Neuronal plasticity and neurotrophic factors in drug responses

Neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF) and other members of the neurotrophin family, are central mediators of the activity-dependent plasticity through which environmental experiences, such as sensory information are translated into the structure and function of neuronal networks. Synthesis, release and action of BDNF is regulated by neuronal activity and BDNF in turn leads to trophic effects such as formation, stabilization and potentiation of synapses through its high-affinity TrkB receptors. Several clinically available drugs activate neurotrophin signaling and neuronal plasticity. In particular, antidepressant drugs rapidly activate TrkB signaling and gradually increase BDNF expression, and the behavioral effects of antidepressants are mediated by and dependent on BDNF signaling through TrkB at least in rodents. These findings indicate that antidepressants, widely used drugs, effectively act as TrkB activators. They further imply that neuronal plasticity is a central mechanism in the action of antidepressant drugs. Indeed, it was recently discovered that antidepressants reactivate a state of plasticity in the adult cerebral cortex that closely resembles the enhanced plasticity normally observed during postnatal critical periods. This state of induced plasticity, known as iPlasticity, allows environmental stimuli to beneficially reorganize networks abnormally wired during early life. iPlasticity has been observed in cortical as well as subcortical networks and is induced by several pharmacological and non-pharmacological treatments. iPlasticity is a new pharmacological principle where drug treatment and rehabilitation cooperate; the drug acts permissively to enhance plasticity and rehabilitation provides activity to guide the appropriate wiring of the plastic network. Optimization of iPlastic drug treatment with novel means of rehabilitation may help improve the efficacy of available drug treatments and expand the use of currently existing drugs into new indications.Peer reviewe

Characterization of a Be(p,xn) neutron source for fission yields measurements

We report on measurements performed at The Svedberg Laboratory (TSL) to characterize a proton-neutron converter for independent fission yield studies at the IGISOL-JYFLTRAP facility (Jyv\"askyl\"a, Finland). A 30 MeV proton beam impinged on a 5 mm water-cooled Beryllium target. Two independent experimental techniques have been used to measure the neutron spectrum: a Time of Flight (TOF) system used to estimate the high-energy contribution, and a Bonner Sphere Spectrometer able to provide precise results from thermal energies up to 20 MeV. An overlap between the energy regions covered by the two systems will permit a cross-check of the results from the different techniques. In this paper, the measurement and analysis techniques will be presented together with some preliminary results.Comment: 3 pages, 3 figures, also submitted as proceedings of the International Conference on Nuclear Data for Science and Technology 201

Time-Resolved IR Spectroscopy Reveals a Mechanism with TiO2 as a Reversible Electron Acceptor in a TiO2 - Re Catalyst CO2 Photoreduction System

Attaching the phosphonated molecular catalyst [Re$^{I}$Br(bpy)(CO)₃]⁰ to the wide-band gap semiconductor TiO₂ strongly enhances the rate of visible-light driven reduction of CO₂ to CO in dimethyl formamide (DMF) with triethanolamine (TEOA) as sacrificial electron donor. Herein, we show by transient mid-IR spectroscopy that the mechanism of catalyst photoreduction is initiated by ultrafast electron injection into TiO₂, followed by rapid (ps-ns) and sequential two-electron oxidation of TEOA that is coordinated to the Re center. The injected electrons can be stored in the conduction band (CB) of TiO₂ on a ms-s time scale, and we propose they lead to further reduction of the Re-catalyst and completion of the catalytic cycle. Thus, the excited Re catalyst gives away one electron and would eventually get three electrons back. The function of an electron reservoir would represent a role for TiO₂ in photo-catalytic CO₂ reduction that has previously not been considered. We propose that the increase in photocatalytic activity upon heterogenisation of the catalyst to TiO₂ is due to the slow charge recombination and the high oxidative power of the ReII species after electron injection, as compared to the excited MLCT state of the unbound Re catalyst or when immobilized on ZrO₂, which results in a more efficient reaction with TEOA.Knut and Alice Wallenberg Foundation, Swedish Energy Agency, Swedish Research Council, Austrian Christian Doppler Research Association, OMV Grou

Rotational excitation of the Hoyle state in 12C

12C is synthesised in stars by fusion of three α particles. This process occurs through a resonance in the 12C nucleus, famously known as the Hoyle state. In this state, the 12C nucleus exists as a cluster of α particles. The state is the band-head for a rotational band with the 2+ rotational excitation predicted in the energy region 9 - 11 MeV. This rotational excitation can affect the triple-α process reaction rate by more than an order of magnitude at high temperatures (109 K). Depending on the energy of the resonance, the knowledge of the state can also help determine the structure of the Hoyle state. In the work presented here, the state of interest is populated by beta decay of radioactive 12N ion beam delivered by the IGISOL facility at JYFL, Jyväskylä

Influences on the triple alpha process beyond the Hoyle state

The triple alpha process is studied using indirect methods. The beta decays of 12N and 12B are used to probe the triple alpha continuum of 12C. Different independent breakup channels are identified, consistently showing that the 10 MeV strength is dominated by a 0+ state interfering with the Hoyle state ghost. The 13.14 MeV region on the other hand is dominated by a 2+ state. Present: National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, Michigan MI-48824, USA.</p

Keratins regulate colonic epithelial cell differentiation through the Notch1 signalling pathway

