bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conservation and Evolutionary Dynamics of the
agr
Cell-to-Cell Communication System across Firmicutes
Authors: Wuster Arthur , Babu M. Madan 
Published: October 2007

ABSTRACT

We present evidence that the
agr
cell-to-cell communication system is present across firmicutes, including the human pathogen
Clostridium perfringens
. Although we find that the
agr
system is evolutionarily conserved and that the general functions which it regulates are similar in different species, the individual regulated genes are not the same. This suggests that the regulatory network controlled by
agr
is dynamic and evolves rapidly.
YhbO Protects Cells against Multiple Stresses
Authors: Abdallah Jad , Caldas Teresa , Kthiri Fatoum , Kern Renée , Richarme Gilbert 
Published: October 2007

ABSTRACTYhbO is a member of the DJ-1/ThiJ/Pfp1 superfamily, which includes chaperones, peptidases, and the Parkinson's disease protein DJ-1. AyhbO-disrupted mutant ofEscherichia coliis highly sensitive to oxidative, thermal, UV, and pH stresses, and the putative nucleophilic cysteine C104 of YhbO is required for stress resistance. These results suggest that YhbO affects a central process in stress management.
Cohabitation of Two DifferentlexARegulons inPseudomonas putida
Authors: Abella Marc , Campoy Susana , Erill Ivan , Rojo Fernando , Barbé Jordi 
Published: October 2007

ABSTRACTIn contrast to the vast majority of the members of the domainBacteria, severalPseudomonasandXanthomonasspecies have twolexAgenes, whose products have been shown to recognize different LexA binding motifs, making them an interesting target for studying the interplay between cohabiting LexA regulons in a single species. Here we report an analysis of the genetic composition of the two LexA regulons ofPseudomonas putidaKT2440 performed with a genomic microarray. The data obtained indicate that one of the two LexA proteins (LexA1) seems to be in control of the conventionalEscherichia coli-like SOS response, while the other LexA protein (LexA2) regulates only its own transcriptional unit, which includes theimuA, imuB, anddnaE2genes, and a gene (PP_3901) from a residentP. putidaprophage. Furthermore, PP_3901 is also regulated by LexA1 and is required for DNA damage-mediated induction of severalP. putidaresident prophage genes. In silico searches suggested that this marked asymmetry in regulon contents also occurs in otherPseudomonasspecies with twolexAgenes, and the implications of this asymmetry in the evolution of the SOS network are discussed.
Functional Organization of the Autotransporter Adhesin Involved in Diffuse Adherence
Authors: Charbonneau Marie-Ève , Mourez Michael 
Published: October 2007

ABSTRACTTheEscherichia coliadhesin involved in diffuse adherence (AIDA-I) is a multifunctional autotransporter protein that mediates bacterial aggregation and biofilm formation, as well as adhesion and invasion of cultured epithelial cells. To elucidate the structure-function relationships of AIDA-I, we performed transposon-based linker scanning mutagenesis and constructed mutants with site-directed deletions. Twenty-nine different mutants with insertions that did not affect protein expression were obtained. Eleven mutants were deficient for one or two but not all of the functions associated with the expression of AIDA-I. Functional characterization of the transposon mutants and of an additional deletion mutant suggested that the N-terminal third of mature AIDA-I is involved in binding of this protein to cultured epithelial cells. The purified product of the putative domain could bind to cultured epithelial cells, confirming the importance of this region in adhesion. We also identified several different mutants in which invasion and adhesion were changed to different extents and two mutants in which autoaggregation and biofilm formation were also affected differently. These results suggest that although conceptually linked, adhesion and invasion, as well as autoaggregation and biofilm formation, are phenomena that may rely on distinct mechanisms when they are mediated by AIDA-I. This study sheds new light on the workings of a protein belonging to an emerging family of strikingly versatile virulence factors.
A Horizontal Gene Transfer Event Defines Two Distinct Groups within
Burkholderia pseudomallei
That Have Dissimilar Geographic Distributions
Authors: Tuanyok Apichai , Auerbach Raymond K. , Brettin Thomas S. , Bruce David C. , Munk A. Christine , Detter J. Chris , Pearson Talima , Hornstra Heidie , Sermswan Rasana W. , Wuthiekanun Vanaporn , Peacock Sharon J. , Currie Bart J. , Keim Paul , Wagner David M. 
Published: October 2007

