A manutenção de espécies de anfíbios anuros na caatinga, um bioma que sofre um processo de aridificação, suscita perguntas sobre quais aspectos fisiológicos e evolutivos estão envolvidos nesse contexto. O argumento de que a plasticidade fenotípica permite que uma população sobreviva perante mudanças ambientais parece uma explicação plausível. A temperatura e sua variação foram eleitas como representativas da alteração ambiental, tendo como referência os valores correspondentes da floresta atlântica. Essa comparação fundamentou-se na evidência de que a caatinga assemelhava-se a uma floresta úmida antes da aridificação. Utilizamos como marco teórico um trabalho central de Smith-Gill e Berven (1979), que mostrou que a sensibilidade térmica da diferenciação é maior que a do crescimento em larvas de anuros. A hipótese central foi que a plasticidade de desenvolvimento da espécie Rhinella granulosa, presente na caatinga, é maior que das espécies Rhinella ornata e Rhinella icterica, habitantes da floresta atlântica. O método principal foi de comparar normas de reação térmicas de taxa de crescimento, tempo de desenvolvimento, massa na metamorfose e temperatura crítica máxima (TCMax) das espécies. Para isso, regimes térmicos foram simulados em laboratório a fim de representarem microhabitats típicos da floresta e da caatinga. A interação entre moda e variação da temperatura foi significativa para as espécies Rhinella ornata e Rhinella icterica. As espécies de floresta foram muito plásticas. Quando submetidas a regimes típicos da caatinga, apresentaram um aumento de duas vezes da taxa média de crescimento e um terço do tempo médio de desenvolvimento, em comparação com regimes de floresta. As larvas apresentaram variação individual de sensibilidade térmica, sendo que uma parte da amostra não seguiu a regra de Smith-Gill e Berven (1979), apresentando sensibilidade da diferenciação similar a do desenvolvimento. Como conseqüência, mantiveram sua massa na metamorfose canalizada em 0,25g mesmo diante de maiores picos de temperatura. A TCMax foi maior para R. granulosa, porém menos plástica que das espécies de floresta. Os resultados não corroboraram a nossa hipótese, uma vez que as espécies de floresta parecem ser mais plásticas que a espécie da caatinga. / The lasting presence of anuran amphibian species in the Caatinga, an environment that has been undergoing a desertification process, raises questions regarding the physiological and evolutionary aspects involved. The argument that phenotypic plasticity allows for the survival of populations in face of environmental changes seems to provide a plausible explanation. Temperature and its variation were elected as representatives of the desertification process. Based on the evidence that the Caatinga was originally a humid forest, correspondent values for the Atlantic forest were used as reference for comparison. The theoretical framework adopted assumes that the thermal sensitivity of differentiation in anuran larvae is higher than growth sensitivity (Smith-Gill and Berven, 1979). Our main hypothesis was that the developmental plasticity of the Caatinga species Rhinella granulosa is greater than those of Atlantic forest species Rhinella ornata and Rhinella icterica. We compared thermal reaction norms of growth rate, development time, metamorphic mass and critical thermal maxima (CTMax) for each species. Larvae were submitted to thermal regimes typical of the Caatinga and the Atlantic forest. A significant interaction between thermal mode and variation was detected for both Rhinella ornata and Rhinella icterica. Forest species appeared very plastic. When submitted to Caatinga thermal regimes, they displayed double growth rate and a third of development time in comparison to when they were submitted to Atlantic forest thermal regimes. The larvae presented individual variation in thermal sensitivity. Indeed, a fraction of the sample did not follow Smith-Gill and Bervens rule and displayed thermal sensitivity of differentiation similar to growth sensitivity. As a consequence, they maintained their metamorphic mass canalized at 0,25g in face of higher temperatures. Although Rhinella granulosa\'s CTMax was higher than for the forest species, it presented less plasticity. The results have not supported our hypothesis as the Atlantic forest species seems more plastic than the Caatinga species.

