bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Inflammatory Response by 3-Methyladenine Involves the Coordinative Actions on Akt and Glycogen Synthase Kinase 3β Rather than Autophagy
Authors: Lin Yi-Chieh , Kuo Hsuan-Cheng , Wang Jang-Shiun , Lin Wan-Wan 
Published: September 2012

Abstract
3-Methyladenine (3-MA) is one of the most commonly used inhibitors in autophagy research today. However, rather than inhibiting class III PI3K that is involved in autophagy suppression, 3-MA might also interfere with class I PI3K and consequently augment autophagy flux. In this study, we aim to get a thorough understanding on the action mechanisms of 3-MA in TLR4-mediated inflammatory responses in RAW264.7 macrophages and, moreover, to decipher the action of 3-MA in modulation of autophagy. We found that 3-MA could enhance LPS-induced NF-κB activation and production of TNF-α, inducible NO synthase (iNOS), cyclooxygenase-2, IL-1β, and IL-12. In contrast, 3-MA suppressed LPS-induced IFN-β production and STAT signaling. Studies revealed that 3-MA can, through inhibition of Akt as a result of class I PI3K interference, positively regulate p38, JNK, and p65, but negatively regulate TANK-binding kinase 1 and IFN regulatory factor 3 mediated by TLR4. As glycogen synthase kinase 3β (GSK3β) is an important Akt substrate, we further explored its involvement in the actions of 3-MA. 3-MA was found to enhance LPS-induced NF-κB activation, iNOS, and pro–IL-1β expression, and these actions were reversed by either GSK3β inhibitors or small interfering GSK3β. Lastly, we demonstrated that 3-MA acts as an autophagy inducer in RAW264.7 macrophages, but the stimulating effects on NF-κB activation and iNOS and cyclooxygenase-2 expression were not affected in LPS-stimulated macrophages with small interfering autophagy protein-5 treatment. These results not only shed new light on the action mechanisms of 3-MA to differentially regulate inflammatory outcomes derived from TLR4-mediated MyD88 and Toll/IL-1R domain-containing adapter inducing IFN-β pathways, but also highlight the necessity to check autophagy status upon taking 3-MA as a general autophagy inhibitor.
IL-10–Producing Regulatory B Cells in the Pathogenesis of Chronic Hepatitis B Virus Infection
Authors: Das Abhishek , Ellis Gidon , Pallant Celeste , Lopes A. Ross , Khanna Pooja , Peppa Dimitra , Chen Antony , Blair Paul , Dusheiko Geoffrey , Gill Upkar , Kennedy Patrick T. , Brunetto Maurizia , Lampertico Pietro , Mauri Claudia , Maini Mala K. 
Published: September 2012

Abstract
A regulatory subset of B cells has been found to modulate immune responses in autoimmunity, infection, and cancer, but it has not been investigated in the setting of human persistent viral infection. IL-10 is elevated in patients with chronic hepatitis B virus infection (CHB), but its cellular sources and impact on antiviral T cells have not been addressed. We investigated the role of IL-10 and regulatory B cells in the pathogenesis of CHB. Serum IL-10 levels were studied longitudinally in patients with CHB undergoing spontaneous disease flares. There was a close temporal correlation between IL-10 levels and fluctuations in viral load or liver inflammation. Blockade of IL-10 in vitro rescued polyfunctional virus-specific CD8 T cell responses. To investigate the potential contribution of regulatory B cells, their frequency was measured directly ex vivo and after exposure to stimuli relevant to hepatitis B virus (HBV) (CpG or HBV Ags). IL-10–producing B cells were enriched in patients, and their frequency correlated temporally with hepatic flares, both after stimulation and directly ex vivo. Phenotypically, these cells were predominantly immature (CD19+CD24hiCD38hi) ex vivo; sorted CD19+CD24hiCD38hi cells suppressed HBV-specific CD8 T cell responses in an IL-10–dependent manner. In summary, these data reveal a novel IL-10–producing subset of B cells able to regulate T cell immunity in CHB.
Extensive Diversification of IgD-, IgY-, and Truncated IgY(ΔFc)-Encoding Genes in the Red-Eared Turtle (Trachemys scripta elegans)
Authors: Li Lingxiao , Wang Tao , Sun Yi , Cheng Gang , Yang Hui , Wei Zhiguo , Wang Ping , Hu Xiaoxiang , Ren Liming , Meng Qingyong , Zhang Ran , Guo Ying , Hammarström Lennart , Li Ning , Zhao Yaofeng 
Published: September 2012

