Impact of kinesin Eg5 inhibition by 3,4-dihydropyrimidin-2(1H)-one derivatives on various breast cancer cell features

Background Breast cancer is a complex heterogeneous disease and is one of the leading causes of death among women. In addressing the need for treatments of this life-threatening illness, we studied 3,4-dihydropyrimidin-2(1H)-one (or thione) derivatives (DHPMs), a class of inhibitor molecules of the Eg5 motor spindle protein that shows pronounced antitumor activity against several cancer cell lines. Methods An in vitro screening was performed for identification of DHPMs with potent antitumor effects on MCF-7 and MDA-MB-231 cells and the selected DHPMs were evaluated for their inhibitory activity on Eg5 both in silico, using Molecular dynamics, and in vitro Eg5 inhibition assays. Analysis of cell death induction, proliferation, cell cycle and cancer stem cells (CSC) profile were performed by flow cytometry to assess the influence of the selected DPHMs on these important tumor features. Finally, the effects of DHPM treatment on tube formation were evaluated in vitro using HUVEC cells, and in vivo using a model on chorioallantoic membrane (CAM) of fertilized eggs. Results We identified five DHPMs with pronounced inhibitory activity on Eg5 motor protein interfering with the proper mitotic spindle assembly during cell division. These compounds impair the correct conclusion of cell cycle of the breast cancer cells and showed to be selective for tumor cells. Moreover, DHPMs modulate the CD44[superscript +]/CD24[superscript −] phenotype leading to a decrease in the CSC population in MDA-MB-231 cells, an important effect since CSC are resistant to many conventional cancer therapies and play a pivotal role in tumor initiation and maintenance. This observation was confirmed by the results which demonstrated that DHPM treated cells had impaired proliferation and were unable to sustain angiogenesis events. Finally, the DHMP treated cells were induced to apoptosis, which is one of the most pursued goals in drug development. Conclusions The results of our study strongly suggest that DHPMs inhibit important tumorigenic features of breast cancer cells leading them to death by apoptosis. These findings firmly point to DHPM molecular architecture as a promising alternative against breast cancer

Poor health and functioning in patients with axial spondyloarthritis during the COVID-19 pandemic and lockdown: REUMAVID study (phase 1)

To evaluate the overall health and functioning in patients with axial spondyloarthritis (axSpA) and related factors affecting these during the COVID-19 pandemic and lockdown measure

Qualidade da madeira e do carvão vegetal de quatro clones de Eucalyptus com idades entre 108 e 120 meses

