24-Hour Rhythms of DNA Methylation and Their Relation with Rhythms of RNA Expression in the Human Dorsolateral Prefrontal Cortex

Circadian rhythms modulate the biology of many human tissues, including brain tissues, and are driven by a near 24-hour transcriptional feedback loop. These rhythms are paralleled by 24-hour rhythms of large portions of the transcriptome. The role of dynamic DNA methylation in influencing these rhythms is uncertain. While recent work in Neurospora suggests that dynamic site-specific circadian rhythms of DNA methylation may play a role in modulating the fungal molecular clock, such rhythms and their relationship to RNA expression have not, to our knowledge, been elucidated in mammalian tissues, including human brain tissues. We hypothesized that 24-hour rhythms of DNA methylation exist in the human brain, and play a role in driving 24-hour rhythms of RNA expression. We analyzed DNA methylation levels in post-mortem human dorsolateral prefrontal cortex samples from 738 subjects. We assessed for 24-hour rhythmicity of 420,132 DNA methylation sites throughout the genome by considering methylation levels as a function of clock time of death and parameterizing these data using cosine functions. We determined global statistical significance by permutation. We then related rhythms of DNA methylation with rhythms of RNA expression determined by RNA sequencing. We found evidence of significant 24-hour rhythmicity of DNA methylation. Regions near transcription start sites were enriched for high-amplitude rhythmic DNA methylation sites, which were in turn time locked to 24-hour rhythms of RNA expression of nearby genes, with the nadir of methylation preceding peak transcript expression by 1–3 hours. Weak ante-mortem rest-activity rhythms were associated with lower amplitude DNA methylation rhythms as were older age and the presence of Alzheimer's disease. These findings support the hypothesis that 24-hour rhythms of DNA methylation, particularly near transcription start sites, may play a role in driving 24-hour rhythms of gene expression in the human dorsolateral prefrontal cortex, and may be affected by age and Alzheimer's disease

Effects of a Behavior-Based Weight Management Program Delivered Through a State Cooperative Extension and Local Public Health Department Network, North Carolina, 2008-2009

Introduction Eat Smart, Move More, Weigh Less (ESMMWL) is an adult weight management program developed in response to North Carolina Obesity Plan recommendations to make weight management interventions accessible to underserved populations. ESMMWL was designed to be delivered through the North Carolina Cooperative Extension and North Carolina Division of Public Health. Program coursework included content on evidence-based eating and physical activity behaviors and incorporated mindful eating concepts. The objectives of this study were to describe participant changes in weight and behaviors and to document the effectiveness of the program. Methods In this prospective pilot study, courses were delivered and data collected from January 2008 through June 2009. Instructors provided feedback about implementation. For participants, height, weight, and waist circumference were measured at baseline and completion. Participants completed a questionnaire about changes in their eating and physical activity behaviors, changes in their confidence to engage in weight management behaviors, and their satisfaction with the course. Results Seventy-nine instructors delivered 101 ESMMWL courses in 48 North Carolina counties. Most of the 1,162 completers were white women. Approximately 83% reported moving toward or attaining their goal. The average weight loss was 8.4 lb. Approximately 92% reported an increase in confidence to eat healthfully, and 82% reported an increase in confidence to be physically active. Instructors made suggestions for program standardization. Conclusion This study demonstrated the effectiveness, diffusion, and implementation of a theoretically based weight management program through a state extension and local public health department network. Study of the sustainability of changes in eating and physical activity behaviors is needed

MGC2214+3550: A New Binary Quasar

We report the discovery of a binary quasar, MGC2214+3550 A,B, whose components have similar optical spectra at a redshift z=0.88. The quasars are separated on the sky by 3.0", and have a magnitude difference of Delta(m_I)=0.5 mag. The VLA radio map at 3.6 cm shows a single 47mJy radio source with a core-jet morphology that is coincident with the brighter optical quasar A. Gravitational lensing is ruled out by the lack of radio emission from quasar B, and the lack of any visible galaxies to act as the lens. We conclude that MGC 2214+3550 A and B are physically associated. With a projected separation of 12.7h^{-1} kpc (Omega_0=1), MGC 2214+3550 A,B is one of the smallest z>0.5 binary quasars.Comment: 13 pages, 3 .ps figs, submitted to ApJ

Circumstellar Structure around Evolved Stars in the Cygnus-X Star Formation Region

We present observations of newly discovered 24 micron circumstellar structures detected with the Multiband Imaging Photometer for Spitzer (MIPS) around three evolved stars in the Cygnus-X star forming region. One of the objects, BD+43 3710, has a bipolar nebula, possibly due to an outflow or a torus of material. A second, HBHA 4202-22, a Wolf-Rayet candidate, shows a circular shell of 24 micron emission suggestive of either a limb-brightened shell or disk seen face-on. No diffuse emission was detected around either of these two objects in the Spitzer 3.6-8 micron Infrared Array Camera (IRAC) bands. The third object is the luminous blue variable candidate G79.29+0.46. We resolved the previously known inner ring in all four IRAC bands. The 24 micron emission from the inner ring extends ~1.2 arcmin beyond the shorter wavelength emission, well beyond what can be attributed to the difference in resolutions between MIPS and IRAC. Additionally, we have discovered an outer ring of 24 micron emission, possibly due to an earlier episode of mass loss. For the two shell stars, we present the results of radiative transfer models, constraining the stellar and dust shell parameters. The shells are composed of amorphous carbon grains, plus polycyclic aromatic hydrocarbons in the case of G79.29+0.46. Both G79.29+0.46 and HBHA 4202-22 lie behind the main Cygnus-X cloud. Although G79.29+0.46 may simply be on the far side of the cloud, HBHA 4202-22 is unrelated to the Cygnus-X star formation region.Comment: Accepted by A

Intermediate Phenotypes Identify Divergent Pathways to Alzheimer's Disease

Background: Recent genetic studies have identified a growing number of loci with suggestive evidence of association with susceptibility to Alzheimer's disease (AD). However, little is known of the role of these candidate genes in influencing intermediate phenotypes associated with a diagnosis of AD, including cognitive decline or AD neuropathologic burden. Methods/Principal Findings: Thirty-two single nucleotide polymorphisms (SNPs) previously implicated in AD susceptibility were genotyped in 414 subjects with both annual clinical evaluation and completed brain autopsies from the Religious Orders Study and the Rush Memory and Aging Project. Regression analyses evaluated the relation of SNP genotypes to continuous measures of AD neuropathology and cognitive function proximate to death. A SNP in the zinc finger protein 224 gene (ZNF224, rs3746319) was associated with both global AD neuropathology (p = 0.009) and global cognition (p = 0.002); whereas, a SNP at the phosphoenolpyruvate carboxykinase locus (PCK1, rs8192708) was selectively associated with global cognition (p = 3.57×10−4). The association of ZNF224 with cognitive impairment was mediated by neurofibrillary tangles, whereas PCK1 largely influenced cognition independent of AD pathology, as well as Lewy bodies and infarcts. Conclusions/Significance: The findings support the association of several loci with AD, and suggest how intermediate phenotypes can enhance analysis of susceptibility loci in this complex genetic disorder

CD33 Alzheimer’s disease locus: Altered monocyte function and amyloid biology

In our functional dissection of the CD33 Alzheimer’s disease susceptibility locus, we find that the rs3865444C risk allele is associated with greater cell surface expression of CD33 in monocytes (t50 = 10.06, pjoint=1.3×10–13) of young and older individuals. It is also associated with (1) diminished internalization of Aβ42) (2) accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging and (3), increased numbers of activated human microglia

Microsatellites Reveal a High Population Structure in Triatoma infestans from Chuquisaca, Bolivia

Chagas disease is a protozoan infection caused by the parasite Trypanosoma cruzi. Chagas is prevalent throughout Central and South America, and it remains a chief concern in Bolivia. A movement that began in 1991 called the Southern Cone Initiative has been successful in reducing the incidence of Chagas disease in the Southern Cone countries of Argentina, Brazil, Chile, and Uruguay; but due to socio-economic and other factors, incidence remains high in Bolivia. The most important mode of transmission of T. cruzi to humans and other mammals is through feces of triatomine bugs. Thus, disease control and transmission prevention focus on elimination of triatomine vectors, and more specifically in Bolivia, it focuses on the elimination of Triatoma infestans. This study focuses on T. infestans in the Department of Chuquisaca, Bolivia. Ten highly variable microsatellite markers were used to analyze the population structure of insects collected in different towns. Statistical analyses show that T. infestans are highly structured, which means that they colonize on a small geographic scale. The results also suggest little active dispersal. These findings should be implemented during control efforts so that insecticide spraying focuses on geographic areas of colonization and re-colonization

Why media representations of corporations matter for public health policy : a scoping review

BACKGROUND: Media representations play a crucial role in informing public and policy opinions about the causes of, and solutions to, ill-health. This paper reviews studies analysing media coverage of non-communicable disease (NCD) debates, focusing on how the industries marketing commodities that increase NCD risk are represented. METHODS: A scoping review identified 61 studies providing information on media representations of NCD risks, NCD policies and tobacco, alcohol, processed food and soft drinks industries. The data were narratively synthesized to describe the sample, media depictions of industries, and corporate and public health attempts to frame the media debates. RESULTS: The findings indicate that: (i) the limited research that has been undertaken is dominated by a focus on tobacco; (ii) comparative research across industries/risk-factors is particularly lacking; and (iii) coverage tends to be dominated by two contrasting frames and focuses either on individual responsibilities ('market justice' frames, often promoted by commercial stakeholders) or on the need for population-level interventions ('social justice' frames, frequently advanced by public health advocates). CONCLUSIONS: Establishing the underlying frameworks is crucial for the analysis of media representation of corporations, as they reflect the strategies that respective actors use to influence public health debates and decision making. The potential utility of media research lies in the insights that it can provide for public health policy advocates about successful framing of public health messages and strategies to counter frames that undermine public health goals. A better understanding of current media debates is of paramount importance to improving global health