361 research outputs found

    Synthetic CO, H2 and H I surveys of the second galactic quadrant, and the properties of molecular gas

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    articleWe present CO, H2, H I and HISA (H I self-absorption) distributions from a set of simulations of grand design spirals including stellar feedback, self-gravity, heating and cooling. We replicate the emission of the second galactic quadrant by placing the observer inside the modelled galaxies and post-process the simulations using a radiative transfer code, so as to create synthetic observations. We compare the synthetic data cubes to observations of the second quadrant of the Milky Way to test the ability of the current models to reproduce the basic chemistry of the Galactic interstellar medium (ISM), as well as to test how sensitive such galaxy models are to different recipes of chemistry and/or feedback. We find that models which include feedback and self-gravity can reproduce the production of CO with respect to H2 as observed in our Galaxy, as well as the distribution of the material perpendicular to the Galactic plane. While changes in the chemistry/feedback recipes do not have a huge impact on the statistical properties of the chemistry in the simulated galaxies, we find that the inclusion of both feedback and self-gravity are crucial ingredients, as our test without feedback failed to reproduce all of the observables. Finally, even though the transition from H2 to CO seems to be robust, we find that all models seem to underproduce molecular gas, and have a lower molecular to atomic gas fraction than is observed. Nevertheless, our fiducial model with feedback and self-gravity has shown to be robust in reproducing the statistical properties of the basic molecular gas components of the ISM in our Galaxy.We thank the referee, Ralf Klessen, for his comments that helped strengthen the paper. ADC and CLD acknowledge funding from the European Research Council for the FP7 ERC starting grant project LOCALSTAR. The calculations for this paper were performed on the DiRAC Complexity machine, jointly funded by STFC and the Large Facilities Capital Fund of BIS, and the University of Exeter Supercomputer, a DiRAC Facility jointly funded by STFC, the Large Facilities Capital Fund of BIS and the University of Exeter. Fig. 1 was produced using SPLASH (Price 2007). We acknowledge the use of NASA’s SkyView facility (http://skyview.gsfc.nasa.gov) located at NASA Goddard Space Flight Center. We also thank A. Rodrigues for providing high-resolution dust column density maps for benchmarking

    Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

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    Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated

    Delta-9 tetrahydrocannabinol (THC) inhibits lytic replication of gamma oncogenic herpesviruses in vitro

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    BACKGROUND: The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC), has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. METHODS: Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Epstein-Barr virus (EBV) replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS) of monkeys, murine gamma herpesvirus 68 (MHV 68), and herpes simplex type 1 (HSV-1) was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. RESULTS: Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. CONCLUSIONS: THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC. These studies may also provide the foundation for the development of antiviral strategies utilizing non-psychoactive derivatives of THC

    Predictors of linkage to care following community-based HIV counseling and testing in rural Kenya

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    Despite innovations in HIV counseling and testing (HCT), important gaps remain in understanding linkage to care. We followed a cohort diagnosed with HIV through a community-based HCT campaign that trained persons living with HIV/AIDS (PLHA) as navigators. Individual, interpersonal, and institutional predictors of linkage were assessed using survival analysis of self-reported time to enrollment. Of 483 persons consenting to follow-up, 305 (63.2%) enrolled in HIV care within 3 months. Proportions linking to care were similar across sexes, barring a sub-sample of men aged 18–25 years who were highly unlikely to enroll. Men were more likely to enroll if they had disclosed to their spouse, and women if they had disclosed to family. Women who anticipated violence or relationship breakup were less likely to link to care. Enrolment rates were significantly higher among participants receiving a PLHA visit, suggesting that a navigator approach may improve linkage from community-based HCT campaigns.Vestergaard Frandse

    Changes in Channel Trafficking and Protein Stability Caused by LQT2 Mutations in the PAS Domain of the HERG Channel

