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We have studied the effects of idebenone on mitochondrial function in cybrids derived from one normal donor (HQB17) and one patient harboring the G3460A/MT-ND1 mutation of Leber's Hereditary Optic Neuropathy (RJ206); and in XTC.UC1 cells bearing a premature stop codon at aminoacid 101 of MT-ND1 that hampers complex I assembly. Addition of idebenone to HQB17 cells caused mitochondrial depolarization and NADH depletion, which were inhibited by cyclosporin (Cs) A and decylubiquinone, suggesting andoi:10.1016/j.bbabio.2011.10.012 pmid:22086148 pmcid:PMC3265671 fatcat:6uvjjv43r5go3hoqv5jzl3j6hy
more »... involvement of the permeability transition pore (PTP). On the other hand, addition of dithiothreitol together with idebenone did not cause PTP opening and allowed maintenance of the mitochondrial membrane potential even in the presence of rotenone. Addition of dithiothreitol plus idebenone, or of idebenol, to HQB17, RJ206 and XTC.UC1 cells sustained membrane potential in intact cells and ATP synthesis in permeabilized cells even in the presence of rotenone and malonate, and restored a good level of coupled respiration in complex I-deficient XTC.UC1 cells. These findings demonstrate that idebenol can feed electrons at complex III. If the quinone is maintained in the reduced state, a task that in some cell types appears to be performed by dicoumarol-sensitive NAD(P)H:quinone oxidoreductase 1 [Haefeli et al. (2011) PLoS One 6, e17963], electron transfer to complex III may allow reoxidation of NADH in complex I deficiencies.
Carelli, E. Maccioni and M. Pizzocaro are with the Department of Physics "Enrico Fermi", Università di Pisa, and CNISM unità di Pisa. E-mail: firstname.lastname@example.org • F. Bosi and A. ...arXiv:1001.0476v1 fatcat:axhspbrc6jgsnhizzylvkwwvn4
Inertial sensors stimulate very large interest, not only for their application but also for fundamental physics tests. Ring laser gyros, which measure angular rotation rate, are certainly among the most sensitive inertial sensors, with excellent dynamic range and bandwidth. Large area ring laser gyros are routinely able to measure fractions of prad/s, with high duty cycle and bandwidth, providing fast, direct and local measurement of relevant geodetic and geophysical signals. Improvements of aarXiv:1904.02533v1 fatcat:epooxttx3fc5bexbtpsofuu57e
more »... actor 10-100 would open the windows for general relativity tests, as the GINGER project, an Earth based experiment aiming at the Lense-Thirring test at 1% level. However, it is well known that the dynamics of the laser induces non-linearities, and those effects are more evident in small scale instruments. Sensitivity and accuracy improvements are always worthwhile, and in general there is demand for high sensitivity environmental study and development of inertial platforms, where small scale transportable instruments should be used. We discuss a novel technique to analyse the data, aiming at studying and removing those non-linearity. The analysis is applied to the two ring laser prototypes GP2 and GINGERINO, and angular rotation rate evaluated with the new and standard methods are compared. The improvement is evident, it shows that the back-scatter problem of the ring laser gyros is negligible with a proper analysis of the data, improving the performances of large scale ring laser gyros, but also indicating that small scale instruments with sensitivity of nrad/s are feasible.
We report on the measurements of tilt noise performed at the Virgo site with a ring laser gyroscope. The apparatus is a He-Ne laser operating in a square cavity mounted on a vertical plane perpendicular to the north-south arm of the inteferometer. We discuss the possibility of using the ring laser signal to improve the performances of the control system of the Virgo seismic suspensions. The comparison between the ring laser signal and the control signals for the longitudinal translations of thearXiv:1108.3236v1 fatcat:kapfkeet75di7okyzw3bkksgta
more »... inverted pendulum (IP) shows remarkable coherence in the frequency range 20-200 mHz.
GINGER (Gyroscopes IN General Relativity) is a proposal for an Earth-based experiment to measure the Lense-Thirring (LT) and de Sitter effects. GINGER is based on ring lasers, which are the most sensitive inertial sensors to measure the rotation rate of the Earth. We show that two ring lasers, one at maximum signal and the other horizontal, would be the simplest configuration able to retrieve the GR effects. Here, we discuss this configuration in detail showing that it would have the capabilitydoi:10.1140/epjp/i2017-11452-6 fatcat:zsitzv7ndjehzorsd3ocfj2ln4
more »... to test LT effect at 1%, provided the accuracy of the scale factor of the instrument at the level of 1 part in 10 12 is reached. In principle, one single ring laser could do the test, but the combination of the two ring lasers gives the necessary redundancy and the possibility to verify that the systematics of the lasers are sufficiently small. The discussion can be generalised to seismology and geodesy and it is possible to say that signals 10-12 orders of magnitude below the Earth rotation rate can be studied; the proposed array can be seen as the basic element of multi-axial systems, and the generalisation to three dimensions is feasible adding one or two devices and monitoring the relative angles between different ring lasers. This simple array can be used to measure with very high precision the amplitude of angular rotation rate (the length of the day, LOD), its short term variations, and the angle between the angular rotation vector and the horizontal ring laser. Finally this experiment could be useful to probe gravity at fundamental level giving indications on violations of Einstein Equivalence Principle and Lorenz Invariance and possible chiral effects in the gravitational field.
