bluuebunny/crossref_metadata_2025_split huggingface dataset:
The RNA-binding protein Sam68 regulates expression and transcription function of the androgen receptor splice variant AR-V7
Authors: Stockley Jacqueline , Markert Elke , Zhou Yan , Robson Craig N. , Elliott David J. , Lindberg Johan , Leung Hing Y. , Rajan Prabhakar 
Published: August 2015

AbstractCastration-resistant (CR) prostate cancer (PCa) partly arises due to persistence of androgen receptor (AR) transcriptional activity in the absence of cognate ligand. An emerging mechanism underlying the CRPCa phenotype and predicting response to therapy is the expression of the constitutively-active AR-V7 splice variant generated by AR cryptic exon 3b inclusion. Here, we explore the role of the RNA-binding protein (RBP) Sam68 (encoded by KHDRBS1), which is over-expressed in clinical PCa, on AR-V7 expression and transcription function. Using a minigene reporter, we show that Sam68 controls expression of exon 3b resulting in an increase in endogenous AR-V7 mRNA and protein expression in RNA-binding-dependent manner. We identify a novel protein-protein interaction between Sam68 and AR-V7 mediated by a common domain shared with full-length AR and observe these proteins in the cell nucleoplasm. Using a luciferase reporter, we demonstrate that Sam68 co-activates ligand-independent AR-V7 transcriptional activity in an RNA-binding-independent manner and controls expression of the endogenous AR-V7-specific gene target UBE2C. Our data suggest that Sam68 has separable effects on the regulation of AR-V7 expression and transcriptional activity, through its RNA-binding capacity. Sam68 and other RBPs may control expression of AR-V7 and other splice variants as well as their downstream functions in CRPCa.
Differences in Clinicopathology of Early Gastric Carcinoma between Proximal and Distal Location in 438 Chinese Patients
Authors: Huang Qin , Fang Cheng , Shi Jiong , Sun Qi , Wu Hongyan , Gold Jason S. , Weber H. Christian , Guan Wenyan , Zhang Yifen , Yu Chenggong , Zou Xiaoping , Mashimo Hiroshi 
Published: August 2015

AbstractEarly gastric carcinoma (EGC) in Chinese patients remains poorly understood and endoscopic therapy has not been well established. Here, we compared endoscopic and clinicopathologic features between early proximal gastric carcinoma (PGC, n = 131) and distal gastric carcinoma (DGC, n = 307) in consecutive 438 EGCs diagnosed with the WHO criteria. By endoscopy, PGCs showed protruding and elevated patterns in 61.9%, while depressed and excavated patterns in 33.6%, which were significantly different from those (32.6% and 64.5%) in DGCs. PGCs were significantly smaller (1.9 cm in average, versus 2.2 cm in DGCs), invaded deeper (22.9% into SM2, versus 13% in DGCs), but had fewer (2.9%, versus 16.7% in DGCs) lymph node metastases. Papillary adenocarcinoma was significantly more frequent (32.1%, versus 12.1% in DGCs), as were mucinous and neuroendocrine carcinomas, carcinoma with lymphoid stroma (6.9%, versus 1.6% in DGCs); but poorly cohesive carcinoma was significantly less frequent (5.3%, versus 35.8% in DGCs). The overall 5-year survival rate was 92.9% in EGCs and PGC patients showed shorter (42.4 months, versus 48.3 in DGCs) survival. Papillary and micropapillary adenocarcinomas and nodal metastasis were independent risk factors for worse survival in EGCs. EGCs in Chinese were heterogeneous with significant differences in endoscopy and clinicopathology between PGC and DGC.
Structural analysis of fungus-derived FAD glucose dehydrogenase
Authors: Yoshida Hiromi , Sakai Genki , Mori Kazushige , Kojima Katsuhiro , Kamitori Shigehiro , Sode Koji 
Published: August 2015

