A characterization of Gaucher iPS-derived astrocytes: Potential implications for Parkinson\u27s disease

While astrocytes, the most abundant cells found in the brain, have many diverse functions, their role in the lysosomal storage disorder Gaucher disease (GD) has not been explored. GD, resulting from the inherited deficiency of the enzyme glucocerebrosidase and subsequent accumulation of glucosylceramide and its acylated derivative glucosylsphingosine, has both non-neuronopathic (GD1) and neuronopathic forms (GD2 and 3). Furthermore, mutations in GBA1, the gene mutated in GD, are an important risk factor for Parkinson\u27s disease (PD). To elucidate the role of astrocytes in the disease pathogenesis, we generated iAstrocytes from induced pluripotent stem cells made from fibroblasts taken from controls and patients with GD1, with and without PD. We also made iAstrocytes from an infant with GD2, the most severe and progressive form, manifesting in infancy. Gaucher iAstrocytes appropriately showed deficient glucocerebrosidase activity and levels and substrate accumulation. These cells exhibited varying degrees of astrogliosis, Glial Fibrillary Acidic Protein (GFAP) up-regulation and cellular proliferation, depending on the level of residual glucocerebrosidase activity. Glutamte uptake assays demonstrated that the cells were functionally active, although the glutamine transporter EEAT2 was upregulated and EEAT1 downregulated in the GD2 samples. GD2 iAstrocytes were morphologically different, with severe cytoskeletal hypertrophy, overlapping of astrocyte processes, pronounced up-regulation of GFAP and S100β, and significant astrocyte proliferation, recapitulating the neuropathology observed in patients with GD2. Although astrocytes do not express α-synuclein, when the iAstrocytes were co-cultured with dopaminergic neurons generated from the same iPSC lines, excessive α-synuclein released from neurons was endocytosed by astrocytes, translocating into lysosomes. Levels of aggregated α-synuclein increased significantly when cells were treated with monomeric or fibrillar α-synuclein. GD1-PD and GD2 iAstrocytes also exhibited impaired Cathepsin D activity, leading to further α-synuclein accumulation. Cytokine and chemokine profiling of the iAstrocytes demonstrated an inflammatory response. Thus, in patients with GBA1-associated parkinsonism, astrocytes appear to play a role in α-synuclein accumulation and processing, contributing to neuroinflammation

First Data On Aquaculture of the Tripletail, \u3ci\u3eLobotes surinamensis\u3c/i\u3e, a Promising Candidate Species For U.S. Marine Aquaculture

The Tripletail, Lobotes surinamensis, is a warm-water pelagic fish that is increasingly targeted by U.S. anglers. The superior quality of Tripletail flesh coupled with the lack of domestic commercial fisheries stimulated interests to develop aquaculture of this species. In this work, photo-thermal conditioning of captive-held broodstocks promoted maturation in females, but spontaneous spawning was not observed. GnRHa slow-release implants induced ovulation in late vitellogenic females but fertility remained below 10% when GnRHa was administered alone. However, spawns with high fertility (up to 85%) were obtained when a dopamine antagonist was administered in conjunction with GnRHa implants indicating dopamine inhibition impaired final gamete maturation, in particular sperm production in males, in aquaculture conditions. Tripletail larvae successfully initiated exogenous feeding on enriched rotifers followed by Artemia nauplii and were weaned to prepared feeds at 25 days post hatch, yet with low survival through the late phases of larval culture. Pilot grow-out trials at low density in recirculating systems revealed impressive growth rates averaging over 170 g/month through a market size above 1 kg. While protocols for hatchery culture and grow-out still need to be optimized, current data suggest that Tripletail could become a successful species for U.S. marine aquaculture

Acute and Chronic Toxicity of Cobalt to Freshwater Organisms: Using a Species Sensitivity Distribution Approach to Establish International Water Quality Standards

Water quality standards for cobalt (Co) have not been developed for the European Union or United States. The objective of the present study was to produce freshwater Co toxicity data that could be used by both the European Union and the United States to develop appropriate regulatory standards (i.e., environmental quality standards or predicted-no-effect concentrations in Europe and ambient water quality criteria or state water quality standards in the United States). Eleven species, including algae, an aquatic plant, and several invertebrate and fish species, were used in the performance of acute and chronic Co toxicity tests. Acute median lethal or median effective concentration (LC50 or EC50) values ranged from 90.1 mu g Co/L for duckweed (Lemna minor) to 157 000 mu g Co/L for midges (Chironomus tentans). Chronic 10% effect concentration (EC10) values ranged from 4.9 mu g Co/L for duckweed to 2170 mu g Co/L for rainbow trout (Oncorhynchus mykiss). Chronic 20% effect concentration (EC20) values ranged from 11.1 mu g Co/L for water flea (Ceriodaphnia dubia) to 2495 mu g Co/L for O. mykiss. Results indicated that invertebrate and algae/plant species are more sensitive to chronic Co exposures than fish. Acute-to-chronic ratios (derived as acute LC50s divided by chronic EC20s) were lowest for juvenile O. mykiss (0.6) and highest for the snail Lymnaea stagnalis (2670). Following the European-based approach and using EC10 values, species sensitivity distributions (SSDs) were developed and a median hazardous concentration for 5% of the organisms of 1.80 mu g Co/L was derived. Chronic EC20 values were used, also in an SSD approach, to derive a US Environmental Protection Agency-style final chronic value of 7.13 mu g Co/L