Body composition after endogenous (Cushing's syndrome) and exogenous (rheumatoid arthritis) exposure to glucocorticoids

Exposure to chronic glucocorticoid (GC) excess determines changes in body composition. The aim of the study was to compare body composition in women exposed to endogenous hypercortisolism (Cushing's syndrome, CS), exogenous glucocorticoid treatment (rheumatoid arthritis, RA) and controls. Fifty-one CS women, 26 RA women treated with low-dose prednisone (5 mg/day or 10 mg/2 days), and 78 female controls were included. Fourteen CS patients were hypercortisolemic, 37 in remission (10 required hydrocortisone substitution after surgery). Body composition parameters were measured by dual-energy X-ray absorptiometry scanning (DEXA). RA patients had a greater waist-hip ratio (WHR) (p<0.01), less lean body mass (LBM) (p<0.01), and lumbar bone mineral density (BMD) (p<0.01) than controls. CS patients, globally and those with cured disease, had more total fat (both percentage and kg) and trunk fat percentage, and less whole body-BMD than RA patients (p<0.05, p<0.01, p<0.05, respectively). Active CS patients had less whole body-BMD and more LBM than RA patients (p<0.05, p=0.01, respectively). Cured CS patients not taking hydrocortisone had more total fat [both percentage (p<0.05) and kg (p<0.05)], trunk fat percentage (p<0.05), lumbar BMD (p<0.01) than RA patients. Cured CS patients requiring hydrocortisone only differed from RA patients by smaller WHR (p<0.01). All the differences in BMD disappeared when the data were reanalyzed including only the estrogen-deficient groups. Hypercortisoliof CS determines an irreversible increase in body fat, greater than in RA. Endogenous and exogenous exposure to GC negatively affects body composition by increasing the WHR. There appears to be no additional effect on BMD in estrogen-deficient women

Heat Shock Response in Yeast Involves Changes in Both Transcription Rates and mRNA Stabilities

We have analyzed the heat stress response in the yeast Saccharomyces cerevisiae by determining mRNA levels and transcription rates for the whole transcriptome after a shift from 25°C to 37°C. Using an established mathematical algorithm, theoretical mRNA decay rates have also been calculated from the experimental data. We have verified the mathematical predictions for selected genes by determining their mRNA decay rates at different times during heat stress response using the regulatable tetO promoter. This study indicates that the yeast response to heat shock is not only due to changes in transcription rates, but also to changes in the mRNA stabilities. mRNA stability is affected in 62% of the yeast genes and it is particularly important in shaping the mRNA profile of the genes belonging to the environmental stress response. In most cases, changes in transcription rates and mRNA stabilities are homodirectional for both parameters, although some interesting cases of antagonist behavior are found. The statistical analysis of gene targets and sequence motifs within the clusters of genes with similar behaviors shows that both transcriptional and post-transcriptional regulons apparently contribute to the general heat stress response by means of transcriptional factors and RNA binding proteins

Study of β-delayed charged particle emission of 11Li: Evidence of new decay channels

5 pags., 3 figs. -- 9th International Conference on Clustering Aspects of Nuclear Structure and Dynamics (CLUSTERS'07) 3–7 September 2007, Stratford upon Avon, UKThe break-up of the 18.2 MeV state in 11Be was studied in a 11Li β-decay experiment. We report here on the study of the dominating breakup channels involving na6He or 3n2α in the final state, with special emphasis dedicated in this contribution to the three-particle channel. The two emitted charged particles were detected in coincidence using a highly segmented experimental set-up. The observed experimental energy-vs-energy scatter plot indicates a sequential breakup where nuclei of mass 4, alpha particles, and mass 7, 7He, are involved. A Monte-Carlo simulation of the sequential channel, 11Be* → α + 7He → nα6He was performed and compared to the experimental data and to a simulation of the direct break-up of the 18.2 MeV state nα6He by phase space energy distribution. The energy-versus-energy plot are explained by the sequential simulation but not by the phase space simulation. © 2008 IOP Publishing Ltd

Factores de riesgo cardiovascular entre pacientes con síndrome de Cushing, curados y no curados con respecto a un grupo control

