Early Life Socioeconomic Circumstance and Late Life Brain Hyperintensities : A Population Based Cohort Study

Funding: Image acquisition and image analysis for this study was funded by the Alzheimer's Research Trust (now Alzheimer's Research UK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments The authors would like to thank the participants of the Aberdeen 1936 Birth Cohort (ABC36), without whom this research would not have been possible.Peer reviewedPublisher PD

Strengthening seasonal marine CO2 variations due to increasing atmospheric CO2

The increase of atmospheric CO2 (ref. 1) has been predicted to impact the seasonal cycle of inorganic carbon in the global ocean2,3, yet the observational evidence to verify this prediction has been missing. Here, using an observation-based product of the oceanic partial pressure of CO2 (pCO2) covering the past 34 years, we find that the winter-to-summer difference of the pCO2 has increased on average by 2.2 ± 0.4 μatm per decade from 1982 to 2015 poleward of 10° latitude. This is largely in agreement with the trend expected from thermodynamic considerations. Most of the increase stems from the seasonality of the drivers acting on an increasing oceanic pCO2 caused by the uptake of anthropogenic CO2 from the atmosphere. In the high latitudes, the concurrent ocean-acidification-induced changes in the buffer capacity of the ocean enhance this effect. This strengthening of the seasonal winter-to-summer difference pushes the global ocean towards critical thresholds earlier, inducing stress to ocean ecosystems and fisheries4. Our study provides observational evidence for this strengthening seasonal difference in the oceanic carbon cycle on a global scale, illustrating the inevitable consequences of anthropogenic CO2 emissions

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

Southern Ocean pteropods at risk from ocean warming and acidification

Early life stages of marine calcifiers are particularly vulnerable to climate change. In the Southern Ocean aragonite undersaturation events and areas of rapid warming already occur and are predicted to increase in extent. Here, we present the first study to successfully hatch the polar pteropod Limacina helicina antarctica and observe the potential impact of exposure to increased temperature and aragonite undersaturation resulting from ocean acidification (OA) on the early life stage survival and shell morphology. High larval mortality (up to 39%) was observed in individuals exposed to perturbed conditions. Warming and OA induced extensive shell malformation and dissolution, respectively, increasing shell fragility. Furthermore, shell growth decreased, with variation between treatments and exposure time. Our results demonstrate that short-term exposure through passing through hotspots of OA and warming poses a serious threat to pteropod recruitment and long-term population viability

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /

Mice have a transcribed L-threonine aldolase/GLY1 gene, but the human GLY1 gene is a non-processed pseudogene

BACKGROUND: There are three pathways of L-threonine catabolism. The enzyme L-threonine aldolase (TA) has been shown to catalyse the conversion of L-threonine to yield glycine and acetaldehyde in bacteria, fungi and plants. Low levels of TA enzymatic activity have been found in vertebrates. It has been suggested that any detectable activity is due to serine hydroxymethyltransferase and that mammals lack a genuine threonine aldolase. RESULTS: The 7-exon murine L-threonine aldolase gene (GLY1) is located on chromosome 11, spanning 5.6 kb. The cDNA encodes a 400-residue protein. The protein has 81% similarity with the bacterium Thermotoga maritima TA. Almost all known functional residues are conserved between the two proteins including Lys242 that forms a Schiff-base with the cofactor, pyridoxal-5'-phosphate. The human TA gene is located at 17q25. It contains two single nucleotide deletions, in exons 4 and 7, which cause frame-shifts and a premature in-frame stop codon towards the carboxy-terminal. Expression of human TA mRNA was undetectable by RT-PCR. In mice, TA mRNA was found at low levels in a range of adult tissues, being highest in prostate, heart and liver. In contrast, serine/threonine dehydratase, another enzyme that catabolises L-threonine, is expressed very highly only in the liver. Serine dehydratase-like 1, also was most abundant in the liver. In whole mouse embryos TA mRNA expression was low prior to E-15 increasing more than four-fold by E-17. CONCLUSION: Mice, the western-clawed frog and the zebrafish have transcribed threonine aldolase/GLY1 genes, but the human homolog is a non-transcribed pseudogene. Serine dehydratase-like 1 is a putative L-threonine catabolising enzyme

The effect of modifiable risk factors on geographic mortality differentials: a modelling study

