Phenotypic impacts of CSF1R deficiencies in humans and model organisms

Mϕ proliferation, differentiation, and survival are controlled by signals from the Mϕ CSF receptor (CSF1R). Mono‐allelic gain‐of‐function mutations in CSF1R in humans are associated with an autosomal‐dominant leukodystrophy and bi‐allelic loss‐of‐function mutations with recessive skeletal dysplasia, brain disorders, and developmental anomalies. Most of the phenotypes observed in these human disease states are also observed in mice and rats with loss‐of‐function mutations in Csf1r or in Csf1 encoding one of its two ligands. Studies in rodent models also highlight the importance of genetic background and likely epistatic interactions between Csf1r and other loci. The impacts of Csf1r mutations on the brain are usually attributed solely to direct impacts on microglial number and function. However, analysis of hypomorphic Csf1r mutants in mice and several other lines of evidence suggest that primary hydrocephalus and loss of the physiological functions of Mϕs in the periphery contribute to the development of brain pathology. In this review, we outline the evidence that CSF1R is expressed exclusively in mononuclear phagocytes and explore the mechanisms linking CSF1R mutations to pleiotropic impacts on postnatal growth and development

A complete pupillometry toolbox for real-time monitoring of locus coeruleus activity in rodents

The locus coeruleus (LC) is a region in the brainstem that produces noradrenaline and is involved in both normal and pathological brain function. Pupillometry, the measurement of pupil diameter, provides a powerful readout of LC activity in rodents, primates and humans. The protocol detailed here describes a miniaturized setup that can screen LC activity in rodents in real-time and can be established within 1–2 d. Using low-cost Raspberry Pi computers and cameras, the complete custom-built system costs only ~300 euros, is compatible with stereotaxic surgery frames and seamlessly integrates into complex experimental setups. Tools for pupil tracking and a user-friendly Pupillometry App allow quantification, analysis and visualization of pupil size. Pupillometry can discriminate between different, physiologically relevant firing patterns of the LC and can accurately report LC activation as measured by noradrenaline turnover. Pupillometry provides a rapid, non-invasive readout that can be used to verify accurate placement of electrodes/fibers in vivo, thus allowing decisions about the inclusion/exclusion of individual animals before experiments begin

Decoupling astrocytes in adult mice impairs synaptic plasticity and spatial learning

The mechanisms by which astrocytes modulate neural homeostasis, synaptic plasticity, and memory are still poorly explored. Astrocytes form large intercellular networks by gap junction coupling, mainly composed of two gap junction channel proteins, connexin 30 (Cx30) and connexin 43 (Cx43). To circumvent developmental perturbations and to test whether astrocytic gap junction coupling is required for hippocampal neural circuit function and behavior, we generate and study inducible, astrocyte-specific Cx30 and Cx43 double knockouts. Surprisingly, disrupting astrocytic coupling in adult mice results in broad activation of astrocytes and microglia, without obvious signs of pathology. We show that hippocampal CA1 neuron excitability, excitatory synaptic transmission, and long-term potentiation are significantly affected. Moreover, behavioral inspection reveals deficits in sensorimotor performance and a complete lack of spatial learning and memory. Together, our findings establish that astrocytic connexins and an intact astroglial network in the adult brain are vital for neural homeostasis, plasticity, and spatial cognition

Rotation Measures of Radio Sources in Hot Galaxy Clusters

The goal of this work is to investigate the Faraday rotation measure (RM) of radio galaxies in hot galaxy clusters in order to establish a possible connection between the magnetic field strength and the gas temperature of the intracluster medium. We performed Very Large Array observations at 3.6 cm and 6 cm of two radio galaxies located in A401 and Ophiuchus, a radio galaxy in A2142, and a radio galaxy located in the background of A2065. All these galaxy clusters are characterized by high temperatures. We obtained detailed RM images at an angular resolution of 3'' for most of the observed radio galaxies. The RM images are patchy and reveal fine substructures of a few kpc in size. Under the assumption that the radio galaxies themselves have no effect on the measured RMs, these structures indicate that the intracluster magnetic fields fluctuate down to such small scales. These new data are compared with RM information present in the literature for cooler galaxy clusters. For a fixed projected distance from the cluster center, clusters with higher temperature show a higher dispersion of the RM distributions (sigmaRM), mostly because of the higher gas density in these clusters. Although the previously known relation between the clusters X-ray surface brightness (Sx) at the radio galaxy location and sigmaRM is confirmed, a possible connection between the sigmaRM-Sx relation and the cluster temperature, if present, is very weak. Therefore, in view of the current data, it is impossible to establish a strict link between the magnetic field strength and the gas temperature of the intracluster medium.Comment: Accepted by Astronomy and Astrophysics, 26 pages, 19 figure

