bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Derived Lactate Modifies Antitumor Immune Response: Effect on Myeloid-Derived Suppressor Cells and NK Cells
Authors: Husain Zaheed , Huang Yannu , Seth Pankaj , Sukhatme Vikas P. 
Published: July 2013

Abstract
In this study, we explore the hypothesis that enhanced production of lactate by tumor cells, because of high glycolytic activity, results in inhibition of host immune response to tumor cells. Lactate dehydrogenase-A (LDH-A), responsible for conversion of pyruvate to lactate, is highly expressed in tumor cells. Lentiviral vector–mediated LDH-A short hairpin RNA knockdown Pan02 pancreatic cancer cells injected in C57BL/6 mice developed smaller tumors than mice injected with Pan02 cells. A decrease occurred in the frequency of myeloid-derived suppressor cells (MDSCs) in the spleens of mice carrying LDH-A–depleted tumors. NK cells from LDH-A–depleted tumors had improved cytolytic function. Exogenous lactate increased the frequency of MDSCs generated from mouse bone marrow cells with GM-CSF and IL-6 in vitro. Lactate pretreatment of NK cells in vitro inhibited cytolytic function of both human and mouse NK cells. This reduction of NK cytotoxic activity was accompanied by lower expression of perforin and granzyme in NK cells. The expression of NKp46 was decreased in lactate-treated NK cells. These studies strongly suggest that tumor-derived lactate inhibits NK cell function via direct inhibition of cytolytic function as well as indirectly by increasing the numbers of MDSCs that inhibit NK cytotoxicity. Depletion of glucose levels using a ketogenic diet to lower lactate production by glycolytic tumors resulted in smaller tumors, decreased MDSC frequency, and improved antitumor immune response. These studies provide evidence for an immunosuppressive role of tumor-derived lactate in inhibiting innate immune response against developing tumors via regulation of MDSC and NK cell activity.
Differential Impact of Age and Cytomegalovirus Infection on the γδ T Cell Compartment
Authors: Roux Antoine , Mourin Gisèle , Larsen Martin , Fastenackels Solène , Urrutia Alejandra , Gorochov Guy , Autran Brigitte , Donner Catherine , Sidi Daniel , Sibony-Prat Joyce , Marchant Arnaud , Stern Marc , Sauce Delphine , Appay Victor 
Published: July 2013

Abstract
γδ T cells represent a subset of unconventional T lymphocytes that are known for their reactivity against different pathogens and considered as intermediate mediators between adaptive and innate immunity. We provide in this paper further insights underlying the changes that affect the γδ T cell compartment with advanced age in humans. We show that both aging and CMV infection impact independently on the γδ T cell compartment. Most γδ T cells are significantly affected by age and present a decreased frequency in the elderly. The decline of the γδ T cell pool appears to be independent from the activity of the thymus, arguing in favor of an extrathymic site of γδ T cell production in humans. Of note, CMV infection, which is directly associated with the activation of the pool of Vδ2− γδ T cells, promotes nonetheless the inflation of this compartment throughout life. CMV seropositivity accentuates further the accumulation of highly differentiated lymphocytes in Vδ2− γδ T cell subsets with time, in contrast to Vδ2+ γδ T cells, which maintain a less differentiated phenotype. This is similar to the effect of CMV on αβ T cells and suggests that γδ T cells may vary in differentiation phenotype according to distinct stimuli or pathogens.
Adipocytes Modulate the Phenotype of Human Macrophages through Secreted Lipids
Authors: Klein-Wieringa Inge R. , Andersen Stefan N. , Kwekkeboom Joanneke C. , Giera Martin , de Lange-Brokaar Badelog J. E. , van Osch Gerjo J. V. M. , Zuurmond Anne-Marie , Stojanovic-Susulic Vedrana , Nelissen Rob G. H. H. , Pijl Hanno , Huizinga Tom W. J. , Kloppenburg Margreet , Toes René E’. M. , Ioan-Facsinay Andreea 
Published: July 2013

