Norovirus 3C-like proteases are crucial to proteolytic processing of norovirus polyproteins. We determined the crystal structure of the 3C-like protease from Chiba virus, a norovirus, at 2.8-Å resolution. An active site including Cys139 and His30 is present, as is a hydrogen bond network that stabilizes the active site conformation. In the oxyanion hole backbone, a structural difference was observed probably upon substrate binding. A peptide substrate/enzyme model shows that several interactions between the two components are critical for substrate binding and that the S1 and S2 sites appropriately accommodate the substrate P1 and P2 residues, respectively. Knowledge of the structure and a previous mutagenesis study allow us to correlate proteolysis and structure.

The aim of this article is to classify two-dimensional split trianguline representations of p-adic fields. This is a generalization of a result of Colmez who classified two-dimensional split trianguline representations of Gal(Q p /Q p ) for p = 2 by using (ϕ, Γ)-modules over a Robba ring. In this article, for any prime p and for any p-adic field K, we classify two-dimensional split trianguline representations of Gal(K/K) using B-pairs as defined by Berger. Contents

The aim of this article is to study the Bloch-Kato exponential map and the Perrin-Riou big exponential map purely in terms of (ϕ, Γ )-modules over the Robba ring. We first generalize the definition of the Bloch-Kato exponential map for all the (ϕ, Γ )-modules without using Fontaine's rings B crys , B dR of p-adic periods, and then generalize the construction of the Perrin-Riou big exponential map for all the de Rham (ϕ, Γ )-modules and prove that this map interpolates our Bloch-Kato exponential map and the dual exponential map. Finally, we prove a theorem concerning the determinant of our big exponential map, which is a generalization of theorem δ(V) of Perrin-Riou. The key ingredients for our study are Pottharst's theory of the analytic Iwasawa cohomology and Berger's construction of p-adic differential equations associated to de Rham (ϕ, Γ )-modules.

ICK (also known as CILK1) is a MAPK-like kinase localized at the ciliary tip. Its deficiency is known to result in the elongation of cilia, and causes ciliopathies in humans. However, little is known about how ICK is transported to the ciliary tip. We here show that the C-terminal noncatalytic region of ICK interacts with the intraflagellar transport (IFT)-B complex of the IFT machinery, and participates in its transport to the ciliary tip. Furthermore, total internal reflection fluorescence microscopy demonstrated that ICK undergoes bidirectional movement within cilia, similarly to IFT particles. Analysis of ICK-knockout cells demonstrated that ICK deficiency severely impairs the retrograde trafficking of IFT particles and ciliary GPCRs. In addition, we found that in ICK-knockout cells, ciliary proteins are accumulated at the bulged ciliary tip, which appeared to be torn off and release into the environment as an extracellular vesicle. The exogenous expression of various ICK constructs in ICK-knockout cells indicated that the IFT-dependent transport of ICK, as well as its kinase activity and phosphorylation at the canonical TDY motif, is essential for ICK function. Thus, we unequivocally show that ICK transported to the ciliary tip is required for retrograde ciliary protein trafficking and consequently for normal ciliary function.

SUMMARYCell death cluster in transplanted cells remains a critical obstacle for regeneration strategies. This study describes a novel platform for cell transplantation (CellSaic) consisting of human mesenchymal stem cells (hMSCs) and petaloid pieces of recombinant peptide (RCP), which can prevent cell death by arranging the cells in a mosaic. When hMSC CellSaics were subcutaneously implanted into NOD/SCID mice, hMSC CellSaics prevented cell death and accelerated angiogenesis in the graft, compared to the findings obtained on solely implanting cell spheroids. Additionally, we examined the application of CellSaic for subcutaneous cotransplantation of 200 rat islets with 2 9 10 5 hMSCs into diabetic mice. As the results of blood glucose levels at 1 M, the islet-only group was 398 AE 30 mg/dl and the islets with hMSCs group were 180 AE 65 mg/dl. On the other hand, the islets with hMSCs CellSaic group showed 129 AE 15 mg/dl and significantly improved glucose tolerance (P < 0.05). Additionally, we showed that the surface texture of the RCP petaloid pieces played an important role in graft survival and angiogenesis. It is anticipated that CellSaic will be used as a new platform for cell transplantation and tissue regeneration.