59 research outputs found
(Not) Keeping the stem straight: a proteomic analysis of maritime pine seedlings undergoing phototropism and gravitropism
<p>Abstract</p> <p>Background</p> <p>Plants are subjected to continuous stimuli from the environment and have evolved an ability to respond through various growth and development processes. Phototropism and gravitropism responses enable the plant to reorient with regard to light and gravity.</p> <p>Results</p> <p>We quantified the speed of maritime pine seedlings to reorient with regard to light and gravity over 22 days. Seedlings were inclined at 15, 30 and 45 degrees with vertical plants as controls. A lateral light source illuminated the plants and stem movement over time was recorded. Depending on the initial angle of stem lean, the apical response to the lateral light source differed. In control and 15° inclined plants, the apex turned directly towards the light source after only 2 h. In plants inclined at 30° and 45°, the apex first reoriented in the vertical plane after 2 h, then turned towards the light source after 24 h. Two-dimensional gel electrophoresis coupled with mass spectrometry was then used to describe the molecular response of stem bending involved in photo- and gravi-tropism after 22 hr and 8 days of treatment. A total of 486 spots were quantitatively analyzed using image analysis software. Significant changes were determined in the protein accumulation of 68 protein spots. Early response gravitropic associated proteins were identified, which are known to function in energy related and primary metabolism. A group of thirty eight proteins were found to be involved in primary metabolism and energy related metabolic pathways. Degradation of Rubisco was implicated in some protein shifts.</p> <p>Conclusions</p> <p>Our study demonstrates a rapid gravitropic response in apices of maritime pine seedlings inclined >30°. Little or no response was observed at the stem bases of the same plants. The primary gravitropic response is concomitant with a modification of the proteome, consisting of an over accumulation of energy and metabolism associated proteins, which may allow the stem to reorient rapidly after bending.</p
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An integrated clinical program and crowdsourcing strategy for genomic sequencing and Mendelian disease gene discovery.
Despite major progress in defining the genetic basis of Mendelian disorders, the molecular etiology of many cases remains unknown. Patients with these undiagnosed disorders often have complex presentations and require treatment by multiple health care specialists. Here, we describe an integrated clinical diagnostic and research program using whole-exome and whole-genome sequencing (WES/WGS) for Mendelian disease gene discovery. This program employs specific case ascertainment parameters, a WES/WGS computational analysis pipeline that is optimized for Mendelian disease gene discovery with variant callers tuned to specific inheritance modes, an interdisciplinary crowdsourcing strategy for genomic sequence analysis, matchmaking for additional cases, and integration of the findings regarding gene causality with the clinical management plan. The interdisciplinary gene discovery team includes clinical, computational, and experimental biomedical specialists who interact to identify the genetic etiology of the disease, and when so warranted, to devise improved or novel treatments for affected patients. This program effectively integrates the clinical and research missions of an academic medical center and affords both diagnostic and therapeutic options for patients suffering from genetic disease. It may therefore be germane to other academic medical institutions engaged in implementing genomic medicine programs
Macrocephaly and developmental delay caused by missense variants in RAB5C
Rab GTPases are important regulators of intracellular vesicular trafficking. RAB5C is a member of the Rab GTPase family that plays an important role in the endocytic pathway, membrane protein recycling and signaling. Here we report on 12 individuals with nine different heterozygous de novo variants in RAB5C. All but one patient with missense variants (n = 9) exhibited macrocephaly, combined with mild-to-moderate developmental delay. Patients with loss of function variants (n = 2) had an apparently more severe clinical phenotype with refractory epilepsy and intellectual disability but a normal head circumference. Four missense variants were investigated experimentally. In vitro biochemical studies revealed that all four variants were damaging, resulting in increased nucleotide exchange rate, attenuated responsivity to guanine exchange factors and heterogeneous effects on interactions with effector proteins. Studies in C. elegans confirmed that all four variants were damaging in vivo and showed defects in endocytic pathway function. The variant heterozygotes displayed phenotypes that were not observed in null heterozygotes, with two shown to be through a dominant negative mechanism. Expression of the human RAB5C variants in zebrafish embryos resulted in defective development, further underscoring the damaging effects of the RAB5C variants. Our combined bioinformatic, in vitro and in vivo experimental studies and clinical data support the association of RAB5C missense variants with a neurodevelopmental disorder characterized by macrocephaly and mild-to-moderate developmental delay through disruption of the endocytic pathway
Non-linear models and learning for Near Infrared spectra
Near Infrared (NIR) spectrometry is a non-destructive and relatively cheap technology which enables automated controls in various domains such as food industry or pharmaceutics. Yet, if the quality of the prediction obtained thanks to NIR spectra is important, identifying the chemical components responsible for the prediction is also an essential issue, often neglected by traditional methods.
