Autophagy is an evolutionarily conserved intracellular degradation system that is involved in cell survival and activated in various diseases, including cancer. Beclin 1 is a central scaffold protein ...that assembles components for promoting or inhibiting autophagy. Association of Beclin 1 with its interacting proteins is regulated by the phosphorylation of Beclin 1 by various Ser/Thr kinases, but the Ser/Thr phosphatases that regulate these phosphorylation events remain unknown. Here we identify Ser-90 in Beclin 1 as a regulatory site whose phosphorylation is markedly enhanced in cells treated with okadaic acid, an inhibitor of protein phosphatase 2A (PP2A). Beclin 1 Ser-90 phosphorylation is induced in skeletal muscle tissues isolated from starved mice. The Beclin 1 S90A mutant blocked starvation-induced autophagy. We found association of PP2A B55α with Beclin 1, which dissociate by starvation. We also found that death-associated protein kinase 3 directly phosphorylates Beclin 1 Ser-90. We propose that physiological regulation of Beclin 1 Ser-90 phosphorylation by PP2A and death-associated protein kinase 3 controls autophagy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This article introduced China's four reasons of offensive to the Senkaku Islands: the first reason China's natural resources demand; the second reason historical issues with Japan that have some ...relationship to Chinese people's wartime memories; the third reason the Senkaku Islands Dispute as a tool of Chinese Communist Party (CCP)'s internal power struggle; the fourth reason the Senkaku Islands Dispute as a tool of CCP for China's national integration. Some reasons of Chinese offensive have been intertwined with each other, though the first reason is the main issue and the origin of the Senkaku Islands Dispute. It seems that other three reasons are supportive reasons for the natural resources demand, and byproducts of the dispute between Japan and China. The author discusses the occurrence and changes of these four reasons and concludes that the third and fourth reasons will be more troublesome than the others because they are unpredictable.
In 1961, the Berlin Wall was built by East Germany all around West Berlin. East Berlin was governed by the Soviet Union, and West Berlin was governed by France, Great Britain, and the United States. ...West Berlin and West Germany were connected by autobahns, railroads and planes, and West Berlin developed with West Germany. On November 9, 1989, the Berlin Wall suddenly collapsed. Many people were destroying the Berlin Wall with a hammer, as if they vented their anger for years. The work to remove the Berlin Wall began the next day, and East and West Germany were unified on October 3, the following year. I tried two studies on liver transplantation in West Germany. One was an experimental study on the effects of the donor’s fasting and graft viability after liver transplantation, and the other was a study on the role of Kupffer cells in the induction of tolerance after liver transplantation. It has been suggested that poor nutritional status of donors promotes preservation injury and contributes to a decrease in the viability of the transplanted liver, and hepatic Kupffer cells are involved in the establishment of induction of specific immunological tolerance in donor specific blood transfusion.
Astrocytes become reactive following various brain insults; however, the functions of reactive astrocytes are poorly understood. Here, we show that reactive astrocytes function as phagocytes after ...transient ischemic injury and appear in a limited spatiotemporal pattern. Following transient brain ischemia, phagocytic astrocytes are observed within the ischemic penumbra region during the later stage of ischemia. However, phagocytic microglia are mainly observed within the ischemic core region during the earlier stage of ischemia. Phagocytic astrocytes upregulate ABCA1 and its pathway molecules, MEGF10 and GULP1, which are required for phagocytosis, and upregulation of ABCA1 alone is sufficient for enhancement of phagocytosis in vitro. Disrupting ABCA1 in reactive astrocytes result in fewer phagocytic inclusions after ischemia. Together, these findings suggest that astrocytes are transformed into a phagocytic phenotype as a result of increase in ABCA1 and its pathway molecules and contribute to remodeling of damaged tissues and penumbra networks.Astrocytic phagocytosis has been shown to play a role in synaptic pruning during development, but whether adult astrocytes possess phagocytic ability is unclear. Here the authors show that following brain ischemia, reactive astrocytes become phagocytic and engulf debris via the ABCA1 pathway.
