The structure of gauge-invariant ideals of labelled graph C∗C^*-algebras

In this paper, we consider the gauge-invariant ideal structure of a $C^*$-algebra $C^*(E,\mathcal{L},\mathcal{B})$ associated to a set-finite, receiver set-finite and weakly left-resolving labelled space $(E,\mathcal{L},\mathcal{B})$, where $\mathcal{L}$ is a labelling map assigning an alphabet to each edge of the directed graph $E$ with no sinks. Under the assumption that an accommodating set $\mathcal{B}$ is closed under taking relative complement, it is obtained that there is a one to one correspondence between the set of all hereditary saturated subsets of $\mathcal{B}$ and the gauge-invariant ideals of $C^*(E,\mathcal{L},\mathcal{B})$. For this, we introduce a quotient labelled space $(E,\mathcal{L},[\mathcal{B}]_R)$ arising from an equivalence relation $\sim_R$ on $\mathcal{B}$ and show the existence of the $C^*$-algebra $C^*(E,\mathcal{L},[\mathcal{B}]_R)$ generated by a universal representation of $(E,\mathcal{L},[\mathcal{B}]_R)$. Also the gauge-invariant uniqueness theorem for $C^*(E,\mathcal{L},[\mathcal{B}]_R)$ is obtained. For simple labelled graph $C^*$-algebras $C^*(E,\mathcal{L},\bar{\mathcal{E}})$, where $\bar{\mathcal{E}}$ is the smallest accommodating set containing all the generalized vertices, it is observed that if for each vertex $v$ of $E$, a generalized vertex $[v]_l$ is finite for some $l$, then $C^*(E,\mathcal{L},\bar{\mathcal{E}})$ is simple if and only if $(E,\mathcal{L},\bar{\mathcal{E}})$ is strongly cofinal and disagreeable. This is done by examining the merged labelled graph $(F,\mathcal{L}_F)$ of $(E,\mathcal{L})$ and the common properties that $C^*(E,\mathcal{L},\bar{\mathcal{E}})$ and $C^*(F,\mathcal{L},\bar{\mathcal{F}})$ share

Phosphorylation of α-syntrophin is responsible for its subcellular localization and interaction with dystrophin in muscle cells

79-85Syntrophin is a well-known adaptor protein that links intracellular proteins with the dystrophin-glycoprotein complex (DGC) at the sarcolemma. However, little is known about the underlying mechanism that regulates the intracellular localization of α-syntrophin and its interaction with dystrophin. In this study, we demonstrate that α-syntrophin phosphorylation determines its intracellular localization and interaction with dystrophin in muscle cells. α-Syntrophin, a predominant isoform in skeletal muscles, directly interacts with ion channels, enzymes, receptors, and DGC proteins. Despite α-syntrophin being a potential signaling molecule, most studies focus on its function as a dystrophin-associated protein. However, we previously reported that α-syntrophin has a variety of DGC-independent functions to modulate cell migration, differentiation, survival, and protein stability. According to the results of the in vitro phosphorylation assays using subcellular fractions, the phosphorylated α-syntrophin accumulated only at the plasma membrane, and this event occurred regardless of dystrophin expression. However, the α-syntrophin interacting with dystrophin at the membrane was not in a phosphorylated state. We also identified that protein kinase C (PKC) was involved in the phosphorylation of α-syntrophin, which restricted α-syntrophin to interact with dystrophin. In conclusion, we demonstrate that the phosphorylation of α-syntrophin by PKC regulates its intracellular localization and interaction with dystrophin

Phosphorylation of α-syntrophin is responsible for its subcellular localization and interaction with dystrophin in muscle cells

Syntrophin is a well-known adaptor protein that links intracellular proteins with the dystrophin-glycoprotein complex (DGC) at the sarcolemma. However, little is known about the underlying mechanism that regulates the intracellular localization of α-syntrophin and its interaction with dystrophin. In this study, we demonstrate that α-syntrophin phosphorylation determines its intracellular localization and interaction with dystrophin in muscle cells. α-Syntrophin, a predominant isoform in skeletal muscles, directly interacts with ion channels, enzymes, receptors, and DGC proteins. Despite α-syntrophin being a potential signaling molecule, most studies focus on its function as a dystrophin-associated protein. However, we previously reported that α-syntrophin has a variety of DGC-independent functions to modulate cell migration, differentiation, survival, and protein stability. According to the results of the in vitro phosphorylation assays using subcellular fractions, the phosphorylated α-syntrophin accumulated only at the plasma membrane, and this event occurred regardless of dystrophin expression. However, the α-syntrophin interacting with dystrophin at the membrane was not in a phosphorylated state. We also identified that protein kinase C (PKC) was involved in the phosphorylation of α-syntrophin, which restricted α-syntrophin to interact with dystrophin. In conclusion, we demonstrate that the phosphorylation of α-syntrophin by PKC regulates its intracellular localization and interaction with dystrophin

