TP73 allelic expression in human brain and allele frequencies in Alzheimer's disease

BACKGROUND: The p73 protein, a paralogue of the p53 tumor suppressor, is essential for normal development and survival of neurons. TP73 is therefore of interest as a candidate gene for Alzheimer's disease (AD) susceptibility. TP73 mRNA is transcribed from three promoters, termed P1 – P3, and there is evidence for an additional complexity in its regulation, namely, a variable allelic expression bias in some human tissues. METHODS: We utilized RT-PCR/RFLP and direct cDNA sequencing to measure allele-specific expression of TP73 mRNA, SNP genotyping to assess genetic associations with AD, and promoter-reporter assays to assess allele-specific TP73 promoter activity. RESULTS: Using a coding-neutral BanI polymorphism in TP73 exon 5 as an allelic marker, we found a pronounced allelic expression bias in one adult brain hippocampus, while 3 other brains (two adult; one fetal) showed approximately equal expression from both alleles. In a tri-ethnic elderly population of African-Americans, Caribbean Hispanics and Caucasians, a G/A single nucleotide polymorphism (SNP) at -386 in the TP73 P3 promoter was weakly but significantly associated with AD (crude O.R. for AD given any -386G allele 1.7; C.I. 1.2–2.5; after adjusting for age and education O.R. 1.5; C.I. 1.1–2.3, N= 1191). The frequency of the -386G allele varied by ethnicity and was highest in African-Americans and lowest in Caucasians. No significant differences in basal P3 promoter activity were detected comparing -386G vs. -386A promoter-luciferase constructs in human SK-NSH-N neuroblastoma cells. CONCLUSIONS: There is a reproducible allelic expression bias in mRNA expression from the TP73 gene in some, though not all, adult human brains, and inter-individual variation in regulatory sequences of the TP73 locus may affect susceptibility to AD. However, additional studies will be necessary to exclude genetic admixture as an alternative explanation for the observed associations

Relationship Between Obesity and Diabetes in a US Adult Population: Findings from the National Health and Nutrition Examination Survey, 1999–2006

# The Author(s) 2010. This article is published with open access at Springerlink.com Background Obesity is one of the most important modifiable risk factors for the prevention of type 2 diabetes. The aim of this study was to examine the prevalence of diabetes with increasing severity of obesity and the distribution of HbA1c levels in diabetics participating in the latest National Health and Nutrition Examination Survey (NHANES). Methods Data from a representative sample of adults with diabetes participating in the NHANES between 1999 and 2006 were reviewed. The prevalence of diabetes and levels of fasting glucose, insulin, c-peptide, and HbA1c were examined across different weight classes with normal weight, overweight, and obesity classes 1, 2, and 3 were defined as body mass index (BMI) of <25.0, 25.0–29.9, 30.0–34.9, 35.0–39.9, and equal to 40.0, respectively. The distribution of HbA1c levels among adults with diabetes was also examined. Results There were 2,894 adults with diabetes (13.6%) among the 21,205 surveyed participants. Among the adults with diabetes, the mean age was 59 years, the mean fasting glucose was 155±2 mg/dl, and the mean HbA1c was 7.2%; 80.3 % of diabetics were considered overweight (BMI≥25) and 49.1 % of diabetics were considered obese (BMI≥30). Presented as a poster presentation at the American Society fo

Changes in Inflammatory Biomarkers Across Weight Classes in a Representative US Population: A Link Between Obesity and Inflammation

Obesity has been linked with a chronic state of inflammation which may be involved in the development of metabolic syndrome, cardiovascular disease, non-alcoholic steatohepatitis, and even cancer. The objective of this study was to examine the association between obesity class and levels of inflammatory biomarkers from men and women who participated in the 1999–2004 National Health and Nutrition Examination Survey (NHANES). Serum concentrations of C-reactive protein (CRP) and fibrinogen were measured among US participants of the 1999–2004 NHANES. We examined biomarker levels across different weight classes with normal weight, overweight, and obesity classes 1, 2, and 3 were defined as BMI of <25.0, 25.0–29.9, 30.0–34.9, 35.0–39.9, and ≥40.0, respectively. With CRP levels for normal weight individuals as a reference, CRP levels nearly doubled with each increase in weight class: +0.11 mg/dl (95% CI, 0.06–0.16) for overweight, +0.21 mg/dl (95% CI, 0.16–0.27) for obesity class 1, +0.43 mg/dl (95% CI, 0.26–0.61) for obesity class 2, and +0.73 mg/dl (95% CI, 0.55–0.90) for obesity class 3. With normal weight individuals as a reference, fibrinogen levels increase with increasing weight class and were highest for obesity class 3 individuals, +93.5 mg/dl (95% CI, 72.9–114.1). Individuals with hypertension or diabetes have higher levels of CRP and fibrinogen levels compared to individuals without hypertension or diabetes, even when stratified according to BMI. There is a direct association between increasing obesity class and the presence of obesity-related comorbidities such as diabetes and hypertension with high levels of inflammatory biomarkers

