563 research outputs found

    Ratphones: an affordable tool for highly controlled sound presentation in freely moving rats

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    [Abstract] Encoding and processing sensory information is key to understanding the environment and to guiding behavior accordingly. Characterizing the behavioral and neural correlates of these processes requires the experimenter to have a high degree of control over stimuli presentation. For auditory stimulation in animals with relatively large heads, this can be accomplished by using headphones. However, it has proven more challenging in smaller species, such as rats and mice, and has been only partially solved using closed-field speakers in anesthetized or head-restrained preparations. To overcome the limitations of such preparations and to deliver sound with high precision to freely moving animals, we have developed a set of miniature headphones for rats. The headphones consist of a small, skull-implantable base attached with magnets to a fully adjustable structure that holds the speakers and keeps them in the same position with respect to the ears

    ¿Cómo conservan los agricultores sus semillas en el trópico húmedo de Cuba, México y Perú? Experiencias de un proyecto de investigación en sistemas informales de semillas de chile, frijoles y maíz

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    Este libro presenta los resultados de un proyecto de investigación donde se evaluó la manera como los sistemas locales de semilla abastecen y mantienen los recursos genéticos de los cultivos importantes para los medios de vida de los agricultores en comunidades de escasos recursos ubicadas en la zona del trópico húmedo de Cuba, México y la región amazónica del Perú. La investigación se enfocó principalmente en el maíz (Zea mays), el frijol común (Phaseolus vulgaris), el frijol pallar (Phaseolus lunatus) y el chile (Capsicum spp.), caracterizando y cuantificando el flujo de semillas en las redes de agricultores. Se analizó la función de los agricultores nudo en estas redes, y se evaluó el rol de hombres y mujeres en el manejo de semillas por parte de los agricultores. Se identificaron también factores que limitan la capacidad de los agricultores para almacenar semilla destinada para la resiembra, o que conducen a la pérdida de semilla, como la deficiencia de métodos y recipientes adecuados para el almacenamiento de las semillas

    Supporting info item, In: "Using SHRIMP zircon dating to unravel tectonothermal events in arc environments. The early Palaeozoic arc of NW Iberia revisited"

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    Dating of zircon cores and rims from granulites developed in a shear zone provides insights into the complex relationship between magmatism and metamorphism in the deep roots of arc environments. The granulites belong to the uppermost allochthonous terrane of the NW Iberian Massif, which forms part of a Cambro-Ordovician magmatic arc developed in the peri-Gondwanan realm. The obtained zircon ages confirm that voluminous calc-alkaline magmatism peaked around 500 Ma and was shortly followed by granulite facies metamorphism accompanied by deformation at c. 480 Ma, giving a time framework for crustal heating, regional metamorphism, deformation and partial melting, the main processes that control the tectonothermal evolution of arc systems. Traces of this arc can be discontinuously followed in different massifs throughout the European Variscan Belt, and we propose that the uppermost allochthonous units of the NW Iberian Massif, together with the related terranes in Europe, constitute an independent and coherent terrane that drifted away from northern Gondwana prior to the Variscan collisional orogenesis

    Low-energy sector quantization of a massless scalar field outside a Reissner-Nordstrom black hole and static sources

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    We quantize the low-energy sector of a massless scalar field in the Reissner-Nordstrom spacetime. This allows the analysis of processes involving soft scalar particles occurring outside charged black holes. In particular, we compute the response of a static scalar source interacting with Hawking radiation using the Unruh (and the Hartle-Hawking) vacuum. This response is compared with the one obtained when the source is uniformly accelerated in the usual vacuum of the Minkowski spacetime with the same proper acceleration. We show that both responses are in general different in opposition to the result obtained when the Reissner-Nordstrom black hole is replaced by a Schwarzschild one. The conceptual relevance of this result is commented.Comment: 12 pages (REVTEX), no figure

