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31.
Lysine degradation through the saccharopine pathway has been shown only in plants and animals. Here, we show that bacteria possess the genes encoding lysine-ketoglutarate reductase (LKR) and saccharopine dehydrogenase (SDH). In Silicibacter, the contiguous lkr and sdh genes are interspersed, in another frame, by a polypeptide of unknown function. The bacterial enzyme does not contain the 110-amino-acid interdomain (ID) that intersperses the LKR and SDH domains of the plant enzyme. The ID was found in Cyanobacteria interspersing polypeptides without similarities and activities of LKR and SDH. The LKR/SDH bifunctional polypeptide of animals and plants may have arisen from a α-proteobacterium with a configuration similar to that of Silicibacter, whereas the ID in the plant enzyme may have been inherited from Cyanobacteria. 相似文献
32.
Amato AA Rajagopalan S Lin JZ Carvalho BM Figueira AC Lu J Ayers SD Mottin M Silveira RL Souza PC Mourão RH Saad MJ Togashi M Simeoni LA Abdalla DS Skaf MS Polikparpov I Lima MC Galdino SL Brennan RG Baxter JD Pitta IR Webb P Phillips KJ Neves FA 《The Journal of biological chemistry》2012,287(33):28169-28179
The recent discovery that peroxisome proliferator-activated receptor γ (PPARγ) targeted anti-diabetic drugs function by inhibiting Cdk5-mediated phosphorylation of the receptor has provided a new viewpoint to evaluate and perhaps develop improved insulin-sensitizing agents. Herein we report the development of a novel thiazolidinedione that retains similar anti-diabetic efficacy as rosiglitazone in mice yet does not elicit weight gain or edema, common side effects associated with full PPARγ activation. Further characterization of this compound shows GQ-16 to be an effective inhibitor of Cdk5-mediated phosphorylation of PPARγ. The structure of GQ-16 bound to PPARγ demonstrates that the compound utilizes a binding mode distinct from other reported PPARγ ligands, although it does share some structural features with other partial agonists, such as MRL-24 and PA-082, that have similarly been reported to dissociate insulin sensitization from weight gain. Hydrogen/deuterium exchange studies reveal that GQ-16 strongly stabilizes the β-sheet region of the receptor, presumably explaining the compound's efficacy in inhibiting Cdk5-mediated phosphorylation of Ser-273. Molecular dynamics simulations suggest that the partial agonist activity of GQ-16 results from the compound's weak ability to stabilize helix 12 in its active conformation. Our results suggest that the emerging model, whereby "ideal" PPARγ-based therapeutics stabilize the β-sheet/Ser-273 region and inhibit Cdk5-mediated phosphorylation while minimally invoking adipogenesis and classical agonism, is indeed a valid framework to develop improved PPARγ modulators that retain antidiabetic actions while minimizing untoward effects. 相似文献
33.
BACKGROUND AND AIMS: Pseudovivipary is an asexual reproductive strategy. Leiothrix spiralis and L. vivipara (Eriocaulaceae) are pseudoviviparous and occur in rupestrian grasslands, a habitat that has a predominance of sandy and shallow soil, with low water retention. This study aims to investigate the seasonal variation effect of moisture availability on L. spiralis and L. vivipara pseudoviviparous reproduction, and to compare their life history attributes, on rupestrian grasslands in Southeastern Brazil. METHODS: A field study was conducted, including observations concerning pseudoviviparous reproduction and measurement of demographic variables in both L. spiralis and L. vivipara. Soil moisture measurements were also performed to study its effect on the pseudoviviparous reproduction of L. spiralis and L. vivipara. KEY RESULTS: Flower head and plantlet production in L. spiralis were highly correlated with soil moisture. All scapes split off in the drier period, indicating that this is a splitter ramet species. Plantlet mortality was positively correlated with scapes splitting off. The L. vivipara phenophases were not synchronized to the variation in soil moisture, since flower heads and plantlets were produced throughout the year. Moreover, the splitting off of scapes was not observed. In addition, plantlets were formed early, as soon as the flower heads appeared, and remained suspended. Therefore, this species was called 'canopy forming'. CONCLUSIONS: Seasonal timing of pseudoviviparous reproduction can be a vital component of the successful establishment of plantlets in L. spiralis, considering that in this species the plantlets are formed only after the flower head touches the ground. In contrast, in L. vivipara, the plantlets are formed early, without touching the ground. Moreover, L. spiralis is a splitter ramet species, while L. vivipara is a canopy-forming species. The pseudoviviparous canopy-forming strategy appears to be more advantageous than the splitter ramet strategy, because even under similar soil moisture conditions, the survival of L. vivipara plantlets was greater than that of L. spiralis. 相似文献
34.
Aromatic amino acids (AAs, phenylalanine and tyrosine) may be specifically required during fish metamorphosis, since they
are the precursors of thyroid hormones which regulate this process. This project attempted to evaluate aromatic AA metabolism
during the ontogenesis of fish species with a marked (Senegalese sole; Solea senegalensis) and a less accentuated metamorphosis (gilthead seabream; Sparus aurata). Fish were tube-fed with three l-[U-14C] AA solutions at pre-metamorphic, metamorphic and post-metamorphic stages of development: controlled AA mixture (Mix), phenylalanine
(Phe) and tyrosine (Tyr). Results showed a preferential aromatic AA retention during the metamorphosis of Senegalese sole,
rather than in gilthead seabream. Senegalese sole’s highly accentuated metamorphosis seems to increase aromatic AA physiological
requirements, possibly for thyroid hormone production. Thus, Senegalese sole seems to be especially susceptible to dietary
aromatic AA deficiencies during the metamorphosis period, and these findings may be important for physiologists, fish nutritionists
and the flatfish aquaculture industry. 相似文献
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Rhizobium leguminosarum bv. viciae strains expressing different degrees of tolerance to metal stress were used in this work to study the basic mechanisms underlying heavy metal tolerance. We used various parameters to evaluate this response. The strains' growth responses under different Cd2+ concentrations were determined and we reported variation in Cd2+ tolerance. Total soluble protein content decreased drastically, revealing the toxic effects that intracellular Cd2+ imposes on cellular metabolism, but this decrease in protein content was particularly evident in sensitive and moderately tolerant strains. Tolerant strains presented the highest intracellular and wall-bound Cd2+ concentrations. Cd2+ induced increases in the expression of some specific proteins, which were identical in all tolerant strains. Glutathione levels remained unaltered in the sensitive strain and increased significantly in tolerant and moderately tolerant strains, suggesting the importance of glutathione in coping with metal stress. This work suggests that efflux mechanisms may not be the only system responsible for dealing with heavy metal tolerance. A clear correlation between glutathione levels and Cd2+ tolerance is reported, thus adding a novel aspect in bacteria protection against heavy metal deleterious effects. 相似文献
38.
Caamaño O Figueira MJ Fernández F García MD Nieto MI De Clercq E Balzarini J 《Nucleosides, nucleotides & nucleic acids》2001,20(4-7):1137-1139
New carbocyclic nucleosides with purine (compounds 3a and 3b), and 8-azapurine (compounds 3c and 3d) as base were prepared and assayed for in vitro activity. 相似文献
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Peripheral arterial disease (PAD) is a common, progressive manifestation of atherothrombotic vascular disease, which should be managed no different to cardiac disease. Indeed, there is growing evidence that PAD patients are a high risk group, although still relatively under-detected and under treated. This is despite the fact that PAD patients are an increased mortality rate comparable to those with pre-existing or established cardiovascular disease [myocardial infarction, stroke]. With a holistic approach to atherothrombotic vascular disease, our management of PAD can only get better. 相似文献