Factors influencing protective behaviours during haze episodes in Singapore: A population-based study.

INTRODUCTION: Haze is a recurrent problem in Southeast Asia. Exposure to haze is linked to ophthalmic, respiratory and cardiovascular diseases, and mortality. In this study, we investigated the role of demographic factors, knowledge and perceived risk in influencing protective behaviours during the 2013 haze in Singapore. METHODS: We evaluated 696 adults in a cross-sectional study. Participants were sampled via a 2-stage simple random sampling without replacement from a large residential district in Singapore in 2015. The questionnaire measured the participant's knowledge, perceived risk and behaviours during the Southeast Asian haze crisis in 2013. Reliability and validity of the questionnaire were assessed using comparative fit index (≥0.96) and root mean square error of approximation (≤0.05). We performed structural equation modelling to examine the relationship between the hypothesised factors and protective behaviours. RESULTS: More than 95% of the individuals engaged in at least 1 form of protective behaviour. Knowledge was strongly associated with protective behaviours via direct effect (ß=0.45, 95% CI 0.19-0.69, P<0.001) and indirect effect through perceived risk (ß=0.18, 95% CI 0.07-0.31, P=0.002). Perceived risk was associated with protective behaviours (ß=0.28, 95% CI:0.11-0.44, P=0.002). A lower household income and ethnic minority were associated with protective behaviours. A lower education level and smokers were associated with lower knowledge of haze. A higher education and ethnic minority were associated with a lower perceived risk. Wearing of N95 masks was associated with other haze-related protective behaviours (ß=0.24, 95% CI 0.08-0.37, P=0.001). CONCLUSION: Knowledge was associated with protective behaviours, suggesting the importance of public education. Efforts should target those of lower education level and smokers. The wearing of N95 masks correlates with uptake of other protective behaviours.

Factors influencing protective behaviours during haze episodes in Singapore: A population-based study

INTRODUCTION@#Haze is a recurrent problem in Southeast Asia. Exposure to haze is linked to ophthalmic, respiratory and cardiovascular diseases, and mortality. In this study, we investigated the role of demographic factors, knowledge and perceived risk in influencing protective behaviours during the 2013 haze in Singapore.@*METHODS@#We evaluated 696 adults in a cross-sectional study. Participants were sampled via a 2-stage simple random sampling without replacement from a large residential district in Singapore in 2015. The questionnaire measured the participant's knowledge, perceived risk and behaviours during the Southeast Asian haze crisis in 2013. Reliability and validity of the questionnaire were assessed using comparative fit index (≥0.96) and root mean square error of approximation (≤0.05). We performed structural equation modelling to examine the relationship between the hypothesised factors and protective behaviours.@*RESULTS@#More than 95% of the individuals engaged in at least 1 form of protective behaviour. Knowledge was strongly associated with protective behaviours via direct effect (β=0.45, 95% CI 0.19-0.69, @*CONCLUSION@#Knowledge was associated with protective behaviours, suggesting the importance of public education. Efforts should target those of lower education level and smokers. The wearing of N95 masks correlates with uptake of other protective behaviours.

Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth.

We aimed to identify novel molecular mechanisms for muscle growth during administration of anabolic agents. Growing pigs (Duroc/(Landrace/Large-White)) were administered Ractopamine (a beta-adrenergic agonist; BA; 20 ppm in feed) or Reporcin (recombinant growth hormone; GH; 10 mg/48 hours injected) and compared to a control cohort (feed only; no injections) over a 27-day time course (1, 3, 7, 13 or 27-days). Longissimus Dorsi muscle gene expression was analyzed using Agilent porcine transcriptome microarrays and clusters of genes displaying similar expression profiles were identified using a modified maSigPro clustering algorithm. Anabolic agents increased carcass (p = 0.002) and muscle weights (Vastus Lateralis: p < 0.001; Semitendinosus: p = 0.075). Skeletal muscle mRNA expression of serine/one-carbon/glycine biosynthesis pathway genes (Phgdh, Psat1 and Psph) and the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase-M (Pck2/PEPCK-M), increased during treatment with BA, and to a lesser extent GH (p < 0.001, treatment x time interaction). Treatment with BA, but not GH, caused a 2-fold increase in phosphoglycerate dehydrogenase (PHGDH) protein expression at days 3 (p < 0.05) and 7 (p < 0.01), and a 2-fold increase in PEPCK-M protein expression at day 7 (p < 0.01). BA treated pigs exhibit a profound increase in expression of PHGDH and PEPCK-M in skeletal muscle, implicating a role for biosynthetic metabolic pathways in muscle growth.

