Glioblastoma cells: A heterogeneous and fatal tumor interacting with the parenchyma

AbstractGlioblastomas (GBMs) are considered to be one of the deadliest human cancers, characterized by a high proliferative rate, aggressive invasiveness and insensitivity to radio- and chemotherapy, as well as a short patient survival period. Moreover, GBMs are among the most vascularized and invasive cancers in humans. Angiogenesis in GBMs is correlated with the grade of malignancy and is inversely correlated with patient survival. One of the first steps in tumor invasions is migration. GBM cells have the ability to infiltrate and disrupt physical barriers such as basement membranes, extracellular matrix and cell junctions. The invasion process includes the overexpression of several members of a super-family of zinc-based proteinases, the Metzincin, in particular a sub-group, metalloproteinases. Another interesting aspect is that, inside the GBM tissue, there are up to 30% of microglia or macrophages. However, little is known about the immune performance and interactions of the microglia with GBMs. These singular properties of GBMs will be described here. A sub-population of cells with stem-like properties may be the source of tumors since, apparently, GBM stem cells (GSCs) are highly resistant to current cancer treatments. These cancer therapies, while killing the majority of tumor cells, ultimately fail in GBM treatment because they do not eliminate GSCs, which survive to regenerate new tumors. Finally, GBM patient prognostic has shown little improvement in decades. In this context, we will discuss how the membrane-acting toxins called cytolysins can be a potential new tool for GBM treatment

Extended DFT+U+V method with on-site and inter-site electronic interactions

In this article we introduce a generalization of the popular DFT+U method based on the extended Hubbard model that includes on-site and inter-site electronic interactions. The novel corrective Hamiltonian is designed to study systems for which electrons are not completely localized on atomic states (according to the general scheme of Mott localization) and hybridization between orbitals from different sites plays an important role. The application of the extended functional to archetypal Mott - charge-transfer (NiO) and covalently bonded insulators (Si and GaAs) demonstrates its accuracy and versatility and the possibility to obtain a unifying and equally accurate description for a broad range of very diverse systems

Towards Olefin Multi-block Copolymers with Tailored Properties: A Molecular Perspective

This is an Accepted Manuscript of an article published by Macromolecular Theory and Simulations (MTS), of Wiley. Mohammadi, Y., Saeb, M. R., Penlidis, A., Jabbari, E., Stadler, F. J., Zinck, P., & Vivaldo‐Lima, E. (2021). Toward olefin multiblock copolymers with tailored properties: A molecular perspective. Macromolecular Theory and Simulations, 30(3), 2100003. https://doi.org/10.1002/mats.202100003Recent progress in macromolecular reaction engineering has enabled the synthesis of sequence-controlled polymers. The advent of Olefin Block Copolymers (OBCs) via chain shuttling polymerization of ethylene with α-olefins has opened new horizons for the synthesis of polyolefins having a dual character of thermoplastics and elastomers. Nevertheless, the use of two catalysts with different comonomer selectivities and a chain shuttling agent, dragging and dropping live chains between active catalyst centers, made precise tailoring of OBCs microstructure containing hard and soft units a feasible challenge. This work discusses the possibility of predicting properties of OBCs from its simulated molecular patterns. The microstructural characteristics of OBCs are discussed in terms of topology-related and property-related features. An intelligent tool, which combines the benefits of Kinetic Monte Carlo simulation and Artificial Neural Network modeling, was used to explore the connection between polymerization recipe (catalyst composition, ethylene to 1-octene monomer ratio, and chain shuttling agent level) and topology-related as well as property-related microstructural features. The properties of target OBCs are reflected in the hard block percent, the number of 1-octene units in the copolymer chains, and the longest ethylene sequence length of the hard and soft segments

Molecular and serological surveys of canine distemper virus : a meta-analysis of crosssectional studies

