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81.
Carew JS Espitia CM Esquivel JA Mahalingam D Kelly KR Reddy G Giles FJ Nawrocki ST 《The Journal of biological chemistry》2011,286(8):6602-6613
Cellular stress induced by nutrient deprivation, hypoxia, and exposure to many chemotherapeutic agents activates an evolutionarily conserved cell survival pathway termed autophagy. This pathway enables cancer cells to undergo self-digestion to generate ATP and other essential biosynthetic molecules to temporarily avoid cell death. Therefore, disruption of autophagy may sensitize cancer cells to cell death and augment chemotherapy-induced apoptosis. Chloroquine and its analog hydroxychloroquine are the only clinically relevant autophagy inhibitors. Because both of these agents induce ocular toxicity, novel inhibitors of autophagy with a better therapeutic index are needed. Here we demonstrate that the small molecule lucanthone inhibits autophagy, induces lysosomal membrane permeabilization, and possesses significantly more potent activity in breast cancer models compared with chloroquine. Exposure to lucanthone resulted in processing and recruitment of microtubule-associated protein 1 light chain 3 (LC3) to autophagosomes, but impaired autophagic degradation as revealed by transmission electron microscopy and the accumulation of p62/SQSTM1. Microarray analysis, qRT-PCR, and immunoblotting determined that lucanthone stimulated a large induction in cathepsin D, which correlated with cell death. Accordingly, knockdown of cathepsin D reduced lucanthone-mediated apoptosis. Subsequent studies using p53(+/+) and p53(-/-) HCT116 cells established that lucanthone induced cathepsin D expression and reduced cancer cell viability independently of p53 status. In addition, lucanthone enhanced the anticancer activity of the histone deacetylase inhibitor vorinostat. Collectively, our results demonstrate that lucanthone is a novel autophagic inhibitor that induces apoptosis via cathepsin D accumulation and enhances vorinostat-mediated cell death in breast cancer models. 相似文献
82.
D.D. Moura Costa F. Filipak Neto M.D.M. Costa R.N. Morais J.R.E. Garcia B.M. Esquivel C.A. Oliveira Ribeiro 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2010,151(2):248-257
This study investigated the effects of different doses of 17-β-estradiol (E2) in Rhamdia quelen. Groups of males exposed to different doses of E2 (0.1 mg kg− 1, 1 mg kg− 1 and 10 mg kg− 1) were compared with non-exposed male and female fish groups. Among the considered biomarkers, no significant differences were observed for micronuclei test, reduced glutathione concentration and lipid peroxidation. All E2-treated individuals had decreased glutathione S-transferase activity. Increased catalase and superoxide dismutase activities, increased vitellogenin expression and decreased metallothionein concentration were observed in males treated with the highest dose. Liver of all test groups showed necrotic areas, but cytoplasm vacuolization was again found only in the individuals exposed to highest dose. E2 causes deleterious hepatic effects to R. quelen, and vitellogenin expression, catalase and superoxide dismutase activity and metallothionein concentration represent appropriate biomarkers for studying E2 effects. Additionally, the response of some biomarkers was similar in males exposed to E2 and unexposed females, and therefore exposure to endocrine disruptors may cause consequences for fish populations. 相似文献
83.
Carew JS Esquivel JA Espitia CM Schultes CM Mülbaier M Lewis JD Janssen B Giles FJ Nawrocki ST 《PloS one》2012,7(1):e31120
Background
Hypoxia-inducible factor (HIF) is an attractive therapeutic target for renal cell carcinoma (RCC) as its high expression due to the loss of von Hippel-Lindau (VHL) promotes RCC progression. Considering this, we hypothesized that ELR510444, a novel orally available small molecule inhibitor of HIF activity, would reduce angiogenesis and possess significant activity in RCC. The mechanism of action and therapeutic efficacy of ELR510444 were investigated in in vitro and in vivo models of RCC.Principal Findings
ELR510444 decreased HIF-1α and HIF-2α levels, reduced RCC cell viability and clonogenic survival, and induced apoptosis. VHL-deficient RCC cells were more sensitive to ELR510444-mediated apoptosis and restoration of VHL promoted drug resistance. Higher concentrations of promoted apoptosis independently of VHL status, possibly due to the microtubule destabilizing properties of this agent. ELR510444 significantly reduced tumor burden in the 786-O and A498 RCC xenograft models. These effects were associated with increased necrosis and apoptosis and inhibition of angiogenesis. ELR51044Conclusions
ELR510444 is a promising new HIF inhibitor that reduced RCC cell viability, induced apoptosis, and diminished tumor burden in RCC xenograft models. ELR510444 also destabilized microtubules suggesting that it possesses vascular disrupting and anti-angiogenic properties. Further investigation of ELR510444 for the therapy of RCC is warranted. 相似文献84.
