Please check your proof carefully and mark all corrections at the appropriate place in the proof (e.g., by using on-screen annotation in the PDF file) or compile them in a separate list.For correction or revision of any artwork, please consult http://www.elsevier.com/artworkinstructions.Any queries or remarks that have arisen during the processing of your manuscript are listed below and highlighted by flags in the proof. Click on the 'Q' link to go to the location in the proof. Location inQuery / Remark: click on the Q link to go article Please insert your reply or correction at the corresponding line in the proof Q1If there are fewer than seven authors, please supply all their names; if there are seven or more authors, please supply the first six authors' names, followed by 'et al.'Thank you for your assistance. Graphical AbstractBiochemical Pharmacology xxx (2010) xxx-xxx pp: xxx-xxx The protein Nod2: An innate receptor more complex than previously assumed

SHIP-1 is an inositol phosphatase predominantly expressed in hematopoietic cells. Over the ten past years, SHIP-1 has been described as an important regulator of immune functions. Here, we characterize a new inhibitory function for SHIP-1 in NOD2 signaling. NOD2 is a crucial cytoplasmic bacterial sensor that activates proinflammatory and antimicrobial responses upon bacterial invasion. We observed that SHIP-1 decreases NOD2-induced NF-κB activation in macrophages. This negative regulation relies on its interaction with XIAP. Indeed, we observed that XIAP is an essential mediator of the NOD2 signaling pathway that enables proper NF-κB activation in macrophages. Upon NOD2 activation, SHIP-1 C-terminal proline rich domain (PRD) interacts with XIAP, thereby disturbing the interaction between XIAP and RIP2 in order to decrease NF-κB signaling.

Background: NOD2 belongs to the NLR family. JNKBP1, a scaffold protein, is characterized by an N-terminal WD-40 domain. Results: JNKBP1 is co-expressed with NOD2 in epithelial and immune cells of intestine mucosa. Binding of JNKB1 to NOD2 attenuates NOD2 signaling by inhibiting its oligomerization. Conclusion: JNKBP1 is a new NOD2 modulator. Significance: JNKBP1, by down-regulating NOD2 signaling, could contribute to maintaining intestinal immune homeostasis.

In the recent decades, biodegradable and biocompatible polyphosphoesters (PPEs) have gained wide attention in the biomedical field as relevant substitutes for conventional aliphatic polyesters. These amorphous materials of low glass transition temperature offer promise for the design of soft scaffolds for tissue engineering. Advantageously, the easy variation of the nature of the lateral pendant groups of PPEs allows the insertion of pendent unsaturations valuable for their further cross-linking. In addition, varying the length of the pendent alkyl chains allows tuning their hydrophilicity. The present work aims at synthesizing PPE networks of well-defined hydrophilicity and mechanical properties. More precisely, we aimed at preparing degradable materials exhibiting identical hydrophilicity but different mechanical properties and vice versa. For that purpose, PPE copolymers were synthesized by ring-opening copolymerization of cyclic phosphate monomers bearing different pendent groups (e.g., methyl, butenyl, and butyl). After UV irradiation, a stable and well-defined cross-linked material is obtained with the mechanical property of the corresponding polymer films controlled by the composition of the starting PPE copolymer. The results demonstrate that cross-linking density could be correlated with the mechanical properties, swelling behavior, and degradation rate of the polymers network. The polymers were compatible to human skin fibroblast cells and did not exhibit significant cytotoxicity up to 0.5 mg mL–1. In addition, degradation products appeared nontoxic to skin fibroblast cells and showed their potential as promising scaffolds for tissue engineering.

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