Abstract
IgY(ΔFc), containing only CH1 and CH2 domains, is expressed in the serum of some birds and reptiles, such as ducks and turtles. The duck IgY(ΔFc) is produced by the same υ gene that expresses the intact IgY form (CH1–4) using different transcriptional termination sites. In this study, we show that intact IgY and IgY(ΔFc) are encoded by distinct genes in the red-eared turtle (Trachemys scripta elegans). At least eight IgY and five IgY(ΔFc) transcripts were found in a single turtle. Together with Southern blotting, our data suggest that multiple genes encoding both IgY forms are present in the turtle genome. Both of the IgY forms were detected in the serum using rabbit polyclonal Abs. In addition, we show that multiple copies of the turtle δ gene are present in the genome and that alternative splicing is extensively involved in the generation of both the secretory and membrane-bound forms of the IgD H chain transcripts. Although a single μ gene was identified, the α gene was not identified in this species.
IFN-α and Lipopolysaccharide Upregulate APOBEC3 mRNA through Different Signaling Pathways
Authors: Mehta Harshini V. , Jones Philip H. , Weiss Jerrold P. , Okeoma Chioma M. 
Published: September 2012

Abstract
APOBEC3 (A3) proteins are virus-restriction factors that provide intrinsic immunity against infections by viruses like HIV-1 and mouse mammary tumor virus. A3 proteins are inducible by inflammatory stimuli, such as LPS and IFN-α, via mechanisms that are not fully defined. Using genetic and pharmacological studies on C57BL/6 mice and cells, we show that IFN-α and LPS induce A3 via different pathways, independently of each other. IFN-α positively regulates mouse APOBEC3 (mA3) mRNA expression through IFN-αR/PKC/STAT1 and negatively regulates mA3 mRNA expression via IFN-αR/MAPKs–signaling pathways. Interestingly, LPS shows some variation in its regulatory behavior. Although LPS-mediated positive regulation of mA3 mRNA occurs through TLR4/TRIF/IRF3/PKC, it negatively modulates mA3 mRNA via TLR4/MyD88/MAPK-signaling pathways. Additional studies on human peripheral blood mononuclear cells reveal that PKC differentially regulates IFN-α and LPS induction of human A3A, A3F, and A3G mRNA expression. In summary, we identified important signaling targets downstream of IFN-αR and TLR4 that mediate A3 mRNA induction by both LPS and IFN-α. Our results provide new insights into the signaling targets that could be manipulated to enhance the intracellular store of A3 and potentially enhance A3 antiviral function in the host.
MicroRNAs Control the Maintenance of Thymic Epithelia and Their Competence for T Lineage Commitment and Thymocyte Selection
Authors: Zuklys Saulius , Mayer Carlos E. , Zhanybekova Saule , Stefanski Heather E. , Nusspaumer Gretel , Gill Jason , Barthlott Thomas , Chappaz Stephane , Nitta Takeshi , Dooley James , Nogales-Cadenas Ruben , Takahama Yousuke , Finke Daniela , Liston Adrian , Blazar Bruce R. , Pascual-Montano Alberto , Holländer Georg A. 
Published: September 2012

