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Development of novel Gemini-cholesterol analogues for retinoid-related orphan receptors

Organic Chemistry Frontiers 2022年第6期9卷 1522-1530页

作者： Uxía Gómez-Bouzó Alioune Fall Judit Osz Yagamare Fall ORCID logo Natacha Rochel hugo santalla Departamento de Química Orgánica Facultade de QuímicaUniversity of VigoCampus Lagoas de Marcosende36310 VigoSpain Department of Integrative Structural Biology IGBMC-CNRS UMR7104-Inserm U9641rue Laurent Fries67400 IllkirchFrance

Retinoic-acid-related Orphan Receptors (RORs) regulate the maintenance of the circadian rhythm and immune response among others and are involved in increasing numbers of pathologies including autoimmune diseases, cancer and neurological disorders leading to huge interest in the development of ROR ligands. Here, we describe the synthesis of six novel Gemini cholesterol analogues and the binding mode of one of them to RORγ.

关键词： analogues synthesis numbers

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Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability:Insights from McArdle disease

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Journal of Sport and Health Science 2024年第3期13卷 398-408页

作者： Pedro L.Valenzuela Alfredo santalla Lidia B.Alejo Andrea Merlo Asuncion Bustos Laura Castellote-Belles Roser Ferrer-Costa Nicola A.Maffiuletti David Barranco-Gil Tomas Pinos Alejandro Lucia Physical Activity and Health Research Group(“PaHerg”) Research Institute of Hospital“12 de Octubre”(“imas12”)Madrid 28041Spain Department of Systems Biology University of AlcalaMadrid 28871Spain Department of Sport and Computer Science Section of Physical Education and SportsFaculty of SportUniversidad Pablo de OlavideSevilla 41013Spain EVOPRED Research Group Universidad Europea de CanariasTenerife 38300Spain Faculty of Sport Sciences Universidad Europea de MadridMadrid 28670Spain Gait&Motion Analysis Laboratory Sol et Salus HospitalTorre Pedrera di Rimini(RN)47922Italy Department of Clinical Biochemistry Laboratoris ClınicsHospital Universitari Vall d’HebronBarcelona 08035Spain Human Performance Lab Schulthess ClinicZurich 8008Switzerland Biomedical Research Networking Center on Rare Disorders(CIBERER) Barcelona 08035Spain Mitochondrial and Neuromuscular Disorders Unit Vall d’Hebron Institut de RecercaUniversitat Autonoma de BarcelonaBarcelona 08035Spain

Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)***:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric *** a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were ***,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the ***,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle ***:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen *** of these benefits are dose dependent.

关键词： Endurance Glycogen storage disease Glycogenosis Nutrition Supplement

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Outcomes of the Clean Development Mechanism in Argentina

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American Journal of Climate Change 2016年第4期5卷 431-447页

作者： Gabriel Blanco Verónica Córdoba Romina Baldi Mónica Fernández Estela santalla Centro de Tecnologías Ambientales y Energía Facultad de Ingeniería UNCPBA Olavarría Argentina

This paper summarizes the results of the implementation of the CDM in Argentina during the first period of commitment of the Kyoto Protocol. From a total of sixty- five projects ideas, forty-four achieved registration under the CDM EB while the rest remained approved at national level (12), under evaluation (2), suspended (5) or rejected (2). Most of the projects focused on the generation of electricity from renewable energy, mainly wind energy and the use of landfill gas and methane for energy. Emissions reductions achieved 33.4% of the expected CERs up to 2012 with strong differences among sectors. Results demonstrated that under the current Argentina’s energy policy framework, the income by the selling of CERs covered less than 6% of the incremental costs for renewable energy projects. A sensitivity analysis to evaluate the impact of CDM in the coverage of incremental costs for renewable energy based on the prices of both the energy in the local market and the CER demonstrated that the best conditions would only cover 15% of those costs. The contribution of CDM to technology transfer in Argentina was minor considering that 45% of the projects qualified as type III where technological learning and capacity building were limited at the level of operation and maintenance of a foreign technology. Domestic and external barriers that prevented a better performance of CDM projects in terms of GHG mitigation, technology transfer and the contribution to a sustainable development were also analyzed.

关键词： Clean Development Mechanism GHG Emissions Incremental Cost Renewable Energy Argentina

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