Genotype moderates the impact of food additives on hyperactive behavior in children

Introduction: The claim of a relationship between artificial food color and additive (AFCs) intake and behavior is highly contentious. We have shown in a previous population-based trial with 3yo children adverse effects of food additives on parentally-rated hyperactive behaviour (Bateman et al, 2004). The possible role of genetic polymorphisms in moderating this adverse effect has not been previously examined. Methods A randomised, double blind, placebo-controlled, within subject crossover food challenge was used for 144, 8 to 9 year old children and 153, 3 year old children. Following baseline assessment children were placed on a diet eliminating food additives and a benzoate preservative for 6 weeks during which time they were challenged for weekly periods with either a placebo mix or a drink containing sodium benzoate (45mg daily) and one of two mixes of AFCs.: Results: The T939C and Thr105Ile polymorphisms of the histamine N-methyltransferase gene (HNMT) moderated the adverse effect s of AFCs but the polymorphisms in catecholamine genes COMT Val108Met and ADRA2A C1291G did not. These findings point to a possible role for histamine in mediating the effects of food additives and help to explain why there has been inconsistency between previous studies. Conclusions: Genes influencing a range of neurotransmitter systems and their interplay with environmental factors, such as diet, need to be examined to understand genetic influences on hyperactivity.<br/

IL-4 Receptor α Is an Important Modulator of IL-4 and IL-13 Receptor Binding: Implications for the Development of Therapeutic Targets

IL-4 is a key cytokine associated with allergy and asthma. Induction of cell signaling by IL-4 involves interaction with its cognate receptors, a complex of IL-4Ralpha with either the common gamma-chain or the IL-13R chain alpha1 (IL-13Ralpha1). We found that IL-4 bound to the extracellular domain of IL-4Ralpha (soluble human (sh)IL-4Ralpha) with high affinity and specificity. In contrast with the sequential mechanism of binding and stabilization afforded by IL-4Ralpha to the binding of IL-13 to IL-13Ralpha1, neither common gamma-chain nor IL-13Ralpha1 contributed significantly to the stabilization of the IL-4:IL-4Ralpha complex. Based on the different mechanisms of binding and stabilization of the IL-4R and IL-13R complexes, we compared the effects of shIL-4Ralpha and an IL-4 double mutein (R121D/Y124D, IL-4R antagonist) on IL-4- and IL-13-mediated responses. Whereas IL-4R antagonist blocked responses to both cytokines, shIL-4Ralpha only blocked IL-4. However, shIL-4Ralpha stabilized and augmented IL-13-mediated STAT6 activation and eotaxin production by primary human bronchial fibroblasts at suboptimal doses of IL-13. These data demonstrate that IL-4Ralpha plays a key role in the binding affinity of both IL-13R and IL-4R complexes. Under certain conditions, shIL-4Ralpha has the potential to stabilize binding IL-13 to its receptor to augment IL-13-mediated responses. Thus, complete understanding of the binding interactions between IL-4 and IL-13 and their cognate receptors may facilitate development of novel treatments for asthma that selectively target these cytokines without unpredicted or detrimental side effects.</p

Rural Revitalization in New Mexico

The Rural Education Bureau of the New Mexico Public Education Department has established a program to address the special needs of schools and communities in the extensive rural areas of the state. High poverty rates, depopulation and a general lack of viable economic opportunity have marked rural New Mexico for decades. The program underway aims at establishing holistic community socioeconomic revitalization at the grass roots level with the schools playing a leading role. Initiatives include community conversations with key leaders to determine necessary steps to take in encouraging economic growth and attracting businesses, the institution of entrepreneurship within the community, the transformation of the school into a community resource and the encouragement of place-based education within schools. In the second year of this program there are 13 school districts actively involved in the enhancement of their schools and community. The program adopted many of the principles for rural revitalization seen in the remote communities of South Australia

Ecological Impacts of the Space Shuttle Program at John F. Kennedy Space Center, Florida

The Space Shuttle Program was one of NASAs first major undertakings to fall under the environmental impact analysis and documentation requirements of the National Environmental Policy Act of 1969 (NEPA). Space Shuttle Program activities at John F. Kennedy Space Center (KSC) and the associated Merritt Island National Wildlife Refuge (MINWR) contributed directly and indirectly to both negative and positive ecological trends in the region through the long-term, stable expenditure of resources over the 40 year program life cycle. These expenditures provided support to regional growth and development in conjunction with other sources that altered land use patterns, eliminated and modified habitats, and contributed to cultural eutrophication of the Indian River Lagoon. At KSC, most Space Shuttle Program related actions were conducted in previously developed facilities and industrial areas with the exception of the construction of the shuttle landing facility (SLF) and the space station processing facility (SSPF). Launch and operations impacts were minimal as a result of the low annual launch rate. The majority of concerns identified during the NEPA process such as potential weather modification, acid rain off site, and local climate change did not occur. Launch impacts from deposition of HCl and particulates were assimilated as a result of the high buffering capacity of the system and low launch and loading rates. Metals deposition from exhaust deposition did not display acute impacts. Sub-lethal effects are being investigated as part of the Resource Conservation and Recovery Act (RCRA) regulatory process. Major positive Space Shuttle Program effects were derived from the adequate resources available at the Center to implement the numerous environmental laws and regulations designed to enhance the quality of the environment and minimize impacts from human activities. This included reduced discharges of domestic and industrial wastewater, creation of stormwater management systems, remediation of past contamination sites, implementation of hazardous waste management systems, and creation of a culture of sustainability. Working with partners such as the USFWS and the St Johns River Water Management District (SJRWMD), wetlands and scrub restoration and management initiatives were implemented to enhance fish and wildlife populations at the Center. KSC remains the single largest preserve on the east coast of Florida in part due to NASAs commitment to stewardship. Ongoing Ecological Program projects are directed at development of information and knowledge to address future KSC management questions including the transition to a joint government and commercial launch facility, enhanced habitat management requirements for wetlands and scrub, potential impacts of emerging contaminants, and adaptation to climate change including projected sea level rise over the next 50-75 years

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease

A High-Resolution Map of Human Evolutionary Constraint Using 29 Mammals

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ~4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ~60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.National Human Genome Research Institute (U.S.)National Institute of General Medical Sciences (U.S.) (Grant number GM82901)National Science Foundation (U.S.). Postdoctural Fellowship (Award 0905968)National Science Foundation (U.S.). Career (0644282)National Institutes of Health (U.S.) (R01-HG004037)Alfred P. Sloan Foundation.Austrian Science Fund. Erwin Schrodinger Fellowshi