bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three Aromatic Residues are Required for Electron Transfer during Iron Mineralization in Bacterioferritin
Authors: Bradley Justin M. , Svistunenko Dimitri A. , Lawson Tamara L. , Hemmings Andrew M. , Moore Geoffrey R. , Le Brun Nick E. 
Published: October 2015

AbstractFerritins are iron storage proteins that overcome the problems of toxicity and poor bioavailability of iron by catalyzing iron oxidation and mineralization through the activity of a diiron ferroxidase site. Unlike in other ferritins, the oxidized di‐Fe3+ site of Escherichia coli bacterioferritin (EcBFR) is stable and therefore does not function as a conduit for the transfer of Fe3+ into the storage cavity, but instead acts as a true catalytic cofactor that cycles its oxidation state while driving Fe2+ oxidation in the cavity. Herein, we demonstrate that EcBFR mineralization depends on three aromatic residues near the diiron site, Tyr25, Tyr58, and Trp133, and that a transient radical is formed on Tyr25. The data indicate that the aromatic residues, together with a previously identified inner surface iron site, promote mineralization by ensuring the simultaneous delivery of two electrons, derived from Fe2+ oxidation in the BFR cavity, to the di‐ferric catalytic site for safe reduction of O2.
Development of a Sensitive Bioluminogenic Probe for Imaging Highly Reactive Oxygen Species in Living Rats
Authors: Kojima Ryosuke , Takakura Hideo , Kamiya Mako , Kobayashi Eiji , Komatsu Toru , Ueno Tasuku , Terai Takuya , Hanaoka Kenjiro , Nagano Tetsuo , Urano Yasuteru 
Published: October 2015

AbstractA sensitive bioluminogenic probe for highly reactive oxygen species (hROS), SO3H‐APL, was developed based on the concept of dual control of bioluminescence emission by means of bioluminescent enzyme‐induced electron transfer (BioLeT) and modulation of cell‐membrane permeability. This probe enables non‐invasive visualization of physiologically relevant amounts of hROS generated deep inside the body of living rats for the first time. It is expected to serve as a practical analytical tool for investigating a wide range of biological functions of hROS in vivo. The design concept should be applicable to other in vivo bioluminogenic probes.
FeCl3‐Mediated Oxidative Spirocyclization of Difluorenylidene Diarylethanes Leading to Dispiro[fluorene‐9,5′‐indeno[2,1‐a]indene‐10′,9′′‐fluorene]s
Authors: Zhao Jian , Xu Zhanqiang , Oniwa Kazuaki , Asao Naoki , Yamamoto Yoshinori , Jin Tienan 
Published: October 2015

AbstractA novel FeCl3‐mediated oxidative spirocyclization for construction of a new class of di‐spirolinked π‐conjugated molecules, dispiro[fluorene‐9,5′‐indeno[2,1‐a]indene‐10′,9′′‐fluorene]s (DSFIIFs), has been reported. The combination of FeCl3 with FeO(OH) triggered an unprecedented double one‐electron oxidation of difluorenylidene diarylethanes to afford the corresponding dispirocycles in high yields. The highest fluorescence quantum yield was up to 0.94 in solution. This protocol is also applicable to the synthesis of the non‐spirolinked dihydroindenoindenes.
Überoxidation als Schlüsselschritt im Mechanismus der MoCl5‐ vermittelten dehydrierenden Arenkupplung
Authors: Schubert Moritz , Franzmann Peter , Wünsche von Leupoldt Anica , Koszinowski Konrad , Heinze Katja , Waldvogel Siegfried R. 
Published: October 2015

AbstractMolybdänpentachlorid ist ein effizientes Reagens für die dehydrierende Kupplung von Arenen. Wegen der hohen Reaktionsgeschwindigkeit bei der Umsetzung mit MoCl5 wird eine Reihe von labilen Molekülbereichen in dieser Transformation toleriert. Der mechanistische Verlauf der Reaktion wurde bislang sehr kontrovers diskutiert, auch wenn vor kurzem Hinweise gefunden wurden, dass ein Ein‐Elektronen‐Transfer die Umsetzung einleitet. Hier kann aus einer kombinierten Studie in Form von systematischen Syntheseversuchen, elektrochemischen Messungen, EPR‐Spektroskopie, DFT‐Rechnungen und Massenspektrometrie eine hochkonsistente mechanistische Vorstellung abgeleitet werden. MoCl5 fungiert als Ein‐Elektronen‐Oxidationsmittel in der Abwesenheit von TiCl4 und als Zwei‐Elektronen‐Oxidationsmittel in Gegenwart von TiCl4. In beiden Fällen führt es zu einem überoxidierten Intermediat, das die Zielstruktur vor Nebenreaktionen schützt. Im Zuge der wässrigen Aufarbeitung wirkt der Reagensabfall (MoIII/IV‐Verbindungen) als Reduktionsmittel und liefert das gewünschte organische C‐C‐Kupplungsprodukt.
Silver‐Catalyzed Amidiniumation of Alkynes: Isolation of a Silver Intermediate, Synthesis of Enamine Amido Carbene Precursors, and an Unprecedented Umpolung of Propiolamide
Authors: Lv Shichang , Wang Jiwei , Zhang Caiyun , Xu Sheng , Shi Min , Zhang Jun 
Published: October 2015

