bluuebunny/crossref_metadata_2025 huggingface dataset:
Steroid treatment increases the recurrence of radiation‐induced organizing pneumonia after breast‐conserving therapy
Authors: Otani Keisuke , Nishiyama Kinji , Ito Yuri , Kawaguchi Yoshifumi , Inaji Hideo
Published: May 2014

Radiation‐induced organizing pneumonia (RIOP) is an important complication of postoperative radiotherapy for breast cancer. Unfortunately, conventional corticosteroid therapy is frequently associated with relapses. The aim of this retrospective study was to evaluate the outcomes of steroid treatment in patients with RIOP. In total, 26 patients diagnosed with RIOP from among 2404 women who received radiotherapy after breast‐conserving surgery for breast cancer were included and classified into steroid (n = 7) and nonsteroid (n = 19) groups. Serum, sputum, and bronchoalveolar lavage composition; subjective symptoms (cough, fever, and dyspnea); migratory progression; and RIOP relapse were compared between the groups. Treatment type did not affect the duration of the subjective symptoms, which was 1.6 and 1.7 months for the steroid and nonsteroid groups, respectively. In contrast, RIOP relapse and new pulmonary lesions developed in five patients in the steroid group and only three patients in the nonsteroid group (P = 0.014). By assessing RIOP duration as the time to resolution of symptoms and discontinuation of therapy, the median duration of RIOP was significantly longer in the steroid (17.1 months) than that in the nonsteroid group (2.3 months, P = 0.005), primarily because of frequent relapses. After remission, persistent pulmonary dysfunction did not occur in the nonsteroid group. This single‐center retrospective study demonstrates that steroid therapy results in frequent relapses and significantly prolongs RIOP duration. Corticosteroid treatment is considered a critical factor in RIOP recurrence.
Role of latent membrane protein 1 in chronic active Epstein–Barr virus infection‐derived T/NK‐cell proliferation
Authors: Ito Takuto , Kawazu Hidetaka , Murata Takayuki , Iwata Seiko , Arakawa Saki , Sato Yoshitaka , Kuzushima Kiyotaka , Goshima Fumi , Kimura Hiroshi
Published: May 2014

Epstein–Barr virus (EBV) predominantly infects B cells and causes B‐cell lymphomas, such as Burkitt lymphoma and Hodgkin lymphoma. However, it also infects other types of cells, including T and natural killer (NK) cells, and causes disorders, such as chronic active EBV infection (CAEBV) and T/NK‐cell lymphoma. The CAEBV is a lymphoproliferative disease with poor prognosis, where EBV‐positive T or NK cells grow rapidly, although the molecular mechanisms that cause the cell expansion still remain to be elucidated. EBV‐encoded latent membrane protein 1 (LMP1) is an oncogene that can transform some cell types, such as B cells and mouse fibroblasts, and thus may stimulate cell proliferation in CAEBV. Here, we examined the effect of LMP1 on EBV‐negative cells using the cells conditionally expressing LMP1, and on CAEBV‐derived EBV‐positive cells by inhibiting the function of LMP1 using a dominant negative form of LMP1. We demonstrated that LMP1 was responsible for the increased cell proliferation in the cell lines derived from CAEBV, while LMP1 did not give any proliferative advantage to the EBV‐negative cell line.
Single‐cell heterogeneity in suppression of PC12 differentiation by direct microinjection of a differentiation inhibitor, U0126
Authors: Chung Jihye , Miura Natsuko , Ito Akio , Sawada Munetaka , Nishikawa Shigemichi , Kuroda Kouichi , Ueda Mitsuyoshi
Published: May 2014

Phenotypic and genomic heterogeneity among single cells in a cell population leads to inaccuracy and obscuration in research about mammalian cell differentiation. In order to address the problems regarding bulk analysis on heterogeneous cell populations, it is necessary to accurately regulate and analyze changes in differentiating cells at the single‐cell level. To investigate the single‐cell changes in PC12 neuronal differentiation that occur when inhibited by U0126, an inhibitor of mitogen‐activated protein kinase kinase (MEK), we directly injected the chemical into individual target cells and analyzed the outcomes (neurite outgrowth) at the single‐cell level. As a result, we could accurately regulate the quantity of U0126 being introduced into each target cell, which was previously not possible using the common method of simply adding the inhibitor to the culture medium. It was possible to analyze the inhibitive effect of U0126 even when the injected quantity was lower than the lower limit for inhibition when added to culture medium (0.1 μM, identical to 1.2 × 108 molecules per cell on dish). In particular, injection of 1.5 × 107 molecules into each cell resulted in a 59% decrease of the mean total neurite length. Time‐course analysis of neurite outgrowth at the single‐cell level using fluorescence staining method showed that the changes in neurite length of differentiating PC12 cells were not homogeneous, but were largely variable across individual target cells.
Nucleolar persistence during spermatogenesis of the genus Rhodnius (Hemiptera, Triatominae)
Authors: Alevi Kaio Cesar Chaboli , da Costa Castro Nayara Fernanda , Lima Anna Claudia Campaner , Ravazi Amanda , Morielle‐Souza Alessandra , de Oliveira Jader , da Rosa João Aristeu , de Azeredo Oliveira Maria Tercília Vilela
Published: May 2014

