bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity and
In Vitro
and
In Vivo
Protective Effects of Antibodies Targeting a Recombinant Form of the Streptococcus mutans P1 Surface Protein
Authors: Batista Milene Tavares , Souza Renata D. , Ferreira Ewerton L. , Robinette Rebekah , Crowley Paula J. , Rodrigues Juliana F. , Brady L. Jeannine , Ferreira Luís C. S. , Ferreira Rita C. C. 
Published: September 2014

ABSTRACT

Streptococcus mutans
is a major etiologic agent of dental caries, a prevalent worldwide infectious disease and a serious public health concern. The surface-localized
S. mutans
P1 adhesin contributes to tooth colonization and caries formation. P1 is a large (185-kDa) and complex multidomain protein considered a promising target antigen for anticaries vaccines. Previous observations showed that a recombinant P1 fragment (P1
39–512
), produced in
Bacillus subtilis
and encompassing a functional domain, induces antibodies that recognize the native protein and interfere with
S. mutans
adhesion
in vitro
. In the present study, we further investigated the immunological features of P1
39–512
in combination with the following different adjuvants after parenteral administration to mice: alum, a derivative of the heat-labile toxin (LT), and the phase 1 flagellin of
S.
Typhimurium LT2 (FliCi). Our results demonstrated that recombinant P1
39–512
preserves relevant conformational epitopes as well as salivary agglutinin (SAG)-binding activity. Coadministration of adjuvants enhanced anti-P1 serum antibody responses and affected both epitope specificity and immunoglobulin subclass switching. Importantly, P1
39–512
-specific antibodies raised in mice immunized with adjuvants showed significantly increased inhibition of
S. mutans
adhesion to SAG, with less of an effect on SAG-mediated bacterial aggregation, an innate defense mechanism. Oral colonization of mice by
S. mutans
was impaired in the presence of anti-P1
39–512
antibodies, particularly those raised in combination with adjuvants. In conclusion, our results confirm the utility of P1
39–512
as a potential candidate for the development of anticaries vaccines and as a tool for functional studies of
S. mutans
P1.
Oxygen-Dependent Control of Respiratory Nitrate Reduction in Mycelium of Streptomyces coelicolor A3(2)
Authors: Fischer Marco , Falke Dörte , Pawlik Tony , Sawers R. Gary 
Published: September 2014

ABSTRACT

Several members of the obligately aerobic genus
Streptomyces
are able to reduce nitrate, catalyzed by Nar-type respiratory nitrate reductases. A unique feature of
Streptomyces coelicolor
A3(2) compared with other streptomycetes is that it synthesizes three nonredundant Nar enzymes. In this study, we show that Nar2 is the main Nar enzyme active in mycelium and could characterize the conditions governing its synthesis. Nar2 was present at low levels in aerobically cultivated mycelium, but synthesis was induced when cultures were grown under oxygen limitation. Growth in the presence of high oxygen concentrations prevented the induction of Nar2 synthesis. Equally, an abrupt shift from aerobiosis to anaerobiosis did not result in the immediate induction of Nar2 synthesis. This suggests that the synthesis of Nar2 is induced during a hypoxic downshift, probably to allow maintenance of a proton gradient during the transition to anaerobiosis. Although no Nar2 could be detected in freshly harvested mature spores, synthesis of the enzyme could be induced after long-term (several days) incubation of these resting spores under anaerobic conditions. Induction of Nar2 synthesis in spores was linked to transcriptional control. Nar2 activity in whole mycelium was strictly dependent on the presence of a putative nitrate transporter, NarK2. The oxygen-dependent inhibition of nitrate reduction by Nar2 was mediated by NarK2-dependent nitrate:nitrite antiport. This antiport mechanism likely prevents the accumulation of toxic nitrite in the cytoplasm. A deletion of the
narK2
gene had no effect on Nar1-dependent nitrate reduction in resting spores. Together, our results indicate redox-dependent transcriptional and posttranslational control of nitrate reduction by Nar2.
Mg
2+
, K
+
, and the Ribosome
Authors: Nierhaus Knud H. 
Published: September 2014