AbstractWe report the first three-dimensional structure of fungus-derived glucose dehydrogenase using flavin adenine dinucleotide (FAD) as the cofactor. This is currently the most advanced and popular enzyme used in glucose sensor strips manufactured for glycemic control by diabetic patients. We prepared recombinant nonglycosylated FAD-dependent glucose dehydrogenase (FADGDH) derived from Aspergillus flavus (AfGDH) and obtained the X-ray structures of the binary complex of enzyme and reduced FAD at a resolution of 1.78 Å and the ternary complex with reduced FAD and D-glucono-1,5-lactone (LGC) at a resolution of 1.57 Å. The overall structure is similar to that of fungal glucose oxidases (GOxs) reported till date. The ternary complex with reduced FAD and LGC revealed the residues recognizing the substrate. His505 and His548 were subjected for site-directed mutagenesis studies and these two residues were revealed to form the catalytic pair, as those conserved in GOxs. The absence of residues that recognize the sixth hydroxyl group of the glucose of AfGDH and the presence of significant cavity around the active site may account for this enzyme activity toward xylose. The structural information will contribute to the further engineering of FADGDH for use in more reliable and economical biosensing technology for diabetes management.
A Rich-Club Organization in Brain Ischemia Protein Interaction Network
Authors: Alawieh Ali , Sabra Zahraa , Sabra Mohammed , Tomlinson Stephen , Zaraket Fadi A. 
Published: August 2015

AbstractIschemic stroke involves multiple pathophysiological mechanisms with complex interactions. Efforts to decipher those mechanisms and understand the evolution of cerebral injury is key for developing successful interventions. In an innovative approach, we use literature mining, natural language processing and systems biology tools to construct, annotate and curate a brain ischemia interactome. The curated interactome includes proteins that are deregulated after cerebral ischemia in human and experimental stroke. Network analysis of the interactome revealed a rich-club organization indicating the presence of a densely interconnected hub structure of prominent contributors to disease pathogenesis. Functional annotation of the interactome uncovered prominent pathways and highlighted the critical role of the complement and coagulation cascade in the initiation and amplification of injury starting by activation of the rich-club. We performed an in-silico screen for putative interventions that have pleiotropic effects on rich-club components and we identified estrogen as a prominent candidate. Our findings show that complex network analysis of disease related interactomes may lead to a better understanding of pathogenic mechanisms and provide cost-effective and mechanism-based discovery of candidate therapeutics.
Synthesis of Structurally Diverse 2,3-Fused Indoles via Microwave-Assisted AgSbF6-Catalysed Intramolecular Difunctionalization of o-Alkynylanilines
Authors: Huang Yuanqiong , Yang Yan , Song Hongjian , Liu Yuxiu , Wang Qingmin 
Published: August 2015

Abstract2,3-Fused indoles are found in numerous natural products and drug molecules. Although several elegant methods for the synthesis of this structural motif have been reported, long reaction times and harsh conditions are sometimes required and the yields tend to be low. Herein, we report a microwave method for straightforward access to various types of 2,3-fused indoles via AgSbF6-catalysed intramolecular difunctionalization of o-alkynylanilines. AgSbF6 played a role in both the hydroamination step and the imine-formation step. This method, which exhibited excellent chemoselectivity (no ring-fused 1,2-dihydroquinolines were formed), was used for formal syntheses of the natural products conolidine and ervaticine and the antihistamine drug latrepirdine.
Water: Promising Opportunities For Tunable All-dielectric Electromagnetic Metamaterials
Authors: Andryieuski Andrei , Kuznetsova Svetlana M. , Zhukovsky Sergei V. , Kivshar Yuri S. , Lavrinenko Andrei V. 
Published: August 2015

AbstractWe reveal an outstanding potential of water as an inexpensive, abundant and bio-friendly high-refractive-index material for creating tunable all-dielectric photonic structures and metamaterials. Specifically, we demonstrate thermal, mechanical and gravitational tunability of magnetic and electric resonances in a metamaterial consisting of periodically positioned water-filled reservoirs. The proposed water-based metamaterials can find applications not only as cheap and ecological microwave devices, but also in optical and terahertz metamaterials prototyping and educational lab equipment.
A subset of ocular adnexal marginal zone lymphomas may arise in association with IgG4-related disease
Authors: Ohno Kyotaro , Sato Yasuharu , Ohshima Koh-ichi , Takata Katsuyoshi , Miyata-Takata Tomoko , Takeuchi Mai , Gion Yuka , Tachibana Tomoyasu , Orita Yorihisa , Ito Toshihiro , Swerdlow Steven H. , Yoshino Tadashi 
Published: August 2015