AbstractThymic epithelial cells provide unique cues for the lifelong selection and differentiation of a repertoire of functionally diverse T cells. Rendered microRNA (miRNA) deficient, these stromal cells in the mouse lose their capacity to instruct the commitment of hematopoietic precursors to a T cell fate, to effect thymocyte positive selection, and to achieve promiscuous gene expression required for central tolerance induction. Over time, the microenvironment created by miRNA-deficient thymic epithelia assumes the cellular composition and structure of peripheral lymphoid tissue, where thympoiesis fails to be supported. These findings emphasize a global role for miRNA in the maintenance and function of the thymic epithelial cell scaffold and establish a novel mechanism how these cells control peripheral tissue Ag expression to prompt central immunological tolerance.
Dendritic Cell-Specific Disruption of TGF-β Receptor II Leads to Altered Regulatory T Cell Phenotype and Spontaneous Multiorgan Autoimmunity
Authors: Ramalingam Rajalakshmy , Larmonier Claire B. , Thurston Robert D. , Midura-Kiela Monica T. , Zheng Song Guo , Ghishan Fayez K. , Kiela Pawel R. 
Published: September 2012

Abstract
In vitro data and transgenic mouse models suggest a role for TGF-β signaling in dendritic cells (DCs) to prevent autoimmunity primarily through maintenance of DCs in their immature and tolerogenic state characterized by low expression of MHC class II (MHCII) and costimulatory molecules and increased expression of IDO, among others. To test whether a complete lack of TGF-β signaling in DCs predisposes mice to spontaneous autoimmunity and to verify the mechanisms implicated previously in vitro, we generated conditional knockout (KO) mice with Cre-mediated DC-specific deletion of Tgfbr2 (DC-Tgfbr2 KO). DC-Tgfbr2 KO mice die before 15 wk of age with multiorgan autoimmune inflammation and spontaneous activation of T and B cells. Interestingly, there were no significant differences in the expression of MHCII, costimulatory molecules, or IDO in secondary lymphoid organ DCs, although Tgfbr2-deficient DCs were more proinflammatory in vitro and in vivo. DC-Tgfbr2 KO showed attenuated Foxp3 expression in regulatory T cells (Tregs) and abnormal expansion of CD25−Foxp3+ Tregs in vivo. Tgfbr2-deficient DCs secreted elevated levels of IFN-γ and were not capable of directing Ag-specific Treg conversion unless in the presence of anti–IFN-γ blocking Ab. Adoptive transfer of induced Tregs into DC-Tgfbr2 KO mice partially rescued the phenotype. Therefore, in vivo, TGF-β signaling in DCs is critical in the control of autoimmunity through both Treg-dependent and -independent mechanisms, but it does not affect MHCII and costimulatory molecule expression.
Blockade of IL-10 Signaling during Bacillus Calmette-Guérin Vaccination Enhances and Sustains Th1, Th17, and Innate Lymphoid IFN-γ and IL-17 Responses and Increases Protection to Mycobacterium tuberculosis Infection
Authors: Pitt Jonathan M. , Stavropoulos Evangelos , Redford Paul S. , Beebe Amy M. , Bancroft Gregory J. , Young Douglas B. , O’Garra Anne 
Published: September 2012

Abstract
Vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) remains the only prophylactic vaccine against tuberculosis, caused by Mycobacterium tuberculosis, but gives variable protection against pulmonary disease. The generation of host Th1 responses following BCG vaccination is accepted as the major mechanism of protection against M. tuberculosis infection. Early production of IL-17 in the lungs following M. tuberculosis challenge of mice previously vaccinated with M. tuberculosis peptides in adjuvant has been shown to be required for efficient Th1 cell recruitment. IL-10 regulates various processes involved in generation of Th1 and Th17 responses. Previous studies have shown IL-10 as a negative regulator of the immune response to primary M. tuberculosis infection, with Il10−/− mice having reduced lung bacterial loads. In this study we show that inhibition of IL-10 signaling during BCG vaccination enhances host-generated Ag-specific IFN-γ and IL-17A responses, and that this regimen gives significantly greater protection against aerogenic M. tuberculosis challenge in both susceptible and relatively resistant strains of mice. In M. tuberculosis-susceptible CBA/J mice, Ab blockade of IL-10R specifically during BCG vaccination resulted in additional protection against M. tuberculosis challenge of &gt;1-log10 compared with equivalent isotype-treated controls. The protection observed following BCG vaccination concurrent with anti–IL-10R mAb treatment was sustained through chronic M. tuberculosis infection and correlated with enhanced lung Th1 and Th17 responses and increased IFN-γ and IL-17A production by γδ T cells and an innate-like Thy1.2+CD3− lymphoid population. We show that IL-10 inhibits optimal BCG-elicited protection, therefore suggesting that antagonists of IL-10 may be of great benefit as adjuvants in preventive vaccination against tuberculosis.
CD11c+ Cells Are Required for Antigen-Induced Increase of Mast Cells in the Lung
Authors: Dahlin Joakim S. , Feinstein Ricardo , Cui Yue , Heyman Birgitta , Hallgren Jenny 
Published: September 2012