The Triatominae subfamily is comprised of 18 genera and six tribes. The tribe Rhodniini is comprised of two genera (Rhodnius and Psammolestes). Nucleolar persistence is defined by the presence of the nucleolus or nucleolar corpuscles during the meiotic metaphase. To date, this phenomenon has been described for 13 species of triatomine that are included in the genera Triatoma, Rhodnius, and Panstrongylus. Thus, because the phenomenon of nucleolar persistence has been described in only two species of the genus Rhodnius, we have analyzed the nucleolar behavior during spermatogenesis of eight species of the genus Rhodnius (R. colombiensis, R. montenegrensis, R. nasutus, R. neglectus, R. neivai, R. pictipes, R. prolixus, and R. robustus), with a focus on nucleolar persistence. By means of cytogenetic analysis with silver ions, nucleolar behavior during spermatogenesis is described in the eight species of Rhodnius analyzed. In all of them nucleolar behavior was similar and the phenomenon of nucleolar persistence was often observed. Therefore, we confirm nucleolar persistence as a peculiarity of the genus Rhodnius. However, it is emphasized that new cytogenetic analysis should be performed in the Triatominae subfamily, more specifically among the 15 genera that do not exhibit the nucleolar behavior described, in order to assess whether this phenomenon is truly a synapomorphy of these hematophagous insects.
Differential mapping of the free barbed and pointed ends of actin filaments in cells
Authors: Ofer Noa , Abu Shah Enas , Keren Kinneret
Published: May 2014

The actin cytoskeleton plays a pivotal role in many cellular processes. Detailed analysis of the architecture of cellular actin networks provides valuable insight into the dynamic self‐organization underlying these processes. In particular, since most of the actin turnover occurs at the tips of actin filaments, it is insightful to map the distribution of filament ends. Here we report a method for differentially labeling the pointed and the barbed ends of actin filaments in cellular networks by permeabilizing cells, following a brief fixation, and introducing labeled actin monomers in the presence or absence of capping protein, respectively. This method quantitatively maps the distributions of free barbed ends and free pointed ends in adherent cells, providing information on the polarity of cytoskeletal structures and mapping active sites available for actin assembly or disassembly. We demonstrate the use of this method by mapping the distribution of actin filament ends in motile fish epithelial keratocytes and in several mammalian cell lines, and show that free barbed ends are enriched near the tip of protruding lamellipodia while free pointed ends concentrate toward the rear. © 2014 Wiley Periodicals, Inc.
Local and commissural IC neurons make axosomatic inputs on large GABAergic tectothalamic neurons
Authors: Ito Tetsufumi , Oliver Douglas L.
Published: May 2014

Large GABAergic (LG) neurons are a distinct type of neuron in the inferior colliculus (IC) identified by their dense vesicular glutamate transporter 2 (VGLUT2)‐containing axosomatic synaptic terminals. Yet the sources of these terminals are unknown. Since IC glutamatergic neurons express VGLUT2, and IC neurons are known to have local collaterals, we tested the hypothesis that these excitatory, glutamatergic axosomatic inputs on LG neurons come from local axonal collaterals and commissural IC neurons. We injected a recombinant viral tracer into the IC which enabled Golgi‐like green fluorescent protein (GFP) labeling in both dendrites and axons. In all cases, we found terminals positive for both GFP and VGLUT2 (GFP+/VGLUT2+) that made axosomatic contacts on LG neurons. One to six axosomatic contacts were made on a single LG cell body by a single axonal branch. The GFP‐labeled neurons giving rise to the VGLUT2+ terminals on LG neurons were close by. The density of GFP+/VGLUT2+ terminals on the LG neurons was related to the number of nearby GFP‐labeled cells. On the contralateral side, a smaller number of LG neurons received axosomatic contacts from GFP+/VGLUT2+ terminals. In cases with a single GFP‐labeled glutamatergic neuron, the labeled axonal plexus was flat, oriented in parallel to the fibrodendritic laminae, and contacted 9‐30 LG cell bodies within the plexus. Our data demonstrated that within the IC microcircuitry there is a convergence of inputs from local IC excitatory neurons on LG cell bodies. This suggests that LG neurons are heavily influenced by the activity of the nearby laminar glutamatergic neurons in the IC. J. Comp. Neurol. 522:3539–3554, 2014. © 2014 Wiley Periodicals, Inc.
High‐performance N‐thread software solutions for mutual exclusion
Authors: Buhr Peter A. , Dice David , Hesselink Wim H.
Published: May 2014

Software solutions for mutual exclusion developed over a 30‐year period, starting with complex ad hoc algorithms and progressing to simpler formal ones. While it is easy to dismiss software solutions for mutual exclusion, as this family of algorithms is antiquated and most platforms support atomic hardware instructions, there is still a need for these algorithms in threaded, embedded systems running on low‐cost processors lacking atomic instructions. While N‐thread solutions are usually short (10–25 lines of code), each is ingenious with exceptionally subtle aspects, often making it difficult to prove correctness or construct an implementation. This work examines correctness and performance of the implementations. An extensive survey of existing algorithms is presented, with explanations of the intuition behind the algorithms and how they work. Several errors were found and corrections made, as well as a few small improvements, in the existing algorithms; two new high‐performance algorithms were developed. Finally, a worst‐case high‐contention performance experiment is performed to compare the algorithms and contrast them with three common locks based on hardware atomic instructions. The results show our two new algorithms are highly competitive with an equivalent hardware lock (Mellor‐Crummey and Scott) over a range of 1–32 processors. Hence, threading is a viable alternative to event‐driven programming for complex embedded systems without atomic instructions. Copyright © 2014 John Wiley & Sons, Ltd.
Structure and photoluminescence properties of SrWO4 3D microspheres synthesized by the surfactant‐assisted hydrothermal method
Authors: Tian Guangru , Sheng Ning , Qiu Xiaomei
Published: May 2014

In this paper, we report large‐scale high‐quality SrWO4 3D microspheres synthesized in aqueous solutions under mild conditions with cetyl trimethyl ammonium bromide as a simple cationic surfactant. These crystals have been characterized by X‐ray diffraction, transmission electron microscopy and field emission scanning electron microscopy techniques. The crystal growth processes were employed to investigate the formation mechanism of SrWO4 3D microspheres. Room‐temperature photoluminescence indicated that the as‐prepared SrWO4 3D microcrystals had strong emission peaks at about 432 and 505 nm, respectively.
Zr‐doped CeO2 Hollow slightly‐truncated nano‐octahedrons: One‐pot synthesis, characterization and their application in catalysis of CO oxidation
Authors: Liu Xiufang , Liu Wei , Zhang Xueying , Han Lu , Zhang Cong , Yang Yanzhao
Published: May 2014

