Equilibrio entre el hombre y la naturaleza: los indígenas costeros de El Médano, Baja California Sur, México.

Sin resume

Tubular Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin: A Possible Role of HIF-1α Expression and Oxygen Metabolism

http://dx.doi.org/10.2337/db10-0655OBJECTIVE : Chronic hypoxia has been recognized as a key regulator in renal tubulointerstitial fibrosis, as seen in diabetic nephropathy, which is associated with the activation of hypoxia-inducible factor (HIF)-1α. We assess here the effects of the biguanide, metformin, on the expression of HIF-1α in diabetic nephropathy using renal proximal tubular cells and type 2 diabetic rats. RESEARCH DESIGN AND METHODS : We explored the effects of metformin on the expression of HIF-1α using human renal proximal tubular epithelial cells (HRPTECs). Male Zucker diabetic fatty (ZDF; Gmi-fa/fa) rats were treated from 9 to 39 weeks with metformin (250 mg/kg^/day^) or insulin. RESULTS : Metformin inhibited hypoxia-induced HIF-1α accumulation and the expression of HIF-1–targeted genes in HRPTECs. Although metformin activated the downstream pathways of AMP-activated protein kinase (AMPK), neither the AMPK activator, AICAR, nor the mTOR inhibitor, rapamycin, suppressed hypoxia-induced HIF-1α expression. In addition, knockdown of AMPK-α did not abolish the inhibitory effects of metformin on HIF-1α expression. The proteasome inhibitor, MG-132, completely eradicated the suppression of hypoxia-induced HIF-1α accumulation by metformin. The inhibitors of mitochondrial respiration similarly suppressed hypoxia-induced HIF-1α expression. Metformin significantly decreased ATP production and oxygen consumption rates, which subsequently led to increased cellular oxygen tension. Finally, metformin, but not insulin, attenuated tubular HIF-1α expression and pimonidazole staining and ameliorated tubular injury in ZDF rats. CONCLUSIONS : Our data suggest that hypoxia-induced HIF-1α accumulation in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxygen consumption

Estrutura e dinâmica do fluxo na confluência de grandes rios tropicais: O exemplo dos rios Ivaí e Paraná, PR

Morphology and dynamics of the confluence environment of the Paraná and Ivaí Rivers (South Brazil) are studied using echo-sounding and velocity profile surveys (ADCP) with suspended and bedload sampling. An area was surveyed in two periods of hydrological cycles: high water in the summer and low water in the winter. It can be considered an anomalous confluence where the tributary waters do not flow directly into the Paraná River, but rather a secondary channel of the same dimension as the Ivaí River. The results show an asymmetrical confluence in which the tributary channel is 30-50% deeper than the collector. The flow momentum ratio indicated that, after the confluence flow is dominated by the Paraná River over the Ivaí. Analysis on bedform dynamics and morphology and their control over flow roughness, turbulence and mixture are also discussed. The studied confluence is completely different from others in the same hydrographic basin and can be used as a model for rare non-impacted large river confluences. Keywords: river confluence, flow dynamics, Ivaí River, Paraná River.A dinâmica e a morfologia da confluência dos rios Ivaí e Paraná são estudadas por meio de levantamento eco-batimétrico e por perfilagem de velocidade (ADCP) juntamente com amostragem da carga suspensa e de fundo transportada, em dois momentos do ciclo hidrológico (inverno e verão). Trata-se de uma confluência anômala onde as águas do tributário não desembocam diretamente no rio Paraná, mas num canal secundário de dimensões semelhantes às do rio Ivaí. Os resultados revelam uma confluência de assimétrica na qual o canal do tributário apresenta-se 30 a 50% mais profundo que o canal do coletor. A componente do fluxo pós-confluência (razão do momento do fluxo) indica o predomínio do fluxo do rio Paraná sobre o do Ivaí. São também feitas análises sobre o comportamento das formas de leito e de sua influência na rugosidade e turbulência do fluxo, como também no processo de mistura dos fluxos após a confluência. A metodologia mostrou-se válida e de fácil aplicação em outros sistemas fluviais de mesmas dimensões. Palavras-chave: confluência, dinâmica de fluxo, morfologia, rio Ivaí, rio Paraná

DINÂMICA DE RAMPA DE COLÚVIO NA SUPERFÍCIE DE PALMAS/ÁGUA DOCE DURANTE O QUATERNÁRIO TARDIO – BASES PARA COMPREENDER A EVOLUÇÃO DAS ENCOSTAS NO PLANALTO DAS ARAUCÁRIAS

