Increased Coupling Efficiency Research Articles

Hypothesis on Skeletal Muscle Aging: Mitochondrial Adenine Nucleotide Translocator Decreases Reactive Oxygen Species Production While Preserving Coupling Efficiency.

Mitochondrial membrane potential is the major regulator of mitochondrial functions, including coupling efficiency and production of reactive oxygen species (ROS). Both functions are crucial for cell bioenergetics. We previously presented evidences for a specific modulation of adenine nucleotide translocase (ANT) appearing during aging that results in a decrease in membrane potential - and therefore ROS production—but surprisingly increases coupling efficiency under conditions of low ATP turnover. Careful study of the bioenergetic parameters (oxidation and phosphorylation rates, membrane potential) of isolated mitochondria from skeletal muscles (gastrocnemius) of aged and young rats revealed a remodeling at the level of the phosphorylation system, in the absence of alteration of the inner mitochondrial membrane (uncoupling) or respiratory chain complexes regulation. We further observed a decrease in mitochondrial affinity for ADP in aged isolated mitochondria, and higher sensitivity of ANT to its specific inhibitor atractyloside. This age-induced modification of ANT results in an increase in the ADP concentration required to sustain the same ATP turnover as compared to young muscle, and therefore in a lower membrane potential under phosphorylating—in vivo—conditions. Thus, for equivalent ATP turnover (cellular ATP demand), coupling efficiency is even higher in aged muscle mitochondria, due to the down-regulation of inner membrane proton leak caused by the decrease in membrane potential. In the framework of the radical theory of aging, these modifications in ANT function may be the result of oxidative damage caused by intra mitochondrial ROS and may appear like a virtuous circle where ROS induce a mechanism that reduces their production, without causing uncoupling, and even leading in improved efficiency. Because of the importance of ROS as therapeutic targets, this new mechanism deserves further studies.

Mitochondrial Respiration in Insulin-Producing β-Cells: General Characteristics and Adaptive Effects of Hypoxia.

ObjectiveTo provide novel insights on mitochondrial respiration in β-cells and the adaptive effects of hypoxia.Methods and DesignInsulin-producing INS-1 832/13 cells were exposed to 18 hours of hypoxia followed by 20–22 hours re-oxygenation. Mitochondrial respiration was measured by high-resolution respirometry in both intact and permeabilized cells, in the latter after establishing three functional substrate-uncoupler-inhibitor titration (SUIT) protocols. Concomitant measurements included proteins of mitochondrial complexes (Western blotting), ATP and insulin secretion.ResultsIntact cells exhibited a high degree of intrinsic uncoupling, comprising about 50% of oxygen consumption in the basal respiratory state. Hypoxia followed by re-oxygenation increased maximal overall respiration. Exploratory experiments in peremabilized cells could not show induction of respiration by malate or pyruvate as reducing substrates, thus glutamate and succinate were used as mitochondrial substrates in SUIT protocols. Permeabilized cells displayed a high capacity for oxidative phosphorylation for both complex I- and II-linked substrates in relation to maximum capacity of electron transfer. Previous hypoxia decreased phosphorylation control of complex I-linked respiration, but not in complex II-linked respiration. Coupling control ratios showed increased coupling efficiency for both complex I- and II-linked substrates in hypoxia-exposed cells. Respiratory rates overall were increased. Also previous hypoxia increased proteins of mitochondrial complexes I and II (Western blotting) in INS-1 cells as well as in rat and human islets. Mitochondrial effects were accompanied by unchanged levels of ATP, increased basal and preserved glucose-induced insulin secretion.ConclusionsExposure of INS-1 832/13 cells to hypoxia, followed by a re-oxygenation period increases substrate-stimulated respiratory capacity and coupling efficiency. Such effects are accompanied by up-regulation of mitochondrial complexes also in pancreatic islets, highlighting adaptive capacities of possible importance in an islet transplantation setting. Results also indicate idiosyncrasies of β-cells that do not respire in response to a standard inclusion of malate in SUIT protocols.

