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21.
By varying the thickness of the nervous tissue immersed in chlorate-osmic-formalin staining fluid (Swank and Davenport, 1935) it was found that a section 1 mm. thick can be completely and adequately stained in 24 hours. Thicker sections require a proportionately longer time. The quality of the Marchi stain in the rapidly prepared section is as good as that in the material stained for 10 days although the background is slightly lighter in the latter preparations. This method can be used where time is an important element and is especially applicable to spinal cord, small animal brains, or portions of larger brains in which serial sections are not required. 相似文献
22.
Giovanna Carr Paolo Nicoli Marcello Francesco Lingua Beatrice Maffeo Antonio Cartell Paola Circosta Mara Brancaccio Guido Parvis Valentina Gaidano Angelo Guerrasio Giuseppe Saglio Riccardo Taulli Alessandro Morotti 《Journal of cellular and molecular medicine》2020,24(2):1650-1657
The development of drugs able to target BTK, PI3k‐delta and BCL2 has dramatically improved chronic lymphocytic leukaemia (CLL) therapies. However, drug resistance to these therapies has already been reported due to non‐recurrent changes in oncogenic pathways and genes expression signatures. In this study, we investigated the cooperative role of the BCL2 inhibitor venetoclax and the BRD4 inhibitor JQ1. In particular, we found that JQ1 shows additional activity with venetoclax, in CLL cell lines and in ex vivo isolated primary CD19+ lymphocytes, arguing in favour of combination strategies. Lastly, JQ1 is also effective in venetoclax‐resistant CLL cell lines. Together, our findings indicated that the BET inhibitor JQ1 could be a promising therapy in CLL, both as first‐line therapy in combination with venetoclax and as second‐line therapy, after the emergence of venetoclax‐resistant clones. 相似文献
23.
Clemens Alexander Boecker Mara A. Olenick Elizabeth R. Gallagher Michael E. Ward Erika L. F. Holzbaur 《Traffic (Copenhagen, Denmark)》2020,21(1):138-155
Induced pluripotent stem cells (iPSCs) hold promise to revolutionize studies of intracellular transport in live human neurons and to shed new light on the role of dysfunctional transport in neurodegenerative disorders. Here, we describe an approach for live imaging of axonal and dendritic transport in iPSC‐derived cortical neurons. We use transfection and transient expression of genetically‐encoded fluorescent markers to characterize the motility of Rab‐positive vesicles, including early, late and recycling endosomes, as well as autophagosomes and mitochondria in iPSC‐derived neurons. Comparing transport parameters of these organelles with data from primary rat hippocampal neurons, we uncover remarkable similarities. In addition, we generated lysosomal‐associated membrane protein 1 (LAMP1)‐enhanced green fluorescent protein (EGFP) knock‐in iPSCs and show that knock‐in neurons can be used to study the transport of endogenously labeled vesicles, as a parallel approach to the transient overexpression of fluorescently labeled organelle markers. 相似文献
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Olga Shomron Inbar Nevo-Yassaf Tamar Aviad Yakey Yaffe Eitan Erez Zahavi Anna Dukhovny Eran Perlson Ilya Brodsky Adva Yeheskel Metsada Pasmanik-Chor Anna Mironov Galina V. Beznoussenko Alexander A. Mironov Ella H. Sklan George H. Patterson Yoji Yonemura Mara Sannai Christoph Kaether Koret Hirschberg 《The Journal of cell biology》2021,220(6)
COPII and COPI mediate the formation of membrane vesicles translocating in opposite directions within the secretory pathway. Live-cell and electron microscopy revealed a novel mode of function for COPII during cargo export from the ER. COPII is recruited to membranes defining the boundary between the ER and ER exit sites, facilitating selective cargo concentration. Using direct observation of living cells, we monitored cargo selection processes, accumulation, and fission of COPII-free ERES membranes. CRISPR/Cas12a tagging, the RUSH system, and pharmaceutical and genetic perturbations of ER-Golgi transport demonstrated that the COPII coat remains bound to the ER–ERES boundary during protein export. Manipulation of the cargo-binding domain in COPII Sec24B prohibits cargo accumulation in ERES. These findings suggest a role for COPII in selecting and concentrating exported cargo rather than coating Golgi-bound carriers. These findings transform our understanding of coat proteins’ role in ER-to-Golgi transport. 相似文献
27.
