Molecular scanning of the human PPARa gene: association of the L162v mutation with hyperapobetalipoproteinemia

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the steroid hormone receptor super family involved in the control of cellular lipid utilization. This makes PPARalpha a candidate gene for type 2 diabetes and dyslipidemia. The aim of this study was to investigate whether genetic variation in the human PPARalpha gene can influence the risk of type 2 diabetes and dyslipidemia among French Canadians. We therefore first determined the genomic structure of human PPARalpha, and then designed intronic primers to sequence the coding region and the exon-intron boundaries of the gene in 12 patients with type 2 diabetes and in 2 nondiabetic subjects. Sequence analysis revealed the presence of a L162V missense mutation in exon 5 of one diabetic patient. Leucine 162 is contained within the DNA binding domain of the human PPARalpha gene, and is conserved among humans, mice, rats, and guinea pigs. We subsequently screened a sample of 121 patients newly diagnosed with type 2 diabetes and their age and sex-matched nondiabetic controls, recruited from the Saguenay-Lac-St-Jean region of Northeastern Quebec, for the presence of the L162V mutation by a PCR-RFLP based method. There was no difference in L162 homozygote or V162 carrier frequencies between diabetics and nondiabetics. However, whether diabetic or not, carriers of the V162 allele had higher plasma apolipoprotein B levels compared to noncarriers (P 5 0.05). To further this association, we screened another sample of 193 nondiabetic subjects recruited in the greater Quebec City area. Carriers of the V162 allele compared with homozygotes of the L162 allele had significantly higher concentrations of plasma total and LDL-apolipoprotein B as well as LDL cholesterol (P 相似文献   

Identification of a gene in the process of being lost from the genus Agrostis

Lineage-specific gene loss is considered one of the processes contributing to speciation and genome diversity. Such gene loss has been inferred from interspecies comparisons of orthologous DNA segments. Examples of intraspecific gene loss are rare. Here we report identification of a gene, designated Crs-1 (creeping specific-1), that appears to be in the process of being lost from heterozygous populations of the species creeping bentgrass (Agrostis stolonifera). The Crs-1 gene encodes a protein with an N-terminal dirigent protein domain and a C-terminal lectin domain and is similar to the maize (Zea mays) beta-glucosidase aggregating factor. Most individual creeping bentgrass plants examined are lacking Crs-1. Some individuals are hemizygous for the Crs-1 locus, indicating major haplotype noncolinearity at that locus. Crs-1 was not detected in several other Agrostis species, indicating it is being lost from the genus. The Crs-1 locus in creeping bentgrass provides a rare example of the evolutionary process of gene loss occurring within a plant species.     

Mapping Biodiversity and Setting Conservation Priorities for SE Queensland’s Rainforests Using DNA Barcoding

Australian rainforests have been fragmented due to past climatic changes and more recently landscape change as a result of clearing for agriculture and urban spread. The subtropical rainforests of South Eastern Queensland are significantly more fragmented than the tropical World Heritage listed northern rainforests and are subject to much greater human population pressures. The Australian rainforest flora is relatively taxonomically rich at the family level, but less so at the species level. Current methods to assess biodiversity based on species numbers fail to adequately capture this richness at higher taxonomic levels. We developed a DNA barcode library for the SE Queensland rainforest flora to support a methodology for biodiversity assessment that incorporates both taxonomic diversity and phylogenetic relationships. We placed our SE Queensland phylogeny based on a three marker DNA barcode within a larger international rainforest barcode library and used this to calculate phylogenetic diversity (PD). We compared phylo- diversity measures, species composition and richness and ecosystem diversity of the SE Queensland rainforest estate to identify which bio subregions contain the greatest rainforest biodiversity, subregion relationships and their level of protection. We identified areas of highest conservation priority. Diversity was not correlated with rainforest area in SE Queensland subregions but PD was correlated with both the percent of the subregion occupied by rainforest and the diversity of regional ecosystems (RE) present. The patterns of species diversity and phylogenetic diversity suggest a strong influence of historical biogeography. Some subregions contain significantly more PD than expected by chance, consistent with the concept of refugia, while others were significantly phylogenetically clustered, consistent with recent range expansions.     

Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants

Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy and T-cell immunity in this vulnerable population is warranted.     

