bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for Nitrogen Fixation by “
Dehalococcoides ethenogenes
” Strain 195
Authors: Lee Patrick K. H. , He Jianzhong , Zinder Stephen H. , Alvarez-Cohen Lisa
Published: October 2009

Genome annotation of the chlorinated ethene-respiring “
Dehalococcoides ethenogenes
” strain 195 indicated the presence of a complete nitrogenase operon. Here, results from long-term growth experiments, gene expression, and
15
N
2
-isotope measurements confirm that strain 195 is capable of fixing atmospheric dinitrogen when a defined fixed-nitrogen source such as ammonium is unavailable.
Detection and Quantification ofDehalogenimonasand “Dehalococcoides” Populations via PCR-Based Protocols Targeting 16S rRNA Genes
Authors: Yan Jun , Rash Brian A. , Rainey Fred A. , Moe William M.
Published: October 2009

Members of the haloalkane dechlorinating genusDehalogenimonasare distantly related to “Dehalococcoides” but share high homology in some variable regions of their 16S rRNA gene sequences. In this study, primers and PCR protocols intended to uniquely targetDehalococcoideswere reevaluated, and primers and PCR protocols intended to uniquely targetDehalogenimonaswere developed and tested. Use of the genus-specific primers revealed the presence of both bacterial groups in groundwater at a Louisiana Superfund site.
Structure and Function of Glycosylated Tandem Repeats from Candida albicans Als Adhesins
Authors: Frank Aaron T. , Ramsook Caleen B. , Otoo Henry N. , Tan Cho , Soybelman Gregory , Rauceo Jason M. , Gaur Nand K. , Klotz Stephen A. , Lipke Peter N.
Published: October 2009

Tandem repeat (TR) regions are common in yeast adhesins, but their structures are unknown, and their activities are poorly understood. TR regions in
Candida albicans
Als proteins are conserved glycosylated 36-residue sequences with cell-cell aggregation activity (J. M. Rauceo, R. De Armond, H. Otoo, P. C. Kahn, S. A. Klotz, N. K. Gaur, and P. N. Lipke, Eukaryot. Cell 5:1664–1673, 2006).
Ab initio
modeling with either Rosetta or LINUS generated consistent structures of three-stranded antiparallel β-sheet domains, whereas randomly shuffled sequences with the same composition generated various structures with consistently higher energies. O- and N-glycosylation patterns showed that each TR domain had exposed hydrophobic surfaces surrounded by glycosylation sites. These structures are consistent with domain dimensions and stability measurements by atomic force microscopy (D. Alsteen, V. Dupres, S. A. Klotz, N. K. Gaur, P. N. Lipke, and Y. F. Dufrene, ACS Nano
3:
1677–1682, 2009) and with circular dichroism determination of secondary structure and thermal stability. Functional assays showed that the hydrophobic surfaces of TR domains supported binding to polystyrene surfaces and other TR domains, leading to nonsaturable homophilic binding. The domain structures are like “classic” subunit interaction surfaces and can explain previously observed patterns of promiscuous interactions between TR domains in any Als proteins or between TR domains and surfaces of other proteins. Together, the modeling techniques and the supporting data lead to an approach that relates structure and function in many kinds of repeat domains in fungal adhesins.
Regulatory Diversity ofTUP1inCryptococcus neoformans
Authors: Lee Hyeseung , Chang Yun C. , Varma Ashok , Kwon-Chung Kyung J.
Published: October 2009

Cryptococcus neoformansserotype A strains, the major cause of cryptococcosis, are distributed worldwide, while serotype D strains are more concentrated in Central Europe. We have previously shown that deletion of the global regulatorTUP1in serotype D isolates results in a novel peptide-mediated, density-dependent growth phenotype that mimics quorum sensing and is not known to exist in other fungi. Unlike fortup1Δ strains of serotype D, the density-dependent growth phenotype was found to be absent intup1Δ strains of serotype A which had been derived from several different genetic clusters. The serotype A H99tup1Δ strain showed less retardation in the growth rate thantup1Δ strains of serotype D, but the mating efficiency was found to be similar in both serotypes. Deletion ofTUP1in the H99 strain resulted in significantly enhanced capsule production and defective melanin formation and also revealed a unique regulatory role of theTUP1gene in maintaining iron/copper homeostasis. Differential expression of various genes involved in capsule formation and iron/copper homeostasis was observed between the wild-type andtup1Δ H99 strains. Furthermore, the H99tup1Δ strain displayed pleiotropic effects which included sensitivity to sodium dodecyl sulfate, susceptibility to fluconazole, and attenuated virulence. These results demonstrate that the global regulatorTUP1has pathobiological significance and plays both conserved and distinct roles in serotype A and D strains ofC. neoformans.
Growth Phase and (p)ppGpp Control of IraD, a Regulator of RpoS Stability, in
Escherichia coli
Authors: Merrikh Houra , Ferrazzoli Alexander E. , Lovett Susan T.
Published: October 2009

