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101.
Eric E. Irons Justin W. Flatt Konstantin Doronin Tara L. Fox Mauro Acchione Phoebe L. Stewart Dmitry M. Shayakhmetov 《Journal of virology》2013,87(17):9610-9619
Adenoviruses (Ads) are promising vectors for therapeutic interventions in humans. When injected into the bloodstream, Ad vectors can bind several vitamin K-dependent blood coagulation factors, which contributes to virus sequestration in the liver by facilitating transduction of hepatocytes. Although both coagulation factors FVII and FX bind the hexon protein of human Ad serotype 5 (HAdv5) with a very high affinity, only FX appears to play a role in mediating Ad-hepatocyte transduction in vivo. To understand the discrepancy between efficacy of FVII binding to hexon and its apparently poor capacity for supporting virus cell entry, we analyzed the HAdv5-FVII complex by using high-resolution cryo-electron microscopy (cryo-EM) followed by molecular dynamic flexible fitting (MDFF) simulations. The results indicate that although hexon amino acids T423, E424, and T425, identified earlier as critical for FX binding, are also involved in mediating binding of FVII, the FVII GLA domain sits within the surface-exposed hexon trimer depression in a different orientation from that found for FX. Furthermore, we found that when bound to hexon, two proximal FVII molecules interact via their serine protease (SP) domains and bury potential heparan sulfate proteoglycan (HSPG) receptor binding residues within the dimer interface. In contrast, earlier cryo-EM studies of the Ad-FX interaction showed no evidence of dimer formation. Dimerization of FVII bound to Ad may be a contributing mechanistic factor for the differential infectivity of Ad-FX and Ad-FVII complexes, despite high-affinity binding of both these coagulation factors to the virus. 相似文献
102.
Mauro I. Schiaffini Magalí Gabrielli Francisco J. Prevosti Yamila P. Cardoso Diego Castillo Roberto Bo Emma Casanave Marta Lizarralde 《Zoological Journal of the Linnean Society》2013,167(2):327-344
Despite recent taxonomic evaluations of Mephitidae and North American hog‐nosed skunks, southern South American species of Conepatus have not been thoroughly examined in a systematic context. Conepatus chinga and Conepatus humboldtii were described more than 150 years ago, based on external characters such as hair coloration and size. Although historically recognized as valid species, to date no detailed systematic analysis has been performed for either of these taxa. Herein, we evaluated the taxonomic status of C. chinga and C. humboldtii within the southern part of South America using geometric morphometrics of the skull and mandible, mitochondrial DNA analysis using the cytochrome b and cytochrome oxidase c subunit I genes, and also control region and pelage pattern variation. We failed to find morphological (skull shape and pelage coloration patterns) or molecular differences between these two species; thus, we considered that the specimens assigned to C. chinga and C. humboldtii belong to the same species. Our results indicate that environmental variation seems to be responsible for shape and size variation in Conepatus skulls from southern South America. © 2013 The Linnean Society of London 相似文献
103.
Sonia Eligini Mauro Crisci Elisa Bono Paola Songia Elena Tremoli Gualtiero I. Colombo Susanna Colli 《Journal of cellular physiology》2013,228(7):1464-1472
Tissue macrophages are resident phagocytes that acquire specific phenotypes according to the microenvironment. Morphological and functional heterogeneity has been evidenced in different homeostatic and pathological conditions. Indeed, the nature of macrophage subsets may have either harmful or beneficial functions in disease progression/resolution. Therefore the possibility to pharmacologically manipulate heterogeneity represents a relevant challenge. Since human tissue macrophages are not easily obtained, various in vitro models are currently used that do not adequately reflect the heterogeneity and plasticity of tissue macrophages. We had previously reported that two dominant and distinct macrophage morphotypes co‐exist in the same culture of human monocytes spontaneously differentiated for 7 days in autologous serum. The present study was aimed to the phenotypic characterization of these morphotypes, that is, round‐ and spindle‐shaped. We observed that, besides substantial differences in cytoskeleton architecture, round monocyte‐derived macrophages (MDMs) showed higher lipid content, increased macropinocytosis/efferocytosis capacity, and overexpression of CD163, interleukin (IL)‐10, and transforming growth factor (TGF) β2. Conversely, spindle MDMs exhibited enhanced respiratory burst and higher expression of the chemokine (C‐C motif) ligands 18 and 24 (CCL18 and CCL24). Overall, round MDMs show functional traits reminiscent of the non‐inflammatory and reparative M2 phenotype, whereas spindle MDMs exhibit a pro‐inflammatory profile and express genes driving lymphocyte activation and eosinophil recruitment. MDMs obtained in the culture condition herein described represent a valuable model to disentangle and manipulate the functional heterogeneity of tissue macrophages that has been disclosed in scenarios spanning from inflammatory and wounding responses to atherosclerotic lesions. J. Cell. Physiol. 228: 1464–1472, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
104.
