Measurement of intra-retinal layer thickness using optical coherence tomography (OCT) has become increasingly prominent in multiple sclerosis (MS) research. Nevertheless, the approaches used for determining the mean layer thicknesses vary greatly. Insufficient data exist on the reliability of different thickness estimates, which is crucial for their application in clinical studies. This study addresses this lack by evaluating the repeatability of different thickness estimates.
Methods
Studies that used intra-retinal layer segmentation of macular OCT scans in patients with MS were retrieved from PubMed. To investigate the repeatability of previously applied layer estimation approaches, we generated datasets of repeating measurements of 15 healthy subjects and 13 multiple sclerosis patients using two OCT devices (Cirrus HD-OCT and Spectralis SD-OCT). We calculated each thickness estimate in each repeated session and analyzed repeatability using intra-class correlation coefficients and coefficients of repeatability.
Results
We identified 27 articles, eleven of them used the Spectralis SD-OCT, nine Cirrus HD-OCT, two studies used both devices and two studies applied RTVue-100. Topcon OCT-1000, Stratus OCT and a research device were used in one study each. In the studies that used the Spectralis, ten different thickness estimates were identified, while thickness estimates of the Cirrus OCT were based on two different scan settings. In the simulation dataset, thickness estimates averaging larger areas showed an excellent repeatability for all retinal layers except the outer plexiform layer (OPL).
Conclusions
Given the good reliability, the thickness estimate of the 6mm-diameter area around the fovea should be favored when OCT is used in clinical research. Assessment of the OPL was weak in general and needs further investigation before OPL thickness can be used as a reliable parameter. 相似文献
The authors monitored five maternity colonies of Plecotus austriacus to obtain data about phenology, roosting, and emergence behaviour. The bats occupied their roosts between April and October, with maximum colony sizes in August. Roosting sites in the attic’s roof ridge and temperatures of 20–25°C were favoured. Also considering the small colony (maximum 59) and cluster sizes (maximum 13 bats), P. austriacus behaved less thermophilic than other attic-dwelling species. During low temperatures, the bats chose small crevice-like roosting sites to compensate for that; during daytime, many bats remained hidden in crevices. Emergence began approximately 30 min after sunset; the bats used multiple, preferably crevice-like openings. P. austriacus left its summer roosts comparatively late; renovation works should, therefore, not start before November. For monitoring purposes, we recommend two to three emergence countings outside the attics in early August during warm weather, alongside two attic inspections 1–2 h before emergence for offspring monitoring.
Ca2+ and Mn2+ promote the binding of the basic isoperoxidase to a crude membrane preparation in extracts from Pharbitis cotyledons. The Ca2+- or Mn2+-induced binding is resistant to high ionic strength and can be saturated by increasing the divalent ion or the isoperoxidase concentrations. Treatments in vitro with glucosaminidase or in vivo with tunicamycin show that the carbohydrate part of the isoperoxidase is necessary for the binding. The amino sugar galactosamine inhibits the binding at rather high concentrations. Pharbitis basic isoperoxidase can be bound to zucchini squash microsomes in the presence of Ca2+ and conversely. 相似文献
Type I interferons (IFN-alpha/beta) were originally discovered by their strong and direct antiviral activity [A. Isaacs, J. Lindenmann, Virus interference. I. The interferon, Proc. R. Soc. Lond. B Biol. Sci. 147 (1957) 258-267]. (see review by J. Lindenmann on p. 719, in this issue). Nevertheless, only very recently it was entirely realized that viruses would not succeed without efficient tools to undermine this potent host defense system. Current investigations are revealing an astonishing variety of viral IFN antagonistic strategies targeting virtually all parts of the IFN system, often in a highly specific manner. Viruses were found to interfere with induction of IFN synthesis, IFN-induced signaling events, the antiviral effector proteins, or simply shut off the host cell macromolecule synthesis machinery to avoid booting of the antiviral host defense. Here, we will describe a few well-characterized examples to illustrate the sophisticated and often multi-layered anti-IFN mechanisms employed by viruses. 相似文献
