Bifurcation and dynamic response analysis of a rotating blade excited by upstream vortices

Acknowledgements The authors acknowledge the projects supported by the National Basic Research Program of China (973 Project)(No. 2015CB057405) and the National Natural Science Foundation of China (No. 11372082) and the State Scholarship Fund of CSC. DW thanks for the hospitality of the University of Aberdeen.

Activation of Serotonin 2C Receptors in Dopamine Neurons Inhibits Binge-like Eating in Mice

This work was supported by the National Institutes of Health (Grant Nos. R01DK093587 and R01DK101379 [to YX], R01DK092605 to [QT], R01DK078056 [to MM]), the Klarman Family Foundation (to YX), the Naman Family Fund for Basic Research (to YX), Curtis Hankamer Basic Research Fund (to YX), American Diabetes Association (Grant Nos. 7-13-JF-61 [to QW] and 1-15-BS-184 [to QT]), American Heart Association postdoctoral fellowship (to PX), Wellcome Trust (Grant No. WT098012 [to LKH]), and Biotechnology and Biological Sciences Research Council (Grant No. BB/K001418/1 [to LKH]). The anxiety tests (e.g., open-field test, light-dark test, elevated plus maze test) were performed in the Mouse Neurobehavior Core, Baylor College of Medicine, which was supported by National Institutes of Health Grant No. P30HD024064. PX and YH were involved in experimental design and most of the procedures, data acquisition and analyses, and writing the manuscript. XC assisted in the electrophysiological recordings; LV-T assisted in the histology study; XY, KS, CW, YY, AH, LZ, and GS assisted in surgical procedures and production of study mice. MGM, QW, QT, and LKH were involved in study design and writing the manuscript. YX is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors report no biomedical financial interests or potential conflicts of interest.

Mutation of SLC35D3 causes metabolic syndrome by impairing dopamine signaling in striatal D1 neurons

Funding: This work was partially supported by grants from National Basic Research Program of China (2013CB530605; 2014CB942803), from National Natural Science Foundation of China 1230046; 31071252; 81101182) and from Chinese Academy of Sciences (KSCX2-EW-R-05, KJZD-EW-L08). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Les mécanismes sous-jacents aux effets pathologiques cardiaques de l’angiotensine II dans le remodelage électrique et contractile entre les sexes

