bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trp53 Deficiency Protects against Acute Intestinal Inflammation
Authors: Spehlmann Martina E. , Manthey Carolin F. , Dann Sara M. , Hanson Elaine , Sandhu Sukhman S. , Liu Linus Y. , Abdelmalak Farid K. , Diamanti Michaela A. , Retzlaff Kristin , Scheller Jürgen , Rose-John Stefan , Greten Florian R. , Wang Jean Y. J. , Eckmann Lars 
Published: June 2013

Abstract
The p53 protein has not only important tumor suppressor activity but also additional immunological and other functions, whose nature and extent are just beginning to be recognized. In this article, we show that p53 has a novel inflammation-promoting action in the intestinal tract, because loss of p53 or the upstream activating kinase, ATM, protects against acute intestinal inflammation in murine models. Mechanistically, deficiency in p53 leads to increased survival of epithelial cells and lamina propria macrophages, higher IL-6 expression owing to enhanced glucose-dependent NF-κB activation, and increased mucosal STAT3 activation. Blockade or loss of IL-6 signaling reverses the protective effects of p53 deficiency. Conversely, IL-6 treatment protects against acute colitis in a manner dependent on STAT3 signaling and induction of cytoprotective factors in epithelial cells. Together, these results indicate that p53 promotes inflammation in the intestinal tract through suppression of epithelium-protective factors, thus significantly expanding the spectrum of physiological and immunological p53 activities unrelated to cancer formation.
Paraoxonase-1 Suppresses Experimental Colitis via the Inhibition of IFN-γ Production from CD4 T Cells
Authors: Yamashita Junji , Iwamura Chiaki , Ito Toshihiro , Narita Masakuni , Hara Yukio , Sasaki Tetsuya , Masuda Daisuke , Takahashi Munehisa , Tsuchiya Manami , Hada Kaori , Ishikawa Makoto , Matsuo Takato , Ohno Yoichi , Tanaka Hitoshi , Maruyama Hideya , Ogawa Yasumasa , Nakayama Toshinori 
Published: June 2013

Abstract
Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, where excessive Th1 cell responses are observed. We performed experiments to identify immunologically bioactive proteins in human plasma and found that paraoxonase (PON)-1, which has esterase activity and is associated with high-density lipoproteins, inhibited the IFN-γ production by both murine and human differentiating Th1 cells. Trinitrobenzene sulfonic acid–induced colitis was attenuated by the administration of PON-1. The beneficial effects of PON-1 were associated with a reduced ratio of IFN-γ–producing CD4 T cells in the mesenteric lymph nodes and decreased production of T cell–related cytokines in the colon. PON-1 inhibited the TCR-induced activation of ERK-MAPK signaling and the nuclear translocation of NF-κB in CD4 T cells. Interestingly, an excessive CD4 T cell response was observed in PON-1–deficient mice under physiological and pathological conditions. Additionally, the efficacy of PON-1 or G3C9-C284A (G3C9), which shows a higher esterase activity than PON-1, on colitis was similar to that of an anti–TNF-α mAb, which is a clinically used CD treatment. Moreover, G3C9 more effectively suppressed CD4+CD45RBhigh cell transfer–induced chronic colitis in mice than did PON-1, and the efficacy of G3C9 against the colitis was similar to that of the anti–TNF-α mAb. Therefore, PON-1 (or G3C9) administration may be clinically beneficial for CD patients.
TLR4 Signaling Augments Monocyte Chemotaxis by Regulating G Protein–Coupled Receptor Kinase 2 Translocation
Authors: Liu Zheng , Jiang Yong , Li Yuehua , Wang Juan , Fan Liyan , Scott Melanie J. , Xiao Guozhi , Li Song , Billiar Timothy R. , Wilson Mark A. , Fan Jie 
Published: June 2013

