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961.
962.
Jorddy N. Cruz José F. S. Costa André S. Khayat Kamil Kuca Carlos A. L. Barros A. M. J. C. Neto 《Journal of biomolecular structure & dynamics》2019,37(6):1616-1627
In this work, the binding mechanism of new Polyketide Synthase 13 (Pks13) inhibitors has been studied through molecular dynamics simulation and free energy calculations. The drug Tam1 and its analogs, belonging to the benzofuran class, were submitted to 100 ns simulations, and according to the results obtained for root mean square deviation, all the simulations converged from approximately 30 ns. For the analysis of backbone flotation, the root mean square fluctuations were plotted for the Cα atoms; analysis revealed that the greatest fluctuation occurred in the residues that are part of the protein lid domain. The binding free energy value (ΔGbind) obtained for the Tam16 lead molecule was of ?51.43 kcal/mol. When comparing this result with the ΔGbind values for the remaining analogs, the drug Tam16 was found to be the highest ranked: this result is in agreement with the experimental results obtained by Aggarwal and collaborators, where it was verified that the IC50 for Tam16 is the smallest necessary to inhibit the Pks13 (IC50 = 0.19 μM). The energy decomposition analysis suggested that the residues which most interact with inhibitors are: Ser1636, Tyr1637, Asn1640, Ala1667, Phe1670, and Tyr1674, from which the greatest energy contribution to Phe1670 was particularly notable. For the lead molecule Tam16, a hydrogen bond with the hydroxyl of the phenol not observed in the other analogs induced a more stable molecular structure. Aggarwal and colleagues reported this hydrogen bonding as being responsible for the stability of the molecule, optimizing its physic-chemical, toxicological, and pharmacokinetic properties. 相似文献
963.
Gilson Stanski Alícia Giolo Hippólito Rogério C. Costa Antonio L. Castilho 《Invertebrate reproduction & development.》2019,63(1):67-75
We aimed to study the fecundity and reproductive investment of Loxopagurus loxochelis under different environmental conditions. In total, 67 ovigerous females were analyzed, 20 from Macaé, 26 from Ubatuba and 21 from Cananéia. The cephalothoracic shield length, fecundity and reproductive investment (Ubatuba 10.2%, Macaé 8.9% and Cananéia 7.5%) were different among the regions (ANCOVA, p < 0.05), caused by different abiotic resources and environmental characteristics found in each sampling region. Cananéia had the smallest individuals and low availability of adequate shells to hermit crabs, a condition that may have affected the growth and reproduction of the animals. Macaé has a continuous transport of nutrients such as nitrogen and phosphorus to the surface promoted by the Cabo Frio Upwelling zone, which may be a favourable condition for plankton production and, consequently, the extended ‘match/mismatch’ adjustment of spawning females of L. loxochelis. We propose that the highest reproductive investment on the Ubatuba coast is a consequence of regional environmental scenarios of waters colder than the Cananéia region, i.e. females concentrate more energy to reproduce seasonally. Thus, we proved that patterns of L. loxochelis’ reproduction can change on a regional scale according to the local condition of shell supply and water temperature. 相似文献
964.
Sofia S Pereira Mariana P Monteiro Madalena M Costa Jorge Ferreira Marco G Alves Pedro F Oliveira Ivana Jarak Duarte Pignatelli 《Journal of cellular biochemistry》2019,120(1):894-906
Unraveling molecular mechanisms that regulate tumor development and proliferation is of the utmost importance in the quest to decrease the high mortality rate of adrenocortical carcinomas (ACC). Our aim was to evaluate the role of two of the mitogen-activated protein kinase (MAPK) signaling pathways (extracellular signal-regulated protein kinases [ERKs 1/2] and p38) in the adrenocortical tumorigenesis, as well as the therapeutic potential of MAPK/ERK inhibition. ERKs 1/2 and p38 activation were evaluated in incidentalomas (INC; n = 10), benign Cushing's syndrome (BCS; n = 12), malignant Cushing's syndrome (MCS; n = 6) and normal adrenal glands (NAG; 8). ACC cell line (H295R) was used to evaluate the ability of PD184352 (0.1, 1, and 10 µM), a specific MEK-MAPK-ERK pathway inhibitor, to modulate cell proliferation, viability, metabolism, and steroidogenesis. ERKs 1/2 activation was significantly higher in MCS (2.83 ± 0.17) compared with NAG (1.00 ± 0.19 “arbitrary units”), INC (1.20 ± 0.13) and BCS (2.09 ± 0.09). Phospho-p38 expression was absent in all the MCS analyzed. MAPK/ERK kinase (MEK) inhibition with PD184352 significantly decreased proliferation as well as steroidogenesis and also increased the redox state of the H295R cells. This data suggests that MEK-MAPK-ERK signaling has a role in adrenocortical tumorigenesis that could be potentially used as a diagnostic marker for malignancy and targeted treatment in ACC. 相似文献
965.
