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61.
We have analyzed the alignment of a long homologous region of the human and baboon genomes (approximately 1.5 Mb). We show that the frequency of gaps between aligned segments decreases slowly with gap length, indicating that several successive nucleotides are often deleted or inserted in one event. By contrast, runs of consecutive mismatches decrease rapidly in frequency with increasing length, following an exponential distribution, indicating that nucleotides are mostly substituted one at a time. Nucleotide substitutions are clumped at the scales of <10 and 1000-10,000 nucleotides, but show almost no aggregation at the scales of <10-100 and over approximately 50,000 nucleotides. Apparently, two rather different factors make the substitution rate not exactly uniform along the DNA sequence. Comparison of regions of very similar genomes that are approximately selectively neutral makes it possible to study spontaneous mutation at a new level of resolution. 相似文献
62.
Cristina W. Vendruscolo Carmen Ferrero Edgardo A.G. Pineda Joana L.M. Silveira Rilton A. Freitas Maria Rosa Jiménez-Castellanos Tania M.B. Bresolin 《Carbohydrate polymers》2009,76(1):86-93
The galactomannan from Mimosa scabrella Bentham was extracted on a pilot plant scale and dried either by vacuum oven (GVO) or by spray-drier (GSD) to evaluate the effect of the drying technique on the powder quality and its applicability as excipient in solid dosage forms. The analysis by high performance size exclusion chromatography (HPSEC) coupled to multiangle laser light scattering (MALLS) suggests that both products behave as semi-flexible polymers, although the GSD showed more aggregation at molecular level (~10%) and higher chain stiffness (Lp 9.1 nm). TG and DSC analysis showed weight loss event with peak at 299.7 and 311.9 °C to GVO and GSD, respectively, as well and higher ash content for GSD sample, in both inert and oxidant atmosphere. The X-ray diffraction confirmed the amorphous nature of both galactomannans although GVO showed high crystallinity. The GSD showed lower density (1.009 g/cm3), higher cohesiveness (repose angle 35.5°, compressibility 32.2% and absence of flow), smaller and more spherical particles than GVO sample, both with high polydispersion. As vacuum oven-drying resulted in a like fibrous material, spray-drying appears as an alternative method easy to extrapolate in industry, requiring a glidant incorporation to improve the powder flowability. 相似文献
63.
Joana T. de Oliveira Ana L. Santos Catarina Gomes Rita Barros Cláudia Ribeiro Nuno Mendes Augusto J. de Matos M. Helena Vasconcelos Maria José Oliveira Celso A. Reis Fátima G?rtner 《PloS one》2015,10(4)
Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor. Sialylation, governed by sialyltransferases and sialidases, is strongly implicated in the oncogenesis and progression of breast cancer. In this study we evaluated the biological behavior of canine mammary tumor cells upon oseltamivir phosphate treatment (a sialidase inhibitor) in vitro and in vivo. Our in vitro results showed that oseltamivir phosphate impairs sialidase activity leading to increased sialylation in CMA07 and CMT-U27 canine mammary cancer cells. Surprisingly, oseltamivir phosphate stimulated, CMT-U27 cell migration and invasion capacity in vitro, in a dose-dependent manner. CMT-U27 tumors xenograft of oseltamivir phosphate-treated nude mice showed increased sialylation, namely α2,6 terminal structures and SLe(x) expression. Remarkably, a trend towards increased lung metastases was observed in oseltamivir phosphate-treated nude mice. Taken together, our findings revealed that oseltamivir impairs canine mammary cancer cell sialidase activity, altering the sialylation pattern of canine mammary tumors, and leading, surprisingly, to in vitro and in vivo increased mammary tumor aggressiveness. 相似文献
64.
Genomic Resources Development Consortium P. Álvarez Wolfgang Arthofer Maria M. Coelho D. Conklin A. Estonba Ana R. Grosso S. J. Helyar J. Langa Miguel P. Machado I. Montes Joana Pinho Alexander Rief Manfred Schartl Birgit C. Schlick‐Steiner Julia Seeber Florian M. Steiner C. Vilas 《Molecular ecology resources》2015,15(6):1510-1512
65.
