Two groups of rhinoviruses revealed by a panel of antiviral compounds present sequence divergence and differential pathogenicity.

A variety of chemically different compounds inhibit the replication of several serotypes of rhinoviruses (common-cold viruses). We noticed that one of these antiviral compounds, WIN 51711, had an antiviral spectrum clearly distinctive from a consensus spectrum or other capsid-binding compounds, although all of them were shown to share the same binding site. A systematic evaluation of all known rhinovirus capsid-binding compounds against all serotyped rhinoviruses was therefore initiated. Multivariate analysis of the results revealed the existence of two groups of rhinoviruses, which we will call antiviral groups A and B. The differential sensitivity of members of these groups to antiviral compounds suggests the existence of a dimorphic binding site. The antiviral groups turned out to be a reflection of a divergence of rhinovirus serotypes on a much broader level. Similarities in antiviral spectra were highly correlated with sequence similarities, not only of amino acids lining the antiviral compound-binding-site, but also of amino acids of the whole VP1 protein. Furthermore, analysis of epidemiological data indicated that group B rhinoviruses produced more than twice as many clinical infections per serotype than group A rhinoviruses did. Rhinoviruses belonging to the minor receptor group were without exception all computed to lie in the same region of antiviral group B.     

Unusual synchronization of Red Sea fish energy expenditures

The highly gregarious goat fish Parupeneus forskalii found in the Red Sea at Eilat, Israel exhibit highly synchronous swimming and feeding activity. Five fish were studied under controlled conditions and highly resolved time‐series of their energy expenditures were measured. All fish demonstrated strong phase synchronization in that their activity levels, although erratic in time and intensity, were collectively coordinated and peaked simultaneously together. The synchronization of these wildly varying, and possibly chaotic signals of energy expenditures, were quantified using phase analysis. We suggest that, ecologically, this collective synchronization is a strategy that increases food‐catch.     

Partial growth hormone deficiency (GHD) in children has more similarities to idiopathic short stature than to severe GHD

INTRODUCTION: Assessment of growth hormone (GH) secretion is based on stimulation tests. Low GH peaks in stimulation tests, together with decreased insulin-like growth factor-I (IGF-I) secretion, confirm a diagnosis of GH deficiency (GHD). However, limitations in interpreting the test results and discrepancies between GH and IGF-I secretion in particular patients have both been reported. GH therapy should improve the prognosis of adult height (PAH). The aim of the study was to compare the deficit of height at diagnosis, IGF-I secretion and PAH in children with either decreased (in varying degrees of severity) or normal GH secretion in stimulation tests. MATERIAL AND METHODS: The analysis comprised 540 short children (373 boys, 167 girls), aged 11.7 +/- 3.2 years. In all the patients two GH stimulation tests were performed, IGF-I serum concentration was measured, bone age was assessed and PAH was calculated. According to the GH peak in the two stimulation tests, the patients were classified into the following groups: severe GHD (sGHD)--GH peak < 5 ng/mL (n = 44), partial GHD (pGHD)--GH peak 5-10 ng/mL (n = 190), idiopathic short stature (ISS)--GH peak at least 10 ng/mL (n = 306). RESULTS: A significantly greater deficit of height, lower IGF-I secretion and worse PAH were observed in sGHD than in both remaining groups, while all the differences between pGHD and ISS in the parameters analysed were insignificant. CONCLUSION: The results obtained indicate the necessity of applying another methods of qualifying short children for GH therapy other than GH stimulation tests with a cut-off value at a level of 10 ng/mL.     

Protein-protein interactions: mechanisms and modification by drugs

Protein-protein interactions form the proteinaceous network, which plays a central role in numerous processes in the cell. This review highlights the main structures, properties of contact surfaces, and forces involved in protein-protein interactions. The properties of protein contact surfaces depend on their functions. The characteristics of contact surfaces of short-lived protein complexes share some similarities with the active sites of enzymes. The contact surfaces of permanent complexes resemble domain contacts or the protein core. It is reasonable to consider protein-protein complex formation as a continuation of protein folding. The contact surfaces of the protein complexes have unique structure and properties, so they represent prospective targets for a new generation of drugs. During the last decade, numerous investigations have been undertaken to find or design small molecules that block protein dimerization or protein(peptide)-receptor interaction, or on the other hand, induce protein dimerization.     

Forced oscillations in a windkessel model

Volume elasticity of the arterial system and its component parts is developed starting from a Windkessel^*-model, which is defined in 4 points. Emphasis is laid on the simplicity of the derived equations and accessibility to experimental verification. The theory is an extension of earlier work achieved by Wetterer and Pieper (1953), who introduced an essentially physical method for the indirect determination of volume elasticity in situ, by creating forced sinusoidal oscillations in the arterial system, using a special pump operated at a considerably lower frequency than the mean heart frequency. The elegance of both experimental technique and the derived equations incited us to investigate the mathematical foundation and possible generalization of the method.     

Kinetic, structural and electrostatic aspects of the reduction of pentacyanoferrate(III) complexes by myoglobin

 The mechanism of the reduction of pentacyanoferrate(III) complexes by oxymyoglobin has been studied by conventional and high-pressure kinetic methods, and also by structural modelling. The results of this and an earlier study show that an outer-sphere mechanism is operating for electron transfer between oxymyoglobin and Fe^III(CN)₅L ^{n –}, independent of the lability of the ligand L. The electron transfer process is preceded by precursor formation at a specific site on the protein close to the protein heme pocket. Received: 10 November 1998 / Accepted: 25 February 1999     

Human Rhinovirus Type 14:Human Immunodeficiency Virus Type 1 (HIV-1) V3 Loop Chimeras from a Combinatorial Library Induce Potent Neutralizing Antibody Responses against HIV-1

In an effort to develop a useful AIDS vaccine or vaccine component, we have generated a combinatorial library of chimeric viruses in which the sequence IGPGRAFYTTKN from the V3 loop of the MN strain of human immunodeficiency virus type 1 (HIV-1) is displayed in many conformations on the surface of human rhinovirus 14 (HRV14). The V3 loop sequence was inserted into a naturally immunogenic site of the cold-causing HRV14, bridged by linkers consisting of zero to three randomized amino acids on each side. The library of chimeric viruses obtained was subjected to a variety of immunoselection schemes to isolate viruses that provided the most useful presentations of the V3 loop sequence for potential use in a vaccine against HIV. The utility of the presentations was assessed by measures of antigenicity and immunogenicity. Most of the immunoselected chimeras examined were potently neutralized by each of the four different monoclonal anti-V3 loop antibodies tested. Seven of eight chimeric viruses were able to elicit neutralizing antibody responses in guinea pigs against the MN and ALA-1 strains of HIV-1. Three of the chimeras elicited HIV neutralization titers that exceeded those of all but a small number of previously described HIV immunogens. These results indicate that HRV14:HIV-1 chimeras may serve as useful immunogens for stimulating immunity against HIV-1. This method can be used to flexibly reconstruct varied immunogens on the surface of a safe and immunogenic vaccine vehicle.