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91.
Griera R Cantos-Llopart C Amat M Bosch J del Castillo JC Huguet J 《Bioorganic & medicinal chemistry letters》2006,16(3):529-531
A synthetic route to a new structural type of potential antibacterials, with a hybrid 3-aryltetrahydroisoquinoline-6,7-diol/N-aryloxazolidinone structure, is reported. The synthesis involves the successive construction of the 3-aryltetrahydroisoquinoline and 4-substituted oxazolidinone moieties, the latter taking advantage of the functionalization at the para position of the aryl group. 相似文献
92.
Fourcade S Ruiz M Camps C Schlüter A Houten SM Mooyer PA Pàmpols T Dacremont G Wanders RJ Giròs M Pujol A 《American journal of physiology. Endocrinology and metabolism》2009,296(1):E211-E221
Peroxisomes are essential organelles exerting key functions in fatty acid metabolism such as the degradation of very long-chain fatty acids (VLCFAs). VLCFAs accumulate in X-adrenoleukodystrophy (X-ALD), a disease caused by deficiency of the Abcd1 peroxisomal transporter. Its closest homologue, Abcd2, exhibits a high degree of functional redundancy on the catabolism of VLCFA, being able to prevent X-ALD-related neurodegeneration in the mouse. In the search for specific roles of Abcd2, we screened fatty acid profiles in organs and primary neurons of mutant knockout mice lacking Abcd2 in basal conditions and under dietary challenges. Our results indicate that ABCD2 plays a role in the degradation of long-chain saturated and omega9-monounsaturated fatty acids and in the synthesis of docosahexanoic acid (DHA). Also, we demonstrated a defective VLCFA beta-oxidation ex vivo in brain slices of Abcd1 and Abcd2 knockouts, using radiolabeled hexacosanoic acid and the precursor of DHA as substrates. As DHA levels are inversely correlated with the incidence of Alzheimer's and several degenerative conditions, we suggest that ABCD2 may act as modulator/modifier gene and therapeutic target in rare and common human disorders. 相似文献
93.
Blanca M Herrera Helen E Lockstone Jennifer M Taylor Quin F Wills Pamela J Kaisaki Amy Barrett Carme Camps Christina Fernandez Jiannis Ragoussis Dominique Gauguier Mark I McCarthy Cecilia M Lindgren 《BMC medical genomics》2009,2(1):1-11
Background
The methods used for sample selection and processing can have a strong influence on the expression values obtained through microarray profiling. Laser capture microdissection (LCM) provides higher specificity in the selection of target cells compared to traditional bulk tissue selection methods, but at an increased processing cost. The benefit gained from the higher tissue specificity realized through LCM sampling is evaluated in this study through a comparison of microarray expression profiles obtained from same-samples using bulk and LCM processing.Methods
Expression data from ten lung adenocarcinoma samples and six adjacent normal samples were acquired using LCM and bulk sampling methods. Expression values were evaluated for correlation between sample processing methods, as well as for bias introduced by the additional linear amplification required for LCM sample profiling.Results
The direct comparison of expression values obtained from the bulk and LCM sampled datasets reveals a large number of probesets with significantly varied expression. Many of these variations were shown to be related to bias arising from the process of linear amplification, which is required for LCM sample preparation. A comparison of differentially expressed genes (cancer vs. normal) selected in the bulk and LCM datasets also showed substantial differences. There were more than twice as many down-regulated probesets identified in the LCM data than identified in the bulk data. Controlling for the previously identified amplification bias did not have a substantial impact on the differences identified in the differentially expressed probesets found in the bulk and LCM samples.Conclusion
LCM-coupled microarray expression profiling was shown to uniquely identify a large number of differentially expressed probesets not otherwise found using bulk tissue sampling. The information gain realized from the LCM sampling was limited to differential analysis, as the absolute expression values obtained for some probesets using this study's protocol were biased during the second round of amplification. Consequently, LCM may enable investigators to obtain additional information in microarray studies not easily found using bulk tissue samples, but it is of critical importance that potential amplification biases are controlled for. 相似文献94.
Carme Gabernet-Castello Joel B. Dacks Mark C. Field 《Traffic (Copenhagen, Denmark)》2009,10(7):894-911
Epsin N-terminal homology (ENTH) domains occur in proteins of either the epsin or epsin-related (epsinR) form. They principally function in clathrin-mediated trafficking and membrane deformation. Both epsin and epsinR possess clathrin-binding motifs, but only epsin incorporates a ubiquitin-interaction motif (UIM). To better understand the origins of ENTH-domain proteins and their functions, we performed detailed comparative genomics and phylogenetics on the epsin family. The epsin ENTH-UIM configuration is an architecture restricted to yeast and animals. Further, we undertook functional analysis in Trypanosoma brucei (T. brucei) , a divergent organism possessing a single ENTH-domain protein (TbEpsinR). TbEpsinR has a cellular location similar to both epsin and epsinR at plasma membrane clathrin budding sites and endosomal compartments, and associates with clathrin, as demonstrated by coimmunoprecipitation. Knockdown of TbEpsinR leads to a significant decrease in the intracellular pools of multiple surface antigens, without affecting bulk membrane internalization. Therefore, despite lacking the UIM, TbEpsinR maintains a similar role to metazoan epsin in endocytosis and participates as a clathrin-associated adaptor. We suggest that recruitment of a UIM to the ENTH-domain proteins was not essential for participation in endocytosis of ubiquitylated molecules, and is presumably a specific innovation restricted to higher eukaryotes. 相似文献
95.
