bluuebunny/crossref_metadata_2025_split huggingface dataset:
RgpF Is Required for Maintenance of Stress Tolerance and Virulence in Streptococcus mutans
Authors: Kovacs C. J. , Faustoferri R. C. , Quivey R. G. 
Published: September 2017

ABSTRACT

Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. In
Streptococcus mutans
, the cell wall is composed primarily of a rhamnose-glucose polysaccharide (RGP) linked to the peptidoglycan. Despite extensive studies describing its formation and composition, the potential roles for RGP in
S. mutans
biology have not been well investigated. The present study characterizes the impact of RGP disruption as a result of the deletion of
rgpF
, the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP. The Δ
rgpF
mutant strain displayed an overall reduced fitness compared to the wild type, with heightened sensitivities to various stress-inducing culture conditions and an inability to tolerate acid challenge. The loss of
rgpF
caused a perturbation of membrane-associated functions known to be critical for aciduricity, a hallmark of
S. mutans
acid tolerance. The proton gradient across the membrane was disrupted, and the Δ
rgpF
mutant strain was unable to induce activity of the F
1
F
o
ATPase in cultures grown under low-pH conditions. Further, the virulence potential of
S. mutans
was also drastically reduced following the deletion of
rgpF
. The Δ
rgpF
mutant strain produced significantly less robust biofilms, indicating an impairment in its ability to adhere to hydroxyapatite surfaces. Additionally, the Δ
rgpF
mutant lost competitive fitness against oral peroxigenic streptococci, and it displayed significantly attenuated virulence in an
in vivo
Galleria mellonella
infection model. Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in
S. mutans
.

IMPORTANCE
The cell wall of
Streptococcus mutans
, the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). While these structures are antigenically distinct to
S. mutans
, the process by which they are formed and the enzymes leading to their construction are well conserved among streptococci. The present study describes the consequences of the loss of RgpF, a rhamnosyltransferase involved in RGP construction. The deletion of
rgpF
resulted in severe ablation of the organism's overall fitness, culminating in significantly attenuated virulence. Our data demonstrate an important link between the RGP and cell wall physiology of
S. mutans
, affecting critical features used by the organism to cause disease and providing a potential novel target for inhibiting the pathogenesis of
S. mutans
.
PYGOPUS2 expression in prostatic adenocarcinoma is a potential risk stratification marker for PSA progression following radical prostatectomy
Authors: Kao Kenneth R , Popadiuk Paul , Thoms John , Aoki Satoko , Anwar Shahgul , Fitzgerald Emily , Andrews Phillip , Voisey Kim , Gai Luis , Challa Satya , He Zhijian , Gonzales-Aguirre Paola , Simmonds Andrea , Popadiuk Catherine 
Published: September 2017

AimsProstate cancer (PrCa) is the most frequently diagnosed non-cutaneous cancer in men. Without clear pathological indicators of disease trajectory at diagnosis, management of PrCa is challenging, given its wide-ranging manifestation from indolent to highly aggressive disease. This study examines the role in PrCa of the Pygopus (PYGO)2 chromatin effector protein as a risk stratification marker in PrCa.MethodsRNA expression was performed in PrCa cell lines using Northern and RT-PCR analyses. Protein levels were assessed using immunoblot and immunofluorescence. Immunohistochemistry was performed on tissue microarrays constructed from radical prostatectomies with 5-year patient follow-up data including Gleason score tumour staging, margin and lymph node involvement and prostate serum antigen (PSA) levels. Biochemical recurrence (BR) was defined as a postoperative PSA level of >0.2 nL. Univariate and multivariate analyses were performed using SAS and Kaplan-Meier curves using graphPad (Prism).ResultsIn vitro depletion of PYGO2 by RNAi in both androgen receptor positive and negative PrCa cell lines attenuated growth and reduced Ki67 and 47S rRNA expression, while PYGO2 protein was localised to the nuclei of tumours as determined by immunohistochemistry. High expression levels of PYGO2 in tumours (n=156) were correlated with BR identified as PSA progression, after 7-year follow-up independent of other traditional risk factors. Most importantly, high PYGO2 levels in intermediate grade tumours suggested increased risk of recurrence over those with negative or weak expression.ConclusionOur data suggest that elevated PYGO2 expression in primary prostate adenocarcinoma is a potential risk factor for BR.
No effects of increased alcohol availability during adolescence on alcohol-related morbidity and mortality during four decades: a natural experiment
Authors: Thern Emelie , Jia Ting , Willmer Mikaela , de Munter Jeroen , Norström Thor , Ramstedt Mats , Davey Smith George , Tynelius Per , Rasmussen Finn 
Published: September 2017

