bluuebunny/crossref_metadata_2025_split huggingface dataset:
Covalently Linked Trimer of the AcrB Multidrug Efflux Pump Provides Support for the Functional Rotating Mechanism
Authors: Takatsuka Yumiko , Nikaido Hiroshi 
Published: December 2008

ABSTRACT

Escherichia coli
AcrB is a proton motive force-dependent multidrug efflux transporter that recognizes multiple toxic chemicals having diverse structures. Recent crystallographic studies of the asymmetric trimer of AcrB suggest that each protomer in the trimeric assembly goes through a cycle of conformational changes during drug export (functional rotation hypothesis). In this study, we devised a way to test this hypothesis by creating a giant gene in which three
acrB
sequences were connected together through short linker sequences. The “linked-trimer” AcrB was expressed well in the inner membrane fraction of Δ
acrB
Δ
recA
strains, as a large protein of ∼300 kDa which migrated at the same rate as the wild-type AcrB trimer in native polyacrylamide gel electrophoresis. The strain expressing the linked-trimer AcrB showed resistance to some toxic compounds that was sometimes even higher than that of the cells expressing the monomeric AcrB, indicating that the linked trimer functions well in intact cells. When we inactivated only one of the three protomeric units in the linked trimer, either with mutations in the salt bridge/H-bonding network (proton relay network) in the transmembrane domain or by disulfide cross-linking of the external cleft in the periplasmic domain, the entire trimeric complex was inactivated. However, some residual activity was seen, presumably as a result of random recombination of monomeric fragments (produced by protease cleavage or by transcriptional/translational truncation). These observations provide strong biochemical evidence for the functionally rotating mechanism of AcrB pump action. The linked trimer will be useful for further biochemical studies of mechanisms of transport in the future.
Pseudomonas aeruginosa
PAO1 Pyocin Production Affects Population Dynamics within Mixed-Culture Biofilms
Authors: Waite Richard D. , Curtis Michael A. 
Published: December 2008

ABSTRACT

Transcriptomic and phenotypic studies showed that pyocins are produced in
Pseudomonas aeruginosa
PAO1 aerobic and anaerobic biofilms. Pyocin activity was found to be high in slow-growing anaerobic biofilms but transient in aerobic biofilms. Biofilm coculture of strain PAO1 and a pyocin-sensitive isolate showed that pyocin production had a significant impact on bacterial population dynamics, particularly under anaerobic conditions.
Toxin-Antitoxin Systems in
Escherichia coli
Influence Biofilm Formation through YjgK (TabA) and Fimbriae
Authors: Kim Younghoon , Wang Xiaoxue , Ma Qun , Zhang Xue-Song , Wood Thomas K. 
Published: December 2008

ABSTRACT

The roles of toxin-antitoxin (TA) systems in bacteria have been debated. Here, the role of five TA systems in regard to biofilm development was investigated (listed as toxin/antitoxin: MazF/MazE, RelE/RelB, ChpB, YoeB/YefM, and YafQ/DinJ). Although these multiple TA systems were reported previously to not impact bacterial fitness, we found that deletion of the five TA systems decreased biofilm formation initially (8 h) on three different surfaces and then increased biofilm formation (24 h) by decreasing biofilm dispersal. Whole-transcriptome profiling revealed that the deletion of the five TA systems induced expression of a single gene,
yjgK
, which encodes an uncharacterized protein; quantitative real-time PCR (qRT-PCR) confirmed consistent induction of this gene (at 8, 15, and 24 h). Corroborating the complex phenotype seen upon deleting the TA systems, overexpression of YjgK decreased biofilm formation at 8 h and increased biofilm formation at 24 h; deletion of
yjgK
also affected biofilm formation in the expected manner by increasing biofilm formation after 8 h and decreasing biofilm formation after 24 h. In addition, YjgK significantly reduced biofilm dispersal. Whole-transcriptome profiling revealed YjgK represses fimbria genes at 8 h (corroborated by qRT-PCR and a yeast agglutination assay), which agrees with the decrease in biofilm formation upon deleting the five TA systems at 8 h, as well as that seen upon overexpressing YjgK. Sand column assays confirmed that deleting the five TA systems reduced cell attachment. Furthermore, deletion of each of the five toxins increased biofilm formation at 8 h, and overexpression of the five toxins repressed biofilm formation at 8 h, a result that is opposite that of deleting all five TA systems; this suggests that complex regulation occurs involving the antitoxins. Also, the ability of the global regulator Hha to reduce biofilm formation was dependent on the presence of these TA systems. Hence, we suggest that one role of TA systems is to influence biofilm formation.
Complete Genome Sequence of the Extremophilic
Bacillus cereus
Strain Q1 with Industrial Applications
Authors: Xiong Zhaohui , Jiang Yan , Qi Danhua , Lu Huaibao , Yang Fan , Yang Jian , Chen Lihong , Sun Lilian , Xu Xingye , Xue Ying , Zhu Yafang , Jin Qi 
Published: December 2008