Abstract
Previous studies have shown accumulation and an enhanced proinflammatory profile of macrophages in adipose tissue of obese mice, indicating the presence of an interaction between adipocytes and macrophages in this tissue. However, the consequences of this interaction in humans are yet incompletely understood. In this study, we explored the modulating effects of adipocytes on the phenotype of macrophages in humans and studied the possible molecular pathways involved. Adipocyte-conditioned media (ACM) treatment of macrophages for 48 h strongly reduced the LPS-induced IL-12p40 secretion by macrophages, whereas the production of TNF-α and other cytokines remained largely unaffected. This effect was independent of the source of adipocytes. Interestingly, the level of inhibition correlated directly with body mass index (BMI) of the adipocyte donor. Because adipocytes release many different cytokines, adipokines, and lipids, we have separated the protein and lipid fractions of ACM, to obtain insight into the molecular nature of the soluble mediators underlying the observed effect. These experiments revealed that the inhibitory effect resided predominantly in the lipid fraction. Further studies revealed that PGE2 and linoleic and oleic acid were potent inhibitors of IL-12p40 secretion. Interestingly, concentrations of these ACM-derived lipids increased with increase in BMI of the adipocyte donor, suggesting that they could mediate the BMI-dependent effects of ACM. To our knowledge, these results provide first evidence that obesity-related changes in adipose tissue macrophage phenotype could be mediated by adipocyte-derived lipids in humans. Intriguingly, these changes appear to be different from those in murine obesity.
The Encephalitogenic, Human Myelin Oligodendrocyte Glycoprotein–Induced Antibody Repertoire Is Directed toward Multiple Epitopes in C57BL/6-Immunized Mice
Authors: Bansal Pankaj , Khan Tarique , Bussmeyer Uta , Challa Dilip K. , Swiercz Rafal , Velmurugan Ramraj , Ober Raimund J. , Ward E. Sally 
Published: July 2013

Abstract
Although Abs specific for myelin oligodendrocyte glycoprotein (MOG) have been detected in patients with multiple sclerosis (MS), their contribution to pathogenesis remains poorly understood. Immunization of C57BL/6 mice with recombinant human MOG (hMOG) results in experimental autoimmune encephalomyelitis involving MOG-specific, demyelinating Abs. This model is therefore informative for understanding anti-MOG humoral responses in MS. In the current study, we have characterized the hMOG-specific Ab repertoire in immunized C57BL/6 mice using both in vitro and in vivo approaches. We demonstrate that hMOG-specific mAbs are not focused on one specific region of MOG, but instead target multiple epitopes. Encephalitogenicity of the mAbs, assessed by the ability of the mAbs to exacerbate experimental autoimmune encephalomyelitis in mice, correlates with the activity of the mAbs in binding to CNS tissue sections, but not with other in vitro assays. The targeting of different MOG epitopes by encephalitogenic Abs has implications for disease pathogenesis, because it could result in MOG cross linking on oligodendrocytes and/or immune complex formation. These studies reveal several novel features concerning pathogenic, humoral responses that may have relevance to human MS.
A Protective Hsp70–TLR4 Pathway in Lethal Oxidant Lung Injury
Authors: Zhang Yi , Zhang Xuchen , Shan Peiying , Hunt Clayton R. , Pandita Tej K. , Lee Patty J. 
Published: July 2013

AbstractAdministering high levels of inspired oxygen, or hyperoxia, is commonly used as a life-sustaining measure in critically ill patients. However, prolonged exposures can exacerbate respiratory failure. Our previous study showed that TLR4 confers protection against hyperoxia-induced lung injury and mortality. Hsp70 has potent cytoprotective properties and has been described as a TLR4 ligand in cell lines. We sought to elucidate the relationship between TLR4 and Hsp70 in hyperoxia-induced lung injury in vitro and in vivo and to define the signaling mechanisms involved. Wild-type, TLR4−/−, and Trif−/− (a TLR4 adapter protein) murine lung endothelial cells (MLECs) were exposed to hyperoxia. We found markedly elevated levels of intracellular and secreted Hsp70 from wild-type mice lungs and MLECs after hyperoxia. We confirmed that Hsp70 and TLR4 coimmunoprecipitate in lung tissue and MLECs. Hsp70-mediated NF-κB activation appears to depend upon TLR4. In the absence of TLR4, Hsp70 loses its protective effects in endothelial cells. Furthermore, these protective properties of Hsp70 are TLR4 adapter Trif dependent and MyD88 independent. Hsp70-deficient mice have increased mortality during hyperoxia, and lung-targeted adenoviral delivery of Hsp70 effectively rescues both Hsp70-deficient and wild-type mice. To our knowledge, our studies are the first to define an Hsp70–TLR4–Trif cytoprotective axis in the lung and endothelial cells. This pathway is a potential therapeutic target against a range of oxidant-induced lung injuries.
Corticosteroids Block Autophagy Protein Recruitment in Aspergillus fumigatus Phagosomes via Targeting Dectin-1/Syk Kinase Signaling
Authors: Kyrmizi Irene , Gresnigt Mark S. , Akoumianaki Tonia , Samonis George , Sidiropoulos Prodromos , Boumpas Dimitrios , Netea Mihai G. , van de Veerdonk Frank L. , Kontoyiannis Dimitrios P. , Chamilos Georgios 
Published: July 2013

