De Novo synthesis of VP16 coordinates the exit from HSV latency in vivo

The mechanism controlling the exit from herpes simplex virus latency (HSV) is of central importance to recurrent disease and transmission of infection, yet interactions between host and viral functions that govern this process remain unclear. The cascade of HSV gene transcription is initiated by the multifunctional virion protein VP16, which is expressed late in the viral replication cycle. Currently, it is widely accepted that VP16 transactivating function is not involved in the exit from latency. Utilizing the mouse ocular model of HSV pathogenesis together with genetically engineered viral mutants and assays to quantify latency and the exit from latency at the single neuron level, we show that in vivo (i) the VP16 promoter confers distinct regulation critical for viral replication in the trigeminal ganglion (TG) during the acute phase of infection and (ii) the transactivation function of VP16 (VP16TF) is uniquely required for the exit from latency. TG neurons latently infected with the VP16TF mutant in 1814 do not express detectable viral proteins following stress, whereas viruses with mutations in the other major viral transcription regulators ICP0 and ICP4 do exit the latent state. Analysis of a VP16 promoter/reporter mutant in the background of in 1814 demonstrates that the VP16 promoter is activated in latently infected neurons following stress in the absence of other viral proteins. These findings support the novel hypothesis that de novo expression of VP16 regulates entry into the lytic program in neurons at all phases of the viral life cycle. HSV reactivation from latency conforms to a model in which stochastic derepression of the VP16 promoter and expression of VP16 initiates entry into the lytic cycl

The Graces of 2020: Catholic Campus Ministry Students Seek Out Blessings Amid a Tumultuous Year

Two staff members at DePaul University’s Catholic Campus Ministry (CCM), Amanda Thompson and Dan Paul Borlik, CM, offer their thoughts and those of CCM student leaders on the COVID-19 pandemic and other societal issues facing the US in 2020. The article relates how these issues affected the DePaul community. It also discusses how the students were formed in the practice of critical theological reflection and how they applied it as they experienced and responded to the crises of this terrible year. The authors note the particular relevance of the Exodus story in coping with 2020’s crises

Sub-surface Expression of Sand Volcanoes in the Avon-Heathcote Estuary Induced by the Darfield Earthquake; Analog for Sedimentary Structures in the Rock Record

Among the deformation features produced in Christchurch by the September 4th Darfield Earthquake were numerous and widespread “sand volcanoes”. Most of these structures occurred in urban settings and “erupted” through a hardened surface of concrete or tarseal, or soil. Sand volcanoes were also widespread in the Avon‐ Heathcote Estuary and offered an excellent opportunity to readily examine shallow subsurface profiles and as such the potential appearance of such structures in the rock record

ATLASGAL - environments of 6.7 GHz methanol masers

Using the 870 micron APEX Telescope large area survey of the Galaxy, we have identified 577 submillimetre continuum sources with masers from the methanol multibeam survey in the region 280deg lt ell lt 20deg; |b| lt 1deg.5 94 per cent of methanol masers in the region are associated with submillimetre dust emission. We estimate masses for tilde450 maser-associated sources and find that methanol masers are preferentially associated with massive clumps. These clumps are centrally condensed, with envelope structures that appear to be scale-free, the mean maser position being offset from the peak column density by 0 plusmn 4 arcsec. Assuming a Kroupa initial mass function and a star formation efficiency of tilde30 per cent, we find that over two-thirds of the clumps are likely to form clusters with masses gt20 M$_?$. Furthermore, almost all clumps satisfy the empirical mass-size criterion for massive star formation. Bolometric luminosities taken from the literature for tilde100 clumps range between tilde100 and 10$^6$ L$_?$. This confirms the link between methanol masers and massive young stars for 90 per cent of our sample. The Galactic distribution of sources suggests that the star formation efficiency is significantly reduced in the Galactic Centre region, compared to the rest of the survey area, where it is broadly constant, and shows a significant drop in the massive star formation rate density in the outer Galaxy. We find no enhancement in source counts towards the southern Scutum-Centaurus arm tangent at ell tilde 315deg, which suggests that this arm is not actively forming stars.Peer reviewe

Targeting microRNA to improve diagnostic and therapeutic approaches for malignant mesothelioma

Malignant mesothelioma is an aggressive and often fatal cancer associated with asbestos exposure. The disease originates in the mesothelial lining of the serosal cavities, most commonly affecting the pleura. Survival rates are low as diagnosis often occurs at an advanced stage and current treatments are limited. Identifying new diagnostic and therapeutic targets for mesothelioma remains a priority, particularly for the new wave of victims exposed to asbestos through do-it-yourself renovations and in countries where asbestos is still mined and used. Recent advances have demonstrated a biological role for the small but powerful gene regulators microRNA (miRNA) in mesothelioma. A number of potential therapeutic targets have been identified. MiRNA have also become popular as potential biomarkers for mesothelioma due to their stable expression in bodily fluid and tissues. In this review, we highlight the current challenges associated with the diagnosis and treatment of mesothelioma and discuss how targeting miRNA may improve diagnostic, prognostic and therapeutic approaches

