The Burkholderia pseudomallei K96243 genome encodes six type VI secretion systems (T6SSs), but little is known about the role of these systems in the biology of B. pseudomallei. In this study, we ...purified recombinant Hcp proteins from each T6SS and tested them as vaccine candidates in the BALB/c mouse model of melioidosis. Recombinant Hcp2 protected 80% of mice against a lethal challenge with K96243, while recombinant Hcp1, Hcp3, and Hcp6 protected 50% of mice against challenge. Hcp6 was the only Hcp constitutively produced by B. pseudomallei in vitro; however, it was not exported to the extracellular milieu. Hcp1, on the other hand, was produced and exported in vitro when the VirAG two-component regulatory system was overexpressed in trans. We also constructed six hcp deletion mutants (Δhcp1 through Δhcp6) and tested them for virulence in the Syrian hamster model of infection. The 50% lethal doses (LD₅₀s) for the Δhcp2 through Δhcp6 mutants were indistinguishable from K96243 (<10 bacteria), but the LD₅₀ for the Δhcp1 mutant was >10³ bacteria. The hcp1 deletion mutant also exhibited a growth defect in RAW 264.7 macrophages and was unable to form multinucleated giant cells in this cell line. Unlike K96243, the Δhcp1 mutant was only weakly cytotoxic to RAW 264.7 macrophages 18 h after infection. The results suggest that the cluster 1 T6SS is essential for virulence and plays an important role in the intracellular lifestyle of B. pseudomallei.
We investigate photoluminescence of nanotube bundles. Their spectra are explained by exciton energy transfer between adjacent tubes, whereby excitation of large gap tubes induces emission from ...smaller gap ones. The consequent relaxation rate is faster than nonradiative recombination, leading to enhanced photoluminescence of acceptor tubes.
Sea-Level Rise by 2100 CHURCH, JOHN A.; CLARK, PETER U.; CAZENAVE, ANNY ...
Science (American Association for the Advancement of Science),
12/2013, Letnik:
342, Številka:
6165
Journal Article
Coexpression patterns of gene expression across many microarray data sets may reveal networks of genes involved in linked processes. To identify factors involved in cellulose biosynthesis, we used a ...regression method to analyze 408 publicly available Affymetrix Arabidopsis microarrays. Expression of genes previously implicated in cellulose synthesis, as well as several uncharacterized genes, was highly coregulated with expression of cellulose synthase (CESA) genes. Four candidate genes, which were coexpressed with CESA genes implicated in secondary cell wall synthesis, were investigated by mutant analysis. Two mutants exhibited irregular xylem phenotypes similar to those observed in mutants with defects in secondary cellulose synthesis and were designated irx8 and irx13. Thus, the general approach developed here is useful for identification of elements of multicomponent processes.
A beam test of GLAST (Gamma-ray Large Area Space Telescope) components was performed at the Stanford Linear Accelerator Center in October, 1997. These beam test components were simple versions of the ...planned flight hardware. Results on the performance of the tracker, calorimeter, and anti-coincidence charged particle veto are presented.
Summary Background In 2011, WHO member states signed up to the 25 × 25 initiative, a plan to cut mortality due to non-communicable diseases by 25% by 2025. However, socioeconomic factors influencing ...non-communicable diseases have not been included in the plan. In this study, we aimed to compare the contribution of socioeconomic status to mortality and years-of-life-lost with that of the 25 × 25 conventional risk factors. Methods We did a multicohort study and meta-analysis with individual-level data from 48 independent prospective cohort studies with information about socioeconomic status, indexed by occupational position, 25 × 25 risk factors (high alcohol intake, physical inactivity, current smoking, hypertension, diabetes, and obesity), and mortality, for a total population of 1 751 479 (54% women) from seven high-income WHO member countries. We estimated the association of socioeconomic status and the 25 × 25 risk factors with all-cause mortality and cause-specific mortality by calculating minimally adjusted and mutually adjusted hazard ratios HR and 95% CIs. We also estimated the population attributable fraction and the years of life lost due to suboptimal risk factors. Findings During 26·6 million person-years at risk (mean follow-up 13·3 years SD 6·4 years), 310 277 participants died. HR for the 25 × 25 risk factors and mortality varied between 1·04 (95% CI 0·98–1·11) for obesity in men and 2 ·17 (2·06–2·29) for current smoking in men. Participants with low socioeconomic status had greater mortality compared with those with high socioeconomic status (HR 1·42, 95% CI 1·38–1·45 for men; 1·34, 1·28–1·39 for women); this association remained significant in mutually adjusted models that included the 25 × 25 factors (HR 1·26, 1·21–1·32, men and women combined). The population attributable fraction was highest for smoking, followed by physical inactivity then s ocioeconomic status. Low socioeconomic status was associated with a 2·1-year reduction in life expectancy between ages 40 and 85 years, the corresponding years-of-life-lost were 0·5 years for high alcohol intake, 0·7 years for obesity, 3·9 years for diabetes, 1·6 years for hypertension, 2·4 years for physical inactivity, and 4·8 years for current smoking. Interpretation Socioeconomic circumstances, in addition to the 25 × 25 factors, should be targeted by local and global health strategies and health risk surveillance to reduce mortality. Funding European Commission, Swiss State Secretariat for Education, Swiss National Science Foundation, the Medical Research Council, NordForsk, Portuguese Foundation for Science and Technology.
