bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do occupational exposures to vinyl chloride cause hepatocellular carcinoma and cirrhosis?
Authors: Lotti Marcello 
Published: January 2017

AbstractControversy exists about the association between occupational exposures to vinyl chloride and hepatocellular carcinoma and cirrhosis. Two large multicentre mortality cohort studies, one American and another European, reported higher mortality for primary cancer of liver and biliary tract. However, the American study was not able to rule out misclassification, because based on death certificates and under the heading primary liver cancers, some angiosarcomas, the typical neoplasia associated with vinyl chloride, may have been included. The American study does not report on cirrhosis mortality. The European study also reports higher mortality of primary liver cancer, but contrary to the American study in a further analysis based on 10 verified cases of hepatocellular carcinoma, an exposure‐response trend with duration of employment and with cumulative exposure to vinyl chloride was detected. A smaller cohort belonging to this multicentre cohort confirmed these results. Meta‐analyses based on the two large cohorts concluded for a small excess of primary liver cancer, although misclassification could not be ruled out. Excess risk of cirrhosis was reported in the European cohort, in a subcohort and in a cross‐sectional study. However, a meta‐analysis did not confirm this excess. Several critical appraisals of the literature reached antithetical conclusions about hepatocellular carcinoma, cirrhosis and occupational exposures to vinyl chloride. For both hepatocellular carcinoma and cirrhosis, a study suggests an additive and multiplicative effect of vinyl chloride exposure with viral hepatitis and alcohol consumption respectively. Pathology reports seem to indicate a possible development of hepatocellular carcinoma but not of cirrhosis after high exposures to vinyl chloride.
Progress in the Study of Bioluminescent Earthworms
Authors: Rodionova Natalja S. , Rota Emilia , Tsarkova Aleksandra S. , Petushkov Valentin N. 
Published: January 2017

AbstractEven though bioluminescent oligochaetes rarely catch people's eyes due to their secretive lifestyle, glowing earthworms sighting reports have come from different areas on all continents except Antarctica. A major breakthrough in the research of earthworm bioluminescence occurred in the 1960s with the studies of the North American Diplocardia longa. Comparative studies conducted on 13 earthworm species belonging to six genera showed that N‐isovaleryl‐3‐aminopropanal (Diplocardia luciferin) is the common substrate for bioluminescence in all examined species, while luciferases appeared to be responsible for the color of bioluminescence. The second momentous change in the situation has occurred with the discovery in Siberia (Russia) of two unknown luminous enchytraeids. The two bioluminescent systems belong to different types, have different spectral characteristics and localization, and different temperature and pH optima. They are unique, and this fact is confirmed by the negative results of all possible cross‐reactions. The bioluminescent system of Henlea sp. comprises four essential components: luciferase, luciferin, oxygen and calcium ion. For Friderica heliota, the luminescent reaction requires five components: luciferase, luciferin, ATP, magnesium ion and oxygen. Along with luciferin, more than a dozen analogues were isolated from worm biomass. These novel peptide‐like natural compounds represent an unprecedented chemistry found in terrestrial organisms.
Changes in Time Spent Outdoors During the Daytime in Rural Populations in Four Geographically Distinct Regions in China: A Retrospective Study
Authors: Gao Qian , Wang Fang , Hu Liwen , Yu Jiaming , Liu Rong , Wang Yang , Liu Yang 
Published: January 2017

AbstractChanges in time‐activity patterns may influence personal exposure to various environmental factors and affect individual health. However, few studies have investigated the changes in patterns of time spent outdoors. To investigate the trends in outdoor activity in recent decades in China, a retrospective questionnaire was used to examine the amount and pattern of time spent outdoors during the day by 2076 subjects in four geographically distinct rural regions of China. Rural Chinese people spent less time outdoors than they used to because of the economic development, increase in education and changes in working conditions that occurred over time. Outdoor time was the shortest during the school stage of life (Sanya: 3.24–3.61; Shaoxing: 3.35–3.68; Lhasa: 4.37–4.54; Xiuyan: 2.94–3.26 h per day). Subjects in wealthy regions spent less time outdoors during their working stage of life. In the four regions in this study, the average daily times spent outdoors were 3–13% lower for subjects aged 40–59 years and 20–38% lower for those under 40 years compared to subjects aged 60 years and over. Certain health‐related issues, such as vitamin D deficiency, will become more prominent in China if this trend continues.
Biofilm Composition and Threshold Concentration for Growth of Legionella pneumophila on Surfaces Exposed to Flowing Warm Tap Water without Disinfectant
Authors: van der Kooij Dick , Bakker Geo L. , Italiaander Ronald , Veenendaal Harm R. , Wullings Bart A. 
Published: January 2017

