45 research outputs found
Clonal hematopoiesis as a pitfall in germline variant interpretation in the context of Mendelian disorders
Clonal hematopoiesis because of somatic mutations in hematopoietic stem/progenitor cells is an age-related phenomenon and commonly observed when sequencing blood DNA in elderly individuals. Several genes that are implicated in clonal hematopoiesis are also associated with Mendelian disorders when mutated in the germline, potentially leading to variant misinterpretation. We performed a literature search to identify genes associated with age-related clonal hematopoiesis followed by an OMIM query to identify the subset of genes in which germline variants are associated with Mendelian disorders. We retrospectively screened for diagnostic cases in which the presence of age-related clonal hematopoiesis confounded exome sequencing data interpretation. We found 58 genes in which somatic mutations are implicated in clonal hematopoiesis, while germline variants in the same genes are associated with Mendelian (mostly neurodevelopmental) disorders. Using five selected cases of individuals with suspected monogenic disorders, we illustrate how clonal hematopoiesis in either variant databases or exome sequencing datasets poses a pitfall, potentially leading to variant misclassification and erroneous conclusions regarding gene-disease associations
25th annual computational neuroscience meeting: CNS-2016
The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong
Estrategias utilizadas en autoevaluaciones de lectura intercomprensiva
El trabajo surge en el marco del proyecto de investigación "Estrategias de aprendizaje para el desarrollo de la intercomprensión en lenguas germánicas en hispanohablantes". Después de etapas anteriores, en las que se diseñó y aplicó material de enseñanza para la lectura intercomprensiva en las lenguas alemán y neerlandés, usando como lengua puente el inglés, la etapa de investigación actual se centra en la recolección y el análisis de datos, con la finalidad de investigar el uso de estrategias de lectura. La recolección de datos se realizó durante el dictado de un curso piloto, en el que se implementó el material de aprendizaje diseñado por el equipo. Se presentarán los resultados de las encuestas realizadas en dos instancias auto-evaluativas. En este trabajo definimos el concepto de estrategias de aprendizaje según lo entienden Bimmel y Rampillon (1996) y nos centramos en las estrategias cognitivas, dentro de la taxonomía de Chamot y O?Malley (1990, 1994). Para el diseño del instrumento se recurrió a las pautas para diseñar encuestas escritas, propuestas por Riemer (2016). Se presentarán los datos que se obtuvieron luego de la cuantificación y comparación de los resultados de las encuestas. Finalmente, a partir de una comparación entre las encuestas de la primera y la última autoevaluación, se concluirá con el registro y la medición de progreso en el uso de las estrategias de lectura intercomprensiva.https://ieslvf-caba.infd.edu.ar/sitio/upload/Actas_IV_Jornadas_Internacionales_2017_2.pdfFil: Merzig, Brigitte. Universidad Nacional de Córdoba. Facultad de Lenguas; Argentina.Fil: Pérez, Susana. Universidad Nacional de Córdoba. Facultad de Lenguas; Argentina.Fil: Goetze, Katharina. Universidad Nacional de Córdoba. Facultad de Lenguas; Argentina.Otras Lengua y Literatur
Actively transcribed rRNA genes in S. cerevisiae are organized in a specialized chromatin associated with the high-mobility group protein Hmo1 and are largely devoid of histone molecules
Synthesis of ribosomal RNAs (rRNAs) is the major transcriptional event in proliferating cells. In eukaryotes, ribosomal DNA (rDNA) is transcribed by RNA polymerase I from a multicopy locus coexisting in at least two different chromatin states. This heterogeneity of rDNA chromatin has been an obstacle to defining its molecular composition. We developed an approach to analyze differential protein association with each of the two rDNA chromatin states in vivo in the yeast Saccharomyces cerevisiae. We demonstrate that actively transcribed rRNA genes are largely devoid of histone molecules, but instead associate with the high-mobility group protein Hmo1
Brief dark exposure restored ocular dominance plasticity in aging mice and after a cortical stroke
In the primary visual cortex (V1), monocular deprivation (MD) induces a shift in the ocular dominance (OD) of binocular neurons towards the open eye (Wiesel and Hubel, 1963; Gordon and Stryker, 1996). In V1 of C57Bl/6J mice, this OD-plasticity is maximal in juveniles, declines in adults and is absent beyond postnatal day (PD) 110 (Lehmann and Lowel, 2008) if mice are raised in standard cages. Since it was recently shown that brief dark exposure (DE) restored OD-plasticity in young adult rats (PD70-100) (He et al., 2006), we wondered whether DE would restore OD-plasticity also in adult and old mice and after a cortical stroke. To this end, we raised mice in standard cages until adulthood and transferred them to a dark room for 10-14 days. Using intrinsic signal optical imaging we demonstrate that short-term DE can restore OD-plasticity after MD in both adult (PD138) and old mice (PD535), and that OD-shifts were mediated by an increase of open eye responses in V1. Interestingly, restored OD-plasticity after DE was accompanied by a reduction of both parvalbumin expressing cells and perineuronal nets and was prevented by increasing intracortical inhibition with diazepam. DE also maintained OD-plasticity in adult mice (PD150) after a stroke in the primary somatosensory cortex. In contrast, short-term DE did not affect basic visual parameters as measured by optomotry. In conclusion, short-termDEwas able to restore OD-plasticity in both adult and aging mice and even preserved plasticity after a cortical stroke, most likely mediated by reducing intracortical inhibition. (C) 2014 The Authors. Published by Elsevier Inc
