Efficient allelic-drive in Drosophila.

Gene-drive systems developed in several organisms result in super-Mendelian inheritance of transgenic insertions. Here, we generalize this "active genetic" approach to preferentially transmit allelic variants (allelic-drive) resulting from only a single or a few nucleotide alterations. We test two configurations for allelic-drive: one, copy-cutting, in which a non-preferred allele is selectively targeted for Cas9/guide RNA (gRNA) cleavage, and a more general approach, copy-grafting, that permits selective inheritance of a desired allele located in close proximity to the gRNA cut site. We also characterize a phenomenon we refer to as lethal-mosaicism that dominantly eliminates NHEJ-induced mutations and favors inheritance of functional cleavage-resistant alleles. These two efficient allelic-drive methods, enhanced by lethal mosaicism and a trans-generational drive process we refer to as "shadow-drive", have broad practical applications in improving health and agriculture and greatly extend the active genetics toolbox

LABORATÓRIO DE EXERGAMES: UM ESPAÇO COMPLEMENTAR PARA AS AULAS DE EDUCAÇÃO FÍSICA

This paper presents a study about the use of exergames in structured Physical Education (PE) classes with students that usually show signs of dissatisfaction with sports activities proposed at regular PE classes. While videogames have been historically associated with issues related to obesity and social introversion, exergames brought a new perspective on those cultural artifacts. Twenty-four 8-14-year-old students participated in the study conducted in a laboratory set up in a school in Southern Brazil. They were observed and their PE teachers were also interviewed at the end of project. Results showed that students that usually did not show interest in Physical Education classes started to demonstrate a positive attitude regarding exergame practices, also expressing willingness to cooperate with their peers. Este artículo presenta un estudio sobre el uso de exergames en prácticas estructuradas en clases de Educación Física con estudiantes que generalmente presentan señales de insatisfacción frente a las actividades deportivas propuestas en las clases regulares de la asignatura. Mientras los videojuegos han sido históricamente asociados a problemas como obesidad e introversión social, los exergames han traído una nueva perspectiva para esos artefactos culturales. Veinticuatro alumnos entre ocho y catorce años de edad han participado en este estudio, desarrollado en un laboratorio organizado en una escuela en el sur de Brasil. Los estudiantes fueron observados y sus profesores de Educación Física entrevistados al final del proyecto. Como resultado, fue posible observar que los estudiantes que normalmente no mostraban interés por las clases de Educación Física, pasaron a presentar una actitud positiva en relación a las prácticas con los exergames, evidenciando también su disposición de colaborar con sus compañeros. Este artigo apresenta um estudo sobre o uso de exergames em práticas estruturadas em aulas de Educação Física envolvendo estudantes que geralmente apresentam sinais de insatisfação com atividades esportivas propostas nas aulas regulares da disciplina. Enquanto os videogames foram historicamente associados a problemas como obesidade e introversão social, os exergames trouxeram uma nova perspectiva para esses artefatos culturais. Vinte e quatro alunos entre oito e 14 anos de idade participaram do estudo, realizado em um laboratório criado em uma escola no sul do Brasil. Os alunos foram observados e seus professores de Educação Física entrevistados ao final do projeto. Como resultado, foi possível observar que os estudantes que normalmente não demonstravam interesse pelas aulas de Educação Física passaram a apresentar uma atitude positiva em relação às práticas com os exergames, evidenciando também sua disposição em colaborar com os colegas.

Exergames experience in physical education : a review

Exergames are consoles that require a higher physical effort to play when compared to traditional video games. Active video games, active gaming, interactive games, movement-controlled video games, exertion games, and exergaming are terms used to define the kinds of video games in which the exertion interface enables a new experience. Exergames have added a component of physical activity to the otherwise motionless video game environment and have the potential to contribute to physical education classes by supplementing the current activity options and increasing student enjoyment. The use of exergames in schools has already shown positive results in the past through their potential to fight obesity. As for the pedagogical aspects of exergames, they have attracted educators’ attention due to the large number of games and activities that can be incorporated into the curriculum. In this way, the school must consider the development of a new physical education curriculum in which the key to promoting healthy physical activity in children and youth is enjoyment, using video games as a tool. In this context, the aim is to conduct a brief review of the use of exergames in physical education curriculum, exploring school curriculum, digital culture, and motivation and enjoyment for the learning processes in the video game environmen

Clinical Utility of Circulating Tumour Cell Androgen Receptor Splice Variant-7 Status in Metastatic Castration-resistant Prostate Cancer.

