bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective Targeting of a Disease-Related Conformational Isoform of Macrophage Migration Inhibitory Factor Ameliorates Inflammatory Conditions
Authors: Thiele Michael , Kerschbaumer Randolf J. , Tam Frederick W. K. , Völkel Dirk , Douillard Patrice , Schinagl Alexander , Kühnel Harald , Smith Jennifer , McDaid John P. , Bhangal Gurjeet , Yu Mei-Ching , Pusey Charles D. , Cook H. Terence , Kovarik Josef , Magelky Erica , Bhan Atul , Rieger Manfred , Mudde Geert C. , Ehrlich Hartmut , Jilma Bernd , Tilg Herbert , Moschen Alexander , Terhorst Cox , Scheiflinger Friedrich 
Published: July 2015

Abstract
Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine and counterregulator of glucocorticoids, is a potential therapeutic target. MIF is markedly different from other cytokines because it is constitutively expressed, stored in the cytoplasm, and present in the circulation of healthy subjects. Thus, the concept of targeting MIF for therapeutic intervention is challenging because of the need to neutralize a ubiquitous protein. In this article, we report that MIF occurs in two redox-dependent conformational isoforms. We show that one of the two isoforms of MIF, that is, oxidized MIF (oxMIF), is specifically recognized by three mAbs directed against MIF. Surprisingly, oxMIF is selectively expressed in the plasma and on the cell surface of immune cells of patients with different inflammatory diseases. In patients with acute infections or chronic inflammation, oxMIF expression correlated with inflammatory flare-ups. In addition, anti-oxMIF mAbs alleviated disease severity in mouse models of acute and chronic enterocolitis and improved, in synergy with glucocorticoids, renal function in a rat model of crescentic glomerulonephritis. We conclude that oxMIF represents the disease-related isoform of MIF; oxMIF is therefore a new diagnostic marker for inflammation and a relevant target for anti-inflammatory therapy.
Langerhans Cells Suppress CD49a+ NK Cell–Mediated Skin Inflammation
Authors: Scholz Felix , Naik Shruti , Sutterwala Fayyaz S. , Kaplan Daniel H. 
Published: July 2015

Abstract
Recruitment of innate immune effector cells into sites of infection is a critical component of resistance to pathogen infection. Using a model of intradermal footpad injection of Candida albicans, we observed that inflammation as measured by footpad thickness and neutrophil recruitment occurred independent of adoptive immunity but was significantly reduced in MyD88−/− and IL-6−/− mice. Unexpectedly, huLangerin-DTA mice (ΔLC) that lack Langerhans cells (LC) developed increased skin inflammation and expressed higher amounts of IL-6, suggesting a suppressive role for LC. Increased inflammation also occurred in Rag1−/− ΔLC mice but was reversed by Ab-mediated ablation of NK cells. CXCR6+CD49a+ NK cells are a liver-resident subset that can mediate inflammatory skin responses. We found that exaggerated skin inflammation was absent in ΔLC × CXCR6−/− mice. Moreover, the exaggerated response in ΔLC mice could be adoptively transferred with liver CD49a+ NK cells. Finally, CD49a+ NK cells in ΔLC but not control mice were recruited to the skin, and inhibition of their recruitment prevented the exaggerated response. Thus, in the absence of LC, CD49a+ liver NK cells display an inappropriately proinflammatory phenotype that results in increased local skin inflammation. These data reveal a novel function for LC in the regulation of this recently described subset of skin tropic NK cells.
CXCR3 Polymorphism and Expression Associate with Spontaneous Preterm Birth
Authors: Karjalainen Minna K. , Ojaniemi Marja , Haapalainen Antti M. , Mahlman Mari , Salminen Annamari , Huusko Johanna M. , Määttä Tomi A. , Kaukola Tuula , Anttonen Julia , Ulvila Johanna , Haataja Ritva , Teramo Kari , Kingsmore Stephen F. , Palotie Aarno , Muglia Louis J. , Rämet Mika , Hallman Mikko 
Published: July 2015

