Haemangioblast commitment is initiated in the primitive streak of the mouse embryo

Haematopoietic and vascular cells are thought to arise from a common progenitor called the haemangioblast. Support for this concept has been provided by embryonic stem (ES) cell differentiation studies that identified the blast colony-forming cell (BL-CFC), a progenitor with both haematopoietic and vascular potential. Using conditions that support the growth of BL-CFCs, we identify comparable progenitors that can form blast cell colonies (displaying haematopoietic and vascular potential) in gastrulating mouse embryos. Cell mixing and limiting dilution analyses provide evidence that these colonies are clonal, indicating that they develop from a progenitor with haemangioblast potential. Embryo-derived haemangioblasts are first detected at the mid-streak stage of gastrulation and peak in number during the neural plate stage. Analysis of embryos carrying complementary DNA of the green fluorescent protein targeted to the brachyury locus demonstrates that the haemangioblast is a subpopulation of mesoderm that co-expresses brachyury (also known as T) and Flk-1 (also known as Kdr). Detailed mapping studies reveal that haemangioblasts are found at highest frequency in the posterior region of the primitive streak, indicating that initial stages of haematopoietic and vascular commitment occur before blood island development in the yolk sac.     

Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Ibeta

Calcium release from the endoplasmic reticulum controls a number of cellular processes, including proliferation and contraction of smooth muscle and other cells. Calcium release from inositol 1,4,5-trisphosphate (IP3)-sensitive stores is negatively regulated by binding of calmodulin to the IP3 receptor (IP3R) and the NO/cGMP/cGMP kinase I (cGKI) signalling pathway. Activation of cGKI decreases IP3-stimulated elevations in intracellular calcium, induces smooth muscle relaxation and contributes to the antiproliferative and pro-apoptotic effects of NO/cGMP. Here we show that, in microsomal smooth muscle membranes, cGKIbeta phosphorylated the IP3R and cGKIbeta, and a protein of relative molecular mass 125,000 which we now identify as the IP3R-associated cGMP kinase substrate (IRAG). These proteins were co-immunoprecipitated by antibodies directed against cGKI, IP3R or IRAG. IRAG was found in many tissues including aorta, trachea and uterus, and was localized perinuclearly after heterologous expression in COS-7 cells. Bradykinin-stimulated calcium release was not affected by the expression of either IRAG or cGKIbeta, which we tested in the absence and presence of cGMP. However, calcium release was inhibited after co-expression of IRAG and cGKIbeta in the presence of cGMP. These results identify IRAG as an essential NO/cGKI-dependent regulator of IP3-induced calcium release.     

Untersuchungen an Ionenaustauschmodellen zum Verständnis der Physiologie biogener Amine. Austauschgleichgewichte zwischen Natrium und Aminen an schwefelsäure-und karboxylgruppen-tragenden Ionenaustauschern

Summary The influence of an inorganic cation (sodium) was studied upon the distribution of physiologically or pharmacologically important amines on two different acid ion exchangers. When cation and amine are added in equivalent amounts to an exchange system of corresponding capacity, the distribution pattern of the amine shows differences which are characteristic of the active groups (SO₃H, COOH) of the relevant exchanger. Such reactions are thought to be of importance in biological activities of polyelectrolytes.     

Increased thermohaline stratification as a possible cause for an ocean anoxic event in the Cretaceous period

Ocean anoxic events were periods of high carbon burial that led to drawdown of atmospheric carbon dioxide, lowering of bottom-water oxygen concentrations and, in many cases, significant biological extinction. Most ocean anoxic events are thought to be caused by high productivity and export of carbon from surface waters which is then preserved in organic-rich sediments, known as black shales. But the factors that triggered some of these events remain uncertain. Here we present stable isotope data from a mid-Cretaceous ocean anoxic event that occurred 112 Myr ago, and that point to increased thermohaline stratification as the probable cause. Ocean anoxic event 1b is associated with an increase in surface-water temperatures and runoff that led to decreased bottom-water formation and elevated carbon burial in the restricted basins of the western Tethys and North Atlantic. This event is in many ways similar to that which led to the more recent Plio-Pleistocene Mediterranean sapropels, but the greater geographical extent and longer duration (approximately 46 kyr) of ocean anoxic event 1b suggest that processes leading to such ocean anoxic events in the North Atlantic and western Tethys were able to act over a much larger region, and sequester far more carbon, than any of the Quaternary sapropels.     

How many-particle interactions develop after ultrafast excitation of an electron-hole plasma.

Electrostatic coupling between particles is important in many microscopic phenomena found in nature. The interaction between two isolated point charges is described by the bare Coulomb potential, but in many-body systems this interaction is modified as a result of the collective response of the screening cloud surrounding each charge carrier. One such system involves ultrafast interactions between quasi-free electrons in semiconductors-which are central to high-speed and future quantum electronic devices. The femtosecond kinetics of nonequilibrium Coulomb systems has been calculated using static and dynamical screening models that assume the instantaneous formation of interparticle correlations. However, some quantum kinetic theories suggest that a regime of unscreened bare Coulomb collisions might exist on ultrashort timescales. Here we monitor directly the temporal evolution of the charge-charge interactions after ultrafast excitation of an electron-hole plasma in GaAs. We show that the onset of collective behaviour such as Coulomb screening and plasmon scattering exhibits a distinct time delay of the order of the inverse plasma frequency, that is, several 10(-14) seconds.     

A matricellular protein and EGF-like repeat signalling in the social amoebozoan Dictyostelium discoideum

Matricellular proteins interact with the extracellular matrix (ECM) and modulate cellular processes by binding to cell surface receptors and initiating intracellular signal transduction. Their association with the ECM and the ability of some members of this protein family to regulate cell motility have opened up new avenues of research to investigate their functions in normal and diseased cells. In this review, we summarize the research on CyrA, an ECM calmodulin-binding protein in Dictyostelium. CyrA is proteolytically cleaved into smaller EGF-like (EGFL) repeat containing cleavage products during development. The first EGFL repeat of CyrA binds to the cell surface and activates a novel signalling pathway that modulates cell motility in this model organism. The similarity of CyrA to the most well-characterized matricellular proteins in mammals allows it to be designated as the first matricellular protein identified in Dictyostelium.     

Heterozyklische Equileninanaloge

Summary The synthesis of heterocyclic equileninanalogues is described. The new compounds are devoid of any significant estrogenic activity.