The Molecular Basis of Selective Permeability of Connexins is Complex and Includes Both Size And Charge

Although gap junction channels are still widely viewed as large, non-specific pores connecting cells, the diversity in the connexin family has led more attention to be focused on their permeability characteristics. We summarize here the current status of these investigations, both published and on-going, that reveal both charge and size selectivity between gap junction channels composed of different connexins. In particular, this review will focus on quantitative approaches that monitor the expression level of the connexins, so that it is clear that differences that are seen can be attributed to channel properties. The degree of selectivity that is observed is modest compared to other channels, but is likely to be significant for biological molecules that are labile within the cell. Of particular relevance to the in vivo function of gap junctions, recent studies are summarized that demonstrate that the connexin phenotype can control the nature of the endogenous traffic between cells, with consequent effects on biological effects of gap junctions such as tumor suppression

The Christiansen Effect in Saturn's narrow dusty rings and the spectral identification of clumps in the F ring

Stellar occultations by Saturn's rings observed with the Visual and Infrared Mapping Spectrometer (VIMS) onboard the Cassini spacecraft reveal that dusty features such as the F ring and the ringlets in the Encke and the Laplace Gaps have distinctive infrared transmission spectra. These spectra show a narrow optical depth minimum at wavelengths around 2.87 microns. This minimum is likely due to the Christiansen Effect, a reduction in the extinction of small particles when their (complex) refractive index is close to that of the surrounding medium. Simple Mie-scattering models demonstrate that the strength of this opacity dip is sensitive to the size distribution of particles between 1 and 100 microns across. Furthermore, the spatial resolution of the occultation data is sufficient to reveal variations in the transmission spectra within and among these rings. For example, in both the Encke Gap ringlets and F ring, the opacity dip weakens with increasing local optical depth, which is consistent with the larger particles being concentrated near the cores of these rings. The strength of the opacity dip varies most dramatically within the F ring; certain compact regions of enhanced optical depth lack an opacity dip and therefore appear to have a greatly reduced fraction of grains in the few-micron size range.Such spectrally-identifiable structures probably represent a subset of the compact optically-thick clumps observed by other Cassini instruments. These variations in the ring's particle size distribution can provide new insights into the processes of grain aggregation, disruption and transport within dusty rings. For example, the unusual spectral properties of the F-ring clumps could perhaps be ascribed to small grains adhering onto the surface of larger particles in regions of anomalously low velocity dispersion.Comment: 42 pages, 15 figures, accepted for publication in Icarus. A few small typographical errors fixed to match correction in proof

Identification of amino acid residues lining the pore of a gap junction channel

Gap junctions represent a ubiquitous and integral part of multicellular organisms, providing the only conduit for direct exchange of nutrients, messengers and ions between neighboring cells. However, at the molecular level we have limited knowledge of their endogenous permeants and selectivity features. By probing the accessibility of systematically substituted cysteine residues to thiol blockers (a technique called SCAM), we have identified the pore-lining residues of a gap junction channel composed of Cx32. Analysis of 45 sites in perfused Xenopus oocyte pairs defined M3 as the major pore-lining helix, with M2 (open state) or M1 (closed state) also contributing to the wider cytoplasmic opening of the channel. Additional mapping of a close association between M3 and M4 allowed the helices of the low resolution map (Unger et al., 1999. Science. 283:1176–1180) to be tentatively assigned to the connexin transmembrane domains. Contrary to previous conceptions of the gap junction channel, the residues lining the pore are largely hydrophobic. This indicates that the selective permeabilities of this unique channel class may result from novel mechanisms, including complex van der Waals interactions of permeants with the pore wall, rather than mechanisms involving fixed charges or chelation chemistry as reported for other ion channels

Results of the First Coincident Observations by Two Laser-Interferometric Gravitational Wave Detectors

We report an upper bound on the strain amplitude of gravitational wave bursts in a waveband from around 800Hz to 1.25kHz. In an effective coincident observing period of 62 hours, the prototype laser interferometric gravitational wave detectors of the University of Glasgow and Max Planck Institute for Quantum Optics, have set a limit of 4.9E-16, averaging over wave polarizations and incident directions. This is roughly a factor of 2 worse than the theoretical best limit that the detectors could have set, the excess being due to unmodelled non-Gaussian noise. The experiment has demonstrated the viability of the kind of observations planned for the large-scale interferometers that should be on-line in a few years time.Comment: 11 pages, 2 postscript figure

Geomorphological significance of Ontario Lacus on Titan: Integrated interpretation of Cassini VIMS, ISS and RADAR data and comparison with the Etosha Pan (Namibia)

International audienceOntario Lacus is the largest lake of the whole southern hemisphere of Titan, Saturn's major moon. It has been imaged twice by each of the Cassini imaging systems (Imaging Science Subsystem (ISS) in 2004 and 2005, Visual and Infrared Mapping Spectrometer (VIMS) in 2007 and 2009 and Radar in 2009 and 2010). In this study, we take advantage of each imaging dataset to establish a global survey of Ontario Lacus' environment from 2005 to 2010. We perform a geomorphological mapping and interpretation of Ontario Lacus, mainly based on a joint analysis of VIMS and Radar SAR datasets, along with the T49 altimetric profile acquired in December 2008. The morphologies observed on Ontario Lacus are compared to landforms of a semi-arid terrestrial analog, which closely resembles Titan's lakes: the pans of the Etosha Basin, located in Namibia. From this comparison, we infer that Ontario Lacus is an extremely flat depression where liquids, only located in the darkest areas in the Radar data, cover topographic lows where the "alkanofer" would raise above the depression floor. The rest of the depression appears rather as a muddy flat surface likely composed of a thick coating of photon-absorbing materials, explaining its still rather dark appearance in the infrared and radar data. We also determined whether surface changes occurred during the 5 years time interval between 2005 and 2010. We found that the depression contour is constant at the resolution of ISS and VIMS data, both being consistent with the depression contour derived from the Radar data. Our interpretation, in which the liquids are located only in some parts of Ontario Lacus, agrees with the lack of significant change of the depression contour between 2007 (and 2005 with more uncertainties) and 2010

