bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surface Layers of Clostridium difficile Endospores
Authors: Permpoonpattana Patima , Tolls Elisabeth H. , Nadem Ramez , Tan Sisareuth , Brisson Alain , Cutting Simon M. 
Published: September 2011

ABSTRACT

Clostridium difficile
is an important human pathogen and one where the primary cause of disease is due to the transmission of spores. We have investigated the proteins found in the outer coat layers of
C. difficile
spores of pathogenic strain 630 (CD630). Five coat proteins, CotA, CotB, CotCB, CotD, and CotE, were shown to be expressed on the outer coat layers of the spore. We demonstrate that purified spores carry catalase, peroxiredoxin, and chitinase activity and that this activity correlates with the predicted functions of three spore coat proteins identified here, CotCB, CotD, and CotE. CotCB and CotD are putative manganese catalases, and CotE is a novel bifunctional protein with peroxiredoxin activity at its amino terminus and chitinase activity at its carboxy terminus. These enzymes could play an important role in coat assembly by polymerizing protein monomers in the coat. CotE, in addition to a role in macromolecular degradation, could play an important role in inflammation, and this may be of direct relevance to the development of the gastrointestinal symptoms that accompany
C. difficile
infection. Although specific enzyme activity has not yet been assigned to the proteins identified here, this work provides the first detailed study of the
C. difficile
spore coat.
Just-in-Time Control of Spo0A Synthesis in Bacillus subtilis by Multiple Regulatory Mechanisms
Authors: Chastanet Arnaud , Losick Richard 
Published: September 2011

ABSTRACT

The response regulator Spo0A governs multiple developmental processes in
Bacillus subtilis
, including most conspicuously sporulation. Spo0A is activated by phosphorylation via a multicomponent phosphorelay. Previous work has shown that the Spo0A protein is not rate limiting for sporulation. Rather, Spo0A is present at high levels in growing cells, rapidly rising to yet higher levels under sporulation-inducing conditions, suggesting that synthesis of the response regulator is subject to a just-in-time control mechanism. Transcription of
spo0A
is governed by a promoter switching mechanism, involving a vegetative, σ
A
-recognized promoter, P
v
, and a sporulation σ
H
-recognized promoter, P
s
, that is under phosphorylated Spo0A (Spo0A∼P) control. The
spo0A
regulatory region also contains four (including one identified in the present work) conserved elements that conform to the consensus binding site for Spo0A∼P binding sites. These are herein designated O
1
, O
2
, O
3
, and O
4
in reverse order of their proximity to the coding sequence. Here we report that O
1
is responsible for repressing P
v
during the transition to stationary phase, that O
2
is responsible for repressing P
s
during growth, that O
3
is responsible for activating P
s
at the start of sporulation, and that O
4
is dispensable for promoter switching. We also report that Spo0A synthesis is subject to a posttranscriptional control mechanism such that translation of mRNAs originating from P
v
is impeded due to RNA secondary structure whereas mRNAs originating from P
s
are fully competent for protein synthesis. We propose that the opposing actions of O
2
and O
3
and the enhanced translatability of mRNAs originating from P
s
create a highly sensitive, self-reinforcing switch that is responsible for producing a burst of Spo0A synthesis at the start of sporulation.
Competence in Streptococcus pneumoniae Is Regulated by the Rate of Ribosomal Decoding Errors
Authors: Stevens Kathleen E. , Chang Diana , Zwack Erin E. , Sebert Michael E. 
Published: September 2011

ABSTRACT

Competence for genetic transformation in
Streptococcus pneumoniae
develops in response to accumulation of a secreted peptide pheromone and was one of the initial examples of bacterial quorum sensing. Activation of this signaling system induces not only expression of the proteins required for transformation but also the production of cellular chaperones and proteases. We have shown here that activity of this pathway is sensitively responsive to changes in the accuracy of protein synthesis that are triggered by either mutations in ribosomal proteins or exposure to antibiotics. Increasing the error rate during ribosomal decoding promoted competence, while reducing the error rate below the baseline level repressed the development of both spontaneous and antibiotic-induced competence. This pattern of regulation was promoted by the bacterial HtrA serine protease. Analysis of strains with the
htrA
(S234A) catalytic site mutation showed that the proteolytic activity of HtrA selectively repressed competence when translational fidelity was high but not when accuracy was low. These findings redefine the pneumococcal competence pathway as a response to errors during protein synthesis. This response has the capacity to address the immediate challenge of misfolded proteins through production of chaperones and proteases and may also be able to address, through genetic exchange, upstream coding errors that cause intrinsic protein folding defects. The competence pathway may thereby represent a strategy for dealing with lesions that impair proper protein coding and for maintaining the coding integrity of the genome.

