TRIDENT: an Infrared Differential Imaging Camera Optimized for the Detection of Methanated Substellar Companions

A near-infrared camera in use at the Canada-France-Hawaii Telescope (CFHT) and at the 1.6-m telescope of the Observatoire du Mont-Megantic is described. The camera is based on a Hawaii-1 1024x1024 HgCdTe array detector. Its main feature is to acquire three simultaneous images at three wavelengths across the methane absorption bandhead at 1.6 microns, enabling, in theory, an accurate subtraction of the stellar point spread function (PSF) and the detection of faint close methanated companions. The instrument has no coronagraph and features fast data acquisition, yielding high observing efficiency on bright stars. The performance of the instrument is described, and it is illustrated by laboratory tests and CFHT observations of the nearby stars GL526, Ups And and Chi And. TRIDENT can detect (6 sigma) a methanated companion with delta H = 9.5 at 0.5" separation from the star in one hour of observing time. Non-common path aberrations and amplitude modulation differences between the three optical paths are likely to be the limiting factors preventing further PSF attenuation. Instrument rotation and reference star subtraction improve the detection limit by a factor of 2 and 4 respectively. A PSF noise attenuation model is presented to estimate the non-common path wavefront difference effect on PSF subtraction performance.Comment: 41 pages, 16 figures, accepted for publication in PAS

Anatomy of a microearthquake sequence on an active normal fault

The analysis of similar earthquakes, such as events in a seismic sequence, is an effective tool with which to monitor and study source processes and to understand the mechanical and dynamic states of active fault systems. We are observing seismicity that is primarily concentrated in very limited regions along the 1980 Irpinia earthquake fault zone in Southern Italy, which is a complex system characterised by extensional stress regime. These zones of weakness produce repeated earthquakes and swarm-like microearthquake sequences, which are concentrated in a few specific zones of the fault system. In this study, we focused on a sequence that occurred along the main fault segment of the 1980 Irpinia earthquake to understand its characteristics and its relation to the loading-unloading mechanisms of the fault system

Antenatal IL-1-dependent inflammation persists postnatally and causes retinal and sub-retinal vasculopathy in progeny

Antenatal inflammation as seen with chorioamnionitis is harmful to foetal/neonatal organ development including to eyes. Although the major pro-inflammatory cytokine IL-1β participates in retinopathy induced by hyperoxia (a predisposing factor to retinopathy of prematurity), the specific role of antenatal IL-1β associated with preterm birth (PTB) in retinal vasculopathy (independent of hyperoxia) is unknown. Using a murine model of PTB induced with IL-1β injection in utero, we studied consequent retinal and choroidal vascular development; in this process we evaluated the efficacy of IL-1R antagonists. Eyes of foetuses exposed only to IL-1β displayed high levels of pro-inflammatory genes, and a persistent postnatal infiltration of inflammatory cells. This prolonged inflammatory response was associated with: (1) a marked delay in retinal vessel growth; (2) long-lasting thinning of the choroid; and (3) long-term morphological and functional alterations of the retina. Antenatal administration of IL-1R antagonists - 101.10 (a modulator of IL-1R) more so than Kineret (competitive IL-1R antagonist) - prevented all deleterious effects of inflammation. This study unveils a key role for IL-1β, a major mediator of chorioamnionitis, in causing sustained ocular inflammation and perinatal vascular eye injury, and highlights the efficacy of antenatal 101.10 to suppress deleterious inflammation.Alexandra Beaudry-Richard, Mathieu Nadeau-Vallée, Élizabeth Prairie, Noémie Maurice ... Sarah A. Robertson ... David M. Olson ... et al

A critical role of interleukin-1 in preterm labor

Preterm birth (PTB) is a leading cause of neonatal mortality and morbidity worldwide, and represents a heavy economic and social burden. Despite its broad etiology, PTB has been firmly linked to inflammatory processes. Pro-inflammatory cytokines are produced in gestational tissues in response to stressors and can prematurely induce uterine activation, which precedes the onset of preterm labor. Of all cytokines implicated, interleukin (IL)-1 has been largely studied, revealing a central role in preterm labor. However, currently approved IL-1-targeting therapies have failed to show expected efficacy in pre-clinical studies of preterm labor. Herein, we (a) summarize animal and human studies in which IL-1 or IL-1-targeting therapeutics are implicated with preterm labor, (b) focus on novel IL-1-targeting therapies and diagnostic tests, and (c) develop the case for commercialization and translation means to hasten their development.Mathieu Nadeau-Vallée, Dima Obari, Christiane Quiniou, William D.Lubell, David M.Olson, Sylvie Girard, Sylvain Chemto

Uric Acid Crystals Induce Placental Inflammation and Alter Trophoblast Function via an IL-1-Dependent Pathway:Implications for Fetal Growth Restriction

