The excited-state chemistry of phycocyanobilin: a semiempirical study.

Based on previous time-resolved absorption studies, phycocyanobilin undergoes a photoreaction from an A- into a B- and C-form, with the latter two photoproducts showing absorption spectra red-shifted from A. To identify the molecular mechanism involved in the excited-state reactions, the structural origin of the red shift in the absorption spectra is investigated. Using semiempirical AM1 calculations that include configuration interaction by pair doubles excitation configuration interaction, the absorption spectra of different conformers as well as different protonation states were calculated.

Global expression analysis of the fibroblast transcriptional response to TGFbeta.

Objectives: Transforming Growth Factor-beta (TGFbeta) is the predominant cytokine in all forms of fibrotic reactions. As well as being secreted by immune modulators of fibrosis such as macrophages, it is involved in an autocrine feedback loop of fibroblast stimulation whose regulation is still poorly understood. We wished to gain some insight into the mechanisms of the fibroblast response to TGFbeta.

Conformational flexibility of phycocyanobilin: an AM1 semiempirical study.

Semiempirical AM1 studies on phycocyanobilin, the most abundant chromophore in the light-harvesting phycobiliproteins and a suitable model of the phytochrome chromophore, have been carried out. For the all-Z isomer, the structures and energies of all possible conformers, which arise from rotation about the single bonds of the exocyclic methine bridges, were calculated. In addition, the rotational barriers between the different conformers were deduced from the computed energy hypersurfaces.

Apoptosis-inducing membrane vesicles. A novel agent with unique properties.

The CD95 ligand (FasL) transmembrane protein is found on activated T cells and cells outside the immune system. A well-known turnover process of membrane FasL is mediated by matrix metalloproteinase, which generates soluble FasL (sFasL). Here, we demonstrate that membrane FasL turnover occurs effectively through the release of membrane vesicles.

First steps in the phytochrome phototransformation: a comparative femtosecond study on the forward (Pr --> Pfr) and back reaction (Pfr --> Pr).

The primary light-induced events in the reversible Pr right harpoon over left harpoon Pfr phototransformation are investigated by femtosecond absorption spectroscopy using a pump-probe technique. After the selective electronic excitation of Pr and Pfr with pulses at 610 and 730 nm, respectively, the transient absorption spectra were measured as a function of the delay time and subjected to a global fit analysis. As a result of this analysis, the decay-associated spectra of the kinetic components involved in the formation of the first photoproducts in the forward and back reaction are obtained.

The promise of transcription profiling for understanding the pathogenesis of scleroderma.

Transcription profiling, expression fingerprinting, and microarray analysis are terms that describe the cataloging of mRNA levels in a given tissue. Recent profiling technologies allow the determination of thousands of mRNA transcript levels simultaneously. The application of this technology to scleroderma has already offered insights into the disease.

CD95 (Fas) ligand-expressing vesicles display antibody-mediated, FcR-dependent enhancement of cytotoxicity.

Bioactive Fas ligand (FasL)-expressing vesicles were generated (vesicle preparation, VP) from two cell lines overexpressing FasL. The effect of NOK-1 anti-FasL mAb (mouse IgG1) on the cytotoxicity of FasL VP against various targets was determined. At high concentrations (1-10 microg/ml), NOK-1 inhibited the cytotoxicity.

Fibroblast heterogeneity in physiological conditions and fibrotic disease.

Inflammation and tissue injury are strong stimuli for fibroblast activation and initiation of reparative processes. In certain disease states, pathological fibrosis occurs. Fibroblasts isolated from these diseased tissues often display a persistently abnormal phenotype characterized by increased synthesis of matrix components such as collagen.

Software for quantitation and visualization of expression array data.

Software is described that facilitates the analysis of phosphoimages from large array hybridizations. The Macintosh PowerPC-compatible application and its manual are available at no charge from http:¿people.bu.

Bioactivities of Fas ligand-expressing retroviral particles.

Culture supernatants from retroviral packaging cells carrying the human Fas ligand (FasL) gene killed both human (Jurkat) and mouse (LB27.4) targets within 5 h of incubation. Cytotoxicity was found both in a fraction >/=500 kDa and a fraction between 50 and 500 kDa.

Retroviral membrane display of apoptotic effector molecules.

Retroviruses have been widely used in gene transmission studies. In this paper, we show that nonviral apoptotic proteins can be displayed on viral membrane surfaces and that the displayed proteins can execute their normal effector functions. We introduced the genes encoding the apoptosis effector proteins, human CD95 ligand (hFasL) or human tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL), into a cell line that packages Moloney murine leukemia virus vectors.

A potential role for protease nexin 1 overexpression in the pathogenesis of scleroderma.

Scleroderma currently affects approximately 75,000-100,000 individuals in the United States. Fibroblasts isolated from lesional skin of scleroderma patients overexpress collagens and other matrix components, and this abnormality is maintained for multiple passages in culture. To understand the molecular basis for matrix gene overexpression, we performed a differential display comparison of fibroblasts from clinically lesional and nonlesional scleroderma skin.

Biology of the scleroderma fibroblast.

Abnormalities of matrix biosynthesis by systemic sclerosis fibroblasts underlie the cutaneous and visceral fibrosis seen in this disease. The fundamental basis of the abnormal fibroblast phenotype has not been determined but primary metabolic abnormalities, responses to abnormal environmental signals, and clonal selection have all been hypothesized to play a role. In the past year, evidence supporting each of these explanations was forthcoming.

The fates of the blastomeres of the 16-cell zebrafish embryo.

We present a fate map for the 16-cell-stage blastomeres of the zebrafish embryo Brachydanio rerio. We injected high molecular weight fluorescent dextran into cleavage-stage cells to observe the contributions of the descendants of the first 16 cells to the adult. The patterns derived from these early cells are similar, but not identical among different embryos.