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排序方式: 共有8501条查询结果,搜索用时 31 毫秒
1.
The calcium pump (sarco/endoplasmic reticulum Ca2+-ATPase, SERCA) plays a major role in calcium homeostasis in muscle cells by clearing cytosolic Ca2+ during muscle relaxation. Active Ca2+ transport by SERCA involves the structural transition from a low-Ca2+ affinity E2 state toward a high-Ca2+ affinity E1 state of the pump. This structural transition is accompanied by the countertransport of protons to stabilize the negative charge and maintain the structural integrity of the transport sites and partially compensate for the positive charges of the two Ca2+ ions passing through the membrane. X-ray crystallography studies have suggested that a hydrated pore located at the C-terminal domain of SERCA serves as a conduit for proton countertransport, but the existence and function of this pathway have not yet been fully characterized. We used atomistic simulations to demonstrate that in the protonated E2 state and the absence of initially bound water molecules, the C-terminal pore becomes hydrated in the nanosecond timescale. Hydration of the C-terminal pore is accompanied by the formation of water wires that connect the transport sites with the cytosol. Water wires are known as ubiquitous proton-transport devices in biological systems, thus supporting the notion that the C-terminal domain serves as a conduit for proton release. Additional simulations showed that the release of a single proton from the transport sites induces bending of transmembrane helix M5 and the interaction between residues Arg762 and Ser915. These structural changes create a physical barrier against full hydration of the pore and prevent the formation of hydrogen-bonded water wires once proton transport has occurred through this pore. Together, these findings support the notion that the C-terminal proton release pathway is a functional element of SERCA and also provide a mechanistic model for its operation in the catalytic cycle of the pump. 相似文献
2.
Bouaziz Youssef Royer Eric Bresson Guillaume Dhome Michel 《Multimedia Tools and Applications》2022,81(16):22449-22480
Multimedia Tools and Applications - Changes in appearance present a tremendous problem for the visual localization of an autonomous vehicle in outdoor environments. Data association between the... 相似文献
3.
Alfonso Martín-Bernab Josep Tarrag-Celada Valrie Cunin Sylvie Michelland Roldn Corts Johann Poignant Cyril Boyault Walid Rachidi Sandrine Bourgoin-Voillard Marta Cascante Michel Seve 《International journal of molecular sciences》2021,22(7)
Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies. 相似文献
4.
Solenn Percelay Jean-Marie Billard Thomas Freret Annie Andrieux Michel Boulouard Valentine Bouet 《International journal of molecular sciences》2021,22(5)
For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility—partial deletion of the MAP6 gene, early-life stress—maternal separation, and pharmacological treatment—chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABAA receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis. 相似文献
5.
Joo H. Kang Eujin Um Alexander Diaz Harry Driscoll Melissa J. Rodas Karel Domansky Alexander L. Watters Michael Super Howard A. Stone Donald E. Ingber 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(42):5657-5666
Magnetic nanoparticles have been employed to capture pathogens for many biological applications; however, optimal particle sizes have been determined empirically in specific capturing protocols. Here, a theoretical model that simulates capture of bacteria is described and used to calculate bacterial collision frequencies and magnetophoretic properties for a range of particle sizes. The model predicts that particles with a diameter of 460 nm should produce optimal separation of bacteria in buffer flowing at 1 L h−1. Validating the predictive power of the model, Staphylococcus aureus is separated from buffer and blood flowing through magnetic capture devices using six different sizes of magnetic particles. Experimental magnetic separation in buffer conditions confirms that particles with a diameter closest to the predicted optimal particle size provide the most effective capture. Modeling the capturing process in plasma and blood by introducing empirical constants (ce), which integrate the interfering effects of biological components on the binding kinetics of magnetic beads to bacteria, smaller beads with 50 nm diameters are predicted that exhibit maximum magnetic separation of bacteria from blood and experimentally validated this trend. The predictive power of the model suggests its utility for the future design of magnetic separation for diagnostic and therapeutic applications. 相似文献
6.
