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41.
Leonard Schmiester Yannik Schlte Frank T. Bergmann Tacio Camba Erika Dudkin Janine Egert Fabian Frhlich Lara Fuhrmann Adrian L. Hauber Svenja Kemmer Polina Lakrisenko Carolin Loos Simon Merkt Wolfgang Müller Dilan Pathirana Elba Raimúndez Lukas Refisch Marcus Rosenblatt Paul L. Stapor Philipp Stdter Dantong Wang Franz-Georg Wieland Julio R. Banga Jens Timmer Alejandro F. Villaverde Sven Sahle Clemens Kreutz Jan Hasenauer Daniel Weindl 《PLoS computational biology》2021,17(1)
Reproducibility and reusability of the results of data-based modeling studies are essential. Yet, there has been—so far—no broadly supported format for the specification of parameter estimation problems in systems biology. Here, we introduce PEtab, a format which facilitates the specification of parameter estimation problems using Systems Biology Markup Language (SBML) models and a set of tab-separated value files describing the observation model and experimental data as well as parameters to be estimated. We already implemented PEtab support into eight well-established model simulation and parameter estimation toolboxes with hundreds of users in total. We provide a Python library for validation and modification of a PEtab problem and currently 20 example parameter estimation problems based on recent studies. 相似文献
42.
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
43.
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
44.
Whitfield Alan K. Adams Janine B. Harrison Trevor D. Lamberth Stephen J. Lemley Daniel A. MacKay Fiona Van Niekerk Lara Weyl Olaf L. F. 《Biological invasions》2021,23(9):2729-2747
Biological Invasions - We review the possible impacts of non-native biota on the indigenous fishes of South African estuaries, including macrophytes, algae, pathogens, invertebrates, and fishes.... 相似文献
45.
Ricardo D. Ekmay Catalina Salas Judy England Sandro Cerrate Craig N. Coon 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2013,164(1):38-43
A study was conducted to determine the changes that occur to proteolysis and related genes due to age, protein, and energy intake in high-yield broiler breeder hens (Gallus gallus). Cobb 700 broiler breeders were randomly assigned to one of six diets in a 2 × 3 factorial fashion. Two levels of energy (390 and 450 kcal/day) and three levels of protein (22, 24, and 26 g CP/day) were utilized. Protein turnover was determined in the left pectoralis at 22, 26, 31 and 44 weeks. Relative mRNA expression of calpain 2 (CAPN2), proteasome C2 subunit (PSMA1), and F box protein 32 (FBXO32) were determined via RT-PCR at 20, 25, and 44 weeks. Contrasts indicate fractional synthesis rate (FSR) and FBXO32 increase to a maximum at 25–26 weeks and a decrease thereafter. A significant drop in PSMA1 and FBXO32 was observed between 25 and 44 weeks and matched the decrease observed in FBR. No differences were detected in the levels of fractional synthesis and degradation, or the expression of CAPN2, PSMA1, and FBXO32, due to protein or energy intake. In summary, protein turnover was upregulated during the transition into sexual maturity and decreased thereafter. The observed changes in degradation appeared to be mediated by the ubiquitin–proteasome pathway. 相似文献
46.
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48.