Acceptability and Use of Portable Drinking Water and Hand Washing Stations in Health Care Facilities and Their Impact on Patient Hygiene Practices,Western Kenya

Many health care facilities (HCF) in developing countries lack access to reliable hand washing stations and safe drinking water. To address this problem, we installed portable, low-cost hand washing stations (HWS) and drinking water stations (DWS), and trained healthcare workers (HCW) on hand hygiene, safe drinking water, and patient education techniques at 200 rural HCFs lacking a reliable water supply in western Kenya. We performed a survey at baseline and a follow-up evaluation at 15 months to assess the impact of the intervention at a random sample of 40 HCFs and 391 households nearest to these HCFs. From baseline to follow-up, there was a statistically significant increase in the percentage of dispensaries with access to HWSs with soap (42% vs. 77%, p<0.01) and access to safe drinking water (6% vs. 55%, p<0.01). Female heads of household in the HCF catchment area exhibited statistically significant increases from baseline to follow-up in the ability to state target times for hand washing (10% vs. 35%, p<0.01), perform all four hand washing steps correctly (32% vs. 43%, p = 0.01), and report treatment of stored drinking water using any method (73% vs. 92%, p<0.01); the percentage of households with detectable free residual chlorine in stored drinking water did not change (6%, vs. 8%, p = 0.14). The installation of low-cost, low-maintenance, locally-available, portable hand washing and drinking water stations in rural HCFs without access to 24-hour piped water helped assure that health workers had a place to wash their hands and provide safe drinking water. This HCF intervention may have also contributed to the improvement of hand hygiene and reported safe drinking water behaviors among households nearest to HCFs.     

Factors That Affect Quality of Life among People Living with HIV Attending an Urban Clinic in Uganda: A Cohort Study

Introduction

With the availability of antiretroviral therapy (ART) and primary general care for people living with HIV (PLHIV) in resource limited settings, PLHIV are living longer, and HIV has been transformed into a chronic illness. People are diagnosed and started on treatment when they are relatively well. Although ART results in clinical improvement, the ultimate goal of treatment is full physical functioning and general well-being, with a focus on quality of life rather than clinical outcomes. However, there has been little research on the relationship of specific factors to quality of life in PLHIV. The objective of this study was to investigate factors associated with quality of life among PLHIV in Uganda receiving basic care and those on ART.

Methods

We enrolled 1274 patients attending an HIV outpatient clinic into a prospective cohort study. Of these, 640 received ART. All were followed up at 3 and 6 months. Health related quality of life was assessed with the MOS-HIV Health Survey and the Global Person Generated Index (GPGI). Multivariate linear regression and logistic regression with generalized estimating equations were used to examine the relationship of social behavioral and disease factors with Physical Health Summary (PHS) score, Mental Health Summary (MHS) score, and GPGI.

Results

Among PLHIV receiving basic care, PHS was associated with: sex (p=0.045) - females had lower PHS; age in years at enrollment (p=0.0001) - older patients had lower PHS; and depression (p<0.001) - depressed patients had lower PHS. MHS was only associated with opportunistic infection (p=0.01) - presence of an opportunistic infection was associated with lower MHS. For the GPG the associated variables were age (p=0.03) - older patients had lower GPGI; education (p=0.01) – higher education associated with higher GPGI; and depression - patients with depression had a lower GPGI (p<0.001). Among patients on ART, PHS was associated with: study visit (p=0.01), with increase in time there was better PHS, and this also improved with increase in education level (p=0.002). Patients with WHO disease stage 3&4 had a lower PHS compared to patients at stage 1&2 (p=0.006), and depressed patients had lower PHS (p<0.001). MHS improved from baseline to six month study visit (p<0.001), and females had lower MHS compared to males (p=0.01). GPGI was associated with higher income (p=0.04), alcohol use was associated with lower GPGI (p=0.004), and depressed patients had a lower GPGI (p<0.001).

Conclusion

Quality of life improved over time for PLHIV on ART. Regardless of treatment status, PLHIV with depression or low education level and female gender were at risk of having a poor quality of life. Clinicians and policy makers should be aware of these findings, and address them to improve quality of life for PLHIV.     

Ecosystem engineering in the Quaternary of the West Coast of South Africa

Despite advances in our understanding of the geographic and temporal scope of the Paleolithic record, we know remarkably little about the evolutionary and ecological consequences of changes in human behavior. Recent inquiries suggest that human evolution reflects a long history of interconnections between the behavior of humans and their surrounding ecosystems (e.g., niche construction). Developing expectations to identify such phenomena is remarkably difficult because it requires understanding the multi‐generational impacts of changes in behavior. These long‐term dynamics require insights into the emergent phenomena that alter selective pressures over longer time periods which are not possible to observe, and are also not intuitive based on observations derived from ethnographic time scales. Generative models show promise for probing these potentially unexpected consequences of human‐environment interaction. Changes in the uses of landscapes may have long term implications for the environments that hominins occupied. We explore other potential proxies of behavior and examine how modeling may provide expectations for a variety of phenomena.