bluuebunny/crossref_metadata_2025 huggingface dataset:
Narrative when in English
Authors: BACHE CARL
Published: May 2016

This article examines the so-called ‘narrative when’ construction in English. No one has come up with an entirely satisfactory description of this construction which accounts appropriately for both its syntax and content. The descriptive challenge is to explain the unusual balance between the main clause and the when clause: unlike an ordinary temporal when clause (which offers circumstantial information in relation to the main clause), a narrative when clause expresses the primary situation while the main clause merely has a supporting textual function. This article suggests a simple framework for the description of all when clauses within which narrative when clauses are very comfortably accommodated as one of the metaphorical extensions of the basic meaning and syntax of when.
MODELING THE PHILLIPS CURVE IN CHINA: A NONLINEAR PERSPECTIVE
Authors: Zhang Lingxiang
Published: May 2016

This paper investigates the nonlinear dynamics of the inflation–output type of Phillips curve based on a multiple-regime smooth transition regression model using data from China. The empirical results indicate significant nonlinearities in China's Phillips curve. The relationship between inflation and output can be modeled by a four-regime smooth transition regression model in which the responses of inflation to output depend on both inflation and economic growth rates. The inflation–output type Phillips curve may be positively sloped, negatively sloped, or even vertical in the short term, depending on different business cycles. Furthermore, we analyze business cycle fluctuations based on the nonlinear Phillips curve, indicating a coexisting zone of stable inflation rate and rapid growth rate.
POLICY PREFERENCES AND POLICY MAKERS' BELIEFS: THE GREAT INFLATION
Authors: Best Gabriela
Published: May 2016

The literature has proposed two potential channels through which monetary policy played a role in the Great Inflation in the United States. One approach posits that the Federal Reserve held misperceptions of the economy. An alternative explanation contends that policy makers shifted preferences from an output gap stabilization goal toward inflation stabilization after 1979. This paper develops a medium-scale macroeconomic model that incorporates real-timelearningby policy makers as well as a (potential) shift in policy makers' preferences. The empirical results show that combining both views—distorted policy makers' beliefs about the persistence of inflation and the inflation-output gap trade-off, accompanied by a stronger preference for inflation stabilization after 1979—illuminates the role played by monetary policy in propagating and ending the Great Inflation.
Photo gallery: Ground zero Nagasaki
Authors: Nakamura Akitoshi
Published: May 2016

This selection of photos is meant as an appeal from the Nagasaki Atomic Bomb Museum to remember the atomic bombing of Nagasaki on 9 August 1945. It was compiled by museum director Akitoshi Nakamura based on the collection at the Nagasaki Atomic Bomb Museum.1 Readers are invited to visit the Nagasaki Atomic Bomb Museum and spend some time viewing its collection of over 1,000 photographs and remnants from the city at that time to get a sense of what happened before and after the atomic bombing that summer seventy years ago, and how devastating the atomic bomb's destructive effects were.
Automatic quantitative analysis of experimental primary and secondary retinal neurodegeneration: implications for optic neuropathies
Authors: Davis B M , Guo L , Brenton J , Langley L , Normando E M , Cordeiro M F
Published: May 2016

Secondary neurodegeneration is thought to play an important role in the pathology of neurodegenerative disease, which potential therapies may target. However, the quantitative assessment of the degree of secondary neurodegeneration is difficult. The present study describes a novel algorithm from which estimates of primary and secondary degeneration are computed using well-established rodent models of partial optic nerve transection (pONT) and ocular hypertension (OHT). Brn3-labelled retinal ganglion cells (RGCs) were identified in whole-retinal mounts from which RGC density, nearest neighbour distances and regularity indices were determined. The spatial distribution and rate of RGC loss were assessed and the percentage of primary and secondary degeneration in each non-overlapping segment was calculated. Mean RGC number (82 592±681) and RGC density (1695±23.3 RGC/mm2) in naïve eyes were comparable with previous studies, with an average decline in RGC density of 71±17 and 23±5% over the time course of pONT and OHT models, respectively. Spatial analysis revealed greatest RGC loss in the superior and central retina in pONT, but significant RGC loss in the inferior retina from 3 days post model induction. In comparison, there was no significant difference between superior and inferior retina after OHT induction, and RGC loss occurred mainly along the superior/inferior axis (~30%)versusthe nasal–temporal axis (~15%). Intriguingly, a significant loss of RGCs was also observed in contralateral eyes in experimental OHT. In conclusion, a novel algorithm to automatically segment Brn3a-labelled retinal whole-mounts into non-overlapping segments is described, which enables automated spatial and temporal segmentation of RGCs, revealing heterogeneity in the spatial distribution of primary and secondary degenerative processes. This method provides an attractive means to rapidly determine the efficacy of neuroprotective therapies with implications for any neurodegenerative disorder affecting the retina.
Design and fabrication of silicon-tessellated structures for monocentric imagers
Authors: Wu Tao , Hamann Stephen S. , Ceballos Andrew C. , Chang Chu-En , Solgaard Olav , Howe Roger T.
Published: May 2016

Compared with conventional planar optical image sensors, a curved focal plane array can simplify the lens design and improve the field of view. In this paper, we introduce the design and implementation of a segmented, hemispherical, CMOS-compatible silicon image plane for a 10-mm diameter spherical monocentric lens. To conform to the hemispherical focal plane of the lens, we use flexible gores that consist of arrays of spring-connected silicon hexagons. Mechanical functionality is demonstrated by assembling the 20-μm-thick silicon gores into a hemispherical test fixture. We have also fabricated and tested a photodiode array on a silicon-on-insulator substrate for use with the curved imager. Optical testing shows that the fabricated photodiodes achieve good performance; the hemispherical imager enables a compact 160 ° field of view camera with >80% fill factor using a single spherical lens.
Domain topology and domain switching kinetics in a hybrid improper ferroelectric
Authors: Huang F. -T. , Xue F. , Gao B. , Wang L. H. , Luo X. , Cai W. , Lu X. -Z. , Rondinelli J. M. , Chen L. Q. , Cheong S. -W.
Published: May 2016