Eduardo López Sandoval Eliane Wajnberg Darci M. S. Esquivel Henrique Lins de Barros Daniel Acosta-Avalos 《Journal of Insect Behavior》2012,25(6):612-619
It is known that magnetic fields affect ants behavior. It has been shown that Solenopsis ants are sensitive to magnetic fields but there is no experimental evidence for magnetic orientation. In this paper experiments were done to verify the magnetic orientation of Solenopsis sp. ants. The spontaneous orientation of ants in a circular arena was studied in two different magnetic conditions: in the natural geomagnetic field and under an altered magnetic field, with the horizontal geomagnetic axis shifted in 90?o. Our results show that ants consistently change their orientation direction when the magnetic field was altered. Axial circular statistics analysis showed that, in the absence of other cues, ants orient spontaneously to the horizontal geomagnetic field axis. The present paper shows for the first time magnetic orientation in Solenopsis sp. ants. 相似文献
85.
Altitude and species identity drive leaf litter decomposition rates of ten species on a 2950 m altitudinal gradient in Neotropical rain forests 总被引:1,自引:0,他引:1
Jimena Esquivel Byung Bae Park Fernando Casanoves Diego Delgado Go-Eun Park Bryan Finegan 《Biotropica》2020,52(1):11-21
Identifying the environmental factors controlling litter decomposition is key to understanding the magnitude and rates of nutrient cycling in tropical forests, and how they may be influenced by climate variability and environmental change. We carried out a leaf litter translocation experiment in mature rain forest over a 2,520 m altitudinal gradient in Costa Rica. Leaf litter decomposition rates (k) of ten tree species, two dominant species from each ecosystem, plus two standard species, were calculated over 540 days in four life zones. k was lowest in montane with 0.83 per year and lower montane forests with 2.21 per year. k did not differ between lowland and premontane forests at 3.12 per year, in spite of the 3℃ difference of mean annual temperature between these life zones. k varied fourfold among species. Species decomposition rates ranked as follows, and were predictably related to leaf economic spectrum traits of the species: Acalypha communis (standard, fast decomposer)» Hyeronima oblonga > Alchornea latifolia, Quercus bumelioides, Jarava ichu (standard, slow decomposer)> Minquartia guianensis > Magnolia sororum > Vochysia allenii > Pourouma bicolor, Carapa guianensis. These two slowest-decomposing species were native premontane and lowland forest dominants, respectively, with tough, low-nutrient leaves. The ranking of species by k varied very little among life zones suggesting that decomposer organisms in very different ecosystems and environments react in similar ways to the litter quality in general. We conclude that while k decreases with temperature in rain forests on tropical mountains, bioclimatic zones defined as premontane may be “functionally lowland.” The effects of species identity on decomposition rates on tropical mountains are consistent and independent of environment for both standard and native species. Under climate change on these mountains, if moisture regimes do not change, decomposition rates will increase due to rising temperatures. Soil carbon storage may therefore decrease. Changes in the altitudinal distributions of currently dominant species will also affect this critically important biogeochemical process. 相似文献
86.
MG Mullender NA Blom M De Kleuver JM Fock WMGC Hitters AMC Horemans CJ Kalkman JEH Pruijs RR Timmer PJ Titarsolej NC Van Haasteren Tol-de MJ Van Jager AJ Van Vught BJ Van Royen 《Scoliosis》2008,3(1):1-14
Background
Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is considered the primary treatment option for correcting severe scoliosis in neuromuscular disorders. Surgery in this population requires a multidisciplinary approach, careful planning, dedicated surgical procedures, and specialized after care.Methods
The guideline is based on scientific evidence and expert opinions. A multidisciplinary working group representing experts from all relevant specialties performed the research. A literature search was conducted to collect scientific evidence in answer to specific questions posed by the working group. Literature was classified according to the level of evidence.Results
For most aspects of the treatment scientific evidence is scarce and only low level cohort studies were found. Nevertheless, a high degree of consensus was reached about the management of patients with scoliosis in neuromuscular disorders. This was translated into a set of recommendations, which are now officially accepted as a general guideline in the Netherlands.Conclusion
In order to optimize the treatment for scoliosis in neuromuscular disorders a Dutch guideline has been composed. This evidence-based, multidisciplinary guideline addresses conservative treatment, the preoperative, perioperative, and postoperative care of scoliosis in neuromuscular disorders. 相似文献87.
