F90927: A New Member in the Class of Cardioactive Steroids

F90927 is a newly developed cardioactive drug with a steroid-like structure. It acts directly and agonistically on the cardiac L-type Ca²⁺ channel by shifting its voltage-dependent activation toward more negative potentials. This leads to an increased influx of Ca²⁺ and, therefore, to a stronger contraction; however, no arrhythmias occur. Calcium current stimulation can already be observed at nanomolar concentrations, but higher concentrations of F90927 elevate intracellular Ca²⁺ concentration, causing a reduction of the myocardial compliance and an increased diastolic blood pressure. Vessels also react to F90927 and contract in its presence. Binding of F90927 with the L-type Ca²⁺ channel presumably occurs in the vicinity of the transmembrane domains III and IV of the α₁ subunit. F90927 exhibits no use dependence and interacts with Ca²⁺ channel inhibitors of all three known classes of channel modulators (dihydropyridines, phenylalkylamines, and benzothiazepines), suggesting that it is a member of a new class of Ca²⁺ channel modulators. Due to its adverse effects on blood pressure and vessel contraction, F90927 is not an ideal drug candidate. It has, however, some unique properties, which makes it a promising tool to study the function of the L-type Ca²⁺ channel.     

Map-based isolation of the leaf rust disease resistance gene Lr10 from the hexaploid wheat (Triticum aestivum L.) genome

More than 50 leaf rust resistance (Lr) genes against the fungal pathogen Puccinia triticina have been identified in the wheat gene pool, and a large number of them have been extensively used in breeding. Of the 50 Lr genes, all are known only from their phenotype and/or map position except for Lr21, which was cloned recently. For many years, the problems of molecular work in the large (1.6 x 10(10) bp), highly repetitive (80%), and hexaploid bread wheat (Triticum aestivum L.) genome have hampered map-based cloning. Here, we report the isolation of the Lr gene Lr10 from hexaploid wheat by using a combination of subgenome map-based cloning and haplotype studies in the genus Triticum. Lr10 is a single-copy gene on chromosome 1AS. It encodes a CC-NBS-LRR type of protein with an N-terminal domain, which is under diversifying selection. When overexpressed in transgenic wheat plants, Lr10 confers enhanced resistance to leaf rust. Lr10 has similarities to RPM1 in Arabidopsis thaliana and to resistance gene analogs in rice and barley, but is not closely related to other wheat Lr genes based on Southern analysis. We conclude that map-based cloning of genes of agronomic importance in hexaploid wheat is now feasible, opening perspectives for molecular bread wheat improvement trough transgenic strategies and diagnostic allele detection.     

The Genovese grading scale is not reliable for MR assessment of collagen meniscus implants

Background

The purpose of the study was to evaluate the intra- and inter-observer reliabilities of the Genovese grading on MRI in patients after collagen meniscus substitution.