Abstract
Monocytes are critical effector cells of the innate immune system that protect the host by migrating to inflammatory sites, differentiating to macrophages and dendritic cells, eliciting immune responses, and killing pathogenic microbes. MCP-1, also known as CCL2, plays an important role in monocyte activation and migration. The chemotactic function of MCP-1 is mediated by binding to the CCR2 receptor, a member of the G protein–coupled receptor (GPCR) family. Desensitization of GPCR chemokine receptors is an important regulator of the intensity and duration of chemokine stimulation. GPCR kinases (GRKs) induce GPCR phosphorylation, and this leads to GPCR desensitization. Regulation of subcellular localization of GRKs is considered an important early regulatory mechanism of GRK function and subsequent GPCR desensitization. Chemokines and LPS are both present during Gram-negative bacterial infection, and LPS often synergistically exaggerates leukocyte migration in response to chemokines. In this study, we investigated the role and mechanism of LPS–TLR4 signaling on the regulation of monocyte chemotaxis. We demonstrate that LPS augments MCP-1–induced monocyte migration. We also show that LPS, through p38 MAPK signaling, induces phosphorylation of GRK2 at serine 670, which, in turn, suppresses GRK2 translocation to the membrane, thereby preventing GRK2-initiated internalization and desensitization of CCR2 in response to MCP-1. This results in enhanced monocyte migration. These findings reveal a novel function for TLR4 signaling in promoting innate immune cell migration.
CIINE Reflects Collagenase-Specific CII Breakdown in Cartilage Explant and Whole Body of Canine
Authors: Matsukawa Satoko , Tanimura Miki , Toyosaki-Maeda Tomoko , Noda Akihiro , Kobayashi Mika , Yamauchi Akira , Onoda Junji , Tsuji Toshinaga , Takahashi Tatsuya , Matsuo Yoshiyuki , Fukui Naoshi 
Published: June 2013

To evaluate collagenase inhibitors for the treatment of osteoarthritis and to correlate them with clinical pathology, canine cartilage explant and anterior cruciate ligament transection (ACLT) models were examined by quantifying the CII neoepitope (CIINE). This peptide is a putative marker for collagenase-specific type II collagen (CII) degradation, which is a critical step in osteoarthritis pathology. The concentration of CIINE in supernatants of canine cartilage explants showed increase upon IL-1β—stimulation and collagenase inhibitors suppressed this elevation of CIINE. In the canine ACLT model, levels of CIINE in urine (uCIINE) increased as lesions of knee joint cartilage developed and decreased in response to collagenase inhibitors. Our results suggest that CIINE reflects collagenase-specific CII degradation in canine explants and whole bodies. It is anticipated that these data will establish a tool for clarifying and bridging the efficacy and mechanism of collagenase inhibitors at the preclinical stage of drug discovery.
Los sitios Web de centros de investigación biosanitaria de Castilla y León. Un análisis cibermétrico
Authors: Sánchez Pita Fernando , Alonso Berrocal José Luis 
Published: June 2013

Los sitios web institucionales son fuentes de contenidos donde entidad y usuario cruzan intereses en busca de objetivos comunes. Desde la presente investigación se aborda el análisis de este tipo de recursos digitales con una visión estructural de los mismos, más allá de su diseño o de la calidad de los contenidos que alojan. Metodología. Para ello se realiza un estudio desde el análisis de redes sociales, apoyado en la cibermetría, para conocer la composición de los sitios web de cada centro de investigación biosanitaria de Castilla y León. Se presentan diferentes propiedades de las estructuras de red, así como medidas topológicas con las que conocer las páginas más importantes de cada sitio web en función de los flujos de información, lo cual repercutirá en la visibilidad de los contenidos que se pretendan difundir. Resultados. Los resultados obtenidos indican que existen ciertos puntos de mejora en la estructura de los sitios web analizados, al detectarse exiguas tramas de relaciones informativas o páginas de inicio con poca relevancia sobre el conjunto. Conclusiones. Finalmente, tras la evaluación de resultados, se ha concluido que existen carencias en los sitios web analizados. Ello supone deficiencias que afectarán a los objetivos en base a los cuales se conciben este tipo de sitios web, dificultando, desde la propia estructura, la difusión de contenidos y la visibilidad de los mismos.
An in vitro Evaluation of Microtensile Bond Strength of Resin-based Sealer with Dentin Treated with Diode and Nd:YAG Laser
Authors: Kumar G Anil , Das Maneesha , Ramesh Sindhu , Garapati Surendranath 
Published: June 2013