ABSTRACT

Mg
2+
and K
+
are the prevalent di- and monovalent cations inside the cells in all three domains, playing a dominant role in structure and function of biological macromolecules. Ribosomes bind a substantial fraction of total Mg
2+
and K
+
cations. In this issue of the
Journal of Bacteriology
, Akanuma and coworkers (G. Akanuma et al., J. Bacteriol. 196:3820–3830, 2014, doi:
10.1128/JB.01896-14
) report a surprising genetic link between ribosome amounts per cell and the intracellular Mg
2+
concentrations.
Restless legs syndrome in patients with type 2 diabetes: effectiveness of pramipexole therapy
Authors: Harashima Shin-Ichi , Nishimura Akiko , Osugi Tomoaki , Wang Yu , Liu Yanyan , Takayama Hiroshi , Inagaki Nobuya 
Published: September 2014

ObjectiveWe investigated the prevalence of restless legs syndrome (RLS) in Japanese patients with type 2 diabetes and assessed the efficacy of pramipexole therapy.DesignOne hundred patients with type 2 diabetes without secondary causes of RLS were sequentially screened for the 12-week, prospective, single arm study. RLS was screened by essential diagnostic criteria developed by the International Restless Legs Study Group. Diabetic neuropathy was diagnosed by nerve conductance study. Severity of RLS and sleep quality were assessed by the International Restless Legs Rating Scale (IRLS) and the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J), respectively. Pramipexole was administered for 12 weeks. The primary end point was change in the IRLS score in 12 weeks and secondary end points were change in PSQI-J and glycated haemoglobin (HbA1c) in 12 weeks.ResultsRLS was diagnosed in 8 of 100 participants (8%). Diabetic neuropathy was most likely associated with RLS (OR 3.81, 95% CI 0.85 to 17.05, p=0.111). The IRLS score was improved from 19.0±5.6 to 5.4±4.8 by pramipexole in 12 weeks (p<0.001). The change in the score was −13.6 (95% CI −15.5 to −11.7; p<0.05). PSQI-J was improved from 6.0±4.4 to 1.5±1.3 in 12 weeks (p<0.05). Change in PSQI-J was −4.5 (95% CI −6.8 to −2.1; p<0.05). HbA1c was slightly decreased from 7.19±0.56% (55±6 mmol/mol) to 6.90±0.48% (52±5 mmol/mol) in 12 weeks (p<0.05). Change in HbA1c was −0.29% (−3 mmol/mol) (95% CI −0.37% to −0.20% (−4 to −2 mmol/mol;) p<0.05).ConclusionsWe find that type 2 diabetes is a possible risk factor for RLS in the Japanese population, and that pramipexole treatment can improve the symptoms of RLS as well as the quality of sleep and glycaemic control in these patients.Trial registration numberUniversity hospital Medical Information Network in Japan (UMIN000008347).
Benzalkonium chloride exposure in cats: a retrospective analysis of 245 cases reported to the Veterinary Poisons Information Service (VPIS)
Authors: Bates N. , Edwards N. 
Published: September 2014

