bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polarity-tunable magnetic tunnel junctions based on ferromagnetism at oxide heterointerfaces
Authors: Ngo Thach D.N. , Chang Jung-Won , Lee Kyujoon , Han Seungju , Lee Joon Sung , Kim Young Heon , Jung Myung-Hwa , Doh Yong-Joo , Choi Mahn-Soo , Song Jonghyun , Kim Jinhee 
Published: August 2015

AbstractComplex oxide systems have attracted considerable attention because of their fascinating properties, including the magnetic ordering at the conducting interface between two band insulators, such as LaAlO3 and SrTiO3. However, the manipulation of the spin degree of freedom at the LaAlO3/SrTiO3 heterointerface has remained elusive. Here, we have fabricated hybrid magnetic tunnel junctions consisting of Co and LaAlO3/SrTiO3 ferromagnets with the insertion of a Ti layer in between, which clearly exhibit magnetic switching and the tunnelling magnetoresistance effect below 10 K. The magnitude and sign of the tunnelling magnetoresistance are strongly dependent on the direction of the rotational magnetic field parallel to the LaAlO3/SrTiO3 plane, which is attributed to a strong Rashba-type spin-orbit coupling in the LaAlO3/SrTiO3 heterostructure. Our study provides a further support for the existence of the macroscopic ferromagnetism at LaAlO3/SrTiO3 heterointerfaces and opens a novel route to realize interfacial spintronics devices.
Loss of NDRG2 enhanced activation of the NF-κB pathway by PTEN and NIK phosphorylation for ATL and other cancer development
Authors: Ichikawa Tomonaga , Nakahata Shingo , Fujii Masahiro , Iha Hidekatsu , Morishita Kazuhiro 
Published: August 2015

AbstractThe activation of nuclear factor kappa B (NF-κB) signaling has a central role in the development of adult T-cell leukemia/lymphoma (ATL) and many other cancers. However, the activation mechanism of the NF-κB pathways remains poorly understood. Recently, we reported that N-myc downstream-regulated gene 2 (NDRG2) is a negative regulator of the phosphoinositide 3-kinase (PI3K)/AKT pathway by promoting the active dephosphorylated form of PTEN at its C-terminus via the recruitment of PP2A. Additionally, the down-regulation of NDRG2 expression promotes the inactive phosphorylated form of PTEN, which results in constitutively active PI3K/AKT signaling in various cancer cell types. Here, we investigated the involvement of NDRG2 in modulating NF-κB signaling. The forced expression of NDRG2 in ATL cells down-regulates not only the canonical pathway by inhibiting AKT signaling but also the non-canonical pathway by inducing NF-κB-inducing kinase (NIK) dephosphorylation via the recruitment of PP2A. Therefore, NDRG2 works as a PP2A recruiter to suppress not only PI3K/AKT signaling but also NF-κB signaling, which is particularly important in host defenses or immune responses to Human T-cell leukemia virus type 1 (HTLV-1) infection. Furthermore, the loss of NDRG2 expression might play an important role in the progression of tumor development after HTLV-1 infection.
The human papillomavirus (HPV) E7 protein antagonises an Imiquimod-induced inflammatory pathway in primary human keratinocytes
Authors: Richards Kathryn H. , Wasson Christopher W. , Watherston Oliver , Doble Rosella , Eric Blair G. , Wittmann Miriam , Macdonald Andrew 
Published: August 2015