Transketolase is a prominent thiamin diphosphate-dependent enzyme in sugar metabolism that catalyzes the reversible transfer of a 2-carbon dihydroxyethyl fragment between a donor ketose and an acceptor aldose. The X-ray structures of transketolase from E. coli in a covalent complex with donor ketoses d-xylulose 5-phosphate (X5P) and d-fructose 6-phosphate (F6P) at 1.47 A and 1.65 A resolution reveal significant strain in the tetrahedral cofactor-sugar adducts with a 25-30 degrees out-of-plane distortion of the C2-Calpha bond connecting the substrates' carbonyl with the C2 of the cofactor's thiazolium part. Both intermediates adopt very similar extended conformations in the active site with a perpendicular orientation of the scissile C2-C3 sugar bond relative to the thiazolium ring. The sugar-derived hydroxyl groups of the intermediates form conserved hydrogen bonds with one Asp side chain, with a cluster of His residues and with the N4' of the aminopyrimidine ring of the cofactor. The phosphate moiety is held in place by electrostatic and hydrogen-bonding interactions with Arg, His, and Ser side chains. With the exception of the thiazolium part of the cofactor, no structural changes are observable during intermediate formation indicating that the active site is poised for catalysis. DFT calculations on both X5P-thiamin and X5P-thiazolium models demonstrate that an out-of-plane distortion of the C2-Calpha bond is energetically more favorable than a coplanar bond. The X-ray structure with the acceptor aldose d-ribose 5-phosphate (R5P) noncovalently bound in the active site suggests that the sugar is present in multiple forms: in a strained ring-closed beta-d-furanose form in C2-exo conformation as well as in an extended acyclic aldehyde form, with the reactive C1 aldo function held close to Calpha of the presumably planar carbanion/enamine intermediate. The latter form of R5P may be viewed as a near attack conformation. The R5P binding site overlaps with those of the leaving group moieties of the covalent donor-cofactor adducts, demonstrating that R5P directly competes with the donor-derived products glyceraldehyde 3-phosphate and erythrose 4-phosphate, which are substrates of the reverse reaction, for the same docking site at the active site and reaction with the DHEThDP enamine. 相似文献
The TNF receptor family member BAFFR is essential for providing mature B cells with pro‐survival signals and has recently been claimed to transduce these, though not exclusively, via a Syk‐dependent signaling hub that feeds into ERK/AKT activation. In this issue of The EMBO Journal, Hobeika et al (2015) describe a synergistic pro‐survival scenario involving BAFFR and CD19, which remains functional under Syk null conditions and is able to maintain mature B‐cell survival. The authors hence propose a BAFFR‐/CD19‐driven mechanism to act in parallel with homeostatic NF‐κB/AKT activation in non‐stimulated B cells. 相似文献
Bacillus methanolicus MGA3 is a model facultative methylotroph of interest for fundamental research and biotechnological applications. Previous research uncovered a number of pathways potentially involved in one‐carbon substrate utilization. Here, we applied dynamic 13C labeling to elucidate which of these pathways operate during growth on methanol and to uncover potentially new ones. B. methanolicus MGA3 uses the assimilatory and dissimilatory ribulose monophosphate (RuMP) cycles for conversion of the central but toxic intermediate formaldehyde. Additionally, the operation of two cofactor‐dependent formaldehyde oxidation pathways with distinct roles was revealed. One is dependent on tri‐ and tetraglutamylated tetrahydrofolate (THF) and is involved in formaldehyde oxidation during growth on methanol. A second pathway was discovered that is dependent on bacillithiol, a thiol cofactor present also in other Bacilli where it is known to function in redox‐homeostasis. We show that bacillithiol‐dependent formaldehyde oxidation is activated upon an upshift in formaldehyde induced by a substrate switch from mannitol to methanol. The genes and the corresponding enzymes involved in the biosynthesis of bacillithiol were identified by heterologous production of bacillithiol in Escherichia coli. The presented results indicate metabolic plasticity of the methylotroph allowing acclimation to fluctuating intracellular formaldehyde concentrations. 相似文献