Abstract
Patients with allergic asthma have more lung mast cells, which likely worsens the symptoms. In experimental asthma, CD11c+ cells have to be present during the challenge phase for several features of allergic inflammation to occur. Whether CD11c+ cells play a role for Ag-induced increases of lung mast cells is unknown. In this study, we used diphtheria toxin treatment of sensitized CD11c-diphtheria toxin receptor transgenic mice to deplete CD11c+ cells. We demonstrate that recruitment of mast cell progenitors to the lung is substantially reduced when CD11c+ cells are depleted during the challenge phase. This correlated with an impaired induction of endothelial VCAM-1 and led to a significantly reduced number of mature mast cells 1 wk after challenge. Collectively, these data suggest that Ag challenge stimulates CD11c+ cells to produce cytokines and/or chemokines required for VCAM-1 upregulation on the lung endothelium, which in turn is crucial for the Ag-induced mast cell progenitor recruitment and the increase in mast cell numbers.
Genetic Ablation of Arginase 1 in Macrophages and Neutrophils Enhances Clearance of an Arthritogenic Alphavirus
Authors: Stoermer Kristina A. , Burrack Adam , Oko Lauren , Montgomery Stephanie A. , Borst Luke B. , Gill Ronald G. , Morrison Thomas E. 
Published: September 2012

Abstract
Chikungunya virus (CHIKV) and Ross River virus (RRV) cause a debilitating, and often chronic, musculoskeletal inflammatory disease in humans. Macrophages constitute the major inflammatory infiltrates in musculoskeletal tissues during these infections. However, the precise macrophage effector functions that affect the pathogenesis of arthritogenic alphaviruses have not been defined. We hypothesized that the severe damage to musculoskeletal tissues observed in RRV- or CHIKV-infected mice would promote a wound-healing response characterized by M2-like macrophages. Indeed, we found that RRV- and CHIKV-induced musculoskeletal inflammatory lesions, and macrophages present in these lesions, have a unique gene-expression pattern characterized by high expression of arginase 1 and Ym1/Chi3l3 in the absence of FIZZ1/Relmα that is consistent with an M2-like activation phenotype. Strikingly, mice specifically deleted for arginase 1 in neutrophils and macrophages had dramatically reduced viral loads and improved pathology in musculoskeletal tissues at late times post-RRV infection. These findings indicate that arthritogenic alphavirus infection drives a unique myeloid cell activation program in inflamed musculoskeletal tissues that inhibits virus clearance and impedes disease resolution in an arginase 1-dependent manner.
B7x in the Periphery Abrogates Pancreas-Specific Damage Mediated by Self-reactive CD8 T Cells
Authors: Lee Jun Sik , Scandiuzzi Lisa , Ray Anjana , Wei Joyce , Hofmeyer Kimberly A. , Abadi Yael M. , Loke P’ng , Lin Juan , Yuan Jianda , Serreze David V. , Allison James P. , Zang Xingxing 
Published: September 2012