Benzalkonium chloride is commonly found in household products. This retrospective study examined 245 cases of feline exposure to benzalkonium chloride‐containing products reported to the Veterinary Poisons Information Service (VPIS). A single route of exposure was reported in 188 cats (ingestion 126, skin 58, buccal 4); 57 cats had multiple routes. The common products involved were household antibacterial cleaners (43.6 per cent), household disinfectants (22.3 per cent) and patio cleaners (17.5 per cent). The most common signs were hypersalivation/drooling (53.9 per cent), tongue ulceration (40.4 per cent), hyperthermia (40.4 per cent) and oral ulceration (22.9 per cent). The mean time recorded for onset of the first clinical sign was 6.4 hours (range five minutes to 48 hours, median 4.5 hours, n=60), however, the VPIS was not contacted until 14.0±13.2 hours after exposure (n=120). This figure also reflects the time of presentation. The most common treatments given were antibiotics (82.0 per cent), fluids (50.2 per cent), analgesia (45.3 per cent), gastroprotectants (31.0 per cent), dermal decontamination (24.1 per cent) and steroids (22.7 per cent). 13 cats (5.3 per cent) received syringe or nasogastric feeding. Of 245 cats, 12 (4.9 per cent) remained asymptomatic, 230 (93.9 per cent) recovered and three died (1.2 per cent). The time to recovery ranged from 1 to 360 hours (n=67) with a mean of 100.4±82.0 hours (4.2±3.4 days, median 72 hours).
Insight into monogenetic eruption processes at Pelagatos volcano, Sierra Chichinautzin, Mexico: a combined melt inclusion and physical volcanology study
Authors: Roberge Julie , Guilbaud Marie-Noëlle , Mercer Celestine N. , Reyes-Luna Paola C. 
Published: September 2014

Abstract

Eruptions and magma evolution of monogenetic volcanoes are thought to be controlled by rapid ascent of magmas over a short period of time. Volatiles degassing from magmas control the ascent velocity and therefore eruption intensity. Complex feedbacks exist between the rate and extent of volatile exsolution at shallow levels and groundmass crystallization, affecting the magma rheology, extent of fragmentation, resulting eruptive style and related hazards. Melt inclusions record the volatile contents and compositions of melts at various stages during their evolution, providing insights into degassing–crystallization processes at shallow crustal levels. Here we present new volatile and major element data from olivine-hosted melt inclusions from Pelagatos scoria cone, Mexico. These new data, combined with recent geochemical and textural data on Pelagatos eruptive products, allow us to propose a model for shallow magmatic processes at this volcano. Discharge of volatile-poor, low-viscosity magma drives early effusive activity along the fissure. Decreasing magma fluxes lead to the clogging of the fissure and the formation of a shallow magma reservoir where degassing and fractional crystallization take place. Subsequent explosive cone-forming activity is triggered by influx of deeper (
c.
5 km), less evolved, more volatile-rich magma into this shallow (
c.
1 km) reservoir.

Supplementary material:

new whole rock and matrix glass date are available at
www.geolsoc.org.uk/SUP18782
.
Mathematical Modeling of Tumor Growth and Metastatic Spreading: Validation in Tumor-Bearing Mice
Authors: Hartung Niklas , Mollard Séverine , Barbolosi Dominique , Benabdallah Assia , Chapuisat Guillemette , Henry Gerard , Giacometti Sarah , Iliadis Athanassios , Ciccolini Joseph , Faivre Christian , Hubert Florence 
Published: September 2014

Abstract
Defining tumor stage at diagnosis is a pivotal point for clinical decisions about patient treatment strategies. In this respect, early detection of occult metastasis invisible to current imaging methods would have a major impact on best care and long-term survival. Mathematical models that describe metastatic spreading might estimate the risk of metastasis when no clinical evidence is available. In this study, we adapted a top-down model to make such estimates. The model was constituted by a transport equation describing metastatic growth and endowed with a boundary condition for metastatic emission. Model predictions were compared with experimental results from orthotopic breast tumor xenograft experiments conducted in Nod/Scidγ mice. Primary tumor growth, metastatic spread and growth were monitored by 3D bioluminescence tomography. A tailored computational approach allowed the use of Monolix software for mixed-effects modeling with a partial differential equation model. Primary tumor growth was described best by Bertalanffy, West, and Gompertz models, which involve an initial exponential growth phase. All other tested models were rejected. The best metastatic model involved two parameters describing metastatic spreading and growth, respectively. Visual predictive check, analysis of residuals, and a bootstrap study validated the model. Coefficients of determination were $R^2 = 0.94$ for primary tumor growth and $R^2 = 0.57$ for metastatic growth. The data-based model development revealed several biologically significant findings. First, information on both growth and spreading can be obtained from measures of total metastatic burden. Second, the postulated link between primary tumor size and emission rate is validated. Finally, fast growing peritoneal metastases can only be described by such a complex partial differential equation model and not by ordinary differential equation models. This work advances efforts to predict metastatic spreading during the earliest stages of cancer. Cancer Res; 74(22); 6397–407. ©2014 AACR.
A Small-Molecule Modulator of the Tumor-Suppressor miR34a Inhibits the Growth of Hepatocellular Carcinoma
Authors: Xiao Zhangang , Li Chi Han , Chan Stephen L. , Xu Feiyue , Feng Lu , Wang Yan , Jiang Jian-Dong , Sung Joseph J.Y. , Cheng Christopher H.K. , Chen Yangchao 
Published: September 2014

