Enhancement of the Gel Hardness of Candelilla Wax through the Addition of Long-chain Ester Wax Behenyl Behenate.

Candelilla wax (CW) is used as an oil-gelling agent in cosmetic sticks. However, its hardness is inadequate compared to those of hydrocarbon waxes such as paraffin. In this study, behenyl behenate (BB), an additive plant-derived wax ester with a high melting point, was shown to improve the oil-gel hardness of CW.Although the gel with BB alone had a relatively low gel hardness, when BB was mixed with CW at a ratio of 70:30 (CW:BB), the gel hardness significantly increased to four times that of the CW gel. The hardness of the CW and BB mixtures was higher than that of paraffin wax, which is used to solidify cosmetic oils. An increase in gel hardness was not observed when additives with chemical structures similar to those of BB, such as stearyl stearate (which has a lower molecular weight than BB) and behenic acid or behenyl alcohol (which are components of BB), were blended.Scanning electron microscopy indicated the presence of many spherical clusters comprising fine crystallites in the CW gel. This morphology was in contrast to that of paraffin wax gel, in which only plate crystals were observed. It was concluded that this heterogeneous structure led to the low gel hardness of CW. When BB was added to CW, the spherical clusters disappeared, and the internal structure changed to a homogeneous card-house structure composed of plate crystals.

Growth arrest specific protein 7 inhibits tau fibrillogenesis.

Here we show that Gas7 inhibits phosphorylated tau fibrillogenesis by binding to phosphorylated tau at its non-WW domain, presumably F-BAR domain. We revealed that Gas7 binds to the third repeat domain of tau, the core element of tau oligomerization and the C-terminal domain of tau and alters the conformation not to form fibrils. These results suggest that Gas7 may serve to protect against Alzheimer's disease and other tauopathies by preventing tau fibrillogenesis.

Prolyl Isomerase Pin1 Directly Regulates Calcium/Calmodulin-Dependent Protein Kinase II Activity in Mouse Brains.

Calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the brain and functions as a mediator of calcium signaling. We found that the relative activity of CaMKII was significantly lower in the WT mouse brains than in the Pin1-/- mouse brains. Pin1 binds to phosphorylated CaMKII and weakens its activity. For this reason, the phosphorylation level of tau in the presence of Pin1 is lower than that in the absence of Pin1, and microtubule polymerization is not downregulated by CaMKII when Pin1 is present. These results suggest a novel mechanism of action of Pin1 to prevent neurodegeneration.

Prolyl isomerase Pin1 promotes proplatelet formation of megakaryocytes via tau.

Here we show that Pin1, a peptidyl-prolyl cis/trans isomerase which catalyzes the isomerization of phosphorylated Ser/Thr-Pro, is a regulatory molecule of thrombopoiesis. We found that mice lacking the Pin1 gene (Pin1-/- mice) formed more megakaryocytes (MKs) than wild type mice (WT mice), and that the proplatelet formation of MKs was poorer in Pin1-/- mice than WT mice. Treatment of Meg-01 cells, a megakaryoblastic floating cell line, with shRNA against Pin1 suppressed the proplatelet formation. Expression of tau, a microtubule associated protein was induced in MKs during proplatelet formation. Pin1 bound tau and promoted microtubule polymerization. Our results show that Pin1 serves as a positive regulatory molecule of proplatelet formation of MKs by enhancing the function of phosphorylated tau.

Prolyl isomerase Pin1 regulates doxorubicin-inducible P-glycoprotein level by reducing Foxo3 stability.

It has been known that the phosphoSer/Thr-Pro-specific peptidyl prolyl cis/trans isomerase Pin1 regulates a variety of intracellular signaling pathways, including the response to the genotoxic drug doxorubicin. Pin1 binds phosphorylated p53 and stabilizes p53 to cause cell cycle arrest and apoptosis quickly in response to doxorubicin. Here we show another mechanism of Pin1 to maintain cell sensitivity to genotoxic stress, irrespective of whether p53 is present or not. In response to the genotoxic drug, Pin1 binds and decreases levels of the phosphorylated Foxo3, the positive transcription factor of P-glycoprotein (P-gp) gene. Through this mechanism of action, Pin1 decreases the level of P-gp and signals the cell to pump the genotoxic drugs out. This shows that Pin1 is implemented in maintaining the susceptibility to the genotoxic drugs by controlling P-gp level as well as p53-dependent apoptosis and cell cycle signaling pathways.

Visualization of NO3⁻/NO2⁻ Dynamics in Living Cells by Fluorescence Resonance Energy Transfer (FRET) Imaging Employing a Rhizobial Two-component Regulatory System.

Nitrate (NO3(-)) and nitrite (NO2(-)) are the physiological sources of nitric oxide (NO), a key biological messenger molecule. NO3(-)/NO2(-) exerts a beneficial impact on NO homeostasis and its related cardiovascular functions. To visualize the physiological dynamics of NO3(-)/NO2(-) for assessing the precise roles of these anions, we developed a genetically encoded intermolecular fluorescence resonance energy transfer (FRET)-based indicator, named sNOOOpy (sensor for NO3(-)/NO2(-) in physiology), by employing NO3(-)/NO2(-)-induced dissociation of NasST involved in the denitrification system of rhizobia. The in vitro use of sNOOOpy shows high specificity for NO3(-) and NO2(-), and its FRET signal is changed in response to NO3(-)/NO2(-) in the micromolar range. Furthermore, both an increase and decrease in cellular NO3(-) concentration can be detected. sNOOOpy is very simple and potentially applicable to a wide variety of living cells and is expected to provide insights into NO3(-)/NO2(-) dynamics in various organisms, including plants and animals.

Role of prolyl isomerase pin1 in pathogenesis of diseases and remedy for the diseases from natural products.

The peptidyl prolyl cis/trans isomerase Pin1, the human ortholog of yeast Ess1 specifically isomerizes peptide bindings of pSer/pThr-Pro residues in various proteins, and regulates the expression levels and functions of phosphorylated proteins. Activation of Pin1 is associated with pathology of a variety of diseases, such as cancer, Alzheimer's disease, infectious diseases and so on. Therefore, regulatory compounds for Pin1 can be applied as a clinical medicine against these diseases. Many chemists have exerted themselves to synthesize the inhibitors based on the 3D structure of Pin1. We have screened for the inhibitors against Pin1 from the natural products including the functional foods. Here we review the Pin1-associated pathology and the known inhibitors identified from natural products. And we introduce the screening methods targeting Pin1 activity.