ABSTRACT

Burkholderia pseudomallei
is the etiologic agent of melioidosis. Many disease manifestations are associated with melioidosis, and the mechanisms causing this variation are unknown; genomic differences among strains offer one explanation. We compared the genome sequences of two strains of
B. pseudomallei
: the original reference strain K96243 from Thailand and strain MSHR305 from Australia. We identified a variable homologous region between the two strains. This region was previously identified in comparisons of the genome of
B. pseudomallei
strain K96243 with the genome of strain E264 from the closely related
B. thailandensis
. In that comparison, K96243 was shown to possess a horizontally acquired
Yersinia
-like fimbrial (YLF) gene cluster. Here, we show that the homologous genomic region in
B. pseudomallei
strain 305 is similar to that previously identified in
B. thailandensis
strain E264. We have named this region in
B. pseudomallei
strain 305 the
B. thailandensis
-like flagellum and chemotaxis (BTFC) gene cluster. We screened for these different genomic components across additional genome sequences and 571
B. pseudomallei
DNA extracts obtained from regions of endemicity. These alternate genomic states define two distinct groups within
B. pseudomallei
: all strains contained either the BTFC gene cluster (group BTFC) or the YLF gene cluster (group YLF). These two groups have distinct geographic distributions: group BTFC is dominant in Australia, and group YLF is dominant in Thailand and elsewhere. In addition, clinical isolates are more likely to belong to group YLF, whereas environmental isolates are more likely to belong to group BTFC. These groups should be further characterized in an animal model.
Characterization of MazF

Sa

, an Endoribonuclease from
Staphylococcus aureus
Authors: Fu Zhibiao , Donegan Niles P. , Memmi Guido , Cheung Ambrose L. 
Published: October 2007

ABSTRACT

The
mazEF
homologs of
Staphylococcus aureus
, designated

mazEF
sa

, have been shown to cotranscribe with the
sigB
operon under stress conditions. In this study, we showed that MazEF

Sa

, as with their
Escherichia coli
counterparts, compose a toxin-antitoxin module wherein MazF

Sa

leads to rapid cell growth arrest and loss in viable CFU upon overexpression. MazF

Sa

is a novel sequence-specific endoribonuclease which cleaves mRNA to inhibit protein synthesis. Using
ctpA
mRNA as the model substrate both in vitro and in vivo, we demonstrated that MazF

Sa

cleaves single-strand RNA preferentially at the 5′ side of the first U or 3′ side of the second U residue within the consensus sequences VUUV′ (where V and V′ are A, C, or G and may or may not be identical). Binding studies confirmed that the antitoxin MazE

Sa

binds MazF

Sa

to form a complex to inhibit the endoribonuclease activity of MazF

Sa

. Contrary to the system in
E. coli
, exposure to selected antibiotics augmented

mazEF
sa

transcription, akin to what one would anticipate from the environmental stress response of the
sigB
system. These data indicate that the
mazEF
system of
S. aureus
differs from the gram-negative counterparts with respect to mRNA cleavage specificity and antibiotic stresses.
Single-Molecule Force Spectroscopy of Mycobacterial Adhesin-Adhesin Interactions
Authors: Verbelen Claire , Raze Dominique , Dewitte Frédérique , Locht Camille , Dufrêne Yves F. 
Published: October 2007

ABSTRACT

The heparin-binding hemagglutinin (HBHA) is one of the few virulence factors identified for
Mycobacterium tuberculosis
. It is a surface-associated adhesin that expresses a number of different activities, including mycobacterial adhesion to nonphagocytic cells and microbial aggregation. Previous evidence indicated that HBHA is likely to form homodimers or homopolymers via a predicted coiled-coil region located within the N-terminal portion of the molecule. Here, we used single-molecule atomic-force microscopy to measure individual homophilic HBHA-HBHA interaction forces. Force curves recorded between tips and supports derivatized with HBHA proteins exposing their N-terminal domains showed a bimodal distribution of binding forces reflecting the formation of dimers or multimers. Moreover, the binding peaks showed elongation forces that were consistent with the unfolding of α-helical coiled-coil structures. By contrast, force curves obtained for proteins exposing their lysine-rich C-terminal domains showed a broader distribution of binding events, suggesting that they originate primarily from intermolecular electrostatic bridges between cationic and anionic residues rather than from specific coiled-coil interactions. Notably, similar homophilic HBHA-HBHA interactions were demonstrated on live mycobacteria producing HBHA, while they were not observed on an HBHA-deficient mutant. Together with the fact that HBHA mediates bacterial aggregation, these observations suggest that the single homophilic HBHA interactions measured here reflect the formation of multimers that may promote mycobacterial aggregation.
Regulation of
d
-Xylose Metabolism in
Caulobacter crescentus
by a LacI-Type Repressor
Authors: Stephens Craig , Christen Beat , Watanabe Kelly , Fuchs Thomas , Jenal Urs 
Published: October 2007

