bluuebunny/crossref_metadata_2025 huggingface dataset:
MINTmap: fast and exhaustive profiling of nuclear and mitochondrial tRNA fragments from short RNA-seq data
Authors: Loher Phillipe , Telonis Aristeidis G. , Rigoutsos Isidore
Published: February 2017

Transfer RNA fragments (tRFs) are an established class of constitutive regulatory molecules that arise from precursor and mature tRNAs. RNA deep sequencing (RNA-seq) has greatly facilitated the study of tRFs. However, the repeat nature of the tRNA templates and the idiosyncrasies of tRNA sequences necessitate the development and use of methodologies that differ markedly from those used to analyze RNA-seq data when studying microRNAs (miRNAs) or messenger RNAs (mRNAs). Here we present MINTmap (for MItochondrial and Nuclear TRF mapping), a method and a software package that was developed specifically for the quick, deterministic and exhaustive identification of tRFs in short RNA-seq datasets. In addition to identifying them, MINTmap is able to unambiguously calculate and report both raw and normalized abundances for the discovered tRFs. Furthermore, to ensure specificity, MINTmap identifies the subset of discovered tRFs that could be originating outside of tRNA space and flags them as candidate false positives. Our comparative analysis shows that MINTmap exhibits superior sensitivity and specificity to other available methods while also being exceptionally fast. The MINTmap codes are available throughhttps://github.com/TJU-CMC-Org/MINTmap/under an open source GNU GPL v3.0 license.
Mass Spectrometric Analysis of TRPM6 and TRPM7 Phosphorylation Reveals Regulatory Mechanisms of the Channel-Kinases
Authors: Cai Na , Bai Zhiyong , Nanda Vikas , Runnels Loren W.
Published: February 2017

TRPM7 and TRPM6 were the first identified bifunctional channels to contain their own kinase domains, but how these channel-kinases are regulated is poorly understood. Previous studies identified numerous phosphorylation sites on TRPM7, but very little is known about TRPM6 phosphorylation or sites on TRPM7 transphosphorylated by TRPM6. Our mass spectrometric analysis of homomeric and heteromeric TRPM7 and TRPM6 channels identified phosphorylation sites on both proteins, as well as several prominent sites on TRPM7 that are commonly modified through autophosphorylation and transphosphorylation by TRPM6. We conducted a series of amino acid substitution analyses and identified S1777, in TRPM7’s catalytic domain, and S1565, in TRPM7’s exchange domain that mediates kinase dimerization, as potential regulatory sites. The phosphomimetic S1777D substitution disrupted catalytic activity, most likely by causing an electrostatic perturbation at the active site. The S1565D phosphomimetic substitution also inactivated the kinase but did so without interfering with kinase dimerization. Molecular modeling indicates that phosphorylation of S1565 is predicted to structurally affect TRPM7’s functionally conserved N/D loop, which is thought to influence the access of substrate to the active site pocket. We propose that phosphorylation of S1565 within the exchange domain functions as a regulatory switch to control TRPM7 catalytic activity.
High quality AlN epilayers grown on nitrided sapphire by metal organic chemical vapor deposition
Authors: Wang Jiaming , Xu Fujun , He Chenguang , Zhang Lisheng , Lu Lin , Wang Xinqiang , Qin Zhixin , Shen Bo
Published: February 2017

Influence of sapphire pretreatment conditions on crystalline quality of AlN epilayers has been investigated by metal organic chemical vapor deposition (MOCVD). Compared to alumination treatment, it is found that appropriate sapphire nitridation significantly straightens the surface atomic terraces and decreases the X-ray diffraction (0002) full width at half maximum (FWHM) to a minimum of 55 arcsec, indicating a great improvement of the tilting feature of the grain structures in the AlN epilayer. More importantly, there is no inversion domains (IDs) found in the AlN epilayers, which clarifies that optimal sapphire nitridation is promising in the growth of high quality AlN. It is deduced that the different interfacial atomic structures caused by various pretreatment conditions influence the orientation of the AlN nucleation layer grains, which eventually determines the tilting features of the AlN epilayers.
Induction of hair follicle dermal papilla cell properties in human induced pluripotent stem cell-derived multipotent LNGFR(+)THY-1(+) mesenchymal cells
Authors: Veraitch Ophelia , Mabuchi Yo , Matsuzaki Yumi , Sasaki Takashi , Okuno Hironobu , Tsukashima Aki , Amagai Masayuki , Okano Hideyuki , Ohyama Manabu
Published: February 2017

The dermal papilla (DP) is a specialised mesenchymal component of the hair follicle (HF) that plays key roles in HF morphogenesis and regeneration. Current technical difficulties in preparing trichogenic human DP cells could be overcome by the use of highly proliferative and plastic human induced pluripotent stem cells (hiPSCs). In this study, hiPSCs were differentiated into induced mesenchymal cells (iMCs) with a bone marrow stromal cell phenotype. A highly proliferative and plastic LNGFR(+)THY-1(+) subset of iMCs was subsequently programmed using retinoic acid and DP cell activating culture medium to acquire DP properties. The resultant cells (induced DP-substituting cells [iDPSCs]) exhibited up-regulated DP markers, interacted with human keratinocytes to up-regulate HF related genes, and when co-grafted with human keratinocytes in vivo gave rise to fibre structures with a hair cuticle-like coat resembling the hair shaft, as confirmed by scanning electron microscope analysis. Furthermore, iDPSCs responded to the clinically used hair growth reagent, minoxidil sulfate, to up-regulate DP genes, further supporting that they were capable of, at least in part, reproducing DP properties. Thus, LNGFR(+)THY-1(+) iMCs may provide material for HF bioengineering and drug screening for hair diseases.
Distinct signatures of dental plaque metabolic byproducts dictated by periodontal inflammatory status
Authors: Sakanaka Akito , Kuboniwa Masae , Hashino Ei , Bamba Takeshi , Fukusaki Eiichiro , Amano Atsuo
Published: February 2017