Abstract Background Detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumour cells (CTCs) is associated with worse outcome in metastatic castration-resistant prostate cancer (mCRPC). However, studies rarely report comparisons with CTC counts and biopsy AR-V7 protein expression. Objective To determine the reproducibility of AdnaTest CTC AR-V7 testing, and associations with clinical characteristics, CellSearch CTC counts, tumour biopsy AR-V7 protein expression and overall survival (OS). Design, setting, and participants CTC AR-V7 status was determined for 227 peripheral blood samples, from 181 mCRPC patients with CTC counts (202 samples; 136 patients) and matched mCRPC biopsies (65 samples; 58 patients). Outcome measurements and statistical analysis CTC AR-V7 status was associated with clinical characteristics, CTC counts, and tissue biopsy AR-V7 protein expression. The association of CTC AR-V7 status and other baseline variables with OS was determined. Results and limitations Of the samples, 35% were CTC+/AR-V7+. CTC+/AR-V7+ samples had higher CellSearch CTC counts (median CTC; interquartile range [IQR]: 60, 19–184 vs 9, 2–64; Mann-Whitney test p Conclusions Studies reporting the prognostic relevance of CTC AR-V7 status must account for CTC counts. Discordant CTC AR-V7 results and AR-V7 protein expression in matched, same-patient biopsies are reported. Patient summary Liquid biopsies that determine circulating tumour cell androgen receptor splice variant-7 status have the potential to impact treatment decisions in metastatic castration-resistant prostate cancer patients. Robust clinical qualification of these assays is required before their routine use

Laboratorio de exergames : un espacio complementario para las clases de educación física

Este artigo apresenta um estudo sobre o uso de exergames em práticas estruturadas em aulas de Educação Física envolvendo estudantes que geralmente apresentam sinais de insatisfação com atividades esportivas propostas nas aulas regulares da disciplina. Enquanto os videogames foram historicamente associados a problemas como obesidade e introversão social, os exergames trouxeram uma nova perspectiva para esses artefatos culturais. Vinte e quatro alunos entre oito e 14 anos de idade participaram do estudo, realizado em um laboratório criado em uma escola no sul do Brasil. Os alunos foram observados e seus professores de Educação Física entrevistados ao final do projeto. Como resultado, foi possível observar que os estudantes que normalmente não demonstravam interesse pelas aulas de Educação Física passaram a apresentar uma atitude positiva em relação às práticas com os exergames, evidenciando também sua disposição em colaborar com os colegas.This paper presents a study about the use of exergames in structured Physical Education (PE) classes with students that usually show signs of dissatisfaction with sports activities proposed at regular PE classes. While videogames have been historically associated with issues related to obesity and social introversion, exergames brought a new perspective on those cultural artifacts. Twenty-four 8-14-year-old students participated in the study conducted in a laboratory set up in a school in Southern Brazil. They were observed and their PE teachers were also interviewed at the end of project. Results showed that students that usually did not show interest in Physical Education classes started to demonstrate a positive attitude regarding exergame practices, also expressing willingness to cooperate with their peers.Este artículo presenta un estudio sobre el uso de exergames en prácticas estructuradas en clases de Educación Física con estudiantes que generalmente presentan señales de insatisfacción frente a las actividades deportivas propuestas en las clases regulares de la asignatura. Mientras los videojuegos han sido históricamente asociados a problemas como obesidad e introversión social, los exergames han traído una nueva perspectiva para esos artefactos culturales. Veinticuatro alumnos entre ocho y catorce años de edad han participado en este estudio, desarrollado en un laboratorio organizado en una escuela en el sur de Brasil. Los estudiantes fueron observados y sus profesores de Educación Física entrevistados al final del proyecto. Como resultado, fue posible observar que los estudiantes que normalmente no mostraban interés por las clases de Educación Física, pasaron a presentar una actitud positiva en relación a las prácticas con los exergames, evidenciando también su disposición de colaborar con sus compañeros