MoDEL (Molecular Dynamics Extended Library): a database of atomistic molecular dynamics trajectories
Meyer T D'Abramo M Hospital A Rueda M Ferrer-Costa C Pérez A Carrillo O Camps J Fenollosa C Repchevsky D Gelpí JL Orozco M 《Structure (London, England : 1993)》2010,18(11):1399-1409
More than 1700 trajectories of proteins representative of monomeric soluble structures in the protein data bank (PDB) have been obtained by means of state-of-the-art atomistic molecular dynamics simulations in near-physiological conditions. The trajectories and analyses are stored in a large data warehouse, which can be queried for dynamic information on proteins, including interactions. Here, we describe the project and the structure and contents of our database, and provide examples of how it can be used to describe the global flexibility properties of proteins. Basic analyses and trajectories stripped of solvent molecules at a reduced resolution level are available from our web server. 相似文献
96.
Davinia Fernández-Espejo Carme Junque Damian Cruse Montserrat Bernabeu Teresa Roig-Rovira Neus Fábregas Eva Rivas Jose M Mercader 《BMC neurology》2010,10(1):77
Background
The rate of recovery from the vegetative state (VS) is low. Currently, little is known of the mechanisms and cerebral changes that accompany those relatively rare cases of good recovery. Here, we combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to study the evolution of one VS patient at one month post-ictus and again twelve months later when he had recovered consciousness. 相似文献97.
Carme Saurina Marc Saez Rafael Marcos-Gragera Maria Antònia Barceló Gemma Renart Carmen Martos 《Cancer epidemiology》2010,34(2):109-115
Objective: To assess the association between the incidence of larynx cancer and socioeconomic conditions in the province of Girona from a spatial viewpoint. Materials and methods: Incidence cases of larynx cancer (CL) in 1994–2004 were provided by the Girona Cancer Registry. A census tract (CT) was assigned to all patients. Socioeconomic data were extracted from the 2001 Census. A deprivation index for each CT was obtained by principal component analysis, using four socioeconomic indicators. The standardised incidence ratio (SIR) was calculated using the CL incidence rates in the men of the province of Girona assuming a Poisson distribution. Relative risk was obtained applying the Besag, York and Mollié model. The deprivation index was introduced into the model and was categorised in quartiles. Results: Four hundred and seventy-six incident cases in men were registered. CTs in the lowest deprivation index had a lower risk of larynx cancer, with a risk increase in the higher quartiles. In the highest quartile it was 1.91 times greater than in the lowest. This association was significant when the whole province was considered. Discussion: The deprivation index explains only part of the geographical variability of CL incidence. Other risk factors without spatial structure may contribute to this explaination. 相似文献
98.
Puig P Borrull F Aguilar C Calull M 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2006,831(1-2):196-204
We present a method for determining eight penicillin antibiotics using microemulsion electrokinetic chromatography (MEEKC). We studied how the composition of the microemulsion affected separation by modifying such parameters as the surfactant or the addition of organic solvents. The best microemulsion system consisted of 0.5% ethyl acetate, 1.2% 1-butanol, 2% Brij 35, 10% 2-butanol and 86.3% 10 mM borate buffer at pH 10. We studied the suitability of this microemulsion composition for analyzing a commercial drug. To improve the sensitivity of the method, we used the stacking technique reversed electrode polarity stacking mode (REPSM), which increased the detection limits by about 40-fold. 相似文献
99.
Agnati LF Ferré S Genedani S Leo G Guidolin D Filaferro M Carriba P Casadó V Lluis C Franco R Woods AS Fuxe K 《Journal of proteome research》2006,5(11):3077-3083
It has been suggested that L-DOPA-induced hyperhomocysteinemia can increase the risk of stroke, heart disease, and dementia and is an additional pathogenetic factor involved in the progression of Parkinson's disease. In Chinese hamster ovary (CHO) cells stably cotransfected with adenosine A(2A) and dopamine D2 receptors, homocysteine selectively decreased the ability of D2 receptor stimulation to internalize adenosine A(2A)-dopamine D2 receptor complexes. Radioligand-binding experiments in the same cell line demonstrated that homocysteine acts as an allosteric D2 receptor antagonist, by selectively reducing the affinity of D2 receptors for agonists but not for antagonists. Mass spectrometric analysis showed that, by means of an arginine (Arg)-thiol electrostatic interaction, homocysteine forms noncovalent complexes with the two Arg-rich epitopes of the third intracellular loop of the D2 receptor, one of them involved in A(2A)-D2 receptor heteromerization. However, homocysteine was unable to prevent or disrupt A(2A)-D2 receptor heteromerization, as demonstrated with Fluorescence Resonance Energy Transfer (FRET) experiments in stably cotransfected HEK cells. The present results could have implications for Parkinson's disease. 相似文献