Onset of chronic periodontitis is associated with an aberrant polymicrobial community, termed dysbiosis. Findings regarding its etiology obtained using high-throughput sequencing technique suggested that dysbiosis holds a conserved metabolic signature as an emergent property. The purpose of this study was to identify robust biomarkers for periodontal inflammation severity. Furthermore, we investigated disease-associated metabolic signatures of periodontal microbiota using a salivary metabolomics approach. Whole saliva samples were obtained from adult subjects before and after removal of supragingival plaque (debridement). Periodontal inflamed surface area (PISA) was employed as an indicator of periodontal inflammatory status. Based on multivariate analyses using pre-debridement salivary metabolomics data, we found that metabolites associated with higher PISA included cadaverine and hydrocinnamate, while uric acid and ethanolamine were associated with lower PISA. Next, we focused on dental plaque metabolic byproducts by selecting salivary metabolites significantly decreased following debridement. Metabolite set enrichment analysis revealed that polyamine metabolism, arginine and proline metabolism, butyric acid metabolism, and lysine degradation were distinctive metabolic signatures of dental plaque in the high PISA group, which may be related to the metabolic signatures of disease-associated communities. Collectively, our findings identified potential biomarkers of periodontal inflammatory status and also provide insight into metabolic signatures of dysbiotic communities.
Status of HBsAg seroprevalence in 15 million rural couples in China: a cross-sectional study
Authors: Zhang Long , Wang Yuan-Yuan , Huang Yan-Jie , Wang Qiao-Mei , Nelson Kenrad E. , Wang An-Qi , Shen Hai-Ping , Liu Xiao-Li , Zhang Yi-Ping , Yan Dong-Hai , Peng Zuo-Qi , Zhang Hong-Guang , Zhang Ya , Zhao Jun , Wang Yan , Yang Ying , He Yuan , Xu Ji-Hong , Liu Du-Jia , Guo Tong-Jun , Xin Xiao-Na , Zhou Hong , Ma Xu
Published: February 2017

A cross-sectional analysis of prevalence of hepatitis B virus infection (HBV) among rural couples was conducted between 2010 and 2014. Serologic HBV markers, including hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), were tested. Primary outcome of interest comprised HBsAg positivity in couples (both positive: F+M+, only wife positive: F+M−, only husband positive: F−M+), and secondary outcome consisted of prevalence and risk factors of HBsAg positivity among husbands or wives. Of 14,816,300 couples included, 0.7% were F+M+; 6.3% were F−M+; 4.4% were F+M−, resulting in the overall seroprevalence of 11.4%. Individually, 6.1% were HBsAg positive with a higher rate seen in husbands (7.0%) than in wives (5.2%). Wife’s HBeAg(+)/HBsAg (+) (AOR = 2.61), HBeAg(−)/HBsAg (+) (AOR = 2.23), positivity of syphilis (AOR = 1.50), living in a high-risk region (AOR = 1.46) were significantly predictors of HBsAg positivity in husbands. Prevalence and predictors of HBsAg positivity in wives had similar results. Our data show a high burden and discordant pattern of HBV infection in rural couples, and partner’s double positivity of HBeAg and HBsAg was the most significant factor of HBV infection in couples. A comprehensive strategy that emphasizes vaccination and education is needed.
SAMHD1 enhances nucleoside-analogue efficacy against HIV-1 in myeloid cells
Authors: Ordonez Paula , Kunzelmann Simone , Groom Harriet C. T. , Yap Melvyn W. , Weising Simon , Meier Chris , Bishop Kate N. , Taylor Ian A. , Stoye Jonathan P.
Published: February 2017

SAMHD1 is an intracellular enzyme that specifically degrades deoxynucleoside triphosphates into component nucleoside and inorganic triphosphate. In myeloid-derived dendritic cells and macrophages as well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosphohydrolase activity by reducing the cellular dNTP pool to a level that cannot support productive reverse transcription. We now show that, in addition to this direct effect on virus replication, manipulating cellular SAMHD1 activity can significantly enhance or decrease the anti-HIV-1 efficacy of nucleotide analogue reverse transcription inhibitors presumably as a result of modulating dNTP pools that compete for recruitment by viral polymerases. Further, a variety of other nucleotide-based analogues, not normally considered antiretrovirals, such as the anti-herpes drugs Aciclovir and Ganciclovir and the anti-cancer drug Clofarabine are now revealed as potent anti-HIV-1 agents, under conditions of low dNTPs. This in turn suggests novel uses for nucleotide analogues to inhibit HIV-1 in differentiated cells low in dNTPs.
Erratum: SOCS1 favors the epithelial-mesenchymal transition in melanoma, promotes tumor progression and prevents antitumor immunity by PD-L1 expression
Authors: Berzaghi R. , Maia V. S. C. , Pereira F. V. , Melo F. M. , Guedes M. S. , Origassa C. S. T. , Scutti J. B. , Matsuo A. L. , Câmara N. O. S. , Rodrigues E. G. , Travassos L. R.
Published: February 2017

Scientific Reports 7: Article number: 40585; published online: 12 January 2017; updated: 21 February 2017 Affiliation 1 was incorrectly listed as ‘Experimental Oncology Unit, Department of Microbiology, Immunology and Parasitology, University of São Paulo, São Paulo, Brazil’ in the original version of the Article.
Correction: Corrigendum: Comparative transcriptomic analysis uncovers the complex genetic network for resistance to Sclerotinia sclerotiorum in Brassica napus
Authors: Wu Jian , Zhao Qing , Yang Qingyong , Liu Han , Li Qingyuan , Yi Xinqi , Cheng Yan , Guo Liang , Fan Chuchuan , Zhou Yongming
Published: February 2017

