The Experts below are selected from a list of 39 Experts worldwide ranked by ideXlab platform
Robert Tampé - One of the best experts on this subject based on the ideXlab platform.
-
mechanistic determinants of the directionality and energetics of Active export by a heterodimeric abc transporter
Nature Communications, 2014Co-Authors: Nina Grossmann, Ahmet S Vakkasoglu, Sabine Hulpke, Rachelle Gaudet, Rupert Abele, Robert TampéAbstract:The ATP-binding cassette (ABC) transporter associated with antigen processing (TAP) participates in immune surveillance by moving proteasomal products into the endoplasmic reticulum (ER) lumen for major histocompatibility complex class I loading and cell surface presentation to cytotoxic T cells. Here we delineate the mechanistic basis for antigen translocation. Notably, TAP works as a molecular diode, translocating peptide substrates against the gradient in a strict unidirectional way. We reveal the importance of the D-loop at the dimer interface of the two nucleotide-binding domains (NBDs) in coupling substrate translocation with ATP hydrolysis and defining transport vectoriality. Substitution of the conserved aspartate, which coordinates the ATP-binding site, decreases NBD dimerization affinity and turns the unidirectional primary Active Pump into a passive bidirectional nucleotide-gated facilitator. Thus, ATP hydrolysis is not required for translocation per se, but is essential for both Active and unidirectional transport. Our data provide detailed mechanistic insight into how heterodimeric ABC exporters operate.
Bart Meyns - One of the best experts on this subject based on the ideXlab platform.
-
exercise physiology in chronic mechanical circulatory support patients vascular function and beyond
Current Opinion in Cardiology, 2016Co-Authors: Christopher S Hayward, Libera Fresiello, Bart MeynsAbstract:PURPOSE OF REVIEW The majority of patients currently implanted with left ventricular assist devices have the expectation of support for more than 2 years. As a result, survival alone is no longer a sufficient distinctive for this technology, and there have been many studies within the last few years examining functional capacity and exercise outcomes. RECENT FINDINGS Despite strong evidence for functional class improvements and increases in simple measures of walking distance, there remains incomplete normalization of exercise capacity, even in the presence of markedly improved resting hemodynamics. Reasons for this remain unclear. Despite current Pumps being run at a fixed speed, it is widely recognized that Pump outputs significantly increase with exercise. The mechanism of this increase involves the interaction between preload, afterload, and the intrinsic Pump function curves. The role of the residual heart function is also important in determining total cardiac output, as well as whether the aortic valve opens with exercise. Interactions with the vasculature, with skeletal muscle blood flow and the state of the autonomic nervous system are also likely to be important contributors to exercise performance. SUMMARY Further studies examining optimization of Pump function with Active Pump speed modulation and options for optimization of the overall patient condition are likely to be needed to allow left ventricular assist devices to be used with the hope of full functional physiological recovery.
Ermertcan Ş. - One of the best experts on this subject based on the ideXlab platform.
-
Quercetin inhibits swarming motility and activates biofilm production of Proteus mirabilis possibly by interacting with central regulators, metabolic status or Active Pump proteins
'Elsevier BV', 2019Co-Authors: Aygül A., Öztürk İ., Çilli F.f., Ermertcan Ş.Abstract:PubMedID: 30668324Background: Via its virulence factors such as swarm differentiation, biofilm and hemolysin production, urease enzyme, Proteus mirabilis causes urinary tract infections (UTIs), especially in complicated cases. Anti-pathogenic compounds attenuate the virulence of bacteria without showing ‘cidal’ activity and carry the potential to be used in the prevention and treatment of infectious diseases. Purpose: Search for anti-pathogenic effects of quercetin, which is a widely known and biologically Active phytochemical, on Proteus mirabilis was the purpose of this study. In this context, the potential inhibitory activity of quercetin on swarming motility and biofilm production of a wild-type strain, P. mirabilis HI4320, was investigated in both phenotypically and genotypically. Methods: Quercetin's effect on swarming motility was examined on LB agar plates, containing quercetin at various concentrations, by measuring the swarming diameter. The effect on biofilm formation, on the other hand, was analyzed by staining the formed biofilm of the bacterium, exposed to quercetin at various concentrations, with crystal violet and reading spectrophotometrically. Differences in expression levels of selected genes involved in swarming regulation were determined by real-time reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) to evaluate the mechanism of inhibitory action on swarming. Further investigations were carried out repeating swarming assays with the clones that derived from the wild-type strain by a TA system kit for direct one-step cloning and overexpressing the relevant genes. Results: Our study revealed that quercetin inhibited swarming motility while activating biofilm production of P. mirabilis in direct proportion to the dose. Although all selected genes are inhibited in the same manner in liquid medium, and no significant differences could be detected in solid medium as demonstrated by RT-qPCR, experiments repeated with the clones overexpressing flhC (a component of flagellar transcriptional activator), speB (an agmatinase enzyme) and ompF (an outer membrane porin) genes showed that the respective clones could restore swarming, compensating for the inhibitory effect of quercetin. Conclusion: Quercetin's inhibitory effect on P. mirabilis swarming was possibly due to interactions with components of swarming regulators, the genes expressing polyamine coding enzymes that trigger swarm differentiation, or Active Pump proteins. © 2018216S357This work was supported by TÜBİTAK (The Scientific and Technological Research Council of Turkey) (Grant number: 216S357 ). Authors thank Mobley Research Laboratory (Ann Arbor, USA) for supplying the wild-type strain used in the study
Ermertcan Safak - One of the best experts on this subject based on the ideXlab platform.
