Human health risk assessment of intake Cd and Cu from agricultural soils in Mostar and Tomislavgrad

The aim of the research was to determine the total content of cadmium (Cd) and copper (Cu) in agricultural soils and to determine the potential toxicity of different intake routes for children and adults. Two locations were selected (Tomislavgrad and Mostar) where field crops were grown. Taking soil samples and determining the content of Cd and Cu was carried out according to the Instructions on determining the permitted amounts of harmful and dangerous substances in the soil and their testing methods (Official Gazette of FBiH, no. 96/22). A health risk assessment model based on the guidelines of the US Environmental Protection Agency (USEPA, 1996; USEPA, 2002; USEPA, 2011) was used to calculate the human health risk assessment. The measured values of the total content of copper and cadmium at the Tomislavgrad location are in accordance with the prescribed limit values. The copper content at the Mostar location was 205.90 mg/kg, which is above the limit value, and the cadmium content is in accordance with the prescribed limit values. When the HI value is less than 1, then there is no risk to human health, but if the values are greater than 1, then there is concern about non-carcinogenic risks (USEPA, 2004). The USEPA considers a carcinogenic risk in the range of 1×10–6 to 1×10−4 to be acceptable to human health. Calculations for non-carcinogenic and cancerous health risks were following the limit value

Analyses of rare collection samples as conservation tool for the last known Italian population of Graphoderus bilineatus (Insecta: Coleoptera)

Graphoderus bilineatus is a predacious diving beetle, widely distributed across Europe. Its poor dispersal ability and the fragmentation and deterioration of its habitats have been indicated as the major causes of decline. In several western European countries, the species is extinct, justifying its inclusion as "vulnerable" in the IUCN red list. Aiming for the conservation of the last known population of G. bilineatus in the northern Italian region of Emilia Romagna, at the lake Pratignano, we surveyed its genetic diversity at the mitochondrial COI gene and compared it to that of other European populations. Two fixed COI haplotypes were found in the Italian and Austrian populations, respectively. Both haplotypes were unique among the European populations surveyed, suggesting these populations suffered a bottleneck and geographic isolation. Populations in western Europe showed lower genetic diversity and higher degree of differentiation than eastern populations. The uniqueness of Pratignano haplotype makes it difficult to choose a source population from which to transfer animals for a possible restocking. Selection of the source population should be based mainly on ecological considerations, but at the same time ensuring a good genetic diversity to maximize the adaptive potential

Towards a more resource-efficient solar future in the EU: an actor-centered approach

Material constraints may slow the pace of energy transition if the materials intensity of renewable energy technologies remains the same. Innovations in solar photovoltaics (PV) can contribute to achieving lower material demands. In this research, the actor-centered institutionalism framework, transitions literature and the science-policy interface framework are used to analyze how the involved actors perceive the transition towards more resource-efficiency in solar PV, what their preferences are, and how government should support this transition. Altogether, resource-efficiency is not sufficiently supported, while it is considered extremely important in the future of solar PV according to various involved actors. Traditional silicon-based solar panels are locked-in into the current policy landscape. Actors prioritizing resource-efficiency interact in a niche space, while actors involved in traditional silicon-based PV form the regime. Improved alignment between science and policy actors would help ease disagreements and prevent or benefit from path-dependency, thus, supporting resource-efficiency in solar PV.​​​​​​​Industrial Ecolog

A social life cycle assessment of vanadium redox flow and lithium-ion batteries for energy storage

Battery energy storage systems (BESS) are expected to fulfill a crucial role in the renewable energy systems of the future. Within current regulatory frameworks, assessing the sustainability as well as the social risks for BESS should be considered. In this research we conducted a social life cycle assessment (S-LCA) of two BESS: the vanadium redox flow battery (VRFB) and the lithium-ion battery (LIB). The S-LCA was conducted based on the guidelines set by UNEP/SETAC and using the PSILCA v.3 database. It was found that most social risks related to the life cycle of the batteries are associated with the raw material extraction stage, while sectors related to chemicals also entail considerable risks. Workers are the stakeholder group affected most. These results apply to supply chains located in both China and Germany, but risks were lower for similar supply chains in Germany. An LIB with a nickel manganese cobalt oxide cathode is associated with considerably larger risks compared to a LIB with lithium manganese oxide cathode. For a VRFB life cycle with an increased vanadium price, the social risks were higher than those of the VRFB supply chain with a regular vanadium price. Our paper shows that S-LCA through the PSILCA database can provide interesting insights into the potential social risks associated with a certain product's life cycle. Generalizations of the results are not recommended, and one should be careful with assessments for technologies that have not yet matured due to the cost sensitivity of the methodology.Horizon 2020(H2020)875637Industrial Ecolog

