Search PubMed⌕ Search

Biomedical subjects

N Barton

Publications and source records attributed to N Barton.

At least 19 recordsLinked to original sources
PubMed2001

Genetic variation for preadult viability in Drosophila melanogaster.

The extent of genetic variation in fitness and its components and genetic variation's dependence on environmental conditions remain key issues in evolutionary biology. We present measurements of genetic variation in preadult viability in a laboratory-adapted population of Drosophila melanogaster, made at four different densities. By crossing flies heterozygous for a wild-type chromosome and one of two different balancers (TM1, TM2), we measure both heterozygous (TM1/+, TM2/+) and homozygous (+/+) viability relative to a standard genotype (TM1/TM2). Forty wild-type chromosomes were tested, of which 10 were chosen to be homozygous viable. The mean numbers produced varied significantly between chromosome lines, with an estimated between-line variance in log(e) numbers of 0.013. Relative viabilities also varied significantly across chromosome lines, with a variance in log(e) homozygous viability of 1.76 and of log(e) heterozygous viability of 0.165. The between-line variance for numbers emerging increased with density, from 0.009 at lowest density to 0.079 at highest. The genetic variance in relative viability increases with density, but not significantly. Overall, the effects of different chromosomes on relative viability were remarkably consistent across densities and across the two heterozygous genotypes (TM1, TM2). The 10 lines that carried homozygous viable wild-type chromosomes produced significantly more adults than the 30 lethal lines at low density and significantly fewer adults at the highest density. Similarly, there was a positive correlation between heterozygous viability and mean numbers at low density, but a negative correlation at high density.

Animals↗
PubMed2000

Ecology. The rapid origin of reproductive isolation.

Darwin's theory of evolution by natural selection has long been accepted, but it has not been clear how selection results in reproductive isolation of two populations. In an elegant Perspective, Barton discusses two reports (Higgie et al. and Hendry et al.) showing that selection can cause reproductive isolation between two populations within a dozen or so generations.

Animals↗
PubMed2000

Limits to natural selection.

We review the various factors that limit adaptation by natural selection. Recent discussion of constraints on selection and, conversely, of the factors that enhance "evolvability", have concentrated on the kinds of variation that can be produced. Here, we emphasise that adaptation depends on how the various evolutionary processes shape variation in populations. We survey the limits that population genetics places on adaptive evolution, and discuss the relationship between disparate literatures.

Animals↗
PubMed2000

Prevalence and genomic variation of Norwalk-like viruses in central Australia in 1995-1997.

Norwalk-like viruses (NLVs) have now been found to be important causes of gastroenteritis amongst infants and young children as well as older children and adults. Although detected, such viruses appeared not to be a major cause amongst infants and young children hospitalized with gastroenteritis in Alice Springs, central Australia over the period January 1995-December 1997. Nine NLV-positive cases were identified amongst stools from 360 different patients. From the nine cases however, eight different NLV strains were identified from comparisons of the sequence of a section of the RNA polymerase gene, and a high degree of genomic diversity was evident amongst them. In general, these strains were more similar to those identified in other countries than to those identified in central Australia over the three year period. Of the strains identified, six (and most probably seven) were classified in genogroup I, while only one was classified in genogroup II. This predominance of genogroup I strains is in contrast to most of the more recent findings made elsewhere, including those made in other parts of Australia. Phylogenetic analysis indicated that the central Australian strains spanned a range of known representative NLV strains, with one of the genogroup I strains showing a 96% nucleotide identity to Saratoga virus.

Amino Acid Sequence↗
PubMed1999

Resistance exercise and supraphysiologic androgen therapy in eugonadal men with HIV-related weight loss: a randomized controlled trial.

