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Layered rare-earth hydroxide crystallites self-assembled at the hexane/water interface were transferred to various substrates to form a monolayer film, which exhibited photoluminescence properties and ion-exchange ability.

Covalent modification of histones by ubiquitylation is a prominent epigenetic mark that features in a variety of chromatin-based events such as histone methylation, gene silencing, and repair of DNA damage. The prototypical example of histone ubiquitylation is that of histone H2B in Saccharomyces cerevisiae. In this case, attachment of ubiquitin to lysine 123 (K123) of H2B is important for regulation of both active and transcriptionally silent genes and participates in trans to signal methylation of histone H3. It is generally assumed that H2B is monoubiquitylated at K123 and that it is this single ubiquitin moiety that influences H2B function. To determine whether this assumption is correct, we have re-examined the ubiquitylation status of endogenous H2B in yeast. We find that, contrary to expectations, H2B is extensively polyubiquitylated. Polyubiquitylation of H2B appears to occur within the context of chromatin and is not associated with H2B destruction. There are at least two distinct modes of H2B polyubiquitylation: one that occurs at K123 and depends on the Rad6-Bre1 ubiquitylation machinery and another that occurs on multiple lysine residues and is catalyzed by an uncharacterized ubiquitin ligase(s). Interestingly, these ubiquitylation events are under the influence of different combinations of ubiquitin-specific proteases, suggesting that they have distinct biological functions. These results raise the possibility that some of the biological effects of ubiquitylation of H2B are exerted via ubiquitin chains, rather than a single ubiquitin group.

We report the synthesis of a new series of layered hydroxides based on rare-earth elements with a composition of RE(OH)2.5Cl(0.5).0.8 H2O (RE: Eu, Tb, etc.) through the homogeneous precipitation of RECl3.x H2O with hexamethylenetetramine (HMT). Rietveld analysis combined with direct methods revealed an orthorhombic layered structure comprising a positively charged layer of [RE(OH)2.5-(H2O)0.8]0.5+ and interlayer Cl- ions. The Cl- ions were readily exchangeable for various anions (NO3-, SO4(2-), dodecylsulfonate, etc.) at ambient temperature. Photoluminescence studies showed that the compounds display typical RE3+ emission. With rare-earth-based host layers and tunable interlayer guests, the new compounds may be of interest for optoelectronic, magnetic, catalytic, and biomedical materials.

Regulation of transcription is a critically important process that controls development, differentiation, and the maintenance of cellular homeostasis. Cells have evolved numerous mechanisms to keep gene transcription tightly in check, some of which involve the ubiquitin-proteasome system. In this chapter, we review evidence supporting the concept that ubiquitin and the proteasome not only control transcription, but provide the biochemical means to drive key steps in the transcription process forward.

ZnS nanostructures with different morphologies of submicrospheres, nanosheets and nanorods were synthesized by solution precipitation of thiourea with Zn(NO(3))(2) in the presence of block copolymer at low temperature. The sizes and morphologies of ZnS can be controlled simply by changing the processing parameters. The results show that the ZnS submicrospheres are of 250-500 nm in diameter, nanosheets are 2.5 µm × 5.5 µm with an estimated thickness of 20-30 nm, and nanorods are 2-5 nm in diameter and 10-30 nm in length. Keeping the precursor system in an autoclave at 105 °C results in the formation of ZnS submicrospheres; ultrasonication and keeping the system at room temperature leads to the formation of ZnS nanosheets; and long-time continuous ultrasonication and keeping the system in an autoclave at 105 °C induces the formation of uniform ZnS nanorods. We argue that the reaction temperature and P123 may play crucial roles in the formation of three ZnS structures in this work. The morphologically controllable synthesis strategies may be extended to the shape-controlled production of nanostructures of other inorganic materials.

Aim: To develop and optimize a sustained release multivesicular liposome (MVL) formulation of interferon (IFN) alpha-2b., Methods: IFN alpha-2b MVL were prepared using a typical double-emulsion procedure. The sustained release effects of IFN alpha-2b MVL were investigated by monitoring the blood IFN alpha-2b concentration using an enzyme-linked immunosorbent assay test after subcutaneous administration to healthy mice., Results: IFN alpha-2b was successfully encapsulated in MVL with high efficiency, and the integrity of encapsulated protein was maintained. After subcutaneous injection, the MVL slowly released IFN alpha-2b into systemic circulation in a sustained manner. The estimated serum half-life of IFN alpha-2b was approximately 30 h. In addition, varying the size of the MVL preparations could further modify the in vivo release profile., Conclusion: IFN alpha-2b MVL may be a useful sustained release formulation in the clinical treatment of viral diseases.

