Impact of actin filament stabilization on adult hippocampal and olfactory bulb neurogenesis

Rearrangement of the actin cytoskeleton is essential for dynamic cellular processes. Decreased actin turnover and rigidity of cytoskeletal structures have been associated with aging and cell death. Gelsolin is a Ca(2+)-activated actin-severing protein that is widely expressed throughout the adult mammalian brain. Here, we used gelsolin-deficient (Gsn(-/-)) mice as a model system for actin filament stabilization. In Gsn(-/-) mice, emigration of newly generated cells from the subventricular zone into the olfactory bulb was slowed. In vitro, gelsolin deficiency did not affect proliferation or neuronal differentiation of adult neural progenitors cells (NPCs) but resulted in retarded migration. Surprisingly, hippocampal neurogenesis was robustly induced by gelsolin deficiency. The ability of NPCs to intrinsically sense excitatory activity and thereby implement coupling between network activity and neurogenesis has recently been established. Depolarization-induced [Ca(2+)](i) increases and exocytotic neurotransmitter release were enhanced in Gsn(-/-) synaptosomes. Importantly, treatment of Gsn(-/-) synaptosomes with mycotoxin cytochalasin D, which, like gelsolin, produces actin disassembly, decreased enhanced Ca(2+) influx and subsequent exocytotic norepinephrine release to wild-type levels. Similarly, depolarization-induced glutamate release from Gsn(-/-) brain slices was increased. Furthermore, increased hippocampal neurogenesis in Gsn(-/-) mice was associated with a special microenvironment characterized by enhanced density of perfused vessels, increased regional cerebral blood flow, and increased endothelial nitric oxide synthase (NOS-III) expression in hippocampus. Together, reduced filamentous actin turnover in presynaptic terminals causes increased Ca(2+) influx and, subsequently, elevated exocytotic neurotransmitter release acting on neural progenitors. Increased neurogenesis in Gsn(-/-) hippocampus is associated with a special vascular niche for neurogenesis

A Real Space Description of Magnetic Field Induced Melting in the Charge Ordered Manganites: I. The Clean Limit

We study the melting of charge order in the half doped manganites using a model that incorporates double exchange, antiferromagnetic superexchange, and Jahn-Teller coupling between electrons and phonons. We primarily use a real space Monte Carlo technique to study the phase diagram in terms of applied field $(h)$ and temperature $(T)$, exploring the melting of charge order with increasing $h$ and its recovery on decreasing $h$. We observe hysteresis in this response, and discover that the `field melted' high conductance state can be spatially inhomogeneous even without extrinsic disorder. The hysteretic response plays out in the background of field driven equilibrium phase separation. Our results, exploring $h$, $T$, and the electronic parameter space, are backed up by analysis of simpler limiting cases and a Landau framework for the field response. This paper focuses on our results in the `clean' systems, a companion paper studies the effect of cation disorder on the melting phenomena.Comment: 16 pages, pdflatex, 11 png fig

Molecular excitation in the Interstellar Medium: recent advances in collisional, radiative and chemical processes

We review the different excitation processes in the interstellar mediumComment: Accepted in Chem. Re

The 2020 UV emitter roadmap

Solid state UV emitters have many advantages over conventional UV sources. The (Al,In,Ga)N material system is best suited to produce LEDs and laser diodes from 400 nm down to 210 nm—due to its large and tuneable direct band gap, n- and p-doping capability up to the largest bandgap material AlN and a growth and fabrication technology compatible with the current visible InGaN-based LED production. However AlGaN based UV-emitters still suffer from numerous challenges compared to their visible counterparts that become most obvious by consideration of their light output power, operation voltage and long term stability. Most of these challenges are related to the large bandgap of the materials. However, the development since the first realization of UV electroluminescence in the 1970s shows that an improvement in understanding and technology allows the performance of UV emitters to be pushed far beyond the current state. One example is the very recent realization of edge emitting laser diodes emitting in the UVC at 271.8 nm and in the UVB spectral range at 298 nm. This roadmap summarizes the current state of the art for the most important aspects of UV emitters, their challenges and provides an outlook for future developments

Structure and Behavior of Human α-Thrombin upon Ligand Recognition: Thermodynamic and Molecular Dynamics Studies

Thrombin is a serine proteinase that plays a fundamental role in coagulation. In this study, we address the effects of ligand site recognition by alpha-thrombin on conformation and energetics in solution. Active site occupation induces large changes in secondary structure content in thrombin as shown by circular dichroism. Thrombin-D-Phe-Pro-Arg-chloromethyl ketone (PPACK) exhibits enhanced equilibrium and kinetic stability compared to free thrombin, whose difference is rooted in the unfolding step. Small-angle X-ray scattering (SAXS) measurements in solution reveal an overall similarity in the molecular envelope of thrombin and thrombin-PPACK, which differs from the crystal structure of thrombin. Molecular dynamics simulations performed with thrombin lead to different conformations than the one observed in the crystal structure. These data shed light on the diversity of thrombin conformers not previously observed in crystal structures with distinguished catalytic and conformational behaviors, which might have direct implications on novel strategies to design direct thrombin inhibitors

The authority of next-of-kin in explicit and presumed consent systems for deceased organ donation: an analysis of 54 nations

Background. The degree of involvement by the next-of-kin in deceased organ procurement worldwide is unclear. We investigated the next-of-kin’s authority in the procure-ment process in nations with either explicit or presumed consent. Methods. We collected data from 54 nations, 25 with presumed consent and 29 with explicit consent. We char-acterized the authority of the next-of-kin in the decision to donate deceased organs. Specifically, we examined whether the next-of-kin’s consent to procure organs was always required and whether the next-of-kin were able to veto procurement when the deceased had expressed a wish to donate. Results. The next-of-kin are involved in the organ procure-ment process in most nations regardless of the consent principle and whether the wishes of the deceased to be a donor were expressed or unknown. Nineteen of the 25 nations with presumed consent provide a method for individuals to express a wish to be a donor. However, health professionals in only four of these nations responded that they do not override a deceased’s expressed wish because of a family’s objection. Similarly, health profes-sionals in only four of the 29 nations with explicit consent proceed with a deceased’s pre-existing wish to be a donor and do not require next-of-kin’s consent, but caveats still remain for when this is done. Conclusions. The next-of-kin have a considerable influ-ence on the organ procurement process in both presumed and explicit consent nations