bluuebunny/crossref_metadata_2025_split huggingface dataset:
First Insights into the Genome of the Gram-Negative, Endospore-Forming Organism Sporomusa ovata Strain H1 DSM 2662
Authors: Poehlein Anja , Gottschalk Gerhard , Daniel Rolf 
Published: September 2013

ABSTRACT

The genome of
Sporomusa ovata
strain H1 DSM 2662, an anaerobic, Gram-negative endospore-forming bacterium, was sequenced.
S. ovata
uses
N
-methyl compounds, primary alcohols, fatty acids, and H
2
and CO
2
as energy and carbon sources to produce acetate. The genome harbors one chromosome, which encodes proteins typical for sporulation.
The Second Messenger Cyclic Di-GMP Regulates Clostridium difficile Toxin Production by Controlling Expression of
sigD
Authors: McKee Robert W. , Mangalea Mihnea R. , Purcell Erin B. , Borchardt Erin K. , Tamayo Rita 
Published: September 2013

ABSTRACT

The Gram-positive obligate anaerobe
Clostridium difficile
causes potentially fatal intestinal diseases. How this organism regulates virulence gene expression is poorly understood. In many bacterial species, the second messenger cyclic di-GMP (c-di-GMP) negatively regulates flagellar motility and, in some cases, virulence. c-di-GMP was previously shown to repress motility of
C. difficile
. Recent evidence indicates that flagellar gene expression is tightly linked with expression of the genes encoding the two
C. difficile
toxins TcdA and TcdB, which are key virulence factors for this pathogen. Here, the effect of c-di-GMP on expression of the toxin genes
tcdA
and
tcdB
was determined, and the mechanism connecting flagellar and toxin gene expressions was examined. In
C. difficile
, increasing c-di-GMP levels reduced the expression levels of
tcdA
and
tcdB
, as well as that of
tcdR
, which encodes an alternative sigma factor that activates
tcdA
and
tcdB
expression. We hypothesized that the
C. difficile
orthologue of the flagellar alternative sigma factor SigD (FliA; σ
28
) mediates regulation of toxin gene expression in response to c-di-GMP. Indeed, ectopic expression of
sigD
in
C. difficile
resulted in increased expression levels of
tcdR
,
tcdA
, and
tcdB
. Furthermore,
sigD
expression enhanced toxin production and increased the cytopathic effect of
C. difficile
on cultured fibroblasts. Finally, evidence is provided that SigD directly activates
tcdR
expression and that SigD cannot activate
tcdA
or
tcdB
expression independent of TcdR. Taken together, these data suggest that SigD positively regulates toxin genes in
C. difficile
and that c-di-GMP can inhibit both motility and toxin production via SigD, making this signaling molecule a key virulence gene regulator in
C. difficile
.
Identification, Purification, and Characterization of a Novel Amino Acid Racemase, Isoleucine 2-Epimerase, from Lactobacillus Species
Authors: Mutaguchi Yuta , Ohmori Taketo , Wakamatsu Taisuke , Doi Katsumi , Ohshima Toshihisa 
Published: September 2013

ABSTRACT

Accumulation of
d
-leucine,
d
-
allo
-isoleucine, and
d
-valine was observed in the growth medium of a lactic acid bacterium,
Lactobacillus otakiensis
JCM 15040, and the racemase responsible was purified from the cells and identified. The N-terminal amino acid sequence of the purified enzyme was GKLDKASKLI, which is consistent with that of a putative γ-aminobutyrate aminotransferase from
Lactobacillus buchneri
. The putative γ-aminobutyrate aminotransferase gene from
L. buchneri
JCM 1115 was expressed in recombinant
Escherichia coli
and then purified to homogeneity. The enzyme catalyzed the racemization of a broad spectrum of nonpolar amino acids. In particular, it catalyzed at high rates the epimerization of
l
-isoleucine to
d
-
allo
-isoleucine and
d
-
allo
-isoleucine to
l
-isoleucine. In contrast, the enzyme showed no γ-aminobutyrate aminotransferase activity. The relative molecular masses of the subunit and native enzyme were estimated to be about 49 kDa and 200 kDa, respectively, indicating that the enzyme was composed of four subunits of equal molecular masses. The

