bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced Cancer Immunotherapy Using STAT3-Depleted Dendritic Cells with High Th1-Inducing Ability and Resistance to Cancer Cell-Derived Inhibitory Factors
Authors: Iwata-Kajihara Tomoko , Sumimoto Hidetoshi , Kawamura Naoshi , Ueda Ryo , Takahashi Tomomi , Mizuguchi Hiroyuki , Miyagishi Makoto , Takeda Kiyoshi , Kawakami Yutaka 
Published: June 2011

Abstract
STAT3 signaling constitutes an important negative feedback mechanism for the maintenance of immune homeostasis, a suppressive signal for the Th1 immune response in murine macrophages, and a cancer immune evasion signal in various immune cells. The strategy for STAT3 signal inhibition should be considered, because these features could impede effective cancer immunotherapy. We have evaluated the effects of STAT3 inactivation in dendritic cells (DCs) on immune responses in mice and humans. DCs derived from LysMcre/STAT3flox/flox mice displayed higher cytokine production in response to TLR stimulation, activated T cells more efficiently, and were more resistant to the suppression of cytokine production by cancer-derived immunosuppressive factors compared with DCs from control littermates. Antitumor activities of STAT3-depleted and control DCs were compared by intratumoral administration of gp70 Ag peptide-pulsed DCs in the therapeutic MC38 tumor model. Intratumoral administration of STAT3-depleted DCs significantly inhibited MC38 tumor growth of both injected and nontreated remote tumors. The inhibition was accompanied by an increase in gp70-specific T cell response as well as in systemic Th1 immune response. STAT3-depleted human DCs with adenoviral STAT3 short hairpin RNA were also capable of producing more cytokines with TLR stimulation and more resistant to cancer-derived factors, and they induced tumor Ag-specific T cells more efficiently than control DCs. The identified role of DC STAT3 signaling in both in vivo therapeutic tumor models in mice and in vitro-specific T cell induction in humans indicates that STAT3-inactivated DCs may be a promising approach for cancer immunotherapy.
Ly49D-Mediated ITAM Signaling in Immature Thymocytes Impairs Development by Bypassing the Pre-TCR Checkpoint
Authors: Merck Estelle , Lees Rosemary K. , Voyle Roger B. , Held Werner , MacDonald H. Robson 
Published: June 2011

Abstract
Activating and inhibitory NK receptors regulate the development and effector functions of NK cells via their ITAM and ITIM motifs, which recruit protein tyrosine kinases and phosphatases, respectively. In the T cell lineage, inhibitory Ly49 receptors are expressed by a subset of activated T cells and by CD1d-restricted NKT cells, but virtually no expression of activating Ly49 receptors is observed. Using mice transgenic for the activating receptor Ly49D and its associated ITAM signaling DAP12 chain, we show in this article that Ly49D-mediated ITAM signaling in immature thymocytes impairs development due to a block in maturation from the double negative (DN) to double positive (DP) stages. A large proportion of Ly49D/DAP12 transgenic thymocytes were able to bypass the pre-TCR checkpoint at the DN3 stage, leading to the appearance of unusual populations of DN4 and DP cells that lacked expression of intracellular (ic) TCRβ-chain. High levels of CD5 were expressed on ic TCRβ− DN and DP thymocytes from Ly49D/DAP12 transgenic mice, further suggesting that Ly49D-mediated ITAM signaling mimics physiological ITAM signaling via the pre-TCR. We also observed unusual ic TCRβ− single positive thymocytes with an immature CD24high phenotype that were not found in the periphery. Importantly, thymocyte development was completely rescued by expression of an Ly49A transgene in Ly49D/DAP12 transgenic mice, indicating that Ly49A-mediated ITIM signaling can fully counteract ITAM signaling via Ly49D/DAP12. Collectively, our data indicate that inappropriate ITAM signaling by activating NK receptors on immature thymocytes can subvert T cell development by bypassing the pre-TCR checkpoint.
Cellular Competition Independent of BAFF/B Lymphocyte Stimulator Results in Low Frequency of an Autoreactive Clonotype in Mature Polyclonal B Cell Compartments
Authors: Nikbakht Neda , Migone Thi-Sau , Ward Chris P. , Manser Tim 
Published: June 2011

