bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between whole peripheral blood fatty acids and DNA methylation in humans
Authors: de la Rocha Carmen , Pérez-Mojica J. Eduardo , León Silvia Zenteno-De , Cervantes-Paz Braulio , Tristán-Flores Fabiola E. , Rodríguez-Ríos Dalia , Molina-Torres Jorge , Ramírez-Chávez Enrique , Alvarado-Caudillo Yolanda , Carmona F. Javier , Esteller Manel , Hernández-Rivas Rosaura , Wrobel Katarzyna , Wrobel Kazimierz , Zaina Silvio , Lund Gertrud
Published: May 2016

Fatty acids (FA) modify DNA methylation in vitro, but limited information is available on whether corresponding associations exist in vivo and reflect any short-term effect of the diet. Associations between global DNA methylation and FAs were sought in blood from lactating infants (LI; n = 49) and adult males (AMM; n = 12) equally distributed across the three conventional BMI classes. AMM provided multiple samples at 2-hour intervals during 8 hours after either a single Western diet-representative meal (post-prandial samples) or no meal (fasting samples). Lipid/glucose profile, HDAC4 promoter and PDK4 5’UTR methylation were determined in AMM. Multiple regression analysis revealed that global (in LI) and both global and PDK4-specific DNA methylation (in AMM) were positively associated with eicosapentaenoic and arachidonic acid. HDAC4 methylation was inversely associated with arachidonic acid post-prandially in AMM. Global DNA methylation did not show any defined within-day pattern that would suggest a short-term response to the diet. Nonetheless, global DNA methylation was higher in normal weight subjects both post-prandially and in fasting and coincided with higher polyunsaturated relative to monounsaturated and saturated FAs. We show for the first time strong associations of DNA methylation with specific FAs in two human cohorts of distinct age, diet and postnatal development stage.
A Targeted Metabolomics MRM-MS Study on Identifying Potential Hypertension Biomarkers in Human Plasma and Evaluating Acupuncture Effects
Authors: Yang Mingxiao , Yu Zheng , Deng Shufang , Chen Xiaomin , Chen Liang , Guo Zhenyu , Zheng Hui , Chen Lin , Cai Dingjun , Wen Bo , Wu Qiaofeng , Liang Fanrong
Published: May 2016

The critical role of metabolic abnormality in hypertension is increasingly recognized, but its biomarkers are not clearly identified. In this study, 47 chemical compounds recorded by literature were employed as target metabolites of essential hypertension (EH). We detected their content in the plasma of EH patients and healthy subjects by using the Multiple Reaction Monitoring-Mass Spectrometry (MRM-MS). After screening the most altered compounds, acupuncture was used to treat patients for 3 months and these plasma metabolites were tested again. The results showed that oleic acid (OA) and myoinositol (MI) were the most important differential metabolites between the hypertensive plasma and the healthy plasma. They were also closely correlated with 24-hour blood pressure and nocturnal dipping. Moreover, plasma OA and MI could be restored to normal levels by acupuncture, accompanying with reduction of 24-hour systolic and diastolic blood pressure [from 145.10 ± 9.28 mm Hg to 140.70 ± 9.59 mm Hg (P < 0.0001) and 88.35 ± 7.92 mm Hg to 85.86 ± 7.95 mm Hg (P = 0.0024), respectively] and improvement of circadian blood pressure rhythm. This study demonstrated that plasma OA and MI were potential hypertension biomarkers and they could be used to preliminarily assess the treating effects such as acupuncture.
Fast machine-learning online optimization of ultra-cold-atom experiments
Authors: Wigley P. B. , Everitt P. J. , van den Hengel A. , Bastian J. W. , Sooriyabandara M. A. , McDonald G. D. , Hardman K. S. , Quinlivan C. D. , Manju P. , Kuhn C. C. N. , Petersen I. R. , Luiten A. N. , Hope J. J. , Robins N. P. , Hush M. R.
Published: May 2016

We apply an online optimization process based on machine learning to the production of Bose-Einstein condensates (BEC). BEC is typically created with an exponential evaporation ramp that is optimal for ergodic dynamics with two-body s-wave interactions and no other loss rates, but likely sub-optimal for real experiments. Through repeated machine-controlled scientific experimentation and observations our ‘learner’ discovers an optimal evaporation ramp for BEC production. In contrast to previous work, our learner uses a Gaussian process to develop a statistical model of the relationship between the parameters it controls and the quality of the BEC produced. We demonstrate that the Gaussian process machine learner is able to discover a ramp that produces high quality BECs in 10 times fewer iterations than a previously used online optimization technique. Furthermore, we show the internal model developed can be used to determine which parameters are essential in BEC creation and which are unimportant, providing insight into the optimization process of the system.
α-Amanitin Restrains Cancer Relapse from Drug-Tolerant Cell Subpopulations via TAF15
Authors: Kume Kohei , Ikeda Miyuki , Miura Sawako , Ito Kohei , Sato Kei A. , Ohmori Yukimi , Endo Fumitaka , Katagiri Hirokatsu , Ishida Kaoru , Ito Chie , Iwaya Takeshi , Nishizuka Satoshi S.
Published: May 2016

Cancer relapse occurs with substantial frequency even after treatment with curative intent. Here we studied drug-tolerant colonies (DTCs), which are subpopulations of cancer cells that survive in the presence of drugs. Proteomic characterization of DTCs identified stemness- and epithelial-dominant subpopulations, but functional screening suggested that DTC formation was regulated at the transcriptional level independent from protein expression patterns. We consistently found that α-amanitin, an RNA polymerase II (RNAPII) inhibitor, effectively inhibited DTCs by suppressing TAF15 expression, which binds to RNA to modulate transcription and RNA processing. Sequential administration of α-amanitin and cisplatin extended overall survival in a cancer-relapse mouse model, namely peritonitis carcinomatosa. Therefore, post-treatment cancer relapse may occur through non-distinct subpopulations and may be effectively prevented by α-amanitin to disrupt transcriptional machinery, including TAF15.
Identifying local-scale wilderness for on-ground conservation actions within a global biodiversity hotspot
Authors: Lin Shiwei , Wu Ruidong , Hua Chaolang , Ma Jianzhong , Wang Wenli , Yang Feiling , Wang Junjun
Published: May 2016