Economic instability scenarios and reduction in charcoal consumption, such as those that occurred in 2009 and 2016, affect production and result in the maintenance of eucalyptus forests and an increase in the rotation age. The objective of this work was to evaluate the quality of wood from four Eucalyptus clones (clones 1, 2, 3, and 4) at the ages of 108 and 120 months and the charcoal produced in a rectangular kiln. We evaluated the heart/sapwood ratio, basic density, dry mass per hectare.year, and chemical composition . The carbonizations were performed in a rectangular kiln (210 m³ of wood). We determined the gravimetric yield and the charcoal properties: density, particle size and percentage of fines, friability index, proximate analysis, and mass of charcoal produced per hectare.year. We verified the significant effect of clones on basic density and dry mass, whose variations were from 494 to 589 kg m-3 and 12.47 to 23.34 ton.ha-1, respectively. The charcoal yield did not differ among clones (34.1%), while the yield of semicarbonized wood varied from 3.2% (clone 4) to 10.7% (clone 3).  The particle size of 65% of the charcoal volume of clones 1 and 3 was greater than 30 mm, and 49.5% of clones 2 and 4. We found medium mechanical resistance for charcoal from all four clones. The apparent density ranged from 356 to 458 kg.m-3, with the highest average value for clone 3. We found the highest charcoal production for clones 1 and 2, 7.5 tons per hectare.year. The fixed carbon did not vary among clones (76.92%). The wood properties of the Eucalyptus clones at ages 108 and 120 months are suitable for charcoal production for metallurgical use. Clones 1 (a hybrid of E. urophylla x E. grandis) and 3 (a hybrid of E. urophylla x E. camaldulensis) stood out from the others.Cenários de instabilidade econômica e redução do consumo de carvão vegetal, como as ocorridas em 2009 e 2016, afetam a produção deste insumo, resultando na manutenção das florestas de eucalipto e aumento da idade de corte. O objetivo deste trabalho foi avaliar a qualidade da madeira de quatro clones de Eucalyptus (clones 1, 2, 3 e 4) com idades entre 108 e 120 meses e do carvão vegetal produzido em forno retangular. Para caracterização da madeira, foram avaliadas a relação cerne/alburno, densidade básica, massa seca por hectare.ano e composição química. As carbonizações foram realizadas em forno retangular, com capacidade de 210 m³ de madeira, e determinaram-se o rendimento gravimétrico e as propriedades do carvão vegetal: densidade do carvão vegetal, granulometria e porcentagem de finos, índice de friabilidade, análise imediata, além da massa de carvão produzida por hectare.ano. Verificou-se efeito significativo dos clones na densidade básica e massa seca, com valores de 494 a 589 kg m-3 e 12,47 a 23,34 ton.ha-1, respectivamente. O rendimento médio em carvão vegetal não diferiu entre os clones e foi igual a 34,1%, enquanto o rendimento em atiço variou de 3,2% para o clone 4 a 10,7% para o clone 3. Os clones 1 e 3 apresentaram em média 65% do volume de carvão vegetal na maior faixa granulométrica (>30 mm), enquanto os clones 2 e 4 tiveram 49,5% nessa granulometria.  O carvão vegetal dos quatro clones foi de média resistência e a densidade aparente variou de 356 a 458 kg.m-3, com maior valor para o clone 3. Os clones 1 e 2 apresentaram a maior produção de carvão vegetal, 7,5 toneladas por hectare.ano. O carbono fixo não variou entre os clones, apresentando média igual a 76,92%. Os clones de Eucalyptus nas idades de 108 e 120 meses apresentam propriedades da madeira adequadas para a produção de carvão vegetal, alcançando rendimento gravimétrico e qualidade satisfatórios para uso metalúrgico, destacando-se os clones 1 (híbrido de E. urophylla x E. grandis) e 3 (híbrido de E. urophylla x E. camaldulensis)

Experimental assessment of low-temperature martensite transformations in Ni-rich polycrystalline Ni-Ti alloys

Ultrasonic velocity and attenuation measurements of a commercially available Ni-rich polycrystalline NieTi alloy were simultaneously obtained upon cooling from room temperature (RT) down to 130 K. The anelastic spectra show multiple anomalies in both velocity and attenuation curves, which evidence a complex nature of structural rearrangements exhibited by NieTi alloy, associated with relaxations and phase transformations. In particular, some evident anomalies at 285 and 180 K, not previously exploited using ultrasonic measurements on Ni-rich polycrystalline NieTi alloy, were associated with austenite to pre-martensitic (B2 / R) and pre-martensitic to martensitic (R/ B19’) phase transitions, respectively. The peculiar temperature separation between these transformations was interpreted based on chemical composition and the NieTi alloy microstructure evolution. X-ray diffraction (XRD), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were also used to add complementary results about phase transformations and thermal events exhibited by NieTi alloy at low temperatures

Semantic segmentation of tree-canopy in urban environment with pixel-wise deep learning

Urban forests are an important part of any city, given that they provide several environmental benefits, such as improving urban drainage, climate regulation, public health, biodiversity, and others. However, tree detection in cities is challenging, given the irregular shape, size, occlusion, and complexity of urban areas. With the advance of environmental technologies, deep learning segmentation mapping methods can map urban forests accurately. We applied a region-based CNN object instance segmentation algorithm for the semantic segmentation of tree canopies in urban environments based on aerial RGB imagery. To the best of our knowledge, no study investigated the performance of deep learning-based methods for segmentation tasks inside the Cerrado biome, specifically for urban tree segmentation. Five state-of-the-art architectures were evaluated, namely: Fully Convolutional Network; U-Net; SegNet; Dynamic Dilated Convolution Network and DeepLabV3+. The experimental analysis showed the effectiveness of these methods reporting results such as pixel accuracy of 96,35%, an average accuracy of 91.25%, F1-score of 91.40%, Kappa of 82.80% and IoU of 73.89%. We also determined the inference time needed per area, and the deep learning methods investigated after the training proved to be suitable to solve this task, providing fast and effective solutions with inference time varying from 0.042 to 0.153 minutes per hectare. We conclude that the semantic segmentation of trees inside urban environments is highly achievable with deep neural networks. This information could be of high importance to decision-making and may contribute to the management of urban systems. It should be also important to mention that the dataset used in this work is available on our website

