The Mitragyna speciosa (Kratom) Genome: a resource for data-mining potent pharmaceuticals that impact human health

Mitragyna speciosa (kratom) produces numerous compounds with pharmaceutical properties including the production of bioactive monoterpene indole and oxindole alkaloids. Using a linked-read approach, a 1,122,519,462 bp draft assembly of M. speciosa “Rifat” was generated with an N50 scaffold size of 1,020,971 bp and an N50 contig size of 70,448 bp that encodes 55,746 genes. Chromosome counting revealed that “Rifat” is a tetraploid with a base chromosome number of 11, which was further corroborated by orthology and syntenic analysis of the genome. Analysis of genes and clusters involved in specialized metabolism revealed genes putatively involved in alkaloid biosynthesis. Access to the genome of M. speciosa will facilitate an improved understanding of alkaloid biosynthesis and accelerate the production of bioactive alkaloids in heterologous hosts

PCDH10 Promoter Hypermethylation is Frequent in most Histologic Subtypes of Mature Lymphoid Malignancies and Occurs Early in Lymphomagenesis

PCDH10 is epigenetically inactivated in multiple tumor types; however, studies in mature lymphoid malignancies are limited. Here, we have investigated the presence of promoter hypermethylation of the PCDH10 gene in a large cohort of well-characterized subsets of lymphomas. PCDH10 promoter hypermethylation was identified by methylation-specific PCR in 57 to 100% of both primary B- and T-cell lymphoma specimens and cell lines. These findings were further validated by Sequenom Mass-array analysis. Promoter hypermethylation was also identified in 28.6% cases of reactive follicular hyperpla- sia, more commonly occurring in states of immune deregulation and associated with rare presence of clonal karyotypic aberrations, suggesting that PCDH10 methylation occurs early in lymphomagenesis. PCDH10 expression was down regu- lated via promoter hypermethylation in T- and B-cell lymphoma cell lines. The transcriptional down-regulation resulting from PCDH10 methylation could be restored by pharmacologic inhibition of DNA methyltransferases in cell lines. Both T- and B-cell lymphoma cell lines harboring methylation-mediated inactivation of PCDH10 were resistant to doxorubicin treatment, suggesting that hypermethylation of this gene might contribute to chemotherapy response

La Citometría de flujo en el análisis citómico: in vivo, in vitro, ¿in fluxo?

La Citometría de flujo en el análisis citómico: in vivo, in vitro, ¿in fluxo

Values clarification in a decision aid about fertility preservation: does it add to information provision?

Background We aimed to evaluate the effect of a decision aid (DA) with information only compared to a DA with values clarification exercise (VCE), and to study the role of personality and information seeking style in DA-use, decisional conflict (DC) and knowledge. Methods Two scenario-based experiments were conducted with two different groups of healthy female participants. Dependent measures were: DC, knowledge, and DA-use (time spent, pages viewed, VCE used). Respondents were randomized between a DA with information only (VCE-) and a DA with information plus a VCE(VCE+) (experiment 1), or between information only (VCE-), information plus VCE without referral to VCE(VCE+), and information plus a VCE with specific referral to the VCE, requesting participants to use the VCE(VCE++) (experiment 2). In experiment 2 we additionally measured personality (neuroticism/conscientiousness) and information seeking style (monitoring/blunting). Results Experiment 1. There were no differences in DC, knowledge or DA-use between VCE- (n=70) and VCE+ (n=70). Both DAs lead to a mean gain in knowledge from 39% at baseline to 73% after viewing the DA. Within VCE+, VCE-users (n=32, 46%) reported less DC compared to non-users. Since there was no difference in DC between VCE- and VCE+, this is likely an effect of VCE-use in a self-selected group, and not of the VCE per se. Experiment 2. There were no differences in DC or knowledge between VCE- (n=65), VCE+ (n=66), VCE++ (n=66). In all groups, knowledge increased on average from 42% at baseline to 72% after viewing the DA. Blunters viewed fewer DA-pages (R=0.38, p<.001). More neurotic women were less certain (R=0.18, p<.01) and felt less supported in decision making (R=0.15, p<.05); conscientious women felt more certain (R=-0.15, p<.05) and had more knowledge after viewing the DA (R=0.15, p<.05). Conclusions Both DAs lead to increased knowledge in healthy populations making hypothetical decisions, and use of the VCE did not improve knowledge or DC. Personality characteristics were associated to some extent with DA-use, information seeking styles with aspects of DC. More research is needed to make clear recommendations regarding the need for tailoring of information provision to personality characteristics, and to assess the effect of VCE use in actual patients

