Refined physical parameters for Chariklo's body and rings from stellar occultations observed between 2013 and 2020

Context. The Centaur (10199) Chariklo has the first ring system discovered around a small object. It was first observed using stellar occultation in 2013. Stellar occultations allow sizes and shapes to be determined with kilometre accuracy, and provide the characteristics of the occulting object and its vicinity. Aims. Using stellar occultations observed between 2017 and 2020, our aim is to constrain the physical parameters of Chariklo and its rings. We also determine the structure of the rings, and obtain precise astrometrical positions of Chariklo. Methods. We predicted and organised several observational campaigns of stellar occultations by Chariklo. Occultation light curves were measured from the datasets, from which ingress and egress times, and the ring widths and opacity values were obtained. These measurements, combined with results from previous works, allow us to obtain significant constraints on Chariklo's shape and ring structure. Results. We characterise Chariklo's ring system (C1R and C2R), and obtain radii and pole orientations that are consistent with, but more accurate than, results from previous occultations. We confirm the detection of W-shaped structures within C1R and an evident variation in radial width. The observed width ranges between 4.8 and 9.1 km with a mean value of 6.5 km. One dual observation (visible and red) does not reveal any differences in the C1R opacity profiles, indicating a ring particle size larger than a few microns. The C1R ring eccentricity is found to be smaller than 0.022 (3σ), and its width variations may indicate an eccentricity higher than ~0.005. We fit a tri-axial shape to Chariklo's detections over 11 occultations, and determine that Chariklo is consistent with an ellipsoid with semi-axes of 143.8-1.5+1.4, 135.2-2.8+1.4, and 99.1-2.7+5.4 km. Ultimately, we provided seven astrometric positions at a milliarcsecond accuracy level, based on Gaia EDR3, and use it to improve Chariklo's ephemeris.Fil: Morgado, B.E.. Centre National de la Recherche Scientifique. Observatoire de Paris; Francia. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; BrasilFil: Sicardy, Bruno. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Braga Ribas, Felipe. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil. Centre National de la Recherche Scientifique. Observatoire de Paris; Francia. Universidade Tecnologia Federal do Parana; BrasilFil: Desmars, Josselin. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Gomes Júnior, Altair Ramos. Universidade de Sao Paulo; BrasilFil: Bérard, D.. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Leiva, Rodrigo. Universidad de Chile; Chile. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Vieira Martins, Roberto. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Benedetti Rossi, G.. Centre National de la Recherche Scientifique. Observatoire de Paris; Francia. Universidade Federal de Sao Paulo; BrasilFil: Santos Sanz, Pablo. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; BrasilFil: Camargo, Julio Ignacio Bueno. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; BrasilFil: Duffard, R.. Universidade Federal do Rio de Janeiro; BrasilFil: Rommel, F.L.. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; BrasilFil: Assafin, M.. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Boufleur, R.C.. Universidad Nacional de Córdoba; ArgentinaFil: Colas, F.. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; BrasilFil: Kretlow, Mike. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; BrasilFil: Beisker, W.. University of North Carolina; Estados UnidosFil: Sfair, Rafael. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Snodgrass, Colin. University of Edinburgh; Reino UnidoFil: Morales, N.. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; ChileFil: Fernández Valenzuela, E.. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; ChileFil: Amaral, L.S.. Massachusetts Institute of Technology; Estados UnidosFil: Amarante, A.. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; BrasilFil: Artola, R.A.. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Backes, M.. Universidad Nacional de Córdoba; ArgentinaFil: Bath, K. L.. University of North Carolina; Estados UnidosFil: Bouley, S.. University of St. Andrews; Reino UnidoFil: Garcia Lambas, Diego Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Schneiter, Ernesto Matías. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Ingeniería Económica y Legal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; Argentin

SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer

© 2024 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).The posttranslational modification of proteins critically influences many biological processes and is a key mechanism that regulates the function of the RNA-binding protein Hu antigen R (HuR), a hub in liver cancer. Here, we show that HuR is SUMOylated in the tumor sections of patients with hepatocellular carcinoma in contrast to the surrounding tissue, as well as in human cell line and mouse models of the disease. SUMOylation of HuR promotes major cancer hallmarks, namely proliferation and invasion, whereas the absence of HuR SUMOylation results in a senescent phenotype with dysfunctional mitochondria and endoplasmic reticulum. Mechanistically, SUMOylation induces a structural rearrangement of the RNA recognition motifs that modulates HuR binding affinity to its target RNAs, further modifying the transcriptomic profile toward hepatic tumor progression. Overall, SUMOylation constitutes a mechanism of HuR regulation that could be potentially exploited as a therapeutic strategy for liver cancer.This work was supported by grants to M.L.M.-C. from Departamento de Industria del Gobierno Vasco, Spain; Ministerio de Ciencia e Innovación, Spain (grant no. PID2020-117116RB-I00); European Regional Development Fund (ERDF), EU; and CIBERehd, which is funded by Instituto de Salud Carlos III (ISCIII), Spain. M.L.M.-C. and J.S. received funding from Ministerio de Ciencia e Innovación (grant no. RTC2019-007125-1) and ISCIII (grant no. DTS20/00138). M.L.M.-C. and R.M.L. acknowledge Ministerio de Ciencia e Innovación (grant no. RED2022-134397-T). M.L.M.-C. and J.M.B. were awarded with a grant from Fundación la Caixa, Spain (grant no. HR17-00601). M.L.M.-C., J.M.B., M.A.A., and J.J.G.M. acknowledge financial support from Fundación Científica de la Asociación Española Contra el Cáncer (AECC), Spain. M.S.R. recognizes funding from Fondo Sectorial de Investigación SRE - CONACYT, Mexico (grant no. 0280365); Horizon 2020 Research and Innovation Program funded under Marie Skłodowska-Curie Actions, EU (grant no. 765445); and REPÈRE and Programme de Prématuration from Région Occitanie, France. M.G., S.D., and K.M.-M. were supported by the National Institute on Aging (NIA), National Institutes of Health (NIH), US (grant no. Z01-AG000511-23). I.D.-M. is grateful for the grants received from Junta de Andalucía, Spain (grant no. BIO-198, US-1254317, P18-FR-3487, and P18-HO-4091); Ministerio de Ciencia, Innovación y Universidades, Spain (grant no. PGC2018-096049-BI00); and Fundación Ramón Areces, Spain. T.D. acknowledges Fondation ARC, France (grant no. 208084). J.J.G.M. was supported by Junta de Castilla y León, Spain (grant no. SA063P17); Fundación La Marató TV3, Spain (grant no. 201916-31); ISCIII (grant no. PI19/00819); CIBERehd; and ERDF (grant no. OLD-HEPAMARKER). M.A.A. recognizes Gobierno de Navarra, Spain (grant no. GºNa 42/21); Eurorregión Nueva Aquitania-Euskadi-Navarra, Spain; Ministerio de Ciencia e Innovación (grant no. PID2019-104878RB-I00); and CIBERehd. A.P. expresses gratitude to the European Research Council (ERC), EU (grant no. 804236) for their support. M.D.G. received financial support from Junta de Andalucía (grant no. PEMP-0036-2020 and BIO-0139); Ministerio de Universidades, Spain (grant no. FPU20/03957); ISCIII (grant no. PI20/01301), Fundación Sociedad Española de Endocrinología y Nutrición (FSEEN), Spain; CIBERehd; and CIBERobn, which is also funded by ISCIII. J.M.B. acknowledges Euskadi RIS3 (grant no. 2019222054, 2020333010, and 2021333003) and Elkartek programs from Gobierno Vasco (grant no. KK-2020/00008); ISCIII (grant no. PI18/01075, CPII19/00008, and PI21/00922); CIBERehd; PSC Support, UK; AMMF The Cholangiocarcinoma Charity, UK (grant no. EU/2019/AMMFt/001); Horizon 2020 Research and Innovation Program (grant no. 825510); ERDF; and PSC Partners Seeking a Cure, US. A.L. received financial support from the Damon Runyon-Rachleff Innovation Award, US (grant no. DR52-18) and the MERIT Award (R37) from the National Cancer Institute (NCI), NIH (grant no. R37CA230636). F.E. expresses his gratitude to ProteoRed from ISCIII (grant no. PT13/0001/0027) and CIBERehd. N.G.A.A. was funded by Ministerio de Ciencia, Innovación y Universidades (grant no. RTI2018-095700-B-I00). R.B. acknowledges financial support from Gobierno Vasco (grant no. IT1165-19); Ministerio de Economía, Industria y Competitividad, Spain (grant no. SAF2017-90900-REDT); Ministerio de Economía, Industria y Competitividad, ERDF (grant no. BFU2017-84653-P); Ministerio de Ciencia e Innovación (grant no. PID2020-114178GB-I00); and Horizon 2020 funded under Marie Skłodowska-Curie Actions (grant no. 765445-EU). A.M.A. acknowledges CIBERehd. L.A.M.-C. obtained grants from Ministerio de Economía y Competitividad (grant no. CSD2008-00005); Ministerio de Economía, Industria y Competitividad (grant no. BFU2016-77408-R); ISCIII; and EJP RD, EU (grant no. EJPRD19-040). I.G.-R. was supported by Ministerio de Economía, Industria y Competitividad (grant no. BES-2017-080435 ). M.S.-M. is grateful to the AECC, Sede de Bizkaia, Spain for the financial support. J.D.Z. was awarded with a grant from Ministerio de Economía, Industria y Competitividad (grant no. SEV-2016-0644-18-2). C.M. acknowledges Gobierno Vasco (grant no. IT-1264-19) and Ministerio de Ciencia e Innovación (grant no. PID2022-136788OB-I00). A.V.-C. was supported by Ministerio de Educación, Cultura y Deporte, Spain (grant no. FPU016/01513). C.F.-R. thanks Tekniker, Spain and CIC bioGUNE, Spain for financial support. A.G.-d.R. was funded by Bikaintek program from Gobierno Vasco (grant no. 48-AF-W1-2019-00012). N.G.-U. obtained a grant from Gobierno Vasco. T.C.D. expresses gratitude to AECC. J.S. received financial support from CIBERehd. C.M.R.-G. was supported by Ayudas a la Recualificación Margarita Salas from Universidad de Extremadura, Ministerio de Universidades financed by NextGenerationEU.Peer reviewe

