bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of circulating proteins associated to knee radiographic osteoarthritis
Authors: Lourido Lucía , Ayoglu Burcu , Fernández-Tajes Juan , Oreiro Natividad , Henjes Frauke , Hellström Cecilia , Schwenk Jochen M. , Ruiz-Romero Cristina , Nilsson Peter , Blanco Francisco J. 
Published: March 2017

AbstractCurrently there are no sufficiently sensitive biomarkers able to reflect changes in joint remodelling during osteoarthritis (OA). In this work, we took an affinity proteomic approach to profile serum samples for proteins that could serve as indicators for the diagnosis of radiographic knee OA. Antibody suspension bead arrays were applied to analyze serum samples from patients with OA (n = 273), control subjects (n = 76) and patients with rheumatoid arthritis (RA, n = 244). For verification, a focused bead array was built and applied to an independent set of serum samples from patients with OA (n = 188), control individuals (n = 83) and RA (n = 168) patients. A linear regression analysis adjusting for sex, age and body mass index (BMI) revealed that three proteins were significantly elevated (P < 0.05) in serum from OA patients compared to controls: C3, ITIH1 and S100A6. A panel consisting of these three proteins had an area under the curve of 0.82 for the classification of OA and control samples. Moreover, C3 and ITIH1 levels were also found to be significantly elevated (P < 0.05) in OA patients compared to RA patients. Upon validation in additional study sets, the alterations of these three candidate serum biomarker proteins could support the diagnosis of radiographic knee OA.
Lysophosphatidic acid counteracts glucagon-induced hepatocyte glucose production via STAT3
Authors: Taddeo Evan P. , Hargett Stefan R. , Lahiri Sujoy , Nelson Marin E. , Liao Jason A. , Li Chien , Slack-Davis Jill K. , Tomsig Jose L. , Lynch Kevin R. , Yan Zhen , Harris Thurl E. , Hoehn Kyle L. 
Published: March 2017

AbstractHepatic glucose production (HGP) is required to maintain normoglycemia during fasting. Glucagon is the primary hormone responsible for increasing HGP; however, there are many additional hormone and metabolic factors that influence glucagon sensitivity. In this study we report that the bioactive lipid lysophosphatidic acid (LPA) regulates hepatocyte glucose production by antagonizing glucagon-induced expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK). Treatment of primary hepatocytes with exogenous LPA blunted glucagon-induced PEPCK expression and glucose production. Similarly, knockout mice lacking the LPA-degrading enzyme phospholipid phosphate phosphatase type 1 (PLPP1) had a 2-fold increase in endogenous LPA levels, reduced PEPCK levels during fasting, and decreased hepatic gluconeogenesis in response to a pyruvate challenge. Mechanistically, LPA antagonized glucagon-mediated inhibition of STAT3, a transcriptional repressor of PEPCK. Importantly, LPA did not blunt glucagon-stimulated glucose production or PEPCK expression in hepatocytes lacking STAT3. These data identify a novel role for PLPP1 activity and hepatocyte LPA levels in glucagon sensitivity via a mechanism involving STAT3.
3D Printed Graphene Based Energy Storage Devices
Authors: Foster Christopher W. , Down Michael P. , Zhang Yan , Ji Xiaobo , Rowley-Neale Samuel J. , Smith Graham C. , Kelly Peter J. , Banks Craig E. 
Published: March 2017

