A computational study of substituted flavylium salts and their quinonoidal conjugate-bases: S0 -> S1 electronic transition, absolute pKa and reduction potential calculations by DFT and semiempirical methods

The electronic transitions for flavylium cations and quinonoidal bases of 17 substituted flavylium salts have been studied at semiempirical and DFT (density functional theory) levels. Solvent effect on electronic spectra was included by Polarizable Continuum Model, PCM. We assigned longest-wavelength absorption maxima to HOMO -> LUMO transition. Both levels of theory gave good results for electronic transitions of flavylium cations whereas only TDDFT-PCM calculations could be used for electronic transitions of their quinonoidal bases. We also performed absolute pKa calculations of nine flavylium salts at DFT level. The pKa calculated values by our PCM parameterization gave excellent results with mean absolute deviation less than a half of one pKa unit. One-electron reduction potentials were carried out for 5 flavylium cations at DFT level. The theoretical results found were in good agreement with experimental values after adjustment for a systematic deviation

Consequences of sexual harassment in sport for female athletes

Sexual harassment research was first undertaken in the workplace and educational settings. Research on sexual harassment in sport is scarce but has grown steadily since the mid-1980s. Even so, very little is known about the causes and/or characteristics and/or consequences of sexual harassment in sport settings. This article reports on the findings from interviews with 25 elite female athletes in Norway who indicated in a prior survey (N =572) that they had experienced sexual harassment from someone in sport. The consequences of the incidents of sexual harassment that were reported were mostly negative, but some also reported that their experiences of sexual harassment had had no consequences for them. “Thinking about the incidents”, a “destroyed relationship to the coach”, and “more negative view of men in general” were the most often negative consequences mentioned. In addition, a surprising number had chosen to move to a different sport or to drop out of elite sport altogether because of the harassment

Legal situation and current practice of waste incineration bottom ash utilisation in Europe

Almost 500 municipal solid waste incineration plants in the EU, Norway, and Switzerland generate about 17.6 Mt/a of incinerator bottom ash (IBA). IBA contains minerals and metals. Metals are mostly separated and sold to the scrap market and minerals are either disposed of in landfills or utilised in the construction sector. Since there is no uniform regulation for IBA utilisation at EU level, countries developed own rules with varying requirements for utilisation. As a result from a cooperation network between European experts an up-to-date overview of documents regulating IBA utilisation is presented. Furthermore, this work highlights the different requirements that have to be considered. Overall, 51 different parameters for the total content and 36 different parameters for the emission by leaching are defined. An analysis of the defined parameter reveals that leaching parameters are significantly more to be considered compared to total content parameters. In order to assess the leaching behaviour nine different leaching tests, including batch tests, up-flow percolation tests and one diffusion test (monolithic materials) are in place. A further discussion of leaching parameters showed that certain countries took over limit values initially defined for landfills for inert waste and adopted them for IBA utilisation. The overall utilisation rate of IBA in construction works is approximately 54 wt.%. It is revealed that the rate of utilisation does not necessarily depend on how well regulated IBA utilisation is, but rather seems to be a result of political commitment for IBA recycling and economically interesting circumstances

Dating stalagmite from Caverna do Diabo (Devil'S Cave) by TL and EPR techniques

A cylindrical fragment of stalagmite from Caverna do Diabo, State of Sao Paulo, Brazil, has been studied and dated by thermoluminescence and electron paramagnetic resonance techniques. The thermoluminescence glow curves of stalagmite samples and subsequently gamma irradiated, have shown rise of three peaks at 135, 180 and 265 degrees C. From electron paramagnetic resonance spectra of stalagmite was possible to clearly identify three paramagnetic centers in the g = 2.0 region: Centers I, II and III are due to, CO3- and CO33-, respectively. The additive method was applied to calculate the accumulated dose using thermoluminescence peak at 265 degrees C and the electron paramagnetic resonance signal at g = 1.9973 of CO2- radical. The ages of the different slices of stalagmite were determined from the D-ac-values and D-an-value, obtaining an average of 86410 for central slice, 53421 for second slice, 31490 for third slice and 46390 years B.P. for the central region of upper end.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Sao Paulo, Inst Fis, Rua Matao,187 Cidade Univ, BR-05508090 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Ciencias Mar, Rua Doutor Carvalho de Mendonca 144, BR-11070100 Santos, SP, BrazilIPEN CNEN SP, Inst Pesquisas Energet & Nucl, Av Prof Lineu Prestes,2242 Cidade Univ, BR-05508000 Sao Paulo, SP, BrazilUniv Nacl San Agustin, Fac Ciencias Nat & Formales, Escuela Profes Fis, Av Independencia S-N, Arequipa, PeruUniv Sao Paulo, Escola Politecn, Dept Engn Met & Mat, Av Prof Mello Moraes 2463, BR-05508030 Sao Paulo, SP, BrazilDepartamento de Ciências do Mar, Universidade Federal de São Paulo, Rua Doutor Carvalho de Mendonça, 144, 11070-100 Santos, SP, BrazilFAPESP: 2014/03085-0CAPES: BEX-9612130Web of Scienc

