Denervated Schwann cells attract macrophages by secretion of leukemia inhibitory factor (LIF) and monocyte chemoattractant protein-1 in a process regulated by interleukin-6 and LIF

Injury to peripheral nerves results in the infiltration of immune cells, which remove axonal- and myelin-derived material. Schwann cells could play a key role in this process by regulating macrophage infiltration. We show here that medium conditioned by primary denervated Schwann cells or the Schwannoma cell line RN22 produces chemotactic activity for macrophages. The presence of blocking antibodies to macrophage chemoattractant protein-1 (MCP-1) or leukemia inhibitory factor (LIF) reduced this activity to similar to35 and 65% of control levels, respectively, and only 15% remained in the presence of both antibodies. The presence of chemotactic LIF in Schwann cell-conditioned medium was confirmed by using cells from lif-/- mice. Although interleukin-6 (IL-6) is not itself a chemotactic factor, we found that medium from il-6-/- nerves showed only 40% of the activity secreted by wild-type nerves. Furthermore, IL-6 rapidly induced LIF mRNA in primary Schwann cells, and LIF rapidly induced MCP-1 mRNA expression. Treatment of RN22 Schwannoma cells with IL-6 or LIF enhanced the secretion of the chemotactic activity of these cells.These observations show that Schwann cells attract macrophages by secreting MCP-1 and LIF. They also provide evidence for an autocrine-signaling cascade involving IL-6, LIF, and MCP-1, which amplifies the Schwann cell-derived chemotactic signals gradually, in agreement with the delayed entry of macrophages to injured nerves

The repair Schwann cell and its function in regenerating nerves.

Nerve injury triggers the conversion of myelin and non-myelin (Remak) Schwann cells to a cell phenotype specialised to promote repair. Distal to damage, these repair Schwann cells provide the necessary signals and spatial cues for the survival of injured neurons, axonal regeneration and target reinnervation. The conversion to repair Schwann cells involves de-differentiation together with alternative differentiation, or activation, a combination that is typical of cell type conversions often referred to as (direct or lineage) reprogramming. Thus, injury-induced Schwann cell reprogramming involves down-regulation of myelin genes combined with activation of set of repair-supportive features, including up-regulation of trophic factors, elevation of cytokines as part of the innate immune response, myelin clearance by activation of myelin autophagy in Schwann cells and macrophage recruitment, and the formation of regeneration tracks, Bungner's bands, for directing axons to their targets. This repair program is controlled transcriptionally by mechanisms involving the transcription factor c-Jun, which is rapidly up-regulated in Schwann cells after injury. In the absence of c-Jun, damage results in the formation of a dysfunctional repair cell, neuronal death and failure of functional recovery. c-Jun, although not required for Schwann cell development, is therefore central to the reprogramming of myelin and non-myelin (Remak) Schwann cells to repair cells after injury. In future, the signalling that specifies this cell requires further analysis so that pharmacological tools that boost and maintain the repair Schwann cell phenotype can be developed. This article is protected by copyright. All rights reserved

TGF beta type II receptor signaling controls Schwann cell death and proliferation in developing nerves

During development, Schwann cell numbers are precisely adjusted to match the number of axons. It is essentially unknown which growth factors or receptors carry out this important control in vivo. Here, we tested whether the type II transforming growth factor (TGF)beta receptor has a role in this process. We generated a conditional knock-out mouse in which the type II TGF beta receptor is specifically ablated only in Schwann cells. Inactivation of the receptor, evident at least from embryonic day 18, resulted in suppressed Schwann cell death in normally developing and injured nerves. Notably, the mutants also showed a strong reduction in Schwann cell proliferation. Consequently, Schwann cell numbers in wild-type and mutant nerves remained similar. Lack of TGF beta signaling did not appear to affect other processes in which TGF beta had been implicated previously, including myelination and response of adult nerves to injury. This is the first in vivo evidence for a growth factor receptor involved in promoting Schwann cell division during development and the first genetic evidence for a receptor that controls normal developmental Schwann cell death

Hydrographic and Acoustic Doppler Current Profiler (ADCP) data from the ONR Eastern Boundary Current Accelerated Research Iniative - June 9-16, 1992

This data report presents hydrographic (CTD) and Acoustic Doppler Current Profiler (ADCP) data from a cruise to the continental slope region near Point Arena, California during 9-16 June 1992. The study area encompassed a region from about 38 deg 0.0' N. to 39 deg 0.0' N. from 20 to 90 km offshore. The sampling grid consisted of five along-shore transects 15 km apart, with five CTD stations 15 km apart in each transect. A total of 28 CTD casts were made. ADCP data were collected throughout the cruise. The data are presented as vertical sections, property distributions on horizontal surfaces, and waterfall plots. Eastern boundary current, CTD Data, Hydrographic data, ADCP Data, Coastal eddiesThis data report presents hydrographic (CTD) and Acoustic Doppler Current Profiler (ADCP) data from a cruise to the continental slope region near Point Arena, California during 9-16 June 1992. The study area encompassed a region from about 38 deg 0.0' N. to 39 deg 0.0' N. from 20 to 90 km offshore. The sampling grid consisted of five along-shore transects 15 km apart, with five CTD stations 15 km apart in each transect. A total of 28 CTD casts were made. ADCP data were collected throughout the cruise. The data are presented as vertical sections, property distributions on horizontal surfaces, and waterfall plots.http://archive.org/details/hydrographicacou59jessApproved for public release; distribution is unlimited

