Keratin is not only a Structural Protein in Hair: Keratin-mediated Hair Growth

Keratin is known to be a major protein in hair, but the biological function of keratin in hair growth is unknown, which led us to conduct a pilot study to elucidate biological function of keratin in hair growth via cellular interactions with hair forming cells. Here, we show hair growth is stimulated by intradermal injection of keratin into mice, and show that outer root sheath cells undergo transforming growth factor-β2-induced apoptosis, resulting in keratin exposure. Keratin exposure appears to be critical for dermal papilla cell condensation and hair germ formation as immunodepletion and silencing keratin prevent dermal papilla cell condensation and hair germ formation. Furthermore, silencing keratin in mice resulted in a marked suppression of anagen follicle formation and hair growth. Our study imply a new finding of how to initiate hair regeneration and suggests the potent application of keratin biomaterial for the treatment of hair loss.

The gravitational condensate of the higgs field

This paper analyses a method of producing the Higgs mass via the gravitational field. This approach has become very popular in recent years, as the consideration of other forces do not help in solving the problem of mass hierarchy. Not understand the difference between scales of the standard model and Grand unification theory. Here, we present a heuristic mechanism which eliminated this difference. The idea is that the density of the condensate of the Higgs is increased so that it is necessary to take into account self gravitational potential energy of the Higgs boson. The result is as follows. The mass of the Higgs is directly proportional to the cell density of the Higgs bosons. Or else the mass of the Higgs is inversely proportional to the cell volume, which is the Higgs boson in the condensate. The most interesting dimension of this cell condensation is equal to the scale of Grand unification. This formula naturally combines the scale of the standard model and Grand unification through gravitational condensation.

The gravitational condensate of the higgs field

This paper analyses a method of producing the Higgs mass via the gravitational field. This approach has become very popular in recent years, as the consideration of other forces do not help in solving the problem of mass hierarchy. Not understand the difference between scales of the standard model and Grand unification theory. Here, we present a heuristic mechanism which eliminated this difference. The idea is that the density of the condensate of the Higgs is increased so that it is necessary to take into account self gravitational potential energy of the Higgs boson. The result is as follows. The mass of the Higgs is directly proportional to the cell density of the Higgs bosons. Or else the mass of the Higgs is inversely proportional to the cell volume, which is the Higgs boson in the condensate. The most interesting dimension of this cell condensation is equal to the scale of Grand unification. This formula naturally combines the scale of the standard model and Grand unification through gravitational condensation.

Pds5 regulators segregate cohesion and condensation pathways in Saccharomyces cerevisiae

Cohesins are required both for the tethering together of sister chromatids (termed cohesion) and subsequent condensation into discrete structures—processes fundamental for faithful chromosome segregation into daughter cells. Differentiating between cohesin roles in cohesion and condensation would provide an important advance in studying chromatin metabolism. Pds5 is a cohesin-associated factor that is essential for both cohesion maintenance and condensation. Recent studies revealed that ELG1 deletion suppresses the temperature sensitivity of pds5 mutant cells. However, the mechanisms through which Elg1 may regulate cohesion and condensation remain unknown. Here, we report that ELG1 deletion from pds5-1 mutant cells results in a significant rescue of cohesion, but not condensation, defects. Based on evidence that Elg1 unloads the DNA replication clamp PCNA from DNA, we tested whether PCNA overexpression would similarly rescue pds5-1 mutant cell cohesion defects. The results indeed reveal that elevated levels of PCNA rescue pds5-1 temperature sensitivity and cohesion defects, but do not rescue pds5-1 mutant cell condensation defects. In contrast, RAD61 deletion rescues the condensation defect, but importantly, neither the temperature sensitivity nor cohesion defects exhibited by pds5-1 mutant cells. In combination, these findings reveal that cohesion and condensation are separable pathways and regulated in nonredundant mechanisms. These results are discussed in terms of a new model through which cohesion and condensation are spatially regulated.

TNF Induces Choroid Plexus Epithelial Cell Barrier Alterations by Apoptotic and Nonapoptotic Mechanisms

The choroid plexus epithelium constitutes the structural basis of the blood-cerebrospinal fluid barrier. Since the cytokine TNF is markedly increased during inflammatory diseases in the blood and the central nervous system, we investigated by which mechanisms TNF induces barrier alteration in porcine choroid plexus epithelial cells. We found a dose-dependent decrease of transepithelial electrical resistance, increase of paracellular inulin-flux, and induction of histone-associated DNA fragmentation and caspase-3 activation after TNF stimulation. This response was strongly aggravated by the addition of cycloheximide and could partially be inhibited by the NF-B inhibitor CAPE, but most effectively by the pan-caspase-inhibitor zVAD-fmk and not by the JNK inhibitor SP600125. Partial loss of cell viability could also be attenuated by CAPE. Immunostaining showed cell condensation and nuclear binding of high-mobility group box 1 protein as a sign of apoptosis after TNF stimulation. Taken together our findings indicate that TNF compromises PCPEC barrier function by caspase and NF-B dependent mechanisms.

Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer Cells

Cathepsin G is a serine protease secreted by activated neutrophils that play a role in the inflammatory response. Because neutrophils are known to be invading leukocytes in various tumors, their products may influence the characteristics of tumor cells such as the growth state, motility, and the adhesiveness between cells or the extracellular matrix. Here, we demonstrate that cathepsin G induces cell-cell adhesion of MCF-7 human breast cancer cells resulting from the contact inhibition of cell movement on fibronectin but not on type IV collagen. Cathepsin G subsequently induced cell condensation, a very compact cell colony, resulting due to the increased strength of E-cadherin-mediated cell-cell adhesion. Cathepsin G action is protease activity-dependent and was inhibited by the presence of serine protease inhibitors. Cathepsin G promotes E-cadherin/catenin complex formation and Rap1 activation in MCF-7 cells, which reportedly regulates E-cadherin-based cell-cell junctions. Cathepsin G also promotes E-cadherin/protein kinase D1 (PKD1) complex formation, and Go6976, the selective PKD1 inhibitor, suppressed the cathepsin G-induced cell condensation. Our findings provide the first evidence that cathepsin G regulates E-cadherin function, suggesting that cathepsin G has a novel modulatory role against tumor cell-cell adhesion.