AbstractA silver‐catalyzed amidiniumation of N‐propiolic formamidines for the synthesis of novel enamine amido carbene precursors is reported. Isolation of a first silver intermediate in silver‐catalyzed amidiniumation of alkynes and other organogold intermediates supports our proposed mechanisms. Several control experiments reveal the unexpected effects of both HOTf and substrate substituents on the choice of either a π or σ,π silver activation mode and the cyclization fashion. Bis(hydroxyimidazol)ium salts were obtained through an unprecedented umpolung of propiolamides. The byproduct Ag2O as either an oxidant or silver source promotes the syntheses of N‐heterocyclic carbene (NHC) precursors or Ag/NHC complexes.
Direct Modulation of Small GTPase Activity and Function
Authors: Cromm Philipp M. , Spiegel Jochen , Grossmann Tom N. , Waldmann Herbert 
Published: October 2015

AbstractSmall GTPases are a family of GDP‐/GTP‐binding proteins that serve as biomolecular switches inside cells to control a variety of essential cellular processes. Aberrant function and regulation of small GTPases is associated with a variety of human diseases, thus rendering these proteins highly interesting targets in drug discovery. However, this class of proteins has been considered “undruggable”, as intensive decade‐long efforts did not yield clinically relevant direct modulators of small GTPases. Recently, the targeting of small GTPases has gained fresh impetus through the discovery of novel transient cavities on the protein surfaces and the application of new targeting strategies. Besides Ras proteins, other small GTPases have attracted increased attention since improved biological insight in combination with novel targeting strategies identified them as promising targets in drug discovery. This Review gives an overview of relevant aspects of the superfamily of small GTPases and summarizes recent progress and perspectives for the direct modulation of these challenging targets.
Nucleobase‐Modified PNA Suppresses Translation by Forming a Triple Helix with a Hairpin Structure in mRNA In Vitro and in Cells
Authors: Endoh Tamaki , Hnedzko Dziyana , Rozners Eriks , Sugimoto Naoki 
Published: October 2015

AbstractCompounds that bind specifically to double‐stranded regions of RNA have potential as regulators of structure‐based RNA function; however, sequence‐selective recognition of double‐stranded RNA is challenging. The modification of peptide nucleic acid (PNA) with unnatural nucleobases enables the formation of PNA–RNA triplexes. Herein, we demonstrate that a 9‐mer PNA forms a sequence‐specific PNA–RNA triplex with a dissociation constant of less than 1 nm at physiological pH. The triplex formed within the 5′ untranslated region of an mRNA reduces the protein expression levels both in vitro and in cells. A single triplet mismatch destabilizes the complex, and in this case, no translation suppression is observed. The triplex‐forming PNAs are unique and potent compounds that hold promise as inhibitors of cellular functions that are controlled by double‐stranded RNAs, such as RNA interference, RNA editing, and RNA localization mediated by protein–RNA interactions.
Untangling a Repetitive Amyloid Sequence: Correlating Biofilm‐Derived and Segmentally Labeled Curli Fimbriae by Solid‐State NMR Spectroscopy
Authors: Schubeis Tobias , Yuan Puwei , Ahmed Mumdooh , Nagaraj Madhu , van Rossum Barth‐Jan , Ritter Christiane 
Published: October 2015

AbstractCurli are functional bacterial amyloids produced by an intricate biogenesis machinery. Insights into their folding and regulation can advance our understanding of amyloidogenesis. However, gaining detailed structural information of amyloids, and their tendency for structural polymorphisms, remains challenging. Herein we compare high‐quality solid‐state NMR spectra from biofilm‐derived and recombinantly produced curli and provide evidence that they adopt a similar, well‐defined β‐solenoid arrangement. Curli subunits consist of five sequence repeats, resulting in severe spectral overlap. Using segmental isotope labeling, we obtained the unambiguous sequence‐specific resonance assignments and secondary structure of one repeat, and demonstrate that all repeats are most likely structurally equivalent.
Cobalt‐Catalyzed Alkylation of Aromatic Amines by Alcohols
Authors: Rösler Sina , Ertl Michael , Irrgang Torsten , Kempe Rhett 
Published: October 2015