    The mechanistic foundation of Weber’s law

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    [Abstract] Although Weber's law is the most firmly established regularity in sensation, no principled way has been identified to choose between its many proposed explanations. We investigated Weber's law by training rats to discriminate the relative intensity of sounds at the two ears at various absolute levels. These experiments revealed the existence of a psychophysical regularity, which we term time-intensity equivalence in discrimination (TIED), describing how reaction times change as a function of absolute level. The TIED enables the mathematical specification of the computational basis of Weber's law, placing strict requirements on how stimulus intensity is encoded in the stochastic activity of sensory neurons and revealing that discriminative choices must be based on bounded exact accumulation of evidence. We further demonstrate that this mechanism is not only necessary for the TIED to hold but is also sufficient to provide a virtually complete quantitative description of the behavior of the rats

    Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders

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    BACKGROUND: With over 50 different disorders and a combined incidence of up to 1/3000 births, lysosomal storage diseases (LSDs) constitute a major public health problem and place an enormous burden on affected individuals and their families. Many factors make LSD diagnosis difficult, including phenotype and penetrance variability, shared signs and symptoms, and problems inherent to biochemical diagnosis. Developing a powerful diagnostic tool could mitigate the protracted diagnostic process for these families, lead to better outcomes for current and proposed therapies, and provide the basis for more appropriate genetic counseling. METHODS: We have designed a targeted resequencing assay for the simultaneous testing of 57 lysosomal genes, using in-solution capture as the enrichment method and two different sequencing platforms. A total of 84 patients with high to moderate-or low suspicion index for LSD were enrolled in different centers in Spain and Portugal, including 18 positive controls. RESULTS: We correctly diagnosed 18 positive blinded controls, provided genetic diagnosis to 25 potential LSD patients, and ended with 18 diagnostic odysseys. CONCLUSION: We report the assessment of a next-generation-sequencing-based approach as an accessory tool in the diagnosis of LSDs, a group of disorders which have overlapping clinical profiles and genetic heterogeneity. We have also identified and quantified the strengths and limitations of next generation sequencing (NGS) technology applied to diagnosis

    Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: regional experience and high incidence of carnitine deficiency

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    Background Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common inherited defect in the mitochondrial fatty acid oxidation pathway, resulting in significant morbidity and mortality in undiagnosed patients. Newborn screening (NBS) has considerably improved MCADD outcome, but the risk of complication remains in some patients. The aim of this study was to evaluate the relationship between genotype, biochemical parameters and clinical data at diagnosis and during follow-up, in order to optimize monitoring of these patients. Methods We carried out a multicenter study in southwest Europe, of MCADD patients detected by NBS. Evaluated NBS data included free carnitine (C0) and the acylcarnitines C8, C10, C10:1 together with C8/C2 and C8/C10 ratios, clinical presentation parameters and genotype, in 45 patients. Follow-up data included C0 levels, duration of carnitine supplementation and occurrence of metabolic crises. Results C8/C2 ratio and C8 were the most accurate biomarkers of MCADD in NBS. We found a high number of patients homozygous for the prevalent c.985A > G mutation (75%). Moreover, in these patients C8, C8/C10 and C8/C2 were higher than in patients with other genotypes, while median value of C0 was significantly lower (23 μmol/L vs 36 μmol/L). The average follow-up period was 43 months. To keep carnitine levels within the normal range, carnitine supplementation was required in 82% of patients, and for a longer period in patients homozygotes for the c.985A>G mutation than in patients with other genotypes (average 31 vs 18 months). Even with treatment, median C0 levels remained lower in homozygous patients than in those with other genotypes (14 μmol/L vs 22 μmol/L). Two patients died and another three suffered a metabolic crisis, all of whom were homozygous for the c.985 A>G mutation. Conclusions Our data show a direct association between homozygosity for c.985A>G and lower carnitine values at diagnosis, and a higher dose of carnitine supplementation for maintenance within the normal range. This study contributes to a better understanding of the relationship between genotype and phenotype in newborn patients with MCADD detected through screening which could be useful in improving follow-up strategies and clinical outcome

    A gap analysis modelling framework to prioritize collecting for ex situ conservation of crop landraces