L’insuffisance cardiaque (IC) est associée à un taux de mortalité et d’hospitalisations élevé causant un fardeau économique important. Les deux causes majeures de décès de l’IC sont les arythmies ventriculaires létales et les sidérations myocardiques. Il est maintenant reconnu que l’angiotensine II (ANGII) est l'un des principaux médiateurs de l’IC. Ses effets délétères découlent de l’activation du récepteur de type 1 de l’ANGII (AT1) et entraînent le développement d’hypertrophie. Toutefois, son rôle dans la genèse d’arythmies demeure incompris. De ce fait, l'étude des mécanismes électriques et contractiles sous-jacents aux effets pathologiques de l’ANGII s’avère essentielle afin de mieux comprendre et soigner cette pathologie. Il est souvent perçu que les femmes sont protégées envers les maladies cardiovasculaires. Cependant, le nombre total de femmes décédant d’IC est plus grand que le nombre d’hommes. Également, l’impact des facteurs de risque diffère entre chaque sexe. Ces différences existent, mais les mécanismes sous-jacents sont encore peu connus. De plus, les femmes reçoivent fréquemment un diagnostic ou un traitement inapproprié en raison d’un manque d’information sur les différences entre les sexes dans la manifestation d’une pathologie. Ce manque de données peut découler du fait que les sujets de sexe féminin sont souvent sous-représentés dans les essais cliniques ou la recherche fondamentale ce qui a grandement limité l’avancement de nos connaissances sur ~50 % de la population. Ainsi, il semble plus que nécessaire d’approfondir notre compréhension des différences entre les sexes, notamment dans la progression de l’IC. L’utilisation d’un modèle de souris transgénique surexprimant le récepteur AT1 (souris AT1R) a permis d’étudier les changements électriques, structurels et contractiles avant et après le développement d’hypertrophie. Premièrement, chez les souris AT1R mâles, un ralentissement de la conduction ventriculaire a été observé indépendamment de l’hypertrophie. Ce résultat était expliqué par une réduction de la densité du courant Na+, mais pas de l’expression du canal. Ensuite, le rôle des protéines kinases C (PKC) dans la régulation du canal Na+ par l’ANGII a été exploré. Les évidences ont suggéré que la PKCα était responsable de la modulation de la diminution du courant Na+ chez les souris AT1R mâles et dans les cardiomyocytes humains dérivés de cellules souches induites pluripotentes (hiPSC-CM) en réponse à un traitement chronique à l’ANGII. Ensuite, les différences entre les sexes ont été comparées chez la souris AT1R. Une plus grande mortalité a été constatée chez les femelles AT1R suggérant qu’elles sont plus sensibles à la surexpression de AT1R. Le remodelage électrique ventriculaire a donc été comparé entre les souris AT1R des deux sexes. Les courants ioniques étaient altérés de façon similaire entre les sexes excluant ainsi leur implication dans la mortalité plus élevée chez les femelles. Ensuite, l’homéostasie calcique et la fonction cardiaque ont été étudiées. Il a été démontré que les femelles développaient une hypertrophie et une dilatation ventriculaire plus sévère que les mâles. De plus, les femelles AT1R avaient de petits transitoires calciques, une extrusion du Ca2+ plus lente ainsi qu’une augmentation de la fréquence des étincelles Ca2+ pouvant participer à des troubles contractiles et à la venue de post-dépolarisations précoces. En conclusion, l’ANGII est impliquée dans le remodelage électrique, structurel et calcique associé à l'émergence de l’IC. De surcroît, ces altérations affectent plus sévèrement les femelles soulignant la présence de différences entre les sexes dans le développement de l’IC.

Targeted Gene Repression Technologies for Regenerative Medicine, Genomics, and Gene Therapy

Gene regulation is a complex and tightly controlled process that defines cell function in physiological and abnormal states. Programmable gene repression technologies enable loss-of-function studies for dissecting gene regulation mechanisms and represent an exciting avenue for gene therapy. Established and recently developed methods now exist to modulate gene sequence, epigenetic marks, transcriptional activity, and post-transcriptional processes, providing unprecedented genetic control over cell phenotype. Our objective was to apply and develop targeted repression technologies for regenerative medicine, genomics, and gene therapy applications. We used RNA interference to control cell cycle regulation in myogenic differentiation and enhance the proliferative capacity of tissue engineered cartilage constructs. These studies demonstrate how modulation of a single gene can be used to guide cell differentiation for regenerative medicine strategies. RNA-guided gene regulation with the CRISPR/Cas9 system has rapidly expanded the targeted repression repertoire from silencing single protein-coding genes to modulation of genes, promoters, and other distal regulatory elements. In order to facilitate its adaptation for basic research and translational applications, we demonstrated the high degree of specificity for gene targeting, gene silencing, and chromatin modification possible with Cas9 repressors. The specificity and effectiveness of RNA-guided transcriptional repressors for silencing endogenous genes are promising characteristics for mechanistic studies of gene regulation and cell phenotype. Furthermore, our results support the use of Cas9-based repressors as a platform for novel gene therapy strategies. We developed an in vivo AAV-based gene repression system for silencing endogenous genes in a mouse model. Together, these studies demonstrate the utility of gene repression tools for guiding cell phenotype and the potential of the RNA-guided CRISPR/Cas9 platform for applications such as causal studies of gene regulatory mechanisms and gene therapy.