Síndrome de Gerstmann: Gerstmann's syndrome

Introdução: A Síndrome de Gerstmann (SG) foi primeiramente descrita pelo neurologista austríaco Joseph Gerstmann, no ano de 1924, descrevendo o caso de um paciente de 53 anos, com a tétrade de sintomas: agrafia, acalculia, desorientação direita e esquerda, agnosia. Apresentação do caso: Paciente do sexo masculino, 60 anos de idade, branco, hipertenso, com histórico de fibrilação atrial em acompanhamento irregular, foi admitido na enfermaria de neurologia com alteração de linguagem e hemiparesia sensório-motora de início súbito. Apresentava-se hemodinamicamente estável. Discussão: A SG não possui cura, sendo necessária a investigação plena para tratar e intervir em qualquer intercorrência que possa se assemelhar com o quadro apresentado, a  conduta terapêutica irá se aplicar focalizando no alívio dos sintomas, fornecendo apoio multidisciplinar, a fim de se obter uma melhora na qualidade de vida do paciente, obtendo uma melhora nos sintomas e diminuição nas limitações trazidas pela síndrome. Conclusão: Percebe-se a importância de novos estudos a respeito da mesma, em busca de um diagnóstico precoce e acompanhamento eficaz. &nbsp

Síndrome de Cimitarra: Scimitar Syndrome

INTRODUÇÃO: A síndrome de Cimitarra é uma condição rara na qual ocorre o retorno venoso de forma anômala do pulmão direito para a veia cava inferior (VCI), podendo estar associada a outras malformações. APRESENTAÇÃO DO CASO: Paciente do sexo masculino, 2 anos, acompanhado da genitora, proveniente do interior do Amapá, relata que o menor há 1 ano começou a apresentar cansaço, fadiga, dificuldade para realizar pequenas atividades do dia, tontura e pneumonias repetidas. Relata, também,  que procurou atendimento na Unidade básica de saúde do seu bairro, e que o menor apresentou, ao exame físico, sopro sistólico ejetivo na borda esternal direita alta e B2 desdobrada constante e fixa com P2 normal. DISCUSSÃO: A forma infantil da síndrome de Cimitarra tem pior prognóstico e sintomas mais graves associados à hipertensão pulmonar e a cardiopatias congênitas. O diagnóstico é feito inicialmente a partir de uma radiografia de tórax que evidencia a veia pulmonar anômala, de configuração curva e paralela a borda direita do coração, que forma uma imagem hipotransparente e remete a espada turca (cimitarra). O tratamento em pacientes assintomáticos, com pressão arterial pulmonar normal e com pequeno shunt esquerda-direita, pode ser conservador. Já em pacientes sintomáticos, é indicada cirurgia de acordo com os dados hemodinâmicos. CONCLUSÃO: Esta síndrome é considerada rara e com diferentes graus de acometimentos, mas, de forma ampla, a sobrevida dos pacientes permanece boa, após correção cirúrgica. Dessa forma, fica clara a necessidade do diagnóstico precoce, ainda intra útero, para um parto e suporte ao recém-nascido adequados

Aerobic exercise training enhances the in vivo cholesterol trafficking from macrophages to the liver independently of changes in the expression of genes involved in lipid flux in macrophages and aorta

