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91.
Delgado A Casas J Llebaria A Abad JL Fabrias G 《Biochimica et biophysica acta》2006,1758(12):1957-1977
Sphingolipids are a family of lipids that play essential roles both as structural cell membrane components and in cell signalling. The cellular contents of the various sphingolipid species are controlled by enzymes involved in their metabolic pathways. In this context, the discovery of small chemical entities able to modify these enzyme activities in a potent and selective way should offer new pharmacological tools and therapeutic agents. 相似文献
92.
Sphingolipids are a family of lipids that play essential roles both as structural cell membrane components and in cell signalling. The cellular contents of the various sphingolipid species are controlled by enzymes involved in their metabolic pathways. In this context, the discovery of small chemical entities able to modify these enzyme activities in a potent and selective way should offer new pharmacological tools and therapeutic agents. 相似文献
93.
The crystalline structure of polyester 6 6 was studied by means of X-ray and electron diffraction and real-space electron microscopy. An orthorhombic unit cell containing eight chain segments with a quasi planar zigzag conformation was derived. The chain axis projection could be defined by a small rectangular cell containing only two molecular segments. Simulation of electron diffraction patterns indicates that molecular segments were arranged with azimuthal angles close to +/-46 degrees . X-ray diffraction patterns suggested that the large dimensions of the unit cell were a consequence of a slight shift between neighboring chains that improved the electrostatic interactions. Chain-folded lamellar crystals were obtained by isothermal crystallization of dilute n-hexanol or n-octanol solutions. The crystalline habit was studied, and the influence of temperature was evaluated. A regular folding surface was observed by using polyethylene decoration techniques. Lamellar crystals were easily degraded with different lipases. A preferential enzymatic attack was, in some cases, observed to occur in the crystal edges, giving rise to highly irregular borders with a fringed texture. 相似文献
94.
Tomás de Las Casas Engel Esther M. Sánchez‐carnerero Ekaterina Sokolovskaya Claudio M. Gallardo‐araya Florencio Moreno JimÉnez Beatriz Lora Maroto Santiago de la Moya Cerero 《Chirality》2012,24(10):771-777
Polystyrene grafted with a chiral zinc‐complexing camphor‐derived N,N‐disubstituted hydroxyamide is proposed as a new type of functional polymer of high reusability for the development of sustainable organozinc‐catalyzed asymmetric reactions. The main goal of this new functional polymer is the ease of the hydroxyamide‐moiety preparation (cheap chiral ligand obtained straightforwardly from an enantiopure starting material coming from the chiral pool), as well as its chemical robustness when compared with other related zinc‐complexing functional groups. The latter allows the polymer to be active after multiple applications, without significant loss of its catalytic activity. This fact is exemplified by the design and preparation of a polymer functionalized with a bis(hydroxyamide) proved previously as active in the homogeneous enantioselective addition of diethylzinc to aldehydes. The result is a cheap functional polymer with a very high reusability (the enantioselectivity and chemical yield are maintained practically constant after 20 applications). Additionally, a methodology for the multicycle use of these functional polymers is presented. Chirality, 2012. © 2012 Wiley Periodicals, Inc. 相似文献
95.
DJ López M Egido-Gabas I López-Montero JV Busto J Casas M Garnier F Monroy B Larijani FM Goñi A Alonso 《Biophysical journal》2012,102(9):2077-2085
We propose that accumulated membrane bending energy elicits a neutral sphingomyelinase (SMase) activity in human erythrocytes. Membrane bending was achieved by osmotic or chemical processes, and SMase activity was assessed by quantitative thin-layer chromatography, high-performance liquid chromatography, and electrospray ionization-mass spectrometry. The activity induced by hypotonic stress in erythrocyte membranes had the pH dependence, ion dependence, and inhibitor sensitivity of mammalian neutral SMases. The activity caused a decrease in SM contents, with a minimum at 6 min after onset of the hypotonic conditions, and then the SM contents were recovered. We also elicited SMase activity by adding lysophosphatidylcholine externally or by generating it with phospholipase A(2). The same effect was observed upon addition of chlorpromazine or sodium deoxycholate at concentrations below the critical micellar concentration, and even under hypertonic conditions. A unifying factor of the various agents that elicit this SMase activity is the accumulated membrane bending energy. Both hypo-and hypertonic conditions impose an increased curvature, whereas the addition of surfactants or phospholipase A(2) activation increases the outer monolayer area, thus leading to an increased bending energy. The fact that this latent SMase activity is tightly coupled to the membrane bending properties suggests that it may be related to the general phenomenon of stress-induced ceramide synthesis and apoptosis. 相似文献
96.
