Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine

Background: Enhanced activity of trigeminal ganglion neurons is thought to underlie neuronal sensitization facilitating the onset of chronic pain attacks, including migraine. Recurrent headache attacks might establish a chronic neuroinflammatory ganglion profile contributing to the hypersensitive phenotype. Since it is difficult to study this process in vivo, we investigated functional crosstalk between macrophages and sensory neurons in primary cultures from trigeminal sensory ganglia of wild-type (WT) or knock-in (KI) mice expressing the Cacna1a gene mutation (R192Q) found in familial hemiplegic migraine-type 1. After studying the number and morphology of resident macrophages in culture, the consequences of adding host macrophages on macrophage phagocytosis and membrane currents mediated by pain-transducing P2X3 receptors on sensory neurons were examined.Results: KI ganglion cultures constitutively contained a larger number of active macrophages, although no difference in P2X3 receptor expression was found. Co-culturing WT or KI ganglia with host macrophages (active as much as resident cells) strongly stimulated single cell phagocytosis. The same protocol had no effect on P2X3 receptor expression in WT or KI co-cultures, but it largely enhanced WT neuron currents that grew to the high amplitude constitutively seen for KI neurons. No further potentiation of KI neuronal currents was observed.Conclusions: Trigeminal ganglion cultures from a genetic mouse model of migraine showed basal macrophage activation together with enhanced neuronal currents mediated by P2X3 receptors. This phenotype could be replicated in WT cultures by adding host macrophages, indicating an important functional crosstalk between macrophages and sensory neurons. \ua9 2012 Franceschini et al.; licensee BioMed Central Ltd

Digitalisering eller transformasjon? Hvordan forstås og håndteres den digitale endringsprosessen av ledere i NAV-kontor

Masteroppgave i kunnskapsledelse (MKL) - Nord universitet 202

Assembly of Pt nanoparticles on graphitized carbon nanofibers as hierarchically structured electrodes

Carbon-based nanofibers decorated with metallic nanoparticles (NPs) as hierarchically structured electrodes offer significant opportunities for use in low-temperature fuel cells, electrolyzers, flow and air batteries, and electrochemical sensors. We present a facile and scalable method for preparing nanostructured electrodes composed of Pt NPs on graphitized carbon nanofibers. Electrospinning directly addresses the issues related to large-scale production of Pt-based fuel cell electrocatalysts. Through precursors containing polyacrylonitrile and Pt salt electrospinning along with an annealing protocol, we obtain approximately 180 nm thick graphitized nanofibers decorated with approximately 5 nm Pt NPs. By in situ annealing scanning transmission electron microscopy, we qualitatively resolve and quantitatively analyze the unique dynamics of Pt NP formation and movement. Interestingly, by very efficient thermal-induced segregation of all Pt from the inside to the surface of the nanofibers, we increase overall Pt utilization as electrocatalysis is a surface phenomenon. The obtained nanomaterials are also investigated by spatially resolved Raman spectroscopy, highlighting the higher structural order in nanofibers upon doping with Pt precursors. The rationalization of the observed phenomena of segregation and ordering mechanisms in complex carbon-based nanostructured systems is critically important for the effective utilization of all metal-containing catalysts, such as electrochemical oxygen reduction reactions, among many other applications

Recent progress in the development of advanced support materials for electrocatalysis

Electrocatalytic materials are pivotal for clean chemical production and energy conversion in devices like electrolyzers and fuel cells. These materials usually consist of metallic nanoparticles which serve as active reaction sites, and support materials which provide high surface area, conductivity and stability. When designing novel electrocatalytic composites, the focus is often on the metallic sites, however, the significance of the support should not be overlooked. Carbon materials, valued for their conductivity and large surface area, are commonly used as support in benchmark electrocatalysts. However, using alternative support materials instead of carbon can be beneficial in certain cases. In this minireview, we summarize recent advancements and key directions in developing novel supports for electrocatalysis, encompassing both carbon and non-carbon materials

SiO2·p-TSA: a green catalyst for solvent-free tetrahydropyranylation of alcohols and thiols

A solvent-free procedure for tetrahydropyranylation of alcohols and thiols based on a simple grinding of the reagents in the presence of silica gel and catalytic amounts of p-TSA is described

Higher risk of renal impairment associated with tenofovir use amongst people living with HIV in India: A comparative cohort analysis between Western India and United Kingdom

Background: Data on the renal safety of Tenofovir (TDF) in Low and Middle Income Countries (LMICs) is scarce. We compared development of various forms of renal impairment with use of TDF-containing antiretroviral therapy (ART) between a cohort from the Institute of Infectious Diseases (IID) Pune, Western India and the Royal Free Hospital (RFH) London, UK. Methods: This is a retrospective analysis of change in estimated glomerular filtration rates (eGFRs) at 6, 12 and 24 months post TDF initiation using the Modification of Diet in Renal Disease (MDRD) equation. In people living with Human Immunodeficiency virus (PLHIV) with pre-TDF eGFR > 90 ml/min/1.73 m2 time to development of and factors associated with progression to eGFR < 60 ml/min/1.73 m2 were calculated using standard survival methods. Results: A total of 574 (59% Caucasian) at the RFH, and 708 (100% Indian ethnicity) PLHIV from IID were included. Baseline median eGFR were similar; RFH 102 (IQR 89, 117), IID 100 (82, 119). At 24 months, mean (SD) decline in eGFR was -7(21) at RFH (p  90 ml/min/1.73 m2 PLHIV at IID were more likely to develop an eGFR < 60 ml/min/1.73 m2 (aHR = 7.6 [95% CI 3.4, 17.4] p < 0.0001) and had a faster rate of progression estimated using Kaplan Meier methods. Risk factors included age (per 10 years older: aHR = 2.21 [1.6, 3.0] p < 0.0001) and receiving concomitant ritonavir boosted Protease Inhibitor (PI/r) (aHR = 2.4 [1.2, 4.8] p = 0.01). Conclusions: There is higher frequency of treatment limiting renal impairment events amongst PLHIV receiving TDF in Western India. As TDF scale up progresses, programs need to develop capacity for monitoring and treatment of renal impairment associated with TDF