Oxo-aglaiastatin-mediated inhibition of translation initiation

We thank Dr. Elias George (McGill University) for the kind gift of Pgp-1-expressing HeLa cells. RIM was supported by a doctoral fellowship from the Cole Foundation. This research was supported by a grant from the Canadian Institutes of Health Research (FDN-148366) to JP. J.A.P., Jr. is supported by NIH Grant R35 GM118173. Work at the Boston University Center for Molecular Discovery is supported by Grant R24 GM111625. (Cole Foundation; FDN-148366 - Canadian Institutes of Health Research; R35 GM118173 - NIH; R24 GM111625)Published versionSupporting documentatio

Optical coherence tomography-based consensus definition for lamellar macular hole.

BackgroundA consensus on an optical coherence tomography definition of lamellar macular hole (LMH) and similar conditions is needed.MethodsThe panel reviewed relevant peer-reviewed literature to reach an accord on LMH definition and to differentiate LMH from other similar conditions.ResultsThe panel reached a consensus on the definition of three clinical entities: LMH, epiretinal membrane (ERM) foveoschisis and macular pseudohole (MPH). LMH definition is based on three mandatory criteria and three optional anatomical features. The three mandatory criteria are the presence of irregular foveal contour, the presence of a foveal cavity with undermined edges and the apparent loss of foveal tissue. Optional anatomical features include the presence of epiretinal proliferation, the presence of a central foveal bump and the disruption of the ellipsoid zone. ERM foveoschisis definition is based on two mandatory criteria: the presence of ERM and the presence of schisis at the level of Henle's fibre layer. Three optional anatomical features can also be present: the presence of microcystoid spaces in the inner nuclear layer (INL), an increase of retinal thickness and the presence of retinal wrinkling. MPH definition is based on three mandatory criteria and two optional anatomical features. Mandatory criteria include the presence of a foveal sparing ERM, the presence of a steepened foveal profile and an increased central retinal thickness. Optional anatomical features are the presence of microcystoid spaces in the INL and a normal retinal thickness.ConclusionsThe use of the proposed definitions may provide uniform language for clinicians and future research

Macular Microcysts in Mitochondrial Optic Neuropathies: Prevalence and Retinal Layer Thickness Measurements.

PurposeTo investigate the thickness of the retinal layers and to assess the prevalence of macular microcysts (MM) in the inner nuclear layer (INL) of patients with mitochondrial optic neuropathies (MON).MethodsAll patients with molecularly confirmed MON, i.e. Leber's Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), referred between 2010 and 2012 were enrolled. Eight patients with MM were compared with two control groups: MON patients without MM matched by age, peripapillary retinal nerve fiber layer (RNFL) thickness, and visual acuity, as well as age-matched controls. Retinal segmentation was performed using specific Optical coherence tomography (OCT) software (Carl Zeiss Meditec). Macular segmentation thickness values of the three groups were compared by one-way analysis of variance with Bonferroni post hoc corrections.ResultsMM were identified in 5/90 (5.6%) patients with LHON and 3/58 (5.2%) with DOA. The INL was thicker in patients with MON compared to controls regardless of the presence of MM [133.1±7μm vs 122.3±9μm in MM patients (p<0.01) and 128.5±8μm vs. 122.3±9μm in no-MM patients (p<0.05)], however the outer nuclear layer (ONL) was thicker in patients with MM (101.4±1mμ) compared to patients without MM [77.5±8mμ (p<0.001)] and controls [78.4±7mμ (p<0.001)]. ONL thickness did not significantly differ between patients without MM and controls.ConclusionThe prevalence of MM in MON is low (5-6%), but associated with ONL thickening. We speculate that in MON patients with MM, vitreo-retinal traction contributes to the thickening of ONL as well as to the production of cystic spaces

