Impact of policy and built environment changes on obesity-related outcomes: a systematic review of naturally occurring experiments.

Policies and changes to the built environment are promising targets for obesity prevention efforts and can be evaluated as 'natural'- or 'quasi'-experiments. This systematic review examined the use of natural- or quasi-experiments to evaluate the efficacy of policy and built environment changes on obesity-related outcomes (body mass index, diet or physical activity). PubMed (Medline) was searched for studies published 2005-2013; 1,175 abstracts and 115 papers were reviewed. Of the 37 studies included, 18 studies evaluated impacts on nutrition/diet, 17 on physical activity and 3 on body mass index. Nutrition-related studies found greater effects because of bans/restrictions on unhealthy foods, mandates offering healthier foods, and altering purchase/payment rules on foods purchased using low-income food vouchers compared with other interventions (menu labelling, new supermarkets). Physical activity-related studies generally found stronger impacts when the intervention involved improvements to active transportation infrastructure, longer follow-up time or measured process outcomes (e.g., cycling rather than total physical activity), compared with other studies. Only three studies directly assessed body mass index or weight, and only one (installing light-rail system) observed a significant effect. Studies varied widely in the strength of their design and studies with weaker designs were more likely to report associations in the positive direction.

Airborne particulate matter exposure and urinary albumin excretion: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVES: Understanding mechanistic pathways linking airborne particle exposure to cardiovascular health is important for causal inference and setting environmental standards. We evaluated whether urinary albumin excretion, a subclinical marker of microvascular function which predicts cardiovascular events, was associated with ambient particle exposure. METHODS: Urinary albumin and creatinine were measured among members of the Multi-Ethnic Study of Atherosclerosis at three visits during 2000-2004. Exposure to PM(2.5) and PM(10) (microg/m(3)) was estimated from ambient monitors for 1 month, 2 months and two decades before visit one. We regressed recent and chronic (20 year) particulate matter (PM) exposure on urinary albumin/creatinine ratio (UACR, mg/g) and microalbuminuria at first examination, controlling for age, race/ethnicity, sex, smoking, second-hand smoke exposure, body mass index and dietary protein (n = 3901). We also evaluated UACR changes and development of microalbuminuria between the first, and second and third visits which took place at 1.5- to 2-year intervals in relation to chronic PM exposure prior to baseline using mixed models. RESULTS: Chronic and recent particle exposures were not associated with current UACR or microalbuminuria (per 10 microg/m(3) increment of chronic PM(10) exposure, mean difference in log UACR = -0.02 (95% CI -0.07 to 0.03) and relative probability of having microalbuminuria = 0.92 (95% CI 0.77 to 1.08)) We found only weak evidence that albuminuria was accelerated among those chronically exposed to particles: each 10 microg/m(3) increment in chronic PM(10) exposure was associated with a 1.14 relative probability of developing microalbuminuria over 3-4 years, although 95% confidence intervals included the null (95% CI 0.96 to 1.36). CONCLUSIONS: UACR is not a strong mechanistic marker for the possible influence of air pollution on cardiovascular health in this sample.

Recent exposure to particulate matter and C-reactive protein concentration in the multi-ethnic study of atherosclerosis.

Ambient levels of particulate matter have been linked to cardiovascular disease. The mechanisms mediating these associations are poorly understood. One candidate mechanism is inflammation. Using data from the Multi-Ethnic Study of Atherosclerosis (2000-2002), the authors investigated the relation between exposure to particulate matter of less than or equal to 2.5 microm in diameter (PM2.5) and C-reactive protein concentration in 5,634 persons aged 45-84 years who were free of cardiovascular disease. Data from US Environmental Protection Agency monitors were used to estimate PM2.5 exposures for the prior day, prior 2 days, prior week, prior 30 days, and prior 60 days. Only the 30-day and 60-day mean exposures showed a weak positive association with C-reactive protein, and confidence intervals were wide: relative increases in C-reactive protein per 10 microg/m3 of PM2.5 adjusted for person-level covariates were 3% (95% confidence interval (CI): -2, 10) for a 30-day mean and 4% (95% CI: -3, 11.0) for a 60-day mean. The means of 7-day, 30-day, and 60-day exposures were weakly, positively, and nonsignificantly associated with the odds of C-reactive protein of greater than or equal to 3 mg/liter: adjusted odds ratios were 1.05 (95% CI: 0.96, 1.15), 1.12 (95% CI: 0.98, 1.29), and 1.12 (95% CI: 0.96, 1.32), respectively. Slightly stronger associations were observed in persons without other risk factors for elevated C-reactive protein, but this heterogeneity was not statistically significant. The authors' results are not compatible with strong effects of particulate matter exposures on population levels of C-reactive protein.