Charged polar interfaces such as charged ferroelectric walls or heterostructured interfaces of ZnO/(Zn,Mg)O and LaAlO3/SrTiO3, across which the normal component of electric polarization changes suddenly, can host large two-dimensional conduction. Charged ferroelectric walls, which are energetically unfavourable in general, were found to be mysteriously abundant in hybrid improper ferroelectric (Ca,Sr)3Ti2O7crystals. From the exploration of antiphase boundaries in bilayer-perovskites, here we discover that each of four polarization-direction states is degenerate with two antiphase domains, and these eight structural variants form a Z4× Z2domain structure with Z3vortices and five distinct types of domain walls, whose topology is directly relevant to the presence of abundant charged walls. We also discover a zipper-like nature of antiphase boundaries, which are the reversible creation/annihilation centres of pairs of two types of ferroelectric walls (and also Z3-vortex pairs) in 90° and 180° polarization switching. Our results demonstrate the unexpectedly rich nature of hybrid improper ferroelectricity.
A wearable chemical–electrophysiological hybrid biosensing system for real-time health and fitness monitoring
Authors: Imani Somayeh , Bandodkar Amay J. , Mohan A. M. Vinu , Kumar Rajan , Yu Shengfei , Wang Joseph , Mercier Patrick P.
Published: May 2016

Flexible, wearable sensing devices can yield important information about the underlying physiology of a human subject for applications in real-time health and fitness monitoring. Despite significant progress in the fabrication of flexible biosensors that naturally comply with the epidermis, most designs measure only a small number of physical or electrophysiological parameters, and neglect the rich chemical information available from biomarkers. Here, we introduce a skin-worn wearable hybrid sensing system that offers simultaneous real-time monitoring of a biochemical (lactate) and an electrophysiological signal (electrocardiogram), for more comprehensive fitness monitoring than from physical or electrophysiological sensors alone. The two sensing modalities, comprising a three-electrode amperometric lactate biosensor and a bipolar electrocardiogram sensor, are co-fabricated on a flexible substrate and mounted on the skin. Human experiments reveal that physiochemistry and electrophysiology can be measured simultaneously with negligible cross-talk, enabling a new class of hybrid sensing devices.
Essential structural elements in tRNAPro for EF-P-mediated alleviation of translation stalling
Authors: Katoh Takayuki , Wohlgemuth Ingo , Nagano Masanobu , Rodnina Marina V. , Suga Hiroaki
Published: May 2016

The ribosome stalls on translation of polyproline sequences due to inefficient peptide bond formation between consecutive prolines. The translation factor EF-P is able to alleviate this stalling by accelerating Pro-Pro formation. However, the mechanism by which EF-P recognizes the stalled complexes and accelerates peptide bond formation is not known. Here, we use genetic code reprogramming through a flexible in-vitro translation (FIT) system to investigate how mutations in tRNAPro affect EF-P function. We show that the 9-nt D-loop closed by the stable D-stem sequence in tRNAPro is a crucial recognition determinant for EF-P. Such D-arm structures are shared only among the tRNAPro isoacceptors and tRNAfMet in Escherichia coli, and the D-arm of tRNAfMet is essential for EF-P-induced acceleration of fMet–puromycin formation. Thus, the activity of EF-P is controlled by recognition elements in the tRNA D-arm.
Potent social synchronization can override photic entrainment of circadian rhythms
Authors: Fuchikawa Taro , Eban-Rothschild Ada , Nagari Moshe , Shemesh Yair , Bloch Guy
Published: May 2016

Circadian rhythms in behaviour and physiology are important for animal health and survival. Studies with individually isolated animals in the laboratory have consistently emphasized the dominant role of light for the entrainment of circadian rhythms to relevant environmental cycles. Although in nature interactions with conspecifics are functionally significant, social signals are typically not considered important time-givers for the animal circadian clock. Our results challenge this view. By studying honeybees in an ecologically relevant context and using a massive data set, we demonstrate that social entrainment can be potent, may act without direct contact with other individuals and does not rely on gating the exposure to light. We show for the first time that social time cues stably entrain the clock, even in animals experiencing conflicting photic and social environmental cycles. These findings add to the growing appreciation for the importance of studying circadian rhythms in ecologically relevant contexts.
The rubber tree genome reveals new insights into rubber production and species adaptation
Authors: Tang Chaorong , Yang Meng , Fang Yongjun , Luo Yingfeng , Gao Shenghan , Xiao Xiaohu , An Zewei , Zhou Binhui , Zhang Bing , Tan Xinyu , Yeang Hoong-Yeet , Qin Yunxia , Yang Jianghua , Lin Qiang , Mei Hailiang , Montoro Pascal , Long Xiangyu , Qi Jiyan , Hua Yuwei , He Zilong , Sun Min , Li Wenjie , Zeng Xia , Cheng Han , Liu Ying , Yang Jin , Tian Weimin , Zhuang Nansheng , Zeng Rizhong , Li Dejun , He Peng , Li Zhe , Zou Zhi , Li Shuangli , Li Chenji , Wang Jixiang , Wei Dong , Lai Chao-Qiang , Luo Wei , Yu Jun , Hu Songnian , Huang Huasun
Published: May 2016

