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At least 307 records · Page 17Linked to original sources
PubMed1984

Biotechnological approach to a new foot-and-mouth disease virus vaccine.

Major contributions towards the development of an absolutely safe FMDV vaccine are evident. With the identification of VP1 as the immunogenic protein, it is possible to manufacture a subunit vaccine via biotechnology. DNA sequences encoding the VP1 protein can be introduced into a bacterium with ease; under the appropriate conditions, large amounts of VP1 can be produced in a short time. The accumulation of amino acid sequences generated by recombinant DNA techniques allows identification of antigenic domains, which are the basis of variability among serotype and subtype viruses. As a result, vaccine production by chemical synthesis of short peptides corresponding to the antigenic determinants is greatly facilitated. At present, results from experimental vaccines employing genetically engineered or chemically synthesized VP1 antigens against homologous virus infection are encouraging. The current approach of preparing vaccine is to utilize the antigenic specificity of the virus. Since FMDV undergoes antigenic drift, variants not neutralized by type-specific serum will arise. An alternative approach is to prepare vaccines based on antigenic sites shared among all serotype and subtype viruses.

Adjuvants, Immunologic↗
PubMedDate not supplied

[The evaluation of the effect of chemical and radiation factors on the health of the population in an industrial city].

Kamensk-Ural'skiy, Sverdlovsk Province, is one of the Russian industrial cities and towns exposed to a combination of radiation and chemical pollutions. This is a large industrial center of the mid-Urals, where enterprises of ferrous and nonferrous metallurgy, power engineering. Intensive chemical and radiation pollutions of Kamensk-Ural'skiy have an adverse impact on its population's health, which is manifested by higher morbidity rates among both children and adolescents. Comparing its matched areas by using routine analytical methods has defined the contribution of radiation to increased morbidity in different age groups, which is caused by a combination of chemical and radiation pollutions of the environment. The incidence of concomitant diseases may be an important additional indicator of the impact of environmental pollution on human health.

Adult↗
PubMed1997

Probing intermolecular main chain hydrogen bonding in serine proteinase-protein inhibitor complexes: chemical synthesis of backbone-engineered turkey ovomucoid third domain.

Intermolecular main chain H-bonding networks are frequently encountered at the interface of complexes of protein proteinase inhibitors and their cognate enzymes. Studies of X-ray crystal structures of many protein inhibitors complexed with serine proteinases have revealed that the amide NH group of the P1 residue in the inhibitor donates an H-bond to the carbonyl C = O group of Ser214 and Ser195 Oy in the enzyme (Ser125 and Ser221 in subtilisins, respectively). To probe the energetic contribution of this backbone H-bond in the complexes of OMTKY3 with several serine proteinases, native chemical ligation was used for the total synthesis of a backbone-engineered analog of OMTKY3, in which the amide peptide bond between Thr17 (P2) and Leu18 (P1) was replaced by an ester bond, i.e., -CONH-to-COO-. This chemical "mutation" effectively eliminated the backbone H-bond donated by the NH group of Leu18. By measuring association equilibrium constants for synthetic wild-type OMTKY3 and the backbone-engineered ester analog interacting with a panel of six serine proteinases, we have determined that the P1 NH-->O substitution weakens the binding of OMTKY3 to its cognate enzymes by an average of 15-fold, i.e., 1.5 +/- 0.3 kcal/mol. These results place a quantitative value on the contribution of the intermolecular backbone H-bond in enzyme-inhibitor recognition.

Amino Acid Sequence↗
PubMed1999

Reductive dechlorination of chlorinated ethene DNAPLs by a culture enriched from contaminated groundwater.

A microbial culture enriched from a trichloroethene-contaminated groundwater aquifer reductively dechlorinated trichloroethene (TCE) and tetrachloroethene (PCE) to ethene. Initial PCE dechlorination rate studies indicated a first-order dependence with respect to substrate at low PCE concentrations, and a zero-order dependence at high concentrations. Studies of TCE and vinyl chloride (VC) dechlorination indicated a first-order dependence at all substrate concentrations. VC had little or no effect on the initial rate of TCE dechlorination. With subsaturating concentrations of chlorinated ethenes, nearly stoichiometric amounts of the toxic intermediate vinyl chloride accumulated prior to its dechlorination to ethene. In contrast, under saturating conditions, in which a dense, nonaqueous-phase liquid existed in equilibrium with the aqueous phase, the chlorinated ethene was dechlorinated to ethene, at a rapid rate, with the accumulation of relatively small amounts of chlorinated intermediates.