Protecting wilderness areas (WAs) is a crucial proactive approach to sustain biodiversity. However, studies identifying local-scale WAs for on-ground conservation efforts are still very limited. This paper investigated the spatial patterns of wilderness in a global biodiversity hotspot – Three Parallel Rivers Region (TPRR) in southwest China. Wilderness was classified into levels 1 to 10 based on a cluster analysis of five indicators, namely human population density, naturalness, fragmentation, remoteness and ruggedness. Only patches characterized by wilderness level 1 and ≥1.0 km2 were considered WAs. The wilderness levels in the northwest were significantly higher than those in the southeast and clearly increased with the increase in elevation. The WAs covered approximately 25% of TPRR’s land, 89.3% of which was located in the >3,000 m elevation zones. WAs consisted of 20 vegetation types, among which temperate conifer forest, cold temperate shrub and alpine ecosystems covered 79.4% of WAs’ total area. Most WAs were still not protected yet by existing reserves. Topography and human activities are the primary influencing factors on the spatial patterns of wilderness. We suggest establishing strictly protected reserves for most large WAs, while some sustainable management approaches might be more optimal solutions for many highly fragmented small WAs.
Reduced cerebral blood flow and oxygen metabolism in extremely preterm neonates with low-grade germinal matrix- intraventricular hemorrhage
Authors: Lin Pei-Yi , Hagan Katherine , Fenoglio Angela , Grant P. Ellen , Franceschini Maria Angela
Published: May 2016

Low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) is the most common complication in extremely premature neonates. The occurrence of GM-IVH is highly associated with hemodynamic instability in the premature brain, yet the long-term impact of low-grade GM-IVH on cerebral blood flow and neuronal health have not been fully investigated. We used an innovative combination of frequency-domain near infrared spectroscopy and diffuse correlation spectroscopy (FDNIRS-DCS) to measure cerebral oxygen saturation (SO2) and an index of cerebral blood flow (CBFi) at the infant’s bedside and compute an index of cerebral oxygen metabolism (CMRO2i). We enrolled twenty extremely low gestational age (ELGA) neonates (seven with low-grade GM-IVH) and monitored them weekly until they reached full-term equivalent age. During their hospital stay, we observed consistently lower CBFiand CMRO2iin ELGA neonates with low-grade GM-IVH compared to neonates without hemorrhages. Furthermore, lower CBFiand CMRO2iin the former group persists even after the resolution of the hemorrhage. In contrast, SO2does not differ between groups. Thus, CBFiand CMRO2imay have better sensitivity than SO2in detecting GM-IVH-related effects on infant brain development. FDNIRS-DCS methods may have clinical benefit for monitoring the evolution of GM-IVH, evaluating treatment response and potentially predicting neurodevelopmental outcome.
Potentiation of Glucose-stimulated Insulin Secretion by the GPR40–PLC–TRPC Pathway in Pancreatic β-Cells
Authors: Yamada Hodaka , Yoshida Masashi , Ito Kiyonori , Dezaki Katsuya , Yada Toshihiko , Ishikawa San-e , Kakei Masafumi
Published: May 2016

G protein-coupled receptors (GPCRs) are expressed in pancreatic beta-cells. G protein-coupled receptor 40 (GPR40) contributes to medium- or long-chain fatty acid-induced amplification of glucose-stimulated insulin secretion (GSIS) and GPR40 agonists are promising therapeutic targets in type 2 diabetes. Recently, we demonstrated that glucagon-like peptide 1, a ligand of pancreatic GPCR, activates a class of nonselective cation channels (NSCCs) and enhances GSIS. The aim of the current study was to determine whether the GPR40 signal interacts with NSCCs. A GPR40 agonist (fasiglifam) potentiated GSIS at 8.3 and 16.7 mM glucose but not 2.8 mM glucose. The NSCC current was activated by fasiglifam at 5.6 mM glucose with 100 μM tolbutamide (−70 mV) and this activation was prevented by the presence of pyrazole-3 (transient receptor potential canonical; a TRPC3 channel blocker). Inhibitors of phospholipase C or protein kinase C (PKC) inhibited the increases in GSIS and the NSCC current induced by GPR40 stimulation. The present study demonstrates a novel mechanism for the regulation of insulin secretion by GPR40 agonist in pancreatic beta-cells. The stimulation of the GPR40–PLC/PKC–TRPC3 channel pathway potentiates GSIS by the depolarization of the plasma membrane in pancreatic beta-cell.
The spin-dependent transport properties of zigzag α-graphyne nanoribbons and new device design
Authors: Ni Yun , Wang Xia , Tao Wei , Zhu Si-Cong , Yao Kai-Lun
Published: May 2016

By performing first-principle quantum transport calculations, we studied the electronic and transport properties of zigzag α-graphyne nanoribbons in different magnetic configurations. We designed the device based on zigzag α-graphyne nanoribbon and studied the spin-dependent transport properties, whose current-voltage curves show obvious spin-polarization and conductance plateaus. The interesting transport behaviours can be explained by the transport spectra under different magnetic configurations, which basically depends on the symmetry matching of the electrodes’ bandstructures. Simultaneously, spin Seebeck effect is also found in the device. Thus, according to the transport behaviours, zigzag α-graphyne nanoribbons can be used as a dual spin filter diode, a molecule signal converter and a spin caloritronics device, which indicates that α-graphyne is a promising candidate for the future application in spintronics.
SOD2 deregulation enhances migration, invasion and has poor prognosis in salivary adenoid cystic carcinoma
Authors: Chang Boyang , Yang Hang , Jiao Yuan , Wang Kefeng , Liu Zhonghua , Wu Peihong , Li Su , Wang Anxun
Published: May 2016

