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Exposure to high manganese (Mn) levels may damage the basal ganglia, leading to a syndrome analogous to Parkinson's disease, with motor and cognitive impairments. The molecular mechanisms underlying Mn neurotoxicity, particularly during development, still deserve further investigation. Herein, we addressed whether early-life Mn exposure affects motor coordination and cognitive function in adulthood and potential underlying mechanisms. Male Wistar rats were exposed intraperitoneally to saline (control) or MnCl2 (5, 10 or 20 mg/kg/day) from post-natal day (PND) 8-12. Behavioral tests were performed on PND 60-65 and biochemical analysis in the striatum and hippocampus were performed on PND14 or PND70. Rats exposed to Mn (10 and 20 mg/kg) performed significantly worse on the rotarod test than controls indicating motor coordination and balance impairments. The object and social recognition tasks were used to evaluate short-term memory. Rats exposed to the highest Mn dose failed to recognize a familiar object when replaced by a novel object as well as to recognize a familiar juvenile rat after a short period of time. However, Mn did not alter olfactory discrimination ability. In addition, Mn-treated rats displayed decreased levels of non-protein thiols (e.g. glutathione) and increased levels of glial fibrillary acidic protein (GFAP) in the striatum. Moreover, Mn significantly increased hippocampal glutathione peroxidase (GPx) activity. These findings demonstrate that acute low-level exposure to Mn during a critical neurodevelopmental period causes cognitive and motor dysfunctions that last into adulthood, that are accompanied by alterations in antioxidant defense system in both the hippocampus and striatum. (C) 2015 Elsevier Inc. All rights reserved.
cis-Diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 mm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose) metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable.
Exposure to organic mercury compounds promotes primarily neurological effects. Although methylmercury is recognized as a potent neurotoxicant, its transfer into the central nervous system (CNS) is not fully evaluated. While methylmercury and thiomersal pass the blood-brain barrier, limited data are available regarding the second brain regulating interface, the blood-cerebrospinal fluid (CSF) barrier. This novel study was designed to investigate the effects of organic as well as inorganic mercury compounds on, and their transfer across, a porcine in vitro model of the blood-CSF barrier for the first time. The barrier system is significantly more sensitive towards organic Hg compounds as compared to inorganic compounds regarding the endpoints cytotoxicity and barrier integrity. Whereas there are low transfer rates from the blood side to the CSF side, our results strongly indicate an active transfer of the organic mercury compounds out of the CSF. These results are the first to demonstrate an efflux of organic mercury compounds regarding the CNS and provide a completely new approach in the understanding of mercury compounds specific transport.
Loss of pdr-1/parkin influences Mn homeostasis through altered ferroportin expression in C-elegans
(2015)
Dopamine (DA) and serotonin (SRT) are monoamine neurotransmitters that play a key role in regulating the central and peripheral nervous system. Their impaired metabolism has been implicated in several neurological disorders, such as Parkinson's disease and depression. Consequently, it is imperative to monitor changes in levels of these low-abundant neurotransmitters and their role in mediating disease. For the first time, a rapid, specific and sensitive isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of DA and SRT in the nematode Caenorhabditis elegans (C. elegans). This model organism offers a unique approach for studying the effect of various drugs and environmental conditions on neurotransmitter levels, given by the conserved DA and SRT biology, including synaptic release, trafficking and formation. We introduce a novel sample preparation protocol incorporating the usage of sodium thiosulfate in perchloric acid as extraction medium that assures high recovery of the relatively unstable neurotransmitters monitored. Moreover, the use of both deuterated internal standards and the multiple reaction monitoring (MRM) technique allows for unequivocal quantification. Thereby, to the best of our knowledge, we achieve a detection sensitivity that clearly exceeds those of published DA and SRT quantification methods in various matrices. We are the first to show that exposure of C elegans to the monoamine oxidase B (MAOB) inhibitor selegiline or the catechol-O-methyltransferase (COMT) inhibitor tolcapone, in order to block DA and SRT degradation, resulted in accumulation of the respective neurotransmitter. Assessment of a behavioral output of the dopaminergic system (basal slowing response) corroborated the analytical LC-MS/MS data. Thus, utilization of the C elegans model system in conjunction with our analytical method is well-suited to investigate drug-mediated modulation of the DA and SRT system in order to identify compounds with neuroprotective or regenerative properties. (C) 2015 Elsevier B.V. All rights reserved.
A seismological network was operated at the junction of the aseismic Walvis Ridge with the northwestern Namibian coast. We mapped crustal thickness and bulk V-p/V-s ratio by the H-k analysis of receiver functions. In the Damara Belt, the crustal thickness is similar to 35km with a V-p/V-s ratio of <1.75. The crust is similar to 30km thick at the coast in the Kaoko Belt. Strong variations in crustal thickness and V-p/V-s ratios are found at the landfall of the Walvis Ridge. Here and at similar to 150km northeast of the coast, the crustal thickness increases dramatically reaching 44km and the V-p/V-s ratios are extremely high (similar to 1.89). These anomalies are interpreted as magmatic underplating produced by the mantle plume during the breakup of Gondwana. The area affected by the plume is smaller than 300km in diameter, possibly ruling out the existence of a large plume head under the continent during the breakup.
Data are presented on young people's sexual victimisation and perpetration from 10 European countries (Austria, Belgium, Cyprus, Greece, Lithuania, the Netherlands, Poland, Portugal, Slovakia and Spain) using a shared measurement tool (N = 3480 participants, aged between 18 and 27 years). Between 19.7 and 52.2% of female and between 10.1 and 55.8% of male respondents reported having experienced at least one incident of sexual victimisation since the age of consent. In two countries, victimisation rates were significantly higher for men than for women. Between 5.5 and 48.7% of male and 2.6 and 14.8% of female participants reported having engaged in a least one act of sexual aggression perpetration, with higher rates for men than for women in all countries. Victimisation rates correlated negatively with sexual assertiveness and positively with alcohol use in sexual encounters. Perpetration rates correlated positively with attitudes condoning physical dating violence and with alcohol use in men, and negatively with sexual assertiveness in women. At the country level, lower gender equality in economic power and in the work domain was related to higher male perpetration rates. Lower gender equality in political power and higher sexual assertiveness in women relative to men were linked to higher male victimisation rates.
Sexual aggression victimization and perpetration among female and male university students in Poland
(2015)
This study examined the prevalence of victimization and perpetration of sexual aggression since age 15 in a convenience sample of 565 Polish university students (356 females). The prevalence of sexual aggression was investigated for both males and females from the perspectives of both victims and perpetrators in relation to three coercive strategies, three different victim–perpetrator relationships, and four types of sexual acts. We also examined the extent to which alcohol was consumed in the context of sexually aggressive incidents. The overall self-reported victimization rate was 34.3% for females and 28.4% for males. The overall perpetration rate was 11.7% for males and 6.5% for females. The gender difference was significant only for perpetration. Prevalence rates of both victimization and perpetration were higher for people known to each other than for strangers. In the majority of victimization and perpetration incidents, alcohol was consumed by one or both parties involved. The findings are discussed in relation to the international evidence and the need for tailored risk prevention and reduction programs.