IMPORTANCE
The signaling pathway that governs competence in the human respiratory tract pathogen
Streptococcus pneumoniae
regulates both genetic transformation and the production of cellular chaperones and proteases. The current study shows that this pathway is sensitively controlled in response to changes in the accuracy of protein synthesis. Increasing the error rate during ribosomal decoding induced competence, while decreasing the error rate repressed competence. This pattern of regulation was promoted by the HtrA protease, which selectively repressed competence when translational fidelity was high but not when accuracy was low. Our findings demonstrate that this organism is able to monitor the accuracy of information used for protein biosynthesis and suggest that errors trigger a response addressing both the immediate challenge of misfolded proteins and, through genetic exchange, upstream coding errors that may underlie protein folding defects. This pathway may represent an evolutionary strategy for maintaining the coding integrity of the genome.
A Novel Mechanism of High-Level, Broad-Spectrum Antibiotic Resistance Caused by a Single Base Pair Change in Neisseria gonorrhoeae
Authors: Ohneck Elizabeth A. , Zalucki Yaramah M. , Johnson Paul J. T. , Dhulipala Vijaya , Golparian Daniel , Unemo Magnus , Jerse Ann E. , Shafer William M. 
Published: September 2011

ABSTRACT

The MtrC-MtrD-MtrE multidrug efflux pump of
Neisseria gonorrhoeae
confers resistance to a diverse array of antimicrobial agents by transporting these toxic compounds out of the gonococcus. Frequently in gonococcal strains, the expression of the
mtrCDE
operon is differentially regulated by both a repressor, MtrR, and an activator, MtrA. The
mtrR
gene lies 250 bp upstream of and is transcribed divergently from the
mtrCDE
operon. Previous research has shown that mutations in the
mtrR
coding region and in the
mtrR
-
mtrCDE
intergenic region increase levels of gonococcal antibiotic resistance and
in vivo
fitness. Recently, a C-to-T transition mutation 120 bp upstream of the
mtrC
start codon, termed
mtr
120
, was identified in strain MS11 and shown to be sufficient to confer high levels of antimicrobial resistance when introduced into strain FA19. Here we report that this mutation results in a consensus −10 element and that its presence generates a novel promoter for
mtrCDE
transcription. This newly generated promoter was found to be stronger than the wild-type promoter and does not appear to be subject to MtrR repression or MtrA activation. Although rare, the
mtr
120
mutation was identified in an additional clinical isolate during sequence analysis of antibiotic-resistant strains cultured from patients with gonococcal infections. We propose that
cis
-acting mutations can develop in gonococci that significantly alter the regulation of the
mtrCDE
operon and result in increased resistance to antimicrobials.

IMPORTANCE
Gonorrhea is the second most prevalent sexually transmitted bacterial infection and a worldwide public health concern. As there is currently no vaccine against
Neisseria gonorrhoeae
, appropriate diagnostics and subsequent antibiotic therapy remain the primary means of infection control. However, the effectiveness of antibiotic treatment is constantly challenged by the emergence of resistant strains, mandating a thorough understanding of resistance mechanisms to aid in the development of new antimicrobial therapies and genetic methods for antimicrobial resistance testing. This study was undertaken to characterize a novel mechanism of antibiotic resistance regulation in
N. gonorrhoeae
. Here we show that a single base pair mutation generates a second, stronger promoter for
mtrCDE
transcription that acts independently of the known efflux system regulators and results in high-level antimicrobial resistance.
Infliximab therapy downregulation of basic fibroblast growth factor/syndecan 1 link: a possible molecular pathway of mucosal healing in ulcerative colitis
Authors: Ierardi Enzo , Giorgio Floriana , Zotti Mariangela , Rosania Rosa , Principi Mariabeatrice , Marangi Stefania , Della Valle Nicola , De Francesco Vincenzo , Di Leo Alfredo , Ingrosso Marcello , Panella Carmine 
Published: September 2011