Hypertension is a risk factor for many cardiovascular and cerebrovascular diseases such as atherosclerosis and stroke. It is therefore important to understand the effect of hypertension on temporal growth and remodeling of arteries. In this study, experimental hypertension was induced in the mini-pig by aortic coarctation. Basilar arteries and aortas were collected for analysis over an eight week period of hypertension with specimens from normotensive animals serving as controls. Changes in mechanical properties of the basilar artery were evaluated by in vitro pressure-diameter tests on intact cylindrical segments at their in situ length. The basilar arteries from hypertensive animals became less distensible, reflecting increases in both structural and material stiffness, compared to their normotensive counterparts. The circumferential stress rapidly returned toward its homeostatic value by increasing the wall thickness within two weeks. Immunohistochemistry, which is capable of illustrating the localization and distribution of protein expression, was performed to examine changes in wall constituents in the aorta. The increased medial thickness observed in hypertensive pigs compared to normotensive pigs was due to hyperplasia of smooth muscle cells (SMCs) and accumulation of extracellular matrix proteins, which were accompanied by the phenotypic modulation of SMCs. The increased interlamellar thickness, collagen fibers, and the thickness of elastic lamina found in the inner media of hypertensive animal may be associated with the gradient of stress decreasing into the outer media. SMC proliferation, if any, was found evenly distributed across the media, however. In cases showing increased proliferation and matrix protein synthesis, the SMC contractile markers were down-regulated whereas the SMC synthetic markers were up-regulated. While the aortic intima appeared normal in the normotensive animals, neointima formation, which may predispose the vessel to atheroma formation, was found in the hypertensive animals. Immunohistochemistry of Hsp47 and procollagen revealed that the endothelial cells (ECs) may produce collagen, specifically type I collagen in response to hypertension and contribute to the thickened intima. In addition, lectin staining for ECs markers and immunostaining for eNOS suggested that endothelial cells may transdifferentiate into intimal SMCs. These findings suggested an alternative role that ECs may play in hypertension-induced atherogenesis.

A manutenção de espécies de anfíbios anuros na caatinga, um bioma que sofre um processo de aridificação, suscita perguntas sobre quais aspectos fisiológicos e evolutivos estão envolvidos nesse contexto. O argumento de que a plasticidade fenotípica permite que uma população sobreviva perante mudanças ambientais parece uma explicação plausível. A temperatura e sua variação foram eleitas como representativas da alteração ambiental, tendo como referência os valores correspondentes da floresta atlântica. Essa comparação fundamentou-se na evidência de que a caatinga assemelhava-se a uma floresta úmida antes da aridificação. Utilizamos como marco teórico um trabalho central de Smith-Gill e Berven (1979), que mostrou que a sensibilidade térmica da diferenciação é maior que a do crescimento em larvas de anuros. A hipótese central foi que a plasticidade de desenvolvimento da espécie Rhinella granulosa, presente na caatinga, é maior que das espécies Rhinella ornata e Rhinella icterica, habitantes da floresta atlântica. O método principal foi de comparar normas de reação térmicas de taxa de crescimento, tempo de desenvolvimento, massa na metamorfose e temperatura crítica máxima (TCMax) das espécies. Para isso, regimes térmicos foram simulados em laboratório a fim de representarem microhabitats típicos da floresta e da caatinga. A interação entre moda e variação da temperatura foi significativa para as espécies Rhinella ornata e Rhinella icterica. As espécies de floresta foram muito plásticas. Quando submetidas a regimes típicos da caatinga, apresentaram um aumento de duas vezes da taxa média de crescimento e um terço do tempo médio de desenvolvimento, em comparação com regimes de floresta. As larvas apresentaram variação individual de sensibilidade térmica, sendo que uma parte da amostra não seguiu a regra de Smith-Gill e Berven (1979), apresentando sensibilidade da diferenciação similar a do desenvolvimento. Como conseqüência, mantiveram sua massa na metamorfose canalizada em 0,25g mesmo diante de maiores picos de temperatura. A TCMax foi maior para R. granulosa, porém menos plástica que das espécies de floresta. Os resultados não corroboraram a nossa hipótese, uma vez