8 research outputs found
Congenital Hyperinsulinism in Humans and Insulin Secretory Dysfunction in Mice Caused by Biallelic DNAJC3 Variants
No full textThe BiP co-chaperone DNAJC3 protects cells during ER stress. In mice, the deficiency of DNAJC3 leads to beta-cell apoptosis and the gradual onset of hyperglycemia. In humans, biallelic DNAJC3 variants cause a multisystem disease, including early-onset diabetes mellitus. Recently, hyperinsulinemic hypoglycemia (HH) has been recognized as part of this syndrome. This report presents a case study of an individual with HH caused by DNAJC3 variants and provides an overview of the metabolic phenotype of individuals with HH and DNAJC3 variants. The study demonstrates that HH may be a primary symptom of DNAJC3 deficiency and can persist until adolescence. Additionally, glycemia and insulin release were analyzed in young DNACJ3 knockout (K.O.) mice, which are equivalent to human infants. In the youngest experimentally accessible age group of 4-week-old mice, the in vivo glycemic phenotype was already dominated by a reduced total insulin secretion capacity. However, on a cellular level, the degree of insulin release of DNAJC3 K.O. islets was higher during periods of increased synthetic activity (high-glucose stimulation). We propose that calcium leakage from the ER into the cytosol, due to disrupted DNAJC3-controlled gating of the Sec61 channel, is the most likely mechanism for HH. This is the first genetic mechanism explaining HH solely by the disruption of intracellular calcium homeostasis. Clinicians should screen for HH in DNAJC3 deficiency and consider DNAJC3 variants in the differential diagnosis of congenital hyperinsulinism
The eclipsing post-common envelope binary CSS21055: a white dwarf with a probable brown-dwarf companion
No full textWe report photometric observations of the eclipsing close binary CSS21055 (SDSS J141126+200911) that strongly suggest that the companion to the carbon-oxygen white dwarf is a brown dwarf with a mass between 0.030 and 0.074 M⊙. The measured orbital period is 121.73 min and the totality of the eclipse lasts 125 s. If confirmed, CSS21055 would be the first detached eclipsing WD+BD binary. Spectroscopy in the eclipse could provide information about the companion’s evolutionary state and atmospheric structure
Robustness and Information Transfer within IL-6-induced JAK/STAT Signalling
No full textCellular communication via intracellular signalling pathways is crucial. Expression and activation of signalling proteins is heterogenous between isogenic cells of the same cell-type. However, mechanisms evolved to enable sufficient communication and to ensure cellular functions. We use information theory to clarify mechanisms facilitating IL-6-induced JAK/STAT signalling despite cell-to-cell variability. We show that different mechanisms enabling robustness against variability complement each other. Early STAT3 activation is robust as long as cytokine concentrations are low. Robustness at high cytokine concentrations is ensured by high STAT3 expression or serine phosphorylation. Later the feedback-inhibitor SOCS3 increases robustness. Channel Capacity of JAK/STAT signalling is limited by cell-to-cell variability in STAT3 expression and is affected by the same mechanisms governing robustness. Increasing STAT3 amount increases Channel Capacity and robustness, whereas increasing STAT3 tyrosine phosphorylation reduces robustness but increases Channel Capacity. In summary, we