Spreading the word through likes on Facebook Swani, Kunal; Milne, George; Brown, Brian P
Journal of research in interactive marketing,
01/2013, Letnik:
7, Številka:
4
Journal Article
Recenzirano
Purpose - This research aims to investigate the message strategies most likely to promote online "word-of-mouth" (WOM) activity for business-to-business (B2B)/business-to-consumer as well as ...product/service Facebook accounts. Design/methodology/approach - Using content analysis and HLM, the authors measure the relationship between three types of message strategies and Facebook message "Likes" by analyzing 1,143 wall post messages of 193 Fortune 500 Facebook accounts. Findings - Research findings suggest that B2B Facebook account posts are more effective if they include corporate brand names and avoid "hard sell" or explicitly commercial statements. Furthermore, results suggest that including emotional sentiments in Facebook posts is a particularly effective social media strategy for B2B and service marketers. Originality/value - This study advances the knowledge of social media and online WOM behavior, as well as B2B and service advertising/communication literature, by relating message content to message popularity. In terms of managerial implications, this research provides explanations and support for the implementation of effective social media message strategies that are likely to promote WOM activity.
Poor adherence to medication regimens and medical record inconsistencies result in incomplete knowledge of medication therapy in polypharmacy patients. By quantitatively identifying medications in ...the blood of patients and reconciling detected medications with the medical record, we have defined the severity of this knowledge gap and created a path toward optimizing medication therapy.
We validated a liquid chromatography-tandem mass spectrometry assay to detect and/or quantify 38 medications across a broad range of chronic diseases to obtain a comprehensive survey of patient adherence, medical record accuracy, and exposure variability in two patient populations. In a retrospectively tested 821-patient cohort representing U.S. adults, we found that 46% of medications assessed were detected in patients as prescribed in the medical record. Of the remaining medications, 23% were detected, but not listed in the medical record while 30% were prescribed to patients, but not detected in blood. To determine how often each detected medication fell within literature-derived reference ranges when taken as prescribed, we prospectively enrolled a cohort of 151 treatment-regimen adherent patients. In this cohort, we found that 53% of medications that were taken as prescribed, as determined using patient self-reporting, were not within the blood reference range. Of the medications not in range, 83% were below and 17% above the lower and upper range limits, respectively. Only 32% of out-of-range medications could be attributed to short oral half-lives, leaving extensive exposure variability to result from patient behavior, undefined drug interactions, genetics, and other characteristics that can affect medication exposure.
This is the first study to assess compliance, medical record accuracy, and exposure as determinants of real-world treatment and response. Variation in medication detection and exposure is greater than previously demonstrated, illustrating the scope of current therapy issues and opening avenues that warrant further investigation to optimize medication therapy.
BACKGROUND: Microplastics are a pervasive contaminant cycling through food webs--leading to concerns regarding exposure and risk to humans. OBJECTIVES: We aimed to quantify and characterize ...anthropogenic particle contamination (including microplastics) in fish caught for human consumption from the Humber Bay region of Lake Ontario. We related quantities of anthropogenic particles to other factors (e.g., fish size) that may help in understanding accumulation of microplastics in fish. METHODS: A total of 45 samples of six fish species collected from Humber Bay in Lake Ontario near Toronto, Ontario, Canada, were examined for anthropogenic particles in their gastrointestinal (GI) tracts and fillets. Using microscopy and spectroscopy, suspected anthropogenic particles were identified and characterized. RESULTS: We observed anthropogenic particles in the GI tracts and fillets of all species. Individual fish had a mean+ or - standard deviation of 138 + or - 231 anthropogenic particles, with a single fish containing up to 1,508 particles. GI tracts had 93 + or - 226 particles/fish (9.8 + or - 32.6 particles/gram), and fillets had 56 + or - 61 particles/fish (0.5 + or - 0.8 particles/gram). Based on a consumption rate of 2 servings/week, the average yearly human exposure through the consumption of these fish fillets would be 12,800 + or - 18,300 particles. DISCUSSION: Our findings suggest that consumption of recreationally caught freshwater fish can be a pathway for human exposure to microplastics. The elevated number of particles observed in fish from Humber Bay highlights the need for large-scale geographic monitoring, especially near sources of microplastics. Currently, it is unclear what the effects of ingesting microplastics are for humans, but given that recreationally caught freshwater fish are one pathway for human exposure, these data can be incorporated into future human health risk assessment frameworks for microplastics.
The 2014 US Surgeon General's report noted research gaps necessary to determine a causal relationship between active cigarette smoking and invasive breast cancer risk, including the role of alcohol ...consumption, timing of exposure, modification by menopausal status and heterogeneity by oestrogen receptor (ER) status.
To address these issues, we pooled data from 14 cohort studies contributing 934 681 participants (36 060 invasive breast cancer cases). Cox proportional hazard regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).
Smoking duration before first birth was positively associated with risk ( P -value for trend = 2 × 10 -7 ) with the highest HR for initiation >10 years before first birth (HR = 1.18, CI 1.12-1.24). Effect modification by current alcohol consumption was evident for the association with smoking duration before first birth ( P -value=2×10 -4 ); compared with never-smoking non-drinkers, initiation >10 years before first birth was associated with risk in every category of alcohol intake, including non-drinkers (HR = 1.15, CI 1.04-1.28) and those who consumed at least three drinks per day (1.85, 1.55-2.21). Associations with smoking before first birth were limited to risk of ER+ breast cancer ( P -value for homogeneity=3×10 -3 ). Other smoking timing and duration characteristics were associated with risk even after controlling for alcohol, but were not associated with risk in non-drinkers. Effect modification by menopause was not evident.
Smoking, particularly if initiated before first birth, was modestly associated with ER+ breast cancer risk that was not confounded by amount of adult alcohol intake. Possible links with breast cancer provide additional motivation for young women to not initiate smoking.
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