Differential regulation of local mRNA dynamics and translation following long-term potentiation and depression

Decades of work have demonstrated that messenger RNAs (mRNAs) are localized and translated within neuronal dendrites and axons to provide proteins for remodeling and maintaining growth cones or synapses. It remains unknown, however, whether specific forms of plasticity differentially regulate the dynamics and translation of individual mRNA species. To address this, we targeted three individual synaptically localized mRNAs, CamkIIa, β-actin, Psd95, and used molecular beacons to track endogenous mRNA movements. We used reporters and CRISPR/Cas9 gene editing to track mRNA translation in cultured neurons. We found alterations in mRNA dynamic properties occurred during two forms of synaptic plasticity, long-term potentiation (cLTP) and depression (mGluR-LTD). Changes in mRNA dynamics following either form of plasticity resulted in an enrichment of mRNA in the vicinity of dendritic spines. Both the reporters and tagging of endogenous proteins revealed the transcript-specific stimulation of protein synthesis following cLTP or mGluR-LTD. As such, the plasticity-induced enrichment of mRNA near synapses could be uncoupled from its translational status. The enrichment of mRNA in the proximity of spines allows for localized signaling pathways to decode plasticity milieus and stimulate a specific translational profile, resulting in a customized remodeling of the synaptic proteome

The median nerve in the carpal tunnel

A study of the variations of the course and branching pattern of the median nerve within the carpal tunnel were carried out on 60 wrists from 30 fresh cadavers autopsied in the Department of Forensic Medicine of Jagiellonian University Medical College. The results were compared with the literature. The study confirmed that the extraligamentous type of motor branch variation is most common. The transligamentous course of the nerve is of special importance: it is usually accompanied by hypertrophic muscle, and the nerve hidden within this muscle can easily be cut during transection of the retinaculum. The results proved the necessity of approaching the median nerve from the ulnar side when opening the carpal tunnel. (Folia Morphol 2011; 70, 1: 41-46

An Obstruction to Quantization of the Sphere

In the standard example of strict deformation quantization of the symplectic sphere $S^2$, the set of allowed values of the quantization parameter $\hbar$ is not connected; indeed, it is almost discrete. Li recently constructed a class of examples (including $S^2$) in which $\hbar$ can take any value in an interval, but these examples are badly behaved. Here, I identify a natural additional axiom for strict deformation quantization and prove that it implies that the parameter set for quantizing $S^2$ is never connected.Comment: 23 page. v2: changed sign conventio

Logical independence and quantum randomness

We propose a link between logical independence and quantum physics. We demonstrate that quantum systems in the eigenstates of Pauli group operators are capable of encoding mathematical axioms and show that Pauli group quantum measurements are capable of revealing whether or not a given proposition is logically dependent on the axiomatic system. Whenever a mathematical proposition is logically independent of the axioms encoded in the measured state, the measurement associated with the proposition gives random outcomes. This allows for an experimental test of logical independence. Conversely, it also allows for an explanation of the probabilities of random outcomes observed in Pauli group measurements from logical independence without invoking quantum theory. The axiomatic systems we study can be completed and are therefore not subject to Goedel's incompleteness theorem.Comment: 9 pages, 4 figures, published version plus additional experimental appendi

Sublingual allergen immunotherapy with a liquid birch pollen product in patients with seasonal allergic rhinoconjunctivitis with or without asthma