Auditory Function in the Tc1 Mouse Model of Down Syndrome Suggests a Limited Region of Human Chromosome 21 Involved in Otitis Media

Down syndrome is one of the most common congenital disorders leading to a wide range of health problems in humans, including frequent otitis media. The Tc1 mouse carries a significant part of human chromosome 21 (Hsa21) in addition to the full set of mouse chromosomes and shares many phenotypes observed in humans affected by Down syndrome with trisomy of chromosome 21. However, it is unknown whether Tc1 mice exhibit a hearing phenotype and might thus represent a good model for understanding the hearing loss that is common in Down syndrome. In this study we carried out a structural and functional assessment of hearing in Tc1 mice. Auditory brainstem response (ABR) measurements in Tc1 mice showed normal thresholds compared to littermate controls and ABR waveform latencies and amplitudes were equivalent to controls. The gross anatomy of the middle and inner ears was also similar between Tc1 and control mice. The physiological properties of cochlear sensory receptors (inner and outer hair cells: IHCs and OHCs) were investigated using single-cell patch clamp recordings from the acutely dissected cochleae. Adult Tc1 IHCs exhibited normal resting membrane potentials and expressed all K+ currents characteristic of control hair cells. However, the size of the large conductance (BK) Ca2+ activated K+ current (IK,f), which enables rapid voltage responses essential for accurate sound encoding, was increased in Tc1 IHCs. All physiological properties investigated in OHCs were indistinguishable between the two genotypes. The normal functional hearing and the gross structural anatomy of the middle and inner ears in the Tc1 mouse contrast to that observed in the Ts65Dn model of Down syndrome which shows otitis media. Genes that are trisomic in Ts65Dn but disomic in Tc1 may predispose to otitis media when an additional copy is active

Therapeutic Benefit of Radial Optic Neurotomy in a Rat Model of Glaucoma

Radial optic neurotomy (RON) has been proposed as a surgical treatment to alleviate the neurovascular compression and to improve the venous outflow in patients with central retinal vein occlusion. Glaucoma is characterized by specific visual field defects due to the loss of retinal ganglion cells and damage to the optic nerve head (ONH). One of the clinical hallmarks of glaucomatous neuropathy is the excavation of the ONH. The aim of this work was to analyze the effect of RON in an experimental model of glaucoma in rats induced by intracameral injections of chondroitin sulfate (CS). For this purpose, Wistar rats were bilaterally injected with vehicle or CS in the eye anterior chamber, once a week, for 10 weeks. At 3 or 6 weeks of a treatment with vehicle or CS, RON was performed by a single incision in the edge of the neuro-retinal ring at the nasal hemisphere of the optic disk in one eye, while the contralateral eye was submitted to a sham procedure. Electroretinograms (ERGs) were registered under scotopic conditions and visual evoked potentials (VEPs) were registered with skull-implanted electrodes. Retinal and optic nerve morphology was examined by optical microscopy. RON did not affect the ocular hypertension induced by CS. In eyes injected with CS, a significant decrease of retinal (ERG a- and b-wave amplitude) and visual pathway (VEP N2-P2 component amplitude) function was observed, whereas RON reduced these functional alterations in hypertensive eyes. Moreover, a significant loss of cells in the ganglion cell layer, and Thy-1-, NeuN- and Brn3a- positive cells was observed in eyes injected with CS, whereas RON significantly preserved these parameters. In addition, RON preserved the optic nerve structure in eyes with chronic ocular hypertension. These results indicate that RON reduces functional and histological alterations induced by experimental chronic ocular hypertension

Disease- and age-related changes in histone acetylation at gene promoters in psychiatric disorders