ABSTRACT

Legionella pneumophila
in potable water installations poses a potential health risk, but quantitative information about its replication in biofilms in relation to water quality is scarce. Therefore, biofilm formation on the surfaces of glass and chlorinated polyvinyl chloride (CPVC) in contact with tap water at 34 to 39°C was investigated under controlled hydraulic conditions in a model system inoculated with biofilm-grown
L. pneumophila
. The biofilm on glass (average steady-state concentration, 23 ± 9 pg ATP cm
−2
) exposed to treated aerobic groundwater (0.3 mg C liter
−1
; 1 μg assimilable organic carbon [AOC] liter
−1
) did not support growth of the organism, which also disappeared from the biofilm on CPVC (49 ± 9 pg ATP cm
−2
) after initial growth.
L. pneumophila
attained a level of 4.3 log CFU cm
−2
in the biofilms on glass (1,055 ± 225 pg ATP cm
−2
) and CPVC (2,755 ± 460 pg ATP cm
−2
) exposed to treated anaerobic groundwater (7.9 mg C liter
−1
; 10 μg AOC liter
−1
). An elevated biofilm concentration and growth of
L. pneumophila
were also observed with tap water from the laboratory. The
Betaproteobacteria Piscinibacter
and
Methyloversatilis
and amoeba-resisting
Alphaproteobacteria
predominated in the clones and isolates retrieved from the biofilms. In the biofilms, the
Legionella
colony count correlated significantly with the total cell count (TCC), heterotrophic plate count, ATP concentration, and presence of
Vermamoeba vermiformis
. This amoeba was rarely detected at biofilm concentrations of <100 pg ATP cm
−2
. A threshold concentration of approximately 50 pg ATP cm
−2
(TCC = 1 × 10
6
to 2 × 10
6
cells cm
−2
) was derived for growth of
L. pneumophila
in biofilms.

IMPORTANCE
Legionella pneumophila
is the etiologic agent in more than 10,000 cases of Legionnaires' disease that are reported annually worldwide and in most of the drinking water-associated disease outbreaks reported in the United States. The organism proliferates in biofilms on surfaces exposed to warm water in engineered freshwater installations. An investigation with a test system supplied with different types of warm drinking water without disinfectant under controlled hydraulic conditions showed that treated aerobic groundwater (0.3 mg liter
−1
of organic carbon) induced a low biofilm concentration that supported no or very limited growth of
L. pneumophila
. Elevated biofilm concentrations and
L. pneumophila
colony counts were observed on surfaces exposed to two types of extensively treated groundwater, containing 1.8 and 7.9 mg C liter
−1
and complying with the microbial water quality criteria during distribution. Control measures in warm tap water installations are therefore essential for preventing growth of
L. pneumophila
.
Diverse Bacteria Affiliated with the Genera Microvirga, Phyllobacterium, and Bradyrhizobium Nodulate Lupinus micranthus Growing in Soils of Northern Tunisia
Authors: Msaddak Abdelhakim , Durán David , Rejili Mokhtar , Mars Mohamed , Ruiz-Argüeso Tomás , Imperial Juan , Palacios José , Rey Luis 
Published: January 2017