Rosane Dias Costa Vanessa Amaral Mendon?a Frederico Marianetti Soriani Sandra Lyon Rachel Adriana Penido Ana Maria Duarte Dias Costa Marina Dias Costa Fabio de Souza Terra Mauro Martins Teixeira Carlos Mauricio de Figueiredo Antunes Antonio Lúcio Teixeira 《Memórias do Instituto Oswaldo Cruz》2013,108(8):1051-1056
Leprosy is an infectious and contagious spectral disease accompanied by a series of
immunological events triggered by the host response to the aetiologic agent,
Mycobacterium leprae . The induction and maintenance of the
immune/inflammatory response in leprosy are linked to multiple cell interactions and
soluble factors, primarily through the action of cytokines. The purpose of the
present study was to evaluate the serum levels of tumour necrosis factor (TNF)-α and
its soluble receptors (sTNF-R1 and sTNF-R2) in leprosy patients at different stages
of multidrug treatment (MDT) in comparison with non-infected individuals and to
determine their role as putative biomarkers of the severity of leprosy or the
treatment response. ELISA was used to measure the levels of these molecules in 30
healthy controls and 37 leprosy patients at the time of diagnosis and during and
after MDT. Our results showed increases in the serum levels of TNF-α and sTNF-R2 in
infected individuals in comparison with controls. The levels of TNF-α, but not
sTNF-R2, decreased with treatment. The current results corroborate previous reports
of elevated serum levels of TNF-α in leprosy and suggest a role for sTNF-R2 in the
control of this cytokine during MDT. 相似文献
105.
Capsule We report on the courtship behaviour of the Eurasian Bittern from direct observation in rice fields. 相似文献
106.
107.
Mauro Ramalho Tereza C. Giannini Katia S. Malagodi-Braga Vera L. Imperatriz-Fonseca 《Grana》2013,52(4-5):239-244
Data on pollen load capacity and flower constancy are discussed for nine stingless bee species. The foragers present high levels of flower constancy and often visit only one flower type (on average 97% of bee foragers), rarely a few flower types (on average 3% of bee foragers), during the same foraging trip. The latter foragers exhibit no tendencies for choosing similar sources, related either to flower type or to pollen type. Pollen load capacity (the ratio between pollen load weight/worker weight) decreases as forager body weight increases, so it is larger in smaller stingless bees species and smaller in larger ones. Nevertheless, it seems that specific load capacity also depends on pollen types. 相似文献
108.
Gamal El-Ghazaly Sumio Nakamura Yuichi Takahashi Mauro Cresti Bjöorn Walles Claudio Milanesi 《Grana》2013,52(6):369-374
The major allergen Bet ver 1 of Betula pendula (= B. verrucosa) pollen grains has been localized by gold labelling with monoclonal antibodies. The allergen is located predominantly in the starch grains and to a slight extent in the exine and intine. The possibility that environmental factors might influence the liberation of allergenic compounds present in birch pollen grains is discussed. 相似文献
109.
Emilay B.T. Diogo Gleiston G. Dias Bernardo L. Rodrigues Tiago T. Guimarães Wagner O. Valença Celso A. Camara Ronaldo N. de Oliveira Mauro G. da Silva Vitor F. Ferreira Yen Galdino de Paiva Marilia O.F. Goulart Rubem F.S. Menna-Barreto Solange L. de Castro Eufrânio N. da Silva Júnior 《Bioorganic & medicinal chemistry》2013,21(21):6337-6348
In our continued search for novel trypanocidal compounds, twenty-six derivatives of para- and ortho-naphthoquinones coupled to 1,2,3-triazoles were synthesized. These compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Compounds 17–24, 28–30 and 36–38 are described herein for the first time. Three of these novel compounds (28–30) were found to be more potent than the standard drug benznidazole, with IC50/24 h values between 6.8 and 80.8 μM. Analysis of the toxicity to heart muscle cells led to LC50/24 h of <125, 63.1 and 281.6 μM for 28, 29 and 30, respectively. Displaying a selectivity index of 34.3, compound 30 will be further evaluated in vivo. The electrochemical properties of selected compounds were evaluated in an attempt to find correlations with trypanocidal activity, and it was observed that more electrophilic quinones were generally more potent. 相似文献
110.
Leonardo Magno Rambo Leandro Rodrigo Ribeiro Iuri Domingues Della-Pace Daniel Neis Stamm Rogério da Rosa Gerbatin Marina Prigol Simone Pinton Cristina Wayne Nogueira Ana Flávia Furian Mauro Schneider Oliveira Michele Rechia Fighera Luiz Fernando Freire Royes 《Amino acids》2013,44(3):857-868
A growing body of evidence indicates that creatine (Cr) exerts beneficial effects on a variety of pathologies where energy metabolism and oxidative stress play an etiological role. However, the benefits of Cr treatment for epileptics are still shrouded in controversy. In the present study, we found that acute Cr treatment (300 mg/kg, p.o.) prevented the increase in electroencephalographic wave amplitude typically elicited by PTZ (30, 45 or 60 mg/kg, i.p.). Cr treatment also increased the latency periods of first myoclonic jerks, lengthened the latency periods of the generalized tonic–clonic seizures and reduced the time spent in the generalized tonic–clonic seizures induced by PTZ (60 mg/kg). Administration of PTZ (all doses) decreased Na+, K+-ATPase activity as well as adenosine triphosphate (ATP) and adenosine diphosphate levels in the cerebral cortex, but Cr treatment prevented these effects. Cr administration also prevented increases in xanthine oxidase activity, adenosine monophosphate levels, adenosine levels, inosine levels and uric acid levels that normally occur after PTZ treatment (60 mg/kg, i.p.). We also showed that Cr treatment increased the total Cr (Cr + PCr) content, creatine kinase activity and the mitochondrial membrane potential (ΔΨ) in the cerebral cortex. In addition, Cr prevented PTZ-induced mitochondrial dysfunction characterized by decreasing ΔΨ, increasing thiobarbituric acid-reactive substance levels and increasing protein carbonylation. These experimental findings reinforce the idea that mitochondrial dysfunction plays a critical role in models of epileptic seizures and suggest that buffering brain energy levels through Cr treatment may be a promising therapeutic approach for the treatment of this neurological disease. 相似文献