Quinolones modulate ghrelin receptor signaling: potential for a novel small molecule scaffold in the treatment of cachexia

Cachexia is a metabolic wasting disorder characterized by progressive weight loss, muscle atrophy, fatigue, weakness, and appetite loss. Cachexia is associated with almost all major chronic illnesses including cancer, heart failure, obstructive pulmonary disease, and kidney disease and significantly impedes treatment outcome and therapy tolerance, reducing physical function and increasing mortality. Current cachexia treatments are limited and new pharmacological strategies are needed. Agonists for the growth hormone secretagogue (GHS-R1a), or ghrelin receptor, prospectively regulate the central regulation of appetite and growth hormone secretion, and therefore have tremendous potential as cachexia therapeutics. Non-peptide GHS-R1a agonists are of particular interest, especially given the high gastrointestinal degradation of peptide-based structures, including that of the endogenous ligand, ghrelin, which has a half-life of only 30 min. However, few compounds have been reported in the literature as non-peptide GHS-R1a agonists. In this paper, we investigate the in vitro potential of quinolone compounds to modulate the GHS-R1a in both transfected human cells and mouse hypothalamic cells. These chemically synthesized compounds demonstrate a promising potential as GHS-R1a agonists, shown by an increased intracellular calcium influx. Further studies are now warranted to substantiate and exploit the potential of these novel quinolone-based compounds as orexigenic therapeutics in conditions of cachexia and other metabolic and eating disorders.Irish Research Council for Science and Technology (IRCSET)Science Foundation Ireland (SFI/12/IP/1315)Science Foundation Ireland (SFI/12/RC/2275)Science Foundation Ireland (SFI/12/RC/2273)Universidad de Sevill

Innovative solutions and challenges to increase the use of poly(3-hydroxybutyrate) in food packaging and disposables

[EN] Poly(3-hydroxybutyrate) (PHB) has gain in recent years a huge interest in the food packaging field due to its renewable origin from waste as well as non-food crops, high mechanical strength, medium-to-high barrier performance, and inherent biodegradability in natural environments. Despite these advantages, PHB also shows a narrow processing window and high brittleness since this homopolyester shows low thermal stability and high crystallinity, limiting its industrial application. The present review provides an updated state of the art of the most relevant aspects in terms of processing and properties of PHB materials with a particular emphasis for their use in sustainable food packaging. It also describes the most potential strategies that can be applied to improve both the processability and mechanical properties of PHB, including the melt blending with green plasticizers and flexible biodegradable polymers as well as the development of more ductile co-polyesters. Finally, the waste management of the newly developed PHB-based articles is discussed, from their potential compostability to develop more biopolymers to more economically favored alternatives such as mechanical and chemical recycling technologies.This work was funded by the Spanish Ministry of Science and Innovation (MICINN, Spain), grant PID2021-123753NA-C32 funded by MCIN/AEI/10.13039/501100011033 and by "ERDF A way of making Europe", by the "European Union"; Comunidad de Madrid (Spain) by CIRCULAGROPLAST, a research Project that has been funded by the Comunidad de Madrid through the call Research Grants for Young Investigators from Universidad Politécnica de Madrid; as well as by the Generalitat Valenciana (Spain) through the BEST Program (CIBEST/2021/94). S. Torres-Giner acknowledges the Spanish Ministry of Science and Innovation (MICINN, Spain) for his Ramón y Cajal contract (RYC2019-027784-I).Garcia-Garcia, D.; Quiles-Carrillo, L.; Balart, R.; Torres-Giner, S.; Arrieta, MP. (2022). Innovative solutions and challenges to increase the use of poly(3-hydroxybutyrate) in food packaging and disposables. European Polymer Journal. 178:1-20. https://doi.org/10.1016/j.eurpolymj.2022.11150512017

Autenticación mediante DNA barcoding de especies de meros legalmente protegidas y en peligro de extinción, sometidas a explotación pesquera, incluyendo el mero Goliat Epinephelus itajara