Equivalence of Conventionally-Derived and Parthenote-Derived Human Embryonic Stem Cells

As human embryonic stem cell (hESC) lines can be derived via multiple means, it is important to determine particular characteristics of individual lines that may dictate the applications to which they are best suited. The objective of this work was to determine points of equivalence and differences between conventionally-derived hESC and parthenote-derived hESC lines (phESC) in the undifferentiated state and during neural differentiation.hESC and phESC were exposed to the same expansion conditions and subsequent neural and retinal pigmented epithelium (RPE) differentiation protocols. Growth rates and gross morphology were recorded during expansion. RTPCR for developmentally relevant genes and global DNA methylation profiling were used to compare gene expression and epigenetic characteristics. Parthenote lines proliferated more slowly than conventional hESC lines and yielded lower quantities of less mature differentiated cells in a neural progenitor cell (NPC) differentiation protocol. However, the cell lines performed similarly in a RPE differentiation protocol. The DNA methylation analysis showed similar general profiles, but the two cell types differed in methylation of imprinted genes. There were no major differences in gene expression between the lines before differentiation, but when differentiated into NPCs, the two cell types differed in expression of extracellular matrix (ECM) genes.These data show that hESC and phESC are similar in the undifferentiated state, and both cell types are capable of differentiation along neural lineages. The differences between the cell types, in proliferation and extent of differentiation, may be linked, in part, to the observed differences in ECM synthesis and methylation of imprinted genes

Nationwide shifts in the double burden of overweight and underweight in Vietnamese adults in 2000 and 2005: two national nutrition surveys

<p>Abstract</p> <p>Background</p> <p>In developing countries, overweight prevalence is increasing while underweight prevalence is still high. This situation is known as the double nutrition burden. Both underweight and overweight are related to increased risk of chronic non-communicable diseases, reduced well-being and quality of life. This study aims to compare the prevalence of overweight and underweight among Vietnamese adults in 2000 and 2005.</p> <p>Methods</p> <p>The study was based on two nationally representative surveys, the National Nutrition Survey 2000 (14,452 subjects) and the National Adult Obesity Survey 2005 (17,213 subjects). Adults aged 25-64 years were sampled to be nationally representative. Multiple multinomial logistic regression analysis was used to investigate the association of underweight and overweight with socio-economic indicators.</p> <p>Results</p> <p>The distribution of BMI across the population and population groups indicated a shift towards higher BMI levels in 2005 as compared to 2000. The nationwide prevalence of overweight (BMI ≥ 25 kg/m²) and obesity (BMI ≥ 30 kg/m²) was 6.6% and 0.4% respectively in 2005, almost twice the rates of 2000 (3.5% and 0.2%). Using the Asian BMI cut-off of 23 kg/m²the overweight prevalence was 16.3% in 2005 and 11.7% in 2000. In contrast, the underweight prevalence (BMI < 18.5 kg/m²) of 20.9% in 2005 was lower than the rate of 25.0% in 2000. Women were more likely to be both underweight and overweight as compared to men in both 2000 and 2005. Urban residents were more likely to be overweight and less likely to be underweight as compared to rural residents in both years. The shifts from underweight to overweight were clearer among the higher food expenditure levels.</p> <p>Conclusions</p> <p>The double nutrition burden was clearly present in Vietnam. The distribution of BMI across the population groups generally indicated a shift towards higher BMI levels in 2005 as compared to 2000. The prevalence of overweight was increased while the declined level of undernutrition was still high in 2005. The shifts of underweight to overweight were most obvious among population groups with higher food expenditure levels.</p

Effects of Water and Nitrogen Addition on Species Turnover in Temperate Grasslands in Northern China