Abstract3D printing technology provides a unique platform for rapid prototyping of numerous applications due to its ability to produce low cost 3D printed platforms. Herein, a graphene-based polylactic acid filament (graphene/PLA) has been 3D printed to fabricate a range of 3D disc electrode (3DE) configurations using a conventional RepRap fused deposition moulding (FDM) 3D printer, which requires no further modification/ex-situ curing step. To provide proof-of-concept, these 3D printed electrode architectures are characterised both electrochemically and physicochemically and are advantageously applied as freestanding anodes within Li-ion batteries and as solid-state supercapacitors. These freestanding anodes neglect the requirement for a current collector, thus offering a simplistic and cheaper alternative to traditional Li-ion based setups. Additionally, the ability of these devices’ to electrochemically produce hydrogen via the hydrogen evolution reaction (HER) as an alternative to currently utilised platinum based electrodes (with in electrolysers) is also performed. The 3DE demonstrates an unexpectedly high catalytic activity towards the HER (−0.46 V vs. SCE) upon the 1000th cycle, such potential is the closest observed to the desired value of platinum at (−0.25 V vs. SCE). We subsequently suggest that 3D printing of graphene-based conductive filaments allows for the simple fabrication of energy storage devices with bespoke and conceptual designs to be realised.
Transcriptome-based repurposing of apigenin as a potential anti-fibrotic agent targeting hepatic stellate cells
Authors: Hicks Daniel F. , Goossens Nicolas , Blas-García Ana , Tsuchida Takuma , Wooden Benjamin , Wallace Michael C. , Nieto Natalia , Lade Abigale , Redhead Benjamin , Cederbaum Arthur I , Dudley Joel T. , Fuchs Bryan C. , Lee Youngmin A. , Hoshida Yujin , Friedman Scott L. 
Published: March 2017

AbstractWe have used a computational approach to identify anti-fibrotic therapies by querying a transcriptome. A transcriptome signature of activated hepatic stellate cells (HSCs), the primary collagen-secreting cell in liver, and queried against a transcriptomic database that quantifies changes in gene expression in response to 1,309 FDA-approved drugs and bioactives (CMap). The flavonoid apigenin was among 9 top-ranked compounds predicted to have anti-fibrotic activity; indeed, apigenin dose-dependently reduced collagen I in the human HSC line, TWNT-4. To identify proteins mediating apigenin’s effect, we next overlapped a 122-gene signature unique to HSCs with a list of 160 genes encoding proteins that are known to interact with apigenin, which identified C1QTNF2, encoding for Complement C1q tumor necrosis factor-related protein 2, a secreted adipocytokine with metabolic effects in liver. To validate its disease relevance, C1QTNF2 expression is reduced during hepatic stellate cell activation in culture and in a mouse model of alcoholic liver injury in vivo, and its expression correlates with better clinical outcomes in patients with hepatitis C cirrhosis (n = 216), suggesting it may have a protective role in cirrhosis progression.These findings reinforce the value of computational approaches to drug discovery for hepatic fibrosis, and identify C1QTNF2 as a potential mediator of apigenin’s anti-fibrotic activity.
The developmental and environmental regulation of gravitropic setpoint angle in Arabidopsis and bean
Authors: Roychoudhry Suruchi , Kieffer Martin , Del Bianco Marta , Liao Che-Yang , Weijers Dolf , Kepinski Stefan 
Published: March 2017

AbstractRoot and shoot branches are major determinants of plant form and critical for the effective capture of resources below and above ground. These branches are often maintained at specific angles with respect to gravity, known as gravitropic set point angles (GSAs). We have previously shown that the mechanism permitting the maintenance of non-vertical GSAs is highly auxin-dependent and here we investigate the developmental and environmental regulation of root and shoot branch GSA. We show that nitrogen and phosphorous deficiency have opposing, auxin signalling-dependent effects on lateral root GSA in Arabidopsis: while low nitrate induces less vertical lateral root GSA, phosphate deficiency results in a more vertical lateral root growth angle, a finding that contrasts with the previously reported growth angle response of bean adventitious roots. We find that this root-class-specific discrepancy in GSA response to low phosphorus is mirrored by similar differences in growth angle response to auxin treatment between these root types. Finally we show that both shaded, low red/far-red light conditions and high temperature induce more vertical growth in Arabidopsis shoot branches. We discuss the significance of these findings in the context of efforts to improve crop performance via the manipulation of root and shoot branch growth angle.
SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules
Authors: Daina Antoine , Michielin Olivier , Zoete Vincent 
Published: March 2017

