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The present study sought to characterize the synthesis pathways producing the essential polyunsaturated fatty acid (PUFA) 20:5n-3 (EPA). For this, the incorporation of 13C was experimentally monitored into 10 fatty acids (FA) during the growth of the diatom Chaetoceros muelleri for 24 h. Chaetoceros muelleri preferentially and quickly incorporated 13C into C18 PUFAs such as 18:2n-6 and 18:3n-6 as well as 16:0 and 16:1n-7, which were thus highly 13C-enriched. During the experiment, 20:5n-3 and 16:3n-4 were among the least-enriched fatty acids. The calculation of the enrichment percentage ratio of a fatty acid B over its suspected precursor A allowed us to suggest that the diatom produced 20:5n-3 (EPA) by a combination between the n-3 (via 18:4n-3) and n-6 (via 18:3n-6 and 20:4n-6) synthesis pathways as well as the alternative &omega, 3 desaturase pathway (via 20:4n-6). In addition, as FA from polar lipids were generally more enriched in 13C than FA from neutral lipids, particularly for 18:1n-9, 18:2n-6 and 18:3n-6, the existence of acyl-editing mechanisms and connectivity between polar and neutral lipid fatty acid pools were also hypothesized. Because 16:3n-4 and 20:5n-3 presented the same concentration and enrichment dynamics, a structural and metabolic link was proposed between these two PUFAs in C. muelleri.

International audience; Carbon isotopic fractionation was studied during the development of the diatom Chaetoceros muelleri grown in batch culture with 13C-depleted CO2 addition. Cellular and growth parameters and isotopic composition of dissolved inorganic carbon and particulate organic carbon were monitored every two days, while the content and isotopic composition of individual fatty acid in polar lipid and neutral lipid were measured on the 5th day (end of exponential phase), 10th and 14th days (stationary phase). Continuous addition of petrochemical CO2 to the algae led to a rapid and strong modification of dissolved inorganic carbon isotopic composition with cascading effects on particulate organic carbon and fatty acid isotopic compositions. Carbon isotope fractionation in Chaetoceros muelleri ranged from 17‰ to 25‰ and changed according to culture ages. Isotopic fractionation into fatty acids, overall, was similar between polar and neutral lipids, and was systematically higher than in particulate organic carbon. At the end of the exponential growth phase, the isotopic composition of individual fatty acids varied from −51.3‰ to −58.4‰. At this culture age, large differences in the isotopic compositions between fatty acids were observed. Polyunsaturated fatty acids such as 16:3n-4, 18:4n-3, and 20:5n-3 were more strongly 13C-depleted than other fatty acids such as 14:0, 16:0, 16:1n-7 or 18:1n-9. These results showed how isotopic effects occur during the desaturation and elongation phases. Such isotopic effects were also supported by the lower δ13C of averaged δ13C of saturated fatty acids and monounsaturated fatty acids as compared to those of polyunsaturated fatty acids. However, during the stationary phase, fatty acid isotopic compositions were less variable and closer to particulate organic carbon, while saturated and monounsaturated fatty acids were more depleted than polyunsaturated fatty acids. Our study underlined the importance of consideration of phytoplankton physiological status when conducting ecological and biogeochemical studies as they appeared to strongly control phytoplankton carbon isotopic composition.

The synthetic pathways responsible for the production of the polyunsaturated fatty acids 22:6n-3 and 20:5n-3 were studied in the Dinophyte Alexandrium minutum. The purpose of this work was to follow the progressive incorporation of an isotopic label (13CO2) into 11 fatty acids to better understand the fatty acid synthesis pathways in A. minutum. The Dinophyte growth was monitored for 54 hours using high-frequency sampling. A. minutum presented a growth in two phases. A lag phase was observed during the first 30 hours of development and had been associated with the probable temporary encystment of Dinophyte cells. An exponential growth phase was then observed after t30. A. minutum rapidly incorporated 13C into 22:6n-3, which ended up being the most 13C-enriched polyunsaturated fatty acid (PUFA) in this experiment, with a higher 13C atomic enrichment than 18:4n-3, 18:5n-3, 20:5n-3, and 22:5n-3. Overall, the 13C atomic enrichment (AE) was inversely proportional to number of carbons in n-3 PUFA. C18 PUFAs, 18:4n-3, and 18:5n-3, were indeed among the least 13C-enriched FAs during this experiment. They were assumed to be produced by the n-3 PUFA pathway. However, they could not be further elongated or desaturated to produce n-3 C20-C22 PUFA, because the AEs of the n-3 C18 PUFAs were lower than those of the n-3 C20-C22 PUFAs. Thus, the especially high atomic enrichment of 22:6n-3 (55.8% and 54.9% in neutral lipids (NLs) and polar lipids (PLs), respectively) led us to hypothesize that this major PUFA was synthesized by an O2-independent Polyketide Synthase (PKS) pathway. Another parallel PKS, independent of the one leading to 22:6n-3, was also supposed to produce 20:5n-3. The inverse order of the 13C atomic enrichment for n-3 PUFAs was also suspected to be related to the possible &beta, oxidation of long-chain n-3 PUFAs occurring during A. minutum encystment.

