Myosin VI and vinculin cooperate during the morphogenesis of cadherin cell–cell contacts in mammalian epithelial cells

Cooperation between cadherins and the actin cytoskeleton controls many aspects of epithelial biogenesis. We report here that myosin VI critically regulates the morphogenesis of epithelial cell–cell contacts. As epithelial monolayers mature in culture, discontinuous cell–cell contacts are initially replaced by continuous (cohesive) contacts. Myosin VI is recruited to cell contacts as they become linear and cohesive, where it forms a biochemical complex with epithelial cadherin (E-cadherin). Myosin VI is necessary for strong cadherin adhesion, for cells to form cohesive linear contacts, and for the integrity of the apical junctional complex. We find that vinculin mediates this effect of myosin VI. Myosin VI is necessary for vinculin and E-cadherin to interact. A combination of gain and loss of function approaches identifies vinculin as a downstream effector of myosin VI that is necessary for the integrity of intercellular contacts. We propose that myosin VI and vinculin form a molecular apparatus that generates cohesive cell–cell contacts in cultured mammalian epithelia

Hubble Space Telescope Imaging of the CFRS and LDSS Redshift Surveys---III. Field elliptical galaxies at 0.2 < z < 1.0

Surface photometry has been performed on a sample of 46 field elliptical galaxies. These galaxies are described well by a deVaucouleurs R^{1/4} profile. The sample was selected from the combined Canada-France and LDSS redshift surveys and spans the range 0.20 < z < 1.00. The relationship between galaxy half-light radius and luminosity evolves such that a galaxy of a given size is more luminous by Delta M_B=-0.97 \pm 0.14 mag at z=0.92 and the mean rest-frame color shifts blueward by Delta (U-V) =-0.68 \pm 0.11 at z=0.92 relative to the local cluster relations. Approximately 1/3 of these elliptical galaxies exhibit [OII] 3727 emission lines with equivalent widths > 15 angstroms indicating ongoing star formation. Estimated star-formation rates imply that \le 5% of the stellar mass in the elliptical galaxy population has been formed since z=1. We see no evidence for a decline in the space density of early-type galaxies with look-back time. The statistics and a comparison with local luminosity functions are both consistent with the view that the population of massive early-type galaxies was largely in place by z~1. This implies that merging is not required since that time to produce the present-day space density of elliptical galaxies.Comment: 21 pages plus 8 figures plus 5 tables. Accepted by Astrophysical Journa

Three Lyman-alpha Emitters at z approx 6: Early GMOS/Gemini Data from the GLARE Project

We report spectroscopic detection of three z~6 Lyman-alpha emitting galaxies, in the vicinity of the Hubble Ultra Deep Field, from the early data of the Gemini Lyman-$\alpha$ at Reionisation Era (GLARE) project. Two objects, GLARE#3001 (z =5.79) and GLARE#3011 (z =5.94), are new detections and are fainter in $z'$ (z'_{AB} =26.37 and 27.15) than any Lyman break galaxy previously detected in Lyman-alpha. A third object, GLARE#1042 (z =5.83) has previously been detected in line emission from the ground; we report here a new spectroscopic continuum detection. Gemini/GMOS-S spectra of these objects, obtained using nod & shuffle, are presented together with a discussion of their photometric properties. All three objects were selected for spectroscopy via the i-drop Lyman Break technique, the two new detections from the GOODS v1.0 imaging data. The red i'-z' colors and high equivalent widths of these objects suggest a high-confidence z>5 Lyman-alpha identification of the emission lines. This brings the total number of known z>5 galaxies within 9 arcmin of the Hubble Ultra Deep Field to four, of which three are at the same redshift (z=5.8 within 2000 km/s suggesting the existence of a large-scale structure at this redshift.Comment: 5 pages, 2 figures. Revised to match accepted versio

HST imaging of CFRS and LDSS galaxies - I: Morphological Properties

(Abridged) We analyse Hubble Space Telescope images of a complete sample of 341 galaxies drawn from both the Canada France and Autofib/Low Dispersion Survey Spectrograph ground-based redshift surveys. We discuss morphological classifications of these galaxies, and quantify possible biases that may arise from various redshift-dependent effects. We then discuss these biases in the context of automated classifications, and quantify the expected misclassification in our system. After allowing for such biases, the redshift distribution for normal spirals, together with their luminosity function derived as a function of redshift, indicates approximately 1 magnitude of luminosity evolution in B(AB) by z=1. The elliptical sample is too small for precise evolutionary constraints. However, we find a substantial increase in the proportion of galaxies with irregular morphology at large redshift. These galaxies also appear to be the dominant cause of the rapid rise with redshift in the blue luminosity density identified in the redshift surveys. Although galaxies with irregular morphology may well comprise a mixture of different physical systems and might not correspond to present day irregulars, it is clear that the apparently declining abundance and luminosities of our distant ``irregulars'' holds an important key to understanding recent evolution in the star formation history of normal galaxies.Comment: 51 pages (14 PS-figures, 3 figures as GIFs) To be published in in Ap

Circadian-Related Sleep Disorders and Sleep Medication Use in the New Zealand Blind Population: An Observational Prevalence Survey