Maternal high-fat feeding in pregnancy programs atherosclerotic lesion size in the ApoE*3 Leiden mouse.

Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high-fat diet in utero, programed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28 days postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (P<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol; however, transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared with wild-type controls (P=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R 2=0.563, P<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol two-fold higher than in chow-fed mothers, P=0.011). The data strongly suggest that maternal hypercholesterolemia programs later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models.

Construction of a doxycycline inducible adipogenic lentiviral expression system.

To provide a tool for research on regulating adipocyte differentiation, tetracycline inducible (Tet on) lentiviral expression vectors under the control of an adipose-specific promoter were constructed. The lowest basal expression in the absence of doxycycline and most efficient dose-dependent, doxycycline-induced transient overexpression was observed using vectors constructed with a combination of Tetracycline Responsive Element (TRE) and reverse tetracycline-controlled TransActivator advanced (rtTAadv), transfected in white (3T3-L1) and brown (HIB-1B) preadipocytes cell lines. The results demonstrate that doxycycline adipogenic inducible expression can be achieved using a pLenti TRE / rtTA adv under the control of the truncated aP2 promoter in HIB-1B preadipocytes.

Development and modeling of arsenic-trioxide-loaded thermosensitive liposomes for anticancer drug delivery.

In this article, a novel delivery system for the anticancer drug, arsenic trioxide (ATO), is characterized. The release of ATO from DPPC liposomes with MPPC lysolipid incorporated into the bilayer was measured. Upon heating the liposomes to 37°C, there was a 15-25% release over 24 hours. The ATO release from the DPPC and DPPC:MPPC (5%) systems leveled off after 10 hours at 37°C, whereas the DPPC:MPPC (10%) liposomes continue to release ATO over the 24-hour time span. Upon heating the liposomes rapidly to 42°C, the release rate was substantially increased. The systems containing lysolipids exhibited a very rapid release of a significant amount of arsenic in the first hour. In the first hour, the DPPC:MPPC (5%) liposomes released 40% of the arsenic and the DPPC:MPPC (10%) liposomes released 55% of the arsenic. Arsenic release from pure DPPC liposomes was comparable at 37 and 42°C, indicating that the presence of a lysolipid is necessary for a significant enhancement of the release rate. A coarse-grained molecular dynamics (CGMD) model was used to investigate the enhanced permeability of lysolipid-incorporated liposomes and lipid bilayers. The CG liposomes did not form a gel phase when cooled due to the high curvature; however, permeability was still significantly lower below the liquid-to-gel phase-transition temperature. Simulations of flat DPPC:MPPC bilayers revealed that a peak in the permeability did coincide with the phase transition from the gel to LC state when the lysolipid, MPPC, was present. No pores were observed in the simulations, so it is unlikely this was the permeability-enhancing mechanism.

Effect of anabolic agents on calpastatin promoters in porcine skeletal muscle and their responsiveness to cyclic adenosine monophosphate- and calcium-related stimuli.

