Synthesis and antioxidant activity of new xanthone-type compounds

3rd Portuguese Meeting on Medicinal Chemistry and 1st Portuguese-Spanish-Brazilian Meeting on Medicinal Chemistry, Aveiro, 28-30 Novembro 2012.Owing to our continuing interest in the synthesis of novel oxygen heterocycles we have recently developed a unique synthetic procedure towards the synthesis of new xanthenodiones (2)[5] and extend the work to their aromatization into xanthones (3). Our aim was also to obtain new derivatives with potential biological activities, therefore their ability to scavenge the DPPH radical and to reduce iron(III) were also evaluated. In the present communication we will present and discussed our last results on the synthetic and potential application of xanthones (3).Thanks are due to the University of Aveiro, Fundação para a Ciência e a Tecnologia (FCT) and FEDER for funding the Organic Chemistry Research Unit (project PEst-C/QUI/UI0062/2011). We are also grateful to the Portuguese National NMR Network (RNRMN) supported with funds from FCT

Xanthenedione derivatives, new promising antioxidant and acetylcholinesterase inhibitor agents

Natural and synthetic xanthone derivatives are well-known for their ability to act as antioxidants and/or enzyme inhibitors. This paper aims to present a successful synthetic methodology towards xanthenedione derivatives and the study of their aromatization to xanthones. Additionally their ability to reduce Fe(III), to scavenge DPPH radicals and to inhibit AChE was evaluated. The results demonstrated that xanthenedione derivative 5e, bearing a catechol unit, showed higher reduction capacity than BHT and similar to quercetin, strong DPPH scavenging activity (EC50 = 3.79 ± 0.06 μM) and it was also showed to be a potent AChEI (IC50 = 31.0 ± 0.09 μM) when compared to galantamine (IC50 = 211.8 ± 9.5 μM)

Development and psychometric evaluation of an observational coding system measuring person-centred care in spouses of people with dementia

YesBackground: The notion of person-centered care has been important in investigating relationships between people with dementia and paid carers, and measures are available to assess this. It has been suggested that person-centered care may be a useful construct to apply to understand family-care relationships. However, no measures of person-centered care in this context exist. The study aimed to develop an observational measure of person-centered care for this purpose. Method: First, a coding system incorporating a range of behaviors that could be considered person-centered or non-person-centered was constructed. Examples included a code relating to whether the person with dementia was involved in planning a task, and a code relating to how the spouse responded to confusion/distress. Second, 11 couples, where one partner had a dementia, were recruited and videotaped cooperating on an everyday task. The system was applied to the care-giving spouse's behaviors, labeling examples of behavior as person-centered or non-person-centered. The final step involved assessing the inter-rater reliability of the system. Results: The system captured nine categories of behavior, which were each divided into person-centered and non-person-centered types. The system had good reliability (Cohen's κ coefficients were: 0.65 for category and whether behaviors needed to be placed in a category; 0.81 for category excluding the decision about whether behaviors needed to be placed in a category; and 0.79 in relation to whether behaviors were person-centered or non-person-centered.) Conclusions: Although the small sample size limits the implications of the results, the system is a promising quantitative measure of spousal person-centered care

Aedes fluviatilis cell lines as new tools to study metabolic and immune interactions in mosquito‑Wolbachia symbiosis

In the present work, we established two novel embryonic cell lines from the mosquito Aedes fluviatilis containing or not the naturally occurring symbiont bacteria Wolbachia, which were called wAflu1 and Aflu2, respectively. We also obtained wAflu1 without Wolbachia after tetracycline treatment, named wAflu1.tet. Morphofunctional characterization was performed to help elucidate the symbiont-host interaction in the context of energy metabolism regulation and molecular mechanisms of the immune responses involved. The presence of Wolbachia pipientis improves energy performance in A. fluviatilis cells; it affects the regulation of key energy sources such as lipids, proteins, and carbohydrates, making the distribution of actin more peripheral and with extensions that come into contact with neighboring cells. Additionally, innate immunity mechanisms were activated, showing that the wAflu1 and wAflu1.tet cells are responsive after the stimulus using Gram negative bacteria. Therefore, this work confirms the natural, mutually co-regulating symbiotic relationship between W. pipientis and A. fluviatilis, modulating the host metabolism and immune pathway activation. The results presented here add important resources to the current knowledge of Wolbachia-arthropod interactions

The role of crustal and eruptive processes versus source variations in controlling the oxidation state of iron in Central Andean magmas