O termo rampa de colúvio consiste em unidade de relevo suavemente inclinada em direção ao fundo dos vales mantida por colúvios, por vezes recobrindo terraços aluviais e reentrâncias (hollows) ou depressões em anfiteatro. O presente trabalho visou determinar a dinâmica de rampa de colúvio da superfície de Palmas/Água Doce, ao longo do Quaternário Tardio, bem como tecer considerações a respeito do ambiente de encostas em superfícies de cimeira do Planalto das Araucárias, sul do Brasil. Aplicou-se a análise pedoestratigráfica em duas seções representativas dos materiais da rampa de colúvio, bem como a geocronologia (métodos 14C e LOE), análise isotópica do carbono e fitolítica. A rampa de colúvio relevou registro pedoestratigráfico caracterizado por camadas delgadas de colúvios (horizontes Cb), por vezes pedogenizadas (horizontes Ab, ACb, CAb, Bb e BCb), com importantes lacunas e truncamentos de níveis pedológicos superficiais (paleohorizontes A). Vales de drenagem de baixa ordem vizinhos às encostas sofreram colmatação durante sucessivas fases de sedimentação. A morfogênese foi contínua no setor analisado do Último Interglacial (Estágio Isotópico Marinho 3 – EIM 3) ao Holoceno (EIM 1). Os sinais isotópicos e fitolíticos sugerem que a estabilidade ambiental favorecendo a pedogênese no Último Interestadial (EIM 3) foi em detrimento de regime climático úmido e relativamente frio. Já a morfogênese registrada no Último Máximo Glacial (EIM 2) decorreu de regime climático relativamente frio e seco, pontuada por fase de flutuação para mais úmido. Enfim, para o Holoceno (EIM 1) o clima mostrou-se no geral mais quente e seco. Do ponto de vista regional, os resultados indicam que: a) as rampas de colúvio são unidades geomórficas de trânsito de sedimentos entre colinas e fundo de vale de baixa ordem nas superfícies de cimeira do Planalto das Araucárias; b) seus registros estratigráficos são delgados em face a recorrentes lacunas (descontinuidades); c) a intensa dinâmica erosiva nas rampas inibe o acúmulo de sedimentos, por outro lado possibilita a colmatação de fundos de vales de baixa ordem vizinhos, até completa homogeneização topográfica lateral; d) nesses fundos de vales estão os principais registros estratigráficos que documentam fases de pedogênese e morfogênese tanto no ambiente de encosta quanto no ambiente fluvial de baixa ordem vinculado a rampa; e) paleohorizontes A húmicos enterrados (Ab), vinculados a fase de pedogênese do Último Máximo Glacial, podem estar preservados em ambos os ambientes.</p

Morphodynamics in the confluence of large regulated rivers: the case of Paraná and Paranapanema Rivers

The confluence of the Paraná and Paranapanema Rivers is studied according to morphology and dynamics. It is probably the only example of this type of fluvial environment involving a large, tropical and intensive regulated river. Confluence channels were monitored along a hydrological cycle (high-low water level) in terms of morphology, flow velocity, magnitude, structure, and bedload dynamics. In this case, hydrology is controlled by the flow of the tributary, which develops a continuous and well-defined thalweg since the collector channel (a secondary channel of the Paraná River) that presents relatively large bedforms that reduce stream power by increasing roughness. Although significant differences in channel morphology were not observed along the hydrological year, bed material texture indicates that the channel bottom is suffering a slight armoring process. This is probably the reason for the large asymmetry of channel confluence where the depth of the tributary channel is larger than that of the main collector channel (the Paraná left branch). The Rosana Dam, closed in 1987 and located 26 km upstream from the confluence, is the cause of the changes in sediment transport and the generation of the channel pavement. With the closing of the Porto Primavera Dam (2000) in the Paraná River (27 km upstream from the confluence) a new morphodynamics is foreseen for this environment, and this paper can be seen a relevant pioneer reference for environmental monitoring and management