Modulation of Mitochondrial Complex I Activity Averts Cognitive Decline in Multiple Animal Models of Familial Alzheimer's Disease

Development of therapeutic strategies to prevent Alzheimer's disease (AD) is of great importance. We show that mild inhibition of mitochondrial complex I with small molecule CP2 reduces levels of amyloid beta and phospho-Tau and averts cognitive decline in three animal models of familial AD. Low-mass molecular dynamics simulations and biochemical studies confirmed that CP2 competes with flavin mononucleotide for binding to the redox center of complex I leading to elevated AMP/ATP ratio and activation of AMP-activated protein kinase in neurons and mouse brain without inducing oxidative damage or inflammation. Furthermore, modulation of complex I activity augmented mitochondrial bioenergetics increasing coupling efficiency of respiratory chain and neuronal resistance to stress. Concomitant reduction of glycogen synthase kinase 3β activity and restoration of axonal trafficking resulted in elevated levels of neurotrophic factors and synaptic proteins in adult AD mice. Our results suggest that metabolic reprogramming induced by modulation of mitochondrial complex I activity represents promising therapeutic strategy for AD.

Narrow-line self-assembled GaAs quantum dots for plasmonics

We demonstrate efficient coupling of excitons in near-surface GaAs quantum dots (QDs) to surface-plasmon polaritons. We observe distinct changes in the photoluminescence of the emitters as the distance between the QDs and the gold interface decreases. Based on an electric point-dipole model, we identify the surface plasmon launching rates for different QD-surface distances. While in conventional far-field experiments only a few percent of the emitted photons can be collected due to the high refractive index semiconductor substrate, already for distances around 30 nm the plasmon launching-rate becomes comparable to the emission rate into bulk photon modes, thus much larger than the photon collection rate. For even smaller distances, the degrading optical properties of the emitter counterweight the increasing coupling efficiency to plasmonic modes.

Optical Fiber Lightening for Fluorescence Signal Detection with Thermal Stability in Dentistry

Dental caries diagnosis system has been made with a fiber lighting, camera module and band pass filter. By simply aligning a 405 nm LED (Light Emitting diode) chips directly connected polymer fibers, a compact lighting for dental fluorescence imaging could be implemented. Special designed fiber holder with proper hole diameter was fabricated to directly connect polymer fibers with 1 mm fiber diameter and increased coupling efficiency between fibers and LEDs. Fibers connected to fiber holder were polished by polishing machine to reduce insertion loss of the fiber. Experimentally, an optical insertion loss of the fiber bundle of up to 0.8 dB was achieved. Further, LED array module was packaged with equally spaced LED chips with fiber holder on metal. Fiber lightening was fabricated with directly coupled between LED array module and fiber bundle by UV epoxy without focusing lens in order to lower the lightening temperature of intraoral camera in the human mouth. The measured temperature of fabricated fiber lightening was about 25 degree celcius. To achieve a fluorescence image and dental caries diagnosis, the proper optical filter, camera module, 405 nm fiber bundle lighting and software were investigated. The performance of the fluorescence intraoral camera with fiber lightening is confirmed by fluorescence image of human tooth.

Influencing mitochondrial membrane composition and bioenergetics through omega-3 supplementation.

Influencing mitochondrial membrane composition and bioenergetics through omega-3 supplementation.

Insulin acutely improves mitochondrial function of rat and human skeletal muscle by increasing coupling efficiency of oxidative phosphorylation

Insulin is essential for the regulation of fuel metabolism and triggers the uptake of glucose by skeletal muscle. The imported glucose is either stored or broken down, as insulin stimulates glycogenesis and ATP synthesis. The mechanism by which ATP production is increased is incompletely understood at present and, generally, relatively little functional information is available on the effect of insulin on mitochondrial function. In this paper we have exploited extracellular flux technology to investigate insulin effects on the bioenergetics of rat (L6) and human skeletal muscle myoblasts and myotubes. We demonstrate that a 20-min insulin exposure significantly increases (i) the cell respiratory control ratio, (ii) the coupling efficiency of oxidative phosphorylation, and (iii) the glucose sensitivity of anaerobic glycolysis. The improvement of mitochondrial function is explained by an insulin-induced immediate decrease of mitochondrial proton leak. Palmitate exposure annuls the beneficial mitochondrial effects of insulin. Our data improve the mechanistic understanding of insulin-stimulated ATP synthesis, and reveal a hitherto undisclosed insulin sensitivity of cellular bioenergetics that suggests a novel way of detecting insulin responsiveness of cells.