The composition of the continental crust is closely tied to subduction zone magmatism. Elevated oxygen fugacity (fO₂) plays a central role in fostering crystallization of oxide minerals and thereby aids in generating the calc-alkaline trend of iron depletion that characterizes the continents. Along continental margins, arc magmas erupt through continental crust and often undergo extensive differentiation that may modify magmatic fO₂. The importance of the subducting slab and mantle wedge relative to the effects of this differentiation on the fO₂ recorded by continental arc magmas remains relatively unconstrained. Here, we focus on the effect of differentiation on magmatic fO₂ using a suite of 14 samples from the Central Volcanic Zone (CVZ) of the Andes where the continental crust is atypically thick (60–80 km). The samples range in composition from ∼55 to 74 wt% SiO₂ and represent the Neogene history of the arc. Samples are basaltic andesite to rhyolite and span a range of radiogenic isotopic compositions (⁸⁷Sr/⁸⁶Sr = ∼0.705–0.712) that represent 30 to 100% crustal assimilation. We use several proxies to estimate the fO₂ recorded by lavas, pumice, and scoria: (1) whole rock Fe³⁺/ΣFe ratios, (2) Fe³⁺+/ΣFe ratios in quartz-hosted melt inclusions, and (3) Fe–Ti oxide oxygen-barometry. Comparison of the fO₂ calculated from bulk Fe³⁺/ΣFe ratios (post-eruptive) with that derived from Fe–Ti oxides or melt inclusion Fe³⁺/ΣFe ratios (pre-eruptive), enables us to quantify the effect of syn- or post-eruptive alteration, and to select rocks for bulk analysis appropriate for the determination of pre-eruptive magmatic fO₂ using a strict criterion developed here. Across our sample suite, and in context with samples from the literature, we do not find evidence for systematic oxidation due to crystal fractionation or crustal contamination. Less evolved samples, ranging from 55 to 61 wt% SiO₂, record a range of >3 orders of magnitude in fO₂, spanning the fO₂ range recorded by all samples in our suite. Among these less evolved magmas, we find that those erupted from volcanic centers located closer to the trench, closer to the Benioff Zone, and with more geochemical evidence of subducted components in the mantle source (elevated La/Nb) result in magmas that record systematically higher fO₂. We conclude that the slab/mantle source can exert greater control on magmatic fO₂ than processes occurring in even the thickest continental crust. Thus, the fO₂ of arc magmas, and hence their calc-alkaline nature, may be inherited from the mantle.Keywords: oxygen fugacity, wet chemistry, subduction, crustal assimilation, Central Andean volcanic zoneKeywords: oxygen fugacity, wet chemistry, subduction, crustal assimilation, Central Andean volcanic zon

Full genome sequence and sfRNA interferon antagonist activity of Zika virus from Recife, Brazil

Background: The outbreak of Zika virus (ZIKV) in the Americas has transformed a previously obscure mosquito-transmitted arbovirus of the Flaviviridae family into a major public health concern. Little is currently known about the evolution and biology of ZIKV and the factors that contribute to the associated pathogenesis. Determining genomic sequences of clinical viral isolates and characterization of elements within these are an important prerequisite to advance our understanding of viral replicative processes and virus-host interactions. Methodology/Principal findings: We obtained a ZIKV isolate from a patient who presented with classical ZIKV-associated symptoms, and used high throughput sequencing and other molecular biology approaches to determine its full genome sequence, including non-coding regions. Genome regions were characterized and compared to the sequences of other isolates where available. Furthermore, we identified a subgenomic flavivirus RNA (sfRNA) in ZIKV-infected cells that has antagonist activity against RIG-I induced type I interferon induction, with a lesser effect on MDA-5 mediated action. Conclusions/Significance: The full-length genome sequence including non-coding regions of a South American ZIKV isolate from a patient with classical symptoms will support efforts to develop genetic tools for this virus. Detection of sfRNA that counteracts interferon responses is likely to be important for further understanding of pathogenesis and virus-host interactions

Ancient bears provide insights into Pleistocene ice age refugia in Southeast Alaska

During the Late Pleistocene, major parts of North America were periodically covered by ice sheets. However, there are still questions about whether ice-free refugia were present in the Alexander Archipelago along the Southeast (SE) Alaska coast during the last glacial maximum (LGM). Numerous subfossils have been recovered from caves in SE Alaska, including American black (Ursus americanus) and brown (U. arctos) bears, which today are found in the Alexander Archipelago but are genetically distinct from mainland bear populations. Hence, these bear species offer an ideal system to investigate long-term occupation, potential refugial survival and lineage turnover. Here, we present genetic analyses based on 99 new complete mitochondrial genomes from ancient and modern brown and black bears spanning the last ~45,000 years. Black bears form two SE Alaskan subclades, one preglacial and another postglacial, that diverged \u3e100,000 years ago. All postglacial ancient brown bears are closely related to modern brown bears in the archipelago, while a single preglacial brown bear is found in a distantly related clade. A hiatus in the bear subfossil record around the LGM and the deep split of their pre-and postglacial subclades fail to support a hypothesis of continuous occupancy in SE Alaska throughout the LGM for either species. Our results are consistent with an absence of refugia along the SE Alaska coast, but indicate that vegetation quickly expanded after deglaciation, allowing bears to recolonize the area after a short-lived LGM peak

Immune-inspired optimization with autocorrentropy function for blind inversion of wiener systems

Blind inversion of nonlinear systems is a complex task that requires some sort of prior information about the source e.g. whether it is composed of independent samples or, particularly in this work, a dependence “signature” which is assumed to be known via the autocorrentropy function. Furthermore, it involves the solution of a nonlinear, multimodal optimization problem to determine the parameters of the inverse model. Thus, we propose a blind method for Wiener systems inversion, which is composed of a correntropy-based criterion in association to the well-known CLONALG immune-inspired optimization metaheuristic. The empirical results validate the methodology for continuous and discrete signals

Do Sleep Disturbances Predict or Moderate the Response to Psychotherapy in Bipolar Disorder?

This study examined whether sleep disturbance predicted or moderated responses to psychotherapy in participants who participated in STEP-BD, a national, multi-site study that examined the effectiveness of different treatment combinations for bipolar disorder. Participants received either a brief psychosocial intervention called collaborative care (CC; n=130), or intensive psychotherapy (IP; n=163), with study-based pharmacotherapy. Participants (N=243) were defined as current (past week) short sleepers (<6 hours/night), normal sleepers (6.5-8.5 hours/night), and long sleepers (≥9 hours/night), according to reported average nightly sleep duration the week before randomization. Sleep disturbances did not predict the likelihood of recovery nor time until recovery from a depressive episode. There was no difference in recovery rates between IP versus CC for normal sleepers, and medium effect sizes were observed for differences in short and long sleepers. In this study, sleep did not play a major role in predicting or moderating response to psychotherapy in bipolar disorder