Fishing strategies are constantly changing to meet the needs for new or alternative food sources. Consequently, management of fishing activities regarding rates of exploitation is essential, as a number of resources have reached situations of overexploitation. The aim of the present study was to use DNA barcoding from the goliath grouper and other exploited epinephelids in order to provide procedures for DNA authentication to be used as evidence for combating putative illegal fishing. The species studied were Epinephelus adscensionis, Mycteroperca bonaci, Mycteroperca interstitialis, Epinephelus itajara, Mycteroperca venenosa, Epinephelus mystacinus, Dermatolepis inermis, Alphestes afer, Cephalopholis fulva, Mycteroperca acutirostris, Rypticus saponaceus, Mycteroperca marginata and Epinephelus morio. Four of these species are the main epinephelids fished in the Atlantic Ocean. Differential patterns of polymerase chain reaction–restriction fragment length polymorphism were obtained from the species and additional single nucleotide polymorphisms were also detected among the four main epinephelids studied. The procedures proved very efficient and we suggest their applicability to the other fish groups as a way to control illegal capture and retail around the world, especially in cases in which filleting and other forms of de-characterization cause a lack of morpho-anatomical key characters.Las estrategias de pesca cambian constantemente para satisfacer las necesidades de fuentes de alimento nuevas o alternativas. En consecuencia, a medida que los recursos alcanzan situaciones de sobreexplotación, resulta esencial establecer procedimientos de inspección de las actividades relacionadas con las tasas de explotación pesquera. El objetivo de este estudio es proponer el uso de la técnica de DNA barcoding para establecer la verificación de la identidad del mero Goliat y otros epinefélidos, a fin de utilizarlo como evidencia para combatir la pesca ilegal cuando se sospeche su ocurrencia. Las especies aquí estudiadas fueron Alphestes afer, Cephalopholis fulva, Dermatolepis inermis, Epinephelus adscensionis, E. itajara, E. morio, E. mystacinus, Mycteroperca acutirostris, M. bonaci, M. interstitialis, M. marginata, M. venenosa y Rypticus saponaceus de las cuales cuatro constituyen las más pescadas en el Océano Atlántico. Fueron encontrados patrones diferenciables de PCR-RFLPs para todas las especies y, además, fue posible detectar SNPs adicionales entre las cuatro especies más explotadas. Los procedimientos aquí empleados fueron muy eficaces por lo que sugerimos su aplicabilidad a otros grupos de peces como medida de control de la captura y comercialización ilegal a nivel mundial, particularmente en aquellos casos en los que el fileteado y otras formas de procesamiento que alteran las características anatómicas y morfológicas impiden su identificación

Prevalence of the Metabolic Syndrome in Latin America and its association with sub-clinical carotid atherosclerosis: the CARMELA cross sectional study

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome increases cardiovascular risk. Limited information on its prevalence in Latin America is available. The Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study included assessment of metabolic syndrome in 7 urban Latin American populations.</p> <p>Methods</p> <p>CARMELA was a cross-sectional, population-based, observational study conducted in Barquisimeto, Venezuela; Bogota, Colombia; Buenos Aires, Argentina; Lima, Peru; Mexico City, Mexico; Quito, Ecuador; and Santiago, Chile. The prevalence of metabolic syndrome, defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and associated carotid atherosclerosis were investigated in 11,502 participants aged 25 to 64 years.</p> <p>Results</p> <p>Across CARMELA cities, metabolic syndrome was most prevalent in Mexico City (27%) and Barquisimeto (26%), followed by Santiago (21%), Bogota (20%), Lima (18%), Buenos Aires (17%), and Quito (14%). In nondiabetic participants, prevalence was slightly lower but followed a comparable ranking. Overall, 59%, 59%, and 73% of women with high triglycerides, hypertension, or glucose abnormalities, respectively, and 64%, 48% and 71% of men with abdominal obesity, hypertension, or glucose abnormalities, respectively, had the full metabolic syndrome. Prevalence of metabolic syndrome increased with age, markedly so in women. Mean common carotid artery intima-media thickness (CCAIMT) and prevalence of carotid plaque increased steeply with increasing numbers of metabolic syndrome components; mean CCAIMT was higher and plaque more prevalent in participants with metabolic syndrome than without.</p> <p>Conclusion</p> <p>The prevalence of metabolic syndrome and its components by NCEP ATP III criteria was substantial across cities, ranging from 14% to 27%. CARMELA findings, including evidence of the association of metabolic syndrome and carotid atherosclerosis, should inform appropriate clinical and public health interventions.</p