A suite of global, cross-scale topographic variables for environmental and biodiversity modeling, links to files in GeoTIFF format

Topographic variation, the spatial variation in elevation and terrain features, underpins a myriad of patterns and processes in geography and ecology and is key to understanding the variation of life on the planet. The characterization of this variation is scale-dependent, i.e. it varies with the distance over which features are assessed and with the spatial grain (grid cell resolution) of analysis. A fully standardized and global multivariate product of different terrain features has the potential to support many large-scale basic research and analytical applications, however to date, such technique is unavailable. Here we used the digital elevation model products of global 250 m GMTED and near-global 90 m SRTM to derive a suite of topographic variables: elevation, slope, aspect, eastness, northness, roughness, terrain roughness index, topographic position index, vector ruggedness measure, profile and tangential curvature, and 10 geomorphological landform classes. We aggregated each variable to 1, 5, 10, 50 and 100 km spatial grains using several aggregation approaches (median, average, minimum, maximum, standard deviation, percent cover, count, majority, Shannon Index, entropy, uniformity). While a global cross-correlation underlines the high similarity of many variables, a more detailed view in four mountain regions reveals local differences, as well as scale variations in the aggregated variables at different spatial grains. All newly-developed variables are available for download at http://www.earthenv.org and can serve as a basis for standardized hydrological, environmental and biodiversity modeling at a global extent.

A história da ciência como subsídio para a construção do conhecimento do conceito da dupla hélice

Acompanha: Dupla-hélice: a construção de um conhecimento

Exploration d’un modèle d’étude simplifié de la spermiogenèse par l’utilisation de la levure à fission

Résumé: Les cellules germinales mâles remodèlent leur chromatine pour compacter leur noyau afin de protéger leur matériel génétique et assurer un transit optimal vers le gamète femelle. Il a été démontré que tous les spermatides de plusieurs mammifères, incluant l’homme et la souris, présentaient ce mécanisme de remodelage de la chromatine. Celui-ci est caractérisé par une augmentation transitoire de cassures d’ADN dont une quantité importante sont bicaténaires. Ce remodelage chromatinien a été étudié et semble être conservé chez plusieurs espèces, allant de l’algue à l’humain. Dans le contexte de la recherche fondamentale sur le phénomène de la spermiogenèse, il devient parfois très difficile d’investiguer certains aspects importants en vertu de l’impossibilité de réaliser des manipulations génétiques simples. Il est donc impératif de développer un nouveau modèle d’étude plus permissif afin de palier à ces difficultés encourues. Comme le processus de maturation des spores chez la levure à fission présente de grandes similitudes avec la spermiogenèse des mammifères, l’utilisation d’un modèle d’étude basé sur la sporulation de la levure à fission Schizosaccharomyces pombe a été proposée comme modèle comparatif de la spermatogenèse murine. À la suite de la synchronisation de la méiose de la souche S. pombe pat1-114, des analyses d’électrophorèse en champ pulsé (PFGE) et de qTUNEL ont permis de déterminer la présence de cassures bicaténaires transitoires de l’ADN lors de la maturation post-méiotique des ascospores nouvellement formés (t>7h). Des analyses par immunobuvardages dirigés contre le variant d’histones H2AS129p suggère la présence d’un remodelage chromatinien postméiotique dix heures suivant l’induction de la méiose, corroborant le modèle murin. Enfin, des analyses protéomiques couplées à l’analyse par spectrométrie de masse ont permis de proposer l’endonucléase Pnu1 comme candidat potentiellement responsable des cassures bicaténaires transitoires dans l’ADN des ascospores en maturation. En somme, bien que le processus de maturation des spores soit encore bien méconnu, quelques parallèles peuvent être tracés entre la maturation des ascospores de la levure à fission et la spermiogenèse des eucaryotes supérieurs. En identifiant un modèle simple du remodelage chromatinien au niveau de la spermiogenèse animale, on s’assurerait ainsi d’un outil beaucoup plus malléable et versatile pour l’étude fondamentale des événements survenant lors de la spermiogenèse humaine.

