Genetic variation in cytokine-related genes and migraine susceptibility

Migraine is classified by the World Health Organization (WHO) as being one of the top 20 most debilitating diseases. According to the neurovascular hypothesis, neuroinflammation may promote the activation and sensitisation of meningeal nociceptors, inducing the persistent throbbing headache characterized in migraine. The tumor necrosis factor (TNF) gene cluster, made up of TNFα, lymphotoxin α (LTA), and lymphotoxin β (LTB), has been implicated to influence the intensity and duration of local inflammation. It is thought that sterile inflammation mediated by LTA, LTB, and TNFα contributes to threshold brain excitability, propagation of neuronal hyperexcitability and thus initiation and maintenance of a migraine attack. Previous studies have investigated variants within the TNF gene cluster region in relation to migraine susceptibility, with largely conflicting results. The aim of this study was to expand on previous research and utilize a large case-control cohort and range of variants within the TNF gene cluster to investigate the role of the TNF gene cluster in migraine. Nine single nucleotide polymorphisms (SNPs) were selected for investigation as follows: rs1800683, rs2229094, rs2009658, rs2071590, rs2239704, rs909253, rs1800630, rs1800629, and rs3093664. No significant association with migraine susceptibility was found for any of the SNPs tested, with further testing according to migraine subtype and gender also showing no association for disease risk. Haplotype analysis showed that none of the tested haplotypes were significantly associated with migraine.

Do twins differ from single-born children on rates of behavioral difficulty in early childhood? A study of sibling relationship risk factors

The hypothesis that twinning raises risk for behavioral difficulties in childhood is persistent, yet there is limited and inconsistent empirical evidence. Simple mean comparison without control for confounders provides data on prevalence rates but cannot provide knowledge about risk or etiology. To assess the effect of twin relationship on behavior, comparison of patterns of association with single-born siblings may be informative. Analyses of data from an Australian sample of twins and single-born children (N = 305, mean age 4 years 9 months, and a follow-up 12 months later) were undertaken. The outcome measure was the Strengths and Difficulties Questionnaire. Predictor and control measures were obtained from parent report on the sibling/co-twin relationship behavior, family demographics, and obstetric history. We assessed difference between twins and single-born children in two respects: (a) mean behavioral difficulties, and (b) patterns of association between sibling relationship and behavioral difficulties, controlling for confounders. Results showed no differences in mean levels of behavioral difficulties between twins and single-born siblings identifying the importance of statistical control for family and obstetric adversity. Differences in patterns of association were found; for twin children, conflict in their co-twin relationship predicted externalizing behaviors, while for single-born children conflict predicted internalizing behaviors. The findings of mean differences between twin and single-born children in social background, but not in behavioral difficulties, underscore the necessity of statistical control to identify risk associated with twinning compared with risk associated with family and obstetric background factors.

Genetic and environmental influences on neuroimaging phenotypes: A meta-analytical perspective on twin imaging studies

Because brain structure and function are affected in neurological and psychiatric disorders, it is important to disentangle the sources of variation in these phenotypes. Over the past 15 years, twin studies have found evidence for both genetic and environmental influences on neuroimaging phenotypes, but considerable variation across studies makes it difficult to draw clear conclusions about the relative magnitude of these influences. Here we performed the first meta-analysis of structural MRI data from 48 studies on >1,250 twin pairs, and diffusion tensor imaging data from 10 studies on 444 twin pairs. The proportion of total variance accounted for by genes (A), shared environment (C), and unshared environment (E), was calculated by averaging A, C, and E estimates across studies from independent twin cohorts and weighting by sample size. The results indicated that additive genetic estimates were significantly different from zero for all metaanalyzed phenotypes, with the exception of fractional anisotropy (FA) of the callosal splenium, and cortical thickness (CT) of the uncus, left parahippocampal gyrus, and insula. For many phenotypes there was also a significant influence of C. We now have good estimates of heritability for many regional and lobar CT measures, in addition to the global volumes. Confidence intervals are wide and number of individuals small for many of the other phenotypes. In conclusion, while our meta-analysis shows that imaging measures are strongly influenced by genes, and that novel phenotypes such as CT measures, FA measures, and brain activation measures look especially promising, replication across independent samples and demographic groups is necessary.