BackgroundIt is known that syndecan 1 in inflammatory bowel diseases is able to migrate from epithelial basolateral site to the stromal area and apical surface of epithelium with a consequent activation and modulation of basic fibroblast growth factor (bFGF), and this process sustains mucosal healing of ulcers. On the other hand, tumour necrosis factor (TNF) α mucosal levels are directly related to the entity of the damage in these disorders.Aim of the studyA ‘post-hoc’ retrospective study was performed to estimate mucosal TNF α in rectal biopsies of subjects with ulcerative colitis (UC) before and after effective infliximab therapy and its relationship with syndecan 1, bFGF and endoscopic mucosal healing.Material and methodsParaffin-embedded rectal samples from 12 patients with UC responders to infliximab were analysed for TNF α, syndecan 1 and bFGF before and 6 months after therapy using a real-time reverse transcriptase polymersase chain reaction. Additionally, syndecan 1 location was evaluated by immunohistochemistry. Samples from 12 subjects with irritable bowel symptoms without endoscopic/histological abnormalities represented the control group. Mucosal healing induced by the treatment was defined by an endoscopic Mayo subscore changing from 2–3 to 0. ANOVA plus Student–Newman–Keuls was used for statistical analysis.ResultsThe authors found that in the active disease, an increase in TNF α (p<0.001) is accompanied by raised levels of both syndecan 1 (p<0.005) and bFGF (p<0.005) compared with the control group. Infliximab-induced TNF α decrease to levels similar to controls is associated with both endoscopic mucosal healing and adhesion molecule/growth factor significant reduction. Additionally, syndecan 1 location, which is predominant in the stromal cells and apical epithelium in the active disorder, is quite exclusively located at the basolateral epithelial area in both healed mucosa and controls.ConclusionsBalanced interaction among TNF α inhibition by infliximab, syndecan 1 migration, bFGF repair modulation and final adhesion molecule reversal to its normal location might represent a suitable molecular pathway of endoscopic mucosal healing in UC.
CT perfusion-guided patient selection for endovascular treatment of acute ischemic stroke is safe and effective
Authors: Turk Aquilla , Magarik Jordan Asher , Chaudry Imran , Turner Raymond D , Nicholas Joyce , Holmstedt Christine A , Chalela Julio , Hays Angela , Lazaridis Christos , Jauch Edward , Chimowitz Marc , Turan Tanya , Adams Robert 
Published: September 2011

BackgroundTraditional treatment in acute ischemic stroke is based on time criteria when administering intravenous and intra-arterial therapies. However, recent evidence suggests that image-based criteria may be useful for selecting patients for intra-arterial interventions. The use of CT perfusion (CTP)-based criteria, regardless of time from symptom onset, in patient selection for intra-arterial treatment of ischemic stroke was assessed.MethodsPatients with ischemic stroke who presented to the emergency department at the Medical University of South Carolina with a National Institute of Health Stroke Scale score of ≥ 8, regardless of time from symptom onset, were assessed retrospectively. CTP maps were qualitatively assessed for the presence of penumbra and infarction. Selected patients underwent mechanical aspiration of their occlusion using the Penumbra system. Functional outcome was then recorded using the modified Rankin scale (mRS) at 90 days or the closest follow-up to 90 days.Results53 patients were included in the study. The median time from symptom onset to groin vascular access was 6.3 h. Eight patients (15%) had bleeding complications including subarachnoid hemorrhage, parenchymal hemorrhage and intraventricular hemorrhage. After CTP-based selection, the patients were divided into two groups for analysis: ≤6 h and >6 h from symptom onset to endovascular procedure. No difference was found in functional outcome between the two groups (38.5% and 40.7% achieved 90-day mRS ≤2, respectively (p=1.0) and 57.7% and 51.9% achieved 90-day mRS ≤3, respectively (p=0.785)). There was no difference in the rate of intracranial hemorrhage between the two groups (11.5 vs 18.5, p=0.704).ConclusionThis study demonstrated similar rates of good functional outcome and intracranial hemorrhage in patients with ischemic stroke when endovascular treatment was performed based on CTP selection rather than time-guided selection. These findings suggest that endovascular reperfusion in ischemic stroke may be effective and safe, and may allow patient selection not solely based on time from symptom onset.
Serum Galectin-2, -4, and -8 Are Greatly Increased in Colon and Breast Cancer Patients and Promote Cancer Cell Adhesion to Blood Vascular Endothelium
Authors: Barrow Hannah , Guo Xiuli , Wandall Hans H. , Pedersen Johannes W. , Fu Bo , Zhao Qicheng , Chen Chen , Rhodes Jonathan M. , Yu Lu-Gang 
Published: September 2011