Carelli and G. Marfia contributed equally to this work. ...doi:10.1155/2011/453179 pmid:21766022 pmcid:PMC3135044 fatcat:mrx3mlvvenhlrit7wyi4u5ekti
This mini-review summarizes our present view of the biochemical alterations associated with mitochondrial DNA (mtDNA) point mutations. Mitochondrial cytopathies caused by mutations of mtDNA are well-known genetic and clinical entities, but the biochemical pathogenic mechanisms are often obscure. Leber's hereditary optic neuropathy (LHON) is due to three main mutations in genes for complex I subunits. Even if the catalytic activity of complex I is maintained except in cells carrying the 3460/ND1doi:10.1016/j.bbabio.2004.03.013 pmid:15282179 fatcat:kmohhydohneb5af25aqq3luobq
more »... mutation, in all cases there is a change in sensitivity to complex I inhibitors and an impairment of mitochondrial respiration, eliciting the possibility of generation of reactive oxygen species (ROS) by the complex. Neurogenic muscle weakness, Ataxia and Retinitis Pigmentosa (NARP), is due to a mutation in the ATPase-6 gene. In NARP patients ATP synthesis is strongly depressed to an extent proportional to the mutation load; nevertheless, ATP hydrolysis and ATP-driven proton translocation are not affected. It is suggested that the NARP mutation affects the ability of the enzyme to couple proton transport to ATP synthesis. A point mutation in subunit III of cytochrome c oxidase is accompanied by a syndrome resembling MELAS: however, no major biochemical defect is found, if we except an enhanced production of ROS. The mechanism of such enhancement is at present unknown. In this review, we draw attention to a few examples in which the overproduction of ROS might represent a common step in the induction of clinical phenotypes and/or in the progression of several human pathologies associated with mtDNA point mutations. D
Plant water resource management is one of the main future challenges to fight recent climatic changes. The knowledge of the plant water content could be indispensable for water saving strategies. Terahertz spectroscopic techniques are particularly promising as a non-invasive tool for measuring leaf water content, thanks to the high predominance of the water contribution to the total leaf absorption. Terahertz quantum cascade lasers (THz QCL) are one of the most successful sources of THzdoi:10.1186/s13007-017-0197-z pmid:28638439 pmcid:PMC5474302 fatcat:pgivtzlvmze4bhd2hqjd4ndk5e
more »... n. Results: Here we present a new method which improves the precision of THz techniques by combining a transmission measurement performed using a THz QCL source, with simple pictures of leaves taken by an optical camera. As a proof of principle, we performed transmission measurements on six plants of Vitis vinifera L. (cv "Colorino"). We found a linear law which relates the leaf water mass to the product between the leaf optical depth in the THz and the projected area. Results are in optimal agreement with the proposed law, which reproduces the experimental data with 95% accuracy. Conclusions: This method may overcome the issues related to intra-variety heterogeneities and retrieve the leaf water mass in a fast, simple, and non-invasive way. In the future this technique could highlight different behaviours in preserving the water status during drought stress.
Inertial sensors are important at application level and also in fundamental physics. Ring laser gyroscopes, which measure angular rotation rates, are among the most sensitive ones. Large area ring laser reach sensitivities at the level of fractions of prad/s, allowing measurements of relevant geophysical signals. Improvements of a factor 10-100 would make these instruments able to measure general relativity effects; this is the goal e.g. of the GINGER project, an Earth based experiment aimingdoi:10.1140/epjc/s10052-019-7089-5 fatcat:re7wyknkgra3jcekweu3rvz6ne
more »... test the Lense-Thirring effect with an accuracy of 1%. However, the laser induces non-linearities, effects larger in small scale instruments. We discuss a novel technique to analyse data, able to reduce nonlinear laser effects. We apply this technique to data from two ring laser prototypes, and compare the precision of the measurement of the angular rotation rate obtained with the new and the standard methods. We show that the back-scatter problem of the ring laser gyroscopes is negligible with a proper analysis of the data. These results not only allow to improve the performance of large scale ring laser gyroscopes but also pave the way to the development of small scale instruments with nrad/s sensitivity, which are precious for environmental studies and as inertial platforms.