Generally speaking, NIR spectra may be considered as high-dimensional vectors, with an important degree of redundancy between components. These properties lead to numerical issues and render the models complex to interpret. A dimensionality reduction step is consequently required. Besides, factors such as experimental conditions induce non-linearities in the relationship between the spectral variables and the parameter of interest, which are ignored by the models traditionally met in this context.
The main goal of this work is therefore to propose a methodology taking the non-linearities into account and leading to an easier interpretation in terms of wavelength bands. This methodology relies on three aspects: spectra and variables normalizations, dimensionality reduction steps and non-linear modeling. In particular, the dimensionality issue is addressed by filters based on the Mutual Information concept, and functional methods such as B-splines representation or variable clustering.
A study over six databases reveals that non-linear models globally outperform linear models. In addition, the proposed methodology enables to identify a reduced number of wavelength ranges which correspond mostly to spectral regions considered as meaningful by the specialists.(FSA 3) -- UCL, 201
Effets de la pré-hypoxie sur l'apoptose et les récepteurs A2A à l'adénosine cérébraux dans un modèle d'hypoxie-ischémie néonatale chez le rat
TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Un gisement moustérien dans le Nord de la Bourgogne à Champlost (Yonne) : premiers résultats
A new mousterian open air site has been discovered in north Burgundy, showing a well-preserved mammalian fauna, traces of fire and a Charentian lithic industry. A preliminary analysis of this industry, previously unknown in this part of France, is preceded by a stratigraphic review showing the evolution of local landscape during the past glacial period.Un gisement moustérien de plein air en place vient d'être découvert dans le nord de l'Yonne, aux confins de la Champagne et de la Bourgogne. Une présentation de l'industrie lithique, de type Charentien et inédite localement, est précédée d'un premier bilan stratigraphique qui permet de suivre l'évolution du modèle du site et suggère que les paléolithiques se sont installés à Champlost à la faveur d'un réchauffement.Girard Catherine, Krier Vincent. Un gisement moustérien dans le Nord de la Bourgogne à Champlost (Yonne) : premiers résultats. In: Bulletin de l'Association française pour l'étude du quaternaire, vol. 19, n°2-3, 1982. pp. 129-134
Une approche orientée données pour la projection de variables spectrales en spectrométrie
Neural modelling of ranking data with an application to stated preference data
Although neural networks are commonly encountered to solve classification problems, ranking data present specificities which require adapting the model Based on a latent utility function defined on the characteristics of the objects to be ranked, the approach suggested in this paper leads to a perception-based algorithm for a highly non linear model. Data on stated preferences obtained through a survey by face-to-face interviews, in the field of freight transport, are used to illustrate the method. Numerical difficulties are pin-pointed and a Pocket type algorithm is shown to provide an efficient heuristic to minimize the discrete error criterion. A substantial merit of this approach is to provide a workable estimation of contextually interpretable parameters along with a statistical evaluation of the goodness of fit
Neural modelling of ranking data with an application to stated preference data
Although neural networks are commonly encountered to solve classification problems, ranking data present specificities which require adapting the model. Based on a latent utility function defined on the characteristics of the ob jects to be ranked, the approach suggested in this paper leads to a perceptron-based algorithm for a highly non linear model. Data on stated preferences obtained through a survey by face-to-face interviews, in the field of freight transport, are used to illustrate the method. Numerical difficulties are pinpointed and a Pocket type algorithm is shown to provide an efficient heuristic to minimize the discrete error criterion. A substantial merit of this approach is to provide a workable estimation of contextually interpretable parameters along with a statistical evaluation of the goodness of fit
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