The cellular magnetic response and biocompatibility of biogenic zinc- and cobalt-doped magnetite nanoparticles.

The magnetic moment and anisotropy of magnetite nanoparticles can be optimised by doping with transition metal cations, enabling their properties to be tuned for different biomedical applications. In this study, we assessed the suitability of bacterially synthesized zinc- and cobalt-doped magnetite nanoparticles for biomedical applications. To do this we measured cellular viability and activity in primary human bone marrow-derived mesenchymal stem cells and human osteosarcoma-derived cells. Using AC susceptibility we studied doping induced changes in the magnetic response of the nanoparticles both as stable aqueous suspensions and when associated with cells. Our findings show that the magnetic response of the particles was altered after cellular interaction with a reduction in their mobility. In particular, the strongest AC susceptibility signal measured in vitro was from cells containing high-moment zinc-doped particles, whilst no signal was observed in cells containing the high-anisotropy cobalt-doped particles. For both particle types we found that the moderate dopant levels required for optimum magnetic properties did not alter their cytotoxicity or affect osteogenic differentiation of the stem cells. Thus, despite the known cytotoxicity of cobalt and zinc ions, these results suggest that iron oxide nanoparticles can be doped to sufficiently tailor their magnetic properties without compromising cellular biocompatibility

The Collins-Roscoe mechanism and D-spaces

We prove that if a space X is well ordered $(\alpha A)$, or linearly semi-stratifiable, or elastic then X is a D-space

A LRRK2-Dependent EndophilinA Phosphoswitch Is Critical for Macroautophagy at Presynaptic Terminals.

Synapses are often far from the soma and independently cope with proteopathic stress induced by intense neuronal activity. However, how presynaptic compartments turn over proteins is poorly understood. We show that the synapse-enriched protein EndophilinA, thus far studied for its role in endocytosis, induces macroautophagy at presynaptic terminals. We find that EndophilinA executes this unexpected function at least partly independent of its role in synaptic vesicle endocytosis. EndophilinA-induced macroautophagy is activated when the kinase LRRK2 phosphorylates the EndophilinA-BAR domain and is blocked in animals where EndophilinA cannot be phosphorylated. EndophilinA-phosphorylation promotes the formation of highly curved membranes, and reconstitution experiments show these curved membranes serve as docking stations for autophagic factors, including Atg3. Functionally, deregulation of the EndophilinA phosphorylation state accelerates activity-induced neurodegeneration. Given that EndophilinA is connected to at least three Parkinson's disease genes (LRRK2, Parkin and Synaptojanin), dysfunction of EndophilinA-dependent synaptic macroautophagy may be common in this disorder

Parity Violation in Proton-Proton Scattering at 221 MeV

TRIUMF experiment 497 has measured the parity violating longitudinal analyzing power, A_z, in pp elastic scattering at 221.3 MeV incident proton energy. This paper includes details of the corrections, some of magnitude comparable to A_z itself, required to arrive at the final result. The largest correction was for the effects of first moments of transverse polarization. The addition of the result, A_z=(0.84 \pm 0.29 (stat.) \pm 0.17 (syst.)) \times 10^{-7}, to the pp parity violation experimental data base greatly improves the experimental constraints on the weak meson-nucleon coupling constants h^{pp}_\rho and h^{pp}_\omega, and has implications for the interpretation of electron parity violation experiments.Comment: 17 pages RevTeX, 14 PostScript figures. Revised version with additions suggested by Phys. Rev.

LincRNA-p21 Activates p21 In cis to Promote Polycomb Target Gene Expression and to Enforce the G1/S Checkpoint

The p53-regulated long noncoding RNA lincRNA-p21 has been proposed to act in trans via several mechanisms ranging from repressing genes in the p53 transcriptional network to regulating mRNA translation and protein stability. To further examine lincRNA-p21 function, we generated a conditional knockout mouse model. We find that lincRNA-p21 predominantly functions in cis to activate expression of its neighboring gene, p21. Mechanistically, we show that lincRNA-p21 acts in concert with hnRNP-K as a coactivator for p53-dependent p21 transcription. Additional phenotypes of lincRNA-p21 deficiency could be attributed to diminished p21 levels, including deregulated expression and altered chromatin state of some Polycomb target genes, a defective G1/S checkpoint, increased proliferation rates, and enhanced reprogramming efficiency. These findings indicate that lincRNA-p21 affects global gene expression and influences the p53 tumor suppressor pathway by acting in cis as a locus-restricted coactivator for p53-mediated p21 expression.National Institutes of Health (U.S.)Howard Hughes Medical InstituteLudwig Center for Molecular OncologyDamon Runyon Cancer Research Foundatio

Parity Violation in Proton-Proton Scattering

Measurements of parity-violating longitudinal analyzing powers (normalized asymmetries) in polarized proton-proton scattering provide a unique window on the interplay between the weak and strong interactions between and within hadrons. Several new proton-proton parity violation experiments are presently either being performed or are being prepared for execution in the near future: at TRIUMF at 221 MeV and 450 MeV and at COSY (Kernforschungsanlage Juelich) at 230 MeV and near 1.3 GeV. These experiments are intended to provide stringent constraints on the set of six effective weak meson-nucleon coupling constants, which characterize the weak interaction between hadrons in the energy domain where meson exchange models provide an appropriate description. The 221 MeV is unique in that it selects a single transition amplitude (3P2-1D2) and consequently constrains the weak meson-nucleon coupling constant h_rho{pp}. The TRIUMF 221 MeV proton-proton parity violation experiment is described in some detail. A preliminary result for the longitudinal analyzing power is Az = (1.1 +/-0.4 +/-0.4) x 10^-7. Further proton-proton parity violation experiments are commented on. The anomaly at 6 GeV/c requires that a new multi-GeV proton-proton parity violation experiment be performed.Comment: 13 Pages LaTeX, 5 PostScript figures, uses espcrc1.sty. Invited talk at QULEN97, International Conference on Quark Lepton Nuclear Physics -- Nonperturbative QCD Hadron Physics & Electroweak Nuclear Processes --, Osaka, Japan May 20--23, 199

Parity Violation in Proton-Proton Scattering at 221 MeV

The parity-violating longitudinal analyzing power, Az, has been measured in pp elastic scattering at an incident proton energy of 221 MeV. The result obtained is Az =(0.84 +/- 0.29 (stat.) +/- 0.17 (syst.)) x 10^{-7}. This experiment is unique in that it selects a single parity violating transition amplitude, 3P2-1D2, and consequently directly constrains the weak meson-nucleon coupling constant h^pp_rho When this result is taken together with the existing pp parity violation data, the weak meson-nucleon coupling constants h^pp_rho and h^pp_omega can, for the first time, both be determined.Comment: 8 pages RevTeX4, 3 PostScript figures. Conclusion revised. New information about weak coupling constants adde

A tall space with a small bottom

We introduce a general method of constructing locally compact scattered spaces from certain families of sets and then, with the help of this method, we prove that if kappa(<kappa) = kappa then there is such a space of height kappa(+) with only kappa many isolated points. This implies that there is a locally compact scattered space of height omega(2) with omega(1) isolated points in ZFC, solving an old problem of the first author