This is the first report to implicate CRB1 as the underlying cause of FFR. This phenotype forms the mildest end of the spectrum of CRB1-related diseases.

No abstract

Diamond-Blackfan anemia is a congenital disorder of erythropoiesis in humans, characterized by a macrocytic anemia often associated with physical anomalies. Mutations at either the W or Steel loci in the mouse also leads to a severe macrocytic anemia, as well as other developmental abnormalities. The W locus encodes the proto-oncogene c- kit, a member of the receptor tyrosine kinase family, while the Steel locus encodes a potent hematopoietic growth factor that is the ligand for c-kit. Growth of clonogenic marrow erythroid progenitor cells in vitro in the presence of the recombinant hematopoietic growth factors interleukin-3 (IL-3) and Steel was used to characterize this disease at the cellular level. Three patterns of in vitro marrow response to both recombinant IL-3 or Steel were observed among 10 Diamond-Blackfan patients: those that responded quantitatively and qualitatively almost as well as cells from normal marrow, those that responded at an intermediate level, and those that did not respond at all. These results provide evidence for cellular heterogeneity underlying the pathogenesis of this disorder and therefore raise the possibility that there may be more than one underlying molecular basis for the disease. No gross abnormalities in the structure of either the c-kit or Steel loci were observed in these patients. The normal response in culture of the progenitor cells from at least some patients to Steel with or without IL-3 raises the possibility of using this novel growth factor as a therapeutic agent in Diamond-Blackfan anemia.

Dental implant failure remains a prevalent problem around the globe. The integration of implants at the interface of soft and hard tissues is complex and susceptible to instability and infections. Modifications to the surface of titanium implants have been developed to improve the performance, yet insufficient integration and biofilm formation remain major problems. Introducing nanostructures on the surface to augment the implant–tissue contact holds promise for facilitated implant integration; however, current coating processes are limited in their versatility or costs. We present a highly modular single-step approach to produce multicomponent porous bioactive nanostructured coatings on implants. Inorganic nanoparticle building blocks with complex compositions and architectures are synthesized in situ and deposited on the implants in a single step using scalable liquid-feed flame spray pyrolysis. We present hybrid coatings based on ceria and bioglass, which render the implant surfaces superhydrophilic, promote cell adhesion, and exhibit antimicrobial properties. By modifications to the bioglass/ceria nanohybrid composition and architecture that prevent biomineralization, the coating can instead be tailored toward soft tissue healing. The one-step synthesis of nano-architected tissue-specific coatings has great potential in dental implantology and beyond.