Background Canine morbillivirus (canine distemper virus, CDV) persists as a serious threat to the health of domestic dogs and wildlife. Although studies have been conducted on the frequency and risk factors associated with CDV infection, there are no comprehensive data on the current epidemiological magnitude in the domestic dog population at regional and national levels. Therefore, we conducted a cross-sectional study and included our results in a meta-analysis to summarize and combine available data on the frequency and potential risk factors associated with CDV infection. Methods For the cross-sectional study, biological samples from dogs suspected to have canine distemper (CD) were collected and screened for viral RNA. Briefly, the PRISMA protocol was used for the meta-analysis, and data analyses were performed using STATA IC 13.1 software. Results CDV RNA was detected in 34% (48/141) of dogs suspected to have CD. Following our meta-analysis, 53 studies were selected for a total of 11,527 dogs. Overall, the pooled frequency of CDV positivity based on molecular and serological results were 33% (95% CI: 23–43) and 46% (95% CI: 36–57), respectively. The pooled subgroup analyses of clinical signs, types of biological samples, diagnostic methods and dog lifestyle had a wide range of CDV positivity (range 8–75%). Free-ranging dogs (OR: 1.44, 95% CI: 1.05–1.97), dogs >24 months old (OR: 1.83, 95% CI: 1.1–3) and unvaccinated dogs (OR: 2.92, 95% CI: 1.26– 6.77) were found to be positively associated with CDV infection. In contrast, dogs <12 months old (OR: 0.36, 95% CI: 0.20–0.64) and dogs with a complete anti-CDV vaccination (OR: 0.18, 95% CI: 0.05–0.59) had a negative association. Conclusion Considering the high frequency of CDV positivity associated with almost all the variables analyzed in dogs, it is necessary to immediately and continuously plan mitigation strategies to reduce the CDV prevalence, especially in determined endemic localities

AVALIAÇÃO DO CONTROLE POSTURAL E DA PRESSÃO PLANTAR EM PESSOAS COM ALTERAÇÃO VISUAL

O estudo objetivou avaliar o controle postural e a pressão plantar em pessoas com alteração visual, utilizando como referência o estrabismo. Participaram do estudo trinta e quatro voluntários, divididos em dois grupos: Grupo com Alteração Visual (GAV) com dezessete indivíduos com estrabismo e um Grupo Controle (GC) formado por dezessete indivíduos com visão normal. Todos os participantes foram submetidos às avaliações da pressão plantar e do equilíbrio através do exame da baropodometria computadorizada. Não houve diferença significativa na distribuição da pressão na região plantar entre os dois grupos. Na avaliação do equilíbrio, a velocidade média de oscilação e o deslocamento látero-lateral, com olhos abertos, apresentaram diferença estatística entre os grupos, bem como o deslocamento ântero-posterior, com olhos fechados. Conclui-se que não houve diferença estatisticamente significante na distribuição da pressão plantar ao comparar os dois grupos. Há alterações significativas no equilíbrio em indivíduos com alteração visual no deslocamento L/L e na velocidade média de oscilação, quando com os olhos abertos, no entanto existe uma correlação positiva em relação ao deslocamento A/P na condição olhos fechados, quando comparados com os indivíduos com visão normal

Microglia/Astrocytes–Glioblastoma Crosstalk: Crucial Molecular Mechanisms and Microenvironmental Factors

In recent years, the functions of glial cells, namely, astrocytes and microglia, have gained prominence in several diseases of the central nervous system, especially in glioblastoma (GB), the most malignant primary brain tumor that leads to poor clinical outcomes. Studies showed that microglial cells or astrocytes play a critical role in promoting GB growth. Based on the recent findings, the complex network of the interaction between microglial/astrocytes cells and GB may constitute a potential therapeutic target to overcome tumor malignancy. In the present review, we summarize the most important mechanisms and functions of the molecular factors involved in the microglia or astrocytes–GB interactions, which is particularly the alterations that occur in the cell’s extracellular matrix and the cytoskeleton. We overview the cytokines, chemokines, neurotrophic, morphogenic, metabolic factors, and non-coding RNAs actions crucial to these interactions. We have also discussed the most recent studies regarding the mechanisms of transportation and communication between microglial/astrocytes – GB cells, namely through the ABC transporters or by extracellular vesicles. Lastly, we highlight the therapeutic challenges and improvements regarding the crosstalk between these glial cells and GB