Biodegradation, Environmental↗
PubMed2004

Mapping domain structures in silks from insects and spiders related to protein assembly.

The exceptional solubility in vivo (20-30%, w/v) of the silk proteins of insects and spiders is dictated by both the need to produce solid fibres with a high packing fraction and the high mesogen concentration required for lyotropic liquid crystalline spinning. A further design requirement for silk proteins is a strong predominance of hydrophobic amino acid residues to provide for the hydrophobic interactions, water exclusion, and beta-crystallite formation required to produce strong insoluble threads. Thus, the domain structure of silk proteins needs to enable nanoscale phase separation to achieve high solubility of hydrophobic proteins in aqueous solutions. Additionally, silk proteins need to avoid premature precipitation as beta-sheets during storage and processing. Here we use mapping of domain types, sizes and distributions in silks to identify consistent design features that have evolved to meet these requirements. We show that silk proteins consist of conspicuously hydrophilic terminal domains flanking a very long central portion constructed from hydrophobic blocks separated by hydrophilic ones, discussing the domain structure in detail. The general rules of construction for silk proteins based on our observations should give a useful guide to the way in which Nature has solved the problem of processing hydrophobic proteins in water and how this can be copied industrially. Following these rules may also help in obtaining adequate expression, soluble products and controllable conformational switches in the production of genetically engineered or chemically synthesized silk analogues. Thus these insights have implications for structural biology and relevance to fundamental and applied questions in material science and engineering.

Animals↗
PubMed2000

Development of bioreaction engineering.

In addition to summarizing the early investigations in bioreaction engineering, the present short review covers the development of the field in the last 50 years. A brief overview of the progress of the fundamentals is presented in the first part of this article and the key issues of bioreaction engineering are advanced in its second part.

Animals↗
PubMed2006

Simplified approach for developing the rate expressions for enzyme-catalyzed reactions.

A Simplified version of rate equations for enzyme-catalyzed reactions has been developed in which the rate equation is analyzed with two different mechanisms: ordered bi-ter and Ping-Pong bi-bi mechanisms. This procedure is able to develop the rate expressions accurately. Random sequential order mechanism can be effectively explained by this approach.

Algorithms↗
PubMed2002

Spin-engineering magnetic media.

The explosion in demand for increased data-storage density is driving the exploration of new magnetic media. Here we describe a new type of magnetic medium in which the spin configurations are engineered in chemically homogeneous magnetic films: regularly arranged in-plane and out-of-plane spin configurations are defined by altering the magnetic anisotropy. These spin-engineered media not only maintain the surface planarity but also the homogeneity of the magnetic materials, and our method is likely to find immediate application on account of its simplicity and ease of integration.

Journal Article↗
PubMed1990

Augmented and sustained plasma concentrations after intramuscular injections of molecular variants and deglycosylated forms of tissue-type plasminogen activators.

We have previously explored induction of coronary thrombolysis with tissue-type plasminogen activator (t-PA) administered intramuscularly. Absorption-enhancing agents that rendered the approach feasible were identified, but large amounts of activator were required and initial elevations of concentrations in plasma could not be sustained. The present study was designed to determine whether more therapeutically favorable plasma concentrations could be induced by genetically engineering or chemically modifying t-PA to prolong its half-life based on the hypothesis that the ratio of absorption to clearance would be increased. Each of four genetically engineered variants (one variant with growth factor and kringle 1 domains deleted and kringle 2 duplicated, a second variant with a cysteine for Arg substitution in the growth factor domain, a third variant with an additional urokinase kringle inserted, and a fourth variant with the growth factor domain deleted) and enzymatically deglycosylated t-PA exhibited prolonged half-life after bolus intravenous injection in rabbits. Each elicited substantially higher and more sustained elevations in plasma after intramuscular injection in rabbits or dogs with absorption-enhancing agents as compared with wild-type t-PA that were not accompanied by a systemic lytic state. Thus, use of molecular variants of t-PA with prolonged half-lives in the circulation permits induction of augmented and sustained elevations of plasma concentrations after intramuscular injection with absorption-enhancing agents as compared with wild-type t-PA, rendering potentially therapeutic blood levels more attainable with relatively modest amounts of material.