ABSTRACT

Bacillus cereus
strain Q1 was isolated from a deep-subsurface oil reservoir in the Daqing oil field in northeastern China. This strain is able to produce biosurfactants and to survive in extreme environments. Here we report the finished and annotated genome sequence of this organism.
Upregulation of Human T-Cell Leukemia Virus Type 1 Antisense Transcription by the Viral Tax Protein
Authors: Landry Sébastien , Halin Marilène , Vargas Amandine , Lemasson Isabelle , Mesnard Jean-Michel , Barbeau Benoit 
Published: December 2008

ABSTRACT
Several studies have recently demonstrated the existence of human T-cell leukemia virus type 1 (HTLV-1) antisense transcripts, which allow the synthesis of the newly described HBZ protein. Although previous reports have been aimed at understanding the potential role of the HBZ protein in HTLV-1 pathogenesis, little is known as to how this viral gene is regulated. Here, using our K30-3′asLuc reporter construct, we show that the viral Tax protein upregulates antisense transcription through its action on the TRE sequences located in the 3′ long terminal repeat. Generation of stable clones in 293T cells demonstrated that Tax-induced HBZ expression is importantly influenced by the integration site in the host genome. The cellular DNA context could thus affect the level of HBZ mRNA expression in infected cells.
High-Resolution Functional Profiling of a Gammaherpesvirus
RTA
Locus in the Context of the Viral Genome
Authors: Arumugaswami Vaithilingaraja , Sitapara Ronika , Hwang Seungmin , Song Moon Jung , Ho Tuyet Ngoc , Su Nancy Qi , Sue Eric Y. , Kanagavel Vidhya , Xing Fangfang , Zhang Xiaolin , Zhao Minglei , Deng Hongyu , Wu Ting-Ting , Kanagavel Sudhakar , Zhang LuLu , Dandekar Sugandha , Papp Jeanette , Sun Ren 
Published: December 2008

ABSTRACT

Gammaherpesviruses Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus are associated with multiple human cancers. Our goal was to develop a quantitative, high-throughput functional profiling system to identify viral
cis
-elements and protein subdomains critical for virus replication in the context of the herpesvirus genome. In gamma-2 herpesviruses, the transactivating factor RTA is essential for initiation of lytic gene expression and viral reactivation. We used the
RTA
locus as a model to develop the functional profiling approach. The mutant murine gammaherpesvirus 68 viral library, containing 15-bp random insertions in the
RTA
locus, was passaged in murine fibroblast cells for multiple rounds of selection. The effect of each 15-bp insertion was characterized using fluorescent-PCR profiling. We identified 1,229 insertions in the 3,845-bp
RTA
locus, of which 393, 282, and 554 were critically impaired, attenuated, and tolerated, respectively, for viral growth. The functional profiling phenotypes were verified by examining several individual RTA mutant clones for transactivating function of the RTA promoter and transcomplementing function of the RTA-null virus. Thus, the profiling approach enabled us to identify several novel functional domains in the
RTA
locus in the context of the herpesvirus genome. Importantly, our study has demonstrated a novel system to conduct high-density functional genetic mapping. The genome-scale expansion of the genetic profiling approach will expedite the functional genomics research on herpesvirus.
Expression of GATA-6 transcription factor in pleural malignant mesothelioma and metastatic pulmonary adenocarcinoma
Authors: Lindholm P M , Soini Y , Myllärniemi M , Knuutila S , Heikinheimo M , Kinnula V L , Salmenkivi K 
Published: December 2008

