No abstract

Hair thinning and loss are prominent aging phenotypes but have an unknown mechanism. We show that hair follicle stem cell (HFSC) aging causes the stepwise miniaturization of hair follicles and eventual hair loss in wild-type mice and in humans. In vivo fate analysis of HFSCs revealed that the DNA damage response in HFSCs causes proteolysis of type XVII collagen (COL17A1/BP180), a critical molecule for HFSC maintenance, to trigger HFSC aging, characterized by the loss of stemness signatures and by epidermal commitment. Aged HFSCs are cyclically eliminated from the skin through terminal epidermal differentiation, thereby causing hair follicle miniaturization. The aging process can be recapitulated by Col17a1 deficiency and prevented by the forced maintenance of COL17A1 in HFSCs, demonstrating that COL17A1 in HFSCs orchestrates the stem cell-centric aging program of the epithelial mini-organ.

To understand the mechanism of noble-metal adhesion in wet processes, the behavior ol Cu adhesion to the Si surface in various chemical solutions, the shape and chemical composition of Cu contaminants adhering to Si surfaces, the surface microroughness of Si surfaces, and the influence of the type of the substrates are investigated. The results show that Cu ion deposits on the Si surface in the form of metallic particles in wet chemical processing, that Cu deposition in HF solutions causes pits to be formed on the Si surface, and that, on a patterned substrate, Cu deposits on the Si surface but not on the SiO2 surface. The experimental results imply a Cu deposition mechanism. In a dilute HF solution, the Si surface beneath the Cu particles is etched away to become SiF~ and a pit is made. Contamination with noble metals is critical. The mechanism for metal deposition may apply to noble metals in general. These metallic impurities must not be introduced into any wet chemical solution or ultrapure water when a bare Si surface is exposed.With continued advances in ultralarge scale integrated (ULSI) fabrication technology, achieving ultraclean wafer surfaces is essential. An ultraclean wafer surface is characterized as a surface which is (i) particle-free, (it) organic contamination-free, (iii) metallic contamination-free, (iv) native oxide-free, (v) completely hydrogen-terminated, and (vi) surface microroughness-free. I It is well known that the metallic contamination on the Si surface can cause fatal effects on semiconductor devices such as: increase the current leakage at the p-n junction, decrease the oxide * Electrochemical Society Active Member.

No abstract

Cellular reprogramming involves profound alterations in genome-wide gene expression that is precisely controlled by a hypothetical epigenetic code. Small molecules have been shown to artificially induce epigenetic modifications in a sequence independent manner. Recently, we showed that specific DNA binding hairpin pyrrole-imidazole polyamides (PIPs) could be conjugated with chromatin modifying histone deacetylase inhibitors like SAHA to epigenetically activate certain pluripotent genes in mouse fibroblasts. In our steadfast progress to improve the efficiency of SAHA-PIPs, we identified a novel compound termed, δ that could dramatically induce the endogenous expression of Oct-3/4 and Nanog. Genome-wide gene analysis suggests that in just 24 h and at nM concentration, δ induced multiple pluripotency-associated genes including Rex1 and Cdh1 by more than ten-fold. δ treated MEFs also rapidly overcame the rate-limiting step of epithelial transition in cellular reprogramming by switching “” the complex transcriptional gene network.