bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intercellular Communication via the
comX
-Inducing Peptide (XIP) of Streptococcus mutans
Authors: Kaspar Justin , Underhill Simon A. M. , Shields Robert C. , Reyes Adrian , Rosenzweig Suzanne , Hagen Stephen J. , Burne Robert A. 
Published: August 2017

ABSTRACT

Gram-positive bacteria utilize exported peptides to coordinate genetic and physiological processes required for biofilm formation, stress responses, and ecological competitiveness. One example is activation of natural genetic competence by ComR and the
com

X

-
i
nducing
p
eptide (XIP) in
Streptococcus mutans
. Although the competence pathway can be activated by the addition of synthetic XIP in defined medium, the hypothesis that XIP is able to function as an intercellular signaling molecule has not been rigorously tested. Coculture model systems were developed that included a “sender” strain that overexpressed the XIP precursor (ComS) and a “responder” strain harboring a green fluorescent protein (GFP) reporter fused to a ComR-activated gene (
comX
) promoter. The ability of the sender strain to provide a signal to activate GFP expression was monitored at the individual cell and population levels using (i) planktonic culture systems, (ii) cells suspended in an agarose matrix, or (iii) cells growing in biofilms. XIP was shown to be freely diffusible, and XIP signaling between the
S. mutans
sender and responder strains did not require cell-to-cell contact. The presence of a sucrose-derived exopolysaccharide matrix diminished the efficiency of XIP signaling in biofilms, possibly by affecting the spatial distribution of XIP senders and potential responders. Intercellular signaling was greatly impaired in a strain lacking the primary autolysin, AtlA, and was substantially greater when the sender strain underwent lysis. Collectively, these data provide evidence that
S. mutans
XIP can indeed function as a peptide signal between cells and highlight the importance of studying signaling with an endogenously produced peptide(s) in populations in various environments and physiologic states.

IMPORTANCE
The
comX
-inducing peptide (XIP) of
Streptococcus mutans
is a key regulatory element in the activation of genetic competence, which allows cells to take up extracellular DNA. XIP has been found in cell culture fluids, and the addition of synthetic XIP to physiologically receptive cells can robustly induce competence gene expression. However, there is a lack of consensus as to whether XIP can function as an intercellular communication signal. Here, we show that XIP indeed signals between cells in
S. mutans
, but that cell lysis may be a critical factor, as opposed to a dedicated secretion/processing system, in allowing for release of XIP into the environment. The results have important implications in the context of the ecology, virulence, and evolution of a ubiquitous human pathogen and related organisms.
Exploring the Interaction of Ethidium Bromide and HOECHST 33258 with DNA by Means of Electrochemical Approach
Authors: Tavadyan Levon A. , Minasyan Seyran H. , Kocharyan Gaspar H. , Antonyan Ara P. , Sahakyan Viktoria G. , Parsadanyan Marine A. , Vardevanyan Poghos O. 
Published: August 2017

The binding of both ethidium bromide (EtBr) and Hoechst 33258 (H33258) to calf thymus DNA differing by the mechanism at different ionic strengths of NaCl water solutions (2, 20 and 150[Formula: see text]mM) has been quantitatively studied by square wave voltammetry (SWV). It was revealed that EtBr binds to DNA by more than one mode: at the solution ionic strengths 2 and 150[Formula: see text]mM, two modes were revealed, at 20[Formula: see text]mM — three modes. Values of EtBr binding constant ([Formula: see text]) to DNA and the number of nucleotides per one binding site ([Formula: see text]) for respective binding modes were determined. For H33258 under the same conditions, two binding modes were found and for both these modes values of [Formula: see text] and [Formula: see text] were determined. Dependence of the binding types and parameters on the solution ionic strength by SWV method was revealed, which differs by the binding type of EtBr and H33258. The obtained data are in good accordance with the ones determined by spectroscopic (absorption and fluorescence) and differential pulse voltammetry (DPV) methods. The obtained data indicate the sensibility and high precision of SWV method which may be applied to studies on interaction of different ligands with DNA, which reveal some peculiarities of their binding to DNA that are hidden and are not found by other methods.
PRC2-Mediated Transcriptomic Alterations at the Embryonic Stage Govern Tumorigenesis and Clinical Outcome in MYCN-Driven Neuroblastoma
Authors: Tsubota Shoma , Kishida Satoshi , Shimamura Teppei , Ohira Miki , Yamashita Satoshi , Cao Dongliang , Kiyonari Shinichi , Ushijima Toshikazu , Kadomatsu Kenji 
Published: August 2017