This study aimed to investigate the role of SOD2 in the progression and metastasis of salivary adenoid cystic carcinoma (SACC). We analyzed the expression of SOD2 in 50 SACC patients. Then, the effects and mechanism of SOD2 on cell metastasis in a pair of different metastatic potential cell lines was investigated. SOD2 was deregulated in patients with SACC. Up-regulation of SOD2 was associated with distant metastasis and reduced overall survival and disease free - survival. Compared to SACC-83 cells (lower metastasis ability), SACC-LM cells (higher metastasis ability) had higher SOD2 activity and intracellular H2O2 concentrations, and protein levels of pERK1/2 and Slug, but had similar catalase protein level and activity. In SACC-LM, reducing the expression of SOD2 by SiRNA inhibited the metastasis ability and reduced the SOD2 activities, intracellular H2O2 concentrations, and protein levels of pERK1/2 and Slug. These effects were revised in SACC-83 after SOD2 overexpression. Moreover, in SACC-83, treated with H2O2, the metastasis was enhanced accompanied by increased protein levels of pERK1/2 and Slug. We confirmed that SOD2 play an important role in the development and prognosis of SACC and SOD2-dependent production of H2O2 contributes to metastasis of SACC through the ERK-Slug signaling pathway.
Variation in fungal microbiome (mycobiome) and aflatoxins during simulated storage of in-shell peanuts and peanut kernels
Authors: Xing Fuguo , Ding Ning , Liu Xiao , Selvaraj Jonathan Nimal , Wang Limin , Zhou Lu , Zhao Yueju , Wang Yan , Liu Yang
Published: May 2016

Internal transcribed spacer 2 (ITS2) sequencing was used to characterize the peanut mycobiome during 90 days storage at five conditions. The fungal diversity in in-shell peanuts was higher with 110 operational taxonomic units (OTUs) and 41 genera than peanut kernels (91 OTUs and 37 genera). This means that the micro-environment in shell is more suitable for maintaining fungal diversity. At 20–30 d,Rhizopus,EurotiumandWallemiawere predominant in in-shell peanuts. In peanut kernels,Rhizopus(>30%) andEurotium(>20%) were predominant at 10–20 d and 30 d, respectively. The relative abundances ofRhizopus,EurotiumandWallemiawere higher thanAspergillus, because they were xerophilic and grew well on substrates with low water activity (aw). During growth, they released metabolic water, thereby favoring the growth ofAspergillus. Therefore, from 30 to 90 d, the relative abundance ofAspergillusincreased while that ofRhizopus,EurotiumandWallemiadecreased. Principal Coordinate Analysis (PCoA) revealed that peanuts stored for 60–90 days and for 10–30 days clustered differently from each other. Due to lowawvalues (0.34–0.72)and low levels ofA. flavus, nine of 51 samples were contaminated with aflatoxins.
Engineering 3D bicontinuous hierarchically macro-mesoporous LiFePO4/C nanocomposite for lithium storage with high rate capability and long cycle stability
Authors: Zhang Qian , Huang Shao-Zhuan , Jin Jun , Liu Jing , Li Yu , Wang Hong-En , Chen Li-Hua , Wang Bin-Jie , Su Bao-Lian
Published: May 2016

A highly crystalline three dimensional (3D) bicontinuous hierarchically macro-mesoporous LiFePO4/C nanocomposite constructed by nanoparticles in the range of 50~100 nm via a rapid microwave assisted solvothermal process followed by carbon coating have been synthesized as cathode material for high performance lithium-ion batteries. The abundant 3D macropores allow better penetration of electrolyte to promote Li+ diffusion, the mesopores provide more electrochemical reaction sites and the carbon layers outside LiFePO4 nanoparticles increase the electrical conductivity, thus ultimately facilitating reverse reaction of Fe3+ to Fe2+ and alleviating electrode polarization. In addition, the particle size in nanoscale can provide short diffusion lengths for the Li+ intercalation-deintercalation. As a result, the 3D macro-mesoporous nanosized LiFePO4/C electrode exhibits excellent rate capability (129.1 mA h/g at 2 C; 110.9 mA h/g at 10 C) and cycling stability (87.2% capacity retention at 2 C after 1000 cycles, 76.3% at 5 C after 500 cycles and 87.8% at 10 C after 500 cycles, respectively), which are much better than many reported LiFePO4/C structures. Our demonstration here offers the opportunity to develop nanoscaled hierarchically porous LiFePO4/C structures for high performance lithium-ion batteries through microwave assisted solvothermal method.
The nuclear receptor NOR-1 regulates the small muscle protein, X-linked (SMPX) and myotube differentiation
Authors: Ferrán Beatriz , Martí-Pàmies Ingrid , Alonso Judith , Rodríguez-Calvo Ricardo , Aguiló Silvia , Vidal Francisco , Rodríguez Cristina , Martínez-González José
Published: May 2016

Recent works have highlighted the role of NOR-1 in both smooth and skeletal muscle and have proposed this nuclear receptor as a nexus that coordinates muscle performance and metabolic capacity. However, no muscle specific genes regulated by NOR-1 have been identified so far. To identify NOR-1 target genes, we over-expressed NOR-1 in human vascular smooth muscle cells (VSMC). These cells subjected to sustained over-expression of supraphysiological levels of NOR-1 experienced marked phenotypic changes and up-regulated the skeletal muscle protein X-linked (SMPX), a protein typically expressed in striated muscle and associated to cell shape. By transcriptional studies and DNA-protein binding assays, we identified a non-consensus NBRE site in human SMPX promoter, critical for NOR-1 responsiveness. The expression of SMPX was higher in human skeletal muscle myoblasts (HSMM) than in human VSMC and further increased in HSMM differentiated to myotubes. NOR-1 silencing prevented SMPX expression in HSMM, as well as their differentiation to myotubes, but the up-regulation of SMPX was dispensable for HSMM differentiation. Our results indicate that NOR-1 regulate SMPX in human muscle cells and acts as a muscle regulatory factor, but further studies are required to unravel its role in muscle differentiation and hypertrophy.
Structural-functional lung imaging using a combined CT-EIT and a Discrete Cosine Transformation reconstruction method
Authors: Schullcke Benjamin , Gong Bo , Krueger-Ziolek Sabine , Soleimani Manuchehr , Mueller-Lisse Ullrich , Moeller Knut
Published: May 2016