Kristina Nystr?m Joana Abrantes Ana Margarida Lopes Béatrice Le Moullac-Vaidye Stéphane Marchandeau Jézabel Rocher Nathalie Ruvo?n-Clouet Pedro J. Esteves Jacques Le Pendu 《PLoS pathogens》2015,11(4)
RHDV (rabbit hemorrhagic disease virus), a virulent calicivirus, causes high mortalities in European rabbit populations (Oryctolagus cuniculus). It uses α1,2fucosylated glycans, histo-blood group antigens (HBGAs), as attachment factors, with their absence or low expression generating resistance to the disease. Synthesis of these glycans requires an α1,2fucosyltransferase. In mammals, there are three closely located α1,2fucosyltransferase genes rSec1, rFut2 and rFut1 that arose through two rounds of duplications. In most mammalian species, Sec1 has clearly become a pseudogene. Yet, in leporids, it does not suffer gross alterations, although we previously observed that rabbit Sec1 variants present either low or no activity. Still, a low activity rSec1 allele correlated with survival to an RHDV outbreak. We now confirm the association between the α1,2fucosyltransferase loci and survival. In addition, we show that rabbits express homogenous rFut1 and rFut2 levels in the small intestine. Comparison of rFut1 and rFut2 activity showed that type 2 A, B and H antigens recognized by RHDV strains were mainly synthesized by rFut1, and all rFut1 variants detected in wild animals were equally active. Interestingly, rSec1 RNA levels were highly variable between individuals and high expression was associated with low binding of RHDV strains to the mucosa. Co-transfection of rFut1 and rSec1 caused a decrease in rFut1-generated RHDV binding sites, indicating that in rabbits, the catalytically inactive rSec1 protein acts as a dominant-negative of rFut1. Consistent with neofunctionalization of Sec1 in leporids, gene conversion analysis showed extensive homogenization between Sec1 and Fut2 in leporids, at variance with its limited degree in other mammals. Gene conversion additionally involving Fut1 was also observed at the C-terminus. Thus, in leporids, unlike in most other mammals where it became extinct, Sec1 evolved a new function with a dominant-negative effect on rFut1, contributing to fucosylated glycan diversity, and allowing herd protection from pathogens such as RHDV. 相似文献
66.
Ribose 5-Phosphate Isomerase B Knockdown Compromises Trypanosoma brucei Bloodstream Form Infectivity
Inês Loureiro Joana Faria Christine Clayton Sandra Macedo-Ribeiro Nuno Santarém Nilanjan Roy Anabela Cordeiro-da-Siva Joana Tavares 《PLoS neglected tropical diseases》2015,9(1)
Ribose 5-phosphate isomerase is an enzyme involved in the non-oxidative branch of the pentose phosphate pathway, and catalyzes the inter-conversion of D-ribose 5-phosphate and D-ribulose 5-phosphate. Trypanosomatids, including the agent of African sleeping sickness namely Trypanosoma brucei, have a type B ribose-5-phosphate isomerase. This enzyme is absent from humans, which have a structurally unrelated ribose 5-phosphate isomerase type A, and therefore has been proposed as an attractive drug target waiting further characterization. In this study, Trypanosoma brucei ribose 5-phosphate isomerase B showed in vitro isomerase activity. RNAi against this enzyme reduced parasites'' in vitro growth, and more importantly, bloodstream forms infectivity. Mice infected with induced RNAi clones exhibited lower parasitaemia and a prolonged survival compared to control mice. Phenotypic reversion was achieved by complementing induced RNAi clones with an ectopic copy of Trypanosoma cruzi gene. Our results present the first functional characterization of Trypanosoma brucei ribose 5-phosphate isomerase B, and show the relevance of an enzyme belonging to the non-oxidative branch of the pentose phosphate pathway in the context of Trypanosoma brucei infection. 相似文献
67.
Background
Anesthetic administration is increasingly guided by electroencephalography (EEG)-based monitoring, such as the bispectral index (BIS). However, during cardiopulmonary bypass (CPB), factors other than the administered hypnotic agents may influence EEG signals, and their effects on BIS values are unknown.Methods
This report is a secondary analysis of data from a prospective, controlled interventional study comparing the effect of sevoflurane administration guided by BIS monitoring (group SevoBIS) and constant administration of sevoflurane (group Sevo1.8Vol%) during CPB. Sevoflurane plasma concentration (SPC) was measured using gas chromatography. The relationships of BIS to SPC, CPB pump flow, arterial pressure, hematocrit, temperature, time on CPB, and patient characteristics were analysed.Results
No association was observed between BIS values and SPC in group SevoBIS. In group Sevo1.8Vol%, a 40 μg ml-1 increase in SPC, which encompassed the entire range of observed values of the SPC in this analysis, was associated with a decrease of 3.6 (95% confidence interval (CI): 1.1–6.1) in BIS values (p = 0.005). Each increase in CPB time of 10 minutes was associated with an increase in BIS values of 0.25 (95%CI: 0.11–0.39, p<0.001). Path analysis revealed that the BIS values of SevoBIS patients were 5.3 (95%CI: 3.2–7.5) units higher than those of Sevo1.8Vol% patients (p<0.001), which was the strongest effect on BIS values. Path analysis revealed a slope of 0.5 (95%CI: 0.3–0.7) BIS units per 1°C body temperature (p<0.001).Conclusion
BIS monitoring is insensitive to clinically relevant changes in SPC in individual patients during CPB. 相似文献68.
