Photoreceptor Differentiation following Transplantation of Allogeneic Retinal Progenitor Cells to the Dystrophic Rhodopsin Pro347Leu Transgenic Pig

Purpose. Transplantation of stem, progenitor, or precursor cells has resulted in photoreceptor replacement and evidence of functional efficacy in rodent models of retinal degeneration. Ongoing work has been directed toward the replication of these results in a large animal model, namely, the pig. Methods. Retinal progenitor cells were derived from the neural retina of GFP-transgenic pigs and transplanted to the subretinal space of rhodopsin Pro347Leu-transgenic allorecipients, in the early stage of the degeneration and the absence of immune suppression. Results. Results confirm the survival of allogeneic porcine RPCs without immune suppression in the setting of photoreceptor dystrophy. The expression of multiple photoreceptor markers by grafted cells included the rod outer segment-specific marker ROM-1. Further evidence of photoreceptor differentiation included the presence of numerous photoreceptor rosettes within GFP-positive grafts, indicative of the development of cellular polarity and self-assembly into rudiments of outer retinal tissue. Conclusion. Together, these data support the tolerance of RPCs as allografts and demonstrate the high level of rod photoreceptor development that can be obtained from cultured RPCs following transplantation. Strategies for further progress in this area, together with possible functional implications, are discussed

Global coral bleaching event detection from satellite monitoring of extreme heat stress

Over the past four decades, coral bleaching events have occurred with increasing frequency and severity, directly linked to increasing ocean temperature due to climate change. For the latter half of that period, satellite monitoring by NOAA Coral Reef Watch in near real-time has provided invaluable insight into bleaching risk. Here, we describe a novel application of those products to develop basin-scale tools for tracking the development of extreme heat events that enable monitoring of global coral bleaching events. Case studies of historical extreme events (1982-2018) across the three tropical ocean basins (Indian, Pacific and Atlantic) were analysed using this basin-scale approach to identify key thresholds of heat stress extent for the definition of global bleaching. Global-scale events are apparent when all three tropical basins experience heat stress in at least 10% of reef-containing locations. An 8-month ‘detection window’ was determined as the optimal period of time through which pixels exposed to heat stress should continue to be counted as part of a basin-scale event to account for seasonal variations across ocean basins. Understanding the broader context of basin-scale conditions can inform management of individual reefs, management networks and other reef stakeholders. Operationalising this product for near real-time delivery will provide an effective communication of the status of coral reefs around the world during an era of unprecedented climate threats

The Influence of Brightness on Functional Assessment by mfERG: A Study on Scaffolds Used in Retinal Cell Transplantation in Pigs

To determine the effect of membrane brightness on multifocal electroretinograms (mfERGs), we implanted poly lactic-co-glycolic acid (PLGA) membranes in the subretinal space of 11 porcine eyes. We compared membranes with their native shiny white color with membranes that were stained with a blue dye (Brilliant Blue). Histological and electrophysiological evaluation of the overlying retina was carried out 6 weeks after implantation. Histologically, both white and blue membranes degraded in a spongiform manner leaving a disrupted outer retina with no preserved photoreceptor segments. Multifocal ERG revealed the white membranes to have a significantly higher P1-amplitude ratio than the blue (P = 0.027), and a correlation between brightness ratio and P1-amplitude ratio was found (r = 0.762). Based on our findings, we conclude that bright subretinal objects can produce normal mfERG amplitude ratios even when the adjacent photoreceptors are missing. Functional assessment with mfERG in scaffold implant studies should therefore be evaluated with care

Subretinal Implantation of Electrospun, Short Nanowire, and Smooth Poly(ε-caprolactone) Scaffolds to the Subretinal Space of Porcine Eyes

Biodegradable scaffolds play an important adjunct role in transplantation of retinal progenitor cells (RPCs) to the subretinal space. Poly(ε-Caprolactone) (PCL) scaffolds with different modifications were subretinally implanted in 28 porcine eyes and evaluated by multifocal electroretinography (mfERG) and histology after 6 weeks of observation. PCL Short Nanowire, PCL Electrospun, and PCL Smooth scaffolds were well tolerated in the subretinal space in pigs and caused no inflammation and limited tissue disruption. PCL Short Nanowire had an average rate of preserved overlying outer retina 17% higher than PCL Electrospun and 25% higher than PCL Smooth. Furthermore, PCL Short Nanowire was found to have the most suitable degree of stiffness for surgical delivery to the subretinal space. The membrane-induced photoreceptor damage could be shown on mfERG, but the reductions in P1 amplitude were only significant for the PCL Smooth. We conclude that of the tested scaffolds, PCL Short Nanowire is the best candidate for subretinal implantation