The antiadaptor protein IraD inhibits the proteolysis of the alternative sigma factor, RpoS, which promotes the synthesis of >100 genes during the general stress response and during stationary phase. Our previous results showed that IraD determines RpoS steady-state levels during exponential growth and mediates its stabilization after DNA damage. In this study, we show by promoter fusions that
iraD
was upregulated during the transition from exponential growth to stationary phase. The levels of RpoS likewise rose during this transition in a partially IraD-dependent manner. The expression of
iraD
was under the control of ppGpp. The expression of
iraD
required RelA and SpoT (p)ppGpp synthetase activities and was dramatically induced by a “stringent” allele of RNA polymerase, culminating in elevated levels of RpoS. Surprisingly, DksA, normally required for transcriptional effects of the stringent response, repressed
iraD
expression, suggesting that DksA can exert regulatory effects independent of and opposing those of (p)ppGpp. Northern blot analysis and 5′ rapid amplification of cDNA ends revealed two transcripts for
iraD
in wild-type strains; the smaller was regulated positively by RelA during growth; the larger transcript was induced specifically upon transition to stationary phase and was RelA SpoT dependent. A reporter fusion to the distal promoter indicated that it accounts for growth-phase regulation and DNA damage inducibility. DNA damage inducibility occurred in strains unable to synthesize (p)ppGpp, indicating an additional mode of regulation. Our results suggest that the induction of RpoS during transition to stationary phase and by (p)ppGpp occurs at least partially through IraD.
Structural Plasticity and Distinct Drug-Binding Modes of LfrR, a Mycobacterial Efflux Pump Regulator
Authors: Bellinzoni Marco , Buroni Silvia , Schaeffer Francis , Riccardi Giovanna , De Rossi Edda , Alzari Pedro M.
Published: October 2009

The TetR-like transcriptional repressor LfrR controls the expression of the gene encoding the
Mycobacterium smegmatis
efflux pump LfrA, which actively extrudes fluoroquinolones, cationic dyes, and anthracyclines from the cell and promotes intrinsic antibiotic resistance. The crystal structure of the apoprotein form of the repressor reveals a structurally asymmetric homodimer exhibiting local unfolding and a blocked drug-binding site, emphasizing the significant conformational plasticity of the protein necessary for DNA and multidrug recognition. Crystallographic and calorimetric studies of LfrR-drug complexes further confirm the intrinsic flexibility of the homodimer, which provides a dynamic mechanism to broaden multidrug binding specificity and may be a general property of transcriptional repressors regulating microbial efflux pump expression.
Mycobacterium tuberculosis
PhoP Recognizes Two Adjacent Direct-Repeat Sequences To Form Head-to-Head Dimers
Authors: Gupta Sankalp , Pathak Anuj , Sinha Akesh , Sarkar Dibyendu
Published: October 2009

Mycobacterium tuberculosis
PhoP of the PhoP-PhoR two-component signaling system orchestrates a complex transcription program and is essential for the growth and virulence of the tubercle bacillus. PhoP comprises a phosphorylation domain at the amino-terminal half and a DNA-binding domain in the carboxy-terminal half of the protein. We show here that the protein recognizes a 23-bp sequence of the
phoP
upstream region comprising two adjacent direct repeat motifs believed to promote transcription regulation. DNA binding, which involves the recruitment of two monomeric PhoP molecules, was dependent on conserved adenines of the repeat sequences and the orientation of the repeat motifs relative to each other. Although response regulators such as PhoB and FixJ dimerize upon phosphorylation, we demonstrate here that PhoP dimerization can also be stimulated by DNA binding. Using the established asymmetric tandem binding model by members of the OmpR/PhoB protein family as a guide, we set out to examine intermolecular interactions between PhoP dimers by protein cross-linking. Our results are consistent with a model in which two PhoP protomers bind the duplex DNA with a symmetric head-to-head orientation to project their N termini toward one another, arguing against previously proposed head-to-tail tandem dimer formation for members of the OmpR/PhoB protein subfamily.
Deletion of Citrate Synthase Restores Growth of
Sinorhizobium meliloti
1021 Aconitase Mutants
Authors: Koziol Uriel , Hannibal Luciana , Rodríguez María Cecilia , Fabiano Elena , Kahn Michael L. , Noya Francisco
Published: October 2009

The symbiotic nitrogen-fixing bacterium
Sinorhizobium meliloti
1021 encodes only one predicted aconitase (AcnA) in its genome. AcnA has a significant degree of similarity with other bacterial aconitases that behave as dual proteins: enzymes and posttranscriptional regulators of gene expression. Similar to the case with these bacterial aconitases, AcnA activity was reversibly labile and was regained upon reconstitution with reduced iron. The aconitase promoter was active in root nodules.
acnA
mutants grew very poorly, had secondary mutations, and were quickly outgrown by pseudorevertants. The
acnA
gene was stably interrupted in a citrate synthase (
gltA
) null background, indicating that the intracellular accumulation of citrate may be deleterious for survival of strain 1021. No aconitase activity was detected in this mutant, suggesting that the
acnA
gene encodes the only functional aconitase of strain 1021. To uncover a function of AcnA beyond its catalytic role in the tricarboxylic acid cycle pathway, the
gltA acnA
double mutant was compared with the
gltA
single mutant for differences in motility, resistance to oxidative stress, nodulation, and growth on different substrates. However, no differences in any of these characteristics were found.
A Comprehensive Analysis of the Peroxiredoxin Reduction System in the Cyanobacterium
Synechocystis
sp. Strain PCC 6803 Reveals that All Five Peroxiredoxins Are Thioredoxin Dependent
Authors: Pérez-Pérez María Esther , Mata-Cabana Alejandro , Sánchez-Riego Ana María , Lindahl Marika , Florencio Francisco J.
Published: October 2009