Abstract
Pediatric cancers such as neuroblastoma are thought to involve a dysregulation of embryonic development. However, it has been difficult to identify the critical events that trigger tumorigenesis and differentiate them from normal development. In this study, we report the establishment of a spheroid culture method that enriches early-stage tumor cells from TH-MYCN mice, a preclinical model of neuroblastoma. Using this method, we found that tumorigenic cells were evident as early as day E13.5 during embryo development, when the MYC and PRC2 transcriptomes were significantly altered. Ezh2, an essential component of PRC2, was expressed in embryonic and postnatal tumor lesions and physically associated with N-MYC and we observed that H3K27me3 was increased at PRC2 target genes. PRC2 inhibition suppressed in vitro sphere formation, derepressed its target genes, and suppressed in situ tumor growth. In clinical specimens, expression of MYC and PRC2 target genes correlated strongly and predicted survival outcomes. Together, our findings highlighted PRC2-mediated transcriptional control during embryogenesis as a critical step in the development and clinical outcome of neuroblastoma. Cancer Res; 77(19); 5259–71. ©2017 AACR.
Nuclear FAK and Runx1 Cooperate to Regulate IGFBP3, Cell-Cycle Progression, and Tumor Growth
Authors: Canel Marta , Byron Adam , Sims Andrew H. , Cartier Jessy , Patel Hitesh , Frame Margaret C. , Brunton Valerie G. , Serrels Bryan , Serrels Alan 
Published: August 2017

Abstract
Nuclear focal adhesion kinase (FAK) is a potentially important regulator of gene expression in cancer, impacting both cellular function and the composition of the surrounding tumor microenvironment. Here, we report in a murine model of skin squamous cell carcinoma (SCC) that nuclear FAK regulates Runx1-dependent transcription of insulin-like growth factor binding protein 3 (IGFBP3), and that this regulates SCC cell-cycle progression and tumor growth in vivo. Furthermore, we identified a novel molecular complex between FAK and Runx1 in the nucleus of SCC cells and showed that FAK interacted with a number of Runx1-regulatory proteins, including Sin3a and other epigenetic modifiers known to alter Runx1 transcriptional function through posttranslational modification. These findings provide important new insights into the role of FAK as a scaffolding protein in molecular complexes that regulate gene transcription. Cancer Res; 77(19); 5301–12. ©2017 AACR.
HNF1B Loss Exacerbates the Development of Chromophobe Renal Cell Carcinomas
Authors: Sun Mianen , Tong Pan , Kong Wen , Dong Baijun , Huang Yiran , Park In Young , Zhou Lijun , Liu Xian-De , Ding Zhiyong , Zhang Xuesong , Bai Shanshan , German Peter , Powell Reid , Wang Quan , Tong Xuefei , Tannir Nizar M. , Matin Surena F. , Rathmell W. Kimryn , Fuller Gregory N. , McCutcheon Ian E. , Walker Cheryl L. , Wang Jing , Jonasch Eric 
Published: August 2017

Abstract
Chromophobe renal cell carcinoma (ChRCC) is characterized by major changes in chromosomal copy number (CN). No model is available to precisely elucidate the molecular drivers of this tumor type. HNF1B is a master regulator of gene expression. Here, we report that the transcription factor HNF1B is downregulated in the majority of ChRCC and that the magnitude of HNF1B loss is unique to ChRCC. We also observed a strong correlation between reduced HNF1B expression and aneuploidy in ChRCC patients. In murine embryonic fibroblasts or ACHN cells, HNF1B deficiency reduced expression of the spindle checkpoint proteins MAD2L1 and BUB1B, and the cell-cycle checkpoint proteins RB1 and p27. Furthermore, it altered the chromatin accessibility of Mad2l1, Bub1b, and Rb1 genes and triggered aneuploidy development. Analysis of The Cancer Genome Atlas database revealed TP53 mutations in 33% of ChRCC where HNF1B expression was repressed. In clinical specimens, combining HNF1B loss with TP53 mutation produced an association with poor patient prognosis. In cells, combining HNF1B loss and TP53 mutation increased cell proliferation and aneuploidy. Our results show how HNF1B loss leads to abnormal mitotic protein regulation and induction of aneuploidy. We propose that coordinate loss of HNF1B and TP53 may enhance cellular survival and confer an aggressive phenotype in ChRCC. Cancer Res; 77(19); 5313–26. ©2017 AACR.
The Phosphatidylinositol 3-Kinase Pathway as a Potential Therapeutic Target in Bladder Cancer
Authors: Zeng Shu-Xiong , Zhu Yanjun , Ma Ai-Hong , Yu Weimin , Zhang Hongyong , Lin Tzu-Yin , Shi Wei , Tepper Clifford G. , Henderson Paul T. , Airhart Susan , Guo Jian-Ming , Xu Chuan-Liang , deVere White Ralph W. , Pan Chong-Xian 
Published: August 2017

