Neurotrophins and Neurotrophin Receptors in Proliferative Diabetic Retinopathy

Neurotrophins (NTs) are emerging as important mediators of angiogenesis and fibrosis. We investigated the expression of the NTs nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) and their receptors TrkA, TrkB, and TrkC in proliferative diabetic retinopathy (PDR). As a comparison, we examined the expression of NTs and their receptors in the retinas of diabetic rats. Vitreous samples from 16 PDR and 15 nondiabetic patients were studied by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Epiretinal membranes from 17 patients with PDR were studied by immunohistochemistry. Rats were made diabetic with a single high dose of streptozotocin and retinas of rats were examined by Western blot analysis. Western blot analysis revealed a significant increase in the expression of NT-3 and NT-4 and the shedding of receptors TrkA and TrkB in vitreous samples from PDR patients compared to nondiabetic controls, whereas NGF and BDNF and the receptor TrkC were not detected with the use of Western blot analysis and ELISA. In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed NT-3 and the receptors TrkA, TrkB and TrkC in situ, whereas NT-4 was not detected. The expression levels of NT-3 and NT-4 and the receptors TrkA and TrkB, both in intact and solubilized forms, were upregulated in the retinas of diabetic rats, whereas the receptor TrkC was not detected. Co-immunoprecipitation studies revealed binding between NT-3 and the receptors TrkA and TrkB in the retinas of diabetic rats. Our findings in diabetic eyes from humans and rats suggest that the increased expression levels within the NT-3 and NT-4/Trk axis are associated with the progression of PDR.     

Spontaneous glycine‐induced calcium transients in spinal cord progenitors promote neurogenesis

Glycine and GABA are depolarizing during early development, but the purpose of this paradoxical chloride‐mediated depolarization remains unclear, especially at early stages. It was previously reported that suppressing glycine signaling from the beginning of development in zebrafish embryos caused an abnormal maintenance of the progenitor population and a specific reduction of spinal interneurons but not of other cell populations. Here, we show that cells including progenitors in the embryonic spinal cord had occasional spontaneous, glycine‐mediated calcium transients that were blocked by the glycine antagonist strychnine and the L‐type calcium channel blocker nifedipine. As shown previously for chronic block by strychnine, block of these transients by nifedipine reduced interneuron differentiation. Our results indicate that glycinergic depolarization of neural progenitors evokes spontaneous calcium transients that may enhance the interneuron neurogenic program. © 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2013     

Role of gangliosides in the differentiation of human mesenchymal-derived stem cells into osteoblasts and neuronal cells

Gangliosides are complex glycosphingolipids that are the major component of cytoplasmic cell membranes, and play a role in the control of biological processes. Human mesenchymal stem cells (hMSCs) have received considerable attention as alternative sources of adult stem cells because of their potential to differentiate into multiple cell lineages. In this study, we focus on various functional roles of gangliosides in the differentiation of hMSCs into osteoblasts or neuronal cells. A relationship between gangliosides and epidermal growth factor receptor (EGFR) activation during osteoblastic differentiation of hMSCs was observed, and the gangliosides may play a major role in the regulation of the differentiation. The roles of gangliosides in osteoblast differentiation are dependent on the origin of hMSCs. The reduction of ganglioside biosynthesis inhibited the neuronal differentiation of hMSCs during an early stage of the differentiation process, and the ganglioside expression can be used as a marker for the identification of neuronal differentiation from hMSCs. [BMB Reports 2013; 46(11): 527-532]     