The site-specific monoubiquitination of FANCD2 is crucial for the Fanconi anemia DNA repair pathway and tumor suppression. This modification is mediated by the E2 enzyme UBE2T and the E3 ligase FANCL ...through a novel allosteric mechanism.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A microwave (MW) heating system induced by a magnetic field was designed and applied for uniform heating of a Pd membrane selectively through hydrogen. This system aimed to control the temperature of ...the membrane and the hydrogen permeation rate. Although the conventional dielectric heating by MWs is not suitable for metal membranes because of the reflection of MWs, a magnetic field can excite the surface current (eddy current) and causes Joule heating. First, this was successfully achieved for thin metal films in a frequency-variable single-mode MW reactor system with a cylindrical cavity. The temperature of the surface was controlled precisely by a resonance frequency autotracking function. Then, for the control of the hydrogen permeation rate through the Pd membrane, this system was applied to a pore-filling-type Pd membrane where the Pd nanoparticles were filled in the nanospace void of the Al2O3 support tube, suggesting high durability. The temperature of Pd membrane could be quickly and precisely controlled due to direct heating by this MW system. Hydrogen permeation rate was well controlled associated with the temperature of the membrane.
•A microwave system used for magnetic field heating was developed for metal membrane.•The magnetic field induces the surface eddy current causing Joule heating.•The system can uniformly heat the tubular Pd membrane and control H2 permeation rate.•Permeation rate of hydrogen can be rapidly controlled by microwave irradiation.•Pore-filling-type Pd membrane with high stability can be well heated by the system.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Autophagy is an evolutionarily conserved intracellular degradation system and is regulated by various signaling pathways including the Beclin 1/Vacuolar protein sorting 34 (Vps34) complex. Protein ...phosphatase 6 (PP6) is an essential serine/threonine phosphatase that regulates various biological processes. Recently, we found that PP6 protein is degraded by p62-dependent selective autophagy. In this study, we show that PP6 conversely inhibits autophagy. PP6 associate with the C-terminal region of Beclin 1, which is close to the binding region of Vps34. The protein levels of PP6 affect Beclin 1/Vps34 complex formation and phosphatase activity of PP6 is not involved in this. We also show that chemically induced PP6/Beclin 1 association leads to Vps34 dissociation from Beclin 1. Overall, our data reveal a novel regulatory mechanism for autophagy by PP6.
•PP6 negatively regulates autophagy in 293T cells and MEFs.•PP6 associates with the C-terminal region of Beclin 1.•PP6 dissociates Vps34 from Beclin 1 in a phosphatase activity-independent manner.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Reported empathy deficits in autism spectrum disorder (ASD) could be attributable to other ASD-related features. We evaluated 28 ASD adults with no intellectual disability and 24 age-matched non-ASD ...control subjects using the Autism-Spectrum Quotient (AQ), Questionnaire of Cognitive and Affective Empathy (QCAE), Interpersonal Reactivity Index (IRI), and NEO Personality Inventory-Revised (NEO). Compared to the controls, ASD participants showed lower scores for perspective taking, online simulation, cognitive empathy, and peripheral responsivity on the QCAE, and lower scores for perspective taking and empathic concern on the IRI. Within the ASD group, the AQ scores showed significant relationships with perspective taking, online simulation and cognitive empathy on the QCAE, and perspective taking on the IRI. The ASD group also showed higher scores for neuroticism and lower scores for extraversion on the NEO compared to the controls. However, there were no relationships between AQ scores and NEO factors within the ASD group. Multiple regression analysis with stepwise linear regression demonstrated that perspective taking score on the QCAE and extraversion score on the NEO were good predictor variables to autistic traits on the AQ. These findings help us to understand empathy and personality traits in ASD adults with no intellectual disability.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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