporal resolution-based method for the quantification of the turnover of fatty acids into triglycerides in live cells without introducing sample preparation artifacts. We performed confocal spectral imaging of intracellular micropolarity in cultured insulin secreting beta cells to detect micropolarity variations as they occur in time and at different pixels of microscope images. Acquired data are then analyzed in the framework of the spectral phasors technique. The method furnishes a metabolic parameter, which quantitatively assesses fatty acids - triacylglycerols turnover and the activation of lipolysis and storage pathways. Moreover, it provides a polarity profile, which represents the contribution of hyperpolar, polar and non-polar classes of lipids. These three different classes can be visualized on the image at a submicrometer resolution, revealing the spatial localization of lipids in cells under physiological and pathological settings. This new method allows for a fine-tuned, real-time visualization of the turnover of fatty acids into triglycerides in live cells with submicrometric resolution. It also detects imbalances between lipid storage and usage, which may lead to metabolic disorders within living cells and organisms

Multifunctional Cyclic d,l‑α-Peptide Architectures Stimulate Non-Insulin Dependent Glucose Uptake in Skeletal Muscle Cells and Protect Them Against Oxidative Stress

Oxidative stress directly correlates with the early onset of vascular complications and the progression of peripheral insulin resistance in diabetes. Accordingly, exogenous antioxidants augment insulin sensitivity in type 2 diabetic patients and ameliorate its clinical signs. Herein, we explored the unique structural and functional properties of the abiotic cyclic d,l-α-peptide architecture as a new scaffold for developing multifunctional agents to catalytically decompose ROS and stimulate glucose uptake. We showed that His-rich cyclic d,l-α-peptide <b>1</b> is very stable under high H₂O₂ concentrations, effectively self-assembles to peptide nanotubes, and increases the uptake of glucose by increasing the translocation of GLUT1 and GLUT4. It also penetrates cells and protects them against oxidative stress induced under hyperglycemic conditions at a much lower concentration than α-lipoic acid (ALA). In vivo studies are now required to probe the mode of action and efficacy of these abiotic cyclic d,l-α-peptides as a novel class of antihyperglycemic compounds