The Para rubber tree (Hevea brasiliensis) is an economically important tropical tree species that produces natural rubber, an essential industrial raw material. Here we present a high-quality genome assembly of this species (1.37 Gb, scaffold N50 = 1.28 Mb) that covers 93.8% of the genome (1.47 Gb) and harbours 43,792 predicted protein-coding genes. A striking expansion of the REF/SRPP (rubber elongation factor/small rubber particle protein) gene family and its divergence into several laticifer-specific isoforms seem crucial for rubber biosynthesis. The REF/SRPP family has isoforms with sizes similar to or larger than SRPP1 (204 amino acids) in 17 other plants examined, but no isoforms with similar sizes to REF1 (138 amino acids), the predominant molecular variant. A pivotal point in Hevea evolution was the emergence of REF1, which is located on the surface of large rubber particles that account for 93% of rubber in the latex (despite constituting only 6% of total rubber particles, large and small). The stringent control of ethylene synthesis under active ethylene signalling and response in laticifers resolves a longstanding mystery of ethylene stimulation in rubber production. Our study, which includes the re-sequencing of five other Hevea cultivars and extensive RNA-seq data, provides a valuable resource for functional genomics and tools for breeding elite Hevea cultivars.
An agricultural survey for more than 9,500 African households
Authors: Waha Katharina , Zipf Birgit , Kurukulasuriya Pradeep , Hassan Rashid M.
Published: May 2016

Surveys for more than 9,500 households were conducted in the growing seasons 2002/2003 or 2003/2004 in eleven African countries: Burkina Faso, Cameroon, Ghana, Niger and Senegal in western Africa; Egypt in northern Africa; Ethiopia and Kenya in eastern Africa; South Africa, Zambia and Zimbabwe in southern Africa. Households were chosen randomly in districts that are representative for key agro-climatic zones and farming systems. The data set specifies farming systems characteristics that can help inform about the importance of each system for a country’s agricultural production and its ability to cope with short- and long-term climate changes or extreme weather events. Further it informs about the location of smallholders and vulnerable systems and permits benchmarking agricultural systems characteristics.
MIMIC-III, a freely accessible critical care database
Authors: Johnson Alistair E.W. , Pollard Tom J. , Shen Lu , Lehman Li-wei H. , Feng Mengling , Ghassemi Mohammad , Moody Benjamin , Szolovits Peter , Anthony Celi Leo , Mark Roger G.
Published: May 2016

MIMIC-III (‘Medical Information Mart for Intensive Care’) is a large, single-center database comprising information relating to patients admitted to critical care units at a large tertiary care hospital. Data includes vital signs, medications, laboratory measurements, observations and notes charted by care providers, fluid balance, procedure codes, diagnostic codes, imaging reports, hospital length of stay, survival data, and more. The database supports applications including academic and industrial research, quality improvement initiatives, and higher education coursework.
Correction: Corrigendum: The genome sequence of the outbreeding globe artichoke constructed de novo incorporating a phase-aware low-pass sequencing strategy of F1 progeny
Authors: Scaglione Davide , Reyes-Chin-Wo Sebastian , Acquadro Alberto , Froenicke Lutz , Portis Ezio , Beitel Christopher , Tirone Matteo , Mauro Rosario , Lo Monaco Antonino , Mauromicale Giovanni , Faccioli Primetta , Cattivelli Luigi , Rieseberg Loren , Michelmore Richard , Lanteri Sergio
Published: May 2016

Scientific Reports 6: Article number: 19427; published online: 20 January 2016; updated: 23 May 2016. In this Article, there are typographical errors in the legend of Figure 5. “(a) Overall distribution of the repetitive fraction. (b) Distributions of insertion ages in different families of LTR elements”.
Monoclonal regulatory T cells provide insights into T cell suppression
Authors: Gubser Céline , Schmaler Mathias , Rossi Simona W. , Palmer Ed
Published: May 2016

Regulatory T cells (Tregs) have a crucial role in maintaining lymphocyte homeostasis. However an understanding of how Tregs function at a cellular and molecular level has not yet been fully elucidated. Here, we make use of a T cell receptor (TCR) transgenic, Rag−/− mouse expressing a Forkhead-Box-Protein P3 (Foxp3) transgene. This mouse provides a source of monoclonal CD4+ Foxp3+ T cells with a defined specificity. Here we show that monoclonal B3K506 Tregs are functional in vitro and in vivo and clearly require cognate antigen to be suppressive. We further show that the strength of Treg stimulation determines the strength of Treg mediated suppression. Finally we analysed various suppressive mechanisms used by monoclonal Tregs and found that Treg-Tconv proximity is a parameter, which correlates with enhanced suppression.
Correction: Corrigendum: ZnCr2O4 Nanoparticles: Facile Synthesis, Characterization, and Photocatalytic Properties
Authors: Mousavi Zahra , Soofivand Faezeh , Esmaeili-Zare Mahdiyeh , Salavati-Niasari Masoud , Bagheri Samira
Published: May 2016

Scientific Reports 6: Article number: 20071; published online: 01 February 2016; updated: 23 May 2016 This Article contains an error in the order of the Figures. Figure 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11 were published as Figure 7, 8, 1, 9, 10, 11, 2, 3, 4, 5 and 6 respectively. The correct Figures appear below as Figures 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11.
Europium Silicide – a Prospective Material for Contacts with Silicon
Authors: Averyanov Dmitry V. , Tokmachev Andrey M. , Karateeva Christina G. , Karateev Igor A. , Lobanovich Eduard F. , Prutskov Grigory V. , Parfenov Oleg E. , Taldenkov Alexander N. , Vasiliev Alexander L. , Storchak Vyacheslav G.
Published: May 2016

