Molecular evolution of viral fusion and matrix protein genes and phylogenetic relationships among the Paramyxoviridae.

Phylogenetic relationships among the Paramyxoviridae, a broad family of viruses whose members cause devastating diseases of wildlife, livestock, and humans, were examined with both fusion (F) and matrix (M) protein-coding sequences. Neighbor-joining trees of F and M protein sequences showed that the Paramyxoviridae was divided into the two traditionally recognized subfamilies, the Paramyxovirinae and the Pneumovirinae. Within the Paramyxovirinae, the results also showed groups corresponding to three currently recognized genera: Respirovirus, Morbillivirus, and Rubulavirus. The relationships among the three genera of the Paramyxovirinae were resolved with M protein sequences and there was significant bootstrap support (100%) showing that members of the genus Respirovirus and the genus Morbillivirus were more closely related to each other than to members of the genus Rubulavirus. Both F and M phylogenies showed that Newcastle disease virus (NDV) was more closely related to the genus Rubulavirus than to the other two genera but were consistent with the proposal (B. S. Seal et al., 2000, Virus Res. 66, 1-11) that NDV be classified as a separate genus within the Paramyxovirinae. Both F and M phylogenies were also consistent with the proposal (L. Wang et al., 2000, J. Virol 74, 9972-9979) that Hendra virus be classified as a new genus closely related and basal to the genus Morbillivirus. Rinderpest was most closely related to measles and a more derived virus than to canine distemper virus, phocine distemper virus, or dolphin morbillivirus.

Simultaneous positive and purifying selection on overlapping reading frames of the tat and vpr genes of simian immunodeficiency virus.

Tat-specific cytotoxic T cells have previously been shown to exert positive Darwinian selection favoring amino acid replacements of an epitope of simian immunodeficiency virus (SIV). The region of the tat gene encoding this epitope falls within a region of overlap between the tat and vpr reading frames, and nonsynonymous nucleotide substitutions in the tat reading frame were found to occur disproportionately in such a way as to cause synonymous changes in the vpr reading frame. Comparison of published complete SIV genomes showed Tat to be the least conserved at the amino acid level of nine proteins encoded by the virus, while Vpr was one of the most conserved. Numerous parallel amino acid changes occurred within the Tat epitope independently in different monkeys, and purifying selection on the vpr reading frame, by limiting acceptable nonsynonymous substitutions in the tat reading frame, evidently has enhanced the probability of parallel evolution.

Nonsteroidal anti-inflammatory drugs, acetaminophen, cyclooxygenase 2, and fever.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used antipyretic agents that most probably exert their antifever effect by inhibiting cyclooxygenase (COX)-2. Thus, COX-2-selective drugs or null mutation of the COX-2 gene reduce or prevent fever. Acetaminophen is antipyretic and analgesic, as are NSAIDs, but it lacks the anti-inflammatory and anticoagulatory properties of these drugs. This has led to the speculation that a COX variant exists that is inhibitable by acetaminophen. An acetaminophen-inhibitable enzyme is inducible in the mouse J774.2 monocyte cell line. Induction of acetaminophen-inhibitable prostaglandin E(2) synthesis parallels induction of COX-2. Thus, inhibition of pharmacologically distinct COX-2 enzyme activity by acetaminophen may be the mechanism of action of this important antipyretic drug.

Mechanism of Rab geranylgeranylation: formation of the catalytic ternary complex.

Rab proteins are geranylgeranylated on one or two C-terminal cysteines by Rab geranylgeranyl transferase (RabGGTase). The reaction is dependent on a Rab-binding protein, termed Rab escort protein (REP). Here, we studied the role of REP in the geranylgeranylation reaction. We first characterized the interaction between REP and ungeranylgeranylated Rab using analytical ultracentrifugation and a fluorescence-based assay. We measured an equilibrium dissociation constant of 0.2 microM for the formation of a 1:1 REP-Rab complex and showed that this interaction relies mostly on ionic bonds and does not involve the two C-terminal cysteine residues. Second, we show that REP is required for recognition of Rab by RabGGTase and therefore that the REP-Rab complex is the true substrate for RabGGTase. Third, we show that free REP inhibits the geranylgeranylation reaction, suggesting that the complex is recognized by RabGGTase primarily via a REP-binding site. Our data suggest a model whereby REP behaves kinetically as an essential activator of the reaction.

The relationship of breastfeeding to oral development and dental concerns.

Infants' oral muscles are exercised strenuously in suckling. Breastfeeding contributes an important influence on the thrust and growth of the mandible, in addition to imparting maternal immunological components in the nutritious milk. Infant feeding practices may affect the life-long health of the child. Appropriate, health-promoting practices, such as breastfeeding, should be encouraged by healthcare professionals.

Effects of increased dietary calcium intake upon the calcium and bone mineral status of lactating adolescent and adult women.

We studied the effectiveness of an increased calcium (Ca) diet in preventing bone mineral loss in lactating adolescent mothers. Three groups of lactating women were studied: 15 control adolescents consuming their usual Ca diet (900 mg/d), 21 experimental adolescents consuming a high-Ca diet (greater than 1600 mg/d), and 12 adults. At 2 and 16 wk postpartum, serum calcium, phosphate, magnesium, albumin, alkaline phosphatase, vitamin D, parathyroid hormone (PTH), and calcitonin (CT) were determined. Bone mineral analyses were performed by photon absorptiometry. By 16 wk the control adolescent group had a 10% decrease in bone mineral content (BMC) and increased PTH and CT. The experimental adolescent and adult groups had no significant change in BMC during the study. There was a positive correlation (r = 0.45, p less than 0.01) between dietary Ca intake and BMC in all adolescents. Data suggest that bone loss during lactation in adolescents may be prevented with adequate dietary Ca intakes.