Transfer-free growth of graphene on SiO2 insulator substrate from sputtered carbon and nickel films

AbstractHere we demonstrate the growth of transfer-free graphene on SiO2 insulator substrates from sputtered carbon and metal layers with rapid thermal processing in the same evacuation. It was found that graphene always grows atop the stack and in close contact with the Ni. Raman spectra typical of high quality exfoliated monolayer graphene were obtained for samples under optimised conditions with monolayer surface coverage of up to 40% and overall graphene surface coverage of over 90%. Transfer-free graphene is produced on SiO2 substrates with the removal of Ni in acid when Ni thickness is below 100nm, which effectively eliminates the need to transfer graphene from metal to insulator substrates and paves the way to mass production of graphene directly on insulator substrates. The characteristics of Raman spectrum depend on the size of Ni grains, which in turn depend on the thickness of Ni, layer deposition sequence of the stack and RTP temperature. The mechanism of the transfer-free growth process was studied by AFM in combination with Raman. A model is proposed to depict the graphene growth process. Results also suggest a monolayer self-limiting growth for graphene on individual Ni grains

CSF1R-dependent macrophages control postnatal somatic growth and organ maturation

Homozygous mutation of the Csf1r locus (Csf1rko) in mice, rats and humans leads to multiple postnatal developmental abnormalities. To enable analysis of the mechanisms underlying the phenotypic impacts of Csf1r mutation, we bred a rat Csf1rko allele to the inbred dark agouti (DA) genetic background and to a Csf1r-mApple reporter transgene. The Csf1rko led to almost complete loss of embryonic macrophages and ablation of most adult tissue macrophage populations. We extended previous analysis of the Csf1rko phenotype to early postnatal development to reveal impacts on musculoskeletal development and proliferation and morphogenesis in multiple organs. Expression profiling of 3-week old wild-type (WT) and Csf1rko livers identified 2760 differentially expressed genes associated with the loss of macrophages, severe hypoplasia, delayed hepatocyte maturation, disrupted lipid metabolism and the IGF1/IGF binding protein system. Older Csf1rko rats developed severe hepatic steatosis. Consistent with the developmental delay in the liver Csf1rko rats had greatly-reduced circulating IGF1. Transfer of WT bone marrow (BM) cells at weaning without conditioning repopulated resident macrophages in all organs, including microglia in the brain, and reversed the mutant phenotypes enabling long term survival and fertility. WT BM transfer restored osteoclasts, eliminated osteopetrosis, restored bone marrow cellularity and architecture and reversed granulocytosis and B cell deficiency. Csf1rko rats had an elevated circulating CSF1 concentration which was rapidly reduced to WT levels following BM transfer. However, CD43hi non-classical monocytes, absent in the Csf1rko, were not rescued and bone marrow progenitors remained unresponsive to CSF1. The results demonstrate that the Csf1rko phenotype is autonomous to BM-derived cells and indicate that BM contains a progenitor of tissue macrophages distinct from hematopoietic stem cells. The model provides a unique system in which to define the pathways of development of resident tissue macrophages and their local and systemic roles in growth and organ maturation

