CXXC5 is a negative-feedback regulator of the Wnt/ß-catenin pathway involved in osteoblast differentiation.

The positive roles of the Wnt/ß-catenin pathway in osteoblast differentiation and bone mineral density (BMD) maintenance have been clearly demonstrated in both animal experiments and clinical investigations. CXXC finger protein 5 (CXXC5), a recently identified negative regulator of the Wnt/ß-catenin pathway, showed altered cellular localization and function, which were dependent on the cell type in previous studies. However, the in vivo function of CXXC5 has not been clearly investigated yet. Here, we characterized CXXC5 as a negative regulator of osteoblast differentiation and bone formation. Deficiency of CXXC5 resulted in elevated BMD in mice without any severe gross developmental abnormalities. CXXC5 exerted a negative-feedback effect on the Wnt/ß-catenin pathway via Wnt-dependent binding to Dishevelled (Dvl) during osteoblast differentiation. Suppression of the Dvl-CXXC5 interaction using a competitor peptide resulted in the activation of the Wnt/ß-catenin pathway and osteoblast differentiation, and accelerated thickness growth of ex vivo-cultured calvariae. Overall, CXXC5 is a negative-feedback regulator induced by Wnt/ß-catenin signaling that inhibits osteoblast differentiation and bone formation via interaction with Dvl.

CT halo sign: the spectrum of pulmonary diseases.

The CT halo sign indicates ground glass attenuation surrounding a pulmonary nodule on CT. Although it was initially proposed as an early, specific finding of invasive pulmonary aspergillosis, it can be caused by many other pathological conditions such as infection, neoplastic and inflammatory diseases. The halo of ground glass attenuation pathologically represents pulmonary haemorrhage, tumour infiltration, or non-haemorrhagic inflammatory processes. Although non-specific, this sign is important because the clinical setting and associated radiological features may give a clue to the differential diagnosis. In this review, we demonstrate the spectrum of pulmonary diseases showing the "CT halo sign" on thin-section CT and discuss their radiological and clinical features.

Approaches to the fully functionalized DEF ring system of ristocetin A via highly selective ruthenium-promoted S(N)Ar reaction.

Ruthenium-promoted intramolecular S(N)Ar reaction has allowed the construction of the fully functionalized 16-membered DEF macrocycle 4 of ristocetin A that incorporates the required arylglycine and arylserine residues as the F and E ring, respectively.