Induction of productive human papillomavirus type 11 life cycle in epithelial cells grown in organotypic raft cultures

AbstractThe study of the human papillomavirus (HPV) life cycle was hampered for more than 50 years by the lack of a conventional cell culture system for propagating HPV. Considerable progress has been made in the production of several HPV types using either organotypic rafts or human epithelial xenografts in immunocompromised mice. In this study, we demonstrated episomal maintenance of HPV-11 DNA in N-Tert cells. HPV-11 episomal DNA containing cell populations grown in raft culture showed induction of the productive viral life cycle. HPV-11 DNA amplification and viral capsid antigen synthesis were detected in differentiated layers of epithelia. The viruses generated were able to infect keratinocytes in vitro, which indicate that viruses generated were infectious. The demonstration of the productive HPV-11 life cycle in raft culture from cloned HPV-11 DNA will facilitate genetic analyses of viral gene functions that was not possible using the human xenograft athymic mouse model

Maps of Tethys' Thermophysical Properties

On 11th April 2015 Cassini's Composite Infrared Spectrometer (CIRS) made a series of observations of Tethys daytime anti-Saturn hemisphere over a nine-hour time period. During this time the sub-spacecraft position was remarkably stable (0.3 S to 3.9 S; 153.2 W to 221.8 W), and so these observations provide unprecedented coverage of diurnal temperature variations on Tethys anti-Saturn hemisphere. In 2012 a thermal anomaly was discovered at low latitudes on Tethys leading hemisphere; it appears cooler during the day and warmer at night than its surroundings (Howett et al., 2012) and is spatially correlated with a decrease in the IR3/UV3 visible color ratio (Schenk et al., 2011). The cause of this anomaly is believed to be surface alteration by high-energy electrons, which preferentially bombard low-latitudes of Tethys leading hemisphere (Schenk et al., 2011; Howett et al., 2012; Paranicas et al. 2014; Schaible et al., 2017). The thermal anomaly was quickly dubbed Pac-Man due to its resemblance to the 1980s video game icon. We use these daytime 2015 CIRS data, along with two sets of nighttime CIRS observations of Tethys (from 27 June 2007 and 17 August 2015) to make maps of bolometric Bond albedo and thermal inertia variations across the anti-Saturn hemisphere of Tethys (including the edge of its Pac-Man region). These maps confirm the presence of the Pac-Man thermal anomaly and show that while Tethys bolometric Bond albedo varies negligibly outside and inside the anomaly (0.69 plus or minus 0.02 inside, compared to 0.71 plus or minus 0.04 outside) the thermal inertia varies dramatically (29 plus or minus 10 J m2 K1 s1/2 inside, compared to 9 plus or minus 4 J m2 K1 s1/2 outside). These thermal inertias are in keeping with previously published values: 25 plus or minus 3 J m2 K1 s1/2 inside, and 5 1 J m2 K1 s1/2 outside the anomaly (Howett et al., 2012). A detailed analysis shows that on smaller spatial-scales the bolometric Bond albedo does vary: increasing to a peak value at 180 W. For longitudes between approximately 100 W and approximately 160 W the thermal inertia increases from northern to southern latitudes, while the reverse is true for bolometric Bond albedo. The thermal inertia on Tethys generally increases towards the center of its leading hemisphere but also displays other notable small-scale variations. These thermal inertia and bolometric Bond albedo variations are perhaps due to differences in competing surface modification by E ring grains and high-energy electrons which both bombard Tethys leading hemisphere (but in different ways). A comparison between the observed temperatures and our best thermal model fits shows notable discrepancies in the morning warming curve, which may provide evidence of regional variations in surface roughness effects, perhaps again due to variations in surface alteration mechanisms

Detecting impaired language processing in patients with mild cognitive impairment using around-the-ear cEEgrid electrodes

Mild cognitive impairment (MCI) is the term used to identify those individuals with subjective and objective cognitive decline but with preserved activities of daily living and an absence of dementia. Although MCI can impact functioning in different cognitive domains, most notably episodic memory, relatively little is known about the comprehension of language in MCI. In this study, we used around-the-ear electrodes (cEEGrids) to identify impairments during language comprehension in patients with MCI. In a group of 23 patients with MCI and 23 age-matched controls, language comprehension was tested in a two-word phrase paradigm. We examined the oscillatory changes following word onset as a function of lexico-semantic single-word retrieval (e.g., swrfeq vs. swift) and multiword binding processes (e.g., horse preceded by swift vs. preceded by swrfeq). Electrophysiological signatures (as measured by the cEEGrids) were significantly different between patients with MCI and controls. In controls, lexical retrieval was associated with a rebound in the alpha/beta range, and binding was associated with a post-word alpha/beta suppression. In contrast, both the single-word retrieval and multiword binding signatures were absent in the MCI group. The signatures observed using cEEGrids in controls were comparable with those signatures obtained with a full-cap EEG setup. Importantly, our findings suggest that patients with MCI have impaired electrophysiological signatures for comprehending single words and multiword phrases. Moreover, cEEGrid setups provide a noninvasive and sensitive clinical tool for detecting early impairments in language comprehension in MCI

