Given that gene duplication is a major driving force of evolutionary change and the key mechanism underlying the emergence of new genes and biological processes, this study sought to use a novel genome-wide approach to identify genes that have undergone lineage-specific duplications or contractions among several hominoid lineages. Interspecies cDNA array-based comparative genomic hybridization was used to individually compare copy number variation for 39,711 cDNAs, representing 29,619 human genes, across five hominoid species, including human. We identified 1,005 genes, either as isolated genes or in clusters positionally biased toward rearrangement-prone genomic regions, that produced relative hybridization signals unique to one or more of the hominoid lineages. Measured as a function of the evolutionary age of each lineage, genes showing copy number expansions were most pronounced in human (134) and include a number of genes thought to be involved in the structure and function of the brain. This work represents, to our knowledge, the first genome-wide gene-based survey of gene duplication across hominoid species. The genes identified here likely represent a significant majority of the major gene copy number changes that have occurred over the past 15 million years of human and great ape evolution and are likely to underlie some of the key phenotypic characteristics that distinguish these species.
We followed up swimming performance times of 321 women and 319 men who participated in the US Masters Swimming Championships over a 12-yr period. All swimmers placed in the top 10 in their age group over 3 yr (mean = 5 yr). A random coefficients model for repeated measures was used to derive a line of best fit from a group of regression lines for each subject. Both 50- and 1,500-m swimming performance declined modestly until ∼70 yr of age, where a more rapid decline was observed in both men and women. Compared with 1,500-m swimming, the 50-m freestyle declined more modestly and slowly with age. The rate and magnitude of declines in swimming performance with age were greater in women than in men in 50-m freestyle; such sex-related differences were not observed in 1,500-m freestyle. Overall, the variability along a population regression line increased markedly with advancing age. The present longitudinal findings indicate that 1) swimming performance declines progressively until age 70, where the decrease becomes quadratic; 2) the rates of the decline in swimming performance with age are greater in a long-duration than in a short-duration event, suggesting a relatively smaller loss of anaerobic muscular power with age compared with cardiovascular endurance; 3) the age-related rates of decline are greater in women than in men only in a short-duration event; and 4) the variability of the age-related decline in performance increases markedly with advancing age.
Rationale: Allergic diseases are an increasing public health concern, and early life environment is critical to immune development. Maternal diet during pregnancy has been linked to offspring allergy risk. In turn, maternal diet is a potentially modifiable factor, which could be targeted as an allergy prevention strategy. In this systematic review, we focused on non-allergen-specific modifying factors of the maternal diet in pregnancy on allergy outcomes in their offspring. Methods: We undertook a systematic review of studies investigating the association between maternal diet during pregnancy and allergic outcomes (asthma/wheeze, hay fever/allergic rhinitis/seasonal allergies, eczema/atopic dermatitis (AD), food allergies, and allergic sensitization) in offspring. Studies evaluating the effect of food allergen intake were excluded. We searched three bibliographic databases (MEDLINE, EMBASE, and Web of Science) through February 26, 2019. Evidence was critically appraised using modified versions of the Cochrane Collaboration Risk of Bias tool for intervention trials and the National Institute for Clinical Excellence methodological checklist for cohort and case-control studies and meta-analysis performed from RCTs. Results: We identified 95 papers: 17 RCTs and 78 observational (case-control, crosssectional, and cohort) studies. Observational studies varied in design and dietary intakes and often had contradictory findings. Based on our meta-analysis, RCTs showed that vitamin D supplementation (OR: 0.72; 95% CI: 0.56-0.92) is associated with a reduced risk of wheeze/asthma. A positive trend for omega-3 fatty acids was observed for asthma/wheeze, but this did not reach statistical significance (OR: 0.70; 95% CI: 0.45-1.08). Omega-3 supplementation was also associated with a non-significant decreased risk of allergic rhinitis (OR: 0.76; 95% CI: 0.56-1.04). Neither vitamin D nor omega-3 fatty acids were associated with an altered risk of AD or food allergy. Conclusions: Prenatal supplementation with vitamin D may have beneficial effects for prevention of asthma. Additional nutritional factors seem to be required for modulating the risk of skin and gastrointestinal outcomes. We found no consistent evidence regarding other dietary factors, perhaps due to differences in study design and host features that were not considered. While confirmatory studies are required, there is also a need for performing RCTs beyond single nutrients/foods.
