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311.
312.
Aurélie Hurtevent Morgan Le Naour Veronique Leclerc Pascal Carato Patricia Melnyk Nathalie Hennuyer 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):524-538
Abstract A series of nitrogen heterocycles containing α–ethoxyphenylpropionic acid derivatives were designed as dual PPARα/γ agonist ligands for the treatment of type 2 diabetes (T2D) and its complications. 6-Benzoyl-benzothiazol-2-one was the most tolerant of the tested heterocycles in which incorporation of O-methyl oxime ether and trifluoroethoxy group followed by enantiomeric resolution led to the (S)-stereoisomer 44?b displaying the best in vitro pharmacological profile. Compound 44?b acted as a very potent full PPARγ agonist and a weak partial agonist on the PPARα receptor subtype. Compound 44?b showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain and could be considered as a selective PPARγ modulator (SPPARγM). 相似文献
313.
314.
Three types of epidermal cultures of fish were used for toxicological investigations, a primary cell culture and a tissue culture prepared from the rainbow trout Oncorhynchus mykiss Walbaum and the cell line EPC, derived from a skin tumour of the carp Cyprinus carpio L. Two studies were carried out to compare the different culture systems. In the first cultures were incubated with nonylphenol and in the second set of experiments the cell cultures were exposed to a wastewater sample containing low concentrations of nonylphenol (NP). Both cell cultures were similarly sensitive to nonylphenol with respect to the endpoints cell viability (LC50 (24 h) 47.1 μM NP (primary cell culture) and 44.2 μM NP (EPC)) values and apoptotic rate (significantly increased apoptotic rate after exposure to 50 μM NP for 24 h, p < 0.001 (primary cell culture), p = 0.008 (EPC)). The explant culture was slightly less sensitive (increased apoptotic rate after exposure to 50 μM NP for 24 h, but not significant: p = 0.385), which could be due to the capabilities of a differentiated tissue, providing more protective repair mechanisms, compared with single cells. All cultures revealed a concentration–response relationship for the endpoint apoptotic rate after the application of nonylphenol for 24 h. After wastewater exposure, a significant decrease in the apoptotic rate was measured in the primary cell culture (dilution wastewater : medium 1:1:p = 0.018; dilution wastewater : medium 1:2:p = 0.003), whereas the cell line EPC did not reveal any effects. Our results show that the endpoint apoptotic rate is more sensitive than the parameter cell viability for detecting adverse effects of a wastewater sample. 相似文献
315.
Lucia Fernandez-Arrojo Barbara Rodriguez-Colinas Patricia Gutierrez-Alonso Maria Fernandez-Lobato Miguel Alcalde Antonio O. Ballesteros Francisco J. Plou 《Process Biochemistry》2013,48(4):677-682
A modification of the classical calcium alginate enzyme entrapment technique is described aiming to overcome some of the limitations of the former gel-based biocatalysts. Dried alginate entrapped enzymes (DALGEEs) were obtained dehydrating calcium alginate gel beads containing entrapped enzymes. A fructosyltransferase from Aspergillus aculeatus, present in Pectinex Ultra SP-L, was entrapped using this technique. The resulting DALGEEs were successfully tested both operating batchwise and in a continuous fixed-bed reactor for fructooligosaccharides (FOS) synthesis from sucrose. Interestingly, DALGEEs did not re-swell upon incubation in concentrated (600 g/L) sucrose solutions, probably due to the lowered water activity (aw) of such media. Confocal laser scanning microscopy of DALGEEs revealed that the enzyme molecules accumulated preferably in the shell of the particles. DALGEEs showed an approximately 30-fold higher volumetric activity (300 U/mL) compared with the calcium alginate gel beads. Moreover, a significant enhancement (40-fold) of the space-time-yield of fixed-bed bioreactors was observed when using DALGEEs as biocatalyst compared with gel beads (4030 g/day L of FOS vs. 103 g/day L). The operational stability of fixed-bed reactors packed with DALGEEs was extraordinary, providing a nearly constant FOS composition of the outlet during at least 700 h. It was also noticeable their resistance against microbial attack, even after long periods of storage at room temperature. The DALGEEs immobilisation strategy may also be useful for other biotransformations, in particular when they take place in low aw media. 相似文献
316.