BackgroundA strict high legal age limit for alcohol purchases decreases adolescents’ access to alcohol, but little is known about long-term health effects. The aim was to estimate the effect of increased alcohol availability during adolescence on alcohol-related morbidity and mortality.MethodsA nationwide register-based study using data from a natural experiment setting. In two regions of Sweden, strong beer (4.5%–5.6% alcohol by volume) became temporarily available for purchase in grocery stores for individuals 16 years or older (instead of 21) in 1967/1968. The intervention group was defined as all individuals living in the intervention area when they were 14–20 years old (n=72 110). The remaining Swedish counties excluding bordering counties, without the policy change, were used as the control group (n=456 224). The outcomes of alcohol-related morbidity and mortality were collected from the Hospital Discharge Register and Cause of Death Register, in which average follow-up times were 38 years and 41 years, respectively. HRs with 95% CIs were obtained by Cox regression analysis.ResultsIn the fully adjusted model, no clear evidence of an association between increased alcohol availability during adolescence and alcohol-related morbidity (HR: 0.99, 95% CI 0.96 to 1.02) or mortality (HR: 1.02, 95% CI 0.95 to 1.10) was found.ConclusionThe initial elevated risk of alcohol-related morbidity and mortality later in life among adolescents exposed to increased access to strong beer in Sweden vanished when a regional measure population density of locality was included in the model, which is important to consider in future research.
Mitosis-Mediated Intravasation in a Tissue-Engineered Tumor–Microvessel Platform
Authors: Wong Andrew D. , Searson Peter C. 
Published: September 2017

Abstract
Intravasation involves the migration of tumor cells across the local endothelium and escape into vessel flow. Although tumor cell invasiveness has been correlated to increased intravasation, the details of transendothelial migration and detachment into circulation are still unclear. Here, we analyzed the intravasation of invasive human breast cancer cells within a tissue-engineered microvessel model of the tumor microenvironment. Using live-cell fluorescence microscopy, we captured 2,330 hours of tumor cell interactions with functional microvessels and provide evidence for a mitosis-mediated mechanism where tumor cells located along the vessel periphery are able to disrupt the vessel endothelium through cell division and detach into circulation. This model provides a framework for understanding the physical and biological parameters of the tumor microenvironment that mediate intravasation of tumor cells across an intact endothelium. Cancer Res; 77(22); 6453–61. ©2017 AACR.
Caveolae-Mediated Endocytosis Is Critical for Albumin Cellular Uptake and Response to Albumin-Bound Chemotherapy
Authors: Chatterjee Moumita , Ben-Josef Edgar , Robb Ryan , Vedaie Marall , Seum Star , Thirumoorthy Krishnan , Palanichamy Kamalakannan , Harbrecht Matthew , Chakravarti Arnab , Williams Terence M. 
Published: September 2017

Abstract
Nab-paclitaxel, a nanoparticle conjugate of paclitaxel to human albumin, exhibits efficacy in pancreatic cancer, non–small cell lung cancer and breast cancer. However, there is a lack of predictive biomarkers to identify patients who might benefit most from its administration. This study addresses this gap in knowledge by identifying that caveolin-1 (Cav-1) is a candidate mechanism-based biomarker. Caveolae are small membrane invaginations important for transendothelial albumin uptake. Cav-1, the principal structural component of caveolae, is overexpressed in the cancers noted above that respond to nab-paclitaxel. Thus, we hypothesized that Cav-1 may be critical for albumin uptake in tumors and perhaps determine their response to this drug. Cav-1 protein levels correlated positively with nab-paclitaxel sensitivity. RNAi-mediated attenuation of Cav-1 expression reduced uptake of albumin and nab-paclitaxel in cancer cells and rendered them resistant to nab-paclitaxel–induced apoptosis. Conversely, Cav-1 overexpression enhanced sensitivity to nab-paclitaxel. Selection for cellular resistance to nab-paclitaxel in cell culture correlated with a loss of Cav-1 expression. In mouse xenograft models, cancer cells, where Cav-1 was attenuated, exhibited resistance to the antitumor effects of nab-paclitaxel therapy. Overall, our findings suggest Cav-1 as a predictive biomarker for the response to nab-paclitaxel and other albumin-based cancer therapeutic drugs. Cancer Res; 77(21); 5925–37. ©2017 AACR.
A Novel Notch–YAP Circuit Drives Stemness and Tumorigenesis in Embryonal Rhabdomyosarcoma
Authors: Slemmons Katherine K. , Crose Lisa E.S. , Riedel Stefan , Sushnitha Manuela , Belyea Brian , Linardic Corinne M. 
Published: September 2017

