bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Pseudomonas aeruginosa Swarming Motility by 1-Naphthol and Other Bicyclic Compounds Bearing Hydroxyl Groups
Authors: Oura Hiromu , Tashiro Yosuke , Toyofuku Masanori , Ueda Kousetsu , Kiyokawa Tatsunori , Ito Satoshi , Takahashi Yurika , Lee Seunguk , Nojiri Hideaki , Nakajima-Kambe Toshiaki , Uchiyama Hiroo , Futamata Hiroyuki , Nomura Nobuhiko 
Published: February 2015

ABSTRACT

Many bacteria convert bicyclic compounds, such as indole and naphthalene, to oxidized compounds, including hydroxyindoles and naphthols.
Pseudomonas aeruginosa
, a ubiquitous bacterium that inhabits diverse environments, shows pathogenicity against animals, plants, and other microorganisms, and increasing evidence has shown that several bicyclic compounds alter the virulence-related phenotypes of
P. aeruginosa
. Here, we revealed that hydroxyindoles (4- and 5-hydroxyindoles) and naphthalene derivatives bearing hydroxyl groups specifically inhibit swarming motility but have minor effects on other motilities, including swimming and twitching, in
P. aeruginosa
. Further analyses using 1-naphthol showed that this effect is also associated with clinically isolated hyperswarming
P. aeruginosa
cells. Swarming motility is associated with the dispersion of cells from biofilms, and the addition of 1-naphthol maintained biofilm biomass without cell dispersion. We showed that this 1-naphthol-dependent swarming inhibition is independent of changes of rhamnolipid production and the intracellular level of signaling molecule cyclic-di-GMP (c-di-GMP). Transcriptome analyses revealed that 1-naphthol increases gene expression associated with multidrug efflux and represses gene expression associated with aerotaxis and with pyochelin, flagellar, and pilus synthesis. In the present study, we showed that several bicyclic compounds bearing hydroxyl groups inhibit the swarming motility of
P. aeruginosa
, and these results provide new insight into the chemical structures that inhibit the specific phenotypes of
P. aeruginosa
.
Corynebacterium glutamicum Methionine Sulfoxide Reductase A Uses both Mycoredoxin and Thioredoxin for Regeneration and Oxidative Stress Resistance
Authors: Si Meiru , Zhang Lei , Chaudhry Muhammad Tausif , Ding Wei , Xu Yixiang , Chen Can , Akbar Ali , Shen Xihui , Liu Shuang-Jiang 
Published: February 2015

ABSTRACT

Oxidation of methionine leads to the formation of the
S
and
R
diastereomers of methionine sulfoxide (MetO), which can be reversed by the actions of two structurally unrelated classes of methionine sulfoxide reductase (Msr), MsrA and MsrB, respectively. Although MsrAs have long been demonstrated in numerous bacteria, their physiological and biochemical functions remain largely unknown in
Actinomycetes
. Here, we report that a
Corynebacterium glutamicum
methionine sulfoxide reductase A (CgMsrA) that belongs to the 3-Cys family of MsrAs plays important roles in oxidative stress resistance. Deletion of the
msrA
gene in
C. glutamicum
resulted in decrease of cell viability, increase of ROS production, and increase of protein carbonylation levels under various stress conditions. The physiological roles of CgMsrA in resistance to oxidative stresses were corroborated by its induced expression under various stresses, regulated directly by the stress-responsive extracytoplasmic-function (ECF) sigma factor SigH. Activity assays performed with various regeneration pathways showed that CgMsrA can reduce MetO via both the thioredoxin/thioredoxin reductase (Trx/TrxR) and mycoredoxin 1/mycothione reductase/mycothiol (Mrx1/Mtr/MSH) pathways. Site-directed mutagenesis confirmed that Cys56 is the peroxidatic cysteine that is oxidized to sulfenic acid, while Cys204 and Cys213 are the resolving Cys residues that form an intramolecular disulfide bond. Mrx1 reduces the sulfenic acid intermediate via the formation of an
S
-mycothiolated MsrA intermediate (MsrA-SSM) which is then recycled by mycoredoxin and the second molecule of mycothiol, similarly to the glutathione/glutaredoxin/glutathione reductase (GSH/Grx/GR) system. However, Trx reduces the Cys204-Cys213 disulfide bond in CgMsrA produced during MetO reduction via the formation of a transient intermolecular disulfide bond between Trx and CgMsrA. While both the Trx/TrxR and Mrx1/Mtr/MSH pathways are operative in reducing CgMsrA under stress conditions
in vivo
, the Trx/TrxR pathway alone is sufficient to reduce CgMsrA under normal conditions. Based on these results, a catalytic model for the reduction of CgMsrA by Mrx1 and Trx is proposed.
Solution Structure of Acidocin B, a Circular Bacteriocin Produced by Lactobacillus acidophilus M46
Authors: Acedo Jeella Z. , van Belkum Marco J. , Lohans Christopher T. , McKay Ryan T. , Miskolzie Mark , Vederas John C. 
Published: February 2015