Mitsainas, George/0000-0003-4976-8275; Lindholm, Anna K/0000-0001-8460-9769; Mathias, Maria da Luz/0000-0003-3876-958X; Foerster, Daniel/0000-0002-6934-0404; Hauffe, Heidi Christine C/0000-0003-3098-8964; Threadgill, David W/0000-0003-3538-1635; Gabriel, Sofia I/0000-0003-3702-4631; Chesler, Elissa/0000-0002-5642-5062; Didion, John/0000-0002-8111-6261; solano, emanuela/0000-0001-8482-9243; Weinstock, George/0000-0002-2997-4592; McMullan, Rachel/0000-0003-0297-4549; Holt, James/0000-0001-6411-9236; Rehermann, Barbara/0000-0001-6832-9951 WOS: 000376170300001 PubMed: 26882987 A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding inmultiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution. National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [T32GM067553, F30MH103925, P50GM076468, K01MH094406, DK-076050, DK-056350, AG038070]; National Science FoundationNational Science Foundation (NSF) [IOS-1121273]; Vaadia-BARD Postdoctoral Fellowship AwardUS-Israel Binational Science Foundation [FI-478-13]; U.S. Army Medical Research and Materiel CommandU.S. Army Medical Research & Materiel Command (USAMRMC) [W81XWH-11-1-0762]; Jackson Laboratory new investigator funds; National Center for Scientific Research, France [ISEM 2016-002]; University of Rome "La Sapienza"; Claraz-Stiftung; Natural Environment Research Council (UK)NERC Natural Environment Research Council; EU Human Capital and Mobility Programme [CHRX-CT93-0192]; Foundation for Science and Technology, PortugalPortuguese Foundation for Science and Technology [PTDC/BIA-EVF/116884/2010, UID/AMB/50017/2013]; Spanish "Ministerio de Ciencia y Tecnologia"Spanish Government [CGL2007-62111]; "Ministerio de Economia y Competitividad"Spanish Government [CGL2010-15243]; School of Medicine at University of North Carolina We wish to thank all the scientists and research personnel who collected and processed the samples used in this study. In particular we acknowledge Luanne Peters and Alex Hong-Tsen Yu for providing critical samples; Ryan Buus and T. Justin Gooch for isolating DNA for high-density genotyping of wild-caught mice; and Vicki Cappa, A. Cerveira, Guila Ganem, Ron and Annabelle Lesher, K. Said, Toni Schelts, Dan Small, and J. Tapisso for aiding in mouse trapping. We thank Muriel Davisson at the Jackson Laboratory for maintaining, for several decades, tissue samples from breeding colonies used to generate wild-derived inbred strains. We also thank Francis Collins, Jim Evans, Matthew Hahn, and Corbin Jones for comments on an earlier version of this manuscript. This work was supported by the National Institutes of Health T32GM067553 to J.P.D. and A.P.M., F30MH103925 to A.P.M., P50GM076468 to E.J.C., G.A.C., and F.P.M.V., K01MH094406 to J.J.C., DK-076050 and DK-056350 to D.P., AG038070 to G.A.C, and the intramural research program to B.R. and S.P.R.; National Science Foundation IOS-1121273 to T.G.; Vaadia-BARD Postdoctoral Fellowship Award FI-478-13 to L.Y.; U.S. Army Medical Research and Materiel Command W81XWH-11-1-0762 to C.J.B.; The Jackson Laboratory new investigator funds to E.J.C.; The National Center for Scientific Research, France to J.B.D. (this is contribution no ISEM 2016-002); the University of Rome "La Sapienza" to R.C. and E.S.; Claraz-Stiftung to S.G. and A.L.; Natural Environment Research Council (UK) to M.D.G., H.C.H., and J.B.S.; EU Human Capital and Mobility Programme (CHRX-CT93-0192) to H.C.H. and J.B.S.; Foundation for Science and Technology, Portugal PTDC/BIA-EVF/116884/2010 and UID/AMB/50017/2013 to S.I.G., M.L.M., and J.B.S.; Spanish "Ministerio de Ciencia y Tecnologia" CGL2007-62111 and "Ministerio de Economia y Competitividad" CGL2010-15243 to J.V.;and the Oliver Smithies Investigator funds provided by the School of Medicine at University of North Carolina to F.P.M.V. All data are made available at http://csbio.unc.edu/r2d2/. The authors declare no competing financial interests. Correspondence and requests for materials should be addressed to F.P.M.V. (fernando@med.unc.edu).

Exercise is known to have beneficial effects on cognitive function. This effect is greatly favored by an exercise-induced increase in neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), especially with high-intensity exercises (HIE). As a complication of type 1 diabetes (T1D), a cognitive decline may occur, mostly ascribed to hypoglycaemia and chronic hyperglycaemia. Therefore, the purpose of this study was to examine the effects of acute HIE on cognitive function and neurotrophins in T1D and matched controls. Ten trained T1D (8 males, 2 females) participants and their matched (by age, sex, fitness level) controls were evaluated on 2 occasions after familiarization: a maximal test to exhaustion and an HIE bout (10 intervals of 60 s at 90% of their maximal wattage followed by 60 s at 50 W). Cognitive tests and analyses of serum BDNF, IGF-1, and free insulin were performed before and after HIE and following 30 min of recovery. At baseline, cognitive performance was better in the controls compared with the T1D participants (p < 0.05). After exercise, no significant differences in cognitive performance were detected. BDNF levels were significantly higher and IGF-1 levels were significantly lower in T1D compared with the control group (p < 0.05) at all time points. Exercise increased BDNF and IGF-1 levels in a comparable percentage in both groups (p < 0.05). In conclusion, although resting levels of serum BDNF and IGF-1 were altered by T1D, comparable increasing effects on BDNF and IGF-1 in T1D and healthy participants were found. Therefore, regularly repeating acute HIE could be a promising strategy for brain health in T1D.