Lysophosphatidic Acid Receptor Agonism: Discovery of Potent Nonlipid Benzofuran Ethanolamine Structures.

Lysophosphatidic acid (LPA) is the natural ligand for two phylogenetically distinct families of receptors (LPA LPA) whose pathways control a variety of physiologic and pathophysiological responses. Identifying the benefit of balanced activation/repression of LPA receptors has always been a challenge because of the high lability of LPA and the limited availability of selective and/or stable agonists. In this study, we document the discovery of small benzofuran ethanolamine derivatives (called CpX and CpY) behaving as LPA agonists.

Decision analysis for the assessment of a record linkage procedure: application to a perinatal network.

Objectives: According to European legislation, we must develop computer software allowing the linkage of medical records previously rendered anonymous. Some of them, like AUTOMATCH, are used in daily practice either to gather medical files in epidemiologic studies or for clinical purpose. In the first situation, the aim is to avoid homonymous errors, and in the second one, synonymous errors.

[Prospective regional study of an epidemic of respiratory syncytial virus (RSV) bronchiolitis].

Unlabelled: This prospective study was designed to identify risk factors associated with admission in pediatric intensive care units (PICU) among infants hospitalized for treatment of RSV induced bronchiolitis. This study was population-based and was conducted in Burgundy, a French region with 1,800,000 inhabitants where passive immunoprophylaxis for RSV bronchiolitis was not set up at the time of the study.

Results: From December 1st 1999 to April 30th 2000, 484 infants were hospitalized for RSV bronchiolitis in Burgundy: 19.

[Using discharge abstracts as a tool to assess a regional perinatal network].

To assess the regional perinatal network of Burgundy (20 obstetrical units; 18,000 births/year), discharge abstracts are collected for all mothers and all neonates. Discharge abstracts are expanded with some additional data. According to the French law, data are rendered anonymous in each hospital before their transmission to the teaching hospital for statistical analysis.

[Medical informatics (hospital information systems) in neonatology: reality and insufficiencies].

The generalized implementation in France of hospital information systems (HIS) is often considered by the medical practitioners as a useless constraint. Nevertheless, they are now largely used by the administrative authorities for their economical evaluation of medical care. In neonatology HIS is applied to the hospitalized sick neonates as well as to the healthy newborn infants during their maternity hospital stay with their mother following birth.

[Current networks in perinatal care. From practice to theory...].

Perinatal care networks have been organized in a conventional way in six different French areas. This paper describes the four successive steps of this organization: description of the perinatal dysfunctions through survey(s), elaboration of medical recommendations, set up of a new organization, evaluation of the efficiency of the new organization.

Refined solution structure of the anti-mammal and anti-insect LqqIII scorpion toxin: comparison with other scorpion toxins.

The solution structure of the anti-mammal and anti-insect LqqIII toxin from the scorpion Leiurus quinquestriatus quinquestriatus was refined and compared with other long-chain scorpion toxins. This structure, determined by 1H-NMR and molecular modeling, involves an alpha-helix (18-29) linked to a three-stranded beta-sheet (2-6, 33-39, and 43-51) by two disulfide bridges. The average RMSD between the 15 best structures and the mean structure is 0.

1H-NMR-derived secondary structure and the overall fold of the potent anti-mammal and anti-insect toxin III from the scorpion Leiurus quinquestriatus quinquestriatus.

We describe the secondary structure and the overall fold of toxin III from the venom of the scorpion Leiurus quinquestriatus quinquestriatus determined using two-dimensional-1H-NMR spectroscopy. This protein, which contains 64 amino acids and 4 disulfide bridges, belongs to the long-chain toxin category and is highly toxic to both mammals and insects. The overall fold was determined on the basis of 1208 inter-proton-distance restraints derived from NOE measurements and 90 psi, phi dihedral-angle restraints derived from NOE connectivities and 3JNH-alphaH coupling constants using the HABAS program.

Refined three-dimensional solution structure of insect defensin A.

Background: Insect defensin A is a basic 4 kDa protein secreted by Phormia terranovae larvae in response to bacterial challenges or injuries. Previous biological tests suggest that the bacterial cytoplasmic membrane is the target of defensin A. The structural study of this protein is the first step towards establishing a structure-activity relationship and forms the basis for understanding its antibiotic activity at the molecular level.

Secondary structure of gp160 and gp120 envelope glycoproteins of human immunodeficiency virus type 1: a Fourier transform infrared spectroscopic study.

The secondary structure of the precursor (gp160) of the envelope protein of human immunodeficiency virus type 1 (BH10) and its receptor-binding subunit (gp120) was studied by Fourier-transformed attenuated total reflection spectroscopy. A higher alpha-helix/beta-sheet ratio in the gp120 subunit than in the precursor indicates a structural heterogeneity between the two subunits (gp120 and gp41), in agreement with classical secondary-structure predictions. The secondary structure of gp41 was estimated and compared with existing models.