Analysis of telephone network traffic based on a complex user network

The traffic in telephone networks is analyzed in this paper. Unlike the classical traffic analysis where call blockings are due to the limited channel capacity, we consider here a more realistic cause for call blockings which is due to the way in which users are networked in a real-life human society. Furthermore, two kinds of user network, namely, the fully-connected user network and the scale-free network, are employed to model the way in which telephone users are connected. We show that the blocking probability is generally higher in the case of the scale-free user network, and that the carried traffic intensity is practically limited not only by the network capacity but also by the property of the user network.Comment: 17 pages, 9 figures, accepted for Physica

No Significant Evidence of Cognitive Biases for Emotional Stimuli in Children At-Risk of Developing Anxiety Disorders.

This paper explores whether the increased vulnerability of children of anxious parents to develop anxiety disorders may be partially explained by these children having increased cognitive biases towards threat compared with children of non-anxious parents. Parents completed questionnaires about their child’s anxiety symptoms. Children aged 5–9 (n = 85) participated in two cognitive bias tasks: 1) an emotion recognition task, and 2) an ambiguous situations questionnaire. For the emotion recognition task, there were no significant differences between at-risk children and children of non-anxious parents in their cognitive bias scores for reaction times or for accuracy in identifying angry or happy facial expressions. In addition, there were no significant differences between at-risk children and children of non-anxious parents in the number of threat interpretations made for the ambiguous situations questionnaire. It is possible that these cognitive biases only become present subsequent to the development of an anxiety disorder, or only in older at-risk children

Eigenvalues of rank one perturbations of unstructured matrices

Let $A$ be a fixed complex matrix and let $u,v$ be two vectors. The eigenvalues of matrices $A+\tau uv^\top$ $(\tau\in\mathbb{R})$ form a system of intersecting curves. The dependence of the intersections on the vectors $u,v$ is studied

On-chip quantum interference between silicon photon-pair sources

Large-scale integrated quantum photonic technologies1, 2 will require on-chip integration of identical photon sources with reconfigurable waveguide circuits. Relatively complex quantum circuits have been demonstrated already1, 2, 3, 4, 5, 6, 7, but few studies acknowledge the pressing need to integrate photon sources and waveguide circuits together on-chip8, 9. A key step towards such large-scale quantum technologies is the integration of just two individual photon sources within a waveguide circuit, and the demonstration of high-visibility quantum interference between them. Here, we report a silicon-on-insulator device that combines two four-wave mixing sources in an interferometer with a reconfigurable phase shifter. We configured the device to create and manipulate two-colour (non-degenerate) or same-colour (degenerate) path-entangled or path-unentangled photon pairs. We observed up to 100.0 ± 0.4% visibility quantum interference on-chip, and up to 95 ± 4% off-chip. Our device removes the need for external photon sources, provides a path to increasing the complexity of quantum photonic circuits and is a first step towards fully integrated quantum technologies

Mitochondria-derived reactive oxygen species drive GANT61-induced mesothelioma cell apoptosis

Gli transcription factors of the Hedgehog (Hh) pathway have been reported to be drivers of malignant mesothelioma (MMe) cell survival. The Gli inhibitor GANT61 induces apoptosis in various cancer cell models, and has been associated directly with Gli inhibition. However various chemotherapeutics can induce cell death through generation of reactive oxygen species (ROS) but whether ROS mediates GANT61-induced apoptosis is unknown. In this study human MMe cells were treated with GANT61 and the mechanisms regulating cell death investigated. Exposure of MMe cells to GANT61 led to G1 phase arrest and apoptosis, which involved ROS but not its purported targets, GLI1 or GLI2. GANT61 triggered ROS generation and quenching of ROS protected MMe cells from GANT61-induced apoptosis. Furthermore, we demonstrated that mitochondria are important in mediating GANT61 effects: (1) ROS production and apoptosis were blocked by mitochondrial inhibitor rotenone; (2) GANT61 promoted superoxide formation in mitochondria; and (3) mitochondrial DNA-deficient LO68 cells failed to induce superoxide, and were more resistant to apoptosis induced by GANT61 than wild-type cells. Our data demonstrate for the first time that GANT61 induces apoptosis by promoting mitochondrial superoxide generation independent of Gli inhibition, and highlights the therapeutic potential of mitochondrial ROS-mediated anticancer drugs in MMe