AbstractPurpose: Adhesion of disseminating tumor cells to the blood vascular endothelium is a pivotal step in metastasis. Previous investigations have shown that galectin-3 concentrations are increased in the bloodstream of patients with cancer and that galectin-3 promotes adhesion of disseminating tumor cells to vascular endothelium in vitro and experimental metastasis in vivo. This study determined the levels of galectin-1, -2, -3, -4, -8, and -9 in the sera of healthy people and patients with colon and breast cancer and assessed the influence of these galectins on cancer-endothelium adhesion.Experimental Design: Serum galectins and auto–anti-MUC1 antibodies were assessed using ELISA and mucin protein (MUC1) glycan microarrays, and cancer-endothelium adhesion was determined using monolayers of human microvascular lung endothelial cells.Results: The levels of serum galectin-2, -3, -4, and -8 were significantly increased up to 31-fold in patients with cancer and, in particular, those with metastases. As previously shown for galectin-3, the presence of these galectins enhances cancer-endothelium adhesion by interaction with the Thomsen-Friedenreich (TF; Galβ1,3GalNAcα-) disaccharide on cancer-associated MUC1. This causes MUC1 cell surface polarization, thus exposing underlying adhesion molecules that promote cancer-endothelium adhesion. Elevated circulating galectin-2 levels were associated with increased mortality in patients with colorectal cancer, but this association was suppressed when anti-MUC1 antibodies with specificity for the TF epitope of MUC1 were also present in the circulation.Conclusions: Increased circulation of several members of the galectin family is common in patients with cancer and these may, like circulating galectin-3, also be involved in metastasis promotion. Clin Cancer Res; 17(22); 7035–46. ©2011 AACR.
Thin-Cap Fibroatheroma as High-Risk Plaque for Microvascular Obstruction in Patients With Acute Coronary Syndrome
Authors: Ozaki Yuichi , Tanaka Atsushi , Tanimoto Takashi , Kitabata Hironori , Kashiwagi Manabu , Kubo Takashi , Takarada Shigeho , Ishibashi Kohei , Komukai Kenichi , Ino Yasushi , Hirata Kumiko , Mizukoshi Masato , Imanishi Toshio , Akasaka Takashi 
Published: September 2011

Background—
Plaque contents can cause microvascular impairment, which is an important determinant of clinical outcomes in patients with acute coronary syndrome (ACS). We hypothesized that percutaneous coronary intervention (PCI) for thin-cap fibroatheroma (TCFA) could easily disrupt the fibrous cap and expose the contents of plaque to coronary flow, possibly resulting in microvascular obstruction (MVO). The purpose of this study was to investigate whether TCFA was associated with MVO after PCI in patients with ACS.

Methods and Results—

We enrolled 115 patients with ACS who were successfully recanalized with PCI. The patients were divided into a ruptured plaque group (n=59), a nonrupture with TCFA group (n=21), and a nonrupture and non-TCFA group (n=35), according to optical coherence tomography findings of the culprit lesion. Using contrast-enhanced MRI, we assessed MVO. There were no statistically significant differences in patient characteristics. The nonrupture with TCFA group more frequently presented MVO (ruptured plaque, 27%; versus nonrupture with TCFA, 43%; versus non-TCFA and nonrupture, 9%;
P
=0.012). The prevalence of MVO increases as cap thickness decreases.

Conclusions—
TCFA is more frequently associated with MVO after PCI. TCFA is a high-risk plaque for MVO after PCI in patients with ACS.
Role of Stromal Cell‐Derived Factor‐1 Expression in the Injured Mouse Auditory Nerve
Authors: Kilpatrick Lauren A. , Zhu Juhong , Lee Fu‐Shing , Lang Hainan 
Published: September 2011