Abstract
The peripheral B cell prosurvival cytokine BAFF/B lymphocyte stimulator (BLyS) has been proposed to participate in the regulation of immunological tolerance. Selective elimination or reconstitution of B cells expressing transgene-encoded, autoreactive BCRs upon systemic BLyS depletion or supplementation, respectively, was observed in two separate studies. Such findings led to a model positing a higher dependency of autoreactive B cells on BLyS. We tested this model by exploiting two targeted IgH transgenic mice (H chain knock-in [HKI]) that produce large numbers of follicular (FO) B cells that are either weakly or strongly autoreactive with nuclear autoantigens. Even though HKI B cells do not exhibit classical features of anergy, we found that mature, naive, autoreactive HKI B cells are outcompeted for representation in the periphery by a polyclonal B cell population. However, this is not due to a higher dependency of HKI B cells on BLyS for survival. Additionally, excess BLyS does not rescue HKI B cells from selective elimination. These findings suggest that some autoreactive FO B cells can fully develop while in competition with non-autoreactive cells for BLyS, but remain at a competitive disadvantage for other trophic factors that regulate peripheral stability. As such, our data indicate the existence of peripheral tolerance mechanisms that regulate the frequency of autoreactive FO B cells independent of the BLyS pathway.
Membrane-Bound IL-22 after De Novo Production in Tuberculosis and Anti-Mycobacterium tuberculosis Effector Function of IL-22+ CD4+ T Cells
Authors: Zeng Gucheng , Chen Crystal Y. , Huang Dan , Yao Shuyu , Wang Richard C. , Chen Zheng W. 
Published: June 2011

Abstract
The role of IL-22–producing CD4+ T cells in intracellular pathogen infections is poorly characterized. IL-22–producing CD4+ T cells may express some effector molecules on the membrane, and therefore synergize or contribute to antimicrobial effector function. This hypothesis cannot be tested by conventional approaches manipulating a single IL-22 cytokine at genetic and protein levels, and IL-22+ T cells cannot be purified for evaluation due to secretion nature of cytokines. In this study, we surprisingly found that upon activation, CD4+ T cells in Mycobacterium tuberculosis-infected macaques or humans could evolve into T effector cells bearing membrane-bound IL-22 after de novo IL-22 production. Membrane-bound IL-22+ CD4+ T effector cells appeared to mature in vivo and sustain membrane distribution in highly inflammatory environments during active M. tuberculosis infection. Near-field scanning optical microscopy/quantum dot-based nanoscale molecular imaging revealed that membrane-bound IL-22, like CD3, distributed in membrane and engaged as ∼100–200 nm nanoclusters or ∼300–600 nm nanodomains for potential interaction with IL-22R. Importantly, purified membrane-bound IL-22+ CD4+ T cells inhibited intracellular M. tuberculosis replication in macrophages. Our findings suggest that IL-22–producing T cells can evolve to retain IL-22 on membrane for prolonged IL-22 t1/2 and to exert efficient cell–cell interaction for anti-M. tuberculosis effector function.
Dichotomous Effects of IFN-γ on Dendritic Cell Function Determine the Extent of IL-12–Driven Antitumor T Cell Immunity
Authors: Harden Jamie L. , Gu Tao , Kilinc Mehmet O. , Rowswell-Turner Rachael B. , Virtuoso Lauren P. , Egilmez Nejat K. 
Published: June 2011

Abstract
Sustained intratumoral delivery of IL-12 and GM-CSF can overcome tumor immune suppression and promote T cell-dependent eradication of established disease in murine tumor models. However, the antitumor effector response is transient and rapidly followed by a T suppressor cell rebound. The mechanisms that control the switch from an effector to a regulatory response in this model have not been defined. Because dendritic cells (DC) can mediate both effector and suppressor T cell priming, DC activity was monitored in the tumors and the tumor-draining lymph nodes (TDLN) of IL-12/GM-CSF–treated mice. The studies demonstrated that therapy promoted the recruitment of immunogenic DC (iDC) to tumors with subsequent migration to the TDLN within 24–48 h of treatment. Longer-term monitoring revealed that iDC converted to an IDO-positive tolerogenic phenotype in the TDLN between days 2 and 7. Specifically, day 7 DC lost the ability to prime CD8+ T cells but preferentially induced CD4+Foxp3+ T cells. The functional switch was reversible, as inhibition of IDO with 1-methyl tryptophan restored immunogenic function to tolerogenic DC. All posttherapy immunological activity was strictly associated with conventional myeloid DC, and no functional changes were observed in the plasmacytoid DC subset throughout treatment. Importantly, the initial recruitment and activation of iDC as well as the subsequent switch to tolerogenic activity were both driven by IFN-γ, revealing the dichotomous role of this cytokine in regulating IL-12–mediated antitumor T cell immunity.
Signal Regulatory Protein α Regulates the Homeostasis of T Lymphocytes in the Spleen
Authors: Sato-Hashimoto Miho , Saito Yasuyuki , Ohnishi Hiroshi , Iwamura Hiroko , Kanazawa Yoshitake , Kaneko Tetsuya , Kusakari Shinya , Kotani Takenori , Mori Munemasa , Murata Yoji , Okazawa Hideki , Ware Carl F. , Oldenborg Per-Arne , Nojima Yoshihisa , Matozaki Takashi 
Published: June 2011

