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71.
Brenner RR 《Prostaglandins, leukotrienes, and essential fatty acids》2003,68(2):151-162
Animal biosynthesis of high polyunsaturated fatty acids from linoleic, alpha-linolenic and oleic acids is mainly modulated by the delta6 and delta5 desaturases through dietary and hormonal stimulated mechanisms. From hormones, only insulin activates both enzymes. In experimental diabetes mellitus type-1, the depressed delta6 desaturase is restored by insulin stimulation of the gene expression of its mRNA. However, cAMP or cycloheximide injection prevents this effect. The depression of delta6 and delta5 desaturases in diabetes is rapidly correlated by lower contents of arachidonic acid and higher contents of linoleic in almost all the tissues except brain. However, docosahexaenoic n-3 acid enhancement, mainly in liver phospholipids, is not explained yet. In experimental non-insulin dependent diabetes, the effect upon the delta6 and delta5 desaturases is not clear. From all other hormones glucagon, adrenaline, glucocorticoids, mineralocorticoids, oestriol, oestradiol, testosterone and ACTH depress both desaturases, and a few hormones: progesterone, cortexolone and pregnanediol are inactive. 相似文献
72.
Juan Núez-Farfn Rodolfo Dirzo 《Evolution; international journal of organic evolution》1994,48(2):423-436
It has been assumed that herbivores constitute a selective agent for the evolution of plant resistance. However, few studies have tested this hypothesis. In this study, we look at the annual weed Datura stramonium for evidence of current natural selection for resistance to herbivorous insects. Paternal half-sib families obtained through controlled crosses were exposed to herbivores under natural conditions. The plants were damaged by two folivorous insects: the tobacco flea beetle Epitrix parvula and the grasshopper Sphenarium purpurascens. Selection was estimated using a multiple-regression analysis of plant size and of damage by the two herbivores on plant fitness measured as fruit production for both individual phenotypes and family breeding values (genetic analysis). Directional phenotypic selection was detected for both larger plant size and lower resistance to the flea beetles, whereas stabilizing phenotypic selection was revealed for resistance to S. purpurascens. However, performing the same analyses on the breeding values of the characters revealed directional and stabilizing selection only for plant size. Thus, no agreement existed between the results of the two types of analyses, nor was there any detectable potential for genetic change in the studied population because of selection on herbivore resistance. The narrow-sense heritability of every trait studied was small (all <0.1) and not different from zero. The potential for evolutionary response to natural selection for higher resistance to herbivores in the studied population of D. stramonium is probably limited by lack of genetic variation. Natural selection acts on phenotypes, and the detection of phenotypic selection on resistance to herbivores confirms their ecological importance in determining plant fitness. However, evolutionary inferences based solely on phenotypic selection analyses must be interpreted with caution. 相似文献
73.
74.
Bianchi M Polticelli F Ascenzi P Botta M Federico R Mariottini P Cona A 《The FEBS journal》2006,273(6):1115-1123
Polyamine oxidase (PAO) and spermine oxidase (SMO) are involved in the catabolism of polyamines--basic regulators of cell growth and proliferation. The discovery of selective inhibitors of PAO and SMO represents an important tool in studying the involvement of these enzymes in polyamine homeostasis and a starting point for the development of novel antineoplastic drugs. Here, a comparative study on murine PAO (mPAO) and SMO (mSMO) inhibition by the polyamine analogues 1,8-diaminooctane, 1,12-diaminododecane, N-prenylagmatine (G3), guazatine and N,N1-bis(2,3-butadienyl)-1,4-butanediamine (MDL72527) is reported. Interestingly, 1,12-Diaminododecane and G3 behave as specific inhibitors of mPAO, values of K(i) for mPAO inhibition being lower than those for mSMO inactivation by several orders of magnitude. The analysis of molecular models of mPAO and mSMO indicates a significant reduction of the hydrophobic pocket located in maize PAO (MPAO) at the wider catalytic tunnel opening. This observation provides a rationale to explain the lower affinity displayed by G3, guazatine and MDL72527 for mPAO and mSMO as compared to MPAO. The different behaviour displayed by 1,12-diaminododecane towards mPAO and mSMO reveals the occurrence of basic differences in the ligand binding mode of the two enzymes, the first enzyme interacting mainly with substrate secondary amino groups and the second one with substrate primary amino groups. Thus, the data reported here provide the basis for the development of novel and selective inhibitors able to discriminate between mammalian SMO and PAO activities. 相似文献
75.
76.
Rodolfo A. Golluscio Amy T. Austin Guillermo C. García Martínez Marina Gonzalez-Polo Osvaldo E. Sala Robert B. Jackson 《Ecosystems》2009,12(4):686-697
We explored the net effects of grazing on soil C and N pools in a Patagonian shrub–grass steppe (temperate South America).
Net effects result from the combination of direct impacts of grazing on biogeochemical characteristics of microsites with
indirect effects on relative cover of vegetated and unvegetated microsites. Within five independent areas, we sampled surface
soils in sites subjected to three grazing intensities: (1) ungrazed sites inside grazing exclosures, (2) moderately grazed
sites adjacent to them, and (3) intensely grazed sites within the same paddock. Grazing significantly reduced soil C and N
pools, although this pattern was clearest in intensely grazed sites. This net effect was due to the combination of a direct
reduction of soil N content in bare soil patches, and indirect effects mediated by the increase of the cover of bare soil
microsites, with lower C and N content than either grass or shrub microsites. This increase in bare soil cover was accompanied
by a reduction in cover of preferred grass species and standing dead material. Finally, stable isotope signatures varied significantly
among grazed and ungrazed sites, with δ15N and δ13C significantly depleted in intensely grazed sites, suggesting reduced mineralization with increased grazing intensity. In
the Patagonian steppe, grazing appears to exert a negative effect on soil C and N cycles; sound management practices must
incorporate the importance of species shifts within life form, and the critical role of standing dead material in maintaining
soil C and N stocks and biogeochemical processes.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Author Contributions RAG designed study, performed research, analyzed data, wrote the paper; ATA designed study, wrote the paper; CGGM designed
study, performed research, analyzed data; MGP performed research; OES designed study; RBJ designed study, contributed new
methods. 相似文献
77.