Access to health care for older persons in the United States: personal, structural, and neighborhood characteristics.

OBJECTIVE: To determine the contributions of personal, structural, and neighborhood characteristics to differential access to health care for older persons in the United States. METHODS: This study used the 1994 National Health Interview Survey, ages 65 and older (n = 12,341), 1990 census block group data, and data on health professional shortage areas. Logistic regression was used to model the probability of problems accessing care. RESULTS: The likelihood of access problems increased sharply with decreasing gradients of family income and for those lacking private health care insurance. Rural areas and poor areas were at a disadvantage in accessing care, whereas residents of neighborhoods that were homogeneous in ancestral heritage appeared better able to access care. DISCUSSION: Considering the high association between neighborhood and personal characteristics, it is notable that any neighborhood effects remained after combining them with personal effects.

The argininosuccinate lyase gene of Chlamydomonas reinhardtii: cloning of the cDNA and its characterization as a selectable shuttle marker.

We describe the cDNA sequence for ARG7, the gene that encodes argininosuccinate lyase--a selectable nuclear marker--in Chlamydomonas reinhardtii. The 5' end of the cDNA contains one more exon and the organisation of the mRNA is different from that predicted from the genomic sequence. When expressed under the control of the endogenous RbcS2 promoter, the 2.22-kb cDNA complements the arg7 mutation as well as the genomic DNA. A linear cDNA fragment lacking promoter sequences is also able to complement, suggesting that it could be used in promoter-trapping experiments. Despite the presence of a sequence encoding a potential chloroplast transit peptide in the cDNA the protein is not targeted to the chloroplast, nor can it complement the arg7 mutation when expressed there. By inserting a T7 bacteriophage promoter into the plasmid, a version of the cDNA which is able to complement both the C. reinhardtii arg7 mutant and the Escherichia coli argH mutant has been created. This modified Arg7 cDNA provides two advantages over the genomic DNA currently in use for gene tagging: it is shorter (6.2 kb versus 11.9 kb for pARG7.8phi3), and the selectable marker used in C. reinhardtii is the same as that used in E. coli, making plasmid rescue of the tag much more likely to succeed.

Requirement for three membrane-spanning alpha-helices in the post-translational insertion of a thylakoid membrane protein.

The insertion of a protein into a lipid bilayer usually involves a short signal sequence and can occur either during or after translation. A light-harvesting chlorophyll a/b-binding protein (LHCP) is synthesized in the cytoplasm of plant cells as a precursor and is post-translationally imported into chloroplasts where it subsequently inserts into the thylakoid membrane. Only mature LHCP is required for insertion into the thylakoid. To define which sequences of the mature protein are necessary and sufficient for thylakoid integration, fusion and deletion proteins and proteins with internal rearrangements were synthesized and incubated with isolated thylakoids and stroma. No evidence is found for the existence of a short signal sequence within LHCP, and, with the exception of the amino terminus and a short lumenal loop, the entire mature protein with consecutively ordered alpha-helices is required for insertion into thylakoid membranes. The addition of positive charges into stromal but not lumenal segments permits the insertion of mutant LHCPs into isolated thylakoids. Replacement of the LHCP transit peptide with the transit peptide from plastocyanin has no effect on LHCP insertion and does not restore insertion of the lumenal charge addition mutants.

Characterization of transcription initiation sites on the soybean mitochondrial genome allows identification of a transcription-associated sequence motif.