Supercapacitance from cellulose and carbon nanotube nanocomposite fibers

Copyright © 2013 American Chemical SocietyACS AuthorChoice open access articleMultiwalled carbon nanotube (MWNT)/cellulose composite nanofibers have been prepared by electrospinning a MWNT/cellulose acetate blend solution followed by deacetylation. These composite nanofibers were then used as precursors for carbon nanofibers (CNFs). The effect of nanotubes on the stabilization of the precursor and microstructure of the resultant CNFs were investigated using thermogravimetric analysis, transmission electron microscopy and Raman spectroscopy. It is demonstrated that the incorporated MWNTs reduce the activation energy of the oxidative stabilization of cellulose nanofibers from 230 to 180 kJ mol–1. They also increase the crystallite size, structural order, and electrical conductivity of the activated CNFs (ACNFs). The surface area of the ACNFs increased upon addition of nanotubes which protrude from the fiber leading to a rougher surface. The ACNFs were used as the electrodes of a supercapacitor. The electrochemical capacitance of the ACNF derived from pure cellulose nanofibers is demonstrated to be 105 F g–1 at a current density of 10 A g–1, which increases to 145 F g–1 upon the addition of 6% of MWNTs.The authors would like to thank the [Engineering and Physical Sciences Research Council] EPSRC (EP/F036914/1 and EP/I023879/1), Guangdong and Shenzhen Innovative Research Team Program (No. 2011D052,KYPT20121228160843692), National Natural Science Foundation of China (Grant No. 21201175), R&D Funds for basic Research Program of Shenzhen (Grant No. JCYJ20120615140007998), and the Universities of Exeter and Manchester for funding this research

Radio halos in nearby (z < 0.4) clusters of galaxies

The Intra-Cluster Medium is characterized by thermal emission, and by the presence of large scale magnetic fields. In some clusters of galaxies a diffuse non-thermal emission is also present, located at the cluster center and named radio halo. These sources indicate the existence of relativistic particles and magnetic fields in the cluster volume. In this paper we collect data on all known nearby cluster radio halos (z < 0.4), to discuss their statistical properties and to investigate their origin. We searched for published data on radio halos and reduced new and archive VLA data to increase the number of known radio halos. We present data on 31 radio halos, 1 new relic source, and 1 giant filament. We note the discovery of a small size diffuse radio emission in a cluster (A1213) with very low X-ray luminosity. Among statistical results we confirm the correlation between the average halo radio spectral index and the cluster temperature. We also discuss the high percentage of clusters where both a relic and a radio halo is present. The sample of radio halos discussed here represents the population of radio halos observable with present radio telescopes. The new telescope generation is necessary for a more detailed multifrequency study, and to investigate the possible existence of a population of radio halos with different properties.Comment: 16 pages, 17 color figures. Accepted for the publication in Astronomy and Astrophysics. A version with full resolution figures is available at http://www.ira.inaf.it/~ggiovann

Search for R-Parity Violating Decays of Scalar Fermions at LEP

A search for pair-produced scalar fermions under the assumption that R-parity is not conserved has been performed using data collected with the OPAL detector at LEP. The data samples analysed correspond to an integrated luminosity of about 610 pb-1 collected at centre-of-mass energies of sqrt(s) 189-209 GeV. An important consequence of R-parity violation is that the lightest supersymmetric particle is expected to be unstable. Searches of R-parity violating decays of charged sleptons, sneutrinos and squarks have been performed under the assumptions that the lightest supersymmetric particle decays promptly and that only one of the R-parity violating couplings is dominant for each of the decay modes considered. Such processes would yield final states consisting of leptons, jets, or both with or without missing energy. No significant single-like excess of events has been observed with respect to the Standard Model expectations. Limits on the production cross- section of scalar fermions in R-parity violating scenarios are obtained. Constraints on the supersymmetric particle masses are also presented in an R-parity violating framework analogous to the Constrained Minimal Supersymmetric Standard Model.Comment: 51 pages, 24 figures, Submitted to Eur. Phys. J.

Measurement of the Hadronic Photon Structure Function F_2^gamma at LEP2

The hadronic structure function of the photon F_2^gamma is measured as a function of Bjorken x and of the factorisation scale Q^2 using data taken by the OPAL detector at LEP. Previous OPAL measurements of the x dependence of F_2^gamma are extended to an average Q^2 of 767 GeV^2. The Q^2 evolution of F_2^gamma is studied for average Q^2 between 11.9 and 1051 GeV^2. As predicted by QCD, the data show positive scaling violations in F_2^gamma. Several parameterisations of F_2^gamma are in agreement with the measurements whereas the quark-parton model prediction fails to describe the data.Comment: 4 pages, 2 figures, to appear in the proceedings of Photon 2001, Ascona, Switzerlan