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61.
Anne Rupprecht Elena A. Sokolenko Valeri Beck Olaf Ninnemann Thorsten Trimbuch Petr Jezek Elena E. Pohl 《Biophysical journal》2010,98(8):1503-1511
The molecular mechanism responsible for the regulation of the mitochondrial membrane proton conductance (G) is not clearly understood. This study investigates the role of the transmembrane potential (ΔΨm) using planar membranes, reconstituted with purified uncoupling proteins (UCP1 and UCP2) and/or unsaturated FA. We show that high ΔΨm (similar to ΔΨm in mitochondrial State IV) significantly activates the protonophoric function of UCPs in the presence of FA. The proton conductance increases nonlinearly with ΔΨm. The application of ΔΨm up to 220 mV leads to the overriding of the protein inhibition at a constant ATP concentration. Both, the exposure of FA-containing bilayers to high ΔΨm and the increase of FA membrane concentration bring about the significant exponential Gm increase, implying the contribution of FA in proton leak. Quantitative analysis of the energy barrier for the transport of FA anions in the presence and absence of protein suggests that FA− remain exposed to membrane lipids while crossing the UCP-containing membrane. We believe this study shows that UCPs and FA decrease ΔΨm more effectively if it is sufficiently high. Thus, the tight regulation of proton conductance and/or FA concentration by ΔΨm may be key in mitochondrial respiration and metabolism. 相似文献
62.
Parikh H Wang Z Pettigrew KA Jia J Daugherty S Yeager M Jacobs KB Hutchinson A Burdett L Cullen M Qi L Boland J Collins I Albert TJ Vatten LJ Hveem K Njølstad I Cancel-Tassin G Cussenot O Valeri A Virtamo J Thun MJ Feigelson HS Diver WR Chatterjee N Thomas G Albanes D Chanock SJ Hunter DJ Hoover R Hayes RB Berndt SI Sampson J Amundadottir L 《Human genetics》2011,129(6):675-685
Measurements of serum prostate-specific antigen (PSA) protein levels form the basis for a widely used test to screen men for prostate cancer. Germline variants in the gene that encodes the PSA protein (KLK3) have been shown to be associated with both serum PSA levels and prostate cancer. Based on a resequencing analysis of a 56?kb region on chromosome 19q13.33, centered on the KLK3 gene, we fine mapped this locus by genotyping tag SNPs in 3,522 prostate cancer cases and 3,338 controls from five case?Ccontrol studies. We did not observe a strong association with the KLK3 variant, reported in previous studies to confer risk for prostate cancer (rs2735839; P?=?0.20) but did observe three highly correlated SNPs (rs17632542, rs62113212 and rs62113214) associated with prostate cancer [P?=?3.41?×?10?4, per-allele trend odds ratio (OR)?=?0.77, 95% CI?=?0.67?C0.89]. The signal was apparent only for nonaggressive prostate cancer cases with Gleason score <7 and disease stage <III (P?=?4.72?×?10?5, per-allele trend OR?=?0.68, 95% CI?=?0.57?C0.82) and not for advanced cases with Gleason score >8 or stage ??III (P?=?0.31, per-allele trend OR?=?1.12, 95% CI?=?0.90?C1.40). One of the three highly correlated SNPs, rs17632542, introduces a non-synonymous amino acid change in the KLK3 protein with a predicted benign or neutral functional impact. Baseline PSA levels were 43.7% higher in control subjects with no minor alleles (1.61?ng/ml, 95% CI?=?1.49?C1.72) than in those with one or more minor alleles at any one of the three SNPs (1.12?ng/ml, 95% CI?=?0.96?C1.28) (P?=?9.70?×?10?5). Together our results suggest that germline KLK3 variants could influence the diagnosis of nonaggressive prostate cancer by influencing the likelihood of biopsy. 相似文献
63.
Maria Valeri Silvia Rossi Paccani Magdalena Kasendra Barbara Nesta Laura Serino Mariagrazia Pizza Marco Soriani 《PloS one》2015,10(3)
SslE is a zinc-metalloprotease involved in the degradation of mucin substrates and recently proposed as a potential vaccine candidate against pathogenic E. coli. In this paper, by exploiting a human in vitro model of mucus-secreting cells, we demonstrated that bacteria expressing SslE have a metabolic benefit which results in an increased growth rate postulating the importance of this antigen in enhancing E. coli fitness. We also observed that SslE expression facilitates E. coli penetration of the mucus favouring bacteria adhesion to host cells. Moreover, we found that SslE-mediated opening of the mucosae contributed to the activation of pro-inflammatory events. Indeed, intestinal cells infected with SslE-secreting bacteria showed an increased production of IL-8 contributing to neutrophil recruitment. The results presented in this paper conclusively designate SslE as an important colonization factor favouring E. coli access to both metabolic substrates and target cells. 相似文献
64.
