bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased NKp46 and NKG2D and elevated PD‐1 are associated with altered NK‐cell function in pediatric transplant patients with PTLD
Authors: Wiesmayr Silke , Webber Steven A. , Macedo Camila , Popescu Iulia , Smith Louise , Luce Jane , Metes Diana 
Published: November 2011

AbstractPost‐transplantation lymphoproliferative disorders (PTLD) are life‐threatening complications of organ transplantation caused by EBV infection and the use of chronic immunosuppression. While T‐cell impairment is known to play a critical role in the immunopathogenesis of EBV complications post‐transplantation, the role of NK cells is still under investigation. Here, we have characterized NK‐cell phenotype and function in peripheral blood from asymptomatic pediatric thoracic transplant patients, patients with PTLD, and healthy controls. Overall, asymptomatic pediatric solid organ transplant (Tx) patients presented significant expansion of the CD56brightCD16± subset and displayed effective NK‐cell function, while PTLD patients accumulated CD56dimCD16− and CD56−CD16+ NK‐cell subsets. In addition, NK cells from PTLD patients down‐regulated NKp46 and NKG2D, and significantly up‐regulated PD‐1. These phenotypic changes were associated with NK functional impairment, resembling cellular exhaustion. Disrupting PD‐1 inhibitory pathway improved IFN‐γ release, but did not enhance cytotoxicity in PTLD patients, suggesting that these defects were partially PD‐1 independent. Our results indicate the important role of NK cells during EBV surveillance post‐transplantation, with implications for the immunopathogenesis of EBV complications, and suggest that monitoring NK cells in transplant patients may hold clinical value.
Sphingosine regulates the NLRP3‐inflammasome and IL‐1β release from macrophages
Authors: Luheshi Nadia M. , Giles James A. , Lopez‐Castejon Gloria , Brough David 
Published: November 2011

AbstractInterleukin‐1β (IL‐1β) is a pro‐inflammatory cytokine that regulates inflammatory responses to injury and infection. IL‐1β secretion requires the protease caspase‐1, which is activated following recruitment to inflammasomes. Endogenous danger‐associated molecular patterns (DAMPs) released from necrotic cells activate caspase‐1 through an NLRP3‐inflammasome. Here, we show that the endogenous lipid metabolite sphingosine (Sph) acts as a DAMP by inducing the NLRP3‐inflammasome‐dependent secretion of IL‐1β from macrophages. This process was dependent upon serine/threonine protein phosphatases since the PP1/PP2A inhibitors okadaic acid and calyculin A inhibited Sph‐induced IL‐1β release. IL‐1β release induced by other well‐characterized NLRP3‐inflammasome activators, such as ATP and uric acid crystals, in addition to NLRC4 and AIM2 inflammasome activators was also blocked by these inhibitors. Thus, we propose Sph as a new DAMP, and that a serine/threonine phosphatase (PP1/PP2A)‐dependent signal is central to the endogenous host mechanism through which diverse stimuli regulate inflammasome activation.
Trimethoxyarene as a Highly Ionizable Tag for Reaction Analysis by Atmospheric Pressure Photoionization Mass Spectrometry (APPI/MS): Exploration of Heterocyclic Synthesis
Authors: Bui The Thuong Mathieu , Catala Cédric , Colas Cyril , Schaeffer Christine , Van Dorsselaer Alain , Mann André , Wagner Alain 
Published: November 2011

AbstractA mass spectrometry (MS) method was developed to rapidly analyze crude reaction mixtures. This method relies on highly effective ionization by atmospheric pressure photoionization (APPI) of molecules with a prosthetic trimethoxyarene (TMOA) residue. In a crude reaction mixture, products resulting from the reaction of the TMOA‐labeled substrate will be selectively ionized to afford an easily readable mass spectrum. Interestingly, we noticed that TMOA‐labeled molecules were not fragmented and gave the preferred [M + H]+ ion peak. This APPI‐MS reaction mixture analysis method was used for the optimization of heterocycle synthesis. By comparing results obtained by APPI/MS, GC, and HPLC analysis, it appeared that a semi‐quantification could be achieved by integrating the MS peak intensities.
Cellulase production from palm oil mill effluent in Malaysia: Economical and technical perspectives
Authors: Hii Kiew‐Ling , Yeap Swee‐Pin , Mashitah Mat Don 
Published: November 2011

