1,171 research outputs found

    Arachnoid cyst with intracystic haemorrhage and subdural haematoma: case report and literature review

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    Arachnoid cysts (AC) are usually asymptomatic. However, very rarely they can become symptomatic due to cyst enlargement or haemorrhage, often after head trauma. In such cases bleeding is often confined to the subdural space, but intracystic haemorrhage has rarely been observed. We report a case of a child who had intracranial hypertension syndrome due to a right middle cranial fossa AC with intracystic bleeding and subdural haematoma

    Tailoring Cellular Function: The Contribution of the Nucleus in Mechanotransduction

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    Cells sense a variety of different mechanochemical stimuli and promptly react to such signals by reshaping their morphology and adapting their structural organization and tensional state. Cell reactions to mechanical stimuli arising from the local microenvironment, mechanotransduction, play a crucial role in many cellular functions in both physiological and pathological conditions. To decipher this complex process, several studies have been undertaken to develop engineered materials and devices as tools to properly control cell mechanical state and evaluate cellular responses. Recent reports highlight how the nucleus serves as an important mechanosensor organelle and governs cell mechanoresponse. In this review, we will introduce the basic mechanisms linking cytoskeleton organization to the nucleus and how this reacts to mechanical properties of the cell microenvironment. We will also discuss how perturbations of nucleus-cytoskeleton connections, affecting mechanotransduction, influence health and disease. Moreover, we will present some of the main technological tools used to characterize and perturb the nuclear mechanical state

    Confinement and Low Adhesion Induce Fast Amoeboid Migration of Slow Mesenchymal Cells

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    The mesenchymal-amoeboid transition (MAT) was proposed as a mechanism for cancer cells to adapt their migration mode to their environment. While the molecular pathways involved in this transition are well documented, the role of the microenvironment in the MAT is still poorly understood. Here, we investigated how confinement and adhesion affect this transition. We report that, in the absence of focal adhesions and under conditions of confinement, mesenchymal cells can spontaneously switch to a fast amoeboid migration phenotype. We identified two main types of fast migration-one involving a local protrusion and a second involving a myosin-II-dependent mechanical instability of the cell cortex that leads to a global cortical flow. Interestingly, transformed cells are more prone to adopt this fast migration mode. Finally, we propose a generic model that explains migration transitions and predicts a phase diagram of migration phenotypes based on three main control parameters: confinement, adhesion, and contractility

    Space exploration by dendritic cells requires maintenance of myosin II activity by IP3 receptor 1

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    Dendritic cells (DCs) patrol the interstitial space of peripheral tissues. The mechanisms that regulate their migration in such constrained environment remain unknown. We here investigated the role of calcium in immature DCs migrating in confinement. We found that they displayed calcium oscillations that were independent of extracellular calcium and more frequently observed in DCs undergoing strong speed fluctuations. In these cells, calcium spikes were associated with fast motility phases. IP3 receptors (IP(3)Rs) channels, which allow calcium release from the endoplasmic reticulum, were identified as required for immature DCs to migrate at fast speed. The IP(3)R1 isoform was further shown to specifically regulate the locomotion persistence of immature DCs, that is, their capacity to maintain directional migration. This function of IP(3)R1 results from its ability to control the phosphorylation levels of myosin II regulatory light chain (MLC) and the back/front polarization of the motor protein. We propose that by upholding myosin II activity, constitutive calcium release from the ER through IP(3)R1 maintains DC polarity during migration in confinement, facilitating the exploration of their environment

    Tracking the coherent generation of polaron pairs in conjugated polymers

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    The optical excitation of organic semiconductors not only generates charge-neutral electron-hole pairs (excitons), but also charge-separated polaron pairs with high yield. The microscopic mechanisms underlying this charge separation have been debated for many years. Here we use ultrafast two-dimensional electronic spectroscopy to study the dynamics of polaron pair formation in a prototypical polymer thin film on a sub-20-fs time scale. We observe multi-period peak oscillations persisting for up to about 1 ps as distinct signatures of vibronic quantum coherence at room temperature. The measured two-dimensional spectra show pronounced peak splittings revealing that the elementary optical excitations of this polymer are hybridized exciton-polaron-pairs, strongly coupled to a dominant underdamped vibrational mode. Coherent vibronic coupling induces ultrafast polaron pair formation, accelerates the charge separation dynamics and makes it insensitive to disorder. These findings open up new perspectives for tailoring light-to-current conversion in organic materials

    Engineering Azobenzene Derivatives to Control the Photoisomerization Process

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    In this work, we show how the structural features of photoactive azobenzene derivatives can influence the photoexcited state behavior and the yield of the trans/cis photoisomerization process. By combining high-resolution transient absorption experiments in the vis-NIR region and quantum chemistry calculations (TDDFT and RASPT2), we address the origin of the transient signals of three poly-substituted push-pull azobenzenes with an increasing strength of the intramolecular interactions stabilizing the planar trans isomer (absence of intramolecular H-bonds, methyl, and traditional H-bond, respectively, for 4-diethyl-4′-nitroazobenzene, Disperse Blue 366, and Disperse Blue 165) and a commercial red dye showing keto-enol tautomerism involving the azo group (Sudan Red G). Our results indicate that the intramolecular H-bonds can act as a “molecular lock” stabilizing the trans isomer and increasing the energy barrier along the photoreactive CNNC torsion coordinate, thus preventing photoisomerization in the Disperse Blue dyes. In contrast, the involvement of the azo group in keto-enol tautomerism can be employed as a strategy to change the nature of the lower excited state and remove the nonproductive symmetric CNN/NNC bending pathway typical of the azo group, thus favoring the productive torsional motion. Taken together, our results can provide guidelines for the structural design of azobenzene-based photoswitches with a tunable excited state behavior

    Cálculo de la longitud mínima de aproximación para una canaleta Parshall a través de la comparación del comportamiento hidráulico entre un modelo numérico y un modelo físico

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    Trabajo de InvestigaciónLa canaleta Parshall es una estructura hidraulica de gran empleabilidad dentro del campo de la Ingenieria, uno de sus usos es aforador de caudal o instrumento medidor. Pero en medio de su funcionalidad presenta problemas a la hora de encontrar obstaculos a la entrada de la canaleta, lo que hace que se alteren las laminas de agua, causando grandes problemas a su funcionalidad. El presente estudio propone un analisis en la longitud de aproximacion a la entrada de la canaleta en donde al interponer obstaculos, no se causara ninguna interferencia a las laminas de agua. Para el estudio efectivo se utiliza la herramienta computacional OpenFoam, con el fin de de determinar que longitud es la más exacta para no alterar las condiciones del flujo. De la misma manera estos resultados son comparados con un modelo a escala de laboratorioINTRODUCCIÓN 1. GENERALIDADES 2. MARCO DE REFERENCIA 3. METODOLOGIA 4. RESULTADOS 5. CONCLUSIONES 6. RECOMENDACIONES 7. ANEXOS 8. BIBLIOGRAFIAPregradoIngeniero Civi

    To respond or not to respond - a personal perspective of intestinal tolerance

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    For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

    A novel treatment of cystic fibrosis acting on-target:cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR

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    We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts ‘on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment
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