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Glycosyl-phosphatidyl inositol-phospholipase type D: A possible candidate for the generation of second messengers

Membrane associated glycosyl-phosphatidylinositols have been shown to be the precursors of inositol phosphoglycan second messengers. Extraction of human liver membranes and purification by serial thin layer chromatography revealed three glycolipids which co-migrated with glycosyl-phosphatidylinositol from rat liver. These lipidic fractions were partially sensitive to treatment with nitrous acid and to hydrolysis by glycosyl-phosphatidylinositol-specific phospholipase D from bovine serum. In parallel, glycosylphosphatidylinositol isolated from rat liver was found to be a substrate for the enzyme generating a biologically active inositol phosphoglycan species (determined by measuring inhibition of protein kinase A activity and stimulation of cell proliferation within the chicken embryo cochleovestibular ganglion). This molecule was recognised by an anti-inositol phosphoglycan antibody. Hence, we propose that glycosyl-phosphatidylinositol-specific phospholipase D could be implicated in cellular signalling.We are grateful to the following sources for financial support: The Royal Society (UK) for D.R.J.; Ministerio de Educación y Ciencia (Spain) for M.A.A. and C.S.; and Dirección General de Investigación, Ciencia y Tecnología, Europharma and Comunidad Autónoma de Madrid (Spain), for I.V.-N.Peer Reviewe

Regulation of rat liver S-adenosylmethionine synthetase during septic shock: Role of nitric oxide

We investigated the modulation of rat liver S-adenosylmethionine (SAM) synthetase in a model of acute sepsis. Our results show that animals treated with bacterial lipopolysaccharide experience a marked decrease in liver SAM synthetase activity. No changes were detected in the hepatic levels of SAM synthetase protein, suggesting that inactivation of the existing enzyme was the cause of the observed activity loss. Lipopolysaccharide treatment resulted in the expression of calcium-independent/cytokine-inducible nitric oxide (NO) synthase in liver and the accumulation in plasma of the NO- derived species nitrite and nitrate. NO implication in the in vivo regulation of SAM synthetase was evaluated in animals treated with the NO donor molecule 3-morpholinosydnonimine. The analysis of liver enzymatic activity, along with protein and messenger RNA levels yielded results similar to those obtained with lipopolysaccharide treatment. To assess directly the sensitivity of SAM synthetase to NO, the rat liver-purified high-and low-molecular weight forms of the enzyme were exposed to various doses of 3-morpholinosydnonimine and other NO donors such as S-nitroso-N-acetylpenicillamine, resulting in a dose- dependent inhibition of enzymatic activity. This effect was reversed by addition of the reducing agents β-mercaptoethanol and glutathione. Finally, cysteine 121 was identified as the site of molecular interaction between NO and rat liver SAM synthetase that is responsible for the inhibition of the enzyme. To reach this conclusion, the 10 cysteine residues of the enzyme were changed to serine by site-directed mutagenesis, and the effect of NO on the various recombinant enzymes was measured.Supported by grants of Fondo de Investigaciones Sanitarias (94/0231 and 95/0966), Dirección General de Investigaciones Científicas (PB 94/0087, PB 93/070), and EC Science Program (SCI*-CT92-0780), Europharma.Peer Reviewe