Zirconium‐doped ceria hollow slightly‐truncated nano‐octahedrons (HTNOs) (Ce1‐xZrxO2) were synthesized by a one‐pot, facile hydrothermal method. The morphology and crystalline structure were characterized with powder X‐ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and the high resolution transmission electron microscopy (HRTEM). The composition and chemical valence on the surface of the as‐prepared Ce1‐xZrxO2 powders were detected by X‐ray photoelectron spectroscopy (XPS) and energy dispersive spectrometry (EDS). The surface area and pore size distribution of as‐obtained Zr‐doped ceria HTNOs were measured by N2 adsorption‐desorption measurement. Mechanisms for the growth of Zr‐doped ceria HTNOs are proposed as both oriented attachment and Ostwald ripening process and the formation of the hollow structure is strongly dependent on the addition of Zr4+ ions. Furthermore, the as‐obtained Zr‐doped ceria HTNOs revealed superior catalytic activity and thermal stability toward CO oxidation compared to pure ceria. It may provide a new path for the fabrication of inorganic hollow structures on introducing alien metal ions.
One‐pot fabrication of large‐scale ordered NiTe nanosheets and its application in lithium‐ion batteries
Authors: Sun Bin , Mi Liwei , Ding Qi , Cui Shizhong
Published: May 2014

Large‐scale sheet‐like nickel telluride (NiTe) nanocrystals in situ grown on nickel foam with three‐dimensional network structure were successfully synthesized by reacting elemental nickel with tellurium powder. The reaction was conducted via a facile solvothermal method in a mixed solvent composed of 1 mL ethylenediamine and 15 mL ethylene glycol at 170°C for 24 h. The growth process and the possible formation mechanism were discussed based on the intermediate products obtained at different reaction stages including different reaction times and temperatures. When the as‐synthesized NiTe nanosheets were employed as anode materials for lithium‐ion batteries, this work enriches the electrode materials for energy materials, and can serve as a good reference for the fabrication of desired materials.
Differential role of NK cells against Candida albicans infection in immunocompetent or immunocompromised mice
Authors: Quintin Jessica , Voigt Jessica , van der Voort Robbert , Jacobsen Ilse D. , Verschueren Ineke , Hube Bernhard , Giamarellos‐Bourboulis Evangelos J. , van der Meer Jos W. M. , Joosten Leo A. B. , Kurzai Oliver , Netea Mihai G.
Published: May 2014

Little is known regarding the role of NK cells during primary and secondary disseminated Candida albicans infection. We assessed the role of NK cells for host defense against candidiasis in immunocompetent, as well as immunodeficient, hosts. Surprisingly, depletion of NK cells in immunocompetent WT mice did not increase susceptibility to systemic candidiasis, suggesting that NK cells are redundant for antifungal defense in otherwise immunocompetent hosts. NK‐cell‐depleted mice were found to be protected as a consequence of attenuation of systemic inflammation. In contrast, the absence of NK cells in T/B/NK‐cell‐deficient NSG (NOD SCID gamma) mice led to an increased susceptibility to both primary and secondary systemic C. albicans infections compared with T/B‐cell‐deficient SCID mice. In conclusion, this study demonstrates that NK cells are an essential and nonredundant component of anti‐C. albicans host defense in immunosuppressed hosts with defective T/B‐lymphocyte immunity, while contributing to hyperinflammation in immunocompetent hosts. The discovery of the importance of NK cells in hosts with severe defects of adaptive immunity might have important consequences for the design of adjunctive immunotherapeutic approaches in systemic C. albicans infections targeting NK‐cell function.
γδ T cells restrain extrathymic development of Foxp3+‐inducible regulatory T cells via IFN‐γ
Authors: Visperas Anabelle , Shen Bo , Min Booki
Published: May 2014

Inducible Treg (iTreg) cells generated from Ag‐stimulated naïve CD4+ T cells in the periphery play an important role in regulating immune responses. TGF‐β is a key cytokine that promotes this conversion process; however, how this process is regulated in vivo remains unclear. Here, we report that γδ T cells play a crucial role in controlling iTreg generation and suppressor function. Ag‐induced iTreg generation was significantly enhanced in C57BL/6 mice in the absence of γδ T cells. Inhibition of iTreg conversion was mediated by IFN‐γ produced by activated γδ T cells but not by activated CD4+ T cells. BM chimera experiments further confirmed γδ‐derived IFN‐γ‐dependent mechanism in regulating iTreg generation in vivo. Lastly, human peripheral blood γδ T cells also interfere with iTreg conversion via IFN‐γ. Our results suggest a novel function of γδ T cells in limiting the generation of iTreg cells, potentially balancing immunity and tolerance.
Sensitive enantioanalysis of β‐blockers via field‐amplified sample injection combined with water removal in microemulsion electrokinetic chromatography
Authors: Ma Yanhua , Zhang Huige , Rahman Zia ur , Wang Weifeng , Li Xi , Chen Hongli , Chen Xingguo
Published: May 2014

