Calcium overload is a fundamental pathogenic event associated with chronic muscle degeneration in muscular dystrophies. The possibility that L-type voltage-dependent calcium channels were involved in ...the etiology of chicken muscular dystrophy was investigated by studying the dihydropyridine receptors in transverse tubule membranes isolated from skeletal muscle of normal (line 412) and dystrophic (line 413) chickens. The yield of T-tubular protein from dystrophic muscle was considerably increased compared with that from normal muscle (2.51 +/- 0.18 vs 1.04 +/- 0.31 mg protein x 100 g muscle-1). The binding of the calcium channel antagonist (+) 3HPN200-110 to the dihydropyridine receptor in transverse tubule preparations was relatively slow, markedly affected by temperature and required divalent cations. (+) 3HPN200-110 equilibrium binding assays revealed a single class of high-affinity sites and showed that maximum binding capacity (Bmax) (3.17 +/- 0.47 for normal and 3.51 +/- 0.52 pmol x mg protein-1 for dystrophic transverse tubules) and dissociation constant (Kd) (0.32 +/- 0.07 and 0.26 +/- 0.09 nM, respectively) were not significantly different in normal and dystrophic membranes. Kinetic studies indicated that normal and dystrophic transverse tubules did not differ significantly in association (2.54 x 10(6) and 2.27 x 10(6) M(-1)s(-1), respectively) and dissociation (8.5 x 10(-4) and 9.3 x 10(-4)s(-1), respectively) rate constants. Since dissociation kinetics for both preparations were monoexponential under all the experimental conditions employed, no low-affinity binding sites for (+) 3HPN200-110 could be detected in chicken transverse tubules membranes. However, immunoblot assay, using a monoclonal antibody, revealed that dystrophic transverse tubules as compared with normal membranes were enriched twofold with the alpha 1-subunit of the dihydropyridine receptor. Therefore, although dihydropyridine-binding sites were not altered in transverse tubule membranes from dystrophic chicken skeletal muscle, both the increased yield in T-tubule vesicles and the enhanced immunodetection of the alpha 1-subunit of the dihydropyridine receptor, suggest that total content in dihydropyridine receptor is higher in dystrophic than in normal muscle.
Aurora-A is a serine/threonine kinase that plays critical roles in centrosome maturation, spindle dynamics, and chromosome orientation and it is frequently over-expressed in human cancers. In this ...work, we show that Aurora-A interacts with the SUMO-conjugating enzyme UBC9 and co-localizes with SUMO1 in mitotic cells. Aurora-A can be SUMOylated in vitro and in vivo. Mutation of the highly conserved SUMOylation residue lysine 249 significantly disrupts Aurora-A SUMOylation and mitotic defects characterized by defective and multipolar spindles ensue. The Aurora-A(K249R) mutant has normal kinase activity but displays altered dynamics at the mitotic spindle. In addition, ectopic expression of the Aurora-A(K249R) mutant results in a significant increase in susceptibility to malignant transformation induced by the Ras oncogene. These data suggest that modification by SUMO residues may control Aurora-A function at the spindle and that deficiency of SUMOylation of this kinase may have important implications for tumor development.
Rhizobium fredii HH103 produces extracellular signal molecules that are able to induce deformation of root hairs and nodule organogenesis of soybean. This strain produces a large variety of ...nodulation factors, consisting of a linear backbone of GlcNAc with different degrees of polymerization, bearing on the non-reducing residue various different
N-acyl residues. The reducing terminal residue is 2-
O-methylfucosylated at position 6. Several analogous molecules substituted with fucose were also detected.
The structures of sixteen Nod factors from
Rhizobium fredii HH103 have been determined
For centuries, the kidney has been considered primarily an organ of elimination and a regulator of salt and ion balance. Although once thought that the kidney was the structural cause of diabetes, ...which in recent years has been ignored as a regulator of glucose homeostasis, is now recognized as a major player in the field of metabolic regulation carbohydrate. During fasting, 55% of the glucose comes from gluconeogenesis. Only 2 organs have this capability: the liver and kidney. The latter is responsible for 20% of total glucose production and 40% of that produced by gluconeogenesis. Today we have a better understanding of the physiology of renal glucose transport via specific transporters, such as type 2 sodium-glucose cotransporter (SGLT2). A natural compound, phlorizin, was isolated in early 1800 and for decades played an important role in diabetes and renal physiology research. Finally, at the nexus of these findings mentioned above, recognized the effect of phlorizin-like compounds in the renal glucose transporter, which has offered a new mechanism to treat hyperglycemia. This has led to the development of several potentially effective treatment modalities for the treatment of diabetes.