ABSTRACTBackgroundSmear layer is a negative factor which prevents adhesion of the filling material to the dentinal walls. Recent advances in dental research have incorporated lasers as a potential adjunct in root canal treatment by removing the smear layer before filling the root canal system, enhancing the adhesion of sealers to dentin and improving the sealing ability.AimTo evaluate the microtensile bond strength of AH-Plus resin-based sealer to dentin after treatment with 980 nm diode and 1,064 nm neodymium-doped:yttrium aluminum garnet (Nd:YAG) laserin vitro.Materials and methodsThirty specimens prepared for three groups namely group I (control), group II (980 nm diode–lased specimens) and group III (Nd:YAG–lased specimens). One tooth from each group was observed under scanning electron microscope for evaluation of intracanal root dentin morphology. Remaining specimens were used for making microsections by hard tissue microtome. Specimens for groups II and III were lased with 980 nm diode and 1,064 nm Nd:YAG laser. AH Plus sealer was applied onto specimens and mounted onto Instron universal testing machine for microtensile bond strength testing. Results were subjected to statistical analysis using one-way analysis of variance (ANOVA) and Tukey's test.ResultsGroup III Nd:YAG had maximum mean microtensile bond strength values (11.558 ± 0.869), followed by group II diode (9.073 ± 0.468) and group I control (6.05 ± 0.036). Statistically significant differences were seen among all the groups. SEM analysis shows removal of smear layer in both groups II and III.ConclusionBoth Nd:YAG and diode laser were more effective than control group in improving the microtensile bond strength of AH Plus sealer to dentin.Clinical significanceLasers have the potential to increase the adhesiveness of root canal sealer to dentin surface, thereby improving the quality of root canal obturation.How to cite this articleManeesha D, Anil KG, Sindhu R, Surendranath G, Deepak S. Anin vitroEvaluation of Microtensile Bond Strength of Resin-based Sealer with Dentin Treated with Diode and Nd:YAG Laser. J Contemp Dent Pract 2013;14(2): 183-187.
Sirenomelia after phenobarbital and carbamazepine therapy in pregnancy
Authors: Tica Oana Sorina , Tica Andrei Adrian , Brailoiu Cristina Gabriela , Cernea Nicolae , Tica Vlad Iustin 
Published: June 2013

BACKGROUNDEpilepsy still remains a serious challenge for any obstetrician due to the potential teratogenicity of all antiepileptics. However, without appropriate maternal therapy the seizures can reappear, with direct negative impact on fetus. Currently, sirenomelia is the most severe caudal pole dysgenesis, consequent to an abnormal vascular supply development in the fetal lower body.CASE REPORTWe report a stillborn, GA/LMP = 37weeks, delivered by an epileptic woman, who received in the first four months of pregnancy phenobarbital (PH) 0.1 g/day and carbamazepine (CMZ) 0.4 g/day, followed only by PH 0.1 g/day, until delivery. The stillborn, weighing 2200 g, presented sirenomelia type II, with some of its “classic” features: oligohydramnios, absence of kidneys, bladder, rectum, uterus, and a single umbilical artery. Some other “particularities” included: no Potter's facies and no significant cardio‐pulmonary abnormalities.DISCUSSIONSince PH and CMZ alone are responsible, commonly, for mild abnormalities, we hypothesized that combined therapy with PH and CMZ (both strong enzyme‐inductors, especially PH) potentiated their teratogenicity, by producing supplementary quantities of epoxides and/or other oxides, which accumulated in the fetal tissues. Except for sirenomelia, all other mild abnormalities, theoretically associated with “fetal CMZ and/or PH syndrome,” are rarely observed, fact which demonstrates the drug–drug interactions between the two antiepileptics.CONCLUSIONThis report highlights the possibility that PH/CBZ therapy during fetal organogenesis can induce sirenomelia, by a synergistic teratogenic effect and support the recommendation to use only one drug in pregnant epileptic women. A careful ultrasound monitoring of these patients is mandatory due to the teratogenic risk of both seizures and therapy. Birth Defects Research (Part A) 97:425–428, 2013. © 2013 Wiley Periodicals, Inc.
Recreating a human trabecular meshwork outflow system on microfabricated porous structures
Authors: Torrejon Karen Y. , Pu Dennis , Bergkvist Magnus , Danias John , Sharfstein Susan T. , Xie Yubing 
Published: June 2013

