bluuebunny/crossref_metadata_2025_split huggingface dataset:
The BROAD study: A randomised controlled trial using a whole food plant-based diet in the community for obesity, ischaemic heart disease or diabetes
Authors: Wright N , Wilson L , Smith M , Duncan B , McHugh P 
Published: March 2017

Abstract
Background/Objective:
There is little randomised evidence using a whole food plant-based (WFPB) diet as intervention for elevated body mass index (BMI) or dyslipidaemia. We investigated the effectiveness of a community-based dietary programme. Primary end points: BMI and cholesterol at 6 months (subsequently extended).

Subjects:
Ages 35–70, from one general practice in Gisborne, New Zealand. Diagnosed with obesity or overweight and at least one of type 2 diabetes, ischaemic heart disease, hypertension or hypercholesterolaemia. Of 65 subjects randomised (control n=32, intervention n=33), 49 (75.4%) completed the study to 6 months. Twenty-three (70%) intervention participants were followed up at 12 months.

Methods:
All participants received normal care. Intervention participants attended facilitated meetings twice-weekly for 12 weeks, and followed a non-energy-restricted WFPB diet with vitamin B12 supplementation.

Results:
At 6 months, mean BMI reduction was greater with the WFPB diet compared with normal care (4.4 vs 0.4, difference: 3.9 kg m−2 (95% confidence interval (CI)±1), P<0.0001). Mean cholesterol reduction was greater with the WFPB diet, but the difference was not significant compared with normal care (0.71 vs 0.26, difference: 0.45 mmol l−1 (95% CI±0.54), P=0.1), unless dropouts were excluded (difference: 0.56 mmol l−1 (95% CI±0.54), P=0.05). Twelve-month mean reductions for the WFPB diet group were 4.2 (±0.8) kg m−2 BMI points and 0.55 (±0.54, P=0.05) mmol l−1 total cholesterol. No serious harms were reported.

Conclusions:
This programme led to significant improvements in BMI, cholesterol and other risk factors. To the best of our knowledge, this research has achieved greater weight loss at 6 and 12 months than any other trial that does not limit energy intake or mandate regular exercise.
USP9X deubiquitylating enzyme maintains RAPTOR protein levels, mTORC1 signalling and proliferation in neural progenitors
Authors: Bridges Caitlin R. , Tan Men-Chee , Premarathne Susitha , Nanayakkara Devathri , Bellette Bernadette , Zencak Dusan , Domingo Deepti , Gecz Jozef , Murtaza Mariyam , Jolly Lachlan A. , Wood Stephen A. 
Published: March 2017

AbstractUSP9X, is highly expressed in neural progenitors and, essential for neural development in mice. In humans, mutations in USP9X are associated with neurodevelopmental disorders. To understand USP9X’s role in neural progenitors, we studied the effects of altering its expression in both the human neural progenitor cell line, ReNcell VM, as well as neural stem and progenitor cells derived from Nestin-cre conditionally deleted Usp9x mice. Decreasing USP9X resulted in ReNcell VM cells arresting in G0 cell cycle phase, with a concomitant decrease in mTORC1 signalling, a major regulator of G0/G1 cell cycle progression. Decreased mTORC1 signalling was also observed in Usp9x-null neurospheres and embryonic mouse brains. Further analyses revealed, (i) the canonical mTORC1 protein, RAPTOR, physically associates with Usp9x in embryonic brains, (ii) RAPTOR protein level is directly proportional to USP9X, in both loss- and gain-of-function experiments in cultured cells and, (iii) USP9X deubiquitlyating activity opposes the proteasomal degradation of RAPTOR. EdU incorporation assays confirmed Usp9x maintains the proliferation of neural progenitors similar to Raptor-null and rapamycin-treated neurospheres. Interestingly, loss of Usp9x increased the number of sphere-forming cells consistent with enhanced neural stem cell self-renewal. To our knowledge, USP9X is the first deubiquitylating enzyme shown to stabilize RAPTOR.
Poly(ethylmethacrylate-co-diethylaminoethyl acrylate) coating improves endothelial re-population, bio-mechanical and anti-thrombogenic properties of decellularized carotid arteries for blood vessel replacement
Authors: López-Ruiz Elena , Venkateswaran Seshasailam , Perán Macarena , Jiménez Gema , Pernagallo Salvatore , Díaz-Mochón Juan J. , Tura-Ceide Olga , Arrebola Francisco , Melchor Juan , Soto Juan , Rus Guillermo , Real Pedro J. , Diaz-Ricart María , Conde-González Antonio , Bradley Mark , Marchal Juan A. 
Published: March 2017

