Role and possible mechanisms of clenbuterol in enhancing reverse remodelling during mechanical unloading in murine heart failure

Aims Combined left ventricular assist device (LVAD) and pharmacological therapy has been proposed to favour myocardial recovery in patients with end-stage heart failure (HF). Clenbuterol (Clen), a b 2 -adrenoceptor (b 2 -AR) agonist, has been used as a part of this strategy. In this study, we investigated the direct effects of clenbuterol on unloaded myocardium in HF. Methods and results Left coronary artery ligation or sham operation was performed in male Lewis rats. After 4-6 weeks, heterotopic abdominal transplantation of the failing hearts into normal recipients was performed to induce LV unloading (UN). Recipient rats were treated with saline (Sal) or clenbuterol (2 mg/kg/day) via osmotic minipumps (HF þ UN þ Sal or HF þ UN þ Clen) for 7 days. Non-transplanted HF animals were treated with Sal (Sham þ Sal, HF þ Sal) or clenbuterol (HF þ Clen). LV myocytes were isolated and studied using optical, fluorescence, and electrophysiological techniques. Conclusion Clenbuterol treatment of failing rat hearts, alone or in combination with mechanical unloading, improves LV function at the whole-heart and cellular levels by affecting cell morphology, excitation-contraction coupling, and myofilament sensitivity to calcium. This study supports the use of this drug in the strategy to enhance recovery in HF patients treated with LVADs and also begins to elucidate some of the possible cellular mechanisms responsible for the improvement in LV function

Sequence stratigraphy, basin morphology and sea-level history for the Permian Kapp Starostin Formation of Svalbard, Norway

Based on seven measured sections from Svalbard, the marine strata of the Permian Kapp Starostin Formation are arranged into seven transgressive–regressive sequences (TR1–TR7) of c. 4–5 Ma average duration, each bound by a maximum regressive surface. Facies, including heterozoan-dominated limestones, spiculitic cherts, sandstones, siltstones and shales, record deposition within inner, middle and outer shelf areas. The lowermost sequence, TR1, comprises most of the basal Vøringen Member, which records a transgression across the Gipshuken Formation following a hiatus of unknown duration. Temperate to cold, storm-dominated facies established in inner to middle shelf areas between the latest Artinskian and Kungurian. Prolonged deepening during sequences TR2 and TR3 was succeeded by a long-term shallowing-upward trend that lasted until the latest Permian (TR4–TR7). A major depocentre existed in central and western Spitsbergen while to the north, Dickson Land remained a shallow platform, leading to a shallow homoclinal ramp in NE Spitsbergen and Nordaustlandet. The Middle Permian extinction (late Capitanian) is recorded near the base of TR6 in deeper parts of the basin only; elsewhere this sequence is not recorded. Likewise the youngest sequence, TR7, extending to the upper formational contact of latest Permian age, is found only in the basin depocentre. Comparison with age-equivalent strata in the Sverdrup Basin of Canada reveals a remarkably similar depositional history, with, for example, two (third-order) sea-level cycles recorded in the Late Permian of both regions, in keeping with the global record. Sequence stratigraphy may therefore be a powerful correlative tool for onshore and offshore Permian deposits across NW Pangaea

Rays, intrusive growth, and storied cambium in the inflorescence stems of Arabidopsis thaliana (L.) Heynh

Arabidopsis thaliana is a model plant used in analysis of different aspects of plant growth and development. Under suitable conditions, secondary growth takes place in the hypocotyl of Arabidopsis plants, a finding which helps in understanding many aspects of xylogenesis. However, not all developmental processes of secondary tissue can be studied here, as no secondary rays and intrusive growth have been detected in hypocotyl. However, results presented here concerning the secondary growth in inflorescence stems of Arabidopsis shows that both secondary rays and intrusive growth of cambial cells can be detected, and that, in the interfascicular regions, a storied cambium can be developed

