Free radicals in alcoholic myopathy: Indices of damage and preventive studies

Chronic alcoholic myopathy affects up to two-thirds of all alcohol misusers and is characterized by selective atrophy of Type If (glycolytic, fast-twitch, anaerobic) fibers. In contrast, the Type I fibers (oxidative, slow-twitch, aerobic) are relatively protected. Alcohol increases the concentration of cholesterol hydroperoxides and malondialdehyde-protein adducts, though protein-carbonyl concentration levels do not appear to be overtly increased and may actually decrease in some studies. In alcoholics, plasma concentrations of a-tocopherol may be reduced in myopathic patients. However, a-tocopherol supplementation has failed to prevent either the loss of skeletal muscle protein or the reductions in protein synthesis in alcohol-dosed animals. The evidence for increased oxidative stress in alcohol-exposed skeletal muscle is thus inconsistent. Further work into the role of ROS in alcoholic myopathy is clearly warranted. (C) 2002 Elsevier Science Inc.

Arsenic inhibits the repair of DNA damage induced by benzo(a)pyrene

In order to study the effect of arsenic on DNA damage, Sprague-Dawley rats were dosed with sodium arsenite (10 mg/kg) with or without 800 mug of benzo(a)pyrene (BP) by intramammilary injection. The animals were sacrificed on day 1, 3, 5, 10 and 27 and the mammary gland tissues were collected for DNA adduct measurement using a P-32 post-labeling assay. Animals dosed with arsenic alone did not show any DNA adducts. DNA adduct levels in rats dosed with BP alone reached a maximum level by day 5, reducing to 13% of this level by day 27. Adduct levels in rats dosed with arsenic and BP also reached a maximum by day 5 but only 80% of the level observed in the BP group. However, 84% of this amount still remained by day 27. The First Nucleotide Change (FNC) technique was used for the screening of 115 samples of various tissues from mice that had been chronically exposed to sodium arsenate for over 2 years revealed that inorganic arsenic did not attack the two putative hotspots (codons 131 and 154) of the hOGG1 gene. These results support the hypothesis that arsenic exerts its biological activity through DNA repair inhibition. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Neuronal calcium-binding proteins and schizophrenia

Calcium-binding proteins (CBPs) such as calbindin, parvalbumin and calretinin are used as immunohistochemical markers for discrete neuronal subpopulations. They are particularly useful in identifying the various subpopulations of GABAergic interneurons that control output from prefrontal and cingulate cortices as well as from the hippocampus. The strategic role these interneurons play in regulating output from these three crucial brain regions has made them a focus for neuropathological investigation in schizophrenia. The number of pathological reports detailing subtle changes in these CBP-containing interneurons in patients with schizophrenia is rapidly growing. These proteins however are more than convenient neuronal markers. They confer survival advantages to neurons and can increase the neuron's ability to sustain firing. These properties may be important in the subtle pathophysiology of nondegenerative phenomena such as schizophrenia. The aim of this review is to introduce the reader to the functional properties of CBPs and to examine the emerging literature reporting alterations in these proteins in schizophrenia as well as draw some conclusions about the significance of these findings. (C) 2002 Elsevier Science B.V. All rights reserved.

Suppressor of cytokine signaling 2 regulates neuronal differentiation by inhibiting growth hormone signaling

The intracellular mechanisms that determine the response of neural progenitor cells to growth factors and regulate their differentiation into either neurons or astrocytes remain unclear. We found that expression of SOCS2, an intracellular regulator of cytokine signaling, was restricted to mouse progenitor cells and neurons in response to leukemia inhibitory factor (LIF)-like cytokines. Progenitors lacking SOCS2 produced fewer neurons and more astrocytes in vitro, and Socs2(-/-) mice had fewer neurons and neurogenin-1 (Ngn1)-expressing cells in the developing cortex, whereas overexpression of SOCS2 increased neuronal differentiation. We also report that growth hormone inhibited Ngn1 expression and neuronal production, and this action was blocked by SOCS2 overexpression. These findings indicate that SOCS2 promotes neuronal differentiation by blocking growth hormone-mediated downregulation of Ngn1.

