Simulação de miócito único via acoplamento de modelos massa-mola e eletromecânico

The synchronous and proper contraction of cardiomyocytes is essential for the correct function of the whole heart. Computational models of a cardiac cell may spam multiple cellular sub-components, scales, and physics. As a result, they are usually computationally expensive. This work proposes a low-cost model to simulate the cardiac myocyte’s electromechanics. The modeling of action potential and active force is performed via a system of six ordinary differential equations. Cardiac myocyte’s deformation that considers details of its geometry is captured using a mass-spring system. The mathematical model is integrated in time using Verlet’s method to obtain the position, velocity, and acceleration of each discretized point of the single cardiac myocyte. Our numerical results show that the obtained action potential, contraction, and deformation reproduces very well physiological data. Therefore, the low-cost mathematical model proposed here can be used as an essential tool for the correct characterization of cardiac electromechanicsA sincronia correta e adequada dos cardiomiócitos é essencial para o funcionamento correto do coração como um todo. Modelos computacionais de células cardíacas podem utilizar múltiplos sub-componentes celulares, além de escalas e físicas diferentes. Como resultado, eles frequentemente são custosos computacionalmente. Este trabalho propõe um modelo de baixo custo computacional para simular a eletromecânica dessas células, que são utilizados para o estudo da relação entre várias doenças cardíacas e suas causas mecânicas, elétricas e químicas, a nível celular. A modelagem do PA e força ativa é feita através de um sistema de seis Equações Diferenciais Ordinárias. Para a modelagem mecânica, foi proposta a utilização de sistema massa mola (SMM) e a resolução do modelo matemático através do Método de Verlet, para obtenção de posição, velocidade e aceleração das massas ao longo do tempo. Os resultados numéricos mostram que o PA, contração e deformação obtidos reproduzem muito bem dados fisiológicos disponíveis. Portanto, o modelo de baixo custo computacional aqui proposto pode ser usado como uma ferramenta essencial para a caracterização correta da eletromecânica cardíaca, em particular em problemas de larga escala a nível de tecido

Postharvest UV-B exposure drives changes in primary metabolism, phenolic concentration, and volatilome profile in berries of different grape (Vitis vinifera L.) varieties

BACKGROUND The ultraviolet-B (UV-B) radiation can alter grape metabolism during berry development, but little is known on the effect of postharvest UV-B exposure. In this study, we evaluated the effect of postharvest UV-B exposure on berry primary and secondary metabolites in four grapevine varieties (Aleatico, Moscato bianco, Sangiovese, and Vermentino) in order to evaluate the possibility to increase the grape quality and its nutraceutical properties. RESULTS The treatment did not significantly affect the berry primary metabolism in terms of organic acids, carbohydrates, and amino acids profile, regardless of the variety. UV-B exposure reduced the total anthocyanin content, particularly the tri-substituted and di-substituted forms in Aleatico and Sangiovese, respectively. An overall negative effect of UV-B irradiation on the flavonols profile of Aleatico, Moscato bianco, and Vermentino berries was found, whereas it enhanced the quercetin, myricetin and kaempferol concentration in Sangiovese. The free fraction of berry volatile organic compounds increased in UV-B-treated Aleatico and Moscato bianco berries, especially C-13-norisoprenoids and volatile phenols, as well as key monoterpenes, such as the linalool derivatives. However, higher concentrations of glycosylated monoterpenes and C-13-norisoprenoids were measured in Sangiovese and Vermentino berries treated with UV-B. CONCLUSION This study provides new insights on the effect of postharvest UV-B radiation on berry secondary metabolism, highlighting a different modulation between varieties and suggesting the potential use of this technique to increase some nutraceutical and quality characteristics of grape berry

ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules.

Correct orientation of cell division is considered an important factor for the achievement of normal brain size, as mutations in genes that affect this process are among the leading causes of microcephaly. Abnormal spindle orientation is associated with reduction of the neuronal progenitor symmetric divisions, premature cell cycle exit, and reduced neurogenesis. This mechanism has been involved in microcephaly resulting from mutation of ASPM, the most frequently affected gene in autosomal recessive human primary microcephaly (MCPH), but it is presently unknown how ASPM regulates spindle orientation. In this report, we show that ASPM may control spindle positioning by interacting with citron kinase (CITK), a protein whose loss is also responsible for severe microcephaly in mammals. We show that the absence of CITK leads to abnormal spindle orientation in mammals and insects. In mouse cortical development, this phenotype correlates with increased production of basal progenitors. ASPM is required to recruit CITK at the spindle, and CITK overexpression rescues ASPM phenotype. ASPM and CITK affect the organization of astral microtubules (MT), and low doses of MT-stabilizing drug revert the spindle orientation phenotype produced by their knockdown. Finally, CITK regulates both astral-MT nucleation and stability. Our results provide a functional link between two established microcephaly proteins

Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-Analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = \uc3\ua2 '0.24 to \uc3\ua2 '0.73; P < 1.49 \uc3\u97 10 \uc3\ua2 '4), and lower thickness in the precentral gyri bilaterally (d = \uc3\ua2 '0.34 to \uc3\ua2 '0.52; P < 4.31 \uc3\u97 10 \uc3\ua2 '6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = \uc3\ua2 '1.73 to \uc3\ua2 '1.91, P < 1.4 \uc3\u97 10 \uc3\ua2 '19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = \uc3\ua2 '0.36 to \uc3\ua2 '0.52; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = \uc3\ua2 '0.29 to \uc3\ua2 '0.54; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = \uc3\ua2 '0.27 to \uc3\ua2 '0.51; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < \uc3\ua2 '0.0018; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed

A systems-level analysis highlights microglial activation as a modifying factor in common forms of human epilepsy

The common human epilepsies are associated with distinct patterns of reduced cortical thickness, detectable on neuroimaging, with important clinical consequences. To explore underlying mechanisms, we layered MRI-based cortical structural maps from a large-scale epilepsy neuroimaging study onto highly spatially-resolved human brain gene expression data, identifying >2,500 genes overexpressed in regions of reduced cortical thickness, compared to relatively-protected regions. The resulting set of differentially-expressed genes shows enrichment for microglial markers, and in particular, activated microglial states. Parallel analyses of cell-specific eQTLs show enrichment in human genetic signatures of epilepsy severity, but not epilepsy causation. Post mortem brain tissue from humans with epilepsy shows excess activated microglia. In an experimental model, depletion of activated microglia prevents cortical thinning, but not the development of chronic seizures. These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control

Treatment of Malignant Gliomas in Elderly Patients: A Concise Overview of the Literature

Gliomas are the most frequent primary brain tumors and the incidence data has increased in the elderly population. Unfortunately, prospective studies on this population are few and so the right treatment is unknown. In the elderly patients no standard treatment has been established and therefore the optimal treatment should be individualized. We performed a review analyzing the prognostic and predictive factors, the clinical studies, and the correct management of this population