Distinct Steps of Neural Induction Revealed by Asterix, Obelix and TrkC, Genes Induced by Different Signals from the Organizer

The amniote organizer (Hensen's node) can induce a complete nervous system when grafted into a peripheral region of a host embryo. Although BMP inhibition has been implicated in neural induction, non-neural cells cannot respond to BMP antagonists unless previously exposed to a node graft for at least 5 hours before BMP inhibitors. To define signals and responses during the first 5 hours of node signals, a differential screen was conducted. Here we describe three early response genes: two of them, Asterix and Obelix, encode previously undescribed proteins of unknown function but Obelix appears to be a nuclear RNA-binding protein. The third is TrkC, a neurotrophin receptor. All three genes are induced by a node graft within 4–5 hours but they differ in the extent to which they are inducible by FGF: FGF is both necessary and sufficient to induce Asterix, sufficient but not necessary to induce Obelix and neither sufficient nor necessary for induction of TrkC. These genes are also not induced by retinoic acid, Noggin, Chordin, Dkk1, Cerberus, HGF/SF, Somatostatin or ionomycin-mediated Calcium entry. Comparison of the expression and regulation of these genes with other early neural markers reveals three distinct “epochs”, or temporal waves, of gene expression accompanying neural induction by a grafted organizer, which are mirrored by specific stages of normal neural plate development. The results are consistent with neural induction being a cascade of responses elicited by different signals, culminating in the formation of a patterned nervous system

Transverse tubule remodelling: a cellular pathology driven by both sides of the plasmalemma?

Transverse (t)-tubules are invaginations of the plasma membrane that form a complex network of ducts, 200–400 nm in diameter depending on the animal species, that penetrates deep within the cardiac myocyte, where they facilitate a fast and synchronous contraction across the entire cell volume. There is now a large body of evidence in animal models and humans demonstrating that pathological distortion of the t-tubule structure has a causative role in the loss of myocyte contractility that underpins many forms of heart failure. Investigations into the molecular mechanisms of pathological t-tubule remodelling to date have focused on proteins residing in the intracellular aspect of t-tubule membrane that form linkages between the membrane and myocyte cytoskeleton. In this review, we shed light on the mechanisms of t-tubule remodelling which are not limited to the intracellular side. Our recent data have demonstrated that collagen is an integral part of the t-tubule network and that it increases within the tubules in heart failure, suggesting that a fibrotic mechanism could drive cardiac junctional remodelling. We examine the evidence that the linkages between the extracellular matrix, t-tubule membrane and cellular cytoskeleton should be considered as a whole when investigating the mechanisms of t-tubule pathology in the failing heart

Cardiovascular control and stabilization via inclination and mobilization during bed rest

Cardiovascular deconditioning has long been recognized as a characteristic of the physiological adaptation to long-term bed rest in patients. The process is thought to contribute to orthostatic intolerance and enhance secondary complications in a significant way. Mobilization is a cost-effective and simple method to maintain the cardiovascular parameters (i.e., blood pressure, heart rate) stable, counter orthostatic intolerance and reduce the risk of secondary problems in patients during long-term immobilization. The aim of this project is to control the cardiovascular parameters such as heart rate and blood pressure of bed rest patients via automated leg mobilization and body tilting. In a first step, a nonlinear model predictive control strategy was designed and evaluated on five healthy subjects and 11 bed rest patients. In a next step, a clinically feasible study was conducted on two patients. The mean values differed on average less than 1 bpm from the predetermined heart rate and less than 2.5 mmHg from the desired blood pressure values. These results of the feasibility study are promising, although heterogeneous disease etiologies and individual medication strongly influence the mechanically induced reactions. The long-term goal is an automation of the control of physiological signals and the mobilization of bed rest patients in an early phase of the rehabilitation process. Therefore, this new approach could help to strengthen the cardiovascular system and prevent secondary health problems arising from long-term bed rest

Nitrogen loss from soil through anaerobic ammonium oxidation coupled to iron reduction

The oxidation of ammonium is a key step in the nitrogen cycle, regulating the production of nitrate, nitrous oxide and dinitrogen. In marine and freshwater ecosystems, anaerobic ammonium oxidation coupled to nitrite reduction, termed anammox, accounts for up to 67% of dinitrogen production. Dinitrogen production through anaerobic ammonium oxidation has not been observed in terrestrial ecosystems, but the anaerobic oxidation of ammonium to nitrite has been observed in wetland soils under iron-reducing conditions. Here, we incubate tropical upland soil slurries with isotopically labelled ammonium and iron(iii) to assess the potential for anaerobic ammonium oxidation coupled to iron(iii) reduction, otherwise known as Feammox, in these soils. We show that Feammox can produce dinitrogen, nitrite or nitrate in tropical upland soils. Direct dinitrogen production was the dominant Feammox pathway, short-circuiting the nitrogen cycle and resulting in ecosystem nitrogen losses. Rates were comparable to aerobic nitrification and to denitrification, the latter being the only other process known to produce dinitrogen in terrestrial ecosystems. We suggest that Feammox could fuel nitrogen losses in ecosystems rich in poorly crystalline iron minerals, with low or fluctuating redox conditions. Includes Supplementary Information