Lara Soares Aleixo de Carvalho Lívia Mara Silva Vinícius Carius de Souza Marcos Paulo Nascimento da Silva Priscila V. S. Z. Capriles Priscila de Faria Pinto Josué de Moraes Ademar Alves Da Silva Filho 《化学与生物多样性》2021,18(11):e2100604
Schistosomiasis, a neglected tropical disease caused by Schistosoma species, harms over 250 million people in several countries. The treatment is achieved with only one drug, praziquantel. Cardamonin, a natural chalcone with in vitro schistosomicidal activity, has not been in vivo evaluated against Schistosoma. In this work, we evaluated the in vivo schistosomicidal activities of cardamonin against Schistosoma mansoni worms and conducted enzymatic apyrase inhibition assay, as well as molecular docking analysis of cardamonin against potato apyrase, S. mansoni NTPDase 1 and S. mansoni NTPDase 2. In a mouse model of schistosomiasis, the oral treatment with cardamonin (400 mg/kg) showed efficacy against S. mansoni, decreasing the total worm load in 46.8 % and reducing in 54.5 % the number of eggs in mice. Cardamonin achieved a significant inhibition of the apyrase activity and the three-dimensional structure of the potato apyrase, obtained by homology modeling, showed that cardamonin may interact mainly through hydrogen bonds. Molecular docking studies corroborate with the action of cardamonin in binding and inhibiting both potato apyrase and S. mansoni NTPDases. 相似文献
28.
Daniel Silva Torres Bruna Alves de Oliveira Lígia Souza d Silveira Marcos Paulo da Silva Vinícius Rodrigues Durães Pereira Josué Moraes Mara Rúbia Costa Couri Rafaella Fortini Grenfell e Queiroz Patrícia Martins Parreiras Márcio Roberto Silva Lara Azevedo Alves Vinícius Carius de Souza Priscila Vanessa Zabala Capriles Goliatt Eveline Gomes Vasconcelos Ademar Alves da Silva Filho Priscila de Faria Pinto 《化学与生物多样性》2021,18(11):e2100439
In this work, two synthetic aurones revealed moderate schistosomicidal potential in in vitro and in vivo assays. Aurones ( 1 ) and ( 2 ) promoted changes in tegument integrity and motor activity, leading to death of adult Schistosoma mansoni worms in in vitro assays. When administered orally (two doses of 50 mg/kg) in experimentally infected animals, synthetic aurones ( 1 ) and ( 2 ) promoted reductions of 56.20 % and 57.61 % of the parasite load and stimulated the displacement towards the liver of the remaining adult worms. The oogram analysis revealed that the treatment with both aurones interferes with the egg development kinetics in the intestinal tissue. Seeking an action target for compounds ( 1 ) and ( 2 ), the connection with NTPDases enzymes, recognized as important therapeutic targets for S. mansoni, was evaluated. Molecular docking studies have shown promising results. The dataset reveals the anthelmintic character of these compounds, which can be used in the development of new therapies for schistosomiasis. 相似文献
29.
Felipe Dal-Pizzol Fábio Klamt Mara S. Benfato Elena A. Bernard José Cláudio F. Moreira 《Free radical research》2013,47(4):395-404
Recent intervention studies revealed that supplementation with retinoids resulted in a higher incidence of lung cancer. Recently the causal mechanism has begun to be clarified. We report here that retinol caused cellular oxidative stress and modulated superoxide dismutase, catalase and glutathione peroxidase activities. Retinol (7 μM) significantly increased TBARS, conjugated dienes, and hydroperoxide-initiated chemiluminescence in cultured Sertoli cells. In response to retinol treatment superoxide dismutase, catalase and glutathione peroxidase activities increased. TBARS content and catalase activities were decreased by a free radical scavenger. These findings suggest that retinol may induce oxidative stress and modulate antioxidant enzyme activities in Sertoli cells. 相似文献
30.
Monalessa Fábia Pereira Carolina Maria de Araújo dos Santos Elza Fernandes de Araújo Marisa Vieira de Queiroz Denise Mara Soares Bazzolli 《Journal of microbiology (Seoul, Korea)》2013,51(1):70-81
Fungi of the Colletotrichum genus are among the most prominent phytopathogens that cause diseases with a considerable economic impact, such as anthracnose. The hemibiotrophic fungus Colletotrichum lindemuthianum (teleomorph Glomerella cingulata f. sp. phaseoli) is the causal agent of the anthracnose of the common bean; and similarly to other phytopathogens, it uses multiple strategies to gain access to different carbon sources from its host. In this study, we examine mfs1, a newly identified C. lindemuthianum hexose transporter. The mfs1 gene is expressed only during the necrotrophic phase of the fungus’ interaction within the plant and allows it to utilize the available sugars during this phase. The deletion of mfs1 gene resulted in differential growth of the fungus in a medium that contained glucose, mannose or fructose as the only carbon source. This study is the first to describe a hexose transporter in the hemibiotrophic pathogen C. lindemuthianum and to demonstrate the central role of this protein in capturing carbon sources during the necrotrophic development of the plant/pathogen interaction. 相似文献