Cyanobacteria perform oxygenic photosynthesis, which gives rise to the continuous production of reactive oxygen species, such as superoxide anion radicals and hydrogen peroxide, particularly under unfavorable growth conditions. Peroxiredoxins, which are present in both chloroplasts and cyanobacteria, constitute a class of thiol-dependent peroxidases capable of reducing hydrogen peroxide as well as alkyl hydroperoxides. Chloroplast peroxiredoxins have been studied extensively and have been found to use a variety of endogenous electron donors, such as thioredoxins, glutaredoxins, or cyclophilin, to sustain their activities. To date, however, the endogenous reduction systems for cyanobacterial peroxiredoxins have not been systematically studied. We have expressed and purified all five
Synechocystis
sp. strain PCC 6803 peroxiredoxins, which belong to the classes 1-Cys Prx, 2-Cys Prx, type II Prx (PrxII), and Prx Q, and we have examined their capacities to interact with and receive electrons from the
m
-,
x
-, and
y
-type thioredoxins from the same organism, which are called TrxA, TrxB, and TrxQ, respectively. Assays for peroxidase activity demonstrated that all five enzymes could use thioredoxins as electron donors, whereas glutathione and
Synechocystis
sp. strain PCC 6803 glutaredoxins were inefficient. The highest catalytic efficiency was obtained for the couple consisting of PrxII and TrxQ thioredoxin. Studies of transcript levels for the peroxiredoxins and thioredoxins under different stress conditions highlighted the similarity between the PrxII and TrxQ thioredoxin expression patterns.
FadD from
Pseudomonas putida
CA-3 Is a True Long-Chain Fatty Acyl Coenzyme A Synthetase That Activates Phenylalkanoic and Alkanoic Acids
Authors: Hume Aisling R. , Nikodinovic-Runic Jasmina , O'Connor Kevin E.
Published: October 2009

A fatty acyl coenzyme A synthetase (FadD) from
Pseudomonas putida
CA-3 is capable of activating a wide range of phenylalkanoic and alkanoic acids. It exhibits the highest rates of reaction and catalytic efficiency with long-chain aromatic and aliphatic substrates. FadD exhibits higher
k
cat
and

K
m

values for aromatic substrates than for the aliphatic equivalents (e.g., 15-phenylpentadecanoic acid versus pentadecanoic acid). FadD is inhibited noncompetitively by both acrylic acid and 2-bromooctanoic acid. The deletion of the
fadD
gene from
P. putida
CA-3 resulted in no detectable growth or polyhydroxyalkanoate (PHA) accumulation with 10-phenyldecanoic acid, decanoic acid, and longer-chain substrates. The results suggest that FadD is solely responsible for the activation of long-chain phenylalkanoic and alkanoic acids. While the CA-3Δ
fadD
mutant could grow on medium-chain substrates, a decrease in growth yield and PHA accumulation was observed. The PHA accumulated by CA-3Δ
fadD
contained a greater proportion of short-chain monomers than did wild-type PHA. Growth of CA-3Δ
fadD
was unaffected, but PHA accumulation decreased modestly with shorter-chain substrates. The complemented mutant regained 70% to 90% of the growth and PHA-accumulating ability of the wild-type strain depending on the substrate. The expression of an extra copy of
fadD
in
P. putida
CA-3 resulted in increased levels of PHA accumulation (up to 1.6-fold) and an increase in the incorporation of longer-monomer units into the PHA polymer.
Tn
917
Targets the Region Where DNA Replication Terminates in
Bacillus subtilis
, Highlighting a Difference in Chromosome Processing in the
Firmicutes
Authors: Shi Qiaojuan , Huguet-Tapia Jose C. , Peters Joseph E.
Published: October 2009

The bacterial transposon Tn
917
inserts preferentially in the terminus region of some members of the
Firmicutes
. To determine what molecular process was being targeted by the element, we analyzed Tn
917
target site selection in
Bacillus subtilis
. We find that Tn
917
insertions accumulate around the central terminators,
terI
and
terII
, in wild-type cells with or without the SPβ lysogen. Highly focused targeting around
terI
and
terII
requires the
trans
-acting termination protein RTP, but it is unaffected in strains compromised in dimer resolution or chromosome translocation. This work indicates that Tn
917
is sensitive to differences in DNA replication termination between the
Firmicutes
.
Elucidation of the Mechanism by Which Catecholamine Stress Hormones Liberate Iron from the Innate Immune Defense Proteins Transferrin and Lactoferrin
Authors: Sandrini Sara M. , Shergill Raminder , Woodward Jonathan , Muralikuttan Remya , Haigh Richard D. , Lyte Mark , Freestone Primrose P.
Published: October 2009

The ability of catecholamine stress hormones and inotropes to stimulate the growth of infectious bacteria is now well established. A major element of the growth induction process has been shown to involve the catecholamines binding to the high-affinity ferric-iron-binding proteins transferrin (Tf) and lactoferrin, which then enables bacterial acquisition of normally inaccessible sequestered host iron. The nature of the mechanism(s) by which the stress hormones perturb iron binding of these key innate immune defense proteins has not been fully elucidated. The present study employed electron paramagnetic resonance spectroscopy and chemical iron-binding analyses to demonstrate that catecholamine stress hormones form direct complexes with the ferric iron within transferrin and lactoferrin. Moreover, these complexes were shown to result in the reduction of Fe(III) to Fe(II) and the loss of protein-complexed iron. The use of bacterial ferric iron uptake mutants further showed that both the Fe(II) and Fe(III) released from the Tf could be directly used as bacterial nutrient sources. We also analyzed the transferrin-catecholamine interactions in human serum and found that therapeutically relevant concentrations of stress hormones and inotropes could directly affect the iron binding of serum-transferrin so that the normally highly bacteriostatic tissue fluid became significantly more supportive of the growth of bacteria. The relevance of these catecholamine-transferrin/lactoferrin interactions to the infectious disease process is considered.
Functional and Biochemical Analysis of theChlamydia trachomatisLigase MurE
Authors: Patin Delphine , Bostock Julieanne , Blanot Didier , Mengin-Lecreulx Dominique , Chopra Ian
Published: October 2009