Movement Sonification: Effects on Motor Learning beyond Rhythmic Adjustments

Motor learning is based on motor perception and emergent perceptual-motor representations. A lot of behavioral research is related to single perceptual modalities but during last two decades the contribution of multimodal perception on motor behavior was discovered more and more. A growing number of studies indicates an enhanced impact of multimodal stimuli on motor perception, motor control and motor learning in terms of better precision and higher reliability of the related actions. Behavioral research is supported by neurophysiological data, revealing that multisensory integration supports motor control and learning. But the overwhelming part of both research lines is dedicated to basic research. Besides research in the domains of music, dance and motor rehabilitation, there is almost no evidence for enhanced effectiveness of multisensory information on learning of gross motor skills. To reduce this gap, movement sonification is used here in applied research on motor learning in sports. Based on the current knowledge on the multimodal organization of the perceptual system, we generate additional real-time movement information being suitable for integration with perceptual feedback streams of visual and proprioceptive modality. With ongoing training, synchronously processed auditory information should be initially integrated into the emerging internal models, enhancing the efficacy of motor learning. This is achieved by a direct mapping of kinematic and dynamic motion parameters to electronic sounds, resulting in continuous auditory and convergent audiovisual or audio-proprioceptive stimulus arrays. In sharp contrast to other approaches using acoustic information as error-feedback in motor learning settings, we try to generate additional movement information suitable for acceleration and enhancement of adequate sensorimotor representations and processible below the level of consciousness. In the experimental setting, participants were asked to learn a closed motor skill (technique acquisition of indoor rowing). One group was treated with visual information and two groups with audiovisual information (sonification vs. natural sounds). For all three groups learning became evident and remained stable. Participants treated with additional movement sonification showed better performance compared to both other groups. Results indicate that movement sonification enhances motor learning of a complex gross motor skill-even exceeding usually expected acoustic rhythmic effects on motor learning.

Efeitos de mudanças sucessivas na definição de produto agregado em metacontingências

Dissertação (mestrado)—Universidade de Brasília, Instituto de Psicologia, Departamento de Processos Psicológicos Básicos, Programa de Pós-Graduação em Ciências do Comportamento, 2015.

Identificação de genes MUTM em BACs da cana-de-açucar e caracterização preliminar destes genes e seus promotores

Sugarcane has an importance in Brazil due to sugar and biofuel production. Considering this aspect, there is basic research being done in order to understand its physiology to improve production. The aim of this research is the Base Excision Repair pathway, in special the enzyme MUTM DNA-glycosylase (formamidopyrimidine) which recognizes oxidized guanine in DNA. The sugarcane scMUTM genes were analyzed using four BACs (Bacterial Artificial Chromosome) from a sugarcane genomic library from R570 cultivar. The resulted showed the presence in the region that had homology to scMUTM the presence of transposable elements. Comparing the similarity, it was observed a highest similarity to Sorghum bicolor sequence, both nucleotide and peptide sequences. Furthermore, promoter regions from MUTM genes in some grass showed different cis-regulatory elements, among which, most were related to oxidative stress, suggesting a gene regulation by oxidative stress

Produção de conhecimento científico e tecnológico nos Institutos Federais de Educação, Ciência e Tecnologia : uma investigação sobre a sua natureza e aplicação

Este artigo é um desdobramento da tese Produção de conhecimento científico e tecnológico nos Institutos Federais de Educação, Ciência e Tecnologia: uma investigação sobre a sua natureza, divulgação e aplicação.