A conceptual approach to enhance the well-being of elderly people

The number of elderly people living alone is increasing. Consequently, a lot of research works have been addressing this issue in order to propose solutions that can enhance the quality of life of elderly people. Most of them have been concerned in dealing with objective issues such as forgetfulness or detecting falls. In this paper, we propose a conceptual approach of a system that intends to enhance the daily sense of user’s well-being. For that, our proposal consists in a system that works as a social network and a smartwatch application that works unobtrusively and collects the user’s physiological data. In addition, we debate how important features such as to detect user’s affective states and to potentiate user’s memory could be implemented. Our study shows that there are still some important limitations which affect the success of applications built in the context of elderly care and which are mostly related with accuracy and usability of this kind of system. However, we believe that with our approach we will be able to address some of those limitations and define a system that can enhance the well-being of elderly people and improve their cognitive capabilities.The work presented in this paper has been developed under the EUREKA - ITEA3 Project PHE (PHE-16040), and by National Funds through FCT (Fundação para a Ciência e a Tecnologia) under the projects UID/EEA/00760/2019 and UID/CEC/00319/2019 and by NORTE-01-0247-FEDER-033275 (AIRDOC - “Aplicação móvel Inteligente para suporte individualizado e monitorização da função e sons Respiratórios de Doentes Obstrutivos Crónicos ”) by NORTE 2020 (Programa Operacional Regional do Norte)

Comparative analysis of bones, mites, soil chemistry, nematodes and soil micro-Eukaryotes from a suspected homicide to estimate the post-mortem interval

Criminal investigations of suspected murder cases require estimating the post-mortem interval (PMI, or time after death) which is challenging for longer periods. Here we present the case of human remains found in a Swiss forest. We have used a multidisciplinary approach involving the analysis of bones, soil chemical characteristics, mites and nematodes (by microscopy) and micro-Eukaryotes (by Illumina high throughput sequencing). We analysed soil samples collected beneath the remains of the head, upper and lower body and “control” samples taken a few meters away. The PMI estimated on hair 14C-data via bomb peak radiocarbon dating gave a time range of 1 to 2 years before the finding of the remains on site. Cluster analyses for chemical constituents, nematodes, mites and micro- Eukaryotes revealed two clusters 1) head and upper body and 2) lower body and controls. From mite evidence, we conclude that the body was likely to have been brought to the site after death. However, chemical analyses, nematode community analyses and the analyses of micro-Eukaryotes indicate that decomposition took place at least partly on site. This study illustrates the usefulness of combining several lines of evidence for the study of homicide cases to better calibrate PMI inference tools

Realist ethical naturalism for ethical non-naturalists

It is common in metaethics today to draw a distinction between “naturalist” and “non-naturalist” versions of moral realism, where the former view maintains that moral properties are natural properties, while the latter view maintains that they are non-natural properties instead. The nature of the disagreement here can be understood in different ways, but the most common way is to understand it as a metaphysical disagreement. In particular, the disagreement here is about the reducibility of moral properties, where the “naturalists” maintain that moral properties are in some way reducible to the lower-level natural properties on which they supervene, while the “non-naturalists” maintain that moral properties are sui generis and robustly irreducible. In this paper I present a novel version of realist ethical naturalism—a view that I call Emergentist Ethical Naturalism—that reveals this common way of understanding the distinction between naturalism and non-naturalism to be flawed by combining a commitment to ethical naturalism with a commitment to the sui generis and irreducible nature of moral properties that typically defines non-naturalism. Then, after presenting the theory and addressing a few worries that one might have about it, I show how it offers some novel, emergence-based responses to the various supervenience challenges that plague moral realism and thereby gives the ethical naturalist a robustly non-reductive option for dealing with these challenges

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13