AbstractThe demand for cellulases has increased tremendously over the last few decades. This is due to its numerous applications in industry and also because it can be used to hydrolyze cellulosic materials into sugars that can be fermented into bioethanol and bio‐based products. This does not only open up a big and significant market for cellulases, but also provides another source of biofuel and bioenergy in the future. Nevertheless, the cost of the existing substrates for cellulase fermentation is very high if required for large‐scale production. Sustainable supplies and an economically feasible biomass are needed to reduce the cost of cellulase production. Palm oil mill effluent (POME) is rich in carbohydrates, proteins, nitrogenous compounds, lipids, minerals, cellulose, hemicelluloses and lignin. It can be used naturally as a fermentation medium, either for cellulase or other value‐added product fermentation. In Malaysia, a large and continually increasing amount of POME is produced every year because of the high global demand for palm oil. Hence, the development of cellulase production from POME is reviewed, covering the POME production, cellulase production and the major challenges together with the future prospects of these processes.
Biosorption of chromium(III) by two brown algae Macrocystis pyrifera and Undaria pinnatifida: Equilibrium and kinetic study
Authors: Cazón Josefina Plaza H. , Benítez Leonardo , Donati Edgardo , Viera Marisa 
Published: November 2011

AbstractTwo brown algae, Macrocystis pyrifera and Undaria pinnatifida, were employed to remove Cr(III) from aqueous solutions. Both seaweeds were characterized in terms of alginate yields. The alginate contents were 20 and 30% of the dry weight for M. pyrifera and U. pinnatifida, respectively. Kinetics experiments were carried out at different initial pH values. Cr(III) biosorption was affected by the solution pH. The highest metal uptake was found at pH 4 for both biosorbents. Different models were applied to elucidate the rate‐controlling mechanism: pseudo‐first‐order, pseudo‐second‐order, external mass transfer and intra‐particle diffusion. The application of Langmuir, Freundlich and Dubinin–Radushkevich models to the equilibrium data showed a better fitting to the first model. The maximum Cr(III) sorption capacity (qm) and the affinity coefficient (b) were very similar for both biosorbents: 0.77 mmol/g and 1.20 L/mmol for M. pyrifera and 0.74 mmol/g and 1.06 L/mmol for U. pinnatifida. The free energy of the sorption process was estimated using the Dubinin–Radushkevich isotherm. The values indicate that the processes are chemical sorptions. To evaluate the significance of the ion‐exchange mechanism, the light metals (Ca2+, Na+, Mg2+ and K+) and pH were measured during the experiments.
Atomic charges of individual reactive chemicals in binary mixtures determine their joint effects: An example of cyanogenic toxicants and aldehydes
Authors: Tian Dayong , Lin Zhifen , Yin Daqiang , Zhang Yalei , Kong Deyang 
Published: November 2011

Abstract
Environmental contaminants are usually encountered as mixtures, and many of these mixtures yield synergistic or antagonistic effects attributable to an intracellular chemical reaction that pose a potential threat on ecological systems. However, how atomic charges of individual chemicals determine their intracellular chemical reactions, and then determine the joint effects for mixtures containing reactive toxicants, is not well understood. To address this issue, the joint effects between cyanogenic toxicants and aldehydes on Photobacterium phosphoreum were observed in the present study. Their toxicological joint effects differed from one another. This difference is inherently related to the two atomic charges of the individual chemicals: the oxygen charge of -CHO (Oaldehyde toxicant) in aldehyde toxicants and the carbon-atom charge of a carbon chain in the cyanogenic toxicant (Ccyanogenic toxicant). Based on these two atomic charges, the following QSAR (quantitative structure–activity relationship) model was proposed: When (Oaldehyde toxicant − Ccyanogenic toxicant) &gt; −0.125, the joint effect of equitoxic binary mixtures at median inhibition (TU, the sum of toxic units) can be calculated as TU = 1.00 ± 0.20; when (Oaldehyde toxicant − Ccyanogenic toxicant) ≤ −0.125, the joint effect can be calculated using (n = 40, r = 0.887, SE = 0.195, F = 140, p &lt; 0.001, q2Loo = 0.748; SE is the standard error of the regression, F is the F test statistic). The result provides insight into the relationship between the atomic charges and the joint effects for mixtures containing cyanogenic toxicants and aldehydes. This demonstrates that the essence of the joint effects resulting from intracellular chemical reactions depends on the atomic charges of individual chemicals. The present study provides a possible approach for the development of a QSAR model for mixtures containing reactive toxicants based on the atomic charges. Environ. Toxicol. Chem. 2012;31:270–278. © 2011 SETAC
Fate of triclosan and triclocarban in soil columns with and without biosolids surface application
Authors: Kwon Jeong-Wook , Xia Kang 
Published: November 2011

