Subcellular organization of UBE3A in human cerebral cortex.

BackgroundLoss of UBE3A causes Angelman syndrome, whereas excess UBE3A activity appears to increase the risk for autism. Despite this powerful association with neurodevelopmental disorders, there is still much to be learned about UBE3A, including its cellular and subcellular organization in the human brain. The issue is important, since UBE3A's localization is integral to its function.MethodsWe used light and electron microscopic immunohistochemistry to study the cellular and subcellular distribution of UBE3A in the adult human cerebral cortex. Experiments were performed on multiple tissue sources, but our results focused on optimally preserved material, using surgically resected human temporal cortex of high ultrastructural quality from nine individuals.ResultsWe demonstrate that UBE3A is expressed in both glutamatergic and GABAergic neurons, and to a lesser extent in glial cells. We find that UBE3A in neurons has a non-uniform subcellular distribution. In somata, UBE3A preferentially concentrates in euchromatin-rich domains within the nucleus. Electron microscopy reveals that labeling concentrates in the head and neck of dendritic spines and is excluded from the PSD. Strongest labeling within the neuropil was found in axon terminals.ConclusionsBy highlighting the subcellular compartments in which UBE3A is likely to function in the human neocortex, our data provide insight into the diverse functional capacities of this E3 ligase. These anatomical data may help to elucidate the role of UBE3A in Angelman syndrome and autism spectrum disorder

Unitary Limit of Two-Nucleon Interactions in Strong Magnetic Fields

Two-nucleon systems are shown to exhibit large scattering lengths in strong magnetic fields at unphysical quark masses, and the trends toward the physical values indicate that such features may exist in nature. Lattice QCD calculations of the energies of one and two nucleons systems are performed at pion masses of $m_\pi\sim 450$ and 806 MeV in uniform, time-independent magnetic fields of strength {\bf B}| \sim 10^{19}$-$10^{20}$ Gauss to determine the response of these hadronic systems to large magnetic fields. Fields of this strength may exist inside magnetars and in peripheral relativistic heavy ion collisions, and the unitary behavior at large scattering lengths may have important consequences for these systems.Comment: Accepted journal versio

The Magnetic Structure of Light Nuclei from Lattice QCD

Lattice QCD with background magnetic fields is used to calculate the magnetic moments and magnetic polarizabilities of the nucleons and of light nuclei with $A\le4$, along with the cross-section for the $M1$ transition $np\rightarrow d\gamma$, at the flavor SU(3)-symmetric point where the pion mass is $m_\pi\sim 806$ MeV. These magnetic properties are extracted from nucleon and nuclear energies in six uniform magnetic fields of varying strengths. The magnetic moments are presented in a recent Letter. For the charged states, the extraction of the polarizability requires careful treatment of Landau levels, which enter non-trivially in the method that is employed. The nucleon polarizabilities are found to be of similar magnitude to their physical values, with $\beta_p=5.22(+0.66/-0.45)(0.23) \times 10^{-4}$ fm$^3$ and $\beta_n=1.253(+0.056/-0.067)(0.055) \times 10^{-4}$ fm$^3$, exhibiting a significant isovector component. The dineutron is bound at these heavy quark masses and its magnetic polarizability, $\beta_{nn}=1.872(+0.121/-0.113)(0.082) \times 10^{-4}$ fm$^3$ differs significantly from twice that of the neutron. A linear combination of deuteron scalar and tensor polarizabilities is determined by the energies of the $j_z=\pm 1$ deuteron states, and is found to be $\beta_{d,\pm 1}=4.4(+1.6/-1.5)(0.2) \times 10^{-4}$ fm$^3$. The magnetic polarizabilities of the three-nucleon and four-nucleon systems are found to be positive and similar in size to those of the proton, $\beta_{^{3}\rm He}=5.4(+2.2/-2.1)(0.2) \times 10^{-4}$ fm$^3$, $\beta_{^{3}\rm H}=2.6(1.7)(0.1) \times 10^{-4}$ fm$^3$, $\beta_{^{4}\rm He}=3.4(+2.0/-1.9)(0.2) \times 10^{-4}$ fm$^3$. Mixing between the $j_z=0$ deuteron state and the spin-singlet $np$ state induced by the background magnetic field is used to extract the short-distance two-nucleon counterterm, ${\bar L}_1$, of the pionless effective theory for $NN$ systems (equivalent to the meson-exchange current contribution in nuclear potential models), that dictates the cross-section for the $np\to d\gamma$ process near threshold. Combined with previous determinations of NN scattering parameters, this enables an ab initio determination of the threshold cross-section at these unphysical masses.Comment: 49 pages, 24 figure