AbstractSpontaneous preterm birth (SPTB) is a major factor associating with deaths and with lowered quality of life in humans. Environmental and genetic factors influence the susceptibility. Previously, by analyzing families with recurrent SPTB in linkage analysis, we identified a linkage peak close to the gene encoding CXCR3. Present objectives were to investigate the association of CXCR3 with SPTB in Finnish mothers (n = 443) and infants (n = 747), to analyze CXCR3 expression levels in human placenta and levels of its ligands in umbilical cord blood, and to verify the influence of Cxcr3 on SPTB-associating cytokines in mice. We detected an association between an intronic CXCR3 polymorphism, rs2280964, and SPTB in infants from families with recurrent preterm births (p = 0.009 versus term controls, odds ratio 0.52, 95% confidence interval 0.32–0.86). The minor allele was protective and undertransmitted to SPTB infants (p = 0.007). In the placenta and fetal membranes, the rs2280964 major allele homozygotes had higher expression levels than minor allele homozygotes; decidual trophoblasts showed strong CXCR3 immunoreactivity. Expression was higher in SPTB placentas compared with those from elective deliveries. Concentration of a CXCR3 ligand, CXCL9, was increased in cord blood from SPTB, and the protective rs2280964 allele was associated with low CXCL9. In CXCR3-deficient mice (Mus musculus), SPTB-associating cytokines were not acutely increased in amniotic fluid after preterm birth–inducing dose of maternal LPS. Our results indicate that CXCR3 contributes to SPTB. Activation of CXCR3 signaling may disturb the maternal–fetal tolerance, and this may promote labor.
Phosphorus budget in the water‐agro‐food system at nested scales in two contrasted regions of the world (ASEAN‐8 and EU‐27)
Authors: Garnier Josette , Lassaletta Luis , Billen Gilles , Romero Estela , Grizzetti Bruna , Némery Julien , Le Thi Phuong Quynh , Pistocchi Chiara , Aissa‐Grouz Najla , Luu Thi Nguyet Minh , Vilmin Lauriane , Dorioz Jean‐Marcel 
Published: July 2015

AbstractPhosphorus (P) plays a strategic role in agricultural production as well as in the occurrence of freshwater and marine eutrophication episodes throughout the world. Moreover, the scarcity and uneven distribution of minable P resources is raising concerns about the sustainability of long‐term exploitation. In this paper we analyze the P cycle in anthropic systems with an original multiscale approach (world region, country, and large basin scales) in two contrasting world regions representative of different trajectories in socioeconomic development for the 1961–2009 period: Europe (EU‐27)/France and the Seine River Basin, and Asia (ASEAN‐8)/Vietnam and the Red River Basin. Our approach highlights different trends in the agricultural and food production systems of the two regions. Whereas crop production increased until the 1980s in Europe and France and has stabilized thereafter, in ASEAN‐8 and Vietnam it began to increase in the 1980s and it is still rising today. These trends are related to the increasing use of fertilizers, although in European countries the amount of fertilizers sharply decreased after the 1980s. On average, the total P delivered from rivers to the sea is 3 times higher for ASEAN‐8 (300 kg P km−2 yr−1) than for EU‐27 countries (100 kg P km−2 yr−1) and is twice as high in the Red River (200 kg P km−2 yr−1) than in the Seine River (110 kg P km−2 yr−1), with agricultural losses to water in ASEAN‐8 3 times higher than in EU‐27. Based on the P flux budgets, this study discusses early warnings and management options according to the particularities of the two world regions, newly integrating the perspective of surface water quality with agricultural issues (fertilizers, crop production, and surplus), food/feed exchanges, and diet, defining the so‐called water‐agro‐food system.
Dependence of the dayside magnetopause reconnection rate on local conditions
Authors: Wang Shan , Kistler Lynn M. , Mouikis Christopher G. , Petrinec Steven M. 
Published: July 2015

AbstractWe estimate the reconnection rates for eight dayside magnetopause reconnection events observed by the Cluster spacecraft and compare them with the predictions of the Cassak‐Shay Formula (Rcs) Cassak and Shay (2007). The measured reconnection rate is determined by calculating the product of the inflow velocity and magnetic field in the magnetosheath inflow region. The predicted reconnection rate is calculated using the plasma parameters on both sides of the current layer, including the contributions of magnetosheath H+, magnetospheric hot H+ and O+, and magnetospheric cold ions. The measured reconnection rates show clear correlations with Rcs with an aspect ratio of 0.07. The O+ and cold ions can contribute up to ~30% of the mass density, which may reduce the reconnection rate for individual events. However, the variation of the reconnection rate is dominated by the variation of the magnetosheath parameters. In addition, we calculated the predicted reconnection rate using only magnetosheath parameters (Rsh). The correlation of the measured rate with Rsh was better than the correlation with Rcs, with an aspect ratio of 0.09. This might indicate deviations from the Cassak‐Shay theory caused by the asymmetric reconnection structure and kinetic effects of different inflow populations. A better aspect ratio is expected to be between the ones determined using Rcs and Rsh. The aspect ratio does not show a clear dependence on the O+ concentration, likely because the O+ contribution is too small in these events. The aspect ratio also does not show a clear correlation with density asymmetry or guide field.
Self‐acceleration and instability of gravity wave packets: 1. Effects of temporal localization
Authors: Fritts David C. , Laughman Brian , Lund Thomas S. , Snively Jonathan B. 
Published: July 2015