Long-chain acyl coenzyme A synthetase 1 overexpression in primary cultured Schwann cells prevents long chain fatty acid-induced oxidative stress and mitochondrial dysfunction.

High circulating long chain fatty acids (LCFAs) are implicated in diabetic neuropathy (DN) development. Expression of the long-chain acyl-CoA synthetase 1 (Acsl1) gene, a gene required for LCFA metabolic activation, is altered in human and mouse diabetic peripheral nerve. We assessed the significance of Acsl1 upregulation in primary cultured Schwann cells. Acsl1 overexpression prevented oxidative stress (nitrotyrosine; hydroxyoctadecadienoic acids [HODEs]) and attenuated cellular injury (TUNEL) in Schwann cells following 12 h exposure to LCFAs (palmitate, linoleate, and oleate, 100 μM). Acsl1 overexpression potentiated the observed increase in medium to long-chain acyl-carnitines following 12 h LCFA exposure. Data are consistent with increased mitochondrial LCFA uptake, largely directed to incomplete beta-oxidation. LCFAs uncoupled mitochondrial oxygen consumption from ATP production. Acsl1 overexpression corrected mitochondrial dysfunction, increasing coupling efficiency and decreasing proton leak. Schwann cell mitochondrial function is critical for peripheral nerve function, but research on Schwann cell mitochondrial dysfunction in response to hyperlipidemia is minimal. We demonstrate that high levels of a physiologically relevant mixture of LCFAs induce Schwann cell injury, but that improved mitochondrial uptake and metabolism attenuate this lipotoxicity. Acsl1 overexpression improves Schwann cell function and survival following high LCFA exposure in vitro; however, the observed endogenous Acsl1 upregulation in peripheral nerve in response to diabetes is not sufficient to prevent the development of DN in murine models of DN. Therefore, targeted improvement in Schwann cell metabolic disposal of LCFAs may improve DN phenotypes.

Orthogonal incidence method for efficient sunlight collection from asymmetric light couplers in tree-structured light guiding systems

Directly transporting sunlight for use in indoor lighting applications is an efficient way to utilize solar energy. This study proposes a tree-structured light guiding system (TLGS) to collect sunlight and transport it for indoor illumination. The use of asymmetric light couplers in a TLGS increases the amount of accumulated sunlight. An analytic ray tracing model of the asymmetric coupler is proposed to present the angle and height distributions of the propagated rays. The cutoff angles were derived, and this cutoff condition was used to determine which rays are able to travel through the coupling region. In simulations, the couplers with coupling angles (θ(coup)) of 30° and 50° were conducted, and the large θ(coup) coupler provided high coupling efficiency (0.450). The orthogonal incidence method was adopted to increase coupling efficiency (0.646), and subsequently the amount of accumulated sunlight. The amount of accumulated sunlight in a TLGS was increased by 44%.

Free space optical communication performance analysis with focal plane based wavefront measurement

In order to decrease the Bit Error Rate (BER) and increase coupling efficiency of free space optical (FSO) communication system, we compute and compensate the wavefront aberrations of the laser signal with the wavefront measurement method based on the focal plane proposed in this paper. The aberrations of laser signal are calculated based on the two images which are respectively generated from focal plane (PF) channel and the defocused plane (DF) channel. Assuming the On–Off Keying (OOK) modulation is used under the condition of weak turbulence, the fundamental of wavefront measurement method based on focal plane is introduced. By numerical simulation, we analyze the variation trend of coupling efficiency and BER, using the method we proposed to measure and compensate the wavefront aberrations for the FSO communication system. The experiment results show that the wavefront measurement error can reach nearly 0.004 wavelengths, the average coupling efficiency increases from 10.32% to 63.82%, and the average BER of FSO communication system decreases from 10−5 to 10−13.