AbstractDecellularized vascular scaffolds are promising materials for vessel replacements. However, despite the natural origin of decellularized vessels, issues such as biomechanical incompatibility, immunogenicity risks and the hazards of thrombus formation, still need to be addressed. In this study, we coated decellularized vessels obtained from porcine carotid arteries with poly (ethylmethacrylate-co-diethylaminoethylacrylate) (8g7) with the purpose of improving endothelial coverage and minimizing platelet attachment while enhancing the mechanical properties of the decellularized vascular scaffolds. The polymer facilitated binding of endothelial cells (ECs) with high affinity and also induced endothelial cell capillary tube formation. In addition, platelets showed reduced adhesion on the polymer under flow conditions. Moreover, the coating of the decellularized arteries improved biomechanical properties by increasing its tensile strength and load. In addition, after 5 days in culture, ECs seeded on the luminal surface of 8g7-coated decellularized arteries showed good regeneration of the endothelium. Overall, this study shows that polymer coating of decellularized vessels provides a new strategy to improve re-endothelialization of vascular grafts, maintaining or enhancing mechanical properties while reducing the risk of thrombogenesis. These results could have potential applications in improving tissue-engineered vascular grafts for cardiovascular therapies with small caliber vessels.
Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer
Authors: Seitz Anna Katharina , Christensen Lise Lotte , Christensen Emil , Faarkrog Kasper , Ostenfeld Marie Stampe , Hedegaard Jakob , Nordentoft Iver , Nielsen Morten Muhlig , Palmfeldt Johan , Thomson Michelle , Jensen Michael Theis Solgaard , Nawroth Roman , Maurer Tobias , Ørntoft Torben Falck , Jensen Jørgen Bjerggaard , Damgaard Christian Kroun , Dyrskjøt Lars 
Published: March 2017

AbstractAberrant expression of long non-coding RNAs (lncRNAs) has been regarded as a critical component in bladder cancer (BC) and lncRNAs have been associated with BC development and progression although their overall expression and functional significance is still unclear. The aim of our study was to identify novel lncRNAs with a functional role in BC carcinogenesis. RNA-sequencing was used to identify aberrantly expressed lncRNAs in 8 normal and 72 BC samples. We identified 89 lncRNAs that were significantly dys-regulated in BC. Five lncRNAs; LINC00958, LINC01296, LINC00355, LNC-CMC1-1 and LNC-ALX1-2 were selected for further analyses. Silencing of LINC00958 or LINC01296 in vitro reduced both cell viability and migration. Knock-down of LINC00958 also affected invasion and resistance to anoikis. These cellular effects could be linked to direct/indirect regulation of protein coding mRNAs involved in cell death/survival, proliferation and cellular movement. Finally, we showed that LINC00958 binds proteins involved in regulation and initiation of translation and in post-transcriptional modification of RNA, including Metadherin, which has previously been associated with BC. Our analyses identified novel lncRNAs in BC that likely act as oncogenic drivers contributing to an aggressive cancerous phenotype likely through interaction with proteins involved in initiation of translation and/or post-transcriptional modification of RNA.
The trimer interface in the quaternary structure of the bifunctional prokaryotic FAD synthetase from Corynebacterium ammoniagenes
Authors: Serrano Ana , Sebastián María , Arilla-Luna Sonia , Baquedano Silvia , Herguedas Beatriz , Velázquez-Campoy Adrián , Martínez-Júlvez Marta , Medina Milagros 
Published: March 2017

AbstractBifunctional FAD synthetases (FADSs) fold in two independent modules; The C-terminal riboflavin kinase (RFK) catalyzes the RFK activity, while the N-terminal FMN-adenylyltransferase (FMNAT) exhibits the FMNAT activity. The search for macromolecular interfaces in the Corynebacterium ammoniagenes FADS (CaFADS) crystal structure predicts a dimer of trimers organization. Within each trimer, a head-to-tail arrangement causes the RFK and FMNAT catalytic sites of the two neighboring protomers to approach, in agreement with active site residues of one module influencing the activity at the other. We analyze the relevance of the CaFADS head-to-tail macromolecular interfaces to stabilization of assemblies, catalysis and ligand binding. With this aim, we evaluate the effect of point mutations in loop L1c-FlapI, loop L6c, and helix α1c of the RFK module (positions K202, E203, F206, D298, V300, E301 and L304), regions at the macromolecular interface between two protomers within the trimer. Although none of the studied residues is critical in the formation and dissociation of assemblies, residues at L1c-FlapI and helix α1c particularly modulate quaternary architecture, as well as ligand binding and kinetic parameters involved with RFK and FMNAT activities. These data support the influence of transient oligomeric structures on substrate accommodation and catalysis at both CaFADS active sites.
A missense single nucleotide polymorphism in the ALDH2 gene, rs671, is associated with hip fracture
Authors: Takeshima Kenichiro , Nishiwaki Yuji , Suda Yasunori , Niki Yasuo , Sato Yuiko , Kobayashi Tami , Miyamoto Kana , Uchida Hisaya , Inokuchi Wataru , Tsuji Takashi , Funayama Atsushi , Nakamura Masaya , Matsumoto Morio , Toyama Yoshiaki , Miyamoto Takeshi 
Published: March 2017