Abstract
The molecular basis for formation of lymphoid follicle and its homeostasis in the secondary lymphoid organs remains unclear. Signal regulatory protein α (SIRPα), an Ig superfamily protein that is predominantly expressed in dendritic cells or macrophages, mediates cell–cell signaling by interacting with CD47, another Ig superfamily protein. In this study, we show that the size of the T cell zone as well as the number of CD4+ T cells were markedly reduced in the spleen of mice bearing a mutant (MT) SIRPα that lacks the cytoplasmic region compared with those of wild-type mice. In addition, the expression of CCL19 and CCL21, as well as of IL-7, which are thought to be important for development or homeostasis of the T cell zone, was markedly decreased in the spleen of SIRPα MT mice. By the use of bone marrow chimera, we found that hematopoietic SIRPα is important for development of the T cell zone as well as the expression of CCL19 and CCL21 in the spleen. The expression of lymphotoxin and its receptor, lymphotoxin β receptor, as well as the in vivo response to lymphotoxin β receptor stimulation were also decreased in the spleen of SIRPα MT mice. CD47-deficient mice also manifested phenotypes similar to SIRPα MT mice. These data suggest that SIRPα as well as its ligand CD47 are thus essential for steady-state homeostasis of T cells in the spleen.
One‐Step Electrochemical Synthesis of Graphene/Polyaniline Composite Film and Its Applications
Authors: Feng Xiao‐Miao , Li Rui‐Mei , Ma Yan‐Wen , Chen Run‐Feng , Shi Nai‐En , Fan Qu‐Li , Huang Wei 
Published: June 2011

AbstractThis work describes a new one‐step large‐scale electrochemical synthesis of graphene/polyaniline (PANI) composite films using graphite oxide (GO) and aniline as the starting materials. The size of the film could be controlled by the area of indium tin oxide (ITO). Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X‐ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and ultraviolet–visible absorption spectrum (UV–vis) results demonstrated that the graphene/PANI composite film was successfully synthesized. The obtained graphene/PANI composite film showed large specific area, high conductivity, good biocompatibility, and fast redox properties and had perfect layered and encapsulated structures. Electrochemical experiments indicated that the composite film had high performances and could be widely used in applied electrochemical fields. As a model, horseradish peroxidase (HRP) was entrapped onto the film‐modiﬁed glassy carbon electrode (GCE) and used to construct a biosensor. The immobilized HRP showed a pair of well‐deﬁned redox peaks and high catalytic activity for the reduction of H2O2. Furthermore, the graphene/PANI composite film could be directly used as the supercapacitor electrode. The supercapacitor showed a high specific capacitance of 640 F g−1 with a retention life of 90% after 1000 charge/discharge cycles.
Fabrication of Releasable Single‐Crystal Silicon–Metal Oxide Field‐Effect Devices and Their Deterministic Assembly on Foreign Substrates
Authors: Chung Hyun‐Joong , Kim Tae‐il , Kim Hoon‐Sik , Wells Spencer A. , Jo Sungjin , Ahmed Numair , Jung Yei Hwan , Won Sang Min , Bower Christopher A. , Rogers John A. 
Published: June 2011

AbstractA new class of thin, releasable single‐crystal silicon semiconductor device is presented that enables integration of high‐performance electronics on nearly any type of substrate. Fully formed metal oxide–semiconductor field–effect transistors with thermally grown gate oxides and integrated circuits constructed with them demonstrate the ideas in devices mounted on substrates ranging from flexible sheets of plastic, to plates of glass and pieces of aluminum foil. Systematic study of the electrical properties indicates field‐effect mobilities of ≈710 cm2 V−1 s−1, subthreshold slopes of less than 0.2 V decade−1 and minimal hysteresis, all with little to no dependence on the properties of the substrate due to bottom silicon surfaces that are passivated with thermal oxide. The schemes reported here require only interconnect metallization to be performed on the final device substrate, which thereby minimizes the need for any specialized processing technology, with important consequences in large‐area electronics for display systems, flexible/stretchable electronics, or other non‐wafer‐based devices.
Which Forces Control Supracrystal Nucleation in Organic Media?
Authors: Goubet Nicolas , Richardi Johannes , Albouy Pierre‐Antoine , Pileni Marie‐Paule 
Published: June 2011

