Mimicking sarcolemmal damage in vitro: a contractile 3D model of skeletal muscle for drug testing in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is the most prevalent neuromuscular disease diagnosed in childhood. It is a progressive and wasting disease, characterized by a degeneration of skeletal and cardiac muscles caused by the lack of dystrophin protein. The absence of this crucial structural protein leads to sarcolemmal fragility, resulting in muscle fiber damage during contraction. Despite ongoing efforts, there is no cure available for DMD patients. One of the primary challenges is the limited efficacy of current preclinical tools, which fail in modeling the biological complexity of the disease. Human-based three-dimensional (3D) cell culture methods appear as a novel approach to accelerate preclinical research by enhancing the reproduction of pathophysiological processes in skeletal muscle. In this work, we developed a patient-derived functional 3D skeletal muscle model of DMD that reproduces the sarcolemmal damage found in the native DMD muscle. These bioengineered skeletal muscle tissues exhibit contractile functionality, as they responded to electrical pulse stimulation. Sustained contractile regimes induced the loss of myotube integrity, mirroring the pathological myotube breakdown inherent in DMD due to sarcolemmal instability. Moreover, damaged DMD tissues showed disease functional phenotypes, such as tetanic fatigue. We also evaluated the therapeutic effect of utrophin upregulator drug candidates on the functionality of the skeletal muscle tissues, thus providing deeper insight into the real impact of these treatments. Overall, our findings underscore the potential of bioengineered 3D skeletal muscle technology to advance DMD research and facilitate the development of novel therapies for DMD and related neuromuscular disorders

Estimación de la humedad de tapones de corcho mediante medida de la resistencia electrica

En este trabajo se exponen los resultados obtenidos en el Departamento de Productos Forestales del CIFOR-INIA sobre la relación entre la resistencia eléctrica y el contenido de humedad de los tapones de corcho. Estos resultados muestran que los medidores de humedad utilizados habitualmente en la industria pueden alcanzar una precisión elevada, siempre y cuando se tenga en cuenta la influencia de los distintos factores que afectan a la relación resistencia eléctrica-humedad: tipo de tapón, dirección de la medida, temperatura del material. Además, se han obtenido los modelos matemáticos que permiten la calibración de cualquier aparato de este tipo de manera rápida y sencill

Invocació explícita versus invocació implícita: anàlisi comparativa de dos enfocaments de disseny de sistemes d'informació

The main goal of this work is to develop an initial characterization of an information systems design approach that we call implicit invocation and to analyse its potential advantatges and disadvantatges with respect to the conventional approach that we call explicit invocation. Our work tries to contribute to this approach at the specific field of object oriented design of information systems. In our analysis we use an example that consist in some simplified banking operations, that we use as basis for the comparation of the alternative designs we explore. We characterize what could be implicit invocation in information systems design, we apply this characterization to the example, and we present a comparative analysis of the two designs.Postprint (published version

The influence of the moisture content on the electrical resistance of two types of cork stoppers

The relationship between the log of the electrical resistance (ER; measured using pin electrodes) and the moisture content (MC) have not been reported in any form of cork. That is important for the cork stoppers industry because it should help in the design and verification of more precise devices for measuring cork moisture content. In this study, using linear regression techniques, different regression models of the type log(Log(R) + 1) = axh + b were derived to describe the relationship ERMC, that was measured using pin electrodes on two types of cork stoppers [natural (N) and agglomerate(AG)]. The results obtained show that in the models proposed, the moisture content of AG cork stoppers can be estimated with an error of ± 0.3%, while that of N stoppers can be estimated with an error of 0.5%. Neither the geographical origin of the N corks nor the surface treatment to which the AG corks were subjected significantly affected the proposed models. Therefore, the moisture content of cork stoppers could be measured at the industrial scale using electrical resistancetype moisture meter

Peak systolic velocity at arterial Doppler ultrasound in pediatric liver transplantation: A predictor of acute severe complications

Pediatria; Ecografia Doppler; Velocitat sistòlica màximaPediatric; Doppler ultrasound; Peak systolic velocityPediatría; Ecografía Doppler; Velocidad sistólica máximaThe diagnosis of arterial complications in children after Liver Transplantation (LT) urges prompt diagnosis and treatment. This study aims to determine whether hepatic artery Doppler Ultrasound (DUS) parameters can predict arterial complications in the immediate period after LT in children. A retrospective review of the pediatric liver database at our tertiary-care pediatric hospital was performed. The study included 70 pediatric patients who underwent a liver transplantation from 2016 to 2021. Clinical, laboratory and Doppler findings were recorded daily the first 5 days after transplantation, with special attention given to post-anastomotic Peak Systolic Velocity (PSV) and Resistive Index (RI). Patients with hepatic artery complications, including acute thrombosis and stenosis, had lower PSV values after surgery compared to the group with non-complications, with a statistical significance (< 0.001). Receiver operating characteristic (ROC) curve analysis determined an optimal cut-off value of PSV less than 29 cm/s the 2nd day after LT, 25.2 cm/s the 3rd day, 28.5 cm/s the 4th day and 29.4 cm/s the 5th day, to discriminate children with and without hepatic arterial complications. Notably, these cut-off values are lower than those proposed in adults. Optimal PSV cutt-off values in children in the immediate period after LT are presented. Knowledge of these cutt-off values improves the interpretation of DUS measurements and thereby, may help to accurately guide the clinical management