Lung EIT is a functional imaging method that utilizes electrical currents to reconstruct images of conductivity changes inside the thorax. This technique is radiation free and applicable at the bedside, but lacks of spatial resolution compared to morphological imaging methods such as X-ray computed tomography (CT). In this article we describe an approach for EIT image reconstruction using morphologic information obtained from other structural imaging modalities. This leads to recon- structed images of lung ventilation that can easily be superimposed with structural CT or MRI images, which facilitates image interpretation. The approach is based on a Discrete Cosine Transformation (DCT) of an image of the considered transversal thorax slice. The use of DCT enables reduction of the dimensionality of the reconstruction and ensures that only conductivity changes of the lungs are reconstructed and displayed. The DCT based approach is well suited to fuse morphological image information with functional lung imaging at low computational costs. Results on simulated data indicate that this approach preserves the morphological structures of the lungs and avoids blurring of the solution. Images from patient measurements reveal the capabilities of the method and demonstrate benefits in possible applications.
A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation
Authors: Ishibashi Ryoichi , Takemoto Minoru , Akimoto Yoshihiro , Ishikawa Takahiro , He Peng , Maezawa Yoshiro , Sakamoto Kenichi , Tsurutani Yuya , Ide Shintaro , Ide Kana , Kawamura Harukiyo , Kobayashi Kazuki , Tokuyama Hirotake , Tryggvason Karl , Betsholtz Christer , Yokote Koutaro
Published: May 2016

Kidney diseases including diabetic nephropathy have become huge medical problems, although its precise mechanisms are still far from understood. In order to increase our knowledge about the patho-physiology of kidney, we have previously identified >300 kidney glomerulus-enriched transcripts through large-scale sequencing and microarray profiling of the mouse glomerular transcriptome. One of the glomerulus-specific transcripts identified was semaphorin 3G (Sema3G) which belongs to the semaphorin family. The aim of this study was to analyze both the in vivo and in vitro functions of Sema3G in the kidney. Sema3G was expressed in glomerular podocytes. Although Sema3G knockout mice did not show obvious glomerular defects, ultrastructural analyses revealed partially aberrant podocyte foot processes structures. When these mice were injected with lipopolysaccharide to induce acute inflammation or streptozotocin to induce diabetes, the lack of Sema3G resulted in increased albuminuria. The lack of Sema3G in podocytes also enhanced the expression of inflammatory cytokines including chemokine ligand 2 and interleukin 6. On the other hand, the presence of Sema3G attenuated their expression through the inhibition of lipopolysaccharide-induced Toll like receptor 4 signaling. Taken together, our results surmise that the Sema3G protein is secreted by podocytes and protects podocytes from inflammatory kidney diseases and diabetic nephropathy.
Differential neuronal vulnerability identifies IGF-2 as a protective factor in ALS
Authors: Allodi Ilary , Comley Laura , Nichterwitz Susanne , Nizzardo Monica , Simone Chiara , Benitez Julio Aguila , Cao Ming , Corti Stefania , Hedlund Eva
Published: May 2016

The fatal disease amyotrophic lateral sclerosis (ALS) is characterized by the loss of somatic motor neurons leading to muscle wasting and paralysis. However, motor neurons in the oculomotor nucleus, controlling eye movement, are for unknown reasons spared. We found that insulin-like growth factor 2 (IGF-2) was maintained in oculomotor neurons in ALS and thus could play a role in oculomotor resistance in this disease. We also showed that IGF-1 receptor (IGF-1R), which mediates survival pathways upon IGF binding, was highly expressed in oculomotor neurons and on extraocular muscle endplate. The addition of IGF-2 induced Akt phosphorylation, glycogen synthase kinase-3β phosphorylation and β-catenin levels while protecting ALS patient motor neurons. IGF-2 also rescued motor neurons derived from spinal muscular atrophy (SMA) patients from degeneration. Finally, AAV9::IGF-2 delivery to muscles of SOD1G93A ALS mice extended life-span by 10%, while preserving motor neurons and inducing motor axon regeneration. Thus, our studies demonstrate that oculomotor-specific expression can be utilized to identify candidates that protect vulnerable motor neurons from degeneration.
Biological strategy for the fabrication of highly ordered aragonite helices: the microstructure of the cavolinioidean gastropods
Authors: Checa Antonio G. , Macías-Sánchez Elena , Ramírez-Rico Joaquín
Published: May 2016

The Cavolinioidea are planktonic gastropods which construct their shells with the so-called aragonitic helical fibrous microstructure, consisting of a highly ordered arrangement of helically coiled interlocking continuous crystalline aragonite fibres. Our study reveals that, despite the high and continuous degree of interlocking between fibres, every fibre has a differentiated organic-rich thin external band, which is never invaded by neighbouring fibres. In this way, fibres avoid extinction. These intra-fibre organic-rich bands appear on the growth surface of the shell as minuscule elevations, which have to be secreted differentially by the outer mantle cells. We propose that, as the shell thickens during mineralization, fibre secretion proceeds by a mechanism of contact recognition and displacement of the tips along circular trajectories by the cells of the outer mantle surface. Given the sizes of the tips, this mechanism has to operate at the subcellular level. Accordingly, the fabrication of the helical microstructure is under strict biological control. This mechanism of fibre-by-fibre fabrication by the mantle cells is unlike that any other shell microstructure.
Accuracy of conization procedure for predicting pathological parameters of radical hysterectomy in stage Ia2–Ib1 (≤2 cm) cervical cancer
Authors: Bai Huimin , Cao Dongyan , Yuan Fang , Wang Huilan , Xiao Meizhu , Chen Jie , Cui Quancai , Shen Keng , Zhang Zhenyu
Published: May 2016