We present the predictions of the SuSAv2-MEC model for the double differential charged-current muonic neutrino (antineutrino) cross section on water for the T2K neutrino (antineutrino) beam. We ...validate our model by comparing with the available inclusive electron scattering data on oxygen and compare our predictions with the recent T2K \(\nu_\mu\)-\(^{16}\)O data, finding good agreement at all kinematics. We show that the results are very similar to those obtained for \(\nu_\mu-^{12}\)C scattering, except at low energies, and we comment on the origin of this difference. A factorized spectral function model of \(^{16}\)O is also included for purposes of comparison.
We compare the charged-current quasielastic neutrino and antineutrino observables obtained in two different nuclear models, the phenomenological SuperScaling Approximation and the relativistic mean ...field approach, with the recent data published by the MINERnuA Collaboration. Both models provide a good description of the data without the need of an ad hoc increase in the mass parameter in the axial-vector dipole form factor. Comparisons are also made with the MiniBooNE results, where different conclusions are reached.
We evaluate and discuss the impact of meson-exchange currents (MECs) on charged-current quasielastic neutrino cross sections. Here, we consider the nuclear transverse response arising from ...two-particle two-hole states excited by the action of electromagnetic, purely isovector meson-exchange currents in a fully relativistic framework based on the work by the Torino Collaboration A. D. Pace, M. Nardi, W. M. Alberico, T. W. Donnelly, and A. Molinari, Nucl. Phys. A726, 303 (2003). An accurate parametrization of this MEC response as a function of the momentum and energy transfers involved is presented. Results of neutrino-nucleus cross sections using this MEC parametrization together with a recent scaling approach for the one-particle one-hole contributions (named SuSAv2) are compared with experimental data.
We evaluate and discuss the impact of meson-exchange currents (MECs) on charged-current quasielastic neutrino cross sections. We consider the nuclear transverse response arising from two-particle ...two-hole states excited by the action of electromagnetic, purely isovector meson-exchange currents in a fully relativistic framework based on the work by the Torino Collaboration A. D. Pace, M. Nardi, W. M. Alberico, T. W. Donnelly, and A. Molinari, Nucl. Phys. A726, 303 (2003). An accurate parametrization of this MEC response as a function of the momentum and energy transfers involved is presented. Results of neutrino-nucleus cross sections using this MEC parametrization together with a recent scaling approach for the one-particle one-hole contributions (named SuSAv2) are compared with experimental data.
In Europe, antimicrobial resistance of invasive pathogens has been monitored since 1998 by the European Antimicrobial Resistance Surveillance System (EARSS). The goal of this study is to analyse the ...susceptibility data of invasive Escherichia coli collected by 27 Spanish laboratories in 2001. Each laboratory identified strains and tested their susceptibility using its own methods. To assess the comparability of susceptibility test results, a quality assurance exercise was performed. We report data from 1962 invasive isolates of E. coli: 1959 from blood and three from cerebrospinal fluid, corresponding to the same number of patients. Resistance to ampicillin, co-trimoxazole, ciprofloxacin and gentamicin was found in 58.46%, 32.91%, 17.19% and 6.39% of isolates, respectively. Extended-spectrum β-lactamase (ESBL) production was detected in 30 strains (1.55%). Ciprofloxacin resistance was higher in isolates from men and in-patients than in those from women and out-patients (P < 0.001). Resistance to ampicillin and co-trimoxazole was more widespread in children than in adults: 70.37% versus 57.87% (P = 0.01) and 41.84% versus 32.53% (P = 0.05). Non-significant differences in resistance to fluoroquinolones were observed between isolates from children (11.1%) and adults (17.54%), despite the fact that fluoroquinolones are not administered to children. Significantly, resistance to non-β-lactam antibiotics (co-trimoxazole, ciprofloxacin and gentamicin) was more prevalent in ampicillin-resistant strains and ESBL-producing strains than in ampicillin-susceptible strains and non-ESBL-producing strains. Multidrug resistance was present in 13.92% of isolates; the most prevalent phenotype was resistance to ampicillin, co-trimoxazole and ciprofloxacin, which was detected in 59.36% of multiresistant strains and in 8.22% of strains overall.
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