ABSTRACTGlaucoma is the leading cause of irreversible blindness, resulting from an increase in intraocular pressure (IOP). IOP is the only modifiable risk factor of glaucoma and is controlled by the outflow of the aqueous humor through the human trabecular meshwork (HTM). Currently, the lack of a proper in vitro HTM model impedes advances in understanding outflow physiology and discovering effective IOP‐lowering anti‐glaucoma therapeutics. Therefore, we designed and constructed an in vitro HTM model using micropatterned, porous SU‐8 scaffolds, which support cells to recapitulate functional HTM morphology and allow the study of outflow physiology. The pore size of SU‐8 scaffolds, surface coating, cell seeding density, and culture duration were evaluated for HTM cell growth. The bioengineered HTM was characterized by F‐actin staining and immunocytochemistry of HTM markers. A stand‐alone perfusion chamber with an integrated pressure sensing system was further constructed and used for the investigation of the outflow facility of the bioengineered HTM treated with latrunculin B—an IOP lowering agent. Cells in the in vitro model exhibited HTM‐like morphology, expression of α‐smooth muscle actin, myocilin, and αB‐crystallin, outflow characteristics and drug responsiveness. Altogether, we have developed an in vitro HTM model system for understanding HTM cell biology and screening of pharmacological or biological agents that affect trabecular outflow facility, expediting discovery of IOP‐lowering, anti‐glaucoma therapeutics. Biotechnol. Bioeng. 2013;110: 3205–3218. © 2013 Wiley Periodicals, Inc.
Automated disposable small scale reactor for high throughput bioprocess development: A proof of concept study
Authors: Bareither Rachel , Bargh Neil , Oakeshott Robert , Watts Kathryn , Pollard David 
Published: June 2013

ABSTRACTThe acceleration of bioprocess development for biologics and vaccines can be enabled by automated high throughput technologies. This will alleviate the significant resource burden from the multi‐factorial statistical experimentation required for controlling product quality attributes of complex biologics. Recent technology advances have improved clone evaluation and screening, but have struggled to combine the scale down criteria required for both high cell density cell culture and microbial processes, with sufficient automation and disposable technologies to accelerate process development. This article describes the proof of concept evaluations of an automated disposable small scale reactor for high throughput upstream process development. Characterization studies established the small scale stirred tank disposable 250 mL reactor as similar to those of lab and pilot scale. The reactor generated equivalent process performance for industrial biologics processes for therapeutic protein and monoclonal antibody production using CHO cell culture, Pichia pastoris and E. coli. This included similar growth, cell viability, product titer, and product quality. The technology was shown to be robust across multiple runs and met the requirements for the ability to run high cell density processes (>400 g/L wet cell weight) with exponential feeds and sophisticated event triggered processes. Combining this reactor into an automated array of reactors will ultimately be part of a high throughput process development strategy. This will combine upstream, small scale purification with rapid analytics that will dramatically shorten timelines and costs of developing biological processes. Biotechnol. Bioeng. 2013;110: 3126–3138. © 2013 Wiley Periodicals, Inc.
Benzene and sulfide removal from groundwater treated in a microbial fuel cell
Authors: Rakoczy Jana , Feisthauer Stefan , Wasmund Kenneth , Bombach Petra , Neu Thomas R. , Vogt Carsten , Richnow Hans H. 
Published: June 2013

AbstractSulfidic benzene‐contaminated groundwater was used to fuel a two‐chambered microbial fuel cell (MFC) over a period of 770 days. We aimed to understand benzene and sulfide removal processes in the anoxic anode chamber and describe the microbial community enriched over the operational time. Operated in batch feeding‐like circular mode, supply of fresh groundwater resulted in a rapid increase in current production, accompanied by decreasing benzene and sulfide concentrations. The total electron recoveries for benzene and sulfide were between 18% and 49%, implying that benzene and sulfide were not completely oxidized at the anode. Pyrosequencing of 16S rRNA genes from the anode‐associated bacterial community revealed the dominance of δ‐Proteobacteria (31%), followed by β‐Proteobacteria, Bacteroidetes, ϵ‐Proteobacteria, Chloroflexi, and Firmicutes, most of which are known for anaerobic metabolism. Two‐dimensional compound‐specific isotope analysis demonstrated that benzene degradation was initiated by monohydroxylation, probably triggered by small amounts of oxygen which had leaked through the cation exchange membrane into the anode chamber. Experiments with [13C6]‐benzene revealed incorporation of 13C into fatty acids of mainly Gram‐negative bacteria, which are therefore candidates for benzene degradation. Our study demonstrated simultaneous benzene and sulfide removal by groundwater microorganisms which use an anode as artificial electron acceptor, thereby releasing an electrical current. Biotechnol. Bioeng. 2013;110: 3104–3113. © 2013 Wiley Periodicals, Inc.
Investigation on alternative disposal methods for froth treatment tailings—part 2, Recovery of asphaltenes
Authors: Xu Yuming , Wu Jianying , Dabros Tadeusz , Rahimi Parviz , Kan Jianmin 
Published: June 2013

