Over-expression of AhR (aryl hydrocarbon receptor) induces neural differentiation of Neuro2a cells: neurotoxicology study

BACKGROUND: Dioxins and related compounds are suspected of causing neurological disruption in human and experimental animal offspring following perinatal exposure during development and growth. The molecular mechanism(s) of the actions in the brain, however, have not been fully investigated. A major participant in the process of the dioxin-toxicity is the dioxin receptor, namely the aryl hydrocarbon receptor (AhR). AhR regulates the transcription of diverse genes through binding to the xenobiotic-responsive element (XRE). Since the AhR has also been detected in various regions of the brain, the AhR may play a key role in the developmental neurotoxicity of dioxins. This study focused on the effect of AhR activation in the developing neuron. METHODS: The influence of the AhR on the developing neuron was assessed using the Neuro2a-AhR transfectant. The undifferentiated murine neuroblastoma Neuro2a cell line (ATCC) was stably transfected with AhR cDNA and the established cell line was named N2a-Rα. The activation of exogenous AhR in N2a-Rα cells was confirmed using RNAi, with si-AhR suppressing the expression of exogenous AhR. The neurological properties of N2a-Rα based on AhR activation were evaluated by immunohistochemical analysis of cytoskeletal molecules and by RT-PCR analysis of mRNA expression of neurotransmitter-production related molecules, such as tyrosine hydroxylase (TH). RESULTS: N2a-Rα cells exhibited constant activation of the exogenous AhR. CYP1A1, a typical XRE-regulated gene, mRNA was induced without the application of ligand to the culture medium. N2a-Rα cells exhibited two significant functional features. Morphologically, N2a-Rα cells bore spontaneous neurites exhibiting axon-like properties with the localization of NF-H. In addition, cdc42 expression was increased in comparison to the control cell line. The other is the catecholaminergic neuron-like property. N2a-Rα cells expressed tyrosine hydroxylase (TH) mRNA as a functional marker of catecholaminergic neurotransmitter production. Thus, exogenous AhR induced catecholaminergic differentiation in N2a-Rα cells. CONCLUSION: The excessive activation of AhR resulted in neural differentiation of Neuro2a cells. This result revealed that dioxins may affect the nervous system through the AhR-signaling pathway. Activated AhR may disrupt the strictly regulated brain formation with irregular differentiation occurring rather than cell death

Adherence measurements and corrosion resistance in primer/hot-dip galvanized steel systems

This paper focuses on the adherence during ageing of a primer (made of polyester resins crosslinked with melamine) applied onto hot-dip galvanized (HDG) steel for coil coating application and its influence on corrosion protection. A chromium-free surface treatment, composed of fluorotitanic acid, phosphoric acid, manganese phosphate, and vinylphenol was applied on the HDG steel to obtain high corrosion resistance and high adherence of a polyester and melamine primer. The influence of the manganese phosphate on the corrosion and adherence was investigated. To measure the adherence between the metal and the primer, a three-point flexure test was set up. The adherence was then linked with corrosion resistance during ageing, using electrochemical impedance spectroscopy

The effect of an intracerebroventricular injection of metformin or AICAR on the plasma concentrations of melatonin in the ewe: potential involvement of AMPK?