Beatriz Aldaz Ainara Sagardoy Lorena Nogueira Elizabeth Guruceaga Lara Grande Jason T. Huse Maria A. Aznar Ricardo Díez-Valle Sonia Tejada-Solís Marta M. Alonso Jose L. Fernandez-Luna Jose A. Martinez-Climent Raquel Malumbres 《PloS one》2013,8(10)
Glioblastoma multiforme (GBM)-initiating cells (GICs) represent a tumor subpopulation with neural stem cell-like properties that is responsible for the development, progression and therapeutic resistance of human GBM. We have recently shown that blockade of NFκB pathway promotes terminal differentiation and senescence of GICs both in vitro and in vivo, indicating that induction of differentiation may be a potential therapeutic strategy for GBM. MicroRNAs have been implicated in the pathogenesis of GBM, but a high-throughput analysis of their role in GIC differentiation has not been reported. We have established human GIC cell lines that can be efficiently differentiated into cells expressing astrocytic and neuronal lineage markers. Using this in vitro system, a microarray-based high-throughput analysis to determine global expression changes of microRNAs during differentiation of GICs was performed. A number of changes in the levels of microRNAs were detected in differentiating GICs, including over-expression of hsa-miR-21, hsa-miR-29a, hsa-miR-29b, hsa-miR-221 and hsa-miR-222, and down-regulation of hsa-miR-93 and hsa-miR-106a. Functional studies showed that miR-21 over-expression in GICs induced comparable cell differentiation features and targeted SPRY1 mRNA, which encodes for a negative regulator of neural stem-cell differentiation. In addition, miR-221 and miR-222 inhibition in differentiated cells restored the expression of stem cell markers while reducing differentiation markers. Finally, miR-29a and miR-29b targeted MCL1 mRNA in GICs and increased apoptosis. Our study uncovers the microRNA dynamic expression changes occurring during differentiation of GICs, and identifies miR-21 and miR-221/222 as key regulators of this process. 相似文献
49.
Lara A. Underkoffler Erikka Carr Anthony Nelson Matthew J. Ryan Reiner Schultz Kathleen M. Loomes 《PloS one》2013,8(12)
Alagille syndrome is an autosomal dominant disorder involving bile duct paucity and cholestasis in addition to cardiac, skeletal, ophthalmologic, renal and vascular manifestations. Mutations in JAG1, encoding a ligand in the Notch signaling pathway, are found in 95% of patients meeting clinical criteria for Alagille syndrome. In order to define the role of Jag1 in the bile duct developmental abnormalities seen in ALGS, we previously created a Jag1 conditional knockout mouse model. Mice heterozygous for the Jag1 conditional and null alleles demonstrate abnormalities in postnatal bile duct growth and remodeling, with portal expansion and increased numbers of malformed bile ducts. In this study we report the results of microarray analysis and identify genes and pathways differentially expressed in the Jag1 conditional/null livers as compared with littermate controls. In the initial microarray analysis, we found that many of the genes up-regulated in the Jag1 conditional/null mutant livers were related to extracellular matrix (ECM) interactions, cell adhesion and cell migration. One of the most highly up-regulated genes was Ddr1, encoding a receptor tyrosine kinase (RTK) belonging to a large RTK family. We have found extensive co-localization of Jag1 and Ddr1 in bile ducts and blood vessels in postnatal liver. In addition, co-immunoprecipitation data provide evidence for a novel protein interaction between Jag1 and Ddr1. Further studies will be required to define the nature of this interaction and its functional consequences, which may have significant implications for bile duct remodeling and repair of liver injury. 相似文献
50.
Timothy C. Roth II Dominique M. Chevalier Lara D. LaDage Vladimir V. Pravosudov 《Developmental neurobiology》2013,73(6):480-485
Enhancements to memory are associated with enhanced neural structures that support those capabilities. A great deal of work has examined this relationship in the context of natural variation in spatial memory capability and hippocampal (Hp) structure. Most studies have focused on volumetric and neuron measures, but have seldom examined the role of glial cells. Once considered involved only in supportive functions associated with neurons, the importance of glial cells in cognitive processes, including memory, is gaining more attention. Building upon our previous study on the relationship between the brain, memory, and environmental severity in food‐caching birds, we compared the total number of Hp glial cells in wild‐sampled and in lab‐reared (common garden) black‐capped chickadees (Poecile atricapillus) originating from two different environmental extremes. We found that birds from more harsh climate tended to have significantly more Hp glial cells than those from more mild climate and that lab‐reared chickadees had significantly fewer Hp glial cells compared to the wild‐sampled birds. These results suggest that population differences in glial numbers may be controlled, at least in part, by heritable mechanisms, but glial numbers appear to be additionally regulated by an individual's environment. The pattern of Hp glial cell abundance among our treatment groups closely followed that of the Hp volume, suggesting that Hp glial cell number may be associated with the Hp volume. Unlike Hp neurons, however, the number of Hp glial cells may be, at least in part, affected by an individual's experiences and environment. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 480–485, 2013 相似文献