IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Analysis of microRNA turnover in mammalian cells following Dicer1 ablation

Although microRNAs (miRNAs) are key regulators of gene expression, little is known of their overall persistence in the cell following processing. Characterization of such persistence is key to the full appreciation of their regulatory roles. Accordingly, we measured miRNA decay rates in mouse embryonic fibroblasts following loss of Dicer1 enzymatic activity. The results confirm the inherent stability of miRNAs, the intracellular levels of which were mostly affected by cell division. Using the decay rates of a panel of six miRNAs representative of the global trend of miRNA decay, we establish a mathematical model of miRNA turnover and determine an average miRNA half-life of 119 h (i.e. ∼5 days). In addition, we demonstrate that select miRNAs turnover more rapidly than others. This study constitutes, to our knowledge, the first in-depth characterization of miRNA decay in mammalian cells. Our findings indicate that miRNAs are up to 10× more stable than messenger RNA and support the existence of novel mechanism(s) controlling selective miRNA cellular concentration and function

Observations of the Antarctic ozone hole from 2003-2010

Póster presentado en: EGU General Assembly 2011 celebrada del 3 al 8 de abril en Viena, Austria.The Global Atmosphere Watch of WMO includes several stations in Antarctica that keep a close eye on the ozone layer during the ozone hole season. Observations made during the ozone holes from 2003 to 2010 will be compared to each other and interpreted in light of the meteorological conditions. Satellite observations will be used to get a more general picture of the size and depth of the ozone hole and will also be used to calculate various metrics for ozone hole severity. In 2003, 2005 and 2006, the ozone hole was relatively large with more ozone loss than normal. This is in particular the case for 2006, which by most ozone hole metrics was the most severe ozone holeon record. On the other hand, the ozone holes of 2004, 2007 and 2010 were less severe than normal, and only the very special ozone hole of 2002 had less ozone depletion when one regards the ozone holes of the last decade. The interannual variability will be discussed with the help of meteorological data, such as temperature conditions, possibility for polar stratospheric clouds, vortex shape and vortex longevity. Observations will also be compared to 3-D chemical transport model calculations

Associations between level and change in physical function and brain volumes

Higher levels of fitness or physical function are positively associated with cognitive outcomes but the potential underlying mechanisms via brain structure are still to be elucidated in detail. We examined associations between brain structure and physical function (contemporaneous and change over the previous three years) in community-dwelling older adults.Participants from the Lothian Birth Cohort 1936 (N=694) underwent brain MRI at age 73 years to assess intracranial volume, and the volumes of total brain tissue, ventricles, grey matter, normal-appearing white matter, and white matter lesions. At ages 70 and 73, physical function was assessed by 6-meter walk, grip strength, and forced expiratory volume. A summary 'physical function factor' was derived from the individual measures using principal components analysis. Performance on each individual physical function measure declined across the three year interval (p<0.001). Higher level of physical function at ages 70 and 73 was associated with larger total brain tissue and white matter volumes, and smaller ventricular and white matter lesion volumes (standardized β ranged in magnitude from 0.07 to 0.17, p<0.001 to 0.034). Decline in physical function from age 70 to 73 was associated with smaller white matter volume (0.08, p<0.01, though not after correction for multiple testing), but not with any other brain volumetric measurements.Physical function was related to brain volumes in community-dwelling older adults: declining physical function was associated with less white matter tissue. Further study is required to explore the detailed mechanisms through which physical function might influence brain structure, and vice versa

In vivo comparison of local versus systemic delivery of immunostimulating siRNA in HPV-driven tumours

Small interfering RNAs (siRNAs) to inhibit oncogene expression and also to activate innate immune responses via Toll-like receptor (TLR) recognition have been shown to be beneficial as anti-cancer therapy in certain cancer models. In this study, we investigated the effects of local versus systemic delivery of such immune-stimulating Dicer-substrate siRNAs (IS-DsiRNAs) on a human papillomavirus (HPV)-driven tumour model. Localized siRNA delivery using intratumour injection of siRNA was able to increase siRNA delivery to the tumour compared with intravenous (IV) delivery and potently activated innate immune responses. However, IV injection remained the more effective delivery route for reducing tumour growth. Although IS-DsiRNAs activated innate immune cells and required interferon-α (IFNα) for full effect on tumour growth, we found that potent silencing siRNA acting independently of IFNα were overall more effective at inhibiting TC-1 tumour growth. Other published work utilising IS-siRNAs have been carried out on tumour models with low levels of major histocompatibility complex (MHC)-class 1, a target of natural killer cells that are potently activated by IS-siRNA. As TC-1 cells used in our study express high levels of MHC-class I, the addition of the immunostimulatory motifs may not be as beneficial in this particular tumour model. Our data suggest that selection of siRNA profile and delivery method based on tumour environment is crucial to developing siRNA-based therapies

High-frequency gravity waves and homogeneous ice nucleation in tropical tropopause layer cirrus

International audienceThe impact of high-frequency gravity waves on homogeneous-freezing ice nucleation in cold cirrus clouds is examined using parcel model simulations driven by superpressure balloon measurements of temperature variability experienced by air parcels in the tropical tropopause region. We find that the primary influence of high-frequency waves is to generate rapid cooling events that drive production of numerous ice crystals. Quenching of ice nucleation events by temperature tendency reversal in the highest-frequency waves does occasionally produce low ice concentrations, but the overall impact of high-frequency waves is to increase the occurrence of high ice concentrations. The simulated ice concentrations are considerably higher than indicated by in situ measurements of cirrus in the tropical tropopause region. One-dimensional simulations suggest that although sedimentation reduces mean ice concentrations, a discrepancy of about a factor of 3 with observed ice concentrations remains. Reconciliation of numerical simulations with the observed ice concentrations will require inclusion of physical processes such as heterogeneous nucleation and entrainment