Macrophage-tropic, non-syncytium-inducing, HIV-1 variants predominate in the asymptomatic phase of infection and may be responsible for establishing infection in an individual exposed to the mixture of HIV-1 variants. Here, genotypical and phenotypical characteristics of virus populations, present in sexual, parenteral, or vertical donor-recipient pairs, were studied. Sequence analysis of the V3 domain confirmed the presence of a homogeneous virus population in recently infected individuals. Biological HIV-1 clones were further characterized for syncytium inducing capacity on the MT2 cell line and for macrophage tropism as defined by the appearance of proviral DNA upon inoculation of monocyte-derived macrophages. Both sexual and parenteral transmission cases revealed a selective outgrowth in the recipient of the most macrophage-tropic variant(s) present in the donor. In three out of five vertical transmission cases, more than one highly macrophage-tropic virus variant was present in the child shortly after birth, suggestive of transmission of multiple variants. In three primary infection cases, homogeneous virus populations of macrophagetropic, non-syncytium-inducing variants were present prior to seroconversion, thus excluding humoral immunity as the selective pressure in favour of macrophage-tropic variants. These observations may have important implications for vaccine development. (J. Clin. Invest. 1994. 94
The glycaemic index (GI) is an in vivo measurement based on the glycaemic response to carbohydratecontaining foods, and allows foods to be ranked on the basis of the rate of digestion and absorption of the carbohydrates that they contain. GI values are normalized to a reference amount of available carbohydrate and do not reflect the amounts of carbohydrate normally present in foods; for example, a food with a low content of carbohydrates will have a high GI value if that carbohydrate is digested and absorbed rapidly in the human small intestine. This is potentially confusing for a person wishing to control his or her blood glucose levels by the choice of foods. The rate and extent of starch digestion in vitro has been measured using a technique that classifies starch into three major fractions: rapidly digestible starch (RDS), slowly digestible starch (SDS) and resistant starch (RS). In addition, this technique gives a value for rapidly available glucose (RAG), which includes RDS, free glucose and the glucose moiety of sucrose. When the values for thirty-nine foods were expressed on the basis of the available carbohydrate content of these foods, highly significant (P < 0001) positive correlations were observed between GI and both RDS and RAG. The measurement of RAG in vitro provides values for direct calculation of the amount of glucose likely to be rapidly absorbed in the human small intestine and, thus, to influence blood glucose and insulin levels. These values can be used to compare foods, as eaten, on an equal-weight basis. Food-table RAG values would allow simple calculation of the total amount of RAG provided by single foods, by whole meals and by whole diets. Studies are planned in which RAG and the glycaemic response in man will be measured for identical food products.
Regulatory peptides are synthesized as part of larger precursors that are subsequently processed into the active substances. After cleavage of the signal peptide, further proteolytic processing occurs predominantly at basic amino acid residues. Rules have been proposed in order to predict which putative proteolytic processing sites are actually used, but these rules have been established for vertebrate peptide precursors and it is unclear whether they are also valid for insects. The aim of this paper is to establish the validity of these rules to predict proteolytic cleavage sites at basic amino acids in insect neuropeptide precursors. Rules describing the cleavage of mono- and dibasic potential processing sites in insect neuropeptide precursors are summarized below. Lys-Arg pairs not followed by an aliphatic or basic amino acid residue are virtually always cleaved in insect regulatory peptide precursors, but cleavages of Lys-Arg pairs followed by either an aliphatic or a basic amino acid residue are ambiguous, as is processing at Arg-Arg pairs. Processing at Arg-Lys pairs has so far not been demonstrated in insects and processing at Lys-Lys pairs appears very rare. Processing at single Arg residues occurs only when there is a basic amino acid residue in position -4, -6, or -8, usually an Arg, but Lys or His residues work also. Although the current number of such sites is too limited to draw definitive conclusions, it seems plausible that cleavage at these sites is inhibited by the presence of aliphatic residues in the +1 position. However, cleavage at single Arg residues is ambiguous. When several potential cleavage sites overlap the one most easily cleaved appears to be processed. It cannot be excluded that some of the rules formulated here will prove less than universal, as only a limited number of cleavage sites have so far been identified. It is likely that, as in vertebrates, ambiguous processing sites exist to allow differential cleavage of the same precursor by different convertases and it seems possible that the precursors of allatostatins and PBAN are differentially cleaved in different cell types. Arch. Insect Biochem. Physiol. 43:49-63, 2000.
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