DomainRBF: a Bayesian regression approach to the prioritization of candidate domains for complex diseases

BACKGROUND: Domains are basic units of proteins, and thus exploring associations between protein domains and human inherited diseases will greatly improve our understanding of the pathogenesis of human complex diseases and further benefit the medical prevention, diagnosis and treatment of these diseases. Within a given domain-domain interaction network, we make the assumption that similarities of disease phenotypes can be explained using proximities of domains associated with such diseases. Based on this assumption, we propose a Bayesian regression approach named domainRBF (domain Rank with Bayes Factor) to prioritize candidate domains for human complex diseases. RESULTS: Using a compiled dataset containing 1,614 associations between 671 domains and 1,145 disease phenotypes, we demonstrate the effectiveness of the proposed approach through three large-scale leave-one-out cross-validation experiments (random control, simulated linkage interval, and genome-wide scan), and we do so in terms of three criteria (precision, mean rank ratio, and AUC score). We further show that the proposed approach is robust to the parameters involved and the underlying domain-domain interaction network through a series of permutation tests. Once having assessed the validity of this approach, we show the possibility of ab initio inference of domain-disease associations and gene-disease associations, and we illustrate the strong agreement between our inferences and the evidences from genome-wide association studies for four common diseases (type 1 diabetes, type 2 diabetes, Crohn\u27s disease, and breast cancer). Finally, we provide a pre-calculated genome-wide landscape of associations between 5,490 protein domains and 5,080 human diseases and offer free access to this resource. CONCLUSIONS: The proposed approach effectively ranks susceptible domains among the top of the candidates, and it is robust to the parameters involved. The ab initio inference of domain-disease associations shows strong agreement with the evidence provided by genome-wide association studies. The predicted landscape provides a comprehensive understanding of associations between domains and human diseases

Functional analysis and binding affinity of tomato ethylene response factors provide insight on the molecular bases of plant differential responses to ethylene

Background : The phytohormone ethylene is involved in a wide range of developmental processes and in mediating plant responses to biotic and abiotic stresses. Ethylene signalling acts via a linear transduction pathway leading to the activation of Ethylene Response Factor genes (ERF)which represent one of the largest gene families of plant transcription factors. How an apparently simple signalling pathway can account for the complex and widely diverse plant responses to ethylene remains yet an unanswered question. Building on the recent release of the complete tomato genome sequence, the present study aims at gaining better insight on distinctive features among ERF proteins. Results : A set of 28 cDNA clones encoding ERFs in the tomato (Solanum lycopersicon) were isolated and shown to fall into nine distinct subclasses characterised by specific conserved motifs most of which with unknown function. In addition of being able to regulate the transcriptional activity of GCC-box containing promoters, tomato ERFs are also shown to be active on promoters lacking this canonical ethylene-responsive-element. Moreover, the data reveal that ERF affinity to the GCC-box depends on the nucleotide environment surrounding this cis-acting element. Site-directed mutagenesis revealed that the nature of the flanking nucleotides can either enhance or reduce the binding affinity, thus conferring the binding specificity of various ERFs to target promoters. Based on their expression pattern, ERF genes can be clustered in two main clades given their preferential expression in reproductive or vegetative tissues. The regulation of several tomato ERF genes by both ethylene and auxin, suggests their potential contribution to the convergence mechanism between the signalling pathways of the two hormones. Conclusions : The data reveal that regions flanking the core GCC-box sequence are part of the discrimination mechanism by which ERFs selectively bind to their target promoters. ERF tissue-specific expression combined to their responsiveness to both ethylene and auxin bring some insight on the complexity and fine regulation mechanisms involving these transcriptional mediators. All together the data support the hypothesis that ERFs are the main component enabling ethylene to regulate a wide range of physiological processes in a highly specific and coordinated manner