AbstractThe implementation of inexpensive, Earth‐abundant metals in typical noble‐metal‐mediated chemistry is a major goal in homogeneous catalysis. A sustainable or green reaction that has received a lot of attention in recent years and is preferentially catalyzed by Ir or Ru complexes is the alkylation of amines by alcohols. It is based on the borrowing hydrogen or hydrogen autotransfer concept. Herein, we report on the Co‐catalyzed alkylation of aromatic amines by alcohols. The reaction proceeds under mild conditions, and selectively generates monoalkylated amines. The observed selectivity allows the synthesis of unsymmetrically substituted diamines. A novel Co complex stabilized by a PN5P ligand catalyzes the reactions most efficiently.
An Enantioselective Total Synthesis of (−)‐Isoschizogamine
Authors: Xu Zhengren , Bao Xu , Wang Qian , Zhu Jieping 
Published: October 2015

AbstractA concise enantioselective total synthesis of (−)‐isoschizogamine, a complex bridged polycyclic monoterpene indole alkaloid, was accomplished. N‐Alkylation of an enantio‐enriched imine with an alkyl iodide afforded an iminium salt, which, upon heating by microwave irradiation in the presence of pivalic acid, was converted into the hexacyclic structure of natural product by a complex but ordered domino sequence. The one‐pot process leading to the formation of one CC bond and three CN bonds created three rings and three contiguous stereogenic centers with complete control of both the relative and absolute stereochemistry.
Regeneration of anion‐exchange resins with Mg/Al double‐metal hydroxides
Authors: Wang Ying , Li Yan‐Sheng , Li Zhun 
Published: October 2015

ABSTRACTAnion‐exchange resins (AERs) were regenerated with Mg/Al double‐metal hydroxides as the regenerant. Electrical conductivity breakthrough curves were adopted to estimate the relatively rapid regenerative effect of the AERs. The results show that the optimal regenerative effect of AER was obtained when the Mg/Al molar ratio was 3 and the dosages of Mg and Al hydroxides were 0.045 and 0.015 mol, respectively. The highest effluent water yield was obtained at an AER/cation‐exchange resin volume ratio of 2:1. Characterization through scanning electron microscopy, X‐ray diffraction, and thermogravimetry–differential thermal analysis showed that the regenerant was transformed and exhibited the distinguishing features of Mg/Al layered double hydrotalcites. Cycle experimentation showed that all calcined products effectively regenerated the fouled resins, and the regenerative mechanism was then established. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42928.
Long‐Lasting Activation of the Transcription Factor CREB in Sensory Neurons by Interleukin‐1β During Antigen‐Induced Arthritis in Rats: A Mechanism of Persistent Arthritis Pain?
Authors: Segond von Banchet Gisela , König Christian , Patzer Jessica , Eitner Annett , Leuchtweis Johannes , Ebbinghaus Matthias , Boettger Michael K. , Schaible Hans‐Georg 
Published: October 2015

ObjectiveIn spite of successful treatment of immune‐mediated arthritis, many patients still experience pain. We undertook this study to investigate whether antigen‐induced arthritis (AIA) in rats triggers neuronal changes in sensory neurons that outlast the inflammatory process.MethodsWe induced unilateral AIA in the knee joint and assessed in sensory neurons the expression of CREB, a transcription factor that regulates genes involved in neuronal plasticity. We tested whether neutralization of the effects of tumor necrosis factor (TNF) by etanercept or infliximab or neutralization of the effects of interleukin‐1β (IL‐1β) by anakinra influences the up‐regulation of phospho‐CREB, and we studied the up‐regulation of phospho‐CREB by IL‐1β and TNF in cultured dorsal root ganglion (DRG) neurons.ResultsUnilateral AIA caused bilateral up‐regulation of phospho‐CREB in lumbar DRG neurons. While inflammation and pain subsided within 21 days, the up‐regulation of phospho‐CREB still persisted on day 42. At this time point mechanical hyperalgesia at the knee reappeared in the absence of swelling. TNF neutralization during AIA significantly reduced pain‐related behavior but did not prevent phospho‐CREB up‐regulation. In contrast, anakinra, which only reduced thermal hyperalgesia, prevented phospho‐CREB up‐regulation, suggesting a role of IL‐1β in this process. In cultured DRG neurons the application of IL‐1β significantly enhanced phospho‐CREB.ConclusionImmune‐mediated arthritis causes neuroplastic changes in sensory neurons that outlast the inflammatory phase. Such changes may facilitate the persistence or recurrence of pain after remission of arthritis. IL‐1β is an important trigger in this process, although its neutralization barely reduced mechanical hyperalgesia during inflammation.
ApoE Receptor 2 Mediation of Trophoblast Dysfunction and Pregnancy Complications Induced by Antiphospholipid Antibodies in Mice
Authors: Ulrich Victoria , Gelber Shari E. , Vukelic Milena , Sacharidou Anastasia , Herz Joachim , Urbanus Rolf T. , de Groot Philip G. , Natale David R. , Harihara Anirudha , Redecha Patricia , Abrahams Vikki M. , Shaul Philip W. , Salmon Jane E. , Mineo Chieko 
Published: October 2015