Abstract
The leaching and transformation behaviors of triclosan (TCS) and triclocarban (TCC) in soil columns (20 cm high, 4 cm in diameter) packed with an agricultural soil (Roxana very fine sandy loam) with and without biosolids surface application were investigated. The column leachates and soil samples were analyzed for TCS, TCC, and their transformation products. Significantly more TCS was transformed compared with TCC. Surface application of biosolids significantly retarded their transformation. Downward movement of TCS and TCC occurred within a 10-cm soil depth. Methyl-TCS was not detectable in the leachates but was detected in the top 5-cm soil layer, with more appearing in the biosolids-applied soil. At the end of the column study, carbanilide (CBA) was the only detectable TCC reductive dechlorination product in the soil. No TCC reductive dechlorination products were detectable in the leachates. Detection of 3,4-dichloroaniline (3,4-DCA) and 4-chloroaniline (4-CA) suggested the occurrence of TCC hydrolysis. Rapid leaching of 4-CA through the soil column was observed. The 3,4-DCA was detected throughout the entire 20-cm depth of the soil column but not in the leachates. The fact that only small percentages of the transformed TCS and TCC appeared, after a 101-d column study, in the forms of the products analyzed suggested that either the investigated transformation pathways were minor pathways or further rapid transformation of those products had occurred. Environ. Toxicol. Chem. 2012;31:262–269. © 2011 SETAC
Dissolved organic carbon reduces the toxicity of aluminum to three tropical freshwater organisms
Authors: Trenfield Melanie A. , Markich Scott J. , Ng Jack C. , Noller Barry , van Dam Rick A. 
Published: November 2011

Abstract
The influence of dissolved organic carbon (DOC) on the toxicity of aluminum (Al) at pH 5 (relevant to acid mine drainage conditions), to the tropical green hydra (Hydra viridissima), green alga (Chlorella sp.), and cladoceran (Moinodaphnia macleayi) was assessed. Two DOC sources, a natural in situ DOC in soft billabong water (SBW) and Suwannee River fulvic acid (SRFA) standard, were compared. The order of sensitivity of the test organisms to dissolved Al (0.1 µm fraction) was Hydra viridissima &gt; Moinodaphnia macleayi &gt; Chlorella sp. with DOC reducing dissolved Al toxicity most for Hydra viridissima. However, colloidal or precipitated Al may contribute indirectly to the toxicity for M. macleayi and Chlorella sp. The toxicity of dissolved Al was up to six times lower in test waters containing 10 mg L−1 DOC (in the form of SRFA), relative to toxicity observed at 1 mg L−1 DOC. In contrast, the toxicity of Al was up to two times lower in SBW containing 10 mg L−1 DOC, relative to water containing 1 mg L−1 DOC. The increased ability of SRFA in reducing Al toxicity was linked to its greater affinity for complexing Al compared with the in situ DOC. This has important implications for studies that use commercial standards of humic substances to predict Al toxicity in local environments. Speciation modeling demonstrated that Al3+ and AlOH2+ provided a strong relationship with toxicity. An empirical relationship is provided for each organism that can be used to predict Al toxicity at a given Al and DOC concentration. Environ. Toxicol. Chem. 2012;31:427–436. © 2011 SETAC
Challenges for the development of a biotic ligand model predicting copper toxicity in estuaries and seas
Authors: de Polo Anna , Scrimshaw Mark D. 
Published: November 2011

Abstract
An effort is ongoing to develop a biotic ligand model (BLM) that predicts copper (Cu) toxicity in estuarine and marine environments. At present, the BLM accounts for the effects of water chemistry on Cu speciation, but it does not consider the influence of water chemistry on the physiology of the organisms. We discuss how chemistry affects Cu toxicity not only by controlling its speciation, but also by affecting the osmoregulatory physiology of the organism, which varies according to salinity. In an attempt to understand the mechanisms of Cu toxicity and predict its impacts, we explore the hypothesis that the common factor linking the main toxic effects of Cu is the enzyme carbonic anhydrase (CA), because it is a Cu target with multiple functions and salinity-dependent expression and activity. According to this hypothesis, the site of action of Cu in marine fish may be not only the gill, but also the intestine, because in this tissue CA plays an important role in ion transport and water adsorption. Therefore, the BLM of Cu toxicity to marine fish should also consider the intestine as a biotic ligand. Finally, we underline the need to incorporate the osmotic gradient into the BLM calculations to account for the influence of physiology on Cu toxicity. Environ. Toxicol. Chem. 2012;31:230–238. © 2011 SETAC
Promoter methylation and loss of p16INK4a gene expression in head and neck cancer
Authors: Demokan Semra , Chuang Alice , Suoğlu Yusufhan , Ulusan Murat , Yalnız Zubeyde , Califano Joseph A. , Dalay Nejat 
Published: November 2011