Metal-silicon junctions are crucial to the operation of semiconductor devices: aggressive scaling demands low-resistive metallic terminals to replace high-doped silicon in transistors. It suggests an efficient charge injection through a low Schottky barrier between a metal and Si. Tremendous efforts invested into engineering metal-silicon junctions reveal the major role of chemical bonding at the interface: premier contacts entail epitaxial integration of metal silicides with Si. Here we present epitaxially grown EuSi2/Si junction characterized by RHEED, XRD, transmission electron microscopy, magnetization and transport measurements. Structural perfection leads to superb conductivity and a record-low Schottky barrier with n-Si while an antiferromagnetic phase invites spin-related applications. This development opens brand-new opportunities in electronics.
Dynamical state of the network determines the efficacy of single neuron properties in shaping the network activity
Authors: Sahasranamam Ajith , Vlachos Ioannis , Aertsen Ad , Kumar Arvind
Published: May 2016

Spike patterns are among the most common electrophysiological descriptors of neuron types. Surprisingly, it is not clear how the diversity in firing patterns of the neurons in a network affects its activity dynamics. Here, we introduce the state-dependent stochastic bursting neuron model allowing for a change in its firing patterns independent of changes in its input-output firing rate relationship. Using this model, we show that the effect of single neuron spiking on the network dynamics is contingent on the network activity state. While spike bursting can both generate and disrupt oscillations, these patterns are ineffective in large regions of the network state space in changing the network activity qualitatively. Finally, we show that when single-neuron properties are made dependent on the population activity, a hysteresis like dynamics emerges. This novel phenomenon has important implications for determining the network response to time-varying inputs and for the network sensitivity at different operating points.
Retention Mechanisms of Citric Acid in Ternary Kaolinite-Fe(III)-Citrate Acid Systems Using Fe K-edge EXAFS and L3,2-edge XANES Spectroscopy
Authors: Yang Jianjun , Wang Jian , Pan Weinan , Regier Tom , Hu Yongfeng , Rumpel Cornelia , Bolan Nanthi , Sparks Donald
Published: May 2016

Organic carbon (OC) stability in tropical soils is strongly interlinked with multivalent cation interaction and mineral association. Low molecular weight organic acids (LMWOAs) represent the readily biodegradable OC. Therefore, investigating retention mechanisms of LMWOAs in mineral-cation-LMWOAs systems is critical to understanding soil C cycling. Given the general acidic conditions and dominance of kaolinite in tropical soils, we investigated the retention mechanisms of citric acid (CA) in kaolinite-Fe(III)-CA systems with various Fe/CA molar ratios at pH ~3.5 using Fe K-edge EXAFS and L3,2-edge XANES techniques. With Fe/CA molar ratios >2, the formed ferrihydrite mainly contributed to CA retention through adsorption and/or coprecipitation. With Fe/CA molar ratios from 2 to 0.5, ternary complexation of CA to kaolinite via a five-coordinated Fe(III) bridge retained higher CA than ferrihydrite-induced adsorption and/or coprecipitation. With Fe/CA molar ratios ≤0.5, kaolinite-Fe(III)-citrate complexation preferentially occurred, but less CA was retained than via outer-sphere kaolinite-CA complexation. This study highlighted the significant impact of varied Fe/CA molar ratios on CA retention mechanisms in kaolinite-Fe(III)-CA systems under acidic conditions and clearly showed the important contribution of Fe-bridged ternary complexation on CA retention. These findings will enhance our understanding of the dynamics of CA and other LMWOAs in tropical soils.
Uncovering three-dimensional gradients in fibrillar orientation in an impact-resistant biological armour
Authors: Zhang Y. , Paris O. , Terrill N. J. , Gupta H. S.
Published: May 2016

The complex hierarchical structure in biological and synthetic fibrous nanocomposites entails considerable difficulties in the interpretation of the crystallographic texture from diffraction data. Here, we present a novel reconstruction method to obtain the 3D distribution of fibres in such systems. An analytical expression is derived for the diffraction intensity from fibres, explaining the azimuthal intensity distribution in terms of the angles of the three dimensional fibre orientation distributions. The telson of stomatopod (mantis shrimp) serves as an example of natural biological armour whose high impact resistance property is believed to arise from the hierarchical organization of alpha chitin nanofibrils into fibres and twisted plywood (Bouligand) structures at the sub-micron and micron scale. Synchrotron microfocus scanning X-ray diffraction data on stomatopod telson were used as a test case to map the 3D fibre orientation across the entire tissue section. The method is applicable to a range of biological and biomimetic structures with graded 3D fibre texture at the sub-micron and micron length scales.
Decellularization of human stromal refractive lenticules for corneal tissue engineering
Authors: Yam Gary Hin-Fai , Yusoff Nur Zahirah Binte M. , Goh Tze-Wei , Setiawan Melina , Lee Xiao-Wen , Liu Yu-Chi , Mehta Jodhbir S.
Published: May 2016