Chaparro-Riggers J Liang H DeVay RM Bai L Sutton JE Chen W Geng T Lindquist K Casas MG Boustany LM Brown CL Chabot J Gomes B Garzone P Rossi A Strop P Shelton D Pons J Rajpal A 《The Journal of biological chemistry》2012,287(14):11090-11097
Target-mediated clearance and high antigen load can hamper the efficacy and dosage of many antibodies. We show for the first time that the mouse, cynomolgus, and human cross-reactive, antagonistic anti-proprotein convertase substilisin kexin type 9 (PCSK9) antibodies J10 and the affinity-matured and humanized J16 exhibit target-mediated clearance, resulting in dose-dependent pharmacokinetic profiles. These antibodies prevent the degradation of low density lipoprotein receptor, thus lowering serum levels of LDL-cholesterol and potently reducing serum cholesterol in mice, and selectively reduce LDL-cholesterol in cynomolgus monkeys. In order to increase the pharmacokinetic and efficacy of this promising therapeutic for hypercholesterolemia, we engineered pH-sensitive binding to mouse, cynomolgus, and human PCSK9 into J16, resulting in J17. This antibody shows prolonged half-life and increased duration of cholesterol lowering in two species in vivo by binding to endogenous PCSK9 in mice and cynomolgus monkeys, respectively. The proposed mechanism of this pH-sensitive antibody is that it binds with high affinity to PCSK9 in the plasma at pH 7.4, whereas the antibody-antigen complex dissociates at the endosomal pH of 5.5-6.0 in order to escape from target-mediated degradation. Additionally, this enables the antibody to bind to another PCSK9 and therefore increase the antigen-binding cycles. Furthermore, we show that this effect is dependent on the neonatal Fc receptor, which rescues the dissociated antibody in the endosome from degradation. Engineered pH-sensitive antibodies may enable less frequent or lower dosing of antibodies hampered by target-mediated clearance and high antigen load. 相似文献
97.
Reina E Camacho L Casas J Van Veldhoven PP Fabrias G 《Chemistry and physics of lipids》2012,165(2):225-231
Sphingosine-1-phosphate lyase (SGPL1) is the last enzyme in the catabolism of sphingolipids. It catalyzes the retroaldolic cleavage of long chain base phosphates into phosphoethanolamine and a fatty aldehyde. In this article we report on an easy and sensitive procedure to determine SPL activity. The assays uses C17-sphinganine-1-phosphate as substrate and the aldehyde product, pentadecanal, is quantified as its pentafluorobenzyloxime derivative by GC/MS. Derivatization of pentadecanal is performed as a one-step reaction, and the oxime product is directly injected for GC/MS analysis without any further purification. Acquisition in selected ion monitoring mode allows very high sensitivity, with a limit of detection of 281fmol. The assay is linear with both protein concentration and incubation time up to 20μg and 40min, respectively. The K(m) value obtained (6μM) is similar to that for the natural substrate sphingosine-1-phosphate. Using this method, FTY720 and deoxypyridoxine phosphate inhibited SPL with similar potencies to those reported. 相似文献
98.
99.
Corominas M Ramos-Quiroga JA Ferrer M Sáez-Francàs N Palomar G Bosch R Casas M 《Attention deficit and hyperactivity disorders》2012,4(2):63-75
Attention deficit hyperactivity disorder (ADHD) is a heterogeneous disease whose neurobiological background is not completely
understood. It has been proposed that deficits of the inhibitory function with an underactive behavioral inhibition system
(BIS) may be in the core of ADHD. In this regard, this review summarizes all studies that examine the involvement of cortisol
in ADHD. Differences in cortisol responses from different ADHD subtypes, hyperactive/impulsive, inattentive, and combined,
are analyzed. In addition, we examine the role of comorbidities as confounding factors in the study of cortisol in ADHD, including
comorbid disruptive behavioral disorder (DBD), as well as anxiety and depressive disorders. Because ADHD is a neurodevelopmental
condition and approximately half of the children enter adulthood with the disorder, we review cortisol studies in adults and
children separately. Two diverse patterns of cortisol have been reported both in children and adults with ADHD. Blunted cortisol
responses to stress are associated with comorbid DBD, whereas high cortisol responses are associated to comorbid anxiety disorders.
Nevertheless, the inhibitory deficits in ADHD do not appear to be related directly to cortisol deficits in either children
or adults. This review increases our understanding of the heterogeneity of ADHD and could help in determining new strategies
for the treatment of these patients. Future studies including gender and a more systematic methodology to study the cortisol
response are needed. 相似文献
100.
F. Casas F. Mougeot I. Sánchez-Barbudo J. A. Dávila J. Vi?uela 《Biological invasions》2012,14(2):295-305
Hybridization is a widespread phenomenon, which plays crucial roles in the speciation of living beings. However, unnatural
mixing of historically isolated taxa due to human-related activities has increased in recent decades, favouring levels of
hybridization and introgression that can have important implications for conservation. The wild red-legged partridge (Alectoris rufa, Phasianidae) populations have recently declined and the releases of farm-reared partridges have become a widespread management
strategy. The native range of the red-legged is limited to the south-west of Europe (from Italy to Portugal). This species
does not breed in sympatry with the chukar partridge (A. chukar), whose range is Eurasian (from Turkey to China). However, red-legged partridges have often been hybridized with chukar partridges
to increase the productivity of farmed birds, and game releases may have spread hybrid birds into the wild. In this study,
we investigated the fitness (survival and breeding) differences between hybrid and “pure” red-legged partridges in a wild
population located in central Spain. Incubation probability was similar in hybrids and “pure” partridges. Hybrid females laid
larger clutches than “pure” ones, but hatching success did not differ between hybrid and “pure” partridges. Hybrid birds had
lower survival rate than “pure” ones, mainly because of higher predation rates. Our results show that, despite lower survival,
hybrid partridges breed in natural populations, so this could increase extinction risk of wild pure partridge populations,
through releases of farmed hybrid birds. The consequences of continued releases could be of vital importance for the long
term conservation of wild red-legged partridges. 相似文献