Properties of HIV membrane reconstituted from its recombinant gp160 envelope glycoprotein.

Human immunodeficiency virus (HIV) membrane has been reconstituted from the recombinant envelope glycoprotein precursor (gp160) by a detergent dialysis technique. Electron microscopy shows that gp160-virosomes are spherical vesicles with a mean diameter identical to that of viral particles. Enzyme-linked immunosorbent assay and immunogold labeling demonstrate efficient association of gp160 with lipid vesicles and proteolysis treatment reveals an asymmetric insertion with about 90% of glycoproteins having their gp120-moiety pointing outside.

Progress in multidimensional NMR investigations of peptide and protein 3-D structures in solution. From structure to functional aspects.

2-D and 3-D NMR techniques were used to investigate the conformations in solution of several peptides and proteins for which crystalline structures are not available yet. Insect defensin A is a small (40 aa) antibiotic protein exhibiting a characteristic 'loop-helix-beta-sheet' structure. A striking analogy was found with charybdotoxin, a scorpion toxin in which a CSH (cysteine stabilized alpha-helix) motif is also present.

Orientation into the lipid bilayer of an asymmetric amphipathic helical peptide located at the N-terminus of viral fusion proteins.

The complete amino-acid sequence of viral fusion proteins has been analyzed by the Eisenberg procedure. The region surrounding the cleavage site contains a highly hydrophilic region immediately followed by a membrane-like region. Since the effective cleavage between these two domains seems required to expose the fusogenic domain (located at the N-terminal sequence of the transmembrane like region) which is assumed to interact with the lipid membrane of the host cell, we have focused our analysis on the conformation and mode of insertion of this membrane-like domain in a lipid monolayer.

Characterization of monoclonal antibodies against the p17 core protein of the human immunodeficiency virus 1.

Five mouse hybridomas which produce monoclonal antibodies against the p17 core protein of HIV-1 have been isolated. Cross-competition assays and mapping with synthetic peptides demonstrate that two closely related epitopes are identified by these antibodies. Directed against two neighbouring peptides at the carboxy-terminal end of the molecule, they can be used for the selective detection of p17 polypeptide in a viral extract or in an infected cell lysate by a solid-phase sandwich enzyme immunoassay.

Virosomes reconstituted from human immunodeficiency virus proteins and lipids.

Purified Human Immunodeficiency Virus (HIV) was solubilized in octylglucopyranoside. After centrifugation, the supernatant was added to lipid-detergent mixed micelles. Formation of virosomes occurred during overnight dialysis.

An interstitial hyperthermia system at 27 MHz.

An interstitial hyperthermia system using thin, flexible wires operating at a frequency of 27 MHz has been evaluated for possible use in combination with (iridium) brachytherapy applications employing flexible nylon afterloading catheters. This method of interstitial heating is argued to be a variation of local-current-field heating, however with the direct galvanic contact between electrode and tissue replaced by a capacitive coupling between wire and tissue. Through a special design of the wire the length of the heated area along the catheter can be chosen freely.

Mode of insertion into a lipid membrane of the N-terminal HIV gp41 peptide segment.

The complete amino-acid sequence of the gp160 polyprotein of HIV (strain WMJ1) has been analyzed by the Eisenberg procedure. The region surrounding the cleavage site between the gp120 and the gp41 subunit contains a receptor-like region immediately followed by a transmembrane-like region containing approximately 13 residues. These two regions are separated by the cleavage site between gp120 and gp41.

Cyclic change in late triassic lacustrine communities.

A new type of lake and shore assemblage has been found in the Late Triassic age rocks of North Carolina and Virginia (Dan River group). It includes abundant aquatic reptiles, fishes, at least seven orders of insects, crustaceans, and a diverse flora. Cyclic changes in the fauna and flora correlate with sedimentary cycles, which together reflect the repetitive development and extinction of large meromictic lakes.

Fossil spores, pollen, and fishes from connecticut indicate early jurassic age for part of the newark group.

Palynologically productive localities have been found in the United States throughout the Newark Group basins, most of which had previously been assumed to be barren. Rich palynoflorules dominated by coniferous pollen of Circulina-Classopollis type, and well-preserved fossil fishes, including possible new semionotids, have been found in the Hartford basin. Palynological data indicate that the Newark Group has considerable time-stratigraphic range: Upper Triassic for the Cumnock Formation (North Carolina), the Vinita Beds (Virginia), and the upper New Oxford Formation (Pennsylvania), Rhaeto-Liassic for the Brunswick Formation (New Jersey), Portland Formation (Connecticut and Massachusetts), and the Shuttle Meadow Formation (Connecticut).