ABSTRACT

Acidocin B, a bacteriocin produced by
Lactobacillus acidophilus
M46, was originally reported to be a linear peptide composed of 59 amino acid residues. However, its high sequence similarity to gassericin A, a circular bacteriocin from
Lactobacillus gasseri
LA39, suggested that acidocin B might be circular as well. Acidocin B was purified from culture supernatant by a series of hydrophobic interaction chromatographic steps. Its circular nature was ascertained by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry and tandem mass spectrometry (MS/MS) sequencing. The peptide sequence was found to consist of 58 amino acids with a molecular mass of 5,621.5 Da. The sequence of the acidocin B biosynthetic gene cluster was also determined and showed high nucleotide sequence similarity to that of gassericin A. The nuclear magnetic resonance (NMR) solution structure of acidocin B in sodium dodecyl sulfate micelles was elucidated, revealing that it is composed of four α-helices of similar length that are folded to form a compact, globular bundle with a central pore. This is a three-dimensional structure for a member of subgroup II circular bacteriocins, which are classified based on their isoelectric points of ∼7 or lower. Comparison of acidocin B with carnocyclin A, a subgroup I circular bacteriocin with four α-helices and a pI of 10, revealed differences in the overall folding. The observed variations could be attributed to inherent diversity in their physical properties, which also required the use of different solvent systems for three-dimensional structural elucidation.
How the Necrotrophic Fungus Alternaria brassicicola Kills Plant Cells Remains an Enigma
Authors: Cho Yangrae 
Published: February 2015

ABSTRACT

Alternaria
species are mainly saprophytic fungi, but some are plant pathogens. Seven pathotypes of
Alternaria alternata
use secondary metabolites of host-specific toxins as pathogenicity factors. These toxins kill host cells prior to colonization. Genes associated with toxin synthesis reside on conditionally dispensable chromosomes, supporting the notion that pathogenicity might have been acquired several times by
A. alternata
.
Alternaria brassicicola
, however, seems to employ a different mechanism. Evidence on the use of host-specific toxins as pathogenicity factors remains tenuous, even after a diligent search aided by full-genome sequencing and efficient reverse-genetics approaches. Similarly, no individual genes encoding lipases or cell wall-degrading enzymes have been identified as strong virulence factors, although these enzymes have been considered important for fungal pathogenesis. This review describes our current understanding of toxins, lipases, and cell wall-degrading enzymes and their roles in the pathogenesis of
A. brassicicola
compared to those of other pathogenic fungi. It also describes a set of genes that affect pathogenesis in
A. brassicicola
. They are involved in various cellular functions that are likely important in most organisms and probably indirectly associated with pathogenesis. Deletion or disruption of these genes results in weakly virulent strains that appear to be sensitive to the defense mechanisms of host plants. Finally, this review discusses the implications of a recent discovery of three important transcription factors associated with pathogenesis and the putative downstream genes that they regulate.
Puf4 Regulates both Splicing and Decay of
HXL1
mRNA Encoding the Unfolded Protein Response Transcription Factor in Cryptococcus neoformans
Authors: Glazier Virginia E. , Kaur Jan Naseer , Brown Nancy T. , Rivera Ashley A. , Panepinto John C. 
Published: February 2015