K
m

and
V
max
values of the enzyme for
l
-isoleucine were 5.00 mM and 153 μmol·min
−1
·mg
−1
, respectively, and those for
d
-
allo
-isoleucine were 13.2 mM and 286 μmol·min
−1
·mg
−1
, respectively. Hydroxylamine and other inhibitors of pyridoxal 5′-phosphate-dependent enzymes completely blocked the enzyme activity, indicating the enzyme requires pyridoxal 5′-phosphate as a coenzyme. This is the first evidence of an amino acid racemase that specifically catalyzes racemization of nonpolar amino acids at the C-2 position.
Diversity of Cobalamin Riboswitches in the Corrinoid-Producing Organohalide Respirer Desulfitobacterium hafniense
Authors: Choudhary Pallavi K. , Duret Aurélie , Rohrbach-Brandt Emmanuelle , Holliger Christof , Sigel Roland K. O. , Maillard Julien 
Published: September 2013

ABSTRACTThe strategic adaptation of prokaryotes in polluted niches involves the efficient regulation of their metabolism. The obligate anaerobe and metabolically versatileDesulfitobacterium hafniensereductively dechlorinates halogenated organic compounds (so-called organohalides). SomeD. hafniensestrains carry out organohalide respiration (OHR), a process which requires the use of corrinoid as a cofactor in reductive dehalogenases, the key enzymes in OHR. We report here the diversity of the cobalamin riboswitches that possibly regulate the corrinoid metabolism forD. hafniense. The analysis of availableD. hafniensegenomes indicates the presence of 18 cobalamin riboswitches located upstream of genes whose products are mainly involved in corrinoid biosynthesis and transport. To obtain insight into their function, the secondary structures of three of these RNA elements were predicted by Mfold, as well as analyzed by in-line probing. These RNA elements both display diversity in their structural elements and exhibit various affinities toward adenosylcobalamin that possibly relates to their role in the regulation of corrinoid metabolism. Furthermore, adenosylcobalamin-inducedin vivorepression of RNA synthesis of the downstream located genes indicates that the corrinoid transporters and biosynthetic enzymes inD. hafniensestrain TCE1 are regulated at the transcriptional level. Taken together, the riboswitch-mediated regulation of the complex corrinoid metabolism inD. hafniensecould be of crucial significance in environments polluted with organohalides both to monitor their intracellular corrinoid level and to coexist with corrinoid-auxotroph OHR bacteria.
MecA Protein Acts as a Negative Regulator of Genetic Competence in Streptococcus mutans
Authors: Tian Xiao-Lin , Dong Gaofeng , Liu Tianlei , Gomez Zubelda A. , Wahl Astrid , Hols Pascal , Li Yung-Hua 
Published: September 2013

ABSTRACT

Streptococcus mutans
develops competence for genetic transformation through a complex network that receives inputs from at least two signaling peptides, competence-stimulating peptide (CSP) and
sigX
-inducing peptide (XIP). The key step of competence induction is the transcriptional activation of
comX
, which encodes an alternative sigma factor, SigX (σ
X
), controlling the expression of late competence genes essential for DNA uptake and recombination. In this study, we provide evidence that MecA acts as a negative regulator in the posttranslational regulation of SigX in
S. mutans
. Using
luxAB
transcriptional reporter strains, we demonstrate that MecA represses the expression of late competence genes in
S. mutans
grown in a complex medium that is subpermissive for competence induction by CSP. The negative regulation of competence by MecA requires the presence of a functional SigX. Accordingly, inactivation of MecA results in a prolonged competence state of
S. mutans
under this condition. We have also found that the AAA+ protease ClpC displays a similar repressing effect on late competence genes, suggesting that both MecA and ClpC function coordinately to regulate competence in the same regulatory circuit in
S. mutans
. This suggestion is strongly supported by the results of bacterial two-hybrid assays, which demonstrate that MecA interacts with both SigX and ClpC, forming a ternary SigX-MecA-ClpC complex. Western blot analysis also confirms that inactivation of MecA or ClpC results in the intracellular accumulation of the SigX in
S. mutans
. Together, our data support the notion that MecA mediates the formation of a ternary SigX-MecA-ClpC complex that sequesters SigX and thereby negatively regulates genetic competence in
S. mutans
.
VhuD Facilitates Electron Flow from H
2
or Formate to Heterodisulfide Reductase in Methanococcus maripaludis
Authors: Costa Kyle C. , Lie Thomas J. , Xia Qin , Leigh John A. 
Published: September 2013

