Comparative study of regulatory T cells expanded ex vivo from cord blood and adult peripheral blood

In this study, we expanded regulatory T cells (Tregs) ex vivo from CD4(+) CD25(+) T cells from cord blood (CB) and CD4(+) CD25(+) CD127(-) T cells from adult peripheral blood (APB) and compared the suppressive functions of the newly generated Tregs. The Tregs from CB and APB were expanded either in two cycles with a polyclonal stimulus or in two cycles with an alloantigen stimulus in the first cycle and a polyclonal stimulus in the second cycle. Cell yield after Treg expansion with polyclonal stimulation was greater than that of Tregs expanded with combined alloantigen and polyclonal stimulation. The expanded Tregs expressed high levels of Foxp3, CD39 and cytotoxic T-lymphocyte antigen-4 and low levels of CD127, interleukin-2 and interferon-γ. After two cycles of expansion, the CB Tregs maintained expression of the GARP gene and showed greater suppressive function than APB Tregs. The CB Tregs that were expanded with two cycles of polyclonal stimulation suppressed not only the polyclonal antigen-driven responder T (T(resp)) cell proliferation but also the HLA mismatched dendritic cell-driven T(resp) cell proliferation. When CB and APB Tregs were expanded with a primary alloantigen stimulus followed by a secondary polyclonal stimulus, the Tregs showed a potent, antigen-specific suppressive capacity. The Tregs expanded with two cycles of polyclonal stimulation from both CB and APB alleviated acute graft-versus-host disease symptoms and prolonged survival in a murine model of graft-versus-host disease. In conclusion, CB Tregs expanded with two cycles of polyclonal stimulation had a stronger immunosuppressive function than APB Tregs. It is feasible to obtain human functional alloantigen-specific Tregs expanded ex vivo from CB and APB in large numbers.     

Impact of mercury exposure on blood pressure and cardiac autonomic activity among Cree adults (James Bay, Quebec, Canada)

Aboriginal populations from Quebec (Canada) are exposed to higher mercury levels than southern regions since these populations consume high quantities of fish. Epidemiological evidence suggests a detrimental impact of mercury on cardiovascular risk factors such as heart rate variability (HRV) and blood pressure (BP). The objective of this study was to assess the impact of mercury exposure on BP, resting heart rate (HR) and HRV among Cree adults. Data were collected among 791 adults ≥18 years old living in seven communities of the James Bay. Blood mercury and hair levels were used as biomarkers of recent and long-term exposure. BP was measured through a standardised protocol while HRV was derived from a 2-h Holter monitoring assessment. The relationship between mercury and the outcomes was studied using ANOVA and ANCOVA analysis. Geometric mean of blood mercury and hair mercury concentration was 17.0 nmol/L (95%CI: 6.1–44.0) and 2.36 nmol/g (95%CI: 2.09–2.65); respectively. After adjusting for confounders, blood mercury was associated with HRV parameters such as LF (β=0.21, P=0.0002), HF (β=0.15, P=0.004) and LF/HF (β=0.06, P=0.003). Similar associations were observed with hair mercury. In contrast, no significant association was observed between blood mercury or hair mercury and BP after adjusting for confounders. In conclusion, mercury exposure seems to affect HRV among Cree adults even after considering fish nutrients (n-3 fatty acids and selenium) and other contaminants (lead and polychlorinated biphenyls) that are also present in the traditional diet of this population.     

Factors associated with eating out of home in Vietnamese adolescents

Eating out of home (OH) is nutritionally important in some developing countries. This study identifies the factors associated with eating OH in Vietnamese adolescents. Data were obtained from a cross-sectional cluster survey of 502 adolescents in rural and urban areas in Vietnam. Factors associated with eating OH were recorded with a Likert scale and analysed using factor analysis. Data on eating OH was collected using a frequency questionnaire and a 1-day 24 h recall. A first pattern “Convenience” incorporated preparation time, price, variety, taste, proximity and social aspects as items associated with eating OH. A second pattern “Nutritional and food safety concerned” reflected concerns with regard to hygiene, fat and salt content of the food prepared OH. Adolescents characterised by the convenience pattern were more likely (OR =1.51, P < 0.001) to eat OH more frequently. The highest tertile of the Nutritional and food safety concerned pattern was less likely (OR = 0.61, P = 0.03) to eat OH compared to lower tertiles. Both patterns were not associated with the % energy from eating OH per day. Convenience and to a lesser extent Nutritional and food safety concerns are significant factors associated with the frequency of eating OH in Vietnamese adolescents.     

