TissueDistributionDBs: a repository of organism-specific tissue-distribution profiles

Tissue-distribution profiles are crucial for understanding the characteristics of cells and tissues in terms of their differential expression of genes. Most of the currently available resources for tissue-distribution profiles are either specialized for a few particular organisms, tissue types and disease stages or do not consider the “tissue ontology” levels for the calculation of the tissue-distribution profiles. Therefore, we have developed “TissueDistributionDBs”, a repository of tissue-distribution profiles based on the expressed sequence tags (ESTs) data extracted from the UniGene database by employing “Tissue Ontology” available at BRENDA. To overcome the occurrence of the natural language variations in the EST’s source tissue-type terms, we have generated a “tissue synonym library” and standardized these tissue-type terms by cross-referencing to the controlled vocabulary for tissue-type terms available at BRENDA “Tissue Ontology”. Furthermore, we have provided a quantitative expression for genes among the tissue types at various anatomical levels by constructing “tissue slims”. Concurrently, the expression among tissue types is used for tissue-distribution calculations. The resulting output profiles can be queried by the Sequence Retrieval System (SRS) and are currently available for 20 different model organisms. We benchmarked our database system against the Swissprot database using a set of 40 different tissue types. This database system is useful for the understanding of the tissue-specific expression patterns of genes, which have implications for the identification of possible new therapeutic drug targets, in gene discovery, and in the design and analysis of micro-arrays. TissueDistributionDBs can be accessed via the World Wide Web (www) at http://genius.embnet.dkfz-heidelberg.de/menu/tissue_db/.     

Radiation processing of natural polymers: The IAEA contribution

Radiation processing offers a clean and additive-free method for preparation of value-added novel materials based on renewable, non-toxic, and biodegradable natural polymers. Crosslinked natural polymers can be used as hydrogel wound dressings, face cleaning cosmetic masks, adsorbents of toxins, and non-bedsore mats; while low molecular weight products show antibiotic, antioxidant, and plant-growth promoting properties. Recognizing the potential benefits that radiation technology can offer for processing of natural polymers into useful products, the IAEA implemented a coordinated research project (CRP) on “Development of Radiation-processed products of Natural Polymers for application in Agriculture, Healthcare, Industry and Environment”. This CRP was launched at the end of 2007 with participation of 16 MS to help connecting radiation technology and end-users to derive enhanced benefits from these new value-added products of radiation-processed natural materials. In this paper the results of activities in participating MS related to this work will be presented.     

Behavior of human serum albumin on strong cation exchange resins: II. Model analysis

Experiments with human serum albumin on a strong cation exchange resin exhibit a peculiar elution pattern: the protein elutes with two peaks in a modifier gradient. This behavior is modeled with a general rate model, where the two elution peaks are modeled with two binding conformations, one of which is at equilibrium conditions, while for the other, the adsorption process is rate limited. Isocratic experiments under nonadsorbing conditions were used to characterize the mass transfer process. The isotherm of both adsorption conformations as well as the kinetic of adsorption and desorption for the second conformation are functions of the modifier concentration. They are evaluated with linear modifier gradient experiments and step experiments with various adsorption times. All experimental features are well reproduced by the proposed modified general rate model.     

Persistent spectral hole-burning in a -doped aluminosilicate glass from 8 to 295 K: Study of the burning and refilling kinetics, and of optical dephasing

High-temperature persistent spectral hole-burning (PSHB), up to room temperature, has been observed in a Eu ³⁺ -doped aluminosilicate glass using a high peak-power nanosecond dye laser. Spontaneous refilling as well as thermal cycling measurements show that at least two mechanisms, a fast and a slow one, are involved in our sample. We suggest that the fast or “easy” component may correspond to a non-photochemical local rearrangement of the host or to photoreduction of the Eu ³⁺ ions and that the second one leading to very stable photoproducts may correspond to transfer of an electron over a sizable distance through a several-step process. The mechanisms we suggest agree with light-induced hole refilling measurements. Line broadening mechanisms are discussed and the temperature-dependent part of the homogeneous width and of the spectral shift is interpreted in terms of a two-phonon (Raman) process involving pseudo-local phonons. Received 28 July 1999     