The calpain proteinases and their specific inhibitor calpastatin have been proposed to influence both the rates of myofibrillar protein turnover in vivo and meat tenderization postmortem. Elevated calpastatin concentrations in particular are associated with certain forms of hypertrophic growth and meat toughness. In the 5'region of the porcine calpastatin gene, there are 3 calpastatin promoters upstream of exons 1xa, 1xb, and 1u, respectively, each of which contain transcription factor-binding motifs, suggesting sensitivity to a variety of growth-promoting stimuli. This study examined the effect of the beta-adrenergic agonist clenbuterol and porcine ST (pST) treatment on calpastatin promoter usage in porcine LM in vivo using real-time PCR and also the responsiveness of transfected calpastatin promoter sequences to cyclic adenosine monophosphate (cAMP) and calcium (Ca2+)-related stimuli in reporter gene systems in cell studies. The effect of clenbuterol and pST on potential signaling pathways in vivo was also assessed by monitoring protein phosphatase 2B (calcineurin), NFATc3, calpain 3, IkappaB alpha, and NFkappaB by quantitative immunoblotting. Total calpastatin mRNA was increased by 52% (P < 0.05) after treatment with clenbuterol for 1 d and reduced by 35% (P < 0.01) after pST treatment for 7 d. Whereas clenbuterol had no significant differential effects on individual mRNA transcripts (types 1 to 3) derived from the 3 upstream promoters, pST significantly reduced all of these by 51, 39, and 40% (P < 0.001, 0.05, and 0.05), respectively. Promoter activity was increased in rat L6G8 cells transfected with a construct derived from exon 1u after treatment with dibutyryl cAMP (68%, P < 0.05) or forskolin (43%, P < 0.05), whereas 1xa activity was reduced by both of these agents (47 and 33%, respectively, P < 0.05). Treatment of cells with the calcium ionophore calcimycin reduced the activity of the 1u promoter by 40% (P < 0.01), with no effect on the other promoter constructs. Cyclosporin A had no effect on any promoter construct. The only signaling pathway component to be significantly altered by the in vivo treatments was calcineurin, which was decreased by 24% (P < 0.05) in clenbuterol-treated animals. In conclusion, 2 types of growth promoter in pigs had contrasting effects on calpastatin expression in LM. Transfected calpastatin promoters were differentially sensitive to cAMP- and Ca2+-related stimuli, in agreement with the proposed mode of action of the 2 growth promoters.

Effects of modified corn gluten meal on quality characteristics of a model emulsified meat product.

The objective of this study was to evaluate the effects of soy protein isolate (SPI), three forms of native corn gluten meal on sensory, color and textural characteristics of an emulsified meat product. The meals included native corn gluten meal (CGM) that had been ph-adjusted from 4.4 to 6.6 and particle size reduced to either ∼38 (MC38) or ∼7 µm (MC7). When judged by a trained sensory panel, all CGM-based substances contributed the same degree of CGM off-odor intensity, but significantly lowered pork odor intensity when compared to SPI-containing products and controls. SPI and all CGM-based substances increased grain-like odor. Visual off-color was apparent in all meat products containing CGM-based substances. Instrumental color evaluation indicated that products containing CGM-based substances were lighter, more yellow colored than control and SPI-containing products. However, sensory denseness, springiness and cohesiveness, and texture profile analyses of meat products were not affected.

Effects of lactic and acetic acid salts on quality characteristics of enhanced pork during retail display.

The objective of this study was to evaluate the sensory and physical characteristics of pork chops from loins enhanced to 110% of original weight with either (1) potassium lactate, potassium diacetate, phosphate and salt, (2) sodium lactate, phosphate and salt, (3) potassium lactate, phosphate and salt, (4) sodium acetate, phosphate and salt, or (5) phosphate and salt. A trained sensory panel evaluated pork flavor, saltiness, bitterness, soapy flavor, acid flavor, juiciness and tenderness of cooked chops. Visual color of raw chops was also evaluated. After 96 h in display, chops enhanced with lactate/diacetate had significantly lower (P<0.01) aerobic plate counts than control (unpumped) chops, or those pumped with other solutions. Lactate/diacetate-enhanced chops maintained higher a* and b* values during display, and had less visual discoloration after 96 h display. Chops pumped with lactate, acetate or the lactate/diacetate mixture were more tender and juicy, and had more pork flavor than controls or those pumped with phosphate/salt only. There appears to be a significant advantage to using a lactate/diacetate enhancement solution over either lactate or acetate alone.

Dietary vitamin E supplementation effects on the color and sensory characteristics of enhanced beef steaks.

The objective of this study was to evaluate the effects of dietary vitamin E supplementation on characteristics of enhanced beef cuts during retail display. Twelve steers were fed either a control (E-) diet or a diet supplemented with dl-alpha tocopheryl acetate (E+) for 117 days prior to slaughter. Paired strip loins, clods, and inside rounds served as the control (C) or were pumped (P) to 110% of raw weight to contain 0.4% sodium chloride and 0.4% phosphate on a finished weight basis. Steaks were cut (2.5 cm) for sensory evaluation and retail display. No flavor or texture differences existed in strip steaks due to vitamin E. Enhanced steaks were more tender, juicy and salty than controls, however they discolored more rapidly than did controls. Steaks from supplemented cattle were slightly, but significantly, less discolored, indicating that vitamin E may provide some improvements in color stability of enhanced meat products. Vitamin E supplementation may improve short term color stability (up to 2 days in display) of retail beef enhanced by injection of a salt-phosphate solution.