The structural and functional integrity of peripheral nerves depends on the glial-derived signal desert hedgehog

We show that desert hedgehog ( dhh), a signaling molecule expressed by Schwann cells, is essential for the structural and functional integrity of the peripheral nerve. Dhh-null nerves display multiple abnormalities that affect myelinating and nonmyelinating Schwann cells, axons, and vasculature and immune cells. Myelinated fibers of these mice have a significantly increased ( more than two times) number of Schmidt-Lanterman incisures ( SLIs), and connexin 29, a molecular component of SLIs, is strongly upregulated. Crossing dhh-null mice with myelin basic protein ( MBP)-deficient shiverer mice, which also have increased SLI numbers, results in further increased SLIs, suggesting that Dhh and MBP control SLIs by different mechanisms. Unmyelinated fibers are also affected, containing many fewer axons per Schwann cell in transverse profiles, whereas the total number of unmyelinated axons is reduced by approximately one-third. In dhh-null mice, the blood-nerve barrier is permeable and neutrophils and macrophage numbers are elevated, even in uninjured nerves. Dhh-null nerves also lack the largest-diameter myelinated fibers, have elevated numbers of degenerating myelinated axons, and contain regenerating fibers. Transected dhh nerves degenerate faster than wild-type controls. This demonstrates that a single identified glial signal, Dhh, plays a critical role in controlling the integrity of peripheral nervous tissue, in line with its critical role in nerve sheath development ( Parmantier et al., 1999). The complexity of the defects raises a number of important questions about the Dhh-dependent cell-cell signaling network in peripheral nerves

Repair Schwann cell update: Adaptive reprogramming, EMT, and stemness in regenerating nerves.

Schwann cells respond to nerve injury by cellular reprogramming that generates cells specialized for promoting regeneration and repair. These repair cells clear redundant myelin, attract macrophages, support survival of damaged neurons, encourage axonal growth, and guide axons back to their targets. There are interesting parallels between this response and that found in other tissues. At the cellular level, many other tissues also react to injury by cellular reprogramming, generating cells specialized to promote tissue homeostasis and repair. And at the molecular level, a common feature possessed by Schwann cells and many other cells is the injury-induced activation of genes associated with epithelial-mesenchymal transitions and stemness, differentiation states that are linked to cellular plasticity and that help injury-induced tissue remodeling. The number of signaling systems regulating Schwann cell plasticity is rapidly increasing. Importantly, this includes mechanisms that are crucial for the generation of functional repair Schwann cells and nerve regeneration, although they have no or a minor role elsewhere in the Schwann cell lineage. This encourages the view that selective tools can be developed to control these particular cells, amplify their repair supportive functions and prevent their deterioration. In this review, we discuss the emerging similarities between the injury response seen in nerves and in other tissues and survey the transcription factors, epigenetic mechanisms, and signaling cascades that control repair Schwann cells, with emphasis on systems that selectively regulate the Schwann cell injury response.Wellcome Trust, Medical Research Council, European Research Counci

Spectroscopy of the 1S0−3P0^1S_0-{}^3P_0 Clock Transition of 87^{87}Sr in an Optical Lattice

We report on the spectroscopy of the $5s^2 {}^1S_0 (F=9/2) \to 5s5p {}^3P_0 (F=9/2)$ clock transition of ${}^{87}{\rm Sr}$ atoms (natural linewidth of 1 mHz) trapped in a one-dimensional optical lattice. Recoilless transitions with a linewidth of 0.7 kHz as well as the vibrational structure of the lattice potential were observed. By investigating the wavelength dependence of the carrier linewidth, we determined the magic wavelength, where the light shift in the clock transition vanishes, to be $813.5\pm0.9$ nm.Comment: 4 pages, 4 figures, submitted to Phys. Rev. Lett. (09/May/2003

Bringing Salary Transparency to the World: Computing Robust Compensation Insights via LinkedIn Salary

The recently launched LinkedIn Salary product has been designed with the goal of providing compensation insights to the world's professionals and thereby helping them optimize their earning potential. We describe the overall design and architecture of the statistical modeling system underlying this product. We focus on the unique data mining challenges while designing and implementing the system, and describe the modeling components such as Bayesian hierarchical smoothing that help to compute and present robust compensation insights to users. We report on extensive evaluation with nearly one year of de-identified compensation data collected from over one million LinkedIn users, thereby demonstrating the efficacy of the statistical models. We also highlight the lessons learned through the deployment of our system at LinkedIn.Comment: Conference information: ACM International Conference on Information and Knowledge Management (CIKM 2017

Coherent transport of neutral atoms in spin-dependent optical lattice potentials

We demonstrate the controlled coherent transport and splitting of atomic wave packets in spin-dependent optical lattice potentials. Such experiments open intriguing possibilities for quantum state engineering of many body states. After first preparing localized atomic wave functions in an optical lattice through a Mott insulating phase, we place each atom in a superposition of two internal spin states. Then state selective optical potentials are used to split the wave function of a single atom and transport the corresponding wave packets in two opposite directions. Coherence between the wave packets of an atom delocalized over up to 7 lattice sites is demonstrated.Comment: 4 pages, 6 figure