The accuracy of conization for the prediction of radical hysterectomy (RH) pathological variables in patients with stage Ia2 to Ib1 (≤2 cm) cervical cancer was retrospectively evaluated in the present study. Endocervical or deep resection margin (RM) involvement in the conization specimens was found to be independently associated with residual disease in the hysterectomy specimens (P < 0.001, = 0.003, respectively). When a tumor width of >20 mm in the final RH pathology analysis was predicted by a tumor width of >2 mm or involvement of endocervical or deep RMs in the conization specimens, the sensitivity and negative predictive value (NPV) of conization were 98.2% and 95.2%, respectively. In addition, when deep stromal invasion in the final RH pathology analysis was predicted by deep stromal invasion or involvement of the endocervical or deep RMs in the conization specimens, the sensitivity and NPV of conization were 98.4% and 95.8%, respectively. The sensitivity and NPV of this prediction model for identifying LVSI in the final RH pathology analysis were both 100%. These findings suggest that conization variables and endocervical and deep resection margin statuses can be analyzed to effectively predict RH pathological parameters.
Cancer-associated DDX3X mutations drive stress granule assembly and impair global translation
Authors: Valentin-Vega Yasmine A. , Wang Yong-Dong , Parker Matthew , Patmore Deanna M. , Kanagaraj Anderson , Moore Jennifer , Rusch Michael , Finkelstein David , Ellison David W. , Gilbertson Richard J. , Zhang Jinghui , Kim Hong Joo , Taylor J. Paul
Published: May 2016

DDX3X is a DEAD-box RNA helicase that has been implicated in multiple aspects of RNA metabolism including translation initiation and the assembly of stress granules (SGs). Recent genomic studies have reported recurrent DDX3X mutations in numerous tumors including medulloblastoma (MB), but the physiological impact of these mutations is poorly understood. Here we show that a consistent feature of MB-associated mutations is SG hyper-assembly and concomitant translation impairment. We used CLIP-seq to obtain a comprehensive assessment of DDX3X binding targets and ribosome profiling for high-resolution assessment of global translation. Surprisingly, mutant DDX3X expression caused broad inhibition of translation that impacted DDX3X targeted and non-targeted mRNAs alike. Assessment of translation efficiency with single-cell resolution revealed that SG hyper-assembly correlated precisely with impaired global translation. SG hyper-assembly and translation impairment driven by mutant DDX3X were rescued by a genetic approach that limited SG assembly and by deletion of the N-terminal low complexity domain within DDX3X. Thus, in addition to a primary defect at the level of translation initiation caused by DDX3X mutation, SG assembly itself contributes to global translation inhibition. This work provides mechanistic insights into the consequences of cancer-related DDX3X mutations, suggesting that globally reduced translation may provide a context-dependent survival advantage that must be considered as a possible contributor to tumorigenesis.
Chemical nature of alkaline polyphosphate boundary film at heated rubbing surfaces
Authors: Wan Shanhong , Tieu A. Kiet , Zhu Qiang , Zhu Hongtao , Cui Shaogang , Mitchell David R. G. , Kong Charlie , Cowie Bruce , Denman John A. , Liu Rong
Published: May 2016

Alkaline polyphosphate has been demonstrated to be able to reduce significant wear and friction of sliding interfaces under heavy loads (>1 GPa) and elevated temperature (800 °C and above) conditions, e.g. hot metal manufacturing. The chemical composition and fine structure of polyphosphate lubricating film is not well understood as well as the role of alkaline elements within the reaction film at hot rubbing surface. This work makes use of the coupling surface analytical techniques on the alkaline polyphosphate tribofilm, XANES, TOF-SIMS and FIB/TEM. The data show the composition in gradient distribution and trilaminar structure of tribofilm: a shorter chain phosphate overlying a long chain polyphosphate that adheres onto oxide steel base through a short chain phosphate. The chemical hardness model well explains the anti-abrasive mechanism of alkaline polyphosphate at elevated temperatures and also predicts a depolymerisation and simultaneous cross-linking of the polyphosphate glass. The role of alkaline elements in the lubrication mechanism is especially explained. This work firstly serves as a basis for a detailed study of alkaline polyphosphate tribofilm at temperature over 600 °C.
Development of passive CLARITY and immunofluorescent labelling of multiple proteins in human cerebellum: understanding mechanisms of neurodegeneration in mitochondrial disease
Authors: Phillips Jonathan , Laude Alex , Lightowlers Robert , Morris Chris M. , Turnbull Doug M. , Lax Nichola Z.
Published: May 2016

CLARITY enables immunofluorescent labelling and imaging of large volumes of tissue to provide a better insight into the three dimensional relationship between cellular morphology and spatial interactions between different cell types. In the current study, we optimise passive CLARITY and immunofluorescent labelling of neurons and mitochondrial proteins in mouse and human brain tissues to gain further insights into mechanisms of neurodegeneration occurring in mitochondrial disease. This is the first study to utilise human cerebellum fixed in paraformaldehyde and cryoprotected in conjunction with formalin-fixed tissues opening up further avenues for use of archived tissue. We optimised hydrogel-embedding and passive clearance of lipids from both mouse (n = 5) and human (n = 9) cerebellum as well as developing an immunofluorescent protocol that consistently labels different neuronal domains as well as blood vessels. In addition to visualising large structures, we were able to visualise mitochondrial proteins in passively cleared tissues to reveal respiratory chain deficiency associated with mitochondrial disease. We also demonstrate multiple use of tissues by stripping antibodies and re-probing the cerebellum. This technique allows interrogation of large volumes intact brain samples for better understanding of the complex pathological changes taking place in mitochondrial disease.
Graphene-clad microfibre saturable absorber for ultrafast fibre lasers
Authors: Liu X. M. , Yang H. R. , Cui Y. D. , Chen G. W. , Yang Y. , Wu X. Q. , Yao X. K. , Han D. D. , Han X. X. , Zeng C. , Guo J. , Li W. L. , Cheng G. , Tong L. M.
Published: May 2016