チュウガッコウ エイゴ キョウカショ ニ ミラレル ジッセンテキ コミュニケーション ノウリョク

The purpose of this study is to analyze English language textbooks authorized by Monbukagakusho for lower secondary schools with special reference to skits to foster students\u27 practical communication ability. First of all, the concept of practical communication ability, which was one of the keywords stated in the course of study published by Monbusho, was discussed and a research framework was established to scrutinize the characteristics of the skits in newly published English textbooks from three perspectives: situation-setting, characteristics of dialogues, and language functions. After analyzing three kinds of textbooks based on the framework, the following characteristics were found. 1) New textbooks provide students with situations to use English which they possibly meet in their daily life. 2) There are some differences among textbooks in the main patterns of conversational structure. 3) The textbooks treat few language functions which show a speaker\u27s subjective request with negative form (e.g. You must not ～. Won\u27t you ～?, etc.). In conclusion, some pedagogical implications of the way of using new textbooks were mentioned according to those findings.国立情報学研究所『研究紀要公開支援事業』により電子化

チュウガッコウ エイゴ キョウカショ ニ ミラレル ジッセンテキ コミュニケーション ノウリョク

The purpose of this study is to analyze English language textbooks authorized by Monbukagakusho for lower secondary schools with special reference to skits to foster students\u27 practical communication ability. First of all, the concept of practical communication ability, which was one of the keywords stated in the course of study published by Monbusho, was discussed and a research framework was established to scrutinize the characteristics of the skits in newly published English textbooks from three perspectives: situation-setting, characteristics of dialogues, and language functions. After analyzing three kinds of textbooks based on the framework, the following characteristics were found. 1) New textbooks provide students with situations to use English which they possibly meet in their daily life. 2) There are some differences among textbooks in the main patterns of conversational structure. 3) The textbooks treat few language functions which show a speaker\u27s subjective request with negative form (e.g. You must not ～. Won\u27t you ～?, etc.). In conclusion, some pedagogical implications of the way of using new textbooks were mentioned according to those findings.国立情報学研究所『研究紀要公開支援事業』により電子化

CD153/CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury

高齢者腎臓病を悪化させる原因細胞・分子の同定に成功. 京都大学プレスリリース. 2021-11-30.A new drug target for kidney disease. 京都大学プレスリリース. 2021-11-30.Tertiary lymphoid tissues (TLTs) facilitate local T- and B-cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here we identify TNF superfamily CD153-CD30 signaling between two unique age-dependent lymphocyte subpopulations, CD153⁺PD-1⁺CD4⁺ senescence-associated T (SAT) cells and CD30+T-bet+ age-associated B cells (ABCs), as a driver for TLT expansion. SAT cells, which produced ABC-inducing factors IL21 and IFNγ, and ABCs progressively accumulated within TLTs in aged kidneys after injury. Notably, in kidney injury models, CD153 or CD30 deficiency impaired functional SAT cell induction, which resulted in reduced ABC numbers and attenuated TLT formation with improved inflammation, fibrosis and renal function. Attenuated TLT formation after transplantation of CD153-deficient bone marrow further supported the importance of CD153 in immune cells. Clonal analysis revealed that SAT cells and ABCs in the kidneys arose from both local differentiation and recruitment from the spleen. In the synovium of aged rheumatoid arthritis patients, T peripheral helper/T follicular helper cells and ABCs also expressed CD153 and CD30, respectively. Together, our data reveal a previously unappreciated function of CD153-CD30 signaling in TLT formation and propose targeting CD153-CD30 signaling pathway as a therapeutic target for slowing kidney disease progression

Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney

Acute kidney injury (AKI) is a common clinical condition defined as a rapid decline in kidney function. AKI is a global health burden, estimated to cause 2 million deaths annually worldwide. Unlike AKI in the young, which is reversible, AKI in the elderly often leads to end-stage renal disease, and the mechanism that prevents kidney repair in the elderly is unclear. Here we demonstrate that aged but not young mice developed multiple tertiary lymphoid tissues (TLTs) in the kidney after AKI. TLT size was associated with impaired renal function and increased expression of proinflammatory cytokines and homeostatic chemokines, indicating a possible contribution of TLTs to sustained inflammation after injury. Notably, resident fibroblasts from a single lineage diversified into p75 neurotrophin receptor(+) (p75NTR(+)) fibroblasts and homeostatic chemokine-producing fibroblasts inside TLTs, and retinoic acid-producing fibroblasts around TLTs. Deletion of CD4(+) cells as well as late administration of dexamethasone abolished TLTs and improved renal outcomes. Importantly, aged but not young human kidneys also formed TLTs that had cellular and molecular components similar to those of mouse TLTs. Therefore, the inhibition of TLT formation may offer a novel therapeutic strategy for AKI in the elderly.</p