The ins and outs of spin: Using the microporous coordination polymer {Fe(pz)[Pt(CN)(4)]} (1, pz=pyrazine), incorporating spin-crossover subunits, two-directional magnetic chemo-switching is achieved at room temperature. In situ magnetic measurements following guest vapor injection show that most guest molecules transform 1 from the low-spin (LS) state to the high-spin (HS) state, whereas CS(2) uniquely causes the reverse HS-to-LS transition.

No abstract

Phorbol esters, the activators of protein kinase C (PKC), induce apoptosis in androgen-sensitive LNCaP prostate cancer cells. The role of individual PKC isozymes as mediators of this effect has not been thoroughly examined to date. To study the involvement of the novel isozyme PKC␦, we used a replication-deficient adenovirus (PKC␦AdV), which allowed for a tightly controlled expression of PKC␦ in LNCaP cells. A significant reduction in cell number was observed after infection of LNCaP cells with PKC␦AdV. Overexpression of PKC␦ markedly enhanced the apoptotic effect of phorbol 12-myristate 13-acetate in LNCaP cells. PKC␦-mediated apoptosis was substantially reduced by the pan-caspase inhibitor z-VAD and by Bcl-2 overexpression. Importantly, and contrary to other cell types, PKC␦-mediated apoptosis does not involve its proteolytic cleavage by caspase-3, suggesting that allosteric activation of PKC␦ is sufficient to trigger apoptosis in LNCaP cells. In addition, phorbol ester-induced apoptosis was blocked by a kinase-deficient mutant of PKC␦, supporting the concept that PKC␦ plays an important role in the regulation of apoptotic cell death in LNCaP prostate cancer cells.

Abstract. TGF-B1 controls the expression of numerous genes, including early response and cellular matrix genes. However, the signal-transducing mechanism underlying this regulation of gene expression is not fully understood. In this study, we investigated whether redox regulation plays a role in the TGF-/31 signal transduction in the mouse osteoblastic cell line (MC3T3-E1). The overall intracellular oxidized state of the cells, when measured using 2',7'-dichlorofluorescin diacetate by laser-scanning confocal microscopy, was increased transiently after the addition of TGF-/~ 1. This increase was abolished by the addition of oxygen radical scavengers such as catalase and N-acetylcysteine. In a variant cell line lacking the TGF-B1 receptor, the intracellular oxidized state was not modulated by treatment with TGF-fll. We then examined the expression of early growth response-1 (egr-1) gene, which is inducible by TGF-fll and H202. Radical scavengers inhibited the induction of egr-1 by TGFill, but not that by 12-O-tetradecanoylphorbol-13 acetate. A nuclear run-on assay indicated that this inhibition was at the transcriptional level. From transient expression experiments using chloramphenicol acetyltransferase gene linked to serially deleted egr-1 gene 5'-upstream region, the CArG element in the 5' flanking region of egr-1 was identified as an essential sequence in the transcriptional activation for both TGF-fll and H202 stimulation. These findings suggest that H202 acts as a mediator for the TGF-Bl-induced transcription of egr-1 gene.

No abstract

We controlled the hydrophilicity of metal-organic frameworks (MOFs) to achieve high proton conductivity and high adsorption of water under low humidity conditions, by employing novel class of MOFs, {NR(3)(CH(2)COOH)}[MCr(ox)(3)]·nH(2)O (abbreviated as R-MCr, where R = Me (methyl), Et (ethyl), or Bu (n-butyl), and M = Mn or Fe): Me-FeCr, Et-MnCr, Bu-MnCr, and Bu-FeCr. The cationic components have a carboxyl group that functions as the proton carrier. The hydrophilicity of the cationic ions was tuned by the NR(3) residue to decrease with increasing bulkiness of the residue: {NMe(3)(CH(2)COOH)}(+) > {NEt(3)(CH(2)COOH)}(+) > {NBu(3)(CH(2)COOH)}(+). The proton conduction of the MOFs increased with increasing hydrophilicity of the cationic ions. The most hydrophilic sample, Me-FeCr, adsorbed a large number of water molecules and showed a high proton conductivity of ~10(-4) S cm(-1), even at a low humidity of 65% relative humidity (RH), at ambient temperature. Notably, this is the highest conductivity among the previously reported proton-conducting MOFs that operate under low RH conditions.

Protein kinase C (PKC) plays a crucial role(s) in regulation of growth and differentiation of cells. In the present study, we examined possible roles of the ␣, ␦, , and isoforms of PKC in squamous differentiation by overexpressing these genes in normal human keratinocytes. Because of the difficulty of introducing foreign genes into keratinocytes, we used an adenovirus vector system, Ax, which allows expression of these genes at a

In the past two decades, several molecular targeted inhibitors have been developed and evaluated clinically to improve the survival of patients with cancer. Molecular targeted inhibitors inhibit the activities of pathogenic tyrosine kinases. Particularly, aberrant receptor tyrosine kinase (RTK) activation is a potential therapeutic target. An increased understanding of genetics, cellular biology and structural biology has led to the development of numerous important therapeutics. Pathogenic RTK mutations, deletions, translocations and amplification/over-expressions have been identified and are currently being examined for their roles in cancers. Therapies targeting RTKs are categorized as small-molecule inhibitors and monoclonal antibodies. Studies are underway to explore abnormalities in 20 types of RTK subfamilies in patients with cancer or other diseases. In this review, we describe representative RTKs important for developing cancer therapeutics and predicting or evaluated resistance mechanisms.