ABSTRACT

The endoplasmic reticulum (ER) responds to errors in protein folding or processing by induction of the unfolded protein response (UPR). During conditions of ER stress, unconventional splicing of an mRNA encoding the UPR-responsive transcription factor occurs at the ER surface, resulting in activation of the UPR. UPR activation is necessary for adaptation to ER stress and for the pathogenic fungus
Cryptococcus neoformans
is an absolute requirement for temperature adaptation and virulence. In this study, we have determined that
C. neoformans
has co-opted a conserved PUF RNA binding protein to regulate the posttranscriptional processing of the
HXL1
mRNA encoding the UPR transcription factor. PUF elements were identified in both the 5′ and 3′ untranslated regions of the
HXL1
transcript, and both elements bound Puf4. Deletion of
PUF4
resulted in delayed unconventional splicing of
HXL1
mRNA and delayed induction of Hxl1 target genes. In addition, the
HXL1
transcript was stabilized in the absence of Puf4. The
puf4
Δ mutant exhibited temperature sensitivity but was as virulent as the wild type, despite a reduction in fungal burden in the brains of infected mice. Our results reveal a novel regulatory role in which a PUF protein influences the unconventional splicing of the mRNA encoding the UPR-responsive transcription factor. These data suggest a unique role for a PUF protein in controlling UPR kinetics via the posttranscriptional regulation of the mRNA encoding the UPR transcription factor Hxl1.
Psychotherapy for depression in children and adolescents: study protocol for a systematic review and network meta-analysis
Authors: Qin Bin , Zhou Xinyu , Michael Kurt D , Liu Yiyun , Whittington Craig , Cohen David , Zhang Yuqing , Xie Peng 
Published: February 2015

IntroductionDepression is common among children and adolescents and is associated with significantly negative effects. A number of structured psychosocial treatments are administered for depression in children and adolescents; however, evidence of their effectiveness is not clear. We describe the protocol of a systematic review and network meta-analysis to evaluate the efficacy, quality of life, tolerability and acceptability of the use of psychological intervention for this young population.Methods and analysisWe will search PubMed, EMBASE, CENTRAL (the Cochrane Central Register of Controlled Trials), Web of Science, PsycINFO, CINAHL, LiLACS, Dissertation Abstracts, European Association for Grey Literature Exploitation (EAGLE) and the National Technical Information Service (NTIS) from inception to July 2014. There will be no restrictions on language, publication year or publication type. Only randomised clinical trials (RCTs) with psychosocial treatments for depression in children and adolescents will be considered. The primary outcome of efficacy will be the mean overall change of the total score in continuous depression severity scales from baseline to end point. Data will be independently extracted by two reviewers. Traditional pairwise meta–analyses will be performed for studies that directly compared different treatment arms. Then we will perform a Bayesian network meta–analyses to compare the relative efficacy, quality of life, tolerability and acceptability of different psychological intervention. Subgroup analyses will be performed by the age of participants and the duration of psychotherapy, and sensitivity analyses will be conducted to assess the robustness of the findings.Ethics and disseminationNo ethical issues are foreseen. The results will be published in a peer–reviewed journal and disseminated electronically and in print. The meta–analysis may be updated to inform and guide management of depression in children and adolescents.Trials registration numberPROSPERO CRD42014010014.
Hip fracture evaluation with alternatives of total hip arthroplasty versus hemiarthroplasty (HEALTH): protocol for a multicentre randomised trial
Authors: Bhandari Mohit , Devereaux P J , Einhorn Thomas A , Thabane Lehana , Schemitsch Emil H , Koval Kenneth J , Frihagen Frede , Poolman Rudolf W , Tetsworth Kevin , Guerra-Farfán Ernesto , Madden Kim , Sprague Sheila , Guyatt Gordon ,   HEALTH Investigators
Published: February 2015