Abstract
Purpose: Activation of the PI3K pathway occurs in over 40% of bladder urothelial cancers. The aim of this study is to determine the therapeutic potential, the underlying action, and the resistance mechanisms of drugs targeting the PI3K pathway.
Experimental Design: Urothelial cancer cell lines and patient-derived xenografts (PDXs) were analyzed for alterations of the PI3K pathway and for their sensitivity to the small-molecule inhibitor pictilisib alone and in combination with cisplatin and/or gemcitabine. Potential predictive biomarkers for pictilisib were evaluated, and RNA sequencing was performed to explore drug resistance mechanisms.
Results: The bladder cancer cell line TCCSUP, which harbors a PIK3CA E545K mutation, was sensitive to pictilisib compared to cell lines with wild-type PIK3CA. Pictilisib exhibited stronger antitumor activity in bladder cancer PDX models with PI3KCA H1047R mutation or amplification than the control PDX model. Pictilisib synergized with cisplatin and/or gemcitabine in vitro, significantly delayed tumor growth, and prolonged survival compared with single-drug treatment in the PDX models. The phosphorylation of ribosomal protein S6 correlated with response to pictilisib both in vitro and in vivo, and could potentially serve as a biomarker to predict response to pictilisib. Pictilisib activated the compensatory MEK/ERK pathway that likely contributed to pictilisib resistance, which was reversed by cotreatment with the RAF inhibitor sorafenib. RNA sequencing of tumors resistant to treatment suggested that LSP1 downregulation correlated with drug resistance.
Conclusions: These preclinical results provide new insights into the therapeutic potential of targeting the PI3K pathway for the treatment of bladder cancer. Clin Cancer Res; 23(21); 6580–91. ©2017 AACR.
Identificação e análise da estrutura espacial dos extremos de temperatura do ar na bacia do rio Paranaíba por meio da técnica de anos-padrão
Authors: Queiroz Arlei Teodoro de , Steinke Ercília Torres 
Published: August 2017

Este trabalho procurou identificar e analisar os extremos de temperatura do ar registrados na bacia do rio Paranaíba, bem como a variação percentual de seus extremos em relação à média, seguindo a metodologia de anos-padrão sugerida por Tavares (1976). Os resultados foram espacializados em mapas, a fim de mostrar a espacialização, consequência da variação estrutura espacial desse parâmetro. Observou-se que, no período estudado, a maior amplitude térmica na bacia foi nas porções sul e oeste, tendo sido registradas as temperaturas máximas e mínimas anuais. Essa dinâmica da bacia pode ser compreendida por meio de sua hipsometria, com altitude mais baixa na porção sudoeste, na direção de seu exutório, tanto quanto pela dinâmica das massas de ar na região.
A Voice without a Muse
Authors: Vespa Marco 
Published: August 2017

Ancient sources often describe non-human primates as imitative animals, i.e., living beings able to reproduce, with different degrees of perfection, gestures and movements carried out by human beings. Indeed monkeys are often characterized asmimeloi, mimetikoi, terms coming from the same semantic field of the nounmimos(< *mim-).But what about the world of sounds? Are non-human primates regarded as good imitators and performers also when it comes to music and singing? Ancient evidence clearly indicates that other animal species (like nightingales or partridges), and not monkeys, were mainly regarded as excellent singers worthy of imitation by human beings. Through a detailed analysis of ancient Greek sources, especially some passages in Galen, this paper aims at investigating why non-human primates were not considered good singers. In particular, this survey tries to shed a new light on some cultural associations, according to which the small and weak voice of monkeys (µικροφωνία) and the voice of other figures in ancient society (like actors, musicians, kids, eunuchs and so on) were described in a similar way.
Post-chemotherapy perforation in cats with discrete intermediate- or large-cell gastrointestinal lymphoma
Authors: Crouse Zachary , Phillips Brenda , Flory Andi , Mahoney Jennifer , Richter Keith , Kidd Linda 
Published: August 2017