Background Australian mortality rates are higher in regional and remote areas than in major cities. The degree to which this is driven by variation in modifiable risk factors is unknown. Methods We applied a risk prediction equation incorporating smoking, cholesterol and blood pressure to a national, population based survey to project all-causes mortality risk by geographic region. We then modelled life expectancies at different levels of mortality risk by geographic region using a risk percentiles model. Finally we set high values of each risk factor to a target level and modelled the subsequent shift in the population to lower levels of mortality risk and longer life expectancy. Results Survival is poorer in both Inner Regional and Outer Regional/Remote areas compared to Major Cities for men and women at both high and low levels of predicted mortality risk. For men smoking, high cholesterol and high systolic blood pressure were each associated with the mortality difference between Major Cities and Outer Regional/Remote areas--accounting for 21.4%, 20.3% and 7.7% of the difference respectively. For women smoking and high cholesterol accounted for 29.4% and 24.0% of the difference respectively but high blood pressure did not contribute to the observed mortality differences. The three risk factors taken together accounted for 45.4% (men) and 35.6% (women) of the mortality difference. The contribution of risk factors to the corresponding differences for inner regional areas was smaller, with only high cholesterol and smoking contributing to the difference in men-- accounting for 8.8% and 6.3% respectively-- and only smoking contributing to the difference in women--accounting for 12.3%. Conclusions These results suggest that health intervention programs aimed at smoking, blood pressure and total cholesterol could have a substantial impact on mortality inequities for Outer Regional/Remote areas. Background: Australian mortality rates are higher in regional and remote areas than in major cities. The degree to which this is driven by variation in modifiable risk factors is unknown. Methods. We applied a risk prediction equation incorporating smoking, cholesterol and blood pressure to a national, population based survey to project all-causes mortality risk by geographic region. We then modelled life expectancies at different levels of mortality risk by geographic region using a risk percentiles model. Finally we set high values of each risk factor to a target level and modelled the subsequent shift in the population to lower levels of mortality risk and longer life expectancy. Results: Survival is poorer in both Inner Regional and Outer Regional/Remote areas compared to Major Cities for men and women at both high and low levels of predicted mortality risk. For men smoking, high cholesterol and high systolic blood pressure were each associated with the mortality difference between Major Cities and Outer Regional/Remote areas - accounting for 21.4%, 20.3% and 7.7% of the difference respectively. For women smoking and high cholesterol accounted for 29.4% and 24.0% of the difference respectively but high blood pressure did not contribute to the observed mortality differences. The three risk factors taken together accounted for 45.4% (men) and 35.6% (women) of the mortality difference. The contribution of risk factors to the corresponding differences for inner regional areas was smaller, with only high cholesterol and smoking contributing to the difference in men - accounting for 8.8% and 6.3% respectively - and only smoking contributing to the difference in women - accounting for 12.3%. Conclusions: These results suggest that health intervention programs aimed at smoking, blood pressure and total cholesterol could have a substantial impact on mortality inequities for Outer Regional/Remote areas

Perinatal Asphyxia Reduces Dentate Granule Cells and Exacerbates Methamphetamine-Induced Hyperlocomotion in Adulthood

Background: Obstetric complications have been regarded as a risk factor for schizophrenia later in life. One of the mechanisms underlying the association is postulated to be a hypoxic process in the brain in the offspring around the time of birth. Hippocampus is one of the brain regions implicated in the late-onset dopaminergic dysfunction associated with hypoxic obstetric complications. Methodology/Principal Findings: We used an animal model of perinatal asphyxia, in which rat pups were exposed to 15 min of intrauterine anoxia during Cesarean section birth. At 6 and 12 weeks after birth, the behavior of the pups was assessed using a methamphetamine-induced locomotion test. In addition, the histopathology of the hippocampus was examined by means of stereology. At 6 weeks, there was no change in the methamphetamine-induced locomotion. However, at 12 weeks of age, we found an elevation in methamphetamine-induced locomotor activity, which was associated with an increase of dopamine release in the nucleus accumbens. At the same age, we also found a reduction of the dentate granule cells of the hippocampus. Conclusions/Significance: These results suggest that the dopaminergic dysregulation after perinatal asphyxia is associated with a reduction in hippocampal dentate granule cells, and this may partly contribute to the pathogenesis of schizophrenia.浜松医科大学学位論文　医博第548号(平成２１年３月１８日