In this study, an on‐line sample preconcentration technique, field‐amplified sample injection combined with water removal by electroosmotic flow (EOF) pump, was applied to realize a highly sensitive chiral analysis of β‐blocker enantiomers by MEEKC. The introduction of a water plug in capillary before the electrokinetic injection provided the effective preconcentration of chiral compounds. And then the water was moving out of the column from the injection end under the effect of the EOF, which avoided dilution of the stacked β‐blocker enantiomers concentration suffering from the presence of water in separation buffer. Moreover, the addition of H3PO4 and methanol in the sample solution greatly improved the enhancement efficiency further. Under optimized conditions, more than 2700‐fold enhancement in sensitivity was obtained for each enantiomer of bupranolol (BU), alprenolol (AL), and propranolol (PRO) via electrokinetic injection. LODs were 0.10, 0.10, 0.12, 0.11, 0.02, and 0.02 ng/mL for S‐BU, R‐BU, S‐AL, R‐AL, S‐PRO, and R‐PRO, respectively. Eventually, the proposed method was successfully applied to the determination of BU, AL, and PRO in serum samples with good recoveries ranging from 93.4 to 98.2%.
An evaluation of fish early life stage tests for predicting reproductive and longer-term toxicity from plant protection product active substances
Authors: Wheeler James R. , Maynard Samuel K. , Crane Mark
Published: May 2014

The chronic toxicity of chemicals to fish is routinely assessed by using fish early life stage (ELS) test results. Fish full life cycle (FLC) tests are generally required only when toxicity, bioaccumulation, and persistence triggers are met or when there is a suspicion of potential endocrine-disrupting properties. This regulatory approach is based on a relationship between the results of fish ELS and FLC studies first established more than 35 yrs ago. Recently, this relationship has been challenged by some regulatory authorities, and it has been recommended that more substances should undergo FLC testing. In addition, a project proposal has been submitted to the Organisation for Economic Cooperation and Development (OECD) to develop a fish partial life cycle (PLC) test including a reproductive assessment. Both FLC and PLC tests are animal- and resource-intensive and technically challenging and should therefore be undertaken only if there is clear evidence that they are necessary for coming to a regulatory decision. The present study reports on an analysis of a database of paired fish ELS and FLC endpoints for plant protection product active substances from European Union draft assessment reports and the US Environmental Protection Agency Office of Pesticide Programs Pesticide Ecotoxicity Database. Analysis of this database shows a clear relationship between ELS and FLC responses, with similar median sensitivity across substances when no-observed-effect concentrations (NOECs) are compared. There was also no indication that classification of a substance as a mammalian reproductive toxicant leads to more sensitive effects in fish FLC tests than in ELS tests. Indeed, the response of the ELS tests was generally more sensitive than the most sensitive reproduction NOEC from a FLC test. This analysis indicates that current testing strategies and guidelines are fit for purpose and that there is no need for fish full or partial life cycle tests for most plant protection product active substances. Environ Toxicol Chem 2014;33:1874–1878. © 2014 SETAC
Development of a regression model to predict copper toxicity to Daphnia magna and site-specific copper criteria across multiple surface-water drainages in an arid landscape
Authors: Fulton Barry A. , Meyer Joseph S.
Published: May 2014

The water effect ratio (WER) procedure developed by the US Environmental Protection Agency is commonly used to derive site-specific criteria for point-source metal discharges into perennial waters. However, experience is limited with this method in the ephemeral and intermittent systems typical of arid climates. The present study presents a regression model to develop WER-based site-specific criteria for a network of ephemeral and intermittent streams influenced by nonpoint sources of Cu in the southwestern United States. Acute (48-h) Cu toxicity tests were performed concurrently with Daphnia magna in site water samples and hardness-matched laboratory waters. Median effect concentrations (EC50s) for Cu in site water samples (n = 17) varied by more than 12-fold, and the range of calculated WER values was similar. Statistically significant (α = 0.05) univariate predictors of site-specific Cu toxicity included (in sequence of decreasing significance) dissolved organic carbon (DOC), hardness/alkalinity ratio, alkalinity, K, and total dissolved solids. A multiple-regression model developed from a combination of DOC and alkalinity explained 85% of the toxicity variability in site water samples, providing a strong predictive tool that can be used in the WER framework when site-specific criteria values are derived. The biotic ligand model (BLM) underpredicted toxicity in site waters by more than 2-fold. Adjustments to the default BLM parameters improved the model's performance but did not provide a better predictive tool compared with the regression model developed from DOC and alkalinity. Environ Toxicol Chem 2014;33:1865–1873. © 2014 SETAC
Giant scaffolding protein AHNAK1 interacts with β‐dystroglycan and controls motility and mechanical properties of schwann cells
Authors: von Boxberg Ysander , Soares Sylvia , Féréol Sophie , Fodil Redouane , Bartolami Sylvain , Taxi Jacques , Tricaud Nicolas , Nothias Fatiha
Published: May 2014

The profound morphofunctional changes that Schwann cells (SCs) undergo during their migration and elongation on axons, as well as during axon sorting, ensheathment, and myelination, require their close interaction with the surrounding laminin‐rich basal lamina. In contrast to myelinating central nervous system glia, SCs strongly and constitutively express the giant scaffolding protein AHNAK1, localized essentially underneath the outer, abaxonal plasma membrane. Using electron microscopy, we show here that in the sciatic nerve of ahnak1−/− mice the ultrastructure of myelinated, and unmyelinated (Remak) fibers is affected. The major SC laminin receptor β‐dystroglycan co‐immunoprecipitates with AHNAK1 shows reduced expression in ahnak1−/− SCs, and is no longer detectable in Cajal bands on myelinated fibers in ahnak1−/− sciatic nerve. Reduced migration velocity in a scratch wound assay of purified ahnak1−/− primary SCs cultured on a laminin substrate indicated a function of AHNAK1 in SC motility. This was corroborated by atomic force microscopy measurements, which revealed a greater mechanical rigidity of shaft and leading tip of ahnak1−/− SC processes. Internodal lengths of large fibers are decreased in ahnak1−/− sciatic nerve, and longitudinal extension of myelin segments is even more strongly reduced after acute knockdown of AHNAK1 in SCs of developing sciatic nerve. Together, our results suggest that by interfering in the cross‐talk between the transmembrane form of the laminin receptor dystroglycan and F‐actin, AHNAK1 influences the cytoskeleton organization of SCs, and thus plays a role in the regulation of their morphology and motility and lastly, the myelination process. GLIA 2014;62:1392–1406
On the Optimal Production Capacity for Influenza Vaccine
Authors: Forslid Rikard , Herzing Mathias
Published: May 2014