Abstract
Small molecules that restore the expression of growth-inhibitory microRNAs (miRNA) downregulated in tumors may have potential as anticancer agents. miR34a functions as a tumor suppressor and is downregulated or silenced commonly in a variety of human cancers, including hepatocellular carcinoma (HCC). In this study, we used an HCC cell–based miR34a luciferase reporter system to screen for miR34a modulators that could exert anticancer activity. One compound identified as a lead candidate, termed Rubone, was identified through its ability to specifically upregulate miR34a in HCC cells. Rubone activated miR34a expression in HCC cells with wild-type or mutated p53 but not in cells with p53 deletions. Notably, Rubone lacked growth-inhibitory effects on nontumorigenic human hepatocytes. In a mouse xenograft model of HCC, Rubone dramatically inhibited tumor growth, exhibiting stronger anti-HCC activity than sorafenib both in vitro and in vivo. Mechanistic investigations showed that Rubone decreased expression of cyclin D1, Bcl-2, and other miR34a target genes and that it enhanced the occupancy of p53 on the miR34a promoter. Taken together, our results offer a preclinical proof of concept for Rubone as a lead candidate for further investigation as a new class of HCC therapeutic based on restoration of miR34a tumor-suppressor function. Cancer Res; 74(21); 6236–47. ©2014 AACR.
Pro-Oncogenic Role of Alternative p38 Mitogen-Activated Protein Kinases p38γ and p38δ, Linking Inflammation and Cancer in Colitis-Associated Colon Cancer
Authors: del Reino Paloma , Alsina-Beauchamp Dayanira , Escós Alejandra , Cerezo-Guisado Ma Isabel , Risco Ana , Aparicio Noelia , Zur Rafal , Fernandez-Estévez Marian , Collantes Elena , Montans Jose , Cuenda Ana 
Published: September 2014

Abstract
p38 MAPK signaling has been implicated in the regulation of processes leading to cancer development and progression. Chronic inflammation is a known risk factor for tumorigenesis, yet the precise mechanism of this association remains largely unknown. The related p38αMAPK (MAPK14) proteins p38γ (MAPK12) and p38δ (MAPK13) were recently shown to modulate the immune response, although their role in tumorigenesis remains controversial and their function in inflammation-associated cancer has not been studied. We analyzed the role of p38γ and p38δ in colon cancer associated to colitis using the azoxymethane/dextran sodium sulphate (AOM/DSS) colitis-associated colon cancer model in wild-type (WT), p38γ-, p38δ-, and p38γ/δ-deficient (p38γ/δ−/−) mice. We found that p38γ/δ deficiency significantly decreased tumor formation, in parallel with a decrease in proinflammatory cytokine and chemokine production. Analysis of leukocyte populations in p38γ/δ−/− mouse colon showed less macrophage and neutrophil recruitment than in WT mice. Furthermore, WT chimeric mice with transplanted p38γ/δ−/− bone marrow had less tumors than WT mice transplanted with WT bone marrow, whereas tumor number was significantly increased in p38γ/δ−/− chimeric mice with WT bone marrow compared with p38γ/δ−/− mice transplanted with p38γ/δ−/− bone marrow. Together, our results establish that p38γ and p38δ are central to colitis-associated colon cancer formation through regulation of hematopoietic cell response to injury, and validate p38γ and p38δ as potential targets for cancer therapy. Cancer Res; 74(21); 6150–60. ©2014 AACR.
Prevalence, Incidence, Clearance, and Associated Factors of Genital Human Papillomavirus Infection among Men: A Population-Based Cohort Study in Rural China
Authors: Liu Mengfei , He Zhonghu , Zhang Chanyuan , Liu Fangfang , Liu Ying , Li Jingjing , Xu Zhongyao , Wang Qiyan , Hang Dong , Shen Na , Pan Yaqi , Guo Chuanhai , Cai Hong , Ke Yang 
Published: September 2014

