Search Results (5)

Biomonitoring based on foliage chemistry was used to study the effects of environmental sulfur (S) pollution on forest stands. The foliage samples were collected in two forest ecosystems exposed to industrial emissions: a zinc (Zn) and lead (Pb) smelter plant in Silesia (HCM) and a reclaimed forest on the site of the former borehole S mine Jeziórko (FJSM), in the Tarnobrzeg S deposit region (southern Poland). Scots pine (Pinus sylvestris L.) and silver birch (Betula pendula Roth.) foliage chemistry was analyzed: S (using a TruMac CNS analyzer, Leco Corporation, Saint Joseph, MI, USA), N, P, K Ca, and Mg, and trace elements (Zn, Cd, Pb, Al, Fe, Mn, Cu) using an ICP OES ICAP 6000 spectrometer, Thermo Fisher Scientific, Waltham, MA, USA),. At the HCM site, 20 monitoring points were located in the forest at different directions and at varying distances from the smelter plant. At the FJSM site, 16 sampling points were distributed depending on vegetation type and tree species abudance. The S content in foliage was generally high at both sites. However, at the HCM site, the highest S content was found in areas close to the smelter plant (1664 mg kg⁻¹) and decreased linearly according to the direction of the dominant wind to the east (1098 mg kg⁻¹). S was correlated with Zn, Cd, and Pb (the main elements produced in the smelter plant). At the FJSM site, high S concentrations were observed in degraded soil areas (4816 mg kg⁻¹ in birch, 1563 mg kg⁻¹ in pine). These areas were hot spots that had the highest amount of S in the soil. These results indicate high biosorption of the pollutant by trees. The S concentration was also higher in birch (B) than in pine (P) foliage (regular forest: 1954 mg kg⁻¹ in B, 1272 mg kg⁻¹ in P; degraded area: 4816 mg kg⁻¹ in B, 1563 mg kg⁻¹ in P), and the differences were significant in the degraded areas. At the FJSM site, S was also correlated with Zn and, to a lesser extent, with Cd and Pb. S also influenced nutrient element supply status, in particular Mg. We confirmed that tree foliage chemistry reflects the state of the environment in highly polluted areas, so biomonitoring should be used to assessment of environmental pollution. Full article

Activating mutations in the RAS/MAPK pathway are observed in relapsed neuroblastoma. Preclinical studies indicate that these tumors have an increased sensitivity to inhibitors of the RAS/MAPK pathway, such as MEK inhibitors. MEK inhibitors do not induce durable responses as single agents, indicating a need to identify synergistic combinations of targeted agents to provide therapeutic benefit. We previously showed preclinical therapeutic synergy between a MEK inhibitor, trametinib, and a monoclonal antibody specific for IGF1R, ganitumab in RAS-mutated rhabdomyosarcoma. Neuroblastoma cells, like rhabdomyosarcoma cells, are sensitive to the inhibition of the RAS/MAPK and IGF1R/AKT/mTOR pathways. We hypothesized that the combination of trametinib and ganitumab would be effective in RAS-mutated neuroblastoma. In this study, trametinib and ganitumab synergistically suppressed neuroblastoma cell proliferation and induced apoptosis in cell culture. We also observed a delay in tumor initiation and prolongation of survival in heterotopic and orthotopic xenograft models treated with trametinib and ganitumab. However, the growth of both primary and metastatic tumors was observed in animals receiving the combination of trametinib and ganitumab. Therefore, more preclinical work is necessary before testing this combination in patients with relapsed or refractory RAS-mutated neuroblastoma. Full article