Carlos Huitrón Rosalba Pérez Luís Gutiérrez Patricia Lappe Pavel Petrosyan Jesús Villegas Cecilia Aguilar Leticia Rocha-Zavaleta Abel Blancas 《Journal of industrial microbiology & biotechnology》2013,40(1):123-132
Agave tequilana fructans are the source of fermentable sugars for the production of tequila. Fructans are processed by acid hydrolysis or by cooking in ovens at high temperature. Enzymatic hydrolysis is considered an alternative for the bioconversion of fructans. We previously described the isolation of Aspergillus niger CH-A-2010, an indigenous strain that produces extracellular inulinases. Here we evaluated the potential application of A. niger CH-A-2010 inulinases for the bioconversion of A. tequilana fructans, and its impact on the production of ethanol. Inulinases were analyzed by Western blotting and thin layer chromatography. Optimal pH and temperature conditions for inulinase activity were determined. The efficiency of A. niger CH-A-2010 inulinases was compared with commercial enzymes and with acid hydrolysis. The hydrolysates obtained were subsequently fermented by Saccharomyces cerevisiae to determine the efficiency of ethanol production. Results indicate that A. niger CH-A-2010 predominantly produces an exo-inulinase activity. Optimal inulinase activity occurred at pH 5.0 and 50 °C. Hydrolysis of raw agave juice by CH-A-2010 inulinases yielded 33.5 g/l reducing sugars, compared with 27.3 g/l by Fructozyme® (Novozymes Corp, Bagsværd, Denmark) and 29.4 g/l by acid hydrolysis. After fermentation of hydrolysates, we observed that the conversion efficiency of sugars into ethanol was 97.5 % of the theoretical ethanol yield for enzymatically degraded agave juice, compared to 83.8 % for acid-hydrolyzed juice. These observations indicate that fructans from raw Agave tequilana juice can be efficiently hydrolyzed by using A. niger CH-A-2010 inulinases, and that this procedure impacts positively on the production of ethanol. 相似文献
317.
Shevin T. Jacob Patricia B. Pavlinac Lydia Nakiyingi Patrick Banura Jared M. Baeten Karen Morgan Amalia Magaret Yuka Manabe Steven J. Reynolds W. Conrad Liles Anna Wald Moses L. Joloba Harriet Mayanja-Kizza W. Michael Scheld 《PloS one》2013,8(8)
Background
When manifested as Mycobacterium tuberculosis (MTB) bacteremia, disseminated MTB infection clinically mimics other serious blood stream infections often hindering early diagnosis and initiation of potentially life-saving anti-tuberculosis therapy. In a cohort of hospitalized HIV-infected Ugandan patients with severe sepsis, we report the frequency, management and outcomes of patients with MTB bacteremia and propose a risk score based on clinical predictors of MTB bacteremia.Methods
We prospectively enrolled adult patients with severe sepsis at two Ugandan hospitals and obtained blood cultures for MTB identification. Multivariable logistic regression modeling was used to determine predictors of MTB bacteremia and to inform the stratification of patients into MTB bacteremia risk categories based on relevant patient characteristics.Results
Among 368 HIV-infected patients with a syndrome of severe sepsis, eighty-six (23%) had MTB bacteremia. Patients with MTB bacteremia had a significantly lower median CD4 count (17 vs 64 lymphocytes/mm3, p<0.001) and a higher 30-day mortality (53% vs 32%, p = 0.001) than patients without MTB bacteremia. A minority of patients with MTB bacteremia underwent standard MTB diagnostic testing (24%) or received empiric anti-tuberculosis therapy (15%). Independent factors associated with MTB bacteremia included male sex, increased heart rate, low CD4 count, absence of highly active anti-retroviral therapy, chief complaint of fever, low serum sodium and low hemoglobin. A risk score derived from a model containing these independent predictors had good predictive accuracy [area under the curve = 0.85, 95% CI 0.80–0.89].Conclusions
Nearly 1 in 4 adult HIV-infected patients hospitalized with severe sepsis in 2 Ugandan hospitals had MTB bacteremia. Among patients in whom MTB was suspected, standard tests for diagnosing pulmonary MTB were inaccurate for correctly classifying patients with or without bloodstream MTB infection. A MTB bacteremia risk score can improve early diagnosis of MTB bacteremia particularly in settings with increased HIV and MTB co-infection. 相似文献318.
