Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile

Caloric restriction (CR) and down-regulation of the insulin/IGF pathway are the most robust interventions known to increase longevity in lower organisms. However, little is known about the molecular adaptations induced by CR in humans. Here, we report that long-term CR in humans inhibits the IGF-1/insulin pathway in skeletal muscle, a key metabolic tissue. We also demonstrate that CR induces dramatic changes of the skeletal muscle transcriptional profile that resemble those of younger individuals. Finally, in both rats and humans, CR evoked similar responses in the transcriptional profiles of skeletal muscle. This common signature consisted of three key pathways typically associated with longevity: IGF-1/insulin signaling, mitochondrial biogenesis, and inflammation. Furthermore, our data identify promising pathways for therapeutic targets to combat age-related diseases and promote health in humans.American Federation for Aging ResearchNational Center for Research Resources (U.S.) (Grant UL1 RR024992)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant P30DK056341

City and segregation shaken by capitalism. Critique of the idealist approaches

It has always been difficult to define what a city is and now even more so as the boom in real-estate business has subjected it and its peri-urban areas to constant transformation. With this, segregation has also acquired a state of constant mutation and in fact, no longer seems to stabilize itself, as it did in the past, into recognizable spatial patterns. This has been happening in Chilean cities, just as it has in many other countries.Thus, the temptation of substituting physical-geographical and planimetric definitions, both of city and segregation, for others that emphasize processes, is understandable. Does this mean to say then, that the physical-spatial dimension of the city implicitly or explicitly lacks importance as neoliberal economists and urbanist devotees of structural-determinist approaches argue? It is true that the COVID-19 pandemic makes the feebleness of these approaches, which ignore the spatial aspect, patently clear, but this does not make it any less relevant to examine their theoretical setup, which we will do based on a critical review of the specialized literature and testimonies of specialists collected in a research project on segregation in three Chilean cities that we recently finished. We conclude these pages in the need to reinforce empirical research of the city and segregation, just as our attention to their subjective dimensions.Siempre ha sido difícil definir qué es una ciudad y ahora lo es más porque el auge de los negocios inmobiliarios la ha tenido sometida a una transformación incesante, incluyendo sus áreas periurbanas. Con ello, también la segregación ha adquirido un estado de mutación constante y, de hecho, ya no parece estabilizarse, como en el pasado, en patrones espaciales reconocibles. Esto ha estado sucediendo en las ciudades chilenas, como en las de muchos otros países. Resulta comprensible, así, la tentación de sustituir las definiciones físico-geográficas y planimétricas, tanto de ciudad como de la segregación, por otras que enfatizan los procesos. ¿Quiere decir, entonces, que la dimensión físico-espacial de la ciudad carece de importancia como, implícita o explícitamente, argumentan los economistas neoliberales y los urbanistas apegados a enfoques estructural-deterministas? Es cierto que la pandemia del COVID19 hace evidentes las flaquezas de estos enfoques que desconsideran lo espacial, pero eso no resta relevancia al examen de su armado teórico, el que se abordará aquí con base en una revisión crítica de la literatura especializada y en testimonios de especialistas recogidos por un estudio sobre segregación en tres ciudades chilenas, del cual este artículo es resultado. Concluiremos estas páginas planteando la necesidad de reforzar la investigación empírica de la ciudad y la segregación, lo mismo que nuestra atención a sus dimensiones subjetivas