Abstract
Rhabdomyosarcoma (RMS), a cancer characterized by skeletal muscle features, is the most common soft-tissue sarcoma of childhood. While low- and intermediate-risk groups have seen improved outcomes, high-risk patients still face a 5-year survival rate of &lt;30%, a statistic that has not changed in over 40 years. Understanding the biologic underpinnings of RMS is critical. The developmental pathways of Notch and YAP have been identified as potent but independent oncogenic signals that support the embryonal variant of RMS (eRMS). Here, the cross-talk between these pathways and the impact on eRMS tumorigenesis is reported. Using human eRMS cells grown as three-dimensional (3D) rhabdospheres, which enriches in stem cells, it was found that Notch signaling transcriptionally upregulates YAP1 gene expression and YAP activity. Reciprocally, YAP transcriptionally upregulates the Notch ligand genes JAG1 and DLL1 and the core Notch transcription factor RBPJ. This bidirectional circuit boosts expression of key stem cell genes, including SOX2, which is functionally required for eRMS spheres. Silencing this circuit for therapeutic purposes may be challenging, because the inhibition of one node (e.g., pharmacologic Notch blockade) can be rescued by upregulation of another (constitutive YAP expression). Instead, dual inhibition of Notch and YAP is necessary. Finally, supporting the existence of this circuit beyond a model system, nuclear Notch and YAP protein expression are correlated in human eRMS tumors, and YAP suppression in vivo decreases Notch signaling and SOX2 expression.
Implications: This study identifies a novel oncogenic signaling circuit driving eRMS stemness and tumorigenesis, and provides evidence and rationale for combination therapies co-targeting Notch and YAP. Mol Cancer Res; 15(12); 1777–91. ©2017 AACR.
Coherent Structures in Large-Eddy Simulations of a Nonprecipitating Stratocumulus-Topped Boundary Layer
Authors: Davini Paolo , D’Andrea Fabio , Park Seung-Bu , Gentine Pierre 
Published: September 2017

Abstract
The properties of coherent convective structures are analyzed in a nonprecipitating marine nocturnal stratocumulus-topped boundary layer (STBL) with a series of high-resolution large-eddy simulations (LESs). A new classification method based on octant analysis—using vertical velocity and two passive scalars—is introduced to systematically define convective structures in both the cloudy and the cloud-free regions. It is therefore possible to detect and track updrafts, downdrafts, and their turbulent shells (both ascending and subsiding), together with the entraining air from the inversion layer or the free troposphere. The geometrical and thermodynamical characteristics (e.g., areal fraction, temperature, liquid and total water mixing ratio, buoyancy) of those structures are then accurately described, and particular attention is given to their respective contributions to the turbulent transport of mass, heat, and moisture. It is shown that updrafts, downdrafts, and entrainment are equally important to describe the STBL dynamics. Conversely, it is found that shells, although they partially contribute to the mass transport, have a negligible contribution to the turbulent fluxes of heat and moisture.
Multiscale Variability of the Atmospheric Boundary Layer during DYNAMO
Authors: Johnson Richard H. , Ciesielski Paul E. 
Published: September 2017