Abstract\ud \ud Background\ud Regular exercise prevents and regresses atherosclerosis by improving lipid metabolism and antioxidant defenses. Exercise ameliorates the reverse cholesterol transport (RCT), an antiatherogenic system that drives cholesterol from arterial macrophages to the liver for excretion into bile and feces. In this study we analyzed the role of aerobic exercise on the in vivo RCT and expression of genes and proteins involved in lipid flux and inflammation in peritoneal macrophages, aortic arch and liver from wild type mice.\ud \ud \ud Methods\ud Twelve-week-old male mice were divided into sedentary and trained groups. Exercise training was performed in a treadmill (15 m/min, 30 min/day, 5 days/week). Plasma lipids were determined by enzymatic methods and lipoprotein profile by fast protein liquid chromatography. After intraperitoneal injection of J774-macrophages the RCT was assessed by measuring the recovery of 3H-cholesterol in plasma, feces and liver. The expression of liver receptors was determined by immunoblot, macrophages and aortic mRNAs by qRT-PCR. 14C-cholesterol efflux mediated by apo A-I and HDL2 and the uptake of 3H-cholesteryl oleoyl ether (3H-COE)-acetylated-LDL were determined in macrophages isolated from sedentary and trained animals 48 h after the last exercise session.\ud \ud \ud Results\ud Body weight, plasma lipids, lipoprotein profile, glucose and blood pressure were not modified by exercise training. A greater amount of 3H-cholesterol was recovered in plasma (24 h and 48 h) and liver (48 h) from trained animals in comparison to sedentary. No difference was found in 3H-cholesterol excreted in feces between trained and sedentary mice. The hepatic expression of scavenger receptor class B type I (SR-BI) and LDL receptor (B-E) was enhanced by exercise. We observed 2.8 and 1.7 fold rise, respectively, in LXR and Cyp7a mRNA in the liver of trained as compared to sedentary mice. Macrophage and aortic expression of genes involved in lipid efflux was not systematically changed by physical exercise. In agreement, 14C-cholestrol efflux and uptake of 3H-COE-acetylated-LDL by macrophages was similar between sedentary and trained animals.\ud \ud \ud Conclusion\ud Aerobic exercise in vivo accelerates the traffic of cholesterol from macrophages to the liver contributing to prevention and regression of atherosclerosis, independently of changes in macrophage and aorta gene expression.Fundação de Amparo à Pesquisa do Estado de Sao Paulo - FAPESP 12/04831-1 to MP, UFM and MLCCG; FAPESP 07/50387-8 to MP, 2011/15153-1 to PR, 06/52702-5 to DDFMRocco, 13/02854-7 to LS\ud Okuda, 12/19112-0 to AML, 10/50108-4 to GC, 12/18724-2 to KS, 11/04631-0 to DJG, 09/53412-9 to RS Pinto; 12/12088-7 to RTI, 14/07155 to GFConselho Nacional de Desenvolvimento Científico e Tecnológico (158314/\ud 2014-0 to DJG

Sementes de Lágrima-de-Nossa-Senhora submetidas a diferentes tratamentos para superação de dormência / Tear-of-Our-Lady seeds submitted to different treatments to overcome dormancy

As informações disponíveis sobre as condições que favorecem o desempenho germinativo das sementes de Lágrima-de-Nossa-Senhora ainda são insuficientes. Assim, o objetivo foi avaliar a germinação de sementes de Coix lacryma-jobi sob diferentes tratamentos para a superação da dormência. Para isso, o trabalho foi dividido em três Ensaios. O Primeiro Ensaio, com os seguintes tratamentos: (i). imersão em solução com 300ml de ácido sulfúrico durante 25 minutos; (ii). imersão em água fervente por 10 minutos; (iii). excesso de água (50 ml, uma vez por semana) e; (iv). tratamento controle (água suficiente para umedecer as sementes e o papel). O Segundo Ensaio com os seguintes tratamentos: (i). controle (fornecimento normal de água); (ii). baixas temperaturas (sementes na geladeira durante uma semana); (iii). imersão em água por 12 horas; (iv); lixa + embebição; (v). embebição + lixamento; (vi). corte na horizontal com tesoura de poda + embebição; (vii). embebição + corte na horizontal com tesoura de poda.  O Terceiro Ensaio, com diferentes concentrações de ácido giberélico (GA): (i). 0 mg de GA (somente imersão água); (ii). 10 mg de GA; (iii). 20 mg de GA; e (iv) 50 mg GA, diluído em 500 ml de água destilada. Para o Primeiro Ensaio, a melhor porcentagem foi no controle e no Segundo Ensaio foi lixamento + embebição apresentou melhor resposta, seguido do corte + embebição; e embebição + lixamento. A aplicação do ácido giberélico foi mais eficaz na concentração de 50 mg. Dos três Ensaios, o melhor foi com aplicação de ácido giberélico. Dessa forma, mais estudos devem ser realizados para verificar outras formas de superação da dormência dessa semente

Prácticas de Aprendizaje-servicio a través de la literatura y el cine en el Grado de Estudios Ingleses: Creación de un archivo virtual de pedagogías y acciones disidentes contra los discursos de miedo

Memoria ID-067 Ayudas de la Universidad de Salamanca para la innovación docente, curso 2020-2021