Objetivos: Describir los factores de riesgo cardiovascular que se presentan en el paciente con Síndrome de Cushing (SC), para establecer programas educativos adaptados a este grupo de pacientes. Método: El ámbito de estudio se desarrolló en el Hospital de Sant Pau, en el Servicio de Endocrinología. Se extrajeron datos de las Historias Clínicas de los pacientes que fueron visitados en consultas con diagnóstico de SC en el 2005, realizándose una recogida retrospectiva. No se excluyó ningún paciente, independientemente de los años de duración de la patología, de las opciones terapéuticas o del tratamiento farmacológico recibido, incluyendo todos los pacientes con SC. Elaboramos una hoja de recogida de datos demográficos, clínicos (peso, índice de masa corporal, tensión arterial, perímetro abdominal) y analíticos (lípidos, glicemia); para el tratamiento informático se utilizó el programa SPSS. Resultados: El perímetro abdominal fue mayor en pacientes no curados (100.8 ±13.9cm) que en controles (89±12.8cm) (p<0.05). Respecto al peso no se encontraron diferencias significativas entre controles (69,9±13,3Kg), curados (69,9±16,5Kg) y no curados (76,4±16,5Kg). El IMC tampoco reflejó diferencias en los tres grupos en estudio: control (26,5±5,2), curados (27,8±6,4) y no curados (29,3±3,8). El colesterol fue más alto en los pacientes curados (5.90±0.92mmol/L) que en controles (5.38±1.07mmol/L) (p<0.05), al igual que los triglicéridos (1.20±0.51mmol/L versus controles 1.05±0.56mmol/L; p<0.05). Ambos grupos de pacientes presentaron presión sistólica mayor que los controles (curados,128.3±16.7mmHg p<0.05; no curados,134.1±13mmHg, p<0.001). Los no curados (78.6±9.2mmHg) presentaron además presión diastólica mayor que los controles (72.3±8.6, p<0.05) Fig.3. No observamos diferencias en la glicemia basal entre los 3 grupos de pacientes. Conclusiones: Los pacientes con SC, curados de su hipercortisolismo y con enfermedad activa presentan mayor riesgo cardiovascular y metabólico, comparados con el grupo control. La enfermera educadora deberá contemplar e incluir en los programas de prevención secundaria a dichos pacientes, para promocionar hábitos saludables, prevenir y controlar sus factores de riesgo. Palabras Clave Síndrome Cushing, educación sanitaria, factores de riesgo cardiovascular

Aberrant upregulation of the glycolytic enzyme PFKFB3 in CLN7 neuronal ceroid lipofuscinosis

CLN7 neuronal ceroid lipofuscinosis is an inherited lysosomal storage neurodegenerative disease highly prevalent in children. CLN7/MFSD8 gene encodes a lysosomal membrane glycoprotein, but the biochemical processes affected by CLN7-loss of function are unexplored thus preventing development of potential treatments. Here, we found, in the Cln7∆ex2 mouse model of CLN7 disease, that failure in autophagy causes accumulation of structurally and bioenergetically impaired neuronal mitochondria. In vivo genetic approach reveals elevated mitochondrial reactive oxygen species (mROS) in Cln7∆ex2 neurons that mediates glycolytic enzyme PFKFB3 activation and contributes to CLN7 pathogenesis. Mechanistically, mROS sustains a signaling cascade leading to protein stabilization of PFKFB3, normally unstable in healthy neurons. Administration of the highly selective PFKFB3 inhibitor AZ67 in Cln7∆ex2 mouse brain in vivo and in CLN7 patients-derived cells rectifies key disease hallmarks. Thus, aberrant upregulation of the glycolytic enzyme PFKFB3 in neurons may contribute to CLN7 pathogenesis and targeting PFKFB3 could alleviate this and other lysosomal storage diseases.This work was funded by the European Regional Development Fund, European Union’s Horizon 2020 Research and Innovation Programme (BATCure grant No. 666918 to J.P.B., S.E.M., D.L.M., S.S., and T.R.M.; PANA grant No. 686009 to A.A.), Agencia Estatal de Investigación (PID2019-105699RB-I00/AEI/10.13039/501100011033 and RED2018‐102576‐T to J.P.B.; SAF2017-90794-REDT to A.A.), Instituto de Salud Carlos III (CB16/10/00282 to J.P.B.; PI18/00285; RD16/0019/0018 to A.A.), Junta de Castilla y León (CS/151P20 and Escalera de Excelencia CLU-2017-03 to J.P.B. and A.A.), Ayudas Equipos Investigación Biomedicina 2017 Fundación BBVA (to J.P.B.), and Fundación Ramón Areces (to J.P.B. and A.A.). SM benefits from MRC funding to the MRC Laboratory for Molecular Cell Biology University Unit at UCL (award code MC_U12266B) towards lab and office space. Part of this work was funded by Gero Discovery L.L.C. M.G.M. is an ISCIII-Sara Borrel contract recipient (CD18/00203)

