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991.
992.
993.
Fernando G. Osorio Álvaro J. Obaya Carlos López-Otín José M. P. Freije 《Transgenic research》2009,18(1):7-15
Ageing research benefits from the study of accelerated ageing syndromes such as Hutchinson-Gilford progeria syndrome (HGPS),
characterized by the early appearance of symptoms normally associated with advanced age. Most HGPS cases are caused by a mutation
in the gene LMNA, which leads to the synthesis of a truncated precursor of lamin A known as progerin that lacks the target sequence for the
metallopotease FACE-1/ZMPSTE24 and remains constitutively farnesylated. The use of Face-1/Zmpste24-deficient mice allowed
us to demonstrate that accumulation of farnesylated prelamin A causes severe abnormalities of the nuclear envelope, hyper-activation
of p53 signalling, cellular senescence, stem cell dysfunction and the development of a progeroid phenotype. The reduction
of prenylated prelamin A levels in genetically modified mice leads to a complete reversal of the progeroid phenotype, suggesting
that inhibition of protein farnesylation could represent a therapeutic option for the treatment of progeria. However, we found
that both prelamin A and its truncated form progerin can undergo either farnesylation or geranylgeranylation, revealing the
need of targeting both activities for an efficient treatment of HGPS. Using Face-1/Zmpste24-deficient mice as model, we found that a combination of statins and aminobisphosphonates inhibits both types of modifications
of prelamin A and progerin, improves the ageing-like symptoms of these mice and extends substantially their longevity, opening
a new therapeutic possibility for human progeroid syndromes associated with nuclear-envelope defects. We discuss here the
use of this and other animal models to investigate the molecular mechanisms underlying accelerated ageing and to test strategies
for its treatment. 相似文献
994.
Antonio Rodríguez-García Alberto Sola-Landa Kristian Apel Fernando Santos-Beneit Juan F. Martín 《Nucleic acids research》2009,37(10):3230-3242
Bacterial growth requires equilibrated concentration of C, N and P sources. This work shows a phosphate control over the nitrogen metabolism in the model actinomycete Streptomyces coelicolor. Phosphate control of metabolism in Streptomyces is exerted by the two component system PhoR-PhoP. The response regulator PhoP binds to well-known PHO boxes composed of direct repeat units (DRus). PhoP binds to the glnR promoter, encoding the major nitrogen regulator as shown by EMSA studies, but not to the glnRII promoter under identical experimental conditions. PhoP also binds to the promoters of glnA and glnII encoding two glutamine synthetases, and to the promoter of the amtB-glnK-glnD operon, encoding an ammonium transporter and two putative nitrogen sensing/regulatory proteins. Footprinting analyses revealed that the PhoP-binding sequence overlaps the GlnR boxes in both glnA and glnII. ‘Information theory’ quantitative analyses of base conservation allowed us to establish the structure of the PhoP-binding regions in the glnR, glnA, glnII and amtB genes. Expression studies using luxAB as reporter showed that PhoP represses the above mentioned nitrogen metabolism genes. A mutant deleted in PhoP showed increased expression of the nitrogen metabolism genes. The possible conservation of phosphate control over nitrogen metabolism in other microorganisms is discussed. 相似文献
995.
Fernando J. Durn Valeria C. Edelsztein Alberto A. Ghini Mariana Rey Hctor Coirini Philippe Dauban Robert H. Dodd Gerardo Burton 《Bioorganic & medicinal chemistry》2009,17(18):6526-6533
The synthesis of new analogues of allopregnanolone with a bridged sulfamidate ring over the β-face of ring A has been achieved from easily available precursors, using an intramolecular aziridination strategy. The methodology also allows the synthesis of 3α-substituted analogues such as the 3α-fluoro derivative. GABAA receptor activity of the synthetic analogues was evaluated by assaying their effect on the binding of [3H]flunitrazepam and [3H]muscimol. The 3α-hydroxy-2,19-sulfamoyl analogue and its N-benzyl derivative were more active than allopregnanolone for stimulating binding of [3H]flunitrazepam. For the binding of [3H]muscimol, both synthetic analogues and allopregnanolone stimulated binding to a similar extent, with the N-benzyl derivative exhibiting a higher EC50. The 3α-fluoro derivative was inactive in both assays. 相似文献
996.
Lucas M. Aguiar Gabriela Ludwig Fernando C. Passos 《Primates; journal of primatology》2009,50(1):74-77
In social mammals, group size, sex and age-class composition are important parameters that are required to understand population
dynamics and determine conservation strategies. These parameters are known only poorly for the black-and-gold howler monkey
(Alouatta caraya). Here, we studied groups of A. caraya on islands and adjacent banks of the Upper Paraná River of southern Brazil, to examine variability in group size and composition.
This location is important for this species because of the high density of howlers. Group size was large, varying from 6 to
18 individuals (average = 11.5, standard deviation = 3.3, n = 13). Groups were multi-male, and adult females outnumbered adult males. On average, groups had the following ratios: 1
adult male: 0.5 subadult male: 1.9 adult females: 0.9 juveniles: 0.5 infants. The ratio of 0.2 infant: 1 adult female is less
than that in other species, but typical of other studies of the black-and-gold howlers. Here, we discuss environmental and
social pressures that may impose structure on large groups of howlers in terms of strategies for living in high densities.