This paper analyzes the profit maximizing capacity choice of a monopolistic vaccine producer facing the uncertain event of a pandemic in a homogenous population of forward‐looking individuals. For any capacity level, the monopolist solves the intertemporal price discrimination problem within the dynamic setting generated by the standard mathematical epidemiological model of infectious diseases. Even though consumers are assumed to be identical, the monopolist will be able to exploit the ex post heterogeneity between infected and susceptible individuals by raising the price of vaccine in response to the increasing hazard rate. The monopolist thus bases its investment decision on the expected profits from the optimal price path given the infection dynamics. It is shown that the monopolist will always choose to invest in a lower production capacity than the social planner. Through numerical simulation, it is demonstrated how the loss to society of having a monopoly producer decreases with the speed of infection transmission. Moreover, it is illustrated how the monopolist's optimal vaccination rate increases as its discount rate rises for cost parameters based on Swedish data. However, the effect of the firm discount rate on its investment decision is sensitive to assumptions regarding the cost of production capacity. Copyright © 2014 John Wiley & Sons, Ltd.
Benzyl alcohol attenuates acetaminophen-induced acute liver injury in a Toll-like receptor-4-dependent pattern in mice
Authors: Cai Changchun , Huang Hai , Whelan Sean , Liu Li , Kautza Benjamin , Luciano Jason , Wang Guoliang , Chen Guoqiang , Stratimirovic Sladjana , Tsung Allan , Billiar Timothy R. , Zuckerbraun Brian S.
Published: May 2014

Acetaminophen (APAP) toxicity is the most common cause of acute liver failure in industrialized countries. Understanding the mechanisms of APAP-induced liver injury as well as other forms of sterile liver injury is critical to improve the care of patients. Recent studies demonstrate that danger signaling and inflammasome activation play a role in APAP-induced injury. The aim of these investigations was to test the hypothesis that benzyl alcohol (BA) is a therapeutic agent that protects against APAP-induced liver injury by modulation of danger signaling. APAP-induced liver injury was dependent, in part, on Toll-like receptor (TLR)9 and receptor for advanced glycation endproducts (RAGE) signaling. BA limited liver injury over a dose range of 135-540 μg/g body weight or when delivered as a pre-, concurrent, or post-APAP therapeutic. Furthermore, BA abrogated APAP-induced cytokines and chemokines as well as high-mobility group box 1 release. Moreover, BA prevented APAP-induced inflammasome signaling as determined by interleukin (IL)-1β, IL-18, and caspase-1 cleavage in liver tissues. Interestingly, the protective effects of BA on limiting liver injury and inflammasome activation were dependent on TLR4 signaling, but not TLR2 or CD14. Cell-type–specific knockouts of TLR4 were utilized to further determine the protective mechanisms of BA. These studies found that TLR4 expression specifically in myeloid cells (LyzCre-tlr4
−/−) were necessary for the protective effects of BA. Conclusion: BA protects against APAP-induced acute liver injury and reduced inflammasome activation in a TLR4-dependent manner. BA may prove to be a useful adjunct in the treatment of APAP and other forms of sterile liver injury. (Hepatology 2014;60:990–1002)
Expansion of prominin-1-expressing cells in association with fibrosis of biliary atresia
Authors: Mavila Nirmala , James David , Shivakumar Pranavkumar , Nguyen Marie V. , Utley Sarah , Mak Katrina , Wu Allison , Zhou Shengmei , Wang Larry , Vendyres Christopher , Groff Megan , Asahina Kinji , Wang Kasper S.
Published: May 2014

Biliary atresia (BA), the most common cause of end-stage liver disease and the leading indication for pediatric liver transplantation, is associated with intrahepatic ductular reactions within regions of rapidly expanding periportal biliary fibrosis. Whereas the extent of such biliary fibrosis is a negative predictor of long-term transplant-free survival, the cellular phenotypes involved in the fibrosis are not well established. Using a rhesus rotavirus-induced mouse model of BA, we demonstrate significant expansion of a cell population expressing the putative stem/progenitor cell marker, PROMININ-1 (PROM1), adjacent to ductular reactions within regions of periportal fibrosis. PROM1positive (pos) cells express Collagen-1α1. Subsets of PROM1pos cells coexpress progenitor cell marker CD49f, epithelial marker E-CADHERIN, biliary marker CYTOKERATIN-19, and mesenchymal markers VIMENTIN and alpha-SMOOTH MUSCLE ACTIN (αSMA). Expansion of the PROM1pos cell population is associated with activation of Fibroblast Growth Factor (FGF) and Transforming Growth Factor-beta (TGFβ) signaling. In vitro cotreatment of PROM1-expressing Mat1a−/−
hepatic progenitor cells with recombinant human FGF10 and TGFβ1 promotes morphologic transformation toward a myofibroblastic cell phenotype with increased expression of myofibroblastic genes Collagen-1α1, Fibronectin, and α-Sma. Infants with BA demonstrate similar expansion of periportal PROM1pos cells with activated Mothers Against Decapentaplegic Homolog 3 (SMAD3) signaling in association with increased hepatic expression of FGF10, FGFR1, and FGFR2 as well as mesenchymal genes SLUG and SNAIL. Infants with perinatal subtype of BA have higher tissue levels of PROM1 expression than those with embryonic subtype. Conclusion: Expansion of collagen-producing PROM1pos cells within regions of periportal fibrosis is associated with activated FGF and TGFβ pathways in both experimental and human BA. PROM1pos cells may therefore play an important role in the biliary fibrosis of BA. (Hepatology 2014;60:941–953)
Pattern separation of emotional information in hippocampal dentate and CA3
Authors: Leal Stephanie L. , Tighe Sarah K. , Jones Craig K. , Yassa Michael A.
Published: May 2014