Objective. To use human cartilage samples and a mouse model of osteoarthritis (OA) to determine whether extracellular superoxide dismutase (EC-SOD) is a constituent of cartilage and to evaluate whether there is a relationship between EC-SOD deficiency and OA.Methods. Samples of human cartilage were obtained from femoral heads at the time of joint replacement surgery for OA or femoral neck fracture. Samples of mouse tibial cartilage obtained from STR/ort mice and CBA control mice were compared at 5, 15, and 35 weeks of age. EC-SOD was measured by enzyme-linked immunosorbent assay, Western blotting, and immunohistochemistry techniques. Real-time quantitative reverse transcription-polymerase chain reaction was used to measure messenger RNA for EC-SOD and for endothelial cell, neuronal, and inducible nitric oxide synthases. Nitrotyrosine formation was assayed by Western blotting in mouse cartilage and by fluorescence immunohistochemistry in human cartilage.Results. Human articular cartilage contained large amounts of EC-SOD (mean ؎ SEM 18.8 ؎ 3.8 ng/gm wet weight of cartilage). Cartilage from patients with OA had an ϳ4-fold lower level of EC-SOD compared with cartilage from patients with hip fracture. Young STR/ort mice had decreased levels of EC-SOD in tibial cartilage before histologic evidence of disease occurred, as well as significantly more nitrotyrosine formation at all ages studied.Conclusion. EC-SOD, the major scavenger of reactive oxygen species in extracellular spaces, is decreased in humans with OA and in an animal model of OA. Our findings suggest that inadequate control of reactive oxygen species plays a role in the pathophysiology of OA.
Resting and exercise fuel metabolism was assessed in three different phases of the menstrual cycle, characterized by different levels of estrogen relative to progesterone: early follicular (EF, low estrogen and progesterone), midfollicular (MF, elevated estrogen, low progesterone), and midluteal (ML, elevated estrogen and progesterone). It was hypothesized that exercise glucose utilization and whole body carbohydrate oxidation would decrease sequentially from the EF to the MF to the ML phase. Normal-weight healthy females, experiencing a regular menstrual cycle, were recruited. Subjects were moderately active but not highly trained. Testing occurred after 3 days of diet control and after an overnight fast (12-13 h). Resting (2 h) and exercise (50% maximal O 2 uptake, 90 min) measurements of whole body substrate oxidation, tracer-determined glucose flux, and substrate and hormone concentrations were made. No significant difference was observed in whole body fuel oxidation during exercise in the three phases (nonprotein respiratory exchange ratio: EF 0.84 ± 0.01, MF 0.85 ± 0.01, ML 0.85 ± 0.01) or in rates of glucose appearance or disappearance. There were, however, significantly higher glucose (P < 0.05) and insulin (P < 0.001) concentrations during the first 45 min of exercise in the ML phase vs. EF and MF phases. In conclusion, whole body substrate oxidation and glucose utilization did not vary significantly across the menstrual cycle in moderately active women, either at rest or during 90 min of moderate-intensity exercise. During the ML phase, however, this similar pattern of substrate utilization was associated with greater glucose and insulin concentrations. Both estrogen and progesterone are elevated during the ML phase of the menstrual cycle, suggesting that one or both of these sex steroids may play a role in this response.Keywords substrate oxidation; female sex steroids; glucose metabolism IN PREMENOPAUSAL WOMEN, the menstrual cycle represents a continuous state of change in terms of the female sex steroid environment. Determining how the menstrual cycle phase affects various aspects of metabolism is necessary to provide a comprehensive understanding of normal physiology in women. It is also important to establish the necessity of controlling for sex steroid hormone status when women are included in metabolic studies. This is relevant both to the resting condition and during perturbations common to everyday life, such as exercise. Copyright © 2002 the American Physiological SocietyAddress for reprint requests and other correspondence: T. J. Horton, Center for Human Nutrition, Box C225, Univ. of Colorado Health Sciences Center, 4200 East 9th Ave., Denver, CO 80262 (E-mail: Tracy.Horton@uchsc.edu).. NIH Public Access Author ManuscriptAm J Physiol Endocrinol Metab. Author manuscript; available in PMC 2011 June 27. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptData would suggest that the normal cyclical variation in estrogen and/or progesterone could affect a number of ...
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