CONTEXT: Repletion of lean body mass (LBM) that patients lose in human immunodeficiency virus (HIV) infection has proved difficult. In healthy, HIV-seronegative men, synergy between progressive resistance exercise (PRE) and very high-dose testosterone therapy has been reported for gains in LBM and muscle strength. OBJECTIVE: To determine whether a moderately supraphysiologic androgen regimen, including an anabolic steroid, would improve LBM and strength gains of PRE in HIV-infected men with prior weight loss and whether protease inhibitor antiretroviral therapy prevents lean tissue anabolism. DESIGN: Double-blind, randomized, placebo-controlled trial; post hoc analysis for effect of HIV-protease inhibitor therapy conducted from January to October 1997. SETTING: Referral center in San Francisco, Calif. PATIENTS: Volunteer sample of 24 eugonadal men with HIV-associated weight loss (mean, 9% body weight loss), recruited from an AIDS clinic and by referral and by advertisement. INTERVENTION: For 8 weeks, all subjects received supervised PRE with physiologic intramuscular testosterone replacement (100 mg/wk) to suppress endogenous testosterone production. Randomization was between an anabolic steroid, oxandrolone, 20 mg/d, and placebo. MAIN OUTCOME MEASURES: Lean body mass, nitrogen balance (10-day metabolic ward measurements), body weight, muscle strength, and androgen status. RESULTS: Twenty-two subjects completed the study (1 1 per group). Both groups showed significant nitrogen retention and increases in LBM, weight, and strength. The mean (SD) gains were significantly greater in the oxandrolone group than in the placebo group (5.6 [2.1] vs 3.8 [1.8] g of nitrogen per day [P=.05]; 6.9 [1.7] vs 3.8 [2.9] kg of LBM [P=.005]; greater strength gains for various upper and lower body muscle groups by maximum weight lifted [P = .02-.05] and dynamometry [P = .01 -.05]). The mean (SD) high-density lipoprotein cholesterol level declined 0.25 (0.14) mmol/L (9.8 [5.4] mg/dL) significantly in the oxandrolone group (P < .001 compared with placebo). Results were similar whether or not patients were taking protease inhibitors. One subject in the oxandrolone group discontinued the study because of elevated liver function test results. CONCLUSIONS: A moderately supraphysiologic androgen regimen that included an anabolic steroid, oxandrolone, substantially increased the lean tissue accrual and strength gains from PRE, compared with physiologic testosterone replacement alone, in eugonadal men with HIV-associated weight loss. Protease inhibitors did not prevent lean tissue anabolism.

Adult↗
PubMed1999

Evaluation of the effects of oxandrolone on malnourished HIV-positive pediatric patients.

OBJECTIVE: To determine the safety and efficacy of anabolic therapy to prevent or reverse wasting and malnutrition in human immunodeficiency virus (HIV)-infected pediatric patients. The anabolic steroid, oxandrolone, was evaluated because of its safe and effective use in other pediatric conditions. METHODS: Nine HIV-positive children who were malnourished or at risk for malnutrition (4 females, 5 males; 4-14 years of age) took oxandrolone for 3 months (.1 mg/kg/day orally). Quantitative HIV ribonucleic acid polymerase chain reaction and CD4(+) T-cell levels, complete blood cell count (CBC) and chemistry profile, endocrinologic studies, resting energy expenditure, respiratory quotient, nutritional measures, body composition assessment with quantitative computed tomography, and skinfold body composition measurements were determined before treatment, during treatment (3 months), and for 3 months after treatment. Statistical analyses were completed using the Friedman two-way analysis of variance and Spearman correlation tests. RESULTS: No adverse clinical or laboratory events or changes in Tanner staging or virilization occurred. Quantitative HIV ribonucleic acid polymerase chain reaction and CD4(+) T-cell levels did not change significantly. Insulin-like growth factor 1 increased, suggesting an anabolic effect of treatment. The rate of weight gain increased during treatment and was maintained after treatment. Linear growth continued and was maintained throughout treatment, whereas bone age did not increase significantly. Anthropometric assessments indicated an increase in muscle mass and a decrease in fat while patients were on treatment, and a mild decrease of muscle and increased fat posttreatment. Likewise, computed tomography scan results demonstrated similar changes in muscle mass. Resting energy expenditure and respiratory quotient remained stable throughout treatment and follow-up. No significant changes were seen in the quality of life questionnaire. CONCLUSIONS: Treatment with oxandrolone for 3 months in HIV-infected children was well-tolerated, safe, and associated with markers of anabolism. The latter effect was maintained partially for 3 months after discontinuation of a 3-month course of therapy. Additional studies are needed to assess the potential benefits and risks of a longer course of therapy or a higher dose of oxandrolone in HIV-infected children.

Adolescent↗
PubMed1995

A new human gene located in the PKD1 region of chromosome 16 is a functional homologue to ERV1 of yeast.

A new human gene has been identified on chromosome 16 in the interval containing the locus for polycystic kidney disease (PKD1) by analysis of a genomic cosmid clone and cDNAs. The gene contains at least one intron and is actively transcribed in tissues from kidney and brain. The putative gene product is predicted to be homologous to the yeast scERV1 protein by virtue of the high degree of identity (42%) over the entire length of the polypeptides. In former studies the yeast scERV1 gene was found to be essential for oxidative phosphorylation, the maintenance of mitochondrial genomes, and the cell-division cycle. In this study a yeast expression vector with a chimeric reading frame coding for the first 21 amino acids of the yeast protein and the terminal 100 amino acid residues of the human factor was transformed into yeast mutants with two different defects for scERV1. The chimeric human gene product was able to complement the yeast mutants and restored near normal viability. This identifies the human gene as a structural and functional homologue of the scERV1 gene.

Amino Acid Sequence↗
PubMed1995

The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin.