Inoculantes rizobianos para alfalfa en suelos ácidos: Una propuesta para Uruguay

Ensifer meliloti establishes symbiosis with Medicago sativa (alfalfa) and other perennial species of Medicago that grow in soils with neutral to alkaline pH, whereas Ensifer medicae makes symbiosis with annual medics adapted to moderately acid soils. The new species Rhizobium favelukesii, whose strain is LPU83, belongs to an alfalfa group of inefficient rhizobia, known as the Oregon type, initially represented by Rhizobium sp. strain Or191. R. favelukesii is considered a potential risk in the acid soils where alfalfa is grown, and could explain the inefficient nodulation observed in different countries. In acidic soils from the «Dairy Basin» of Uruguay, producers inoculate alfalfa with E. melliloti U143 strain. This edaphic condition is often marginal because the maximum potential of rhizobia-alfalfa symbiosis is not achieved at acid pH. Although Uruguay has an outstanding position in the production and use of rhizobial inoculants, the commercial strains currently used in Trifolium, Lotus and alfalfa were selected about 50 years ago in different conditions that the present ones as a consequence of: i) the displacement of cultivated pastures to other sites, ii) the sowing method, and iii) the use of new cultivars. In this review, alfalfa inoculation is analyzed in some countries and a strategy for the development of an inoculant suitable for Uruguayan acid soils is proposed. This strategy is based on the selection of efficient and competitive strains, as the first selection criteria, and persistency in soil as the second one.Ensifer meliloti establece simbiosis con Medicago sativa (alfalfa) y otras especies perennes de Medicago que crecen en suelos con pH neutro a alcalino, mientras que Ensifer medicae lo hace con especies anuales adaptadas a suelos moderadamente ácidos. La nueva especie Rhizobium favelukesii, cuya cepa tipo es LPU83, pertenece a un grupo de rizobios ineficientes en alfalfa conocidos como tipo Oregon, representados inicialmente por Rhizobium sp. cepa Or191. R. favelukesii; se considera un riesgo potencial en suelos ácidos en los que se cultiva alfalfa, y podría explicar la nodulación ineficiente en diferentes países. En suelos ácidos de la «Cuenca lechera» de Uruguay los productores inoculan alfalfa con E. meliloti cepa U143. Esa condición edáfica a veces resulta marginal para la simbiosis rizobio-alfalfa porque a pH ácido no se logra su máximo potencial. Si bien Uruguay tiene una posición destacada en la producción y uso de inoculantes rizobianos, las cepas comerciales usadas actualmente en especies de Trifolium, Lotus y alfalfa se seleccionaron hace unos 50 años en condiciones diferentes a las actuales, consecuencia de: i) el desplazamiento de pasturas cultivadas a otros sitios, ii) el tipo de siembra y iii) el uso de nuevos cultivares. En esta revisión se analiza la inoculación de la alfalfa en algunos países y se propone una estrategia para el desarrollo de un inoculante apto para suelos ácidos en Uruguay. Esta estrategia se basa en la selección de cepas eficientes y competitivas como primer criterio y persistencia en suelos, como segundo.Fil: Tabares da Rosa, Sofía. Universidad de la República; UruguayFil: Signorelli, Santiago. Universidad de la República; UruguayFil: del Papa, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Sabatini, Ornella. Universidad de la República; UruguayFil: Reyno, Rafael. Instituto Nacional de Investigación Agropecuaria; UruguayFil: Lattanzi, Fernando. Instituto Nacional de Investigación Agropecuaria; UruguayFil: Rebuffo, Mónica. Instituto Nacional de Investigación Agropecuaria; UruguayFil: Sanjuán, Juan. Consejo Superior de Investigaciones Científicas; EspañaFil: Monza Galetti, Jorge. Universidad de la República; Urugua