ObjectiveThe degeneration of hair cells and spiral ganglion neurons (SGNs) is an important pathologic process in the development of sensorineural hearing loss. In a murine model, predictable and reproducible damage to SGNs occurs through the application of ouabain to the round window. Recent evidence has shown that the chemokine stromal cell–derived factor‐1 (SDF‐1) is a potent chemoattractant of hematopoietic stem cells (HSCs) and provides trophic support to injured tissues during development and maturation. The hypothesis for the current study is that expression of SDF‐1 plays an important role in protecting SGNs and preventing further degeneration in the setting of cochlear injury.Study DesignProspective, controlled.SettingAcademic research laboratory.Subject and MethodsAuditory brainstem response (ABR) and the expression of SDF‐1 mRNA and protein were examined 1, 3, 7, 14, and 30 days after application of ouabain in 35 adult mice.ResultsFollowing ouabain application, real‐time reverse‐transcription polymerase chain reaction for SDF demonstrates increased mRNA expression following ouabain injury in nontransplanted mice. A significant increase in SDF protein expression was also observed using immunolabeling techniques and Western blot analysis.ConclusionsSDF‐1 expression is increased in the auditory nerve following cochlear injury. Further knowledge about the cochlear microenvironment, including SDF‐1, is critical to maximizing HSC engraftment in the injured cochlea and providing a therapeutic option for sensorineural hearing loss.
Radiofrequency Inferior Turbinate Reduction
Authors: Garzaro Massimiliano , Pezzoli Matteo , Landolfo Vincenzo , Defilippi Simona , Giordano Carlo , Pecorari Giancarlo 
Published: September 2011

ObjectiveThe aim of this study was to assess the long‐term effects of radiofrequency inferior turbinate reduction (RITR) on nasal function in patients affected by nasal obstruction secondary to turbinate hypertrophy, focusing attention on increased sense of smell and its persistence after a 2‐year follow‐up.Study DesignCase series with planned data collection.SettingENT division, university hospital.Subjects and MethodsA total of 40 consecutive patients undergoing RITR for allergic or nonallergic chronic rhinitis with inferior turbinate hypertrophy were included. We planned a series of tests, including the “Sniffin’ Sticks” test battery, anterior rhinomanometry, and the nasal Obstruction Symptom Evaluation (NOSE) scale, on the day of the procedure and at the 2‐month and 2‐year follow‐up visits.ResultsOf the 40 patients, 35 completed all the objective and subjective examinations on the day of the procedure and at the 2‐month and 2‐year follow‐up visits. The authors found a significant decrease in nasal resistances from a mean of 1.13 Pa/cm3s−1 preoperatively to a mean of 0.29 Pa/cm3s−1 2 years postoperatively and improvement in odor threshold, discrimination, and identification scores 2 years postoperatively. The NOSE score diminished significantly 2 years after surgery from a mean of 23.14 to a mean of 4.14 (all P <. 01 with the t test for repeated measures).ConclusionThis long‐term evaluation showed that radiofrequency treatment for allergic or nonallergic inferior turbinate hypertrophy appeared to provide improvement in olfaction, decrease nasal resistances, and have subjective benefits, maintained 2 years after the procedure.
Return-to-Sport Outcomes at 2 to 7 Years After Anterior Cruciate Ligament Reconstruction Surgery
Authors: Ardern Clare L. , Taylor Nicholas F. , Feller Julian A. , Webster Kate E. 
Published: September 2011

Background: Most people have not returned to their preinjury level of sports participation at 12 months after anterior cruciate ligament (ACL) reconstruction surgery. Twelve months’ follow-up may be too early to assess return-to-sport outcomes accurately. Purpose: This study was undertaken to evaluate the medium-term return-to-sport outcomes after ACL reconstruction surgery. Study Design: Case series; Level of evidence, 3. Methods: A self-report questionnaire was used to collect data at 2 to 7 years after ACL reconstruction surgery regarding preinjury sports participation, postoperative sports participation, and subjective knee function. The main inclusion criteria were participation in regular sports activity before injury and the attendance at routine surgical follow-up appointments. Results: A total of 314 participants (mean age, 32.5 ± 10.2 years) were included at a mean 39.6 ± 13.8 months after ACL reconstruction surgery. At follow-up, 45% were playing sport at their preinjury level and 29% were playing competitive sport. Ninety-three percent of the study sample had attempted sport at some time after their ACL reconstruction surgery. Those who had not attempted their preinjury level of sport by 12 months after surgery were just as likely to have returned to preinjury level by 39 months after surgery as those who had played sport by 12 months (risk ratio, 1.1; 95% confidence interval, 0.76-1.6). Conclusion: Less than 50% of the study sample had returned to playing sport at their preinjury level or returned to participating in competitive sport when surveyed at 2 to 7 years after ACL reconstruction surgery. Return to the preinjury level of sport at 12 months after surgery was not predictive of participation at the preinjury level in the medium term, which suggests that people who return to sport within 12 months may not maintain their sports participation.