Studies on the properties of the singlet oxygen-like factor produced during lipid peroxidation

The singlet oxygen reaction product of various trapping agents is observed during enzymic and nonenzymic peroxidation of microsomes as well as during the peroxidation of pure lipids extracted from microsomes. We now wish to report that purified fatty acid hydroperoxide alone, as well as peroxidized microsomal lipid and cumene hydroperoxide also form the singlet oxygen reaction product with 2,5-diphenylfuran. The reaction product (cis-1,2-dibenzoylethylene) was observed to be formed in an anaerobic system, with or without EDTA. The data indicate that a reaction of hydroxyl radicals with 2,5-diphenylfuran cannot account for the formation of dibenzoylethylene in these systems. These results are consistent with a hypothesis that the singlet oxygen-like factor was formed from the lipid peroxides per se and, in addition, supports the possibility that either the peroxides can react directly with diphenylfuran to produce dibenzoylethylene or that the self-reaction of organic peroxides may form an intermediate product which can react directly with singlet oxygen-trapping agents to produce substances which are identical to a reaction of the trapping agents with singlets oxygen.     

Urbanisation lowers great tit Parus major breeding success at multiple spatial scales

While numerous studies have reported negative effects of urbanisation on birds, few have examined the role of urban scale in influencing breeding success. Furthermore, many studies have relied on qualitative rather than quantitative assessments of urbanisation. This study sought to address these issues by testing the effects of urbanisation, measured at two spatial scales, on the breeding success of great tits Parus major. A nested study design, incorporating over 400 nestboxes, was used in study sites across northern Belgium with a priori quantified degrees of urbanisation at both local and regional scales. All measured breeding parameters were found to vary at one or both spatial scales of urbanisation; in more urbanised areas great tits displayed advanced laying dates but lower breeding success compared to rural areas, with smaller clutch sizes, lower nestling masses and fewer fledglings per egg. Importantly, urbanisation effects were not limited to big cities as birds breeding in gardens or parks in small towns also had comparatively low success. We found that both regional‐ and local‐scale urbanisation had consistent significant effects on laying date, clutch size and nestling mass, while the number of fledglings per egg was negatively influenced by local‐scale urbanisation only. Results of this study therefore highlight the importance of utilising multiple spatial scales in analysing urbanisation effects, as well as the potential negative impact of local urbanisation on breeding success. This calls for further investigation into mechanisms driving urbanisation effects and how these may vary at different scales.     

Widespread Backtracking by RNA Pol II Is a Major Effector of Gene Activation, 5′ Pause Release,Termination, and Transcription Elongation Rate

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Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons

The triglycerides in chylomicrons are hydrolyzed by lipoprotein lipase (LpL) along the luminal surface of the capillaries. However, the endothelial cell molecule that facilitates chylomicron processing by LpL has not yet been defined. Here, we show that glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) plays a critical role in the lipolytic processing of chylomicrons. Gpihbp1-deficient mice exhibit a striking accumulation of chylomicrons in the plasma, even on a low-fat diet, resulting in milky plasma and plasma triglyceride levels as high as 5000 mg/dl. Normally, Gpihbp1 is expressed highly in heart and adipose tissue, the same tissues that express high levels of LpL. In these tissues, GPIHBP1 is located on the luminal face of the capillary endothelium. Expression of GPIHBP1 in cultured cells confers the ability to bind both LpL and chylomicrons. These studies strongly suggest that GPIHBP1 is an important platform for the LpL-mediated processing of chylomicrons in capillaries.     

A DIGE analysis of developing poplar leaves subjected to ozone reveals major changes in carbon metabolism

Tropospheric ozone pollution is described as having major negative effects on plants, compromising plant survival. Carbon metabolism is especially affected. In the present work, the effects of chronic ozone exposure were evaluated at the proteomic level in developing leaves of young poplar plants exposed to 120 ppb of ozone for 35 days. Soluble proteins (excluding intrinsic membrane proteins) were extracted from leaves after 3, 14 and 35 days of ozone exposure, as well as 10 days after a recovery period. Proteins (pI 4 to 7) were analyzed by 2-D DIGE experiments, followed by MALDI-TOF-TOF identification. Additional observations were obtained on growth, lesion formation, and leaf pigments analysis. Although treated plants showed large necrotic spots and chlorosis in mature leaves, growth decreased only slightly and plant height was not affected. The number of abscised leaves was higher in treated plants, but new leaf formation was not affected. A decrease in chlorophylls and lutein contents was recorded. A large number of proteins involved in carbon metabolism were identified. In particular, proteins associated with the Calvin cycle and electron transport in the chloroplast were down-regulated. In contrast, proteins associated with glucose catabolism increased in response to ozone exposure. Other identified enzymes are associated with protein folding, nitrogen metabolism and oxidoreductase activity.     