Small incision lenticule extraction (SMILE) becomes a procedure to correct myopia. The extracted lenticule can be used for other clinical scenarios. To prepare for allogeneic implantation, lenticule decellularization with preserved optical property, stromal architecture and chemistry would be necessary. We evaluated different methods to decellularize thin human corneal stromal lenticules created by femtosecond laser. Treatment with 0.1% sodium dodecylsulfate (SDS) followed by extensive washes was the most efficient protocol to remove cellular and nuclear materials. Empty cell space was found inside the stroma, which displayed aligned collagen fibril architecture similar to native stroma. The SDS-based method was superior to other treatments with hyperosmotic 1.5 M sodium chloride, 0.1% Triton X-100 and nucleases (from 2 to 10 U/ml DNase and RNase) in preserving extracellular matrix content (collagens, glycoproteins and glycosaminoglycans). The stromal transparency and light transmittance was indifferent to untreated lenticules. In vitro recellularization showed that the SDS-treated lenticules supported corneal stromal fibroblast growth. In vivo re-implantation into a rabbit stromal pocket further revealed the safety and biocompatibility of SDS-decellularized lenticules without short- and long-term rejection risk. Our results concluded that femtosecond laser-derived human stromal lenticules decellularized by 0.1% SDS could generate a transplantable bioscaffold with native-like stromal architecture and chemistry.
Biodegradable Magnesium (Mg) Implantation Does Not Impose Related Metabolic Disorders in Rats with Chronic Renal Failure
Authors: Wang Jiali , Xu Jiankun , Liu Waiching , Li Yangde , Qin Ling
Published: May 2016

Mg and its alloys have been considered as one of the most promising biodegradable medical devices, but it was still unclear whether hypermagnesemia involved health risks would occur in persons with kidney disease due to their deteriorated kidney function for Mg ions excretion from their body. In this study, we established a chronic renal failure (CRF) model in rats induced by adenine administration prior to Mg implantation, aiming to predict if CRF patients are suitable for the use of Mg implants. The results showed that Mg levels in serum, urine, feces and internal organs had no significant changes after Mg implantation for both normal and CRF rats. Biochemical indices detection and histopathological analysis in kidney, liver and heart tissue confirmed that Mg implants did not induce any extra damage in animals even with renal failure. Our study indicates that Mg based orthopaedic medical device may be considered for use in CRF patients without biosafety concerns.
Big Data Analytics for Scanning Transmission Electron Microscopy Ptychography
Authors: Jesse S. , Chi M. , Belianinov A. , Beekman C. , Kalinin S. V. , Borisevich A. Y. , Lupini A. R.
Published: May 2016

Electron microscopy is undergoing a transition; from the model of producing only a few micrographs, through the current state where many images and spectra can be digitally recorded, to a new mode where very large volumes of data (movies, ptychographic and multi-dimensional series) can be rapidly obtained. Here, we discuss the application of so-called “big-data” methods to high dimensional microscopy data, using unsupervised multivariate statistical techniques, in order to explore salient image features in a specific example of BiFeO3 domains. Remarkably, k-means clustering reveals domain differentiation despite the fact that the algorithm is purely statistical in nature and does not require any prior information regarding the material, any coexisting phases, or any differentiating structures. While this is a somewhat trivial case, this example signifies the extraction of useful physical and structural information without any prior bias regarding the sample or the instrumental modality. Further interpretation of these types of results may still require human intervention. However, the open nature of this algorithm and its wide availability, enable broad collaborations and exploratory work necessary to enable efficient data analysis in electron microscopy.
Assembling Composite Dermal Papilla Spheres with Adipose-derived Stem Cells to Enhance Hair Follicle Induction
Authors: Huang Chin-Fu , Chang Ya-Ju , Hsueh Yuan-Yu , Huang Chia-Wei , Wang Duo-Hsiang , Huang Tzu-Chieh , Wu Yi-Ting , Su Fong-Chin , Hughes Michael , Chuong Cheng-Ming , Wu Chia-Ching
Published: May 2016

Intradermal adipose tissue plays an essential role for hair follicles (HFs) regeneration by regulating hair cycles. However, the effect of reconstruction of HFs and the involvement of adipose-related cells are poorly understood. We investigated assembly strategies for the interactions of dermal papilla (DP) cells with adipose-derived stem cells (ASCs) in promoting hair formation. DP cells lose DP traits during adherent culture, but preserved DP markers with a unified sphere diameter by seeding on chitosan-coated microenvironments. Next, ASCs isolated from rats were co-cultured with DP spheres by different assembling approaches to determine their interactions; a mixed sphere of ASCs with DP cells (MA-DPS), or a core-shell structure, outer ASCs shell and an inner DP core (CSA-DPS). CSA-DPS exhibited superior DP characteristics compared to MA-DPS. Conditional medium from ASCs, but not differentiated adipocytes, promoted DP markers and functional alkaline phosphatase activity from the DP cells. In vivo patch assay showed the core-shell assembling of CSA-DPS can reconstruct cellular arrangements and microenvironmental niches as dominated by PPARα signal in ASCs to induce the greater hair induction than MA-DPS or DP spheres alone. Therefore, the assembling of a core-shell sphere for DP with ASCs could reconstruct the HF cellular arrangement for hair formation. This paper set the groundwork for further evaluation of the input of other cell types.
Mechanism of p27 Unfolding for CDK2 Reactivation
Authors: Rath Soumya Lipsa , Senapati Sanjib
Published: May 2016

Cell-cycle regulatory protein, CDK2 is active when bound to its complementary partner protein, CyclinA or E. Recent discovery of the Kip/Cip family of proteins has indicated that the activity of CDK2 is also regulated by a member protein, p27. Although, the mechanism of CDK2 inhibition by p27 binding is known from crystal structure, little is known about the mechanism of CDK2 reactivation. Here, we execute classical and accelerated molecular dynamics simulations of unphosphorylated- and phosphorylated-p27 bound CDK2/CyclinA to unravel the CDK2 reactivation mechanism at molecular-to-atomic detail. Results suggest that the phosphorylation of p27 Y88 residue (pY88-p27) first disrupts the p27/CDK2 hybrid β-sheet and subsequently ejects the p27 310 helix from CDK2 catalytic cleft. The unbinding of p27 from CDK2/CyclinA complex, thus, follows a two-step unfolding mechanism, where the 310 helix ejection constitutes the rate-limiting step. Interestingly, the unfolding of p27 leaves CDK2/CyclinA in an active state, where the prerequisite CDK2-CyclinA interfacial contacts were regained and ATP achieved its native position for smooth transfer of phosphate. Our findings match very well with NMR chemical shift data that indicated the flip-out of p27 310 helix from CDK2 pocket and kinetic experiments that exhibited significant kinase activity of CDK2 when saturated with pY88-p27.
GBIQ: a non-arbitrary, non-biased method for quantification of fluorescent images
Authors: Ninomiya Youichirou , Zhao Wei , Saga Yumiko
Published: May 2016