Keratins (K) are intermediate filament proteins important in stress protection and mechanical support of epithelial tissues. K8, K18 and K19 are the main colonic keratins, and K8-knockout (K8(-/-)) mice display a keratin dose-dependent hyperproliferation of colonic crypts and a colitis-phenotype. However, the impact of the loss of K8 on intestinal cell differentiation has so far been unknown. Here we show that K8 regulates Notch1 signalling activity and differentiation in the epithelium of the large intestine. Proximity ligation and immunoprecipitation assays demonstrate that K8 and Notch1 co-localize and interact in cell cultures, and in vivo in the colonic epithelial cells. K8 with its heteropolymeric partner K18 enhance Notch1 protein levels and activity in a dose dependent manner. The levels of the full-length Notch1 receptor (FLN), the Notch1 intracellular domain (NICD) and expression of Notch1 downstream target genes are reduced in the absence of K8, and the K8-dependent loss of Notch1 activity can be rescued with re-expression of K8/K18 in K8-knockout CRISPR/Cas9 Caco-2 cells protein levels. In vivo, K8 deletion with subsequent Notch1 downregulation leads to a shift in differentiation towards a goblet cell and enteroendocrine phenotype from an enterocyte cell fate. Furthermore, the K8(-/-) colonic hyperproliferation results from an increased number of transit amplifying progenitor cells in these mice. K8/K18 thus interact with Notch1 and regulate Notch1 signalling activity during differentiation of the colonic epithelium

IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper

Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen.info:eu-repo/semantics/publishedVersio

First evidence of multiple beta-delayed neutron emission for isotopes with A > 100

The beta-delayed neutron emission probability, P-n, of very neutron-rich nuclei allows us to achieve a better understanding of the nuclear structure above the neutron separation energy, S-n. The emission of neutrons can become the dominant decay process in neutron-rich astrophysical phenomena such as the rapid neutron capture process (r-process). There are around 600 accessible isotopes for which beta-delayed one-neutron emission (beta 1n) is energetically allowed, but the branching ratio has only been determined for about one third of them. beta 1n decays have been experimentally measured up to the mass A similar to 1 5 0, plus a single measurement of Tl-210. Concerning two-neutron emitters (beta 2n), similar to 3 0 0 isotopes are accessible and only 24 have been measured so far up to the mass A = 100. In this contribution, we report recent experiments which allowed the measurement of beta 1n emitters for masses beyond A > 200 and N > 1 2 6 and identified the heaviest beta 2n emitter measured so far, Sb-136.Peer reviewe

Measurement of the heaviest beta-delayed 2-neutron emitter : Sb-136

The beta-delayed neutron emission probability, P-n, of very exotic nuclei is crucial for the understanding of nuclear structure properties of many isotopes and astrophysical processes such as the rapid neutron capture process (r-process). In addition beta-delayed neutrons are important in a nuclear power reactor operated in a prompt sub-critical, delayed critical condition, as they contribute to the decay heat inducing fission reactions after a shut down. The study of neutron-rich isotopes and the measurement of beta-delayed one-neutron emitters (beta 1n) is possible thanks to the Rare Isotope Beam (RIB) facilities, where radioactive beams allow the production of exotic nuclei of interest, which can be studied and analyzed using specific detection systems. This contribution reports two recent measurements of beta-delayed neutron emitters which allowed the determination of half-lives and the neutron branching ratio of isotopes in the mass region above A = 200 and N > 126, and a second experiment which confirmed Sb-136 as the heaviest double neutron emitter (beta 2n) measured so far.The beta-delayed neutron emission probability, P-n, of very exotic nuclei is crucial for the understanding of nuclear structure properties of many isotopes and astrophysical processes such as the rapid neutron capture process (r-process). In addition beta-delayed neutrons are important in a nuclear power reactor operated in a prompt sub-critical, delayed critical condition, as they contribute to the decay heat inducing fission reactions after a shut down. The study of neutron-rich isotopes and the measurement of beta-delayed one-neutron emitters (beta 1n) is possible thanks to the Rare Isotope Beam (RIB) facilities, where radioactive beams allow the production of exotic nuclei of interest, which can be studied and analyzed using specific detection systems. This contribution reports two recent measurements of beta-delayed neutron emitters which allowed the determination of half-lives and the neutron branching ratio of isotopes in the mass region above A = 200 and N > 126, and a second experiment which confirmed Sb-136 as the heaviest double neutron emitter (beta 2n) measured so far.The beta-delayed neutron emission probability, P-n, of very exotic nuclei is crucial for the understanding of nuclear structure properties of many isotopes and astrophysical processes such as the rapid neutron capture process (r-process). In addition beta-delayed neutrons are important in a nuclear power reactor operated in a prompt sub-critical, delayed critical condition, as they contribute to the decay heat inducing fission reactions after a shut down. The study of neutron-rich isotopes and the measurement of beta-delayed one-neutron emitters (beta 1n) is possible thanks to the Rare Isotope Beam (RIB) facilities, where radioactive beams allow the production of exotic nuclei of interest, which can be studied and analyzed using specific detection systems. This contribution reports two recent measurements of beta-delayed neutron emitters which allowed the determination of half-lives and the neutron branching ratio of isotopes in the mass region above A = 200 and N > 126, and a second experiment which confirmed Sb-136 as the heaviest double neutron emitter (beta 2n) measured so far.Peer reviewe

The β-decay approach for studying 12C

6 pags., 3 figs. -- 9th International Conference on Clustering Aspects of Nuclear Structure and Dynamics (CLUSTERS'07) 3–7 September 2007, Stratford upon Avon, UKThe β-decays of the mirror nuclei 12B and 12N both populate states in 12C and they are therefore a precious source of information about this nucleus. Due to the selection rules of β-decay only 0+, 1+ and 2+ states are populated. This allows a very clean study of unbound states just above the 3α-threshold with those spin and parities. This probe has been applied in two experiments using two complementary experimental techniques: in the first the three α-particles emitted after β-decay are measured in coincidence in separate detectors using the ISOL method, while in the second method 12B and 12N are implanted in a detector and the summed energy of the three α-particles is measured directly. Preliminary results from the two approaches are presented. © 2008 IOP Publishing Ltd