Scientific Reports 6: Article number: 19007; published online: 08 January 2016; updated: 21 February 2017. The original version of this Article contained an incorrect version of Supplementary Table S7. This error has now been corrected in the HTML version of this Article; the PDF version was correctat the time of publication.
FOXO1 expression in keratinocytes promotes connective tissue healing
Authors: Zhang Chenying , Lim Jason , Liu Jian , Ponugoti Bhaskar , Alsadun Sarah , Tian Chen , Vafa Rameen , Graves Dana T.
Published: February 2017

Wound healing is complex and highly orchestrated. It is well appreciated that leukocytes, particularly macrophages, are essential for inducing the formation of new connective tissue, which requires the generation of signals that stimulate mesenchymal stem cells (MSC), myofibroblasts and fibroblasts. A key role for keratinocytes in this complex process has yet to be established. To this end, we investigated possible involvement of keratinocytes in connective tissue healing. By lineage-specific deletion of the forkhead box-O 1 (FOXO1) transcription factor, we demonstrate for the first time that keratinocytes regulate proliferation of fibroblasts and MSCs, formation of myofibroblasts and production of collagen matrix in wound healing. This stimulation is mediated by a FOXO1 induced TGFβ1/CTGF axis. The results provide direct evidence that epithelial cells play a key role in stimulating connective tissue healing through a FOXO1-dependent mechanism. Thus, FOXO1 and keratinocytes may be an important therapeutic target where healing is deficient or compromised by a fibrotic outcome.
RSPO3-LGR4 Regulates Osteogenic Differentiation Of Human Adipose-Derived Stem Cells Via ERK/FGF Signalling
Authors: Zhang Min , Zhang Ping , Liu Yunsong , Lv Longwei , Zhang Xiao , Liu Hao , Zhou Yongsheng
Published: February 2017

The four R-spondins (RSPOs) and their three related receptors, LGR4, 5 and 6, have emerged as a major ligand-receptor system with critical roles in development and stem cell survival. However, the exact roles of the RSPO-LGR system in osteogenesis remain largely unknown. In the present study, we showed that RSPO3-shRNA increased the osteogenic potential of human adipose-derived stem cells (hASCs) significantly. Mechanistically, we demonstrated that RSPO3 is a negative regulator of ERK/FGF signalling. We confirmed that inhibition of the ERK1/2 signalling pathway blocked osteogenic differentiation in hASCs, and the increased osteogenic capacity observed after RSPO3 knockdown in hASCs was reversed by inhibition of ERK signalling. Further, silencing of LGR4 inhibited the activity of ERK signalling and osteogenic differentiation of hASCs. Most importantly, we found that loss of LGR4 abrogated RSPO3-regulated osteogenesis and RSPO3-induced ERK1/2 signalling inhibition. Collectively, our data show that ERK signalling works downstream of LGR4 and RSPO3 regulates osteoblastic differentiation of hASCs possibly via the LGR4-ERK signalling.
Effects of abiotic factors on ecosystem health of Taihu Lake, China based on eco-exergy theory
Authors: Wang Ce , Bi Jun , Fath Brian D.
Published: February 2017

A lake ecosystem is continuously exposed to environmental stressors with non-linear interrelationships between abiotic factors and aquatic organisms. Ecosystem health depicts the capacity of system to respond to external perturbations and still maintain structure and function. In this study, we explored the effects of abiotic factors on ecosystem health of Taihu Lake in 2013, China from a system-level perspective. Spatiotemporal heterogeneities of eco-exergy and specific eco-exergy served as thermodynamic indicators to represent ecosystem health in the lake. The results showed the plankton community appeared more energetic in May, and relatively healthy in Gonghu Bay with both higher eco-exergy and specific eco-exergy; a eutrophic state was likely discovered in Zhushan Bay with higher eco-exergy but lower specific eco-exergy. Gradient Boosting Machine (GBM) approach was used to explain the non-linear relationships between two indicators and abiotic factors. This analysis revealed water temperature, inorganic nutrients, and total suspended solids greatly contributed to the two indicators that increased. However, pH rise driven by inorganic carbon played an important role in undermining ecosystem health, particularly when pH was higher than 8.2. This implies that climate change with rising CO2 concentrations has the potential to aggravate eutrophication in Taihu Lake where high nutrient loads are maintained.
Early hepatitis B surface antigen decline predicts treatment response to entecavir in patients with chronic hepatitis B
Authors: Peng Cheng-Yuan , Lai Hsueh-Chou , Su Wen-Pang , Lin Chia-Hsin , Chuang Po-Heng , Chen Sheng-Hung , Chen Ching-Hsiang
Published: February 2017

Early declines in serum hepatitis B surface (HBsAg) levels, their optimal cutoffs, and association with therapeutic endpoints in chronic hepatitis B (CHB) patients receiving entecavir treatment remain unclear. We prospectively enrolled 529 patients (195 hepatitis B e antigen [HBeAg]-positive and 334 HBeAg-negative) with a median treatment duration of 49.2 months. Median HBsAg levels declined significantly in both groups at Month 3, but only at Months 6–12 in the HBeAg-negative group. Both groups exhibited a significant HBsAg decline with each successive year of treatment. An HBsAg decline of ≥75% from baseline, assessed at Months 3 and 12 of treatment in the HBeAg-positive and -negative patients, respectively, independently predicted a virological response and HBeAg seroconversion in the HBeAg-positive patients, an HBsAg level of <100 IU/mL in the HBeAg-negative patients, and HBsAg loss in all the patients during treatment. HBsAg levels of <3,000 IU/mL at baseline combined with an HBsAg decline of ≥75% from baseline provided a predictive algorithm for HBsAg loss (positive and negative predictive values: 70% and 100%, respectively) during 5 years of treatment. The proposed cutoffs for defining an HBsAg decline may assist clinicians in early assessments of treatment responses in genotype B-infected or C-infected CHB patients receiving entecavir therapy.
Nucleobindin 1 binds to multiple types of pre-fibrillar amyloid and inhibits fibrillization
Authors: Bonito-Oliva Alessandra , Barbash Shahar , Sakmar Thomas P. , Graham W Vallen
Published: February 2017

During amyloid fibril formation, amyloidogenic polypeptides misfold and self assemble into soluble pre-fibrillar aggregates, i.e., protofibrils, which elongate and mature into insoluble fibrillar aggregates. An emerging class of chaperones, chaperone-like amyloid binding proteins (CLABPs), has been shown to interfere with aggregation of particular misfolded amyloid peptides or proteins. We have discovered that the calcium-binding protein nuclebindin-1 (NUCB1) is a novel CLABP. We show that NUCB1 inhibits aggregation of islet-amyloid polypeptide associated with type 2 diabetes mellitus, a-synuclein associated with Parkinson’s disease, transthyretin V30M mutant associated with familial amyloid polyneuropathy, and Aβ42 associated with Alzheimer’s disease by stabilizing their respective protofibril intermediates. Kinetic studies employing the modeling software AmyloFit show that NUCB1 affects both primary nucleation and secondary nucleation. We hypothesize that NUCB1 binds to the common cross-β-sheet structure of protofibril aggregates to “cap” and stabilize soluble macromolecular complexes. Transmission electron microscopy and atomic force microscopy were employed to characterize the size, shape and volume distribution of multiple sources of NUCB1-capped protofibrils. Interestingly, NUCB1 prevents Aβ42 protofibril toxicity in a cellular assay. NUCB1-stabilized amyloid protofibrils could be used as immunogens to prepare conformation-specific antibodies and as novel tools to develop screens for anti-protofibril diagnostics and therapeutics.
Successive extraction of As(V), Cu(II) and P(V) ions from water using spent coffee powder as renewable bioadsorbents
Authors: Hao Linlin , Wang Peng , Valiyaveettil Suresh
Published: February 2017

For the first time, renewable and easy accessible pre-bleached spent coffee powder coated with polyethylenimine (PEI) and ferric ions (Coffee-PEI-Fe) was used for the successive adsorption of As(V), Cu(II) and P(V) ions from spiked water samples. Fully characterized coffee-PEI-Fe was employed for batch mode experiments. Kinetic regression analysis showed that the adsorption processes of As(V) and P(V) anions follows a pseudo-second-order model, while the adsorption of Cu(II) ions fit with a pseudo-first-order model. The maximum adsorption capacities estimated by Langmuir model for As(V), Cu(II) and P(V) ions were 83.3, 200.1, and 50.2 mg/g, respectively. The simulated results revealed that the internal diffusion is the rate-determining step for the adsorptions of As(V) and Cu(II) ions, while film diffusion is the mass transfer resistance for the adsorption of P(V) ions on the surface of coffee-PEI-Fe. The successive adsorptions of adsorbates were achieved through electrostatic attraction between adsorbent surface and adsorbates. The dynamic column adsorption behavior of the adsorbent was described by Thomas model, which showed a good agreement with the experimental values (qexp). The results presented in this paper could be used for developing efficient adsorbent from renewable materials for water purification.
Epigenetic determinants of space radiation-induced cognitive dysfunction
Authors: Acharya Munjal M. , Baddour Al Anoud D. , Kawashita Takumi , Allen Barrett D. , Syage Amber R. , Nguyen Thuan H. , Yoon Nicole , Giedzinski Erich , Yu Liping , Parihar Vipan K. , Baulch Janet E.
Published: February 2017

Among the dangers to astronauts engaging in deep space missions such as a Mars expedition is exposure to radiations that put them at risk for severe cognitive dysfunction. These radiation-induced cognitive impairments are accompanied by functional and structural changes including oxidative stress, neuroinflammation, and degradation of neuronal architecture. The molecular mechanisms that dictate CNS function are multifaceted and it is unclear how irradiation induces persistent alterations in the brain. Among those determinants of cognitive function are neuroepigenetic mechanisms that translate radiation responses into altered gene expression and cellular phenotype. In this study, we have demonstrated a correlation between epigenetic aberrations and adverse effects of space relevant irradiation on cognition. In cognitively impaired irradiated mice we observed increased 5-methylcytosine and 5-hydroxymethylcytosine levels in the hippocampus that coincided with increased levels of the DNA methylating enzymes DNMT3a, TET1 and TET3. By inhibiting methylation using 5-iodotubercidin, we demonstrated amelioration of the epigenetic effects of irradiation. In addition to protecting against those molecular effects of irradiation, 5-iodotubercidin restored behavioral performance to that of unirradiated animals. The findings of this study establish the possibility that neuroepigenetic mechanisms significantly contribute to the functional and structural changes that affect the irradiated brain and cognition.
Different brain structures associated with artistic and scientific creativity: a voxel-based morphometry study
Authors: Shi Baoguo , Cao Xiaoqing , Chen Qunlin , Zhuang Kaixiang , Qiu Jiang
Published: February 2017

Creativity is the ability to produce original and valuable ideas or behaviors. In real life, artistic and scientific creativity promoted the development of human civilization; however, to date, no studies have systematically investigated differences in the brain structures responsible for artistic and scientific creativity in a large sample. Using voxel-based morphometry (VBM), this study identified differences in regional gray matter volume (GMV) across the brain between artistic and scientific creativity (assessed by the Creative Achievement Questionnaire) in 356 young, healthy subjects. The results showed that artistic creativity was significantly negatively associated with the regional GMV of the supplementary motor area (SMA) and anterior cingulate cortex (ACC). In contrast, scientific creativity was significantly positively correlated with the regional GMV of the left middle frontal gyrus (MFG) and left inferior occipital gyrus (IOG). Overall, artistic creativity was associated with the salience network (SN), whereas scientific creativity was associated with the executive attention network and semantic processing. These results may provide an effective marker that can be used to predict and evaluate individuals’ creative performance in the fields of science and art.
A recovery principle provides insight into auxin pattern control in the Arabidopsis root
Authors: Moore Simon , Liu Junli , Zhang Xiaoxian , Lindsey Keith
Published: February 2017

Regulated auxin patterning provides a key mechanism for controlling root growth and development. We have developed a data-driven mechanistic model using realistic root geometry and formulated a principle to theoretically investigate quantitative auxin pattern recovery following auxin transport perturbation. This principle reveals that auxin patterning is potentially controlled by multiple combinations of interlinked levels and localisation of influx and efflux carriers. We demonstrate that (1) when efflux carriers maintain polarity but change levels, maintaining the same auxin pattern requires non-uniform and polar distribution of influx carriers; (2) the emergence of the same auxin pattern, from different levels of influx carriers with the same nonpolar localisation, requires simultaneous modulation of efflux carrier level and polarity; and (3) multiple patterns of influx and efflux carriers for maintaining an auxin pattern do not have spatially proportional correlation. This reveals that auxin pattern formation requires coordination between influx and efflux carriers. We further show that the model makes various predictions that can be experimentally validated.
DUSP1 promoter methylation in peripheral blood leukocyte is associated with triple-negative breast cancer risk
Authors: Li Jing , Chen Yanbo , Yu Hongyuan , Tian Jingshen , Yuan Fengshun , Fan Jialong , Liu Yupeng , Zhu Lin , Wang Fan , Zhao Yashuang , Pang Da
Published: February 2017

DNA methylation is one of the most common epigenetic alterations, providing important information regarding cancer risk and prognosis. A case-control study (423 breast cancer cases, 509 controls) and a case-only study (326 cases) were conducted to evaluate the association of DUSP1 promoter methylation with breast cancer risk and clinicopathological characteristics. No significant association between DUSP1 methylation in peripheral blood leukocyte (PBL) DNA and breast cancer risk was observed. DUSP1 methylation was significantly associated with ER/PR-negative status; in particular, triple-negative breast cancer patients showed the highest frequency of DUSP1 methylation in both tumour DNA and PBL DNA. Soybean intake was significantly correlated with methylated DUSP1 only in ER-negative (OR 2.978; 95% CI 1.245–7.124) and PR negative (OR 2.735; 95% CI 1.315–5.692) patients. Irregular menstruation was significantly associated with methylated DUSP1 only in ER-positive (OR 3.564; 95% CI 1.691–7.511) and PR-positive (OR 3.902, 95% CI 1.656–9.194) patients. Thus, DUSP1 methylation is a cancer-associated hypermethylation event that is closely linked with triple-negative status. Further investigations are warranted to confirm the association of environmental factors, including fruit and soybean intake, irregular menstruation, and ER/PR status, with DUSP1 methylation in breast tumour DNA.
The long-term anterior segment configuration after pediatric cataract surgery and the association with secondary glaucoma
Authors: Chen Ding , Gong Xian-hui , Xie He , Zhu Xue-ning , Li Jin , Zhao Yun-e
Published: February 2017

Secondary glaucoma constitutes major sight-threatening complication of pediatric cataract surgery, yet the etiology remains unclear. The purpose of this study was to investigate the long-term anterior segment configuration and the association with secondary glaucoma in pediatric pseudophakia. Ultrasound biomicroscopy (UBM) was performed on 40 eyes of 26 children underwent pediatric cataract surgery and intraocular lens (IOL) implantation. The anterior chamber depth (ACD), angle-opening distance at 500 μm (AOD500), trabecular-iris angle (TIA), central corneal thickness (CCT), structural abnormities, IOL position, IOP, and incidence of glaucoma were evaluated. High insertion of iris, in which the iris root is attached more anteriorly than normal, was seen in 13 eyes (32.50%). IOL was located in the capsular bag in 19 eyes and in the ciliary sulcus in 21 eyes. Logistic regression analysis identified high insertion of iris (OR 3.40, 95% CI 1.03–11.17, p = 0.03) and IOL implantation in sulcus (OR 1.39, 95% CI 1.07–4.85, p = 0.04) as independent risk factors for glaucoma. The presence of high insertion of iris and IOL implantation in ciliary sulcus may increase the long-term risk of the development of secondary glaucoma after pediatric cataract surgery.
Transfer of monolayer TMD WS2 and Raman study of substrate effects
Authors: Mlack Jerome T. , Masih Das Paul , Danda Gopinath , Chou Yung-Chien , Naylor Carl H. , Lin Zhong , López Néstor Perea , Zhang Tianyi , Terrones Mauricio , Johnson A. T. Charlie , Drndić Marija
Published: February 2017

A facile transfer process for transition metal dichalcogenide WS2 flakes is reported and the effect of the underlying substrate on the flake properties is investigated using Raman spectroscopy. The flakes are transferred from their growth substrate using polymethyl methacrylate (PMMA) and a wet etch to allow the user to transfer the flakes to a final substrate using a microscope and micromanipulator combined with semi-transparent Kapton tape. The substrates used range from insulators such as industry standard high-k dielectric HfO2 and “green polymer” parylene-C, to conducting chemical vapor deposition (CVD) grown graphene. Raman spectroscopy is used first to confirm the material quality of the transferred flakes to the substrates and subsequently to analyze and separate the effects arising from material transfer from those arising from interactions with the substrate. We observe changes in the Raman spectra associated with the interactions between the substrates in the flakes. These interactions affect both in-plane and out-of-plane modes in different ways depending on their sources, for example strain or surface charge. These changes vary with final substrate, with the strongest effects being observed for WS2 transferred onto graphene and HfO2, demonstrating the importance of understanding substrate interaction for fabrication of future devices.
Prime factorization using quantum annealing and computational algebraic geometry
Authors: Dridi Raouf , Alghassi Hedayat
Published: February 2017