AbstractHere, two mechanisms of fcc Au supracrystal (assembly of Au nanocrystals) growth are proposed. The sizes of the Au nanocrystals and the solvent in which they are dispersed are major parameters that determine the final morphology of nanocrystal assemblies; films by layer‐by‐layer growth (heterogeneous growth), characterized by their plastic deformation, or well‐defined shapes grown in solution (homogeneous growth). Experiments supported by simulations demonstrate that supracrystal nucleation is mainly driven by solvent‐mediated interactions and not solely by the van der Waals attraction between nanocrystal cores, as widely assumed in the literature.
Does achieving an intensive versus usual blood pressure level prevent stroke?
Authors: Lee Meng , Saver Jeffrey L. , Hong Keun‐Sik , Hao Qing , Ovbiagele Bruce 
Published: June 2011

AbstractObjective:The purpose of this study was to compare the impact of achieving tight versus usual systolic blood pressure (SBP) control on stroke prevention through meta‐analysis of randomized controlled trials.Methods:We searched PubMed and bibliographies of recent review articles. Relative risk with 95% confidence interval was used as a measure of the association between an active treatment group with achieved SBP <130mmHg versus a comparator group with achieved SBP 130 to 139mmHg, and risk of stroke after pooling data across trials.Results:The search identified 11 studies with 42,572 participants and 794 stroke events. The final SBPs, weighted for trial size, were a mean of 126.5mmHg in the intensive treatment arms and 132.6mmHg in the conventional arms (mean SBP reduction, 6.1mmHg). Achieving a tight SBP level was associated with a lower stroke risk (relative risk, 0.80; 95% confidence interval, 0.70–0.92; p < 0.01) and a lower risk of major vascular events (0.91; 0.86–0.96; p < 0.001). In subgroup analyses, subjects with risk factors but no established cardiovascular disease showed substantial reduction of future stroke risk with tight control (0.49; 0.34–0.69), but those with established cardiovascular disease at entry did not experience stroke risk reduction with tight control (0.92; 0.83–1.03).Interpretation:Achieving an SBP <130mmHg compared to 130 to 139mmHg appears to provide additional stroke protection only among people with risk factors but no established cardiovascular disease. ANN NEUROL 2012;71:133–140
Head injury, alpha‐synuclein Rep1, and Parkinson's disease
Authors: Goldman Samuel M. , Kamel Freya , Ross G. Webster , Jewell Sarah A. , Bhudhikanok Grace S. , Umbach David , Marras Connie , Hauser Robert A. , Jankovic Joseph , Factor Stewart A. , Bressman Susan , Lyons Kelly E. , Meng Cheryl , Korell Monica , Roucoux Diana F. , Hoppin Jane A. , Sandler Dale P. , Langston J. William , Tanner Caroline M. 
Published: June 2011

AbstractObjective:To test the hypothesis that variability in SNCA Rep1, a polymorphic dinucleotide microsatellite in the promoter region of the gene encoding α‐synuclein, modifies the association between head injury and Parkinson's disease (PD) risk.Methods:Participants in the Farming and Movement Evaluation (FAME) and the Study of Environmental Association and Risk of Parkinsonism using Case‐Control Historical Interviews (SEARCH), 2 independent case‐control studies, were genotyped for Rep1 and interviewed regarding head injuries with loss of consciousness or concussion prior to Parkinson's disease (PD) diagnosis. Logistic regression modeling adjusted for potential confounding variables and tested interaction between Rep1 genotype and head injury.Results:Consistent with prior reports, relative to medium‐length Rep1, short Rep1 genotype was associated with reduced PD risk (pooled odds ratio [OR], 0.7; 95% confidence interval [CI], 0.5–0.9), and long Rep1 with increased risk (pooled OR, 1.4; 95% CI, 0.95–2.2). Overall, head injury was not significantly associated with PD (pooled OR, 1.3; 95% CI, 0.9–1.8). However, head injury was strongly associated with PD in those with long Rep1 (FAME OR, 5.4; 95% CI, 1.5–19; SEARCH OR, 2.3; 95% CI, 0.6–9.2; pooled OR, 3.5; 95% CI 1.4–9.2, p‐interaction = 0.02). Individuals with both head injury and long Rep1 were diagnosed 4.9 years earlier than those with neither risk factor (p = 0.03).Interpretation:While head injury alone was not associated with PD risk, our data suggest head injury may initiate and/or accelerate neurodegeneration when levels of synuclein are high, as in those with Rep1 expansion. Given the high population frequency of head injury, independent verification of these results is essential. ANN NEUROL 2012;71:40–48
Preparation and properties of environmental friendly nonhalogen flame retardant melamine cyanurate/nylon 66 composites
Authors: Lu Xiushou , Qiao Xiuying , Yang Tao , Sun Kang , Chen Xiaodong 
Published: June 2011

AbstractMelamine cyanurate (MCA) was utilized as an environmental friendly additive to prepare the nonhalogen flame retardant MCA/Nylon 66 composites by melt blending technique. Because of the strong hydrogen bond interactions and fine interfacial compatibility between MCA and Nylon 66, the resultant even dispersion of MCA filler in polymer matrix leads to the better toughness and strength of MCA/Nylon 66 composites than those of neat Nylon 66. Both Nylon 66 and MCA/Nylon 66 composites exhibit similar α‐crystalline structure, but the presence of MCA influences the distribution of α1 and α2 crystalline phases in Nylon 66 by inducing its hydrogen‐bonded sheet separation. Moreover, the blending of MCA and Nylon 66 increases the crystallization temperature and exothermicity but decreases the thermal stability of Nylon 66 and accelerates the degradation of MCA. The MCA/Nylon 66 composites show better flame retardancy at intermediate MCA contents of 10 and 15 wt %. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
The Anatomy of the Dog Soft Palate. II. Histological Evaluation of the Caudal Soft Palate in Brachycephalic Breeds With Grade I Brachycephalic Airway Obstructive Syndrome
Authors: Pichetto Michela , Arrighi Silvana , Roccabianca Paola , Romussi Stefano 
Published: June 2011

AbstractIn brachycephalic dogs, the skull bone shortening is not paralleled by a decreased development of soft tissues. Relatively longer soft palate is one of the main factors contributing to pharyngeal narrowing during normal respiratory activity of these dog breeds, which are frequent carriers of the brachycephalic airway obstructive syndrome (BAOS), which affects most part of them during their postnatal life. No histological studies assessing the morphology and the normal tissue composition of the soft palate in brachycephalic dogs are available, neither has ever been determined whether the elongated soft palate is a primary or secondary event. Aim of this study was to describe the morphology of the caudal soft palate in brachycephalic dogs with Grade I BAOS to identify potential features possibly favoring the pathogenesis of BAOS. Specimens from brachycephalic dogs (N = 11) that underwent preventive surgery were collected from surgery, processed for histology, and examined at six transversal levels. The brachycephalic soft palates showed peculiar features such as thickened superficial epithelium, extensive oedema of the connective tissue, and mucous gland hyperplasia. Several muscular alterations were evidenced in addition. The results of this investigation add to the general knowledge of the anatomy of soft palate in the canine species and establish baseline information on the morphological basis of the soft palate thickening in brachycephalic dogs. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
Glutamate Microinjected in the Posterodorsal Medial Amygdala Induces Subtle Increase in the Consumption of a Three‐Choice Macronutrient Self‐Selection Diet in Male Rats
Authors: Rosa Carolina Böettge , Goularte Jéferson F. , Trindade Nathália A. , De Oliveira Alexandre P. , Rasia‐Filho Alberto A. 
Published: June 2011

AbstractPrevious studies have involved the “posterodorsal” amygdaloid area with the control of food intake and the development of obesity in rats. Within this wide region, the posterodorsal medial amygdala (MePD) has connections with specific hypothalamic nuclei that increase feeding behavior and modulate energy balance. Glutamate is the major brain excitatory neurotransmitter, remarkably enhances centrally mediated food consumption, and is abundantly found in the MePD. Here, it was studied the effects of saline (0.3 μL) and glutamate (45 nM or 45 mM/0.3 μL) directly microinjected in the MePD of adult male rats on the consumption of a three‐choice (high‐carbohydrate, high‐protein, or high‐lipid) macronutrient selective diet. The rat adaptation to the experimental procedures and its body weight gain were continuously evaluated. Control data for all groups and results following microinjections were obtained after a fasting protocol. Feeding behavior was evaluated during the subsequent 2‐hr period of free access to the selective diets. Both doses of glutamate microinjected in the MePD did not lead to a higher percentage of animals consuming any of the different diets (P > 0.05), although glutamate 45 mM induced a higher consumption of the high‐carbohydrate diet when compared with presurgery control values (P < 0.01). Interestingly, present data indicate that glutamate in the male MePD induces only a subtle modification in the feeding behavior and suggest that large electrolytic lesions of the “posterodorsal” amygdaloid region might have affected other regions to alter drastically meal size consumption in rats. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.