| 1. |
- Bécoulet, A., et al.
(författare)
-
Science and technology research and development in support to ITER and the Broader Approach at CEA
- 2013
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10
-
Tidskriftsartikel (refereegranskat)abstract
- In parallel to the direct contribution to the procurement phase of ITER and Broader Approach, CEA has initiated research & development programmes, accompanied by experiments together with a significant modelling effort, aimed at ensuring robust operation, plasma performance, as well as mitigating the risks of the procurement phase. This overview reports the latest progress in both fusion science and technology including many areas, namely the mitigation of superconducting magnet quenches, disruption-generated runaway electrons, edge-localized modes (ELMs), the development of imaging surveillance, and heating and current drive systems for steady-state operation. The WEST (W Environment for Steady-state Tokamaks) project, turning Tore Supra into an actively cooled W-divertor platform open to the ITER partners and industries, is presented.
|
|
| 2. |
- Roa, J., et al.
(författare)
-
Dicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice
- 2022
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Kiss1 neurons, producing kisspeptins, are essential for puberty and fertility, but their molecular regulatory mechanisms remain unfolded. Here, we report that congenital ablation of the microRNA-synthesizing enzyme, Dicer, in Kiss1 cells, causes late-onset hypogonadotropic hypogonadism in both sexes, but is compatible with pubertal initiation and preserved Kiss1 neuronal populations at the infantile/juvenile period. Yet, failure to complete puberty and attain fertility is observed only in females. Kiss1-specific ablation of Dicer evokes disparate changes of Kiss1-cell numbers and Kiss1/kisspeptin expression between hypothalamic subpopulations during the pubertal-transition, with a predominant decline in arcuate-nucleus Kiss1 levels, linked to enhanced expression of its repressors, Mkrn3, Cbx7 and Eap1. Our data unveil that miRNA-biosynthesis in Kiss1 neurons is essential for pubertal completion and fertility, especially in females, but dispensable for initial reproductive maturation and neuronal survival in both sexes. Our results disclose a predominant miRNA-mediated inhibitory program of repressive signals that is key for precise regulation of Kiss1 expression and, thereby, reproductive function. Kiss1 neurons are essential for puberty and fertility. Here, the authors show that canonical microRNA biosynthesis in Kiss1 neurons plays an essential role in the control of puberty and fertility, especially in females, likely via repression of repressors on the Kiss1 gene.
|
|
| 3. |
- Velasco, I., et al.
(författare)
-
Gonadal hormone-dependent vs. -independent effects of kisspeptin signaling in the control of body weight and metabolic homeostasis
- 2019
-
Ingår i: Metabolism: Clinical and Experimental. - : Elsevier BV. - 0026-0495. ; 98:September, s. 84-94
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Kisspeptins, encoded by Kiss1, have emerged as essential regulators of puberty and reproduction by primarily acting on GnRH neurons, via their canonical receptor, Gpr54. Mounting, as yet fragmentary, evidence strongly suggests that kisspeptin signaling may also participate in the control of key aspects of body energy and metabolic homeostasis. However, characterization of such metabolic dimension of kisspeptins remains uncomplete, without an unambiguous discrimination between the primary metabolic actions of kisspeptins vs. those derived from their ability to stimulate the secretion of gonadal hormones, which have distinct metabolic actions on their own. In this work, we aimed to tease apart primary vs. secondary effects of kisspeptins in the control of key aspects of metabolic homeostasis using genetic models of impaired kisspeptin signaling and/or gonadal hormone status. Methods: Body weight (BW) gain and composition, food intake and key metabolic parameters, including glucose tolerance, were comparatively analyzed, in lean and obesogenic conditions, in mice lacking kisspeptin signaling due to global inactivation of Gpr54 (displaying profound hypogonadism; Gpr54−/−) vs. Gpr54 null mice with selective re-introduction of Gpr54 expression only in GnRH cells (Gpr54−/−Tg), where kisspeptin signaling elsewhere than in GnRH neurons is ablated but gonadal function is preserved. Results: In male mice, global elimination of kisspeptin signaling resulted in decreased BW, feeding suppression and increased adiposity, without overt changes in glucose tolerance, whereas Gpr54−/− female mice displayed enhanced BW gain at adulthood, increased adiposity and perturbed glucose