Abstract
Aspergillus fumigatus is the predominant airborne fungal pathogen in immunocompromised patients. Genetic defects in NADPH oxidase (chronic granulomatous disease [CGD]) and corticosteroid-induced immunosupression lead to impaired killing of A. fumigatus and unique susceptibility to invasive aspergillosis via incompletely characterized mechanisms. Recent studies link TLR activation with phagosome maturation via the engagement of autophagy proteins. In this study, we found that infection of human monocytes with A. fumigatus spores triggered selective recruitment of the autophagy protein LC3 II in phagosomes upon fungal cell wall swelling. This response was induced by surface exposure of immunostimulatory β-glucans and was mediated by activation of the Dectin-1 receptor. LC3 II recruitment in A. fumigatus phagosomes required spleen tyrosine kinase (Syk) kinase–dependent production of reactive oxygen species and was nearly absent in monocytes of patients with CGD. This pathway was important for control of intracellular fungal growth, as silencing of Atg5 resulted in impaired phagosome maturation and killing of A. fumigatus. In vivo and ex vivo administration of corticosteroids blocked LC3 II recruitment in A. fumigatus phagosomes via rapid inhibition of phosphorylation of Src and Syk kinases and downstream production of reactive oxygen species. Our studies link Dectin-1/Syk kinase signaling with autophagy-dependent maturation of A. fumigatus phagosomes and uncover a potential mechanism for development of invasive aspergillosis in the setting of CGD and corticosteroid-induced immunosupression.
Ficolin-1–PTX3 Complex Formation Promotes Clearance of Altered Self-Cells and Modulates IL-8 Production
Authors: Ma Ying Jie , Doni Andrea , Romani Luigina , Jürgensen Henrik Jessen , Behrendt Niels , Mantovani Alberto , Garred Peter 
Published: July 2013

AbstractThe long pentraxin 3 (PTX3) has been shown to be important in maintaining internal tissue homeostasis and in protecting against fungal Aspergillus fumigatus infection. However, the molecular mechanisms of how these functions are elicited are poorly delineated. Ficolin-1 is a soluble pattern recognition molecule that interacts with PTX3. We hypothesized that heterocomplexes between ficolin-1 and PTX3 might mediate the signals necessary for sequestration of altered self-cells and A. fumigatus. We were able to show that ficolin-1 interacts with PTX3 via its fibrinogen-like domain. The interaction was affected in a pH- and divalent cation–sensitive manner. The primary binding site for ficolin-1 on PTX3 was located in the N-terminal domain portion of PTX3. Ficolin-1 and PTX3 heterocomplex formation occurred on dying host cells, but not on A. fumigatus. The heterocomplex formation was a prerequisite for enhancement of phagocytosis by human monocyte–derived macrophages and downregulation of IL-8 production during phagocytosis. On A. fumigatus, PTX3 exposed the C-terminal portion of the molecule, probably resulting in steric hindrance of ficolin-1 interaction with PTX3. These results demonstrate that ficolin-1 and PTX3 heterocomplex formation acts as a noninflammatory “find me and eat me” signal to sequester altered-host cells. The fact that the ficolin-1–PTX3 complex formation did not occur on A. fumigatus shows that PTX3 uses different molecular effector mechanisms, depending on which domains it exposes during ligand interaction.
Deficiency of Phospholipase A2 Receptor Exacerbates Ovalbumin-Induced Lung Inflammation
Authors: Tamaru Shun , Mishina Hideto , Watanabe Yosuke , Watanabe Kazuhiro , Fujioka Daisuke , Takahashi Soichiro , Suzuki Koji , Nakamura Takamitsu , Obata Jun-ei , Kawabata Kenichi , Yokota Yasunori , Murakami Makoto , Hanasaki Kohji , Kugiyama Kiyotaka 
Published: July 2013

