Multi-omic profiling reveals the ataxia protein sacsin is required for integrin trafficking and synaptic organization

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset cerebellar ataxia caused by mutations in SACS, which encodes the protein sacsin. Cellular ARSACS phenotypes include mitochondrial dysfunction, intermediate filament disorganization, and progressive death of cerebellar Purkinje neurons. It is unclear why the loss of sacsin causes these deficits or why they manifest as cerebellar ataxia. Here, we perform multi-omic profiling in sacsin knockout (KO) cells and identify alterations in microtubule dynamics and mislocalization of focal adhesion (FA) proteins, including multiple integrins. Deficits in FA structure, signaling, and function can be rescued by targeting PTEN, a negative regulator of FA signaling. ARSACS mice possess mislocalization of ITGA1 in Purkinje neurons and synaptic disorganization in the deep cerebellar nucleus (DCN). The sacsin interactome reveals that sacsin regulates interactions between cytoskeletal and synaptic adhesion proteins. Our findings suggest that disrupted trafficking of synaptic adhesion proteins is a causal molecular deficit in ARSACS

Fish Nutrition and Current Issues in Aquaculture: The Balance in Providing Safe and Nutritious Seafood, in an Environmentally Sustainable Manner

Global aquaculture production has increased in recent years and it is predicted that aquaculture will provide the most reliable supply of seafood in the future. However, there are many controversial issues in aquaculture regarding food safety, nutrition, and sustainability; many of which are directly related to the nutrition and feeds for farmed fish. These nutrition-related issues must be considered in order to achieve balance in safe and nutritious food production and sustainability in aquaculture. This review highlights recent studies and discusses new and innovative aspects in fish nutrition. Some issues in the area of fish nutrition require consideration and improvement, such as: feed and nutrient efficiency, overfeeding and waste, fish meal and fish oil replacements, fish health, biotechnology, and human health concerns. The findings reviewed in this manuscript demonstrate promise toward improvement of the aquaculture industry through nutrition. This review is an update in fish nutrition research, and provides insight on the progression and evolution of this field in order to meet the needs of the industry with the purpose to achieve a balance in seafood production and environmental sustainability. The outcome of this review encourages the use of biotechnology as a tool to meet seafood production and environmental sustainability, in order to ensure global food security in the future and to improve our resource use

Use of ω3 rich oilseed Camelina (Camelina sativa) as a fish oil replacement in aquaculture feeds: implications for growth and lipid biochemistry of farmed Atlantic cod (Gadus morhua), Rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar).

Camelina oil (CO) is a potential lipid replacement for fish oil (FO) in aquaculture feeds due to its high lipid content (40%), high levels of α-linolenic acid (ALA, 18:3ω3) (30%), antioxidants, and low levels of saturated fatty acids. Five feeding experiments were conducted to determine the effectiveness of CO as a FO substitute for three farmed fish species relevant to Canadian aquaculture: Atlantic cod (Gadus morhua), rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar). Three experiments were conducted with Atlantic cod. In the first experiment, a fish oil control (FO), 40% (CO40) and 80% (CO80) replacement of FO with CO were fed to cod for 9 weeks. There was no effect of replacing FO with CO on growth performance. The second study tested diets with 100% replacement of FO with CO (100CO), solvent extracted fish meal (100COSEFM) and partially substituted fish meal (FM) with 15% inclusion of camelina meal (CM) (100CO15CM) for 13 weeks. Cod fed CO had a lower final weight than cod fed FO, while cod fed 100CO15CM had a lower final weight than all other groups. Cod tissue lipid and fatty acid profiles were significantly affected by CO inclusion. In the third experiment, cod were unintentionally exposed to the parasite Loma morhua, which was a significant factor that affected growth in this experiment. In the rainbow trout experiment, CO replaced 50% and 100% of FO. Growth was not affected after the 12 week feeding trial. Tissue lipid and fatty acid profiles were significantly affected by the addition of CO. Compound-specific stable isotope analysis indicated that 27% of docosahexaenoic acid (DHA, 22:6ω3) was synthesized de novo from the CO diet. The Atlantic salmon study tested diets with 100% CO, SEFM and 10% inclusion of CM, in a 16 week feeding trial. Growth was not affected by using 100% CO; however, it was lower in groups fed SEFM and 10% CM diets. Total lipid in salmon flesh fed a diet with CO, SEFM and CM was significantly higher than FO. Amounts of DHA in salmon fed any CO diet were similar to FO-fed salmon due to increased flesh lipid. The sensory quality of salmon fillets was not affected by CO

Lipid and fatty acid digestibility in Calanus copepod and krill oil by Atlantic halibut (Hippoglossus hippoglossus L.)