AbstractIn collaboration with Total E&P Canada (TEPCA), CanmetENERGY conducted an extensive research program to investigate possible alternatives for TSRU tailings disposal. We have reported on alternative methods for TSRU tailings disposal without recovery of asphaltenes in an earlier publication.[1] Because the asphaltenes are high‐molecular‐weight hydrocarbons and may have potential for use as fuel or paving material, in this work, we investigate possible approaches for recovery of the asphaltenes from TSRU tailings. Two methods were tested, solvent extraction and aggregation. In the first method aromatic solvent is mixed with TSRU tailings to dissolve the asphaltenes followed by centrifugation to remove mineral solids and water. The experimental results demonstrated that more than 90% of the asphaltenes in the tailings can be recovered from the tailings. The recovered asphaltenes contained only a small fraction of mineral solids and may be useable as coker feed. In the second method, TSRU tailings are agitated at elevated temperature (80°C) at which the asphaltene particles form large aggregates and separate from the tailings, giving an asphaltene‐rich phase and almost asphaltene‐free tailings. The recovered asphaltene aggregates still contain significant amounts of mineral solids and water, and would require further treatment. Several coking tests were conducted using the recovered asphaltenes and the asphaltene aggregates. The results demonstrated that about 40 wt% of the recovered asphaltenes can be converted to lighter oil fractions under the coking conditions used in this work.
Evaluation on the effect of conical geometry on flow behaviours in spouted beds
Authors: Liu Xuejiao , Zhong Wenqi , Shao Yingjuan , Ren Bing , Jin Baosheng 
Published: June 2013

AbstractEvaluation on the effect of conical section geometry on the gas–solid flow behaviours in conical–cylindrical spouted beds were carried out by three‐dimensional computational fluid dynamics (CFD) coupling with two‐fluid model (TFM). The simulations were implemented in seven columns with their conical angles ranging from 30° to 180°. The solid flow pattern, particle velocity, voidage, fountain height and the spout diameter were investigated. It was found that unstable spouting would occur when the conical angle is less than 30°. In addition, the conical angle of 105° might be a borderline value for gas–solid flow behaviours in the spout. In this region, increasing conical angle leads to a decrease in fountain height, particle velocity and voidage and an increase in the spout diameter when the conical angle is within 105°, while reverse trends could be found when the conical angle is beyond 105°. The smallest fountain height, particle velocity and voidage and largest spout diameter could be found when the angle is 105°. In spite of these, the particle velocity in the annulus continually increases with increasing conical angle.
Strongly unforgeable threshold multi‐proxy multi‐signature scheme with different proxy groups
Authors: Liu D. , Wang X. , Huang M. 
Published: June 2013

ABSTRACTIn the majority of threshold multi‐proxy multi‐signature (TMPMS) schemes, only one proxy group is authorized to sign on behalf of all the original members. However, the original signers in various practical applications are often from different organizations. Each original signer should be able to designate a proxy group in his own organization; thus, each original signer could have distinct proxy members. However, this practical requirement of TMPMS schemes is seldom considered. To satisfy this requirement, we propose a new TMPMS scheme in which each original member can designate a proxy group in his own organization. Moreover, the threshold value of each proxy group is unique. We develop a security model to prove the high security and strong unforgeability of the proposed scheme. We analyze the security of our scheme based on the four types of adversaries tested in the security model. Compared with previous schemes, the new scheme offers higher security and superior computational efficiency. Copyright © 2013 John Wiley & Sons, Ltd.
Differences in amygdala cell proliferation between adolescent and young adult rats
Authors: Saul Michele L. , Helmreich Dana L. , Callahan Linda M. , Fudge Julie L. 
Published: June 2013

ABSTRACTAdolescence is characterized by changes in both behavior and neural organization. During this period, the amygdala, a structure that mediates social and emotional behaviors, is changing in terms of neural and glia density. We examined cell proliferation within the amygdala of adolescent (post natal day (PND) 31) and adult (PND 70) male Sprague–Dawley rats using BrdU (bromodeoxyuridine) to label dividing cells. BrdU‐labeled cells were distributed throughout the amygdala, often found in fibers surrounding major nuclei. Using two independent cell counting strategies under light and confocal microcopy, respectively, we found significantly more labeled cells in the amygdala in adolescent compared to adult animals (239.3 ± 87.18 vs. 44.75 ± 13.68; n = 4/group; p < .05). BrdU/doublecortin (DCX) positive cells constitute approximately 30% of all dividing cells in the amygdala in both adolescents and adults. These data suggest that compared to young adulthood, adolescence is a relatively active period of cell proliferation in the amygdala. Moreover, the normal decline in dividing cells with age does not preferentially affect cells co‐containing DCX‐immunoreactivity. © 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 517–528, 2014.