Global nitrogen (N) deposition and climate change have been identified as two of the most important causes of current plant diversity loss. However, temporal patterns of species turnover underlying diversity changes in response to changing precipitation regimes and atmospheric N deposition have received inadequate attention. We carried out a manipulation experiment in a steppe and an old-field in North China from 2005 to 2009, to test the hypothesis that water addition enhances plant species richness through increase in the rate of species gain and decrease in the rate of species loss, while N addition has opposite effects on species changes. Our results showed that water addition increased the rate of species gain in both the steppe and the old field but decreased the rates of species loss and turnover in the old field. In contrast, N addition increased the rates of species loss and turnover in the steppe but decreased the rate of species gain in the old field. The rate of species change was greater in the old field than in the steppe. Water interacted with N to affect species richness and species turnover, indicating that the impacts of N on semi-arid grasslands were largely mediated by water availability. The temporal stability of communities was negatively correlated with rates of species loss and turnover, suggesting that water addition might enhance, but N addition would reduce the compositional stability of grasslands. Experimental results support our initial hypothesis and demonstrate that water and N availabilities differed in the effects on rate of species change in the temperate grasslands, and these effects also depend on grassland types and/or land-use history. Species gain and loss together contribute to the dynamic change of species richness in semi-arid grasslands under future climate change

High body mass index is not associated with atopy in schoolchildren living in rural and urban areas of Ghana

<p>Abstract</p> <p>Background</p> <p>Factors which determine the development of atopy and the observed rural-urban gradient in its prevalence are not fully understood. High body mass index (BMI) has been associated with asthma and potentially atopy in industrialized countries. In developing countries, the transition from rural to urban areas has been associated with lifestyle changes and an increased prevalence of high BMI; however, the effect of high BMI on atopy remains unknown in this population. We therefore investigated the association between high BMI and atopy among schoolchildren living in rural and urban areas of Ghana.</p> <p>Methods</p> <p>Data on skin prick testing, anthropometric, parasitological, demographic and lifestyle information for 1,482 schoolchildren aged 6-15 years was collected. Atopy was defined as sensitization to at least one tested allergen whilst the Centres for Disease Control and Prevention (CDC, Atlanta) growth reference charts were used in defining high BMI as BMI ≥ the 85^thpercentile. Logistic regression was performed to investigate the association between high BMI and atopy whilst adjusting for potential confounding factors.</p> <p>Results</p> <p>The following prevalences were observed for high BMI [Rural: 16%, Urban: 10.8%, p < 0.001] and atopy [Rural: 25.1%, Urban: 17.8%, p < 0.001]. High BMI was not associated with atopy; but an inverse association was observed between underweight and atopy [OR: 0.57, 95% CI: 0.33-0.99]. Significant associations were also observed with male sex [Rural: OR: 1.49, 95% CI: 1.06-2.08; Urban: OR: 1.90, 95% CI: 1.30-2.79], and in the urban site with older age [OR: 1.76, 95% CI: 1.00-3.07], family history of asthma [OR: 1.58, 95% CI: 1.01-2.47] and occupational status of parent [OR: 0.33, 95% CI: 0.12-0.93]; whilst co-infection with intestinal parasites [OR: 2.47, 95% CI: 1.01-6.04] was associated with atopy in the rural site. After multivariate adjustment, male sex, older age and family history of asthma remained significant.</p> <p>Conclusions</p> <p>In Ghanaian schoolchildren, high BMI was not associated with atopy. Further studies are warranted to clarify the relationship between body weight and atopy in children subjected to rapid life-style changes associated with urbanization of their environments.</p

Suicidal thoughts and depressive feelings amongst Estonian schoolchildren: effect of family relationship and family structure

Depressive feelings and suicidal ideation in a non-clinical sample of adolescents in Estonia were analysed in the context of family structure, mutual relationships amongst family members and schoolchildren's preferences regarding intimate personal contacts with particular family members. Data from the WHO collaborative study 'Health Behaviour in School-aged Children 2005/2006' (HBSC) were used. A representative sample of schoolchildren aged 11, 13 and 15 years completed the semi-structured questionnaire. The analyses included only adolescents living in households with at least one birth parent. The subjects were 4,389 schoolchildren (2,178 boys and 2,211 girls), who were divided into three groups based on: (1) suicidal thoughts, with or without depressive feelings; (2) depressive feelings; and (3) neither suicidal thoughts nor depressive feelings. Multinomial logistic regression was used. The proportion of depressive feelings increased with age for both boys and girls. Girls expressed depressive feelings more frequently than boys from ages 13 and 15 years, and suicidal thoughts from age 15 years. Self-reported satisfaction with relationships in the family reduced the likelihood of depressive feelings and suicidal thoughts. Good communication with the parents reduced the likelihood of suicidal thoughts in all age groups. Adolescents who were satisfied with their family relationships suffered less frequently from depressive feelings and suicidal thoughts. The best environment for an adolescent was a family with both birth parents. Of the adolescents in 'non-intact' families, those with a step-parent in the family showed suicidal thoughts more frequently than those in single-parent families. Associations between family-related variables and suicidal thoughts were significant even after adjusting for family economic deprivation score