The origin of the 1500-year climate cycles in Holocene North-Atlantic records

© 2007 Author(s) et al. This is an open-access article distributed under a Creative Commons License. The definitive version was published in Climate of the Past 3 (2007): 569-575, doi:10.5194/cp-3-569-2007Since the first suggestion of 1500-year cycles in the advance and retreat of glaciers (Denton and Karlen, 1973), many studies have uncovered evidence of repeated climate oscillations of 2500, 1500, and 1000 years. During last glacial period, natural climate cycles of 1500 years appear to be persistent (Bond and Lotti, 1995) and remarkably regular (Mayewski et al., 1997; Rahmstorf, 2003), yet the origin of this pacing during the Holocene remains a mystery (Rahmstorf, 2003), making it one of the outstanding puzzles of climate variability. Solar variability is often considered likely to be responsible for such cyclicities, but the evidence for solar forcing is difficult to evaluate within available data series due to the shortcomings of conventional time-series analyses. However, the wavelets analysis method is appropriate when considering non-stationary variability. Here we show by the use of wavelets analysis that it is possible to distinguish solar forcing of 1000- and 2500- year oscillations from oceanic forcing of 1500-year cycles. Using this method, the relative contribution of solar-related and ocean-related climate influences can be distinguished throughout the 10 000 yr Holocene intervals since the last ice age. These results reveal that the 1500-year climate cycles are linked with the oceanic circulation and not with variations in solar output as previously argued (Bond et al., 2001). In this light, previously studied marine sediment (Bianchi and McCave, 1999; Chapman and Shackleton, 2000; Giraudeau et al., 2000), ice core (O'Brien et al., 1995; Vonmoos et al., 2006) and dust records (Jackson et al., 2005) can be seen to contain the evidence of combined forcing mechanisms, whose relative influences varied during the course of the Holocene. Circum-Atlantic climate records cannot be explained exclusively by solar forcing, but require changes in ocean circulation, as suggested previously (Broecker et al., 2001; McManus et al., 1999).This work is supported by ANR project: “Integration des contraintes Paleoclimatiques pour reduire les Incertitudes sur l’evolution du Climat pendant les periodes Chaudes”- PICC (ANR-05-BLAN- 0312-02)

Substrate availability and not thermal acclimation controls microbial temperature sensitivity response to long‐term warming

Microbes are responsible for cycling carbon (C) through soils, and predicted changes in soil C stocks under climate change are highly sensitive to shifts in the mechanisms assumed to control the microbial physiological response to warming. Two mechanisms have been suggested to explain the long-term warming impact on microbial physiology: microbial thermal acclimation and changes in the quantity and quality of substrates available for microbial metabolism. Yet studies disentangling these two mechanisms are lacking. To resolve the drivers of changes in microbial physiology in response to long-term warming, we sampled soils from 13- and 28-year-old soil warming experiments in different seasons. We performed short-term laboratory incubations across a range of temperatures to measure the relationships between temperature sensitivity of physiology (growth, respiration, carbon use efficiency, and extracellular enzyme activity) and the chemical composition of soil organic matter. We observed apparent thermal acclimation of microbial respiration, but only in summer, when warming had exacerbated the seasonally-induced, already small dissolved organic matter pools. Irrespective of warming, greater quantity and quality of soil carbon increased the extracellular enzymatic pool and its temperature sensitivity. We propose that fresh litter input into the system seasonally cancels apparent thermal acclimation of C-cycling processes to decadal warming. Our findings reveal that long-term warming has indirectly affected microbial physiology via reduced C availability in this system, implying that earth system models including these negative feedbacks may be best suited to describe long-term warming effects on these soils

Promover os direitos das crianças - apostar na construção de melhores políticas públicas para a criança

Comunicação apresentada no 3º Encontro de Conhecimento e Cooperação, INA, Lisboa, 17 de setembro de 201

Prospective three-dimensional analysis of structure and function in vitreomacular adhesion cured by pharmacologic vitreolysis

