Characterization of Chicken Tumor Necrosis Factor-alpha, a Long Missed Cytokine in Birds

Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine playing critical roles in host defense and acute and chronic inflammation. It has been described in fish, amphibians, and mammals but was considered to be absent in the avian genomes. Here, we report on the identification and functional characterization of the avian ortholog. The chicken TNF-alpha (chTNF-alpha) is encoded by a highly GC-rich gene, whose product shares with its mammalian counterpart 45% homology in the extracellular part displaying the characteristic TNF homology domain. Orthologs of chTNF-alpha were identified in the genomes of 12 additional avian species including Palaeognathae and Neognathae, and the synteny of the closely adjacent loci with mammalian TNF-alpha orthologs was demonstrated in the crow (Corvus cornix) genome. In addition to chTNF-alpha, we obtained full sequences for homologs of TNF-alpha receptors 1 and 2 (TNFR1, TNFR2). chTNF-a mRNA is strongly induced by lipopolysaccharide (LPS) stimulation of monocyte derived, splenic and bone marrow macrophages, and significantly upregulated in splenic tissue in response to i.v. LPS treatment. Activation of T-lymphocytes by TCR crosslinking induces chTNF-alpha expression in CD4(+) but not in CD8(+) cells. To gain insights into its biological activity, we generated recombinant chTNF-alpha in eukaryotic and prokaryotic expression systems. Both, the full-length cytokine and the extracellular domain rapidly induced an NF kappa B-luciferase reporter in stably transfected CEC-32 reporter cells. Collectively, these data provide strong evidence for the existence of a fully functional TNF-alpha/TNF-alpha receptor system in birds thus filling a gap in our understanding of the evolution of cytokine systems

Interband photorefraction in Sn2P2S6 at visible wavelengths

International audienceContinuous-wave photorefractive experiments in Sn2P2S6 crystals and interband photorefraction at the visible wavelengths of 514 and 488nm are presented. Two-wave mixing and Bragg diffraction measurements at 514nm show grating response times of around 100μs at moderate light intensities of 0.6W/cm2, i.e., 2 orders of magnitude faster than measured in the same crystal in the conventional photorefractive regime. A large two-wave mixing gain of up to Γ=60±8cm−1 is measured, and holes are identified as dominant charge carriers for the interband photorefractive effect

Photoacoustic absorption spectrometer for highly transparent dielectrics with parts-per-million sensitivity

A sensitive photoacoustic absorption spectrometer for highly transparent solids has been built and tested. As the light source an optical parametrical oscillator pumped by a nanosecond pulse laser with 10 Hz repetition rate is employed, covering the complete wavelength range from 407 to 2600 nm. A second-harmonic-generation unit extends the range of accessible wavelengths down to 212 nm. A lead-zirconate-titanate piezo transducer, directly coupled to the sample, detects the photoacoustically generated sound waves. Absorption spectra of lithium triborate, lithium niobate, and alpha barium borate crystals with absorption coefficients down to 10−5 cm−1 are presented

Methylomic profiling in trisomy 21 identifies cognition- and Alzheimer's disease-related dysregulation

Background: Trisomy 21 (T21) is associated with intellectual disability that ranges from mild to profound with an average intellectual quotient of around 50. Furthermore, T21 patients have a high risk of developing Alzheimer's disease (AD) early in life, characterized by the presence of senile plaques of amyloid protein and neurofibrillary tangles, leading to neuronal loss and cognitive decline. We postulate that epigenetic factors contribute to the observed variability in intellectual disability, as well as at the level of neurodegeneration seen in T21 individuals. Materials and Methods: A genome-wide DNA methylation study was performed using Illumina Infinium (R) MethylationEPIC BeadChips on whole blood DNA of 3 male T21 patients with low IQ, 8 T21 patients with high IQ (4 males and 4 females), and 21 age- and sex-matched control samples (12 males and 9 females) in order to determine whether DNA methylation alterations could help explain variation in cognitive impairment between individuals with T21. In view of the increased risk of developing AD in T21 individuals, we additionally investigated the T21-associated sites in published blood DNA methylation data from the AgeCoDe cohort (German study on Ageing, Cognition, and Dementia). AgeCoDe represents a prospective longitudinal study including non-demented individuals at baseline of which a part develops AD dementia at follow-up. Results: Two thousand seven hundred sixteen differentially methylated sites and regions discriminating T21 and healthy individuals were identified. In the T21 high and low IQ comparison, a single CpG located in the promoter of PELI1 was differentially methylated after multiple testing adjustment. For the same contrast, 69 differentially methylated regions were identified. Performing a targeted association analysis for the significant T21-associated CpG sites in the AgeCoDe cohort, we found that 9 showed significant methylation differences related to AD dementia, including one in the ADAM10 gene. This gene has previously been shown to play a role in the prevention of amyloid plaque formation in the brain. Conclusion: The differentially methylated regions may help understand the interaction between methylation alterations and cognitive function. In addition, ADAM10 might be a valuable blood-based biomarker for at least the early detection of AD