tolerance, despite reduced food intake. Gpr54−/−Tg rescued mice showed altered postnatal BW gain in males and mildly perturbed glucose tolerance in females, with intermediate phenotypes between control and global KO animals. Yet, body composition and leptin levels were similar to controls in gonadal-rescued mice. Exposure to obesogenic insults, such as high fat diet (HFD), resulted in exaggerated BW gain and adiposity in global Gpr54−/− mice of both sexes, and worsening of glucose tolerance, especially in females. Yet, while rescued Gpr54−/−Tg males displayed intermediate BW gain and feeding profiles and impaired glucose tolerance, rescued Gpr54−/−Tg females behaved as controls, except for a modest deterioration of glucose tolerance after ovariectomy. Conclusion: Our data support a global role of kisspeptin signaling in the control of body weight and metabolic homeostasis, with a dominant contribution of gonadal hormone-dependent actions. However, our results document also discernible primary effects of kisspeptin signaling in the regulation of body weight gain, feeding and responses to obesogenic insults, which occur in a sexually-dimorphic manner. Summary of translational relevance: Kisspeptins, master regulators of reproduction, may also participate in the control of key aspects of body energy and metabolic homeostasis; yet, the nature of such metabolic actions remains debatable, due in part to the fact that kisspeptins modulate gonadal hormones, which have metabolic actions on their own. By comparing the metabolic profiles of two mouse models with genetic inactivation of kisspeptin signaling but different gonadal status (hypogonadal vs. preserved gonadal function), we provide herein a systematic dissection of gonadal-dependent vs. -independent metabolic actions of kisspeptins. Our data support a global role of kisspeptin signaling in the control of body weight and metabolic homeostasis, with a dominant contribution of gonadal hormone-dependent actions. However, our results document also discernible primary effects of kisspeptin signaling in the regulation of body weight gain, feeding and responses to obesogenic insults, which occur in a sexually-dimorphic manner. These data pave the way for future analyses addressing the eventual contribution of altered kisspeptin signaling in the development of metabolic alterations especially in conditions linked to reproductive dysfunction. © 2019 Elsevier Inc.
|
|
| 4. |
- Franssen, D, et al.
(författare)
-
AMP-activated protein kinase (AMPK) signaling in GnRH neurons links energy status and reproduction.
- 2021
-
Ingår i: Metabolism: clinical and experimental. - 1532-8600. ; 115
-
Tidskriftsartikel (refereegranskat)abstract
- Reproduction is tightly coupled to body energy and metabolic status. GnRH neurons, master elements and final output pathway for the brain control of reproduction, directly or indirectly receive and integrate multiple metabolic cues to regulate reproductive function. Yet, the molecular underpinnings of such phenomenon remain largely unfolded. AMP-activated protein kinase (AMPK), the fundamental cellular sensor that becomes activated in conditions of energy deficit, has been recently shown to participate in the control of Kiss1 neurons, essential gatekeepers of the reproductive axis, by driving an inhibitory valence in situations of energy scarcity at puberty. However, the contribution of AMPK signaling specifically in GnRH neurons to the metabolic control of reproduction remains unknown.Double immunohistochemistry (IHC) was applied to evaluate expression of active (phosphorylated) AMPK in GnRH neurons and a novel mouse line, named GAMKO, with conditional ablation of the AMPK α1 subunit in GnRH neurons, was generated. GAMKO mice of both sexes were subjected to reproductive characterization, with attention to puberty and gonadotropic responses to kisspeptin and metabolic stress.A vast majority (>95%) of GnRH neurons co-expressed pAMPK. Female (but not male) GAMKO mice displayed earlier puberty onset and exaggerated LH (as surrogate marker of GnRH) responses to kisspeptin-10 at the prepubertal age. In adulthood, GAMKO females retained increased LH responsiveness to kisspeptin and showed partial resilience to the inhibitory effects of conditions of negative energy balance on the gonadotropic axis. The modulatory role of AMPK in GnRH neurons required preserved ovarian function, since the differences in LH pulsatility detected between GAMKO and control mice subjected to fasting were abolished in ovariectomized animals.Altogether, our data document a sex-biased, physiological role of AMPK signaling in GnRH neurons, as molecular conduit of the inhibitory actions of conditions of energy deficit on the female reproductive axis.
|
|
| 5. |
- Zamora, Juan Carlos, et al.