elucidate mechanisms preventing dysregulated signalling by enabling reliable JAK/STAT signalling despite cell-to-cell heterogeneity.sponsorship: We acknowledge the funding of this study by German Federal Ministry of Education and Research (BMBF; 031A300A; Project InTraSig) to F.S. and A.D. T.J. was supported by the European Commission Research Executive Agency under grant CIG PCIG12-GA-2012-334298, M.K. by the Polish National Science Centre under grant 2015/17/B/NZ2/03692. The authors of this article are responsible for the content of this publication. The funding sources had no involvement in the study design, in the collection, analysis and interpretation of data, in writing of the report, or in the decision to submit the article for publication. We thank Oliver Klepsch and Hannes Bongartz for experimental assistance. We acknowledge Valeria Poli, Gerhard Muller-Newen and Akihiko Yoshimura for generous support of our study with MEF cells and Stefan Rose-John for the supply of Hy-IL-6. (German Federal Ministry of Education and Research (BMBF)|031A300A, European Commission Research Executive Agency|CIG PCIG12-GA-2012-334298, Polish National Science Centre|2015/17/B/NZ2/03692)status: Publishe
Congenital Hyperinsulinism in Humans and Insulin Secretory Dysfunction in Mice Caused by Biallelic DNAJC3 Variants
No full textPancreatic islet protection at the expense of secretory function involves serine-linked mitochondrial one-carbon metabolism
No full textType 2 diabetes is characterized by insulin hypersecretion followed by reduced glucose-stimulated insulin secretion (GSIS). Here we show that acute stimulation of pancreatic islets with the insulin secretagogue dextrorphan (DXO) or glibenclamide enhances GSIS, whereas chronic treatment with high concentrations of these drugs reduce GSIS but protect islets from cell death. Bulk RNA sequencing of islets shows increased expression of genes for serine-linked mitochondrial one-carbon metabolism (OCM) after chronic, but not acute, stimulation. In chronically stimulated islets, more glucose is metabolized to serine than to citrate, and the mitochondrial ATP/ADP ratio decreases, whereas the NADPH/NADP+ ratio increases. Activating transcription factor-4 (Atf4) is required and sufficient to activate serine-linked mitochondrial OCM genes in islets, with gain- and loss-of-function experiments showing that Atf4 reduces GSIS and is required, but not sufficient, for full DXO-mediated islet protection. In sum, we identify a reversible metabolic pathway that provides islet protection at the expense of secretory function
ANDES, the high resolution spectrograph for the ELT: science goals, project overview and future developments
No full textMarconi, A. et al.-- Full list of authors: Marconi, A.; Abreu, M.; Adibekyan, V.; Alberti, V.; Albrecht, S.; Alcaniz, J.; Aliverti, M.; Allende Prieto, C.; Alvarado-Gomez, J. D.; Alves, C. S.; Amado, P. J.; Amate, M.; Andersen, M. I.; Antoniucci, S.; Artigau, E.; Bailet, C.; Baker, C.; Baldini, V.; Balestra, A.; Barnes, S. A.; Baron, F.; Barros, S. C. C.; Bauer, S. M.; Beaulieu, M.; Bellido-Tirado, O.; Benneke, B.; Bensby, T.; Bergin, E. A.; Berio, P.; Biazzo, K.; Bigot, L.; Bik, A.; Birkby, J. L.; Blind, N.; Boebion, O.; Boisse, I.; Bolmont, E.; Bolton, J. S.; Bonaglia, M.; Bonfils, X.; Bonhomme, L.; Borsa, F.; Bouret, J. -C.; Brandeker, A.; Brandner, W.; Broeg, C. H.; Brogi, M.; Brousseau, D.; Brucalassi, A.; Brynnel, J.; Buchhave, L. A.; Buscher, D. F.; Cabona, L.; Cabral, A.; Calderone, G.; Calvo-Ortega, R.; Cantalloube, F.; Canto