Inhibitory effect of curcumin on mammalian phospholipase D activity

AbstractCurcumin, the major yellow pigment of turmeric (Curcuma longa), has strong anti-carcinogenic and anti-inflammatory activities. We examined the effects of curcumin on enzyme activities of the following phospholipases in a cell-free system: G protein-mediated phospholipase D (PLD), phosphatidylinositol-specific phospholipase C, and phospholipase A2 from mouse macrophage-like cell line J774.1 cells, sphingomyelinase from bovine brain, and phosphatidylcholine-phospholipase C from Bacillus cereus. Curcumin inhibited several types of phospholipases, most effectively PLD among those tested. It also inhibited 12-O-tetradecanoylphorbol-13-acetate-induced PLD activation in intact J774.1 cells in a dose-dependent manner. These results suggest that the anti-inflammatory and anti-carcinogenic action of curcumin is partly due to the inhibition of PLD

The CCR4–NOT deadenylase complex safeguards thymic positive selection by down-regulating aberrant pro-apoptotic gene expression

A repertoire of T cells with diverse antigen receptors is selected in the thymus. However, detailed mechanisms underlying this thymic positive selection are not clear. Here we show that the CCR4-NOT complex limits expression of specific genes through deadenylation of mRNA poly(A) tails, enabling positive selection. Specifically, the CCR4-NOT complex is up-regulated in thymocytes before initiation of positive selection, where in turn, it inhibits up-regulation of pro-apoptotic Bbc3 and Dab2ip. Elimination of the CCR4-NOT complex permits up-regulation of Bbc3 during a later stage of positive selection, inducing thymocyte apoptosis. In addition, CCR4-NOT elimination up-regulates Dab2ip at an early stage of positive selection. Thus, CCR4-NOT might control thymocyte survival during two-distinct stages of positive selection by suppressing expression levels of pro-apoptotic molecules. Taken together, we propose a link between CCR4-NOT-mediated mRNA decay and T cell selection in the thymus

Identification and structural analysis of C-terminally truncated collapsin response mediator protein-2 in a murine model of prion diseases

<p>Abstract</p> <p>Background</p> <p>Prion diseases are fatal neurodegenerative disorders that accompany an accumulation of the disease-associated form(s) of prion protein (PrP^Sc) in the central nervous system. The neuropathological changes in the brain begin with focal deposits of PrP^Sc, followed by pathomorphological abnormalities of axon terminal degeneration, synaptic loss, atrophy of dendritic trees, and eventual neuronal cell death in the lesions. However, the underlying molecular basis for these neuropathogenic abnormalities is not fully understood.</p> <p>Results</p> <p>In a proteomic analysis of soluble proteins in the brains of mice challenged intracerebrally with scrapie prion (Obihiro I strain), we found that the amount of the full-length form of collapsin response mediator protein-2 (CRMP-2; 61 kDa) decreased in the late stages of the disease, while the amount of its truncated form (56 kDa) increased to comparable levels observed for the full-length form. Detailed analysis by liquid chromatography-electrospray ionization-tandem mass spectrometry showed that the 56-kDa form (named CRMP-2-ΔC) lacked the sequence from serine⁵¹⁸to the C-terminus, including the C-terminal phosphorylation sites important for the regulation of axonal growth and axon-dendrite specification in developing neurons. The invariable size of the mRNA transcript in Northern blot analysis suggested that the truncation was due to post-translational proteolysis. By overexpression of CRMP-2-ΔC in primary cultured neurons, we observed the augmentation of the development of neurite branch tips to the same levels as for CRMP-2^T514A/T555A, a non-phosphorylated mimic of the full-length protein. This suggests that the increased level of CRMP-2-ΔC in the brain modulates the integrity of neurons, and may be involved in the pathogenesis of the neuronal abnormalities observed in the late stages of the disease.</p> <p>Conclusions</p> <p>We identified the presence of CRMP-2-ΔC in the brain of a murine model of prion disease. Of note, C-terminal truncations of CRMP-2 have been recently observed in models for neurodegenerative disorders such as ischemia, traumatic brain injury, and Wallerian degeneration. While the structural identity of CRMP-2-ΔC in those models remains unknown, the present study should provide clues to the molecular pathology of degenerating neurons in prion diseases in connection with other neurodegenerative disorders.</p

Joint Observation of the Galactic Center with MAGIC and CTA-LST-1

MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes (IACTs), designed to detect very-high-energy gamma rays, and is operating in stereoscopic mode since 2009 at the Observatorio del Roque de Los Muchachos in La Palma, Spain. In 2018, the prototype IACT of the Large-Sized Telescope (LST-1) for the Cherenkov Telescope Array, a next-generation ground-based gamma-ray observatory, was inaugurated at the same site, at a distance of approximately 100 meters from the MAGIC telescopes. Using joint observations between MAGIC and LST-1, we developed a dedicated analysis pipeline and established the threefold telescope system via software, achieving the highest sensitivity in the northern hemisphere. Based on this enhanced performance, MAGIC and LST-1 have been jointly and regularly observing the Galactic Center, a region of paramount importance and complexity for IACTs. In particular, the gamma-ray emission from the dynamical center of the Milky Way is under debate. Although previous measurements suggested that a supermassive black hole Sagittarius A* plays a primary role, its radiation mechanism remains unclear, mainly due to limited angular resolution and sensitivity. The enhanced sensitivity in our novel approach is thus expected to provide new insights into the question. We here present the current status of the data analysis for the Galactic Center joint MAGIC and LST-1 observations

MAGIC and H.E.S.S. detect VHE gamma rays from the blazar OT081 for the first time: a deep multiwavelength study

https://pos.sissa.it/395/815/pdfPublished versio

How much can increase in expected product lifetime contribute to extending actual product use duration? A case study of refrigerators

The expected lifetime of a product is a consumer-oriented factor that needs to be considered when assessing product lifetime extension. While numerous studies have analysed the expected lifetime of appliances, only a study for air conditioners has assessed the effect of changes in the expected product lifetime on the actual product use duration. Consequently, the impact for another product needs to be examined in order to develop appropriate product lifetime extension policies. This study estimated the impact of the expected product lifetime on the actual product use duration of refrigerators. We employed a dynamic discrete choice model (DDCM) to examine consumers’ product replacement decisions as they are related to refrigerators. Also, we quantitatively analyzed the impact of the expected product lifetime on product use by using the parameters of the DDCM. The results showed that an increase in the expected product lifetime of refrigerators can contribute to prolonging actual product use for refrigerators. If the expected product lifetime is extended by 1, 2, and 3 years, the actual product use duration can be extended by 0.52, 1.05, and 1.59 years, respectively, which are shorter than the estimates obtained for air conditioners in a previous study. The results imply that the degree of product lifetime extension differs between products. Therefore, clarifying factors which causes the difference in the product lifetime extension effects is important to achieve product lifetime extension effectively