In this study, significantly higher expression of Gal3ST-2 (Gal: 3-O-sulfotransferase-2) and 3'-sulfated glycoconjugates were observed in highly metastastic cancer cells and in larynx cancer tissues with lymph node metastasis than those in lowly metastatic cancer cells and larynx cancer tissues without metastasis (P<0.01, n=42). These results indicated that there was a marked correlation between the expression of Gal3ST-2 and tumor metastasis potential. After RNAi transfection, a striking morphological change of SMMC7721 hepatoma cells from polygon to shuttle shape and significant decrease in adhesion to sL-selectin and HUVEC were observed. Interestingly, the expression of integrin subunit alphaV was markedly downregulated and 3'-sulfated subunit alphaV almost disappeared in the transfectants, but integrin subunit beta3 almost had no change. These results suggested that Gal3ST-2 was involved in tumor metastasis process by regulation of adhesion ability to selectins and expression of integrins.

Micro/nano-particle drug delivery systems are being developed for improving therapeutic effects. However, most studies can only evaluate the delivery properties by indirectly measuring the pharmacokinetic changes of the drugs. It had been difficult to directly assay the drug carrier status and distribution in vivo. We described here a method using intravital microscopy to visualize individual drug carriers traveling through blood vessels. The transportation and extravasation process of these particles were monitored. The in vivo distribution patterns were also confirmed by fluorescence microscopy studies of the various tissue samples.

A liposomal CT contrast formulation with high iodine loading capacity was developed. The multivesicular liposome (MVL) structure was adopted and the encapsulated iodine concentrations were higher than 50mg/ml. Small MVLs were made with mean diameter at less than 5 micron. They were shown to distribute evenly in the hepatic sinusoid between hepatic plates and the endothelium after intravenous injection. A significant and persistent enhancement of CT value in the liver was observed in CT imaging studies. Compared to conventional extracellular iodine agents Iohexol, the MVL formulation is easier to administer, requires much lower doses, however the resulted liver imaging enhancement is greater and last longer. Therefore, we believe it has great potentials as a new and superior contrast enhancement agent for CT imaging of the liver.

It is well documented that the glycosylation of E-cadherin is correlated with cancer metastasis, but whether E-cadherin could be core fucosylated remains largely unknown. We found that E-cadherin was core fucosylated in highly metastatic lung cancer cells while absent in lowly metastatic lung cancer cells. Since alpha-1,6 Fucosyltransferase (alpha-1,6 FucT) is known to catalyze the reaction of core fucosylation, we investigated the biological function of core fucosylation on E-cadherin by alpha-1,6 FucT targeted RNAi and transfecting alpha-1,6 FucT expression vector. As a result, calcium dependent cell-cell adhesion mediated by E-cadherin was strengthened with the reduction of core fucosylation on E-cadherin after RNAi and was weakened with the elevated core fucosylation on E-cadherin after alpha-1,6 FucT over expression. Our data indicated that alpha-1,6 FucT could regulate E-cadherin mediated cell adhesion and thus play an important role in cancer development and progression. Computer modeling showed that core fucosylation on E-cadherin could significantly impair three-dimensional conformation of N-glycan on E-cadherin and produce conformational asymmetry so as to suppress the function of E-cadherin. Furthermore, the relationship between the expression of core fucosylated E-cadherin and clinicopathological background of lung cancer patients was explored in lung cancer tissue of patients. It turns out to demonstrate that core fucosylated E-cadherin could serve as a promising prognostic indicator for lung cancer patients.

Eucaryotic gene expression requires chromatin-remodeling activities. We show by time-course studies that transcriptional induction of the yeast glucose-regulated SUC2 gene is rapid and shows a striking biphasic pattern, the first phase of which is partly mediated by the general stress transcription factors Msn2p/Msn4p. The SWI/SNF ATP-dependent chromatin-remodeling complex associates with the promoter in a similar biphasic manner and is essential for both phases of transcription. Two different histone acetyltransferases, Gcn5p and Esa1p, enhance the binding of SWI/SNF to the promoter during early transcription and are required for optimal SUC2 induction. Gcn5p is recruited to SUC2 simultaneously with SWI/SNF, whereas Esa1p associates constitutively with the promoter. This study reveals an unusual transcription pattern of a metabolic gene and suggests a novel strategy by which distinct chromatin remodelers cooperate for the dynamic activation of transcription.

The paper develops two-dimensional (2D), nonseparable, piecewise cubic convolution (PCC) for image interpolation. Traditionally, PCC has been implemented based on a one-dimensional (1D) derivation with a separable generalization to two dimensions. However, typical scenes and imaging systems are not separable, so the traditional approach is suboptimal. We develop a closed-form derivation for a two-parameter, 2D PCC kernel with support [-2,2] x [-2,2] that is constrained for continuity, smoothness, symmetry, and flat-field response. Our analyses, using several image models, including Markov random fields, demonstrate that the 2D PCC yields small improvements in interpolation fidelity over the traditional, separable approach. The constraints on the derivation can be relaxed to provide greater flexibility and performance.