Pluto's global surface composition through pixel-by-pixel Hapke modeling of New Horizons Ralph/LEISA data

On July 14th 2015, NASA's New Horizons mission gave us an unprecedented detailed view of the Pluto system. The complex compositional diversity of Pluto's encounter hemisphere was revealed by the Ralph/LEISA infrared spectrometer on board of New Horizons. We present compositional maps of Pluto defining the spatial distribution of the abundance and textural properties of the volatiles methane and nitrogen ices and non-volatiles water ice and tholin. These results are obtained by applying a pixel-by-pixel Hapke radiative transfer model to the LEISA scans. Our analysis focuses mainly on the large scale latitudinal variations of methane and nitrogen ices and aims at setting observational constraints to volatile transport models. Specifically, we find three latitudinal bands: the first, enriched in methane, extends from the pole to 55deg N, the second dominated by nitrogen, continues south to 35deg N, and the third, composed again mainly of methane, reaches 20deg N. We demonstrate that the distribution of volatiles across these surface units can be explained by differences in insolation over the past few decades. The latitudinal pattern is broken by Sputnik Planitia, a large reservoir of volatiles, with nitrogen playing the most important role. The physical properties of methane and nitrogen in this region are suggestive of the presence of a cold trap or possible volatile stratification. Furthermore our modeling results point to a possible sublimation transport of nitrogen from the northwest edge of Sputnik Planitia toward the south.Comment: 43 pages, 7 figures; accepted for publication in Icaru

From impulses to maladaptive actions: the insula is a neurobiological gate for the development of compulsive behavior.

Impulsivity is an endophenotype of vulnerability for compulsive behaviors. However, the neural mechanisms whereby impulsivity facilitates the development of compulsive disorders, such as addiction or obsessive compulsive disorder, remain unknown. We first investigated, in rats, anatomical and functional correlates of impulsivity in the anterior insular (AI) cortex by measuring both the thickness of, and cellular plasticity markers in, the AI with magnetic resonance imaging and in situ hybridization of the immediate early gene zif268, respectively. We then investigated the influence of bilateral AI cortex lesions on the high impulsivity trait, as measured in the five-choice serial reaction time task (5-CSRTT), and the associated propensity to develop compulsivity as measured by high drinking levels in a schedule-induced polydipsia procedure (SIP). We demonstrate that the AI cortex causally contributes to individual vulnerability to impulsive-compulsive behavior in rats. Motor impulsivity, as measured by premature responses in the 5-CSRTT, was shown to correlate with the thinness of the anterior region of the insular cortex, in which highly impulsive (HI) rats expressed lower zif268 mRNA levels. Lesions of AI reduced impulsive behavior in HI rats, which were also highly susceptible to develop compulsive behavior as measured in a SIP procedure. AI lesions also attenuated both the development and the expression of SIP. This study thus identifies the AI as a novel neural substrate of maladaptive impulse control mechanisms that may facilitate the development of compulsive disorders.This research was carried-out within the Department of Psychology and the Department of Pharmacology of the University of Cambridge as well as the INSERM AVENIR team Psychobiology of Compulsive Disorders of the University of Poitiers. It was supported by an INSERM AVENIR grant and a FYSSEN foundation grant to DB. MLD was supported by a PhD fellowship from the Fondation pour la Recherche Médicale (FRM) and ABR was supported by a post-doctoral fellowship from the INSERM. BJE was supported by the United Kingdom Medical Research Council (MRC) Grant 9536855.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/mp.2015.14

The near-surface electron radiation environment of Saturn's moon Mimas

Saturn's inner mid-size moons are exposed to a number of external weathering processes, including charged particle bombardment and UV photolysis, as well as deposition of E-ring grains and interplanetary dust. While optical remote sensing observations by several instruments onboard the Cassini spacecraft have revealed a number of weathering patterns across the surfaces of these moons, it is not entirely clear which external process is responsible for which observed weathering pattern. Here we focus on Saturn's moon Mimas and model the effect of energetic electron bombardment across its surface. By using a combination of a guiding center, bounce-averaged charged particle tracing approach and a particle physics code, we investigate how the radiation dose due to energetic electrons is deposited with depth at different locations. We predict a lens-shaped electron energy deposition pattern that extends down to ∼cm depths at low latitudes centered around the apex of the leading hemisphere (90° W). These results are consistent with previous remote sensing observations of a lens-shaped color anomaly observed by the Imaging Science Subsystem (ISS) instrument as well as a thermal inertia anomaly observed by the Visual and Infrared Mapping Spectrometer (VIMS) and the Composite Infrared Spectrometer (CIRS). Our results confirm that these features are produced by MeV electrons that have a penetration depth into the surface comparable to the effective sampling depths of these instruments. On the trailing hemisphere we predict a similar lens-shaped electron energy deposition pattern, whose effects have to date not been observed by the Cassini remote sensing instruments. We suggest that no corresponding lens-shaped weathering pattern has been observed on the trailing hemisphere because of the comparatively short range of lower energy (<1 MeV) electrons into surface ice, as well as competing effects from cold plasma, neutral, and dust bombardment