Immune reactions are characterized by the rapid immigration of phagocytes into sites of inflammation. Meticulous regulation of these migratory processes is crucial for preventing uncontrolled and harmful phagocyte extravasation. S100A8/S100A9 is the major calcium-binding protein complex expressed in phagocytes. After release, this complex acts as a proinflammatory alarmin in the extracellular space, but the intracellular functions of these highly abundant proteins are less clear. Results of this study reveal an important role of S100A8/S100A9 in coordinated cytoskeleton rearrangement during migration. We found that S100A8/S100A9 was able to cross-link F-actin and microtubules in a calcium- and phosphorylation-dependent manner. Cells deficient in S100A8/S100A9 showed abnormalities in cell adhesion and motility. Missing cytoskeletal interactions of S100A8/S100A9 caused differences in the surface expression and activation of β1-integrins as well as in the regulation of Src/Syk kinase family members. Loss of S100A8/S100A9 led to dysregulated integrin-mediated adhesion and migration, resulting in an overall higher dynamic activity of non-activated S100A8/S100A9-deficient phagocytes. Our data suggest that intracellular S100A8/S100A9 is part of a novel regulatory mechanism that ensures the precise control necessary to facilitate the change between the quiescent and activated state of phagocytes. Full article

Beginning at 16 weeks of age and continuing for 44 weeks, male C57BL/6J were fed either a control (CON) diet; a high-fat (HF) diet (60% unsaturated); or the HF diet containing an extract of unripe avocados (AvX) enriched in the 7-carbon sugar mannoheptulose (MH), designed to act as a glycolytic inhibitor (HF + MH). Compared to the CON diet, mice on the HF diet exhibited higher body weights; body fat; blood lipids; and leptin with reduced adiponectin levels, insulin sensitivity, VO2max, and falls from a rotarod. Mice on the HF + MH diet were completely protected against these changes in the absence of significant diet effects on food intake. Compared to the CON diet, oxidative stress was also increased by the HF diet indicated by higher levels of total reactive oxygen species, superoxide, and peroxynitrite measured in liver samples by electron paramagnetic resonance spectroscopy, whereas the HF + MH diet attenuated these changes. Compared to the CON, the HF diet increased signaling in the mechanistic target of the rapamycin (mTOR) pathway, and the addition of the MH-enriched AvX to this diet attenuated these changes. Beyond generating further interest in the health benefits of avocados, these results draw further new attention to the effects of this rare sugar, MH, as a botanical intervention for preventing obesity. Full article

This paper examines the ethical failure of theodicies by integrating the perspectives of philosophical argumentation and literary reading and analysis. The paper consists of two main parts. In the first part, we propose an ethical critique of metaphysical realism by analyzing its inability to recognize the perspectival plurality and diversity of suffering. As theodicies seek to explain how an omnipotent, omniscient, and absolutely benevolent God could allow the world to contain evil and suffering, it can be argued that metaphysical realism—i.e., the thesis that the world possesses its own fundamental structure independently of human perspectives of conceptualization and inquiry—is a problematic starting point of theodicism. We examine the failure of recognition of others’ suffering inherent in theodicies as a failure based on the search for an overall reductive and objectifying picture (a “God’s-Eye View”) that is constitutive of metaphysical realism. The second part of the paper shows why we should include insights from imaginative literature in our attempts to understand the recognition failures of theodicies. Emphasizing the literary, philosophical, and theological relevance of various modern rewritings of the Book of Job, which has been a crucially important sub-text for many later literary works in which the protagonists render a particular kind of human experience—unmerited suffering—we turn more closely to some literary examples, such as Joseph Roth’s novels Hiob and Die Rebellion. The tensions that are created around the moral controversy of the experiences of injustice and suffering and the human and religious reasoning and justification of violence are examined. The ambiguous ending of Hiob that adds an apparently hopeful and almost fairytale-like redemption to the story plays a crucial role in the interpretation provided in the paper. By analyzing some literary examples and their relation to the literary Job tradition, the recognition-failures of theodicist attempts to provide meaning into suffering—attempts based on metaphysical realism, as argued in the first part of the paper—are highlighted. Finally, we also critically consider the charge that theodicism could only be theoretically formulated and argue that a sharp distinction between theory and practice in this area is itself an act of non-recognition, or a failure to recognize suffering. Full article