MRI characteristics of lumbosacral dural arteriovenous fistulas

Background and purposeSpinal dural arteriovenous fistulas located in the lumbosacral region are rare and present with nonspecific clinical signs. The purpose of this study was to find out the specific radiologic features of these fistulas.MethodsWe retrospectively reviewed the clinical and radiological data of 38 patients diagnosed with lumbosacral spinal dural arteriovenous fistulas in our institution from September 2016 to September 2021. All patients underwent time-resolved contrast-enhanced three-dimensional MRA and DSA examinations, and were treated with either endovascular or neurosurgical strategies.ResultsMost of the patients (89.5%) had motor or sensory disorders in both lower limbs as the first symptoms. On MRA, the dilated filum terminale vein or radicular vein was seen in 23/30 (76.7%) patients with lumbar spinal dural arteriovenous fistulas and 8/8 (100%) patients with sacral spinal dural arteriovenous fistulas. T2W intramedullary abnormally high signal intensity areas were found in all lumbosacral spinal dural arteriovenous fistula patients, with involvement of the conus present in 35/38 (92.1%) patients. The “missing piece sign” in the intramedullary enhancement area was seen in 29/38 (76.3%) patients.ConclusionDilatation of the filum terminale vein or radicular vein is powerful evidence for diagnosis of lumbosacral spinal dural arteriovenous fistulas, especially for sacral spinal dural arteriovenous fistulas. T2W intramedullary hyperintensity in the thoracic spinal cord and conus, and the missing-piece sign could be indicative of lumbosacral spinal dural arteriovenous fistula

Drying intensification by vibration: fundamental study of liquid water inside a pore

[EN] Vibration is a promising way to intensify the drying process through heating-up due to viscous dissipation, activation of internal liquid transfer and increase of external transfer. To better assess the possible contribution of these effects, we choose a multiscale approach. This paper is focused on the pore scale, simulated by a capillary tube partially filled with water subjected to sinusoidal vibrations. We studied the displacement of water inside this tube through image analysis. This configuration mimics the moisture transfer inside the pores of a porous media during drying. The experimental device developed in this study is applicable to a wide range of configurations, such as symmetrical or asymmetrical vibrations.Chen, W.; Colin, J.; Casalinho, J.; Ben Amara, M.; Stambouli, M.; Perré, P. (2010). Drying intensification by vibration: fundamental study of liquid water inside a pore. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 1911-1918. https://doi.org/10.4995/IDS2018.2018.7961OCS1911191

Étude microscopique du comportement de l'eau dans un pore unique soumis à des vibrations pour intensifier le séchage

A better economic performance of industrial drying consists both in product quality improvement and energy efficiency enhancement. Several technologies can be applied to intensify the drying process. This work is focused on the effect of vibration that can assist the drying through heating-up due to viscous dissipation, enhancement of liquid and vapor migration inside the porous medium and the increase of the external heat and mass transfer. However, despite previous numerical and experimental studies, the assessment of the relative importance of these intensification mechanisms has still to be improved.This work is focused on the pore scale, simulated by a capillary tube, partially filled with water subjected to sinusoidal vibrations. A full experimental device was conceived, developed and used. Thanks to a relevant image processing chain, the behavior of water inside the tube (displacement and meniscus radius), was investigated for various vibration configurations (frequency, amplitude, tube size). Experiments with both symmetrical and asymmetrical geometries are intended to mimic the moisture transfer during drying of a porous medium. Whatever the configuration, the drying intensification was clearly confirmed.For the symmetrical configuration, a new 2D dimensionless number map is set to summarize the capillary and viscous effects and thus to explain the water behavior depending on vibration conditions (tube radius, frequency and amplitude). For the asymmetrical configuration, the experimental results are discussed and compared to the simulations obtained with two computational models (a 0-D model and 1-D model). The potential of modeling was evidenced but still limited by the surrounding physical assumptions. Further developments are proposed to increase the validity range and further investigate this physical systemUne meilleure performance économique du séchage industriel consiste à la fois en l'amélioration de la qualité des produits et de l’optimisation énergétique. Plusieurs technologies peuvent être appliquées pour intensifier le processus de séchage. Ce travail s’intéresse à l'effet des vibrations, qui peuvent accélérer le séchage via un échauffement par dissipation visqueuse, une amélioration de la migration de l’eau liquide et de la vapeur à l'intérieur du milieu poreux et une augmentation des coefficients de transferts externes de chaleur de masse. Toutefois, malgré les études numériques et expérimentales antérieures, l'évaluation de l'importance relative de ces mécanismes d'intensification doit encore être améliorée.Ce travail porte sur l'échelle du pore, simulée par un tube capillaire, partiellement rempli d'eau soumis à des vibrations sinusoïdales. Un dispositif expérimental complet a été conçu, développé et utilisé. Grâce à une procédure de traitement d'images pertinente, le comportement de l'eau à l'intérieur du tube (déplacement et le rayon du ménisque) ont été étudiés pour différentes configurations de vibrations (fréquence, amplitude, taille du tube). Les expériences avec des géométries symétriques et asymétriques sont destinées à imiter le transfert d'humidité pendant le séchage d'un milieu poreux. Quelle que soit la configuration étudiée, l'intensification du séchage a été clairement confirmée.Pour la configuration symétrique, une nouvelle cartographie 2D basée sur des nombres adimensionnels est définie pour résumer les effets capillaires et visqueux, et ainsi expliquer le comportement de l'eau en fonction des conditions vibratoires (rayon du tube, fréquence et amplitude). Pour la configuration asymétrique, les résultats expérimentaux sont discutés et comparés aux simulations obtenues avec deux modèles numériques (un modèle 0-D et un modèle 1-D). Le potentiel de la modélisation a été mis en évidence, mais il est encore limité par les hypothèses physiques aux interfaces. D'autres développements sont proposés afin d'augmenter la plage de validité et d'approfondir l'étude de ce système physique