aircfaft construction factory where adhesives containing chromium were used showed that the exposure risk was negligible but that it could be further reduced by using personal protective equipment. 4) Carelli ...doi:10.2486/indhealth.36.74 pmid:9473863 fatcat:ywuewzegubbqlc4shabunzp3ry
The debate on gravity theories to extend or modify General Relativity is very active today because of the issues related to ultra-violet and infra-red behavior of Einstein's theory. In the first case, we have to address the Quantum Gravity problem. In the latter, dark matter and dark energy, governing the large scale structure and the cosmological evolution, seem to escape from any final fundamental theory and detection. The state of art is that, up to now, no final theory, capable ofarXiv:2103.15135v1 fatcat:mi32wlpovvg7bpnaevmpvv7qtu
more »... gravitational interaction at any scale, has been formulated. In this perspective, many research efforts are devoted to test theories of gravity by space-based experiments. Here we propose straightforward tests by the GINGER experiment, which, being Earth based, requires little modeling of external perturbation, allowing a thorough analysis of the systematics, crucial for experiments where sensitivity breakthrough is required. Specifically, we want to show that it is possible to constrain parameters of gravity theories, like scalar-tensor or Horava-Lifshitz gravity, by considering their post-Newtonian limits matched with experimental data. In particular, we use the Lense-Thirring measurements provided by GINGER to find out relations among the parameters of theories and finally compare the results with those provided by LARES and Gravity Probe-B satellites.
Allergic rhinitis (AR) is a relevant risk factor for the development of asthma in children. We recruited a cohort of 104 children with AR and re-evaluated them after 5 years. We considered the ARIA classification. All patients, who had moderate to severe persistent AR at baseline, developed asthma symptoms. These results strongly indicate that the severity of AR may be an important factor that increases the risk of asthma development in children.doi:10.1186/s40413-015-0061-4 pmid:26023322 pmcid:PMC4439609 fatcat:a2uk4i7m5jhjjefrxmgmamnruy
G-Pisa is an experiment dealing with a high sensitivity laser gyroscope with area of the order of 1 m 2 . It aims at improving the performances of the mirrors suspensions of the future generations gravitational wave antenna Virgo. The experimental set-up consists in a He-Ne ring laser with a 4 mirrors square cavity. The device is operational on a stable regime, with the laser operating both single mode or multi mode. The low-frequency sensitivity, 0.001−1 Hz, is limited by the environmentaldoi:10.1088/0264-9381/27/8/084033 fatcat:wubd5uobxze4japcjvzi3lu2c4
more »... e, but it has been checked that the requirements for the Inverted Pendulum tilts control given for AdVirgo are fulfilled, (10 −8 rad/ √ Hz at 30mHz).
Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease associated with point mutations in mitochondrial DNA. The most frequent of these mutations is the G-to-A substitution at nucleotide position 11,778 which changes an evolutionarily conserved arginine with a histidine at position 340 in subunit ND4 of NADH : ubiquinone reductase (respiratory complex I). We report that this amino acid substitution alters the affinity of complex I for the ubiquinone substrate and inducesdoi:10.1016/0014-5793(94)00971-6 pmid:7926004 fatcat:t3kzjmvnpbeudlutxcbzyxewhm
more »... sistance towards its potent inhibitor rotenone in mitochondria of LHON patients. Such changes could reflect a substantial loss in the energy conserving function of NADH: ubiquinone reductase and thus explain the pathological effect of the ND4/11,778 mutation.
Recent advances in large ring laser gyroscopes (RLG) technologies opened the possibility to observe rotations of the ground with sensitivities up to 10^-11 rad/s over the frequency band of seismological interest (0.01-1Hz), thus opening the way to a new geophysical discipline, i.e. rotational seismology. A measure of rotations in seismology is of fundamental interest for (a) the determination of all the six degrees of freedom that characterize a rigid body motion, and (b) the quantitativearXiv:1601.05960v1 fatcat:j2r3i4v6vnbkde26whlcskqonm
more »... te of the rotational motions contaminating ground translation measurements obtained from standard seismometers. Within this framework, this paper presents and describes GINGERino, a new large observatory-class RLG located in Gran Sasso underground laboratory (LNGS), one national laboratories of the INFN (Istituto Nazionale di Fisica Nucleare). We also report unprecedented observations and analyses of the roto-translational signals from a tele-seismic event observed in such a deep underground environment.
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