RELAÇÃO ENTRE OS NÍVEIS SÉRICOS DE PCR AS E COLESTEROL-HDL EM TRABALHADORES DE EMPRESAS PRIVADAS

Este trabalho determinou os níveis séricos de colesterol- HDL e de proteína C reativa de alta sensibilidade (PCR-AS) em 172 funcionários de empresas privadas visando verificar se diminuições do colesterol- HDL são acompanhadas de elevações do PCR AS. Após jejum de 10-14 horas, amostras de sangue venoso foram colhidas e processadas para obtenção de soro usado para dosagem de PCR AS e colesterol- HDL por meio de metodologia imunoturbidimétrica e enzimático- colorimétrica, respectivamente. Os funcionários preencheram um questionário para levantamento dos dados sócio- demográficos, terapêuticos, patológicos e relacionados ao estilo de vida, que foram analisados pelo teste One-Way ANOVA (e não-paramétrico), seguido de Bonferroni pelo teste Exato de Fisher ou pelo teste do qui-quadrado (p<0,05). A análise da frequência de distribuição dos trabalhadores nas diferentes faixas de colesterol-HDL permitiu observar uma frequência de distribuição significativamente maior de trabalhadores com idade superior a 51 anos (p=0,0372*) e com Índice de Massa Corporal (IMC) entre 30 e 34,9 (p=0,0498*) na faixa de colesterol-HDL considerada baixa. Em relação às faixas de PCR AS, verificou-se uma prevalência significativamente maior de funcionários obesos (p=0,0002*) e usuários de medicamentos(p=0,0416*) com valores elevados de PCR AS. Os resultados deste projeto mostram que os níveis de PCR AS são maiores quanto menores os valores de colesterol-HDL. Isto não só reforça a importância do colesterol-HDL como lipoproteína antiaterogênica, como também a possibilidade de se utilizar o exame de PCR AS em pacientes com baixos níveis de HDL independentemente de outras alterações no perfil lipídic

High Speed Two-Photon Imaging of Calcium Dynamics in Dendritic Spines: Consequences for Spine Calcium Kinetics and Buffer Capacity

Rapid calcium concentration changes in postsynaptic structures are crucial for synaptic plasticity. Thus far, the determinants of postsynaptic calcium dynamics have been studied predominantly based on the decay kinetics of calcium transients. Calcium rise times in spines in response to single action potentials (AP) are almost never measured due to technical limitations, but they could be crucial for synaptic plasticity. With high-speed, precisely-targeted, two-photon point imaging we measured both calcium rise and decay kinetics in spines and secondary dendrites in neocortical pyramidal neurons. We found that both rise and decay kinetics of changes in calcium-indicator fluorescence are about twice as fast in spines. During AP trains, spine calcium changes follow each AP, but not in dendrites. Apart from the higher surface-to-volume ratio (SVR), we observed that neocortical dendritic spines have a markedly smaller endogenous buffer capacity with respect to their parental dendrites. Calcium influx time course and calcium extrusion rate were both in the same range for spines and dendrites when fitted with a dynamic multi-compartment model that included calcium binding kinetics and diffusion. In a subsequent analysis we used this model to investigate which parameters are critical determinants in spine calcium dynamics. The model confirmed the experimental findings: a higher SVR is not sufficient by itself to explain the faster rise time kinetics in spines, but only when paired with a lower buffer capacity in spines. Simulations at zero calcium-dye conditions show that calmodulin is more efficiently activated in spines, which indicates that spine morphology and buffering conditions in neocortical spines favor synaptic plasticity

Correlação da Escala de Sonolência de Epworth com alterações na polissonografia na avaliação da sonolência excessiva diurna em pacientes com síndrome da apneia-hipopneia obstrutiva do sono