IntroductionHip fractures are a leading cause of mortality and disability worldwide, and the number of hip fractures is expected to rise to over 6 million per year by 2050. The optimal approach for the surgical management of displaced femoral neck fractures remains unknown. Current evidence suggests the use of arthroplasty; however, there is lack of evidence regarding whether patients with displaced femoral neck fractures experience better outcomes with total hip arthroplasty (THA) or hemiarthroplasty (HA). The HEALTH trial compares outcomes following THA versus HA in patients 50 years of age or older with displaced femoral neck fractures.Methods and analysisHEALTH is a multicentre, randomised controlled trial where 1434 patients, 50 years of age or older, with displaced femoral neck fractures from international sites are randomised to receive either THA or HA. Exclusion criteria include associated major injuries of the lower extremity, hip infection(s) and a history of frank dementia. The primary outcome is unplanned secondary procedures and the secondary outcomes include functional outcomes, patient quality of life, mortality and hip-related complications—both within 2 years of the initial surgery. We are using minimisation to ensure balance between intervention groups for the following factors: age, prefracture living, prefracture functional status, American Society for Anesthesiologists (ASA) Class and centre number. Data analysts and the HEALTH Steering Committee are blinded to the surgical allocation throughout the trial. Outcome analysis will be performed using a χ2test (or Fisher's exact test) and Cox proportional hazards modelling estimate. All results will be presented with 95% CIs.Ethics and disseminationThe HEALTH trial has received local and McMaster University Research Ethics Board (REB) approval (REB#: 06-151).ResultsOutcomes from the primary manuscript will be disseminated through publications in academic journals and presentations at relevant orthopaedic conferences. We will communicate trial results to all participating sites. Participating sites will communicate results with patients who have indicated an interest in knowing the results.Trial registration numberThe HEALTH trial is registered with clinicaltrials.gov (NCT00556842).
Self-rated health and standard risk factors for myocardial infarction: a cohort study
Authors: Waller Göran , Janlert Urban , Norberg Margareta , Lundqvist Robert , Forssén Annika 
Published: February 2015

ObjectiveTo investigate the relationship between self-rated health, adjusted for standard risk factors, and myocardial infarction.DesignPopulation-based prospective cohort study.SettingEnrolment took place between 1990 and 2004 in Västerbotten County, SwedenParticipantsEvery year, persons in the total population, aged 40, 50 or 60 were invited. Participation rate was 60%. The cohort consisted of 75 386 men and women. After exclusion for stroke or myocardial infarction before, or within 12 months after enrolment or death within 12 months after enrolment, 72 530 persons remained for analysis. Mean follow-up time was 13.2 years.Outcome measuresCox regression analysis was used to estimate HRs for the end point of first non-fatal or fatal myocardial infarction. HR were adjusted for age, sex, systolic blood pressure, total cholesterol, smoking, diabetes, body mass index, education, physical activity and self-rated health in the categories very good; pretty good; somewhat good; pretty poor or poor.ResultsIn the cohort, 2062 persons were diagnosed with fatal or non-fatal myocardial infarction. Poor self-rated health adjusted for sex and age was associated with the outcome with HR 2.03 (95% CI 1.45 to 2.84). All categories of self-rated health worse than very good were statistically significant and showed a dose–response relationship. In a multivariable analysis with standard risk factors (not including physical activity and education) HR was attenuated to 1.61 (95% CI 1.13 to 2.31) for poor self-rated health. All categories of self-rated health remained statistically significant. We found no interaction between self-rated health and standard risk factors except for poor self-rated health and diabetes.ConclusionsThis study supports the use of self-rated health as a standard risk factor among others for myocardial infarction. It remains to demonstrate whether self-rated health adds predictive value for myocardial infarction in combined algorithms with standard risk factors.
The Belgian policy of funding antimicrobial stewardship in hospitals and trends of selected quality indicators for antimicrobial use, 1999–2010: a longitudinal study
Authors: Lambert Marie-Laurence , Bruyndonckx Robin , Goossens Herman , Hens Niel , Aerts Marc , Catry Boudewijn , Neely Fiona , Vogelaers Dirk , Hammami Naima 
Published: February 2015

ObjectivesIn order to improve antimicrobial (AM) use, a policy of providing technical and financial support to AM management teams (AMTs) was rolled out in all Belgian hospitals between 2002 and 2008. We aimed to analyse the association of this policy with AM use for the two indications accounting for the largest number of patients receiving AM: prophylaxis for major lower limb orthopaedic surgery and pneumonia.Design, setting, participantsWe used patient-level data routinely collected in all Belgian acute care hospitals between 1999 and 2010. We modelled trends for selected quality indicators (QIs) using the year of AMT implementation in each hospital as the main ‘change point’, with fine-tuned case-mix adjustment. Of all admissions for lower limb orthopaedic surgery, and pneumonia between 1999 and 2010, 90% (325 094) and 95% (327 635), respectively, were found eligible for analyses.OutcomesThe surgery QI was defined as: cefazolin, dose in the expected range, and no use of other AM. For pneumonia, QIs were: ratio of oral/parenteral defined daily doses (DDD, O/P QI), and mean number of DDD minus penicillin, per 100 days of hospitalisation (DDD QI).ResultsBetween 1999 and 2010, the surgery QI improved from 59% to 71%, the O/P QI from 0.72 to 0.97, and the DDD QI from 96 to 64. Heterogeneity between hospitals was high. Overall, no association was found with the year of implementation of the AMT.ConclusionsImprovements have been observed but could not be related at the national level to the policy under study. However, these results cannot be extrapolated to other QIs for AM use in hospitals. Our findings do not question the need for AMT, nor the need for continuation of AMT funding. Several recommendations can be made in order to make the best of Belgium's unique political and financial commitments in that field.
Smad4 inactivation predicts for worse prognosis and response to fluorouracil-based treatment in colorectal cancer
Authors: Kozak Margaret M , von Eyben Rie , Pai Jonathan , Vossler Stephen R , Limaye Maneesha , Jayachandran Priya , Anderson Eric M , Shaffer Jenny L , Longacre Teri , Pai Reetesh K , Koong Albert C , Chang Daniel T 
Published: February 2015