A VSA search for the extended Sunyaev-Zel'dovich Effect in the Corona Borealis Supercluster

We present interferometric imaging at 33 GHz of the Corona Borealis supercluster, using the extended configuration of the Very Small Array. A total area of 24 deg^2 has been imaged, with an angular resolution of 11 arcmin and a sensitivity of 12 mJy/beam. The aim of these observations is to search for Sunyaev-Zel'dovich (SZ) detections from known clusters of galaxies in this supercluster and for a possible extended SZ decrement due to diffuse warm/hot gas in the intercluster medium. We measure negative flux values in the positions of the ten richest clusters in the region. Collectively, this implies a 3.0-sigma detection of the SZ effect. In the clusters A2061 and A2065 we find decrements of approximately 2-sigma. Our main result is the detection of two strong and resolved negative features at -70+-12 mJy/beam (-157+-27 microK) and -103+-10 mJy/beam (-230+-23 microK), respectively, located in a region with no known clusters, near the centre of the supercluster. We discuss their possible origins in terms of primordial CMB anisotropies and/or SZ signals related to either unknown clusters or to a diffuse extended warm/hot gas distribution. Our analyses have revealed that a primordial CMB fluctuation is a plausible explanation for the weaker feature (probability of 37.82%). For the stronger one, neither primordial CMB (probability of 0.33%) nor SZ can account alone for its size and total intensity. The most reasonable explanation, then, is a combination of both primordial CMB and SZ signal. Finally, we explore what characteristics would be required for a filamentary structure consisting of warm/hot diffuse gas in order to produce a significant contribution to such a spot taking into account the constraints set by X-ray data.Comment: 16 pages, 10 figures. Accepted in MNRA

War and economy. Rediscovering the eighteenth-century military entrepreneur

The detrimental effects traditionally assigned to warfare in the development of pre-industrial economies have obscured the prominent role that military entrepreneurs played in economic development in this period. Historiography minimises the extent to which war and the concomitant strengthening of the central state provided a whole new range of opportunities for capital investment, a tendency that has been strengthened by the paradigm of Redlich's decline of the soldier-entrepreneur' and the technological determinism of the debate on the Military Revolution among others. The aim of this introduction is to look into the background of this relative lack of interest and to reaffirm the mutual dependence of eighteenth-century state-formation and the business of war

Equivalence regimes for geometric quantum discord and local quantum uncertainty

The concept of quantum discord aims at unveiling quantum correlations that go beyond those described by entanglement. Its original formulation [L. Henderson and V. Vedral, J. Phys. A: Math. Gen. 34, 6899 (2001); H. Ollivier and W. H. Zurek, Phys. Rev. Lett. 88, 017901 (2001)] is difficult to compute even for the simplest case of two-qubits systems. Alternative formulations have been developed to address this drawback, such as the geometric measure of quantum discord [L. Chang and S. Luo, Phys. Rev. A 87, 062303 (2013)] and the local quantum uncertainty [D. Girolami, T. Tufarelli, and G. Adesso, Phys. Rev. Lett. 110, 240402 (2013)] that can be evaluated in closed form for some quantum systems, such as two-qubit systems. We show here that these two measures of quantum discord are equivalent for 2×D dimensional bipartite quantum systems. By considering the relevant example of N00N states for phase estimation in lossy environments, we also show that both metrics of quantum discord quantify the decrease of quantum Fisher information of the phase estimation protocol. Given their ease of computation in 2×D bipartite systems, the geometric measure of quantum discord and the local quantum uncertainty demonstrate their relevance as computable measures of quantum discord.We acknowledge support from the Spanish Ministry of Economy and Competitiveness (“Severo Ochoa” program for Centres of Excellence in R&D No. SEV-2015-0522), from Fundacio Privada Cellex, from Fundacio Mir-Puig, and from Generalitat de Catalunya through the CERCA program. This work was partially funded through the EMPIR project 17FUN01-BeCOMe. The EMPIR initiative is cofunded by the European Union Horizon 2020 Research and Innovation Programme and the EMPIR participating states. A.V. acknowledges financial support from PREBIST that has received funding from the European Union Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement No. 754558. J.R.A. acknowledges funding by the European Union Horizon 2020 Research and Innovation Programme (Marie Sklodowska- Curie 765075-LIMQUET). R.J.L.M. thankfully acknowledges financial support by CONACyT under the project CB-2016-01/284372, and by Direcci n General de Asuntos del Personal Acad mico, Universidad Nacional Aut noma de M xico (DGAPA-UNAM), under the project UNAM-PAPIIT IN102920.Peer ReviewedPostprint (author's final draft

