Mehanizam akutne neurotoksičnosti u Sprague-Dawley štakora izazvane trovanjem endosulfanom

The purpose of this study was to investigate the molecular mechanism underlying oxidative and inflammatory neuronal cell death induced by endosulfan, a pesticide belonging to the chemical family of organochlorines. The cortical and hippocampal tissues derived from Sprague-Dawley (SD) rats treated with endosulfan exhibited increased intracellular accumulation of reactive oxygen species and oxidative damages to cellular macromolecules such as depletion of glutathione, lipid peroxidation, and protein carbonylation. Conversely, the expression of antioxidant enzymes including γ-glutamylcysteine ligase (GCL), superoxide dismutase (SOD), and heme oxygenase-1 (HO-1) was markedly reduced in the brain tissues exposed to endosulfan. Moreover, during endosulfan-induced neuronal cell death, mRNA expression of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was elevated, which seemed to be mediated by the activation of nuclear factor-kappa B (NF-κB) by phosphorylation of p65 subunit. These results suggest a new molecular mechanism underlying the endosulfan-induced acute neurotoxicity via induction of oxidative stress and pro-inflammatory responses.Istražen je molekularni mehanizam koji dovodi do smrti neurona potaknute oksidativnim i upalnim procesima uzrokovanim organoklornim pesticidom endosulfanom. U tkivima korteksa i hipokampusa Sprague-Dawley (SD) štakora tretiranih endosulfanom uočena su oksidativna oštećenja staničnih makromolekula, poput smanjene razine glutationa, lipidne peroksidacije i karbonilacije proteina, te povećane unutarstanične akumulacije reaktivnih kisikovih spojeva. Isto tako, u moždanom tkivu nakon izlaganja endosulfanu značajno je smanjena ekspresija enzimskih antioksidansa, uključujući i γ-glutamilcistein ligazu (GCL), superoksidnu dismutazu (SOD) i hem oksigenazu-1 (HO-1). Tijekom endosulfanom izazvane smrti neurona povećala se i ekspresija mRNA pro-upalnih citokina poput čimbenika nekroze tumora-α (TNF-α) i interleukina-1β (IL-1β), što je čini se bilo posredovano aktivacijom nuklearnoga faktora kapa B (NF-κB) putem fosforilacije podjedinice p65. Navedeni rezultati upućuju na novi molekularni mehanizam koji stoji iza akutne neurotoksičnosti izazvane endosulfanom putem indukcije oksidativnoga stresa i pro-upalnih odgovora

Multiple steady states in exchange flows across faults and the dissolution of CO2

We develop a model of the steady exchange flows which may develop between two aquifers at different levels in the geological strata and across which there is an unstable density stratification, as a result of their connection through a series of fractures. We show that in general there are multiple steady exchange flows which can develop, depending on the initial conditions, and which may involve a net upwards or downwards volume flux. We also show that there is a family of equilibrium exchange flows with zero net volume flux, each characterised by a different interlayer flux of buoyancy. We present experiments which confirm our simplified model of the exchange flow. Such exchange flows may supply unsaturated water from a deep aquifer to drive dissolution of a structurally trapped pool of geologically stored $\text{CO}_{2}$, once the water in the aquifer containing the trapped pool of $\text{CO}_{2}$ has become saturated in $\text{CO}_{2}$, and hence relatively dense. Such exchange flows may also lead to cross-contamination of aquifer fluids, which may be of relevance in assessing risks of geological storage systems.This is the author accepted manuscript. The final version is available from CUP via http://journals.cambridge.org/download.php?file=%2FFLM%2FFLM769%2FS0022112015001007a.pdf&code=58f6f56d3a1302266ca4bcf617ba24df

Role of G{alpha}12 and G{alpha}13 as Novel Switches for the Activity of Nrf2, a Key Antioxidative Transcription Factor