AbstractWe previously suggested a relationship between ocular immunoglobulin (Ig)G4-related disease (IgG4-RD) and marginal zone lymphomas (MZLs). However, the cytokine background associated with these disorders and whether it differs between ocular adnexal MZLs with (IgG4-associated MZL) and without (IgG4-negative MZL) numerous IgG4+ plasma cells are unknown. In this study, we identified the mRNA expression pattern of Th2 and regulatory T-cell (Treg) cytokines in IgG4-RD and in IgG4-associated MZL and IgG4-negative MZL using real-time polymerase chain reaction analysis. Ocular IgG4-RD and IgG4-associated MZL exhibited significantly higher expression ratios of interleukin (IL)-4/β-actin, IL-10/β-actin, IL-13/β-actin, transforming growth factor (TGF) β1/β-actin and FOXP3/β-actin than did IgG4-negative MZL (p < 0.05). This finding further supports our prior observations that a significant subset of ocular MZLs arises in the setting of IgG4-RD. Furthermore, the presence of a different inflammatory background in IgG4-negative MZLs suggests that IgG4-associated MZLs may have a different pathogenesis.
Discovery of γ-Mangostin as an Amyloidogenesis Inhibitor
Authors: Yokoyama Takeshi , Ueda Mitsuharu , Ando Yukio , Mizuguchi Mineyuki 
Published: August 2015

AbstractTransthyretin (TTR) is a homotetrameric protein involved in human hereditary amyloidoses. The discovery and development of small molecules that inhibit the amyloid fibril formation of TTR is one of the therapeutic strategies for these diseases. Herein, we discovered that γ-mangostin (γ-M) is an effective inhibitor against the amyloid fibril formation of V30M amyloidogenic TTR. In-vitro binding assays revealed that γ-M was the most potent of the selected xanthone derivatives and it bound to the thyroxine (T4)-binding sites and stabilized the TTR tetramer. X-ray crystallographic analysis revealed the diagonal binding mode of γ-M and the two binding sites of chloride ions at the T4-binding site. One of the chloride ions was replaced with a water molecule in the α-mangostin complex, which is a methylated derivative of γ-M. The stronger inhibitory potency of γ-M could be explained by the additional hydrogen bonds with the chloride ion. The present study establishes γ-M as a novel inhibitor of TTR fibrillization.
Computational DNA hole spectroscopy: A new tool to predict mutation hotspots, critical base pairs and disease ‘driver’ mutations
Authors: Suárez Martha Y. , Villagrán  , Miller John H. 
Published: August 2015

AbstractWe report on a new technique, computational DNA hole spectroscopy, which creates spectra of electron hole probabilities vs. nucleotide position. A hole is a site of positive charge created when an electron is removed. Peaks in the hole spectrum depict sites where holes tend to localize and potentially trigger a base pair mismatch during replication. Our studies of mitochondrial DNA reveal a correlation between L-strand hole spectrum peaks and spikes in the human mutation spectrum. Importantly, we also find that hole peak positions that do not coincide with large variant frequencies often coincide with disease-implicated mutations and/or (for coding DNA) encoded conserved amino acids. This enables combining hole spectra with variant data to identify critical base pairs and potential disease ‘driver’ mutations. Such integration of DNA hole and variance spectra could ultimately prove invaluable for pinpointing critical regions of the vast non-protein-coding genome. An observed asymmetry in correlations, between the spectrum of human mtDNA variations and the L- and H-strand hole spectra, is attributed to asymmetric DNA replication processes that occur for the leading and lagging strands.
FABP4 reversed the regulation of leptin on mitochondrial fatty acid oxidation in mice adipocytes
Authors: Gan Lu , Liu Zhenjiang , Cao Weina , Zhang Zhenzhen , Sun Chao 
Published: August 2015

AbstractFatty acid binding protein 4 (FABP4), plays key role in fatty acid transportation and oxidation and increases with leptin synergistically during adipose inflammation process. However, the regulation mechanism between FABP4 and leptin on mitochondrial fatty acid oxidation remains unclear. In this study, we found that FABP4 reduced the expression of leptin, CPT-1 and AOX1 in mice adipocytes. Conversely, FABP4 was down-regulated in a time-dependent manner by leptin treatment. Additionally, forced expression of FABP4 attenuated the expression of PGC1-α, UCP2, CPT-1, AOX1 and COX2 compared with leptin incubation. Moreover, mitochondrial membrane potential, fatty acid oxidation enzyme medium-chain acyl-CoA dehydrogenase (MCAD), long-chain acyl-CoA dehydrogenase (LCAD) and Cyt C levels were reduced in response to the overexpression of FABP4. These reductions correspond well with the reduced release of free fatty acid and the inactivation of mitochondrial complexes I and III by FABP4 overexpression. Furthermore, addition of the Akt/mTOR pathway-specific inhibitor (MK2206) blocked the mitochondrial fatty acid oxidation and respiration factors, whereas interference of FABP4 overcame these effects. Taken together, FABP4 could reverse the activation of the leptin-induced mitochondrial fatty acid oxidation and the inhibition of Akt/mTOR signal pathway played a key role in this process.
Rice α-fucosidase active against plant complex type N-glycans containing Lewis a epitope: purification and characterization
Authors: Rahman Md Ziaur , Fujishige Makoto , Maeda Megumi , Kimura Yoshinobu 
Published: August 2015

Abstract
Rice α-fucosidase (α-fucosidase Os, 58 kDa) that is active for α1-4 fucosyl linkage in Lewis a unit of plant N-glycans was purified to homogeneity. α-fucosidase Os showed activity against α1-3 fucosyl linkage in Lacto-N-fucopentaose III but not α1-3 fucosyl linkage in the core of plant N-glycans. The N-terminal sequence of α-fucosidase Os was identified as A-A-P-T-P-P-P-L-, and this sequence was found in the amino acid sequence of the putative rice α-fucosidase 1 (Os04g0560400).
Creatine co‐ingestion with carbohydrate or cinnamon extract provides no added benefit to anaerobic performance
Authors: Islam Hashim , Yorgason Nick J. , Hazell Tom J. 
Published: August 2015

AbstractThe insulin response following carbohydrate ingestion enhances creatine transport into muscle. Cinnamon extract is promoted to have insulin‐like effects, therefore this study examined if creatine co‐ingestion with carbohydrates or cinnamon extract improved anaerobic capacity, muscular strength, and muscular endurance. Active young males (n = 25; 23.7 ± 2.5 y) were stratified into 3 groups: (1) creatine only (CRE); (2) creatine+ 70 g carbohydrate (CHO); or (3) creatine+ 500 mg cinnamon extract (CIN), based on anaerobic capacity (peak power·kg−1) and muscular strength at baseline. Three weeks of supplementation consisted of a 5 d loading phase (20 g/d) and a 16 d maintenance phase (5 g/d). Pre‐ and post‐supplementation measures included a 30‐s Wingate and a 30‐s maximal running test (on a self‐propelled treadmill) for anaerobic capacity. Muscular strength was measured as the one‐repetition maximum 1‐RM for chest, back, quadriceps, hamstrings, and leg press. Additional sets of the number of repetitions performed at 60% 1‐RM until fatigue measured muscular endurance. All three groups significantly improved Wingate relative peak power (CRE: 15.4% P = .004; CHO: 14.6% P = .004; CIN: 15.7%, P = .003), and muscular strength for chest (CRE: 6.6% P < .001; CHO: 6.7% P < .001; CIN: 6.4% P < .001), back (CRE: 5.8% P < .001; CHO: 6.4% P < .001; CIN: 8.1% P < .001), and leg press (CRE: 11.7% P = .013; CHO: 10.0% P = .007; CIN: 17.3% P < .001). Only the CRE (10.4%, P = .021) and CIN (15.5%, P < .001) group improved total muscular endurance. No differences existed between groups post‐supplementation. These findings demonstrate that three different methods of creatine ingestion lead to similar changes in anaerobic power, strength, and endurance.
Executive Summary: 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adultsa
Authors: Berbari Elie F. , Kanj Souha S. , Kowalski Todd J. , Darouiche Rabih O. , Widmer Andreas F. , Schmitt Steven K. , Hendershot Edward F. , Holtom Paul D. , Huddleston Paul M. , Petermann Gregory W. , Osmon Douglas R. 
Published: August 2015