Abstract
Secretory phospholipase A2 (sPLA2) plays a critical role in the genesis of lung inflammation through proinflammatory eicosanoids. A previous in vitro experiment showed a possible role of cell surface receptor for sPLA2 (PLA2R) in the clearance of extracellular sPLA2. PLA2R and groups IB and X sPLA2 are expressed in the lung. This study examined a pathogenic role of PLA2R in airway inflammation using PLA2R-deficient (PLA2R−/−) mice. Airway inflammation was induced by immunosensitization with OVA. Compared with wild-type (PLA2R+/+) mice, PLA2R−/− mice had a significantly greater infiltration of inflammatory cells around the airways, higher levels of groups IB and X sPLA2, eicosanoids, and Th2 cytokines, and higher numbers of eosinophils and neutrophils in bronchoalveolar lavage fluid after OVA treatment. In PLA2R−/− mice, intratracheally instilled [125I]-labeled sPLA2-IB was cleared much more slowly from bronchoalveolar lavage fluid compared with PLA2R+/+ mice. The degradation of the instilled [125I]-labeled sPLA2-IB, as assessed by trichloroacetic acid-soluble radioactivity in bronchoalveolar lavage fluid after instillation, was lower in PLA2R−/− mice than in PLA2R+/+ mice. In conclusion, PLA2R deficiency increased sPLA2-IB and -X levels in the lung through their impaired clearance from the lung, leading to exaggeration of lung inflammation induced by OVA treatment in a murine model.
Dendritic Cells Regulate High-Speed Interstitial T Cell Migration in the Lymph Node via LFA-1/ICAM-1
Authors: Katakai Tomoya , Habiro Katsuyoshi , Kinashi Tatsuo 
Published: July 2013

Abstract
T lymphocytes vigorously migrate within the paracortex of lymph nodes (LNs) in search of cognate Ags that are presented by dendritic cells (DCs). However, the mechanisms that support T cells to exert the highest motility in a densely packed LN microenvironment are not fully understood. Two-photon microscopy using LN tissue slices revealed that LFA-1 and ICAM-1 were required for high-velocity migration (&gt;10 μm/min) with relatively straight movement. Importantly, ICAM-1 expressed by myeloid lineages, most likely DCs, but not stromal cells or lymphocytes, was sufficient to support the high-velocity migration. Visualizing DCs in the LN from CD11c-EYFP mice showed that T cells traveled over thin dendrites and the body of DCs. Interestingly, DCs supported T cell motility in vitro in chemokine- and ICAM-1–dependent manners. Moreover, an acute lymphopenic environment in the LN significantly increased LFA-1 dependency for T cell migration, indicating that lymphocyte density modulates the use of LFA-1. Therefore, our results indicate that LFA-1/ICAM-1–dependent interactions between T cells and DCs play a crucial role not only in supporting firm arrest during Ag recognition but also in facilitating the Ag scanning processes.
Assouad–Nagata Dimension of Wreath Products of Groups
Authors: Brodskiy N. , Dydak J. , Lang U. 
Published: July 2013

AbstractConsider the wreath product H ≀ G, where H ≠ 1 is finite and G is finitely generated. We show that the Assouad–Nagata dimension dimAN(H ≀ G) of H ≀ G depends on the growth of G as follows: if the growth of G is not bounded by a linear function, then dimAN(H ≀ G) = ∞; otherwise dimAN(H ≀ G) = dimAN(G) ≤ 1.
The 1 : 1 Adduct of 1,3-Diisopropyl-4,5-dimethyl-2,3-dihydroimidazol-2- ylidene and Nitrous Oxide
Authors: Göhner M. , Haiss P. , Kuhn N. , Ströbele M. , Zeller K.-P. 
Published: July 2013

Abstract
The nucleophilic carbene 1,3-diisopropyl-4,5-dimethyl-2,3-dihydroimidazol-2-ylidene (7) captures nitrous oxide under formation of both syn- (8) and anti-1,3-diisopropyl-4,5-imidazolium diazotate (9). The syn-isomer is the thermodynamically more stable form. As shown by X-ray crystallography, the two isomers are statistically distributed in the crystalline state
Activation of C–Cl Bonds: Synthesis and Structural Characterization of [Ru2(μ-Cl)(μ-PtBu2)(μ- Ph2PN(H)PPh2)(CO)4]
Authors: Mayer Tobias , Böttcher Hans-Christian 
Published: July 2013

Abstract
The synthesis and structural characterization of the complex [Ru2(μ-Cl)(μ-PtBu2)(μ-dppa)(CO)4] (4, dppa = Ph2PN(H)PPh2) are reported. The title compound and two other related complexes were obtained in high yields by the reaction of the coordinatively unsaturated species [Ru2(μ-H)(μ-PtBu2)(μ-PˆP)(CO)4] (PˆP = dppa, 3; PˆP =Ph2PN(Ph)PPh2, 5; PˆP =Ph2PN(CH2Ph)PPh2, 6) with carbon tetrachloride. Single crystals of 4 grown from dichloromethane-acetone have been analyzed by X-ray crystallography
Infinite Anionic Chains Formed by Alternating Bidentately Acting [SbS4]3- Anions and [Mn(dien)]2+ Complexes in the Compound [Mn(dien)2][Mn(dien)SbS4]2
Authors: Näther Christian , Herzberg Nicola , Bensch Wolfgang 
Published: July 2013

Abstract
The new compound [Mn(dien)2][Mn(dien)SbS4]2 (dien=diethylenetriamine) was synthesized under solvothermal conditions. It crystallizes in the non-centrosymmetric monoclinic space group P21 with a=7.5736(5), b=19.1081(16), c=13.1174(11) Å, b =90:022(9) , V =1898.3(3) Å3, and Z =2. The crystal structure is composed of one [Mn(dien)2]2+ cation and an anionic chain composed of [SbS4]3- anions and [Mn(dien)2]2+ cations. The [SbS4]3- anions connect [Mn(dien)2]2+ ions in a μ2-fashion to form an undulated {[Mn(dien)SbS4]}-2 chain running along [001]. The Mn2+ ions in the chain are in a rare distorted rectangular pyramidal coordination environment with 3 N and 1 S atom forming the base and one S atom being located at the apex of the pyramid. The anionic chains and the cations alternate along [010]. Several relatively strong intra- and inter-chain N-H-S bonding interactions are observed. From the Raman spectrum the reduction of the ideal Td symmetry of the [SbS4]3- anions is obvious because more resonances occur than expected for the undistorted geometry
A Dinuclear Palladium(II) Complex of the {N(SPPh2)2}- Ligand – Synthesis and Structure
Authors: Marks Sebastian , Roesky Peter W. 
Published: July 2013

Abstract
The synthesis and characterization including the crystal structure of the dinuclear palladium( II) complex [(k-S,S’)-{N(SPPh2)2}Pd(m-{k2-S'',S'''})-{N(SPPh2)2}PdCl2] (1) are reported. Compound 1 was obtained from the reaction of [PdCl2(COD)] (COD=1,5-cyclooctadiene) and HN(SPPh2)2 in a 1:1 molar ratio in CH2Cl2. The {N(SPPh2)2}- ligands act both as bridging and/or terminally chelating units
Synthesis of a 30-Membered Macrocycle Incorporating Two Ruthenium Sandwich Complexes
Authors: Schmid Alexander , Polborn Kurt , Lindel Thomas 
Published: July 2013

