330 resultados para Koppinen, Jouko
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Kirjallisuusarvostelu
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Kirjallisuusarvostelu
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Kirjallisuusarvostelu
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Kirjallisuusarvostelu
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Monográfico con el título: 'Buenas prácticas docentes en la enseñanza universitaria'. Resumen basado en el de la publicación
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Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
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This study aims at the determination of a Fram Strait cyclone track and of the cyclone’s impact on ice edge, drift, divergence, and concentration. A 24 h period on 13–14 March 2002 framed by two RADARSAT images is analyzed. Data are included from autonomous ice buoys, a research vessel, Special Sensor Microwave Imager (SSM/I) and QuikSCAT satellite, and the operational European Centre for Medium-Range Weather Forecasts (ECMWF) model. During this 24 h period the cyclone moved northward along the western ice edge in the Fram Strait, crossed the northern ice edge, made a left-turn loop with 150 km diameter over the sea ice, and returned to the northern ice edge. The ECMWF analysis places the cyclone track 100 km too far west over the sea ice, a deviation which is too large for representative sea ice simulations. On the east side of the northward moving cyclone, the ice edge was pushed northward by 55 km because of strong winds. On the rear side, the ice edge advanced toward the open water but by a smaller distance because of weaker winds there. The ice drift pattern as calculated from the ice buoys and the two RADARSAT images is cyclonically curved around the center of the cyclone loop. Ice drift divergence shows a spatial pattern with divergence in the loop center and a zone of convergence around. Ice concentration changes as retrieved from SSM/I data follow the divergence pattern such that sea ice concentration increased in areas of divergence and decreased in areas of convergence.
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Abstract Background Many important toxins and antibiotics are produced by non-ribosomal biosynthetic pathways. Microcystins are a chemically diverse family of potent peptide toxins and the end-products of a hybrid NRPS and PKS secondary metabolic pathway. They are produced by a variety of cyanobacteria and are responsible for the poisoning of humans as well as the deaths of wild and domestic animals around the world. The chemical diversity of the microcystin family is attributed to a number of genetic events that have resulted in the diversification of the pathway for microcystin assembly. Results Here, we show that independent evolutionary events affecting the substrate specificity of the microcystin biosynthetic pathway have resulted in convergence on a rare [D-Leu1] microcystin-LR chemical variant. We detected this rare microcystin variant from strains of the distantly related genera Microcystis, Nostoc, and Phormidium. Phylogenetic analysis performed using sequences of the catalytic domains within the mcy gene cluster demonstrated a clear recombination pattern in the adenylation domain phylogenetic tree. We found evidence for conversion of the gene encoding the McyA2 adenylation domain in strains of the genera Nostoc and Phormidium. However, point mutations affecting the substrate-binding sequence motifs of the McyA2 adenylation domain were associated with the change in substrate specificity in two strains of Microcystis. In addition to the main [D-Leu1] microcystin-LR variant, these two strains produced a new microcystin that was identified as [Met1] microcystin-LR. Conclusions Phylogenetic analysis demonstrated that both point mutations and gene conversion result in functional mcy gene clusters that produce the same rare [D-Leu1] variant of microcystin in strains of the genera Microcystis, Nostoc, and Phormidium. Engineering pathways to produce recombinant non-ribosomal peptides could provide new natural products or increase the activity of known compounds. Our results suggest that the replacement of entire adenylation domains could be a more successful strategy to obtain higher specificity in the modification of the non-ribosomal peptides than point mutations.
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This study compares the frequencies of attempted suicide among immigrants and their hosts, between different immigrant groups, and between immigrants and their countries of origin.
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The associations between life events in the 12 months preceding an episode of self-poisoning resulting in hospital attendance (the index episode), and the suicide intent of this episode were compared in individuals for whom the index episode was their first, episode and in individuals in whom it was a recurrence of DSH. Results indicated a significant interaction between independent life events, repetition status, and gender in the prediction of suicide intent, the association between life events and intent being moderated by repetition status in women only. The results provide preliminary evidence to suggest the presence of a suicidal process in women, in which the impact of negative life events on suicide intent diminishes across episodes.
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Enterococcus faecium has emerged as an important cause of nosocomial infections over the last two decades. We recently demonstrated collagen type I (CI) as a common adherence target for some E. faecium isolates and a significant correlation was found to exist between acm-mediated CI adherence and clinical origin. Here, we evaluated 60 diverse E. faecium isolates for their adherence to up to 15 immobilized host extracellular matrix and serum components. Adherence phenotypes were most commonly observed to fibronectin (Fn) (20% of the 60 isolates), fibrinogen (17%) and laminin (Ln) (13%), while only one or two of the isolates adhered to collagen type V (CV), transferrin or lactoferrin and none to the other host components tested. Adherence to Fn and Ln was almost exclusively restricted to clinical isolates, especially the endocarditis-enriched nosocomial genogroup clonal complex 17 (CC17). Thus, the ability to adhere to Fn and Ln, in addition to CI, may have contributed to the emergence and adaptation of E. faecium, in particular CC17, as a nosocomial pathogen.
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We recently identified 15 genes encoding putative surface proteins with features of MSCRAMMs and/or pili in the Enterococcus faecium TX0016 (DO) genome, including four predicted pilus-encoding gene clusters; we also demonstrated that one of these, ebpABC(fm), is transcribed as an operon, that its putative major pilus subunit, EbpC(fm) (also called pilB), is polymerized into high molecular weight complexes, and that it is enriched among clinical E. faecium isolates. Here, we created a deletion of the ebpABC(fm) operon in an endocarditis-derived E. faecium strain (TX82) and showed, by a combination of whole-cell ELISA, flow cytometry, immunoblot and immunogold electron microscopy, that this deletion abolished EbpC(fm) expression and eliminated EbpC(fm)-containing pili from the cell surface. However, transcription of the downstream sortase, bps(fm), was not affected. Importantly, the ebpABC(fm) deletion resulted in significantly reduced biofilm formation (p < 0.0001) and initial adherence (p < 0.0001) versus the wild-type; both were restored by complementing ebpABC(fm) in trans, which also restored cell surface expression of EbpC(fm) and pilus production. Furthermore, the deletion mutant was significantly attenuated in two independent mixed infection mouse urinary tract experiments, i.e., outnumbered by the wild-type in kidneys (p = 0.0003 and < 0.0001, respectively) and urinary bladders (p = 0.0003 and = 0.002). In conclusion, we have shown that the ebpABC(fm) locus encodes pili on the E. faecium TX82 cell surface and provide the first evidence that pili of this emerging pathogen are important for its ability to form biofilm and to cause infection in an ascending UTI model.