Mariana Ilha Ketlen da Silveira Moraes Francieli Rohden Leo Anderson Meira Martins Radovan Borojevic Guido Lenz Florencia Barbé-Tuana Fátima Costa Rodrigues Guma 《Journal of cellular biochemistry》2019,120(11):19031-19043
Caveolin-1 (Cav-1) expression is increased in hepatic stellate cells (HSC) upon liver cirrhosis and it functions as an integral membrane protein of lipid rafts and caveolae that regulates and integrates multiple signals as a platform. This study aimed to evaluate the role of Cav-1 in HSC. Thus, the effects of exogenous expression of Cav-1 in GRX cells, a model of activated HSC, were determined. Here, we demonstrated through evaluating well-known HSC activation markers – such as α-smooth muscle actin, collagen I, and glial fibrillary acidic protein – that up regulation of Cav-1 induced GRX to a more activated phenotype. GRXEGFP-Cav1 presented an increased migration, an altered adhesion pattern, a reorganization f-actin cytoskeleton, an arrested cell cycle, a modified cellular ultrastructure, and a raised endocytic flux. Based on this, GRX EGFP-Cav1 represents a new cellular model that can be an important tool for understanding of events related to HSC activation. Furthermore, our results reinforce the role of Cav-1 as a molecular marker of HSC activation. 相似文献
966.
Antonio Marinho da Silva Neto Samuel Reghim Silva Michele Vendruscolo Carlo Camilloni Rinaldo Wander Montalvão 《Proteins》2019,87(4):302-312
Here a differential geometry (DG) representation of protein backbone is explored on the analyses of protein conformational ensembles. The protein backbone is described by curvature, κ, and torsion, τ, values per residue and we propose 1) a new dissimilarity and protein flexibility measurement and 2) a local conformational clustering method. The methods were applied to Ubiquitin and c-Myb-KIX protein conformational ensembles and results show that κ\τ metric space allows to properly judge protein flexibility by avoiding the superposition problem. The dmax measurement presents equally good or superior results when compared to RMSF, especially for the intrinsically unstructured protein. The clustering method is unique as it relates protein global to local dynamics by providing a global clustering solutions per residue. The methods proposed can be especially useful to the analyses of highly flexible proteins. The software written for the analyses presented here is available at https://github.com/AMarinhoSN/FleXgeo for academic usage only. 相似文献
967.
Lopes João Victor Saraiva Raimondi Young Robert John de Azevedo Cristiano Schetini 《Acta ethologica》2019,22(2):113-123
acta ethologica - Chemical pollution of aquatic environments has been increasing in recent times, causing great damage to the ecosystems and to the fishery sector. Pollutants can negatively alter... 相似文献
968.
João Paulo Araújo Fernandes de Queiroz João Batista Freire de Souza Jr Vanessa Raquel de Morais Oliveira Thibério de Souza Castelo Maiko Roberto Tavares Dantas Leonardo Lelis de Macedo Costa 《Biological Rhythm Research》2019,50(2):232-244
This study aimed to evaluate the diurnal variation of the sensible heat transfer in red-rumped agoutis (Dasyprocta leporina) bred in captivity in a semi-arid environment. In addition, we seek to identify thermal windows by infrared thermography during the daytime period (07:00, 09:00, 11:00, 14:00, and 16:00). The body surface temperature was higher in the pinna (36.84 ± 0.11 °C), followed by the hind limbs (36.55 ± 0.11 °C). These body regions were primarily responsible for heat loss by radiation (which was 10.13 ± 1.17 W m?2 and 11.19 ± 1.17 W m?2, respectively), and acted like biological thermal windows. Heat transfer by convection was more intense in the body trunk and hind limbs at all times of the day. Thus, sensible heat transfer is important for maintaining homeothermy in red-rumped agouti in hot environments. In conclusion, these rodents use specialized body regions (pinna and hind limbs) for heat transfer. 相似文献
969.
