Exercise-induced increases in the expression and activity of cardiac sarcoplasmic reticulum calcium-ATPase 2 (SERCA2) is attenuated in AMPKα2 kinase-dead mice

Exercise enhances cardiac sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) function through unknown mechanisms. The present study tested the hypothesis that the positive effects of exercise on SERCA2a expression and function in the left ventricle is dependent on adenosine-monophosphate-activated protein kinase (AMPK) α2 function. AMPKα2 kinase-dead (KD) transgenic mice, which overexpress inactivated AMPKα2 subunit, and wild-type C57Bl/6 (WT) mice were randomized into sedentary groups or groups with access to running wheels. After 5 months, exercised KD mice exhibited shortened deceleration time compared with sedentary KD mice. In left ventricular tissue, the ratio of phosphorylated AMPKαThr172:total AMPKα was 65% lower (P < 0.05) in KD mice compared with WT mice. The left ventricle of KD mice had 37% lower levels of SERCA2a compared with WT mice. Although exercise increased SERCA2a protein levels in WT mice by 53%, this response of exercise was abolished in exercised KD mice. Exercise training reduced total phospholamban protein content by 23% in both the WT and KD mice but remained 20% higher overall in KD mice. Collectively, these data suggest that AMPKα influences SERCA2a and phospholamban protein content in the sedentary and exercised heart, and that exercise-induced changes in SERCA2a protein are dependent on AMPKα function.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Sites for the Global Validation and Intercomparison of Land Biophysical Products: Proposition of the CEOS-BELMANIP

Abstract—This study investigates the representativeness of land cover and leaf area index (LAI) sampled by a global network of sites to be used for the evaluation of land biophysical products, such as LAI or fAPAR, derived from current satellite systems. The networks of sites considered include 100 sites where ground measurements of LAI or fAPAR have been performed for the validation of medium resolution satellite land biophysical products, 188 FLUXNET sites and 52 AERONET sites. All the sites retained had less than 25 % of water bodies within a 8 8kmPwindow, and were separated by more than 20 km. The ECOCLIMAP global classification was used to quantify the representativeness of the networks. It allowed describing the Earth’s surface with seven main types and proposed a climatology for monthly LAI values at a spatial resolution around 1 km. The site distribution indicates a large over representation of the northern midlatitudes relative to other regions, and an under-representation of bare surfaces, grass, and evergreen broadleaf forests. These three networks represent all together 295 sites after elimination of sites that were too close. They were thus completed by 76 additional sites to improve the representativeness in latitude, longitude, and surface type. This constitutes the BELMANIP network proposed as a benchmark for intercomparison of land biophysical products. Suitable approaches to conducting intercomparison at the sites are recommended. Index Terms—Global land biophysical products, intercomparison, leaf area index (LAI), validation

sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance

Cancer is a disease of aging, and aged cancer patients have a poorer prognosis. This may be due to accumulated cellular damage, decreases in adaptive immunity, and chronic inflammation. However, the effects of the aged microenvironment on tumor progression have been largely unexplored. Since dermal fibroblasts can have profound impacts on melanoma progression(1–4) we examined whether age-related changes in dermal fibroblasts could drive melanoma metastasis and response to targeted therapy. We find that aged fibroblasts secrete a Wnt antagonist, sFRP2, which activates a multi-step signaling cascade in melanoma cells that results in a decrease in β-catenin and MITF, and ultimately the loss of a key redox effector, APE1. Loss of APE1 attenuates the response of melanoma cells to ROS-induced DNA damage, rendering them more resistant to targeted therapy (vemurafenib). Age-related increases in sFRP2 also augment both angiogenesis and metastasis of melanoma cells. These data provide an integrated view of how fibroblasts in the aged microenvironment contribute to tumor progression, offering new paradigms for the design of therapy for the elderly

Crystal Polymorphism and Multiple Crystal Forms

This chapter discusses the phenomenon of polymorphism in organic and organometallic compounds. Polymorphism is first introduced and then, to give the work some context, background information is given concerning properties and techniques for characterizing the solid phases. In particular, desolvation and interconverstion are examined, and the gas\u2013solid reactions are presented as a successful route to obtaining new crystalline phases. Co-crystal definition is then described and the problem in distinguishing co-crystals and salts is evaluated