Martins Silvia S.; Mazzotti Guido; Chilcoat Howard D. 《Canadian Metallurgical Quarterly》2006,14(3):275
Background: Despite increases in ecstasy (MDMA) use in the United States, little is known about characteristics linked with recent-onset ecstasy use, especially psychiatric symptoms and deviant behaviors. Aims: To test whether individuals with high levels of other drug use are more likely to be recent-onset ecstasy users; to test whether psychiatric symptoms in adults are associated with recent-onset ecstasy use; to explore the association between recent-onset ecstasy use and concomitant deviant behaviors in adolescents and adults. Methods: Data from the 2001 National Survey on Drug Use and Health. Findings: Recent-onset ecstasy use was significantly more likely to occur among adolescents and adults (18-34 years old) who engaged in deviant behaviors during the past year as compared with those who did not engage in deviant behaviors during the past year. Higher levels of deviancy indicated a higher likelihood of being a recent-onset ecstasy user, and associations were strongest with nonviolent deviant behaviors such as selling illegal drugs and stealing. Associations between deviant behaviors and recent-onset ecstasy use were similar in strength to associations between deviant behaviors and recent-onset cocaine and marijuana use, respectively. Adults who had past-year psychiatric symptoms (both depressive and panic symptoms) were twice as likely to be recent-onset ecstasy users as compared with those without past-year psychiatric symptoms. Greater levels of drug involvement increased the odds of being a recent-onset ecstasy user. Conclusion: Recent-onset ecstasy use seems to be associated with a range of other behavioral problems and may reflect one aspect of a larger problem behavior syndrome. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
7.
Superconducting qubits are solid state electrical circuits fabricated using techniques borrowed from conventional integrated circuits. They are based on the Josephson tunnel junction, the only non-dissipative, strongly non-linear circuit element available at low temperature. In contrast to microscopic entities such as spins or atoms, they tend to be well coupled to other circuits, which make them appealling from the point of view of readout and gate implementation. Very recently, new designs of superconducting qubits based on multi-junction circuits have solved the problem of isolation from unwanted extrinsic electromagnetic perturbations. We discuss in this review how qubit decoherence is affected by the intrinsic noise of the junction and what can be done to improve it.
PACS: 03.67.-a, 03.65.Yz, 85.25.-j, 85.35.Gv 相似文献
8.
This report details procedures to measure annihilation anxiety, a concept derived from Freud's 1926 formulation of traumatic anxiety. A 25-item pencil-and-paper inventory administered to patient and to nonpatient samples is described, along with a brief summary of earlier findings. The delineation of nine interrelated experiential components of annihilation anxiety provides the background for the construction of Rorschach and TAT measures of the concept. Findings comparing the pencil-and-paper inventory and the projective test measures are presented as well as examples of responses judged to reflect annihilation anxiety from Rorschach and TAT protocols. 相似文献
9.
Xavier Gerbaux Armand Hadni Michel Josse 《Journal of Infrared, Millimeter and Terahertz Waves》1994,15(5):775-782
Finesse as high as 260 and peak transmission close to 98% at frequencies around 30 cm?1 are predicted at 10 K by coating the Perot-Fabry (PF) mirrors with a suitable thickness of High Tc (HTC) superconductor YBaCuO. In fact, Finesse will be limited by the lack of parallelism and the lack of perfect flatness of the mirrors to values around 100. These predictions are based upon phenomenological models for both the YBaCuO coating and the MgO support, i.e. from direct transmission measurements of MgO and YBaCuO in the Far IR, which had to be fitted by the models. 相似文献
10.
A historical review of licensing among industrial/organizational (I/O) psychologists demonstrates that the American Psychological Association (APA) policy on such licensing is inconsistent. Arguments for and against licensure for this group are presented. Job analysis and APA data are drawn upon to show that few I/O activities may pose the personal risk that would seem to require the protection of a license. Alternatives are discussed for changes in present APA policy and state licensing requirements. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献