Specific activation of Smad1 signaling pathways by the BMP7 type I receptor, ALK2

BMP7 and activin are members of the transforming growth factor beta superfamily. Here we characterize endogenous activin and BMP7 signaling pathways in P19 embryonic carcinoma cells. We show that BMP7 and activin bind to the same type II receptors, ActRII and IIB, but recruit distinct type I receptors into heteromeric receptor complexes. The major BMP7 type I receptor observed was ALK2, while activin bound exclusively to ALK4 (ActRIB). BMP7 and activin elicited distinct biological responses and activated different Smad pathways. BMP7 stimulated phosphorylation of endogenous Smad1 and 5, formation of complexes with Smad4 and induced the promoter for the homeobox gene, Tlx2. In contrast, activin induced phosphorylation of Smad2, association with Smad4, and induction of the activin response element from the Xenopus Mix.2 gene. Biochemical analysis revealed that constitutively active ALK2 associated with and phosphorylated Smad1 on the COOH-terminal SSXS motif, and also regulated Smad5 and Smad8 phosphorylation. Activated ALK2 also induced the Tlx2 promoter in the absence of BMP7. Furthermore, we show that ALK1 (TSRI), an orphan receptor that is closely related to ALK2 also mediates Smad1 signaling. Thus, ALK1 and ALK2 induce Smad1-dependent pathways and ALK2 functions to mediate BMP7 but not activin signaling.     

Differential effect of thyroid-stimulating hormone (TSH) on intracellular free calcium and cAMP in cells transfected with the human TSH receptor

The major part of research dealing with the biophysical and biochemical properties of airway smooth muscle is based on the assumption that the cells constituting the tissue are homogenous. For striated muscle this has been shown untenable. In recent years almost every property of vascular smooth muscle has been also demonstrated to be heterogeneous. This realization has been late in arriving on the airway smooth muscle research scene. Our own studies have shown that mechanical properties are, in quantitative terms, heterogeneously distributed down the airways and that contractility, for example, in extrapulmonary and intrapulmonary airways differs markedly. Another indication of heterogeneity is derived from studies of the biochemical properties of airway smooth muscle cells (ASMCs) in culture. Dramatic changes in phenotype expression were found with days in culture. Just after isolation from the tissue, the cells were of contractile type and contained mature isoforms of contractile, regulatory and cytoskeletal proteins. After the fourth day in culture the cellular phenotype changed such that contractile filaments diminished rapidly with smooth muscle isoforms being replaced by non-muscle isoforms. The cell assumed secretory or synthetic properties and commenced proliferating rapidly. It is possible that similar changes in phenotype could occur in vivo in cells undergoing hypertrophy or hyperplasia. Thus, a thickened medial layer of the type seen in the walls of airways from asthmatic airways is not necessarily one endowed with increased contractility and, in fact, the latter may be subnormal. Finally, using the so-called motility assay, we studied the velocity of translation of actin filaments by myosin molecules obtained from antigen-sensitized and control airway smooth muscle. We found no change in maximum velocity of actin translation. This was under conditions where the myosin light chain (MLC) was fully phosphorylated. However, in these tissues we found heterogeneity in myosin light chain kinase (MLCK) content which, we inferred, accounted for the difference in shortening velocity between control and sensitized muscle strips in vitro.     

Behavioral evaluation of the unilateral lesion model in rats using 6-hydroxydopamine. Correlation between the rotations induced by D-amphetamine, apomorphine and the manual dexterity test

INTRODUCTION: Evaluation of rotatory activity induced by dopaminergic agonists is the most widely used test of conduct for the measurement of dopaminergic depletion of a unilateral lesion of the striatonigral pathway caused by 6-hydroxydopamine (6-OHDA) in rats, since it is quantitatively related to the extension of the dopaminergic denervation. OBJECTIVE: The objective of this study was to evaluate, from different angles, the changes in conduct seen in the model of unilateral lesion with 6-OHDA and to establish correlation with the rotation induced by D-amphetamine and by apomorphine and the ladder test. MATERIAL AND METHODS: Male Wistar rats were used. Lesions were produced in the SNpc by stereotactic injection of 6-OHDA into the right hemisphere and the effectiveness of the lesions was studied using the rotary conduct induced by D-amphetamine and apomorphine. The motor ability of the front legs was measured by the ladder test, carried out under standard and forced conditions. RESULTS: All the animals with lesions had difficulty in reaching food with both legs, although the most pronounced deficit was in the leg contralateral to the lesion. The ladder test correlated better with rotatory activity induced by apomorphine than by D-amphetamine. CONCLUSION: The animals with most dopamine loss showed most deficient use of their front legs.     

Increase in the annual energy production due to a retrofit of vortex generators on blades

The aim of the current work was to analyze the effect of retrofitting vortex generators (VGs) on the blades of a constant RPM, pitch‐regulated, megawatt‐sized turbine suffering from surface roughness. Engineering modelling and experimental work were utilized, indicating that the degradation of energy production may be mitigated by the VGs. The modelling results indicated that the optimal configuration of VGs to maximize the annual energy production (AEP) depends on the degree of severity of surface roughness. Depending on blade surface condition and turbine characteristics, installation of VGs on an incorrect blade span or installation of too large VGs too far out on the blade may cause loss in the AEP. Therefore, engineering modelling is necessary before VGs may be retrofitted on a specific turbine. The modelling results indicated that the worse blade surface, the more gain may be obtained from the VGs. The work included a full‐scale experimental validation of the present engineering model, lasting 27 months and comprising six turbines where VGs were mounted on three, each with a neighboring turbine as a reference. The turbines were analyzed in pairs, and the influence of the VGs was judged upon the relative difference in energy production before and after the installation. The reason was to limit measurement uncertainty. The results showed that all three turbines increased their energy production after the installation. Results from the three pairs showed an average increase in the energy production of 3.3%, being satisfactorily close to the average 2.8% predicted by the present engineering tool.     

Kinetic limitations in the Mg-Si-H system

Magnesium silicide (Mg₂Si) has attracted interest as a hydrogen storage material due to favorable thermodynamics (ΔH_desorption = 36 kJ/mol H₂) for room temperature operation. To date, direct hydriding of Mg₂Si under hydrogen gas to form MgH₂ and Si has only been attempted at low pressure and has been hindered by poor kinetics of absorption. In this paper we study the dehydrogenation reaction with in-situ neutron powder diffraction and present results of our attempts to hydrogenate Mg₂Si under both hydrogen and deuterium gas up to temperatures of 350 °C and pressures of 1850 bar. Even under these extreme absorption conditions Mg₂Si does not absorb any measureable quantity of hydrogen or deuterium.