Background:Malignant mesothelioma (MM) is a highly aggressive tumour with poor prognosis and limited response to therapy. New markers for the prediction of prognosis in MM and in pulmonary adenocarcinoma of the pleura are valuable. GATA-6 belongs to a six member zinc finger transcription factor family named after their recognition motif W-GATA-R.Aim:To clarify the distribution and possible function of GATA-6 transcription factor in MM and in pleural metastasis of lung adenocarcinomas.Methods:63 pleural MM and 36 pleural metastatic pulmonary adenocarcinomas were studied for GATA-6 expression by immunohistochemistry using tissue microarrays. Expression of GATA-6 was examined in relation to thyroid transcription factor-1 expression, survival, proliferation and apoptosis.Results:Nuclear immunoreactivity for GATA-6 was stronger and more frequent in MM than in metastatic pleural adenocarcinoma. Prognosis was better in patients with GATA-6 expression when compared to those with no GATA-6 expression (p = 0.002); in the subgroup analysis the difference was significant in epithelial and sarcomatous mesothelioma. GATA-6 was not associated with spontaneous proliferation or apoptosis of the tumour cells in situ.Conclusion:Results suggest that GATA-6 plays a role in pleural malignancies, predicting longer survival in subgroups of MM.
Geographic density of landfill sites and risk of congenital anomalies in England
Authors: Elliott P , Richardson S , Abellan J J , Thomson A , de Hoogh C , Jarup L , Briggs D J 
Published: December 2008

Objective:To investigate the risk of congenital anomalies in relation to an index of geographic density of landfill sites across 5×5 km grid squares in England.Methods:2 km zones were constructed in a geographical information system around 8804 landfill sites, including 607 that handled special (hazardous) wastes, and intersected with postcode coordinates of over 10 million births (136 821 with congenital anomalies), 1983–98. A landfill exposure index was calculated to represent the geographic density of landfill sites within 2 km of births for each 5×5 km grid square, calculated separately for landfill sites handling special, and non-special or unknown, waste. For each group of landfills, the index was classified into four categories of intensity, and risks for the second, third and top categories were compared to the bottom category, comprising areas with no such landfill sites within 2 km (index of zero). We used hierarchical logistic regression modelling in a Bayesian framework, with adjustment for potential confounding.Results:For special waste sites, adjusted odds ratios were significant for the third category of the landfill exposure index for all anomalies combined and cardiovascular defects (OR 1.08 (95% credible interval 1.02 to 1.13) and 1.16 (1.00 to 1.33), respectively) and for hypospadias and epispadias for the third and top categories (OR 1.11 (1.02 to 1.21) and 1.12 (1.02 to 1.22), respectively). After adjustment, there were no excess risks in relation to sites handling non-special or unknown waste types.Conclusions:There was a weak spatial association between risk of certain congenital anomalies and geographic density of special (hazardous) waste sites at the level of 5×5 km grid squares. Exposure pathways and mechanisms to help interpret these findings are not well-established.
A retrospective assessment of occupational noise exposures for a longitudinal epidemiological study
Authors: Davies H W , Teschke K , Kennedy S M , Hodgson M R , Demers P A 
Published: December 2008

Objectives:Chronic exposure to high levels of noise may be associated with increased risk of cardiovascular disease. We therefore undertook a quantitative retrospective exposure assessment using predictive statistical modelling to estimate historical exposures to noise among a cohort of 27 499 sawmill workers as part of an investigation of acute myocardial infarction mortality.Methods:Noise exposure data were gathered from research, industry and regulatory sources. An exposure data matrix was defined and exposure level estimated for job title/mill/time period combinations utilising regression analysis to model determinants of noise exposure. Cumulative exposure and duration of exposure metrics were calculated for each subject. These were merged with work history data, and exposure–response associations were tested in subsequent epidemiological studies, reported elsewhere.Results:Over 14 000 noise measurements were obtained from British Columbia sawmills. A subset, comprising 1901 full-shift dosimetry measurements from cohort mills was used in producing a predictive model (R2 = 0.51). The model was then used to estimate noise exposures for 3809 “cells” of an exposure data matrix representing 81 jobs at 14 mills over several decades. Various exposure metrics were then calculated for subjects; mean cumulative exposure was 101 dBA*year. Mean durations of employment in jobs with exposure above thresholds of 85, 90 and 95 dBA, were 9.9, 7.0 and 3.2 years, respectively.Conclusions:The utility of predictive statistical modelling for occupational noise exposure was demonstrated. The model required input data that were relatively easily obtained, even retrospectively. Remaining issues include adequate handling of the use of hearing protectors that likely bias exposure estimation.
Maternal levels of dichlorodiphenyl-dichloroethylene (DDE) may increase weight and body mass index in adult female offspring
Authors: Karmaus W , Osuch J R , Eneli I , Mudd L M , Zhang J , Mikucki D , Haan P , Davis S 
Published: December 2008

