Kaufmanernst8137

Animal defense system constitutes a series of distinct mechanisms that specifically defend against microbial invasion. Understanding these complex biological mechanisms is of paramount importance for implementing disease prevention strategies. In this study, the transcription factor, Akirin-2 was identified from ornamental fish Amphiprion clarkii and its involvement in immune response was characterized. A. clarkii Akirin-2 (AcAkirin-2) was identified as a highly conserved protein with two nuclear localization signals. In-vitro localization analysis in fathead minnow cells revealed that AcAkirin-2 is strictly localized to the nucleus. With regard to tissue-specific expression without immune challenge, AcAkirin-2 expression was highest in the brain and lowest in the liver. Immune challenge experiments revealed that AcAkirin-2 expression was the strongest in response to poly IC. Overexpression of AcAkirin-2 alone did not enhanced NF-ĸB activity significantly in HEK293T cells; however, it significantly enhanced NF-ĸB activity in the presence of poly IC. AcAkirin-2-mediated expression of antiviral genes was analyzed using qPCR in mullet kidney cells and plaque assay was performed to decipher the involvement of AcAkirin-2 in antiviral immunity. AcAkirin-2 overexpression significantly enhanced the expression of Viperin but not of Mx. Plaque assays revealed the ability of AcAkirin-2 to enervate VHSV titers. Taken together, this study unveiled the involvement of AcAkirin-2 in NF-ĸB-mediated transcription of antiviral genes.Glial cells, both astrocytes and microglia, play important roles in the induction and maintenance of neuroinflammation resulting in neuropathic pain. Pulsed radiofrequency (PRF) is applied to various nerves for the treatment of pain, although the molecular mechanism underlying its effects is still unclear. We herein investigated the genomic effects of PRF on a mouse cultured astrocyte cell line. PRF was applied to the cultured astrocytes in 20-msec pulses of 480 kHz every 500 msec, delivered at the rate of 2 Hz, for 30 min. PRF increased the expression of 2,431 genes and decreased that of 209 genes. Among these genes, 435 genes were upregulated >10-fold and 89 genes >30-fold, while no genes showed a 10-fold decrease in expression. A gene ontology analysis using the list of >10-fold upregulated genes showed that PRF treatment activated immune responses. A pathway analysis using the Kyoto Encyclopedia of Gene and Genomes with the same list detected seven pathways related to neuropathic pain. NSC 70931 These findings suggest that PRF improves neuropathic pain via neuroimmunomodulation.The effects of online Transcranial Magnetic Stimulation (TMS) can qualitatively vary as a function of brain state. For example, TMS intensities which normally impair performance can have a facilitatory effect if the targeted neuronal representations are in a suppressed state. These phenomena have been explained in terms of the existence of distinct facilitatory and suppressive ranges as a function of TMS intensity which are shifted by changes in neural excitability. We tested this model by applying TMS at a low (60 % of phosphene threshold) or high (120 % of phosphene threshold) intensity during a priming paradigm. Our results show that state-dependent TMS effects vary qualitatively as a function of TMS intensity. Whereas the application of TMS at 120 % of participants' phosphene threshold impaired performance on fully congruent trials (in effect, reducing the benefit of priming), TMS applied at a lower intensity (60 % of phosphene threshold), facilitated performance on congruent trials. These results demonstrate that behavioral effects of TMS reflect a nonlinear interaction between initial activation state and TMS intensity. They also provide support for the existence of facilitatory/suppressive ranges of TMS effects which shift when neural excitability changes.Microglia are the resident immune cells of the central nervous system (CNS). In physiological conditions, microglia contribute to maintaining brain homeostasis by scanning the surrounding parenchyma and acting as scavenger cells. Following different insults to the CNS, microglia turn into a "reactive" state characterized by the production of inflammatory mediators that promote tissue repair to restore homeostasis. Brain insults such as traumatic brain injury, therapeutic brain irradiation and galactic cosmic ray exposure are associated with chronic microglia activation. Chronic microglia activation contributes to injury-related impairments in cognitive functions. Microglia depletion achieved either by pharmacological or genetic techniques represents not only a useful tool for more extensive investigations of microglia roles, but also a potential therapeutic approach to ameliorate or prevent cognitive dysfunctions following brain injury.Rho kinase (ROCK) inhibitors are of therapeutic value for the treatment of disorders such as hypertension and glaucoma, and potentially of wider use against diseases such as cancer and multiple sclerosis. We previously reported a series of potent and selective ROCK inhibitors based on a substituted 7-azaindole scaffold. Here we extend the SAR exploration of the 7-azaindole series to identify leads for further evaluation. New compounds such as 16, 17, 19, 21 and 22 showed excellent ROCK potency and protein kinase A (PKA) selectivity, combined with microsome and hepatocyte stability.Flavones are valuable scaffolds in medicinal chemistry, especially as they display activity as antioxidants and neuroprotective agents. The need to incorporate a fluorine atom on flavones has driven much of the recent synthetic work in this area. We now report a route for the production of 3-fluorinated derivatives of 3',4',5'-trihydroxyflavone and 3',4',5'-trimethoxyflavone. Biological evaluation of these agents, along with their non-fluorinated counterparts, demonstrate that antioxidant activity may be enhanced whereas neuroprotective activity is conserved. Also, the 3-fluoro-3',4',5'-trihydroxyflavone can act as an NMR probe to detect structural changes during its action as a radical scavenger.