ABSTRACT

In the oligotrophic freshwater bacterium
Caulobacter crescentus
,
d
-xylose induces expression of over 50 genes, including the
xyl
operon, which encodes key enzymes for xylose metabolism. The promoter (P

xylX

) controlling expression of the
xyl
operon is widely used as a tool for inducible heterologous gene expression in
C. crescentus
. We show here that P

xylX

and at least one other promoter in the xylose regulon (P

xylE

) are controlled by the CC3065 (
xylR
) gene product, a LacI-type repressor. Electrophoretic gel mobility shift assays showed that operator binding by XylR is greatly reduced in the presence of
d
-xylose. The data support the hypothesis that there is a simple regulatory mechanism in which XylR obstructs xylose-inducible promoters in the absence of the sugar; the repressor is induced to release DNA upon binding
d
-xylose, thereby freeing the promoter for productive interaction with RNA polymerase. XylR also has an effect on glucose metabolism, as
xylR
mutants exhibit reduced expression of the Entner-Doudoroff operon and their ability to utilize glucose as a sole carbon and energy source is compromised.
Isolation of Cold-Sensitive
yidC
Mutants Provides Insights into the Substrate Profile of the YidC Insertase and the Importance of Transmembrane 3 in YidC Function
Authors: Yuan Jijun , Phillips Gregory J. , Dalbey Ross E. 
Published: October 2007

ABSTRACT

YidC, a 60-kDa integral membrane protein, plays an important role in membrane protein insertion in bacteria. YidC can function together with the SecYEG machinery or operate independently as a membrane protein insertase. In this paper, we describe two new
yidC
mutants that lead to a cold-sensitive phenotype in bacterial cell growth. Both alleles impart a cold-sensitive phenotype and result from point mutations localized to the third transmembrane (TM3) segment of YidC, indicating that this region is crucial for YidC function. We found that the
yidC
(
C423R
) mutant confers a weak phenotype on membrane protein insertion while a
yidC
(
P431L
) mutant leads to a stronger phenotype. In both cases, the affected substrates include the Pf3 coat protein and ATP synthase F
1
F
o
subunit c (F
o
C), while CyoA (the quinol binding subunit of the cytochrome
bo3
quinol oxidase complex) and wild-type procoat are slightly affected or not affected in either cold-sensitive mutant. To determine if the different substrates require various levels of YidC activity for membrane insertion, we performed studies where YidC was depleted using an arabinose-dependent expression system. We found that −3M-PC-Lep (a construct with three negatively charged residues inserted into the middle of the procoat-Lep [PC-Lep] protein) and Pf3 P2 (a construct with the Lep P2 domain added at the C terminus of Pf3 coat) required the highest amount of YidC and that CyoA-N-P2 (a construct with the amino-terminal part of CyoA fused to the Lep P2 soluble domain) and PC-Lep required the least, while F
o
C required moderate YidC levels. Although the cold-sensitive mutations can preferentially affect one substrate over another, our results indicate that different substrates require different levels of YidC activity for membrane insertion. Finally, we obtained several intragenic suppressors that overcame the cold sensitivity of the C423R mutation. One pair of mutations suggests an interaction between TM2 and TM3 of YidC. The studies reveal the critical regions of the YidC protein and provide insight into the substrate profile of the YidC insertase.
The role of a recombinant hybrid protein based ELISA for the serodiagnosis ofOnchocerca volvulus
Authors: Andrews J A , Bligh W J , Chiodini P L , Bradley J E , Nde P N , Lucius R 
Published: October 2007

