402 research outputs found
Evaluation of 64Cu-based radiopharmaceuticals that target Aβ peptide aggregates as diagnostic tools for Alzheimer’s disease
A Pseudo-tRNA Modulates Antibiotic Resistance in Bacillus cereus
Bacterial genomic islands are often flanked by tRNA genes, which act as sites for the integration of foreign DNA into the host chromosome. For example, Bacillus cereus ATCC14579 contains a pathogenicity island flanked by a predicted pseudo-tRNA, tRNA(Other), which does not function in translation. Deletion of tRNA(Other) led to significant changes in cell wall morphology and antibiotic resistance and was accompanied by changes in the expression of numerous genes involved in oxidative stress responses, several of which contain significant complementarities to sequences surrounding tRNA(Other). This suggested that tRNA(Other) might be expressed as part of a larger RNA, and RACE analysis subsequently confirmed the existence of several RNA species that significantly extend both the 39 and 5\u27-ends of tRNA(Other). tRNA(Other) expression levels were found to be responsive to changes in extracellular iron concentration, consistent with the presence of three putative ferric uptake regulator (Fur) binding sites in the 59 leader region of one of these larger RNAs. Taken together with previous data, this study now suggests that tRNA(Other) may function by providing a tRNA-like structural element within a larger regulatory RNA. These findings illustrate that while integration of genomic islands often leaves tRNA genes intact and functional, in other instances inactivation may generate tRNA-like elements that are then recruited to other functions in the cell
A Pseudo-tRNA Modulates Antibiotic Resistance in \u3cem\u3eBacillus cereus\u3c/em\u3e
Bacterial genomic islands are often flanked by tRNA genes, which act as sites for the integration of foreign DNA into the host chromosome. For example, Bacillus cereus ATCC14579 contains a pathogenicity island flanked by a predicted pseudo-tRNA, tRNAOther, which does not function in translation. Deletion of tRNAOther led to significant changes in cell wall morphology and antibiotic resistance and was accompanied by changes in the expression of numerous genes involved in oxidative stress responses, several of which contain significant complementarities to sequences surrounding tRNAOther. This suggested that tRNAOther might be expressed as part of a larger RNA, and RACE analysis subsequently confirmed the existence of several RNA species that significantly extend both the 3′ and 5′-ends of tRNAOther. tRNAOther expression levels were found to be responsive to changes in extracellular iron concentration, consistent with the presence of three putative ferric uptake regulator (Fur) binding sites in the 5′ leader region of one of these larger RNAs. Taken together with previous data, this study now suggests that tRNAOther may function by providing a tRNA-like structural element within a larger regulatory RNA. These findings illustrate that while integration of genomic islands often leaves tRNA genes intact and functional, in other instances inactivation may generate tRNA-like elements that are then recruited to other functions in the cell
Discrimination in Healthcare Settings is Associated with Disability in Older Adults: Health and Retirement Study, 2008–2012
BACKGROUNDAs our society ages, improving medical care for an older population will be crucial. Discrimination in healthcare may contribute to substandard experiences with the healthcare system, increasing the burden of poor health in older adults. Few studies have focused on the presence of healthcare discrimination and its effects on older adults.OBJECTIVEWe aimed to examine the relationship between healthcare discrimination and new or worsened disability.DESIGNThis was a longitudinal analysis of data from the nationally representative Health and Retirement Study administered in 2008 with follow-up through 2012.PARTICIPANTSSix thousand and seventeen adults over the age of 50 years (mean age 67years, 56.3% female, 83.1% white) were included in this study.MAIN MEASURESHealthcare discrimination assessed by a 2008 report of receiving poorer service or treatment than other people by doctors or hospitals (never, less than a year=infrequent; more than once a year=frequent). Outcome was self-report of new or worsened disability by 2012 (difficulty or dependence in any of six activities of daily living). We used a Cox proportional hazards model adjusting for age, race/ethnicity, gender, net worth, education, depression, high blood pressure, diabetes, cancer, lung disease, heart disease, stroke, and healthcare utilization in the past 2years.KEY RESULTSIn all, 12.6 % experienced discrimination infrequently and 5.9% frequently. Almost one-third of participants (29%) reporting frequent healthcare discrimination developed new or worsened disability over 4years, compared to 16.8% of those who infrequently and 14.7% of those who never experienced healthcare discrimination (p < 0.001). In multivariate analyses, compared to no discrimination, frequent healthcare discrimination was associated with new or worsened disability over 4years (aHR = 1.63, 95% CI 1.16–2.27).CONCLUSIONSOne out of five adults over the age of 50 years experiences discrimination in healthcare settings. One in 17 experience frequent healthcare discrimination, and this is associated with new or worsened disability by 4years. Future research should focus on the mechanisms by which healthcare discrimination influences disability in older adults to promote better health outcomes for an aging population.Electronic supplementary materialThe online version of this article (doi:10.1007/s11606-015-3233-6) contains supplementary material, which is available to authorized users