Abstract
These guidelines are intended for use by infectious disease specialists, orthopedic surgeons, neurosurgeons, radiologists, and other healthcare professionals who care for patients with native vertebral osteomyelitis (NVO). They include evidence and opinion-based recommendations for the diagnosis and management of patients with NVO treated with antimicrobial therapy, with or without surgical intervention.
The Problem of Income Inequality: Lord Wedderburn on Fat Cats, Corporate Governance and Workers
Authors: Njoya Wanjiru 
Published: August 2015

Abstract
This article evaluates Lord Wedderburn’s scholarship on the role of workers in company law and corporate governance, focusing on Wedderburn’s proposal that worker representatives should be included in the remuneration committees of large corporations as a starting point in tackling the growing disparity between the highest and lowest paid workers in the firm. The article addresses the efficiency implications of worker participation in setting executive pay, highlighting the complementarity between the normative framework of efficiency and Wedderburn’s commitment to social justice. On that premise the article formulates a critique of growing wage disparity by reference to the firm’s decision-making processes: who makes the decisions about pay, what are the key factors taken into account by the decision-makers and what role can be played by worker participation in making pay awards more acceptable?
Toroidal vortices and the conglomeration of dust into rings in protoplanetary discs
Authors: Lorén-Aguilar Pablo , Bate Matthew R. 
Published: August 2015

Abstract
We identify a new hydrodynamical instability in protoplanetary discs that may arise due to variations in the dust-to-gas ratio and may lead to concentration of dust grains within a disc. The instability can arise due to dust settling, which produces a vertical compositional entropy gradient. The entropy gradient drives a baroclinic instability that is capable of creating toroidal gas vortices that gather dust into rings. Such dust rings are potentially observable via continuum emission of the dust or scattered light. Indeed, this instability may offer an explanation for the rings recently observed in the discs around the young stars HL Tau and TW Hya that does not rely on clearing by protoplanets. The instability may also have wider ramifications, potentially aiding dust agglomeration, altering the radial migration of larger planetesimals, and modifying angular momentum transport within a disc.
Compliance with reporting guidelines by Australian pathologists: an audit of the quality of histopathology reporting in high-grade glioma
Authors: White Alison , Fabian Vicki , McDonald Kerrie , Nowak Anna K. 
Published: August 2015

AbstractBackgroundDiagnostic pathology reports inform management plans for patients with glioma, and there is an increasing clinical need for molecular testing. We assessed the quality of histopathology reports of grade III/IV gliomas.MethodsReports were obtained as part of a tumor biobank. From 720 pathology reports, 594 eligible reports were assessed for 28 elements derived from published checklists. A summary quality score incorporated 9 critical parameters for clinical decision making: diagnosis using World Health Organization 2007 criteria; cell type; grade; narrative supporting cell type and grade; absence of equivocal language; conclusion reporting cell type and grade; and conclusion aligned with report narrative.ResultsOf 594 eligible reports, the final conclusion was not supported by the report narrative in 122 (21%). Tumor classification and grade were not supported by the narrative in 105 (18%) and 36 (6%) reports, respectively. Only 145 (24%) reports fulfilled all 9 quality criteria, while 25% contained 6 or fewer key quality indices. Report quality was higher when pathologists had neuropathology subspecialization, when a grade IV tumor was reported, and when the specimen was from an initial resection or grade-progressed tumor rather than recurrent high-grade glioma. Use of molecular testing increased over time, from 29% to 48% over four quartiles of the study. Molecular testing was more frequently done where oligodendroglial elements were reported.ConclusionA significant proportion of reports failed to meet key indicators of report quality. Pathology reporting is critical in communicating between pathologists and treating clinicians. Clinicians should be aware of reporting quality and seek clarification when required.
Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens
Authors: Arama Charles , Skinner Jeff , Doumtabe Didier , Portugal Silvia , Tran Tuan M. , Jain Aarti , Traore Boubacar , Doumbo Ogobara K. , Davies David Huw , Troye-Blomberg Marita , Dolo Amagana , Felgner Philip L. , Crompton Peter D. 
Published: August 2015

Abstract
Background.  People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to &lt;0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig)M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections.
Methods.  In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity.
Results.  We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups.
Conclusions.  These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection.