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131.
132.
Andreas D. Kistler Geetika Singh Mehmet M. Altintas Hao Yu Isabel C. Fernandez Changkyu Gu Cory Wilson Sandeep Kumar Srivastava Alexander Dietrich Katherina Walz Dontscho Kerjaschki Phillip Ruiz Stuart Dryer Sanja Sever Amit K. Dinda Christian Faul Jochen Reiser 《The Journal of biological chemistry》2013,288(51):36598-36609
Gain-of-function mutations in the calcium channel TRPC6 lead to autosomal dominant focal segmental glomerulosclerosis and podocyte expression of TRPC6 is increased in some acquired human glomerular diseases, particularly in membranous nephropathy. These observations led to the hypothesis that TRPC6 overactivation is deleterious to podocytes through pathological calcium signaling, both in genetic and acquired diseases. Here, we show that the effects of TRPC6 on podocyte function are context-dependent. Overexpression of TRPC6 alone did not directly affect podocyte morphology and cytoskeletal structure. Unexpectedly, however, overexpression of TRPC6 protected podocytes from complement-mediated injury, whereas genetic or pharmacological TRPC6 inactivation increased podocyte susceptibility to complement. Mechanistically, this effect was mediated by Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation. Podocyte-specific TRPC6 transgenic mice showed stronger CaMKII activation, reduced podocyte foot process effacement and reduced levels of proteinuria during nephrotoxic serum nephritis, whereas TRPC6 null mice exhibited reduced CaMKII activation and higher levels of proteinuria compared with wild type littermates. Human membranous nephropathy biopsy samples showed podocyte staining for active CaMKII, which correlated with the degree of TRPC6 expression. Together, these data suggest a dual and context dependent role of TRPC6 in podocytes where acute activation protects from complement-mediated damage, but chronic overactivation leads to focal segmental glomerulosclerosis. 相似文献
133.
Gabriela Turk Yanina Ghiglione Juliana Falivene María Eugenia Socias Natalia Laufer Romina Soledad Coloccini Ana María Rodriguez María Julia Ruiz María ángeles Pando Luis David Giavedoni Pedro Cahn Omar Sued Horacio Salomon María Magdalena Gherardi 《Journal of virology》2013,87(13):7445-7462
The important role of the CD8+ T-cell response on HIV control is well established. Moreover, the acute phase of infection represents a proper scenario to delineate the antiviral cellular functions that best correlate with control. Here, multiple functional aspects (specificity, ex vivo viral inhibitory activity [VIA] and polyfunctionality) of the HIV-specific CD8+ T-cell subset arising early after infection, and their association with disease progression markers, were examined. Blood samples from 44 subjects recruited within 6 months from infection (primary HIV infection [PHI] group), 16 chronically infected subjects, 11 elite controllers (EC), and 10 healthy donors were obtained. Results indicated that, although Nef dominated the anti-HIV response during acute/early infection, a higher proportion of early anti-Gag T cells correlated with delayed progression. Polyfunctional HIV-specific CD8+ T cells were detected at early time points but did not associate with virus control. Conversely, higher CD4+ T-cell set points were observed in PHI subjects with higher HIV-specific CD8+ T-cell VIA at baseline. Importantly, VIA levels correlated with the magnitude of the anti-Gag cellular response. The advantage of Gag-specific cells may result from their enhanced ability to mediate lysis of infected cells (evidenced by a higher capacity to degranulate and to mediate VIA) and to simultaneously produce IFN-γ. Finally, Gag immunodominance was associated with elevated plasma levels of interleukin 2 (IL-2) and macrophage inflammatory protein 1β (MIP-1β). All together, this study underscores the importance of CD8+ T-cell specificity in the improved control of disease progression, which was related to the capacity of Gag-specific cells to mediate both lytic and nonlytic antiviral mechanisms at early time points postinfection. 相似文献
134.
The stridulatory organ of the Crematogaster scutellaris (Olivier 1792) workers is being described, comparing their pars stridens present in six nests of this species, with one nest of Crematogaster auberti Emery 1869 and with the bibliographical data regarding other neighbouring species at our disposal. Both species and some Crematogaster scutellaris nests have shown significant differences. We propose several hypotheses which could explain these differences. 相似文献
135.
Alexandre G. Rodrigues Liu Yu Ping Priscyla D. Marcato Oswaldo L. Alves Maria C. P. Silva Rita C. Ruiz Itamar S. Melo Ljubica Tasic Ana O. De Souza 《Applied microbiology and biotechnology》2013,97(2):775-782
Aspergillus tubingensis and Bionectria ochroleuca showed excellent extracellular ability to synthesize silver nanoparticles (Ag NP), spherical in shape and 35?±?10 nm in size. Ag NP were characterized by transmission electron microscopy, X-ray diffraction analysis, and photon correlation spectroscopy for particle size and zeta potential. Proteins present in the fungal filtrate and in Ag NP dispersion were analyzed by electrophoresis (sodium dodecyl sulfate polyacrylamide gel electrophoresis). Ag NP showed pronounced antifungal activity against Candida sp, frequently occurring in hospital infections, with minimal inhibitory concentration in the range of 0.11–1.75 μg/mL. Regarding antibacterial activity, nanoparticles produced by A. tubingensis were more effective compared to the other fungus, inhibiting 98.0 % of Pseudomonas. aeruginosa growth at 0.28 μg/mL. A. tubingensis synthesized Ag NP with surprisingly high and positive surface potential, differing greatly from all known fungi. These data open the possibility of obtaining biogenic Ag NP with positive surface potential and new applications. 相似文献
136.
Fernanda Luna da Silva Eduardo Coelho Cerqueira Mônica Santos de Freitas Daniela Leão Gonçalves Lilian Terezinha Costa Cristian Follmer 《Neurochemistry international》2013
In the last decades, a series of compounds, including quinones and polyphenols, has been described as having anti-fibrillogenic action on α-synuclein (α-syn) whose aggregation is associated to the pathogenesis of Parkinson’s disease (PD). Most of these molecules act as promiscuous anti-amyloidogenic agents, interacting with the diverse amyloidogenic proteins (mostly unfolded) through non-specific hydrophobic interactions. Herein we investigated the effect of the vitamins K (phylloquinone, menaquinone and menadione), which are 1,4-naphthoquinone (1,4-NQ) derivatives, on α-syn aggregation, comparing them with other anti-fibrillogenic molecules such as quinones, polyphenols and lipophilic vitamins. Vitamins K delayed α-syn fibrillization in substoichiometric concentrations, leading to the formation of short, sheared fibrils and amorphous aggregates, which are less prone to produce leakage of synthetic vesicles. In seeding conditions, menadione and 1,4-NQ significantly inhibited fibrils elongation, which could be explained by their ability to destabilize preformed fibrils of α-syn. Bidimensional NMR experiments indicate that a specific site at the N-terminal α-syn (Gly31/Lys32) is involved in the interaction with vitamins K, which is corroborated by previous studies suggesting that Lys is a key residue in the interaction with quinones. Together, our data suggest that 1,4-NQ, recently showed up by our group as a potential scaffold for designing new monoamine oxidase inhibitors, is also capable to modulate α-syn fibrillization in vitro. 相似文献
137.
Romeo A. Saldaña‐Vázquez Alejandro A. Castro‐Luna Cesar A. Sandoval‐Ruiz Jesús R. Hernández‐Montero Kathryn E. Stoner 《Biotropica》2013,45(3):351-356
Studies comparing the abundance of frugivorous bats in shade‐coffee plantations and forest fragments report contradictory results, and have not taken into account the landscape context in which coffee plantations are immersed. Variables of population composition such as abundance, sex proportion, and reproductive condition, together with biological tags (i.e., bat fly prevalence), can provide information about spatiotemporal dynamics of habitats used by bats. In the central part of Veracruz, Mexico, we compared population variables and ectoparasite prevalence of the highland yellow‐shouldered bat (Sturnira ludovici) in two landscapes, one dominated by shade‐coffee plantations and another by forest fragments. Comparing these attributes between these two landscapes will increase our knowledge about the role of this agro‐ecosystem in the conservation of this species, which is an important seed disperser of cloud forest vegetation. Total abundance and proportion of females was greater in forest fragments than in coffee plantations, whereas the percentage of reproductive females and bat fly prevalence was similar between landscapes. Our results show that landscapes with forest fragments harbor the greatest abundance of S. ludovici, but shade‐coffee plantations also are utilized by S. ludovici and likely adjacent forest remnants provide enough food resources for this species and other frugivores. Moreover, this study provides more evidence documenting the importance of preserving the last cloud forest fragments in the central region of Veracruz, Mexico, and suggests that using shade‐coffee plantations to connect forest fragments may be an effective way of maintaining populations of S. ludovici and likely other volant frugivores. 相似文献
138.
Cristian A. Lasagna-Reeves Audra L. Clos Diana Castillo-Carranza Urmi Sengupta Marcos Guerrero-Muñoz Brent Kelly Richard Wagner Rakez Kayed 《Biochemical and biophysical research communications》2013,430(3):963-968
The tumor suppressor p53 plays an important role in genome integrity. It is frequently mutated in all types of human cancers, making p53 a key factor in cancer progression. Two phenotypic consequences of these alterations are dominant; a loss of function and a gain of function of p53, which, in several cases, accumulates in intracellular aggregates. Although the nature of such aggregates is still unclear, recent evidence indicates that p53 can undergo conformational transitions leading to amyloid formation. Amyloid diseases, such as, Alzheimer’s disease, are characterized by the accumulation of insoluble aggregates displaying the fibrillar conformation. We decided to investigate the propensity of wild type p53 to aggregate and its consequent assembly into different amyloid species, such as oligomers and fibrils; and to determine if these changes in conformation lead to a loss of function of p53. Furthermore, we analyzed cases of Basal Cell Carcinoma (BCC), for the presence of p53 amyloids. Here, we show that p53 forms amyloid oligomers and fibrils, which coincide with p53 inability of binding to DNA consensus sequences. Both p53 amyloid oligomers and fibrils were detected in BCC cancer samples. Additionally, we demonstrate that p53 oligomers are the most cytotoxic to human cell cultures.Our study reveals p53 amyloid formation and demonstrates its dual role in the pathogenesis of cancer by producing a loss of protein function and a gain of toxic function, extensively described in several amyloidogenic diseases. Our results suggest that under certain circumstances, cancer could be considered a protein-conformation disease. 相似文献
139.
Vicente Castro-Castillo Cristian Suárez-Rozas Adriana Pabón Edwin G. Pérez Bruce K. Cassels Silvia Blair 《Bioorganic & medicinal chemistry letters》2013,23(1):327-329
Some synthetic 1-azabenzanthrones (7H-dibenzo[de,h]quinolin-7-ones) are weakly to moderately cytotoxic, suggesting that they might also show antiparasitic activity. We have now tested a small collection of these compounds in vitro against a chloroquine-resistant Plasmodium falciparum strain, comparing their cytotoxicity against normal human fibroblasts. Our results indicate that 5-methoxy-1-azabenzanthrone and its 2,3-dihydro analogue have low micromolar antiplasmodial activities and showed more than 10-fold selectivity against the parasite, indicating that the dihydro compound, in particular, might serve as a lead compound for further development. 相似文献
140.
Manuel de Lera Ruiz Junying Zheng Michael Y. Berlin Kevin D. McCormick Robert G. Aslanian Robert West Joyce Hwa Jean Lachowicz Margaret van Heek 《Bioorganic & medicinal chemistry letters》2013,23(21):6004-6009
A novel series of non-imidazole bicyclic and tricyclic histamine H3 receptor antagonists has been discovered. Compound 17 was identified as a centrally penetrant molecule with high receptor occupancy which demonstrates robust oral activity in rodent models of obesity. In addition compound 17 possesses clean CYP and hERG profiles and shows no behavioral changes in the Irwin test. 相似文献