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    Inherited human long-QT2 syndrome (LQTS) results from mutations in the gene encoding the HERG channel. Several LQT2-associated mutations have been mapped to the amino terminal cytoplasmic Per-Arnt-Sim (PAS) domain of the HERG1a channel subunit. Here we have characterized the trafficking properties of some LQT2-associated PAS domain mutants and analyzed rescue of the trafficking mutants by low temperature (27°C) or by the pore blocker drug E4031. We show that the LQT2-associated mutations in the PAS domain of the HERG channel display molecular properties that are distinct from the properties of LQT2-associated mutations in the trans-membrane region. Unlike the latter, many of the tested PAS domain LQT2-associated mutations do not result in trafficking deficiency of the channel. Moreover, the majority of the PAS domain mutations that cause trafficking deficiencies are not rescued by a pore blocking drug. We have also explored the in vitro folding stability properties of isolated mutant PAS domain proteins using a thermal unfolding fluorescence assay and a chemical unfolding assay

    Water-induced modulation of Helicobacter pylori virulence properties

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    While the influence of water in Helicobacter pylori culturability and membrane integrity has been extensively studied, there are little data concerning the effect of this environment on virulence properties. Therefore, we studied the culturability of water-exposed H. pylori and determined whether there was any relation with the bacterium’s ability to adhere, produce functional components of pathogenicity and induce inflammation and alterations in apoptosis in an experimental model of human gastric epithelial cells. H. pylori partially retained the ability to adhere to epithelial cells even after complete loss of culturability. However, the microorganism is no longer effective in eliciting in vitro host cell inflammation and apoptosis, possibly due to the non-functionality of the cag type IV secretion system. These H. pylori-induced host cell responses, which are lost along with culturability, are known to increase epithelial cell turnover and, consequently, could have a deleterious effect on the initial H. pylori colonisation process. The fact that adhesion is maintained by H. pylori to the detriment of other factors involved in later infection stages appears to point to a modulation of the physiology of the pathogen after water exposure and might provide the microorganism with the necessary means to, at least transiently, colonise the human stomach.FCT (SFRH/BD/24579/2005) (to NMG

    The mammals of Angola

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    Scientific investigations on the mammals of Angola started over 150 years ago, but information remains scarce and scattered, with only one recent published account. Here we provide a synthesis of the mammals of Angola based on a thorough survey of primary and grey literature, as well as recent unpublished records. We present a short history of mammal research, and provide brief information on each species known to occur in the country. Particular attention is given to endemic and near endemic species. We also provide a zoogeographic outline and information on the conservation of Angolan mammals. We found confirmed records for 291 native species, most of which from the orders Rodentia (85), Chiroptera (73), Carnivora (39), and Cetartiodactyla (33). There is a large number of endemic and near endemic species, most of which are rodents or bats. The large diversity of species is favoured by the wide range of habitats with contrasting environmental conditions, while endemism tends to be associated with unique physiographic settings such as the Angolan Escarpment. The mammal fauna of Angola includes 2 Critically Endangered, 2 Endangered, 11 Vulnerable, and 14 Near-Threatened species at the global scale. There are also 12 data deficient species, most of which are endemics or near endemics to the countryinfo:eu-repo/semantics/publishedVersio

    Frustrated hierarchical synchronization and emergent complexity in the human connectome network

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    The spontaneous emergence of coherent behavior through synchronization plays a key role in neural function, and its anomalies often lie at the basis of pathologies. Here we employ a parsimonious (mesoscopic) approach to study analytically and computationally the synchronization (Kuramoto) dynamics on the actual human-brain connectome network. We elucidate the existence of a so-far-uncovered intermediate phase, placed between the standard synchronous and asynchronous phases, i.e. between order and disorder. This novel phase stems from the hierarchical modular organization of the connectome. Where one would expect a hierarchical synchronization process, we show that the interplay between structural bottlenecks and quenched intrinsic frequency heterogeneities at many different scales, gives rise to frustrated synchronization, metastability, and chimera-like states, resulting in a very rich and complex phenomenology. We uncover the origin of the dynamic freezing behind these features by using spectral graph theory and discuss how the emerging complex synchronization patterns relate to the need for the brain to access –in a robust though flexible way– a large variety of functional attractors and dynamical repertoires without ad hoc fine-tuning to a critical pointWe acknowledge financial support from J. de Andalucía, grant P09-FQM-4682 and we thank O. Sporns for providing us access to the human connectome data
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