que as espécies de floresta parecem ser mais plásticas que a espécie da caatinga. / The lasting presence of anuran amphibian species in the Caatinga, an environment that has been undergoing a desertification process, raises questions regarding the physiological and evolutionary aspects involved. The argument that phenotypic plasticity allows for the survival of populations in face of environmental changes seems to provide a plausible explanation. Temperature and its variation were elected as representatives of the desertification process. Based on the evidence that the Caatinga was originally a humid forest, correspondent values for the Atlantic forest were used as reference for comparison. The theoretical framework adopted assumes that the thermal sensitivity of differentiation in anuran larvae is higher than growth sensitivity (Smith-Gill and Berven, 1979). Our main hypothesis was that the developmental plasticity of the Caatinga species Rhinella granulosa is greater than those of Atlantic forest species Rhinella ornata and Rhinella icterica. We compared thermal reaction norms of growth rate, development time, metamorphic mass and critical thermal maxima (CTMax) for each species. Larvae were submitted to thermal regimes typical of the Caatinga and the Atlantic forest. A significant interaction between thermal mode and variation was detected for both Rhinella ornata and Rhinella icterica. Forest species appeared very plastic. When submitted to Caatinga thermal regimes, they displayed double growth rate and a third of development time in comparison to when they were submitted to Atlantic forest thermal regimes. The larvae presented individual variation in thermal sensitivity. Indeed, a fraction of the sample did not follow Smith-Gill and Bervens rule and displayed thermal sensitivity of differentiation similar to growth sensitivity. As a consequence, they maintained their metamorphic mass canalized at 0,25g in face of higher temperatures. Although Rhinella granulosa\'s CTMax was higher than for the forest species, it presented less plasticity. The results have not supported our hypothesis as the Atlantic forest species seems more plastic than the Caatinga species.

Indiana University-Purdue University Indianapolis (IUPUI) / Metabolic syndrome (MetS) affects 1/3 of all Americans and is the clustering of three or more of the following cardiometabolic risk factors: obesity, hypertension, dyslipidemia, glucose intolerance, and insulin resistance. MetS drastically increases the incidence of coronary artery disease (CAD), which is the leading cause of mortality globally. A cornerstone of CAD is arterial remodeling associated with coronary smooth muscle (CSM) cytodifferentiation from a contractile phenotype to proliferative and osteogenic phenotypes. This cytodifferentiation is tightly coupled to changes in intracellular Ca2+ handling that regulate several key cellular functions, including contraction, transcription, proliferation, and migration. Our group has recently elucidated the time course of Ca2+ dysregulation during MetS-induced CAD development. Ca2+ transport mechanisms, including voltage-gated calcium channels, sarcoplasmic reticulum (SR) Ca2+ store, and sarco-endoplasmic reticulum Ca2+ ATPase (SERCA), are enhanced in early, mild disease and diminished in late, severe disease in the Ossabaw miniature swine. Using this well-characterized large animal model, I tested the hypothesis that this Ca2+ dysregulation pattern occurs in multiple etiologies of CAD, including diabetes and aging. The fluorescent intracellular Ca2+ ([Ca2+]i) indicator fura-2 was utilized to measure [Ca2+]i handling in CSM from lean and diseased swine. I found that [Ca2+]i handling is enhanced in mild disease with minimal CSM phenotypic switching and diminished in severe disease with greater phenotypic switching, regardless of CAD etiology. We are confident of the translatability of this research, as the Ca2+ influx, SR Ca2+ store, and SERCA functional changes in CSM of humans with CAD are similar to those found in Ossabaw swine with MetS. Single-cell RNA sequencing revealed that CSM cells from an organ culture model of CAD exhibited many different phenotypes, indicating that phenotypic modulation is not a discreet event, but a continuum. Transcriptomic analysis revealed differential expression of many genes that are involved in the osteogenic signaling pathway and in cellular inflammatory responses across phenotypes. These genes may be another regulatory mechanism common to the different CAD etiologies. This study is the first to show that CSM Ca2+ dysregulation is common among different CAD etiologies in a clinically relevant animal model.