Formation of the muscular layer of the heart, the myocardium, involves the medial movement of bilateral progenitor fields; driven primarily by shortening of the endoderm during foregut formation. Using a combination of time-lapse imaging, microsurgical perturbations and computational modeling, we show that the speed of the medial-ward movement of the myocardial progenitors is similar, but not identical to that of the adjacent endoderm. Further, the extracellular matrix microenvironment separating the two germ layers also moves with the myocardium, indicating that collective tissue motion and not cell migration drives tubular heart assembly. Importantly, as myocardial cells approach the midline, they perform distinct anterior-directed movements relative to the endoderm. Based on the analysis of microincision experiments and computational models, we propose two characteristic, autonomous morphogenetic activities within the early myocardium: 1) an active contraction of the medial portion of the heart field and 2) curling - the tendency of the unconstrained myocardial tissue to form a spherical surface with a concave ventral side. In the intact embryo, these deformations are constrained by the endoderm and the adjacent mesoderm, nevertheless the corresponding mechanical stresses contribute to the proper positioning of myocardial primordia.
Ribosomal protein (rp)S5 belongs to the family of the highly conserved rp’s that contains rpS7 from prokaryotes and rpS5 from eukaryotes. Alignment of rpS5/rpS7 from metazoans (Homo sapiens), fungi (Saccharomyces cerevisiae) and bacteria (Escherichia coli) shows that the proteins contain a conserved central/C-terminal core region and possess variable N-terminal regions. Yeast rpS5 is 69 amino acids (aa) longer than the E. coli rpS7 protein; and human rpS5 is 48 aa longer than the rpS7, respectively. To investigate the function of the yeast rpS5 and in particular the role of its N-terminal region, we obtained and characterized yeast strains in which the wild-type yeast rpS5 was replaced by its truncated variants, lacking 13, 24, 30 and 46 N-terminal amino acids, respectively. All mutant yeast strains were viable and displayed only moderately reduced growth rates, with the exception of the strain lacking 46 N-terminal amino acids, which had a doubling time of about 3 h. Biochemical analysis of the mutant yeast strains suggests that the N-terminal part of the eukaryotic and, in particular, yeast rpS5 may impact the ability of 40S subunits to function properly in translation and affect the efficiency of initiation, specifically the recruitment of initiation factors eIF3 and eIF2.
Ribosomal protein (rp) S5 belongs to a family of ribosomal proteins that includes bacterial rpS7. rpS5 forms part of the exit (E) site on the 40S ribosomal subunit and is essential for yeast viability. Human rpS5 is 67% identical and 79% similar to Saccharomyces cerevisiae rpS5 but lacks a negatively charged (pI ;3.27) 21 amino acid long N-terminal extension that is present in fungi. Here we report that replacement of yeast rpS5 with its human homolog yielded a viable yeast strain with a 20%-25% decrease in growth rate. This replacement also resulted in a moderate increase in the heavy polyribosomal components in the mutant strain, suggesting either translation elongation or termination defects, and in a reduction in the polyribosomal association of the elongation factors eEF3 and eEF1A. In addition, the mutant strain was characterized by moderate increases in +1 and À1 programmed frameshifting and hyperaccurate recognition of the UAA stop codon. The activities of the cricket paralysis virus (CrPV) IRES and two mammalian cellular IRESs (CAT-1 and SNAT-2) were also increased in the mutant strain. Consistently, the rpS5 replacement led to enhanced direct interaction between the CrPV IRES and the mutant yeast ribosomes. Taken together, these data indicate that rpS5 plays an important role in maintaining the accuracy of translation in eukaryotes and suggest that the negatively charged N-terminal extension of yeast rpS5 might affect the ribosomal recruitment of specific mRNAs.