Increased TUNEL positive cells in human alcoholic brains

Alcohol-sensitive neuronal cell loss, which has been reported in the superior frontal cortex and hippocampus, may underlie the pathogenesis of subsequent cognitive deficits. In the present study, we have used the TUNEL labeling to detect the DNA damage in human alcoholic brains. Seven out of eleven alcoholics exhibited TUNEL-positive cells in both superior frontal cortex and hippocampus, which were co-localized with GFAP immunoreactivity. In contrast, almost no positive cells were detected in the non-alcoholic controls. None of the TUNEL-positive cells showed any typical morphological features of apoptosis or necrosis. TUNEL-positive cells observed in the present study may indicate DNA damage induced by ethanol-related overproduction of reactive oxygen species. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Linkage and Association Analysis of Radiation Damage Repair Genes XRCC3 and XRCC5 with Nevus Density in Adolescent Twins

Previous studies have shown that a deficiency in DNA damage repair is associated with increased cancer risk, and exposure to UV radiation is a major risk factor for the development of malignant melanoma. High density of common nevi (moles) is a major risk factor for cutaneous melanoma. A nevus may result from a mutation in a single UV-exposed melanocyte which failed to repair DNA damage in one or more critical genes. XRCC3 and XRCC5 may have an effect on nevus count through their function as components of DNA repair processes that may be involved directly or indirectly in the repair of DNA damage due to UV radiation. This study aims to test the hypothesis that the frequency of flat or raised moles is associated with polymorphism at or near these DNA repair genes, and that certain alleles are associated with less efficient DNA repair, and greater nevus density. Twins were recruited from schools in south eastern Queensland and were examined close to their 12th birthday. Nurses examined each individual and counted all moles on the entire body surface. A 10cM genome scan of 274 families (642 individuals) was performed and microsatellite polymorphisms in XRCC3 and adjacent to XRCC5 were also typed. Linkage and association of nevus count to these loci were tested simultaneously using a structural-equation modeling approach implemented in MX. There is weak evidence for linkage of XRCC5 to a QTL influencing raised mole count, and also weak association. There is also weak evidence for association between flat mole count and XRCC3. No tests were significant after correction for testing multiple alleles, nor were any of the tests for total association significant. If variation in XRCC3 or XRCC5 influences UV sensitivity, and indirectly affects nevus density, then the effects are small.

A molecular mechanism for mRNA trafficking in neuronal dendrites

Specific neuronal mRNAs are localized in dendrites, often concentrated in dendritic spines and spine synapses, where they are translated. The molecular mechanism of localization is mostly unknown. Here we have explored the roles of A2 response element (A2RE), a cis-acting signal for oligodendrocyte RNA trafficking, and its cognate trans-acting factor, heterogeneous nuclear ribonucleoprotein ( hnRNP) A2, in neurons. Fluorescently labeled chimeric RNAs containing A2RE were microinjected into hippocampal neurons, and RNA transport followed using confocal laser scanning microscopy. These RNA molecules, but not RNA lacking the A2RE sequence, were transported in granules to the distal neurites. hnRNP A2 protein was implicated as the cognate trans-acting factor: it was colocalized with RNA in cytoplasmic granules, and RNA trafficking in neurites was compromised by A2RE mutations that abrogate hnRNP A2 binding. Coinjection of antibodies to hnRNP A2 halved the number of trafficking cells, and treatment of neurons with antisense oligonucleotides also disrupted A2RE - RNA transport. Colchicine inhibited trafficking, whereas cells treated with cytochalasin were unaffected, implicating involvement of microtubules rather than microfilaments. A2RE-like sequences are found in a subset of dendritically localized mRNAs, which, together with these results, suggests that a molecular mechanism based on this cis-acting sequence may contribute to dendritic RNA localization.