-
Quercetin inhibits swarming motility and activates biofilm production of Proteus mirabilis possibly by interacting with central regulators, metabolic status or Active Pump proteins
'Elsevier BV', 2019Co-Authors: Aygul Abdurrahman, Ozturk Ismail, Cilli, Fatma Feriha, Ermertcan SafakAbstract:WOS: 000465081700008PubMed ID: 30668324Background: Via its virulence factors such as swarm differentiation, biofilm and hemolysin production, urease enzyme, Proteus mirabilis causes urinary tract infections (UTIs), especially in complicated cases. Anti-pathogenic compounds attenuate the virulence of bacteria without showing 'cidal' activity and carry the potential to be used in the prevention and treatment of infectious diseases. Purpose: Search for anti-pathogenic effects of quercetin, which is a widely known and biologically Active phytochemical, on Proteus mirabilis was the purpose of this study. In this context, the potential inhibitory activity of quercetin on swarming motility and biofilm production of a wild-type strain, P. mirabilis HI4320, was investigated in both phenotypically and genotypically. Methods: Quercetin's effect on swarming motility was examined on LB agar plates, containing quercetin at various concentrations, by measuring the swarming diameter. The effect on biofilm formation, on the other hand, was analyzed by staining the formed biofilm of the bacterium, exposed to quercetin at various concentrations, with crystal violet and reading spectrophotometrically. Differences in expression levels of selected genes involved in swarming regulation were determined by real-time reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) to evaluate the mechanism of inhibitory action on swarming. Further investigations were carried out repeating swarming assays with the clones that derived from the wild-type strain by a TA system kit for direct one-step cloning and overexpressing the relevant genes. Results: Our study revealed that quercetin inhibited swarming motility while activating biofilm production of P. mirabilis in direct proportion to the dose. Although all selected genes are inhibited in the same manner in liquid medium, and no significant differences could be detected in solid medium as demonstrated by RT-qPCR, experiments repeated with the clones overexpressing flhC (a component of flagellar transcriptional activator), speB (an agmatinase enzyme) and ompF (an outer membrane porin) genes showed that the respective clones could restore swarming, compensating for the inhibitory effect of quercetin. Conclusion: Quercetin's inhibitory effect on P. mirabilis swarming was possibly due to interactions with components of swarming regulators, the genes expressing polyamine coding enzymes that trigger swarm differentiation, or Active Pump proteins.TUBITAK (The Scientific and Technological Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [216S357]This work was supported by TUBITAK (The Scientific and Technological Research Council of Turkey) (Grant number: 216S357). Authors thank Mobley Research Laboratory (Ann Arbor, USA) for supplying the wild-type strain used in the study
Nina Grossmann - One of the best experts on this subject based on the ideXlab platform.
-
mechanistic determinants of the directionality and energetics of Active export by a heterodimeric abc transporter
Nature Communications, 2014Co-Authors: Nina Grossmann, Ahmet S Vakkasoglu, Sabine Hulpke, Rachelle Gaudet, Rupert Abele, Robert TampéAbstract:The ATP-binding cassette (ABC) transporter associated with antigen processing (TAP) participates in immune surveillance by moving proteasomal products into the endoplasmic reticulum (ER) lumen for major histocompatibility complex class I loading and cell surface presentation to cytotoxic T cells. Here we delineate the mechanistic basis for antigen translocation. Notably, TAP works as a molecular diode, translocating peptide substrates against the gradient in a strict unidirectional way. We reveal the importance of the D-loop at the dimer interface of the two nucleotide-binding domains (NBDs) in coupling substrate translocation with ATP hydrolysis and defining transport vectoriality. Substitution of the conserved aspartate, which coordinates the ATP-binding site, decreases NBD dimerization affinity and turns the unidirectional primary Active Pump into a passive bidirectional nucleotide-gated facilitator. Thus, ATP hydrolysis is not required for translocation per se, but is essential for both Active and unidirectional transport. Our data provide detailed mechanistic insight into how heterodimeric ABC exporters operate.