Background: Sublingual allergen immunotherapy (SLIT) has been demonstrated to be both clinically efficacious and safe. However, in line with the current regulatory guidance from the European Medicines Agency, allergen immunotherapy (AIT) products must demonstrate their efficacy and safety in pivotal phase III trials for registration. Objective: We sought to investigate the efficacy and safety of sublingual high-dose liquid birch pollen extract (40,000 allergy units native [AUN]/mL) in adults with birch pollen allergy. Methods: A randomized, double-blind, placebo-controlled, parallel-group multicenter trial was conducted in 406 adult patients with moderate-to-severe birch pollen-induced allergic rhinoconjunctivitis with or without mild-to-moderate controlled asthma. Treatment was started 3 to 6 months before the birch pollen season and continued during the season in 40 clinical study centers in 5 European countries. For primary end point assessment, the recommended combined symptom and medication score of the European Academy of Allergy and Clinical Immunology was used. Secondary end points included quality-of-life assessments, immunologic parameters, and safety. Results: Primary efficacy results demonstrated a significant (P < .0001) and clinically relevant (32%) reduction in the combined symptom and medication score compared with placebo after 3 to 6 months of SLIT. Significantly better rhinoconjunctivitis quality-of-life scores (P < .0001) and the patient's own overall assessment of his or her health status, including the visual analog scale score (Euro Quality of Life Visual Analogue Scale; P = .0025), were also demonstrated. In total, a good safety profile of SLIT was observed. Conclusion: This study confirmed both the clinical efficacy and safety of a sublingual liquid birch pollen extract in adults with birch pollen allergy in a pivotal phase III trial (EudraCT: 2013-005550-30; ClinicalTrials. gov: NCT02231307)

Regular black holes in an asymptotically de Sitter universe

A regular solution of the system of coupled equations of the nonlinear electrodynamics and gravity describing static and spherically-symmetric black holes in an asymptotically de Sitter universe is constructed and analyzed. Special emphasis is put on the degenerate configurations (when at least two horizons coincide) and their near horizon geometry. It is explicitly demonstrated that approximating the metric potentials in the region between the horizons by simple functions and making use of a limiting procedure one obtains the solutions constructed from maximally symmetric subspaces with different absolute values of radii. Topologically they are $AdS_{2}\times S^{2}$ for the cold black hole, $dS_{2}\times S^{2}$ when the event and cosmological horizon coincide, and the Pleba\'nski- Hacyan solution for the ultraextremal black hole. A physically interesting solution describing the lukewarm black holes is briefly analyze

Convergence and multiplicities for the Lempert function

Given a domain $\Omega \subset \mathbb C$, the Lempert function is a functional on the space Hol (\D,\Omega) of analytic disks with values in $\Omega$, depending on a set of poles in $\Omega$. We generalize its definition to the case where poles have multiplicities given by local indicators (in the sense of Rashkovskii's work) to obtain a function which still dominates the corresponding Green function, behaves relatively well under limits, and is monotonic with respect to the indicators. In particular, this is an improvement over the previous generalization used by the same authors to find an example of a set of poles in the bidisk so that the (usual) Green and Lempert functions differ.Comment: 24 pages; many typos corrected thanks to the referee of Arkiv for Matemati

Opinion Formation in Laggard Societies

We introduce a statistical physics model for opinion dynamics on random networks where agents adopt the opinion held by the majority of their direct neighbors only if the fraction of these neighbors exceeds a certain threshold, p_u. We find a transition from total final consensus to a mixed phase where opinions coexist amongst the agents. The relevant parameters are the relative sizes in the initial opinion distribution within the population and the connectivity of the underlying network. As the order parameter we define the asymptotic state of opinions. In the phase diagram we find regions of total consensus and a mixed phase. As the 'laggard parameter' p_u increases the regions of consensus shrink. In addition we introduce rewiring of the underlying network during the opinion formation process and discuss the resulting consequences in the phase diagram.Comment: 5 pages, eps fig

Schumpeterian economic dynamics as a quantifiable minimum model of evolution

We propose a simple quantitative model of Schumpeterian economic dynamics. New goods and services are endogenously produced through combinations of existing goods. As soon as new goods enter the market they may compete against already existing goods, in other words new products can have destructive effects on existing goods. As a result of this competition mechanism existing goods may be driven out from the market - often causing cascades of secondary defects (Schumpeterian gales of destruction). The model leads to a generic dynamics characterized by phases of relative economic stability followed by phases of massive restructuring of markets - which could be interpreted as Schumpeterian business `cycles'. Model timeseries of product diversity and productivity reproduce several stylized facts of economics timeseries on long timescales such as GDP or business failures, including non-Gaussian fat tailed distributions, volatility clustering etc. The model is phrased in an open, non-equilibrium setup which can be understood as a self organized critical system. Its diversity dynamics can be understood by the time-varying topology of the active production networks.Comment: 21 pages, 11 figure