Doubly responsive polymersomes towards monosaccharides and temperature under physiologically relevant conditions

Organoboronic acid-containing polymers and block copolymers have recently attracted attention because of their ability to recognize important natural diol compounds such as saccharides and nucleotides under physiologically relevant conditions at neutral pH. In particular, polymers and block copolymers that are responsive toward multiple stimuli can be utilized to create smart delivery vehicles for use in applications in a complex environment. Here we report the monosaccharide-responsive polymers and block copolymers comprising styreneboroxole and oligo(ethylene glycol)-functionalized styrenes (OEG-STs) as repeating units. We have shown that homopolymers and copolymers of OEG-STs are thermally responsive by demonstrating that they possess the characteristic of tunable lower critical solution temperature (LCST) in water. When copolymerized with OEG-STs, styreneboroxole units function as a switch to change the solubility of the resulting polymers in aqueous solution by recognizing mono-saccharides via the formation of boronate ester. By introducing the minimum number of monosaccharide-responsive styreneboroxole units onto the thermally responsive OEG-ST backbone, we demonstrated the monosaccharide-responsive behavior of the resulting copolymers and their amphiphilic block copolymers in aqueous solution at physiologically relevant pH and temperature. A strategy based on doubly responsive block copolymers reported here could be utilized as new delivery vehicles for cargo molecules such as insulin, due to their ability to function in an in vivo environmentopen

Crystal structure of Cmr5 from Pyrococcus furiosus and its functional implications

AbstractThe bacterial acquired immune system consists of clustered regularly interspaced short palindromic repeats (CRISPRs) and CRIPSR-associated (Cas) genes, which include Cas-module repeat-associated mysterious proteins (Cmr). The six Cmr proteins of Pyrococcus furiosus (pfCmr1–pfCmr6) form a Cmr effector complex that functions against exogenous nucleic acid. Among the Cmr proteins, the role of pfCmr5 and its involvement in the complex’s cleavage activity have been obscure. The elucidated pfCmr5 structure has two inserted α-helices compared with the other trimeric Cmr5 structure. However, pfCmr5 exists as a monomeric protein both in the crystalline state and in solution. In vitro assays indicate that pfCmr5 interacts with pfCmr4. These structural and biophysical data might help in understanding the complicated and ill-characterized Cmr effector complex.Structured summary of protein interactionspfCmr4 and pfCmr5 bind by molecular sieving (View interaction)pfCmr4 and pfCmr4 bind by molecular sieving (View interaction)pfCmr5 and pfCmr4 bind by ion exchange chromatography (View interaction

Comparisons of ELISA and Western blot assays for detection of autophagy flux

We analyzed autophagy/mitophagy flux in vitro (C2C12 myotubes) and in vivo (mouse skeletal muscle) following the treatments of autophagy inducers (starvation, rapamycin) and a mitophagy inducer (carbonyl cyanide m-chlorophenylhydrazone, CCCP) using two immunodetection methods, ELISA and Western blotting, and compared their working range, accuracy, and reliability. The ELISAs showed a broader working range than that of the LC3 Western blots (Table 1). Table 2 showed that data value distribution was tighter and the average standard error from the ELISA was much smaller than those of the Western blot, directly relating to the accuracy of the assay. Test-retest reliability analysis showed good reliability for three individual ELISAs (interclass correlation, ≥ 0.7), but poor reliability for three individual Western blots (interclass correlation, ≤ 0.4) (Table 3). Keywords: Autophagy, Mitophagy, ELISA, Western blot, Skeletal muscl

Agonistic Anti-CD137 Monoclonal Antibody Treatment Induces CD11b+Gr-1+ Myeloid-derived Suppressor Cells

CD137 (4-1BB/tnfrsf9) has been shown to co-stimulate T cells. However, agonistic anti-CD137 monoclonal antibody (mAb) treatment can suppress CD4+ T cells, ameliorating autoimmune diseases, whereas it induces activation of CD8+ T cells, resulting in diverse therapeutic activity in cancer, viral infection. To investigate the CD137-mediated T cell suppression mechanism, we examined whether anti-CD137 mAb treatment could affect CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). Intriguingly, anti-CD137 mAb injection significantly increased CD11b+Gr-1+ cells, peaking at days 5 to 10 and continuing for at least 25 days. Furthermore, this cell population could suppress both CD8+ T cells and CD4+ T cells. Thus, this study demonstrated that, for the first time, anti-CD137 mAb treatment could induce CD11b+Gr-1+ MDSCs under normal conditions, suggesting a possible relationship between myeloid cell induction and CD137-mediated immune suppression