Predicting top predator habitats in the Southwest Indian Ocean

Top predators need to develop optimal strategies of resources and habitats utilization in order to optimize their foraging success. At the individual scale, a predator has to maximize his intake of food while minimizing his cost of foraging to optimize his energetic gain. At the ecosystem scale, we hypothesized that foraging strategies of predators also respond to their general energetic constraints. Predators with energetically costly lifestyles may be constrained to select high quality habitats whereas more phlegmatic predators may occupy both low and high quality habitats. The objectives of this study were 1) to investigate predator responses to heterogeneity in habitat quality with reference to their energetic strategies and 2) to evaluate their responses to contemporaneous versus averaged habitat quality. We collected cetacean and seabird data from an aerial survey in the Southwest Indian Ocean, a region characterized by heterogeneous oceanographic conditions. We classified cetaceans and seabirds into energetic guilds and described their habitats using remotely sensed covariates at contemporaneous and time‐averaged resolutions and static covariates. We used generalized additive models to predict their habitats at the regional scale. Strategies of habitat utilization appeared in accordance with predators energetic constraints. Cetaceans responded to the heterogeneity in habitat quality, with higher densities predicted in more productive areas. However, the costly Delphininae appeared to be more dependent on habitat quality (showing a 1‐to‐13 ratio between the lowest and highest density sectors) than the more phlegmatic sperm and beaked whales (showing only a 1‐to‐3 ratio). For seabirds, predictions primarily reflected colony locations, although the colony effect was stronger for costly seabirds. Moreover, our results suggest that predators may respond better to persistent oceanographic features. To provide a third dimension to habitat quality, cetacean strategies of utilization of the vertical habitat could be related to the distribution of micronekton in the water column.     

How much are stranding records affected by variation in reporting rates? A case study of small delphinids in the Bay of Biscay

Marine vertebrate strandings offer an opportunistic sampling scheme that can provide abundant data over long periods. Because the stranding process involves biological, physical and sociological parameters, confounding complicates the interpretation of results. The statistical analysis of these data relies on generalized linear or additive models in order to infer long-term trends, but does not easily account for drift or variation in reporting rates. Here, we capitalized on county-level (administrative) variation following the passing of a law for compulsory reporting of stranded marine mammals in France to investigate how variation in reporting rates may affect the observed trend in stranded small delphinids in the Bay of Biscay. Using a time-series spanning more than 30 years across eight administrative counties, we built variance partitioning models for the analysis of count data. We discussed the choice of an appropriate likelihood to conclude the Negative Binomial useful and interpretable in the context of small delphinid strandings. We expanded the model with a recent methodology to detect structural breaks in the time series, focusing on overdispersion. We performed statistical robustness checks with respect to variations in reporting rates and discuss their causal interpretation in the context of observational data. Stranding frequencies increased on average 7-fold over 30 years. We conclude that reporting rates to the French stranding network have been stable since the early 1990s, and the average 3-fold increase in stranded small delphinids observed in the Bay of Biscay since 1990 is due to other factors, including bycatch. Codes and data are available to replicate the analysis to other national stranding networks.     

Improved allometric models to estimate the aboveground biomass of tropical trees

Terrestrial carbon stock mapping is important for the successful implementation of climate change mitigation policies. Its accuracy depends on the availability of reliable allometric models to infer oven‐dry aboveground biomass of trees from census data. The degree of uncertainty associated with previously published pantropical aboveground biomass allometries is large. We analyzed a global database of directly harvested trees at 58 sites, spanning a wide range of climatic conditions and vegetation types (4004 trees ≥ 5 cm trunk diameter). When trunk diameter, total tree height, and wood specific gravity were included in the aboveground biomass model as covariates, a single model was found to hold across tropical vegetation types, with no detectable effect of region or environmental factors. The mean percent bias and variance of this model was only slightly higher than that of locally fitted models. Wood specific gravity was an important predictor of aboveground biomass, especially when including a much broader range of vegetation types than previous studies. The generic tree diameter–height relationship depended linearly on a bioclimatic stress variable E, which compounds indices of temperature variability, precipitation variability, and drought intensity. For cases in which total tree height is unavailable for aboveground biomass estimation, a pantropical model incorporating wood density, trunk diameter, and the variable E outperformed previously published models without height. However, to minimize bias, the development of locally derived diameter–height relationships is advised whenever possible. Both new allometric models should contribute to improve the accuracy of biomass assessment protocols in tropical vegetation types, and to advancing our understanding of architectural and evolutionary constraints on woody plant development.     

Spatial Analysis of Anthropogenic Landscape Disturbance and Buruli Ulcer Disease in Benin

Background

Land use and land cover (LULC) change is one anthropogenic disturbance linked to infectious disease emergence. Current research has focused largely on wildlife and vector-borne zoonotic diseases, neglecting to investigate landscape disturbance and environmental bacterial infections. One example is Buruli ulcer (BU) disease, a necrotizing skin disease caused by the environmental pathogen Mycobacterium ulcerans (MU). Empirical and anecdotal observations have linked BU incidence to landscape disturbance, but potential relationships have not been quantified as they relate to land cover configurations.