Martins, B. L.; Carbonaro, L.; Caujolle, Y.; Chauvin, G.; Chazelas, B.; Cheffot, A. -L.; Cheng, Y. S.; Chiavassa, A.; Christensen, L.; Cirami, R.; Cirasuolo, M.; Cook, N. J.; Cooke, R. J.; Coretti, I.; Covino, S.; Cowan, N.; Cresci, G.; Cristiani, S.; Cunha Parro, V.; Cupani, G.; D'Odorico, V.; Dadi, K.; de Castro Leão, I.; De Cia, A.; De Medeiros, J. R.; Debras, F.; Debus, M.; Delorme, A.; Demangeon, O.; Derie, F.; Dessauges-Zavadsky, M.; Di Marcantonio, P.; Di Stefano, S.; Dionies, F.; Domiciano de Souza, A.; Doyon, R.; Dunn, J.; Egner, S.; Ehrenreich, D.; Faria, J. P.; Ferruzzi, D.; Feruglio, C.; Fisher, M.; Fontana, A.; Frank, B. S.; Fuesslein, C.; Fumagalli, M.; Fusco, T.; Fynbo, J.; Gabella, O.; Gaessler, W.; Gallo, E.; Gao, X.; Genolet, L.; Genoni, M.; Giacobbe, P.; Giro, E.; Gonçalves, R. S.; Gonzalez, O. A.; González-Hernández, J. I.; Gouvret, C.; Gracia Témich, F.; Haehnelt, M. G.; Haniff, C.; Hatzes, A.; Helled, R.; Hoeijmakers, H. J.; Hughes, I.; Huke, P.; Ivanisenko, Y.; Järvinen, A. S.; Järvinen, S. P.; Kaminski, A.; Kern, J.; Knoche, J.; Kordt, A.; Korhonen, H.; Korn, A. J.; Kouach, D.; Kowzan, G.; Kreidberg, L.; Landoni, M.; Lanotte, A. A.; Lavail, A.; Lavie, B.; Lee, D.; Lehmitz, M.; Li, J.; Li, W.; Liske, J.; Lovis, C.; Lucatello, S.; Lunney, D.; MacIntosh, M. J.; Madhusudhan, N.; Magrini, L.; Maiolino, R.; Maldonado, J.; Malo, L.; Man, A. W. S.; Marquart, T.; Marques, C. M. J.; Marques, E. L.; Martinez, P.; Martins, A.; Martins, C. J. A. P.; Martins, J. H. C.; Maslowski, P.; Mason, C.; Mason, E.; McCracken, R. A.; Melo e Sousa, M. A. F.; Mergo, P.; Micela, G.; Milaković, D.; Mollière, P.; Monteiro, M. A.; Montgomery, D.; Mordasini, C.; Morin, J.; Mucciarelli, A.; Murphy, M. T.; N'Diaye, M.; Nardetto, N.; Neichel, B.; Neri, N.; Niedzielski, A. T.; Niemczura, E.; Nisini, B.; Nortmann, L.; Noterdaeme, P.; Nunes, N. J.; Oggioni, L.; Olchewsky, F.; Oliva, E.; Önel, H.; Origlia, L.; Östlin, G.; Ouellette, N. N. -Q.; Pallé, E.; Papaderos, P.; Pariani, G.; Pasquini, L.; Peñate Castro, J.; Pepe, F.; Peroux, C.; Perreault Levasseur, L.; Perruchot, S.; Petit, P.; Pfuhl, O.; Pino, L.; Piqueras, J.; Piskunov, N.; Pollo, A.; Poppenhaeger, K.; Porru, M.; Puschnig, J.; Quirrenbach, A.; Rauscher, E.; Rebolo, R.; Redaelli, E. M. A.; Reffert, S.; Reid, D. T.; Reiners, A.; Richter, P.; Riva, M.; Rivoire, S.; Rodríguez-López, C.; Roederer, I. U.; Romano, D.; Roth, M.; Rousseau, S.; Rowe, J.; Saccardi, A.; Salvadori, S.; Sanna, N.; Santos, N. C.; Santos Diaz, P.; Sanz-Forcada, J.; Sarajlic, M.; Sauvage, J. -F.; Savio, D.; Scaudo, A.; Schäfer, S.; Schiavon, R. P.; Schmidt, T. M.; Selmi, C.; Simoes, R.; Simonnin, A.; Sivanandam, S.; Sordet, M.; Sordo, R.; Sortino, F.; Sosnowska, D.; Sousa, S. G.; Spang, A.; Spiga, R.; Stempels, E.; Stevenson, J. R. Y.; Strassmeier, K. G.; Suárez Mascareño, A.; Sulich, A.; Sun, X.; Tanvir, N. R.; Tenegi-Sanginés, F.; Thibault, S.; Thompson, S. J.; Tisserand, P.; Tozzi, A.; Turbet, M.; Véran, J. -P.; Vallée, P.; Vanni, I.; Varas, R.; Vega-Moreno, A.; Venn, K. A.; Verma, A.; Vernet, J.; Viel, M.; Wade, G.; Waring, C.; Weber, M.; Weder, J.; Wehbé, B.; Weingrill, J.; Woche, M.; Xompero, M.; Zackrisson, E.; Zanutta, A.; Zapatero Osorio, M. R.; Zechmeister, M.; Zimara, J.