Built environment change and change in BMI and waist circumference: Multi‐ethnic S tudy of A therosclerosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109571/1/oby20873.pd

Changes in the Built Environment and Changes in the Amount of Walking Over Time: Longitudinal Results From the Multi-Ethnic Study of Atherosclerosis

Lack of longitudinal research hinders causal inference on the association between the built environment and walking. In the present study, we used data from 6,027 adults in the Multi-Ethnic Study of Atherosclerosis who were 45–84 years of age at baseline to investigate the association of neighborhood built environment with trends in the amount of walking between 2000 and 2012. Walking for transportation and walking for leisure were assessed at baseline and at 3 follow-up visits (median follow-up = 9.15 years). Time-varying built environment measures (measures of population density, land use, number of destinations, bus access, and street connectivity) were created using geographic information systems. We used linear mixed models to estimate the associations between baseline levels of and a change in each built environment feature and a change in the frequency of walking. After adjustment for potential confounders, we found that higher baseline levels of population density, area zoned for retail, social destinations, walking destinations, and street connectivity were associated with greater increases in walking for transportation over time. Higher baseline levels of land zoned for residential use and distance to buses were associated with less pronounced increases (or decreases) in walking for transportation over time. Increases in the number of social destinations, the number of walking destinations, and street connectivity over time were associated with greater increases in walking for transportation. Higher baseline levels of both land zoned for retail and walking destinations were associated with greater increases in leisure walking, but no changes in built environment features were associated with leisure walking. The creation of mixed-use, dense developments may encourage adults to incorporate walking for transportation into their everyday lives

Unraveling the Early Events of Amyloid-β Protein (Aβ) Aggregation: Techniques for the Determination of Aβ Aggregate Size

The aggregation of proteins into insoluble amyloid fibrils coincides with the onset of numerous diseases. An array of techniques is available to study the different stages of the amyloid aggregation process. Recently, emphasis has been placed upon the analysis of oligomeric amyloid species, which have been hypothesized to play a key role in disease progression. This paper reviews techniques utilized to study aggregation of the amyloid-β protein (Aβ) associated with Alzheimer’s disease. In particular, the review focuses on techniques that provide information about the size or quantity of oligomeric Aβ species formed during the early stages of aggregation, including native-PAGE, SDS-PAGE, Western blotting, capillary electrophoresis, mass spectrometry, fluorescence correlation spectroscopy, light scattering, size exclusion chromatography, centrifugation, enzyme-linked immunosorbent assay, and dot blotting

Changes in the Built Environment and Changes in the Amount of Walking Over Time: Longitudinal Results From the Multi-Ethnic Study of Atherosclerosis

Lack of longitudinal research hinders causal inference on the association between the built environment and walking. In the present study, we used data from 6,027 adults in the Multi-Ethnic Study of Atherosclerosis who were 45–84 years of age at baseline to investigate the association of neighborhood built environment with trends in the amount of walking between 2000 and 2012. Walking for transportation and walking for leisure were assessed at baseline and at 3 follow-up visits (median follow-up = 9.15 years). Time-varying built environment measures (measures of population density, land use, number of destinations, bus access, and street connectivity) were created using geographic information systems. We used linear mixed models to estimate the associations between baseline levels of and a change in each built environment feature and a change in the frequency of walking. After adjustment for potential confounders, we found that higher baseline levels of population density, area zoned for retail, social destinations, walking destinations, and street connectivity were associated with greater increases in walking for transportation over time. Higher baseline levels of land zoned for residential use and distance to buses were associated with less pronounced increases (or decreases) in walking for transportation over time. Increases in the number of social destinations, the number of walking destinations, and street connectivity over time were associated with greater increases in walking for transportation. Higher baseline levels of both land zoned for retail and walking destinations were associated with greater increases in leisure walking, but no changes in built environment features were associated with leisure walking. The creation of mixed-use, dense developments may encourage adults to incorporate walking for transportation into their everyday lives

Stress and IGF-I Differentially Control Cell Fate through Mammalian Target of Rapamycin (mTOR) and Retinoblastoma Protein (pRB)*

Significant discoveries have recently contributed to our knowledge of intracellular growth factor and nutrient signaling via mTOR (mammalian target of rapamycin). This signaling pathway is essential in cellular metabolism and cell survival by enhancing protein translation through phosphorylation of 4EBP-1 and p70S6K. Growth factors like insulin-like growth factor-I induce mTOR to prevent cell death during cellular stress. Agents targeting mTOR are of major interest as anticancer agents. We show here, using human breast cancer cells, that certain types of stress activate mTOR leading to 4E-BP1 and p70S6K phosphorylation. UV treatment increased phosphorylation of the translation inhibitor eIF2α, suggesting a potential mechanism for UV activation of Akt and mTOR. c-Myc, a survival protein regulated by cap-dependent protein translation, increased with IGF-I treatment, but this response was not inhibited by rapamycin. Additionally, UV treatment potently increased c-Myc degradation, which was reduced by co-treatment with the proteasomal inhibitor, MG-132. Together, these data suggest that protein translation does not strongly mediate cell survival in these models. In contrast, the phosphorylation status of retinoblastoma protein (pRB) was mediated by mTOR through its inhibitory effects on phosphatase activity. This effect was most notable during DNA damage and rapamycin treatment. Hypophosphorylated pRB was susceptible to inactivation by caspase-mediated cleavage, resulting in cell death. Reduction of pRB expression inhibited IGF-I survival effects. Our data support an important role of phosphatases and pRB in IGF-I/mTOR-mediated cell survival. These studies provide new directions in optimizing anticancer efficacy of mTOR inhibitors when used in combination with DNA-damaging agents

Record-setting algal bloom in Lake Erie caused by agricultural and meteorological trends consistent with expected future conditions

In 2011, Lake Erie experienced the largest harmful algal bloom in its recorded history, with a peak intensity over three times greater than any previously observed bloom. Here we show that long-term trends in agricultural practices are consistent with increasing phosphorus loading to the western basin of the lake, and that these trends, coupled with meteorological conditions in spring 2011, produced record-breaking nutrient loads. An extended period of weak lake circulation then led to abnormally long residence times that incubated the bloom, and warm and quiescent conditions after bloom onset allowed algae to remain near the top of the water column and prevented flushing of nutrients from the system. We further find that all of these factors are consistent with expected future conditions. If a scientifically guided management plan to mitigate these impacts is not implemented, we can therefore expect this bloom to be a harbinger of future blooms in Lake Erie.close1

Disparities in physical activity resource availability in six US regions

We conducted an ecologic study to determine physical activity resource availability overall and by sociodemographic groups in parts of six states (CA, IL, MD, MN, NC, NY). Data on parks and recreational facilities were collected from 3 sources in 2009–2012. Three measures characterized park and recreational facility availability at the census tract level: presence of ≥1 resource, number of resources, and resource kernel density. Associations between resource availability and census tract characteristics (predominant racial/ethnic group, median income, and proportion of children and older adults) were estimated using linear, binomial, and zero-inflated negative binomial regression in 2014. Pooled and stratified analyses were conducted. The study included 7,139 census tracts, comprising 9.5% of the 2010 US population. Overall the availability of parks and recreational facilities was lower in predominantly minority relative to non-Hispanic white census tracts. Low-income census tracts and those with a higher proportion of children had an equal or greater availability of park resources but fewer recreational facilities. Stratification revealed substantial variation in resource availability by state. The availability of physical activity resources varied by sociodemographic characteristics and across regions. Improved knowledge of resource distribution can inform strategies to provide equitable access to parks and recreational facilities