AbstractHigh-risk human papillomaviruses (HPV) are the etiological pathogen of cervical and a number of ano-genital cancers. How HPVs overcome the significant barriers of the skin immune system has been the topic of intensive research. The E6 and E7 oncoproteins have emerged as key players in the deregulation of host innate immune pathways that are required for the recruitment of effector cells of the immune response. Here we demonstrate that E7 and to a lesser extend E6, strongly reduce NFκB activation in response to the inflammatory mediator imiquimod. Moreover, we establish that undifferentiated keratinocytes do not express the putative receptor for imiquimod, TLR7 and as such are stimulated by imiquimod through a novel pathway. Inhibition of imiquimod induced cytokine production required residues in the CR1 and CR3 regions of E7 and resulted in reduced nuclear translocation and acetylation of the p65 sub-unit of NFκB. The results provide further evidence for a TLR7-independent role of imiquimod in the epithelial immune response and reinforce the ability of the HPV oncoproteins to disrupt the innate immune response, which may have important consequences for establishment of a chronic infection.
Pharmacokinetics of a multicomponent herbal preparation in healthy Chinese and African volunteers
Authors: Alolga Raphael N. , Fan Yong , Zhang Gang , Li Jin , Zhao Yi-Jing , Lelu Kakila Jimmy , Chen Yan , Li Ping , Qi Lian-Wen 
Published: August 2015

AbstractK-601 is an herbal formulation for influenza consisting of Lonicera japonica, Isatis indigotica, Rheum palmatum, Phellodendron chinense and Scutellaria baicalensis. In this work, we characterized the chemical constituents in K-601, identified the absorbed compounds and determined their pharmacokinetics in 6 Chinese and African volunteers by liquid chromatography with time-of-flight mass spectrometry. Similarity evaluation for chromatographic fingerprint of nine different batches showed values above 0.983. Totally, 50 components were identified in K-601. Then, 15 major prototype compounds and 17 metabolites were identified in human plasma. Major metabolic pathways included glucuronidation, sulfation, methylation, demethylation and reduction. The pharmacokinetics of the most abundant prototype compounds, berberine, jatrorrhizine, palmatine and magnoflorine were determined. Significant pharmacokinetic differences were observed between the African and Chinese subjects. The AUCs of the African is about 4–10 fold higher than that of the Chinese for the three benzylisoquinoline alkaloids. Magnoflorine, an aporphine alkaloid, was absorbed better in the Chinese than in the African. The biotransformation of K-601 by human intestinal microflora was also investigated. The major reactions included hydroxylation, methylation, demethylation, acetylation and reduction. Glucuronidation and sulfation were not observed with fecal flora. These results may be important and useful in linking data from pharmacological assays and clinical effects.
The selective post-translational processing of transcription factor Nrf1 yields distinct isoforms that dictate its ability to differentially regulate gene expression
Authors: Zhang Yiguo , Li Shaojun , Xiang Yuancai , Qiu Lu , Zhao Huakan , Hayes John D. 
Published: August 2015

AbstractUpon translation, the N-terminal homology box 1 (NHB1) signal anchor sequence of Nrf1 integrates it within the endoplasmic reticulum (ER) whilst its transactivation domains [TADs, including acidic domain 1 (AD1), the flanking Asn/Ser/Thr-rich (NST) domain and AD2] are transiently translocated into the ER lumen, whereupon the NST domain is glycosylated to yield an inactive 120-kDa glycoprotein. Subsequently, these TADs are retrotranslocated into extra-luminal subcellular compartments, where Nrf1 is deglycosylated to yield an active 95-kDa isoform. Herein, we report that AD1 and AD2 are required for the stability of the 120-kDa Nrf1 glycoprotein, but not that of the non-glycosylated/de-glycosylated 95-kDa isoform. Degrons within AD1 do not promote proteolytic degradation of the 120-kDa Nrf1 glycoprotein. However, repositioning of AD2-adjoining degrons (i.e. DSGLS-containing SDS1 and PEST2 sequences) into the cyto/nucleoplasm enables selective topovectorial processing of Nrf1 by the proteasome and/or calpains to generate a cleaved active 85-kDa Nrf1 or a dominant-negative 36-kDa Nrf1γ. Production of Nrf1γ is abolished by removal of SDS1 or PEST2 degrons, whereas production of the cleaved 85-kDa Nrf1 is blocked by deletion of the ER luminal-anchoring NHB2 sequence (aa 81–106). Importantly, Nrf1 activity is positively and/or negatively regulated by distinct doses of proteasome and calpain inhibitors.
Copy number variations and gene polymorphisms of Complement components in ocular Behcet’s disease and Vogt-Koyanagi-Harada syndrome
Authors: Xu Dengfeng , Hou Shengping , Zhang Jun , Jiang Yanni , Kijlstra Aize , Yang Peizeng 
Published: August 2015