AbstractHip fracture is the most severe bone fragility fracture among osteoporotic injuries. Family history is a known risk factor for fracture and now included among criteria for osteoporosis diagnosis and treatment; however, genetic factors underlying family history favoring fracture remain to be elucidated. Here we demonstrate that a missense SNP in the ALDH2 gene, rs671 (ALDH2*2), is significantly associated with hip fracture (odds ratio = 2.48, 95% confidence interval: 1.20–5.10, p = 0.021). The rs671 SNP was also significantly associated with osteoporosis development (odds ratio = 2.04, 95% confidence interval: 1.07–3.88, p = 0.040). For analysis we enrolled 92 hip fracture patients plus 48 control subjects without bone fragility fractures with higher than −2.5 SD bone mineral density. We also recruited 156 osteoporosis patients diagnosed as below −2.5 SD in terms of bone mineral density but without hip fracture. Association of rs671 with hip fracture and osteoporosis was significant even after adjustment for age and body mass index. Our results provide new insight into the pathogenesis of hip fracture.
Meta-analysis of the changes of peripheral blood regulatory T cell to CD4+ T cell ratio in patients with systemic sclerosis
Authors: Deng Chuiwen , Li Wenli , Chen Si , Li Yongzhe 
Published: March 2017

AbstractCurrent reports on the changes in peripheral blood regulatory T cell (Tregs) to CD4+T cell ratio in systemic sclerosis (SSc) patients are varied in their conclusions. We therefore performed a meta-analysis to identify the actual change in the proportion of peripheral Tregs in SSc. Three databases, namely EMBASE, ISI web of knowledge, and Pubmed were systematically searched for relevant literature. Approximately 250 SSc patients and controls from several studies were included in this analysis. Comprehensive Meta Analysis Version 2.0 software was used to conduct the meta-analysis. Six studies were included in the meta-analysis. Results of the meta-analysis showed high degree of heterogeneity (I2 = 96.98), and a random-effect model was used in the subsequent analysis. The ratio of circulating Tregs to CD4+T cell in SSc was lower than in controls, but not statistically significantly so (−0.61 ± 0.94, P = 0.52). Subgroup analysis did not identify any potential source of heterogeneity. This meta-analysis indicated that Tregs might play a less prominent immunosuppressive role in the immune system in SSc patients, but needs further confirmation.
Regulation of NF-κB by PML and PML-RARα
Authors: Ahmed Abrar , Wan Xiaochun , Mitxitorena Izaskun , Lindsay Andrew J. , Paolo Pandolfi Pier , McCaffrey Mary W. , Keeshan Karen , Chen Youhai H. , Carmody Ruaidhrí J. 
Published: March 2017

AbstractPromyelocytic Leukemia (PML) is a nuclear protein that forms sub-nuclear structures termed nuclear bodies associated with transcriptionally active genomic regions. PML is a tumour suppressor and regulator of cell differentiation. We demonstrate that PML promotes TNFα-induced transcriptional responses by promoting NF-κB activity. TNFα-treated PML−/− cells show normal IκBα degradation and NF-κB nuclear translocation but significantly reduced NF-κB DNA binding and phosphorylation of NF-κB p65. We also demonstrate that the PML retinoic acid receptor-α (PML-RARα) oncofusion protein, which causes acute promyelocytic leukemia, inhibits TNFα induced gene expression and phosphorylation of NF-κB. This study establishes PML as an important regulator of NF-κB and demonstrates that PML-RARα dysregulates NF-κB.
On the determination of χ(2) in thin films: a comparison of one-beam second-harmonic generation measurement methodologies
Authors: Hermans Artur , Kieninger Clemens , Koskinen Kalle , Wickberg Andreas , Solano Eduardo , Dendooven Jolien , Kauranen Martti , Clemmen Stéphane , Wegener Martin , Koos Christian , Baets Roel 
Published: March 2017