ObjectivePregnancies in women with the antiphospholipid syndrome (APS) are frequently complicated by fetal loss and intrauterine growth restriction (IUGR). How circulating antiphospholipid antibodies (aPL) cause pregnancy complications in APS is poorly understood. We sought to determine whether the low‐density lipoprotein receptor family member apolipoprotein E receptor 2 (ApoER2) mediates trophoblast dysfunction and pregnancy complications induced by aPL.MethodsPlacental and trophoblast ApoER2 expression was evaluated by immunohistochemistry and immunoblotting. Normal human IgG and aPL were purified from healthy individuals and APS patients, respectively. The role of ApoER2 in aPL‐induced changes in trophoblast proliferation and migration and in kinase activation was assessed using RNA interference in HTR‐8/SVneo cells. The participation of ApoER2 in aPL‐induced pregnancy loss and IUGR was evaluated in pregnant ApoER2+/+ and ApoER2–/– mice injected with aPL or normal human IgG.ResultsWe found that ApoER2 is abundant in human and mouse placental trophoblasts and in multiple trophoblast‐derived cell lines, including HTR‐8/SVneo cells. ApoER2 and its interaction with the cell surface protein β2‐glycoprotein I were required for aPL‐induced inhibition of cultured trophoblast proliferation and migration. In parallel, aPL antagonism of Akt kinase activation by epidermal growth factor in trophoblasts was mediated by ApoER2. Furthermore, in a murine passive‐transfer model of pregnancy complications of APS, ApoER2–/– mice were protected from both aPL‐induced fetal loss and aPL‐induced IUGR.ConclusionApoER2 plays a major role in the attenuation of trophoblast function by aPL, and the receptor mediates aPL‐induced pregnancy complications in vivo in mice. ApoER2‐directed interventions can now potentially be developed to combat the pregnancy complications associated with APS.
Autoantibodies From Single Circulating Plasmablasts React With Citrullinated Antigens and Porphyromonas gingivalis in Rheumatoid Arthritis
Authors: Li Song , Yu Yangsheng , Yue Yinshi , Liao Hongyan , Xie Wanqin , Thai Jessica , Mikuls Ted R. , Thiele Geoffrey M. , Duryee Michael J. , Sayles Harlan , Payne Jeffrey B. , Klassen Lynell W. , O'Dell James R. , Zhang Zhixin , Su Kaihong 
Published: October 2015