Emotional arousal, mediated by the amygdala, is known to modulate episodic memories stored by the hippocampus, a region involved in pattern separation (the process by which similar representations are independently stored). While emotional modulation and pattern separation have been examined independently, this study attempts to link the two areas of research to propose an alternative account for how emotion modulates episodic memory. We used an emotional discrimination task designed to tax pattern separation of emotional information by concurrently varying emotional valence and similarity of stimuli. To examine emotional modulation of memory at the level of hippocampal subfields, we used high‐resolution fMRI (1.5 mm isotropic) of the medial temporal lobe. Consistent with prior reports, we observed engagement of the hippocampal dentate gyrus (DG) and CA3 during accurate discrimination of highly similar items (behavioral correlate of pattern separation). Furthermore, we observed an emotional modulation of this signal (negative > neutral) specific to trials on which participants accurately discriminated similar emotional items. The amygdala was also modulated by emotion, regardless of the accuracy of discrimination. Additionally, we found aberrant amygdala‐hippocampal network activity in a sample of adults with depressive symptoms. In this sample, amygdala activation was enhanced and DG/CA3 activation was diminished during emotional discrimination compared to those without depressive symptoms. Depressive symptom severity was also negatively correlated with DG/CA3 activity. This study suggests a novel mechanistic account for how emotional information is processed by hippocampal subfields as well as how this network may be altered in mood disorders. © 2014 Wiley Periodicals, Inc.
Vegetation pattern as an indicator of saturated areas in a Czech headwater catchment
Authors: Kulasova Alena , Blazkova Sarka , Beven Keith , Rezacova Daniela , Cajthaml Jiri
Published: May 2014

To test whether models give a good description of hydrological processes, some spatial mapping of the characteristics of wetness in the catchment is needed. One way is the observation of dynamic saturated areas, which in many small catchments, will be strongly related to the generation of fast run‐off. Areas that are frequently saturated are also often strongly related to vegetation types. In this contribution, we describe mapping based on the vegetation patterns in a small catchment at the foothills of the Jizera Mountains in the Czech Republic. A Monte Carlo method is used to compare the vegetation pattern with saturation mapping using a boot method, mapping based on piezometer levels, and with the pattern of a topographic index. In the Smrzovsky Brook catchment, the vegetation communities are well correlated with the topographic index. Copyright © 2014 John Wiley & Sons, Ltd.
Preventive Effect of CuCl2on Behavioral Alterations and Mercury Accumulation in Central Nervous System Induced by HgCl2in Newborn Rats
Authors: Moraes‐Silva L. , Siqueira L. F. , Oliveira V. A. , Oliveira C. S. , Ineu R. P. , Pedroso T. F. , Fonseca M. M. , Pereira M. E.
Published: May 2014

This study investigated the benefits of Cu preexposition on Hg effects on behavioral tests, acetylcholinesterase (AChE) activity and Hg, and essential metal contents in the cerebrum and cerebellum of neonate rats. Wistar rats received (subcutaneous) saline or CuCl2·2H2O (6.9 mg/kg/day) when they were 3 to 7 days old and saline or HgCl2(5.0 mg/kg/day) when they were 8 to 12 days old. Mercury exposure reduced the performance of rats in the negative geotaxis (3–13 days) and beaker test (17–20 days), inhibited cerebellum AChE activity (13 days), increased cerebrum and cerebellum Hg (13 days), cerebrum Cu (13 days), and cerebrum and cerebellum Zn levels (33 days). The performance of rats in the tail immersion and rotarod tests as well as Fe and Mg levels were not altered by treatments. Copper prevented all alterations induced by mercury. These results are important to open a new perspective of prevention and/or therapy for mercury exposure.
Simulations of remote mutants of dihydrofolate reductase reveal the nature of a network of residues coupled to hydride transfer
Authors: Roston Daniel , Kohen Amnon , Doron Dvir , Major Dan T.
Published: May 2014

Recent experimental and theoretical studies have proposed that enzymes involve networks of coupled residues throughout the protein that participate in motions accompanying chemical barrier crossing. Here, we have examined portions of a proposed network in dihydrofolate reductase (DHFR) using quantum mechanics/molecular mechanics simulations. The simulations use a hybrid quantum mechanics‐molecular mechanics approach with a recently developed semiempirical AM1‐SRP Hamiltonian that provides accurate results for this reaction. The simulations reproduce experimentally determined catalytic rates for the wild type and distant mutants of E. coli DHFR, underscoring the accuracy of the simulation protocol. Additionally, the simulations provide detailed insight into how residues remote from the active site affect the catalyzed chemistry, through changes in the thermally averaged properties along the reaction coordinate. The mutations do not greatly affect the structure of the transition state near the bond activation, but we observe differences somewhat removed from the point of CH cleavage that affect the rate. The mutations have global effects on the thermally averaged structure that propagate throughout the enzyme and the current simulations highlight several interactions that appear to be particularly important. © 2014 Wiley Periodicals, Inc.
Modeling the electrostatic potential of asymmetric lipopolysaccharide membranes: The MEMPOT algorithm implemented in DelPhi
Authors: Dias Roberta P. , Li Lin , Soares Thereza A. , Alexov Emil
Published: May 2014