AbstractTo be effective as a drug, a potent molecule must reach its target in the body in sufficient concentration, and stay there in a bioactive form long enough for the expected biologic events to occur. Drug development involves assessment of absorption, distribution, metabolism and excretion (ADME) increasingly earlier in the discovery process, at a stage when considered compounds are numerous but access to the physical samples is limited. In that context, computer models constitute valid alternatives to experiments. Here, we present the new SwissADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar. Easy efficient input and interpretation are ensured thanks to a user-friendly interface through the login-free website http://www.swissadme.ch. Specialists, but also nonexpert in cheminformatics or computational chemistry can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavours.
Wavelength tunable InGaN/GaN nano-ring LEDs via nano-sphere lithography
Authors: Wang Sheng-Wen , Hong Kuo-Bin , Tsai Yu-Lin , Teng Chu-Hsiang , Tzou An-Jye , Chu You-Chen , Lee Po-Tsung , Ku Pei-Cheng , Lin Chien-Chung , Kuo Hao-Chung 
Published: March 2017

AbstractIn this research, nano-ring light-emitting diodes (NRLEDs) with different wall width (120 nm, 80 nm and 40 nm) were fabricated by specialized nano-sphere lithography technology. Through the thinned wall, the effective bandgaps of nano-ring LEDs can be precisely tuned by reducing the strain inside the active region. Photoluminescence (PL) and time-resolved PL measurements indicated the lattice-mismatch induced strain inside the active region was relaxed when the wall width is reduced. Through the simulation, we can understand the strain distribution of active region inside NRLEDs. The simulation results not only revealed the exact distribution of strain but also predicted the trend of wavelength-shifted behavior of NRLEDs. Finally, the NRLEDs devices with four-color emission on the same wafer were demonstrated.
Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma
Authors: Chow Yock Ping , Tan Lu Ping , Chai San Jiun , Abdul Aziz Norazlin , Choo Siew Woh , Lim Paul Vey Hong , Pathmanathan Rajadurai , Mohd Kornain Noor Kaslina , Lum Chee Lun , Pua Kin Choo , Yap Yoke Yeow , Tan Tee Yong , Teo Soo Hwang , Khoo Alan Soo-Beng , Patel Vyomesh 
Published: March 2017

AbstractIn this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies.
Magnetic nanoparticles: a strategy to target the choroidal layer in the posterior segment of the eye
Authors: Giannaccini Martina , Pedicini Lucia , De Matienzo Guglielma , Chiellini Federica , Dente Luciana , Raffa Vittoria 
Published: March 2017

AbstractDespite the higher rate of blindness due to population aging, minimally invasive and selective drug delivery to the eye still remains an open challenge, especially in the posterior segment. The retina, the retinal pigment epithelium (RPE) and the choroid are posterior segment cell layers, which may be affected by several diseases. In particular, damages to the choroid are associated with poor prognosis in the most severe pathologies. A drug delivery approach, able to target the choroid, is still missing. Recently, we demonstrated that intravitreally injected magnetic nanoparticles (MNP) are able to rapidly and persistently localise within the RPE in an autonomous manner. In this work we functionalised the MNP surface with the vascular endothelial growth factor, a bioactive molecule capable of transcytosis from the RPE towards more posterior layers. Such functionalisation successfully addressed the MNPs to the choroid, while MNP functionalised with a control polypeptide (poly-L-lysine) showed the same localisation pattern of the naked MNP particles. These data suggest that the combination of MNP with different bioactive molecules could represent a powerful strategy for cell-specific targeting of the eye posterior segment.
Nicotinic acid inhibits glioma invasion by facilitating Snail1 degradation
Authors: Li Jiejing , Qu Jiagui , Shi Yu , Perfetto Mark , Ping Zhuxian , Christian Laura , Niu Hua , Mei Shuting , Zhang Qin , Yang Xiangcai , Wei Shuo 
Published: March 2017