Aims:Onchocerca volvulusinfection is traditionally diagnosed by examination of skin snips for the presence of microfilariae. A disadvantage of this method is the low sensitivity particularly with light or prepatent infection. Serodiagnosis using recombinant-antigen-based assays may provide a more sensitive diagnostic test. An ELISA based on a recombinant antigen OvH3 has previously been validated using sera from endemic areas. This study investigated the role of this ELISA-based assay for use in the serodiagnosis of onchocerciasis in non-endemic areas.Methods:The ELISA-based assay was tested on sera from untreated patients with known onchocerciasis and on untreated and treated patients with definite or probable onchocerciasis identified from a hospital diagnostic database. The assay was also tested on sera from patients with other helminthic infections to determine the sensitivity and specificity of this assay in a tertiary referral laboratory dealing with sera from a variety of patients.Results:The sensitivity and specificity of the OvH3 assay were 93.2% and 93.5%, respectively, when tested on non-endemic patients with clinical diagnosis of onchocerciasis.Conclusions:This study demonstrates the potential role of the assay as a sensitive and specific test for use in the serodiagnosis of onchocerciasis in a reference laboratory dealing with sera from patients in non-endemic setting.
A study of the prevalence of vitamin K deficiency in patients with cancer referred to a hospital palliative care team and its association with abnormal haemostasis
Authors: Harrington D J , Western H , Seton-Jones C , Rangarajan S , Beynon T , Shearer M J 
Published: October 2007

Background:Many patients with advanced cancer are malnourished. Anorexia is common, as is the use of chemotherapy, which may cause nausea and poor appetite. Ten per cent of these patients experience haemorrhagic events.Aim:Since vitamin K deficiency (VKD) causes bleeding, to establish the prevalence of VKD in patients with advanced cancer receiving palliative care.Methods:Serum concentrations of vitamin K1and undercarboxylated factor II (PIVKA-II) were determined in 46 (17 male/29 female) inpatients aged 26–85 (mean 58) years. INR and liver function tests (bilirubin, ALT, GGT and ALP) were also performed.Results:Vitamin K1was below the lower limit of the reference range (0.33 nmol/l) in 22% of patients. 78% of patients had some degree of functional VKD indicated by raised (>0.2 AU/ml) PIVKA-II. Six patients (13%) had a prolonged INR, all of whom had raised PIVKA-II and GGT; 4 also had vitamin K1<0.33 nmol/l. Three patients (6.5%) had clinically significant VKD characterised by INR >1.5, PIVKA-II >10 AU/ml, and undetectable vitamin K1.Conclusions:Patients with advanced cancer are prone to VKD which, while usually subclinical, may develop to a clinically relevant prolongation of the INR. Serum measurements of vitamin K1and PIVKA-II can be used to detect VKD and monitor vitamin K status before an increased risk of bleeding develops.
Distribution of neural cell adhesion molecule (NCAM/CD56) in gastrointestinal stromal tumours and their intra-abdominal mesenchymal mimics
Authors: Agaimy A , Wünsch P H 
Published: October 2007

Background:The distribution and reactivity pattern of neural cell adhesion molecule (NCAM/CD56) in gastrointestinal stromal tumours (GISTs) and their mesenchymal mimics have not been investigated in the KIT era.Methods:275 histologically and immunohistochemically well characterised primary and metastatic intra-abdominal mesenchymal lesions were analysed by conventional immunohistochemistry, with emphasis on GIST and GI smooth muscle neoplasms.Results:CD56 expression was seen in 18/21 (86%), 4/5 (80%), 26/34 (76%), and 32/168 (19%) of primary GI leiomyomas, schwannomas, leiomyosarcomas, and GISTs, respectively. Reactivity in GISTs was mostly focal. Of 6% strongly staining GISTs, 71% were either malignant clinically or assigned a high risk prognostic group. CD56 expression in GISTs varied greatly with histological type (seen in 50% and 7% of epithelioid and spindled GISTs, respectively) and anatomical site (in 33%, 10%, 1%, and 0% of rectal, gastric, small intestinal and oesophageal GISTs, respectively). A variable, but inconsistent expression was seen in miscellaneous lesions including dedifferentiated liposarcoma, abdominopelvic PEComa, myo/fibroblastic sarcoma and malignant fibrous histiocytoma. Mesenteric fibromatoses, angiosarcoma/Kaposi sarcoma, reactive tumefactive fibrogenic lesions and 12/13 primary anorectal and oesophageal melanomas were negative.Conclusion:Results confirmed the ubiquity and non-specificity of CD56 as a neurogenic marker. Except for a subset of epithelioid gastric and high-grade rectal GISTs, CD56 expression is rare in GISTs, contrasting with true leiomyomatous and neurogenic neoplasms. CD56 plays a limited role in the differential diagnosis of GIST. Its potential role as a marker of adverse outcome in GISTs remains to be further investigated.
Effects of PCBs, p,p′-DDT, p,p′-DDE, HCB and β-HCH on thyroid function in preschool children
Authors: Álvarez-Pedrerol M , Ribas-Fitó N , Torrent M , Carrizo D , Grimalt J O , Sunyer J 
Published: October 2007