Graphene, whose absorbance is approximately independent of wavelength, allows broadband light–matter interactions with ultrafast responses. The interband optical absorption of graphene can be saturated readily under strong excitation, thereby enabling scientists to exploit the photonic properties of graphene to realize ultrafast lasers. The evanescent field interaction scheme of the propagating light with graphene covered on a D-shaped fibre or microfibre has been employed extensively because of the nonblocking configuration. Obviously, most of the fibre surface is unused in these techniques. Here, we exploit a graphene-clad microfibre (GCM) saturable absorber in a mode-locked fibre laser for the generation of ultrafast pulses. The proposed all-surface technique can guarantee a higher efficiency of light–graphene interactions than the aforementioned techniques. Our GCM-based saturable absorber can generate ultrafast optical pulses within 1.5 μm. This saturable absorber is compatible with current fibre lasers and has many merits such as low saturation intensities, ultrafast recovery times and wide wavelength ranges. The proposed saturable absorber will pave the way for graphene-based wideband photonics.
Streptococcal pyrogenic exotoxin B inhibits apoptotic cell clearance by macrophages through protein S cleavage
Authors: Chen Chia-Ling , Wu Yueh-Ying , Lin Chiou-Feng , Kuo Chih-Feng , Han Chia-Li , Wang Shuying , Chuang Woei-Jer , Chen Chiu-Yueh , Wu Jiunn-Jong , Tsai Pei-Jane , Liu Ching-Chuan , Lin Yee-Shin
Published: May 2016

Clearance of apoptotic cells by macrophages plays an important role in maintaining tissue homeostasis. Previous study indicated that streptococcal pyrogenic exotoxin B (SPE B) reduces phagocytic activity in group A streptococcus (GAS) infection. Here, we demonstrate that SPE B causes an inhibitory effect on protein S-mediated phagocytosis. In the presence of SPE B, serum- and purified protein S-mediated phagocytosis of apoptotic cells were significantly inhibited. The binding abilities of protein S to apoptotic cells were decreased by treatment with SPE B. Bacterial culture supernatants from GAS NZ131 strain also caused a reduction of protein S binding to apoptotic cells, but speB mutant strain did not. SPE B directly cleaved protein S in vitro and in vivo, whereas a lower level of cleavage occurred in mice infected with a speB isogenic mutant strain. SPE B-mediated initial cleavage of protein S caused a disruption of phagocytosis and also resulted in a loss of binding ability of protein S-associated C4b-binding protein to apoptotic cells. Taken together, these results suggest a novel pathogenic role of SPE B that initiates protein S degradation followed by the inhibition of apoptotic cell clearance by macrophages.
Self-regenerating and hybrid irreversible/reversible PDMS microfluidic devices
Authors: Shiroma Letícia S. , Piazzetta Maria H. O. , Duarte-Junior Gerson F. , Coltro Wendell K. T. , Carrilho Emanuel , Gobbi Angelo L. , Lima Renato S.
Published: May 2016

This paper outlines a straightforward, fast, and low-cost method to fabricate polydimethylsiloxane (PDMS) chips. Termed sandwich bonding (SWB), this method requires only a laboratory oven. Initially, SWB relies on the reversible bonding of a coverslip over PDMS channels. The coverslip is smaller than the substrate, leaving a border around the substrate exposed. Subsequently, a liquid composed of PDMS monomers and a curing agent is poured onto the structure. Finally, the cover is cured. We focused on PDMS/glass chips because of their key advantages in microfluidics. Despite its simplicity, this method created high-performance microfluidic channels. Such structures featured self-regeneration after leakages and hybrid irreversible/reversible behavior. The reversible nature was achieved by removing the cover of PDMS with acetone. Thus, the PDMS substrate and glass coverslip could be detached for reuse. These abilities are essential in the stages of research and development. Additionally, SWB avoids the use of surface oxidation, half-cured PDMS as an adhesive, and surface chemical modification. As a consequence, SWB allows surface modifications before the bonding, a long time for alignment, the enclosure of sub-micron channels, and the prototyping of hybrid devices. Here, the technique was successfully applied to bond PDMS to Au and Al.
Polycomb repressive complex 1 controls uterine decidualization
Authors: Bian Fenghua , Gao Fei , Kartashov Andrey V. , Jegga Anil G. , Barski Artem , Das Sanjoy K.
Published: May 2016

Uterine stromal cell decidualization is an essential part of the reproductive process. Decidual tissue development requires a highly regulated control of the extracellular tissue remodeling; however the mechanism of this regulation remains unknown. Through systematic expression studies, we detected that Cbx4/2, Rybp, and Ring1B [components of polycomb repressive complex 1 (PRC1)] are predominantly utilized in antimesometrial decidualization with polyploidy. Immunofluorescence analyses revealed that PRC1 members are co-localized with its functional histone modifier H2AK119ub1 (mono ubiquitination of histone-H2A at lysine-119) in polyploid cell. A potent small-molecule inhibitor of Ring1A/B E3-ubiquitin ligase or siRNA-mediated suppression ofCbx4caused inhibition of H2AK119ub1, in conjunction with perturbation of decidualization and polyploidy development, suggesting a role for Cbx4/Ring1B-containing PRC1 in these processes. Analyses of genetic signatures by RNA-seq studies showed that the inhibition of PRC1 function affects 238 genes (154 up and 84 down) during decidualization. Functional enrichment analyses identified that about 38% genes primarily involved in extracellular processes are specifically targeted by PRC1. Furthermore, ~15% of upregulated genes exhibited a significant overlap with the upregulatedBmp2null-induced genes in mice. Overall, Cbx4/Ring1B-containing PRC1 controls decidualization via regulation of extracellular gene remodeling functions and sheds new insights into underlying molecular mechanism(s) through transcriptional repression regulation.
High-pressure minerals in eucrite suggest a small source crater on Vesta
Authors: Pang Run-Lian , Zhang Ai-Cheng , Wang Shu-Zhou , Wang Ru-Cheng , Yurimoto Hisayoshi
Published: May 2016

High-pressure minerals in meteorites are important records of shock events that have affected the surfaces of planets and asteroids. A widespread distribution of impact craters has been observed on the Vestan surface. However, very few high-pressure minerals have been discovered in Howardite-Eucrite-Diogenite (HED) meteorites. Here we present the first evidence of tissintite, vacancy-rich clinopyroxene, and super-silicic garnet in the eucrite Northwest Africa (NWA) 8003. Combined with coesite and stishovite, the presence of these high-pressure minerals and their chemical compositions reveal that solidification of melt veins in NWA 8003 began at a pressure of >~10 GPa and ceased when the pressure dropped to <~8.5 GPa. The shock temperature in the melt veins exceeded 1900 °C. Simulation results show that shock events that create impact craters of ~3 km in diameter (subject to a factor of 2 uncertainty) are associated with sufficiently high pressures to account for the occurrence of the high-pressure minerals observed in NWA 8003. This indicates that HED meteorites containing similar high-pressure minerals should be observed more frequently than previously thought.
One-pot conversion of disaccharide into 5-hydroxymethylfurfural catalyzed by imidazole ionic liquid
Authors: Qu Yongshui , Li Li , Wei Quanyuan , Huang Chongpin , Oleskowicz-Popiel Piotr , Xu Jian
Published: May 2016

Conversion of carbohydrate into 5-hydroxymethylfurfural (5- HMF), a versatile, key renewable platform compound is regarded as an important transformation in biomass-derived carbohydrate chemistry. A variety of ILs, not only acidic but also alkaline ILs, were synthesized and used as catalyst in the production of 5-HMF from disaccharide. Several factors including reaction temperature, IL dosage, solvent and reaction time,were found to influence the yield of 5-HMF from cellobiose. Of the ILs tested, hydroxy-functionalized ionic liquid (IL), 1-hydroxyethyl-3-methylimidazolium tetrafluoroborate ([AEMIM]BF4) showed the highest catalytic activity and selectivity. 5-HMF yield of 68.71% from sucrose was obtained after 6 hrs at 160 °C. At the same condition with cellobiose as substrate, 5-HMF yield was 24.73%. In addition, 5-HMF also exhibited good stablity in this reaction system. Moreover, a kinetic analysis was carried out in both acidic and alkaline IL-catalyzed system, suggesting main side reaction in the conversion of fructose catalyzed by acidic and alkaline IL was polymerization of fructose and 5-HMF degradation, respectively.
Premartensitic transition and relevant magnetic effects in Ni50Mn34In15.5Al0.5 alloy
Authors: Wu Yuqin , Guo Shaopu , Yu Shuyun , Cheng Hui , Wang Ruilong , Xiao Haibo , Xu Lingfang , Xiong Rui , Liu Yong , Xia Zhengcai , Yang Changping
Published: May 2016

Resistance measurement, in situ optical microscopic observation, thermal and magnetic measurements have been carried out on Ni50Mn34In15.5Al0.5 alloy. The existence of a pronounced premartensitic transition prior to martensitic transition can be characterized by microstructure evolution as well as exothermic peak and smooth decrease of resistance and magnetization with obvious hysteresis over a wide temperature range upon cooling. Consequently, the alloy undergoes two successive magneto-structural transitions consisting of premartensitic and martensitic transitions. Magnetoelastic coupling between magnetic and structural degrees of freedom would be responsible for the appearance of premartensitic transition, as evinced by the distinct shift of transitions temperatures to lower temperature with external applied field of 50 kOe. The inverse premartensitic transition induced by magnetic field results in large magnetoresistance and contributes to the enhanced inverse magnetocaloric effect through enlarging the peak value and temperature interval of magnetic entropy change ΔSm.
Notch signalling regulates asymmetric division and inter-conversion between lgr5 and bmi1 expressing intestinal stem cells
Authors: Srinivasan Tara , Than Elaine Bich , Bu Pengcheng , Tung Kuei-Ling , Chen Kai-Yuan , Augenlicht Leonard , Lipkin Steven M. , Shen Xiling
Published: May 2016

Rapidly cycling LGR5+ intestinal stem cells (ISCs) located at the base of crypts are the primary driver of regeneration. Additionally, BMI1 expression is correlated with a slow cycling pool of ISCs located at +4 position. While previous reports have shown interconversion between these two populations following tissue injury, we provide evidence that NOTCH signaling regulates the balance between these two populations and promotes asymmetric division as a mechanism for interconversion in the mouse intestine. In both in vitro and in vivo models, NOTCH suppression reduces the ratio of BMI1+/LGR5+ ISCs while NOTCH stimulation increases this ratio. Furthermore, NOTCH signaling can activate asymmetric division after intestinal inflammation. Overall, these data provide insights into ISC plasticity, demonstrating a direct interconversion mechanism between slow- and fast-cycling ISCs.
Smooth and flat phase-locked Kerr frequency comb generation by higher order mode suppression
Authors: Huang S.-W. , Liu H. , Yang J. , Yu M. , Kwong D.-L. , Wong C. W.
Published: May 2016

