Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons.

Neurotrophins are key regulators of neuronal survival and differentiation during development. Activation of their cognate receptors, Trk receptors, a family of receptor tyrosine kinases (RTKs), is pivotal for mediating the downstream functions of neurotrophins. Recent studies reveal that cyclin-dependent kinase 5 (Cdk5), a serine/threonine kinase, may modulate RTK signaling through phosphorylation of the receptor.

K+-induced ion-exchanges trigger trypsin activation in pancreas acinar zymogen granules.

Trypsin premature activation has been thought to be a key event in the initiation phase of acute pancreatitis. Here we test a hypothesis that a sustained increase of cytosolic Ca(2+) concentration ([Ca(2+)](C)) can trigger K(+) influx into pancreas acinar zymogen granules (ZGs) via a Ca(2+)-activated K(+) channel (K(Ca)), and this influx of K(+) then mobilizes bound-Ca(2+) by K(+)/Ca(2+) ion-exchange to increase free Ca(2+) concentration in the ZGs ([Ca(2+)](G)) and release bound-H(+) by K(+)/H(+) ion-exchange to decrease the pH in ZGs (pH(G)). Both the increase of [Ca(2+)](G) and the decrease of pH(G) will facilitate trypsinogen autoactivation and stabilize active trypsin inside ZGs that could lead to acute pancreatitis.

Superiority of N-methyl pyrrolidone over albumin with hypericin for fluorescence diagnosis of human bladder cancer cells implanted in the chick chorioallantoic membrane model.

Formulations of hypericin (HY) with plasma protein have been conventionally used, but to date, no alternative pharmaceutical formulation has been developed for clinical use. Previously, it was reported that formulation of HY containing a biocompatible solvent and penetration enhancer, N-methyl pyrrolidone (NMP) was found to be effective for the delivery of HY across in vivo chick chorioallantoic membrane (CAM). This present study reports further investigations on the HY-NMP formulations in CAM implanted with human bladder cancer cells as a potential fluorescence diagnostic agent of cancer.

The potential application of chlorin e6-polyvinylpyrrolidone formulation in photodynamic therapy.

Much research has been focused on developing effective drug delivery systems for the preparation of chlorins as potential photosensitizers for PDT. This report describes the evaluation of a new water-soluble formulation of chlorin e6 consisting of a complex of trisodium salt chlorin e6 and polyvinylpyrrolidone (Ce6-PVP) for application in photodynamic therapy (PDT) with 2 specific aims: (i) to investigate its fluorescence kinetics in skin, normal and tumor tissue after intravenous administration, and (ii) to investigate its PDT efficacy. Our results demonstrate that this new formulation possesses photosensitizing properties with rapid accumulation in tumor tissue observed within 1 h after intravenous administration.

Successful treatment of disseminated scedosporium infection in 2 lung transplant recipients: review of the literature and recommendations for management.

Scedosporium species (sp) can cause disseminated disease in lung transplant recipients with almost universal mortality. We present 2 cases of disseminated disease, which responded to voriconazole therapy. In the first case, polymerase chain reaction was used to make a rapid diagnosis and allow differentiation from Aspergillus sp.

Ethanol augments elevated-[Ca2+]C induced trypsin activation in pancreatic acinar zymogen granules.

It has been long recognized that significant percentage of patients with acute pancreatitis often presents with a history of excessive alcohol consumption; however, the patho-physiological effect of ethanol on acute pancreatitis remains poorly understood. Abnormally elevated cytosolic Ca2+ ([Ca2+]C) has been found to be a shared phenomenon in acute pancreatitis that could induce trypsin premature activation. Here, we present the effects of ethanol to sensitize zymogen granules (ZGs) of pancreas acinar cells to elevated [Ca2+]C leading to zymogen premature activation that could result in acute pancreatitis.

Shape-controlled synthesis of zinc oxide: a simple method for the preparation of metal oxide nanocrystals in non-aqueous medium.

A general and facile approach has been developed to prepare various metal oxide nanocrystals from commercially available metal acetate precursors using an amine-mediated reaction. The influence of temperature and capping agents on the yield and final morphology of the metal oxides nanocrystals was investigated. The approach was applied in the synthesis of shape-controlled ZnO nanocrystals.

Surfaces and interfacial water: evidence that hydrophilic surfaces have long-range impact.

It is generally thought that the impact of surfaces on the contiguous aqueous phase extends to a distance of no more than a few water-molecule layers. Older studies, on the other hand, suggest a more extensive impact. We report here that colloidal and molecular solutes suspended in aqueous solution are profoundly and extensively excluded from the vicinity of various hydrophilic surfaces.

Dodecanethiol-protected copper/silver bimetallic nanoclusters and their surface properties.