ABSTRACT

The genetic diversity of bacterial populations nodulating
Lupinus micranthus
in five geographical sites from northern Tunisia was examined. Phylogenetic analyses of 50 isolates based on partial sequences of
recA
and
gyrB
grouped strains into seven clusters, five of which belong to the genus
Bradyrhizobium
(28 isolates), one to
Phyllobacterium
(2 isolates), and one, remarkably, to
Microvirga
(20 isolates). The largest
Bradyrhizobium
cluster (17 isolates) grouped with the
B. lupini
species, and the other five clusters were close to different recently defined
Bradyrhizobium
species. Isolates close to
Microvirga
were obtained from nodules of plants from four of the five sites sampled. We carried out an in-depth phylogenetic study with representatives of the seven clusters using sequences from housekeeping genes (
rrs
,
recA
,
glnII
,
gyrB
, and
dnaK
) and obtained consistent results. A phylogeny based on the sequence of the symbiotic gene
nodC
identified four groups, three formed by
Bradyrhizobium
isolates and one by the
Microvirga
and
Phyllobacterium
isolates. Symbiotic behaviors of the representative strains were tested, and some congruence between symbiovars and symbiotic performance was observed. These data indicate a remarkable diversity of
L. micranthus
root nodule symbionts in northern Tunisia, including strains from the
Bradyrhizobiaceae
,
Methylobacteriaceae
, and
Phyllobacteriaceae
families, in contrast with those of the rhizobial populations nodulating lupines in the Old World, including
L. micranthus
from other Mediterranean areas, which are nodulated mostly by
Bradyrhizobium
strains.

IMPORTANCE
Lupinus micranthus
is a legume broadly distributed in the Mediterranean region and plays an important role in soil fertility and vegetation coverage by fixing nitrogen and solubilizing phosphate in semiarid areas. Direct sowing to extend the distribution of this indigenous legume can contribute to the prevention of soil erosion in pre-Saharan lands of Tunisia. However, rhizobial populations associated with
L. micranthus
are poorly understood. In this context, the diversity of endosymbionts of this legume was investigated. Most
Lupinus
species are nodulated by
Bradyrhizobium
strains. This work showed that about half of the isolates from northern Tunisian soils were in fact
Bradyrhizobium
symbionts, but the other half were found unexpectedly to be bacteria within the genera
Microvirga
and
Phyllobacterium
. These unusual endosymbionts may have a great ecological relevance. Inoculation with the appropriate selected symbiotic bacterial partners will increase
L. micranthus
survival with consequent advantages for the environment in semiarid areas of Tunisia.
Large-Scale Transposition Mutagenesis of Streptomyces coelicolor Identifies Hundreds of Genes Influencing Antibiotic Biosynthesis
Authors: Xu Zhong , Wang Yemin , Chater Keith F. , Ou Hong-Yu , Xu H. Howard , Deng Zixin , Tao Meifeng 
Published: January 2017

ABSTRACT

Gram-positive
Streptomyces
bacteria produce thousands of bioactive secondary metabolites, including antibiotics. To systematically investigate genes affecting secondary metabolism, we developed a hyperactive transposase-based Tn
5
transposition system and employed it to mutagenize the model species
Streptomyces coelicolor
, leading to the identification of 51,443 transposition insertions. These insertions were distributed randomly along the chromosome except for some preferred regions associated with relatively low GC content in the chromosomal core. The base composition of the insertion site and its flanking sequences compiled from the 51,443 insertions implied a 19-bp expanded target site surrounding the insertion site, with a slight nucleic acid base preference in some positions, suggesting a relative randomness of Tn
5
transposition targeting in the high-GC
Streptomyces
genome. From the mutagenesis library, 724 mutants involving 365 genes had altered levels of production of the tripyrrole antibiotic undecylprodigiosin (RED), including 17 genes in the RED biosynthetic gene cluster. Genetic complementation revealed that most of the insertions (more than two-thirds) were responsible for the changed antibiotic production. Genes associated with branched-chain amino acid biosynthesis, DNA metabolism, and protein modification affected RED production, and genes involved in signaling, stress, and transcriptional regulation were overrepresented. Some insertions caused dramatic changes in RED production, identifying future targets for strain improvement.

