Children's Common Grounds: A Study of Intergroup Relations Among Children in Public Settings

This article discusses successful common grounds for children—public settings that enable the harmonious intermingling of children of different backgrounds, races, and ethnicities and that encourage their social interchange, play, educational development, and collaboration. Our study focused on three types of public space that tend to bring these children together: the public school, the park, and the neighborhood community center. The research employed a variety of methods to study the interaction of children 9 to 12 years of age. Field work took place at four sites in West Los Angeles, Santa Monica, and the San Fernando Valley that enjoy a high level of intermixing and have a reputation for promoting diversity. Subjects in the research included children, teachers, and administrators. The article highlights the findings of the field work and concludes with a comparative analysis of the different settings and a discussion of the environmental and programmatic attributes that contribute to their success.     

Modulating mTOR Signaling as a Promising Therapeutic Strategy for Atherosclerosis

For more than a decade, atherosclerosis has been one of the leading causes of death in developed countries. The issue of treatment and prevention of the disease is especially acute. Despite the huge amount of basic and clinical research, a significant number of gaps remain in our understanding of the pathogenesis of atherosclerosis, and only their closure will bring us closer to understanding the causes of the disease at the cellular and molecular levels and, accordingly, to the development of an effective treatment. One of the seemingly well-studied elements of atherogenesis is the mTOR signaling pathway. However, more and more new details are still being clarified. Therapeutic strategies associated with rapamycin have worked well in a number of different diseases, and there is every reason to believe that targeting components of the mTOR pathway may pay off in atherosclerosis as well.     

The Territorial Impact Assessment of transport: the case of the Egnatia motorway system in the cohesion potential of Southeast Europe

Territorial Impact Assessment (TIA) is proposed as a critical tool in order to investigate the way policies affect spatial development and hence territorial cohesion. The paper introduces a TIA methodological model in relation to transport sector. The design of the methodological model is based on a quantitative evaluation framework that comprises a set of selected indicators applied in a cross-border area of southeast Europe, influenced by the operation of the Greek motorway system of Egnatia and its vertical axes. The indicators are grouped into three main fields of TIA, i.e. transport intermodality, polycentric spatial organization and cross-border territorial cooperation. The TIA’s indicators are approximated by quantitative analysis. The procedure concludes to an overall composite indicator measuring the ‘level of territorial cohesion’ along with some core results and the expected added value. It also highlights some key technical aspects about the routines used and proceeds to suggestions for further refinement.     

Crack redirection with thermal secondary loading

In the current paper crack redirection due to a strategic placing of a heat source in the vicinity of a crack tip is studied. Analysis suggests that for PMMA and considered temperature range the only factor responsible for the deviation of crack trajectory is thermal stress. The simulation of crack growth in PMMA under external tension and secondary heat loading shows that a moving heat source in the vicinity of a crack tip can serve as a pointer for the crack trajectory. In highly conductive materials, redirection can be possibly effected with low-power thermal dipoles.     

Peripheral Inflammatory Markers TNF-α and CCL2 Revisited: Association with Parkinson’s Disease Severity

One of the major mediators of neuroinflammation in PD is tumour necrosis factor alpha (TNF-α), which, similar to other cytokines, is produced by activated microglia and astrocytes. Although TNF-α can be neuroprotective in the brain, long-term neuroinflammation and TNF release can be harmful, having a neurotoxic role that leads to death of oligodendrocytes, astrocytes, and neurons and, therefore, is associated with neurodegeneration. Apart from cytokines, a wide family of molecules with homologous structures, namely chemokines, play a key role in neuro-inflammation by drawing cytotoxic T-lymphocytes and activating microglia. The objective of the current study was to examine the levels of the serum TNF-α and CCL2 (Chemokine (C-C motif) ligand 2), also known as MCP-1 (Monocyte Chemoattractant Protein-1), in PD patients compared with healthy controls. We also investigated the associations between the serum levels of these two inflammatory mediators and a number of clinical symptoms, in particular, disease severity and cognition. Such an assessment may point to their prognostic value and provide some treatment hints. PD patients with advanced stage on the Hoehn–Yahr scale showed an increase in TNF-α levels compared with PD patients with stages 1 and 2 (p = 0.01). Additionally, the UPDRS score was significantly associated with TNF-α levels. CCL2 levels, however, showed no significant associations.     

Low Sulfur Amino Acid,High Polyunsaturated Fatty Acid Diet Inhibits Breast Cancer Growth

Cancer cells may acquire resistance to stress signals and reprogram metabolism to meet the energetic demands to support their high proliferation rate and avoid death. Hence, targeting nutrient dependencies of cancer cells has been suggested as a promising anti-cancer strategy. We explored the possibility of killing breast cancer (BC) cells by modifying nutrient availability. We used in vitro models of BC (MCF7 and MDA-MB-231) that were maintained with a low amount of sulfur amino acids (SAAs) and a high amount of oxidizable polyunsatured fatty acids (PUFAs). Treatment with anti-apoptotic, anti-ferroptotic and antioxidant drugs were used to determine the modality of cell death. We reproduced these conditions in vivo by feeding BC-bearing mice with a diet poor in proteins and SAAs and rich in PUFAs (LSAA/HPUFA). Western blot analysis, qPCR and histological analyses were used to assess the anti-cancer effects and the molecular pathways involved. We found that BC cells underwent oxidative damage to DNA and proteins and both apoptosis and ferroptosis were induced. Along with caspases-mediated PARP1 cleavage, we found a lowering of the GSH-GPX4 system and an increase of lipid peroxides. A LSAA/HPUFA diet reduced tumor mass and its vascularization and immune cell infiltration, and induced apoptosis and ferroptotic hallmarks. Furthermore, mitochondrial mass was found to be increased, and the buffering of mitochondrial reactive oxygen species limited GPX4 reduction and DNA damage. Our results suggest that administration of custom diets, targeting the dependency of cancer cells on certain nutrients, can represent a promising complementary option for anti-cancer therapy.     

The Role of Leptin in Childhood Immune Thrombocytopenia (ITP): An Anti-Inflammatory Agent?

To investigate the effect of leptin in childhood ITP, we measured plasma leptin in 39 children with acute ITP, after treatment and in remission, and in 33 healthy age/BMI-matched controls. We also cultured ITP and control peripheral blood mononuclear cells (PBMCs) with recombinant leptin to assess its direct effect on pro/anti-inflammatory cytokine gene expression. A significant increase in leptin was observed in children with active disease compared to controls. A significant inverse correlation of leptin with platelet count was also observed in children with acute ITP. Leptin remained high after treatment with IVIg, whereas steroid treatment lowered leptin below control levels. In remission, leptin was in the control range. Cytokine gene expression was significantly increased in children with acute ITP compared with controls, with highest expression for IFN-γ and IL-10. IVIg/steroid treatment significantly decreased IFN-γ and IL-10 expression. In remission, IFN-γ and IL-10 expression remained low. Addition of leptin to PBMCs isolated from patients in remission resulted in a significant increase in IL-10 gene expression compared to controls. Further experiments with purified T-cells and monocytes identified monocytes as the source of leptin-induced IL-10. We suggest that leptin acts as an active anti-inflammatory agent in childhood ITP by promoting IL-10 secretion by monocytes.