-- Part of the Proceedings of SPIE - The International Society for Optical Engineering Volume 1309 Article number 1309613 Ground-based and Airborne Instrumentation for Astronomy X 2024 Yokohama 16 June 2024 through 21 June 2024 Code 202825.The first generation of ELT instruments includes an optical-infrared high resolution spectrograph, indicated as ELT-HIRES and recently christened ANDES (ArmazoNes high Dispersion Echelle Spectrograph). ANDES consists of three fibre-fed spectrographs ([U]BV, RIZ, YJH) providing a spectral resolution of ∼100,000 with a minimum simultaneous wavelength coverage of 0.4-1.8 μm with the goal of extending it to 0.35-2.4 μm with the addition of an U arm to the BV spectrograph and a separate K band spectrograph. It operates both in seeing- and diffraction-limited conditions and the fibre-feeding allows several, interchangeable observing modes including a single conjugated adaptive optics module and a small diffraction-limited integral field unit in the NIR. Modularity and fibre-feeding allows ANDES to be placed partly on the ELT Nasmyth platform and partly in the Coudé room. ANDES has a wide range of groundbreaking science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars, tests on the stability of Nature's fundamental couplings, and the direct detection of the cosmic acceleration. The ANDES project is carried forward by a large international consortium, composed of 35 Institutes from 13 countries, forming a team of almost 300 scientists and engineers which include the majority of the scientific and technical expertise in the field that can be found in ESO member states. © 2024 SPIEThe Italian effort for ANDES is supported by the Italian National Institute for Astrophysics (INAF).
AIP received financial support by the German Federal Ministry of Education and Research (BMBF/DESY-PH:
05A23BAB)
The Portuguese team thanks the Portuguese Space Agency for the provision of financial support in the framework of the PRODEX Programme of the European Space Agency (ESA) under contract number 4000143136
as well as from funds by the European Union (ERC, FIERCE, 101052347). Views and opinions expressed are
however those of the author(s) only and do not necessarily reflect those of the European Union or the European
Research Council. Neither the European Union nor the granting authority can be held responsible for them.
This work further was supported by FCT - Fundação para a Ciência e a Tecnologia through national funds
and by FEDER through COMPETE2020 - Programa Operacional Competitividade e Internacionalização by
these grants: UIDB/04434/2020; UIDP/04434/2020. The ANDES project is partially funded through the SNSF
FLARE programme for large infrastructures under grants 20FL21_173604, 20FL20_186177 and 20FL20_216577 Swedish participation in the ANDES project is made possible through the national Swedish ELT Instrumentation Consortium (SELTIC), suppored by the Swedish Research Council (VR). CJM acknowledges FCT and
POCH/FSE (EC) support through Investigador FCT Contract 2021.01214.CEECIND/CP1658/CT0001 and
project 2022.04048.PTDC (Phi in the Sky, DOI 10.54499/2022.04048.PTDC) NCS acknowledges funding by the
European Union (ERC, FIERCE, 101052347). Views and opinions expressed are however those of the author(s)
only and do not necessarily reflect those of the European Union or the European Research Council. Neither
the European Union nor the granting authority can be held responsible for them. This work was supported
by FCT - Fundação para a Ciência e a Tecnologia through national funds and by FEDER through COMPETE2020 - Programa Operacional Competitividade e Internacionalização by these grants: UIDB/04434/2020;
UIDP/04434/2020.