We investigate prime factorization from two perspectives: quantum annealing and computational algebraic geometry, specifically Gröbner bases. We present a novel autonomous algorithm which combines the two approaches and leads to the factorization of all bi-primes up to just over 200000, the largest number factored to date using a quantum processor. We also explain how Gröbner bases can be used to reduce the degree of Hamiltonians.
Time-reversal-breaking induced quantum spin Hall effect
Authors: Luo Wei , Shao D. X. , Deng Ming-Xun , Deng W. Y. , Sheng L.
Published: February 2017

We show that quantum spin Hall (QSH) effect does not occur in a square lattice model due to cancellation of the intrinsic spin-orbit coupling coming from different hopping paths. However, we show that QSH effect can be induced by the presence of staggered magnetic fluxes alternating directions square by square. When the resulting Peierls phase takes a special value "Equation missing", the system has a composite symmetry ΘΡ−"Equation missing" with Θ the time-reversal operator and Ρ−"Equation missing" transforming the Peierls phase from γ to γ − "Equation missing", which protects the gapless edge states. Once the phase deviates from "Equation missing", the edge states open a gap, as the composite symmetry is broken. We further investigate the effect of a Zeeman field on the QSH state, and find that the edge states remain gapless for "Equation missing". This indicates that the QSH effect is immune to the magnetic perturbation.
Parenteral administration of factor Xa/IIa inhibitors limits experimental aortic aneurysm and atherosclerosis
Authors: Moran Corey S. , Seto Sai-Wang , Krishna Smriti M. , Sharma Surabhi , Jose Roby J. , Biros Erik , Wang Yutang , Morton Susan K. , Golledge Jonathan
Published: February 2017

Intraluminal thrombus is a consistent feature of human abdominal aortic aneurysm (AAA). Coagulation factor Xa (FXa) catalyses FII to thrombin (FIIa). We examined the effect of FXa/FIIa inhibition on experimental aortic aneurysm in apolipoprotein E-deficient (ApoE−/−) mice infused with angiotensin II (AngII). The concentration of FXa within the supra-renal aorta (SRA) correlated positively with SRA diameter. Parenteral administration of enoxaparin (FXa/IIa inhibitor) and fondaparinux (FXa inhibitor) over 14 days reduced to severity of aortic aneurysm and atherosclerosis in AngII-infused ApoE−/− mice. Enteral administration of the FIIa inhibitor dabigatran had no significant effect. Aortic protease-activated receptor (PAR)-2 expression increased in response to AngII infusion. Fondaparinux reduced SRA levels of FXa, FIIa, PAR-2, matrix metalloproteinase (MMP)2, Smad2/3 phosphorylation, and MOMA-2 positive cells in the mouse model. FXa stimulated Smad2/3 phosphorylation and MMP2 expression in aortic vascular smooth muscle cells (VSMC) in vitro. Expression of MMP2 in FXa-stimulated VSMC was downregulated in the presence of a PAR-2 but not a PAR-1 inhibitor. These findings suggest that FXa/FIIa inhibition limits aortic aneurysm and atherosclerosis severity due to down-regulation of vascular PAR-2-mediated Smad2/3 signalling and MMP2 expression. Inhibition of FXa/FIIa may be a potential therapy for limiting aortic aneurysm.
Nitric oxide is involved in the oxytetracycline-induced suppression of root growth through inhibiting hydrogen peroxide accumulation in the root meristem
Authors: Yu Qing-Xiang , Ahammed Golam Jalal , Zhou Yan-Hong , Shi Kai , Zhou Jie , Yu Yunlong , Yu Jing-Quan , Xia Xiao-Jian
Published: February 2017

Use of antibiotic-contaminated manure in crop production poses a severe threat to soil and plant health. However, few studies have studied the mechanism by which plant development is affected by antibiotics. Here, we used microscopy, flow cytometry, gene expression analysis and fluorescent dyes to study the effects of oxytetracycline (OTC), a widely used antibiotic in agriculture, on root meristem activity and the accumulation of hydrogen peroxide (H2O2) and nitric oxide (NO) in the root tips of tomato seedlings. We found that OTC caused cell cycle arrest, decreased the size of root meristem and inhibited root growth. Interestingly, the inhibition of root growth by OTC was associated with a decline in H2O2 levels but an increase in NO levels in the root tips. Diphenyliodonium (DPI), an inhibitor of H2O2 production, showed similar effects on root growth as those of OTC. However, exogenous H2O2 partially reversed the effects on the cell cycle, meristem size and root growth. Importantly, cPTIO (the NO scavenger) and tungstate (an inhibitor of nitrate reductase) significantly increased H2O2 levels in the root tips and reversed the inhibition of root growth by OTC. Out results suggest that OTC-induced NO production inhibits H2O2 accumulation in the root tips, thus leading to cell cycle arrest and suppression of root growth.
Inhibition of N1-Src kinase by a specific SH3 peptide ligand reveals a role for N1-Src in neurite elongation by L1-CAM
Authors: Keenan Sarah , Wetherill Sarah J. , Ugbode Christopher I. , Chawla Sangeeta , Brackenbury William J. , Evans Gareth J. O.
Published: February 2017