Four chemotypes of the rough lipopolysaccharides (LPS) membrane from Pseudomonas aeruginosa were investigated by a combined approach of explicit water molecular dynamics (MD) simulations and Poisson–Boltzmann continuum electrostatics with the goal to deliver the distribution of the electrostatic potential across the membrane. For the purpose of this investigation, a new tool for modeling the electrostatic potential profile along the axis normal to the membrane, MEMbrane POTential (MEMPOT), was developed and implemented in DelPhi. Applying MEMPOT on the snapshots obtained by MD simulations, two observations were made: (a) the average electrostatic potential has a complex profile but is mostly positive inside the membrane due to the presence of Ca2+ ions, which overcompensate for the negative potential created by lipid phosphate groups; and (b) correct modeling of the electrostatic potential profile across the membrane requires taking into account the water phase, while neglecting it (vacuum calculations) results in dramatic changes including a reversal of the sign of the potential inside the membrane. Furthermore, using DelPhi to assign different dielectric constants for different regions of the LPS membranes, it was investigated whether a single frame structure before MD simulations with appropriate dielectric constants for the lipid tails, inner, and the external leaflet regions, can deliver the same average electrostatic potential distribution as obtained from the MD‐generated ensemble of structures. Indeed, this can be attained by using smaller dielectric constant for the tail and inner leaflet regions (mostly hydrophobic) than for the external leaflet region (hydrophilic) and the optimal dielectric constant values are chemotype‐specific. © 2014 Wiley Periodicals, Inc.
Soluble l‐Selectin as an Independent Biomarker of Bronchial Asthma
Authors: Nadi Ebrahim , Hajilooi Mehrdad , Pajouhan Saeed , Haidari Mehran
Published: May 2014

Background

We sought to determine the association of plasma level of soluble l‐selectin (sL‐selectin) and F206L polymorphism of l‐selectin with asthma.

Methods

A total of 90 asthmatic patients and 90 sex‐ and age‐matched healthy controls were enrolled. The plasma level of sl‐selectin was measured by enzyme‐linked immunosorbent assay (ELISA) method. An amplification refractory mutation system polymerase chain reaction was performed to detect F206L polymorphism of l‐selectin.

Results

The mean plasma levels of sl‐selectin was significantly higher in the patients with asthma than the controls (2113 ± 466 vs. 1664 ± 322 ng/ml, P = 0.001). Logistic regression analysis after adjustment for age, sex, and body mass index demonstrated that plasma levels of sl‐selectin are an independent biomarkers for asthma (odds ratio [OR], 1.86; 95% confidence interval [95% CI], 1.42–2.24). The area under the receiver operating characteristic (ROC) curve for sl‐selectin was 0.792, 95% CI (0.732–0.862), P = 0.0001. Individuals with the minor homozygote of F206L polymorphism of l‐selectin demonstrated a higher level of sl‐selectin than the major homozygous (2319 ± 732 vs. 1917 ± 453 ng/ml, P = 0.02). No association was found between F206L polymorphism of l‐selectin with asthma.

Conclusion

Our study suggests that plasma level of sl‐selectin is an independent biomarker for asthma.
Developing and Evaluating the HRM Technique for Identifying Cytochrome P450 2D6 Polymorphisms
Authors: Lu Hsiu‐Chin , Chang Ya‐Sian , Chang Chun‐Chi , Lin Ching‐Hsiung , Chang Jan‐Gowth
Published: May 2014

Background

Cytochrome P450 2D6 is one of the important enzymes involved in the metabolism of many widely used drugs. Genetic polymorphisms of CYP2D6 can affect its activity. Therefore, an efficient method for identifying CYP2D6 polymorphisms is clinically important.

Methods

We developed a high‐resolution melting (HRM) analysis to investigate CYP2D6 polymorphisms. Genomic DNA was extracted from peripheral blood samples from 71 healthy individuals. All nine exons of the CYP2D6 gene were sequenced before screening by HRM analysis. This method can detect the most genotypes (*1, *2, *4, *10, *14, *21 *39, and *41) of CYP2D6 in Chinese.

Results

All samples were successfully genotyped. The four most common mutant CYP2D6 alleles (*1, *2, *10, and *41) can be genotyped. The single nucleotides polymorphism (SNP) frequencies of 100C > T (rs1065852), 1039C > T (rs1081003), 1661G > C (rs1058164), 2663G > A (rs28371722), 2850C > T (rs16947), 2988G > A (rs28371725), 3181A > G, and 4180G > C (rs1135840) were 58%, 61%, 73%, 1%, 13%, 3%, 1%, 73%, respectively. We identified 100% of all heterozygotes without any errors. The two homozygous genotypes (1661G > C and 4180G > C) can be distinguished by mixing with a known genotype sample to generate an artificial heterozygote for HRM analysis. Therefore, all samples could be identified using our HRM method, and the results of HRM analysis are identical to those obtained by sequencing. Our method achieved 100% sensitivity, specificity, positive prediction value and negative prediction value.

Conclusion

HRM analysis is a nongel resolution method that is faster and less expensive than direct sequencing. Our study shows that it is an efficient tool for typing CYP2D6 polymorphisms.
A case study of a pilot high rate algal pond for the treatment of fish farm and domestic wastewaters
Authors: Posadas Esther , Muñoz Adriana , García‐González Mari‐Cruz , Muñoz Raul , García‐Encina Pedro Antonio
Published: May 2014

BACKGROUND

Microalgae‐based technologies have emerged as a promising approach for simultaneous wastewater treatment and fish food production able to overcome the main limitations in the aquaculture sector. The current study focused on the mechanisms of carbon and nutrient removal from fish farm and domestic wastewaters in a 180 L outdoors pilot high rate algal pond (HRAP) at different hydraulic retention times (HRTs) considering water evaporation losses.