STUDY OBJECTIVES: To determine the prevalence of self-reported circadian-related sleep disorders, sleep medication and melatonin use in the New Zealand blind population. DESIGN: A telephone survey incorporating 62 questions on sleep habits and medication together with validated questionnaires on sleep quality, chronotype and seasonality. PARTICIPANTS: PARTICIPANTS WERE GROUPED INTO: (i) 157 with reduced conscious perception of light (RLP); (ii) 156 visually impaired with no reduction in light perception (LP) matched for age, sex and socioeconomic status, and (iii) 156 matched fully-sighted controls (FS). SLEEP HABITS AND DISTURBANCES: The incidence of sleep disorders, daytime somnolence, insomnia and sleep timing problems was significantly higher in RLP and LP compared to the FS controls (p<0.001). The RLP group had the highest incidence (55%) of sleep timing problems, and 26% showed drifting sleep patterns (vs. 4% FS). Odds ratios for unconventional sleep timing were 2.41 (RLP) and 1.63 (LP) compared to FS controls. For drifting sleep patterns, they were 7.3 (RLP) and 6.0 (LP). MEDICATION USE: Zopiclone was the most frequently prescribed sleep medication. Melatonin was used by only 4% in the RLP group and 2% in the LP group. CONCLUSIONS: Extrapolations from the current study suggest that 3,000 blind and visually impaired New Zealanders may suffer from circadian-related sleep problems, and that of these, fewer than 15% have been prescribed melatonin. This may represent a therapeutic gap in the treatment of circadian-related sleep disorders in New Zealand, findings that may generalize to other countries

Comparable Ages for the Independent Origins of Electrogenesis in African and South American Weakly Electric Fishes

One of the most remarkable examples of convergent evolution among vertebrates is illustrated by the independent origins of an active electric sense in South American and African weakly electric fishes, the Gymnotiformes and Mormyroidea, respectively. These groups independently evolved similar complex systems for object localization and communication via the generation and reception of weak electric fields. While good estimates of divergence times are critical to understanding the temporal context for the evolution and diversification of these two groups, their respective ages have been difficult to estimate due to the absence of an informative fossil record, use of strict molecular clock models in previous studies, and/or incomplete taxonomic sampling. Here, we examine the timing of the origins of the Gymnotiformes and the Mormyroidea using complete mitogenome sequences and a parametric Bayesian method for divergence time reconstruction. Under two different fossil-based calibration methods, we estimated similar ages for the independent origins of the Mormyroidea and Gymnotiformes. Our absolute estimates for the origins of these groups either slightly postdate, or just predate, the final separation of Africa and South America by continental drift. The most recent common ancestor of the Mormyroidea and Gymnotiformes was found to be a non-electrogenic basal teleost living more than 85 millions years earlier. For both electric fish lineages, we also estimated similar intervals (16–19 or 22–26 million years, depending on calibration method) between the appearance of electroreception and the origin of myogenic electric organs, providing rough upper estimates for the time periods during which these complex electric organs evolved de novo from skeletal muscle precursors. The fact that the Gymnotiformes and Mormyroidea are of similar age enhances the comparative value of the weakly electric fish system for investigating pathways to evolutionary novelty, as well as the influences of key innovations in communication on the process of species radiation

Minimizing Variability of Cascade Impaction Measurements in Inhalers and Nebulizers

The purpose of this article is to catalogue in a systematic way the available information about factors that may influence the outcome and variability of cascade impactor (CI) measurements of pharmaceutical aerosols for inhalation, such as those obtained from metered dose inhalers (MDIs), dry powder inhalers (DPIs) or products for nebulization; and to suggest ways to minimize the influence of such factors. To accomplish this task, the authors constructed a cause-and-effect Ishikawa diagram for a CI measurement and considered the influence of each root cause based on industry experience and thorough literature review. The results illustrate the intricate network of underlying causes of CI variability, with the potential for several multi-way statistical interactions. It was also found that significantly more quantitative information exists about impactor-related causes than about operator-derived influences, the contribution of drug assay methodology and product-related causes, suggesting a need for further research in those areas. The understanding and awareness of all these factors should aid in the development of optimized CI methods and appropriate quality control measures for aerodynamic particle size distribution (APSD) of pharmaceutical aerosols, in line with the current regulatory initiatives involving quality-by-design (QbD)

Hubble Space Telescope imaging of the CFRS and LDSS redshift surveys. II. structural parameters and the evolution of disk galaxies to z ∼ 1

Several aspects of the evolution of star-forming galaxies are studied using measures of the 2-dimensional surface brightness profiles of a sample of 341 faint objects selected from the CFRS and LDSS redshift surveys that have been observed with the Hubble Space Telescope. The size function of disk scale lengths in disk-dominated galaxies (i.e. bulge to total ratios, B/T ≤ 0.5) is found to stay roughly constant to z ~ 1, at least for those larger disks with exponential scale lengths α-1&gt; 3.2 h-1 50 kpc, where the sample is most complete and where the disk and bulge decompositions are most reliable. This result, which is strengthened by inclusion of the local de Jong et al (1996) size function, suggests that the scale lengths of typical disks can not have grown substantially with cosmic epoch since z ~ 1, unless a corresponding number of large disks have been destroyed through merging. In addition to a roughly constant number density, the galaxies with large disks, α-1 ≥ 4 h-1 50 kpc, have, as a set, properties consistent with the idea that they are similar galaxies observed at different cosmic epochs. However, on average, they show higher B-band disk surface brightnesses, bluer overall (U-V) colors, higher [OII] 372