Dodecanethiol-protected copper/silver bimetallic nanoclusters were prepared by a liquid-phase method using different copper to silver feed ratios. The morphology and size of the prepared nanoclusters were analyzed with X-ray diffraction (XRD) and transmission electron microscopy (TEM), while their spectroscopic and surface properties were characterized by infrared (IR) and X-ray photoelectron spectroscopy (XPS), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), and 13C cross-polarization magic angle spinning NMR (13C CPMAS NMR). TEM analysis indicated that all the bimetallic clusters prepared are approximately 4-6 nm in size.

Characterization of the conformational probability of N-acetyl-phenylalanyl-NH2 by RHF, DFT, and MP2 computation and AIM analyses, confirmed by jet-cooled infrared data.

Computational and experimental determinations were carried out in parallel on the conformational probability of N-Acetyl-Phenylalanine-NH2 (NAPA). Ab initio computations were completed at the BLYP/6-311G(df,p), B3LYP/6-31G(d), B3LYP/6-31G(d,p), and B3LYP/6-31+G(d) levels of theory, labeled L/61fp, B/6, B/6p, and B/6+, respectively. Three experimentally identified conformers were compared with theoretical data, confirming their identities as the betaLanti, gammaLgauche+, and gammaLgauche- (BACKBONESIDECHAIN) conformers.

The gas-phase dipeptide analogue acetyl-phenylalanyl-amide: a model for the study of side chain/backbone interactions in proteins.

The issue of the influence of the side chain/backbone interaction on the local conformational preferences of a phenylalanine residue in a peptide chain is addressed. A synergetic approach is used, which combines gas-phase UV spectroscopy as well as gas-phase IR/UV double-resonance experiments with DFT and post Hartree-Fock calculations. N-Acetyl-Phe-amide was chosen as a model system for which three different conformers were observed.

Probing the competition between secondary structures and local preferences in gas phase isolated peptide backbones.

Combining laser desorption with a supersonic expansion together with the selectivity of IR/UV double resonance spectroscopy makes it possible to isolate and characterise the gas phase of remarkable backbone conformations of short peptide chains mimicking protein segments. A systematic bottom-up approach involving a conformer-specific IR study of peptide sequences of increasing sizes has enabled us to map the spectral signatures of the intramolecular interactions, which shape the peptide backbone, in particular H-bonds. The precise data collected are directly comparable to the most sophisticated quantum chemistry calculations of these species and therefore constitute a stringent test for the theoretical methods used.

Effect of molecular weight on the transfection efficiency of novel polyurethane as a biodegradable gene vector.

New polyurethane 2-diethylaminoethylamine-polyurethane (LGEA-PU) containing poly(ethylene glycol) segments and tertiary amines was synthesized. LGEA-PU self-assembled readily with the plasmid DNA (pCMV-betagal) in HEPES buffer and was characterized by dynamic light scattering, zeta potential, atomic force microscopy, and XTT cell viability assays. To examine the effect of molecular weight of LGEA-PU systems on transfection, LGEA-PU systems of four different molecular weights (LGEA-PU99, LGEA-PU59, LGEA-PU24, and LGEA-PU7) were prepared.

Mechanisms of signal transduction in photo-stimulated secretion in Phaeocystis globosa.

Phaeocystis globosa, a leading agent in marine carbon cycling, releases its photosynthesized biopolymers via regulated exocytosis. Release is elicited by blue light and relayed by a characteristic cytosolic Ca(2+) signal. However, the source of Ca(2+) in these cells has not been established.

A simple way to prepare PbS nanocrystals with morphology tuning at room temperature.

A simple way to synthesize PbS nanocrystals with the ability to tune their morphology at room temperature is reported. The preparation utilizes an amine-catalyzed decomposition of a precursor and the amine was found to play dual roles as both the catalyst and the capping agent. Spherical PbS nanocrystals of diameters 5 to 10 nm were obtained when long chain alkylamines were used in the pot.

Perylenequinones in photodynamic therapy: cellular versus vascular response.

Photodynamic therapy (PDT) is a promising new modality in the treatment of cancers, which employs the interaction between a tumor-localizing photosensitizer and light of an appropriate wavelength to bring about molecular oxygen-induced cell death. We have investigated the efficacy of photosensitizers from the family perylenequinone, namely Hypericin, Hypocrellin A and B, in the treatment of cancer. These photosensitizers are known as potent second generation natural photosensitizers that have phototherapeutic advantages over the presently used porphyrins.

Fluorescence imaging and phototoxicity effects of new formulation of chlorin e6-polyvinylpyrrolidone.

Evaluations of the efficiency of a new formulation of chlorin consisting of a complex of trisodium salt chlorin e6 (Ce6) and polyvinylpyrrolidone (PVP) in photodynamic therapy (PDT) and fluorescence diagnosis was performed on poorly differentiated human bladder carcinoma murine model with the following specific aims: (i) to qualitatively evaluate the fluorescence accumulation in human bladder tumor, (ii) to determine fluorescence distribution of Ce6-PVP using the tissue extraction technique and fluorescence imaging technique, (iii) to compare the fluorescence distribution of Ce6, Ce6-PVP and Photofrin in skin of nude mice, and (iv) to investigate phototoxicity caused by different parameters (drug-light interval, drug dose, irradiation fluence rate and total light fluence) in PDT. The fluorescence of the Ce6-PVP formulation was determined either by fluorescence imaging measurements or by chemical extraction from the tissues displaying similar trends of distribution. Our results demonstrated that the Ce6-PVP formulation possesses less in vivo phototoxic effect compared to Ce6 alone.

