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51.
Mice have proved to be powerful models for understanding obesity in humans and farm animals. Single-gene mutants and genetically modified mice have been used successfully to discover genes and pathways that can regulate body weight. For polygenic obesity, the most common pattern of inheritance, many quantitative trait loci (QTLs) have been mapped in crosses between selected and inbred mouse lines. Most QTL effects are additive, and diet, age and gender modify the genetic effects. Congenic, recombinant inbred, advanced intercross, and chromosome substitution strains are needed to map QTLs finely, to identify the genes underlying the traits, and to examine interactions between them. 相似文献
52.
Teplova M Wilds CJ Wawrzak Z Tereshko V Du Q Carrasco N Huang Z Egli M 《Biochimie》2002,84(9):849-858
Selenium was incorporated into an oligodeoxynucleotide in the form of 2'-methylseleno-uridine (U(Se)). The X-ray crystal structure of the duplex left open bracket d(GCGTA)U(Se)d(ACGC) right open bracket (2) was determined by the multiwavelength anomalous dispersion (MAD) technique and refined to a resolution of 1.3 A, demonstrating that selenium can selectively substitute oxygen in DNA and that the resulting compounds are chemically stable. Since derivatization at the 2'-alpha-position with selenium does not affect the preference of the sugar for the C3'-endo conformation, this strategy is suitable for incorporating selenium into RNA. The availability of selenium-containing nucleic acids for crystallographic phasing offers an attractive alternative to the commonly used halogenated pyrimidines. 相似文献
53.
The human MDR1 (ABCB1) gene product, P-glycoprotein (Pgp), functions as an ATP-dependent efflux pump for a variety of chemotherapeutic drugs. In this study, we assessed the role of conserved glutamate residues in the Walker B domain of the two ATP sites (E556 and E1201, respectively) during the catalytic cycle of human Pgp. The mutant Pgps (E556Q, E556A, E1201Q, E1201A, E556/1201Q, and E556/1201A) were characterized using a vaccinia virus based expression system. Although steady-state ATP hydrolysis and drug transport activities were abrogated in both E556Q and E1201Q mutant Pgps, [alpha-(32)P]-8-azidoADP was trapped in the presence of vanadate (Vi), and the release of trapped [alpha-(32)P]-8-azidoADP occurred to a similar extent as in wild-type Pgp. This indicates that these mutations do not affect either the first hydrolysis event or the ADP release step. Similar results were also obtained when Glu residues were replaced with Ala (E556A and E1201A). Following the first hydrolysis event and release of [alpha-(32)P]-8-azidoADP, both E556Q and E1201Q mutant Pgps failed to undergo another cycle of Vi-induced [alpha-(32)P]-8-azidoADP trapping. Interestingly, the double mutants E556/1201Q and E556/1201A trapped [alpha-(32)P]-8-azidoADP even in the absence of Vi, and the occluded nucleotide was not released after incubation at 37 degrees C for an extended period. In addition, the properties of transition state conformation of the double mutants generated in the absence of Vi were found to be similar to that of the wild-type protein trapped in the presence of Vi (Pgp x [alpha-(32)P]-8-azidoADP xVi). Thus, in contrast to the single mutants, the double mutants appear to be defective in the ADP release step. In aggregate, these data suggest that E556 and E1201 residues in the Walker B domains may not be critical as catalytic carboxylates for the cleavage of the bond between the gamma-P and the beta-P of ATP during hydrolysis but are essential for the second ATP hydrolysis step and completion of the catalytic cycle. 相似文献
54.
Newkirk MM Goldbach-Mansky R Lee J Hoxworth J McCoy A Yarboro C Klippel J El-Gabalawy HS 《Arthritis research & therapy》2003,5(2):R82-R90
Advanced glycation end-product (AGE)-damaged IgG occurs as a result of hyperglycemia and/or oxidative stress. Autoantibodies
to IgG-AGE were previously demonstrated in patients with severe, longstanding rheumatoid arthritis (RA). We investigated whether
IgG-AGE and anti-IgG-AGE antibodies were present early in the course of RA and other inflammatory arthropathies. We prospectively
followed a cohort of 238 patients with inflammatory arthritis of duration less than 1 year. Patients were evaluated clinically
and serologically, and radiographs were obtained at initial and 1-year visits. Sera were assayed for IgG-AGE and anti-IgG-AGE
antibodies by enzyme-linked immunosorbent assay (ELISA). Rheumatoid factor (RF) was determined by nephelometry and ELISA.
Of all patients, 29% had RF-positive RA, 15% had RF-negative RA, 18% had spondyloarthropathy, and 38% had undifferentiated
arthritis. IgG-AGE was present in 19% of patients, and was similar in amount and frequency in all groups. Patients with elevated
IgG-AGE levels had significantly higher levels of the inflammatory markers C-reactive protein and erythrocyte sedimentation
rate, but there was no correlation with blood glucose levels. Overall, 27% of the patients had IgM anti-IgG-AGE antibodies.