G{alpha}12 and G{alpha}13 function as molecular regulators responding to extracellular stimuli. NF-E2-related factor 2 (Nrf2) is involved in a protective adaptive response to oxidative stress. This study investigated the regulation of Nrf2 by G{alpha}12 and G{alpha}13. A deficiency of G{alpha}12, but not of G{alpha}13, enhanced Nrf2 activity and target gene transactivation in embryo fibroblasts. In mice, G{alpha}12 knockout activated Nrf2 and thereby facilitated heme catabolism to bilirubin and its glucuronosyl conjugations. An oligonucleotide microarray demonstrated the transactivation of Nrf2 target genes by G{alpha}12 gene knockout. G{alpha}12 deficiency reduced Jun N-terminal protein kinase (JNK)-dependent Nrf2 ubiquitination required for proteasomal degradation, and so did G{alpha}13 deficiency. The absence of G{alpha}12, but not of G{alpha}13, increased protein kinase C {delta} (PKC {delta}) activation and the PKC {delta}-mediated serine phosphorylation of Nrf2. G{alpha}13 gene knockout or knockdown abrogated the Nrf2 phosphorylation induced by G{alpha}12 deficiency, suggesting that relief from G{alpha}12 repression leads to the G{alpha}13-mediated activation of Nrf2. Constitutive activation of G{alpha}13 promoted Nrf2 activity and target gene induction via Rho-mediated PKC {delta} activation, corroborating positive regulation by G{alpha}13. In summary, G{alpha}12 and G{alpha}13 transmit a JNK-dependent signal for Nrf2 ubiquitination, whereas G{alpha}13 regulates Rho-PKC {delta}-mediated Nrf2 phosphorylation, which is negatively balanced by G{alpha}12

A Multilevel Study Of Supportive Leadership And Individual Work Outcomes: The Mediating Roles Of Team Cooperation, Job Satisfaction, And Team Commitment

Due to increasing empowerment in work teams, team leaders’ supportive role in helping team members perform their tasks is deemed important. The present study aimed at exploring the multilevel dynamics involving team leaders’ supportive leadership and individual work outcomes. Longitudinal survey data were collected from 536 employees in 69 teams of a large engineering company located in South Korea. The results of multilevel structural equation modeling showed that individuals’ perceptions of supportive leadership were positively related to their subsequent task performance, and that this relationship was mediated by team commitment. The relationship between individual-level perceptions of supportive leadership and organizational citizenship behavior (OCB) was mediated by job satisfaction and team commitment. On the other hand, team cooperation mediated the relationship between team-level perceptions of supportive leadership and OCB. These findings provide meaningful insights into multilevel mediation processes involving different levels of supportive leadership perceptions

In Utero Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Affects the Development of Reproductive System in Mouse

PURPOSE: Exposure of male reproductive organs to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) has been reported to cause developmental changes. In this study, we evaluated the effects of in utero TCDD exposure on male reproductive development. MATERIALS AND METHODS: Pregnant C57BL/6 mice were administered a single intraperitoneal injection of TCDD (1microgram/kg) on gestation day (GD) 15. The offspring were examined in the immature stage on postnatal day (PND) 30 and in the mature stage on PND 60. The testes were examined for histological changes, androgen receptor (AR), proliferating cell nuclear antigen (PCNA) and apoptosis following the measurement of morphological changes. RESULTS: Anogenital distance (AGD) and testis weights were reduced by TCDD exposure both on PND 30 and PND 60 while body weights and length of male offspring were not affected by TCDD. The regular sperm developmental stage was impaired with TCDD treatment on PND 30. However, no difference was found between the control group and TCDD groups on PND 60. Simultaneously, the expression of AR was also reduced on PND 30, while it was increased on PND 60 compared with the control group. The expression of PCNA was decreased whereas apoptosis was not affected by TCDD both on PND 30 and PND 60. CONCLUSION: These results suggest that in utero exposure to TCDD influences the development of testes by inhibiting the expression of AR and PCNA. Moreover, the adverse effects of TCDD on male offspring reduced over timeope