Objective:Several studies have shown that some organochlorine compounds (OCs) can interfere with the thyroid system. As thyroid hormones (THs) are essential for normal brain development, it is important to study the association between THs and OCs during pregnancy and childhood. We have evaluated the relationship between thyroid function and OCs in preschool children.Methods:Children from a general population birth cohort in Menorca (n = 259), Spain were assessed at the age of 4 years. Concentrations of THs (free T4 and total T3), thyrotropin (TSH) and a range of OCs were measured in peripheral blood.Results:Blood levels of dichlorodiphenyl trichloroethane (p,p′-DDT), β-hexachlorocylcohexane (β-HCH), polychlorinated biphenyls (congeners PCB-138, PCB-153 and PCB-118) were related to lower total T3 levels (p<0.05). In addition, free T4 was inversely associated with PCB-118, while no relationship was found between TSH and any of the measured OCs.Conclusions:This study suggests that even at background levels of exposure, OCs may affect the thyroid system, particularly total T3 levels.
An occupational health intervention programme for workers at high risk for sickness absence. Cost effectiveness analysis based on a randomised controlled trial
Authors: Taimela S , Justén S , Aronen P , Sintonen H , Läärä E , Malmivaara A , Tiekso J , Aro T 
Published: October 2007

Objectives:To determine whether, from a healthcare perspective, a specific occupational health intervention is cost effective in reducing sickness absence when compared with usual care in occupational health in workers with high risk of sickness absence.Methods:Economic evaluation alongside a randomised controlled trial. 418 workers with high risk of sickness absence from one corporation were randomised to intervention (n = 209) or to usual care (n = 209). The subjects in the intervention group were invited to occupational health service for a consultation. The intervention included, if appropriate, a referral to specialist treatment. Register data of sickness absence were available for 384 subjects and questionnaire data on healthcare costs from 272 subjects. Missing direct total cost data were imputed using a two-part regression model. Primary outcome measures were sickness absence days and direct healthcare costs up to 12 months after randomisation. Cost effectiveness (CE) was expressed as an incremental CE ratio, CE plane and CE acceptability curve with both available direct total cost data and missing total cost data imputed.Results:After one year, the mean of sickness absence was 30 days in the usual care group (n = 192) and 11 days less (95% CI 1 to 20 days) in the intervention group (n = 192). Among the employees with available cost data, the mean days of sickness absence were 22 and 24, and the mean total cost €974 and €1049 in the intervention group (n = 134) and in the usual care group (n = 138), respectively. The intervention turned out to be dominant—both cost saving and more effective than usual occupational health care. The saving was €43 per sickness absence day avoided with available direct total cost data, and €17 with missing total cost data imputed.Conclusions:One year follow-up data show that occupational health intervention for workers with high risk of sickness absence is a cost effective use of healthcare resources.
A normative study of levels of uranium in the urine of British Forces personnel
Authors: Miller B G , Colvin A P , Hutchison P A , Tait H , Dempsey S , Lewis D , Soutar C A 
Published: October 2007

Objectives:The UK Ministry of Defence (MoD) controls a biological monitoring programme that includes testing for uranium in personnel who served in the conflict in Iraq in 2003. To help interpret the results, the MoD commissioned this study to quantify a normative reference distribution of urinary uranium concentrations in military personnel who had not served in that conflict.Methods:The study selected and visited various military establishments to recruit a representative mix of ranks, genders and occupational groups (combat, support and auxiliary). A standardised protocol and recruitment questionnaire were used. The 125 ml spot urine samples collected were analysed for uranium and creatinine concentrations and (where possible) for uranium isotope238U/235U ratio.Results:Samples from 732 eligible subjects were analysed. Adjusted uranium concentrations ranged up to 556 ng.g−1creatinine, somewhat higher than reference values quoted for the USA but much lower than recorded in granite areas such as Finland. Isotope ratio measurements were available for 125 samples (17) with the highest concentrations; these all had a natural isotope signature and no evidence of depleted uranium (DU). On average, urinary uranium concentrations were somewhat lower in officers than in other ranks; they differed also across the services, the Navy being lowest and the Army highest. The levels give no concern regarding health risks in the personnel studied.Conclusion:Since even the highest values were from natural sources, we assume the differences represent differences in ingestion of natural uranium. Definition of a reference distribution or normal values will depend on the subpopulation of interest.