N-acetyl-1-(p-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivative (PS3Ac) has been determined in brain tissues by high performance liquid chromatography (HPLC) coupled with a diode array detection. In a previous paper we presented a validation method for detecting PS3Ac and its metabolites in plasma samples after intraperitoneal administration to Wistar rats. In the present paper, we report the results of the determination of PS3Ac and its N-deacetyl (PS3) and O-demethyl (PS3OH) metabolites, in the brain after extraction based on a polymeric matrix with a high hydrophilic-lipophilic balance, using Oasis cartridges. The chromatographic separation was performed in an octadecylsilica stationary phase at 25 degrees C using a mixture of 10 mM potassium dihydrogen orthophosphate (pH 2.24) and acetonitrile in ratio of 30:70 (v/v) as mobile phase, with a flow rate of 0.8 ml/min. The method exhibited a large linear range from 0.05 to 2 microg/ml for all studied compounds (n=6). In the within-day assay (n=4), the accuracy ranged from 87.5% determined with 0.05 microg/ml of PS3 to 110.1% determined with 0.2 microg/ml of PS3OH. In the between-day assay the coefficient of variation ranged from 2.4 determined with 0.05 microg/ml of PS3 to 9.7 determined with 0.2 microg/ml of PS3OH. The extraction efficiency ranged from 77.8% for PS3OH at 0.2 microg/ml to 94.3 for PS3Ac at 0.5 microg/ml. The limit of detection for all the tetrahydroisoquinoline derivatives ranged around 50 ng/ml. The method proved to be highly sensitive and specific to determinate PS3Ac and its metabolites and has been successfully applied to value their concentrations in brain matrix over the time. 相似文献
The integrity of articular cartilage depends on the proper functioning and mechanical stimulation of chondrocytes, the cells
that synthesize extracellular matrix and maintain tissue health. The biosynthetic activity of chondrocytes is influenced by
genetic factors, environmental influences, extracellular matrix composition, and mechanical factors. The mechanical environment
of chondrocytes is believed to be an important determinant for joint health, and chondrocyte deformation in response to mechanical
loading is speculated to be an important regulator of metabolic activity. In previous studies of chondrocyte deformation,
articular cartilage was described as a biphasic material consisting of a homogeneous, isotropic, linearly elastic solid phase,
and an inviscid fluid phase. However, articular cartilage is known to be anisotropic and inhomogeneous across its depth. Therefore,
isotropic and homogeneous models cannot make appropriate predictions for tissue and cell stresses and strains. Here, we modelled
articular cartilage as a transversely isotropic, inhomogeneous (TI) material in which the anisotropy and inhomogeneity arose
naturally from the microstructure of the depth-dependent collagen fibril orientation and volumetric fraction, as well as the
chondrocyte shape and volumetric fraction. The purpose of this study was to analyse the deformation behaviour of chondrocytes
using the TI model of articular cartilage. In order to evaluate our model against experimental results, we simulated indentation
and unconfined compression tests for nominal compressions of 15%. Chondrocyte deformations were analysed as a function of
location within the tissue. The TI model predicted a non-uniform behaviour across tissue depth: in indentation testing, cell
height decreased by 43% in the superficial zone and between 11 and 29% in the deep zone. In unconfined compression testing,
cell height decreased by 32% in the superficial zone, 25% in the middle, and 18% in the deep zones. This predicted non-uniformity
is in agreement with experimental studies. The novelty of this study is the use of a cartilage material model accounting for
the intrinsic inhomogeneity and anisotropy of cartilage caused by its microstructure. 相似文献
Aquatic Ecology - Jellyfish blooms are an increasingly common event in our seas. Occurring via polyps’ asexual reproduction induced by human stresses, they represent a hazard for ecosystems... 相似文献
The genus Ctenomys includes a high number of taxa, with at least ten species from Patagonia and three recently described species for northeastern Chubut Province (Argentina). Ctenomys sociabilis is a social species of the genus Ctenomys and is currently distributed in the surrounding area of Sierra Cuyin Manzano (Neuquén Province), with a recently extinct population that occurred in Laguna Nahuelquir (Cushamen, Chubut Province). Molecular analyses have placed C. sociabilis at the base of Ctenomys clade, as the sister species to all other Ctenomys. Based on a morphological assessment (qualitative and quantitative) and DNA sequencing, we describe a new species of Ctenomys from Esquel, Chubut Province. Phylogenetic analysis shows the new species to be closely related to C. sociabilis, with evidence of solitary behavior. This new species is the first reported to be closely related phylogenetically to Ctenomys sociabilis at the base of the Ctenomys phylogeny. We provide anatomical comparisons between the new species and other species of Ctenomys from Patagonia, especially C. sociabilis.
Plant Cell, Tissue and Organ Culture (PCTOC) - In the original publication, only affiliation number 2 was indicated as the last author’s affiliation. In fact, the author works for both... 相似文献
Treadmilling protein filaments perform essential cellular functions by growing from one end while shrinking from the other, driven by nucleotide hydrolysis. Bacterial cell division relies on the primitive tubulin homolog FtsZ, a target for antibiotic discovery that assembles into single treadmilling filaments that hydrolyse GTP at an active site formed upon subunit association. We determined high-resolution filament structures of FtsZ from the pathogen Staphylococcus aureus in complex with different nucleotide analogs and cations, including mimetics of the ground and transition states of catalysis. Together with mutational and biochemical analyses, our structures reveal interactions made by the GTP γ-phosphate and Mg2+ at the subunit interface, a K+ ion stabilizing loop T7 for co-catalysis, new roles of key residues at the active site and a nearby crosstalk area, and rearrangements of a dynamic water shell bridging adjacent subunits upon GTP hydrolysis. We propose a mechanistic model that integrates nucleotide hydrolysis signaling with assembly-associated conformational changes and filament treadmilling. Equivalent assembly mechanisms may apply to more complex tubulin and actin cytomotive filaments that share analogous features with FtsZ.Bacterial cell division critically relies on the tubulin homolog FtsZ, which assembles into filaments that treadmill, fuelled by GTP hydrolysis. This structural and biochemical study of FtsZ from Staphylocuccus aureus reveals the mechanism of GTP hydrolysis and its connection with filament dynamics. 相似文献
Beta-N-oxalylamino-l-alanine (BOAA), a non-protein amino acid present in the seeds of Lathyrus Sativus (LS), is one of several neuroactive glutamate analogs reported to stimulate excitatory receptors and, in high concentrations, cause neuronal degeneration. In the present study, the in vivo acute effects of synthetic BOAA and LS seed extract were investigated on rat cerebellar cyclic GMP following intraperitoneal (10–100 mg/kg) or oral (100 mg/kg) administration of subconvulsive doses of toxin. Furthermore, the BOAA content in LS seeds and in the cerebellum of injected rats was determined by high performance liquid chromatograph analysis. A dose- and time-dependent increase of cerebellar cyclic guanosine monophosphate (cGMP) level was observed after intraperitoneal administration of synthetic BOAA or LS extract. The neurotoxin evoked a maximum stimulation 90 min after injection within the dose range of 50–75 mg/kg, elevating cGMP from basal levels of 5.3±0.5 pmol/mg protein to 15±1.3 pmol/mg protein. Similarly, the oral intake of LS-extracted neurotoxin resulted in the elevation of cGMP content. Kynurenic acid (300 mg/kg i.p.), a non specific excitatory amino acid antagonist, was effective in blocking LS BOAA-elicited cGMP enhancement. The data suggest that in the cerebellum acute administration of low concentrations of BOAA exert in vivo activation of glutamate receptors involved in the regulation of cGMP level. 相似文献