Cardiac Contractility: How Calcium Activates the Myofilaments

2+   concentrations tropomyosin is located at the edge of the thin filament, thereby interfering with the formation of strong actin-myosin linkages (blocked state). An increase in Ca²⁺ activity causes an azimuthal shift of tropomyosin around the filament (by about 30°), thereby increasing the probability of low-force crossbridge interaction, a process which by cooperative effects induces further tropomyosin movement (by an additional 10°) which results in the open state of the filament characterized by forceful crossbridge interaction. (This mechanism may be analogous to that in ligand-gated ion channels, where ligand binding increases the open probability of the pore.) The extent of activation then depends on the free Ca²⁺ concentration and on the calcium sensitivity of the thin filament that may be affected by protein phosphorylation, crossbridge attachment, the troponin isoform composition of the filament, and novel calcium-sensitizing drugs that act on the contractile or regulatory proteins and thus increase the force of the heart.     

Latest precambrian (Cadomian) zircon ages, Nd isotopic systematics and P-T evolution of granitoid orthogneisses of the Erzgebirge, Saxony and Czech Republic

Single zircons from two orthogneiss complexes, the Grey Gneiss and Red Gneiss, the lowermost tectonic units in the Erzgebirge, were dated. The grey Freiberg Gneiss is of igneous origin and has a ²⁰⁷Pb/²⁰⁶Pb emplacement age of 550±7 Ma. A quartz monzonite from Lauenstein contains idiomorphic zircons with a mean ²⁰⁷Pb/²⁰⁶Pb age of 555±7 Ma as well as xenocrysts ranging in age between 850 and 1910 Ma. Red gneisses from the central Erzgebirge contain complex zircon populations, including numerous xenocrysts up to 2464 Ma in age. The youngest, idiomorphic, zircons in all samples yielded uniform ²⁰⁷Pb/²⁰⁶Pb ages between 550±9 and 554±10 Ma. Nd isotopic data support the interpretation of crustal anatexis for the origin of both units. _Nd(t) values for the grey gneisses are –7.5 and –6.0 respectively, (mean crustal residence ages of 1.7–1.8 Ga). The red gneisses have a wider range in _Nd(t) values from –7.7 to –2.8 (T _DM ages of 1.4–1.8 Ga). The zircon ages document a distinct late Proterozoic phase of granitoid magmatism, similar in age to granitoids in the Lusatian block farther north-east. However, Palaeozoic deformation as well as medium pressure metamorphism ( 8 kbar/600–650° C) are identical in both gneiss units and distinguish these rocks from the Lusatian granitoids. The grey and red gneisses were overthrust by units with abundant high-pressure relicts and a contrasting P-T evolution. Zircon xenocryst and Nd model ages in the range 1000–1700 Ma are similar to those in granitoid rocks of Lusatia and the West-Sudetes, and document a pre-Cadomian basement in parts of east-central Europe that, chronologically, has similarities with the Sveconorwegian domain in the Baltic Shield.     

Use of the chemical cleavage of mismatch method for prenatal deficiency diagnosis of alpha-1-antitrypsin

The most common mutation in alpha-1-antitrypsin deficiency, conversion of a G to an A at base 9989 (PI-Z), was detected with the chemical cleavage of mismatch method, demonstrating the power of the method for prenatal diagnosis. Exon V of the gene was amplified using the polymerase chain reaction and heteroduplexes were formed to test for the presence of the mutation. The predicted C mismatch was readily detectable with hydroxylamine, and by making the probe from the chorionic villus sample it was possible to determine that the fetus was heterozygous, not homozygous, for the mutation.