Hianara A. Bustamante Andrés Rivera-Dictter Viviana A. Cavieres Vanessa C. Mu?oz Alexis González Yimo Lin Gonzalo A. Mardones Patricia V. Burgos 《PloS one》2013,8(12)
Alzheimer’s disease (AD) is characterized by the buildup of amyloid-β peptides (Aβ) aggregates derived from proteolytic processing of the β-amyloid precursor protein (APP). Amyloidogenic cleavage of APP by β-secretase/BACE1 generates the C-terminal fragment C99/CTFβ that can be subsequently cleaved by γ-secretase to produce Aβ. Growing evidence indicates that high levels of C99/CTFβ are determinant for AD. Although it has been postulated that γ-secretase-independent pathways must control C99/CTFβ levels, the contribution of organelles with degradative functions, such as the endoplasmic reticulum (ER) or lysosomes, is unclear. In this report, we investigated the turnover and amyloidogenic processing of C99/CTFβ in human H4 neuroglioma cells, and found that C99/CTFβ is localized at the Golgi apparatus in contrast to APP, which is mostly found in endosomes. Conditions that localized C99/CTFβ to the ER resulted in its degradation in a proteasome-dependent manner that first required polyubiquitination, consistent with an active role of the ER associated degradation (ERAD) in this process. Furthermore, when proteasomal activity was inhibited C99/CTFβ was degraded in a chloroquine (CQ)-sensitive compartment, implicating lysosomes as alternative sites for its degradation. Our results highlight a crosstalk between degradation pathways within the ER and lysosomes to avoid protein accumulation and toxicity. 相似文献
319.
Rosa Ana Sánchez-Guillén Jesús Mu?oz Gerardo Rodríguez-Tapia T. Patricia Feria Arroyo Alex Córdoba-Aguilar 《PloS one》2013,8(11)
Many ectotherms have altered their geographic ranges in response to rising global temperatures. Current range shifts will likely increase the sympatry and hybridisation between recently diverged species. Here we predict future sympatric distributions and risk of hybridisation in seven Mediterranean ischnurid damselfly species (I. elegans, I. fountaineae, I. genei, I. graellsii, I. pumilio, I. saharensis and I. senegalensis). We used a maximum entropy modelling technique to predict future potential distribution under four different Global Circulation Models and a realistic emissions scenario of climate change. We carried out a comprehensive data compilation of reproductive isolation (habitat, temporal, sexual, mechanical and gametic) between the seven studied species. Combining the potential distribution and data of reproductive isolation at different instances (habitat, temporal, sexual, mechanical and gametic), we infer the risk of hybridisation in these insects. Our findings showed that all but I. graellsii will decrease in distributional extent and all species except I. senegalensis are predicted to have northern range shifts. Models of potential distribution predicted an increase of the likely overlapping ranges for 12 species combinations, out of a total of 42 combinations, 10 of which currently overlap. Moreover, the lack of complete reproductive isolation and the patterns of hybridisation detected between closely related ischnurids, could lead to local extinctions of native species if the hybrids or the introgressed colonising species become more successful. 相似文献
320.
Bateman’s experimental study of Drosophila melanogaster produced conclusions that are now part of the bedrock premises of modern sexual selection. Today it is the most cited experimental study in sexual selection, and famous as the first experimental demonstration of sex differences in the relationship between number of mates and relative reproductive success. We repeated the experimental methodology of the original to evaluate its reliability. The results indicate that Bateman’s methodology of visible mutations to assign parentage and reproductive success to subject adults is significantly biased. When combined in offspring, the mutations decrease offspring survival, so that counts of mate number and reproductive success are mismeasured. Bateman’s method overestimates the number of subjects with no mates and underestimates the number with one or more mates for both sexes. Here we discuss why Bateman’s paper is important and present additional analyses of data from our monogamy trials. Monogamy trials can inform inferences about the force of sexual selection in populations because in monogamy trials male–male competition and female choice are absent. Monogamy trials also would have provided Bateman with an a priori test of the fit of his data to Mendel’s laws, an unstated, but vital assumption of his methodology for assigning parentage from which he inferred the number of mates per individual subject and their reproductive success. Even under enforced monogamous mating, offspring frequencies of double mutant, single mutant and no mutant offspring were significantly different from Mendelian expectations proving that Bateman’s method was inappropriate for answering the questions he posed. Double mutant offspring (those with a mutation from each parent) suffered significant inviability as did single mutant offspring whenever they inherited their mother’s marker but the wild-type allele at their father’s marker locus. These inviability effects produced two important inaccuracies in Bateman’s results and conclusions. (1) Some matings that actually occurred were invisible and (2) reproductive success of some mothers was under-estimated. Both observations show that Bateman’s conclusions about sex differences in number of mates and reproductive success were unwarranted, based on biased observations. We speculate about why Bateman’s classic study remained without replication for so long, and we discuss why repetition almost 60 years after the original is still timely, necessary and critical to the scientific enterprise. We highlight overlooked alternative hypotheses to urge that modern tests of Bateman’s conclusions go beyond confirmatory studies to test alternative hypotheses to explain the relationship between mate number and reproductive success. 相似文献