(författare)
-
Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
-
Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
-
Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Barroso, A., et al.
(författare)
-
Neonatal exposure to androgens dynamically alters gut microbiota architecture
- 2020
-
Ingår i: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 247:1, s. 69-85
-
Tidskriftsartikel (refereegranskat)abstract
- Gonadal steroids strongly contribute to the metabolic programming that shapes the susceptibility to the manifestation of diseases later in life, and the effect is often sexually dimorphic. Microbiome signatures, together with metabolic traits and sex steroid levels, were analyzed at adulthood in neonatally androgenized female rats, and compared with those of control male and female rats. Exposure of female rats to high doses of androgens on early postnatal life resulted in persistent alterations of the sex steroid profile later on life, namely lower progesterone and higher estr adiol and estrone levels, with no effect on endogenous androgens. Neonatally androgenized females were heavier (10% at early adulthood and 26% at adulthood) than controls and had impaired glucose homeostasis observed by higher AUC of glucose in GTT and ITT when subjected to obesogenic manipulations. Androgenized female displayed overt alterations in gut microbiota, indicated especially by higher Bacteroidetes and lower Firmicutes abundance at early adulthood, which disappeared when animals were concurrently overfed at adulthood. Notably, these changes in gut microbiota were related with the intestinal expression of several miRNAs, such as miR-27a-3p, miR-29a-5p, and miR-100-3p. Our results suggest that nutritional and hormonal disruption at early developmental periods not only alters the metabolic programming of the individual later in life but also perturbs the architecture of gut microbiota, which may interact with the host by a cross-talk mediated by intestinal miRNAs; phenomena that may contribute to amplify the metabolic derangement caused by obesity, as seen in neonatally androgenized female rats.
|
|
| 14. |
- Dey, R., et al.
(författare)
-
Exploring advanced phycoremediation strategies for resource recovery from secondary wastewater using a large scale photobioreactor
- 2024
-
Ingår i: Bioresource Technology. - 0960-8524. ; 391
-
Tidskriftsartikel (refereegranskat)abstract
- This study aimed to investigate the operation of a 1000L microalgae-based membrane photobioreactor system in a greenhouse for continuous secondary wastewater treatment using Desmodesmus sp., a green microalgae strain originally isolated from a German sewage plant. The research spanned both summer and winter seasons, seeking to comprehend key trends and optimization strategies. Maintaining low cell concentrations in the photobioreactor during periods of light inhibition proved advantageous for nutrient uptake rates. Effective strategies for enhancing algae-based wastewater treatment included cell mass recycling, particularly during periods of high light availability. In comparison to conventional continuous cultivation methods, employing cell recycling and high dilution rates during times of abundant light, alongside using low cell concentrations and dilution rates during light inhibition, resulted in an 80 % and 10 % increase in overall biomass productivity during summer and winter, respectively. Furthermore, nitrogen/phosphorus (N/P) removal rates exhibited a 23 % improvement during winter, while remaining unchanged in summer.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Martínez-Sánchez, Noelia, et al.
(författare)
-
Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
- 2017
-
Ingår i: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 26:1, s. 212-229.e12
-
Tidskriftsartikel (refereegranskat)abstract
- Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Ruohonen, S. T., et al.