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Measurements and Models for Hazardous chemical and Mixed Wastes
Mixed solvent aqueous waste of various chemical compositions constitutes a significant fraction of the total waste produced by industry in the United States. Not only does the chemical process industry create large quantities of aqueous waste, but the majority of the waste inventory at the DOE sites previously used for nuclear weapons production is mixed solvent aqueous waste. In addition, large quantities of waste are expected to be generated in the clean-up of those sites. In order to effectively treat, safely handle, and properly dispose of these wastes, accurate and comprehensive knowledge of basic thermophysical properties is essential. The goal of this work is to develop a phase equilibrium model for mixed solvent aqueous solutions containing salts. An equation of state was sought for these mixtures that (a) would require a minimum of adjustable parameters and (b) could be obtained from a available data or data that were easily measured. A model was developed to predict vapor composition and pressure given the liquid composition and temperature. It is based on the Peng-Robinson equation of state, adapted to include non-volatile and salt components. The model itself is capable of predicting the vapor-liquid equilibria of a wide variety of systems composed of water, organic solvents, salts, nonvolatile solutes, and acids or bases. The representative system o water + acetone + 2-propanol + NaNo3 was selected to test and verify the model. Vapor-liquid equilibrium and phase density measurements were performed for this system and its constituent binaries
Aflatoxin Contamination of Commercial Maize Products during an Outbreak of Acute Aflatoxicosis in Eastern and Central Kenya
In April 2004, one of the largest aflatoxicosis outbreaks occurred in rural Kenya, resulting in 317 cases and 125 deaths. Aflatoxin-contaminated homegrown maize was the source of the outbreak, but the extent of regional contamination and status of maize in commercial markets (market maize) were unknown. We conducted a cross-sectional survey to assess the extent of market maize contamination and evaluate the relationship between market maize aflatoxin and the aflatoxicosis outbreak. We surveyed 65 markets and 243 maize vendors and collected 350 maize products in the most affected districts. Fifty-five percent of maize products had aflatoxin levels greater than the Kenyan regulatory limit of 20 ppb, 35% had levels > 100 ppb, and 7% had levels > 1,000 ppb. Makueni, the district with the most aflatoxicosis case-patients, had significantly higher market maize aflatoxin than did Thika, the study district with fewest case-patients (geometric mean aflatoxin = 52.91 ppb vs. 7.52 ppb, p = 0.0004). Maize obtained from local farms in the affected area was significantly more likely to have aflatoxin levels > 20 ppb compared with maize bought from other regions of Kenya or other countries (odds ratio = 2.71; 95% confidence interval, 1.12–6.59). Contaminated homegrown maize bought from local farms in the affected area entered the distribution system, resulting in widespread aflatoxin contamination of market maize. Contaminated market maize, purchased by farmers after their homegrown supplies are exhausted, may represent a source of continued exposure to aflatoxin. Efforts to successfully interrupt exposure to aflatoxin during an outbreak must consider the potential role of the market system in sustaining exposure
Cross-inhibition of NMBR and GRPR signaling maintains normal histaminergic itch transmission
We previously showed that gastrin-releasing peptide receptor (GRPR) in the spinal cord is important for mediating nonhistaminergic itch. Neuromedin B receptor (NMBR), the second member of the mammalian bombesin receptor family, is expressed in a largely nonoverlapping pattern with GRPR in the superficial spinal cord, and its role in itch transmission remains unclear. Here, we report that Nmbr knock-out (KO) mice exhibited normal scratching behavior in response to intradermal injection of pruritogens. However, mice lacking both Nmbr and Grpr (DKO mice) showed significant deficits in histaminergic itch. In contrast, the chloroquine (CQ)-evoked scratching behavior of DKO mice is not further reduced compared with Grpr KO mice. These results suggest that NMBR and GRPR could compensate for the loss of each other to maintain normal histamine-evoked itch, whereas GRPR is exclusively required for CQ-evoked scratching behavior. Interestingly, GRPR activity is enhanced in Nmbr KO mice despite the lack of upregulation of Grpr expression; so is NMBR in Grpr KO mice. We found that NMB acts exclusively through NMBR for itch transmission, whereas GRP can signal through both receptors, albeit to NMBR to a much lesser extent. Although NMBR and NMBR(+) neurons are dispensable for histaminergic itch, GRPR(+) neurons are likely to act downstream of NMBR(+) neurons to integrate NMB-NMBR-encoded histaminergic itch information in normal physiological conditions. Together, we define the respective function of NMBR and GRPR in itch transmission, and reveal an unexpected relationship not only between the two receptors but also between the two populations of interneurons in itch signaling
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