AimsTo determine whether expression of Smad4, a tumour suppressor found to be absent in 10% of colorectal cancer (CRC), is associated with outcomes in patients with CRC.MethodsTumour samples from 241 consecutive patients with CRC who underwent upfront colon resection between 2005 and 2009 were obtained. Triplicate tissue cores from resected primary colon tumours and matched normal controls were used to construct the tissue microarrays (TMAs). We examined the expression of Smad4 using immunohistochemistry. Clinicopathological records were obtained for all patients. TMAs were reviewed by two pathologists and scored as either ‘positive’ or ‘negative’ for nuclear staining. In total, 21 of 241 tumours (8.6%) were Smad4 negative.ResultsLoss of Smad4 expression correlated with significantly worse overall survival (OS) (p=0.011) and disease-free survival (DFS) (p=0.024). Patients with loss of Smad4 expression had a median OS of 31 months compared with 89 months positive Smad4 expression. Loss of Smad4 remained significant on multivariate analysis for OS (p=0.0097). In patients with node-positive disease, loss of Smad4 predicts for worse DFS (p=0.012). In patients with metastatic and recurrent disease, Smad4 loss predicts for worse OS (p=0.012). Of the patients that received capecitabine over the course of their treatment, those with Smad4 loss (n=13) had significantly worse DFS (p=0.003) and OS (p=0.0007).ConclusionsLoss of Smad4 expression is associated with worse DFS and OS in multiple subsets of patients with CRC. Further studies are required to validate our findings and ascertain the role of Smad4 status in the management of this disease.
A multistep cytological approach for patients with jaundice and biliary strictures of indeterminate origin
Authors: Boldorini Renzo , Paganotti Alessia , Andorno Silvano , Orlando Stefania , Mercalli Francesca , Orsello Marco , Ballarè Marco , Magnani Corrado , Sartori Massimo 
Published: February 2015

AimsFluorescence in situ hybridisation (FISH) increases the sensitivity for detecting pancreatobiliary tract cancer over routine cytology. In this study, diagnostic accuracy and costs of cytology and FISH in detecting cancer in patients with jaundice with biliary strictures were assessed.MethodsBrushing specimens from 109 patients with jaundice were obtained during endoscopic retrograde cholangiopancreatography and examined by cytology and FISH. The specimens were considered FISH-positive for malignancy if at least five polysomic cells or 10 cells with homozygous or heterozygous 9p21/p16 deletion were detected. Definitive diagnosis of the stricture as benign or malignant relied on surgical pathology (45 cases) or clinical-radiological follow-up >18 months (64 cases). We calculated costs of cytology and FISH based on the reimbursement from the Piedmont region, Italy (respectively, €33 and €750).ResultsNinety of 109 patients had evidence of malignancy (44 pancreatic carcinomas, 36 cholangiocarcinomas, 5 gallbladder carcinomas, 5 other cancers), while 19 had benign strictures. Routine cytology showed 42% sensitivity, but 100% specificity for the diagnosis of malignancy, while FISH-polysomy showed 70% sensitivity with 100% specificity and FISH-polysomy plus homozygous or heterozygous 9p21/p16 deletion showed 76% sensitivity with 100% specificity. The cost per additional correct diagnosis of cancer obtained by FISH, in comparison with cytology, was €1775 using a sequential cytological approach (ie, performing FISH only in patients with negative or indeterminate cytology).ConclusionsFISH should be recommended as the second step in detecting cancer in patients with jaundice with pancreatobiliary tract strictures and cytology negative or indeterminate for malignancy.