In vertebrates, 14-3-3 proteins form a family of seven highly conserved isoforms with chaperone activity, which bind phosphorylated substrates mostly involved in regulatory and checkpoint pathways. ...14-3-3 proteins are the most abundant protein in the brain and are abundantly found in the cerebrospinal fluid in neurodegenerative diseases, suggesting a critical role in neuron physiology and death. Here we show that 14-3-3eta-deficient mice displayed auditory impairment accompanied by cochlear hair cells' degeneration. We show that 14-3-3eta is highly expressed in the outer and inner hair cells, spiral ganglion neurons of cochlea and retinal ganglion cells. Screening of
, the gene encoding the 14-3-3eta isoform, in non-syndromic and syndromic deafness, revealed seven non-synonymous variants never reported before. Among them, two were predicted to be damaging in families with syndromic deafness.
, variants of
induce mild mitochondrial fragmentation and severe susceptibility to apoptosis, in agreement with a reduced capacity of mutated 14-3-3eta to bind the pro-apoptotic Bad protein. This study demonstrates that
variants can have a substantial effect on 14-3-3eta function and that 14-3-3eta could be a critical factor in the survival of outer hair cells.
Hereditary optic neuropathies, resulting from retinal ganglion cell degeneration, are a heterogeneous group of diseases ranging from asymptomatic forms to legal blindness.
Two most frequent ...phenotypes are Kjer's disease, an autosomal dominant optic atrophy caused by OPA1 gene mutations, and Leber's disease due to maternally inherited mitochondrial DNA mutations.
Both optic neuropathies usually isolated are sometimes associated with extraocular symptoms, especially neurological symptoms, thus justifying a systematic neurological evaluation and brain imaging.
Wavelet-based methods have proven their efficiency for visualization at different levels of detail, progressive transmission, and compression of large data sets. The required core of all ...wavelet-based methods is a hierarchy of meshes that satisfies subdivision-connectivity. This hierarchy has to be the result of a subdivision process starting from a base mesh. Examples include quadtree uniform 2D meshes, octree uniform 3D meshes, or 4-to-1 split triangular meshes. In particular, the necessity of subdivision-connectivity prevents the application of wavelet-based methods on irregular triangular meshes. In this paper, a "wavelet-like" decomposition is introduced that works on piecewise constant data sets over irregular triangular surface meshes. The decomposition/reconstruction algorithms are based on an extension of wavelet-theory allowing hierarchical meshes without property. Among others, this approach has the following features: it allows exact reconstruction of the data set, even for nonregular triangulations, and it extends previous results on Haar-wavelets over 4-to-1 split triangulations.
Precision sound velocity measurements can simultaneously determine binary gas composition and flow. We have developed an analyzer with custom electronics, currently in use in the ATLAS inner ...detector, with numerous potential applications. The instrument has demonstrated similar to 0.3% mixture precision for C sub(3)F sub(8)/C sub(2)F sub(6) mixtures and < 10 super(-4) resolution for N sub(2)/C sub(3)F sub(8) mixtures. Moderate and high flow versions of the instrument have demonstrated flow resolutions of plus or minus 2% of full scale for flows up to 250 1 min super(-1), and plus or minus 1.9% of full scale for linear flow velocities up to 15 m s super(-1); the latter flow approaching that expected in the vapour return of the thermosiphon fluorocarbon coolant recirculator being built for the ATLAS silicon tracker.
Custom ultrasonic instruments have been developed for continuous monitoring and real-time measurement of composition and flow in binary gas mixtures. These characteristics are derived from ...measurements of sound transit time along two opposite directions - parallel or tilted to the gas flow direction. The flow rate is then calculated from the transit time difference while the average is used to compute sound velocity by comparison with a sound velocity/composition database. Five devices are integrated in the Detector Control System of the ATLAS experiment at the CERN Large Hadron Collider. Three instruments monitor C3F8 and CO2 coolant leaks into the nitrogen-purged envelopes of the inner silicon tracker; respectively with precisions better than ±2 × 10-5 and ±10-4. Two further instruments are used to monitor the new thermosiphon C3F8 evaporative coolant recirculator. One of these measures C3F8 vapour return flow to the condenser while the other tracks air ingress into the condenser with a precision better than 10-3. The precision of these instruments highlights their potential in other applications requiring continuous binary gas composition monitoring.
The heterozygous R445H mutation in OPA1 was found in five patients with optic atrophy and deafness. Audiometry suggested that the sensorineural deafness resulted from auditory neuropathy. Skin ...fibroblasts showed hyperfragmentation of the mitochondrial network, decreased mitochondrial membrane potential, and adenosine triphosphate synthesis defect. In addition, OPA1 was found to be widely expressed in the sensory and neural cochlear cells of the guinea pig. Thus, optic atrophy and deafness may be related to energy defects due to a fragmented mitochondrial network. Ann Neurol 2005
Leber's hereditary optic neuropathy (LHON) is caused by mutations in the complex I subunits of the respiratory chain. Although patients have been treated with idebenone since 1992, the efficacy of ...the drug is still a matter of debate.
We evaluated the effect of idebenone in fibroblasts from LHON patients using enzymatic and polarographic measurements.
Complex I activity was 42% greater in treated fibroblasts compared to controls (p = 0.002). Despite this complex I activity improvement, the effects on mitochondrial respiration were contradictory, leading to impairment in some cases and stimulation in others.
These results indicate that idebenone is able to compensate the complex I deficiency in LHON patient cells with variable effects on respiration, indicating that the patients might not be equally likely to benefit from the treatment.
The CLAS drift chamber system Mestayer, M.D; Carman, D.S; Asavapibhop, B ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
07/2000, Letnik:
449, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Experimental Hall B at Jefferson Laboratory houses the CEBAF Large Acceptance Spectrometer, the magnetic field of which is produced by a superconducting toroid. The six coils of this toroid divide ...the detector azimuthally into six sectors, each of which contains three large multi-layer drift chambers for tracking charged particles produced from a fixed target on the toroidal axis. Within the 18 drift chambers are a total of 35,148 individually instrumented hexagonal drift cells. The novel geometry of these chambers provides for good tracking resolution and efficiency, along with large acceptance. The design and construction challenges posed by these large-scale detectors are described, and detailed results are presented from in-beam measurements.
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