Ultra-Low-Field MRI and Spin-Lattice Relaxation Time of $^{1}\hbox{H}$ in the Presence of $\hbox{Fe}_{3}\hbox{O}_{4}$ Magnetic Nano-Particles Detected With a High-$T_{\rm C}$ DC-SQUID

We have carried out ultra-low-field nuclear magnetic resonance (NMR) and magnetic resonance imaging experiments in microtesla magnetic fields using a high-Tc dc-SQUID sensor. The measurements were carried out in a home-made magnetically shielded room. NMR spectra of 1H from tap water and other substance samples were obtained in the field range from 10-200 μT. By adapting a transformer coupled detection system, the signal-to-noise ratio of NMR peak in a single-shot measurement for 10 ml tap water was increased significantly as compared with our previously used direct detection method. The improvement was attributed to the increased coupling efficiency and reduced SQUID noise. By applying magnetic field gradient in three directions, one- and two-dimensional imaging results were obtained from water phantom samples. Furthermore, the effect of Fe3O4 magnetic nanoparticles on the spin-lattice relaxation time T1 was studied.

Spherical distribution structure of the semiconductor laser diode stack for pumping

A semiconductor laser diode stack is used for pumping and 8 semiconductor laser diode arrays of the stack are put on a sphere, and the output of every bar is specially off-axis compressed to realize high coupling efficiency. The output beam of this semiconductor laser diode stack is shaped by a hollow duct to the laser active medium. The efficiency of the hollow light pipe, which is used for semiconductor laser diode stack coupling, is analyzed by geometric optics and ray tracing. Geometric optics analysis diagnoses the reasons for coupling loss and guides the design of the structure. Ray tracing analyzes the relation between the structural parameters and the output characteristics of this pumping system, and guides parameter optimization. Simulation and analysis results show that putting the semiconductor laser diode arrays on a spherical surface can increase coupling efficiency, reduce the optimum duct length and improve the output energy field distribution.

Photoactivated capture molecule immobilization in plasmonic nanoapertures in the ultraviolet

We demonstrate a photoactivated surface coupling scheme for achieving spatial overlap between biomolecules of interest and optical near field excitation. Using aluminium nanoapertures, we obtained increased coupling efficiency of biotinylated capture probe oligos to the photoactivated surface due to ~3× nanoaperture enhancement of UV light. We further validate DNA sensor functionality via the hybridization of Cy-5 labeled target oligos, with up to 8× fluorescence enhancement obtained from a commercial microarray scanner. This generic photoimmobilization strategy is an essential step to realizing miniaturized plasmon enhanced detection arrays by virtue of localizing capture molecules to the region of plasmonic enhancement.

Light Coupling Between Photonic Crystal and Standard Photonic Waveguides in a Compact Photonic Integrated Circuitry Using 2D FDTD

Finite difference time domain (FDTD) analysis was used to design a photonic integrated circuitry (PIC) based on a Silicon-on-Insulator (SOI) structure. Light coupling efficiency from a single mode photonic crystal waveguide (PCW) into a single mode fibre (SMF) through adiabatic tapered waveguide and microrings based on resonance acting as spot-size converters (SSCs), is demonstrated. Optimisation of each component and their integration into a single optical chip is presented. SSCs are optimised in order to reduce back reflection and increased coupling efficiency between all devices constituting the optical chip. Significant reduction of back-reflections, insertion losses and the Fabry-Perrot noise are obtained by optimising each component and when mode and impedance matching conditions are achieved. The transmission characteristics of each component are investigated and low propagation losses in the PIC are reported.

Modulating the coupling efficiency of human cytochrome P450 CYP3A4 at electrode surfaces through protein engineering

This study shows that regulating the electron flow to the heme of human cytochrome P450 CYP3A4, using artificial redox chains, can significantly enhance its coupling efficiency and catalytic activity at electrode surfaces. The human CYP3A4 was fused at the genetic level either to the reductase domain of CYP102A1 (BMR) to create the CYP3A4/BMR or to Desulfovibrio vulgaris flavodoxin (FLD) to create the CYP3A4/FLD . Direct electrochemistry of the CYP3A4, CYP3A4/BMR and CYP3A4/FLD on glassy carbon and gold electrodes showed that the BMR and FLD flavo-proteins reduced the electron transfer rate to the CYP3A4 heme. Electrocatalysis resulted in appreciably higher product formation with the immobilized CYP3A4/BMR and CYP3A4/FLD on both surfaces due to an increased coupling efficiency. Rotating disk electrode studies and quantification of hydrogen peroxide were consistent with the proposed mechanism of a longer lived iron-peroxy species in the immobilized CYP3A4/BMR and CYP3A4/FLD. The approaches in this study provide a better understanding of cytochrome P450 uncoupling at electrode surfaces and aids in the construction of improved cytochrome P450 biosensors and bioelectrocatalysts.