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    Aim: The conservation and effective use of crop genetic diversity are crucial to over-come challenges related to human nutrition and agricultural sustainability. Farmers’ traditional varieties (“landraces”) are major sources of genetic variation. The degree of representation of crop landrace diversity in ex situ conservation is poorly under-stood, partly due to a lack of methods that can negotiate both the anthropogenic and environmental determinants of their geographic distributions. Here, we describe a novel spatial modelling and ex situ conservation gap analysis modelling framework for crop landraces, using common bean (Phaseolus vulgaris L.) as a case study.Location: The Americas.Methods: The modelling framework includes five main steps: (a) determining relevant landrace groups using literature to develop and test classification models; (b) model-ling the potential geographic distributions of these groups using occurrence (landrace presences) combined with environmental and socioeconomic predictor data; (c) cal-culating geographic and environmental gap scores for current genebank collections; (d) mapping ex situ conservation gaps; and (e) compiling expert inputs.Results: Modelled distributions and conservation gaps for the two genepools of com-mon bean (Andean and Mesoamerican) were robustly predicted and align well with expert opinions. Both genepools are relatively well conserved, with Andean ex situ collections representing 78.5% and Mesoamerican 98.2% of their predicted geo-graphic distributions. Modelling revealed additional collection priorities for Andean landraces occur primarily in Chile, Peru, Colombia and, to a lesser extent, Venezuela. Mesoamerican landrace collecting priorities are concentrated in Mexico, Belize and Guatemala.Conclusions: The modelling framework represents an advance in tools that can be deployed to model the geographic distributions of cultivated crop diversity, to as-sess the comprehensiveness of conservation of this diversity ex situ and to highlight geographic areas where further collecting may be conducted to fill gaps in ex situ conservation

    Analysis of blood and nasal epithelial transcriptomes to identify mechanisms associated with control of SARS-CoV-2 viral load in the upper respiratory tract

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    Objectives: The amount of SARS-CoV-2 detected in the upper respiratory tract (URT viral load) is a key driver of transmission of infection. Current evidence suggests that mechanisms constraining URT viral load are different from those controlling lower respiratory tract viral load and disease severity. Understanding such mechanisms may help to develop treatments and vaccine strategies to reduce transmission. Combining mathematical modelling of URT viral load dynamics with transcriptome analyses we aimed to identify mechanisms controlling URT viral load. Methods: COVID-19 patients were recruited in Spain during the first wave of the pandemic. RNA sequencing of peripheral blood and targeted NanoString nCounter transcriptome analysis of nasal epithelium were performed and gene expression analysed in relation to paired URT viral load samples collected within 15 days of symptom onset. Proportions of major immune cells in blood were estimated from transcriptional data using computational differential estimation. Weighted correlation network analysis (adjusted for cell proportions) and fixed transcriptional repertoire analysis were used to identify associations with URT viral load, quantified as standard deviations (z-scores) from an expected trajectory over time. Results Eighty-two subjects (50% female, median age 54 years (range 3–73)) with COVID-19 were recruited. Paired URT viral load samples were available for 16 blood transcriptome samples, and 17 respiratory epithelial transcriptome samples. Natural Killer (NK) cells were the only blood cell type significantly correlated with URT viral load z-scores (r = −0.62, P = 0.010). Twenty-four blood gene expression modules were significantly correlated with URT viral load z-score, the most significant being a module of genes connected around IFNA14 (Interferon Alpha-14) expression (r = −0.60, P = 1e-10). In fixed repertoire analysis, prostanoid-related gene expression was significantly associated with higher viral load. In nasal epithelium, only GNLY (granulysin) gene expression showed significant negative correlation with viral load. Conclusions: Correlations between the transcriptional host response and inter-individual variations in SARS-CoV-2 URT viral load, revealed many molecular mechanisms plausibly favouring or constraining viral replication. Existing evidence corroborates many of these mechanisms, including likely roles for NK cells, granulysin, prostanoids and interferon alpha-14. Inhibition of prostanoid production and administration of interferon alpha-14 may be attractive transmission-blocking interventions
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