ABSTRACT

Flavin-based electron bifurcation has recently been characterized as an essential energy conservation mechanism that is utilized by hydrogenotrophic methanogenic
Archaea
to generate low-potential electrons in an ATP-independent manner. Electron bifurcation likely takes place at the flavin associated with the α subunit of heterodisulfide reductase (HdrA). In
Methanococcus maripaludis
the electrons for this reaction come from either formate or H
2
via formate dehydrogenase (Fdh) or Hdr-associated hydrogenase (Vhu). However, how these enzymes bind to HdrA to deliver electrons is unknown. Here, we present evidence that the δ subunit of hydrogenase (VhuD) is central to the interaction of both enzymes with HdrA. When
M. maripaludis
is grown under conditions where both Fdh and Vhu are expressed, these enzymes compete for binding to VhuD, which in turn binds to HdrA. Under these conditions, both enzymes are fully functional and are bound to VhuD in substoichiometric quantities. We also show that Fdh copurifies specifically with VhuD in the absence of other hydrogenase subunits. Surprisingly, in the absence of Vhu, growth on hydrogen still occurs; we show that this involves F
420
-reducing hydrogenase. The data presented here represent an initial characterization of specific protein interactions centered on Hdr in a hydrogenotrophic methanogen that utilizes multiple electron donors for growth.
Excellent reliability for MRI grading and prognostic parameters in acute hamstring injuries
Authors: Hamilton B , Whiteley R , Almusa E , Roger B , Geertsema C , Tol Johannes L 
Published: September 2013

BackgroundCategorical grading and other measurable MRI parameters are frequently utilised for predicting the outcome of hamstring injuries. However, the reliability and smallest detectable difference (SDD) have not been previously evaluated. It therefore remains unclear if the variability in previously reported results reflects reporting variation or actual injury status.Methods25 hamstring injuries were scored by two experienced radiologists using the Peetrons grading and specific prognostic MRI parameters: distance from ischial tuberosity (cm), extent (cranio to caudal, anterior to posterior, medial to lateral; (cm)), maximum cross-sectional area (%), volume (cm3) of the oedema. The interobserver and intraobserver reliability was calculated along with the SDDs for each scale variable.ResultsThere were 3 Grade 0 (12%), 11 grade 1 (44%), 9 grade 2 (36%) and 2 grade 3 (8%) injuries. Cronbach's α values for grading were 1.00 (inter) and 0.96 (intra), respectively. The intraclass correlation coefficients for the prognostic MRI parameters were between 0.77 and 1.0. The SDDs varied between each parameter.ConclusionsExcellent interobserver and intraobserver reliability was found for grading and prognostic MRI parameters in acute hamstring injuries. In daily practice and research, we can be confident that scoring hamstring injuries by experienced radiologists is reproducible. The documented SDDs allow meaningful clinical inferences to be made when assessing observed and reported changes in MRI status.
Physical activity during pregnancy and the risk of gestational diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials
Authors: Yin Ya-nan , Li Xiang-lian , Tao Tie-jun , Luo Bi-ru , Liao Shu-juan 
Published: September 2013

ObjectivesWe performed a systematic review and meta-analysis to assess the effects of physical activity in preventing gestational diabetes mellitus (GDM).Search strategyWe searched the literature in six electronic databases and bibliographies of relevant articles.Selection criteriaWe included randomised controlled trials on pregnant women who did not have GDM and other complications previously and had increased physical activity as the only intervention. The risk of developing GDM was documented separately for the intervention and control groups.Data collection and analysisTwo reviewers extracted data and assessed quality independently. Data from the included trials were combined using a fixed-effects model. The effect size was expressed as relative risk (RR) and 95% CI.Main resultsOf the 1110 studies identified, six randomised controlled trials met the inclusion criteria. In three trials, the incidence of GDM was lower in the intervention group than in the control group, whereas two trials showed a higher incidence of GDM in the intervention group and the remaining trial found no GDM in either the intervention or control group. The meta-analysis resulted in a relative risk (RR) of GDM of 0.91 (95% CI 0.57 to 1.44), suggesting no significant difference in the risk of developing GDM between the intervention and the control groups. No indication of publication bias was found.ConclusionsEvidence was insufficient to suggest that physical activity during pregnancy might be effective to lower the risk of developing GDM.
Impairment of brainstem implicit learning paradigms differentiates multiple system atrophy (MSA) from idiopathic Parkinson syndrome
Authors: von Lewinski Friederike , Schwan Michaela , Paulus Walter , Trenkwalder Claudia , Sommer Martin 
Published: September 2013