Alzheimer's disease risk gene, GAB2, is associated with regional brain volume differences in 755 young healthy twins

The development of late-onset Alzheimer's disease (LOAD) is under strong genetic control and there is great interest in the genetic variants that confer increased risk. The Alzheimer's disease risk gene, growth factor receptor bound protein 2-associated protein (GAB2), has been shown to provide a 1.27- 1.51 increased odds of developing LOAD for rs7101429 major allele carriers, in case-control analysis. GAB2 is expressed across the brain throughout life, and its role in LOAD pathology is well understood. Recent studies have begun to examine the effect of genetic variation in the GAB2 gene on differences in the brain. However, the effect of GAB2 on the young adult brain has yet to be considered. Here we found a significant association between the GAB2 gene and morphological brain differences in 755 young adult twins (469 females) (M = 23.1, SD = 3.1 years), using a gene-based test with principal components regression (PCReg). Detectable differences in brain morphology are therefore associated with variation in the GAB2 gene, even in young adults, long before the typical age of onset of Alzheimer's disease.

Neuroimaging and genetics: Exploring, searching, and finding

This issue on the genetics of brain imaging phenotypes is a celebration of the happy marriage between two of science's highly interesting fields: neuroscience and genetics. The articles collected here are ample evidence that a good deal of synergy exists in this marriage. A wide selection of papers is presented that provide many different perspectives on how genes cause variation in brain structure and function, which in turn influence behavioral phenotypes (including psychopathology). They are examples of the many different methodologies in contemporary genetics and neuroscience research. Genetic methodology includes genome-wide association (GWA), candidate-gene association, and twin studies. Sources of data on brain phenotypes include cortical gray matter (GM) structural/volumetric measures from magnetic resonance imaging (MRI); white matter (WM) measures from diffusion tensor imaging (DTI), such as fractional anisotropy; functional- (activity-) based measures from electroencephalography (EEG), and functional MRI (fMRI). Together, they reflect a combination of scientific fields that have seen great technological advances, whether it is the single-nucleotide polymorphism (SNP) array in genetics, the increasingly high-resolution MRI imaging, or high angular resolution diffusion imaging technique for measuring WM connective properties.

Low birth weight in MZ twins discordant for birth weight is associated with shorter telomere length and lower IQ, but not anxiety/depression in later life

Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intra-pair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight.

Independent replication and meta-analysis for endometriosis risk loci

Endometriosis is a complex disease that affects 6-10% of women in their reproductive years and 20-50% of women with infertility. Genome-wide and candidate-gene association studies for endometriosis have identified 10 independent risk loci, and of these, nine (rs7521902, rs13394619, rs4141819, rs6542095, rs1519761, rs7739264, rs12700667, rs1537377, and rs10859871) are polymorphic in European populations. Here we investigate the replication of nine SNP loci in 998 laparoscopically and histologically confirmed endometriosis cases and 783 disease-free controls from Belgium. SNPs rs7521902, rs13394619, and rs6542095 show nominally significant (p <.05) associations with endometriosis, while the directions of effect for seven SNPs are consistent with the original reports. Association of rs6542095 at the IL1A locus with 'All' (p =.066) and 'Grade-B' (p =.01) endometriosis is noteworthy because this is the first successful replication in an independent population. Meta-analysis with the published results yields genome-wide significant evidence for rs7521902, rs13394619, rs6542095, rs12700667, rs7739264, and rs1537377. Notably, three coding variants in GREB1 (near rs13394619) and CDKN2B-AS1 (near rs1537377) also showed nominally significant associations with endometriosis. Overall, this study provides important replication in a uniquely characterized independent population, and indicates that the majority of the original genome-wide association findings are not due to chance alone. © The Author(s) 2015.