Chlamydiae are unusual obligately intracellular bacteria that do not synthesize detectable peptidoglycan. However, they possess genes that appear to encode products with peptidoglycan biosynthetic activity. Bioinformatic analysis predicts that chlamydial MurE possesses UDP-MurNAc-l-Ala-d-Glu:meso-diaminopimelic acid (UDP-MurNAc-l-Ala-d-Glu:meso-A2pm) ligase activity. Nevertheless, there are no experimental data to confirm this hypothesis. In this paper we demonstrate that themurEgene fromChlamydia trachomatisis capable of complementing a conditionalEscherichia colimutant impaired in UDP-MurNAc-l-Ala-d-Glu:meso-A2pm ligase activity. Recombinant MurE fromC. trachomatis(MurECt) was overproduced in and purified fromE. coliin order to investigate its kinetic parameters in vitro. By use of UDP-MurNAc-l-Ala-d-Glu as the nucleotide substrate, MurECtdemonstrated ATP-dependentmeso-A2pm ligase activity with pH and magnesium ion optima of 8.6 and 30 mM, respectively. Other amino acids (meso-lanthionine, thellandddisomers of A2pm,d-lysine) were also recognized by MurECt.However, the activities for these amino acid substrates were weaker than that formeso-A2pm. The specificity of MurECtfor three possibleC. trachomatispeptidoglycan nucleotide substrates was also determined in order to deduce which amino acid might be present at the first position of the UDP-MurNAc-pentapeptide. Relativekcat/Kmratios for UDP-MurNAc-l-Ala-d-Glu, UDP-MurNAc-l-Ser-d-Glu, and UDP-MurNAc-Gly-d-Glu were 100, 115, and 27, respectively. Our results are consistent with the synthesis in chlamydiae of a UDP-MurNAc-pentapeptide in which the third amino acid ismeso-A2pm. However, due to the lack of specificity of MurECtfor nucleotide substrates in vitro, it is not obvious which amino acid is present at the first position of the pentapeptide.
Pathway Evolution by Horizontal Transfer and Positive Selection Is Accommodated by Relaxed Negative Selection upon Upstream Pathway Genes in Purple Bacterial Carotenoid Biosynthesis
Authors: Klassen Jonathan L.
Published: October 2009

Horizontal gene transfer and selection are major forces driving microbial evolution. However, interactions between them are rarely studied. Phylogenetic analyses of purple bacterial carotenoid biosynthesis genes suggest two lineages: one producing spheroidenone and the other producing spirilloxanthin. Of the latter lineage,
Rubrivivax gelatinosus
S1 and
Hoeflea phototrophica
DFL-43 also or instead produce spheroidenone. Evolution of the spheroidenone pathway from that producing spirilloxanthin theoretically requires changes in the substrate specificity of upstream pathway enzymes and acquisition of a terminal ketolase (CrtA). In
R. gelatinosus
and likely also in
H. phototrophica
, CrtA was acquired from the
Bacteroidetes
, in which it functions as a hydroxylase. Estimation of nonsynonymous and synonymous mutations using several pairwise methods indicated positive selection upon both genes, consistent with their functional changes from hydroxylases to ketolases. Relaxed negative selection upon all other carotenoid biosynthetic genes in these organisms was also apparent, likely facilitating changes in their substrate specificities. Furthermore, all genes responsible for terminal carotenoid biosynthetic pathway steps were under reduced negative selection compared to those known to govern biosynthetic pathway specificity. Horizontal transfer of
crtA
into
R. gelatinosus
and
H. phototrophica
has therefore likely been promoted by (i) the apparent selective advantage of spheroidenone production relative to spirilloxanthin production, (ii) reduced negative selection upon other carotenoid biosynthetic genes, facilitating changes in their substrate specificities, and (iii) preexisting low enzyme substrate specificities due to relaxed negative selection. These results highlight the importance and complexity of selection acting upon both a horizontally transferred gene and the biochemical network into which it is integrating.
A Typhus Group-Specific Protease Defies Reductive Evolution in Rickettsiae
Authors: Ammerman Nicole C. , Gillespie Joseph J. , Neuwald Andrew F. , Sobral Bruno W. , Azad Abdu F.
Published: October 2009

Phylogenomics reveals extreme gene loss in typhus group (TG) rickettsiae relative to the levels for other rickettsial lineages. We report here a curious protease-encoding gene (
ppcE
) that is conserved only in TG rickettsiae. As a possible determinant of host pathogenicity,
ppcE
warrants consideration in the development of therapeutics against epidemic and murine typhus.
AlipA(yutB) Mutant, Encoding Lipoic Acid Synthase, Provides Insight into the Interplay between Branched-Chain and Unsaturated Fatty Acid Biosynthesis inBacillus subtilis
Authors: Martin Natalia , Lombardía Esteban , Altabe Silvia G. , de Mendoza Diego , Mansilla María C.
Published: October 2009