(författare)
-
Selective loss of kisspeptin signaling in oocytes causes progressive premature ovulatory failure
- 2022
-
Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 37:4, s. 806-821
-
Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION Does direct kisspeptin signaling in the oocyte have a role in the control of follicular dynamics and ovulation? SUMMARY ANSWER Kisspeptin signaling in the oocyte plays a relevant physiological role in the direct control of ovulation; oocyte-specific ablation of kisspeptin receptor, Gpr54, induces a state of premature ovulatory failure in mice that recapitulates some features of premature ovarian insufficiency (POI). WHAT IS KNOWN ALREADY Kisspeptins, encoded by the Kiss1 gene, are essential for the control of ovulation and fertility, acting primarily on hypothalamic GnRH neurons to stimulate gonadotropin secretion. However, kisspeptins and their receptor, Gpr54, are also expressed in the ovary of different mammalian species, including humans, where their physiological roles remain contentious and poorly characterized. STUDY DESIGN, SIZE, DURATION A novel mouse line with conditional ablation of Gpr54 in oocytes, named OoGpr54(-/-), was generated and studied in terms of follicular and ovulatory dynamics at different age-points of postnatal maturation. A total of 59 OoGpr54(-/-) mice and 47 corresponding controls were analyzed. In addition, direct RNA sequencing was applied to ovarian samples from 8 OoGpr54(-/-) and 7 control mice at 6 months of age, and gonadotropin priming for ovulatory induction was conducted in mice (N = 7) from both genotypes. PARTICIPANTS/MATERIALS, SETTING, METHODS Oocyte-selective ablation of Gpr54 in the oocyte was achieved in vivo by crossing a Gdf9-driven Cre-expressing transgenic mouse line with a Gpr54 LoxP mouse line. The resulting OoGpr54(-/-) mouse line was subjected to phenotypic, histological, hormonal and molecular analyses at different age-points of postnatal maturation (Day 45, and 2, 4, 6 and 10-11 months of age), in order to characterize the timing of puberty, ovarian follicular dynamics and ovulation, with particular attention to identification of features reminiscent of POI. The molecular signature of ovaries from OoGpr54(-/-) mice was defined by direct RNA sequencing. Ovulatory responses to gonadotropin priming were also assessed in OoGpr54(-/-) mice. MAIN RESULTS AND THE ROLE OF CHANCE Oocyte-specific ablation of Gpr54 caused premature ovulatory failure, with some POI-like features. OoGpr54(-/-) mice had preserved puberty onset, without signs of hypogonadism. However, already at 2 months of age, 40% of OoGpr54(-/-) females showed histological features reminiscent of ovarian failure and anovulation. Penetrance of the phenotype progressed with age, with >80% and 100% of OoGpr54(-/-) females displaying complete ovulatory failure by 6- and 10 months, respectively. This occurred despite unaltered hypothalamic Gpr54 expression and gonadotropin levels. Yet, OoGpr54(-/-) mice had decreased sex steroid levels. While the RNA signature of OoGpr54(-/-) ovaries was dominated by the anovulatory state, oocyte-specific ablation of Gpr54 significantly up- or downregulated of a set of 21 genes, including those encoding pituitary adenylate cyclase-activating polypeptide, Wnt-10B, matrix-metalloprotease-12, vitamin A-related factors and calcium-activated chloride channel-2, which might contribute to the POI-like state. Notably, the anovulatory state of young OoGpr54(-/-) mice could be rescued by gonadotropin priming. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Conditional ablation of Gpr54 in oocytes unambiguously caused premature ovulatory failure in mice; yet, the ultimate molecular mechanisms for such state of POI can be only inferred on the basis of RNAseq data and need further elucidation, since some of the molecular changes observed in OoGpr54(-/-) ovaries were secondary to the anovulatory state. Direct translation of mouse findings to human disease should be made with caution since, despite the conserved expression of Kiss1/kisspeptin and Gpr54 in rodents and humans, our mouse model does not recapitulate all features of common forms of POI. WIDER IMPLICATIONS OF THE FINDINGS Deregulation of kisspeptin signaling in the oocyte might be an underlying, and previously unnoticed, cause for some forms of POI in women. STUDY FUNDING/COMPETING INTEREST(S) This work was primarily supported by a grant to M.P. and M.T.-S. from the FiDiPro (Finnish Distinguished Professor) Program of the Academy of Finland. Additional financial support came from grant BFU2017-83934-P (M.T.-S.; Ministerio de Economia y Competitividad, Spain; co-funded with EU funds/FEDER Program), research funds from the IVIRMA International Award in Reproductive Medicine (M.T.-S.), and EFSD Albert Renold Fellowship Programme (S.T.R.). The authors have no conflicts of interest to declare in relation to the contents of this work.
|
|
| 21. |
|
|
| 22. |
|
|