Graph similarity through entropic manifold alignment

In this paper we decouple the problem of measuring graph similarity into two sequential steps. The first step is the linearization of the quadratic assignment problem (QAP) in a low-dimensional space, given by the embedding trick. The second step is the evaluation of an information-theoretic distributional measure, which relies on deformable manifold alignment. The proposed measure is a normalized conditional entropy, which induces a positive definite kernel when symmetrized. We use bypass entropy estimation methods to compute an approximation of the normalized conditional entropy. Our approach, which is purely topological (i.e., it does not rely on node or edge attributes although it can potentially accommodate them as additional sources of information) is competitive with state-of-the-art graph matching algorithms as sources of correspondence-based graph similarity, but its complexity is linear instead of cubic (although the complexity of the similarity measure is quadratic). We also determine that the best embedding strategy for graph similarity is provided by commute time embedding, and we conjecture that this is related to its inversibility property, since the inverse of the embeddings obtained using our method can be used as a generative sampler of graph structure.The work of the first and third authors was supported by the projects TIN2012-32839 and TIN2015-69077-P of the Spanish Government. The work of the second author was supported by a Royal Society Wolfson Research Merit Award

Olive phenology as a sensitive indicator of future climatic warming in the Mediterranean

Experimental and modelling work suggests a strong dependence of olive flowering date on spring temperatures. Since airborne pollen concentrations reflect the flowering phenology of olive populations within a radius of 50 km, they may be a sensitive regional indicator of climatic warming. We assessed this potential sensitivity with phenology models fitted to flowering dates inferred from maximum airborne pollen data. Of four models tested, a thermal time model gave the best fit for Montpellier, France, and was the most effective at the regional scale, providing reasonable predictions for 10 sites in the western Mediterranean. This model was forced with replicated future temperature simulations for the western Mediterranean from a coupled ocean-atmosphere general circulation model (GCM). The GCM temperatures rose by 4·5 °C between 1990 and 2099 with a 1% per year increase in greenhouse gases, and modelled flowering date advanced at a rate of 6·2 d per °C. The results indicated that this long-term regional trend in phenology might be statistically significant as early as 2030, but with marked spatial variation in magnitude, with the calculated flowering date between the 1990s and 2030s advancing by 3–23 d. Future monitoring of airborne olive pollen may therefore provide an early biological indicator of climatic warming in the Mediterranean

Optimal spatiotemporal scales to aggregate satellite ocean color data for nearshore reefs and tropical coastal waters: two case studies

Remotely sensed ocean color data are useful for monitoring water quality in coastal environments. However, moderate resolution (hundreds of meters to a few kilometers) satellite data are underutilized in these environments because of frequent data gaps from cloud cover and algorithm complexities in shallow waters. Aggregating satellite data over larger space and time scales is a common method to reduce data gaps and generate a more complete time series, but potentially smooths out the small-scale, episodic changes in water quality that can have ecological influences. By comparing aggregated satellite estimates of Kd(490) with related in-water measurements, we can understand the extent to which aggregation methods are viable for filling gaps while being able to characterize ecologically relevant water quality conditions. In this study, we tested a combination of six spatial and seven temporal scales for aggregating data from the VIIRS instrument at several coral reef locations in Maui, Hawai‘i and Puerto Rico and compared these with in situ measurements of Kd(490) and turbidity. In Maui, we found that the median value of a 5-pixels, 7-days spatiotemporal cube of satellite data yielded a robust result capable of differentiating observations across small space and time domains and had the best correlation among spatiotemporal cubes when compared with in situ Kd(490) across 11 nearshore sites (R2 = 0.84). We also found long-term averages (i.e., chronic condition) of VIIRS data using this aggregation method follow a similar spatial pattern to onshore turbidity measurements along the Maui coast over a three-year period. In Puerto Rico, we found that the median of a 13-pixels, 13-days spatiotemporal cube of satellite data yielded the best overall result with an R2 = 0.54 when compared with in situ Kd(490) measurements for one nearshore site with measurement dates spanning 2016–2019. As spatiotemporal cubes of different dimensions yielded optimum results in the two locations, we recommend local analysis of spatial and temporal optima when applying this technique elsewhere. The use of satellite data and in situ water quality measurements provide complementary information, each enhancing understanding of the issues affecting coastal ecosystems, including coral reefs, and the success of management efforts

Low Speed Automation, a French Initiative

Nowadays, vehicle safety is constantly increasing thanks to the improvement of vehicle passive and active safety. However, on a daily usage of the car, traffic jams remains a problem. With limited space for road infrastructure, automation of the driving task on specific situation seems to be a possible solution. The French project ABV, which stands for low speed automation, tries to demonstrate the feasibility of the concept and to prove the benefits. In this article, we describe the scientific background of the project and expected outputs