Exergames Experience in Physical Education: A Review

Exergames are consoles that require a higher physical effort to play when compared to traditional video games. Active video games, active gaming, interactive games, movement-controlled video games, exertion games, and exergaming are terms used to define the kinds of video games in which the exertion interface enables a new experience. Exergames have added a component of physical activity to the otherwise motionless video game environment and have the potential to contribute to physical education classes by supplementing the current activity options and increasing student enjoyment. The use of exergames in schools has already shown positive results in the past through their potential to fight obesity. As for the pedagogical aspects of exergames, they have attracted educators’ attention due to the large number of games and activities that can be incorporated into the curriculum. In this way, the school must consider the development of a new physical education curriculum in which the key to promoting healthy physical activity in children and youth is enjoyment, using video games as a tool. In this context, the aim is to conduct a brief review of the use of exergames in physical education curriculum, exploring school curriculum, digital culture, and motivation and enjoyment for the learning processes in the video game environmen

Transcriptomic and functional analyses of the piRNA pathway in the Chagas disease vector Rhodnius prolixus.

The piRNA pathway is a surveillance system that guarantees oogenesis and adult fertility in a range of animal species. The pathway is centered on PIWI clade Argonaute proteins and the associated small non-coding RNAs termed piRNAs. In this study, we set to investigate the evolutionary conservation of the piRNA pathway in the hemimetabolous insect Rhodnius prolixus. Our transcriptome profiling reveals that core components of the pathway are expressed during previtellogenic stages of oogenesis. Rhodnius' genome harbors four putative piwi orthologs. We show that Rp-piwi2, Rp-piwi3 and Rp-ago3, but not Rp-piwi1 transcripts are produced in the germline tissues and maternally deposited in the mature eggs. Consistent with a role in Rhodnius oogenesis, parental RNAi against the Rp-piwi2, Rp-piwi3 and Rp-ago3 results in severe egg laying and female adult fertility defects. Furthermore, we show that the reduction of the Rp-piwi2 levels by parental RNAi disrupts oogenesis by causing a dramatic loss of trophocytes, egg chamber degeneration and oogenesis arrest. Intriguingly, the putative Rp-Piwi2 protein features a polyglutamine tract at its N-terminal region, which is conserved in PIWI proteins encoded in the genome of other Triatomine species. Together with R. prolixus, these hematophagous insects are primary vectors of the Chagas disease. Thus, our data shed more light on the evolution of the piRNA pathway and provide a framework for the development of new control strategies for Chagas disease insect vectors

Sensing a binding event through charge transport variations using an aromatic oligoamide capsule

The selective binding properties of a 13-mer oligoamide foldamer capsule composed of 4 different aromatic subunits are reported. The capsule was designed to recognize dicarboxylic acids through multiple-point interactions owing to a combination of protonation/deprotonation events, H-bonding, and geometrical constraints imparted by the rigidity of the foldamer backbone. Compared to tartaric acid, binding of 2,2-difluorosuccinic acid or 2,2,3,3-tetrafluorosuccinic acid resulted in symmetry breaking due to deprotonation of only one of the two carboxylic acid groups of the encapsulated species as shown by NMR studies in solution and by single-crystal X-ray diffraction in the solid state. An analogous 14-mer foldamer capsule terminated with a thiol anchoring group was used to probe the complexation event in self-assembled monolayers on Au substrates. Ellipsometry and polarization-modulation infrared absorption-reflection spectroscopy studies were consistent with the formation of a single molecule layer of the foldamer capsule oriented vertically with respect to the surface. The latter underwent smooth complexation of 2,2-difluorosuccinic acid with deprotonation of one of the two carboxylic acid groups. A significant (80-fold) difference in the charge transport properties of the monolayer upon encapsulation of the dicarboxylic acid was evidenced from conducting-AFM measurements (S = 1.1 x 10(-9)vs. 1.4 x 10(-11) ohm(-1) for the empty and complexed capsule, respectively). The modulation in conductivity was assigned to protonation of the aromatic foldamer backbone.Les voies de signalisation du récepteur 5-HT6: de nouvelles cibles pour le traitement de la douleur neuropathique?Aryl amide metallofoldamersas selective saccharide sensor