Effect of dietary vitamin E supplementation on textural and aroma attributes of enhanced beef clod roasts in a cook/hot-hold situation.

The objective of this study was to evaluate the effects of supplementing vitamin E into the diets of finishing cattle on quality characteristics of beef pumped with a phosphate/salt solution (enhanced) the cooked and held in a simulated foodservice situation. Twelve steers were fed either a control (E-) diet or a diet supplemented with dl-α-tocopheryl-acetate (E+). Paired clod roasts were either used as controls (C) or were pumped (P) to 110% of raw weight to contain 0.4% sodium chloride and 0.4% phosphate in the finished product. Following injection, clods were allowed to equilibrate then frozen. A flavor profile panel evaluated texture attributes and aroma characteristics of roasts immediately after cooking and after 1 and 2 h of hot-holding. Pumping improved taste and textural attributes of the hot-held clod roasts. Dietary vitamin E supplementation reduced thiobarbituric acid reactive substances (TBARS) from ∼0.61 to ∼0.42, but over the 2-h time period, did not significantly improve aroma quality of beef roasts.

Consumer attitudes towards beef and acceptability of enhanced beef.

The objective of this study was to evaluate consumer quality characteristics of enhanced steaks and roasts derived from cattle supplemented with vitamin E during finishing, and to assess the attitudes of these consumers towards beef. Twelve steers were fed either a control (E-) diet or a diet supplemented with dl-alpha tocopheryl acetate (E+). Paired strip loins and rounds were either used as controls (C) or were pumped (P) to 110% of raw weight to contain 0.4% sodium chloride and 0.4% sodium tripolyphosphate in the final product. Consumers (n=103) evaluated roasts and steaks for juiciness, tenderness, saltiness, and overall acceptability on a 9-point hedonic scale. Enhanced steaks and roasts were more acceptable than non-enhanced controls; E+ steaks were less acceptable than E- steaks. A beef quality questionnaire revealed that color, price, visible fat and cut were the most important factors underlying beef steak purchase, while tenderness, flavor and juiciness were weighted most heavily with regard to eating satisfaction.

Assembly and preferential localization of Nup116p on the cytoplasmic face of the nuclear pore complex by interaction with Nup82p.

The yeast Saccharomyces cerevisiae nucleoporin Nup116p serves as a docking site for both nuclear import and export factors. However, the mechanism for assembling Nup116p into the nuclear pore complex (NPC) has not been resolved. By conducting a two-hybrid screen with the carboxy (C)-terminal Nup116p region as bait, we identified Nup82p. The predicted coiled-coil region of Nup82p was not required for Nup116p interaction, making the binding requirements distinct from those for the Nsp1p-Nup82p-Nup159p subcomplex (N. Belgareh, C. Snay-Hodge, F. Pasteau, S. Dagher, C. N. Cole, and V. Doye, Mol. Biol. Cell 9:3475-3492, 1998). Immunoprecipitation experiments using yeast cell lysates resulted in the coisolation of a Nup116p-Nup82p subcomplex. Although the absence of Nup116p had no effect on the NPC localization of Nup82p, overexpression of C-terminal Nup116p in a nup116 null mutant resulted in Nup82p mislocalization. Moreover, NPC localization of Nup116p was specifically diminished in a nup82-Delta108 mutant after growth at 37 degrees C. Immunoelectron microscopy analysis showed Nup116p was localized on both the cytoplasmic and nuclear NPC faces. Its distribution was asymmetric with the majority at the cytoplasmic face. Taken together, these results suggest that Nup82p and Nup116p interact at the cytoplasmic NPC face, with nucleoplasmic Nup116p localization utilizing novel binding partners.

The politics and ethics of human embryo and stem cell research.