IMPORTANCE
High-GC Gram-positive streptomycetes and related actinomycetes have provided more than 100 clinical drugs used as antibiotics, immunosuppressants, and antitumor drugs. Their genomes harbor biosynthetic genes for many more unknown compounds with potential as future drugs. Here we developed a useful genome-wide mutagenesis tool based on the transposon Tn
5
for the study of secondary metabolism and its regulation. Using
Streptomyces coelicolor
as a model strain, we found that chromosomal insertion was relatively random, except at some hot spots, though there was evidence of a slightly preferred 19-bp target site. We then used prodiginine production as a model to systematically survey genes affecting antibiotic biosynthesis, providing a global view of antibiotic regulation. The analysis revealed 348 genes that modulate antibiotic production, among which more than half act to reduce production. These might be valuable targets in future investigations of regulatory mechanisms, for strain improvement, and for the activation of silent biosynthetic gene clusters.
Increasing Growth Yield and Decreasing Acetylation in Escherichia coli by Optimizing the Carbon-to-Magnesium Ratio in Peptide-Based Media
Authors: Christensen David G. , Orr James S. , Rao Christopher V. , Wolfe Alan J. 
Published: January 2017

ABSTRACT

Complex media are routinely used to cultivate diverse bacteria. However, this complexity can obscure the factors that govern cell growth. While studying protein acetylation in buffered tryptone broth supplemented with glucose (TB7-glucose), we observed that
Escherichia coli
did not fully consume glucose prior to stationary phase. However, when we supplemented this medium with magnesium, the glucose was completely consumed during exponential growth, with concomitant increases in cell number and biomass but reduced cell size. Similar results were observed with other sugars and other peptide-based media, including lysogeny broth. Magnesium also limited cell growth for
Vibrio fischeri
and
Bacillus subtilis
in TB7-glucose. Finally, magnesium supplementation reduced protein acetylation. Based on these results, we conclude that growth in peptide-based media is magnesium limited. We further conclude that magnesium supplementation can be used to tune protein acetylation without genetic manipulation. These results have the potential to reduce potentially deleterious acetylated isoforms of recombinant proteins without negatively affecting cell growth.

IMPORTANCE
Bacteria are often grown in complex media. These media are thought to provide the nutrients necessary to grow bacteria to high cell densities. In this work, we found that peptide-based media containing a sugar are magnesium limited for bacterial growth. In particular, magnesium supplementation is necessary for the bacteria to use the sugar for cell growth. Interestingly, in the absence of magnesium supplementation, the bacteria still consume the sugar. However, rather than use it for cell growth, the bacteria instead use the sugar to acetylate lysines on proteins. As lysine acetylation may alter the activity of proteins, this work demonstrates how lysine acetylation can be tuned through magnesium supplementation. These findings may be useful for recombinant protein production, when acetylated isoforms are to be avoided. They also demonstrate how to increase bacterial growth in complex media.
YMC-2011, a Temperate Phage of Streptococcus salivarius 57.I
Authors: Chou Wen-Chun , Huang Szu-Chuan , Chiu Cheng-Hsun , Chen Yi-Ywan M. 
Published: January 2017

ABSTRACT

Streptococcus salivarius
is an abundant isolate of the oral cavity. The genome of
S. salivarius
57.I consists of a 2-Mb chromosome and a 40,758-bp circular molecule, designated YMC-2011. Annotation of YMC-2011 revealed 55 open reading frames, most of them associated with phage production, although plaque formation is not observed in
S. salivarius
57.I after lytic induction using mitomycin C. Results from Southern hybridization and quantitative real-time PCR confirmed that YMC-2011 exists extrachromosomally, with an estimated copy number of 3 to 4. Phage particles were isolated from the supernatant of mitomycin C-treated
S. salivarius
57.I cultures, and transmission electron microscopic examination indicated that YMC-2011 belongs to the
Siphoviridae
family. Phylogenetic analysis suggests that phage YMC-2011 and the
cos
-type phages of
Streptococcus thermophilus
originated from a common ancestor. An extended −10 element (p

L

) and a σ
70
-like promoter (p

R

) were mapped 5′ to Ssal_phage00013 (encoding a CI-like repressor) and Ssal_phage00014 (encoding a hypothetical protein), respectively, using 5′ rapid amplification of cDNA ends, indicating that YMC-2011 transcribes at least two mRNAs in opposite orientations. Studies using promoter-chloramphenicol acetyltransferase reporter gene fusions revealed that p

R

, but not p

L

, was sensitive to mitomycin C induction, suggesting that the switch from lysogenic growth to lytic growth was controlled mainly by the activity of these two promoters. In conclusion, a lysogenic state is maintained in
S. salivarius
57.I, presumably by the repression of genes encoding proteins for lytic growth.