Litterfall, litter decomposition and associated nutrient fluxes in Pinus halepensis: influence of tree removal intensity in a Mediterranean forest

The online version of this article (doi:10.1007/s10342-015-0893-z) contains supplementary material, which is available to authorized users[EN] Our knowledge about the influence of silvicultural treatments on nutrient cycling processes in Mediterranean forests is still limited. Four levels of tree removal were compared in an Aleppo pine forest in eastern Spain to determine the effects on litterfall, litter decomposition and the associated nutrient fluxes after 12 years. Removal treatments included clearfelling, two shelterwood intensities (60 and 75 % of basal area removed) and untreated controls. Twelve years later, the basal area removed still explained 60 % of litterfall mass variance and 60 % of C, 52 % of N, 45 % of P, 17 % of K, 47 % of Ca and 60 % of Mg return variances. Litter decomposed somewhat more slowly in clearfellings compared to controls (p = 0.049), accumulated more Ca and released less K compared to the other three treatments. This was explained by contamination with mineral particles due to the poorly developed O horizon in clearfellings. We conclude that the management practices reduced the nutrient return via litterfall, but the nutrient release through decomposition seems poorly sensitive to canopy disturbance. In order to accurately quantify the harvesting impacts on nutrient cycling in this Mediterranean forest system, it is necessary to measure the litterfall of the understory layer.This work has been supported by a fellowship from the Generalitat Valenciana, Conselleria de Educacion, Formacion y Empleo awarded to L. Lado-Monserrat (BFPI/2008/041). Silvicultural treatments were carried out by the Mediterranean Centre for Environmental Studies (CEAM) through programme "I + D en relacion con la restauracion de la cubierta vegetal y otros aspectos de investigacion forestal". Dataloggers and probes were provided by the Generalitat Valenciana through Project "Efecto de diferentes sistemas de aclareo de masa forestal sobre la disponibilidad de agua, nutrientes y la regeneracion de la masa arborea y arbustiva en parcelas de pinar" (GV06/126). We acknowledge Joana Oliver, Ruth M. Tavera and Daniel Fortanet for their help in the laboratory and in the field. The authors wish to thank Francisco Galiana for his assistance, including help in fieldwork and providing information about the experimental design of the silvicultural treatments. Thanks also go to Rafael Herrera from the Centro de Ecologia, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela and two anonymous reviewers for critically reviewing the manuscript.Lado Monserrat, L.; Lidón, A.; Bautista, I. (2015). Litterfall, litter decomposition and associated nutrient fluxes in Pinus halepensis: influence of tree removal intensity in a Mediterranean forest. European Journal of Forest Research. 134(5):833-844. https://doi.org/10.1007/s10342-015-0893-zS8338441345Almagro M, Martínez-Mena M (2012) Exploring short-term leaf-litter decomposition dynamics in a Mediterranean ecosystem: dependence on litter type and site conditions. Plant Soil 358:323–335Alvarez A, Gracia M, Vayreda J, Retana J (2012) Patterns of fuel types and crown fire potential in Pinus halepensis forests in the Western Mediterranean Basin. For Ecol Manage 270:282–290Austin AT, Vivanco L (2006) Plant litter decomposition in a semi-arid ecosystem controlled by photodegradation. Nature 442:555–558Bates JD, Svejcar TS, Miller RF (2007) Litter decomposition in cut and uncut western juniper woodlands. J Arid Environ 70:222–236Binkley D (2008) Three key points in the design of forest experiments. For Ecol Manage 255:2022–2023Blair JM, Crossley DA Jr (1988) Litter decomposition, nitrogen dynamics and litter microarthropods in a southern Appalachian hardwood forest 8 years following clearcutting. J Appl Ecol 25:683–698Blanco JA, Zavala MA, Imbert JB, Castillo FJ (2005) Sustainability of forest management practices: evaluation through a