RESULTS

Maximum chemical oxygen demand, total Kjeldahl nitrogen and total phosphorus removal efficiencies of 77 ± 9%, 83 ± 10% and 94 ± 6%, respectively, were recorded during the treatment of fish farm wastewater at 10 d of HRT. Carbon and nitrogen were removed by assimilation into biomass (52 ± 12% and 74 ± 22%, respectively) and stripping, while phosphorus was mainly assimilated into biomass (69 ± 23%). Carbon stripping, along with the low carbon and nutrient loading rates supplied, resulted in low biomass productivities (maximum of 5 g m−2 d−1). A successful solids removal was achieved in the settler (82 ± 18%), which entailed effluent solid concentrations below the maximum permissible discharge limit.

CONCLUSION

Despite the successful wastewater treatment supported by the HRAP, the high water evaporation losses (up of 15 L m−2 d−1) could compromise the technical and environmental viability of this green wastewater treatment technology. © 2014 Society of Chemical Industry
Double papillary fibroelastoma: Beautiful, innocent flowers in the left heart
Authors: Floria Mariana , Gerard Marina , Louagie Yves , Weynand Birgit , Schroeder Erwin
Published: May 2014

Papillary fibroelastoma is a rare, benign tumor, and multiple papillary fibroelastomas are even more uncommon. In an asymptomatic patient scheduled for carotid endarterectomy, transthoracic echocardiography discovered a fibroelastoma on the mitral valve. Then, transesophageal echocardiography showed another fibroelastoma on the aortic valve. Because he also needed a right coronary artery bypass, the patient underwent surgical excision of both masses. Fibroelastomas are not always as innocent as they seem, and surgical excision is necessary because of their potential for systemic or coronary embolization. Transoesophageal echocardiography may improve the diagnosis of multiple papillary fibroelastomas. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 42:574–575, 2014
A Catalyst‐free Green Protocol for the Synthesis of Pyranopyrazoles Using Room Temperature Ionic Liquid Choline Chloride‐urea
Authors: Swaroop Toreshettahally R. , Sharath Kumar Kothanahally S. , Palanivelu Mariyappan , Chaitanya Somu , Rangappa Kanchugarakoppal S.
Published: May 2014

An efficient and rapid four component reaction of aldehydes, malanonitrile, β‐ketoesters and hydrazine hydrate (or phenyl hydrazine) in environmentally benign room temperature ionic liquid choline chloride‐urea has been developed for the synthesis of substituted 4H‐pyrano[2,3‐c]pyrazoles.
Quinolone Analogs 16: A Facile D–H Exchange for 3‐H Proton of 2‐Substituted 4‐Quinolones in Acidic Media
Authors: Kurasawa Yoshihisa , Yoshida Kiminari , Yamazaki Naoki , Sasaki Kenji , Zamami Yoshito , Min Zhao , Togi Atsumi , Ito Hideyuki , Kaji Eisuke , Fukaya Haruhiko
Published: May 2014

The 4‐quinolones having the urea or carbamate moiety at the 2‐position showed the facile deuterium–hydrogen (D–H) exchange of the 3‐H proton in deuteriotrifluoroacetic acid‐deuteriodimethyl sulfoxide (3:1) at 60°C, whereas the 4‐quinolones possessing the carboxylate or carbohydrazide group at the 2‐position and 2‐substituted 4‐methoxyquinolines represented no D–H exchange of the 3‐H proton under the same condition. The aforementioned D–H exchange was found to require both the tautomerization of the 4‐quinolone into 4‐hydroxyquinoline in strongly acidic media and the nitrogen functional group at the 2‐position.
Free‐breathing 3D late gadolinium enhancement imaging of the left ventricle using a stack of spirals at 3T
Authors: Pierce Iain T. , Keegan Jennifer , Drivas Peter , Gatehouse Peter D. , Firmin David N.
Published: May 2014

Purpose

To develop navigator‐gated free‐breathing 3D spiral late gadolinium enhancement (LGE) imaging of the left ventricle at 3T and compare it with conventional breath‐hold 2D Cartesian imaging.

Materials and Methods

Equivalent slices from 3D spiral and multislice 2D Cartesian acquisitions were compared in 15 subjects in terms of image quality (1, nondiagnostic to 5, excellent), sharpness (1–3), and presence of artifacts (0–2). Blood signal‐to‐noise ratio (SNR), blood/myocardium contrast‐to‐noise ratio (CNR), and quantitative sharpness were also compared.

Results

All 3D spiral scans were completed faster than an equivalent 2D Cartesian short‐axis stack (85 vs. 230 sec, P < 0.001). Image quality was significantly higher for 2D Cartesian images than 3D spiral images (3.7 ± 0.87 vs. 3.4 ± 1.05, P = 0.03) but not for mid or apical slices specifically. There were no significant differences in qualitative and quantitative sharpness (95% confidence interval [CI]: 1.91 ± 0.67 vs. 1.93 ± 0.69, P = 0.83 and 95% CI: 0.41 ± 0.07 vs. 0.40 ± 0.09, P = 0.25, respectively), artifact scores (95% CI: 0.16 ± 0.37 vs. 0.40 ± 0.58, P = 0.16), SNR (95% CI: 121.5 ± 55.3 vs. 136.4 ± 77.9, P = 0.13), and CNR (95% CI: 101.6 ± 48.4 vs. 102.7 ± 61.8, P = 0.98). Similar enhancement ratios (0.65 vs. 0.62) and volumes (13.8 vs. 14.1cm3) were measured from scar regions of three patients.

Conclusio

Navigator‐gated 3D spiral LGE imaging can be performed in significantly and substantially shorter acquisition durations, although with some reduced image quality, than multiple breath‐hold 2D Cartesian imaging while providing higher resolution and contiguous coverage. J. Magn. Reson. Imaging 2015;41:1030–1037. © 2014 Wiley Periodicals, Inc.