Introdução: A sonolência excessiva diurna (SED) é um importante transtorno do sono e frequentemente é associado à síndrome da apneia-hipopneia obstrutiva do sono (SAHOS). É conhecido como um fator predisponente comum para acidentes, redução da produtividade, comprometimento neurocognitivo e interpessoal e/ou problemas sociais. Portanto, a detecção precoce da SED é fundamental. Objetivo: Avaliar a correlação da escala de sonolência de Epworth (ESE) com parâmetros polissonográficos nos pacientes com SAHOS. Métodos: O estudo avaliou 1264 laudos de exames de polissonografia de pacientes com SAHOS admitidos de janeiro de 2009 até dezembro de 2013 no Instituto do Sono dos Campos Gerais. Os laudos foram divididos inicialmente em grupos de acordo com a gravidade da SAHOS e em seguida de acordo com a pontuação obtida na ESE e avaliados de acordo com os resultados dos parâmetros polissonográficos. Resultados: Dos laudos analisados, 822 (65,03%) eram de pacientes do sexo masculino e 442 (34,97%) do sexo feminino. A análise da pontuação da ESE evidenciou uma relação com a SAHOS (r = 0,175, p &lt; 0,00001). Quando analisado os subgrupos de gravidade, apenas a SAHOS grave apresentou correlação significativa com a ESE (r = 0,136, p = 0,0004). Conclusões: A escala possui correlação com a SAHOS grave. Devido à importância da detecção precoce da sonolência, a ESE pode ser utilizada como método de avaliação rápida em pacientes com a SAHOS, estimando sua gravidade e a existência de SEDIntroduction: Excessive daytime sleepiness (EDS) is an important sleep disorder, frequently associated to the obstructive sleep apnea hypopnea syndrome (OSAHS). It is known to be an important predisposing factor to accidents, decreased productivity, neurocognitive disorders and social issues. Thus, early detection of EDS is crucial. Objective: To evaluate the correlation of the Epworth Sleepiness Scale (ESS) with polysomnographic parameters in patients with OSAHS. Method: The study evaluated 1264 reports of polysomnography of patients with OSAHS admitted from January 2009 to December 2013 at the Instituto do Sono dos Campos Gerais. The reports were initially divided into groups according to the severity of OSAHS and then according to the score obtained in ESE and evaluated according to the results of the polysomnographic parameters. Results: From the analyzed reports, 822 (65.03%) were male patients, and 442 (34.87%) were female patients. According to the ESS scores analysis, a relation was observed between the scale and OSAHS (r = 0.175, p &lt; 0.,00001). However, when divided into subgroups only severe OSAHS presented a significant correlation (r = 0.136, p = 0.0004). Conclusion: The scale is more strongly related with severe OSAHS, which is also more likely to develop EDS. Due to the importance of early detection of sleepiness, the ESS can be used as a method of rapid assessment in patients with OSAHS, to estimate its severity and the presence of SE

Rhizobia Inoculants for Alfalfa in Acid Soils: A Proposal for Uruguay

Ensifer meliloti establishes symbiosis with Medicago sativa (alfalfa) and other perennial species of Medicago that grow in soils with neutral to alkaline pH, whereas Ensifer medicae makes symbiosis with annual medics adapted to moderately acid soils. The new species Rhizobium favelukesii, whose strain is LPU83, belongs to an alfalfa group of inefficient rhizobia, known as the Oregon type, initially represented by Rhizobium sp. strain Or191. R. favelukesii is considered a potential risk in the acid soils where alfalfa is grown, and could explain the inefficient nodulation observed in different countries. In acidic soils from the «Dairy Basin» of Uruguay, producers inoculate alfalfa with E. melliloti U143 strain. This edaphic condition is often marginal because the maximum potential of rhizobia-alfalfa symbiosis is not achieved at acid pH. Although Uruguay has an outstanding position in the production and use of rhizobial inoculants, the commercial strains currently used in Trifolium, Lotus and alfalfa were selected about 50 years ago in different conditions that the present ones as a consequence of: i) the displacement of cultivated pastures to other sites, ii) the sowing method, and iii) the use of new cultivars. In this review, alfalfa inoculation is analyzed in some countries and a strategy for the development of an inoculant suitable for Uruguayan acid soils is proposed. This strategy is based on the selection of efficient and competitive strains, as the first selection criteria, and persistency in soil as the second one.Instituto de Biotecnologia y Biologia Molecula

Gestión urbana en América Latina: problemas y posibilidades

Compilación de artículos que abordan la caracterización de los problemas urbanos en America Latina y analizan las limitaciones y perspectivas de la gestión urbana, en particular en el contexto de las grandes ciudades y de la crisis económica mundial. En general, aporta elementos para la conceptualización de las formas de gestión urbana y propuestas para su desarrollo en las condiciones específicas de la región. Reseña experiencias concretas en San José de Costa Rica y Managua durante los años 1980, en Lima durante el gobierno de Izquierda Unida (1984-1987) y sobre la ingerencia de los ámbitos de gobierno nacional y local en la gestión urbana en el Brasil en el período 1960-1990