These antibodies were highly significantly associated with RFs (P < 0.0001) and with swollen joint count (P < 0.01). In early onset arthritis, IgG damaged by AGE was detected in all patient groups. The ability to make IgM anti-IgG-AGE
antibodies, however, was restricted to a subset of RF-positive RA patients with more active disease. The persistence of the
anti-IgG-AGE response was more specific to RA, and was transient in the patients with spondyloarthropathy and with undifferentiated
arthritis who were initially found to be positive for anti-IgG-AGE antibodies. 相似文献
55.
56.
Luca Salvatore De Santo Michele Torella Gianpaolo Romano Ciro Maiello Marianna Buonocore Ciro Bancone Alessandro Della Corte Nicola Galdieri Gianantonio Nappi Cristiano Amarelli 《PloS one》2015,10(5)
MethodsData on 362 consecutive recipients (mean age: 47.8±13.7, 20.2% female, 18.2% diabetics, 22.1% with previous cardiac operations, 27.6% hospitalized, 84.9±29.4 ml/min preoperative glomerular filtration rate) were analyzed using multivariable logistic regression modeling. Target outcomes were determinants of troponin release, early graft failure (EGF), acute kidney injury (AKI) and operative death.ResultsMean cTnI release measured 24 hours after transplant was 10.9±11.6 μg/L. Overall hospital mortality was 10.8%, EGF 10.5%, and AKI was 12.2%. cTnI release>10 μg/L proved an independent predictor of EGF (OR 2.2; 95% CI, 1.06–4.6) and AKI (OR 1.031; 95% CI, 1.001-1.064). EGF, in turn, proved a determinant of hospital mortality. Risk factors for cTnI>10 μg/L release were: status 2B (OR 0.35; 95% CI, 0.18-0.69, protective), duration of the ischemic period (OR 1.006; 95% CI, 1.001-1.011), previous cardiac operation (OR 2.9; 95% CI, 1.67-5.0), and left ventricular hypertrophy (OR 3.3; 95% CI, 1.9-5.6).ConclusionsMyocardial enzyme leakage clearly emerged as an epiphenomenon of more complicated clinical course. The complex interplay between surgical procedure features, graft characteristics and recipient end-organ function highlights cTnI release as a risk marker of graft failure and acute kidney injury. The search for optimal myocardial preservation is still an issue. 相似文献
57.
58.
Federica Zito Marino Giuseppina Liguori Gabriella Aquino Elvira La Mantia Silvano Bosari Stefano Ferrero Lorenzo Rosso Gabriella Gaudioso Nicla De Rosa Marianna Scrima Nicola Martucci Antonello La Rocca Nicola Normanno Alessandro Morabito Gaetano Rocco Gerardo Botti Renato Franco 《PloS one》2015,10(10)
59.
Francesco Cerritelli Gianfranco Pizzolorusso Cinzia Renzetti Vincenzo Cozzolino Marianna D’Orazio Mariacristina Lupacchini Benedetta Marinelli Alessandro Accorsi Chiara Lucci Jenny Lancellotti Silvia Ballabio Carola Castelli Daniela Molteni Roberto Besana Lucia Tubaldi Francesco Paolo Perri Paola Fusilli Carmine D’Incecco Gina Barlafante 《PloS one》2015,10(5)
BackgroundDespite some preliminary evidence, it is still largely unknown whether osteopathic manipulative treatment improves preterm clinical outcomes.ResultsA total of 695 newborns were randomly assigned to either the study group (n= 352) or the control group (n=343). A statistical significant difference was observed between the two groups for the primary outcome (13.8 and 17.5 days for the study and control group respectively, p<0.001, effect size: 0.31). Multivariate analysis showed a reduction of the length of stay of 3.9 days (95% CI -5.5 to -2.3, p<0.001). Furthermore, there were significant reductions with treatment as compared to usual care in cost (difference between study and control group: 1,586.01€; 95% CI 1,087.18 to 6,277.28; p<0.001) but not in daily weight gain. There were no complications associated to the intervention.ConclusionsOsteopathic treatment reduced significantly the number of days of hospitalization and is cost-effective on a large cohort of preterm infants. 相似文献
60.
Francesco Pantano Matteo Santoni Giuseppe Procopio Mimma Rizzo Roberto Iacovelli Camillo Porta Alessandro Conti Antonio Lugini Michele Milella Luca Galli Cinzia Ortega Francesco Maria Guida Marianna Silletta Giovanni Schinzari Elena Verzoni Daniela Modica Pierfilippo Crucitti Annamaria Rauco Alessandra Felici Valentina Ballatore Stefano Cascinu Giuseppe Tonini Giacomo Carteni Antonio Russo Daniele Santini 《PloS one》2015,10(4)