Linear and nonlinear optical properties of cumulenes and polyenynes: a model exact study

Model exact static and frequency-dependent polarizabilities, static second hyperpolarizabilities and THG coefficents of cumulenes and polyenynes, calculated within the correlated Pariser-Parr-Pople (PPP) model defined over the pi-framework are reported and compared with the results for the polyenes. It is found that for the same chain length, the polarizabilities and THG coefficients of the cumulenes are largest and those of the polyenynes smallest with the polyenes having an intermediate value. The optical gap of the infinite cumulene is lowest (0.75 eV) and is associated with a low transition dipole moment for an excitation involving transfer of an electron between the two orthogonal conjugated pi-systems. The polyenynes have the largest optical gap (4.37 eV), with the magnitude being nearly independent of the chain length. This excitation involves charge transfer between the conjugated bonds in the terminal triple bond. Chain length and frequency dependence of alpha(ij) and gamma(ijkl) of these systems are also reported. The effect of a heteroatom on the polarizability and THG coefficients of acetylenic systems is also reported. It has been found that the presence of the heteroatom reduces the polarizability and THG coefficients of these systems, an effect opposite to that found in the polyenes and cyanine dyes. This result has been associated with the different nature of the charge transfer in the acetylenic systems.

利用晶体串接实现高效宽带三倍频

从耦合波方程出发,分别在小信号、高功率(1.5 GW/cm2)条件下研究KDP晶体串接三次谐波转换。当两块混频晶体的长度选择为8 mm和6 mm,晶体分别偏离原混频匹配角0.35 mrad和-0.25 mrad时可以有0.3 nm的谐波转换带宽,同时系统的三次谐波转换效率与两块混频晶体之间的距离有密切关系,当两块晶体之间的距离使从第一块混频晶体出射的光波之间的相位差改变π时,会使第一块混频晶体产生的三次谐波大部分回流到基频和倍频光,从而使转换效率大幅度下降,最合适的距离应当使光波之间的相位差改变为2π。

利用晶体串接实现宽带三次谐波转换

从耦合波方程出发，分别在小信号、高功率密度（1．5GW／cm^2）条件下研究了晶体串接三次谐波（THG）转换方案，并利用实验验证了该方案。实验观察到这种方案可以有效提高宽带激光三次谐波转换效率，但混频晶体之间的距离对宽带三次谐波转换效率影响明显。在1．5GW／cm^2平均功率密度下，实验中最佳距离25mm处，对带宽3．5nm的啁啾脉冲取得了19．75％的三倍频效率，这对于高功率激光宽带三次谐波转换的解决很有意义。

Elementos-traço (mercúrio total, selênio e cobre) em penas de pinguins do gênero Pygoscelis da Ilha Rei George, Antártica

Este estudo teve como objetivo avaliar a magnitude da exposição de pinguins do gênero Pygoscelis da Antártica ao mercúrio total (HgT), selênio (Se) e cobre (Cu) e verificar a variabilidade destes elementos-traço de acordo com suas características biológicas, para tal foram utilizadas penas do peito de Pygoscelis papua (n=30), P. antarctica (n=21) e P. adeliae (n=48) que corresponderam àquelas coletadas em animais da Ilha Rei George, Antártica. Encontrou-se níveis aparentemente inferiores de HgT e Se em P. papua tendo também sido a espécie que mais se distinguiu das outras duas. Além disto, houve correlação entre os níveis de HgT e Se para as espécies P. antarctica e P. adeliae indicando que é possível que ocorra nos pinguins um processo de destoxificação do mercúrio orgânico por meio do selênio, porém isto não pôde foi confirmado. Ressalta-se que o atual estudo é o primeiro a relatar níveis de HgT em penas do peito da espécie P. antarctica, sendo esta informação relevante para o entendimento e conservação desta espécie de pinguim da Antártica. De modo geral o cobre (8346/32545 ng/g p.s. mín/máx) foi o elemento que apareceu em concentrações maiores se comparado ao selênio (618,7/7923,5 ng/g p.s. mín/máx) e mercúrio total (114,6/1180,2 ng/g p.s. mín/máx). Estas elevadas concentrações de cobre nas penas possivelmente se deve a incorporação via alimentação composta essencialmente de krill, que é um crustáceo de altas concentrações deste elemento essencial. Genericamente foi possível observar que todas as informações reportadas no atual trabalho, tais como as correlações entre os elementos-traço (HgT e Se) e características biológicas, mostram que as três espécies de pinguins analisadas seguem padrões distintos de distribuição de elementos-traço possivelmente porque apresentam dieta diferenciada, além disto, é provável que as características individuais influenciem nestes padrões, e por isto devem ser avaliadas para um melhor entendimento da distribuição dos elementos-traço nestes animais. Observa-se que as concentrações do elemento-traço não essencial HgT aparentemente não constituiu uma ameaça aos pinguins porque foi inferior ao nível considerado prejudicial a aves, enquanto o selênio é um elemento que deve ser constantemente monitorado pois exibiu concentrações próximas àquelas considerada danosa para aves quando incorporadas via dieta. Verificou-se que a presença dos elementos-traço não constitui uma ameaça a saúde dos Pygoscelis da Ilha Rei George, apesar disso, faz-se necessária a realização de um programa de monitoramento constante nesta região, que é uma área ainda considerada como não impactada pela ação antrópica.

Mercúrio total em Orthopristis ruber (Haemulidae) de quatro regiões costeiras do Estado do Rio de Janeiro, Brasil

O objetivo do presente estudo foi investigar as concentrações de mercúrio total (HgT) nos músculos de Orthopristis ruber de quatro ecossitemas costeiros e identificar possíveis correlações existentes entre comprimento, peso, sexo, estação do ano e índices biológicos. O HgT foi analisado nas regiões de Cabo Frio (CF, n=31), Baía de Guanabara (BG, n=61), Baía de Sepetiba (BS, n=43) e Baía da Ilha Grande (BIG, n=32), as quais apresentam diferentes níveis de degradação ambiental. A BG recebe grande quantidade de efluentes domésticos e industriais de toda região metropolitana do Rio de Janeiro e tem sido considerada como uma das áreas mais poluídas do Brasil. Já na BS, a intensa atividade metalúrgica no seu entorno faz com que esta possa ser tida com nível de degradação intermadiária, enquanto CF e BIG são duas áreas vistas como áreas bem preservadas. As concentrações de HgT foram determinadas através de CV-AAS (FIMS - 400,Perkin Elmer) - utilizando boridreto de sódio como agente redutor. Foi utilizado DORM 3 (National Research Council, Canada) como material de referência (média da recuperação DP =99,2 4,9 %). As concentrações médias de HgT DP para BIG e CF foram, respectivamente, 209,8 118,9 ng/g, e 199,9 88,2 ng/g. Estas regiões apresentaram concentrações significativamente mais elevadas, enquanto a BG mostrou concentrações intermediárias (112,9 88,0 ng/g; ANCOVA, p<0,03). Por outro lado, a BS foi a região com as menores concentrações de HgT (11,3 11,5 ng/g). Tais resultados sugerem que, mesmo sendo áreas degradadas, o HgT não está totalmente biodisponível para BG e BS. Ademais, provavelmente as correntes oceânicas são uma fonte de mercúrio para CF e BIG, carreando mercúrio biodisponível para essas áreas. Para BG análises adicionais foram feitas a fim de identificar a acumulação de HgT ao longo do desenvolvimento ontogenético de O. ruber, uma vez que as concentrações do metal foram maiores em adultos do que em juvenis (PERMANOVA, p< 0,0001). As concentrações de HgT foram positivamente relacionadas tanto com o comprimento (Spearman test; r = 0,85; p <0,001) quanto com o peso (Spearman test; r =0,85; p <0,001) dos peixes da BG, mostrando que o O.ruber acumula HgT ao longo da vida. Diferenças entre sexos foram encontradas apenas para os O. ruber da BIG, onde fêmeas (300 ng/g) apresentaram maiores concentrações de HgT que os machos (~150 ng/g). Dentre os índices biológicos analisados, o índice gonadossomático foi o de maior relevância devido sua correlação negativa entre os níveis de HgT com todos os dados em conjunto (p<0.001), tanto para fêmeas (p<0.001) quanto para machos (p<0.02), sugerindo que o mercúrio pode afetar negativamente a reprodução de O.ruber.

Bioacumulação de mercúrio total (HgT) em tecidos de atuns e afins coletados no Sudeste do Brasil

O mercúrio é um metal pesado que vem sendo reconhecido como um poluente potencialmente perigoso no ecossistema marinho devido à sua alta toxicidade e tendência a sofrer bioacumulação nos organismos e biomagnificação através das teias tróficas, podendo ser encontrado em elevadas concentrações em predadores de topo, como os atuns. O objetivo do presente estudo foi utilizar atuns e afins (Thunnus atlanticus, Thunnus albacares, Katsuwonus pelamis, Euthynnus alletteratus, Coryphaena hippurus e Sarda sarda) como indicadores da disponibilidade de mercúrio total (HgT) nas teias tróficas oceânicas do Rio de Janeiro. Os indivíduos foram coletados no período entre Fevereiro de 2009 a Janeiro de 2010, no desembarque pesqueiro da cidade de Cabo Frio, no Estado do Rio de Janeiro, no Sudeste do Brasil. A determinação das concentrações de mercúrio total foi baseada em Malm et al. (1989) e Bastos et al. (1998). As alíquotas de músculo e fígado foram digeridas através de uma mistura de ácidos e as concentrações de mercúrio total foram determinadas por espectrofotometria a vapor frio (FIMS-400, Perkin-Elmer). A precisão e exatidão dos métodos analíticos foram determinadas utilizando os materiais certificados, DORM-3 e DOLT-4, (NRC, Canadá). Os dados foram analisados estatisticamente através do programa STATISTICS 7.0 for Windows. As concentrações de mercúrio total (HgT) encontradas nos atuns e afins variaram significativamente entre as espécies para o músculo e fígado. As menores concentrações foram registradas em Coryphaena hippurus, (0,008 mg. Kg-1 no músculo e 0,003 mg. Kg-1 no fígado), enquanto as maiores concentrações foram reportadas no músculo de Thunnus atlanticus (1,300 mg. Kg-1) e no fígado de Sarda sarda (2,495 mg. Kg-1). Foram encontradas diferenças significativas entre as concentrações de mercúrio total musculares e hepáticas para Katsuwonus pelamis, Euthynnus alletteratus e Sarda sarda, com as concentrações mais elevadas encontradas no fígado. Além disso, o tamanho e o peso dos indivíduos foram fatores importantes, sendo positivamente correlacionados com as concentrações de mercúrio total em todas as espécies, com exceção das concentrações hepáticas encontradas em Katsuwonus pelamis e Euthynnus alleteratus. Ademais, nove indivíduos mostraram altas concentrações musculares, acima de 0,5 mg.Kg-1, limite máximo estabelecido pela Organização Mundial de Saúde (OMS) em peixes predadores para consumo humano. Estes resultados são preocupantes, uma vez que podem representar potencial risco à saúde. Considerando o mercúrio um micro poluente tóxico, as elevadas concentrações encontradas nesses peixes, podem causar efeitos neles e em seus consumidores. Portanto, é importante um contínuo monitoramento de peixes para auxiliar na sua conservação e permitir identificar quais espécies podem ser consumidas e com qual frequência.