simulation model of nutrient cycling. For Ecol Manage 213:209–228Blanco JA, Imbert JB, Castillo FJ (2006) Influence of site characteristics and thinning intensity on litterfall production in two Pinus sylvestris L. forests in the western Pyrenees. For Ecol Manage 237:342–352Blanco JA, Imbert JB, Castillo FJ (2008) Nutrient return via litterfall in two contrasting Pinus sylvestris forests in the Pyrenees under different thinning intensities. For Ecol Manage 256:1840–1852Blanco JA, Imbert JB, Castillo FJ (2011) Thinning affects Pinus sylvestris needle decomposition rates and chemistry differently depending on site conditions. Biogeochemistry 106:397–414Caldentey J, Ibarra M, Hernández J (2001) Litter fluxes and decomposition in Nothofagus pumilio stands in the region of Magallanes, Chile. For Ecol Manage 148:145–157Christensen JH, Krishna Kumar K, et al. (2013) Climate phenomena and their relevance for future regional climate change. In: Stocker TF, Qin D, Plattner G-K et al (Eds.) Climate change 2013: the physical science basis. Contribution of Working Group I to the Fifth Assessment Report of the Intergovernmental Panel on Climate Change. Cambridge University Press, Cambridge, United Kingdom and New York, NY, USACortina J, Vallejo VR (1994) Effects of clearfelling on forest floor accumulation and litter decomposition in a radiata pine plantation. For Ecol Manage 70:299–310Entry JA, Rose CL, Cromack K Jr (1991) Litter decomposition and nutrient release in ectomycorrhizal mat soils of a Douglas fir ecosystem. Soil Biol Biochem 23:285–290Fabbio G, Merlo M, Tosi V (2003) Silvicultural management in maintaining biodiversity and resistance of forests in Europe—the Mediterranean region. J Environ Manage 67:67–76Galiana F, Pérez-Badía R, Camarero E, Estruch V, Currás R (2001) Estimación de la Radiación solar incidente en pinares de Pinus halepensis sometidos a tratamientos selvícolas de cortas finales. In: Junta de Andalucía. Consejería de Medio Ambiente (Ed.) Actas del III Congreso Forestal Español. Junta de Andalucía. Granada (Original in Spanish)García-Plé C, Vanrell P, Morey M (1995) Litter fall and decomposition in a Pinus halepensis forest on Mallorca. J Veg Sci 6:17–22González Utrillas N, González Pérez E, Galiana F (2005) Variación del crecimiento diametral de la masa de pinar de carrasco en cortas finales experimentales, en los montes de Tuejar y Chelva (Valencia). IV Congreso Forestal Español. Zaragoza. Soc. Esp. Cien. For. (Original in Spanish)Guo LB, Sims REH (1999) Litter decomposition and nutrient release via litter decomposition in New Zealand eucalypt short rotation forests. Agric Ecosyst Environ 75:133–140GVA (1995) Mapa de Suelos de la Comunidad Valenciana. Chelva (666). Proyecto LUCDEME (Icona), Centro de Investigaciones sobre Desertificación y Conselleria d’Agricultura i Mig Ambient. Generalitat Valenciana. Valencia, Spain. (Original in Spanish)Hennessey TC, Dougherty PM, Cregg BM, Wittwer RF (1992) Annual variation in needle fall of a loblolly pine stand in relation to climate and stand density. For Ecol Manage 51:329–338Inagaki Y, Kuramoto S, Torii A, Shinomiya Y, Fukata H (2008) Effects of thinning on leaf-fall and leaf-litter nitrogen concentration in hinoki cypress (Chamaecyparis obtusa Endlicher) plantation stands in Japan. For Ecol Manage 255:1859–1867Jonard M, Misson L, Ponette Q (2006) Long-term thinning effects on the forest floor and the foliar nutrient status of Norway spruce stands in the Belgian Ardennes. Can J For Res 36:2684–2695Kim C, Sharik TL, Jurgensen MF (1996a) Canopy cover effects on mass loss, and nitrogen and phosphorus dynamics from decomposing litter in oak and pine stands in northern Lower Michigan. For Ecol Manage 80:13–20Kim C, Sharik TL, Jurgensen MF (1996b) Litterfall, nitrogen and phosphorus inputs at various levels of canopy removal in oak and pine stands in northern lower Michigan. Am Midl Nat 135:195–204Kim C, Son Y, Lee WK, Jeong J, Noh NJ, Kim SR, Yang AR, Ju NG (2012) Influence of forest tending (Soopkakkugi) works on litterfall and nutrient inputs in a Pinus