AbstractAn anelastic numerical model is used to explore the dynamics accompanying the attainment of large amplitudes by gravity waves (GWs) that are localized in altitude and time. GW momentum transport induces mean flow variations accompanying a GW packet that grows exponentially with altitude, is localized in altitude, and induces significant GW phase speed, and phase, variations across the GW packet. These variations arise because the GW occupies the region undergoing accelerations, with the induced phase speed variations referred to as “self‐acceleration.” Results presented here reveal that self‐acceleration of a GW packet localized in time and altitude ultimately leads to stalling of the vertical propagation of the GW packet and accompanying two‐ and three‐dimensional (2‐D and 3‐D) instabilities of the superposed GW and mean motion field. The altitudes at which these effects occur depend on the initial GW amplitude, intrinsic frequency, and degree of localization in time and altitude. Larger amplitudes and higher intrinsic frequencies yield strong self‐acceleration effects at lower altitudes, while smaller amplitudes yield similar effects at higher altitudes, provided the Reynolds number, Re, is sufficiently large. Three‐dimensional instabilities follow 2‐D “self‐acceleration instability” for sufficiently high Re. GW packets can also exhibit self‐acceleration dynamics at more than one altitude because of continued growth of the GW packet leading edge above the previous self‐acceleration event.
Conjoint use of Dibenzosilole and Indan‐1,3‐dione Functionalities to Prepare an Efficient Non‐Fullerene Acceptor for Solution‐Processable Bulk‐Heterojunction Solar Cells
Authors: Patil Hemlata , Gupta Akhil , Alford Ben , Ma Di , Privér Steven H. , Bilic Ante , Sonar Prashant , Bhosale Sheshanath V. 
Published: July 2015

AbstractA solution‐processable, non‐fullerene electron acceptor, 2,2′‐(((5,5‐dioctyl‐5 H‐dibenzo[b,d]silole‐3,7‐diyl)bis(thiophene‐5,2‐diyl))bis(methanylylidene))bis(1 H‐indene‐1,3(2 H)‐dione) (called N5) comprised of dibenzosilole and 1,3‐indanedione building blocks was designed, synthesized, and fully characterized. N5 is highly soluble in various organic solvents, has high thermal stability, and has energy levels matching those of archetypal donor poly(3‐hexylthiophene). Solution‐processable, bulk‐heterojunction solar cells afforded promising power conversion efficiency of 2.76 % when N5 was used as a non‐fullerene electron acceptor along with the conventional donor polymer poly(3‐hexylthiophene). As per our knowledge, the material reported herein is the first example in the literature where synchronous use of such building blocks is demonstrated in the design an efficient, non‐fullerene acceptor.
Modulation der Stereoselektivität einer DNA‐katalysierten Michael‐Addition durch kovalente Modifizierung
Authors: Dey Surjendu , Jäschke Andres 
Published: July 2015

AbstractG‐Quadruplex‐DNA fand – im Komplex mit CuII‐Ionen – bereits Anwendung als Katalysator in asymmetrischen Reaktionen. Die größtenteils unspezifische nichtkovalente Wechselwirkung erschwerte jedoch das Verständnis der strukturellen Grundlage der Katalyse. Mit dem Ziel, die Bildung katalytisch aktiver Spezies präziser kontrollieren zu können, beschreiben wir hier die Synthese von DNA‐Quadruplexen, die ortsspezifisch mit Linker‐bpy‐CuII‐Komplexen derivatisiert wurden, sowie ihre Anwendung in asymmetrischen wässrigen Michael‐Additionen. Die modifizierten Quadruplexe zeichnen sich durch eine hohe Reaktionsbeschleunigung und Stereoselektivität aus, wobei unterschiedliche Faktoren das katalytische Verhalten beeinflussen. Dazu zählen unter anderem die Position der Modifizierung, die Topologie der Quadruplexe, die Art des Liganden und die Länge des Linkers zwischen Ligand und DNA. Erstaunlicherweise führte das Versetzen des gleichen Liganden um lediglich zwei Nukleotide zu einer Umkehr der Stereochemie der Reaktion. Während Quadruplexe, die an Position 10 modifiziert wurden, vorzugsweise das (−)‐Enantiomer mit einem Enantiomerenüberschuss von bis zu 92 % bildeten, lieferte die an Position 12 derivatisierte DNA bevorzugt das (+)‐Enantiomer mit bis zu 75 % ee. Diese entgegengesetzte Stereopräferenz wurde auch bei strukturell unterschiedlichen Michael‐Akzeptoren beobachtet. Unsere Arbeit zeigt einen neuen und einfachen Weg auf, die Stereoselektivität in der DNA‐basierten asymmetrischen Katalyse zu modulieren.
Synthetic Enterobacterial Common Antigen (ECA) for the Development of a Universal Immunotherapy for Drug‐Resistant Enterobacteriaceae
Authors: Liu Lin , Zha Jingying , DiGiandomenico Antonio , McAllister Douglas , Stover C. Kendall , Wang Qun , Boons Geert‐Jan 
Published: July 2015