AbstractBackgroundSilencing of tumor suppressor genes plays a vital role in head and neck carcinogenesis. In this study we aimed to evaluate aberrant p16INK4a gene promoter methylation in patients with head and neck cancer.MethodsMethylation of the gene was investigated by bisulfite modification/methylation‐specific polymerase chain reaction and gene expression levels were analyzed by quantitative reverse transcription–polymerase chain reaction in tumors and matched normal tissue samples from Turkish patients with head and neck cancer.ResultsThe promoter region of the p16INK4a gene was methylated in 67.5% and 28.6% of the primary tumors and the corresponding normal tissue, respectively. This difference was highly significant. In concordance, p16INK4a gene expression was downregulated in 67.5% of the tumor samples. Methylation and the absence of expression in the tumors were observed in 48% of the patients.ConclusionsOur data indicate that methylation of the p16INK4a gene is a frequent event in primary head and neck cancer and that it plays a major role in the silencing of p16INK4a gene expression during tumor development. © 2011 Wiley Periodicals, Inc. Head Neck, 2011
Thrombospondin-1 is a novel negative regulator of liver regeneration after partial hepatectomy through transforming growth factor-beta1 activation in mice
Authors: Hayashi Hiromitsu , Sakai Keiko , Baba Hideo , Sakai Takao 
Published: November 2011

Abstract

The matricellular protein, thrombospondin-1 (TSP-1), is prominently expressed during tissue repair. TSP-1 binds to matrix components, proteases, cytokines, and growth factors and activates intracellular signals through its multiple domains. TSP-1 converts latent transforming growth factor-beta1 (TGF-β1) complexes into their biologically active form. TGF-β plays significant roles in cell-cycle regulation, modulation of differentiation, and induction of apoptosis. Although TGF-β1 is a major inhibitor of proliferation in cultured hepatocytes, the functional requirement of TGF-β1 during liver regeneration remains to be defined

in vivo

. We generated a TSP-1-deficient mouse model of a partial hepatectomy (PH) and explored TSP-1 induction, progression of liver regeneration, and TGF-β-mediated signaling during the repair process after hepatectomy. We show here that TSP-1-mediated TGF-β1 activation plays an important role in suppressing hepatocyte proliferation. TSP-1 expression was induced in endothelial cells (ECs) as an immediate early gene in response to PH. TSP-1 deficiency resulted in significantly reduced TGF-β/Smad signaling and accelerated hepatocyte proliferation through down-regulation of p21 protein expression. TSP-1 induced in ECs by reactive oxygen species (ROS) modulated TGF-β/Smad signaling and proliferation in hepatocytes

in vitro

, suggesting that the immediately and transiently produced ROS in the regenerating liver were the responsible factor for TSP-1 induction.

Conclusions:

We have identified TSP-1 as an inhibitory element in regulating liver regeneration by TGF-β1 activation. Our work defines TSP-1 as a novel immediate early gene that could be a potential therapeutic target to accelerate liver regeneration. (Hepatology 2011)
Elevated hepatic multidrug resistance-associated protein 3/ATP-binding cassette subfamily C 3 expression in human obstructive cholestasis is mediated through tumor necrosis factor alpha and c-Jun NH2-terminal kinase/stress-activated protein kinase–signaling pathway
Authors: Chai Jin , He Yu , Cai Shi-Ying , Jiang Zhongyong , Wang Huaizhi , Li Qiong , Chen Lei , Peng Zhihong , He Xiaochong , Wu Xiaoping , Xiao Tianli , Wang Rongquan , Boyer James L. , Chen Wensheng 
Published: November 2011

