Reconstitution of an active human CENP-E motor

CENP-E is a large kinesin motor protein which plays pivotal roles in mitosis by facilitating chromosome capture and alignment, and promoting microtubule flux in the spindle. So far, it has not been possible to obtain active human CENP-E to study its molecular properties. Xenopus CENP-E motor has been characterized in vitro and is used as a model motor; however, its protein sequence differs significantly from human CENP-E. Here, we characterize human CENP-E motility in vitro. Full-length CENP-E exhibits an increase in run length and longer residency times on microtubules when compared to CENP-E motor truncations, indicating that the C-terminal microtubule-binding site enhances the processivity when the full-length motor is active. In contrast with constitutively active human CENP-E truncations, full-length human CENP-E has a reduced microtubule landing rate in vitro, suggesting that the non-motor coiled-coil regions self-regulate motor activity. Together, we demonstrate that human CENP-E is a processive motor, providing a useful tool to study the mechanistic basis for how human CENP-E drives chromosome congression and spindle organization during human cell division

Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity.

CD38 genetic variation has been associated with autism spectrum disorders and social anxiety disorder, which may result from CD38's regulation of oxytocin secretion. Converging evidence has found that the rs3796863 A-allele contributes to increased social sensitivity compared to the CC genotype. The current study examined the moderating role of CD38 genetic variants (rs3796863 and rs6449182) that have been associated with enhanced (or reduced) social sensitivity on neural activation related to neuroticism, which is commonly elevated in individuals with social anxiety and depression. Adults (n = 72) with varying levels of social anxiety and depression provided biological samples for DNA extraction, completed a measure of neuroticism, and participated in a standardized emotion processing task (affect matching) while undergoing fMRI. A significant interaction effect was found for rs3796863 x neuroticism that predicted right amygdala-subgenual anterior cingulate cortex (sgACC) functional connectivity. Simple slopes analyses showed a positive association between neuroticism and right amygdala-sgACC connectivity among rs3796863 A-allele carriers. Findings suggest that the more socially sensitive rs3796863 A-allele may partially explain the relationship between a known risk factor (i.e. neuroticism) and promising biomarker (i.e. amygdala-sgACC connectivity) in the development and maintenance of social anxiety and depression

Transcranial Focused Ultrasound Targeting the Amygdala May Increase Psychophysiological and Subjective Negative Emotional Reactivity in Healthy Older Adults.

BACKGROUND: The amygdala is highly implicated in an array of psychiatric disorders but is not accessible using currently available noninvasive neuromodulatory techniques. Low-intensity transcranial focused ultrasound (TFUS) is a neuromodulatory technique that has the capability of reaching subcortical regions noninvasively. METHODS: We studied healthy older adult participants (N = 21, ages 48-79 years) who received TFUS targeting the right amygdala and left entorhinal cortex (active control region) using a 2-visit within-participant crossover design. Before and after TFUS, behavioral measures were collected via the State-Trait Anxiety Inventory and an emotional reactivity and regulation task utilizing neutral and negatively valenced images from the International Affective Picture System. Heart rate and self-reported emotional valence and arousal were measured during the emotional reactivity and regulation task to investigate subjective and physiological responses to the task. RESULTS: Significant increases in both self-reported arousal in response to negative images and heart rate during emotional reactivity and regulation task intertrial intervals were observed when TFUS targeted the amygdala; these changes were not evident when the entorhinal cortex was targeted. No significant changes were found for state anxiety, self-reported valence to the negative images, cardiac response to the negative images, or emotion regulation. CONCLUSIONS: The results of this study provide preliminary evidence that a single session of TFUS targeting the amygdala may alter psychophysiological and subjective emotional responses, indicating some potential for future neuropsychiatric applications. However, more work on TFUS parameters and targeting optimization is necessary to determine how to elicit changes in a more clinically advantageous way

Diseño de un manual de detección de ansiedad social en adolescentes

Curso de Especial InterésEl objetivo de este trabajo de grado ha sido diseñar un manual dirigido a padres y docentes, en el que se establezcan técnicas de detección de ansiedad social en adolescentes; el diseño de este manual permite un aprendizaje significativo de una forma diferente, en un lenguaje claro y preciso, en formato digital para un fácil acceso y portabilidad del material, logrando de esta forma, que la población adolescente sea beneficiada a través de las acciones que se emprenderán por parte de los padres de familia, docentes y profesionales.142 p.RESUMEN 1. JUSTIFICACIÓN 2. OBJETIVOS 3. ESTUDIO DEL MERCADO 4. PRESENTACIÓN DEL PRODUCTO 5. CLIENTES – SEGMENTACIÓN 6. COMPETENCIA 7. CANALES DE DISTRIBUCIÓN 8. RESULTADOS DEL ESTUDIO DE MERCADO 9. DISCUSIÓN DEL ESTUDIO DE MERCADO 10. PRESUPUESTO 11. RESULTADOS 12. CONCLUSIONES REFERENCIAS APÉNDICESPregradoPsicólog