AbstractAll Enterobacteriaceae express a polysaccharide known as enterobacterial common antigen (ECA), which is an attractive target for the development of universally acting immunotherapies. The first chemical synthesis of ECA‐derived oligosaccharides for the development of such therapies is described. A number of synthetic challenges had to be addressed, including the development of concise synthetic procedures for unusual monosaccharides, the selection of appropriate orthogonal protecting groups, the development of stereoselective glycosylation methods, appropriate timing for the introduction of the carboxylic acid groups on the ManpNAcA moieties, and the selection of appropriate conditions for the reduction of multiple azido moieties. The synthetic compounds were employed to uncover immunodominant moieties of ECA. Furthermore, a monoclonal antibody (mAb) was developed that binds to ECA and can selectively recognize a wide range of Enterobacteriaceae species.
Proteome‐Wide Profiling of Targets of Cysteine reactive Small Molecules by Using Ethynyl Benziodoxolone Reagents
Authors: Abegg Daniel , Frei Reto , Cerato Luca , Prasad Hari Durga , Wang Chao , Waser Jerome , Adibekian Alexander 
Published: July 2015

AbstractIn this study, we present a highly efficient method for proteomic profiling of cysteine residues in complex proteomes and in living cells. Our method is based on alkynylation of cysteines in complex proteomes using a “clickable” alkynyl benziodoxolone bearing an azide group. This reaction proceeds fast, under mild physiological conditions, and with a very high degree of chemoselectivity. The formed azide‐capped alkynyl–cysteine adducts are readily detectable by LC‐MS/MS, and can be further functionalized with TAMRA or biotin alkyne via CuAAC. We demonstrate the utility of alkynyl benziodoxolones for chemical proteomics applications by identifying the proteomic targets of curcumin, a diarylheptanoid natural product that was and still is part of multiple human clinical trials as anticancer agent. Our results demonstrate that curcumin covalently modifies several key players of cellular signaling and metabolism, most notably the enzyme casein kinase I gamma. We anticipate that this new method for cysteine profiling will find broad application in chemical proteomics and drug discovery.
Local Joint Inflammation and Histone Citrullination in a Murine Model of the Transition From Preclinical Autoimmunity to Inflammatory Arthritis
Authors: Sohn Dong Hyun , Rhodes Christopher , Onuma Kazuhiro , Zhao Xiaoyan , Sharpe Orr , Gazitt Tal , Shiao Rani , Fert‐Bober Justyna , Cheng Danye , Lahey Lauren J. , Wong Heidi H. , Van Eyk Jennifer , Robinson William H. , Sokolove Jeremy 
Published: July 2015