Abstract
The first macrocycle incorporating two ruthenium sandwich complexes has been synthesised. Key step is a cyclodimerisation by double etherification of a p-chlorophenylalanine-derived [RuCp*]+ complex. Silica-based cation exchange chromatography allowed the separation of dicationic diastereomers. Assignment of the relative configurations was possible by X-ray structure determination. Partial demetalation in acetonitrile proceeded in high yield by irradiation in the presence of biphenyl
A Base-stabilized Iodoborylene Complex of Platinum(II)
Authors: Braunschweig Holger , Brenner Peter B. , Dewhurst Rian D. , Radacki Krzysztof 
Published: July 2013

Abstract
The first base-stabilized iodoborylene platinum complex was prepared through the addition of 4-picoline (4-Pic) to a suspension of an iodo-bridged binuclear iodoboryl complex. An X-ray structure determination of the title compound has characterized the molecular structure as cis-[Pt{BI(4- Pic)}I2(PCy3)]. The bond lengths lie in the expected range for neutral, base-stabilized borylene complexes. The strong trans influence of the borylene moiety is reflected in the longer Pt-1 distance for the iodo ligand opposite the borylene, compared to that opposite the phosphine ligand
Cobalt(III)-Binding of Gluconate and 2-Amino-2-Deoxy-Gluconate
Authors: Pfister Max , Illi Sarah , Klüfers Peter 
Published: July 2013

Abstract
Two isomers of the [Co(tren)(D-Glc1A1,2H-2-K2O1,2)]+ (1) chelate are formed in equal parts in the reaction of [Co(tren)Cl2]Cl and sodium gluconate. In contrast, the gluconate’s 2-amino-2-deoxy derivative glucosaminate formed a single isomer of [Co(tren)(D-Glc1A2N1H-1-k2N,O2)]2+ (2). Crystals of the OC-6-34 isomer of 1, [1a]PF6 H2O, showed the support of the metal-binding site by intramolecular hydrogen bonds. Due to the inertness of the cobalt(III) chelates, spectroscopy on redissolved crystals of [1a]PF6 H2O allowed the separation of the two 13C NMR signal sets of the isomeric mixture. In a DFT approach, a small energy difference explained the formation of two isomers in the case of the gluconate. A larger difference was obtained for the glucosaminate, in line with the known rules for the stereospecific amino acid-Co(tren) chelation
Facile 1,1-Carboboration Reaction of a Diarylphosphino-substituted Conjugated Diyne with Tris(pentafluorophenyl)borane
Authors: Feldhaus Philipp , Kehr Gerald , Fröhlich Roland , Daniliuc Constantin G. , Erker Gerhard 
Published: July 2013

Abstract
Bis(dimesitylphosphanyl)butadiyne (14) reacts with B(C6F5)3 by a 1,1-carboboration sequence. The selective attack at a single phosphanyl-alkyne moiety is observed. First a phosphirenium-borate zwitterion 15 is formed at r. t. Thermolysis (80 °C) results in the E-selective formation of the 1,1- carboboration product, the frustrated Lewis pair (FLP) E-16, which upon heating to 160 °C eventually undergoes isomerization followed by an internal nucleophilic aromatic substitution reaction to give the product 17 featuring a -B(F)(C6F5)2 substituent at the five-membered P-heterocycle. Finally, the FLP E-16 was reacted with n-butylisocyanide to yield the five-membered heterocyclic product 18, formed by P,B addition to the isonitrile carbon atom. Compounds 14, 15, 17, and 18 were characterized by X-ray crystal structure analyses
Nickel(II) and Iron(II) Complexes with Tetradentate NHC/Amide Hybrid Ligands
Authors: Klawitter Iris , Meyer Steffen , Demeshko Serhiy , Meyer Franc 
Published: July 2013

Abstract
Two methylene-bridged bis(imidazolium) salts [H4L1](PF6)2 and [H4L2](PF6)2 with appended amide groups have been synthesized which, after deprotonation, may serve as potentially tetradentate ligands providing two bis(imidazole-2-ylidene) and two amide donors. Using [H4L1](PF6)2, a square-planar nickel(II) complex [NiL1] and a six-coordinate bis(ligand) iron(II) complex [Fe(HL1)2] have been isolated and structurally characterized. Their low-spin states have been confirmed spectroscopically, and their redox properties have been studied by cyclic voltammetry. Oxidations are metal-centered to give NiIII and FeIII species, respectively