Monitoring of the mass transfer in porous media by coupling technologies of imaging

International audienceThe mass transfer in porous media is commonly monitored through the evolution of the sample weight. This method is robust but requiresa mechanical link between the instrument and the sample, andcannot reveal the complexity of internal and exchange phenomena. In this paper, two complementary imaging technologies are used to investigate the coupling between internal and external transfer. On the one hand, X-rayimagingcan be used to assess the moisture content profile inside the porous medium. On the other hand, thanks to the coupling between heat and mass transfer, infrared radiationsallow the external mass transfer to be investigated through the surface temperature.Thesemethodswill be used in ongoing works for studying the efficiency of the transfer, with or without intensification methods, such as vibrations

The PUMCH Conservative Classification System for Young Idiopathic Scoliosis Patients

Objective  To establish a new method of scoliosis specific exercise(SSE) classification foryoung idiopathic scoliosis(IS) patients and evaluate its clinical practicability.  Methods  This study consists of two parts, the first part, a retrospective analysis, aimed at establishing Peking Union Medical College Hospital(PUMCH) conservative classification system for young IS patients and evaluating its reliability and repeatability. The research subjects were young IS patients in PUMCH from January 2013 to June 2020. The standing X-ray(A-P and lateral) and clinical appearance (bending and standing) were analyzed. The PUMCH conservative classification system was established based on PUMC surgical classification system, and the consistency test was conducted for the inter group reliability and intra group repeatability of the observers. The second part, an ambispective cohort study, aimed at verifying the role of PUMCH conservative classification system in guiding clinical treatment and evaluating its clinical practicability. The research subjects were young IS patients(4 to 17 years old) who received conservative treatment in PUMCH from July 2020 to August 2020. According to the wishes of patients and their families, they were divided into training group and control group. The control group only had regular reexamination without clinical intervention, while the training group conducted SSE based on PUMCH conservative classification system (continuous treatment for 1 year). Cobb angle difference and patient satisfaction were compared between the two groups after 1 year.  Results  (1) A total of 899 young IS patients who met the inclusion and exclusion criteria were selected for the retrospective study. PUMCH conservative classification system finally included 4 types and 9 subtypes after revising the single-curve(type Ⅰ), double-curve(type Ⅱ) and triple-curve(type Ⅲ) in PUMC surgical classification, and adding a micro-curve (type 0). The mean inter-observer reliability was 88.23%, with Kappa coefficient 0.862, while mean intra-observer repeatability was 92.78%, with Kappa coefficient 0.908. (2) Ambispective cohort study included 90 young IS patients who met the inclusion and exclusion criteria. There were 51 cases in the training group and 39 cases in the control group. The Cobb angle of the training group decreased from (16.61±2.88)°to (12.16±9.97)° after 1 year of treatment(P=0.002), while the Cobb angle of the control group increased from (15.74±2.75)° to (17.64±5.60)° after 1 year(P=0.014). There was clinical significance between the two groups(Cobb angle difference≥5°). After 1 year, the satisfaction score of the training group increased from 3(3, 3) to 5(3, 5)(P≤0.001), while that of the control group decreased from 3(3, 3) to 3(1, 3) (P=0.004).  Conclusions  A new conservative classification system for young IS patients is established. The PUMCH conservative classification system not only has good reliability and repeatability, but also has clinical practicability in guiding SSE