Multipotent skin stem cells give rise to epidermis and its appendages, including the hair follicle. The Lef-1/Tcf family of Wnt-regulated transcription factors plays a major role in specification of the hair shaft, but little is known about how the equally important hair channel, the inner root sheath (IRS), develops in concert to shape and guide the hair. In a microarray screen to search for transcriptional regulators of hair follicle morphogenesis, we identified GATA-3, a key regulator of T-cell lineage determination. Surprisingly, this transcription factor is essential for stem cell lineage determination in skin, where it is expressed at the onset of epidermal stratification and IRS specification in follicles. GATA-3-null/lacZ knock-in embryos can survive up to embryonic day 18.5 (E18.5), when they fail to form the IRS. Skin grafting unveiled additional defects in GATA-3-null hairs and follicles. IRS progenitors failed to differentiate, whereas cortical progenitors differentiated, but produced an aberrant hair structure. Curiously, some GATA-3-null progenitor cells expressed mixed IRS and hair shaft markers. Taken together, these findings place GATA-3 with Lef-1/Wnts at the crossroads of the IRS versus hair shaft cell fate decision in hair follicle morphogenesis. This newfound function for GATA-3 in skin development strengthens the parallels between the differentiation programs governing hair follicle and lymphocyte differentiation.
Polydopamine (PDA) coating provides a promising approach for immobilization of biomolecules onto almost all kinds of solid substrates. However, the deposition kinetics of PDA coating as a function of temperature and reaction method is not well elucidated. Since dopamine self-polymerization usually takes a long time, therefore, rapid-formation of PDA film becomes imperative for surface modification of biomaterials and medical devices. In the present study, a practical method for preparation of rapidly-deposited PDA coating was developed using a uniquely designed device, and the kinetics of dopamine self-polymerization was investigated by QCM sensor system. It was found that high temperature and vigorous stirring could dramatically speed up the formation of PDA film on QCM chip surface. Surface characterization, BSA binding study, cell viability assay and antibacterial test demonstrates that the polydopamine coating after polymerization for 30 min by our approach exhibits similar properties to those of 24 h counterpart. The method has a great potential for rapid-deposition of polydopamine films to modify biomaterial surfaces.
Implant-associated infections, which are normally induced by microbial adhesion and subsequent biofilm formation, are a major cause of morbidity and mortality. Therefore, practical approaches to prevent implant-associated infections are in great demand. Inspired by adhesive proteins in mussels, here we have developed a novel antibiotic-decorated titanium (Ti) material with enhanced antibacterial activity. In this study, Ti substrate was coated by one-step pH-induced polymerization of dopamine followed by immobilization of the antibiotic cefotaxime sodium (CS) onto the polydopamine-coated Ti through catechol chemistry. Contact angle measurement and X-ray photoelectron spectroscopy confirmed the presence of CS grafted on the Ti surface. Our results demonstrated that the antibiotic-grafted Ti substrate showed good biocompatibility and well-behaved haemocompatibility. In addition, the antibiotic-grafted Ti could effectively prevent adhesion and proliferation of Escherichia coli (Gram-negative) and Streptococcus mutans (Gram-positive). Moreover, the inhibition of biofilm formation on the antibiotic-decorated Ti indicated that the grafted CS could maintain its long-term antibacterial activity. This modified Ti substrate with enhanced antibacterial activity holds great potential as implant material for applications in dental and bone graft substitutes.
Positive ion mode matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was used to explore nonspecific interactions between proteins and oligonucleotides. The formation of noncovalent complexes showed correlation with the type of oligonucleotide bases and with the amino acid composition of the proteins. Among the four DNA homooligomers, abundant protein-nucleic acid complexes were detected for pd(T)n, whereas negligible attachment was evident for pd(A)n, pd(C)n, and pd(G)n. Mixed base sequence nucleic acids (pd(AGCTCAGCTT) and d(TTAGCAGCTT) also showed affinity to Arg-Lys. The protein affinity of pd(T)n turned out to be nonspecific and produced a larger variety of complexes when the number of basic residues in the protein was increased. Complexation of pd(T)n with small basic dipeptides (Arg-Lys or His-His) led to significant improvement in the mass resolution for positive ions. For example, the mass resolution of the pd(T)20/Arg-Lys complex exhibited about 4 times improvement over pd(T)20 alone. The protein--oligonucleotide interactions were also pH and matrix dependent. Lowering the pH from its original value (pH = 1.7) led to diminishing complex related signal, whereas increasing the pH resulted in the appearance of a larger variety of complexes. 2,5-Dihydroxybenzoic acid matrix demonstrated much greater tendency to produce complex ions than did the three other matrix materials we tested. A possible explanation of the observed phenomena was based on pH-controlled ion pair formation between oligonucleotides and proteins.
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