Abstract

Multidrug resistance-associated protein 3 (MRP3, ABC subfamily C [ABCC]3) plays an important role in protecting hepatocytes and other tissues by excreting an array of toxic organic anion conjugates, including bile salts. MRP3/ABCC3 expression is increased in the liver of some cholestatic patients, but the molecular mechanism of this up-regulation remains elusive. In this report, we assessed liver MRP3/ABCC3 expression in patients (n = 22) with obstructive cholestasis caused by gallstone blockage of bile ducts and noncholestatic patient controls (n = 22). MRP3/ABCC3 messenger RNA (mRNA) and protein expression were significantly increased by 3.4- and 4.6-fold, respectively, in these cholestatic patients where elevated plasma tumor necrosis factor alpha (TNFα) (4.7-fold;

P

< 0.01) and hepatic specificity protein 1 transcription factor (SP1) and liver receptor homolog 1 expression (3.1- and 2.1-fold at mRNA level, 3.5- and 2.5-fold at protein level, respectively) were also observed. The induction of hepatic MRP3/ABCC3 mRNA expression is significantly positively correlated with the level of plasma TNFα in these patients. In HepG2 cells, TNFα treatment induced SP1 and MRP3/ABCC3 expression in a dose- and time-dependent manner, where increased phosphorylation of c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) was also detected. These inductions were significantly reduced in the presence of the JNK inhibitor, SP600125. TNFα treatment enhanced HepG2 cell nuclear extract-binding activity to the MRP3/ABCC3 promoter, but was abolished by SP600125, as demonstrated by electrophoretic mobility shift assay (EMSA). An increase in nuclear protein-binding activity to the MRP3/ABCC3 promoter, consisting primarily of SP1, was also observed in liver samples from cholestatic patients, as assessed by supershift EMSA assays.

Conclusions:

Our findings indicate that up-regulation of hepatic MRP3/ABCC3 expression in human obstructive cholestasis is likely triggered by TNFα, mediated by activation of JNK/SAPK and SP1. (Hepatology 2012)
Inhibition of heat shock protein (molecular weight 90 kDa) attenuates proinflammatory cytokines and prevents lipopolysaccharide-induced liver injury in mice
Authors: Ambade Aditya , Catalano Donna , Lim Arlene , Mandrekar Pranoti 
Published: November 2011

Abstract

Endotoxin-mediated proinflammatory cytokines play a significant role in the pathogenesis of acute and chronic liver diseases. Heat shock protein 90 (molecular weight, 90 kDa) (hsp90) functions as an important chaperone of lipopolysaccharide (LPS) signaling and is required for the production of proinflammatory cytokines. We hypothesized that inhibition of hsp90 would prevent LPS-induced liver injury by decreasing proinflammatory cytokines. C57BL/6 mice were injected intraperitoneally with an hsp90 inhibitor, 17-dimethylamino-ethylamino-17-demethoxygeldanamycin (17-DMAG), and LPS. Parameters of liver injury, proinflammatory cytokines, and associated mechanisms were studied by

in vivo

and

in vitro

experiments. Inhibition of hsp90 by 17-DMAG prevented LPS-induced increases in serum alanine aminotransferase activity and significantly reduced serum tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) protein as well as messenger RNA (mRNA) in liver. Enhanced DNA-binding activity of heat shock transcription factor 1 (HSF1) and induction of target gene heat shock protein 70 (molecular weight, 70 kDa) confirmed hsp90 inhibition in liver. 17-DMAG treatment decreased cluster of differentiation 14 mRNA and LPS-induced nuclear factor kappa light-chain enhancer of activated B cells (NFκB) DNA binding without affecting Toll-like receptor 4 mRNA in liver. Mechanistic studies revealed that 17-DMAG-mediated inhibition of TNFα showed no effect on LPS-induced NFκB promoter-driven reporter activity, but significantly decreased TNFα promoter-driven reporter activity. Chromatin immunoprecipitation assays showed that 17-DMAG enhanced HSF1 binding to the TNFα promoter, but not the IL-6 promoter, suggesting HSF1 mediated direct inhibition of TNFα, but not IL-6. We show that HSF1 indirectly regulates IL-6 by the induction of another transcription factor, activating transcription factor 3. Inhibition of HSF1, using small interfering RNA, prevented 17-DMAG-mediated down-regulation of NFκB-binding activity, TNFα, and IL-6 induction, supporting a repressive role for HSF1 on proinflammatory cytokine genes during hsp90 inhibition.

Conclusion:

Hsp90 inhibition

in vivo

reduces proinflammatory cytokines and prevents LPS-induced liver injury likely through repressive action of HSF1. Our results suggest a novel application for 17-DMAG in alleviating LPS-induced liver injury. (Hepatology 2011)