Marine zooplankton represent a significant biomass of marine lipid that could supply lipid in diets for farmed marine fish. Digestibility of lipid and fatty acids of the copepod, Calanus finmarchicus and Antarctic krill, Euphausia superba by farmed juvenile Atlantic halibut (Hippoglossus hippoglossus) was investigated. Halibut were fed diets containing one of the following test oils at 15% inclusion level: fish oil (FO), Calanus copepod oil (CO) and Euphausia krill oil (KO). KO contained the highest level of saturates (SFA; 39%) and monounsaturates (MUFA; 38%), and was low in polyunsaturated fatty acids (PUFA; 24%) compared to CO (50%) and FO (43%). CO and FO contained lower levels of SFA (31% and 33%, respectively) and MUFA (19% and 24%, respectively). Lipid digestibility of the CO diet (81%) was significantly lower than that of KO (90%) and FO (93%) diets (P < 0.05), likely due to wax esters in CO. Digestibility of SFA in the CO diet (70%) was significantly lower than FO (75%) and KO (77%) and MUFA in CO (84%) was significantly lower than KO (93%) and FO (93%). Digestibility of PUFA was significantly higher in FO (97%) than CO (94%) and KO (95%). Generally the CO diet was significantly less digestible than FO and KO diets

Production, Distribution, and Abundance of Long-Chain Omega-3 Polyunsaturated Fatty Acids: A Fundamental Dichotomy between Freshwater and Terrestrial Ecosystems

Long-chain polyunsaturated fatty acids (LC-PUFA) are critical for the health of aquatic and terrestrial organisms; therefore, understanding the production, distribution, and abundance of these compounds is very important. Although the dynamics of LC-PUFA production and distribution in aquatic environments has been well documented, a systematic and comprehensive comparison to LC-PUFA in terrestrial environments has not been rigorously investigated. Here we use a data synthesis approach to compare and contrast fatty acid profiles of 369 aquatic and terrestrial organisms. Habitat and trophic level were interacting factors that determined the proportion of individual omega-3 (n-3) or omega-6 (n-6) PUFA in aquatic and terrestrial organisms. Higher total n-3 content compared with n-6 PUFA and a strong prevalence of the n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) characterized aquatic versus terrestrial organisms. Conversely, terrestrial organisms had higher linoleic acid (LNA) and alpha-linolenic acid (ALA) contents than aquatic organisms; however, the ratio of ALA: LNA was higher in aquatic organisms. The EPA + DHA content was higher in aquatic animals than terrestrial organisms, and increased from algae to invertebrates to vertebrates in the aquatic environment. An analysis of covariance revealed that fatty acid composition was highly dependent on the interaction between habitat and trophic level. We conclude that freshwater ecosystems provide an essential service through the production of n-3 LC-PUFA that are required to maintain the health of terrestrial organisms including humans.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Long-Chain Omega-3 Polyunsaturated Fatty Acids Have Developmental Effects on the Crop Pest, the Cabbage White Butterfly <i>Pieris rapae</i>

<div><p>Nutritional enhancement of crops using genetic engineering can potentially affect herbivorous pests. Recently, oilseed crops have been genetically engineered to produce the long-chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at levels similar to that found in fish oil; to provide a more sustainable source of these compounds than is currently available from wild fish capture. We examined some of the growth and development impacts of adding EPA and DHA to an artificial diet of <i>Pieris rapae</i>, a common pest of Brassicaceae plants. We replaced 1% canola oil with EPA: DHA (11:7 ratio) in larval diets, and examined morphological traits and growth of larvae and ensuing adults across 5 dietary treatments. Diets containing increasing amounts of EPA and DHA did not affect developmental phenology, larval or pupal weight, food consumption, nor larval mortality. However, the addition of EPA and DHA in larval diets resulted in progressively heavier adults (F _{4, 108} = 6.78; p = 0.011), with smaller wings (p < 0.05) and a higher frequency of wing deformities (R = 0.988; p = 0.001). We conclude that the presence of EPA and DHA in diets of larval <i>P</i>. <i>rapae</i> may alter adult mass and wing morphology; therefore, further research on the environmental impacts of EPA and DHA production on terrestrial biota is advisable.</p></div

Example of cabbage butterflies (pinned to insect boards) fed experimental diets 48 hours after emergence: butterfly with deformed wings (left panel, 100% EPA + DHA diet) compared to a butterfly with intact wings (right panel, control diet).

<p>Example of cabbage butterflies (pinned to insect boards) fed experimental diets 48 hours after emergence: butterfly with deformed wings (left panel, 100% EPA + DHA diet) compared to a butterfly with intact wings (right panel, control diet).</p

Larval, pupal, and butterfly weights (wet weight, mg), and morphological measurements¹,² (cm) in <i>Pieris rapae</i> larvae fed experimental diets containing EPA and DHA.

<p>Larval, pupal, and butterfly weights (wet weight, mg), and morphological measurements<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0152264#t003fn001" target="_blank">¹</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0152264#t003fn002" target="_blank">²</a> (cm) in <i>Pieris rapae</i> larvae fed experimental diets containing EPA and DHA.</p

Incidence of wing deformities in Pieris rapae butterflies fed EPA and DHA enhanced diets in larval stage.

<p>The incidence of wing deformities correlates significantly with the level of EPA and DHA in the diet (correlation coefficient R = 0.988; p = 0.001).</p