Damage level of the two-spotted spider mite Tetranychus urticae Koch (acari: tetranychidae) in soybeans

Among phytophagous spider mites, the two-spotted spider mite Tetranychus urticae Koch, 1836 is one of the most important agricultural pests, not only because of the damage it causes, but also because it has a wide host range, infesting many commercial crops such as leafy greens, cotton, beans, and soybeans, among others. This study was carried out in a greenhouse of the Faculdade de Ciências Agrárias (FCA) of the Universidade Federal da Grande Dourados (UFGD), located in the city of Dourados, state of Mato Grosso do Sul. The experiment was arranged in a randomized block design with 5 treatments and 4 replicates. The treatments consisted of 5 levels in percentage of chlorotic symptoms (indicating mite damage): 0%, 25%, 50%, 75%, and 100%. All of the characteristics evaluated, except for number of pods per plant, the number of seeds per plant, the total weight (productivity), and the weight of 1000 seeds, were significantly influenced by the different levels of chlorotic symptoms. The economic damage level for the two-spotted spider mite Tetranychus urticae, according to the equation y = 66.63-0.51 x, based on the price of US$ 11.00 per bag of soybeans and a control cost of US$ 16.00, would be 15.80% chlorotic symptoms. At a price of US$ 29.00 per bag with the same control cost, the economic damage level would be 13% of chlorotic symptoms.

Criminal Liability of Organizations, Corporations, Legal Persons, and Similar Entities on Law of Portuguese Cybercrime: A Brief Discussion on the Issue of Crimes of “False Information,” the “Damage on Other Programs or Computer Data,” the “Computer-Software Sabotage,” the “Illegitimate Access,” the “Unlawful Interception,” and “Illegitimate Reproduction of the Protected Program”

Abstract: in Portugal, and in much of the legal systems of Europe, «legal persons» are likely to be criminally responsibilities also for cybercrimes. Like for example the following crimes: «false information»; «damage on other programs or computer data»; «computer-software sabotage»; «illegitimate access»; «unlawful interception» and «illegitimate reproduction of protected program». However, in Portugal, have many exceptions. Exceptions to the «question of criminal liability» of «legal persons». Some «legal persons» can not be blamed for cybercrime. The legislature did not leave! These «legal persons» are v.g. the following («public entities»): legal persons under public law, which include the public business entities; entities utilities, regardless of ownership; or other legal persons exercising public powers. In other words, and again as an example, a Portuguese public university or a private concessionaire of a public service in Portugal, can not commit (in Portugal) any one of cybercrime pointed. Fair? Unfair. All laws should provide that all legal persons can commit cybercrimes. PS: resumo do artigo em inglês.

Effects of physical exercise training in DNA damage and repair - could the difference be in hOGG1 Ser326Cys polymorphism?