Pablo A. Goloboff James M. Carpenter J. Salvador Arias Daniel Rafael Miranda Esquivel 《Cladistics : the international journal of the Willi Hennig Society》2008,24(5):758-773
The problem of character weighting in cladistic analysis is revisited. The finding that, in large molecular data sets, removal of third positions (with more homoplasy) decreases the number of well supported groups has been interpreted by some authors as indicating that weighting methods are unjustified. Two arguments against that interpretation are advanced. Characters that collectively determine few well‐supported groups may be highly reliable when taken individually (as shown by specific examples), so that inferring greater reliability for sets of characters that lead to an increase in jackknife frequencies may not always be warranted. But even if changes in jackknife frequencies can be used to infer reliability, we demonstrate that jackknife frequencies in large molecular data sets are actually improved when downweighting characters according to their homoplasy but using properly rescaled functions (instead of the very strong standard functions, or the extreme of inclusion/exclusion); this further weakens the argument that downweighting homoplastic characters is undesirable. Last, we show that downweighting characters according to their homoplasy (using standard homoplasy‐weighting methods) on 70 morphological data sets (with 50–170 taxa), produces clear increases in jackknife frequencies. The results obtained under homoplasy weighting also appear more stable than results under equal weights: adding either taxa or characters, when weighting against homoplasy, produced results more similar to original analyses (i.e., with larger numbers of groups that continue being supported after addition of taxa or characters), with similar or lower error rates (i.e., proportion of groups recovered that subsequently turn out to be incorrect). Therefore, the same argument that had been advanced against homoplasy weighting in the case of large molecular data sets is an argument in favor of such weighting in the case of morphological data sets. © The Willi Hennig Society 2008. 相似文献
88.
Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) enzymes from different species differ with respect to carboxylation catalytic efficiency and CO2/O2 specificity, but the structural basis for these differences is not known. Whereas much is known about the chloroplast-encoded large subunit, which contains the alpha/beta-barrel active site, much less is known about the role of the nuclear-encoded small subunit in Rubisco structure and function. In particular, a loop between beta-strands A and B contains 21 or more residues in plants and green algae, but only 10 residues in prokaryotes and nongreen algae. To determine the significance of these additional residues, a mutant of the green alga Chlamydomonas reinhardtii, which lacks both small-subunit genes, was used as a host for transformation with directed-mutant genes. Although previous studies had indicated that the betaA-betaB loop was essential for holoenzyme assembly, Ala substitutions at residues conserved among land plants and algae (Arg-59, Tyr-67, Tyr-68, Asp-69, and Arg-71) failed to block assembly or eliminate function. Only the Arg-71 --> Ala substitution causes a substantial decrease in holoenzyme thermal stability. Tyr-68 --> Ala and Asp-69 --> Ala enzymes have lower K(m)(CO2) values, but these improvements are offset by decreases in carboxylation V(max) values. The Arg-71 --> Ala enzyme has a decreased carboxylation V(max) and increased K(m)(CO2) and K(m)(O2) values, which account for an observed 8% decrease in CO2/O2 specificity. Despite the fact that Arg-71 is more than 20 A from the large-subunit active site, it is apparent that the small-subunit betaA-betaB loop region can influence catalytic efficiency and CO2/O2 specificity. 相似文献
89.
Haptoglobin 1F allele frequency is high among indigenous populations in the state of Durango, Mexico
Delanghe J Langlois M Alvarado Esquivel C De Haene H De Buyzere M 《Human heredity》2000,50(4):263-265
We studied haptoglobin polymorphism in Mexican populations with high Indian ancestry living in isolated and urban areas in the state of Durango. Analysis with respect to the HP*1F and HP*1S allelic subtypes by isoelectric focusing showed unusually high HP*1F allele frequencies among urban (0.370) and isolated Mexican Indians (0.383). Comparison with other population studies demonstrated a geographical cline of the HP*1F allele increasing in the same direction of the HP*1 allele, while HP*1S frequency does not show racial differences. 相似文献
90.
Estimation of receptor-ligand interactions by the use of a two-marker system in affinity capillary electrophoresis 总被引:1,自引:0,他引:1
The study of receptor-ligand interactions by affinity capillary electrophoresis (ACE) requires an accurate form of analysis. Here, we examine the use of two noninteracting standards (markers) in the analysis of binding constant data in ACE studies. This concept is demonstrated using two model systems: carbonic anhydrase B (CAB, EC 4.2.1.1) and arylsulfonamides, and vancomycin (Van) from Streptomyces orientalis and the dipeptide N-acetyl-d-Ala-d-Ala. In this procedure a plug of receptor and noninteracting standards is injected, and analysis of the change in the relative migration time ratio of the receptor, relative to the noninteracting standards, as a function of the concentration of the ligand yields a value for the binding constant. The findings described here demonstrate that data from ACE studies can best be analyzed using two noninteracting standards, yielding values comparable to those estimated using other binding and ACE techniques. 相似文献