[reaction: see text] The sequential addition of 5-methylcyclopentyllithium and propynyllithium to diisopropyl squarate results in the efficient formation of a functionalized angular triquinane having two of its five-membered rings substituted precisely as in the target sesquiterpene. Only seven additional steps are then required to access pentalenene.

[structure: see text] A highly convergent synthesis of the proposed structure of amphidinolide A is reported. Instructive applications of several organometallic processes are illustrated, including a highly selective ring-closing metathesis reaction.

The first applications of the squarate ester cascade to natural products synthesis have been realized. Only 10 laboratory steps mediate the conversion of diisopropyl squarate to (+/-)-hypnophilin (8). Key reactions include a combination of chlorination, reduction, dehydration, and oxidation maneuvers in the proper sequence. A penultimate precursor to 8 has previously been converted into coriolin (9), thereby allowing a formal synthesis of racemic 9 also to be claimed. A rather different strategy was employed to arrive at (+/-)-ceratopicanol (10). Of the seven steps involved, three consisted of the use of lithium in liquid ammonia. The three divergent synthetic objectives realized in these experiments involved (a) generation of an extended enolate anion and its regioselective C-methylation at the gamma-carbon; (b) unprecedented reductive cleavage of a beta-isopropoxy group in a 2,3-diisopropoxy-2-cyclopentenone setting; and (c) conventional conversion of an alpha-alkoxy ketone to the parent carbonyl system. Thus, the appreciable enhancement in structural complexity offered by the squarate cascade holds considerable potential for the concise synthesis of constitutionally intricate targets.

[reaction: see text] A squarate ester cascade is used to provide in one step, via the coupling of three reactants, a highly oxygenated linear triquinane product. The latter is transformed in nine steps into hypnophilin. The access route involves a combination of chlorination, reduction, dehydration, and oxidation maneuvers in the proper sequence.

Snf-Swi, the prototypical ATP-dependent nucleosome-remodeling complex, regulates transcription of a subset of yeast genes. With the exception of Snf2p, the ATPase subunit, the functions of the other components are unknown. We have investigated the role of the conserved Snf-Swi core subunit Snf5p through characterization of two conditional snf5 mutants. The mutants contain single amino acid alterations of invariant or conserved residues that abolish Snf-Swi-dependent transcription by distinct mechanisms. One mutation impairs Snf-Swi assembly and, consequently, its stable association with a target promoter. The other blocks a postrecruitment catalytic remodeling step. These findings suggest that Snf5p coordinates the assembly and nucleosome-remodeling activities of Snf-Swi.

[formula: see text] Lewis acid-catalyzed reaction of allyl and benzyl trichloroacetimidates with alpha-silyl alcohols was found to be a general method for the synthesis of alpha-alkoxysilanes. Upon exposure to CsF, these alpha-alkoxysilanes could be made to undergo [2,3]-Wittig rearrangement with an efficiency similar to that realized by the analogous but inherently more toxic alpha-alkoxystannanes.

[formula: see text] The Wittig rearrangements of alpha-alkoxysilanes, promoted by the action of methyllithium were studied. Depending on both the substrate and reaction conditions employed, [2,3]-, [1,2]-, or [1,4]-Wittig rearrangements can be realized. These rearrangements were shown to be initiated by either Si/Li exchange or deprotonation alpha to the silane. Furthermore the sigmatropic shifts can often be followed by other synthetically useful in situ chemical events.

To further understand the folding of nascent peptide during the early course of peptide synthesis, two short N-terminal fragments of staphylococcal nuclease R (SNase R), SNR52 and SNR79, were made by deleting 97 and 70 amino acid residues from the C-terminus. The conformations of SNR52 and SNR79 were studied by FTIR and far-ultraviolet CD. The results demonstrate that even the short N-terminal fragments of SNase R still have a certain amount of residual ordered secondary structure in the physiological condition. The ordered secondary structures were mainly assigned as beta-strands and turns, which corresponds well to the structures of the N-terminal part in the native protein. The conformational changes during unfolding and refolding in different concentrations of guanidine hydrochloride (GuHCl), monitored by far-ultraviolet CD and intrinsic fluorescence, show that the interaction between amino acid residues, which governs the formation of their conformation are not random. Considered together with earlier studies (Jing et al., Biochim Biophys Acta 1995;1250:189-196; Zhou et al., J Biochem 1996:120: 881-888), the results suggest that the folding of nascent peptide chains begins early in the synthesis process and that the amount of ordered structure increases with increasing peptide chain length until the conformation of the biologically active protein is generated.