Lipoic acid is an essential cofactor required for the function of key metabolic pathways in most organisms. We report the characterization of aBacillus subtilismutant obtained by disruption of thelipA(yutB) gene, which encodes lipoyl synthase (LipA), the enzyme that catalyzes the final step in the de novo biosynthesis of this cofactor. The function oflipAwas inferred from the results of genetic and physiological experiments, and this study investigated its role inB. subtilisfatty acid metabolism. Interrupting lipoate-dependent reactions strongly inhibits growth in minimal medium, impairing the generation of branched-chain fatty acids and leading to accumulation of copious amounts of straight-chain saturated fatty acids inB. subtilismembranes. Although depletion of LipA induces the expression of the Δ5 desaturase, controlled by a two-component system that senses changes in membrane properties, the synthesis of unsaturated fatty acids is insufficient to support growth in the absence of precursors for branched-chain fatty acids. However, unsaturated fatty acids generated by deregulated overexpression of the Δ5 desaturase functionally replaces lipoic acid-dependent synthesis of branched-chain fatty acids. Furthermore, we show that the cold-sensitive phenotype of aB. subtilisstrain deficient in Δ5 desaturase is suppressed by isoleucine only if LipA is present.
Draft Genome Sequences of
Yersinia pestis
Isolates from Natural Foci of Endemic Plague in China
Authors: Eppinger Mark , Guo Zhaobiao , Sebastian Yinong , Song Yajun , Lindler Luther E. , Yang Ruifu , Ravel Jacques
Published: October 2009

To gain insights into the evolutionary origin, emergence, and pathogenicity of the etiologic agent of plague, we have sequenced the genomes of four
Yersinia pestis
strains isolated from the zoonotic rodent reservoir in foci of endemic plague in China. These resources enable in-depth studies of
Y. pestis
sequence variations and detailed whole-genome comparisons of very closely related genomes from the supposed site of the origin and the emergence of global pandemics of plague.
Complete Genome Sequence of the Probiotic
Lactobacillus rhamnosus
ATCC 53103
Authors: Morita Hidetoshi , Toh Hidehiro , Oshima Kenshiro , Murakami Masaru , Taylor Todd D. , Igimi Shizunobu , Hattori Masahira
Published: October 2009

Lactobacillus rhamnosus
is a facultatively heterofermentative lactic acid bacterium and is frequently isolated from human gastrointestinal mucosa of healthy individuals.
L. rhamnosus
ATCC 53103, isolated from a healthy human intestinal flora, is one of the most widely used and well-documented probiotics. Here, we report the finished and annotated genome sequence of this organism.
Dengue fever and El Niño/Southern Oscillation in Queensland, Australia: a time series predictive model
Authors: Hu Wenbiao , Clements Archie , Williams Gail , Tong Shilu
Published: October 2009

Background

It remains unclear over whether it is possible to develop an epidemic forecasting model for transmission of dengue fever in Queensland, Australia.

Objectives

To examine the potential impact of El Niño/Southern Oscillation on the transmission of dengue fever in Queensland, Australia and explore the possibility of developing a forecast model of dengue fever.

Methods

Data on the Southern Oscillation Index (SOI), an indicator of El Niño/Southern Oscillation activity, were obtained from the Australian Bureau of Meteorology. Numbers of dengue fever cases notified and the numbers of postcode areas with dengue fever cases between January 1993 and December 2005 were obtained from the Queensland Health and relevant population data were obtained from the Australia Bureau of Statistics. A multivariate Seasonal Auto-regressive Integrated Moving Average model was developed and validated by dividing the data file into two datasets: the data from January 1993 to December 2003 were used to construct a model and those from January 2004 to December 2005 were used to validate it.

Results

A decrease in the average SOI (ie, warmer conditions) during the preceding 3–12 months was significantly associated with an increase in the monthly numbers of postcode areas with dengue fever cases (β=−0.038; p = 0.019). Predicted values from the Seasonal Auto-regressive Integrated Moving Average model were consistent with the observed values in the validation dataset (root-mean-square percentage error: 1.93%).

Conclusions

Climate variability is directly and/or indirectly associated with dengue transmission and the development of an SOI-based epidemic forecasting system is possible for dengue fever in Queensland, Australia.
Ambient air pollution and risk of congenital anomalies in England, 1991–1999
Authors: Dolk H , Armstrong B , Lachowycz K , Vrijheid M , Rankin J , Abramsky L , Boyd P A , Wellesley D
Published: October 2009

Objectives

To investigate whether there is an association between risk of congenital anomaly and annual ward level exposure to air pollution in England during the 1990s.

Methods

A geographical study was conducted across four regions of England using population-based congenital anomaly registers, 1991–1999. Exposure was measured as 1996 annual mean background sulphur dioxide (SO2), nitrogen dioxide (NO2) and particulate matter (PM10) concentrations at census ward level (n=1474). Poisson regression, controlling for maternal age, area socioeconomic deprivation and hospital catchment area, was used to estimate relative risk for an increase in pollution from the 10th to the 90th centile.

Results

For non-chromosomal anomalies combined, relative risks were 0.99 (95% CI 0.93 to 1.05) for SO2, 0.97 (95% CI 0.84 to 1.11) for NO2and 0.89 (95% CI 0.75 to 1.07) for PM10. For chromosomal anomalies, relative risks were 1.06 (95% CI 0.98 to 1.15) for SO2, 1.11 (95% CI 0.95 to 1.30) for NO2and 1.18 (95% CI 0.97 to 1.42) for PM10. Raised risks were found for tetralogy of Fallot and SO2(RR=1.38, 95% CI 1.07 to 1.79), NO2(RR=1.44, 95% CI 0.71 to 2.93) and PM10(RR=1.48, 95% CI 0.57 to 3.84), which is of interest in light of previously reported associations between this cardiac anomaly and other air pollutants.

Conclusions

While air pollution in the 1990s did not lead to sustained geographical differences in the overall congenital anomaly rate in England, further research regarding specific anomalies is indicated.
Cause-specific mortality in British coal workers and exposure to respirable dust and quartz
Authors: Miller Brian G , MacCalman Laura
Published: October 2009

Objectives

In the 1950s the Pneumoconiosis Field Research (PFR) programme was set up to study the health of British coal workers. Studies included regular health surveys, an intensive characterisation of workers' individual exposures, and entry to a cohort followed up to the present for cause-specific mortality. This study reports on analyses of cause-specific mortality in a cohort of almost 18 000 men from 10 British collieries.