AbstractThe determination of the second-order susceptibility (χ(2)) of thin film samples can be a delicate matter since well-established χ(2) measurement methodologies such as the Maker fringe technique are best suited for nonlinear materials with large thicknesses typically ranging from tens of microns to several millimeters. Here we compare two different second-harmonic generation setups and the corresponding measurement methodologies that are especially advantageous for thin film χ(2) characterization. This exercise allows for cross-checking the χ(2) obtained for identical samples and identifying the main sources of error for the respective techniques. The development of photonic integrated circuits makes nonlinear thin films of particular interest, since they can be processed into long waveguides to create efficient nonlinear devices. The investigated samples are ABC-type nanolaminates, which were reported recently by two different research groups. However, the subsequent analysis can be useful for all researchers active in the field of thin film χ(2) characterization.
Evidence for coseismic subsidence events in a southern California coastal saltmarsh
Authors: Leeper Robert , Rhodes Brady , Kirby Matthew , Scharer Katherine , Carlin Joseph , Hemphill-Haley Eileen , Avnaim-Katav Simona , MacDonald Glen , Starratt Scott , Aranda Angela 
Published: March 2017

AbstractPaleoenvironmental records from a southern California coastal saltmarsh reveal evidence for repeated late Holocene coseismic subsidence events. Field analysis of sediment gouge cores established discrete lithostratigraphic units extend across the wetland. Detailed sediment analyses reveal abrupt changes in lithology, percent total organic matter, grain size, and magnetic susceptibility. Microfossil analyses indicate that predominantly freshwater deposits bury relic intertidal deposits at three distinct depths. Radiocarbon dating indicates that the three burial events occurred in the last 2000 calendar years. Two of the three events are contemporaneous with large-magnitude paleoearthquakes along the Newport-Inglewood/Rose Canyon fault system. From these data, we infer that during large magnitude earthquakes a step-over along the fault zone results in the vertical displacement of an approximately 5-km2area that is consistent with the footprint of an estuary identified in pre-development maps. These findings provide insight on the evolution of the saltmarsh, coseismic deformation and earthquake recurrence in a wide area of southern California, and sensitive habitat already threatened by eustatic sea level rise.
Direct Evidence of Lack of Colocalisation of Fluorescently Labelled Gold Labels Used in Correlative Light Electron Microscopy
Authors: Miles Benjamin T. , Greenwood Alexander B. , Benito-Alifonso David , Tanner Hugh , Galan M. Carmen , Verkade Paul , Gersen Henkjan 
Published: March 2017

AbstractFluorescently labelled nanoparticles are routinely used in Correlative Light Electron Microscopy (CLEM) to combine the capabilities of two separate microscope platforms: fluorescent light microscopy (LM) and electron microscopy (EM). The inherent assumption is that the fluorescent label observed under LM colocalises well with the electron dense nanoparticle observed in EM. Herein we show, by combining single molecule fluorescent imaging with optical detection of the scattering from single gold nanoparticles, that for a commercially produced sample of 10 nm gold nanoparticles tagged to Alexa-633 there is in fact no colocalisation between the fluorescent signatures of Alexa-633 and the scattering associated with the gold nanoparticle. This shows that the attached gold nanoparticle quenches the fluorescent signal by ~95%, or less likely that the complex has dissociated. In either scenario, the observed fluorescent signal in fact arises from a large population of untagged fluorophores; rendering these labels potentially ineffective and misleading to the field.
Recruitment of bone marrow CD11b+Gr-1+ cells by polymeric nanoparticles for antigen cross-presentation
Authors: Yang Ya-Wun , Luo Wen-Hui 
Published: March 2017

AbstractThe objective of this study was to investigate the function of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on the activation of antigen-specific CD8+T cell responses via the CD11b+Gr−1+myeloid subpopulations in murine bone marrow (BM). PLGA NPs containing ovalbumin (OVA) were fabricated by the double-emulsion method. The CD11b+Gr-1lowLy-6Chighand CD11b+Gr-1highLy-6Clowsubsets from mice bone marrow were sorted and treated with the PLGA/OVA NPs, followed by co-culture with the carboxyfluorescein succinimidyl ester (CFSE)-labelled OT-I CD8+cells. Co-culture of OT-I CD8+T cells with PLGA/OVA NPs-primed CD11b+Gr-1+subsets upregulated the expression of IL-2, TNF-α, INF-γ, granzyme B, and perforin, resulting in proliferation of CD8+T cells and differentiation into effector cytotoxic T lymphocytes (CTLs).In vivoproliferation of CFSE-labelled OT-I CD8+cells in response to OVA was also obtained in the animals immunized with PLGA/OVA NPs. The results presented in this study demonstrate the ability of polymeric NPs to recruit two CD11b+Gr−1+myeloid subsets for effective presentation of exogenous antigen to OT-I CD8+T cells in the context of major histocompatibility complex (MHC) class I, leading to an induction of antigen-specific cell proliferation and differentiation into effector cells.
Cyclooxygenase‐2 facilitates dengue virus replication and serves as a potential target for developing antiviral agents
Authors: Lin Chun-Kuang , Tseng Chin-Kai , Wu Yu-Hsuan , Liaw Chih-Chuang , Lin Chun-Yu , Huang Chung-Hao , Chen Yen-Hsu , Lee Jin-Ching 
Published: March 2017

AbstractCyclooxygenase-2 (COX-2) is one of the important mediators of inflammation in response to viral infection, and it contributes to viral replication, for example, cytomegalovirus or hepatitis C virus replication. The role of COX-2 in dengue virus (DENV) replication remains unclear. In the present study, we observed an increased level of COX-2 in patients with dengue fever compared with healthy donors. Consistent with the clinical data, an elevated level of COX-2 expression was also observed in DENV-infected ICR suckling mice. Using cell-based experiments, we revealed that DENV-2 infection significantly induced COX-2 expression and prostaglandin E2 (PGE2) production in human hepatoma Huh-7 cells. The exogenous expression of COX-2 or PGE2 treatment dose-dependently enhanced DENV-2 replication. In contrast, COX-2 gene silencing and catalytic inhibition sufficiently suppressed DENV-2 replication. In an ICR suckling mouse model, we identified that the COX-2 inhibitor NS398 protected mice from succumbing to life-threatening DENV-2 infection. By using COX-2 promoter-based analysis and specific inhibitors against signaling molecules, we identified that NF-κB and MAPK/JNK are critical factors for DENV-2-induced COX-2 expression and viral replication. Altogether, our results reveal that COX-2 is an important factor for DENV replication and can serve as a potential target for developing therapeutic agents against DENV infection.
High Thermoelectric Power Factor of a Diketopyrrolopyrrole-Based Low Bandgap Polymer via Finely Tuned Doping Engineering
Authors: Jung In Hwan , Hong Cheon Taek , Lee Un-Hak , Kang Young Hun , Jang Kwang-Suk , Cho Song Yun 
Published: March 2017

AbstractWe studied the thermoelectric properties of a diketopyrrolopyrrole-based semiconductor (PDPP3T) via a precisely tuned doping process using Iron (III) chloride. In particular, the doping states of PDPP3T film were linearly controlled depending on the dopant concentration. The outstanding Seebeck coefficient of PDPP3T assisted the excellent power factors (PFs) over 200 μW m−1K−2 at the broad range of doping concentration (3–8 mM) and the maximum PF reached up to 276 μW m−1K−2, which is much higher than that of poly(3-hexylthiophene), 56 μW m−1K−2. The high-mobility of PDPP3T was beneficial to enhance the electrical conductivity and the low level of total dopant volume was important to maintain high Seebeck coefficients. In addition, the low bandgap PDPP3T polymer effiectively shifted its absorption into near infra-red area and became more colorless after doping, which is great advantage to realize transparent electronic devices. Our results give importance guidance to develop thermoelectric semiconducting polymers and we suggest that the use of low bandgap and high-mobility polymers, and the accurate control of the doping levels are key factors for obtaining the high thermoelectric PF.
Minocycline treatment suppresses juvenile development and growth by attenuating insulin/TOR signaling in Drosophila animal model
Authors: Yun Hyun Myoung , Noh Sujin , Hyun Seogang 
Published: March 2017

AbstractMinocycline is a broad spectrum, semi-synthetic tetracycline analog that is used to treat bacterial infection. Recently, this drug has been receiving increasing attention for its non-antibiotic properties, including anti-inflammatory, tumor suppressive, and neuroprotective effects. Drosophila is a useful model organism for studying human metabolism and disease. In this study, we investigated the effects of minocycline on juvenile development and growth in Drosophila. Feeding minocycline to Drosophila larvae suppresses larval body growth and delays the timing of pupation in a dose-dependent manner. We found that the drug treatment decreased the activated form of Akt and S6K in peripheral tissues, which suggested that the insulin/target of rapamycin (TOR) signaling had been attenuated. Specifically enhancing TOR activity in the prothoracic gland (PG), the ecdysone-generating organ, attenuated the drug-induced developmental delay, which is consistent with the critical role of PG’s TOR signaling in determining pupation time. Our results reveal previously unrecognized effects of minocycline and offer a new potential therapeutic opportunity for various pathological conditions associated with insulin/TOR signaling.