Identification and characterization of noncalcemic, tissue-selective, nonsecosteroidal vitamin D receptor modulators.

Vitamin D receptor (VDR) ligands are therapeutic agents for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. VDR ligands also show immense potential as therapeutic agents for autoimmune diseases and cancers of skin, prostate, colon, and breast as well as leukemia. However, the major side effect of VDR ligands that limits their expanded use and clinical development is hypercalcemia that develops as a result of the action of these compounds mainly on intestine.

Chlorin e6-polyvinylpyrrolidone as a fluorescent marker for fluorescence diagnosis of human bladder cancer implanted on the chick chorioallantoic membrane model.

The use of fluorescence diagnosis as a modern cancer diagnostic modality is rapidly gaining importance in the field of urology. It is based on the detection of distinctive light emission of tissues sensitized by fluorescent dyes, commonly referred to as photosensitizers, after irradiation with a specific light source. Therefore, the search for specific fluorescent dyes with high sensitivity and specificity for bladder cancer is constantly being sought after.

The interaction of TRbeta1-N terminus with steroid receptor coactivator-1 (SRC-1) serves a full transcriptional activation function of SRC-1.

Steroid receptor coactivator-1 (SRC-1) plays a crucial role in nuclear receptor-mediated transcription including thyroid hormone receptor (TR)-dependent gene expression. Interaction of the TR-ligand binding domain and SRC-1 through LXXLL motifs is required for this action. However, potential interactions between the TRbeta1-N terminus (N) and SRC-1 have not been explored and thus are examined in this manuscript.

SLAM-associated protein as a potential negative regulator in Trk signaling.

Neurotrophin signaling plays important roles in regulating the survival, differentiation, and maintenance of neurons in the nervous system. Binding of neurotrophins to their cognate receptors Trks induces transactivation and phosphorylation of the receptor at several tyrosine residues. These phosphorylated tyrosine residues then serve as crucial docking sites for adaptor proteins containing a Src homology 2 or phosphotyrosine binding domain, which upon association with the receptor initiates multiple signaling events to mediate the action of neurotrophins.

Gas-phase models of gamma turns: effect of side-chain/backbone interactions investigated by IR/UV spectroscopy and quantum chemistry.

The conformations of laser-desorbed jet-cooled short peptide chains Ac-Phe-Xxx-NH2 (Xxx=Gly, Ala, Val, and Pro) have been investigated by IR/UV double resonance spectroscopy and density-functional-theory (DFT) quantum chemistry calculations. Singly gamma-folded backbone conformations (betaL-gamma) are systematically observed as the most stable conformers, showing that in these two-residue peptide chains, the local conformational preference of each residue is retained (betaL for Phe and gamma turn for Xxx). Besides, beta turns are also spontaneously formed but appear as minor conformers.

Gas phase formation of a 3(10)-helix in a three-residue peptide chain: role of side chain-backbone interactions as evidenced by IR-UV double resonance experiments.

The first spectroscopic evidence for the gas-phase formation of helical structures in short peptide chains is reported, using the IR-UV double resonance technique and DFT quantum chemistry calculations. The study involves three chemically protected peptides, all based on the same Ac-(Ala)3-NH2, (Ac = acetyl, Ala = alanine) tripeptide, in which one of the Ala residues is substituted by the aromatic phenylalanine residue. For the three molecules, only one main conformer is observed in the supersonic expansion.

Human splicing factor SPF45 (RBM17) confers broad multidrug resistance to anticancer drugs when overexpressed--a phenotype partially reversed by selective estrogen receptor modulators.

The splicing factor SPF45 (RBM17) is frequently overexpressed in many solid tumors, and stable expression in HeLa cells confers resistance to doxorubicin and vincristine. In this study, we characterized stable transfectants of A2780 ovarian carcinoma cells. In a 3-day cytotoxicity assay, human SPF45 overexpression conferred 3- to 21-fold resistance to carboplatin, vinorelbine, doxorubicin, etoposide, mitoxantrone, and vincristine.

Enhanced photodynamic activity of hypericin by penetration enhancer N-methyl pyrrolidone formulations in the chick chorioallantoic membrane model.

Hypericin (HY) was examined for photodynamic therapy (PDT)-induced vascular damage using the chick chorioallantoic membrane (CAM) model. Clinically, plasma protein was used to solubilize HY. Upon binding to albumin, free HY available to be transported through the membrane may be limited.