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991.
992.
Silvana Galderisi Alessandro Rossi Paola Rocca Alessandro Bertolino Armida Mucci Paola Bucci Paola Rucci Dino Gibertoni Eugenio Aguglia Mario Amore Antonello Bellomo Massimo Biondi Roberto Brugnoli Liliana Dell'Osso Diana De Ronchi Gabriella Di Emidio Massimo Di Giannantonio Andrea Fagiolini Carlo Marchesi Palmiero Monteleone Lucio Oldani Federica Pinna Rita Roncone Emilio Sacchetti Paolo Santonastaso Alberto Siracusano Antonio Vita Patrizia Zeppegno Mario Maj Italian Network For Research on Psychoses 《World psychiatry》2014,13(3):275-287
In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real‐life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real‐life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness‐related variables, personal resources and context‐related factors. Some of these variables were never investigated before in relationship with real‐life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real‐life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real‐life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real‐life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real‐life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia. 相似文献
993.
Ruiz E Siow RC Bartlett SR Jenner AM Sato H Bannai S Mann GE 《Free radical biology & medicine》2003,34(1):103-110
Adaptive increases in intracellular glutathione (GSH) in response to oxidative stress are mediated by induction of L-cystine uptake via the anionic amino acid transport system x(c)(-). The recently cloned transporter xCT forms a heteromultimeric complex with the heavy chain of 4F2 cell surface antigen (4F2hc/CD98). Depletion of GSH by the electrophile diethylmaleate (DEM) induces the activity and expression of xCT in peritoneal macrophages. We here examine the effects of vitamin C on induction of xCT by DEM in human umbilical artery smooth muscle cells. DEM caused time- (3-24 h) and concentration- (25-100 microM) dependent increases in L-cystine transport, with GSH depleted by 50% after 6 h and restored to basal values after 24 h. xCT mRNA levels increased after 4 h DEM treatment with negligible changes detected for 4F2hc mRNA. DEM caused a rapid (5-30 min) phosphorylation of p38(MAPK). Inhibition of p38(MAPK) by SB203580 (10 microM) enhanced DEM-induced increases in L-cystine transport and GSH, whereas inhibition of p42/p44(MAPK) (PD98059, 10 microM) had no effect. Pretreatment of cells with vitamin C (100 microM, 24 h) attenuated DEM-induced adaptive increases in L-cystine transport and GSH levels. Inhibition of p38(MAPK), but not p42/p44(MAPK), reduced the cytoprotective action of vitamin C. Our findings suggest that DEM induces activation of xCT via intracellular signaling pathways involving p38(MAPK), and that vitamin C, in addition to its antioxidant properties, may modulate this signaling pathway to protect smooth muscle cells from injury. 相似文献
994.
Willoughby CA Rosauer KG Hale JJ Budhu RJ Mills SG Chapman KT MacCoss M Malkowitz L Springer MS Gould SL DeMartino JA Siciliano SJ Cascieri MA Carella A Carver G Holmes K Schleif WA Danzeisen R Hazuda D Kessler J Lineberger J Miller M Emini EA 《Bioorganic & medicinal chemistry letters》2003,13(3):427-431
A new class of 4-(aminoheterocycle)piperidine derived 1,3,4 trisubstituted pyrrolidine CCR5 antagonists is reported. Compound 4a is shown to have good binding affinity (1.8 nM) and antiviral activity in PBMC's (IC(95)=50 nM). Compound 4a also has improved PK properties relative to 1. 相似文献
995.
Duffy JL Rano TA Kevin NJ Chapman KT Schleif WA Olsen DB Stahlhut M Rutkowski CA Kuo LC Jin L Lin JH Emini EA Tata JR 《Bioorganic & medicinal chemistry letters》2003,13(15):2569-2572
A biaryl pyridylfuran P(3) substituent on the hydroxyethylene isostere scaffold affords HIV protease inhibitors (PI's) with picomolar (IC(50)) potency against the protease enzymes from PI-resistant HIV-1 strains. Inclusion of a gem-dimethyl substituent afforded compound 3 with 100% oral bioavailability (dogs) and more than double the t(1/2) of indinavir. Inhibition of multiple P450 isoforms is dependent on the regiochemistry of the pyridyl nitrogen in these compounds. 相似文献
996.
