bluuebunny/crossref_metadata_2025 huggingface dataset:
REST is a crucial regulator for acquiring EMT-like and stemness phenotypes in hormone-refractory prostate cancer
Authors: Chang Yi-Ting , Lin Tzu-Ping , Campbell Mel , Pan Chin-Chen , Lee Shu-Hui , Lee Hsin-Chen , Yang Muh-Hwa , Kung Hsing-Jien , Chang Pei-Ching
Published: March 2017

Castration-resistance prostate cancer (CRPC), also known as hormone-refractory prostate cancer (HRPC), requires immediate attention since it is not only resistant to androgen ablation, chemo- and radiotherapy, but also highly metastatic. Increasing evidence suggests that enrichment of neuroendocrine (NE) cells is associated with CRPC. Here, combined RNA-seq and ChIP-seq analysis reveals that REST is involved in epithelial-mesenchymal transition (EMT) and stemness acquisition in NE differentiated prostate cancer (PCa) cells via direct transcriptional repression of Twist1 and CD44. Specifically we show that short-term knockdown of REST induces NE differentiation of LNCaP cells. Long-term REST knockdown enhanced the expression of Twist1 and CD44, cell migration and sphere formation. Overexpression of REST in hormone-refractory CWR22Rv1 PCa cells significantly reduces Twist1 and CD44 expression, cell migration and sphere formation. Collectively, our study uncovers REST in regulating EMT and stemness properties of NE PCa cells and suggests that REST is a potential therapeutic target for CRPC.
Chitosan-coated mesoporous MIL-100(Fe) nanoparticles as improved bio-compatible oral nanocarriers
Authors: Hidalgo T. , Giménez-Marqués M. , Bellido E. , Avila J. , Asensio M. C. , Salles F. , Lozano M. V. , Guillevic M. , Simón-Vázquez R. , González-Fernández A. , Serre C. , Alonso M. J. , Horcajada P.
Published: March 2017

Nanometric biocompatible Metal-Organic Frameworks (nanoMOFs) are promising candidates for drug delivery. Up to now, most studies have targeted the intravenous route, related to pain and severe complications; whereas nanoMOFs for oral administration, a commonly used non-invasive and simpler route, remains however unexplored. We propose here the biofriendly preparation of a suitable oral nanocarrier based on the benchmarked biocompatible mesoporous iron(III) trimesate nanoparticles coated with the bioadhesive polysaccharide chitosan (CS). This method does not hamper the textural/structural properties and the sorption/release abilities of the nanoMOFs upon surface engineering. The interaction between the CS and the nanoparticles has been characterized through a combination of high resolution soft X-ray absorption and computing simulation, while the positive impact of the coating on the colloidal and chemical stability under oral simulated conditions is here demonstrated. Finally, the intestinal barrier bypass capability and biocompatibility of CS-coated nanoMOF have been assessed in vitro, leading to an increased intestinal permeability with respect to the non-coated material, maintaining an optimal biocompatibility. In conclusion, the preservation of the interesting physicochemical features of the CS-coated nanoMOF and their adapted colloidal stability and progressive biodegradation, together with their improved intestinal barrier bypass, make these nanoparticles a promising oral nanocarrier.
Scale effect of slip boundary condition at solid–liquid interface
Authors: Nagayama Gyoko , Matsumoto Takenori , Fukushima Kohei , Tsuruta Takaharu
Published: March 2017

Rapid advances in microelectromechanical systems have stimulated the development of compact devices, which require effective cooling technologies (e.g., microchannel cooling). However, the inconsistencies between experimental and classical theoretical predictions for the liquid flow in microchannel remain unclarified. Given the larger surface/volume ratio of microchannel, the surface effects increase as channel scale decreases. Here we show the scale effect of the boundary condition at the solid–liquid interface on single-phase convective heat transfer characteristics in microchannels. We demonstrate that the deviation from classical theory with a reduction in hydraulic diameters is due to the breakdown of the continuum solid–liquid boundary condition. The forced convective heat transfer characteristics of single-phase laminar flow in a parallel-plate microchannel are investigated. Using the theoretical Poiseuille and Nusselt numbers derived under the slip boundary condition at the solid–liquid interface, we estimate the slip length and thermal slip length at the interface.
High-frequency torsional Alfvén waves as an energy source for coronal heating
Authors: Srivastava Abhishek Kumar , Shetye Juie , Murawski Krzysztof , Doyle John Gerard , Stangalini Marco , Scullion Eamon , Ray Tom , Wójcik Dariusz Patryk , Dwivedi Bhola N.
Published: March 2017

The existence of the Sun’s hot atmosphere and the solar wind acceleration continues to be an outstanding problem in solar-astrophysics. Although magnetohydrodynamic (MHD) modes and dissipation of magnetic energy contribute to heating and the mass cycle of the solar atmosphere, yet direct evidence of such processes often generates debate. Ground-based 1-m Swedish Solar Telescope (SST)/CRISP, Hα 6562.8 Å observations reveal, for the first time, the ubiquitous presence of high frequency (~12–42 mHz) torsional motions in thin spicular-type structures in the chromosphere. We detect numerous oscillating flux tubes on 10 June 2014 between 07:17 UT to 08:08 UT in a quiet-Sun field-of-view of 60” × 60” (1” = 725 km). Stringent numerical model shows that these observations resemble torsional Alfvén waves associated with high frequency drivers which contain a huge amount of energy (~105 W m−2) in the chromosphere. Even after partial reflection from the transition region, a significant amount of energy (~103 W m−2) is transferred onto the overlying corona. We find that oscillating tubes serve as substantial sources of Alfvén wave generation that provide sufficient Poynting flux not only to heat the corona but also to originate the supersonic solar wind.
Yield Optimisation of Hepatitis B Virus Core Particles in E. coli Expression System for Drug Delivery Applications
Authors: Bin Mohamed Suffian Izzat Fahimuddin , Garcia-Maya Mitla , Brown Paul , Bui Tam , Nishimura Yuya , Palermo Amir Rafiq Bin Mohammad Johari , Ogino Chiaki , Kondo Akihiko , Al-Jamal Khuloud T.
Published: March 2017

AnE. coliexpression system offers a mean for rapid, high yield and economical production of Hepatitis B Virus core (HBc) particles. However, high-level production of HBc particles in bacteria is demanding and optimisation of HBc particle yield fromE. coliis required to improve laboratory-scale productivity for further drug delivery applications. Production steps involve bacterial culture, protein isolation, denaturation, purification and finally protein assembly. In this study, we describe a modifiedE. colibased method for purifying HBc particles and compare the results with those obtained using a conventional purification method. HBc particle morphology was confirmed by Atomic Force Microscopy (AFM). Protein specificity and secondary structure were confirmed by Western Blot and Circular Dichroism (CD), respectively. The modified method produced ~3-fold higher yield and greater purity of wild type HBc particles than the conventional method. Our results demonstrated that the modified method produce a better yield and purity of HBc particles in anE. coli-expression system, which are fully characterised and suitable to be used for drug delivery applications.
A Predictive Structural Model of the Primate Connectome
Authors: Beul Sarah F. , Barbas Helen , Hilgetag Claus C.
Published: March 2017

Anatomical connectivity imposes strong constraints on brain function, but there is no general agreement about principles that govern its organization. Based on extensive quantitative data, we tested the power of three factors to predict connections of the primate cerebral cortex: architectonic similarity (structural model), spatial proximity (distance model) and thickness similarity (thickness model). Architectonic similarity showed the strongest and most consistent influence on connection features. This parameter was strongly associated with the presence or absence of inter-areal connections and when integrated with spatial distance, the factor allowed predicting the existence of projections with very high accuracy. Moreover, architectonic similarity was strongly related to the laminar pattern of projection origins, and the absolute number of cortical connections of an area. By contrast, cortical thickness similarity and distance were not systematically related to connection features. These findings suggest that cortical architecture provides a general organizing principle for connections in the primate brain, providing further support for the well-corroborated structural model.
Cell Type-Specific Epigenomic Analysis Reveals a Uniquely Closed Chromatin Architecture in Mouse Rod Photoreceptors
Authors: Hughes Andrew E. O. , Enright Jennifer M. , Myers Connie A. , Shen Susan Q. , Corbo Joseph C.
Published: March 2017

Rod photoreceptors are specialized neurons that mediate vision in dim light and are the predominant photoreceptor type in nocturnal mammals. The rods of nocturnal mammals are unique among vertebrate cell types in having an ‘inverted’ nuclear architecture, with a dense mass of heterochromatin in the center of the nucleus rather than dispersed clumps at the periphery. To test if this unique nuclear architecture is correlated with a unique epigenomic landscape, we performed ATAC-seq on mouse rods and their most closely related cell type, cone photoreceptors. We find that thousands of loci are selectively closed in rods relative to cones as well as >60 additional cell types. Furthermore, we find that the open chromatin profile of photoreceptors lacking the rod master regulator Nrl is nearly indistinguishable from that of native cones, indicating that Nrl is required for selective chromatin closure in rods. Finally, we identified distinct enrichments of transcription factor binding sites in rods and cones, revealing key differences in the cis-regulatory grammar of these cell types. Taken together, these data provide insight into the development and maintenance of photoreceptor identity, and highlight rods as an attractive system for studying the relationship between nuclear organization and local changes in gene regulation.
Myofibroblast differentiation and its functional properties are inhibited by nicotine and e-cigarette via mitochondrial OXPHOS complex III
Authors: Lei Wei , Lerner Chad , Sundar Isaac K. , Rahman Irfan
Published: March 2017

Nicotine is the major stimulant in tobacco products including e-cigarettes. Fibroblast to myofibroblast differentiation is a key process during wound healing and is dysregulated in lung diseases. The role of nicotine and e-cigarette derived nicotine on cellular functions including profibrotic response and other functional aspects is not known. We hypothesized that nicotine and e-cigarettes affect myofibroblast differentiation, gel contraction, and wound healing via mitochondria stress through nicotinic receptor-dependent mechanisms. To test the hypothesis, we exposed human lung fibroblasts with various doses of nicotine and e-cigarette condensate and determined myofibroblast differentiation, mitochondrial oxidative phosphorylation (OXPHOS), wound healing, and gel contraction at different time points. We found that both nicotine and e-cigarette inhibit myofibroblast differentiation as shown by smooth muscle actin and collagen type I, alpha 1 abundance. Nicotine and e-cigarette inhibited OXPHOS complex III accompanied by increased MitoROS, and this effect was augmented by complex III inhibitor antimycin A. These mitochondrial associated effects by nicotine resulted in inhibition of myofibroblast differentiation. These effects were associated with inhibition of wound healing and gel contraction suggesting that nicotine is responsible for dysregulated repair during injurious responses. Thus, our data suggest that nicotine causes dysregulated repair by inhibition of myofibroblast differentiation via OXPHOS pathway.
Effects of RET, NRG1 and NRG3 Polymorphisms in a Chinese Population with Hirschsprung Disease
Authors: Yang Dehua , Yang Jun , Li Shuai , Jiang Meng , Cao Guoqing , Yang Li , Zhang Xi , Zhou Ying , Li Kang , Tang Shao-tao
Published: March 2017

The RET proto-oncogene was identified as a major locus involved in Hirschsprung disease (HSCR). A genome-wide association study (GWAS) and whole exome sequencing identified NRG1 and NRG3 as additional HSCR susceptibility loci. We investigated the effects of RET (rs2506030 and rs2435357), NRG1 (rs2439302, rs16879552 and rs7835688) and NRG3 (rs10748842, rs10883866 and rs6584400) polymorphisms in a Chinese population with HSCR. We assessed single nucleotide polymorphisms (SNPs) in the RET, NRG1 and NRG3 genes in a cohort of 362 sporadic HSCR patients and 1,448 normal controls using a TaqMan genotyping assay. Significant associations were found between HSCR risk and rs2506030, rs2435357, rs2439302 and rs7835688 (odds ratio [OR] 1.64, P = 1.72E-06; 2.97, P = 5.15E-33; 1.84, P = 9.36E-11; and 1.93, P = 1.88E-12, respectively). Two locus analyses of SNPs indicated increased disease risks of HSCR between NRG1 rs2439302 and RET rs2435357 or rs2506030. RET rs2506030 (GG genotype) and rs2435357 (TT genotype), in combination with NRG1 rs2439302 (GG genotype), were strongly associated with the highest risk of HSCR (OR = 56.53, P = 4.50E-07) compared with the two loci or a single SNP of either RET or NRG1. Our results support the association between genetic variation of RET and NRG1 and susceptibility to HSCR in the Chinese population.
Deriving Flood-Mediated Connectivity between River Channels and Floodplains: Data-Driven Approaches
Authors: Zhao Tongtiegang , Shao Quanxi , Zhang Yongyong
Published: March 2017

The flood-mediated connectivity between river channels and floodplains plays a fundamental role in flood hazard mapping and exerts profound ecological effects. The classic nearest neighbor search (NNS) fails to derive this connectivity because of spatial heterogeneity and continuity. We develop two novel data-driven connectivity-deriving approaches, namely, progressive nearest neighbor search (PNNS) and progressive iterative nearest neighbor search (PiNNS). These approaches are illustrated through a case study in Northern Australia. First, PNNS and PiNNS are employed to identify flood pathways on floodplains through forward tracking. That is, progressive search is performed to associate newly inundated cells in each time step to previously inundated cells. In particular, iterations in PiNNS ensure that the connectivity is continuous – the connection between any two cells along the pathway is built through intermediate inundated cells. Second, inundated floodplain cells are collectively connected to river channel cells through backward tracing. Certain river channel sections are identified to connect to a large number of inundated floodplain cells. That is, the floodwater from these sections causes widespread floodplain inundation. Our proposed approaches take advantage of spatial–temporal data. They can be applied to achieve connectivity from hydro-dynamic and remote sensing data and assist in river basin planning and management.
Human eyelid adipose tissue-derived Schwann cells promote regeneration of a transected sciatic nerve
Authors: Wang Gangyang , Cao Lingling , Wang Yang , Hua Yingqi , Cai Zhengdong , Chen Jun , Chen Lulu , Jin Yuqing , Niu Lina , Shen Hua , Lu Yan , Shen Zunli
Published: March 2017

Schwann cells (SCs) can promote the regeneration of injured peripheral nerves while the clinical application is limited by donor site complications and the inability to generate an ample amount of cells. In this study, we have isolated human eyelid adipose-derived Schwann cells (hE-SCs) from human eyelid adipose tissue and identified the cell phenotype and function. Using immunofluorescence and H & E staining, we detected subtle nerve fibers and SCs in human eyelid adipose tissue. Immunofluorescence staining indicated that hE-SCs expressed glial markers, such as S100, p75NTR GFAP, Sox10 and Krox20. To explore whether hE-SCs promote the regeneration of injured peripheral nervesin vivo,a Balb/c-nu mice model was used in the study, and mice were randomly assigned to five groups: Matrigel; hE-SCs/P0; hE-SCs/P2; hE-FLCs/P2; and Autograft. After 12 weeks, functional and histological assessments of the regenerated nerves showed that sciatic nerve defect was more effectively repaired in the hE-SCs/P2 group which achieved 66.1 ± 6.5% purity, than the other three groups and recovered to similar level to the Autograft group. These results indicated that hE-SCs can promote the regeneration of injured peripheral nerve and the abundant, easily accessible supply of adipose tissue might be a promising source of SCs for peripheral nerve repair.
Personalized chemotherapy selection for breast cancer using gene expression profiles
Authors: Yu Kaixian , Sang Qing-Xiang Amy , Lung Pei-Yau , Tan Winston , Lively Ty , Sheffield Cedric , Bou-Dargham Mayassa J. , Liu Jun S. , Zhang Jinfeng
Published: March 2017

Choosing the optimal chemotherapy regimen is still an unmet medical need for breast cancer patients. In this study, we reanalyzed data from seven independent data sets with totally 1079 breast cancer patients. The patients were treated with three different types of commonly used neoadjuvant chemotherapies: anthracycline alone, anthracycline plus paclitaxel, and anthracycline plus docetaxel. We developed random forest models with variable selection using both genetic and clinical variables to predict the response of a patient using pCR (pathological complete response) as the measure of response. The models were then used to reassign an optimal regimen to each patient to maximize the chance of pCR. An independent validation was performed where each independent study was left out during model building and later used for validation. The expected pCR rates of our method are significantly higher than the rates of the best treatments for all the seven independent studies. A validation study on 21 breast cancer cell lines showed that our prediction agrees with their drug-sensitivity profiles. In conclusion, the new strategy, called PRES (Personalized REgimen Selection), may significantly increase response rates for breast cancer patients, especially those with HER2 and ER negative tumors, who will receive one of the widely-accepted chemotherapy regimens.
Family-based case-control study of homotopic connectivity in first-episode, drug-naive schizophrenia at rest
Authors: Guo Wenbin , Liu Feng , Chen Jindong , Wu Renrong , Li Lehua , Zhang Zhikun , Zhao Jingping
Published: March 2017

Family-based case-control design is rarely used but powerful to reduce the confounding effects of environmental factors on schizophrenia. Twenty-eight first-episode, drug-naive patients with schizophrenia, 28 family-based controls (FBC), and 40 healthy controls (HC) underwent resting-state functional MRI. Voxel-mirrored homotopic connectivity (VMHC), receiver operating characteristic curve (ROC), and support vector machine (SVM) were used to process the data. Compared with the FBC, the patients showed lower VMHC in the precuneus, fusiform gyrus/cerebellum lobule VI, and lingual gyrus/cerebellum lobule VI. The patients exhibited lower VMHC in the precuneus relative to the HC. ROC analysis exhibited that the VMHC values in these brain regions might not be ideal biomarkers to distinguish the patients from the FBC/HC. However, SVM analysis indicated that a combination of VMHC values in the precuneus and lingual gyrus/cerebellum lobule VI might be used as a potential biomarker to distinguish the patients from the FBC with a sensitivity of 96.43%, a specificity of 89.29%, and an accuracy of 92.86%. Results suggested that patients with schizophrenia have decreased homotopic connectivity in the motor and low level sensory processing regions. Neuroimaging studies can adopt family-based case-control design as a viable option to reduce the confounding effects of environmental factors on schizophrenia.
Formation of the 2015 Shenzhen landslide as observed by SAR shape-from-shading
Authors: Wang Chisheng , Li Qingquan , Zhu Jiasong , Gao Wei , Shan Xinjian , Song Jun , Ding Xiaoli
Published: March 2017

The time-series topography change of a landfill site before its failure has rarely been surveyed in detail. However, this information is important for both landfill management and early warning of landslides. Here, we take the 2015 Shenzhen landslide as an example, and we use the radar shape-from-shading (SFS) technique to retrieve time-series digital elevation models of the landfill. The results suggest that the total filling volume reached 4,074,300 m3 in the one and a half years before the landslide, while 2,817,400 m3 slid down in the accident. Meanwhile, the landfill rate in most areas exceeded 2 m/month, which is the empirical upper threshold in landfill engineering. Using topography captured on December 12, 2015, the slope safety analysis gives a factor of safety of 0.932, suggesting that this slope was already hazardous before the landslide. We conclude that the synthetic aperture radar (SAR) SFS technique has the potential to contribute to landfill failure monitoring.
Associations between Tumor Vascularity, Vascular Endothelial Growth Factor Expression and PET/MRI Radiomic Signatures in Primary Clear-Cell–Renal-Cell-Carcinoma: Proof-of-Concept Study
Authors: Yin Qingbo , Hung Sheng-Che , Wang Li , Lin Weili , Fielding Julia R. , Rathmell W. Kimryn , Khandani Amir H. , Woods Michael E. , Milowsky Matthew I. , Brooks Samira A. , Wallen Eric. M. , Shen Dinggang
Published: March 2017

Studies have shown that tumor angiogenesis is an essential process for tumor growth, proliferation and metastasis. Also, tumor angiogenesis is an important prognostic factor of clear cell renal cell carcinoma (ccRCC), as well as a factor in guiding treatment with antiangiogenic agents. Here, we attempted to find the associations between tumor angiogenesis and radiomic imaging features from PET/MRI. Specifically, sparse canonical correlation analysis was conducted on 3 feature datasets (i.e., radiomic imaging features, tumor microvascular density (MVD), and vascular endothelial growth factor (VEGF) expression) from 9 patients with primary ccRCC. In order to overcome the potential bias of intratumoral heterogeneity of angiogenesis, this study investigated the relationship between regional expressions of angiogenesis and VEGF, and localized radiomic features from different parts within the tumors. Our study highlighted the significant strong correlations between radiomic features and MVD, and also demonstrated that the spatiotemporal features extracted from DCE-MRI provided stronger radiomic correlation to MVD than the textural features extracted from Dixon sequences and FDG PET. Furthermore, PET/MRI, which takes advantage of the combined functional and structural information, had higher radiomics correlation to MVD than solely utilizing PET or MRI alone.
Circulating TNF Receptors 1 and 2 Predict Mortality in Patients with End-stage Renal Disease Undergoing Dialysis
Authors: Gohda Tomohito , Maruyama Shuntaro , Kamei Nozomu , Yamaguchi Saori , Shibata Terumi , Murakoshi Maki , Horikoshi Satoshi , Tomino Yasuhiko , Ohsawa Isao , Gotoh Hiromichi , Nojiri Shuko , Suzuki Yusuke
Published: March 2017

Relatively high circulating levels of soluble tumor necrosis factor (TNF) receptors (TNFRs: TNFR1, TNFR2) have been associated with not only progression to end-stage renal disease but also mortality in patients with diabetes. It remains unknown whether elevated TNFR levels in haemodialysis patients are associated with mortality. We studied 319 patients receiving maintenance haemodialysis who were followed for a median of 53 months. Circulating markers of TNF pathway (TNFα and TNFRs) were measured with immunoassay. Strong positive correlations between TNFR1 and TNFR2 were observed (r = 0.81, P < 0.0001). During follow-up, 88 (27.6%) patients died of any cause (40 [45.5%] died of cardiovascular disease). In the Cox multivariate model, either TNFR but not TNFα remained a significant independent predictor of all-cause mortality (TNFR1: hazard ratio [HR] 2.34, 95% confidence interval [CI], 1.50–3.64; TNFR2: HR 2.13, 95% CI 1.38–3.29) after adjustment for age, prior cardiovascular disease, predialysis systolic blood pressure, and large systolic blood pressure decline during dialysis session. For cardiovascular mortality, significance was only observed in TNFR1 (TNFR1: HR 2.15, 95% CI 1.13–4.10). Elevated TNFRs levels were associated with the risk of cardiovascular and/or all-cause mortality independent of all relevant covariates in patients undergoing haemodialysis.
Nucleophosmin Interacts with PIN2/TERF1-interacting Telomerase Inhibitor 1 (PinX1) and Attenuates the PinX1 Inhibition on Telomerase Activity
Authors: Cheung Derek Hang-Cheong , Ho Sai-Tim , Lau Kwok-Fai , Jin Rui , Wang Ya-Nan , Kung Hsiang-Fu , Huang Jun-Jian , Shaw Pang-Chui
Published: March 2017

Telomerase activation and telomere maintenance are critical for cellular immortalization and transformation. PIN2/TERF1-interacting telomerase inhibitor 1 (PinX1) is a telomerase regulator and the aberrant expression of PinX1 causes telomere shortening. Identifying PinX1-interacting proteins is important for understanding telomere maintenance. We found that PinX1 directly interacts with nucleophosmin (NPM), a protein that has been shown to positively correlate with telomerase activity. We further showed that PinX1 acts as a linker in the association between NPM and hTERT, the catalytic subunit of telomerase. Additionally, the recruitment of NPM by PinX1 to the telomerase complex could partially attenuate the PinX1-mediated inhibition on telomerase activity. Taken together, our data reveal a novel mechanism that regulates telomerase activation through the interaction between NPM, PinX1 and the telomerase complex.
A Peptide Amphiphile Organogelator of Polar Organic Solvents
Authors: Rouse Charlotte K. , Martin Adam D. , Easton Christopher J. , Thordarson Pall
Published: March 2017

A peptide amphiphile is reported, that gelates a range of polar organic solvents including acetonitrile/water, N,N-dimethylformamide and acetone, in a process dictated by β-sheet interactions and facilitated by the presence of an alkyl chain. Similarities with previously reported peptide amphiphile hydrogelators indicate analogous underlying mechanisms of gelation and structure-property relationships, suggesting that peptide amphiphile organogel design may be predictably based on hydrogel precedents.
Mapping sites of herpes simplex virus type 1 glycoprotein D that permit insertions and impact gD and gB receptors usage
Authors: Fan Qing , Kopp Sarah , Connolly Sarah A. , Muller William J. , Longnecker Richard
Published: March 2017

Glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) is one of four glycoproteins essential for HSV entry and cell fusion. The purpose of this study was to determine the plasticity of gD to tolerate insertion or deletion mutations and to construct an oncolytic HSV-1 that utilizes the disialoganglioside GD2 as a HSV-1 entry receptor. We found that the N-terminus of gD tolerates long insertions, whereas residues adjacent to the gD Ig-like V-type core tolerated shorter insertions (up to 15 amino acids), but not greater than 60 amino acids. Recombinant HSV-1 containing the ch14.18 single chain variable fragment (scFv) at the N-terminus of gD failed to mediate entry, even though the ch14.18 scFv-gD chimera Fc bound to neuroblastoma cells expressing GD2. Finally, we found that hyperfusogenic gB mutants enhanced fusion to a greater degree with the gB receptor the paired immunoglobulin-like type 2 receptor alpha (PILRα) than with gD receptors HVEM and nectin-1. Hyperfusogenic gB could restore the fusion function with PILRα when a gD constructed contained only the “profusion domain” (PFD), suggesting the hyperfusogenic form of gB may regulate fusion of PILRα via a novel mechanism through gH/gL and the gD PFD.
Time-lapse imaging reveals highly dynamic structural maturation of postnatally born dentate granule cells in organotypic entorhino-hippocampal slice cultures
Authors: Radic Tijana , Jungenitz Tassilo , Singer Mathias , Beining Marcel , Cuntz Hermann , Vlachos Andreas , Deller Thomas , Schwarzacher Stephan W.
Published: March 2017

Neurogenesis of hippocampal granule cells (GCs) persists throughout mammalian life and is important for learning and memory. How newborn GCs differentiate and mature into an existing circuit during this time period is not yet fully understood. We established a method to visualize postnatally generated GCs in organotypic entorhino-hippocampal slice cultures (OTCs) using retroviral (RV) GFP-labeling and performed time-lapse imaging to study their morphological development in vitro. Using anterograde tracing we could, furthermore, demonstrate that the postnatally generated GCs in OTCs, similar to adult born GCs, grow into an existing entorhino-dentate circuitry. RV-labeled GCs were identified and individual cells were followed for up to four weeks post injection. Postnatally born GCs exhibited highly dynamic structural changes, including dendritic growth spurts but also retraction of dendrites and phases of dendritic stabilization. In contrast, older, presumably prenatally born GCs labeled with an adeno-associated virus (AAV), were far less dynamic. We propose that the high degree of structural flexibility seen in our preparations is necessary for the integration of newborn granule cells into an already existing neuronal circuit of the dentate gyrus in which they have to compete for entorhinal input with cells generated and integrated earlier.
Protein-ligand binding affinity determination by the waterLOGSY method: An optimised approach considering ligand rebinding
Authors: Huang Renjie , Bonnichon Arnaud , Claridge Timothy D. W. , Leung Ivanhoe K. H.
Published: March 2017

WaterLOGSY is a popular ligand-observed NMR technique to screen for protein-ligand interactions, yet when applied to measure dissociation constants (KD) through ligand titration, the results were found to be strongly dependent on sample conditions. Herein, we show that accurate KDs can be obtained by waterLOGSY with optimised experimental setup.
Copper-catalyzed Direct 2-Arylation of Benzoxazoles and Benzoimidazoles with Aryl Bromides and Cytotoxicity of Products
Authors: Jia Nan-Nan , Tian Xin-Chuan , Qu Xiao-Xia , Chen Xing-Xiu , Cao Ya-Nan , Yao Yun-Xin , Gao Feng , Zhou Xian-Li
Published: March 2017

An efficient copper-catalyzed direct 2-arylation of benzoxazoles and benzoimidazoles with aryl bromides is presented. The CuI/PPh3-based catalyst promotes the installation of various aryl and heteroaryl groups through a C-H activation process in good to excellent yields. The cytotoxicity of obtained 2-aryl benzoxazoles (benzoimidazoles) was also evaluated and 1-methyl-2-(naphthalen-1-yl)benzoimidazole showed potential cytotoxicity.
Coexistence of spin ordering on ladders and spin dimer formation in a new-structure-type compound Sr2Co3S2O3
Authors: Lai Kwing To , Valldor Martin
Published: March 2017

We report on the syntheses and characterizations of single crystalline and polycrystalline Sr2Co3S2O3with a novel crystal structure type. It contains Co–O 2-leg rectangular ladders and necklace ladders. The two ladders share common legs and construct ahybrid spin ladder. A rare meridional heteroleptic octahedral coordination is found for the Co2+ions in the 2-leg ladder. Within the necklace ladders, the Co2+ions are intrans-octahedral coordination. An antiferromagnetic order is observed at TN ~ 267 K, while a broad maximum in magnetic susceptibility is found below TN. This relatively high ordering temperature among Co-based ladder compounds is related to the highly anisotropicmer-coordination of the Co2+ions. Thetrans-octahedrally coordinated Co2+ions, on the other hand, corresponds to the possible short-range magnetic correlations through dimers with an effective "Equation missing". This results in a rare situation that spin ordering and spin dimers coexist down to 2 K.
Adiponectin deficiency contributes to the development and progression of benign prostatic hyperplasia in obesity
Authors: Fu Shi , Xu Huan , Gu Meng , Liu Chong , Wang Qiong , Wan Xiang , Chen Yanbo , Chen Qi , Peng Yubing , Cai Zhikang , Zhou Juan , Wang Zhong
Published: March 2017

The incidence of benign prostatic hyperplasia (BPH) is increasing among obese individuals, but few studies have fully explained the underlying mechanisms. We aimed to elucidate the relationship between obesity and BPH. Herein, we show that in prostatic epithelial and stromal cells, adiponectin exerts multifunctional effects including anti-proliferation, blocking of G1/S-phase progression and the promotion of apoptosis via inhibiting the MEK-ERK-p90RSK axis. Furthermore, we found that a high-fat diet (HFD) led to adiponectin deficiency and microscopic BPH in a mouse model of obesity. And an adiponectin supplement protected the obese mice from microscopic BPH. The present study provides evidence that adiponectin is a protective regulator in the development and progression of BPH and that adiponectin deficiency causally links BPH with obesity.
Ebola virus infection kinetics in chimeric mice reveal a key role of T cells as barriers for virus dissemination
Authors: Lüdtke Anja , Ruibal Paula , Wozniak David M. , Pallasch Elisa , Wurr Stephanie , Bockholt Sabrina , Gómez-Medina Sergio , Qiu Xiangguo , Kobinger Gary P. , Rodríguez Estefanía , Günther Stephan , Krasemann Susanne , Idoyaga Juliana , Oestereich Lisa , Muñoz-Fontela César
Published: March 2017

Ebola virus (EBOV) causes severe systemic disease in humans and non-human primates characterized by high levels of viremia and virus titers in peripheral organs. The natural portals of virus entry are the mucosal surfaces and the skin where macrophages and dendritic cells (DCs) are primary EBOV targets. Due to the migratory properties of DCs, EBOV infection of these cells has been proposed as a necessary step for virus dissemination via draining lymph nodes and blood. Here we utilize chimeric mice with competent hematopoietic-driven immunity, to show that EBOV primarily infects CD11b+ DCs in non-lymphoid and lymphoid tissues, but spares the main cross-presenting CD103+ DC subset. Furthermore, depletion of CD8 and CD4 T cells resulted in loss of early control of virus replication, viremia and fatal Ebola virus disease (EVD). Thus, our findings point out at T cell function as a key determinant of EVD progress and outcome.
Elevated Fibroblast growth factor 21 (FGF21) in obese, insulin resistant states is normalised by the synthetic retinoid Fenretinide in mice
Authors: Morrice Nicola , Mcilroy George D. , Tammireddy Seshu R. , Reekie Jennifer , Shearer Kirsty D. , Doherty Mary K. , Delibegović Mirela , Whitfield Phillip D. , Mody Nimesh
Published: March 2017

Fibroblast growth factor 21 (FGF21) has emerged as an important beneficial regulator of glucose and lipid homeostasis but its levels are also abnormally increased in insulin-resistant states in rodents and humans. The synthetic retinoid Fenretinide inhibits obesity and improves glucose homeostasis in mice and has pleotropic effects on cellular pathways. To identify Fenretinide target genes, we performed unbiased RNA-seq analysis in liver from mice fed high-fat diet ± Fenretinide. Strikingly, Fgf21 was the most downregulated hepatic gene. Fenretinide normalised elevated levels of FGF21 in both high-fat diet-induced obese mice and in genetically obese-diabetic Leprdbmice. Moreover, Fenretinide-mediated suppression of FGF21 was independent of body weight loss or improved hepatic insulin sensitivity and importantly does not induce unhealthy metabolic complications. In mice which have substantially decreased endogenous retinoic acid biosynthesis, Fgf21 expression was increased, whereas acute pharmacological retinoid treatment decreased FGF21 levels. The repression of FGF21 levels by Fenretinide occurs by reduced binding of RARα and Pol-II at the Fgf21 promoter. We therefore establish Fgf21 as a novel gene target of Fenretinide signalling via a retinoid-dependent mechanism. These results may be of nutritional and therapeutic importance for the treatment of obesity and type-2 diabetes.
Aberrant Epicardial Adipose Tissue Extracellular Matrix Remodeling in Patients with Severe Ischemic Cardiomyopathy: Insight from Comparative Quantitative Proteomics
Authors: Jiang Ding-Sheng , Zeng Hao-Long , Li Rui , Huo Bo , Su Yun-Shu , Fang Jing , Yang Qing , Liu Li-Gang , Hu Min , Cheng Cai , Zhu Xue-Hai , Yi Xin , Wei Xiang
Published: March 2017

There is ample evidence indicating that epicardial adipose tissue (EAT) volume and thickness is positively associated with coronary artery disease (CAD). However, the exact pathological changes in the human EAT after myocardial ischemia remains largely unclear. In the current study, we applied a comparative quantitative proteomics to elucidate the altered biological processes in the EAT of ischemic cardiomyopathy (ICM) patients. A total of 1649 proteins were successfully quantified in our study, among which 165 proteins were significantly changed (ratio <0.8 or >1.2 fold and p < 0.05 in both repetitions) in EAT of ICM individuals. Gene ontology (GO) enrichment analysis revealed that cardiac structure and cellular metabolism were over-represented among these regulated proteins. The hypertrophic cardiomyopathy, adrenergic signaling in cardiomyocytes, extracellular matrix (ECM)-receptor interaction, phagosome, Glycolysis/Gluconeogenesis, and PPAR signaling pathway were highlighted by the KEGG PATHWAY analysis. More importantly, we found that the proteins responsible for extracellular matrix organization were dramatically increased in EAT of ICM patients. In addition, the picrosirius red (PSR) staining results showed that the collagen fiber content was prominently increased, which indicated the EAT of ICM individuals underwent extracellular matrix remodeling and ERK1/2 activation maybe responsible for these pathological changes partially.
Passion fruit-like nano-architectures: a general synthesis route
Authors: Cassano D. , David J. , Luin S. , Voliani V.
Published: March 2017

Noble metal nanostructures have demonstrated a number of intriguing features for both medicine and catalysis. However, accumulation issues have prevented their clinical translation, while their use in catalysis has shown serious efficiency and stability hurdles. Here we introduce a simple and robust synthetic protocol for passion fruit-like nano-architectures composed by a silica shell embedding polymeric arrays of ultrasmall noble metal nanoparticles. These nano-architectures show interesting features for both oncology and catalysis. They avoid the issue of persistence in organism thanks to their fast biodegradation in renal clearable building blocks. Furthermore, their calcination results in yolk-shell structures composed by naked metal or alloy nanospheres shielded from aggregation by a silica shell.
Strain-tuned enhancement of ferromagnetic TC to 176 K in Sm-doped BiMnO3 thin films and determination of magnetic phase diagram
Authors: Choi Eun-Mi , Kleibeuker Josée E. , MacManus-Driscoll Judith L.
Published: March 2017

BiMnO3 is a promising multiferroic material but it’s ferromagnetic TC is well below room temperature and the magnetic phase diagram is unknown. In this work, the relationship between magnetic transition temperature (TC) and the substrate induced (pseudo-) tetragonal distortion (ratio of out-of-plane to in-plane lattice parameters, c/a) in BiMnO3 thin films, lightly doped to optimize lattice dimensions, was determined. For c/a > 0.99, hidden antiferromagnetism was revealed and the magnetisation versus temperature curves showed a tail behaviour, whereas for c/a < 0.99 clear ferromagnetism was observed. A peak TC of up to 176 K, more than 70 K higher than for bulk BiMnO3, was achieved through precise strain tuning. The TC was maximised for strong tensile in-plane strain which produced weak octahedral rotations in the out-of-plane direction, an orthorhombic-like structure, and strong ferromagnetic coupling.
LRP1 influences trafficking of N-type calcium channels via interaction with the auxiliary α2δ-1 subunit
Authors: Kadurin Ivan , Rothwell Simon W. , Lana Beatrice , Nieto-Rostro Manuela , Dolphin Annette C.
Published: March 2017

Voltage-gated Ca2+ (CaV) channels consist of a pore-forming α1 subunit, which determines the main functional and pharmacological attributes of the channel. The CaV1 and CaV2 channels are associated with auxiliary β- and α2δ-subunits. The molecular mechanisms involved in α2δ subunit trafficking, and the effect of α2δ subunits on trafficking calcium channel complexes remain poorly understood. Here we show that α2δ-1 is a ligand for the Low Density Lipoprotein (LDL) Receptor-related Protein-1 (LRP1), a multifunctional receptor which mediates trafficking of cargoes. This interaction with LRP1 is direct, and is modulated by the LRP chaperone, Receptor-Associated Protein (RAP). LRP1 regulates α2δ binding to gabapentin, and influences calcium channel trafficking and function. Whereas LRP1 alone reduces α2δ-1 trafficking to the cell-surface, the LRP1/RAP combination enhances mature glycosylation, proteolytic processing and cell-surface expression of α2δ-1, and also increase plasma-membrane expression and function of CaV2.2 when co-expressed with α2δ-1. Furthermore RAP alone produced a small increase in cell-surface expression of CaV2.2, α2δ-1 and the associated calcium currents. It is likely to be interacting with an endogenous member of the LDL receptor family to have these effects. Our findings now provide a key insight and new tools to investigate the trafficking of calcium channel α2δ subunits.
Vlasouliolides A-D, four rare C17/C15 sesquiterpene lactone dimers with potential anti-inflammatory activity from Vladimiria souliei
Authors: Chen Li-Ping , Wu Guo-Zhen , Zhang Jian-Ping , Ye Ji , Liu Qing-Xin , Shen Yun-Heng , Li Hui-Liang , Zhang Wei-Dong
Published: March 2017

Vlasouliolides A-D (1–4), four rare sesquiterpene lactone dimers, were isolated from Vladimiria souliei. The common structural characteristic of 1–4 is the C32 skeleton comprising two sesquiterpene lactone units linked by a C11-C13′ single bond with one acetyl connected to the C-13 position of one of the two sesquiterpene lactone units. The stereochemistries of 1–4 were assigned by a combination of NOESY correlations and Cu-Κα X-ray crystallographic analyses. Compounds 1–4 strongly inhibited the production of NO in LPS-stimulated RAW 264.7 cells. Furthermore, 1 and 2 inhibited the activation of NF-κB in LPS-induced 293T cells.
Glycol Derived Carbon- TiO2 as Low Cost and High Performance Anode Material for Sodium-Ion Batteries
Authors: Tao Hongwei , Zhou Min , Wang Kangli , Cheng Shijie , Jiang Kai
Published: March 2017

Carbon coated TiO2 (TiO2@C) is fabricated by a convenient and green one-pot solvothermal method, in which ethylene glycol serve as both the reaction medium and carbon source without the addition of any other carbon additives. During the solvothermal process, ethylene glycol polymerize and coordinate with Ti4+ to form the polymeric ligand precursor, then the polymer brushes carbonize and convert to homogeneous carbon layer firmly anchored on the TiO2 nanoparticles (~1 nm thickness). The polymerization and carbonization process of the ethylene glycol is confirmed by FT-IR, Raman, TG and TEM characterizations. Benefiting from the well-dispersed nanoparticles and uniform carbon coating, the as-prepared TiO2@C demonstrate a high reversible capacity of 317 mAh g−1 (94.6% of theoretical value), remarkable rate capability of 125 mAh g−1 at 3.2 A g−1 and superior cycling stability over 500 cycles, possibly being one of the highest capacities reported for TiO2.
Treatment of steroid-induced osteonecrosis of the femoral head using porous Se@SiO2 nanocomposites to suppress reactive oxygen species
Authors: Deng Guoying , Niu Kerun , Zhou Feng , Li Buxiao , Kang Yingjie , Liu Xijian , Hu Junqing , Li Bo , Wang Qiugen , Yi Chengqing , Wang Qian
Published: March 2017

Reducing oxidative stress (ROS) have been demonstrated effective for steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH). Selenium (Se) plays an important role in suppressing oxidative stress and has huge potential in ONFH treatments. However the Se has a narrow margin between beneficial and toxic effects which make it hard for therapy use in vivo. In order to make the deficiency up, a control release of Se (Se@SiO2) were realized by nanotechnology modification. Porous Se@SiO2 nanocomposites have favorable biocompatibility and can reduced the ROS damage effectively. In vitro, the cck-8 analysis, terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) stain and flow cytometry analysis showed rare negative influence by porous Se@SiO2 nanocomposites but significantly protective effect against H2O2 by reducing ROS level (detected by DCFH-DA). In vivo, the biosafety of porous Se@SiO2 nanocomposites were confirmed by the serum biochemistry, the ROS level in serum were significantly reduced and the curative effect were confirmed by Micro CT scan, serum Elisa assay (inflammatory factors), Western blotting (quantitative measurement of ONFH) and HE staining. It is expected that the porous Se@SiO2 nanocomposites may prevent steroid-induced ONFH by reducing oxidative stress.
Optical and electrical characterizations of multifunctional silver phosphate glass and polymer-based optical fibers
Authors: Rioux Maxime , Ledemi Yannick , Morency Steeve , de Lima Filho Elton Soares , Messaddeq Younès
Published: March 2017

In recent years, the fabrication of multifunctional fibers has expanded for multiple applications that require the transmission of both light and electricity. Fibers featuring these two properties are usually composed either of a single material that supports the different characteristics or of a combination of different materials. In this work, we fabricated (i) novel single-core step-index optical fibers made of electrically conductive AgI-AgPO3-WO3 glass and (ii) novel multimaterial fibers with different designs made of AgI-AgPO3-WO3 glass and optically transparent polycarbonate and poly (methyl methacrylate) polymers. The multifunctional fibers produced show light transmission over a wide range of wavelengths from 500 to 1000 nm for the single-core fibers and from 400 to 1000 nm for the multimaterial fibers. Furthermore, these fibers showed excellent electrical conductivity with values ranging between 10−3 and 10−1 S·cm−1 at room temperature within the range of AC frequencies from 1 Hz to 1 MHz. Multimodal taper-tipped fibre microprobes were then fabricated and were characterized. This advanced design could provide promising tools for in vivo electrophysiological experiments that require light delivery through an optical core in addition to neuronal activity recording.
Redox-responsive dextran based theranostic nanoparticles for near-infrared/magnetic resonance imaging and magnetically targeted photodynamic therapy
Authors: Ding Zexuan , Liu Peng , Hu Dehong , Sheng Zonghai , Yi Huqiang , Gao Guanhui , Wu Yayun , Zhang Pengfei , Ling Shaozhi , Cai Lintao
Published: March 2017

A multifunctional theranostic nanoparticle system for near-infrared (NIR)/magnetic resonance (MR) dual-modality imaging and magnetic targeting.
In search of the best DFT functional for dealing with organic anionic species
Authors: Borioni José L. , Puiatti Marcelo , Vera D. Mariano A. , Pierini Adriana B.
Published: March 2017

“And the winner is…” This work assesses the ability of different Density Functional Theory (DFT) functionals for a proper treatment of organic anionic species.
Identifying the optimal anticancer targets from the landscape of a cancer–immunity interaction network
Authors: Li Chunhe
Published: March 2017

The landscape and optimization of transition actions provide a new physical and quantitative way to understand the mechanisms of cancer immunotherapy and identify the optimal combinations of targets for the cancer–immunity interplay.