In the mammalian brain the ubiquitous tyrosine kinase, C-Src, undergoes splicing to insert short sequences in the SH3 domain to yield N1- and N2-Src. We and others have previously shown that the N-Srcs have altered substrate specificity and kinase activity compared to C-Src. However, the exact functions of the N-Srcs are unknown and it is likely that N-Src signalling events have been misattributed to C-Src because they cannot be distinguished by conventional Src inhibitors that target the kinase domain. By screening a peptide phage display library, we discovered a novel ligand (PDN1) that targets the unique SH3 domain of N1-Src and inhibits N1-Src in cells. In cultured neurons, PDN1 fused to a fluorescent protein inhibited neurite outgrowth, an effect that was mimicked by shRNA targeting the N1-Src microexon. PDN1 also inhibited L1-CAM-dependent neurite elongation in cerebellar granule neurons, a pathway previously shown to be disrupted in Src−/− mice. PDN1 therefore represents a novel tool for distinguishing the functions of N1-Src and C-Src in neurons and is a starting point for the development of a small molecule inhibitor of N1-Src.
Human enterovirus 71 protein interaction network prompts antiviral drug repositioning
Authors: Han Lu , Li Kang , Jin Chaozhi , Wang Jian , Li Qingjun , Zhang Qiling , Cheng Qiyue , Yang Jing , Bo Xiaochen , Wang Shengqi
Published: February 2017

As a predominant cause of human hand, foot, and mouth disease, enterovirus 71 (EV71) infection may lead to serious diseases and result in severe consequences that threaten public health and cause widespread panic. Although the systematic identification of physical interactions between viral proteins and host proteins provides initial information for the recognition of the cellular mechanism involved in viral infection and the development of new therapies, EV71-host protein interactions have not been explored. Here, we identified interactions between EV71 proteins and host cellular proteins and confirmed the functional relationships of EV71-interacting proteins (EIPs) with virus proliferation and infection by integrating a human protein interaction network and by functional annotation. We found that most EIPs had known interactions with other viruses. We also predicted ATP6V0C as a broad-spectrum essential host factor and validated its essentiality for EV71 infection in vitro. EIPs and their interacting proteins were more likely to be targets of anti-inflammatory and neurological drugs, indicating their potential to serve as host-oriented antiviral targets. Thus, we used a connectivity map to find drugs that inhibited EIP expression. We predicted tanespimycin as a candidate and demonstrated its antiviral efficiency in vitro. These findings provide the first systematic identification of EV71-host protein interactions, an analysis of EIP protein characteristics and a demonstration of their value in developing host-oriented antiviral therapies.
Correction: Corrigendum: Establishment and Characterization of Human Germline Stem Cell Line with Unlimited Proliferation Potentials and no Tumor Formation
Authors: Hou Jingmei , Niu Minghui , Liu Linhong , Zhu Zijue , Wang Xiaobo , Sun Min , Yuan Qingqing , Yang Shi , Zeng Wenxian , Liu Yang , Li Zheng , He Zuping
Published: February 2017

Scientific Reports 5: Article number: 16922; published online: 20 November 2015; updated: 21 February 2017. The export of human derived tissues and related materials from China is currently subject to regulatory restrictions. Consequently, we are unable to share the human cell line described in thispaper with researchers outside of China at the present time.
Eyeblink rate watching classical Hollywood and post-classical MTV editing styles, in media and non-media professionals
Authors: Andreu-Sánchez Celia , Martín-Pascual Miguel Ángel , Gruart Agnès , Delgado-García José María
Published: February 2017

While movie edition creates a discontinuity in audio-visual works for narrative and economy-of-storytelling reasons, eyeblink creates a discontinuity in visual perception for protective and cognitive reasons. We were interested in analyzing eyeblink rate linked to cinematographic edition styles. We created three video stimuli with different editing styles and analyzed spontaneous blink rate in participants (N = 40). We were also interested in looking for different perceptive patterns in blink rate related to media professionalization. For that, of our participants, half (n = 20) were media professionals, and the other half were not. According to our results, MTV editing style inhibits eyeblinks more than Hollywood style and one-shot style. More interestingly, we obtained differences in visual perception related to media professionalization: we found that media professionals inhibit eyeblink rate substantially compared with non-media professionals, in any style of audio-visual edition.
Disrupted iron regulation in the brain and periphery in cocaine addiction
Authors: Ersche K D , Acosta-Cabronero J , Jones P S , Ziauddeen H , van Swelm R P L , Laarakkers C M M , Raha-Chowdhury R , Williams G B
Published: February 2017

Stimulant drugs acutely increase dopamine neurotransmission in the brain, and chronic use leads to neuroadaptive changes in the mesolimbic dopamine system and morphological changes in basal ganglia structures. Little is known about the mechanisms underlying these changes but preclinical evidence suggests that iron, a coenzyme in dopamine synthesis and storage, may be a candidate mediator. Iron is present in high concentrations in the basal ganglia and stimulant drugs may interfere with iron homeostasis. We hypothesised that morphological brain changes in cocaine addiction relate to abnormal iron regulation in the brain and periphery. We determined iron concentration in the brain, using quantitative susceptibility mapping, and in the periphery, using iron markers in circulating blood, in 44 patients with cocaine addiction and 44 healthy controls. Cocaine-addicted individuals showed excess iron accumulation in the globus pallidus, which strongly correlated with duration of cocaine use, and mild iron deficiency in the periphery, which was associated with low iron levels in the red nucleus. Our findings show that iron dysregulation occurs in cocaine addiction and suggest that it arises consequent to chronic cocaine use. Putamen enlargement in these individuals was unrelated to iron concentrations, suggesting that these are co-occurring morphological changes that may respectively reflect predisposition to, and consequences of cocaine addiction. Understanding the mechanisms by which cocaine affects iron metabolism may reveal novel therapeutic targets, and determine the value of iron levels in the brain and periphery as biomarkers of vulnerability to, as well as progression and response to treatment of cocaine addiction.
Erratum: Neuroprotection after a first episode of mania: a randomized controlled maintenance trial comparing the effects of lithium and quetiapine on grey and white matter volume
Authors: Berk M , Dandash O , Daglas R , Cotton S M , Allott K , Fornito A , Suo C , Klauser P , Liberg B , Henry L , Macneil C , Hasty M , McGorry P , Pantelis Cs , Yücel M
Published: February 2017