Purpose: To prospectively characterize macular structure and function as assessed by combined three-dimensional spectral-domain optical coherence tomography and scanning laser ophthalmoscopy and 3D computer-automated threshold Amsler grid, respectively, in a patient undergoing pharmacologic vitreolysis for vitreomacular adhesion with tractional cysts. Methods: Combined 3D optical coherence tomography and scanning laser ophthalmoscopy measured macular volume and 3D computer-automated threshold Amsler grid quantified central visual field function by determining the absolute percent magnitude lost (cumulative value of total visual field loss over all tested levels) before and for a period of 6 months after pharmacologic vitreolysis for vitreomacular adhesion with a single intravitreal injection of microplasmin (125 μg; ThromboGenics). Results: Ocriplasmin pharmacologic vitreolysis released vitreomacular adhesion by 2 weeks and decreased macular volume from 0.32 μL to 0.15 μL by 1 year after injection. There was a concomitant 4-fold improvement in visual function as measured by 3D computer-automated threshold Amsler grid (percent of central visual field lost) and Snellen visual acuity improved from 20/200 to 20/40. Conclusion: For assessing macular function improvement in conjunction with structural reintegration after pharmacologic vitreolysis for vitreomacular adhesion, 3D computer-automated threshold Amsler grid is a useful tool. Both 3D measurements quantitatively characterized the resolution of this patient's vitreomacular adhesion, suggesting that this is a useful approach to quantifying macular structure and function as indices of the severity of disease and the response to therapy

Monitoring Astronaut Health at the Nanoscale Cellular Level Through the Eye

A user friendly goggles-like head-mounted device equipped with a suite of instruments for several non-invasive and quantitative medical evaluation of the eye, skin, and brain is desired for monitoring the health of astronauts during space travel and exploration of neighboring and distant planets. Real-time non-invasive evaluation of the different structures within the above organs can provide indices of the health of not just these organs, but the entire body. The techniques such as dynamic light scattering (for the early detection of uveitis, cholesterol levels, cataract, changes in the vitreous and possibly Alzheimer's disease), corneal autofluorescence (to assess extracellular matrix biology e.g., in diabetes), optical activity measurements (of anterior ocular fluid to evaluate blood-glucose levels), laser Doppler velocimetry (to assess retinal, optic nerve, and choroidal blood flow), reflectometry/oximetry (for assessing ocular and central nervous system oxygen metabolism), optical coherence tomography (to determine retinal tissue microstructure) and possibly scanning laser technology (for intraocular tissue imaging and scanning) will he integrated into this compact device. Skin sensors will also be mounted on the portion of the device in contact with the periocular region. This will enable monitoring of body temperature, EEG, and electrolyte status. This device will monitor astronaut health during long-duration space travel by detecting aberrations from pre-established "nonns", enabling prompt diagnosis and possibly the initiation of early preventative/curative therapy. The non-invasive nature of the device technologies permits frequent repetition of tests, enabling real-time complete crew health monitoring. This device may ultimately be useful in tele-medicine to bring modern healthcare to under-served areas on Earth as well as in so-called "advanced" care settings (e.g. diabetes in the USA)

Posterior vitreous detachment following panretinal laser photocoagulation

A total of 30 eyes of 19 patients with type I diabetes, varying severity of retinopathy, and no posterior vitreous detachment (PVD) were studied clinically, and vitreous examination was performed by preset lens biomicroscopy. Follow-up was 4.0-7.5 years. A total of 15 eyes underwent panretinal laser photocoagulation (PRP) and 15 eyes were left untreated. The incidence of PVD was 8 of 15 (53%) after PRP and 1 of 15 (7%) in untreated eyes (P\u3c0.02). Minimal vitreous hemorrhage occurred in 4 of 7 treated eyes (57%) that did not develop PVD and in only 2 of 8 (25%) that did. In treated eyes with no history of vitreous hemorrhage, the incidence of PVD was 6/9 (67%); in treated eyes with minimal vitreous hemorrhage at any time, it was 2/6 (33%). In treated eyes, the presence of Diabetic Retinopathy Study (DRS) high-risk characteristics was equally frequent in eyes that developed PVD as in those that did not. These data suggest that PVD occurs following PRP, independent of the severity of diabetic retinopathy or prior vitreous hemorrhage. © 1990 Springer-Verlag