Synergistic activation of AMPK prevents from polyglutamine-inducedtoxicity inCaenorhabditis elegans

11 páginas, 4 figuras. Supplementary material related to this article can be found, in the online version, at doi: https://doi.org/10.1016/j.phrs.2020.105105.Expression of abnormally long polyglutamine (polyQ) tracks is the source of a range of dominant neurodegenerative diseases, such as Huntington disease. Currently, there is no treatment for this devastating disease, although some chemicals, e.g., metformin, have been proposed as therapeutic solutions. In this work, we show that metformin, together with salicylate, can synergistically reduce the number of aggregates produced after polyQ expression in Caenorhabditis elegans. Moreover, we demonstrate that incubation polyQ-stressed worms with low doses of both chemicals restores neuronal functionality. Both substances are pleitotropic and may activate a range of different targets. However, we demonstrate in this report that the beneficial effect induced by the combination of these drugs depends entirely on the catalytic action of AMPK, since loss of function mutants of aak-2/AMPKα2 do not respond to the treatment. To further investigate the mechanism of the synergetic activity of metformin/salicylate, we used CRISPR to generate mutant alleles of the scaffolding subunit of AMPK, aakb-1/AMPKβ1. In addition, we used an RNAi strategy to silence the expression of the second AMPKβ subunit in worms, namely aakb-2/AMPKβ2. In this work, we demonstrated that both regulatory subunits of AMPK are modulators of protein homeostasis. Interestingly, only aakb-2/AMPKβ2 is required for the synergistic action of metformin/salicylate to reduce polyQ aggregation. Finally, we showed that autophagy acts downstream of metformin/salicylate-related AMPK activation to promote healthy protein homeostasis in worms.We thank the CGC, funded by the NIH Office of ResearchInfrastructure Programs (P40 OD010440), for worm strains. [...] RPVMis aMiguel Servet type IIresearcher (CPII16/00004) funded by Institutode Salud Carlos III (ISCIII, Madrid, Spain). Grants from the ISCIII wereused to perform this work (PI14/00949 and PI17/00011). All grantsfrom ISCIII are co-financed by the European Development RegionalFund”A way to achieve Europe”(ERDF). JBY holds a grant from theGeneralitat Valenciana and the European Social Fund (ACIF/2019/249). Some equipment used in this work has been funded in partnershipbetween the Generalitat Valenciana (Conselleria de Sanitat I SalutPública, Valencian Community, Spain) and European Funds (ERDF/FSE), through the call "Improvement of research infrastructures for rarediseases”CV FEDER 2014-2020. This work has been partially supportedby a grant from the Fundació Telemarató de la TV3 (Reference 559),which covered the work of MDS. The funds from the ISCIII are partiallysupported by the European Regional Development Fund. RPVM is also aMarie Curie fellow (CIG322034, EU). This work has been partiallysupported by a grant from the CIBERER (ACCI2016), a grant from theFundación Ramón Areces (CIVP19S8119) and anAyuda Miguel Gilgrantto RPVM (VII Convocatoria Ayudas a la Investigación MHER, 2019Peer reviewe