Abstract
B7x (B7-H4 or B7S1) is the seventh member of the B7 family, and its in vivo function remains largely unknown. Despite new genetic data linking the B7x gene with autoimmune diseases, how exactly it contributes to peripheral tolerance and autoimmunity is unclear. In this study, we showed that B7x protein was not detected on APCs or T cells in both human and mice, which is unique in the B7 family. Because B7x protein is expressed in some peripheral cells such as pancreatic β cells, we used a CD8 T cell-mediated diabetes model (AI4αβ) in which CD8 T cells recognize an endogenous self-Ag, and found that mice lacking B7x developed more severe diabetes than control AI4αβ mice. Conversely, mice overexpressing B7x in the β cells (Rip-B7xAI4αβ) were diabetes free. Furthermore, adoptive transfer of effector AI4αβ CD8 T cells induced diabetes in control mice, but not in Rip-B7xAI4αβ mice. Mechanistic studies revealed that pathogenic effector CD8 T cells were capable of migrating to the pancreas but failed to robustly destroy tissue when encountering local B7x in Rip-B7xAI4αβ mice. Although AI4αβ CD8 T cells in Rip-B7xAI4αβ and AI4αβ mice showed similar cytotoxic function, cell death, and global gene expression profiles, these cells had greater proliferation in AI4αβ mice than in RIP-B7xAI4αβ mice. These results suggest that B7x in nonlymphoid organs prevents peripheral autoimmunity partially through inhibiting proliferation of tissue-specific CD8 T cells, and that local overexpression of B7x on pancreatic β cells is sufficient to abolish CD8 T cell-induced diabetes.
Autophagy Regulates IL-23 Secretion and Innate T Cell Responses through Effects on IL-1 Secretion
Authors: Peral de Castro Celia , Jones Sarah A. , Ní Cheallaigh Clíona , Hearnden Claire A. , Williams Laura , Winter Jan , Lavelle Ed C. , Mills Kingston H. G. , Harris James 
Published: September 2012

Abstract
Autophagy controls IL-1β secretion by regulating inflammasome activation and by targeting pro–IL-1β for degradation. In this article, we show that inhibition of autophagy, either with the PI3K inhibitors 3-methyladenine, wortmannin, and LY294002 or with small interfering RNA against autophagy proteins augmented the secretion of IL-23 by human and mouse macrophages and dendritic cells in response to specific TLR agonists. This process occurred at the transcriptional level and was dependent on reactive oxygen species and IL-1R signaling; it was abrogated with an IL-1R antagonist or with IL-1–neutralizing Abs, whereas treatment with either rIL-1α or IL-1β induced IL-23 secretion. Dendritic cells treated with LPS and 3-methyladenine secreted enhanced levels of both IL-1β and IL-23, and supernatants from these cells stimulated the innate secretion of IL-17, IFN-γ, and IL-22 by γδ T cells. These data demonstrate that autophagy has a potentially pivotal role to play in the induction and regulation of inflammatory responses by innate immune cells, largely driven by IL-1 and its consequential effects on IL-23 secretion.
Liquid–Solid Sample Preparation Followed by Headspace Solid-Phase Microextraction Determination of Multiclass Pesticides in Soil
Authors: Ðurović Rada D , Ðorðević Tijana M , Šantrić Ljiljana R 
Published: September 2012

Abstract
This paper describes development and validation of a multiresidue method for the determination of five pesticides (terbufos, prochloraz, chloridazon, pendimethalin, and fluorochloridone) belonging to different pesticide groups in soil samples by GC/MS, followed by its application in the analysis of some agricultural soil samples. The method is based on a headspace solid-phase microextraction method. Microextraction conditions, namely temperature, extraction time, and NaCl content, were tested and optimized using a 100 μm polydimethylsiloxane fiber. Three extraction solvents [methanol, methanol–acetone (1 + 1, v/v), and methanol–acetone–hexane (2 + 2 + 1, v/v/v)] and the optimum number of extraction steps within the sample preparation stage were optimized for the extraction procedure. LOD values for all the studied compounds were less than 12 μg/kg. Recovery values for multiple analyses of soil samples fortified at 30 μg/kg of each pesticide were higher than 64%. The method was proven to be repeatable, with RSD lower than 15%.
Application of RP-HPLC-Diode Array Detector after SPE to the Determination of Pesticides in Pepper Samples
Authors: Tuzimski Tomasz 
Published: September 2012