Methodology/Principal Findings

A landscape ecological approach utilizing Bayesian hierarchical models with spatial random effects was used to test study hypotheses that land cover configurations indicative of anthropogenic disturbance were related to Buruli ulcer (BU) disease in southern Benin, and that a spatial structure existed for drivers of BU case distribution in the region. A final objective was to generate a continuous, risk map across the study region. Results suggested that villages surrounded by naturally shaped, or undisturbed rather than disturbed, wetland patches at a distance within 1200m were at a higher risk for BU, and study outcomes supported the hypothesis that a spatial structure exists for the drivers behind BU risk in the region. The risk surface corresponded to known BU endemicity in Benin and identified moderate risk areas within the boundary of Togo.

Conclusions/Significance

This study was a first attempt to link land cover configurations representative of anthropogenic disturbances to BU prevalence. Study results identified several significant variables, including the presence of natural wetland areas, warranting future investigations into these factors at additional spatial and temporal scales. A major contribution of this study included the incorporation of a spatial modeling component that predicted BU rates to new locations without strong knowledge of environmental factors contributing to disease distribution.     

Facial Expression Wrinkles and Their Relaxation by a Synthetic Peptide

International Journal of Peptide Research and Therapeutics - Expression wrinkles form over time due to repeated facial movements such as smiling and frowning. They have an imprint on facial skin in...     

Biased correlated random walk and foray loop: which movement hypothesis drives a butterfly metapopulation?

Animals in fragmented landscapes have a major challenge to move between high-quality habitat patches through lower-quality matrix. Two current mechanistic hypotheses that describe the movement used by animals outside of their preferred patches (e.g., high-quality habitat or home range) are the biased, correlated random walk (BCRW) and the foray loop (FL). There is also a variant of FL with directed movement (FL_dm). While these have been most extensively tested on butterflies, they have never been tested simultaneously with data across a whole metapopulation and over multiple generations, two key scales for population dynamics. Using the pattern-oriented approach, we compare support for these competing hypotheses with a spatially explicit individual-based simulation model on an 11-year dataset that follows 12 patches of the federally endangered Fender’s blue butterfly (Plebejus icarioides fenderi) in Oregon’s Willamette Valley. BCRW and medium-scale FL and FL_dm scenarios predicted the annual total metapopulation size for ≥9 of 12 patches as well as patch extinctions. The key difference, however, was that the FL scenarios predicted patch colonizations and persistence poorly, failing to adequately capture movement dynamics; BCRW and one FL_dm scenario predicted the observed patch colonization and persistence with reasonable probabilities. This one FL_dm scenario, however, had larger prediction intervals. BCRW, the biologically simplest and thus most parsimonious movement hypothesis, performed consistently well across all nine different tests, resulting in the highest quality metapopulation predictions for butterfly conservation.     

Genetic diversity of the Andean tuber-bearing species, oca (Oxalis tuberosa Mol.), investigated by inter-simple sequence repeats.

The Andean tuber-bearing species, Oxalis tuberosa Mol., is a vegetatively propagated crop cultivated in the uplands of the Andes. Its genetic diversity was investigated in the present study using the inter-simple sequence repeat (ISSR) technique. Thirty-two accessions originating from South America (Argentina, Bolivia, Chile, and Peru) and maintained in vitro were chosen to represent the ecogeographic diversity of its cultivation area. Twenty-two primers were tested and 9 were selected according to fingerprinting quality and reproducibility. Genetic diversity analysis was performed with 90 markers. Jaccard's genetic distance between accessions ranged from 0 to 0.49 with an average of 0.28 +/- 0.08 (mean +/- SD). Dendrogram (UPGMA (unweighted pair-group method with arithmetic averaging)) and factorial correspondence analysis (FCA) showed that the genetic structure was influenced by the collection site. The two most distant clusters contained all of the Peruvian accessions, one from Bolivia, none from Argentina or Chile. Analysis by country revealed that Peru presented the greatest genetic distances from the other countries and possessed the highest intra-country genetic distance (0.30 +/- 0.08). This suggests that the Peruvian oca accessions form a distinct genetic group. The relatively low level of genetic diversity in the oca species may be related to its predominating reproduction strategy, i.e., vegetative propagation. The extent and structure of the genetic diversity of the species detailed here should help the establishment of conservation strategies.