AbstractMalignant glioma is a formidable disease that commonly leads to death, mainly due to the invasion of tumor cells into neighboring tissues. Therefore, inhibition of tumor cell invasion may provide an effective therapy for malignant glioma. Here we report that nicotinic acid (NA), an essential vitamin, inhibits glioma cell invasion in vitro and in vivo. Treatment of the U251 glioma cells with NA in vitro results in reduced invasion, which is accompanied by a loss of mesenchymal phenotype and an increase in cell-cell adhesion. At the molecular level, transcription of the adherens junction protein E-cadherin is upregulated, leading to accumulation of E-cadherin protein at the cell-cell boundary. This can be attributed to NA’s ability to facilitate the ubiquitination and degradation of Snail1, a transcription factor that represses E-cadherin expression. Similarly, NA transiently inhibits neural crest migration in Xenopus embryos in a Snail1-dependent manner, indicating that the mechanism of action for NA in cell migration is evolutionarily conserved. We further show that NA injection blocks the infiltration of tumor cells into the adjacent brain tissues and improves animal survival in a rat model of glioma. These results suggest that NA treatment may be developed into a potential therapy for malignant glioma.
Phthalocyanine Doped Metal Oxide Nanoparticles on Multiwalled Carbon Nanotubes Platform for the detection of Dopamine
Authors: Mphuthi Ntsoaki G. , Adekunle Abolanle S. , Fayemi Omolola E. , Olasunkanmi Lukman O. , Ebenso Eno E. 
Published: March 2017

AbstractThe electrocatalytic properties of metal oxides (MO = Fe3O4, ZnO) nanoparticles doped phthalocyanine (Pc) and functionalized MWCNTs, decorated on glassy carbon electrode (GCE) was investigated. Successful synthesis of the metal oxide nanoparticles and the MO/Pc/MWCNT composite were confirmed using UV-Vis, EDX, XRD and TEM techniques. Successful modification of GCE with the MO and their composite was also confirmed using cyclic voltammetry (CV) technique. GCE-MWCNT/ZnO/29H,31H-Pc was the best electrode towards DA detection with very low detection limit (0.75 μM) which compared favourably with literature, good sensitivity (1.45 μA/μM), resistance to electrode fouling, and excellent ability to detect DA without interference from AA signal. Electrocatalytic oxidation of DA on GCE-MWCNT/ZnO/29H,31H-Pc electrode was diffusion controlled but characterized with some adsorption of electro-oxidation reaction intermediates products. The fabricated sensors are easy to prepare, cost effective and can be applied for real sample analysis of dopamine in drug composition. The good electrocatalytic properties of 29H,31H-Pc and 2,3-Nc were related to their (quantum chemically derived) frontier molecular orbital energies and global electronegativities. The better performance of 29H,31H-Pc than 2,3-Nc in aiding electrochemical oxidation of DA might be due to its better electron accepting ability, which is inferred from its lower ELUMOand higher χ.
Physico-mechanical and morphological features of zirconia substituted hydroxyapatite nano crystals
Authors: Mansour S. F. , El-dek S. I. , Ahmed M. K. 
Published: March 2017

AbstractZirconia doped Hydroxyapatite (HAP) nanocrystals [Ca10(PO4)6−x(ZrO2)x(OH)2]; (0 ≤ x ≤ 1 step 0.2) were synthesized using simple low cost facile method. The crystalline phases were examined by X-ray diffraction (XRD). The crystallinity percentage decreased with increasing zirconia content for the as-synthesized samples. The existence of zirconia as secondary phase on the grain boundaries; as observed from scanning electron micrographs (FESEM); resulted in negative values of microstrain. The crystallite size was computed and the results showed that it increased with increasing annealing temperature. Thermo-gravimetric analysis (TGA) assured the thermal stability of the nano crystals over the temperature from room up to 1200 °C depending on the zirconia content. The corrosion rate was found to decrease around 25 times with increasing zirconia content from x = 0.0 to 1.0. Microhardness displayed both compositional and temperature dependence. For the sample (x = 0.6), annealed at 1200 °C, the former increased up to 1.2 times its original value (x = 0.0).
Repression of Human T-lymphotropic virus type 1 Long Terminal Repeat sense transcription by Sp1 recruitment to novel Sp1 binding sites
Authors: Fauquenoy Sylvain , Robette Gwenaëlle , Kula Anna , Vanhulle Caroline , Bouchat Sophie , Delacourt Nadège , Rodari Anthony , Marban Céline , Schwartz Christian , Burny Arsène , Rohr Olivier , Van Driessche Benoit , Van Lint Carine 
Published: March 2017