Encinas MV González-Nilo FD Andreu JM Alfonso C Cardemil E 《The international journal of biochemistry & cell biology》2002,34(6):645-656
ATP-dependent phosphoenolpyruvate (PEP) carboxykinases are found in plants and microorganisms, and catalyse the reversible formation of PEP, ADP, and CO(2) from oxaloacetate plus ATP. These enzymes vary in quaternary structure although there is significant sequence identity among the proteins isolated from different sources. To help understand the influence of quaternary structure in protein stability, the urea-induced unfolding of free- and substrate-bound tetrameric Saccharomyces cerevisiae PEP carboxykinase is described and compared with the unfolding characteristics of the monomeric Escherichia coli enzyme [Eur. J. Biochem. 255 (1998) 439]. The urea-induced denaturation of S. cerevisiae PEP carboxykinase was studied by monitoring the enzyme activity, intrinsic protein fluorescence, circular dichroism (CD) spectra, and 1-anilino-8-naphthalenesulfonate (ANS) binding. The unfolding profiles were multi-steps, and formation of hydrophobic structures were detected. The data indicate that unfolding and dissociation of the enzyme tetramer are simultaneous events. Ligand binding, most notably PEP in the presence of MnCl(2), conferred a marked protection against urea-induced denaturation. A similar protection effect was found when N-iodoacetyl-N'-(5-sulfo-1-napthyl)ethylene diamine (1,5-I-AEDANS) was covalently bound at Cys(365), within the active site region. Refolding experiments indicated that total recovery of tertiary structure was only obtained from samples previously unfolded to less than 30%. In the presence of substrates, complete refolding was achieved from samples originally denatured up to 50%. The unfolding behaviour of S. cerevisiae PEP carboxykinase was found to be similar to that of E. coli PEP carboxykinase, however all steps take place at lower urea concentrations. These findings show that, at least for monomeric and tetrameric ATP-dependent PEP carboxykinases, quaternary structure does not contribute to protein conformational stability. 相似文献
997.
Comparative genomics is an essential tool to unravel how genomes change over evolutionary time and to gain clues on the links between functional genomics and evolution. In prokaryotes, the large, good quality, genome sequences available in public databases and the recently developed large-scale computational methods, offer an unprecedent view on the ecology and evolution of microorganisms through comparative genomics. In this work, we examined the links among genome structure (i.e., the sequential distribution of nucleotides itself by detrended fluctuation analysis, DFA) and genomic diversity (i.e., gene functionality by Clusters of Orthologous Genes, COGs) in 828 full sequenced prokaryotic genomes from 548 different bacteria and archaea species. DFA scaling exponent α indicated persistent long-range correlations (fractality) in each genome analyzed. Higher resolution power was found when considering the sequential succession of purine (AG) vs. pyrimidine (CT) bases than either keto (GT) to amino (AC) forms or strongly (GC) vs. weakly (AT) bonded nucleotides. Interestingly, the phyla Aquificae, Fusobacteria, Dictyoglomi, Nitrospirae, and Thermotogae were closer to archaea than to their bacterial counterparts. A strong significant correlation was found between scaling exponent α and COGs distribution, and we consistently observed that the larger α the more heterogeneous was the gene distribution within each functional category, suggesting a close relationship between primary nucleotides sequence structure and functional genes composition. 相似文献
998.