There is great promise for stem cell research to develop cells and tissues for transplantation and treatment of diseases such as Alzheimer and Parkinson disease, diabetes, and heart problems. There is also promise to advance understanding and treatment of cancer and congenital defects. Human embryo research is fundamentally the only way to understand human fertilization, implantation, and early development. For years, federal funding of human embryo research has been held hostage to a congressional prolife agenda. Any reasonable solution to these political disputes that so greatly affect women's reproductive interests and the promise of health benefits from embryo and stem cell research should mandate that governmental sponsorship proceed.

Binding of PurH to a muscle-specific splicing enhancer functionally correlates with exon inclusion in vivo.

Regulated alternative splicing of avian cardiac troponin T (cTNT) pre-mRNA requires multiple intronic elements called muscle-specific splicing enhancers (MSEs) that flank the alternative exon 5 and promote muscle-specific exon inclusion. To understand the function of the MSEs in muscle-specific splicing, we sought to identify trans-acting factors that bind to these elements. MSE3, which is located 66-81 nucleotides downstream of exon 5, assembles a complex that is both sequence- and muscle-specific. Purification and characterization of the MSE3 complex identified one component as 5-aminoimidazole-4-carboxamide ribonucleotideformyltransferase/IMP cyclohydrolase (PurH), an enzyme involved in de novo purine synthesis. Recombinant human PurH protein directly binds MSE3 RNA and PurH is the primary determinant of sequence-specific binding in the native complex. Furthermore, we show a direct correlation between the in vitro binding affinity of both the MSE3 complex and recombinant PurH with functional activation of exon inclusion in vivo. Together, these results strongly suggest that PurH performs a second function as a component of a complex that regulates MSE3-dependent exon inclusion.

The nuclear pore complex: a protein machine bridging the nucleus and cytoplasm.

Compositional analysis of nuclear pore complexes (NPCs) is nearing completion, and efforts are now focused on understanding how these protein machines work. Recent analysis of soluble transport factor interactions with NPC proteins reveals distinct and overlapping pathways for movement between the nucleus and cytoplasm. New fluorescence- and microscopy-based strategies have been used to monitor the pathway of NPC assembly and to reveal the dynamics of the NPC during transport.

Research misconduct in clinical research--the American experience and response.

Research misconduct in the United States has occurred sporadically since 1961 in the laboratories of some of our most distinguished scientists. In view of the enormous number of research grants funded, cases of this kind are relatively uncommon, but have none the less attracted governmental supervision and calls for reform. The scientific community, universities and government have addressed the issue in various ways and changes have been proposed and some actually instituted. In view of human nature, no one seriously believes that dishonesty in research can be prevented to any greater extent than in any other human activity. However, some practices may discourage and mitigate such occurrences. These include: education in sound laboratory research practices, a fair distribution of authorship assignment, and adequate supervision of research personnel including appropriate reviewing of primary data. Other measures which might be considered include: an adequate check of the credentials of all new personnel, audits for clinical research, especially for those involving significant numbers of patients and multiple institutions, and the introduction of quality control concepts into research procedures. The hope is that the senior individual scientist responsible for the quality and integrity of the research will institute such measures as needed, and that institutional and government supervision will not interfere with the creative process.

Experimental determination of section sensitivity profiles and image noise in electron beam computed tomography.

To determine the effect of continuous-volume scanning (CVS) on z-axis resolution, section sensitivity profiles were measured on an electron beam computed tomography (CT) scanner and compared with those obtained using the step-volume scanning (SVS) mode. A steel bead was imaged using different scan parameters, and the mean CT number over the bead was plotted against the z-axis position to determine section sensitivity profiles. From these profiles, full width at half maximum (FWHM), full width at tenth maximum (FWTM), and full width at tenth area (FWTA) were calculated. A uniform water phantom was imaged to measure noise. To determine the visual significance of changes in the section sensitivity profile, a section thickness and contiguity phantom was imaged. All section sensitivity profiles measured had an FWHM value within 0.5 mm of the nominal scan width. The FWTM and FWTA values increased with the CVS mode compared with the SVS mode. This broadening of the section sensitivity profiles was most significant with larger collimator widths. However, use of smaller collimator widths increased image noise. When all other parameters remained constant, increasing the exposure time to reduce image noise did not affect the section sensitivity profile. The CVS mode produced wider section sensitivity profiles than the SVS mode. This effect was minimized when the smallest collimator width was used, but at the expense of increased image noise.