Lipopolysaccharide-induced inflammation attenuates taste progenitor cell proliferation and shortens the life span of taste bud cells

Background  

The mammalian taste bud, a complex collection of taste sensory cells, supporting cells, and immature basal cells, is the structural unit for detecting taste stimuli in the oral cavity. Even though the cells of the taste bud undergo constant turnover, the structural homeostasis of the bud is maintained by balancing cell proliferation and cell death. Compared with nongustatory lingual epithelial cells, taste cells express higher levels of several inflammatory receptors and signalling proteins. Whether inflammation, an underlying condition in some diseases associated with taste disorders, interferes with taste cell renewal and turnover is unknown. Here we report the effects of lipopolysaccharide (LPS)-induced inflammation on taste progenitor cell proliferation and taste bud cell turnover in mouse taste tissues.     

Penetration depth and pinning effects in high-Tc superconductors La-Sr-Cu-O and (Er,Ho)-Ba-Cu-O studies by μSR

We report the results of μSR investigations of the ceramic samples La_2-xSr_xCuO_4-σ (x=0.1, 0.15, 0.25) and ReBa₂Cu₃O_7-σ (Re=Er, Ho, Y_0.5Ho_0.5) in the external magnetic field 0–800 Oe. The measurements were performed by the ZFC and FC methods. The irreversibility effects were studied at several temperatures by measuring the mean value and the width of the magnetic field distribution on the muon in the step by step procedure of increasing and subsequent decreasing of the external field. The temperature dependences of the magnetic penetration depth perpendicular to the basal plane λ_⊥ were obtained. For the lanthanum sample with 0.15 of Sr its value at the zero temperature is λ_⊥ (0)=2400 Å, for Er-Ba-Cu-O λ_⊥ (0)=1600 Å.     

A theoretical analysis of a piezoelectric ultrasound device with an active matching layer

This paper investigates the use of magnetically active materials in the matching layer of a piezoelectric transducer. This then allows the performance of the device to be dynamically altered by applying an external field. The effect that this new matching layer has on the performance of a typical device is theoretically investigated here. It transpires that the additional flexibility of an active matching layer can be used to maintain the efficiency of the device as the external load is varied.     

Production of the Bengamide Class of Marine Natural Products in Myxobacteria: Biosynthesis and Structure–Activity Relationships

The bengamides, sponge‐derived natural products that have been characterized as inhibitors of methionine aminopeptidases (MetAPs), have been intensively investigated as anticancer compounds. We embarked on a multidisciplinary project to supply bengamides by fermentation of the terrestrial myxobacterium M. virescens, decipher their biosynthesis, and optimize their properties as drug leads. The characterization of the biosynthetic pathway revealed that bacterial resistance to bengamides is conferred by Leu 154 of the myxobacterial MetAP protein, and enabled transfer of the entire gene cluster into the more suitable production host M. xanthus DK1622. A combination of semisynthesis of microbially derived bengamides and total synthesis resulted in an optimized derivative that combined high cellular potency in the nanomolar range with high metabolic stability, which translated to an improved half‐life in mice and antitumor efficacy in a melanoma mouse model.     

In vitro evolution of ligands to the membrane protein caveolin

Membrane proteins comprise a third of the human genome, yet present challenging targets for reverse chemical genetics. For example, although implicated in numerous diseases including multiple myeloma, the membrane protein caveolin-1 appears to offer a poor target for the discovery of synthetic ligands due to its largely unknown structure and insolubility. To break this impasse and identify new classes of caveolae controlling lead compounds, we applied phage-based, reverse chemical genetics for the discovery of caveolin-1 ligands derived from the anti-HIV therapeutic T20. Substitution of homologous residues into the T20 sequence used a process analogous to medicinal chemistry for the affinity maturation to bind caveolin. The resultant caveolin-1 ligands bound with >1000-fold higher affinity than wild-type T20. Two types of ELISAs and isothermal titration calorimetry (ITC) measurements demonstrated high affinity binding to caveolin by the T20 variants with K(d) values in the 150 nM range. Microscopy experiments with the highest affinity caveolin ligands confirmed colocalization of the ligands with endogenous caveolin in NIH 3T3 cells. The results establish the foundation for targeting caveolin and caveolae formation in living cells.