Abstract
The application of HPLC-diode array detector (DAD) after SPE for identification and quantitative analysis of pesticides in red and green pepper samples is demonstrated. An HPLC procedure on an RP column (C18) was developed for analysis of selected pesticides from different chemical groups: metamitron, metalaxyl, linuron, and prometryn. Average recoveries for C18 Polar Plus cartridges and solvents by the proposed RP-HPLC-DAD method after SPE are presented. Average recoveries from the spiked samples and the SDs were 22.5 ± 2.2, 138.0 ± 4.1, 78.6 ± 2.8, and 109.2 ± 2.3% for metamitron, metalaxyl, linuron, and prometryn, respectively, at concentrations of 7 μg/g in the plant material. The efficiency of the SPE procedure was evaluated using real food samples. The quantities of prometryn, linuron, metalaxyl, and metamitron determined were in the ranges of 0.02–2.24 μg/g (n = 24), 0.08–1.01 μg/g (n = 9), 1.61–2.28 μg/g (n = 4), and 0.05–1.07 μg/g (n = 3), respectively, in plant material sampled in 2011. The method was validated for precision, repeatability, and accuracy.
Selenium Proteins Containing SelenocysteineUpdate based on the original article by August Böck,Encyclopedia of Inorganic ChemistrySecond Edition, © 2005, John Wiley & Sons, Ltd.
Authors: Self William T. 
Published: September 2012

AbstractSelenium is incorporated in the form of the nonstandard amino acid selenocysteine into selected proteins of organisms belonging to all three lines of descent. The majority of these proteins, which contain selenocysteine in the active site, catalyze oxidation–reduction reactions and are involved in numerous biochemical and regulatory processes, which in many cases are indispensable for the organism. Because of significant differences in the chemical reactivity of selenocysteine in comparison to cysteine, selenoenzymes display a greatly increased rate of catalysis and, in some cases, have an extended substrate specificity. Apart from its biochemical function, selenocysteine is also unique since its incorporation is DNA‐encoded and its cotranslational insertion follows a route independent in many features from the path of insertion of the 20 classical amino acids. Selenocysteine, therefore, can be considered the 21st amino acid.
Precursor‐Bound Nif
EN
: Insights into Nitrogenase Cofactor Assembly
Authors: Wiig Jared A. , Lee Chi Chung , Hu Yilin , Ribbe Markus W. 
Published: September 2012

Abstract
The biosynthesis of the iron–molybdenum cofactor (FeMoco) of nitrogenase is one of the most complicated processes in metalloprotein biochemistry. Here we review the recent progress on the investigation of NifEN, an important scaffold protein for the maturation of an iron‐only precursor to a molybdenum‐ and homocitrate‐containing FeMoco. The recently solved crystal structure of the precursor‐bound form of NifEN is discussed in detail, which provides important insights into the biosynthetic mechanism of nitrogenase. In addition, the functional and spectroscopic features of NifEN are discussed.
Control of rotation extrusion over shish‐kebab crystal alignment in polyethylene pipe and its effect on the pipe's crack resistance
Authors: Nie Min , Wang Qi 
Published: September 2012

AbstractA self‐designed rotation extrusion system was adopted to extrude polyethylene (PE) pipe. The experimental results showed that when the mandrel and die rotated in the same directions during the PE pipe extrusion, apart from the axial stress, all polymer melts in PE pipes were also subjected to the hoop stress so that the formed shish‐kebab crystal in the whole pipe deviated from the axial direction greatly, which was further fixed by the double cooling on both inner and outer walls. As a result, the PE pipe with better resistance to slow crack growth was prepared. As compared to the PE pipe produced by the convention extrusion, the crack initiation time of the PE pipe manufactured by the novel method increased from 27 to 174 h, by 544%. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013