Male Head Secretion Triggers Copulation in the Dwarf SpiderDiplocephalus permixtus

AbstractThe term nuptial feeding is applied for any possible form of transfer of substances during the course of mating. However, the underlying functions can range from increased coupling efficiency or increased male survival to various levels of sexual selection. Males of many dwarf spider species (Erigoninae: Linyphiidae; Araneae) produce secretions from conspicuous grooves or elevations on their prosoma that seem to play a role during the mating episode. We asked if these structures represent a survival strategy, a mating effort in that they function as a mate attractant or as a mechanism to secure matings or if they simply facilitate successful genital coupling. InDiplocephalus permixtusmales possess a deep groove in the ocular area into which females sink their chelicerae before mating commences. Secretory glands in the area of the groove produce a substance, which is taken up by the female in the process of mating. We experimentally prevented females from taking up secretion by covering the head structures of one group of males and compared the behaviour with controls. We investigated effects in a single male setting as well as in a competitive two‐males setting. Under both experimental conditions the probability that copulation occurred was significantly reduced in head covered males: females bit into male head structures irrespective of male treatment but covered males did not commence pedipalp insertion despite optimal mating position. Our data suggest that in contrast to other gustatorial arthropod species investigated so far the head–mouth contact between the sexes primarily triggers the mating behaviour of the male and not that of the female. Clearly, the secretion does not function as a mate attractant as mating position was achieved with similar probability in covered and control males. A function as a survival strategy can be excluded as well, because sexual cannibalism never occurred. Potential stimulating or manipulative effects of the secretion during copulatory and post‐copulatory phases remain to be investigated.

Losing RGS2 and a Taste for GHB

Depending on concentration, agonists of the γ-aminobutyric acid type B (GABA B ) receptor can either potentiate or inhibit the activity of dopaminergic neurons arising in the ventral tegmentum (a pathway involved in addiction). Labouèbe et al.-- researchers who provided a plausible mechanism for these opposing effects by showing that the coupling efficiency of GABA B receptors to G protein-activated inwardly rectifying potassium (GIRK) channels was greater in inhibitory GABAergic neurons than in dopaminergic neurons--explored regulation of GABA B -GIRK coupling. Immunoelectron microscopy of transgenic mice lacking different GIRK subunits showed that GIRK2 and GIRK3 were present in both ventral tegmental neurons in which they could detect tyrosine hydroxylase (TH, the rate-limiting enzyme for dopamine synthesis) and in neurons lacking TH, whereas GIRK1 was not found in TH-containing neurons. Both GIRK2 and GIRK3 contributed to currents evoked in dopaminergic neurons by the high-affinity GABA B agonist baclofen. Pharmacological analysis indicated that inhibition of regulator of G protein signaling proteins (RGS proteins, which act as GTPase-activating proteins) increased coupling efficiency (lowered EC 50 ) of GABA B to GIRK. Furthermore, RGS2 was preferentially expressed in dopaminergic neurons and coupling efficiency was increased in mice lacking RGS2. Fluorescence resonance energy transfer (FRET) analysis, as well as electrophysiological analysis of knockout mice, indicated that RGS2 interacted directly with GIRK3 but not GIRK2. Repeated exposure of mice to γ-hydroxybutyrate (GHB, an addictive, low-affinity GABA B receptor agonist) or morphine over several days led to an increase in coupling efficiency between GABA B receptors and GIRK in dopaminergic neurons, as well as a decrease in RGS2 mRNA in the ventral tegmentum. Intriguingly, chronic exposure to GHB caused mice to lose their preference for solutions containing it and instead to avoid them. The authors suggest that these data may provide insight into new approaches to targeting dopaminergic activity in the ventral tegmentum to treat addiction. G. Labouèbe, M. Lomazzi, H. G. Cruz, C. Creton, R. Luján, M. Li, Y. Yanagawa, K. Obata, M. Watanabe, K. Wickman, S. B. Boyer, P. A. Slesinger, C. Lüscher, RGS2 modulates coupling between GABA B receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Nat. Neurosci. 10 , 1559-1568 (2007). [PubMed]