JLB acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon
2020 research and innovation program under grant agreement No 805445. MTM acknowledges the support of the
Australian Research Council through Future Fellowship grant FT180100194 SS acknowledges funding from the
European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program
under grant agreement No 804240. TMS acknowledges support from the SNF synergia grant CRSII5-193689
(BLUVES). CAP, JIGH, RR, ASM, MA, FGT, JPC, FTS, AVM, and RS acknowledge financial support from
the Spanish Ministry of Science and Innovation (MICINN) project PID2020-117493GB-I00. PJA, CRL, RCO,
RV acknowledge financial support from the Agencia Estatal de Investigación (AEI/10.13039/501100011033) of
the Ministerio de Ciencia e Innovación and the ERDF “A way of making Europe” through projects PID2022-
137241NB-C43 and the Centre of Excellence “Severo Ochoa” award to the Instituto de Astrofísica de Andalucía
(CEX2021-001131-S). With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2021-001131-S).Peer reviewe
ANDES, the high resolution spectrograph for the ELT: science goals, project overview, and future developments
No full textThe first generation of ELT instruments includes an optical-infrared high resolution spectrograph, indicated as ELT-HIRES and recently christened ANDES (ArmazoNes high Dispersion Echelle Spectrograph).ANDES consists of three fibre-fed spectrographs ([U]BV, RIZ, YJH) providing a spectral resolution of ∼100,000 with a minimum simultaneous wavelength coverage of 0.4-1.8 µm with the goal of extending it to 0.35-2.4 µm with the addition of an U arm to the BV spectrograph and a separate K band spectrograph.It operates both in seeing- and diffraction-limited conditions and the fibre-feeding allows several, interchangeable observing modes including a single conjugated adaptive optics module and a small diffraction-limited integral field unit in the NIR.Modularity and fibre-feeding allows ANDES to be placed partly on the ELT Nasmyth platform and partly in the Coudé room.ANDES has a wide range of groundbreaking science cases spanning nearly all areas of research in astrophysics and even fundamental physics.Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars, tests on the stability of Nature's fundamental couplings, and the direct detection of the cosmic acceleration.The ANDES project is carried forward by a large international consortium, composed of 35 Institutes from 13 countries, forming a team of almost 300 scientists and engineers which include the majority of the scientific and technical expertise in the field that can be found in ESO member states.</p
ANDES, the high resolution spectrograph for the ELT: science goals, project overview, and future developments
No full textInternational audienceThe first generation of ELT instruments includes an optical-infrared high resolution spectrograph, indicated as ELT-HIRES and recently christened ANDES (ArmazoNes high Dispersion Echelle Spectrograph). ANDES consists of three fibre-fed spectrographs ([U]BV, RIZ, YJH) providing a spectral resolution of ∼100,000 with a minimum simultaneous wavelength coverage of 0.4-1.8 μm with the goal of extending it to 0.35-2.4 μm with the addition of an U arm to the BV spectrograph and a separate K band spectrograph. It operates both in seeing- and diffraction-limited conditions and the fibre-feeding allows several, interchangeable observing modes including a single conjugated adaptive optics module and a small diffraction-limited integral field unit in the NIR. Modularity and fibre-feeding allows ANDES to be placed partly on the ELT Nasmyth platform and partly in the Coudé room. ANDES has a wide range of groundbreaking science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars, tests on the stability of Nature’s fundamental couplings, and the direct detection of the cosmic acceleration. The ANDES project is carried forward by a large international consortium, composed of 35 Institutes from 13 countries, forming a team of almost 300 scientists and engineers which include the majority of the scientific and technical expertise in the field that can be found in ESO member states