High-Q microresonator is perceived as a promising platform for optical frequency comb generation, via dissipative soliton formation. In order to achieve a higher quality factor and obtain the necessary anomalous dispersion, multi-mode waveguides were previously implemented in Si3N4 microresonators. However, coupling between different transverse mode families in multi-mode waveguides results in periodic disruption of dispersion and quality factor and consequently causes perturbation to dissipative soliton formation and amplitude modulation to the corresponding spectrum. Careful choice of pump wavelength to avoid the mode crossing region is thus critical in conventional Si3N4 microresonators. Here, we report a novel design of Si3N4 microresonator in which single-mode operation, high quality factor and anomalous dispersion are attained simultaneously. The novel microresonator is consisted of uniform single-mode waveguides in the semi-circle region, to eliminate bending induced mode coupling and adiabatically tapered waveguides in the straight region, to avoid excitation of higher order modes. The intrinsic quality factor of the microresonator reaches 1.36 × 106 while the group velocity dispersion remains to be anomalous at −50 fs2/mm. With this novel microresonator, we demonstrate that broadband phase-locked Kerr frequency combs with flat and smooth spectra can be generated by pumping at any resonances in the optical C-band.
Toxicity of dimercaptosuccinate-coated and un-functionalized magnetic iron oxide nanoparticles towards aquatic organisms
Authors: Zhang Ya-Qi , Dringen Ralf , Petters Charlotte , Rastedt Wiebke , Köser Jan , Filser Juliane , Stolte Stefan
Published: May 2016

Investigations on colloidal stability and ecotoxicological effects of DMSA-coated and uncoated IONP with Raphidocelis, Daphnia and Lemna.
FRET-based fluorescence ratiometric and colorimetric sensor to discriminate Fe3+ from Fe2+
Authors: Das Sangita , Aich Krishnendu , Goswami Shyamaprosad , Quah Ching Kheng , Fun Hoong-Kun
Published: May 2016

A new benzothiazole–quinoline–rhodamine-6G-based probe was synthesised. The probe can exclusively detect Fe3+ through a ratiometric manner in a mixed aqueous system with a detection limit in the 10−8 M range.
Recent topics on single-molecule fluctuation analysis using blinking in surface-enhanced resonance Raman scattering: clarification by the electromagnetic mechanism
Authors: Itoh Tamitake , Yamamoto Yuko S.
Published: May 2016

Fluctuating single sp2carbon clusters at single hotspots of silver nanoparticle dimers investigated by surface-enhanced Raman scattering (SERS), indicating that SERS has become an ultrasensitive tool for clarifying molecular functions on plasmonic metal nanoparticles (NPs).
Optimization and kinetic studies of photodegradation of Rhodamine B with immobilized Ag-, S-, and N-doped TiO2 under visible irradiation: using Box–Behnken designs (BBDs), multivariate curve resolution (MCR-ALS) and parallel factor (PARAFAC) analysis
Authors: Khalilian H. , Semnani A. , Rinnan Å. , Haddadi H.
Published: May 2016

This study is based on a two-stage approach.
Inhibition of fibrous dysplasia via blocking Gsα with suramin sodium loaded with an alendronate-conjugated polymeric drug delivery system
Authors: Lv Mingming , Li Xiao , Huang Yu , Wang Nan , Zhu Xinyuan , Sun Jian
Published: May 2016

A bone-targeted polymeric drug delivery system was constructed to inhibit fibrous dysplasia efficiently via blocking Gsα with suramin sodium.
Improving the hydrogen selectivity of graphene oxide membranes by reducing non-selective pores with intergrown ZIF-8 crystals
Authors: Wang Xuerui , Chi Chenglong , Tao Jifang , Peng Yongwu , Ying Shaoming , Qian Yuhong , Dong Jinqiao , Hu Zhigang , Gu Yuandong , Zhao Dan
Published: May 2016

The large defects of graphene oxide membranes were reduced by the intergrown ZIF-8 crystals, affording dramatically increased gas separation performance.
N-Acetyl glycals are tight-binding and environmentally insensitive inhibitors of hexosaminidases
Authors: Santana A. G. , Vadlamani G. , Mark B. L. , Withers S. G.
Published: May 2016

Mono-, di- and trisaccharide derivatives of 1,2-unsaturated N-acetyl-d-glucal have been synthesized and shown to function as tight-binding inhibitors/slow substrates of representative hexosaminidases.
A thermoresponsive poly(ionic liquid) membrane enables concentration of proteins from aqueous media
Authors: Kohno Yuki , Gin Douglas L. , Noble Richard D. , Ohno Hiroyuki
Published: May 2016

A new type of poly(ionic liquid) membrane, which shows switchable hydrated states via lower critical solution temperature-type phase behaviour, enables concentration of some water-soluble proteins from aqueous media.
Ligand-controlled gold-catalyzed cycloisomerization of 1,n-enyne esters toward synthesis of dihydronaphthalene
Authors: Thummanapelli Sravan K. , Hosseyni Seyedmorteza , Su Yijin , Akhmedov Novruz G. , Shi Xiaodong
Published: May 2016

We describe herein a gold-catalyzed rearrangement of propargyl esters followed by allene–ene cyclization to afford substituted bicyclic [4.4.0] dihydronaphthalene compounds.
Sandwich phosphate complexes of macrocyclic tris(urea) ligands and their rotation around the anion
Authors: Ji Liguo , Yang Zaiwen , Zhao Yanxia , Sun Meng , Cao Liping , Yang Xiao-Juan , Wang Yao-Yu , Wu Biao
Published: May 2016

Sandwich-type phosphate complexes were formed by macrocyclic ligands incorporating both anion- (tris-urea unit) and cation-binding sites (polyether), which display a reversible rotation around the anion upon protonation/deprotonation of phosphate and binding of the cation (Emim+).