Summary Extended longevity is often correlated with increased resistance against various stressors. Insulin/IGF-1-like signaling (IIS) is known to have a conserved role in aging and cellular mechanisms against stress. In C. elegans, genetic studies suggest that heat-shock transcription factor HSF-1 is required for IIS to modulate longevity. Here we report that the activity of HSF-1 is regulated by IIS. This regulation might occur at an early step of HSF-1 activation via two HSF-1 regulators, DDL-1 and DDL-2. Inhibition of DDL-1/2 increases longevity and thermotolerance in an hsf-1 dependent manner. Furthermore, biochemical analyses suggest that DDL-1/2 negatively regulates HSF-1 activity by forming a protein complex with HSF-1. The formation of this complex (DHIC) is affected by the phosphorylation status of DDL-1. Both the formation of DHIC and the phosphorylation of DDL-1 are controlled by IIS. Therefore, DDL-1/2 may serve as the link between IIS and HSF-1 pathway.

Evolution of supramolecular chirality from self-assembly of achiral compounds and control over its handedness is closely related to the evolution of life and development of supramolecular materials with desired handedness. Here we report a system where the entire process of induction, control and locking of supramolecular chirality can be manipulated by light. Combination of triphenylamine and diacetylene moieties in the molecular structure allows photoinduced self-assembly of the molecule into helical aggregates in a chlorinated solvent by visible light and covalent fixation of the aggregate via photopolymerization by ultraviolet light, respectively. By using visible circularly polarized light, the supramolecular chirality of the resulting aggregates is selectively and reversibly controlled by its rotational direction, and the desired supramolecular chirality can be arrested by irradiation with ultraviolet circularly polarized light. This methodology opens a route to ward the formation of supramolecular chiral conducting nanostructures from the self-assembly of achiral molecules.

The capability of assembling nanoparticles into a desired ordered pattern is a key to realize novel devices which are based not only on the unique properties of nanoparticles but also on the arrangements of nanoparticles. While two-dimensional arrays of nanoparticles have been successfully demonstrated by various techniques, a controlled way of building ordered arrays of three-dimensional (3D) nanoparticle structures remains challenging. We report that a variety of 3D nanoparticle structures can be formed in a controlled way based on the ion-induced focusing, electrical scaffold, and antenna effects from charged aerosols. Particle trajectory calculations successfully predict the whole process of 3D assembly. New surface enhanced Raman scattering substrates based on our 3D assembly were constructed as an example showing the viability of the present approach. This report extends the current capability of positioning nanoparticles on surface to another spatial dimension, which can serve as the foundation of future optical, magnetic, and electronic devices taking the advantage of multidimensions.

In Saccharomyces cerevisiae, heme directly mediates the effects of oxygen on transcription through the heme activator protein Hap1. In the absence of heme, Hap1 is bound by at least four cellular proteins, including Hsp90 and Ydj1, forming a higher-order complex, termed HMC, and its activity is repressed. Here we purified the HMC and showed by mass spectrometry that two previously unidentified major components of the HMC are the Ssa-type Hsp70 molecular chaperone and Sro9 proteins. In vivo functional analysis, combined with biochemical analysis, strongly suggests that Ssa proteins are critical for Hap1 repression in the absence of heme. Ssa may repress the activities of both Hap1 DNA-binding and activation domains. The Ssa cochaperones Ydj1 and Sro9 appear to assist Ssa in Hap1 repression, and only Ydj1 residues 1 to 172 containing the J domain are required for Hap1 repression. Our results suggest that Ssa-Ydj1 and Sro9 act together to mediate Hap1 repression in the absence of heme and that molecular chaperones promote heme regulation of Hap1 by a mechanism distinct from the mechanism of steroid signaling.

We previously reported that lysozyme accounts for anti-HIV activity associated with the beta-core fraction of human chorionic gonadotropin [Lee-Huang, S., Huang, P. L., Sun, Y., Kung, H. F., Blithe, D. L. & Chen, H. C. (1999) Proc Natl Acad Sci U S A 96, 2678-81]. To define the structural and sequence requirements for anti-HIV activity, we carried out peptide fragmentation and activity mapping of human lysozyme. We identified two peptides that consist of 18 and 9 amino acids of human lysozyme (HL18 and HL9), corresponding to residues 98-115 and 107-115. HL18 and HL9 are potent inhibitors of HIV-1 infection and replication with EC(50)s of 50 to 55 nM, comparable to intact lysozyme. Scrambling the sequence or substitution of key arginine or tryptophan residues results in loss of antiviral activity. HL9, with the sequence RAWVAWRNR, is the smallest peptide we identified with full anti-HIV activity. It forms a pocket with its basic residues on the surface of the molecule. HL9 exists as an alpha-helix in native human lysozyme, in a region of the protein distinct from the muramidase catalytic site. Monte Carlo peptide folding energy minimizing simulation modeling and CD studies indicate that helical propensity does not correlate with antiviral activity. HL9 blocks HIV-1 viral entrance and replication, and modulates gene expression of HIV-infected cells, affecting pathways involved in survival, stress, TGFbeta, p53, NFkappaB, protein kinase C and hedgehog signaling.