Abstract
Background: The natural history of human papillomavirus (HPV) infection in men on a population base has rarely been studied in general, particularly among Chinese men.
Methods: A total of 1,286 men ages 25 to 65 years from rural China were enrolled during 2009–2010 and their genital HPV infection status was assessed biannually for up to seven visits using PCR and sequencing methods. Prevalence analysis was performed among men with at least one valid HPV result (N = 1,279) and men with at least two consecutive HPV results (N = 1,059) were included in incidence and clearance analyses (median follow-up time, 31.8 months; interquartile range, 15.4–37.9 months).
Results: The prevalence and incidence of any HPV type, oncogenic, and nononcogenic HPV were 17.8%, 6.4%, 12.4%, and 14.6, 4.9, 10.8 per 1,000 person months, respectively. The median duration of infection with any HPV type, oncogenic, and nononcogenic HPV was 11.5, 6.8, and 11.5 months, respectively. The number of lifetime sexual partners was consistently associated with increased risk of prevalent and incident infection of HPV. Men ages 25 to 50 years had a higher incidence and longer duration of HPV infection than older men (51–65 years).
Conclusions and Impact: This epidemiologic investigation provides basic information of genital HPV infection among the Chinese male population; these data are crucial for the consideration of primary strategies against HPV-related carcinoma in the Chinese male and female population. Cancer Epidemiol Biomarkers Prev; 23(12); 2857–65. ©2014 AACR.
Deoxycytidine Kinase Expression Underpins Response to Gemcitabine in Bladder Cancer
Authors: Kerr Martin , Scott Helen E. , Groselj Blaz , Stratford Michael R.L. , Karaszi Katalin , Sharma Naomi L. , Kiltie Anne E. 
Published: September 2014

Abstract
Purpose: In a recent phase II clinical trial, low-dose (100 mg/m2) gemcitabine showed promise as a radiosensitizer in bladder cancer, but underlying mechanisms lack elucidation. Here, we investigated the mechanism of radiosensitization by low-dose gemcitabine in bladder cancer cell lines.
Experimental Design: Four bladder cancer cell lines were screened for radiosensitization by low-dose gemcitabine using clonogenic assay, and gemcitabine-resistant RT112gem and CALgem cells created by exposure to increasing gemcitabine doses. Four key gemcitabine-regulatory genes were knocked down by transient siRNA. Nude mice carrying CALgem subcutaneous xenografts were exposed to 100 mg/kg gemcitabine ± ionizing radiation (IR) and response assessed by tumor growth delay.
Results: Gemcitabine was cytotoxic in the low nanomolar range (10–40 nmol/L) in four bladder cancer cell lines and radiosensitized all four lines. Sensitizer enhancement ratios at 10% survival were: RT112 1.42, CAL29 1.55, T24 1.63, and VMCUB1 1.47. Transient siRNA knockdown of deoxycytidine kinase (dCK) significantly reduced radiosensitization by gemcitabine (P = 0.02). RT112gem and CALgem cells displayed robust decreases of dCK mRNA and protein levels; reexpression of dCK restored gemcitabine sensitivity. However, CALgem xenografts responded better to combination gemcitabine/IR than either treatment alone (P &lt; 0.001) with dCK strongly expressed in the tumor vasculature and stroma.
Conclusions: Gemcitabine resistance in bladder cancer cell lines was associated with decreased dCK expression, but gemcitabine-resistant xenografts were responsive to combination low-dose gemcitabine/IR. We propose that dCK activity in tumor vasculature renders it gemcitabine sensitive, which is sufficient to invoke a tumor response and permit tumor cell kill in gemcitabine-resistant tumors. Clin Cancer Res; 20(21); 5435–45. ©2014 AACR.
Human Atrial Fibrillation Initiates via Organized Rather Than Disorganized Mechanisms
Authors: Schricker Amir A. , Lalani Gautam G. , Krummen David E. , Rappel Wouter-Jan , Narayan Sanjiv M. 
Published: September 2014