Volatile Compounds in Citrus Essential Oils: A Comprehensive Review

[EN] The essential oil fraction obtained from the rind of Citrus spp. is rich in chemical compounds of interest for the food and perfume industries, and therefore has been extensively studied during the last decades. In this manuscript, we provide a comprehensive review of the volatile composition of this oil fraction and rind extracts for the 10 most studied Citrus species: C. sinensis (sweet orange), C. reticulata (mandarin), C. paradisi (grapefruit), C. grandis (pummelo), C. limon (lemon), C. medica (citron), C. aurantifolia (lime), C. aurantium (bitter orange), C. bergamia (bergamot orange), and C. junos (yuzu). Forty-nine volatile organic compounds have been reported in all 10 species, most of them terpenoid (90%), although about half of the volatile compounds identified in Citrus peel are non-terpenoid. Over 400 volatiles of different chemical nature have been exclusively described in only one of these species and some of them could be useful as species biomarkers. A hierarchical cluster analysis based on volatile composition arranges these Citrus species in three clusters which essentially mirrors those obtained with genetic information. The first cluster is comprised by C. reticulata, C. grandis, C. sinensis, C. paradisi and C. aurantium, and is mainly characterized by the presence of a larger abundance of non-terpenoid ester and aldehyde compounds than in the other species reviewed. The second cluster is comprised by C. junos, C. medica, C. aurantifolia, and C. bergamia, and is characterized by the prevalence of mono- and sesquiterpene hydrocarbons. Finally, C. limon shows a particular volatile profile with some sulfur monoterpenoids and non-terpenoid esters and aldehydes as part of its main differential peculiarities. A systematic description of the rind volatile composition in each of the species is provided together with a general comparison with those in leaves and blossoms. Additionally, the most widely used techniques for the extraction and analysis of volatile Citrus compounds are also described.This work was supported in part by the European Commission Horizon 2020 program TRADITOM grant 634561 and TomGEM grant 679796 to JR and AG.González-Mas, M.; Rambla Nebot, JL.; López-Gresa, MP.; Blazquez, M.; Granell Richart, A. (2019). Volatile Compounds in Citrus Essential Oils: A Comprehensive Review. Frontiers in Plant Science. 10:1-18. https://doi.org/10.3389/fpls.2019.00012S11810Abreu, I., Da Costa, N. C., van Es, A., Kim, J.-A., Parasar, U., & Poulsen, M. L. (2017). Natural Occurrence of Aldol Condensation Products in Valencia Orange Oil. Journal of Food Science, 82(12), 2805-2815. doi:10.1111/1750-3841.13948Ahmed, M., Arpaia, M. L., & Scora, R. W. (2001). Seasonal Variation in Lemon (Citrus limonL. Burm. f) Leaf and Rind Oil Composition. 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Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Mechanistic and functional insights into the human kinesin motor CENP-E in cell division

During mitosis, chromosomes align at the spindle equator and biorient in order to equally distribute the genome into two daughter cells. A macromolecular protein complex, known as the kinetochore, facilitates the end-on attachment of chromosomes to spindle microtubules. CENP-E is a very large mitotic kinesin motor protein which is recruited to the outer kinetochore and fibrous corona of unattached kinetochores in prometaphase. Human CENP-E motor activity is essential for the alignment of chromosomes close to the spindle poles, but also for the stabilisation of kinetochore-microtubule attachments and microtubule flux in the mitotic spindle. Until now, biochemical characterisation studies and reconstitutions of CENP-E activity have used the Xenopus laevis CENP-E orthologue as a model motor. However, human and X. laevis CENP-E share only 49% sequence similarity and the human model system is typically used for cell biology, functional and structural studies of human kinetochores. The aim of my thesis was to define the mechanistic properties of human CENP-E and define how interactions with associated proteins direct its function in mitosis. First, I reconstituted motor activity of truncated and full-length human CENP-E using reconstitution approaches and single molecule imaging. Truncated CENP-E is constitutively active and processive in vitro, capable of unidirectional movement along microtubules. Active full-length CENP-E molecules are more processive than their truncated CENP-E counterparts in vitro, but exhibit slower average speeds and lower landing rates on microtubules. This work indicates that the non-motor regions of human CENP-E contribute to the regulation of motor activity. CENP-E has been suggested to interact with several distinct binding partners, but it is unclear whether many of these reported interactions are direct. Using biochemistry and isothermal titration calorimetry (ITC), I reconstituted binding between human CENP-E and Protein Phosphatase 1 (PP1). Finally, I studied the role of CENP-E at the spindle midzone. As cells progress into anaphase and the chromosomes segregate to opposite poles, CENP-E is gradually lost from kinetochores and relocalises to the midzone in a PRC1-dependent manner. Thus, I used in vitro reconstitution approaches to gain molecular insights into the function of CENP-E at the overlapping microtubule bundles of the spindle midzone and midbody. I demonstrated that PRC1 is able to recruit CENP-E to overlapping microtubule bundles. PRC1 facilitates microtubule sliding activity of CENP-E in vitro, providing important molecular insight into how CENP-E contributes to microtubule flux and organisation of the spindle midzone in vivo. This study defines the molecular properties of human CENP-E which underpin the essential functions of the motor in chromosome transport, kinetochore-microtubule attachments and mitotic spindle organisation in vivo

Pavlovian Learning Processes in Pediatric Anxiety Disorders: A Critical Review

Deficits in associative and Pavlovian learning are thought to lie at the center of anxiety-related disorders. However, the majority of studies have been carried out in adult populations. The aim of this review was to critically examine the behavioral and neuroimaging literature on Pavlovian learning in pediatric anxiety disorders. We conclude that although there is evidence for deficits in Pavlovian processes (e.g., heightened reactivity to safety cues in anxious samples), the extant literature suffers from key methodological and theoretical issues. We conclude with theoretical and methodological recommendations for future research in order to further elucidate the role of Pavlovian learning in the etiology, maintenance, and treatment of pediatric anxiety disorders