IMPORTANCE
The movement of mobile genetic elements such as bacteriophages and the establishment of lysogens may have profound effects on the balance of microbial ecology where lysogenic bacteria reside. The discovery of phage YMC-2011 from
Streptococcus salivarius
57.I suggests that YMC-2011 and
Streptococcus thermophilus
-infecting phages share an ancestor. Although
S. salivarius
and
S. thermophilus
are close phylogenetically,
S. salivarius
is a natural inhabitant of the human mouth, whereas
S. thermophilus
is commonly found in the mammary mucosa of bovine species. Thus, the identification of YMC-2011 suggests that horizontal gene transfer via phage infection could take place between species from different ecological niches.
Open-source mobile digital platform for clinical trial data collection in low-resource settings
Authors: van Dam Joris , Omondi Onyango Kevin , Midamba Brian , Groosman Nele , Hooper Norman , Spector Jonathan , Pillai Goonaseelan (Colin) , Ogutu Bernhards 
Published: January 2017

BackgroundGovernments, universities and pan-African research networks are building durable infrastructure and capabilities for biomedical research in Africa. This offers the opportunity to adopt from the outset innovative approaches and technologies that would be challenging to retrofit into fully established research infrastructures such as those regularly found in high-income countries. In this context we piloted the use of a novel mobile digital health platform, designed specifically for low-resource environments, to support high-quality data collection in a clinical research study.ObjectiveOur primary aim was to assess the feasibility of a using a mobile digital platform for clinical trial data collection in a low-resource setting. Secondarily, we sought to explore the potential benefits of such an approach.MethodsThe investigative site was a research institute in Nairobi, Kenya. We integrated an open-source platform for mobile data collection commonly used in the developing world with an open-source, standard platform for electronic data capture in clinical trials. The integration was developed using common data standards (Clinical Data Interchange Standards Consortium (CDISC) Operational Data Model), maximising the potential to extend the approach to other platforms. The system was deployed in a pharmacokinetic study involving healthy human volunteers.ResultsThe electronic data collection platform successfully supported conduct of the study. Multidisciplinary users reported high levels of satisfaction with the mobile application and highlighted substantial advantages when compared with traditional paper record systems. The new system also demonstrated a potential for expediting data quality review.Discussion and ConclusionsThis pilot study demonstrated the feasibility of using a mobile digital platform for clinical research data collection in low-resource settings. Sustainable scientific capabilities and infrastructure are essential to attract and support clinical research studies. Since many research structures in Africa are being developed anew, stakeholders should consider implementing innovative technologies and approaches.
Basic life support education in secondary schools: a cross-sectional survey in London, UK
Authors: Salciccioli Justin D , Marshall Dominic C , Sykes Mark , Wood Alexander D , Joppa Stephanie A , Sinha Madhurima , Lim P Boon 
Published: January 2017

ObjectivesBasic life support (BLS) training in schools is associated with improved outcomes from cardiac arrest. International consensus statements have recommended universal BLS training for school-aged children. The current practice of BLS training in London schools is unknown. The aim of this study was to assess current practices of BLS training in London secondary schools.Setting, population and outcomesA prospective audit of BLS training in London secondary schools was conducted. Schools were contacted by email, and a subsequent telephone interview was conducted with staff familiar with local training practices. Response data were anonymised and captured electronically. Universal training was defined as any programme which delivers BLS training to all students in the school. Descriptive statistics were used to summarise the results.ResultsA total of 65 schools completed the survey covering an estimated student population of 65 396 across 19 of 32 London boroughs. There were 5 (8%) schools that provide universal training programmes for students and an additional 31 (48%) offering training as part of an extracurricular programme or chosen module. An automated external defibrillator (AED) was available in 18 (28%) schools, unavailable in 40 (61%) and 7 (11%) reported their AED provision as unknown. The most common reasons for not having a universal BLS training programme are the requirement for additional class time (28%) and that funding is unavailable for such a programme (28%). There were 5 students who died from sudden cardiac arrest over the period of the past 10 years.ConclusionsBLS training rates in London secondary schools are low, and the majority of schools do not have an AED available in case of emergency. These data highlight an opportunity to improve BLS training and AEDs provision. Future studies should assess programmes which are cost-effective and do not require significant amounts of additional class time.