Seasonal variations of semidiurnal tidalperturbations in mesopause region temperature and zonal and meridional winds above Fort Collins, Colorado(40.6°N, 105.1°W)

On the basis of Colorado State University (CSU) Na lidar observations over full diurnal cycles from May 2002 to April 2006, a harmonic analysis was performed to extract semidiurnal perturbations in mesopause region temperature and zonal and meridional winds over Fort Collins, Colorado (40.6°N, 105.1°W). The observed monthly results are in good agreement with MF radar tidal climatology for Urbana, Illinois, and with predictions of the Hamburg Model of the Neutral and Ionized Atmosphere (HAMMONIA), sampled at the CSU Na lidar coordinates. The observed semidiurnal tidal period perturbation within the mesopause region is found to be dominated by propagating modes in winter and equinoctial months with a combined vertical wavelength varying from 50 km to almost 90 km and by a mode with evanescent behavior and longer vertical wavelength (100–150 km) in summer months, most likely due to dominance of (2, 2) and (2, 3) tidal (Hough) modes. The observed semidiurnal tidal amplitude shows strong seasonal variation, with a large amplitude during the winter months, with a higher growth rate above ∼85–90 km, and minimal amplitudes during the summer months. Maximum tidal amplitudes over 50 m/s for wind and 12 K for temperature occur during fall equinox. A detailed comparison with HAMMONIA predictions shows excellent agreement in semidiurnal phases. HAMMONIA-predicted semidiurnal amplitudes generally agree well with observations; however, HOMMONIA underestimates temperature amplitudes in some of the nonsummer months as well as zonal wind and meridional wind amplitudes in April and September but overestimates them in February. To reveal the effects of the atmospheric background on vertical propagation of tidal modes and their relative importance in the composite semidiurnal tide during different seasons, we use the lidar-observed monthly mean temperature and zonal wind from the same data set as well as HAMMONIA output to calculate the vertical wave number seasonal variations of the major tidal modes of the migrating semidiurnal tide. This leads to a qualitative understanding of the lidar-observed and HAMMONIA-predicted seasonal variation of the semidiurnal tidal perturbation

Characterisation of transmembrane protein 114 (TMEM114), a protein associated with juvenile onset cataract

Transmembrane protein 114 (TMEM114) is an uncharacterised predicted transmembrane protein expressed in the lens epithelium. A balanced translocation that transects the putative promoter of TMEM114 is associated with autosomal dominant congenital cataract (ADCC), however, coding sequence variants in TMEM114 were not identified in a panel of ADCC patients. Subsequent to the identification of TMEM114 a similar novel transmembrane protein named TMEM114-like protein 1 (TMLP1) was identified. This study aimed to functionally characterise the two novel proteins TMEM114 and TMLP1.TMEM114 and TMLP1 showed homology to voltage dependent calcium channel gamma (γ) subunits, but TMEM114 and TMLP1 lacked some of the key domains present in these proteins. Expression of TMEM114 and TMLP1 in the developing human eye was identified. TMLP1 was also expressed in developing neural tissue. To aid functional characterisation, the murine orthologues of Tmem114 and Tmlp1 were cloned and polyclonal antibodies were generated. Bioinformatic tools predicted co-and post-translational modifications. The predicted plasma membrane localisation of Tmem114 was confirmed in vitro in polarised MDCK II cells and the membrane localisation was shown to be dependent on the presence of N-linked oligosaccharides. Murine Tmlp1 was localised in the endoplasmic reticulum (ER) in MDCK II cells, possibly due to the fact that murine Tmlp1 lacks an N-glycosylation site present in other species.The knockdown of Tmem114 in Xenopus tropicalis using antisense morpholinos results in microphthalmia (small eye) confirming the protein's role in eye development and growth. Sequencing of patients with microphthalmia and anophthalmia identified a novel heterozygous missense mutation (p.R2Q) not present in controls. The p.R2Q variant was not found to affect the expression or localisation of the protein. The p.A147V variant, previously reported as a SNP, mis-localises to the endoplasmic reticulum.In conclusion, this study identifies that TMEM114 is a transmembrane glycoprotein with an important role in ocular development in vertebrates, although its precise functional role remains to be elucidated. Knockdown of Tmem114 in X. tropicalis results in microphthalmia, suggesting that loss of function mutations in TMEM114 may be associated with human ocular disease. Further characterisation of TMLP1 is required to identify its role in human biology.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Zonal mean and tidal dynamics from space: An empirical examination of aliasing and sampling issues