We investigate nanopillars in which two thin ferromagnetic particles are separated by a nanometer thin nonmagnetic spacer and can be set into stable spin vortex-pair configurations. We find that the previously unexplored limit of strong vortex core-core coupling can dominate the spin dynamics in the system. We observe experimentally and explain analytically and numerically how the 0.2 GHz gyrational resonance modes of the individual vortices are transformed into a 2 GHz collective rotational resonance mode in the configurations where the two cores form a bound pair.
The dispersion relations of collective oscillations of the magnetic moment of magnetic dots arranged in square-planar arrays and having magnetic moments perpendicular to the array plane are calculated. The presence of the external magnetic field perpendicular to the plane of array, as well as the uniaxial anisotropy for single dot are taken into account. The ferromagnetic state with all the magnetic moments parallel, and chessboard antiferromagnetic state are considered. The dispersion relation yields information about the stability of different states of the array. There is a critical magnetic field below which the ferromagnetic state is unstable. The antiferromagnetic state is stable for small enough magnetic fields. The dispersion relation is non-analytic as the value of the wave vector approaches zero. Non-trivial Van Hove anomalies are also found for both ferromagnetic and antiferromagnetic states.
Dipole-dipole interactions in a square planar array of sub-micron magnetic disks (magnetic dots) have been studied theoretically. Under a normal magnetic field the ground-state of the array undergoes many structural transitions between the limiting chessboard antiferromagnetic state at zero field and the ferromagnet at a threshold field. At intermediate fields, numerous ferrimagnetic states having mean magnetic moments between zero and that of the ferromagnetic state are favorable energetically. The structures and energies of a selection of states are calculated and plotted, as are the fields required to optimally reverse the magnetic moment of a single dot within them. Approximate formulae for the dipolar energy and anhysteretic magnetization curve are presented.I.
The 9-aminoacridine (9AA) derivative quinacrine (QC) has a long history of safe human use as an antiprotozoal and antirheumatic agent. QC intercalates into DNA and RNA and can inhibit DNA replication, RNA transcription, and protein synthesis. The extent of QC intercalation into RNA depends on the complexity of its secondary and tertiary structure. Internal ribosome entry sites (IRESs) that are required for initiation of translation of some viral and cellular mRNAs typically have complex structures. Recent work has shown that some intercalating drugs, including QC, are capable of inhibiting hepatitis C virus IRES-mediated translation in a cell-free system. Here, we show that QC suppresses translation directed by the encephalomyocarditis virus (EMCV) and poliovirus IRESs in a cell-free system and in virus-infected HeLa cells. In contrast, IRESs present in the mammalian p53 transcript that are predicted to have less-complex structures were not sensitive to QC. Inhibition of IRES-mediated translation by QC correlated with the affinity of binding between QC and the particular IRES. Expression of viral capsid proteins, replication of viral RNAs, and production of virus were all strongly inhibited by QC (and 9AA). These results suggest that QC and similar intercalating drugs could potentially be used for treatment of viral infections.
The dispersion relations for collective magnon modes for square-planar arrays of vortex-state magnetic dots, having closure magnetic flux are calculated. The array dots have no direct contact between each other, and the sole source of their interaction is the magnetic dipolar interaction.The magnon formalism using Bose operators along with translational symmetry of the lattice, with the knowledge of mode structure for the isolated dot, allows the diagonalization of the system Hamiltonian giving the dispersion relation. Arrays of vortex-state dots show a large variety of collective mode properties, such as positive or negative dispersion for different modes.For their description, not only dipolar interaction of effective magnetic dipoles, but non-dipolar terms common to higher multipole interaction in classical electrodynamics can be important. The dispersion relation is shown to be non-analytic as the value of the wavevector approaches zero for all dipolar active modes of the single dot. For vortex-state dots the interdot interaction is not weak, because, the dynamical part (in contrast to the static magnetization of the vortex state) dot does not contain the small parameter, the ratio of vortex core size to the dot radius. This interaction can lead to qualitative effects like the formation of modes of angular standing waves instead of modes with definite azimuthal number known for the insolated vortex state dot.
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