ObjectivesLearning as measured by eyeblink classical conditioning is preserved in patients with idiopathic Parkinson's disease, but severely affected in patients with progressive supranuclear palsy. We here sought to clarify whether procedural learning is impaired in multiple system atrophy (MSA), and whether it may be helpful for the differentiation of parkinsonian syndromes.DesignWe investigated learning using (1) eyeblink classical conditioning with a delay (interstimulus interval 0 ms) and a trace (600 ms) paradigm and (2) a serial reaction time task.SettingParticipants were recruited from academic research centres.Participants11 patients with MSA and 11 healthy controls.ResultsImplicit learning in eyeblink classical conditioning (acquisition of conditioned responses) as well as the serial reaction time task measures of implicit learning (reaction time change) are impaired in patients with MSA as compared with controls, whereas explicit learning as measured by the sequence recall of the serial reaction time task is relatively preserved.AnalysisWe hypothesise that the learning deficits of patients with MSA are due to lesions of cerebellar and connected brainstem areas.ConclusionsA retrospective synopsis of these novel data on patients with MSA and groups of patients with idiopathic Parkinson's disease and progressive supranuclear palsy studied earlier suggest that eyeblink classical conditioning may contribute to the early differentiation of atypical Parkinson syndromes from idiopathic Parkinson's disease. This hypothesis should be tested in a prospective trial.
Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: a retrospective case control study
Authors: Hozumi Hironao , Nakamura Yutaro , Johkoh Takeshi , Sumikawa Hiromitsu , Colby Thomas V , Kono Masato , Hashimoto Dai , Enomoto Noriyuki , Fujisawa Tomoyuki , Inui Naoki , Suda Takafumi , Chida Kingo 
Published: September 2013

ObjectivesTo investigate the risk factors and prognosis associated with acute exacerbation (AE) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).DesignA retrospective case–control study.SettingA single academic hospital.Participants51 consecutive patients diagnosed with RA-ILD between 1995 and 2012. All patients fulfilled the diagnostic criteria of the American College of Rheumatology for RA. ILD was diagnosed on the basis of clinical presentation, pulmonary function tests, high-resolution CT (HRCT) findings and lung biopsy findings.Main outcome measuresOverall survival and cumulative AE incidence were analysed using Kaplan-Meier method. Cox hazards analysis was used to determine significant variables associated with AE occurrence and survival status.ResultsA total of 11 patients (22%) developed AE, with an overall 1-year incidence of 2.8%. Univariate analysis revealed that older age at ILD diagnosis (HR 1.11; 95% CI 1.02 to 1.21; p=0.01), usual interstitial pneumonia (UIP) pattern on HRCT (HR 1.95; 95% CI 1.07 to 3.63; p=0.03) and methotrexate usage (HR 3.04; 95% CI 1.62 to 6.02; p=0.001) were associated with AE. Of 11 patients who developed AE during observation period, 7 (64%) died of initial AE. In survival, AE was a prognostic factor for poor outcome (HR 2.47; 95% CI 1.39 to 4.56; p=0.003).ConclusionsIn patients with RA-ILD, older age at ILD diagnosis, UIP pattern on HRCT and methotrexate usage are associated with the development of AE. Furthermore, AE has a serious impact on their survival.
The value of personalised risk information: a qualitative study of the perceptions of patients with prostate cancer
Authors: Han Paul K J , Hootsmans Norbert , Neilson Michael , Roy Bethany , Kungel Terence , Gutheil Caitlin , Diefenbach Michael , Hansen Moritz 
Published: September 2013

ObjectiveTo explore the experiences of patients with prostate cancer with risk information and their perceptions of the value of personalised risk information in treatment decisions.DesignA qualitative study was conducted using focus groups. Semistructured interviews explored participants’ experiences with using risk information, and their perceptions of the potential value of personalised risk information produced by clinical prediction models.ParticipantsEnglish-speaking patients, ages 54–82, diagnosed with prostate cancer within the past 3 years, residing in rural and non-rural geographic locations in Maine (USA), and attending prostate cancer patient support groups.Setting6 focus groups were conducted with 27 patients; separate groups were held for patients with low-risk, medium-risk and high-risk disease defined by National Comprehensive Cancer Network guidelines.ResultsSeveral participants reported receiving risk information that was imprecise rather than precise, qualitative rather than quantitative, indirect rather than direct and focused on biomarker values rather than clinical outcomes. Some participants felt that personalised risk information could be useful in helping them make better informed decisions, but expressed scepticism about its value. Many participants favoured decision-making strategies that were heuristic-based and intuitive rather than risk-based and deliberative, and perceived other forms of evidence—emotions, recommendations of trusted physicians, personal narratives—as more reliable and valuable in treatment decisions.ConclusionsPatients with prostate cancer appear to have little experience using personalised risk information, may favour heuristic-based over risk-based decision-making strategies and may perceive personalised risk information as less valuable than other types of evidence. These decision-making approaches and perceptions represent potential barriers to the clinical use of personalised risk information. Overcoming these barriers will require providing patients with greater exposure to risk information, education about the nature and value of personalised risk information and training in deliberative decision-making strategies. More research is needed to confirm these findings and address these needs.
Representativeness and optimal use of body mass index (BMI) in the UK Clinical Practice Research Datalink (CPRD)
Authors: Bhaskaran Krishnan , Forbes Harriet J , Douglas Ian , Leon David A , Smeeth Liam 
Published: September 2013