Interpretations of space-based measurements of atmospheric parameters in the mesosphere and thermosphere are complicated by large local-time variations at these altitudes. For this reason, satellite orbits are often preferred which precess through all local times one or more times per season. However, the local-time structure of the atmosphere is inherently non-stationary, which can lead to sampling and aliasing difficulties when attempting to deconvolve the measurements into zonal mean and tidal components. In the present study, hourly radar measurements of mesopause-region winds are used to form a mock data base which can be used to gain insight into implications of the aforementioned problems; the use of actual measurements introduces a realistic element of geophysical temporal variability. Assuming zonal symmetry (i.e., migrating tides superimposed on a zonal mean circulation), the radar measurements are sampled from the satellite perspective for orbital inclinations of 57° and 70°, and compared to the ground or true perspective. These comparisons provide realistic estimates of the errors to be expected when attempting to derive mean and tidal components from space-based measurements. For both diurnal and semidiurnal components, and the quoted satellite inclinations, acceptable errors (3–4m/srms) are obtained for data covering 24h local time (i.e., ascending plus descending nodes); the corresponding errors for single-node data (12h local-time coverage) are of order 8–11m/s, and therefore may not represent reliable estimates of the actual tidal components. There exist certain caveats in connection with the latter conclusion which are discussed

Global distribution and interannual variations of mesospheric and lower thermospheric neutral wind diurnal tide: 1. Migrating tide

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95689/1/jgra18975.pd

Twelve‐hour tides in the winter northern polar mesosphere and lower thermosphere

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94767/1/jgra16221.pd

RPGR-associated retinal degeneration in human X-linked RP and a murine model

PURPOSE. We investigated the retinal disease due to mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene in human patients and in an Rpgr conditional knockout (cko) mouse model. METHODS. XLRP patients with RPGR-ORF15 mutations (n = 35, ages at first visit 5–72 years) had clinical examinations, and rod and cone perimetry. Rpgr-cko mice, in which the proximal promoter and first exon were deleted ubiquitously, were back-crossed onto a BALB/c background, and studied with optical coherence tomography and electroretinography (ERG). Retinal histopathology was performed on a subset. RESULTS. Different patterns of rod and cone dysfunction were present in patients. Frequently, there were midperipheral losses with residual rod and cone function in central and peripheral retina. Longitudinal data indicated that central rod loss preceded peripheral rod losses. Central cone-only vision with no peripheral function was a late stage. Less commonly, patients had central rod and cone dysfunction, but preserved, albeit abnormal, midperipheral rod and cone vision. Rpgr-cko mice had progressive retinal degeneration detectable in the first months of life. ERGs indicated relatively equal rod and cone disease. At late stages, there was greater inferior versus superior retinal degeneration. CONCLUSIONS. RPGR mutations lead to progressive loss of rod and cone vision, but show different patterns of residual photoreceptor disease expression. Knowledge of the patterns should guide treatment strategies. Rpgr-cko mice had onset of degeneration at relatively young ages and progressive photoreceptor disease. The natural history in this model will permit preclinical proof-of-concept studies to be designed and such studies should advance progress toward human therapy

Restoration of mutant bestrophin-1 expression, localisation and function in a polarised epithelial cell model

Autosomal recessive bestrophinopathy (ARB) is a retinopathy caused by mutations in the bestrophin-1 protein, which is thought to function as a Ca2+-gated Cl− channel in the basolateral surface of the retinal pigment epithelium (RPE). Using a stably transfected polarised epithelial cell model, we show that four ARB mutant bestrophin-1 proteins were mislocalised and subjected to proteasomal degradation. In contrast to the wild-type bestrophin-1, each of the four mutant proteins also failed to conduct Cl− ions in transiently transfected cells as determined by whole-cell patch clamp. We demonstrate that a combination of two clinically approved drugs, bortezomib and 4-phenylbutyrate (4PBA), successfully restored the expression and localisation of all four ARB mutant bestrophin-1 proteins. Importantly, the Cl− conductance function of each of the mutant bestrophin-1 proteins was fully restored to that of wild-type bestrophin-1 by treatment of cells with 4PBA alone. The functional rescue achieved with 4PBA is significant because it suggests that this drug, which is already approved for long-term use in infants and adults, might represent a promising therapy for the treatment of ARB and other bestrophinopathies resulting from missense mutations in BEST1