Schwann cells migrate along axons in the absence of GDNF signaling

BACKGROUND: During development neural crest derived Schwann Cell (SC) precursors migrate to nerve trunks and populate nascent nerves. Axonal ensheathment by SC is a prerequisite for normal nerve function and the integrity of myelinated as well as nonmyelinated axons. To provide adequate support functions, SC colonize entire nerves. One important prerequisite for this is their migration into distal axonal regions. RESULTS: Here, we studied the role of Glial cell line derived neurotrophic factor (GDNF), a TGF-beta related growth factor, for SC migration. To this end we used a superior cervical ganglion (SCG) explant-SC migration assay, GDNF null mutant mouse embryos and a chemical inhibitor for GDNF signaling in combination with time-lapse imaging. We found that GDNF signaling is dispensable for SC migration along murine embryonic sympathetic axons. Furthermore, in vivo analyzes revealed that SC migration along the sciatic nerve is also not dependent on GDNF. CONCLUSIONS: In contrast to previous in vitro findings in the sciatic nerve and a SC precursor cell line, our results clearly indicate that GDNF is dispensable for embryonic SC migration. This is demonstrated for the sympathetic nervous system and also for the sciatic nerve in mouse

The instability of Alexander-McTague crystals and its implication for nucleation

We show that the argument of Alexander and McTague, that the bcc crystalline structure is favored in those crystallization processes where the first order character is not too pronounced, is not correct. We find that any solution that satisfies the Alexander-McTague condition is not stable. We investigate the implication of this result for nucleation near the pseudo- spinodal in near-meanfield systems.Comment: 20 pages, 0 figures, submitted to Physical Review

Functional expression of electrogenic sodium bicarbonate cotransporter 1 (NBCe1) in mouse cortical astrocytes is dependent on S255-257 and regulated by mTOR

The electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), is the major bicarbonate transporter expressed in astrocytes. It is highly sensitive for bicarbonate and the main regulator of intracellular, extracellular, and synaptic pH, thereby modulating neuronal excitability. However, despite these essential functions, the molecular mechanisms underlying NBCe1-mediated astrocytic response to extracellular pH changes are mostly unknown. Using primary mouse cortical astrocyte cultures, we investigated the effect of long-term extracellular metabolic alkalosis on regulation of NBCe1 and elucidated the underlying molecular mechanisms by immunoblotting, biotinylation of surface proteins, intracellular H+ recording using the H+ -sensitive dye 2',7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein, and phosphoproteomic analysis. The results showed significant downregulation of NBCe1 activity following metabolic alkalosis without influencing protein abundance or surface expression of NBCe1. During alkalosis, the rate of intracellular H+ changes upon challenging NBCe1 was decreased in wild-type astrocytes, but not in cortical astrocytes from NBCe1-deficient mice. Alkalosis-induced decrease of NBCe1 activity was rescued after activation of mTOR signaling. Moreover, mass spectrometry revealed constitutively phosphorylated S255-257 and mutational analysis uncovered these residues being crucial for NBCe1 transport activity. Our results demonstrate a novel mTOR-regulated mechanism by which NBCe1 functional expression is regulated. Such mechanism likely applies not only for NBCe1 in astrocytes, but in epithelial cells as well

Nucleation in Systems with Elastic Forces

Systems with long-range interactions when quenced into a metastable state near the pseudo-spinodal exhibit nucleation processes that are quite different from the classical nucleation seen near the coexistence curve. In systems with long-range elastic forces the description of the nucleation process can be quite subtle due to the presence of bulk/interface elastic compatibility constraints. We analyze the nucleation process in a simple 2d model with elastic forces and show that the nucleation process generates critical droplets with a different structure than the stable phase. This has implications for nucleation in many crystal-crystal transitions and the structure of the final state

Phase Transitions in a Two-Component Site-Bond Percolation Model

A method to treat a N-component percolation model as effective one component model is presented by introducing a scaled control variable $p_{+}$. In Monte Carlo simulations on $16^{3}$, $32^{3}$, $64^{3}$ and $128^{3}$ simple cubic lattices the percolation threshold in terms of $p_{+}$ is determined for N=2. Phase transitions are reported in two limits for the bond existence probabilities $p_{=}$ and $p_{\neq}$. In the same limits, empirical formulas for the percolation threshold $p_{+}^{c}$ as function of one component-concentration, $f_{b}$, are proposed. In the limit $p_{=} = 0$ a new site percolation threshold, $f_{b}^{c} \simeq 0.145$, is reported.Comment: RevTeX, 5 pages, 5 eps-figure

Superdiffusion in a Model for Diffusion in a Molecularly Crowded Environment

We present a model for diffusion in a molecularly crowded environment. The model consists of random barriers in percolation network. Random walks in the presence of slowly moving barriers show normal diffusion for long times, but anomalous diffusion at intermediate times. The effective exponents for square distance versus time usually are below one at these intermediate times, but can be also larger than one for high barrier concentrations. Thus we observe sub- as well as super-diffusion in a crowded environment.Comment: 8 pages including 4 figure

Mathematical modeling reveals threshold mechanism in CD95-induced apoptosis

Mathematical modeling is required for understanding the complex behavior of large signal transduction networks. Previous attempts to model signal transduction pathways were often limited to small systems or based on qualitative data only. Here, we developed a mathematical modeling framework for understanding the complex signaling behavior of CD95(APO-1/Fas)-mediated apoptosis. Defects in the regulation of apoptosis result in serious diseases such as cancer, autoimmunity, and neurodegeneration. During the last decade many of the molecular mechanisms of apoptosis signaling have been examined and elucidated. A systemic understanding of apoptosis is, however, still missing. To address the complexity of apoptotic signaling we subdivided this system into subsystems of different information qualities. A new approach for sensitivity analysis within the mathematical model was key for the identification of critical system parameters and two essential system properties: modularity and robustness. Our model describes the regulation of apoptosis on a systems level and resolves the important question of a threshold mechanism for the regulation of apoptosis

Promiscuous Feeding Across Multiple Honey Bee Hosts Amplifies the Vectorial Capacity of \u3ci\u3eVarroa destructor\u3c/i\u3e

Varroa destructor is a cosmopolitan pest and leading cause of colony loss of the European honey bee. Historically described as a competent vector of honey bee viruses, this arthropod vector is the cause of a global pandemic of Deformed wing virus, now endemic in honeybee populations in all Varroa-infested regions. Our work shows that viral spread is driven by Varroa actively switching from one adult bee to another as they feed. Assays using fluorescent microspheres were used to indicate the movement of fluids in both directions between host and vector when Varroa feed. Therefore, Varroa could be in either an infectious or naïve state dependent upon the disease status of their host. We tested this and confirmed that the relative risk of a Varroa feeding depended on their previous host’s infectiousness. Varroa exhibit remarkable heterogeneity in their host-switching behavior, with some Varroa infrequently switching while others switch at least daily. As a result, relatively few of the most active Varroa parasitize the majority of bees. This multiple-feeding behavior has analogs in vectorial capacity models of other systems, where promiscuous feeding by individual vectors is a leading driver of vectorial capacity. We propose that the honeybee-Varroa relationship offers a unique opportunity to apply principles of vectorial capacity to a social organism, as virus transmission is both vectored and occurs through multiple host-to-host routes common to a crowded society