The N-ethylmaleimide-sensitive fusion protein (NSF) plays an essential role in intracellular membrane fusion events and has been implicated in the exocytosis of synaptic vesicles. NSF binds through soluble NSF attachment proteins (SNAPs) to a complex of neuronal membrane proteins comprised of synaptobrevin, syntaxin, and SNAP-25. Disassembly of this complex by NSF is thought to be a critical step in the molecular events which lead to vesicle fusion with the plasma membrane. Here we have studied the interaction of alpha-SNAP and NSF with individual components of this complex and have identified syntaxin as a primary substrate for NSF/alpha-SNAP. We find that alpha-SNAP binds directly to syntaxin 1A as well as weakly to SNAP-25, while it does not bind to synaptobrevin II. NSF binds to syntaxin through alpha-SNAP and in the presence of ATP catalyzes a conformational rearrangement which abolishes binding of itself and alpha-SNAP. This reaction leads to the previously described disassembly of the fusion complex, since synaptobrevin binding to syntaxin is also reduced. alpha-SNAP binds to a carboxyl-terminal syntaxin fragment (residues 194-288) that also binds synaptobrevin and SNAP-25. However, NSF action on this syntaxin fragment has no effect on the binding of alpha-SNAP or synaptobrevin. This suggests that the conformational change normally induced by NSF in syntaxin depends on an interaction between carboxyl- and amino-terminal domains of syntaxin.

Base Sequence↗
PubMed1994

SNAP-25, a t-SNARE which binds to both syntaxin and synaptobrevin via domains that may form coiled coils.

The membrane proteins SNAP-25, syntaxin, and synaptobrevin (vesicle-associated membrane protein) have recently been implicated as central elements of an exocytotic membrane fusion complex in neurons. Here we report that SNAP-25 binds directly to both syntaxin and synaptobrevin. The SNAP-25-binding domain of syntaxin lies between residues 199 and 243, within the region previously shown to mediate synaptobrevin binding (Calakos, N., Bennett, M. K., Peterson, K. E., and Scheller, R. H. (1994) Science 263, 1146-1149). The syntaxin-binding domain of SNAP-25 encompasses most of the amino-terminal half of SNAP-25, including its putative palmitoylation sites. Truncation of the carboxyl-terminal 9 residues of SNAP-25, which yields a fragment corresponding to that generated by botulinum neurotoxin A, diminishes the interaction of SNAP-25 with synaptobrevin, but not with syntaxin. Sequence analysis revealed that the regions that mediate the interaction between SNAP-25 and syntaxin contain heptad repeats characteristic of certain classes of alpha-helices. Similar repeats are also present at the carboxyl terminus of SNAP-25 and in synaptobrevin. These domains have a moderate to high probability of forming coiled coils. We conclude that SNAP-25 can interact with both syntaxin and synaptobrevin and that binding may be mediated by alpha-helical domains that form intermolecular coiled-coil structures.

Animals↗
PubMed1994

Linkage disequilibrium in the region of the autosomal dominant polycystic kidney disease gene (PKD1).

The gene for autosomal dominant polycystic kidney disease (PKD1) is located on chromosome 16p, between the flanking markers D16S84 and D16S125 (26.6prox). This region is 750 kb long and has been cloned. We have looked at the association of 10 polymorphic markers from the region, with the disease and with each other. This was done in a set of Scottish families that had previously shown association with D16S94, a marker proximal to the PKD1 region. We report significant association between two CA repeat markers and the disease but have not found evidence for a single founder haplotype in these families, indicating the presence of several mutations in this population. Our results favor a location of the PKD1 gene in the proximal part of the candidate region.

Alleles↗
PubMed1992

The gene for autosomal dominant polycystic kidney disease lies in a 750-kb CpG-rich region.

PKD1, the locus most commonly affected by mutations that produce autosomal dominant polycystic kidney disease (ADPKD), has previously been localized to chromosome 16p13.3. Since no cytogenetic abnormalities have been found in association with ADPKD, flanking genetic markers have been required to define an interval--the PKD1 region--that contains the PKD1 gene. In this report we demonstrate, through the construction of a long-range restriction map that links the flanking genetic markers GGG1 (D16S84) and 26.6PROX (D16S125), that the PKD1 gene lies within an extremely CpG-rich 750-kb segment of chromosome 16p13.3. Approximately 90% of this region has been cloned in three extensive cosmid/bacteriophage contigs. The cloned DNA is a valuable resource for identifying new closer flanking genetic markers and for isolating candidate genes from the region.

Chromosomes, Human, Pair 16↗
PubMed1992

Tophaceous pyrophosphate deposition with extensor tendon rupture.

Tophaceous deposition of calcium pyrophosphate dihydrate (CPPD) crystals is considered unusual as is deposition within tendon sheaths. Associated tendon rupture is described but is rare. We report a lady with tophaceous CPPD deposition at the wrist, a previously unreported site. Contrary to previous cases, this occurred in the setting of symptomatic, polyarticular, pyrophosphate arthropathy. An additional point of interest was development of associated extensor tendon rupture with features favouring a non-inflammatory mechanism of tendon damage.

Aged↗