Acute physical exercise is associated with increased oxygen consumption, which could result in an increased formation of reactive oxygen species (ROS). ROS can react with several organic structures, namely DNA, causing strand breaks and a variety of modified bases in DNA. Physical exercise training seems to decrease the incidence of oxidative stress-associated diseases, and is considered as a key component of a healthy lifestyle. This is a result of exercise-induced adaptation, which has been associated with the possible increase in antioxidant activity and in oxidative damage repair enzymes, leading to an improved physiological function and enhanced resistance to oxidative stress (Radak et al. 2008). Human 8-oxoguanine DNA glycosylase 1 (hOGG1) is involved in the base excision repair (BER) pathway and encodes an enzyme responsible for removing the most common product of oxidative damage in DNA, 8-hydroxyguanine (8-OH-G). The genetic polymorphism of hOGG1 at codon 326 results in a serine (Ser) to cysteine (Cys) amino acid substitution (Ser326Cys). It has been suggested that the carriers of at least one hOGG1Cys variant allele exhibit lower 8-OH-G excision activity than the wild-type (Wilson et al. 2011). The aim of this study was to investigate the possible influence of hOGG1 Ser326Cys polymorphism on DNA damage and repair activity in response to 16 weeks of combined physical exercise training, in thirty healthy Caucasian men. Comet assay was carried out using peripheral blood lymphocytes and enabled the evaluation of DNA damage, both strand breaks and FPG-sensitive sites, and DNA repair activity. Genotypes were determined by PCR-RFLP analysis. The subjects with Ser/Ser genotype were considered as wild-type group (n=20), Ser/Cys and Cys/Cys genotype were analyzed together as mutant group (n=10). Regarding differences between pre and post-training in the wild-type group, the results showed a significant decrease in DNA strand breaks (DNA SBs) (p=0.002) and also in FPG-sensitive sites (p=0.017). No significant differences were observed in weight (p=0.389) and in lipid peroxidation (MDA) (p=0.102). A significant increase in total antioxidant capacity (evaluated by ABTS) was observed (p=0.010). Regarding mutant group, the results showed a significant decrease in DNA SBs (p=0.008) and in weight (p=0.028). No significant differences were observed in FPG-sensitive sites (p=0.916), in ABTS (p=0.074) and in MDA (p=0.086). No significant changes in DNA repair activity were observed in both genotype groups. This preliminary study suggests the possibility of different responses in DNA damage to physical exercise training, considering the hOGG1 Ser326Cys polymorphism.

A influência da hipertonia biomecânica VS neuronal na selecção das estratégias de intervenção em sujeitos com sequelas de acidente vascular encefálico no território da artéria cerebral média

Introdução: Após lesão do SNC o músculo pode perder a sua variabilidade e flexibilidade, tal como se verifica em indivíduos após AVE. A caracterização do tónus muscular tem sido um indicador a ter em atenção para o diagnóstico clínico. As alterações do tónus podem resultar de uma combinação de alterações neurais, como consequência dos processos inerentes à neuroplasticidade e alterações biomecânicas. Objectivo: Verificar quais as modificações no tónus muscular, segundo a escala de Tardieu, após a aplicação de um programa de reabilitação neuromotora baseado no conceito de Bobath em dois indivíduos com sequelas de AVE. Pretendeu-se também verificar as repercussões nas actividades funcionais. Participantes e métodos: Foram seleccionados dois indivíduos e aplicado um programa de reabilitação, durante onze semanas, e avaliados em dois momentos, antes da intervenção (PRE) e após a intervenção (APÓS). Aplicaram-se vários instrumentos de avaliação, nomeadamente a escala de Tardieu. O programa de reabilitação realizado baseou-se no conceito de Bobath. Resultados: Na escala de Tardieu, foi comum aos dois indivíduos melhorias a nível da qualidade de reacção muscular. Ambos os indivíduos apresentaram melhorias no controlo postural e equilíbrio, que se evidenciaram na CIF. Conclusão: Foi possível observar modificações no tónus muscular após aplicação de um programa de reabilitação e, consequentemente modificações na distribuição da carga na base de suporte, no alinhamento das estruturas articulares e musculares e na marcha. Ao longo da intervenção, observaram-se repercussões positivas em ambos os indivíduos, permitindo a estes realizar as AVDs com menor dificuldade

Damage detection and quantification using transmissibility

Structures experience various types of loads along their lifetime, which can be either static or dynamic and may be associated to phenomena of corrosion and chemical attack, among others. As a consequence, different types of structural damage can be produced; the deteriorated structure may have its capacity affected, leading to excessive vibration problems or even possible failure. It is very important to develop methods that are able to simultaneously detect the existence of damage and to quantify its extent. In this paper the authors propose a method to detect and quantify structural damage, using response transmissibilities measured along the structure. Some numerical simulations are presented and a comparison is made with results using frequency response functions. Experimental tests are also undertaken to validate the proposed technique. (C) 2011 Elsevier Ltd. All rights reserved.

Potential distribution and cost estimation of the damage caused by Cryptotermes brevis (Isoptera: Kalotermitidae) in the Azores

Copyright © 2014 Entomological Society of America.