The purpose of this study is to illustrate, with a controlled example, the influence of raw material variability on the excipient’s functionality during processing. Soluble starch was used as model raw material to investigate the effect of variability on its compaction properties. Soluble starch used in pharmaceutical applications has undergone a purification procedure including washing steps. In this study, a lot of commercially available starch was divided into two parts. One was left intact and the other was subjected to an extra washing step. The two resulting lots were subjected to a series of physical characterization tests typical of those used to qualify raw materials. The two resulting lots gave virtually identical results from the tests. From the physical testing point of view, the two lots can be considered as two equivalent lots of the same excipient. However, when tested for their functionality when subjected to a compaction process, the two lots were found to be completely different. The compaction properties of the two lots were distinctly different under all environmental and processing conditions tested. From the functionality point of view, the two lots are two very different materials. The similar physical testing results but different functionality can be reconciled by considering the surface properties of the powders. It was found that the washing step significantly altered the surface energetic properties of the excipient. The washed lot consistently produced stronger compacts. These results are attributable to the measurably higher surface energy of induced by the additional washing step. 相似文献
78.
A near infrared spectroscopic method was developed to determine drug content in a 20% (wt/wt) ibuprofen and spray-dried hydous
lactose blend. A blending profile was obtained after blending for 0.5, 1, 3, 5, 10, and 20 minutes. Stream sampling was used
to collect about 20 blend samples at each of the blending times from a laboratory scale V-blender. The samples collected were
used to develop a near infrared calibration model. The calibration model was then used to determine the drug content of unknown
samples from 2 validation blends. The validation blends were not included in the calibration model; they were used to evaluate
the effectiveness of the calibration model. A total of 45 samples from the 2 validation blends were predicted by the near
infrared calibration model and then analyzed by a validated UV spectrophotometric method. The root mean square error of prediction
for the first validation blend was 5.69 mg/g and 3.30 mg/g for the samples from the second blend. A paired t test at the 95%
confidence level did not indicate any differences between the drug content predicted by the near infrared spectroscopy (NIRS)
method and the validated UV method for the 2 blends. The results show that the NIRS method could be developed while the blending
profile is generated and used to thoroughly characterize a new formulation during development by analyzing a large number
of samples. The new formulation could be transferred to a manufacturing plant with an NIRS method to facilitate blend uniformity
analysis. 相似文献
79.
Anna Santoro Javier Conde Morena Scotece Vanessa Abella Ana Lois Veronica Lopez Jesus Pino Rodolfo Gomez Juan J. Gomez-Reino Oreste Gualillo 《PloS one》2015,10(8)
Objectives
Osteoarthritis (OA) is a chronic joint disease, characterized by a progressive loss of articular cartilage. During OA, proinflammatory cytokines, such as interleukin IL-1, induce the expression of matrix metalloproteinases (MMPs) in chondrocytes, contributing thus to the extracellular matrix (ECM) degradation. Members of Serpine family, including plasminogen activator inhibitors have been reported to participate in ECM regulation. The aim of this study was to assess the expression of serpin peptidase inhibitor clade E member 2 (SERPINE2), under basal conditions and in response to increasing doses of IL-1α, in human cultured chondrocytes. We also examined the effects of SERPINE2 on IL-1α-induced MMP-13 expression. For completeness, the signaling pathway involved in this process was also explored.Methods
SERPINE2 mRNA and protein expression were evaluated by RT-qPCR and western blot analysis in human T/C-28a2 cell line and human primary chondrocytes. These cells were treated with human recombinant SERPINE2, alone or in combination with IL-1α. ERK 1/2, NFκB and AP-1 activation were assessed by western blot analysis.Results
Human cultured chondrocytes express SERPINE2 in basal condition. This expression increased in response to IL-1α stimulation. In addition, recombinant SERPINE2 induced a clear inhibition of MMP-13 expression in IL-1α-stimulated chondrocytes. This inhibitory effect is likely regulated through a pathway involving ERK 1/2, NF-κB and AP-1.Conclusions
Taken together, these data demonstrate that SERPINE2 might prevent cartilage catabolism by inhibiting the expression of MMP-13, one of the most relevant collagenases, involved in cartilage breakdown in OA. 相似文献80.
Summary The effect of three different carbon sources on the biosynthesis of polyunsaturated fatty acids of the-linolenic acid series was investigated in hepatoma tissue culture (HTC) cells. Alpha linolenic acid was converted to higher homologs by a desaturating route that synthetized mainly 18:4 (6, 9, 12, 15), 20:4 (8, 11, 14, 17) and 20:5 (5, 8, 11, 14, 17) and an elongating route that produced 20:3 (11, 14, 17) and 20:4 (5, 11, 14, 17) acids. Fasting decreased both biosynthetic routes whereas glucose reactivated only the elongating pathway. Lactalbumin hydrolysate enhanced significantly only the desaturating route whereas glycerol was inactive. Glucose and aminoacids increased similarly the incorporation of labeled linolenic acid in the cells. The results are independent of hormonal effects.Members of the Carrera del Investigador Científico of the Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina. 相似文献