Methods

External analyses used standardised mortality ratios (SMRs), comparing observed mortality with reference rates from the regions in which the collieries were situated. Causes investigated include lung and stomach cancers, chronic obstructive pulmonary disease and cardiovascular endpoints. Internal analyses used Cox regression models with time-dependent exposures adjusting for the confounding effects of age, smoking, cohort entry date and regional differences in population mortality rates.

Results

Several causes showed evidence of a healthy worker effect early in the follow-up, with a deficit in the SMR diminishing over time. For most of the causes there was a significant excess in the latter part of follow-up.

Internal analyses found evidence of an association between increased risks of lung cancer and increased quartz exposure, particularly at a lag of 15 years.

Risks of mortality from non-malignant respiratory disease showed increases with increased exposure to respirable dust.

Conclusions

This paper adds to the evidence on the long-term effects of exposure to coalmine dust on mortality from respiratory diseases.
Particulate matter and out-of-hospital coronary deaths in eight Italian cities
Authors: Serinelli Maria , Vigotti Maria Angela , Stafoggia Massimo , Berti Giovanna , Bisanti Luigi , Mallone Sandra , Pacelli Barbara , Tessari Roberta , Forastiere Francesco
Published: October 2009

Objectives

We evaluated the association between PM10concentration and out-of-hospital coronary deaths in eight Italian cities during 1997–2004.

Methods

16 989 subjects aged >35 years who died out-of-hospital from coronary causes were studied and hospital admissions in the previous 2 years identified. We studied the effect of the mean of current and previous day PM10values (lag 0–1). A city-specific case-crossover analysis was applied using a time-stratified approach considering as confounders weather, holidays, influenza epidemics, and summer decrease in population. The pooled percentage increase (95% CI) in mortality per 10 μg/m3increase in PM10was estimated.

Results

A statistically significant increase in out-of-hospital coronary deaths was related to a 10 μg/m3increase in PM10: 1.46% (95% CI 0.50 to 2.43). Although no statistically significant effect modification by age was found, the effect was stronger among subjects aged >65 years (1.60%, 0.59 to 2.63), particularly those aged 65–74 (3.01%, 0.74 to 5.34). People in the lowest socio-economic category (3.34%, 1.28 to 5.45) had a stronger effect than those in the highest category. No clear effect modification was seen for gender, season or any specific comorbidity. An indication of negative effect modification was seen for previous admission for cardiac dysrhythmias. Subjects without hospital admissions in the previous 2 years were slightly more affected by PM10effects (1.91%, 0.28 to 3.47) than those with at least one previous hospital admission (1.44%, 0.09 to 2.82).

Conclusions

Our results show that short term exposure to PM10is associated with coronary mortality especially among the elderly and socio-economically disadvantaged. No clear effect modification by previous hospitalisations was detected except for cardiac dysrhythmias, possibly due to protective treatment.
The bibliographic impact of epidemiological studies: what can be learnt from citations?: Table 1
Authors: Leclerc Annette , Chastang Jean-François , Kaniewski Nadine , Cyr Diane , Ozguler Anna , Descatha Alexis
Published: October 2009

Objective

To document one dimension of the impact of an epidemiological study through citations in scientific journals.

Methods

Two sets of articles from studies performed in France were considered. They presented original results on occupational risk factors for low back pain and upper limb disorders. Citations of these articles were retrieved through the Web of Science and Google Scholar, and selected according to several criteria. Most citations present in the Web of Science were also retrieved from Google Scholar, except for the most recent articles. In the Web of Science, after exclusion of self-citations and duplicates, the total number of citations was 109 from 23 different countries for the low back pain articles, with 96 citations from 18 countries for upper limb disorders. A relatively large number of the citations belonged to clinical journals outside the fields of occupational health, ergonomics and public health.

Conclusion

This study suggests that results dealing with occupational health disseminate into various fields of clinical research. However, this is only one dimension of the impact of a study.
Mortality from myocardial infarction in relation to exposure to vibration and dust among a cohort of iron-ore miners in Sweden
Authors: Björ Bodil , Burström Lage , Eriksson Kåre , Jonsson Håkan , Nathanaelsson Lena , Nilsson Tohr
Published: October 2009

Objectives

The aim of this study was to investigate myocardial infarction (MI) mortality in relation to exposure to hand/arm vibration (HAV) and whole body vibration (WBV) as well as exposure to dust among men employed in two Swedish iron-ore mines.

Methods

This study comprised employed men at two iron-ore mines in Sweden who had been employed for at least 1 year from 1923 up to 1996. The causes of death were obtained from the national cause of death register from 1952 to 2001. Myocardial infarction mortality was obtained by linking personal identification numbers to the national cause of death register. Poisson regression was used for risk estimations on exposure–response relation, and analyses were made on the two age groups ≤60 years and >60 years.

Results

Relative risks for MI mortality in relation to exposure were significantly increased for exposure (0/>0) to WBV (RR 1.18, 95% CI 1.06 to 1.31) and dust (RR 1.15, 95% CI 1.02 to 1.31), and the results indicated an exposure–response relation for WBV and dust separately. For 60 years and younger, exposure to HAV (0/>0) (RR 1.34, 95% CI 1.03 to 1.74) and WBV (0/>0) (RR 1.39, 95% CI 1.13 to 1.72) increased the risk of MI mortality. An exposure–response was found for HAV and WBV, as the medium and high exposed categories showed significantly increased risk estimates. None of the exposures significantly increased the risk in the group above 60 years. The increased risk estimates for exposure to WBV remained when adjusting for exposure to dust.

