X-ray He-like ions diagnostics: New Computations for Photoionized Plasmas: I. preliminary considerations

Using the new version of the photoionization code Titan designed for plane-parallel photoionized thick hot media, which is unprecedented from the point of view of line transfer, we have undertaken a study of the influence of different parameters on the He-like and H-like emission of a medium photoionized by an X-ray source. We explain why in modelling the emitting medium it is important to solve in a self-consistent way the thermal and ionization equilibria and to take into account the interconnection between the different ions. We give the equivalent widths of the sum of the He-like triplets and the triplet intensity ratios $G$ and $R$, for the most important He-like ions, for a range of density, column density, and ionization parameter, in the case of constant density media. We show that the line intensities from a given ion can be accounted for, either by small values of both the column density and of the ionization parameter, or by large values of both quantities, and it is necessary to take into account several ions to disentangle these possibilities. We show also that a "pure recombination spectrum" almost never exists in a photoionized medium: either it is thin, and resonance lines are formed by radiative excitation, or it is thick, and free-bound absorption destroys the resonance photons as they undergo resonant diffusion.Comment: 19 pages, 14 figures, accepted in A &

Genetic Analysis of Genome-Scale Recombination Rate Evolution in House Mice

The rate of meiotic recombination varies markedly between species and among individuals. Classical genetic experiments demonstrated a heritable component to population variation in recombination rate, and specific sequence variants that contribute to recombination rate differences between individuals have recently been identified. Despite these advances, the genetic basis of species divergence in recombination rate remains unexplored. Using a cytological assay that allows direct in situ imaging of recombination events in spermatocytes, we report a large (∼30%) difference in global recombination rate between males of two closely related house mouse subspecies (Mus musculus musculus and M. m. castaneus). To characterize the genetic basis of this recombination rate divergence, we generated an F2 panel of inter-subspecific hybrid males (n = 276) from an intercross between wild-derived inbred strains CAST/EiJ (M. m. castaneus) and PWD/PhJ (M. m. musculus). We uncover considerable heritable variation for recombination rate among males from this mapping population. Much of the F2 variance for recombination rate and a substantial portion of the difference in recombination rate between the parental strains is explained by eight moderate- to large-effect quantitative trait loci, including two transgressive loci on the X chromosome. In contrast to the rapid evolution observed in males, female CAST/EiJ and PWD/PhJ animals show minimal divergence in recombination rate (∼5%). The existence of loci on the X chromosome suggests a genetic mechanism to explain this male-biased evolution. Our results provide an initial map of the genetic changes underlying subspecies differences in genome-scale recombination rate and underscore the power of the house mouse system for understanding the evolution of this trait

INVENTÁRIO E DIAGNÓSTICO DA ARBORIZAÇÃO URBANA VIÁRIA DE RIO BRANCO, AC

O presente trabalho foi desenvolvido dentro do perímetro urbano da cidade de Rio BrancoAC, localizada entre as coordenadas geográficas de 9°58’29’’ de latitude sul e 67°48’36’’ de longitude oeste. Teve como objetivo geral o levantamento e diagnóstico da arborização viária. A metodologia estatística utilizada foi definida tomando-se como unidade amostral o quarteirão. Encontrou-se pouquíssimos espécimes nas calçadas dos quarteirões amostrados, totalizando 292 indivíduos distribuídos por 39 espécies, sendo 11 nativas e 28 exóticas. A média por quarteirão foi de 1,83 árvores, e por quilômetro de calçada foi de 4,57 árvores. Concluiu-se que o número de árvores existentes nas calçadas foi muito pequeno, tendo-se como referência 100 árvores por quilômetro de calçada como ideal. A maioria das espécies encontrada era exótica (78,57%), a despeito da cidade encontrar-se numa região com uma das maiores diversidades de espécies arbóreas do planeta. Quanto ao estado físico, a copa normal foi predominante, exceto na região central. As recomendações indicadas foram primeiramente de se elaborar um plano de arborização urbana para o município, contendo referências técnicas para escolha das espécies, técnicas de manejo e programa de educação ambiental

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Human pharmacology of positive GABA-A subtype-selective receptor modulators for the treatment of anxiety

Anxiety disorders arise from disruptions among the highly interconnected circuits that normally serve to process the streams of potentially threatening stimuli. The resulting imbalance among these circuits can cause a fundamental misinterpretation of neural sensory information as threatening and can lead to the inappropriate emotional and behavioral responses observed in anxiety disorders. There is considerable preclinical evidence that the GABAergic system, in general, and its alpha 2-and/or alpha 5-subunitcontaining GABA(A) receptor subtypes, in particular, are involved in the pathophysiology of anxiety disorders. However, the clinical efficacy of GABA-A alpha 2-selective agonists for the treatment of anxiety disorders has not been unequivocally demonstrated. In this review, we present several human pharmacological studies that have been performed with the aim of identifying the pharmacologically active doses/exposure levels of several GABA-A subtype-selective novel compounds with potential anxiolytic effects. The pharmacological selectivity of novel alpha 2-subtype-selective GABA(A) receptor partial agonists has been demonstrated by their distinct effect profiles on the neurophysiological and neuropsychological measurements that reflect the functions of multiple CNS domains compared with those of benzodiazepines, which are nonselective, full GABA(A) agonists. Normalizing the undesired pharmacodynamic side effects against the desired on-target effects on the saccadic peak velocity is a useful approach for presenting the pharmacological features of GABA(A)-ergic modulators. Moreover, combining the anxiogenic symptom provocation paradigm with validated neurophysiological and neuropsychological biomarkers may provide further construct validity for the clinical effects of novel anxiolytic agents. In addition, the observed drug effects on serum prolactin levels support the use of serum prolactin levels as a complementary neuroendocrine biomarker to further validate the pharmacodynamic measurements used during the clinical pharmacological study of novel anxiolytic agents.Stress-related psychiatric disorders across the life spa