Capsaicin, a pungent ingredient of hot peppers, causes excitation of small sensory neurons, and thereby produces severe pain. A nonselective cation channel activated by capsaicin has been identified in sensory neurons and a cDNA encoding the channel has been cloned recently. However, an endogenous activator of the receptor has not yet been found. In this study, we show that several products of lipoxygenases directly activate the capsaicinactivated channel in isolated membrane patches of sensory neurons. Among them, 12-and 15-(S)-hydroperoxyeicosatetraenoic acids, 5-and 15-(S)-hydroxyeicosatetraenoic acids, and leukotriene B4 possessed the highest potency. The eicosanoids also activated the cloned capsaicin receptor (VR1) expressed in HEK cells. Prostaglandins and unsaturated fatty acids failed to activate the channel. These results suggest a novel signaling mechanism underlying the pain sensory transduction.

Adult neurogenesis occurs in mammals and provides a mechanism for continuous neural plasticity in the brain. However, little is known about the molecular mechanisms regulating hippocampal neural progenitor cells (NPCs) and whether their fate can be pharmacologically modulated to improve neural plasticity and regeneration. Here, we report the characterization of a small molecule (KHS101) that selectively induces a neuronal differentiation phenotype. Mechanism of action studies revealed a link of KHS101 to cell cycle exit and specific binding to the TACC3 protein, whose knockdown in NPCs recapitulates the KHS101-induced phenotype. Upon systemic administration, KHS101 distributed to the brain and resulted in a significant increase in neuronal differentiation in vivo. Our findings indicate that KHS101 accelerates neuronal differentiation by interaction with TACC3 and may provide a basis for pharmacological intervention directed at endogenous NPCs.

Tantalum (Ta) and tantalum nitride films (Ta2N and TaN) of about 50 nm thickness were reactively sputter deposited onto (100) Si substrate by using dc magnetron sputtering and their diffusion barrier properties in between Cu and Si were investigated by using sheet resistance measurement, x-ray diffraction, Auger electron spectroscopy, and Secco etching. With increasing amounts of nitrogen in the sputtering gas, the phases in the as-deposited film have been identified as a mixture of β-Ta and bcc-Ta, bcc-Ta, amorphous Ta2N, and crystalline fcc-TaN. Diffusion barrier tests indicate that there are two competing mechanisms for the barrier failure; one is the migration of Cu into the Si substrate and another is the interfacial reaction between the barrier layer and the Si substrate. For instance, we identified that elemental Ta barrier failure occurs initially by the diffusion of Cu into the Si substrate through the barrier layer at 500 °C. On the other hand, the Ta2N barrier fails at 700 °C by the interfacial reaction between Ta2N and Si substrate instead of the migration of Cu into the Si substrate. For the case of TaN, the barrier failure occurs by the migration of Cu into the Si substrate at 750 °C. It is also demonstrated that the diffusion barrier property is enhanced as the nitrogen concentration in the film is increased.

Brain power: An image‐based screen of a chemical library was carried out to identify molecules that regulate the differentiation of adult rat hippocampal neural stem cells. Neuropathiazol (1) induces selective neuronal differentiation and competitively suppresses astrocyte differentiation. This compound should be a useful tool to study the processes that control stem‐cell fate both in vitro and in vivo.

MiRNAs have shown to regulate aging process at the level of cellular senescence, tissue aging, and lifespan of whole organism. Given that many miRNAs also function as important regulators of hematopoietic system as well as aging process, it is highly likely that miRNAs would be involved in the changes of myeloid function and differentiation during aging. Therefore, here we examine differential expression of miRNAs in aged myeloid lineage cells and assess if altered miRNA expression pattern would reflect the change of miRNA targets and related function. We demonstrated that the expressions of myelogenic miRNAs such as miR-155, miR-223, miR-146a, miR-146b, miR-132, miR-142-5p, and miR-142-3p were increased in aged bone marrow derived dendritic cells (BMDC) under normal and activated conditions. We also observed that the expressions of IRAK1 and TRAF6, the targets of miR-146a, and DC-SIGN, a target of miR-155 were diminished while miR-146a and miR-155 were augmented during aging. In addition, we found that the production of pro-inflammatory cytokines, which is mediated by the activation of NF-kB pathway via IRAK1 and TRAF6, was greatly reduced in aged BMDC. Taken together, our data reveal that age-associated changes occur in miRNA expression in BMDC, and this altered miRNA expression affects miRNA target expression and compromises BMDC function such as cytokine production during aging.