ObjectiveAnti–citrullinated protein antibodies (ACPAs) are characteristic of rheumatoid arthritis (RA). However, their presence years before the onset of clinical RA is perplexing. Although multiple putative citrullinated antigens have been identified, no studies have demonstrated the specific capacity of these antigens to initiate inflammatory arthritis. This study was undertaken to recapitulate the transition from preclinical to clinical RA and to demonstrate the capacity of local citrullination to facilitate this transition.MethodsWe performed proteomic analysis of activated human neutrophils to identify citrullinated proteins, including those targeted as part of the RA immune response. Using enzyme‐linked immunosorbent assay, we compared RA and osteoarthritis synovial fluid for levels of citrullinated histone H2B and its immune complex. Using macrophage activation assays, we assessed the effect of histone citrullination on immunostimulatory capacity and evaluated the stimulatory capacity of native and citrullinated H2B immune complexes. Finally, we assessed the potential for anti–citrullinated H2B antibodies to mediate arthritis in vivo.ResultsWe identified robust targeting of neutrophil‐derived citrullinated histones by the ACPA immune response. More than 90% of the RA patients had anti–citrullinated H2B antibodies. Histone citrullination increased innate immunostimulatory capacity, and immune complexes containing citrullinated histones activated macrophage cytokine production and propagated neutrophil activation. Finally, we demonstrated that immunization with H2B was arthritogenic, but only in the setting of underlying articular inflammation.ConclusionOur findings indicate that citrullinated histones, specifically citrullinated H2B, are an antigenic target of the ACPA immune response. Furthermore, local generation of citrullinated antigen during low‐grade articular inflammation provides a mechanistic model for the conversion from preclinical autoimmunity to inflammatory arthritis.
The use of the acute Pd/Pa drop after intracoronary nitroglycerin infusion to rule out significant FFR: CANICA (Can intracoronary nitroglycerin predict fractional flow reserve without adenosine?) multicenter study
Authors: Martin‐Reyes R. , de la Torre Hernandez J.M. , Franco‐Pelaez J. , Lopez‐Palop R. , Telleria Arrieta M. , Amat Santos I.J. , Carrillo Saez P. , Sanchez‐Recalde A. , Sanmartin Pena J.C. , Garcia Camarero T. , Brugaletta S. , Gimeno de Carlos F. , Pinero A. , Sorto Sanchez D.C. , Frutos A. , Lasa Larraya G. , Navarro F. , Farre J. 
Published: July 2015

ObjectiveFunctional assessment of coronary artery stenosis is performed by measuring the fractional flow reserve (FFR) under hyperemic conditions (Adenosine). However, the use of adenosine portends limitations.ObjectiveWe sought to investigate the relationship and correlation between FFR and the Pd/Pa value obtained just after the intracoronary infusion (acute drop) of nitroglycerin (Pd/Pa‐NTG) and if this parameter enhances diagnostic accuracy for FFR prediction compared to the resting baseline Pd/Pa.MethodsWe conducted a multicenter study including prospectively patients presenting intermediate coronary artery stenosis (30–70%) evaluated with pressure wire. Resting baseline Pd/Pa, Pd/Pa‐NTG and FFR were measured.Results283 patients (335 lesions) were included. Resting baseline Pd/Pa value was 0.72 to 1.0 (0.93 ± 0.04), Pd/Pa‐NTG was 0.60 to 1.0 (0.87 ± 0.07) and FFR 0.55 to 1.0 (0.83 ± 0.08). The ROC curves for resting baseline Pd/Pa and for Pd/Pa‐NTG, using a FFR ≤ 0.80 showed an AUC of 0.88 (95% CI: 0.84–0.92, P < 0.001) and 0.94 (95% CI: 0.92–0.96, P < 0.001) respectively. The optimal cutoff values of resting baseline Pd/Pa and Pd/Pa‐NTG for an FFR > 0.80, were >0.96 and >0.88, respectively. These values were present in a 29.8% (n = 100) and a 47.1% (n = 158), of the total lesions. Scatter plots showed a better correlation and agreement points with Pd/Pa‐NTG than resting baseline Pd/Pa. The cutoff value of Pd/Pa‐NTG > 0.88 showed an excellent NPV (96.2% for FFR > 0.8 and 100% for FFR > 0.75) and sensitivity (95% for FFR > 0.8 and 100% for FFR > 0.75) which were consistently high across all the subgroups analysis.ConclusionThe cutoff value of acute Pd/Pa‐NTG > 0.88 has a high NPV meaning adenosine‐FFR can be avoided in almost half of lesions. © 2015 Wiley Periodicals, Inc.
A Striking Case of Enantioinversion in Gold Catalysis and Its Probable Origins
Authors: Ilg Marina K. , Wolf Larry M. , Mantilli Luca , Farès Christophe , Thiel Walter , Fürstner Alois 
Published: July 2015

AbstractThe cyclization of the hydroxy‐allene 2 to the tetrahydrofuran 3 catalyzed by the gold‐phosphoramidite complex 1, after ionization with an appropriate silver salt AgX, is one of the most striking cases of enantioinversion known to date. The major reason why the sense of induction can be switched from (S) to (R) solely by changing either the solvent or the temperature or the nature of the counterion X is likely found in the bias of the organogold intermediates to undergo assisted proto‐deauration. Such assistance can be provided by a protic solvent, a reasonably coordinating counterion or even by a second substrate molecule itself; in this case, the reaction free energy profile gains a strong entropic component that can ultimately dictate the stereochemical course.