Exosomes are small membrane vesicles that are secreted from a variety of cell types into various body fluids including the blood and urine. These vesicles are thought to play a role in cell–cell ...interactions. CD24 is a small but extensively glycosylated protein linked to the cell surface by means of a glycosyl-phosphatidylinositol anchor. In this study we found that CD24 is present in membrane vesicles characterized as exosomes that were isolated from the urine of normal individuals. CD24 was expressed by both tubule cells and podocytes and treatment of the latter with a cholesterol-extracting agent, but not with a calcium ionophore, caused the release of CD24-containing exosomes. Using CD24 as a marker, we found exosomes in the urine of newborn infants and in the amniotic fluid of pregnant women with similar findings made in mice. Interestingly, studies with CD24 knockout mice showed that the exosomes are released from the fetus but not from the mother; however, exosome release was similar from both the knockout and the wild-type mice. This indicates that CD24 is not essential for exosome formation or release but may be a convenient exosome marker. Our studies suggest that exosomal secretion from the embryonic kidney could play a biological role at the fetal–maternal interphase.
Adult hippocampal neurogenesis is a remarkable form of brain plasticity through which new neurons are generated throughout life. Despite its important roles in cognition and emotion and its ...modulation in various preclinical disease models, the functional importance of adult hippocampal neurogenesis in human health has not been revealed because of a lack of tools for monitoring adult neurogenesis in vivo. Therefore, we performed an unbiased proteomics screen to identify novel proteins expressed during neuronal differentiation using a human neural stem cell model, and we identified the proteoglycan Glypican-2 (Gpc2) as a putative secreted marker of immature neurons. Exogenous Gpc2 binds to FGF2 and inhibits FGF2-induced neural progenitor cell proliferation. Gpc2 is enriched in neurogenic regions of the adult brain. Its expression is increased by physiological stimuli that increase hippocampal neurogenesis and decreased in transgenic models in which neurogenesis is selectively ablated. Changes in neurogenesis also result in changes in Gpc2 protein level in cerebrospinal fluid (CSF). Gpc2 is detectable in adult human CSF, and first pilot experiments with a longitudinal cohort indicate a decrease over time. Thus, Gpc2 may serve as a potential marker to monitor adult neurogenesis in both animal and human physiology and disease, warranting future studies.
Photoproduction of π0π0 and π0π± pairs from nuclei has been measured over a wide mass range (2H, 7Li, 12C, 40Ca, and natPb) for photon energies from threshold to 600 MeV. The experiments were ...performed at the MAMI accelerator in Mainz, using the Glasgow photon tagging spectrometer and a 4π electromagnetic calorimeter consisting of the Crystal Ball and TAPS detectors. A shift of the pion–pion invariant-mass spectra for heavy nuclei to small invariant masses has been observed for π0 pairs but also for the mixed-charge pairs. The precise results allow for the first time a model-independent analysis of the influence of pion final-state interactions. The corresponding effects are found to be large and must be carefully considered in the search for possible in-medium modifications of the σ-meson. Results from a transport model calculation reproduce the shape of the invariant-mass distributions for the mixed-charge pairs better than for the neutral pairs, but also for the latter differences between model results and experiment are not large, leaving not much room for σ-in-medium modification.
Magnetic drug targeting (MDT) is an effective alternative for common drug applications, which reduces the systemic drug load and maximizes the effect of, eg, chemotherapeutics at the site of ...interest. After the conjugation of a magnetic carrier to a chemotherapeutic agent, the intra-arterial injection into a tumor-afferent artery in the presence of an external magnetic field ensures the accumulation of the drug within the tumor tissue.
In this study, we used superparamagnetic iron oxide nanoparticles (SPIONs) coated with lauric acid and human serum albumin as carriers for paclitaxel (SPION
). To investigate whether this particle system is suitable for a potential treatment of cancer, we investigated its physicochemical properties by dynamic light scattering, ζ potential measurements, isoelectric point titration, infrared spectroscopy, drug release quantification, and magnetic susceptibility measurements. The cytotoxic effects were evaluated using extensive toxicological methods using flow cytometry, IncuCyte
live-cell imaging, and growth experiments on different human breast cancer cell lines in two- and three-dimensional cell cultures.
The data showed that next to their high magnetization capability, SPION
have similar cytostatic effects on human breast cancer cells as pure paclitaxel, suggesting their usage for future MDT-based cancer therapy.
The photoproduction of η′-mesons off different nuclei has been measured with the CBELSA/TAPS detector system for incident photon energies between 1500–2200 MeV. The transparency ratio has been ...deduced and compared to theoretical calculations describing the propagation of η′-mesons in nuclei. The comparison indicates a width of the η′-meson of the order of Γ=15–25 MeV at ρ=ρ0 for an average momentum pη′=1050 MeV/c, at which the η′-meson is produced in the nuclear rest frame. The inelastic η′N cross section is estimated to be 3–10 mb. Parameterizing the photoproduction cross section of η′-mesons by σ(A)=σ0Aα, a value of α=0.84±0.03 has been deduced.
The differential cross sections and unpolarized spin-density matrix elements for the reaction γp→pω were measured using the CBELSA/TAPS experiment for initial photon energies ranging from the ...reaction threshold to 2.5 GeV. These observables were measured from the radiative decay of the ω meson, ω→π0γ. The cross sections cover the full angular range and show the full extent of the t-channel forward rise. The overall shape of the angular distributions in the differential cross sections and unpolarized spin-density matrix elements are in fair agreement with previous data. In addition, for the first time, a beam of linearly-polarized tagged photons in the energy range from 1150 MeV to 1650 MeV was used to extract polarized spin-density matrix elements.
These data were included in the Bonn–Gatchina partial wave analysis (PWA). The dominant contribution to ω photoproduction near threshold was found to be the 3/2+ partial wave, which is primarily due to the sub-threshold N(1720)3/2+ resonance. At higher energies, pomeron-exchange was found to dominate whereas π-exchange remained small. These t-channel contributions as well as further contributions from nucleon resonances were necessary to describe the entire dataset: the 1/2−, 3/2−, and 5/2+ partial waves were also found to contribute significantly.
.
Precise data for quasi-free photoproduction of
η
-mesons off the deuteron have been measured at the Bonn ELSA accelerator with the combined Crystal Barrel/TAPS detector for incident photon energies ...up to 2.5GeV. The
η
-mesons have been detected in coincidence with recoil protons and neutrons. Possible nuclear effects like Fermi motion and re-scattering can be studied via a comparison of the quasi-free reaction off the bound proton to
η
-production off the free proton. No significant effects beyond the folding of the free cross-section with the momentum distribution of the bound protons have been found. These Fermi motion effects can be removed by an analysis using the invariant mass of the
η
-nucleon pairs reconstructed from the final-state four-momenta of the particles. The total cross-section for quasi-free
η
-photoproduction off the neutron reveals even without correction for Fermi motion a pronounced bump-like structure around 1GeV of incident photon energy, which is not observed for the proton. This structure is even narrower in the invariant-mass spectrum of the
η
-neutron pairs. Position and width of the peak in the invariant-mass spectrum are
W
≈ 1665 MeV and FWHM
Γ
≈ 25 MeV. The data are compared to the results of different models.