Saturn's icy satellites and rings investigated by Cassini - VIMS. III. Radial compositional variability

In the last few years Cassini-VIMS, the Visible and Infared Mapping Spectrometer, returned to us a comprehensive view of the Saturn's icy satellites and rings. After having analyzed the satellites' spectral properties (Filacchione et al. (2007a)) and their distribution across the satellites' hemispheres (Filacchione et al. (2010)), we proceed in this paper to investigate the radial variability of icy satellites (principal and minor) and main rings average spectral properties. This analysis is done by using 2,264 disk-integrated observations of the satellites and a 12x700 pixels-wide rings radial mosaic acquired with a spatial resolution of about 125 km/pixel. The comparative analysis of these data allows us to retrieve the amount of both water ice and red contaminant materials distributed across Saturn's system and the typical surface regolith grain sizes. These measurements highlight very striking differences in the population here analyzed, which vary from the almost uncontaminated and water ice-rich surfaces of Enceladus and Calypso to the metal/organic-rich and red surfaces of Iapetus' leading hemisphere and Phoebe. Rings spectra appear more red than the icy satellites in the visible range but show more intense 1.5-2.0 micron band depths. The correlations among spectral slopes, band depths, visual albedo and phase permit us to cluster the saturnian population in different spectral classes which are detected not only among the principal satellites and rings but among co-orbital minor moons as well. Finally, we have applied Hapke's theory to retrieve the best spectral fits to Saturn's inner regular satellites using the same methodology applied previously for Rhea data discussed in Ciarniello et al. (2011).Comment: 44 pages, 27 figures, 7 tables. Submitted to Icaru

Controversies and priorities in amyotrophic lateral sclerosis

Two decades after the discovery that 20% of familial amyotrophic lateral sclerosis (ALS) cases were linked to mutations in the superoxide dismutase-1 (SOD1) gene, a substantial proportion of the remainder of cases of familial ALS have now been traced to an expansion of the intronic hexanucleotide repeat sequence in C9orf72. This breakthrough provides an opportunity to re-evaluate longstanding concepts regarding the cause and natural history of ALS, coming soon after the pathological unification of ALS with frontotemporal dementia through a shared pathological signature of cytoplasmic inclusions of the ubiquitinated protein TDP-43. However, with profound clinical, prognostic, neuropathological, and now genetic heterogeneity, the concept of ALS as one disease appears increasingly untenable. This background calls for the development of a more sophisticated taxonomy, and an appreciation of ALS as the breakdown of a wider network rather than a discrete vulnerable population of specialised motor neurons. Identification of C9orf72 repeat expansions in patients without a family history of ALS challenges the traditional division between familial and sporadic disease. By contrast, the 90% of apparently sporadic cases and incomplete penetrance of several genes linked to familial cases suggest that at least some forms of ALS arise from the interplay of multiple genes, poorly understood developmental, environmental, and age-related factors, as well as stochastic events

Comparison of advanced gravitational-wave detectors

We compare two advanced designs for gravitational-wave antennas in terms of their ability to detect two possible gravitational wave sources. Spherical, resonant mass antennas and interferometers incorporating resonant sideband extraction (RSE) were modeled using experimentally measurable parameters. The signal-to-noise ratio of each detector for a binary neutron star system and a rapidly rotating stellar core were calculated. For a range of plausible parameters we found that the advanced LIGO interferometer incorporating RSE gave higher signal-to-noise ratios than a spherical detector resonant at the same frequency for both sources. Spheres were found to be sensitive to these sources at distances beyond our galaxy. Interferometers were sensitive to these sources at far enough distances that several events per year would be expected

Occultation observations of Saturn's rings with Cassini VIMS

We describe the prediction, design, execution and calibration of stellar and solar occultation observations of Saturn's rings by the Visual and Infrared Mapping Spectrometer (VIMS) instrument on the Cassini spacecraft. Particular attention is paid to the technique developed for onboard acquisition of the stellar target and to the geometric and photometric calibration of the data. Examples of both stellar and solar occultation data are presented, highlighting several aspects of the data as well as the different occultation geometries encountered during Cassini's 13-year orbital tour. Complete catalogs of ring stellar and solar occultations observed by Cassini-VIMS are presented, as a guide to the standard data sets which have been delivered to the Planetary Data System's Ring Moon Systems Node (Hedman and Nicholson, 2019b)

Experimental study of the hydrodynamic behaviour of slug flow in a horizontal pipe

This paper investigates the unsteady hydrodynamic behaviour of slug flow occurring within an air–silicone oil mixture, within a horizontal 67 mm internal diameter pipe. A series of slug flow regime experiments were performed for a range of injected air superficial velocities (0.29–1.4 m s−1) and for liquid flows with superficial velocities of between 0.05–0.47 m s−1. A pair of Electrical Capacitance Tomography (ECT) probes was used to determine: the slug translational velocities of the elongated bubbles and liquid slugs, the slug frequencies, the lengths of elongated bubbles and the liquid slugs, the void fractions within the elongated bubbles and liquid slugs. The pressure drop experienced along the pipe was measured using a differential pressure transducer cell (DP cell). A comparative analysis of the current experimental data and that previously published experimental confirms good agreement