AbstractHuman T-lymphotropic Virus type 1 (HTLV-1) infection is characterized by viral latency in the majority of infected cells and by the absence of viremia. These features are thought to be due to the repression of viral sense transcriptionin vivo. Here, ourin silicoanalysis of the HTLV-1 Long Terminal Repeat (LTR) promoter nucleotide sequence revealed, in addition to the four Sp1 binding sites previously identified, the presence of two additional potential Sp1 sites within the R region. We demonstrated that the Sp1 and Sp3 transcription factors boundin vitroto these two sites and compared the binding affinity for Sp1 of all six different HTLV-1 Sp1 sites. By chromatin immunoprecipitation experiments, we showed Sp1 recruitmentin vivoto the newly identified Sp1 sites. We demonstrated in the nucleosomal context of an episomal reporter vector that the Sp1 sites interfered with both the sense and antisense LTR promoter activities. Interestingly, the Sp1 sites exhibited together a repressor effect on the LTR sense transcriptional activity but had no effect on the LTR antisense activity. Thus, our results demonstrate the presence of two new functional Sp1 binding sites in the HTLV-1 LTR, which act as negativecis-regulatory elements of sense viral transcription.
High-density genetic map and identification of QTLs for responses to temperature and salinity stresses in the model brown alga Ectocarpus
Authors: Avia Komlan , Coelho Susana M. , Montecinos Gabriel J. , Cormier Alexandre , Lerck Fiona , Mauger Stéphane , Faugeron Sylvain , Valero Myriam , Cock J. Mark , Boudry Pierre 
Published: March 2017

AbstractDeciphering the genetic architecture of adaptation of brown algae to environmental stresses such as temperature and salinity is of evolutionary as well as of practical interest. The filamentous brown algaEctocarpussp. is a model for the brown algae and its genome has been sequenced. As sessile organisms, brown algae need to be capable of resisting the various abiotic stressors that act in the intertidal zone (e.g. osmotic pressure, temperature, salinity, UV radiation) and previous studies have shown that an important proportion of the expressed genes is regulated in response to hyposaline, hypersaline or oxidative stress conditions. Using the double digest RAD sequencing method, we constructed a dense genetic map with 3,588 SNP markers and identified 39 QTLs for growth-related traits and their plasticity under different temperature and salinity conditions (tolerance to high temperature and low salinity). GO enrichment tests within QTL intervals highlighted membrane transport processes such as ion transporters. Our study represents a significant step towards deciphering the genetic basis of adaptation ofEctocarpussp. to stress conditions and provides a substantial resource to the increasing list of tools generated for the species.
Prolonged high-fat diet induces gradual and fat depot-specific DNA methylation changes in adult mice
Authors: Zwamborn Ramona A. J. , Slieker Roderick C. , Mulder Petra C. A. , Zoetemelk Inge , Verschuren Lars , Suchiman H. Eka D. , Toet Karin H. , Droog Simone , Slagboom P. Eline , Kooistra Teake , Kleemann Robert , Heijmans Bastiaan T. 
Published: March 2017

AbstractHigh-fat diets (HFD) are thought to contribute to the development of metabolism-related diseases. The long-term impact of HFD may be mediated by epigenetic mechanisms, and indeed, HFD has been reported to induce DNA methylation changes in white adipose tissue (WAT) near metabolism related genes. However, previous studies were limited to a single WAT depot, a single time-point and primarily examined the pre-pubertal period. To define dynamic DNA methylation patterns specific for WAT depots, we investigated DNA methylation of Pparg2 and Leptin in gonadal adipose tissue (GAT) and subcutaneous adipose tissue (SAT), at baseline and after 6, 12 and 24 weeks of HFD exposure in adult mice. HFD induced hypermethylation of both the Leptin promoter (max. 19.6% at week 24, P = 2.6·10−3) and the Pparg2 promoter in GAT (max. 10.5% at week 12, P = 0.001). The differential methylation was independent of immune cell infiltration upon HFD exposure. In contrast, no differential methylation in the Pparg2 and Leptin promoter was observed in SAT. Leptin and Pparg2 DNA methylation were correlated with gene expression in GAT. Our study shows that prolonged exposure to HFD in adulthood is associated with a gradually increasing DNA methylation level at the Leptin and Pparg2 promoters in a depot-specific manner.