Non-arbitrary and non-biased quantification of fluorescent images is an essential tool for the data-centric approach to biological systems. Typical application is high-content analysis, where various phenotypic changes in cellular components and/or morphology are measured from fluorescent image data. A standard protocol to detect cellular phenotypes is cell-segmentation, in which boundaries of cellular components, such as cell nucleus and plasma membrane, are first identified to define cell segments, then acquiring various phenotypic data of each segment. To achieve reliable outcome, cell-segmentation requires manual adjustments of many parameters; this requirement could hamper automated image processing in high-throughput workflow, whose quantification must be non-arbitrary and non-biased. As a practical alternative to the segmentation-based method, we developed GBIQ (Grid Based Image Quantification), which allows comparison of cellular information without identification of single cells. GBIQ divides an image with tiles of fixed size grids and records statistics of the grids with their location coordinates, minimizing arbitrary intervenes. GBIQ requires only one parameter (size of grid) to be set; nonetheless it robustly produces results suitable for further statistical evaluation. The simplicity of GBIQ allows it to be readily implemented in an automated high-throughput image analysis workflow.
An essential role for the baseplate protein Gp45 in phage adsorption to Staphylococcus aureus
Authors: Li Xuehua , Koç Cengiz , Kühner Petra , Stierhof York-Dieter , Krismer Bernhard , Enright Mark C. , Penadés José R. , Wolz Christiane , Stehle Thilo , Cambillau Christian , Peschel Andreas , Xia Guoqing
Published: May 2016

Despite the importance of phages in driving horizontal gene transfer (HGT) among pathogenic bacteria, the underlying molecular mechanisms mediating phage adsorption to S. aureus are still unclear. Phage ϕ11 is a siphovirus with a high transducing efficiency. Here, we show that the tail protein Gp45 localized within the ϕ11 baseplate. Phage ϕ11 was efficiently neutralized by anti-Gp45 serum and its adsorption to host cells was inhibited by recombinant Gp45 in a dose-dependent manner. Flow cytometry analysis demonstrated that biotin-labelled Gp45 efficiently stained the wild-type S. aureus cell but not the double knockout mutant ΔtarM/S, which lacks both α- and β-O-GlcNAc residues on its wall teichoic acids (WTAs). Additionally, adsorption assays indicate that GlcNAc residues on WTAs and O-acetyl groups at the 6-position of muramic acid residues in peptidoglycan are essential components of the ϕ11 receptor. The elucidation of Gp45-involved molecular interactions not only broadens our understanding of siphovirus-mediated HGT, but also lays the groundwork for the development of sensitive affinity-based diagnostics and therapeutics for S. aureus infection.
Unique 1D Co3O4 crystallized nanofibers with (220) oriented facets as high-performance lithium ion battery anode material
Authors: Tan Yanli , Gao Qiuming , Li Zeyu , Tian Weiqian , Qian Weiwei , Yang Chunxiao , Zhang Hang
Published: May 2016

A novel one-step hydrothermal and calcination strategy was developed to synthesize the unique 1D oriented Co3O4 crystal nanofibers with (220) facets on the carbon matrix derived from the natural, abundant and low cost wool fibers acting as both carbon precursor and template reagent. The resultant W2@Co3O4 nanocomposite exhibited very high specific capacity and favorable high-rate capability when used as anode material of lithium ion battery. The high reversible Li+ ion storage capacity of 986 mAh g−1 was obtained at 100 mA g−1 after 150 cycles, higher than the theoretical capacity of Co3O4 (890 mAh g−1). Even at the higher current density of 1 A g−1, the electrode could still deliver a remarkable discharge capacity of 720 mAh g−1 over 150 cycles.
Interaction of single and multi wall carbon nanotubes with the biological systems: tau protein and PC12 cells as targets
Authors: Zeinabad Hojjat Alizadeh , Zarrabian Alireza , Saboury Ali Akbar , Alizadeh Ali Mohammad , Falahati Mojtaba
Published: May 2016

Subtle changes in the structure of nanoparticles influence their surface tension and corresponding interaction with cells and proteins. Here, the interaction of the single wall carbon nanotube (SWCNT) and multiwall carbon nanotube (MWCNT) with different surface tension with tau protein was evaluated using a variety of techniques including far and near circular dichroism, fluorescence spectroscopy, dynamic light scattering, Zeta potential, and TEM evaluation. Also the cytotoxicity of SWCNT and MWCNT on the PC12 cell line as a model of nervous system cell line was investigated by the MTT, LDH, acridine orange/ethidium bromide staining, flow cytometry, caspase 3 activity, cell and membrane potential assays. It was observed that SWCNT induced more structural changes of tau protein relative to MWCNT/tau protein interaction. It was also revealed that SWCNT and MWCNT impaired the viability and complexity of PC12 cells in different modes of cytotoxicity. Analysis of cellular outcomes indicated that MWCNT in comparison with SWCNT resulted in induction of necrotic modes of cell death, whereas apoptotic modes of cell death were activated in SWCNT-incubated cells. Together these findings suggest that surface tension may be used to determine how nanoparticle structure affects neurotoxicity and protein conformational changes.
Small molecule activation of NOTCH signaling inhibits acute myeloid leukemia
Authors: Ye Qi , Jiang Jue , Zhan Guanqun , Yan Wanyao , Huang Liang , Hu Yufeng , Su Hexiu , Tong Qingyi , Yue Ming , Li Hua , Yao Guangmin , Zhang Yonghui , Liu Hudan
Published: May 2016

