Late Replication Domains in Polytene and Non-Polytene Cells of Drosophila melanogaster

In D. melanogaster polytene chromosomes, intercalary heterochromatin (IH) appears as large dense bands scattered in euchromatin and comprises clusters of repressed genes. IH displays distinctly low gene density, indicative of their particular regulation. Genes embedded in IH replicate late in the S phase and become underreplicated. We asked whether localization and organization of these late-replicating domains is conserved in a distinct cell type. Using published comprehensive genome-wide chromatin annotation datasets (modENCODE and others), we compared IH organization in salivary gland cells and in a Kc cell line. We first established the borders of 60 IH regions on a molecular map, these regions containing underreplicated material and encompassing ∼12% of Drosophila genome. We showed that in Kc cells repressed chromatin constituted 97% of the sequences that corresponded to IH bands. This chromatin is depleted for ORC-2 binding and largely replicates late. Differences in replication timing between the cell types analyzed are local and affect only sub-regions but never whole IH bands. As a rule such differentially replicating sub-regions display open chromatin organization, which apparently results from cell-type specific gene expression of underlying genes. We conclude that repressed chromatin organization of IH is generally conserved in polytene and non-polytene cells. Yet, IH domains do not function as transcription- and replication-regulatory units, because differences in transcription and replication between cell types are not domain-wide, rather they are restricted to small “islands” embedded in these domains. IH regions can thus be defined as a special class of domains with low gene density, which have narrow temporal expression patterns, and so displaying relatively conserved organization

Subcortical volumetric abnormalities in bipolar disorder.

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10(-7)) and thalamus (d=-0.148; P=4.27 × 10(-3)) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10(-5)) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.Molecular Psychiatry advance online publication, 9 February 2016; doi:10.1038/mp.2015.227

Sole coloration as an unusual aposematic signal in a Neotropical toad

Many animals have evolved remarkable strategies to avoid predation. In diurnal, toxic harlequin toads (Atelopus) from the Amazon basin, we find a unique colour signal. Some Atelopus populations have striking red soles of the hands and feet, visible only when walking. When stationary, the toads are hard to detect despite their yellow-black dorsal coloration. Consequently, they switch between high and low conspicuousness. Interestingly, some populations lack the extra colour display of the soles. We found comprehensive support that the red coloration can act as an aposematic signal directed towards potential predators: red soles are significantly more conspicuous than soles lacking red coloration to avian predators and the presence of the red signal significantly increases detection. Further, toads with red soles show bolder behaviour by using higher sites in the vegetation than those lacking this signal. Field experiments hint at a lower attack risk for clay models with red soles than for those lacking the signal, in a population where the red soles naturally occur. We suggest that the absence of the signal may be explained by a higher overall attack risk or potential differences of predator community structure between populations. © 2019, The Author(s)

Effects of a balanced translocation between chromosomes 1 and 11 disrupting the DISC1 locus on white matter integrity

Objective Individuals carrying rare, but biologically informative genetic variants provide a unique opportunity to model major mental illness and inform understanding of disease mechanisms. The rarity of such variations means that their study involves small group numbers, however they are amongst the strongest known genetic risk factors for major mental illness and are likely to have large neural effects. DISC1 (Disrupted in Schizophrenia 1) is a gene containing one such risk variant, identified in a single Scottish family through its disruption by a balanced translocation of chromosomes 1 and 11; t(1;11) (q42.1;q14.3). Method Within the original pedigree, we examined the effects of the t(1;11) translocation on white matter integrity, measured by fractional anisotropy (FA). This included family members with (n = 7) and without (n = 13) the translocation, along with a clinical control sample of patients with psychosis (n = 34), and a group of healthy controls (n = 33). Results We report decreased white matter integrity in five clusters in the genu of the corpus callosum, the right inferior fronto-occipital fasciculus, acoustic radiation and fornix. Analysis of the mixed psychosis group also demonstrated decreased white matter integrity in the above regions. FA values within the corpus callosum correlated significantly with positive psychotic symptom severity. Conclusions We demonstrate that the t(1;11) translocation is associated with reduced white matter integrity in frontal commissural and association fibre tracts. These findings overlap with those shown in affected patients with psychosis and in DISC1 animal models and highlight the value of rare but biologically informative mutations in modeling psychosis

Lender learning and entry under general demand uncertainty

Entry, Information, Learning, Contracts, D4, D8,

Efeitos de diferentes esforços de luta de judô na atividade enzimática, atividade elétrica muscular e parâmetros biomecânicos de atletas de elite Los efectos de diferentes esfuerzos de lucha del judo en la actividad enzimática, actividad eléctrica muscular y biomecánica de los parámetros de atletas de élite Effects of different strengths in the judo fights, muscular electrical activity and biomechanical parameters in elite athletes

O treinamento esportivo provoca adaptações neuromusculares e alterações metabólicas visando a performance durante a competição. Nas competições de judô, o número de lutas a que os atletas são submetidos e suas respectivas durações e intervalos são aleatórios, fatores que podem influenciar a performance objetivada no treinamento. O presente estudo investigou a hipótese de que diferentes durações de lutas, 90s, 180s e 300s, poderiam influenciar a atividade enzimática, elétrica muscular e a produção do pico de torque. Antes e após cada luta, foram coletadas amostras sanguíneas dos atletas; em seguida, os mesmos realizaram cinco contrações dinâmicas (90º/s) com a utilização de um dinamômetro isocinético (Biodex System 3). Simultaneamente registrou-se o sinal eletromiográfico dos músculos agonista, antagonista e sinergista do movimento avaliado. Não se verificou alteração no torque. As enzimas AST e ALT apresentaram aumento na atividade, nas lutas de 90s (p = 0,0033/p = 0,00059), 180s (p = 0,0044/p = 0,0033) e 300s (p = 0,0044/p = 0,0033). Aumento (p = 0,0180) da atividade da CK após a luta de 300s foi verificado. A LDH diminuiu após a luta de 90s (p = 0,0392). Na análise intermuscular observou-se após a luta de 90s aumento do sinal eletromiográfico do agonista (p = 0,005); na luta de 180s, aumento do antagonista (p = 0,0129) e na luta de 300s, diminuição (p = 0,0137) da atividade do músculo agonista. Observou-se que os esforços da luta de 300s podem ter induzido lesões no tecido muscular caracterizadas pela elevação da CK plasmática, embora a lesão não tenha sido suficiente para detectar fadiga através da dinamometria isocinética. Conclui-se que o protocolo proposto foi suficiente para alteração enzimática e eletromiográfica, sugerindo adaptações metabólicas e neurais a partir do estresse das lutas de judô.<br>El entrenamiento deportivo provoca adaptaciones neuromusculares y alteraciones metabólicas que buscan una actuación durante la competición. En las competencias de judo, el número de luchas a que los atletas se someten así como la duración respectiva y los intervalos son al azar, factores estos que influencian en la actuación y en el entrenamiento. El estudio presente investigó la hipótesis de que las duraciones diferentes de luchas, 90s 180s y 300s, podrían influir en la actividad enzimático, eléctrico muscular y la producción del pico del cambio. Antes y después de cada lucha, fueron obtenidas las muestras sanguíneas de los atletas, tan pronto después de que los mismos lograron cinco reducciones dinámicas (90º/s) con el uso de un dinamômetro isocinético (Biodex Sistema 3). Simultáneamente se consignaron la señal electromiográfica de los músculos agonistas, antagonistas y sinérgica de los movimientos estimados. El estudio no verificó si hubo una alteración en el torque. Las enzimas AST y ALT presentaran aumento en la actividad, en las luchas de 90s (p = 0,0033/p = 0,00059), 180s (p = 0,0044/p = 0,0033) y 300s (p = 0,0044/p = 0,0033). Un aumento (p = 0,0180) de la actividad de CK después de que la lucha de 300s fue verificada. LDH disminuyó después de la lucha de 90s (p = 0,0392). En el análisis intermuscular se observó después de la lucha 90s un aumento de la señal electromiográfica del agonista (p = 0,005), en la lucha 180s un aumento de la del antagonista (p = 0,0129) y en la lucha 300s una disminución (p = 0,0137) de la actividad del músculo agonista. Fue observado, además, que los esfuerzos de la lucha de 300s podrían haber inducido lesiones en el tejido muscular caracterizado por una elevación de CK plasmático, aunque la lesión no ha sido bastante para descubrir la fatiga a través de la dinamometría isocinética. Ha mostrado que el protocolo propuesto era bastante para determinar las alteraciones enzimáticas y eletromiográficas, mientras hace pensar en las adaptaciones metabólicas y neurológicas que ocurren por la tensión de las luchas del judo.<br>The sportive training causes neuromuscular adaptations and metabolic alterations aiming the competition performance. In judo competitions, the number of fights to what athletes are submitted, as well as their respective endurance and intervals are randomized, and these factors may influence the aimed training performance. This study investigated the hypothesis that different fight endurances, 90s, 180s, and 300s could influence the enzymatic and muscular electrical activity, as well as the torque peak production. Before and after each fighting, a blood sampling was collected from each athlete. After and before each fight, they performed five dynamic contractions (90º/s) using an isokinetic Dynamometer (Biodex System 3). Simultaneously, it was recorded the electromyographic signal of the agonist, antagonist and synergistic muscles of the movement assessed. It was observed no alterations in the torque. The AST and ALT enzymes presented an increasing activity in the 90 sec. (p = 0.0033/p = 0.00059), 180 sec. (p = 0.0044/p = 0.0033), and in the 300 sec. (p = 0.0044/p = 0.0033) fights. It was verified an increase (p = 0.0180) in the CK activity after the 300 sec. fight. LDH decreased after the 90 sec. fight (p = 0.0392). Upon the intermuscular analysis, it was observed an increase in the electromyographic signal of the agonist muscle after the 90 sec. fight (p = 0.005), an increase of the antagonist muscle in the 180 sec. fight (p = 0.0129), and a decrease (p = 0.0137) in the activity of the agonist muscle in the 300 sec. fight. It was observed that the strength in the 300 sec. fight might reduced the injuries in the muscular tissue characterized by a raise in the plasmatic CK, although the injury was not sufficient to detect the fatigue through the isokinetic dynamometry. It can be concluded that the proposed protocol was sufficient to the enzymatic and electromyographic alteration, suggesting metabolic and neural adaptations from stress caused by the judo fights