Conclusions

The results for the working age (≤60 years) group showed significantly increased MI mortality for univariate exposure to HAV, WBV and dust. We found an association between increased mortality from MI and occupational exposure to WBV, and the risk remained after adjustment for dust exposure.
Fatal occupational injuries in Taiwan, 1994–2005
Authors: Ho Shu-Chen , Wang Li-Yu , Ho Chi-Kung , Yang Chun-Yuh
Published: October 2009

Objectives

This study examines the trends in rates of fatal occupational injuries in Taiwan by demographic group and occupation for 1994–2005.

Methods

Data on deaths due to injuries at work from 1994 through 2005 were obtained from the Department of Health which is responsible for the death registration system in Taiwan. Employment data, which were used as the denominators of fatality rates in this study, were retrieved from the Directorate-General of Budget and Accounting Statistics ‘Employment and Earnings’ database. A Poisson regression model was used to examine the trends in rates of fatal occupational injuries in various occupations while controlling for demographic characteristics.

Results

Overall fatal occupational injury rates declined during the study period among all demographic groups and occupations. Adjusted annual changes in rates of fatal injuries ranged from a decrease of 13.6% a year in machine operators/related workers to a decrease of 35.9% in clerks. The annual decrement was faster for males than for females and for older workers compared to young workers.

Conclusions

Despite declining rates, the number of fatal occupational injuries in Taiwan remains significant because of the growing work force. Future research should focus on the disparities in fatal injury trends.
Do pre-employment influences explain the association between psychosocial factors at work and coronary heart disease? The Whitehall II study
Authors: Hintsa Taina , Shipley Martin J , Gimeno David , Elovainio Marko , Chandola Tarani , Jokela Markus , Keltikangas-Järvinen Liisa , Vahtera Jussi , Marmot Michael G , Kivimäki Mika
Published: October 2009

Objectives

To examine whether the association between psychosocial factors at work and incident coronary heart disease (CHD) is explained by pre-employment factors, such as family history of CHD, education, paternal education and social class, number of siblings and height.

Methods

A prospective cohort study of 6435 British men aged 35–55 years at phase 1 (1985–1988) and free from prevalent CHD at phase 2 (1989–1990) was conducted. Psychosocial factors at work were assessed at phases 1 and 2 and mean scores across the two phases were used to determine long-term exposure. Selected pre-employment factors were assessed at phase 1. Follow-up for coronary death, first non-fatal myocardial infarction or definite angina between phase 2 and 1999 was based on clinical records (250 events, follow-up 8.7 years).

Results

The selected pre-employment factors were associated with risk for CHD: HRs (95% CI) were 1.33 (1.03 to 1.73) for family history of CHD, 1.18 (1.05 to 1.32) for each quartile decrease in height and 1.16 (0.99 to 1.35) for each category increase in number of siblings. Psychosocial work factors also predicted CHD: 1.72 (1.08 to 2.74) for low job control and 1.72 (1.10 to 2.67) for low organisational justice. Adjustment for pre-employment factors changed these associations by 4.1% or less.

Conclusions

In this occupational cohort of British men, the association between psychosocial factors at work and CHD was largely independent of family history of CHD, education, paternal educational attainment and social class, number of siblings and height.
Myocardial fibrosis and apoptosis, but not inflammation, are present in long-term experimental diabetes
Authors: Ares-Carrasco S. , Picatoste B. , Benito-Martín A. , Zubiri I. , Sanz A. B. , Sánchez-Niño M. D. , Ortiz A. , Egido J. , Tuñón J. , Lorenzo O.
Published: October 2009

The aim of this paper is to study the myocardial damage secondary to long-term streptozotocin-induced type 1 diabetes mellitus (DM1). Normotensive and spontaneously hypertensive rats (SHR) received either streptozotocin injections or vehicle. After 22 or 6 wk, DM1, SHR, DM1/SHR, and control rats were killed, and the left ventricles studied by histology, quantitative PCR, Western blot, ELISA, and electromobility shift assay. Cardiomyocyte cultures were also performed. The expression of profibrotic factors, transforming growth factor-β (TGF-β1), connective tissue growth factor, and matrix proteins was increased, and the TGF-β1-linked transcription factors phospho-Smad3/4 and activator protein-1 were activated in the DM1 myocardium. Proapoptotic molecules FasL, Fas, Bax, and cleaved caspase-3 were also augmented. Myocardial injury in long-term hypertension shared these features. In addition, hypertension was associated with activation of NF-κB, increased inflammatory cell infiltrate, and expression of the mediators [interleukin-1β (IL-1β), tumor necrosis factor-α, monocyte chemoattractant protein 1, vascular cell adhesion molecule 1, angiotensinogen, and oxidants], which were absent in long-term DM1. At this stage, the combination of DM1 and hypertension resulted in nonsignificant additive effects. Moreover, the coexistence of DM1 blunted the inflammatory response to hypertension. Anti-inflammatory IL-10 and antioxidants were induced in long-term DM1 and DM1/SHR hearts. Myocardial inflammation was, however, observed in the short-term model. In cultured cardiomyocytes, IL-10, TGF-β1, and catalase blocked the glucose-stimulated expression of proinflammatory genes. Fibrosis and apoptosis are features of long-term myocardial damage in experimental DM1. Associated hypertension does not induce additional changes. Myocardial inflammation is present in hypertension and short-term DM1, but is not a key feature in long-term DM1. Local reduction of proinflammatory factors and expression of anti-inflammatory and antioxidant molecules may underlie this effect.
Generation of nitric oxide from nitrite by carbonic anhydrase: a possible link between metabolic activity and vasodilation
Authors: Aamand Rasmus , Dalsgaard Thomas , Jensen Frank B. , Simonsen Ulf , Roepstorff Andreas , Fago Angela
Published: October 2009