Increased gene coverage and Alu frequency in large linkage disequilibrium blocks of the human genome

The human genome has linkage disequilibrium (LD) blocks, within which single-nucleotide polymorphisms show strong association with each other. We examined data from the International HapMap Project to define LD blocks and to detect DNA sequence features inside of them. We used permutation tests to determine the empirical significance of the association of LD blocks with genes and Alu repeats. Very large LD blocks (>200 kb) have significantly higher gene coverage and Alu frequency than the outcome obtained from permutation-based simulation, whereas there was no significant positive correlation between gene density and block size. We also observed a reduced frequency of Alu repeats at the gaps between large LD blocks, indicating that their enrichment in large LD blocks does not introduce recombination hotspots that would cause these gaps.     

BMI, obesity, and sickness absence in the Whitehall II study

Objective: To study BMI and change in BMI from age 25 as predictors of sickness absence. Research Methods and Procedures: Data were collected from 2564 women and 5853 men, who were British civil servants (35 to 55 years) on entry to the Whitehall II study (Phase 1, 1985 to 1988). Employer's records provided annual medically certified (long, >7 days) and self‐certified (short, 1 to 7 days) spells of sickness absence. BMI at age 25 and Phase 1 were examined in relation to absences from Phase 1 to the end of 1998 (mean follow‐up, 7.0 years). Results: After adjustment for employment grade, health‐related behaviors, and health status, overweight (BMI = 25.0 to 29.9 kg/m²) and obesity (BMI > 30.0 kg/m²) at Phase 1 were significant predictors of short and long absences in both sexes; rate ratios (95% confidence intervals) ranged from 1.13 (1.05 to 1.21) to 1.51 (1.30 to 1.76) compared with a BMI of 21.0 to 22.9 kg/m². Additionally, a BMI of 23.0 to 24.9 kg/m² at Phase 1 predicted long absences in women, and underweight (BMI < 21.0 kg/m²) predicted short absences in men. Obesity at age 25 predicted long absences, and obesity at Phase 1 predicted short and long absences in both sexes. Chronic obesity was a particularly strong predictor of long absences in men, with a rate ratio of 2.61 (1.88 to 3.63). Discussion: Findings from this well‐characterized cohort suggest that the obesity epidemic in industrialized countries may result in significant increases in sickness absence. Further research is needed to determine the underlying mechanisms. Policy to reduce sickness absence needs to tackle the problem of excess weight in the working population.     

Chefs' opinions of restaurant portion sizes

Objectives: The objectives were to determine who establishes restaurant portion sizes and factors that influence these decisions, and to examine chefs’ opinions regarding portion size, nutrition information, and weight management. Research Methods and Procedures: A survey was distributed to chefs to obtain information about who is responsible for determining restaurant portion sizes, factors influencing restaurant portion sizes, what food portion sizes are being served in restaurants, and chefs’ opinions regarding nutrition information, health, and body weight. The final sample consisted of 300 chefs attending various culinary meetings. Results: Executive chefs were identified as being primarily responsible for establishing portion sizes served in restaurants. Factors reported to have a strong influence on restaurant portion sizes included presentation of foods, food cost, and customer expectations. While 76% of chefs thought that they served “regular” portions, the actual portions of steak and pasta they reported serving were 2 to 4 times larger than serving sizes recommended by the U.S government. Chefs indicated that they believe that the amount of food served influences how much patrons consume and that large portions are a problem for weight control, but their opinions were mixed regarding whether it is the customer's responsibility to eat an appropriate amount when served a large portion of food. Discussion: Portion size is a key determinant of energy intake, and the results from this study suggest that cultural norms and economic value strongly influence the determination of restaurant portion sizes. Strategies are needed to encourage chefs to provide and promote portions that are appropriate for customers’ energy requirements.     

Microbial pathogen-induced necrotic cell death mediated by the inflammasome components CIAS1/cryopyrin/NLRP3 and ASC

Cryopyrin (CIAS1, NLRP3) and ASC are components of the inflammasome, a multiprotein complex required for caspase-1 activation and cytokine IL-1beta production. CIAS1 mutations underlie autoinflammation characterized by excessive IL-1beta secretion. Disease-associated cryopyrin also causes a program of necrosis-like cell death in macrophages, the mechanistic details of which are unknown. We find that patient monocytes carrying disease-associated CIAS1 mutations exhibit excessive necrosis-like death by a process dependent on ASC and cathepsin B, resulting in spillage of the proinflammatory mediator HMGB1. Shigella flexneri infection also causes cryopyrin-dependent macrophage necrosis with features similar to the death caused by mutant CIAS1. This necrotic death is independent of caspase-1 and IL-1beta, and thus independent of the inflammasome. Furthermore, necrosis of primary macrophages requires the presence of Shigella virulence genes. While similar proteins mediate pathogen-induced cell death in plants, this report identifies cryopyrin as an important host regulator of programmed pathogen-induced necrosis in animals, a process we term pyronecrosis.