International audienceExcessive placental inflammation is associated with several pathological conditions, including stillbirth and fetal growth restriction. Although infection is a known cause of inflammation, a significant proportion of pregnancies have evidence of inflammation without any detectable infection. Inflammation can also be triggered by endogenous mediators, called damage associated molecular patterns or alarmins. One of these damage-associated molecular patterns, uric acid, is increased in the maternal circulation in pathological pregnancies and is a known agonist of the Nlrp3 inflammasome and inducer of inflammation. However, its effects within the placenta and on pregnancy outcomes remain largely unknown. We found that uric acid (monosodium urate [MSU]) crystals induce a proinflammatory profile in isolated human term cytotrophoblast cells, with a predominant secretion of IL-1β and IL-6, a result confirmed in human term placental explants. The proinflammatory effects of MSU crystals were shown to be IL-1-dependent using a caspase-1 inhibitor (inhibits IL-1 maturation) and IL-1Ra (inhibits IL-1 signaling). The proinflammatory effect of MSU crystals was accompanied by trophoblast apoptosis and decreased syncytialization. Correspondingly, administration of MSU crystals to rats during late gestation induced placental inflammation and was associated with fetal growth restriction. These results make a strong case for an active proinflammatory role of MSU crystals at the maternal-fetal interface in pathological pregnancies, and highlight a key mediating role of IL-1. Furthermore, our study describes a novel in vivo animal model of noninfectious inflammation during pregnancy, which is triggered by MSU crystals and leads to reduced fetal growth

Novel noncompetitive IL-1 receptor-biased ligand prevents infection- and inflammation-induced preterm birth

Preterm birth (PTB) is firmly linked to inflammation regardless of the presence of infection. Proinflammatory cytokines, including IL-1β, are produced in gestational tissues and can locally upregulate uterine activation proteins. Premature activation of the uterus by inflammation may lead to PTB, and IL-1 has been identified as a key inducer of this condition. However, all currently available IL-1 inhibitors are large molecules that exhibit competitive antagonism properties by inhibiting all IL-1R signaling, including transcription factor NF-κB, which conveys important physiological roles. We hereby demonstrate the efficacy of a small noncompetitive (all-d peptide) IL-1R-biased ligand, termed rytvela (labeled 101.10) in delaying IL-1β-, TLR2-, and TLR4-induced PTB in mice. The 101.10 acts without significant inhibition of NF-κB, and instead selectively inhibits IL-1R downstream stress-associated protein kinases/transcription factor c-jun and Rho GTPase/Rho-associated coiled-coil-containing protein kinase signaling pathways. The 101.10 is effective at decreasing proinflammatory and/or prolabor genes in myometrium tissue and circulating leukocytes in all PTB models independently of NF-κB, undermining NF-κB role in preterm labor. In this work, biased signaling modulation of IL-1R by 101.10 uncovers a novel strategy to prevent PTB without inhibiting NF-κB.Mathieu Nadeau-Vallée, Christiane Quiniou, Julia Palacios, Xin Hou, Atefeh Erfani, Ankush Madaan, Mélanie Sanchez, Kelycia Leimert, Amarilys Boudreault, François Duhamel, José Carlos Rivera, Tang Zhu, Baraa Noueihed, Sarah A. Robertson, Xin Ni, David M. Olson, William Lubell, Sylvie Girard, and Sylvain Chemto

A mixed seismic–aseismic stress release episode in the Andean subduction zone

International audienceIn subduction zones, stress is released by earthquakes and transient aseismic slip. The latter falls into two categories: slow slip and afterslip. Slow-slip events emerge spontaneously during the interseismic phase, and show a progressive acceleration of slip with a negligible contribution of synchronous tremors or microseismicity to the energy, or moment release1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. In contrast, afterslip occurs immediately after large and moderate earthquakes, decelerates over time, and releases between 20 and 400% of the moment released by the preceding earthquake13, 14, 15, 16, 17, 18. Here we use seismic and GPS data to identify transient aseismic slip that does not fit into either of these categories. We document a seismic–aseismic slip sequence which occurred at shallow depths along a weakly coupled part of the Andean subduction zone19 in northern Peru and lasted seven months. The sequence generated several moderate earthquakes that together account for about 25% of the total moment released during the full sequence, equivalent to magnitude 6.7. Transient slip immediately followed two of the earthquakes, with slip slowing at a logarithmic rate. Considered separately, the moment released by transient slip following the second earthquake was more than 1,000% of the moment released during the earthquake itself, a value incompatible with classical models of afterslip. Synchronous seismic swarms and aseismic slip may therefore define a stress-release process that is distinct from slow-slip events and afterslip