In catalyzing the reversible hydration of CO2to bicarbonate and protons, the ubiquitous enzyme carbonic anhydrase (CA) plays a crucial role in CO2transport, in acid-base balance, and in linking local acidosis to O2unloading from hemoglobin. Considering the structural similarity between bicarbonate and nitrite, we hypothesized that CA uses nitrite as a substrate to produce the potent vasodilator nitric oxide (NO) to increase local blood flow to metabolically active tissues. Here we show that CA readily reacts with nitrite to generate NO, particularly at low pH, and that the NO produced in the reaction induces vasodilation in aortic rings. This reaction occurs under normoxic and hypoxic conditions and in various tissues at physiological levels of CA and nitrite. Furthermore, two specific inhibitors of the CO2hydration, dorzolamide and acetazolamide, increase the CA-catalyzed production of vasoactive NO from nitrite. This enhancing effect may explain the known vasodilating effects of these drugs and indicates that CO2and nitrite bind differently to the enzyme active site. Kinetic analyses show a higher reaction rate at high pH, suggesting that anionic nitrite participates more effectively in catalysis. Taken together, our results reveal a novel nitrous anhydrase enzymatic activity of CA that would function to link the in vivo main end products of energy metabolism (CO2/H+) to the generation of vasoactive NO. The CA-mediated NO production may be important to the correlation between blood flow and metabolic activity in tissues, as occurring for instance in active areas of the brain.
Refined approach for quantification of in vivo ischemia-reperfusion injury in the mouse heart
Authors: Bohl Steffen , Medway Debra J. , Schulz-Menger Jeanette , Schneider Jurgen E. , Neubauer Stefan , Lygate Craig A.
Published: October 2009

Cardiac ischemia-reperfusion experiments in the mouse are important in vivo models of human disease. Infarct size is a particularly important scientific readout as virtually all cardiocirculatory pathways are affected by it. Therefore, such measurements must be exact and valid. The histological analysis, however, remains technically challenging, and the resulting quality is often unsatisfactory. For this report we have scrutinized each step involved in standard double-staining histology. We have tested published approaches and challenged their practicality. As a result, we propose an improved and streamlined protocol, which consistently yields high-quality histology, thereby minimizing experimental noise and group sizes.
Viability Assessment With Global Left Ventricular Longitudinal Strain Predicts Recovery of Left Ventricular Function After Acute Myocardial Infarction
Authors: Mollema Sjoerd A. , Delgado Victoria , Bertini Matteo , Antoni M. Louisa , Boersma Eric , Holman Eduard R. , Stokkel Marcel P.M. , van der Wall Ernst E. , Schalij Martin J. , Bax Jeroen J.
Published: October 2009

Background—

The extent of viable myocardial tissue is recognized as a major determinant of recovery of left ventricular (LV) function after myocardial infarction. In the current study, the role of global LV strain assessed with novel automated function imaging (AFI) to predict functional recovery after acute infarction was evaluated.

Methods and Results—

A total of 147 patients (mean age, 61�11 years) admitted for acute myocardial infarction were included. All patients underwent 2D echocardiography within 48 hours of admission. Significant relations were observed between baseline AFI global LV strain and peak level of troponin T (
r
=0.64), peak level of creatine phosphokinase (
r
=0.62), wall motion score index (
r
=0.52), and viability index assessed with single-photon emission computed tomography (
r
=0.79). At 1-year follow-up, LV ejection fraction was reassessed. Patients with absolute improvement in LV ejection fraction ≥5% at 1-year follow-up (n=70; 48%) had a higher (more negative) baseline AFI global LV strain (
P
<0.0001). Baseline AFI global LV strain was a predictor for change in LV ejection fraction at 1-year follow-up. A cutoff value for baseline AFI global LV strain of −13.7% yielded a sensitivity of 86% and a specificity of 74% to predict LV functional recovery at 1-year follow-up.

Conclusions—

AFI global LV strain early after acute myocardial infarction reflects myocardial viability and predicts recovery of LV function at 1-year follow-up.
Building Sport Countries’ Overseas Identity and Reputation: A Case Study of Public Paradiplomacy
Authors: Xifra Jordi
Published: October 2009

The aim of this article is to analyze public diplomacy efforts of noncentral governments through sport. The object of the study is Catalonia, a Spanish autonomous region with its own government but without power over national foreign affairs. Public diplomacy links up with relationship building between governments of nation-states and other nation-states and its citizens. However, noncentral governments, as Catalonia, and other organizations with powerful national identity symbols, such as sports organizations, also develop public relations activities to build an international reputation of regions. In the field of sports, some of these territories were given the name of sport countries in the 2003 Barcelona Conference. This article concludes by considering the notion of soft power as coined by Nye to frame the role of sports diplomacy efforts of regional actors.
The Poetics of Aging and Dementia
Authors: Shabahangi Nader Robert
Published: October 2009

This article suggests a unique way of viewing aging. Focusing on the process of aging, the author examines the manner in which we age and the meaning(s) we create while we go through the various stages of life. A literal and metaphorical analysis of aging is explored in great depth. Using poetry as a vehicle for meaning-making in aging, this article brings to light how we can apply ourselves creatively, and author our own life story as we age.