Joana A. Moscoso Tina Jaeger Martina Valentini Kailyn Hui Urs Jenal Alain Filloux 《Journal of bacteriology》2014,196(23):4081-4088
Pseudomonas aeruginosa is a Gram-negative opportunistic human pathogen and a threat for immunocompromised and cystic fibrosis patients. It is responsible for acute and chronic infections and can switch between these lifestyles upon taking an informed decision involving complex regulatory networks. The RetS/LadS/Gac/Rsm network and the cyclic-di-GMP (c-di-GMP) signaling pathways are both central to this phenomenon redirecting the P. aeruginosa population toward a biofilm mode of growth, which is associated with chronic infections. While these two pathways were traditionally studied independently from each other, we recently showed that cellular levels of c-di-GMP are increased in the hyperbiofilm retS mutant. Here, we have formally established the link between the two networks by showing that the SadC diguanylate cyclase is central to the Gac/Rsm-associated phenotypes, notably, biofilm formation. Importantly, SadC is involved in the signaling that converges onto the RsmA translational repressor either via RetS/LadS or via HptB/HsbR. Although the level of expression of the sadC gene does not seem to be impacted by the regulatory cascade, the production of the SadC protein is tightly repressed by RsmA. This adds to the growing complexity of the signaling network associated with c-di-GMP in P. aeruginosa. While this organism possesses more than 40 c-di-GMP-related enzymes, it remains unclear how signaling specificity is maintained within the c-di-GMP network. The finding that SadC but no other diguanylate cyclase is related to the formation of biofilm governed by the Gac/Rsm pathway further contributes to understanding of this insulation mechanism. 相似文献
69.
Melyssa Negri Margarida Martins Mariana Henriques Terezinha I. E. Svidzinski Joana Azeredo Rosário Oliveira 《Mycopathologia》2010,169(3):175-182
Candida tropicalis has been reported to be one of the Candida species which is most likely to cause bloodstream and urinary tract infections in hospitalized patients. Accordingly, the
aim of this study was to characterize the virulence of C. tropicalis by assessing antifungal susceptibility and comparing the expression of several virulence factors. This study was conducted
with seven isolates of C. tropicalis from urine and blood cultures and from central venous catheter. C. tropicalis ATCC 750 was used as reference strain. Yeasts adhered (2 h) to epithelial cells and silicone and 24 h biofilm biomass were
determined by crystal violet staining. Pseudohyphae formation ability was determined after growth in fetal bovine serum. Enzymes
production (hemolysins, proteases, phospholipases) was assessed by halo formation on agar plates. Susceptibility to antifungal
agents was determined by E-test. Regarding adhesion, it can be highlighted that C. tropicalis strains adhered significantly more to epithelium than to silicone. Furthermore, all C. tropicalis strains were able to form biofilms and to express total hemolytic activity. However, protease was only produced by two isolates
from urine and by the isolates from catheter and blood. Moreover, only one C. tropicalis (from catheter) was phospholipase positive. All isolates were susceptible to voriconazole, fluconazole and amphotericin B.
Four strains were susceptible-dose dependent to itraconazole and one clinical isolate was found to be resistant. 相似文献
70.
Joana Vicente Paulo Alves Christophe Randin Antoine Guisan João Honrado 《Ecography》2010,33(6):1081-1092
Understanding and predicting biological invasions can focus either on traits that favour species invasiveness or on features of the receiving communities, habitats or landscapes that promote their invasibility. Here, we address invasibility at the regional scale, testing whether some habitats and landscapes are more invasible than others by fitting models that relate alien plant species richness to various environmental predictors. We use a multi‐model information‐theoretic approach to assess invasibility by modelling spatial and ecological patterns of alien invasion in landscape mosaics, and by testing competing hypotheses of environmental factors that may control invasibility. Because invasibility may be mediated by particular characteristics of invasiveness, we classified alien species according to their C‐S‐R plant strategies. We illustrate this approach with a set of 86 alien species in northern Portugal. We first focus on predictors influencing species richness and expressing invasibility, and then evaluate whether distinct plant strategies respond to the same or different groups of environmental predictors. We confirmed climate as a primary determinant of alien invasions, and as a primary environmental gradient determining landscape invasibility. The effects of secondary gradients were detected only when the area was sub‐sampled according to predictions based on the primary gradient. Then, multiple predictor types influenced patterns of alien species richness, with some types (landscape composition, topography and fire regime) prevailing over others. Alien species richness responded most strongly to extreme land management regimes, suggesting that intermediate disturbance induces biotic resistance by favouring native species richness. Land‐use intensification facilitated alien invasion, whereas conservation areas hosted few invaders, highlighting the importance of ecosystem stability in preventing invasions. Plants with different strategies exhibited different responses to environmental gradients, particularly when the variations of the primary gradient were narrowed by sub‐sampling. Such differential responses of plant strategies suggest using distinct control and eradication approaches for different areas and alien plant groups. 相似文献