Objectives Gastrointestinal (GI) perforation is a well described complication of GI lymphoma in people, commonly occurring within days of initiation of chemotherapy. There are no studies documenting the prevalence of GI perforation in cats with intermediate- or large-cell GI lymphoma or whether it is associated with induction of chemotherapy. The objectives of this study were to document the prevalence and timing of post-chemotherapy perforation in cats with discrete GI masses caused by intermediate- or large-cell lymphoma. Methods Cats with a diagnosis of intermediate- or large-cell lymphoma based on cytologic or histopathologic examination of a mass lesion of the GI tract and treated with chemotherapy were identified by searching the patient record database of three large specialty referral hospitals. Cats undergoing surgical resection of a GI mass prior to chemotherapy were excluded from the study. A clinical diagnosis of GI perforation was made using ultrasound findings and analysis of abdominal fluid. Results Twenty-three cats with intermediate- (n = 3) or large-cell (n = 20) lymphoma were included in the study. GI perforation was confirmed in 4/23 cats (17%), and occurred at 23, 56, 59 and 87 days after induction. There was no association between tumor size, the presence of hypoproteinemia or suppurative inflammation within the mass at the time of diagnosis and subsequent perforation. Post-hoc analysis revealed that the magnitude of weight loss within 15–28 days of diagnosis was greater in cats with perforation. Conclusions and relevance In this pilot study, we found that post-chemotherapy GI perforation in cats with intermediate- or large-cell GI lymphoma occurs. Acute perforation after induction of chemotherapy was not documented. Larger prospective studies are needed to determine risk factors associated with perforation and whether surgical excision would reduce the risk of subsequent GI perforation in these patients.
Preoperative Leg Pain Score Predicts Patient Satisfaction After Transforaminal Lumbar Interbody Fusion Surgery
Authors: Lim Jason Beng Teck , Yeo William , Chen John Li Tat 
Published: August 2017

Study Design: Retrospective cohort study. Objectives: This study aims to determine the preoperative predictors of postoperative satisfaction in transforaminal lumbar interbody fusion (TLIF) surgery in order to improve management of patient groups at high risk of dissatisfaction. We retrospectively reviewed prospectively collected data on patients who underwent open TLIF in a tertiary hospital between 2008 and 2012 with 2-year follow-up and performed multivariate analysis for their preoperative variables. Methods: A multivariate regression analysis was performed for the 217 patients to identify preoperative predictors of postoperative satisfaction. Clinical outcomes were evaluated using Oswestry Disability Index (ODI), North American Spine Society (NASS) Neurogenic Symptom Score (NSS), 36-item Short-Form Survey (SF-36; mean Physical and Mental Health scores), numerical pain rating scale (NPRS) for pain, and NASS Questionnaire. Results: Significant improvements were seen in the postoperative ODI, NSS, SF-36, and NPRS scores at 2 years ( P < .05). Eighty-six percent of the patients had their expectations of surgery met, and 94.7% of the patients were satisfied with the results of treatment at 2 years. From the multivariate regression model, patients with higher preoperative NPRS pain score (odds ratio = 1.323; 95% confidence interval = 1.071-1.633; P = .009) was more likely to be satisfied at 2 years. Conclusions: TLIF surgery provided significant health-related quality-of-life scores and symptom improvement in terms of SF-36, ODI, NSS, and NPRS, with a high proportion of patients being satisfied with the results of surgery. Patients with higher preoperative NPRS leg pain were more likely to be satisfied at 2 years. Patient-reported satisfaction may be largely influenced by the improvement of radicular leg pain.
Do Tibial Plateau Fractures Worsen Outcomes of Knee Ligament Injuries? A Matched Cohort Analysis
Authors: Cinque Mark E. , Godin Jonathan A. , Moatshe Gilbert , Chahla Jorge , Kruckeberg Bradley M. , Pogorzelski Jonas , LaPrade Robert F. 
Published: August 2017