Ab initio calculation of the np→dγnp \to d \gamma radiative capture process

Lattice QCD calculations of two-nucleon systems are used to isolate the short-distance two-body electromagnetic contributions to the radiative capture process $np \to d\gamma$, and the photo-disintegration processes $\gamma^{(\ast)} d \to np$. In nuclear potential models, such contributions are described by phenomenological meson-exchange currents, while in the present work, they are determined directly from the quark and gluon interactions of QCD. Calculations of neutron-proton energy levels in multiple background magnetic fields are performed at two values of the quark masses, corresponding to pion masses of $m_\pi \sim 450$ and 806 MeV, and are combined with pionless nuclear effective field theory to determine these low-energy inelastic processes. Extrapolating to the physical pion mass, a cross section of $\sigma^{lqcd}(np\to d\gamma)=332.4({\tiny \begin{array}{l}+5.4 \\ - 4.7\end{array}})\ mb$ is obtained at an incident neutron speed of $v=2,200\ m/s$, consistent with the experimental value of$\sigma^{expt}(np \to d\gamma) = 334.2(0.5)\ mb$

Single-cell epigenomic variability reveals functional cancer heterogeneity.

BackgroundCell-to-cell heterogeneity is a major driver of cancer evolution, progression, and emergence of drug resistance. Epigenomic variation at the single-cell level can rapidly create cancer heterogeneity but is difficult to detect and assess functionally.ResultsWe develop a strategy to bridge the gap between measurement and function in single-cell epigenomics. Using single-cell chromatin accessibility and RNA-seq data in K562 leukemic cells, we identify the cell surface marker CD24 as co-varying with chromatin accessibility changes linked to GATA transcription factors in single cells. Fluorescence-activated cell sorting of CD24 high versus low cells prospectively isolated GATA1 and GATA2 high versus low cells. GATA high versus low cells express differential gene regulatory networks, differential sensitivity to the drug imatinib mesylate, and differential self-renewal capacity. Lineage tracing experiments show that GATA/CD24hi cells have the capability to rapidly reconstitute the heterogeneity within the entire starting population, suggesting that GATA expression levels drive a phenotypically relevant source of epigenomic plasticity.ConclusionSingle-cell chromatin accessibility can guide prospective characterization of cancer heterogeneity. Epigenomic subpopulations in cancer impact drug sensitivity and the clonal dynamics of cancer evolution

Photodegradation and Photoprotection of Wood Surfaces

Photodegradation of southern yellow pine and its protection have been studied. Scanning electron micrographs showed that most of the cell walls on exposed transverse surfaces were separated at the middle lamella region after only 500 h of ultraviolet light irradiation. Fibers at the surface were degraded severely after 1,000 h of irradiation. Half-bordered pits and bordered pits on exposed radial surfaces were severely damaged by ultraviolet light. Enlargement of pit apertures as well as loss of pit domes was observed. However, wood irradiated on tangential surfaces was quite resistant to UV irradiation; only microchecks were observed. The photodegradative effect on wood surfaces can be mitigated by treating with aqueous solutions of chromic acid or ferric chloride. Only relatively small amounts of these chemicals are needed for effective protection. Possible chemistry and mechanisms of degradation and protection are discussed