The presence of the antimicrobial peptide (AMP) biosynthetic genes srfAA (surfactin), bacA (bacylisin), fenD (fengycin), bmyB (bacyllomicin), spaS (subtilin), and ituC (iturin) was examined in 184 isolates of Bacillus spp. obtained from plant environments (aerial, rhizosphere, soil) in the Mediterranean land area of Spain. Most strains had between two and four AMP genes whereas strains with five genes were seldom detected and none of the strains had six genes. The most frequent AMP gene markers were srfAA, bacA, bmyB, and fenD, and the most frequent genotypes srfAA-bacA-bmyB and srfAAbacA- bmyB-fenD. The dominance of these particular genes in Bacillus strains associated with plants reinforces the competitive role of surfactin, bacyllomicin, fengycin, and bacilysin in the fitness of strains in natural environments. The use of these AMP gene markers may assist in the selection of putative biological control agents of plant pathogens. 相似文献
999.
Ignacio Barrasa J Olmo N Pérez-Ramos P Santiago-Gómez A Lecona E Turnay J Antonia Lizarbe M 《Apoptosis : an international journal on programmed cell death》2011,16(10):1054-1067
The continuous exposure of the colonic epithelium to high concentrations of bile acids may exert cytotoxic effects and has
been related to pathogenesis of colon cancer. A better knowledge of the mechanisms by which bile acids induce toxicity is
still required and may be useful for the development of new therapeutic strategies. We have studied the effect of deoxycholic
acid (DCA) and chenodeoxycholic acid (CDCA) treatments in BCS-TC2 human colon adenocarcinoma cells. Both bile acids promote
cell death, being this effect higher for CDCA. Apoptosis is detected after 30 min–2 h of treatment, as observed by cell detachment,
loss of membrane asymmetry, internucleosomal DNA degradation, appearance of mitochondrial transition permeability (MPT), and
caspase and Bax activation. At longer treatment times, apoptosis is followed in vitro by secondary necrosis due to impaired
mitochondrial activity and ATP depletion. Bile acid-induced apoptosis is a result of oxidative stress with increased ROS generation
mainly by activation of plasma membrane enzymes, such as NAD(P)H oxidases and, to a lower extent, PLA2. These effects lead to a loss of mitochondrial potential and release of pro-apoptotic factors to the cytosol, which is confirmed
by activation of caspase-9 and -3, but not caspase-8. This initial apoptotic steps promote cleavage of Bcl-2, allowing Bax
activation and formation of additional pores in the mitochondrial membrane that amplify the apoptotic signal. 相似文献
1000.
Luca Pietro Casacci Magdalena Witek Francesca Barbero Dario Patricelli Gaetano Solazzo Emilio Balletto Simona Bonelli 《Journal of Insect Conservation》2011,15(1-2):103-110
Projections of climate-change scenarios indicate that many Maculinea arion populations will disappear from Europe over the next 50 years. Extinctions will be particularly concentrated around the southern limits of the species?? range, such as the Italian peninsula, except mountain populations, mainly in the Alps. M. arion is a social parasite of Myrmica ants and its survival depends on the presence and abundance of two resources, i.e. (1) a specific larval foodplant and (2) a suitable Myrmica host ant. We collected data on Thymus plants distribution, Myrmica ants abundance, turf height around Myrmica nests, distance between nests and the closest thyme plant (Thymus pulegioides), and vegetation structure at 14 patches of a M. arion fragmented population occurring in the Western Italian Alps (Val Ferret: Aosta). We found that patches with the highest abundance of M. arion had significantly higher foodplant abundance. Among 407 nests belonging to nine Myrmica species, we found M. arion larvae in one Myrmica lonae and in two Myrmica sulcinodis nests. The distribution of M. sulcinodis nests showed the best spatial overlap with Thymus plants. M. sulcinodis was also significantly more abundant on pastures showing high M. arion density, and therefore offered higher adoption probabilities to develop butterfly larvae. On M. arion habitat patches, the mean turf height around Myrmica nests varied from 10.5 to 22.3 cm and best matched the habitat requirements of T. pulegioides. Thus, we suggest that extensive grazing is needed to maintain the two most important resources for M. arion. Moreover, patches where M. arion was abundant included more numerous plant species characteristic of these mountain pastures, as well as higher plant diversity (Shannon index). As a consequence, M. arion represents an umbrella species and a good indicator for the conservation status of mountain grasslands. 相似文献