Adenosine Receptors and Angiogenesis

See related article, pages 1130–1138 As originally hypothesized by Berne,1 adenosine is formed in the heart during hypoxia or ischemia and serves as a negative feedback signal to maintain oxygen delivery within a normal physiological range. Adenosine is formed by the metabolism of ATP and transported into the extracellular space by various nucleoside transport proteins.2 In a more localized manner that provides the opportunity for coordinated signaling with the diverse P2 purinoreceptor family that recognizes ATP and ADP, adenosine is also formed from the extracellular metabolism of adenine nucleotides released from stored granules (sympathetic nerves, platelets, mast cells) or through hemichannels (neutrophils, endothelial cells, epithelial cells) by ecto-apyrases and ecto-nucleotidases.3–5 Adenosine signals through activation of widely distributed cell surface G protein–coupled receptors, of which 4 different subtypes have been identified designated A1, A2A, A2B, and A3.6 By activating A2A receptors that are abundantly expressed in coronary vascular smooth muscle, adenosine generated under hypoxic conditions produces potent vasodilation thereby increasing nutrient and oxygen delivery. Although less appreciated, adenosine also serves to maintain tissue oxygenation in response to chronic ischemic/hypoxic stress by increasing the formation of new blood vessels; that is, by stimulating angiogenesis.7,8 Using adenosine receptor agonists or modulators of adenosine metabolism, an important role for adenosine has been established in in vivo models of angiogenesis.7,8 In cell culture systems, adenosine stimulates endothelial cell migration, proliferation, and tube formation,7–11 actions required for the formation of new capillary networks. This action occurs at concentrations of adenosine that are …

Enhanced Ryanodine‐Mediated Calcium Release in Mutant PS1‐Expressing Alzheimer's Mouse Models

Intracellular Ca(2+) signaling involves Ca(2+) liberation through both inositol triphosphate and ryanodine receptors (IP(3)R and RyR). However, little is known of the functional interactions between these Ca(2+) sources in either neuronal physiology, or during Ca(2+) disruptions associated with Alzheimer's disease (AD). By the use of whole-cell recordings and 2-photon Ca(2+) imaging in cortical slices we distinguished between IP(3)R- and RyR-mediated Ca(2+) components in nontransgenic (non-Tg) and AD mouse models and demonstrate powerful signaling interactions between these channels. Ca(2+)-induced Ca(2+) release (CICR) through RyR contributed modestly to Ca(2+) signals evoked by photoreleased IP(3) in cortical neurons from non-Tg mice. In contrast, the exaggerated signals in 3xTg-AD and PS1(KI) mice resulted primarily from enhanced CICR through RyR, rather than through IP(3)R, and were associated with increased RyR expression levels. Moreover, membrane hyperpolarizations evoked by IP(3) in neurons from AD mouse models were even greater than expected simply from the exaggerated Ca(2+) signals, pointing to an increased coupling efficiency between cytosolic [Ca(2+)] and K(+) channel regulation. Our results highlight the critical roles of RyR-mediated Ca(2+) signaling in both neuronal physiology and pathophysiology, and point to presenilin-linked disruptions in RyR signaling as an important genetic factor in AD.

A hybrid AlGaInAs-silicon evanescent preamplifier and photodetector

We report the integration of a hybrid silicon evanescent waveguide photodetector with a hybrid silicon evanescent optical amplifier. The device operates at 1550 nm with a responsivity of 5.7 A/W and a receiver sensitivity of -17.5 dBm at 2.5 Gb/s. The transition between the passive silicon waveguide and the hybrid waveguide of the amplifier is tapered to increase coupling efficiency and to minimize reflections.