Studying the role of the strawberry Fra protein family in the flavonoid metabolism during fruit ripening

Strawberry fruits are highly appreciated worldwide due to their pleasant flavor and aroma and to the health benefits associated to their consumption. An important part of these properties is due to their content in secondary metabolites, especially phenolic compounds, of which flavonoids are the most abundant in the strawberry fruit. Although the flavonoid biosynthesis pathway is uncovered, little is known about its regulation. The strawberry Fra a (Fra) genes constitute a large family of homologs of the major birch pollen allergen Bet v 1 and for which no equivalents exist in Arabidopsis. Our group has shown that Fra proteins are involved in the formation of colored compounds in strawberries (Muñoz et al., 2010), which mainly depends on the production of certain flavonoids; that they are structurally homologs to the PYR/PYL/RCAR Arabidopsis ABA receptor, and that they are able to bind flavonoids (Casañal et al., 2013). With these previous results, our working hypothesis is that the Fra proteins are involved in the regulation of the flavonoids pathway. They would mechanistically act as the ABA receptor, binding a protein interactor and a ligand to regulate a signaling cascade and/or act as molecular carriers. The main objective of this research is to characterize the Fra family in strawberry and gain insight into their role in the flavonoid metabolism. By RNAseq expression analysis in ripening fruits we have identified transcripts for 10 members of the Fra family. Although expressed in all tissues analyzed, each family member presents a unique pattern of expression, which suggests functional specialization for each Fra protein. Then, our next approach was to identify the proteins that interact with Fras and their ligands to gain knowledge on the role that these proteins play in the flavonoids pathway. To identify the interacting partners of Fras we have performed a yeast two hybrid (Y2H) screening against cDNA libraries of strawberry fruits at the green and red stages. A protein that shares a 95% homology to the Heat stress transcription factor A-4-C like of Fragaria vesca (HSA4C) interacts specifically with Fra1 and not with other family members, which suggests functional diversification of Fra proteins in specific signaling pathways. The Y2H screening is not yet saturated, so characterization of other interacting proteins with other members of the Fra family will shed light on the functional diversity within this gene family. This research will contribute to gain knowledge on how the flavonoid pathway, and hence, the fruit ripening, is regulated in strawberry; an economically important crop but for which basic research is still very limited. References: Muñoz, C, et al. (2010). The Strawberry Fruit Fra a Allergen Functions in Flavonoid Biosynthesis. Molecular Plant, 3(1): 113–124. Casañal, A, et al (2013). The Strawberry Pathogenesis-related 10 (PR-10) Fra a Proteins Control Flavonoid Biosynthesis by Binding Metabolic Intermediates. Journal of Biological Chemistry, 288(49): 35322–35332.

Early markers for myocardial ischemia and sudden cardiac death.

The post-mortem diagnosis of acute myocardial ischemia remains a challenge for both clinical and forensic pathologists. We performed an experimental study (ligation of left anterior descending coronary artery in rats) in order to identify early markers of myocardial ischemia, to further apply to forensic and clinical pathology in cases of sudden cardiac death. Using immunohistochemistry, Western blots, and gene expression analyses, we investigated a number of markers, selected among those which are currently used in emergency departments to diagnose myocardial infarction and those which are under investigation in basic research and autopsy pathology studies on cardiovascular diseases. The study was performed on 44 adult male Lewis rats, assigned to three experimental groups: control, sham-operated, and operated. The durations of ischemia ranged between 5 min and 24 h. The investigated markers were troponins I and T, myoglobin, fibronectin, C5b-9, connexin 43 (dephosphorylated), JunB, cytochrome c, and TUNEL staining. The earliest expressions (≤30 min) were observed for connexin 43, JunB, and cytochrome c, followed by fibronectin (≤1 h), myoglobin (≤1 h), troponins I and T (≤1 h), TUNEL (≤1 h), and C5b-9 (≤2 h). By this investigation, we identified a panel of true early markers of myocardial ischemia and delineated their temporal evolution in expression by employing new technologies for gene expression analysis, in addition to traditional and routine methods (such as histology and immunohistochemistry). Moreover, for the first time in the autopsy pathology field, we identified, by immunohistochemistry, two very early markers of myocardial ischemia: dephosphorylated connexin 43 and JunB.