Objectives:To investigate the effect of prenatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyl-dichloroethylene (DDE) on weight, height and body mass index (BMI) in adult female offspring of the Michigan fisheater cohort examined between 1973 and 1991.Methods:259 mothers from the Michigan fisheater cohort were studied. Prenatal exposure to PCBs and DDE was estimated by extrapolating maternal measurements to the time that the women gave birth. 213 daughters aged 20–50 years in 2000 were identified and 83% of them participated in at least one of two repeated investigations in 2001/02 (n = 151) and 2006/07 (n = 129). To assess the effect of prenatal PCB and DDE exposure on anthropometric measurements, generalised estimating equations nested for repeated measurements (2001/02 and 2006/07) and for sharing the same mother were used. We controlled for maternal height and BMI and for daughters’ age, birth weight, having been breastfed and number of pregnancies.Results:Maternal height and BMI were significant predictors of the daughters’ height, weight and BMI. Low birth weight (<2500 g) was significantly associated with reduced adult offspring weight and BMI. The weight and BMI of adult offspring were statistically significantly associated with the extrapolated prenatal DDE levels of their mothers. Controlling for confounders and compared to maternal DDE levels of <1.503 μg/l, offspring BMI was increased by 1.65 when prenatal DDE levels were 1.503–2.9 μg/l and by 2.88 if levels were >2.9 μg/l. Prenatal PCB levels showed no effect.Conclusion:Prenatal exposure to the oestrogenic endocrine-disrupting chemical DDE may contribute to the obesity epidemic in women.
Physical workload, low back pain and neck–shoulder pain: a Swedish twin study
Authors: Nyman T , Mulder M , Iliadou A , Svartengren M , Wiktorin C 
Published: December 2008

Objectives:To investigate if high physical workload is associated with low back pain (LBP) and/or neck–shoulder pain (NSP) when taking into account the influence of genetic and shared environmental factors. Further, the study aims to explore the potential influence of genetic and shared environmental factors in the associations between high physical workload and the three disorder subgroups: solely LBP, solely NSP, and concurrent LBP and NSP.Methods:Data on 16 107 monozygotic and dizygotic twins, born during 1959–1985, were obtained from a cross-sectional study, performed in 2005–2006 by the Swedish Twin Registry. Odds ratios (ORs) calculated in cohort analyses and co-twin control analyses were used to assess the associations between high physical workload and LBP and NSP when controlling for genetic and shared environmental factors.Results:In the cohort analysis, the association between high physical workload and the group with any one symptom (LBP and/or NSP) was OR 1.47 (95% CI 1.37 to 1.57). The co-twin control analyses indicated that the association was not confounded by genetic and shared environmental factors with OR 1.34 (95% CI 1.02 to 1.75) for dizygotic twins and OR 1.44 (95% CI 1.06 to 1.95) for monozygotic twins.In the cohort analyses the association with high physical workload was higher for concurrent LBP and NSP (OR 1.80 (95% CI 1.62 to 1.99)) than for solely LBP (OR 1.41 (95% CI 1.27 to 1.57)) and solely NSP (OR 1.31 (95% CI 1.20 to 1.43)). Concurrent LBP and NSP was the only group that showed a stepwise decrease of the point estimates between the cohort analysis and the co-twin control analyses, OR 1.71 (95% CI 1.00 to 2.94) for dizygotic twins, and OR 1.29 (95% CI 0.64 to 2.59) for monozygotic twins indicating confounding by genetic and shared environmental factors.Conclusions:High physical workload was associated with LBP and/or NSP even after adjusting for genetic or shared environmental factors. Only for concurrent LBP and NSP, genetic and shared environmental factors seemed to have an influence on the association with high physical workload.
Exhaled nitric oxide in endotoxin-exposed adults: effect modification by smoking and atopy
Authors: Smit L A M , Heederik D , Doekes G , Wouters I M 
Published: December 2008