Animals↗
PubMed1993

A soluble divalent class I major histocompatibility complex molecule inhibits alloreactive T cells at nanomolar concentrations.

Genetically engineered or chemically purified soluble monovalent major histocompatibility complex (MHC) molecules, which have previously been used to study T cells, have not blocked cytotoxic T-cell responses. Here we describe a genetically engineered divalent class I MHC molecule which inhibits lysis of target cells by alloreactive cytotoxic T cells. This protein, H-2Kb/IgG, was generated as a fusion protein between the extracellular domains of a murine class I polypeptide, H-2Kb, and an immunoglobulin heavy chain polypeptide. The chimeric protein has serological and biochemical characteristics of both the MHC and IgG polypeptides. Nanomolar concentrations of H-2Kb/IgG inhibited lysis of H-2Kb-expressing target cells not only by alloreactive H-2Kb-specific T-cell clones but also by alloreactive H-2Kb-specific primary T-cell cultures. A direct binding assay showed high-affinity binding between the H-2Kb/IgG molecule and an H-2Kb-specific alloreactive T-cell clone. Unlabeled H-2Kb/IgG displaced 125I-labeled H-2Kb/IgG from T cells with an IC50 of 1.2 nM.

Amino Acid Sequence↗
PubMed2003

Preparation and characterization of novel coenzyme Q10 nanoparticles engineered from microemulsion precursors.

The purpose of these studies was to prepare and characterize nanoparticles into which Coenzyme Q10 (CoQ10) had been incorporated (CoQ10-NPs) using a simple and potentially scalable method. CoQ10-NPs were prepared by cooling warm microemulsion precursors composed of emulsifying wax, CoQ10, Brij 78, and/or Tween 20. The nanoparticles were lyophilized, and the stability of CoQ10-NPs in both lyophilized form and aqueous suspension was monitored over 7 days. The release of CoQ10 from the nanoparticles was investigated at 37 degrees C. Finally, an in vitro study of the uptake of CoQ10-NPs by mouse macrophage, J774A.1, was completed. The incorporation efficiency of CoQ10 was approximately 74% +/- 5%. Differential Scanning Calorimetry (DSC) showed that the nanoparticle was not a physical mixture of its individual components. The size of the nanoparticles increased over time if stored in aqueous suspension. However, enhanced stability was observed when the nanoparticles were stored at 4 degrees C. Storage in lyophilized form demonstrated the highest stability. The in vitro release profile of CoQ10 from the nanoparticles showed an initial period of rapid release in the first 9 hours followed by a period of slower and extended release. The uptake of CoQ10-NPs by the J774A.1 cells was over 4-fold higher than that of the CoQ10-free nanoparticles (P < .05). In conclusion, CoQ10-NPs with potential application for oral CoQ10 delivery were engineered readily from microemulsion precursors.

Animals↗
PubMed2005

Can topological indices transmit information on properties but not on structures?

A survey of several topological indices (TIs) is provided according to the nature (integers or real numbers) of the local vertex invariants (LOVIs) and of the resulting molecular descriptor (TI). The 1st generation TIs such as the Wiener index when both the LOVIs and the TI are integers have a very high degeneracy. This fact can become an asset for the problem under discussion: when confronted with the "inverse problem" (reverse engineering) such indices lead to a combinatorial explosion of possible solutions. On the other extreme, TIs with very low degeneracy may also offer the possibility to transmit information on properties but not on structures, because they may be too difficult to lend themselves to reverse engineering in a reasonable amount of time. Several such indices are discussed: the novel second-generation index G (derived from the average distance-based connectivity index J in order to include a dependence on graph size and cyclicity), and third-generation indices such as the triplet TI denoted by DN2S(4) or the Kier-Hall index TOTOP. The intercorrelation of these indices is discussed: G is almost linearly-correlated with DN2S(4), and shows a different type of correlation with TOTOP.

Alkanes↗
PubMed2001

Chemical and biological strategies for engineering cell surface glycosylation.

Oligosaccharides play a crucial role in many of the recognition, signaling, and adhesion events that take place at the surface of cells. Abnormalities in the synthesis or presentation of these carbohydrates can lead to misfolded and inactive proteins, as well as to several debilitating disease states. However, their diverse structures, which are the key to their function, have hampered studies by biologists and chemists alike. This review presents an overview of techniques for examining and manipulating cell surface oligosaccharides through genetic, enzymatic, and chemical strategies.

Animals↗