Human leukocyte antigen associations with humoral and cellular immunity following a second dose of measles-containing vaccine: persistence, dampening, and extinction of associations found after a first dose

Previously we found human leukocyte antigen (HLA) associations with humoral immunity following a single dose of measles-containing vaccine. In this study, we sought to determine if HLA associations exist with humoral and cellular immunity following a second dose of measles-containing vaccine and if the associations we found with humoral immunity after the first dose persist following a second dose.We recruited a population-based sample of 346 schoolchildren, all who previously received two doses of a measles-containing vaccine. Molecular HLA classes I and II typing as well as humoral and cellular immune assays (measles-specific IgG antibody levels and lymphoproliferative response) were performed in these subjects.We found significant associations with class I HLA-B (p = 0.05) as well as class II HLA-DPB1 (p = 0.01) and -DPA1 (p = 0.03) genes for measles vaccine-induced antibody levels after the second dose. Similarly, we found significant associations with class II HLA-DQB1 (p = 0.05) and -DRB1 (p = 0.01) genes for measles-specific lymphoproliferation after the second dose.While we found HLA associations after the second dose that we previously found after the first dose of measles containing vaccine, fewer alleles had statistically significant associations, suggesting that the second dose had a dampening or extinguishing effect on the HLA associations. It appears that the second dose overcomes HLA restriction through an as yet unknown mechanism. Future studies of HLA associations should consider both the effect of dose and the role that subsequent doses might play on genetic associations found with the response to a first dose.     

Polyploidy and ecological adaptation in wild yarrow

Chromosome evolution in flowering plants is often punctuated by polyploidy, genome duplication events that fundamentally alter DNA content, chromosome number, and gene dosage. Polyploidy confers postzygotic reproductive isolation and is thought to drive ecological divergence and range expansion. The adaptive value of polyploidy, however, remains uncertain; ecologists have traditionally relied on observational methods that cannot distinguish effects of polyploidy per se from genic differences that accumulate after genome duplication. Here I use an experimental approach to test how polyploidy mediates ecological divergence in Achillea borealis (Asteraceae), a widespread tetraploid plant with localized hexaploid populations. In coastal California, tetraploids and hexaploids occupy mesic grassland and xeric dune habitats, respectively. Using field transplant experiments with wild-collected plants, I show that hexaploids have a fivefold fitness advantage over tetraploids in dune habitats. Parallel experiments with neohexaploids--first-generation mutants screened from a tetraploid genetic background--reveal that a 70% fitness advantage is achieved via genome duplication per se. These results suggest that genome duplication transforms features of A. borealis in a manner that confers adaptation to a novel environment.     

Evolution of cold-tolerant fungal symbionts permits winter fungiculture by leafcutter ants at the northern frontier of a tropical ant-fungus symbiosis

The obligate mutualism between leafcutter ants and their Attamyces fungi originated 8 to 12 million years ago in the tropics, but extends today also into temperate regions in South and North America. The northernmost leafcutter ant Atta texana sustains fungiculture during winter temperatures that would harm the cold-sensitive Attamyces cultivars of tropical leafcutter ants. Cold-tolerance of Attamyces cultivars increases with winter harshness along a south-to-north temperature gradient across the range of A. texana, indicating selection for cold-tolerant Attamyces variants along the temperature cline. Ecological niche modeling corroborates winter temperature as a key range-limiting factor impeding northward expansion of A. texana. The northernmost A. texana populations are able to sustain fungiculture throughout winter because of their cold-adapted fungi and because of seasonal, vertical garden relocation (maintaining gardens deep in the ground in winter to protect them from extreme cold, then moving gardens to warmer, shallow depths in spring). Although the origin of leafcutter fungiculture was an evolutionary breakthrough that revolutionized the food niche of tropical fungus-growing ants, the original adaptations of this host-microbe symbiosis to tropical temperatures and the dependence on cold-sensitive fungal symbionts eventually constrained expansion into temperate habitats. Evolution of cold-tolerant fungi within the symbiosis relaxed constraints on winter fungiculture at the northern frontier of the leafcutter ant distribution, thereby expanding the ecological niche of an obligate host-microbe symbiosis.