ObjectivesTo assess the completeness and representativeness of body mass index (BMI) data in the Clinical Practice Research Datalink (CPRD), and determine an optimal strategy for their use.DesignDescriptive study.SettingElectronic healthcare records from primary care.ParticipantsA million patient random sample from the UK CPRD primary care database, aged ≥16 years.Primary and secondary outcome measuresBMI completeness in CPRD was evaluated by age, sex and calendar period. CPRD-based summary BMI statistics for each calendar year (2003–2010) were age-standardised and sex-standardised and compared with equivalent statistics from the Health Survey for England (HSE).ResultsBMI completeness increased over calendar time from 37% in 1990–1994 to 77% in 2005–2011, was higher among females and increased with age. When BMI at specific time points was assigned based on the most recent record, calendar–year-specific mean BMI statistics underestimated equivalent HSE statistics by 0.75–1.1 kg/m2. Restriction to those with a recent (≤3 years) BMI resulted in mean BMI estimates closer to HSE (≤0.28 kg/m2underestimation), but excluded up to 47% of patients. An alternative strategy of imputing up-to-date BMI based on modelled changes in BMI over time since the last available record also led to mean BMI estimates that were close to HSE (≤0.37 kg/m2underestimation).ConclusionsCompleteness of BMI in CPRD increased over time and varied by age and sex. At a given point in time, a large proportion of the most recent BMIs are unlikely to reflect current BMI; consequent BMI misclassification might be reduced by employing model-based imputation of current BMI.
Myocardial infarction incidence and survival by ethnic group: Scottish Health and Ethnicity Linkage retrospective cohort study
Authors: Bansal Narinder , Fischbacher Colin M , Bhopal Raj S , Brown Helen , Steiner Markus FC , Capewell Simon ,   on behalf of the Scottish Health and Ethnicity Linkage Study
Published: September 2013

ObjectiveInequalities in coronary heart disease mortality by country of birth are large and poorly understood. However, these data misclassify UK-born minority ethnic groups and provide little detail on whether excess risk is due to increased incidence, poorer survival or both.DesignRetrospective cohort study.SettingGeneral resident population of Scotland.ParticipantsAll those residing in Scotland during the 2001 Census were eligible for inclusion: 2 972 120 people were included in the analysis. The number still residing in Scotland at the end of the study in 2008 is not known.Primary and secondary outcome measuresAs specified in the analysis plan, the primary outcome measures were first occurrence of admission or death due to myocardial infarction and time to event. There were no secondary outcome measures.ResultsAcute myocardial infarction (AMI) incidence risk ratios (95% CIs) relative to white Scottish populations (100) were highest among Pakistani men (164.1 (142.2 to 189.2)) and women (153.7 (120.5, 196.1)) and lowest for men and women of Chinese (39.5 (27.1 to 57.6) and 59.1 (38.6 to 90.7)), other white British (77 (74.2 to 79.8) and 72.2 (69.0 to 75.5)) and other white (83.1 (75.9 to 91.0) and 79.9 (71.5 to 89.3)) ethnic groups. Adjustment for educational qualification did not eliminate these differences. Cardiac intervention uptake was similar across most ethnic groups. Compared to white Scottish, 28-day survival did not differ by ethnicity, except in Pakistanis where it was better, particularly in women (0.44 (0.25 to 0.78)), a difference not removed by adjustment for education, travel time to hospital or cardiac intervention uptake.ConclusionsPakistanis have the highest incidence of AMI in Scotland, a country renowned for internationally high cardiovascular disease rates. In contrast, survival is similar or better in minority ethnic groups. Clinical care and policy should focus on reducing incidence among Pakistanis through more aggressive prevention.