Dolichol: A Component of the Cellular Antioxidant Machinery

Dolichol, an end product of the mevalonate pathway, has been proposed a biomarker of aging, but its biological role, not to mention its catabolism, has not been fully understood. UV-B radiation was used to induce oxidative stress in isolated rat hepatocytes by the collagenase method. Effects on dolichol, phospholipids-bound polyunsaturated fatty acids (PL PUFA) and known lipid soluble antioxidants [coenzyme Q (CoQ) and α-tocopherol] were studied. The increase in oxidative stress was detected by a probe sensitive to reactive oxygen species (ROS). Peroxidation of lipids was assessed by measuring the release of thiobarbituric acid reactive substances (TBARS). Dolichol, CoQ and α-tocopherol were assessed by high-pressure liquid chromatography (HPLC), PL PUFA by gas-liquid chromatography (GC). UV-B radiation caused an immediate increase in ROS as well as lipid peroxidation and a simultaneous decrease in the levels of dolichol and lipid soluble antioxidants. Decrease in dolichol paralleled changes in CoQ levels and was smaller than that in α-tocopherol. The addition of mevinolin, a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoAR), magnified the loss of dolichol and was associated with an increase in TBARS production. Changes in PL PUFA were minor. These findings highlight that oxidative stress has very early and similar effects on dolichol and lipid soluble antioxidants. Lower levels of dolichol are associated with enhanced peroxidation of lipids, which suggest that dolichol may have a protective role in the antioxidant machinery of cell membranes and perhaps be a key to understanding some adverse effects of statin therapy

The Human Affectome

Over the last decades, the interdisciplinary field of the affective sciences has seen proliferation rather than integration of theoretical perspectives. This is due to differences in metaphysical and mechanistic assumptions about human affective phenomena (what they are and how they work) which, shaped by academic motivations and values, have determined the affective constructs and operationalizations. An assumption on the purpose of affective phenomena can be used as a teleological principle to guide the construction of a common set of metaphysical and mechanistic assumptions—a framework for human affective research. In this capstone paper for the special issue “Towards an Integrated Understanding of the Human Affectome”, we gather the tiered purpose of human affective phenomena to synthesize assumptions that account for human affective phenomena collectively. This teleologically-grounded framework offers a principled agenda and launchpad for both organizing existing perspectives and generating new ones. Ultimately, we hope Human Affectome brings us a step closer to not only an integrated understanding of human affective phenomena, but an integrated field for affective research

Ionic liquids at electrified interfaces

Until recently, “room-temperature” (<100–150 °C) liquid-state electrochemistry was mostly electrochemistry of diluted electrolytes(1)–(4) where dissolved salt ions were surrounded by a considerable amount of solvent molecules. Highly concentrated liquid electrolytes were mostly considered in the narrow (albeit important) niche of high-temperature electrochemistry of molten inorganic salts(5-9) and in the even narrower niche of “first-generation” room temperature ionic liquids, RTILs (such as chloro-aluminates and alkylammonium nitrates).(10-14) The situation has changed dramatically in the 2000s after the discovery of new moisture- and temperature-stable RTILs.(15, 16) These days, the “later generation” RTILs attracted wide attention within the electrochemical community.(17-31) Indeed, RTILs, as a class of compounds, possess a unique combination of properties (high charge density, electrochemical stability, low/negligible volatility, tunable polarity, etc.) that make them very attractive substances from fundamental and application points of view.(32-38) Most importantly, they can mix with each other in “cocktails” of one’s choice to acquire the desired properties (e.g., wider temperature range of the liquid phase(39, 40)) and can serve as almost “universal” solvents.(37, 41, 42) It is worth noting here one of the advantages of RTILs as compared to their high-temperature molten salt (HTMS)(43) “sister-systems”.(44) In RTILs the dissolved molecules are not imbedded in a harsh high temperature environment which could be destructive for many classes of fragile (organic) molecules

Human and machine validation of 14 databases of dynamic facial expressions

With a shift in interest toward dynamic expressions, numerous corpora of dynamic facial stimuli have been developed over the past two decades. The present research aimed to test existing sets of dynamic facial expressions (published between 2000 and 2015) in a cross-corpus validation effort. For this, 14 dynamic databases were selected that featured facial expressions of the basic six emotions (anger, disgust, fear, happiness, sadness, surprise) in posed or spontaneous form. In Study 1, a subset of stimuli from each database (N = 162) were presented to human observers and machine analysis, yielding considerable variance in emotion recognition performance across the databases. Classification accuracy further varied with perceived intensity and naturalness of the displays, with posed expressions being judged more accurately and as intense, but less natural compared to spontaneous ones. Study 2 aimed for a full validation of the 14 databases by subjecting the entire stimulus set (N = 3812) to machine analysis. A FACS-based Action Unit (AU) analysis revealed that facial AU configurations were more prototypical in posed than spontaneous expressions. The prototypicality of an expression in turn predicted emotion classification accuracy, with higher performance observed for more prototypical facial behavior. Furthermore, technical features of each database (i.e., duration, face box size, head rotation, and motion) had a significant impact on recognition accuracy. Together, the findings suggest that existing databases vary in their ability to signal specific emotions, thereby facing a trade-off between realism and ecological validity on the one end, and expression uniformity and comparability on the other