Aberrant activation of the NOTCH signaling pathway is crucial for the onset and progression of T cell leukemia. Yet recent studies also suggest a tumor suppressive role of NOTCH signaling in acute myeloid leukemia (AML) and reactivation of this pathway offers an attractive opportunity for anti-AML therapies. N-methylhemeanthidine chloride (NMHC) is a novel Amaryllidaceae alkaloid that we previously isolated from Zephyranthes candida, exhibiting inhibitory activities in a variety of cancer cells, particularly those from AML. Here, we report NMHC not only selectively inhibits AML cell proliferation in vitro but also hampers tumor development in a human AML xenograft model. Genome-wide gene expression profiling reveals that NMHC activates the NOTCH signaling. Combination of NMHC and recombinant human NOTCH ligand DLL4 achieves a remarkable synergistic effect on NOTCH activation. Moreover, pre-inhibition of NOTCH by overexpression of dominant negative MAML alleviates NMHC-mediated cytotoxicity in AML. Further mechanistic analysis using structure-based molecular modeling as well as biochemical assays demonstrates that NMHC docks in the hydrophobic cavity within the NOTCH1 negative regulatory region (NRR), thus promoting NOTCH1 proteolytic cleavage. Our findings thus establish NMHC as a potential NOTCH agonist that holds great promises for future development as a novel agent beneficial to patients with AML.
Participants’ above-chance recognition of own-heart sound combined with poor metacognitive awareness suggests implicit knowledge of own heart cardiodynamics
Authors: Azevedo Ruben T. , Aglioti Salvatore Maria , Lenggenhager Bigna
Published: May 2016

Mounting evidence suggests that interoceptive signals are fundamentally important for the experience of the self. Thus far, studies on interoception have mainly focused on the ability to monitor the timing of ongoing heartbeats and on how these influence emotional and self-related processes. However, cardiac afferent signalling is not confined to heartbeat timing and several other cardiac parameters characterize cardiodynamic functioning. Building on the fact that each heart has its own self-specific cardio-dynamics, which cannot be expressed uniquely by heart rate, we devised a novel task to test whether people could recognize the sound of their own heart even when perceived offline and thus not in synchrony with ongoing heartbeats. In a forced-choice paradigm, participants discriminated between sounds of their own heartbeat (previously recorded with a Doppler device) versus another person’s heart. Participants identified the sound of their own heart above chance, whereas their metacognition of performance – as calculated by contrasting performance against ratings of confidence - was considerably poorer. These results suggest an implicit access to fine-grained neural representations of elementary cardio-dynamic parameters beyond heartbeat timing.
Inappropriate cadherin switching in the mouse epiblast compromises proper signaling between the epiblast and the extraembryonic ectoderm during gastrulation
Authors: Basilicata M. Felicia , Frank Marcus , Solter Davor , Brabletz Thomas , Stemmler Marc P.
Published: May 2016

Cadherin switching from E-cadherin (E-cad) to N-cadherin (N-cad) is a key step of the epithelial-mesenchymal transition (EMT) processes that occurs during gastrulation and cancer progression. We investigate whether cadherins actively participate in progression of EMT by crosstalk to signaling pathways. We apply ectopic cadherin switching before the onset of mouse gastrulation. Mutants with an induced E-cad to N-cad switch (Ncadki) die around E8.5. Severe morphological changes including a small epiblast, a rounded shape, an enlarged extra-embryonic compartment and lack of the amnion, combined with a massive cell detachment from the ectodermal layer are detected. In contrast to epiblast-specific E-cad depletion, gastrulation is initiated in Ncadki embryos, but patterning of the germ-layers is abnormal. An overall reduction in BMP signaling, expansion ofNodalandEomesdomains, combined with reducedWnt3aexpression at the primitive streak is observed. Our results show that in addition to cadherin-dependent adhesion, proper embryonic development requires E-cad mediated signaling function to facilitate a feedback loop that stabilizesBmp4andBmp2expression in the extraembryonic ectoderm and sustained downstream activity in the epiblast. Moreover, for proper morphogenesis a fine-tuned spatio-temporal control of cadherin switching is required during EMT at gastrulation to avoid premature cell detachment and migration.
Engineering a 3D microfluidic culture platform for tumor-treating field application
Authors: Pavesi Andrea , Adriani Giulia , Tay Andy , Warkiani Majid Ebrahimi , Yeap Wei Hseun , Wong Siew Cheng , Kamm Roger D.
Published: May 2016