Differential regulation of RasGAPs in cancer

Ever since their discovery as cellular counterparts of viral oncogenes more than 25 years ago, much progress has been made in understanding the complex networks of signal transduction pathways activated by oncogenic Ras mutations in human cancers. The activity of Ras is regulated by nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), and much emphasis has been put into the biochemical and structural analysis of the Ras/GAP complex. The mechanisms by which GAPs catalyze Ras-GTP hydrolysis have been clarified and revealed that oncogenic Ras mutations confer resistance to GAPs and remain constitutively active. However, it is yet unclear how cells coordinate the large and divergent GAP protein family to promote Ras inactivation and ensure a certain biological response. Different domain arrangements in GAPs to create differential protein-protein and protein-lipid interactions are probably key factors determining the inactivation of the 3 Ras isoforms H-, K-, and N-Ras and their effector pathways. In recent years, in vitro as well as cell- and animal-based studies examining GAP activity, localization, interaction partners, and expression profiles have provided further insights into Ras inactivation and revealed characteristics of several GAPs to exert specific and distinct functions. This review aims to summarize knowledge on the cell biology of RasGAP proteins that potentially contributes to differential regulation of spatiotemporal Ras signaling

Annexin A6 improves anti-migratory and anti-invasive properties of tyrosine kinase inhibitors in EGFR overexpressing human squamous epithelial cells

Annexin A6 (AnxA6), a member of the calcium (Ca2+ ) and membrane binding annexins, is known to stabilize and establish the formation of multifactorial signaling complexes. At the plasma membrane, AnxA6 is a scaffold for protein kinase Cα (PKCα) and GTPase-activating protein p120GAP to promote downregulation of epidermal growth factor receptor (EGFR) and Ras/mitogen-activated protein kinase (MAPK) signaling. In human squamous A431 epithelial carcinoma cells, which overexpress EGFR, but lack endogenous AnxA6, restoration of AnxA6 expression (A431-A6) promotes PKCα-mediated threonine 654 (T654)-EGFR phosphorylation, which inhibits EGFR tyrosine kinase activity. This is associated with reduced A431-A6 cell growth, but also decreased migration and invasion in wound healing, matrigel, and organotypic matrices. Here, we show that A431-A6 cells display reduced EGFR activity in vivo, with xenograft analysis identifying increased pT654-EGFR levels, but reduced tyrosine EGFR phosphorylation compared to controls. In contrast, PKCα depletion in A431-A6 tumors is associated with strongly reduced pT654 EGFR levels, yet increased EGFR tyrosine phosphorylation and MAPK activity. Moreover, tyrosine kinase inhibitors (TKIs; gefitinib, erlotinib) more effectively inhibit cell viability, clonogenic growth, and wound healing of A431-A6 cells compared to controls. Likewise, the ability of AnxA6 to inhibit A431 motility and invasiveness strongly improves TKI efficacy in matrigel invasion assays. This correlates with a greatly reduced invasion of the surrounding matrix of TKI-treated A431-A6 when cultured in 3D spheroids. Altogether, these findings implicate that elevated AnxA6 scaffold levels contribute to improve TKI-mediated inhibition of growth and migration, but also invasive properties in EGFR overexpressing human squamous epithelial carcinoma

Annexin A6 and late endosomal cholesterol modulate integrin recycling and cell migration.

Annexins are a family of proteins that bind to phospholipids in a calcium-dependent manner. Earlier studies implicated annexin A6 (AnxA6) to inhibit secretion and participate in the organization of the extracellular matrix. We recently showed that elevated AnxA6 levels significantly reduced secretion of the extracellular matrix protein fibronectin (FN). Because FN is directly linked to the ability of cells to migrate, this prompted us to investigate the role of AnxA6 in cell migration. Up-regulation of AnxA6 in several cell models was associated with reduced cell migration in wound healing, individual cell tracking and three-dimensional migration/invasion assays. The reduced ability of AnxA6-expressing cells to migrate was associated with decreased cell surface expression of αVβ3 and α5β1 integrins, both FN receptors. Mechanistically, we found that elevated AnxA6 levels interfered with syntaxin-6 (Stx6)-dependent recycling of integrins to the cell surface. AnxA6 overexpression caused mislocalization and accumulation of Stx6 and integrins in recycling endosomes, whereas siRNA-mediated AnxA6 knockdown did not modify the trafficking of integrins. Given our recent findings that inhibition of cholesterol export from late endosomes (LEs) inhibits Stx6-dependent integrin recycling and that elevated AnxA6 levels cause LE cholesterol accumulation, we propose that AnxA6 and blockage of LE cholesterol transport are critical for endosomal function required for Stx6-mediated recycling of integrins in cell migration