Alternative Chromatin Structures of the 35S rRNA Genes in Saccharomyces cerevisiae Provide a Molecular Basis for the Selective Recruitment of RNA Polymerases I and II▿
In all eukaryotes, a specialized enzyme, RNA polymerase I (Pol I), is dedicated to transcribe the 35S rRNA gene from a multicopy gene cluster, the ribosomal DNA (rDNA). In certain Saccharomyces cerevisiae mutants, 35S rRNA genes can be transcribed by RNA polymerase II (Pol II). In these mutants, rDNA silencing of Pol II transcription is impaired. It has been speculated that upstream activating factor (UAF), which binds to a specific DNA element within the Pol I promoter, plays a crucial role in forming chromatin structures responsible for polymerase specificity and silencing at the rDNA locus. We therefore performed an in-depth analysis of chromatin structure and composition in different mutant backgrounds. We demonstrate that chromatin architecture of the entire Pol I-transcribed region is substantially altered in the absence of UAF, allowing RNA polymerases II and III to access DNA elements flanking a Pol promoter-proximal Reb1 binding site. Furthermore, lack of UAF leads to the loss of Sir2 from rDNA, correlating with impaired Pol II silencing. This analysis of rDNA chromatin provides a molecular basis, explaining many phenotypes observed in previous genetic analyses
Response to azacitidine is independent of p53 expression in higher-risk myelodysplastic syndromes and secondary acute myeloid leukemia
No abstract available
Diversification of Bromelioideae (Bromeliaceae) in the Brazilian Atlantic rainforest: a case study in Aechmea subgenus Ortgiesia
Aechmea subgenus Ortgiesia comprises ca. 20 species distributed in Brazil, Argentina, Paraguay, and Uruguay, with a center of diversity in the Brazilian Atlantic rainforest. We examined interspecific relationships of Ortgiesia based on Amplified Fragment Length Polymorphisms (AFLP). Ninety-six accessions belonging to 14 species of Ortgiesia were sampled, and genotyped with 11 AFLP primer combinations. The neighbor joining (NJ) tree depicted two main genetic groups within Aechmea subgenus Ortgiesia, and four subgroups. The NJ tree showed short internal branches, indicating an overall shallow genetic divergence among Ortgiesia species as expected for the recently radiated subfamily Bromelioideae. Our results suggest that hybridization and/or incomplete lineage sorting may have hampered the reconstruction of interspecific relationships in Aechmea subgenus Ortgiesia. The mapping of petal color (yellow, blue, pink, or white), inflorescence type (simple or compound), and inflorescence shape (ellipsoid, subcylindric, cylindric, or pyramidal) against the NJ tree indicated that these characters are of limited taxonomic use in Aechmea subgenus Ortgiesia due to homoplasy. An analysis of the current distribution of Ortgiesia identified the southern region of the Brazilian Atlantic rainforest, between latitudes of 26° and 27°S, as the center of diversity for the subgenus
Bee pollination increases yield quantity and quality of cash crops in Burkina Faso, West Africa
Mutualistic biotic interactions as among flowering plants and their animal pollinators are a key component of biodiversity. Pollination, especially by insects, is a key element in ecosystem functioning, and hence constitutes an ecosystem service of global importance. Not only sexual reproduction of plants is ensured, but also yields are stabilized and genetic variability of crops is maintained, counteracting inbreeding depression and facilitating system resilience. While experiencing rapid environmental change, there is an increased demand for food and income security, especially in sub-Saharan communities, which are highly dependent on small scale agriculture. By combining exclusion experiments, pollinator surveys and field manipulations, this study for the first time quantifies the contribution of bee pollinators to smallholders’ production of the major cash crops, cotton and sesame, in Burkina Faso. Pollination by honeybees and wild bees significantly increased yield quantity and quality on average up to 62%, while exclusion of pollinators caused an average yield gap of 37% in cotton and 59% in sesame. Self-pollination revealed inbreeding depression effects on fruit set and low germination rates in the F1-generation. Our results highlight potential negative consequences of any pollinator decline, provoking risks to agriculture and compromising crop yields in sub-Saharan West Africa