The limitations of current cancer therapies highlight the urgent need for a more effective therapeutic strategy. One promising approach uses an alternating electric field; however, the mechanisms involved in the disruption of the cancer cell cycle as well as the potential adverse effects on non-cancerous cells must be clarified. In this study, we present a novel microfluidic device with embedded electrodes that enables the application of an alternating electric field therapy to cancer cells in a 3D extracellular matrix. To demonstrate the potential of our system to aid in designing and testing new therapeutic approaches, cancer cells and cancer cell aggregates were cultured individually or co-cultured with endothelial cells. The metastatic potential of the cancer cells was reduced after electric field treatment. Moreover, the proliferation rate of the treated cancer cells was lower compared with that of the untreated cells, whereas the morphologies and proliferative capacities of the endothelial cells were not significantly affected. These results demonstrate that our novel system can be used to rapidly screen the effect of an alternating electric field on cancer and normal cells within an in vivo-like microenvironment with the potential to optimize treatment protocols and evaluate synergies between tumor-treating field treatment and chemotherapy.
Cultured pericytes from human brain show phenotypic and functional differences associated with differential CD90 expression
Authors: Park Thomas I-H. , Feisst Vaughan , Brooks Anna E. S. , Rustenhoven Justin , Monzo Hector J. , Feng Sheryl X. , Mee Edward W. , Bergin Peter S. , Oldfield Robyn , Graham E. Scott , Curtis Maurice A. , Faull Richard L. M. , Dunbar P. Rod , Dragunow Mike
Published: May 2016

The human brain is a highly vascular organ in which the blood-brain barrier (BBB) tightly regulates molecules entering the brain. Pericytes are an integral cell type of the BBB, regulating vascular integrity, neuroinflammation, angiogenesis and wound repair. Despite their importance, identifying pericytes amongst other perivascular cell types and deciphering their specific role in the neurovasculature remains a challenge. Using primary adult human brain cultures and fluorescent-activated cell sorting, we identified two CD73+CD45− mesenchymal populations that showed either high or low CD90 expression. CD90 is known to be present on neurons in the brain and peripheral blood vessels. We found in the human brain, that CD90 immunostaining localised to the neurovasculature and often associated with pericytes. In vitro, CD90+ cells exhibited higher basal proliferation, lower expression of markers αSMA and CD140b, produced less extracellular matrix (ECM) proteins, and exhibited lesser pro-inflammatory responses when compared to the CD90− population. Thus, CD90 distinguishes two interrelated, yet functionally distinct pericyte populations in the adult human brain that may have discrete roles in neurovascular function, immune response and scar formation.
Structure-based site-directed photo-crosslinking analyses of multimeric cell-adhesive interactions of voltage-gated sodium channel β subunits
Authors: Shimizu Hideaki , Miyazaki Haruko , Ohsawa Noboru , Shoji Shisako , Ishizuka-Katsura Yoshiko , Tosaki Asako , Oyama Fumitaka , Terada Takaho , Sakamoto Kensaku , Shirouzu Mikako , Sekine Shun-ichi , Nukina Nobuyuki , Yokoyama Shigeyuki
Published: May 2016

The β1, β2 and β4 subunits of voltage-gated sodium channels reportedly function as cell adhesion molecules. The present crystallographic analysis of the β4 extracellular domain revealed an antiparallel arrangement of the β4 molecules in the crystal lattice. The interface between the two antiparallel β4 molecules is asymmetric and results in a multimeric assembly. Structure-based mutagenesis and site-directed photo-crosslinking analyses of the β4-mediated cell-cell adhesion revealed that the interface between the antiparallel β4 molecules corresponds to that in the trans homophilic interaction for the multimeric assembly of β4 in cell-cell adhesion. This trans interaction mode is also employed in the β1-mediated cell-cell adhesion. Moreover, the β1 gene mutations associated with generalized epilepsy with febrile seizures plus (GEFS+) impaired the β1-mediated cell-cell adhesion, which should underlie the GEFS+ pathogenesis. Thus, the structural basis for the β-subunit-mediated cell-cell adhesion has been established.
Selective serotonin 5-HT1A receptor biased agonists elicitdistinct brain activation patterns: a pharmacoMRI study
Authors: Becker G. , Bolbos R. , Costes N. , Redouté J. , Newman-Tancredi A. , Zimmer L.
Published: May 2016

Serotonin 1A (5-HT1A) receptors are involved in several physiological and pathological processes and constitute therefore an important therapeutic target. The recent pharmacological concept of biased agonism asserts that highly selective agonists can preferentially direct receptor signaling to specific intracellular responses, opening the possibility of drugs targeting a receptor subtype in specific brain regions. The present study brings additional support to this concept thanks to functional magnetic resonance imaging (7 Tesla-fMRI) in anaesthetized rats. Three 5-HT1A receptor agonists (8-OH-DPAT, F13714 and F15599) and one 5-HT1A receptor antagonist (MPPF) were compared in terms of influence on the brain blood oxygen level-dependent (BOLD) signal. Our study revealed for the first time contrasting BOLD signal patterns of biased agonists in comparison to a classical agonist and a silent antagonist. By providing functional information on the influence of pharmacological activation of 5-HT1A receptors in specific brain regions, this neuroimaging approach, translatable to the clinic, promises to be useful in exploring the new concept of biased agonism in neuropsychopharmacology.
Probing the doping mechanisms and electrical properties of Al, Ga and In doped ZnO prepared by spray pyrolysis
Authors: Maller Robert , Porte Yoann , Alshareef Husam N. , McLachlan Martyn A.
Published: May 2016

The measured structural, optical and electrical properties of Al, Ga and In doped ZnO films deposited using spray pyrolysis are reported over the doping range 0.1–3 at%.
Iron(ii)-triazole core–shell nanocomposites: toward multistep spin crossover materials
Authors: Wang Yu-Xia , Qiu Dan , Xi Sai-Fei , Ding Zheng-Dong , Li Zaijun , Li Yunxing , Ren Xuehong , Gu Zhi-Guo
Published: May 2016

The unprecedented SCO@SCO core–shell nanocomposites with three-step spin crossover behaviour at around room temperature were prepared by a facile step-by-step microemulsion method.