Correction to: Translational Psychiatry (2017) 7, e1011; doi:10.1038/tp.2016.281; published online 24 January 2017 The 14th author’s name was presented incorrectly. The correct listing is C Pantelis.
Chemistry-based molecular signature underlying the atypia of clozapine
Authors: Cardozo T , Shmelkov E , Felsovalyi K , Swetnam J , Butler T , Malaspina D , Shmelkov S V
Published: February 2017

The central nervous system is functionally organized as a dynamic network of interacting neural circuits that underlies observable behaviors. At higher resolution, these behaviors, or phenotypes, are defined by the activity of a specific set of biomolecules within those circuits. Identification of molecules that govern psychiatric phenotypes is a major challenge. The only organic molecular entities objectively associated with psychiatric phenotypes in humans are drugs that induce psychiatric phenotypes and drugs used for treatment of specific psychiatric conditions. Here, we identified candidate biomolecules contributing to the organic basis for psychosis by deriving an in vivo biomolecule-tissue signature for the atypical pharmacologic action of the antipsychotic drug clozapine. Our novel in silico approach identifies the ensemble of potential drug targets based on the drug’s chemical structure and the region-specific gene expression profile of each target in the central nervous system. We subtracted the signature of the action of clozapine from that of a typical antipsychotic, chlorpromazine. Our results implicate dopamine D4 receptors in the pineal gland and muscarinic acetylcholine M1 (CHRM1) and M3 (CHRM3) receptors in the prefrontal cortex (PFC) as significant and unique to clozapine, whereas serotonin receptors 5-HT2A in the PFC and 5-HT2C in the caudate nucleus were common significant sites of action for both drugs. Our results suggest that D4 and CHRM1 receptor activity in specific tissues may represent underappreciated drug targets to advance the pharmacologic treatment of schizophrenia. These findings may enhance our understanding of the organic basis of psychiatric disorders and help developing effective therapies.
High dilution surface-enhanced Raman spectroscopy for rapid determination of nicotine in e-liquids for electronic cigarettes
Authors: Itoh Nobuyasu , Bell Steven E. J.
Published: February 2017

The nicotine concentration in e-liquids can be determined by SERS even after the samples are diluted to remove matrix effects.
Rapid and specific detection of cell-derived microvesicles using a magnetoresistive biochip
Authors: Cherré Solène , Fernandes Elisabete , Germano José , Dias Tomás , Cardoso Susana , Piedade Moisés S. , Rozlosnik Noemi , Oliveira Marta I. , Freitas Paulo P.
Published: February 2017

Specific and sensitive detection of endothelial MVs within physiologically relevant concentrations using a magnetoresistive biochip platform.
Electrochemical synthesis of polyaniline in the micropores of activated carbon for high-performance electrochemical capacitors
Authors: Itoi Hiroyuki , Hayashi Shinya , Matsufusa Hidenori , Ohzawa Yoshimi
Published: February 2017

Polyaniline synthesized exclusively inside the micropores of activated carbon exhibits excellent energy and power densities.
Boron monoxide dimer as a building block for boroxine based buckyballs and related cages: a theoretical study
Authors: Liu Y. , Liu C. , Pu L. , Zhang Z. , King R. B.
Published: February 2017

The stability of B2O2 cage oligomers depends highly on the B2nOn (n = 3, 4, 5) cavities corresponding to the polyhedral faces. All such polyhedral oligomers are found to have larger cohesive energies (Ec's) than corresponding planar structures, except for the smallest (B2O2)6 tetrahedron with extremely high strained four B6O3 cavities.
Evaporation rate-based selection of supramolecular chirality
Authors: Hattori Shingo , Vandendriessche Stefaan , Koeckelberghs Guy , Verbiest Thierry , Ishii Kazuyuki
Published: February 2017

The supramolecular chirality of aggregates of π-conjugated polymers can be reversed by changing the evaporation rate.
Hierarchical structure and porosity in UiO-66 polyMOFs
Authors: Ayala Sergio , Zhang Zhenjie , Cohen Seth M.
Published: February 2017

The first polymer–MOF hybrid material (polyMOF) with a UiO-66 architecture is reported, prepared from polymers with varying alkyl spacers, molecular weights, and dispersities.
Gold-catalyzed highly regio- and enantioselective vinylcarbene insertion into O–H bonds of 2-pyridones
Authors: Huang Daorui , Xu Guangyang , Peng Shiyong , Sun Jiangtao
Published: February 2017

The first gold-catalyzed enantioselective carbene insertion into O–H bonds has been achieved.
Formation of coronene:water complexes: FTIR study in argon matrices and theoretical characterisation
Authors: Simon A. , Noble J. A. , Rouaut G. , Moudens A. , Aupetit C. , Iftner C. , Mascetti J.
Published: February 2017

Coronene preferentially forms σ-type rather than π-type complexes with water in low temperature argon matrices.
IR spectroscopic investigations of chemical and photochemical reactions on metal oxides: bridging the materials gap
Authors: Wang Yuemin , Wöll Christof
Published: February 2017

In this review, we highlight recent progress (2008–2016) in infrared reflection absorption spectroscopy (IRRAS) studies on oxide powders achieved by using different types of metal oxide single crystals as reference systems.