Increasing evidence suggests that epigenetic factors have critical roles in gene regulation in neuropsychiatric disorders and in aging, both of which are typically associated with a wide range of gene expression abnormalities. Here, we have used chromatin immunoprecipitation-qPCR to measure levels of acetylated histone H3 at lysines 9/14 (ac-H3K9K14), two epigenetic marks associated with transcriptionally active chromatin, at the promoter regions of eight schizophrenia-related genes in n=82 postmortem prefrontal cortical samples from normal subjects and those with schizophrenia and bipolar disorder. We find that promoter-associated ac-H3K9K14 levels are correlated with gene expression levels, as measured by real-time qPCR for several genes, including, glutamic acid decarboxylase 1 (GAD1), 5-hydroxytryptamine receptor 2C (HTR2C), translocase of outer mitochondrial membrane 70 homolog A (TOMM70A) and protein phosphatase 1E (PPM1E). Ac-H3K9K14 levels of several of the genes tested were significantly negatively associated with age in normal subjects and those with bipolar disorder, but not in subjects with schizophrenia, whereby low levels of histone acetylation were observed in early age and throughout aging. Consistent with this observation, significant hypoacetylation of H3K9K14 was detected in young subjects with schizophrenia when compared with age-matched controls. Our results demonstrate that gene expression changes associated with psychiatric disease and aging result from epigenetic mechanisms involving histone acetylation. We further find that treatment with a histone deacetylase (HDAC) inhibitor alters the expression of several candidate genes for schizophrenia in mouse brain. These findings may have therapeutic implications for the clinical use of HDAC inhibitors in psychiatric disorders

Modeling Activity and Target-Dependent Developmental Cell Death of Mouse Retinal Ganglion Cells Ex Vivo

Programmed cell death is widespread during the development of the central nervous system and serves multiple purposes including the establishment of neural connections. In the mouse retina a substantial reduction of retinal ganglion cells (RGCs) occurs during the first postnatal week, coinciding with the formation of retinotopic maps in the superior colliculus (SC). We previously established a retino-collicular culture preparation which recapitulates the progressive topographic ordering of RGC projections during early post-natal life. Here, we questioned whether this model could also be suitable to examine the mechanisms underlying developmental cell death of RGCs. Brn3a was used as a marker of the RGCs. A developmental decline in the number of Brn3a-immunolabelled neurons was found in the retinal explant with a timing that paralleled that observed in vivo. In contrast, the density of photoreceptors or of starburst amacrine cells increased, mimicking the evolution of these cell populations in vivo. Blockade of neural activity with tetrodotoxin increased the number of surviving Brn3a-labelled neurons in the retinal explant, as did the increase in target availability when one retinal explant was confronted with 2 or 4 collicular slices. Thus, this ex vivo model reproduces the developmental reduction of RGCs and recapitulates its regulation by neural activity and target availability. It therefore offers a simple way to analyze developmental cell death in this classic system. Using this model, we show that ephrin-A signaling does not participate to the regulation of the Brn3a population size in the retina, indicating that eprhin-A-mediated elimination of exuberant projections does not involve developmental cell death

Environmental chemical stressors as epigenome modifiers:a new horizon in assessment of toxicological effects

In eukaryotic cells, chromatin transformation from euchromatin into heterochromatin as a means of controlling gene expression and replication has been known as the ?accessibility hypothesis?. The interplay of epigenetic changes including histone modifications, DNA methylation, RNA interference (RNAi) and other functional epigenetic components are intricate. It is believed that these changes are well-programmed, inherited and can be modified by environmental contaminant stressors. Environmentally-driven epigenetic alterations during development, e.g. embryonic, foetal or neonatal stage, may influence disease susceptibility in adulthood. Therefore, understanding how epigenome modifications develop in response to environmental chemicals and, how epigenetic-xenobiotic interactions influence human health will shed new insights into gene-environment interactions in the epidemiology of several diseases including cancer. In this review, we consider studies of chemical modifiers including nutritional and xenobiotic effects on epigenetic components in vitro or in vivo. By examining the most-studied epigenome modifications and how their respective roles are interlinked, we highlight the central role of xenbiotic-modified epigenetic mechanisms. A major requirement will be to study and understand effects following environmentally-relevant exposures. We suggest that the study of epigenetic toxicology will open up new opportunities to devise strategies for the prevention or treatment of at-risk populations