AbstractComplement is involved in many immune-mediated diseases. However, the association of its copy number variations (CNVs) and polymorphisms with Behcet’s disease (BD) and Vogt-Koyanagi-Harada syndrome (VKH) is unknown. We examined copy number and mRNA expression by real-time PCR. Cytokine production by stimulated peripheral blood mononuclear cells (PBMCs) in genotyped individuals was measured by ELISA. The frequencies of having more than two copies of C3 were significantly increased in BD and VKH, whereas CNV of C5 was only associated with BD. Increased frequencies of the GG genotype of C3 rs408290 and C5 rs2269067 were found in BD. No association was observed between C3 and C5 SNPs and VKH. mRNA expression in the high CNV group and GG cases of C3 and C5 was significantly higher compared to other genotypes. Increased interleukin-17 and IFN-γ was observed in the high CNV group and GG genotype cases of C3. Interleukin-17 but not IFN-γ was increased in the high CNV group and GG genotype cases of C5. No effect of C3 or C5 genetic variants was seen on the production of TNF-α, IL-10, IL-1β, MCP-1, IL-6 and IL-8. Our study thus provides further evidence for a role of complement in the pathogenesis of uveitis.
Triplex DNA: A new platform for polymerase chain reaction – based biosensor
Authors: Li Yubin , Miao Xiangmin , Ling Liansheng 
Published: August 2015

AbstractNon - specific PCR amplification and DNA contamination usually accompany with PCR process, to overcome these problems, here we establish a sensor for thrombin by sequence - specific recognition of the PCR product with molecular beacon through triplex formation. Probe A and probe B were designed for the sensor, upon addition of thrombin, two probes hybridized to each other and the probe B was extended in the presence of Klenow Fragment polymerase and dNTPs. The PCR amplification occurred with further addition of Taq DNA Polymerase and two primers, the PCR product was recognized by molecular beacon through triplex formation. The fluorescence intensity increased with the logarithm of the concentration of thrombin over the range from 1.0 × 10−12 M to 1.0 × 10−7 M, with a detection limit of 261 fM. Moreover, the effect of DNA contamination and non - specific amplification could be ignored completely in the proposed strategy.
Discovery of Some Piperine-Based Phenylsulfonylhydrazone Derivatives as Potent Botanically Narcotic Agents
Authors: Qu Huan , Lv Min , Yu Xiang , Lian Xihong , Xu Hui 
Published: August 2015

AbstractBy structural modification of piperine, some piperine-based phenylsulfonylhydrazone derivatives exhibited an unprecedented and potent narcotic activity against the oriental armyworm, Mythimna separata (Walker). The ND50 values of compounds 6c and 6e against the third-instar larvae of M. separata, which were more potent than those of wilfortrine and wilforgine, were 0.0074 μmol (after 3.5 h) and 0.0075 μmol (after 7 h) per larvae, respectively. By transmission electron microscope, it demonstrated that mitochondria were vacuolated and swollen in the ganglion cell of M. separata after treatment with 6c. More importantly, 6c selectively displayed the inhibition activity on acetylcholine esterase (AchE) of M. separata. This work paved the way for further studying the insecticidal mechanism of 6c as a new and promising botanical narcotic agent.
Long-term Surgical Outcomes of Epiretinal Membrane in Patients with Retinitis Pigmentosa
Authors: Ikeda Yasuhiro , Yoshida Noriko , Murakami Yusuke , Nakatake Shunji , Notomi Shoji , Hisatomi Toshio , Enaida Hiroshi , Ishibashi Tatsuro 
Published: August 2015