ObjectiveAnti–citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA). However, the molecular basis for ACPA production is still unclear. The purpose of this study was to determine if circulating plasmablasts from RA patients produce ACPAs and whether Porphyromonas gingivalis facilitates the generation of ACPAs.MethodsUsing a single‐cell antibody cloning approach, we generated 217 and 110 monoclonal recombinant antibodies from circulating plasmablasts from 7 RA patients and 4 healthy controls, respectively. Antibody reactivity with citrullinated antigens was tested by a second‐generation anti–cyclic citrullinated peptide (anti‐CCP) kit and by enzyme‐linked immunosorbent assays (ELISAs) against citrullinated human antigens. Antibody reactivity with P gingivalis was tested by ELISAs against outer membrane antigens (OMAs) and citrullinated enolase from P gingivalis.ResultsApproximately 19.5% of plasmablast‐derived antibodies from anti‐CCP–positive RA patients, but none from 1 anti‐CCP–negative RA patient or the healthy controls, specifically recognized citrullinated antigens. The immunoglobulin genes encoding these ACPAs were highly mutated, with increased ratios of replacement mutations to silent mutations, suggesting the involvement of active antigen selection in ACPA generation. Interestingly, 63% of the ACPAs cross‐reacted with OMAs and/or citrullinated enolase from P gingivalis. The reactivity of ACPAs against citrullinated proteins from P gingivalis was confirmed by immunoblotting and mass spectrometry. Furthermore, some germline‐reverted ACPAs retained their reactivity with P gingivalis antigens but completely lost their reactivity with citrullinated human antigens.ConclusionThese results suggest that circulating plasmablasts in RA patients produce ACPAs and that this process may be facilitated by anti–P gingivalis immune responses.
Sexual Dimorphism in the Th17 Signature of Ankylosing Spondylitis
Authors: Gracey Eric , Yao YuChen , Green Blerta , Qaiyum Zoya , Baglaenko Yuriy , Lin Aifeng , Anton Ammepa , Ayearst Renise , Yip Paul , Inman Robert D. 
Published: October 2015

ObjectiveTo identify an immunologic basis for the male sex bias in ankylosing spondylitis (AS).MethodsCohorts of male and female patients with AS and age‐ and sex‐matched healthy control subjects were selected, and the levels of serum cytokines (interferon‐γ [IFNγ], tumor necrosis factor α, interleukin‐17A [IL‐17A], and IL‐6) were examined by enzyme‐linked immunosorbent assay, the frequencies of Th1 and Th17 cells were assessed by flow cytometry, and whole blood gene expression was analyzed using both microarray and NanoString approaches.ResultsThe frequency of IL‐17A and Th17 cells, both of which are key factors in the inflammatory Th17 axis, was elevated in male patients with AS but not in female patients with AS. In contrast, AS‐associated alterations in the Th1 axis, such as the frequency of IFNγ and Th1 cells in serum, were independent of a patient's sex. Results of microarray analysis supported an altered Th17 axis in male patients, with a specific increase in IL17RA. In addition, male and female patients with AS displayed shared gene expression patterns, while male patients with AS had additional alterations in gene expression that were not seen in female patients with AS. The differential sex‐related immune profiles were independent of HLA–B27 status, clinical disease activity (as measured by the Bath Ankylosing Spondylitis Disease Activity Index), or treatment (with nonsteroidal antiinflammatory drugs or biologic agents), implicating intrinsic sexual dimorphism in AS.ConclusionThe results of this study demonstrate distinct sexual dimorphism in the activation status of the immune system in patients with AS, particularly in the Th17 axis. This dimorphism could underlie sex‐related differences in the clinical features of AS and could provide a rationale for sex‐specific treatment of AS.
The Prevalence of Symptomatic Knee Osteoarthritis in China: Results From the China Health and Retirement Longitudinal Study
Authors: Tang Xu , Wang Shengfeng , Zhan Siyan , Niu Jingbo , Tao Ke , Zhang Yuqing , Lin Jianhao 
Published: October 2015

ObjectiveTo estimate the prevalence of symptomatic knee osteoarthritis (OA) in China.MethodsUsing data collected from the China Health and Retirement Longitudinal Study, a population‐based longitudinal survey conducted between 2011 and 2012, we estimated the prevalence of symptomatic knee OA according to sex, age, rural/urban area, socioeconomic status, and geographic region.ResultsAmong 17,128 individuals (8,367 men and 8,761 women; mean age 59.8 years) included in the analysis, 8.1% had symptomatic knee OA. The prevalence of symptomatic knee OA was higher in women (10.3%) compared with men (5.7%) (adjusted odds ratio [OR] 1.88 [95% confidence interval 1.64–2.17]). The prevalence of symptomatic knee OA increased with age (P for trend <0.01). Symptomatic knee OA was more common in rural areas than in urban areas (OR 1.84 [95% confidence interval 1.46–2.31]). The prevalence of symptomatic knee OA was lower among individuals who had received more years of education and who lived in more developed areas (P for trend <0.01). The North and East regions of China had the lowest prevalence of symptomatic knee OA (5.4% and 5.5%, respectively), followed by the North‐East (7.0%), South‐Central (7.8%), and North‐West (10.8%) regions. The prevalence was highest (13.7%) in subjects living in the South‐West region.ConclusionSymptomatic knee OA in China was prevalent, and the prevalence varied according to sociodemographic, economic, and geographic factors. Epidemiologic studies identifying risk factors that contribute to variation in the prevalence of symptomatic knee OA in China are warranted.