Objectives:Occupational exposure to endotoxin is associated with non-allergic asthma and other airway inflammatory reactions. Little is known about the role of mucosal nitric oxide (NO) production in endotoxin-induced airway inflammation. The objective was to explore exposure–response relationships between occupational endotoxin exposure and fractional concentrations of exhaled NO (FENO) and study the role of FENOas an intermediate factor in the relationship between endotoxin exposure and asthma-like symptoms.Methods:FENOwas measured online in 425 farmers and agricultural processing workers. For each participant (cumulative) endotoxin level was modelled on the basis of 249 personal measurements and job history. Atopy was assessed as specific serum IgE to common inhalant allergens, and other health data and personal characteristics by standardised questionnaires.Results:A significant positive exposure–response relationship was found between endotoxin and FENO, but only in non-atopic, non-smoking subjects (p = 0.001). FENOwas significantly associated with current wheeze and other asthma-like symptoms irrespective of atopy and current smoking. Associations between endotoxin exposure and symptoms changed slightly after adjusting for FENO.Conclusions:A positive association was found between occupational endotoxin exposure and exhaled nitric oxide in non-smoking, non-atopic adults. Increased FENOwas associated with asthma-like symptoms, but the role of FENOas an intermediate factor between endotoxin exposure and airway symptoms appears to be limited.
Bayesian modelling of lung cancer risk and bitumen fume exposure adjusted for unmeasured confounding by smoking
Authors: de Vocht F , Kromhout H , Ferro G , Boffetta P , Burstyn I 
Published: December 2008

Objectives:Residual confounding can be present in epidemiological studies because information on confounding factors was not collected. A Bayesian framework, which has the advantage over frequentist methods that the uncertainty in the association between the confounding factor and exposure and disease can be reflected in the credible intervals of the risk parameter, is proposed to assess the magnitude and direction of this bias.Methods:To illustrate this method, bias from smoking as an unmeasured confounder in a cohort study of lung cancer risk in the European asphalt industry was assessed. A Poisson disease model was specified to assess lung cancer risk associated with career average, cumulative and lagged bitumen fume exposure. Prior distributions for the exposure strata, as well as for other covariates, were specified as uninformative normal distributions. The priors on smoking habits were specified as Dirichlet distributions based on smoking prevalence estimates available for a sub-cohort and assumptions about precision of these estimates.Results:Median bias in this example was estimated at 13%, and suggested an attenuating effect on the original exposure–disease associations. Nonetheless, the results still implied an increased lung cancer risk, especially for average exposure.Conclusions:This Bayesian framework provides a method to assess the bias from an unmeasured confounding factor taking into account the uncertainty surrounding the estimate and from random sampling error. Specifically for this example, the bias arising from unmeasured smoking history in this asphalt workers’ cohort is unlikely to explain the increased lung cancer risk associated with average bitumen fume exposure found in the original study.
The Ottoman Execution of Zayn al-Dīn al-'Āmilī
Authors: Stewart Devin 
Published: December 2008

AbstractThis study attempts to sort out the partial and contradictory accounts of the last years and martyrdom of the prominent Twelver Shiite jurist Zayn al-Dīn al-'Āmilī (d. 965/1558), drawing on Shiite biographical works, Zayn al-Dīn's writings and the scholarly paraphernalia attached to them, Safavid chronicles, and a recently published travelogue that includes an eye-witness account of his execution in Istanbul. It argues in particular that the influential account of Zayn al-Dīn's arrest and execution included in al-Hurr al-'Āmilī's biographical work Amal al-āmil is a forgery from the late seventeenth century and should be discarded as evidence for Zayn al-Dīn's biography.
Defining the Enemy: Abū Muhammad al-Maqdisīs Radical Reading of Sūrat al-Mumtahana
Authors: Wagemakers Joas 
Published: December 2008

AbstractThis article examines the interpretation of “the enemies” in Sūrat al-Mumtahana (60) by the Jordanian ideologue Abū Muhammad al-Maqdisī, one of the most influential jihādī-Salafī theorists alive. Al-Maqdisī's reading of the sūra's text and his interpretation of its context turn this part of the Qur'ān, which seems to have been meant to warn the early Medinan Muslims of the dangers of befriending hostile Meccan idolaters, into the basis of a radical ideology. Special attention is paid to the far-reaching consequences of al-Maqdisī's political interpretation of the text, especially when combined with his views on kufr (unbelief) and al-walā' wa-l-barā' (loyalty and disavowal), which he adopts from Wahhābī scholars and bases mostly on this sūra. Al-Maqdisī's particular combination of the text and context of sūra 60 yields a definition of “the enemy” that is rooted in the Qur'ān and Sunna but differs greatly from its traditional interpretations as well as Wahhābī writings by evolving into a radical ideology to overthrow the political rulers of the Muslim world.