Abstract
Properties of the atmospheric boundary layer (ABL) over the central Indian Ocean are investigated using sounding data obtained during the Dynamics of the MJO (DYNAMO) field campaign in 2011/12. Observations from Gan Island on Addu Atoll, the R/V Revelle, and Malé in the Maldives are used to determine the frequency of well-mixed layers and their mean thermodynamic and wind profiles. Well-mixed boundary layers or mixed layers were observed 68% of the time from the three sites, ranging from ~100-m depth in recovering convective downdraft wakes to ~925 m in undisturbed conditions, with a mean depth of 508 m. At Revelle, the site most representative of the open ocean, the ABL displayed a distinct signal of modulation by the October and November MJOs, with mixed-layer depths gradually increasing through the suppressed phases as the sea surface temperature (SST) increased leading up to the active phases, followed by frequent ABL stabilization and shallow mixed layers in recovering wakes. A distinct diurnal cycle of mixed-layer depths and properties was observed during the MJO suppressed phases in response to a diurnal cycle of the SST under the mostly light-wind, clear-sky conditions. The daytime growth of the mixed layer contributed to an afternoon maximum in cumulus cloud development and rainfall during the suppressed periods by allowing more boundary layer thermals to reach their condensation levels. The variability of the ABL on time scales ranging from convective to diurnal to monthly poses significant challenges for numerical simulations of the MJO and the tropical circulation in general.
Objective Assessment of Technical Skills in Otorhinolaryngology–Head and Neck Surgery Residents: A Systematic Review
Authors: Mercier Érika , Chagnon‐Monarque Ségolène , Lavigne François , Ayad Tareck 
Published: September 2017

ObjectivesThe primary goal is the indexation of validated methods used to assess surgical competency in otorhinolaryngology–head and neck surgery (ORL‐HNS) residents. Secondary goals include assessment of the reliability and validity of these tools, as well as the documentation of specific procedures in ORL‐HNS involved.Data SourcesMEDBASE, OVID, Medline, CINAHL, and EBM, as well as the printed references, available through the Université de Montréal library.Review MethodsThe PRISMA method was used to review digital and printed databases. Publications were reviewed by 2 independent reviewers, and selected articles were fully analyzed to classify evaluation methods and categorize them by procedure and subspecialty of ORL‐HNS involved. Reliability and validity were assessed and scored for each assessment tool.ResultsThrough the review of 30 studies, 5 evaluation methods were described and validated to assess the surgical competency of ORL‐HNS residents. The evaluation method most often described was the combined Global Rating Scale and Task‐Specific Checklist tool. Reliability and validity for this tool were overall high; however, considerable data were unavailable. Eleven distinctive surgical procedures were studied, encompassing many subspecialties of ORL‐HNS: facial plastics, general ear‐nose‐throat, laryngology, otology, pediatrics, and rhinology.ConclusionsAlthough assessment tools have been developed for an array of surgical procedures, involving most ORL‐HNS subspecialties, the use of combined checklists has been repeatedly validated in the literature and shown to be easily applicable in practice. It has been applied to many ORL‐HNS procedures but not in oncologic surgery to date.
Single‐Blinded Prospective Implementation of a Preoperative Imaging Checklist for Endoscopic Sinus Surgery
Authors: Error Marc , Ashby Shaelene , Orlandi Richard R. , Alt Jeremiah A. 
Published: September 2017

ObjectiveTo determine if the introduction of a systematic preoperative sinus computed tomography (CT) checklist improves identification of critical anatomic variations in sinus anatomy among patients undergoing endoscopic sinus surgery.Study DesignSingle‐blinded prospective cohort study.SettingTertiary care hospital.Subjects and MethodsOtolaryngology residents were asked to identify critical surgical sinus anatomy on preoperative CT scans before and after introduction of a systematic approach to reviewing sinus CT scans. The percentage of correctly identified structures was documented and compared with a 2‐sample t test.ResultsA total of 57 scans were reviewed: 28 preimplementation and 29 postimplementation. Implementation of the sinus CT checklist improved identification of critical sinus anatomy from 24% to 84% correct (P <. 001). All residents, junior and senior, demonstrated significant improvement in identification of sinus anatomic variants, including those not directly included in the systematic review implemented.ConclusionThe implementation of a preoperative endoscopic sinus surgery radiographic checklist improves identification of critical anatomic sinus variations in a training population.
Radiosensitization by CpG ODN7909 in an epidermoid laryngeal carcinoma Hep-2 cell line
Authors: Wang Shu , Liu Xiaoqun , Qiao Tiankui , Zhang Qi 
Published: September 2017