Mercury bioaccumulation in pike (Esox lucius) food chain from Anzali Lagoon, Iran

A number of wide-ranging monitoring studies have been performed in order to estimate the degree of mercury (Hg) contamination in freshwater ecosystems. Knowledge regarding contamination of different levels of the food chain is necessary for estimation of total pollutant input fluxes and subsequent partitioning among different phases in the aquatic system. The growing international concern about this environmental data is closely related to the strongly developing ecological risk assessment activities. In addition,freshwater monitoring outputs hold a key position in the estimation of the Hg dose consumed by the human population as it is highly dependent on fish consumption. So monitoring of Hg in the tissue of edible fish is extremely important because of contaminated fish has caused serious neurological damage to new born babies and adults. Mercury tends to accumulate in fish tissue, particularly, in the form of methyl mercury, which is about 10 times more toxic than inorganic mercury. The Anzali lagoon is one of the biggest wetland of Guilan province, which joins to the Caspian sea. Many Chemical and industrial factories plus agricultural runoffs and urban and rural sewages are major polluting sources of the Anzali wetland. Since many of those polluting sources drain their wastes directly or indirectly into the Anzali wetland and their sewages may be polluted with Hg, this study was conducted to find out the bioaccumulation of Hg bioaccumulation in pike (Esox lucius) food chain from Anzali lagoon, Iran. Sampling were carried out from July 2004 to July 2005, in addition 318 speciments of 9 fish species were collected. T-Hg was measured by LECO AMA 254 Advanced Mercury Analyzer (USA) according to ASTM standard No D-6722. Each sample was analyzed 3 times. Accuracy of T-Hg analysis was checked by running three samples of Standard Reference Materials; SRM 1633b, SRM 2711 & Sra 2709. Detection limit was 0.001 mg/kg in dry weight. The Accuracy degree of analyzor equipment with RSD<%0.05 (N=7) was between %95.5 and %105. In overal eigth fish species were distingushed in the gut content of 87 speciments of pike with age 1-5 year and maximum length 550mm. The max. and min. concentration of T-Hg in dorsal muscle of pjke was 0.2ppm in one year and 1.2ppm in five year class. The mean of T-Hg significantly increased with age and length increased (P<0.05).Mercury accumulation pattern in pike was as well as muscle > liver > spleen (P<0.05). THg content in female was higher than male(P<0.05). In contrast the mean of THg concentration in dorsal muscle of eigth fish species as prey was 0.282, 0.261, 0.328, 0.254, 0.256, 0.286, 0.322 and 0.241 ppm for Carassius auratus gibelio, Hemiculter leucisculus, Blicca bjoerkna transcaucasica, Chalcalburnus mossulensis, Rhodeus sericeus amarus, Gambusia holbrooki, Alburnus charusini hohenackeri & Scardinius Erythrophthalmus respectively.Liner regresion indicated that high degree of relationship between age of pike and Uptak/Intake ratio (R2=%99.12) and indicated that the mercury bioaccumulation in the pike dorsal muscle increased with age increased. BFA was >1 and and indicating the mercury biomagnification in the pike food chain. Trophy level of pike in the Anzali lagoon was estimated as well as 3.5 and 4 . It is generally agreed that Hg concentration in carnivorous fish are higher than in noncarnivorous species.

Phase mismatching analysis of third harmonic generation in BBO crystal

对BBO晶体三次谐波转换过程中相位失配情况进行了研究。当BBO 晶体按Ⅰ类相位匹配(oo→e)进行三次谐波转换时，如果保持基频光正入射，当倍频光从两个相互独立的平面方向(晶体主截面及主截面的垂面)偏离预期方向时，相位失配将出现变化，并且在两个面内的偏离量对转换效率的影响程度不同。我们分别数值模拟了两个方向上的相位失配情况，并给出了谐波转换效率同入射角度偏差的关系。数值模拟结果表明，在主截面内的相位匹配容限角为0.2°，在主截面垂面内的相位匹配容限角为4.5°。同时，开展了实验研究，实验结果与数值模拟结果高度吻合，表明在主截面内的角度偏差对转换效率的影响更大。