AbstractMacular complications such as an epiretinal membrane (ERM), a cystoid macular edema and a macular hole lead to unexpected central vision impairment especially for patients with retinitis pigmentosa (RP). To evaluate the long-term surgical outcomes of pars plana vitrectomy (PPV) for ERM in patients with RP, we retrospectively reviewed the charts of a consecutive series of 10 RP patients who underwent PPV for ERM at Kyushu University Hospital. Visual acuity (VA) testing, a fundus examination and an optical coherence tomography (OCT) analysis were conducted. The standard PPV using three sclerotomies was performed for ERM. PPV was performed in 12 eyes of 10 patients. One eye was excluded from the outcome assessment due to short period observation (18 months). There was no significantly deleterious change from the baseline to final VA between the operation eyes and the fellow eyes (P = 0.19). Moreover, morphological improvement was obtained in 9 of 11 eyes based on OCT. Our present data suggest that PPV may be tolerable in the management for ERM in RP patients over the long-term. Furthermore, the appearance of the ellipsoid zone was an important factor in the prediction of visual outcome and determination of surgical indication.
A radon-thoron isotope pair as a reliable earthquake precursor
Authors: Hwa Oh Yong , Kim Guebuem 
Published: August 2015

AbstractAbnormal increases in radon (222Rn, half-life = 3.82 days) activity have occasionally been observed in underground environments before major earthquakes. However, 222Rn alone could not be used to forecast earthquakes since it can also be increased due to diffusive inputs over its lifetime. Here, we show that a very short-lived isotope, thoron (220Rn, half-life = 55.6 s; mean life = 80 s), in a cave can record earthquake signals without interference from other environmental effects. We monitored 220Rn together with 222Rn in air of a limestone-cave in Korea for one year. Unusually large 220Rn peaks were observed only in February 2011, preceding the 2011 M9.0 Tohoku-Oki Earthquake, Japan, while large 222Rn peaks were observed in both February 2011 and the summer. Based on our analyses, we suggest that the anomalous peaks of 222Rn and 220Rn activities observed in February were precursory signals related to the Tohoku-Oki Earthquake. Thus, the 220Rn-222Rn combined isotope pair method can present new opportunities for earthquake forecasting if the technique is extensively employed in earthquake monitoring networks around the world.
Efficacy and safety of femtosecond laser-assisted cataract surgery versus conventional phacoemulsification for cataract: a meta-analysis of randomized controlled trials
Authors: Chen Xiaoyun , Xiao Wei , Ye Shaobi , Chen Weirong , Liu Yizhi 
Published: August 2015

AbstractThe aim of this study was to evaluate the efficacy and safety of femtosecond laser-assisted cataract surgery (FLACS) versus conventional phacoemulsification cataract surgery (CPCS) in the treatment of cataract. Randomized controlled trials (RCTs) were searched in PubMed, Embase and the Cochrane Central Register of Controlled Trials. Nine qualified studies with a total of 989 eyes were included. Compared with CPCS, FLACS significantly reduced mean phaco energy and effective phacoemulsification time (EPT) required in the surgery. Central corneal thickness (CCT) was significantly lower in FLACS at 1 day of follow-up, but CCT and corneal endothelial cells count was comparable at 1 week of follow-up or longer. FLACS achieved a better visual outcome at postoperative 1 week and 6 months, but the difference was not significant at postoperative 1–3 months. Regard to surgical complications, the incidences of intraoperative anterior capsule tear, postoperative macular edema and elevated intraocular pressure were similar. In conclusion, femtosecond laser pretreatment can reduce phaco energy and EPT, which may reduce the heat damage to ocular tissues by ultrasound. This novel technique might be beneficial for patients with dense cataract and/or low preoperative endothelial cell values. Well-designed RCTs with longer follow-up are still necessary to provide more reliable evidence.
Extensive shift in placental transcriptome profile in preeclampsia and placental origin of adverse pregnancy outcomes
Authors: Sõber Siim , Reiman Mario , Kikas Triin , Rull Kristiina , Inno Rain , Vaas Pille , Teesalu Pille , Marti Jesus M. Lopez , Mattila Pirkko , Laan Maris 
Published: August 2015