Background—
It is unknown how atrial fibrillation (AF) is actually initiated by triggers. Based on consistencies in atrial structure and function in individual patients between episodes of AF, we hypothesized that human AF initiates when triggers interact with deterministic properties of the atria and may engage organized mechanisms.

Methods and Results—
In 31 patients with AF, we mapped AF initiation after spontaneous triggers or programmed stimulation. We used 64-pole basket catheters to measure regional dynamic conduction slowing and to create biatrial activation maps during transitions to AF. Sixty-two AF initiations were recorded (spontaneous, n=28; induced, n=34). Notably, AF did not initiate by disorganized mechanisms, but by either a dominant reentrant spiral wave (76%) or a repetitive focal driver. Both mechanisms were located 21±17 mm from their triggers. AF-initiating spirals formed at the site showing the greatest rate-dependent slowing in each patient. Accordingly, in 10 of 12 patients with multiple observed AF episodes, AF initiated using spatially conserved mechanisms despite diverse triggers.

Conclusions—
Human AF initiates from triggers by organized rather than disorganized mechanisms, either via spiral wave re-entry at sites of dynamic conduction slowing or via repetitive focal drivers. The finding that diverse triggers initiate AF at predictable, spatially conserved functional sites in each individual provides a novel deterministic paradigm for AF with therapeutic implications.
Idiopathic Ventricular Arrhythmia Originating From the Cardiac Crux or Inferior Septum
Authors: Kawamura Mitsuharu , Gerstenfeld Edward P. , Vedantham Vasanth , Rodrigues Derek M. , Burkhardt J. David , Kobayashi Youichi , Hsia Henry H. , Marcus Gregory M. , Marchlinski Francis E. , Scheinman Melvin M. , Badhwar Nitish 
Published: September 2014

Background—
Idiopathic ventricular arrhythmia (VA) can arise from the epicardium near the posteroseptal region (cardiac crux). There are only 2 prior reports describing idiopathic VA from the cardiac crux. The purpose of this study was to characterize the clinical and the electrocardiographic features of idiopathic crux VA.

Methods and Results—
Crux VA was identified in 18 patients undergoing catheter ablation. We divided patients into 2 groups, those with VA originating from the apical crux (n=9) and the basal crux (n=9). We described the clinical and electrocardiographic characteristics of crux VA as well as the ablation results. Furthermore, we compared clinical features of crux VA with other sites of idiopathic VA. Fifteen crux VA patients (83%) had sustained ventricular tachycardia and 3 patients required implantable cardioverter defibrillator implantation because of syncope. All patients had a left superior axis and 16 patients had R>S wave in V2. In apical crux VA, all patients had a deep S wave in V6 and 8 patients (89%) had R>S wave in aVR. All apical crux patients underwent attempted ablation in the middle cardiac vein without success. In 4 of these patients, epicardial ablation with subxiphoid approach was performed successfully. All basal crux VA patients had either negative or isoelectric pattern in V1 and had R>S in V6. Patients had successful ablation within the middle cardiac vein.

Conclusions—
Apical versus basal crux VA is identified as a new category of idiopathic VA with distinctive electrocardiographic characteristics; ablation via the middle cardiac vein is effective for eliminating basal crux VA, whereas apical crux VA often requires a subxiphoid epicardial approach.