Background: Tibial plateau fractures account for a small portion of all fractures; however, these fractures can pose a surgical challenge when occurring concomitantly with ligament injuries. Purpose/Hypothesis: The purpose of this study was to compare 2-year outcomes of soft tissue reconstruction with or without a concomitant tibial plateau fracture and open reduction internal fixation. We hypothesized that patients with a concomitant tibial plateau fracture at the time of soft tissue surgery would have inferior outcomes compared with patients without an associated tibial plateau fracture. Study Design: Cohort study; Level of evidence, 3. Methods: Forty patients were included in this study: 8 in the fracture group and 32 in the matched control group. Inclusion criteria for the fracture group included patients who were at least 18 years old at the time of surgery and sustained a tibial plateau fracture and a concomitant injury of the anterior cruciate ligament, posterior cruciate ligament, medial collateral ligament, or fibular collateral ligament in isolation or any combination of cruciate or collateral ligaments and who subsequently underwent isolated or combined ligament reconstruction. Patients were excluded if they underwent prior ipsilateral knee surgery, sustained additional bony injuries, or sustained an isolated extra-articular ligament injury at the time of injury. Each patient with a fracture was matched with 4 patients from a control group who had no evidence of a tibial plateau fracture but underwent the same soft tissue reconstruction procedure. Results: Patients in the fracture group improved significantly from preoperatively to postoperatively with respect to Short Form–12 ( P < .05) and Western Ontario and McMaster Universities Osteoarthritis Index total scores ( P < .05). The Lysholm ( P = .075) and Tegner scores ( P = .086) also improved, although this was not statistically significant. Patients in the control group improved significantly from preoperatively to postoperatively across all measured scores. A comparison of the postoperative results between the 2 groups showed no statistically significant difference. Conclusion: The presence of a tibial plateau fracture in conjunction with a ligamentous knee injury did not have a negative effect on postoperative patient-reported outcomes. Patient-reported outcome scores after surgery in both the fracture and control groups improved beyond the minimally clinically important difference, indicating that the presence of a fracture did not detract from the outcomes observed in patients without fractures undergoing concomitant ligament reconstruction.
C/EBPβ is required for survival of Ly6C− monocytes
Authors: Tamura Akihiro , Hirai Hideyo , Yokota Asumi , Kamio Naoka , Sato Atsushi , Shoji Tsukimi , Kashiwagi Takahiro , Torikoshi Yusuke , Miura Yasuo , Tenen Daniel G. , Maekawa Taira 
Published: August 2017

Key PointsIn Cebpb−/− mice, the number of Ly6C− monocytes was specifically decreased in a cell-intrinsic manner due to their accelerated death. C/EBPβ supports the survival of Ly6C− monocytes, at least in part through direct upregulation of Csf1r.
Fibrin and D-dimer bind to monomeric GPVI
Authors: Onselaer Marie-Blanche , Hardy Alexander T. , Wilson Clare , Sanchez Ximena , Babar Amir K. , Miller Jeanette L. C. , Watson Callum N. , Watson Stephanie K. , Bonna Arkadiusz , Philippou Helen , Herr Andrew B. , Mezzano Diego , Ariëns Robert A. S. , Watson Steve P. 
Published: August 2017

Key Points
GPVI is the major signaling receptor for fibrin in human platelets; the GPVI binding site is located in the fibrin D-dimer region. D-dimer blocks platelet aggregation by fibrin and collagen but not by a collagen-related peptide, suggesting a distinct binding epitope.
Surgical versus percutaneous isolated pelvic perfusion (IPP) for advanced melanoma: comparison in terms of melphalan pharmacokinetic pelvic bio-availability
Authors: Guadagni Stefano , Palumbo Giancarlo , Fiorentini Giammaria , Clementi Marco , Marsili Luca , Giordano Aldo Victor , Masedu Francesco , Valenti Marco 
Published: August 2017

Abstract
Background
Isolated pelvic perfusion (IPP) can be used to treat unresectable melanoma metastases of the pelvis. IPP can be performed either by surgical or percutaneous approaches, using different balloon catheters. The aim of this study was to examine whether the surgical and percutaneous approaches were comparable with respect to tumor drug exposure in the pelvis.

Methods
A pharmacokinetic study was performed in 5 melanoma patients treated with surgical IPP and five with percutaneous IPP. Both groups received melphalan at the dose of 30 mg/m2. Melphalan pharmacokinetic analyses were performed and the main parameter used to evaluate pelvic tumor drug-exposure was the ratio of areas under the melphalan plasma concentration curves in the pelvis and the systemic compartment, during the perfusion time (AUC0 to 20). Non-parametric Mann–Whitney tests were employed for statistical comparisons.

Results
The median and interquartile range (IQR) values of the ratios between melphalan AUC0 to 20 in pelvic and systemic compartments were 7.9 (IQR 7.2 to 9.9) and 5 (IQR 4 to 7.9) for surgical and percutaneous IPPs, respectively (p = 0.209).

Conclusions
Tumor exposure to drug using these two methods did not statistically differ and both methods, therefore, can be adopted interchangeably, utilizing a perfusion blood flow rate of approximately 120 ml/min. The small sample size is a limitation of this study but our preliminary results can be used to calculate the effect size of a larger trial.
Trial Registration Clinical Trials.gov Identifier NCT01920516; date of trial registration: August 6, 2013
RETRACTED ARTICLE: Proofs to one inequality conjecture for the non-integer part of a nonlinear differential form
Authors: Chen Mei 
Published: August 2017

AbstractWe prove the conjecture for the non-integer part of a nonlinear differential form representing primes presented in (Lai in J. Inequal. Appl. 2015:Article ID 357, 2015) by using Tumura-Clunie type inequalities. Compared with the original proof, the new one is simpler and more easily understood. Similar problems can be treated with the same procedure.