densiflora stand. For Sci Technol 8:83–88Kimmins JP (2004) Forest ecology, a foundation for sustainable management and environmental ethics in forestry. Prentice-Hall, New JerseyKimmins JP, Mailly D, Seely B (1999) Modelling forest ecosystem net primary production: the hybrid simulation approach used in FORECAST. Ecol Modell 122:195–224Klemmedson JO, Meier CE, Campbell RE (1990) Litter fall transfers of dry matter and nutrients in ponderosa pine stands. Can J For Res 20:1105–1115Kunhamu TK, Kumar BM, Viswanath S (2009) Does thinning affect litterfall, litter decomposition, and associated nutrient release in Acacia mangium stands of Kerala in peninsular India? Can J For Res 39:792–801Lytle DE, Cronan CS (1998) Comparative soil CO2 evolution, litter decay, and root dynamics in clearcut and uncut spruce–fir forest. For Ecol Manage 103:121–128Molina AJ, Del Campo AD (2012) The effects of experimental thinning on throughfall and stemflow: a contribution towards hydrology-oriented silviculture in Aleppo pine plantations. For Ecol Manage 269:206–213Navarro FB, Romero-Freire A, Del Castillo T, Foronda A, Jiménez MN, Ripoll MA, Sánchez-Miranda A, Hutsinger L, Fernández-Ondoño E (2013) Effects of thinning on litterfall were found after years in a Pinus halepensis afforestation area at tree and stand levels. For Ecol Manage 289:354–362Olson JS (1963) Energy storage and the balance of producers and decomposers in ecological systems. Ecology 44:322–331Pérez Cueva AJ (1994) Atlas Climático de la Comunidad Valenciana. Colección Territori nº 4. Generalitat Valenciana. Conselleria d’Obres Publiques, Urbanisme i Transport, ValenciaPetritsch R, Hasenauer H, Pietsch SA (2007) Incorporating forest growth response to thinning within biome-BGC. For Ecol Manage 242:324–336Prescott CE (1997) Effects of clearcutting and alternative silvicultural systems on rates of decomposition and nitrogen mineralization in a coastal montane coniferous forest. For Ecol Manage 95:253–260Prescott CE (2002) The influence of the forest canopy on nutrient cycling. Tree Physiol 22:1193–1200Prescott CE, Blevins LL, Staley CL (2000) Effects of clear-cutting on decomposition rates of litter and forest floor in forests of British Columbia. Can J For Res 30:1751–1757Roig S, Del Río M, Cañellas I, Montero G (2005) Litter fall in Mediterranean Pinus pinaster Ait. stands under different thinning regimes. For Ecol Manage 206:179–190Sardans J, Peñuelas J, Rodà F (2005) Changes in nutrient use efficiency, status and retranslocation in young post-fire regeneration Pinus halepensis in response to sudden N and P input, irrigation and removal of competing vegetation. Trees 19:233–250Scarascia-Mugnozza G, Oswald H, Piussi P, Radoglou K (2000) Forests of the Mediterranean region: gaps in knowledge and research needs. For Ecol Manage 132:97–109Slovik S (1997) Tree physiology. In: Hüttl RF, Schaaf W (eds) Magnesium deficiency in forest ecosystems. Kluwer Academic Publishers, London, pp 101–214Taylor BR, Parkinson D (1988) Does repeated freezing and thawing accelerate decay of leaf litter? Soil Biol Biochem 20:657–665Torras O, Saura S (2008) Effects of silvicultural treatments on forest biodiversity indicators in the Mediterranean. For Ecol Manage 255:3322–3330Trofymow JA, Barclay HJ, McCullough KM (1991) Annual rates and elemental concentrations of litter fall in thinned and fertilized Douglas-fir. Can J For Res 21:1601–1615Wallace ES, Freedman B (1986) Forest floor dynamics in a chronosequence of hardwood stands in central Nova Scotia. Can J For Res 16:293–302Whitford WG, Meentemeyer V, Seastedt TR, Cromack Jr K, Crossley Jr DA, Santos P, Todd RL, Waide JB (1981) Exceptions to the AET model: deserts and clear-cut forest. Ecology 62:275–277Yin X, Perry JA, Dixon RK (1989) Influence of canopy removal on oak forest floor decomposition. Can J For Res 19:204–21

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

HE-LHC: The High-Energy Large Hadron Collider – Future Circular Collider Conceptual Design Report Volume 4

In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries