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831.
Frank?Kozielski Tahira?Riaz Salvatore?DeBonis Christian?J.?Koehler Mario?Kroening Isabel?Panse Margarita?Strozynski Ian?M.?Donaldson Bernd?ThiedeEmail author 《Amino acids》2011,41(2):363-385
The microtubule (MT) cytoskeleton is essential for a variety of cellular processes. MTs are finely regulated by distinct classes
of MT-associated proteins (MAPs), which themselves bind to and are regulated by a large number of additional proteins. We
have carried out proteome analyses of tubulin-rich and tubulin-depleted MAPs and their interacting partners isolated from
bovine brain. In total, 573 proteins were identified giving us unprecedented access to brain-specific MT-associated proteins
from mammalian brain. Most of the standard MAPs were identified and at least 500 proteins have been reported as being associated
with MTs. We identified protein complexes with a large number of subunits such as brain-specific motor/adaptor/cargo complexes
for kinesins, dynein, and dynactin, and proteins of an RNA-transporting granule. About 25% of the identified proteins were
also found in the synaptic vesicle proteome. Analysis of the MS/MS data revealed many posttranslational modifications, amino
acid changes, and alternative splice variants, particularly in tau, a key protein implicated in Alzheimer’s disease. Bioinformatic
analysis of known protein–protein interactions of the identified proteins indicated that the number of MAPs and their associated
proteins is larger than previously anticipated and that our database will be a useful resource to identify novel binding partners. 相似文献
832.
Bjorn Steffensen Zhihua ChenSanjay Pal Margarita MikhailovaJianrong Su Yao WangXiaoping Xu 《Matrix biology》2011,30(1):34-42
Fibronectin (FN) purified by gelatin affinity chromatography is unstable and undergoes fragmentation. The cleavage has been ascribed to inherent autolytic protease activities as well as co-purified matrix metalloproteinases (MMP). Understanding the mechanism by which the proteolysis of FN occurs is important, because the FN fragments have biological activities that differ from those of intact FN. Having excluded contributions of other plasma-derived proteases, the present experiments demonstrated that cleavage of FN by MMP-2 to distinct fragments occurred in synergy with inherent FN activities. Limited heat treatment of FN at 56 °C for 30 min inactivated the inherent protease activities sharply reducing autolysis of FN in a manner similar to that seen in the presence of serine proteinase inhibitors. Heat treatment did not alter cell attachment to FN, but significantly increased the susceptibility of FN to enzymatic cleavage by MMP-2. The carboxyl-terminal hemopexin-like domain (PEX) of MMP-2 was shown to possess critical exodomain properties required for the interactions of MMP-2 with FN, and FN was cleaved at a significantly reduced rate by an MMP-2 variant with deletion of PEX. Verifying the specificity of interactions, isolated PEX competed FN cleavage by MMP-2 in a concentration-dependent manner. These results have further elucidated the synergistic contributions of inherent autolytic serine protease-like activities and MMP-2 to fragmentation of FN and provide the rationale and basis for modified preparation and handling of FN used in biological research. 相似文献
833.
Patricia Veiga-Crespo Lucia Blasco Fernando Rosa-Dos-Santos Margarita Poza Tomas G Villa 《International microbiology》2005,8(1):55-58
Commercial interest in the use of natural pigments isolated from microorganisms has increased in recent years; hence, molecules belonging to the polyisoprenoid group (i.e. beta-carotene, astaxanthin, and canthaxanthin) have been the focus of much attention. The bacterium Gordonia jacobaea readily synthesizes and accumulates large amounts of canthaxanthin (beta-beta'-carotene-4,4'-dione), which is widely used in the food and cosmetics industries. In the present work, the effects of different low-cost raw materials on fermentation and canthaxanthin accumulation by a hyperpigmented strain of G. jacobaea were studied. Canthaxanthin production and peak levels of accumulation varied according to the different media used. 相似文献
834.
835.
836.
Margarita Pons-Salort Jordi Serra-Cobo Flora Jay Marc López-Roig Rachel Lavenir Didier Guillemot Véronique Letort Hervé Bourhy Lulla Opatowski 《PloS one》2014,9(4)
Rabies is a worldwide zoonosis resulting from Lyssavirus infection. In Europe, Eptesicus serotinus is the most frequently reported bat species infected with Lyssavirus, and thus considered to be the reservoir of European bat Lyssavirus type 1 (EBLV-1). To date, the role of other bat species in EBLV-1 epidemiology and persistence remains unknown. Here, we built an EBLV-1−transmission model based on local observations of a three-cave and four-bat species (Myotis capaccinii, Myotis myotis, Miniopterus schreibersii, Rhinolophus ferrumequinum) system in the Balearic Islands, for which a 1995–2011 serological dataset indicated the continuous presence of EBLV-1. Eptesicus serotinus was never observed in the system during the 16-year follow-up and therefore was not included in the model. We used the model to explore virus persistence mechanisms and to assess the importance of each bat species in the transmission dynamics. We found that EBLV-1 could not be sustained if transmission between M. schreibersii and other bat species was eliminated, suggesting that this species serves as a regional reservoir. Global sensitivity analysis using Sobol''s method revealed that following the rate of autumn−winter infectious contacts, M. schreibersii''s incubation- and immune-period durations, but not the infectious period length, were the most relevant factors driving virus persistence. 相似文献
837.
Early social isolation provokes electrophysiological and structural changes in cutaneous sensory nerves of adult male rats
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Bertha Segura Angel I. Melo Alison S. Fleming Maria Eugenia Mendoza‐Garrido Margarita González del Pliego Elsa L. Aguirre‐Benitez Jesús Hernández‐Falcón Ismael Jiménez‐Estrada 《Developmental neurobiology》2014,74(12):1184-1193
Sensory and social deprivation from the mother and littermates during early life disturbs the development of the central nervous system, but little is known about its effect on the development of the peripheral nervous system. To assess peripheral effects of early isolation, male rat pups were reared artificially in complete social isolation (AR); reared artificially with two same‐age conspecifics (AR‐Social); or reared by their mothers and with littermates (MR). As adults, the electrophysiological properties of the sensory sural (SU) nerve were recorded. We found that the amplitude and normalized area (with respect to body weight) of the compound action potential (CAP) response provoked by single electrical pulses of graded intensity in the SU nerves of AR animals were shorter than the CAP recorded in SU nerves from MR and AR‐Social animals. The slope of the stimulus‐response curve of AR SU nerves was smaller than that of the other nerves. The histological characterization of axons in the SU nerves was made and showed that the myelin thickness of axons in AR SU nerves was significant lower (2–7µm) than that of the axons in the other nerves. Furthermore, the area and axon diameter of SU nerves of both AR and AR‐Social animals were significant lower than in MR animals. This is the first report to show that maternal and littermate deprivation by AR disturbs the development of the myelination and electrophysiological properties of axons in the SU nerve; the replacement of social cues prevents most of the effects. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1184–1193, 2014 相似文献
838.
Variability in sperm form and function in the context of sperm competition risk in two Tupinambis lizards
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Cecilia S. Blengini Naretto Sergio Cardozo Gabriela Laura C. Giojalas Chiaraviglio Margarita 《Ecology and evolution》2014,4(21):4080-4092
In polyandrous species, sperm morphometry and sperm velocity are under strong sexual selection. Although several hypotheses have been proposed to explain the role of sperm competition in sperm trait variation, this aspect is still poorly understood. It has been suggested that an increase in sperm competition pressure could reduce sperm size variation or produce a diversity of sperm to maximize male fertilization success. We aim at elucidating the variability of sperm morphometric traits and velocity in two Tupinambis lizards in the context of sperm competition risk. Sperm traits showed substantial variation at all levels examined: between species, among males within species, and within the ejaculate of individual males. Sperm velocity was found to be positively correlated with flagellum: midpiece ratio, with relatively longer flagella associated with faster sperm. Our results document high variability in sperm form and function in lizards. 相似文献
839.
Jaime Altcheh Guillermo Moscatelli Guido Mastrantonio Samanta Moroni Norberto Giglio Maria Elena Marson Griselda Ballering Margarita Bisio Gideon Koren Facundo García-Bournissen 《PLoS neglected tropical diseases》2014,8(5)
Introduction
Chagas disease, caused by the parasite Trypanosoma cruzi, can lead to long term cardiac morbidity. Treatment of children with benznidazole is effective, but no pediatric pharmacokinetics data are available and clinical pharmacology information on the drug is scarce.Patients and Methods
Prospective population pharmacokinetic (PK) cohort study in children 2–12 years old with Chagas disease treated with oral benznidazole 5–8 mg/kg/day BID for 60 days. (clinicaltrials.gov #). NCT00699387Results
Forty children were enrolled in the study. Mean age was 7.3 years. A total of 117 samples were obtained from 38 patients for PK analysis. A one compartment model best fit the data. Weight-corrected clearance rate (CL/F) showed a good correlation with age, with younger patients having a significantly higher CL/F than older children and adults. Simulated median steady-state benznidazole concentrations, based on model parameters, were lower for children in our study than for adults and lowest for children under 7 years of age. Treatment was efficacious in the 37 patients who completed the treatment course, and well tolerated, with few, and mild, adverse drug reactions (ADRs).Discussion
Observed benznidazole plasma concentrations in children were markedly lower than those previously reported in adults (treated with comparable mg/kg doses), possibly due to a higher CL/F in smaller children. These lower blood concentrations were nevertheless associated to a high therapeutic response in our cohort. Unlike adults, children have few adverse reactions to the drug, suggesting that there may be a direct correlation between drug concentrations and incidence of ADRs. Our results suggest that studies with lower doses in adults may be warranted.Trial Registration
ClinicalTrails.gov NCT00699387相似文献840.
Patricia M. Gaffney Denise M. Imai Deana L. Clifford Majid Ghassemian Roman Sasik Aaron N. Chang Timothy D. O’Brien Judith Coppinger Margarita Trejo Eliezer Masliah Linda Munson Christina Sigurdson 《PloS one》2014,9(11)
Amyloid A (AA) amyloidosis is a debilitating, often fatal, systemic amyloid disease associated with chronic inflammation and persistently elevated serum amyloid A (SAA). Elevated SAA is necessary but not sufficient to cause disease and the risk factors for AA amyloidosis remain poorly understood. Here we identify an extraordinarily high prevalence of AA amyloidosis (34%) in a genetically isolated population of island foxes (Urocyon littoralis) with concurrent chronic inflammatory diseases. Amyloid deposits were most common in kidney (76%), spleen (58%), oral cavity (45%), and vasculature (44%) and were composed of unbranching, 10 nm in diameter fibrils. Peptide sequencing by mass spectrometry revealed that SAA peptides were dominant in amyloid-laden kidney, together with high levels of apolipoprotein E, apolipoprotein A-IV, fibrinogen-α chain, and complement C3 and C4 (false discovery rate ≤0.05). Reassembled peptide sequences showed island fox SAA as an 111 amino acid protein, most similar to dog and artic fox, with 5 unique amino acid variants among carnivores. SAA peptides extended to the last two C-terminal amino acids in 5 of 9 samples, indicating that near full length SAA was often present in amyloid aggregates. These studies define a remarkably prevalent AA amyloidosis in island foxes with widespread systemic amyloid deposition, a unique SAA sequence, and the co-occurrence of AA with apolipoproteins. 相似文献