<p>Abstract</p> <p>Background</p> <p>It is now widely accepted that AMP-activated protein kinase (AMPK) is a critical regulator of energy homeostasis. Recently, it has been shown to regulate circadian clocks. In seasonal breeding species such as sheep, the circadian clock controls the secretion of an endogenous rhythm of melatonin and, as a consequence, is probably involved in the generation of seasonal rhythms of reproduction. Considering this, we identified the presence of the subunits of AMPK in different hypothalamic nuclei involved in the pre- and post-pineal pathways that control seasonality of reproduction in the ewe and we investigated if the intracerebroventricular (i.c.v.) injection of two activators of AMPK, metformin and AICAR, affected the circadian rhythm of melatonin in ewes that were housed in constant darkness. In parallel the secretion of insulin was monitored as a peripheral metabolic marker. We also investigated the effects of i.c.v. AICAR on the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in brain structures along the photoneuroendocrine pathway to the pineal gland.</p> <p>Results</p> <p>All the subunits of AMPK that we studied were identified in all brain areas that were dissected but with some differences in their level of expression among structures. Metformin and AICAR both reduced (p < 0.001 and p < 0.01 respectively) the amplitude of the circadian rhythm of melatonin secretion independently of insulin secretion. The i.c.v. injection of AICAR only tended (p = 0.1) to increase the levels of phosphorylated AMPK in the paraventricular nucleus but significantly increased the levels of phosphorylated ACC in the paraventricular nucleus (p < 0.001) and in the pineal gland (p < 0.05).</p> <p>Conclusions</p> <p>Taken together, these results suggest a potential role for AMPK on the secretion of melatonin probably acting trough the paraventricular nucleus and/or directly in the pineal gland. We conclude that AMPK may act as a metabolic cue to modulate the rhythm of melatonin secretion.</p

Under the Skin of a Lion: Unique Evidence of Upper Paleolithic Exploitation and Use of Cave Lion (Panthera spelaea) from the Lower Gallery of La Garma (Spain)

ABSTRACT: Pleistocene skinning and exploitation of carnivore furs have been previously inferred from archaeological evidence. Nevertheless, the evidence of skinning and fur processing tends to be weak and the interpretations are not strongly sustained by the archaeological record. In the present paper, we analyze unique evidence of patterned anthropic modification and skeletal representation of fossil remains of cave lion (Panthera spelaea) from the Lower Gallery of La Garma (Cantabria, Spain). This site is one of the few that provides Pleistocene examples of lion exploitation by humans. Our archaeozoological study suggests that lion-specialized pelt exploitation and use might have been related to ritual activities during the Middle Magdalenian period (ca. 14800 cal BC). Moreover, the specimens also represent the southernmost European and the latest evidence of cave lion exploitation in Iberia. Therefore, the study seeks to provide alternative explanations for lion extinction in Eurasia and argues for a role of hunting as a factor to take into account

Key findings from the UKCCMP cohort of 877 patients with haematological malignancy and COVID-19: disease control as an important factor relative to recent chemotherapy or anti-CD20 therapy

Patients with haematological malignancies have a high risk of severe infection and death from SARS-CoV-2. In this prospective observational study, we investigated the impact of cancer type, disease activity, and treatment in 877 unvaccinated UK patients with SARS-CoV-2 infection and active haematological cancer. The primary end-point was all-cause mortality. In a multivariate analysis adjusted for age, sex and comorbidities, the highest mortality was in patients with acute leukaemia [odds ratio (OR) = 1·73, 95% confidence interval (CI) 1·1–2·72, P = 0·017] and myeloma (OR 1·3, 95% CI 0·96–1·76, P = 0·08). Having uncontrolled cancer (newly diagnosed awaiting treatment as well as relapsed or progressive disease) was associated with increased mortality risk (OR = 2·45, 95% CI 1·09–5·5, P = 0·03), as was receiving second or beyond line of treatment (OR = 1·7, 95% CI 1·08–2·67, P = 0·023). We found no association between recent cytotoxic chemotherapy or anti-CD19/anti-CD20 treatment and increased risk of death within the limitations of the cohort size. Therefore, disease control is an important factor predicting mortality in the context of SARS-CoV-2 infection alongside the possible risks of therapies such as cytotoxic treatment or anti-CD19/anti-CD20 treatments

Industrie pré-acheuléenne sur les bords du fleuve Niger en amont de Bamako (Mali)

En décembre 1988, des recherches conduites dans le cadre d'un projet d'inventaire des sites archéologiques du Mali, ont permis la découverte d'un outillage de type "pebble tools" sur les berges du fleuve Niger, à Farabana, en amont de Bamako. Cette découverte fait reculer les débuts connus de l'occupation humaine de l'Ouest africain, Sud saharien, à une époque antérieure à l'Acheuléen. (Résumé d'auteur