Pietro Marini Luca Romanelli Daniela Valeri Maria Grazia Cascio Paolo Tucci Pacifico Valeri Maura Palmery 《Peptides》2012
In isolated guinea-pig ileum (GPI), the κ-opioid acute withdrawal response is under the control of several neuronal signaling systems, including the μ-opioid, the A1-adenosine and the CB1 receptors, which are involved in the inhibitory control of the κ-withdrawal response. After κ-opioid system stimulation, indirect activation of μ-opioid, A1-adenosine and CB1 systems is prevented by the peptide cholecystokinin-8 (CCk-8). In the present study, we have investigated whether the NOP system is also involved in the regulation of the acute κ-withdrawal response. Interestingly, we found that in GPI preparation, the NOP system is not indirectly activated by the κ-opioid receptor stimulation, but instead this system is able by itself to directly regulate the acute κ-withdrawal response. Specifically, our results clearly highlight first the existence of an endogenous tone of the NOP system in GPI, and second that it behaves as a functional anti-opioid system. We also found that, the NOP receptor system is involved in the regulation of the CCk-8-induced contracture intensity, only when in the presence of the κ-opioid receptor stimulation. This effect seems to be regulated by an activation threshold mechanism. In conclusion, the NOP system could act as neuromodulatory system, whose action is strictly related to the modulation of both excitatory and inhibitory neurotransmitters released in GPI enteric nervous system. 相似文献
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68.
Beck V Jabůrek M Breen EP Porter RK Jezek P Pohl EE 《Biochimica et biophysica acta》2006,1757(5-6):474-479
Electrophysiological characterisation of the vast number of annotated channel and transport proteins in the postgenomic era would be greatly facilitated by the introduction of rapid and robust methods for the functional incorporation of membrane proteins into defined lipid bilayers. Here, we describe an automated technique for reconstitution of membrane proteins into lipid bilayer membranes, which substantially reduces both the reconstitution time and the amount of protein required for the membrane formation. The method allows the investigation of single protein channels as well as insertion of multiple copies (approximately 10(7)) into a single bilayer. Despite a comparatively large membrane area (up to 300 microm diameter), the high stability of the membrane permits the application of transmembrane voltages up to 300 mV. This feature is especially important for studies of inner membrane mitochondrial proteins, since they act at potentials up to approximately 200 mV under physiological conditions. It is a combination of these advantages that enables the detailed investigation of the minuscule single protein conductances typical for proton transporters. We have applied the new technique for the reconstitution and electrophysiological characterisation of human recombinant uncoupling protein 1, hUCP1, that has been overexpressed in E. coli and purified from inclusion bodies. We demonstrate that hUCP1 activity in the presence of fatty acids is comparable to the activity of UCP1 isolated from brown adipose tissue. 相似文献
69.
Bio-diesel fuels are non-petroleum-based diesel fuels consisting of long chain alkyl esters produced by the transesterification of vegetable oils, that are intended for use (neat or blended with conventional fuels) in unmodified diesel engines. There have been few reports of studies proposing theoretical models for bio-diesel combustion simulations. In this study, we developed combustion models based on ones developed previously. We compiled the liquid fuel properties, and the existing detailed mechanism of methyl butanoate ester (MB, C5H10O2) oxidation was supplemented by sub-mechanisms for two proposed fuel constituent components, C7H16 and C7H8O (and then, by mp2d, C4H6O2 and propyne, C3H4) to represent the combustion model for rapeseed methyl ester described by the chemical formula, C19H34O2 (or C19H36O2). The main fuel vapor thermal properties were taken as those of methyl palmitate C19H36O2 in the NASA polynomial form of the Burcat database. The special global reaction was introduced to “crack” the main fuel into its constituent components. This general reaction included 309 species and 1472 reactions, including soot and NOx formation processes. The detailed combustion mechanism was validated using shock-tube ignition-delay data under diesel engine conditions. For constant volume and diesel engine (Volvo D12C) combustion modeling, this mechanism could be reduced to 88 species participating in 363 reactions. 相似文献
70.
José Antonio Villacorta-Atienza Manuel G. Velarde Valeri A. Makarov 《Biological cybernetics》2010,103(4):285-297
Animals for survival in complex, time-evolving environments can estimate in a “single parallel run” the fitness of different
alternatives. Understanding of how the brain makes an effective compact internal representation (CIR) of such dynamic situations
is a challenging problem. We propose an artificial neural network capable of creating CIRs of dynamic situations describing
the behavior of a mobile agent in an environment with moving obstacles. The network exploits in a mental world model the principle
of causality, which enables reduction of the time-dependent structure of real situations to compact static patterns. It is
achieved through two concurrent processes. First, a wavefront representing the agent’s virtual present interacts with mobile
and immobile obstacles forming static effective obstacles in the network space. The dynamics of the corresponding neurons
in the virtual past is frozen. Then the diffusion-like process relaxes the remaining neurons to a stable steady state, i.e.,
a CIR is given by a single point in the multidimensional phase space. Such CIRs can be unfolded into real space for execution
of motor actions, which allows a flexible task-dependent path planning in realistic time-evolving environments. Besides, the
proposed network can also work as a part of “autonomous thinking”, i.e., some mental situations can be supplied for evaluation
without direct motor execution. Finally we hypothesize the existence of a specific neuronal population responsible for detection
of possible time-space coincidences of the animal and moving obstacles. 相似文献