Objective To evaluate the radiosensitivity effect of CpG oligodeoxyribonucleotide (ODN) 7909 on human epidermoid cancer strain-2 (Hep-2) cells in vitro and discuss the potential for improved radiotherapy treatment in patients with laryngeal squamous cell carcinoma. Methods Toll-like receptor ( TLR) 9 expression was assessed in Hep-2 cells using Western blots and reverse transcription polymerase chain reaction. Cell Counting Kit-8 was used to detect Hep-2 cell viability at 24 and 48 h following treatment with different CpG ODN7909 concentrations. Cellular colonization was evaluated using microscopy. Cell cycle distribution and apoptosis rate was determined with flow cytometry. Interleukin (IL)-12 and tumour necrosis factor (TNF)-α concentrations were detected by enzyme-linked immunosorbent assay. Results Hep-2 cells were found to express TLR9, and CpG ODN7909 treatment suppressed Hep-2 cell viability in a dose- and time-dependent manner. Cell survival curve analyses revealed a sensitivity enhancement ratio of the mean death dose of 1.225 for CpG ODN7909 plus irradiation versus irradiation alone. Furthermore, the population of Gap 2/mitotic-phase cells, apoptosis rate and secreted IL-12 and TNF-α levels were significantly increased in Hep-2 cells treated with CpG ODN7909 plus irradiation versus IR alone. Conclusion CpG ODN7909 enhanced the radiosensitivity of Hep-2 cells in vitro.
Balloon dilation for the treatment of nasopharyngeal stenosis in seven cats
Authors: Pollack Stefeny Z , Chapman Peter S , Klag Alan 
Published: September 2017

Objectives The objective of this study was to evaluate the effectiveness of balloon dilation for the treatment of nasopharyngeal stenosis in cats. Methods The medical records of seven cats with nasopharyngeal stenosis treated with balloon dilation were reviewed. The most common presenting clinical signs included upper airway noise, sneezing, nasal and/or ocular discharge. All seven cats were confirmed to have nasopharyngeal stenosis via nasopharyngeal endoscopy and were treated with balloon dilation under endoscopic guidance. Results All seven cats had acceptable short-term control (median 14 days) of clinical signs after the procedure. Two of six cats had successful long-term control (median 34 days) of clinical signs after one balloon dilation and an additional 2/6 cats had acceptable long-term control of clinical signs after a second balloon dilation procedure. The most significant complication of balloon dilation was the recurrence of stenosis. Conclusions and relevance The findings of this study indicate that balloon dilation is a safe and effective treatment option for the relief of clinical signs associated with nasopharyngeal stenosis in cats. Multiple procedures may be necessary for the best chance of long-term success.
Molecular prevalence of Cryptosporidium species among household cats and pet shop kittens in Japan
Authors: Ito Yoichi , Itoh Naoyuki , Iijima Yuko , Kimura Yuya 
Published: September 2017

Objectives To address the lack of up-to-date published data, the present study evaluates the PCR-based prevalence of Cryptosporidium species infection and molecular characteristics of isolates among household cats and pet shop kittens in Japan. Methods A total of 357 and 329 fresh faecal samples were collected from household cats and pet shop kittens, respectively, with or without clinical signs of infection. A nested PCR assay targeting the 18S rRNA gene was employed for the detection of Cryptosporidium species. After specific DNA fragments (approximately 826 base pairs) were confirmed, the amplicons were sequenced to determine species. Results Seven (2.0%) household cats and one (0.3%) pet shop kitten tested positive for the presence of Cryptosporidium species. In household cats, there was a significant difference in prevalence between cats aged <1 year (4.6%) and those aged ⩾1 year (0.4%). No significantly different prevalence was observed with regard to faecal condition in either household cats or pet shop kittens. A total of eight Cryptosporidium species isolates, seven from household cats and one from a pet shop kitten, were identified as Cryptosporidium felis. Conclusions and relevance The present study demonstrates the risk of zoonotic transmission of Cryptosporidium species from household cats and pet shop kittens to humans is low in Japan.