Transcription initiation sites on the soybean mitochondrial genome have been characterized by sequence analysis of in vitro-capped soybean mtRNAs and corresponding mtDNA regions. The most abundant, discrete soybean mtRNA species labeled by guanylyltransferase and [alpha-32P]GTP are shown to correspond to the major transcript of the atp9 gene and to a group of small RNAs consisting of a discrete 80 nucleotide (nt) species plus heterogeneous species ranging in size from 133 to 148 nt. The 133-148 nt RNAs represent a set of transcripts with a common 5' terminus and ragged 3' ends, while the 80 nt RNA corresponds to positions 53-133 of the 133 nt species. The major, discrete in vitro-capped RNA species thus correspond to primary transcripts originating at three sites located in two regions of the soybean mitochondrial genome. The sequences extending from 13 nucleotides upstream to 8 nucleotides downstream of the initiation sites for the atp9 and 133-148 nt transcripts are identical at 18 of 21 positions. Sequences closely resembling this motif are located at some other 5' transcript termini of dicot plant mitochondria. Less closely related sequences are found at transcription initiation sites of wheat and maize mitochondria.

Integration of a chlorophyll-binding protein into Escherichia coli membranes in the absence of chlorophyll.

The mechanism by which a protein integrates posttranslationally into a membrane can involve the composition of the membrane itself, domains within the inserting polypeptide, and a number of associating proteins. Some integral membrane proteins do not accumulate to normal levels when certain pigments are deficient, and this has been interpreted to mean that such proteins may be rapidly degraded when not in a correct complex. Alternatively, pigments could facilitate the movement of some proteins from an aqueous to a lipid environment. To determine whether chlorophyll is absolutely required for the membrane integration of the light-harvesting chlorophyll-binding protein (LHCP) of chloroplast thylakoid membranes, we have expressed LHCP in Escherichia coli that lacks photosynthetic pigments. LHCP is targeted to the bacterial inner membrane by the addition of a bacterial signal peptide and cannot be extracted from these membranes by NaOH, NaBr, or Na2HCO3 but is extracted by 0.2% Triton X-100. Treatment of isolated right-side-out and inside-out bacterial inner membrane vesicles with trypsin reveals that only the amino terminus of LHCP is exposed on the cytoplasmic face, and the remaining portion of the protein is inaccessible. Treatment of the inside-out vesicles with trypsin followed by alkaline extraction shows that LHCP is intrinsic to the membrane and is not anchored solely by the bacterial signal peptide. Chlorophyll, therefore, is not required for LHCP to integrate into a membrane, but in the absence of these pigments this process is observed to be inefficient.

Nuclear endo-exonuclease of Neurospora crassa. Evidence for a role in DNA repair.

The major nuclease activity in nuclei of mycelia of Neurospora crassa has been identified as that of endoexonuclease, an enzyme purified and characterized previously from mitochondria and vacuoles which acts endonucleolytically on single-stranded DNA and RNA and possesses highly processive exonuclease activity with double-stranded DNA. Cross-contamination from the other organelles was eliminated as a source of the activity. Endo-exonuclease of nucleoplasm, chromatin, and nuclear matrix showed 80-100% cross-reaction with antisera raised to purified extranuclear endoexonuclease and was also strongly inhibited by 20 microM aurin tricarboxylic acid. In addition, it yielded some of the same-sized polypeptides on activity gel analysis. Nuclei also contained immunochemically cross-reactive trypsin-activable endo-exonuclease activity, a form of enzyme that was shown previously to occur in high amounts in the cytosol and in a tightly bound form associated with the mitochondrial inner membrane. Pretreatment of wild-type mycelia for 1 h with 4-16 micrograms/ml the DNA-damaging agent, 4-nitroquinoline-1-oxide (4-NQO), which caused about 50-80% growth inhibition, resulted in a dose-dependent loss of up to 80% of inactive endo-exonuclease from nuclei. At low doses of 4-NQO, this was accompanied by increases in the level of active enzyme. Nuclei of the DNA repair-deficient uvs-3 mutant were found to contain only 12% of the active enzyme and about 32% of inactive enzyme as that in wild-type nuclei. Mycelial growth of this mutant was 10 times more sensitive to 4-NQO than the wild-type. At a dose which resulted in equivalent growth inhibition, 4-NQO had no effect on the level of active endo-exonuclease in uvs-3 nuclei and caused an increase (over 30%) in the level of inactive enzyme. These data are consistent with a role of endo-exonuclease in the repair of nuclear DNA.