Limb-girdle muscular dystrophy 1F is caused by a microdeletion in the transportin 3 gene

In 2001, we reported linkage of an autosomal dominant form of limb-girdle muscular dystrophy, limb-girdle muscular dystrophy 1F, to chromosome 7q32.1-32.2, but the identity of the mutant gene was elusive. Here, using a whole genome sequencing strategy, we identified the causative mutation of limb-girdle muscular dystrophy 1F, a heterozygous single nucleotide deletion (c.2771del) in the termination codon of transportin 3 (TNPO3). This gene is situated within the chromosomal region linked to the disease and encodes a nuclear membrane protein belonging to the importin beta family. TNPO3 transports serine/arginine-rich proteins into the nucleus, and has been identified as a key factor in the HIV-import process into the nucleus. The mutation is predicted to generate a 15-amino acid extension of the C-terminus of the protein, segregates with the clinical phenotype, and is absent in genomic sequence databases and a set of >200 control alleles. In skeletal muscle of affected individuals, expression of the mutant messenger RNA and histological abnormalities of nuclei and TNPO3 indicate altered TNPO3 function. Our results demonstrate that the TNPO3 mutation is the cause of limb-girdle muscular dystrophy 1F, expand our knowledge of the molecular basis of muscular dystrophies and bolster the importance of defects of nuclear envelope proteins as causes of inherited myopathies

Experimental Demonstration of a Cognitive Optical Network for Reduction of Restoration Time

This paper presents the implementation and performance evaluation of a cognitive heterogeneous optical network testbed. The testbed integrates the CMP, the data plane and the cognitive system and reduces by 48% the link restoration time. This paper presents the implementation and performance evaluation of a cognitive heterogeneous optical network testbed. The testbed integrates the CMP, the data plane and the cognitive system and reduces by 48% the link restoration time

The Free and Cued Selective Reminding Test in Parkinson's Disease Mild Cognitive Impairment : Discriminative Accuracy and Neural Correlates

Altres ajuts: This work was partially supported by grants from La Marató TV3 (20142910, 2014/U/477); FIS (PI14/02058, PI15/00962); CIBERNED.Introduction: Memory alterations are common in Parkinson's disease (PD) patients but the mechanisms involved in these deficits remain poorly understood. The study aims to explore the profile of episodic memory deficits in non-demented early PD patients. Methods: We obtained neurological, cognitive and behavioral data from 114 PD patients and 41 healthy controls (HC). PD participants were grouped as normal cognition (PD-NC) and mild cognitive impairment (PD-MCI) according to the Level II criteria of the Movement Disorders Society Task Force (MDS-TF). We evaluate the performance amongst groups on an episodic memory task using the Free and Cued Selective Reminding Test (FCSRT). Additionally, gray matter volume (GMV) voxel based morphometry, and mean diffusivity (MD) analyses were conducted in a subset of patients to explore the structural brain correlates of FCSRT performance. Results: Performance on all subscores of the FCSRT was significantly worse in PD-MCI than in PD-NC and HC. Delayed total recall (DTR) subscore was the best at differentiating PD-NC from PD-MCI. Using crosstabulation, DTR allowed identification of PD-MCI patients with an accuracy of 80%. Delayed free and cued recall was associated with decreased GMV and increased MD in multiple fronto-temporal and parietal areas. Conclusion: Encoding and retrieval deficits are a main characteristic of PD-MCI and are associated with structural damage in temporal, parietal and prefrontal areas

The PAU Survey: A Forward Modeling Approach for Narrow-band Imaging

Weak gravitational lensing is a powerful probe of the dark sector, once measurement systematic errors can be controlled. In Refregier & Amara (2014), a calibration method based on forward modeling, called MCCL, was proposed. This relies on fast image simulations (e.g., UFig; Berge et al. 2013) that capture the key features of galaxy populations and measurement effects. The MCCL approach has been used in Herbel et al. (2017) to determine the redshift distribution of cosmological galaxy samples and, in the process, the authors derived a model for the galaxy population mainly based on broad-band photometry. Here, we test this model by forward modeling the 40 narrow-band photometry given by the novel PAU Survey (PAUS). For this purpose, we apply the same forced photometric pipeline on data and simulations using Source Extractor (Bertin & Arnouts 1996). The image simulation scheme performance is assessed at the image and at the catalogues level. We find good agreement for the distribution of pixel values, the magnitudes, in the magnitude-size relation and the interband correlations. A principal component analysis is then performed, in order to derive a global comparison of the narrow-band photometry between the data and the simulations. We use a `mixing' matrix to quantify the agreement between the observed and simulated sets of Principal Components (PCs). We find good agreement, especially for the first three most significant PCs. We also compare the coefficients of the PCs decomposition. While there are slight differences for some coefficients, we find that the distributions are in good agreement. Together, our results show that the galaxy population model derived from broad-band photometry is in good overall agreement with the PAUS data. This offers good prospect for incorporating spectral information to the galaxy model by adjusting it to the PAUS narrow-band data using forward modeling.Comment: Submitted to JCAP, 28 pages, 15 figures, 3 appendice