Lívio S. Amaral Daniel Debona Lilian C. Costa Ana Luiza R. Silva Jos R. Oliveira Fabrício A. Rodrigues 《Journal of Phytopathology》2019,167(7-8):390-403
Black rot, caused by Xanthomonas campestris pv. campestris (Xcc), is the most devastating disease of brassica, but the mechanisms of basal or induced resistance in cabbage remain largely unknown. Here, we performed three experiments to investigate biochemical features associated with cabbage resistance to black rot. In the first experiment, biochemical changes were assessed in plants that were inoculated with a highly (UFPR 5) or a moderately (Xcc 10) aggressive Xcc isolate. In the second experiment, we examined the biochemical responses in two cultivars (Chato de Quintal [CQ] and Louco de Verão [LV], susceptible and moderately resistant to Xcc, respectively). Finally, we examined whether acibenzolar‐S‐methyl (ASM) could induce cabbage resistance to Xcc. Plants inoculated with the Xcc 10 isolate displayed higher activities of superoxide dismutase (SOD), peroxidase (POX) and ascorbate peroxidase (APX), whereas activities of chitinase (CHI), β‐1,3‐glucanase (GLU) and polyphenol oxidase (PPO) as well as the concentrations of hydrogen peroxide (H2O2) and malondialdehyde (MDA) were lower compared to plants inoculated with the UFPR 5 isolate. The resistance of the cultivar LV to Xcc was linked to increases in the activities of CHI, GLU, and PPO and decreases in the activities of SOD, POX and APX as well as in the concentrations of H2O2 and MDA relative to the cultivar CQ. In general, ASM‐sprayed plants displayed higher activities for the enzymes studied, which was associated with decreased disease symptoms and oxidative stress. Taken together, our results demonstrated that high activities of both defence and antioxidant enzymes played a major role in both basal and induced resistance of cabbage to black rot. 相似文献
970.
Ileana Vera‐Reyes Itandehui Juanita Erendira Esparza‐Arredondo Ricardo Hugo Lira‐Saldivar Carlos Alejandro Granados‐Echegoyen Rocío Alvarez‐Roman Alfonso Vsquez‐Lpez Gladys De los Santos‐Villarreal Enrique Díaz‐Barriga Castro 《Journal of Phytopathology》2019,167(7-8):461-469
In this research, the in vitro antimicrobial effect of zinc oxide (ZnO), copper oxide (CuO) and iron oxide (Fe2O3) nanoparticles (NPs)—with average sizes of 20, 46 and 30 nm, respectively—on the root rot disease caused by the fungus Fusarium oxysporum and on blight disease caused by the fungus Alternaria solani were studied. Also, bacterial diseases caused by Clavibacter michiganensis and Pseudomonas syringae that infects a wide range of plant species were assessed. Different concentrations of NPs (0, 100, 250, 500, 700 and 1,000 mg/L) were prepared on PDA agar or King's B medium in a complete randomized design with four replicates. According to the results, ZnO NPs exhibited an outstanding inhibitory effect against fungi and bacteria strains. The above results were associated with the smaller particle size. Fungi strains showed a differential sensitivity depending on the kind of NPs used. A. solani showed the highest sensitivity to ZnO NPs at 1,000 mg/L (99%), followed by CuO NPs at the same dose (95%). Fe2O3 NPs at all evaluated doses had no inhibitory effects on the mycelia growth of this strain, although F. oxysporum revealed greater effectiveness of the CuO NPs (96%) compared with ZnO NPs since it only inhibited 91% of the mycelial growth. The antibacterial activity was studied through optical density. C. michiganensis was found to be more sensitive to ZnO NPs because a lesser dose (700 mg/L) was required to reduce the bacterial growth (90%); in comparison, P. syringae required a dose of 1,000 mg/L to inhibit its growth (67%). CuO NPs displayed the smallest growth inhibition against the bacteria strains analysed. The antimicrobial effect of the metallic NPs that were assayed increased with higher doses. 相似文献