We also compare these data with those of the area of sympatry shared between A. caraya and A. clamitans, and suggest that competition may occur between the two species and that reduced fitness may be a consequence of mixed groups.
Contribution number 1,746 of the Departamento de Zoologia of Universidade Federal do Paraná (UFPR). 相似文献
997.
Researchers have often assumed that scent marking serves a territorial function in callitrichines, although some controversy
exists. To fulfill such a function, scent marks should 1) prevent intrusions, 2) ensure access to feeding resources, 3) enable
avoidance of intergroup encounters, or 4) play an important role in the aggressive encounters between groups. We studied 13
saddleback tamarins (Saguinus fuscicollis) belonging to 3 free-ranging groups, which formed mixed-species troops with moustached tamarins (S. mystax) in the Amazonian rain forest of Peru. None of the predictions were confirmed. The tamarins used a border-marking strategy,
marking more on the periphery of their territory. However, feeding trees in overlap and encounter areas received more scent
marking but were still visited by neighboring groups. Intergroup encounters occurred more often than expected, and scent-marking
frequency was not higher during them than when no other group was present. It appears that instead of defending a territory
in the classic sense, the tamarins are optimizing signal transmission by depositing their scents where the probability of
detection by neighbors is higher. Saddleback tamarins may use shared areas of their home ranges to exchange information with
neighboring groups, perhaps regarding reproductive opportunities. 相似文献
998.
Achondroplasia, the most common type of dwarfism, is characterized by a mutation in the fibroblast growth factor receptor
3 (FGFR3). Achondroplasia is an orphan pathology with no pharmacological treatment so far. However, the possibility of using
the dinucleotide diadenosine tetraphosphate (Ap4A) with therapeutic purposes in achondroplasia has been previously suggested. The pathogenesis involves the constitutive activation
of FGFR3, resulting in altered biochemical and physiological processes in chondrocytes. Some of these altered processes can
be influenced by changes in cell volume and ionic currents. In this study, the action of mutant FGFR3 on chondrocyte size
and chloride flux in achondroplastic chondrocytes was investigated as well as the effect of the Ap4A on these processes triggered by mutant FGFR3. Stimulation with the fibroblast growth factor 9 (FGF9), the preferred ligand
for FGFR3, induced an enlarged achondroplastic chondrocyte size and an increase in the intracellular chloride concentration,
suggesting the blockade of chloride efflux. Treatment with the Ap4A reversed the morphological changes triggered by FGF9 and restored the chloride efflux. These data provide further evidence
for the therapeutic potential of this dinucleotide in achondroplasia treatment. 相似文献
999.
Luís Fernando Parizi Kiyoko Uemura Utiumi Saiki Imamura Misao Onuma Kazuhiko Ohashi Aoi Masuda Itabajara da Silva Vaz Jr. 《Experimental parasitology》2011,(1):113-118
Recombinant Glutathione S-transferase of Haemaphysalis longicornis (rGST-Hl) was expressed in Escherichia coli, purified by affinity chromatography and used in the immunization of cattle. Western blot analysis showed positive antibody response in cattle immunized with rGST-Hl. The tests also showed that immunized bovine sera recognize native Rhipicephalus microplus proteins in different tissue extracts. Furthermore, the vaccine potential of rGST-Hl was investigated against infestation of Hereford cattle by R. microplus. Vaccination of cattle with rGST-Hl conferred partial cross-protection immunity against R. microplus. Considering the effect on number of engorged ticks, egg laying capacity and egg fertility, the overall efficacy of vaccination was of 57%, as compared with control group. 相似文献
1000.
Alponti RF Zambotti-Villela L Murena-Nunes C Marinho CE do Amaral Olivo R Silveira PF 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2005,141(3):336-352
The relationship between plasma osmolality and cystyl aminopeptidase was characterized in the snake Bothrops jararaca and comparisons were made with the emerging picture of this relationship in rats. The profile of cystyl aminopeptidase activity under basal conditions was determined in the soluble and membrane-bound forms in visceral organs and in the central nervous system in comparison with that of alanyl aminopeptidase. The regional localization of cystyl and alanyl aminopeptidase activities was studied in the central nervous system. The basal level of plasma cystyl aminopeptidase, four- to six-fold higher than in rats, suggests its importance to help regulate circulating levels of neurohypophysial peptides in B. jararaca snake. The osmotic sensitivity of this plasma enzyme, undetectable in male, but about three-fold higher in female snakes than in rats, reveals a sexual dimorphism. In marked contrast to those observed in rats, low levels of soluble and particulate forms in the kidney indicate that cystyl aminopeptidase plays a minor metabolizing role at this anatomical location in B. jararaca. Despite of the regional-specific divergence between the levels of rat and snake enzymes, the bilaterally symmetric pattern of the diencephalic distribution of alanyl aminopeptidase reflects functional homologies between these two distantly related species. 相似文献