AbstractOne in five pregnant women suffer from gestational complications, prevalently driven by placental malfunction. Using RNASeq, we analyzed differential placental gene expression in cases of normal gestation, late-onset preeclampsia (LO-PE), gestational diabetes (GD) and pregnancies ending with the birth of small-for-gestational-age (SGA) or large-for-gestational-age (LGA) newborns (n = 8/group). In all groups, the highest expression was detected for small noncoding RNAs and genes specifically implicated in placental function and hormonal regulation. The transcriptome of LO-PE placentas was clearly distinct, showing statistically significant (after FDR) expressional disturbances for hundreds of genes. Taqman RT-qPCR validation of 45 genes in an extended sample (n = 24/group) provided concordant results. A limited number of transcription factors includingLRF, SP1andAP2were identified as possible drivers of these changes. Notable differences were detected in differential expression signatures of LO-PE subtypes defined by the presence or absence of intrauterine growth restriction (IUGR). LO-PE with IUGR showed higher correlation with SGA and LO-PE without IUGR with LGA placentas. Whereas changes in placental transcriptome in SGA, LGA and GD cases were less prominent, the overall profiles of expressional disturbances overlapped among pregnancy complications providing support to shared placental responses. The dataset represent a rich catalogue for potential biomarkers and therapeutic targets.
Lys39-Lysophosphatidate Carbonyl Oxygen Interaction Locks LPA1 N-terminal Cap to the Orthosteric Site and partners Arg124 During Receptor Activation
Authors: Omotuyi Olaposi I. , Nagai Jun , Ueda Hiroshi 
Published: August 2015

AbstractLysophosphatidic acid (LPA) receptor 1 (LPA1) is a member of the G protein-coupled receptors mediating the biological response to LPA species. Lack of detailed mechanism underlying LPA/LPA1interaction has hampered the development of specific antagonists. Here, novel N-terminal Lys39 has been identified as a key residue during LPA-type agonist binding and LPA1activation. Analysis of the molecular dynamics (MD) trajectories showed that LPA-type agonist but not VPC-32183 (antagonist) evolved structures with classical GPCR activation signatures such as reduced cytoplasmic transmembrane (TM) 3/TM6 dynamic network, ruptured ionic lock and formation of a continuous and highly ordered internal water pathway was also observed. In activated state, LPA-type agonists interact with Arg124 (R3.28), Gln125 (Q3.29), Lys294 (K7.36) and a novel N-terminal Lys39. Site-directed mutagenesis showed complete loss of intracellular calcium mobilization in B103 cells expressing R3.28A and Lys39Ala when treated with LPA-type agonists. Structurally, LPA-type agonist via Carbonyl-oxygen/Lys39 interaction facilitated the formation of a hypothetical N-terminal cap tightly packed over LPA1heptahelical bundle. This packing may represent a key mechanism to distinguish an apo-receptor from bound LPA1.
The binding of cupric ions to bovine pancreatic ribonuclease studied with diligand metal-ion buffers
Authors: Saundry R. H. , Stein W D 
Published: August 2015

A procedure has been developed for the use of metal-ion buffers that depends on the formation of 2:1 complexes between suitable chelators and metal ions. β-Alanine has been used as the chelator for Cu2+ ions in a study of Cu2+ binding by bovine pancreatic ribonuclease by the equilibrium-dialysis technique at pH7·0, 6·1 and 5·2. The results indicated the presence of two avid binding sites, the more avid group being implicated in the inhibition of enzyme activity by Cu2+ ions.
The binding constants of the more avid site were 2·97×107, 7·97×105 and 1·25×104 at pH7·0, 6·1 and 5·2 respectively, and the binding constants of the less avid site were 5·27×106 and 1·71×105 at pH7·0 and 6·1 respectively.
The data show that the Cu2+ is chelated to the protein through at least two ligand groups on the ribonuclease molecule.
The solution structures of native and patient monomeric human IgA1 reveal asymmetric extended structures: implications for function and IgAN disease
Authors: Hui Gar Kay , Wright David W. , Vennard Owen L. , Rayner Lucy E. , Pang Melisa , Yeo See Cheng , Gor Jayesh , Molyneux Karen , Barratt Jonathan , Perkins Stephen J. 
Published: August 2015

Native IgA1, for which no crystal structure is known, contains an O-galactosylated 23-residue hinge region that joins its Fab and Fc regions. IgA nephropathy (IgAN) is a leading cause of chronic kidney disease in developed countries. Because IgA1 in IgAN often has a poorly O-galactosylated hinge region, the solution structures of monomeric IgA1 from a healthy subject and three IgAN patients with four different O-galactosylation levels were studied. Analytical ultracentrifugation showed that all four IgA1 samples were monomeric with similar sedimentation coefficients, s020,w. X-ray scattering showed that the radius of gyration (Rg) slightly increased with IgA1 concentration, indicating self-association, although their distance distribution curves, P(r), were unchanged with concentration. Neutron scattering indicated similar Rg values and P(r) curves, although IgA1 showed a propensity to aggregate in heavy water buffer. A new atomistic modelling procedure based on comparisons with 177000 conformationally-randomized IgA1 structures with the individual experimental scattering curves revealed similar extended Y-shaped solution structures for all four differentially-glycosylated IgA1 molecules. The final models indicated that the N-glycans at Asn263 were folded back against the Fc surface, the C-terminal tailpiece conformations were undefined and hinge O-galactosylation had little effect on the solution structure. The solution structures for full-length IgA1 showed extended hinges and the Fab and Fc regions were positioned asymmetrically to provide ample space for the functionally-important binding of two FcαR receptors to its Fc region. Whereas no link between O-galactosylation and the IgA1 solution structure was detected, an increase in IgA1 aggregation with reduced O-galactosylation may relate to IgAN.
Konzeption und Erfassung der gesundheitsbezogenen Transitionskompetenz von Jugendlichen mit chronischen Erkrankungen – Entwicklung und Prüfung eines Selbstbeurteilungsinstrumentes
Authors: Herrmann-Garitz C. , Muehlan H. , Bomba F. , Thyen U. , Schmidt S. 
Published: August 2015

Zusammenfassung
Hintergrund: Es hat sich gezeigt, dass gesundheitsbezogene Versorgungs- und Selbstmanagementkompetenzen bei Jugendlichen erforderlich sind, um den Übergang in die Erwachsenenversorgung zu ermöglichen. Ziel ist, ein Instrument zur Erfassung der gesundheitsbezogenen Transitionskompetenz (TK) zu entwickeln und psychometrisch zu testen.
Methodik: Die Instrumentenentwicklung wurde in mehreren Schritten mit konzeptuellen und psychometrischen Analysen durchgeführt. Basierend auf qualitativen Analysen von Fokusgruppen mit chronisch kranken Jugendlichen und Experteninterviews wurde ein Itempool zur Erfassung von TK entwickelt. Das Instrument wurde in einer Pilotstudie mit N=323 Jugendlichen mit chronischen Erkrankungen getestet und finalisiert.
Ergebnisse: Es konnten die drei Subskalen „Arbeitswelt“ (3 Items), „krankheitsbezogenes Wissen“ (3 Items) und „Versorgungskompetenz“ (4 Items) mit guten psychometrischen Werten identifiziert werden, die sich auch zu einer Globalskala zusammenfassen lassen.
Schlussfolgerungen: Die Skalen bieten eine ökonomische Möglichkeit, die notwendigen Kompetenzen im Vorfeld und im Verlauf der Transition standardisiert zu erfassen. Dies ermöglicht auch die Erfassung der Wirksamkeit von transitionsbezogenen Maßnahmen (z. B. Schulungen).