Members of the fatty acid binding protein family are differentiation factors for the mammary gland

Mammary gland development is controlled by systemic hormones and by growth factors that might complement or mediate hormonal action. Peptides that locally signal growth cessation and stimulate differentiation of the developing epithelium have not been described. Here, we report that recombinant and wild-type forms of mammary-derived growth inhibitor (MDGI) and heart-fatty acid binding protein (FABP), which belong to the FABP family, specifically inhibit growth of normal mouse mammary epithelial cells (MEC), while growth of stromal cells is not suppressed. In mammary gland organ culture, inhibition of ductal growth is associated with the appearance of bulbous alveolar end buds and formation of fully developed lobuloalveolar structures. In parallel, MDGI stimulates its own expression and promotes milk protein synthesis. Selective inhibition of endogenous MDGI expression in MEC by antisense phosphorothioate oligonucleotides suppresses appearance of alveolar end buds and lowers the beta-casein level in organ cultures. Furthermore, MDGI suppresses the mitogenic effects of epidermal growth factor, and epidermal growth factor antagonizes the activities of MDGI. Finally, the regulatory properties of MDGI can be fully mimicked by an 11-amino acid sequence, represented in the COOH terminus of MDGI and a subfamily of structurally related FABPs. This peptide does not bind fatty acids. To our knowledge, this is the first report about a growth inhibitor promoting mammary gland differentiation

Formation of nanoscale ferromagnetic MnAs crystallites in low-temperature grown GaAs

3 páginas, 3 figuras, 1 tabla.We report the formation of nanosize ferromagnetic MnAs crystallites imbedded in low-temperature grown GaAs using Mn+ ion implantation and subsequent annealing. The structural and magnetic properties of the crystallites have been characterized by transmission electron microscopy, electron beam induced x-ray fluorescence, and superconducting quantum interference device magnetometry. After an optimized thermal annealing at 750 °C, MnAs crystallites of 50 nm in size are formed. These nanomagnets show room temperature ferromagnetism.This work has been supported by QUEST, an NSF Science and Technology center (Grant No. DMR91.20007). P.J.W. is a postdoctoral fellow of the Deutsche Forschungsgemeinschaft (DFG) J.M.G. is a postdoctoral fellow of the Spanish Ministry of Education and Science.Peer reviewe

Barrier and internal wave contributions to the quantum probability density and flux in light heavy-ion elastic scattering

We investigate the properties of the optical model wave function for light heavy-ion systems where absorption is incomplete, such as $\alpha + ^{40}$Ca and $\alpha + ^{16}$O around 30 MeV incident energy. Strong focusing effects are predicted to occur well inside the nucleus, where the probability density can reach values much higher than that of the incident wave. This focusing is shown to be correlated with the presence at back angles of a strong enhancement in the elastic cross section, the so-called ALAS (anomalous large angle scattering) phenomenon; this is substantiated by calculations of the quantum probability flux and of classical trajectories. To clarify this mechanism, we decompose the scattering wave function and the associated probability flux into their barrier and internal wave contributions within a fully quantal calculation. Finally, a calculation of the divergence of the quantum flux shows that when absorption is incomplete, the focal region gives a sizeable contribution to nonelastic processes.Comment: 16 pages, 15 figures. RevTeX file. To appear in Phys. Rev. C. The figures are only available via anonynous FTP on ftp://umhsp02.umh.ac.be/pub/ftp_pnt/figscat

Prevalence of pemphigus and pemphigoid autoantibodies in the general population

Background: Mucocutaneous blistering is characteristic of autoimmune bullous dermatoses (AIBD). Blisters are caused by autoantibodies directed against structural components of the skin. Hence, detection of specific autoantibodies has become a hallmark for AIBD diagnosis. Studies on prevalence of AIBD autoantibodies in healthy individuals yielded contradictory results. Methods: To clarify this, samples from 7063 blood donors were tested for presence of anti-BP180-NC16A, anti-BP230 and anti-Dsg1/3 IgG by indirect immunofluorescence (IF) microscopy using a biochip. Results: Cumulative prevalence of these autoantibodies was 0.9 % (CI: 0.7-1.1 %), with anti-BP180-NC16A IgG being most prevalent. Validation of IF findings using ELISA confirmed presence of autoantibodies in 7/15 (anti-Dsg1), 6/7 (anti-Dsg3), 35/37 (anti-BP180-NC16A) and 2/3 (anti-BP230) cases. Moreover, in 16 samples, anti-BP180-NC16A autoantibody concentrations exceeded the cut-off for the diagnosis of bullous pemphigoid. Interestingly, these anti-BP180-NC16A autoantibodies from healthy individuals formed immune complexes with recombinant antigen and dose-dependently activated neutrophils in vitro. However, fine-epitope mapping within NC16A showed a different binding pattern of anti-BP180-NC16A autoantibodies from healthy individuals compared to bullous pemphigoid patients, while IgG subclasses were identical. Conclusions: Collectively, we here report a low prevalence of AIBD autoantibodies in a large cohort of healthy individuals. Furthermore, functional analysis shows differences between autoantibodies from healthy donors and AIBD patients

Serological and clinical characterization of anti-dsDNA and anti-PM/Scl double-positive patients

Antibodies to double-stranded desoxyribonucleic acid (dsDNA) and to the polymyositis/scleroderma (PM/Scl) complex are regarded as serological markers for systemic lupus erythematosus (SLE) and PM/Scl overlap syndrome, respectively. In a previous study, serum samples were identified that contained antibodies specific for both dsDNA and PM/Scl. Fourteen of these sera were available for more detailed investigation including the autoantibody profile as determined by several methods including an addressable laser bead assay, Crithidia luciliae indirect immunofluorescence test (CLIFT) and a PM1-Alpha ELISA. Moreover, 300 samples from connective tissue disease patients and 30 PM/Scl positive samples were screened for anti-dsDNA(+)/PM/Scl(+) specimens by CLIFT, dsDNA ELISA, and PM1-Alpha ELISA. We confirmed anti-dsDNA and anti-PM/Scl reactivity in 2/7 samples from the previous study. One sample had also anti-chromatin and anti-SS-A reactivity and the second sample was oligoreactive. In addition, 2/300 (0.7%) unselected samples from connective tissue disease patients were identified with anti-dsDNA and anti-PM/Scl reactivity. In a panel of PM1-Alpha positive samples (n = 30) collected regardless of the diagnosis of the patients, no anti-dsDNA reactivity was found. All anti-dsDNA(+)/anti-PM/Scl(+) patients identified fulfilled sufficient criteria to be classified as definite SLE and also had at least one feature of systemic sclerosis (i.e., sclerodactyly and/or Raynaud's phenomenon). Only 1/4 patients had clinical evidence of dermatomyositis. The combination of anti-dsDNA(+)/anti-PM/Scl(+) in patients suffering from connective tissue disease is less frequently found than previously described when newer assays are used. Clinically, anti-dsDNA(+)/anti-PM/Scl(+) patients may define a small subgroup of SLE patients with additional features of systemic sclerosis