bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial communities reflect temporal changes in cyanobacterial composition in a shallow ephemeral freshwater lake
Authors: Woodhouse Jason Nicholas , Kinsela Andrew Stephen , Collins Richard Nicholas , Bowling Lee Chester , Honeyman Gordon L , Holliday Jon K , Neilan Brett Anthony
Published: December 2015

The frequency of freshwater cyanobacterial blooms is at risk of increasing as a consequence of climate change and eutrophication of waterways. It is increasingly apparent that abiotic data are insufficient to explain variability within the cyanobacterial community, with biotic factors such as heterotrophic bacterioplankton, viruses and protists emerging as critical drivers. During the Australian summer of 2012–2013, a bloom that occurred in a shallow ephemeral lake over a 6-month period was comprised of 22 distinct cyanobacteria, including Microcystis, Dolichospermum, Oscillatoria and Sphaerospermopsis. Cyanobacterial cell densities, bacterial community composition and abiotic parameters were assessed over this period. Alpha-diversity indices and multivariate analysis were successful at differentiating three distinct bloom phases and the contribution of abiotic parameters to each. Network analysis, assessing correlations between biotic and abiotic variables, reproduced these phases and assessed the relative importance of both abiotic and biotic factors. Variables possessing elevated betweeness centrality included temperature, sodium and operational taxonomic units belonging to the phyla Verrucomicrobia, Planctomyces, Bacteroidetes and Actinobacteria. Species-specific associations between cyanobacteria and bacterioplankton, including the free-living Actinobacteria acI, Bacteroidetes, Betaproteobacteria and Verrucomicrobia, were also identified. We concluded that changes in the abundance and nature of freshwater cyanobacteria are associated with changes in the diversity and composition of lake bacterioplankton. Given this, an increase in the frequency of cyanobacteria blooms has the potential to alter nutrient cycling and contribute to long-term functional perturbation of freshwater systems.
MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours
Authors: Perlman Elizabeth J. , Gadd Samantha , Arold Stefan T. , Radhakrishnan Anand , Gerhard Daniela S. , Jennings Lawrence , Huff Vicki , Guidry Auvil Jaime M. , Davidsen Tanja M. , Dome Jeffrey S. , Meerzaman Daoud , Hsu Chih Hao , Nguyen Cu , Anderson James , Ma Yussanne , Mungall Andrew J. , Moore Richard A. , Marra Marco A. , Mullighan Charles G. , Ma Jing , Wheeler David A. , Hampton Oliver A. , Gastier-Foster Julie M. , Ross Nicole , Smith Malcolm A.
Published: December 2015

Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar nephrogenic rests. These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour.
In situ X-ray diffraction and the evolution of polarization during the growth of ferroelectric superlattices
Authors: Bein Benjamin , Hsing Hsiang-Chun , Callori Sara J. , Sinsheimer John , Chinta Priya V. , Headrick Randall L. , Dawber Matthew
Published: December 2015

In epitaxially strained ferroelectric thin films and superlattices, the ferroelectric transition temperature can lie above the growth temperature. Ferroelectric polarization and domains should then evolve during the growth of a sample, and electrostatic boundary conditions may play an important role. In this work, ferroelectric domains, surface termination, average lattice parameter and bilayer thickness are simultaneously monitored using in situ synchrotron X-ray diffraction during the growth of BaTiO3/SrTiO3 superlattices on SrTiO3 substrates by off-axis radio frequency magnetron sputtering. The technique used allows for scan times substantially faster than the growth of a single layer of material. Effects of electric boundary conditions are investigated by growing the same superlattice alternatively on SrTiO3 substrates and 20 nm SrRuO3 thin films on SrTiO3 substrates. These experiments provide important insights into the formation and evolution of ferroelectric domains when the sample is ferroelectric during the growth process.
Enhancing the magnetic anisotropy of maghemite nanoparticles via the surface coordination of molecular complexes
Authors: Prado Yoann , Daffé Niéli , Michel Aude , Georgelin Thomas , Yaacoub Nader , Grenèche Jean-Marc , Choueikani Fadi , Otero Edwige , Ohresser Philippe , Arrio Marie-Anne , Cartier-dit-Moulin Christophe , Sainctavit Philippe , Fleury Benoit , Dupuis Vincent , Lisnard Laurent , Fresnais Jérôme
Published: December 2015

Superparamagnetic nanoparticles are promising objects for data storage or medical applications. In the smallest—and more attractive—systems, the properties are governed by the magnetic anisotropy. Here we report a molecule-based synthetic strategy to enhance this anisotropy in sub-10-nm nanoparticles. It consists of the fabrication of composite materials where anisotropic molecular complexes are coordinated to the surface of the nanoparticles. Reacting 5 nm γ-Fe2O3 nanoparticles with the [CoII(TPMA)Cl2] complex (TPMA: tris(2-pyridylmethyl)amine) leads to the desired composite materials and the characterization of the functionalized nanoparticles evidences the successful coordination—without nanoparticle aggregation and without complex dissociation—of the molecular complexes to the nanoparticles surface. Magnetic measurements indicate the significant enhancement of the anisotropy in the final objects. Indeed, the functionalized nanoparticles show a threefold increase of the blocking temperature and a coercive field increased by one order of magnitude.
Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation
Authors: Artigas María Soler , Wain Louise V. , Miller Suzanne , Kheirallah Abdul Kader , Huffman Jennifer E. , Ntalla Ioanna , Shrine Nick , Obeidat Ma’en , Trochet Holly , McArdle Wendy L. , Alves Alexessander Couto , Hui Jennie , Zhao Jing Hua , Joshi Peter K. , Teumer Alexander , Albrecht Eva , Imboden Medea , Rawal Rajesh , Lopez Lorna M. , Marten Jonathan , Enroth Stefan , Surakka Ida , Polasek Ozren , Lyytikäinen Leo-Pekka , Granell Raquel , Hysi Pirro G. , Flexeder Claudia , Mahajan Anubha , Beilby John , Bossé Yohan , Brandsma Corry-Anke , Campbell Harry , Gieger Christian , Gläser Sven , González Juan R. , Grallert Harald , Hammond Chris J. , Harris Sarah E. , Hartikainen Anna-Liisa , Heliövaara Markku , Henderson John , Hocking Lynne , Horikoshi Momoko , Hutri-Kähönen Nina , Ingelsson Erik , Johansson Åsa , Kemp John P. , Kolcic Ivana , Kumar Ashish , Lind Lars , Melén Erik , Musk Arthur W. , Navarro Pau , Nickle David C. , Padmanabhan Sandosh , Raitakari Olli T. , Ried Janina S. , Ripatti Samuli , Schulz Holger , Scott Robert A. , Sin Don D. , Starr John M. ,   UK BiLEVE, Deloukas Panos , Hansell Anna L. , Hubbard Richard , Jackson Victoria E. , Marchini Jonathan , Pavord Ian , Thomson Neil C. , Zeggini Eleftheria , Viñuela Ana , Völzke Henry , Wild Sarah H. , Wright Alan F. , Zemunik Tatijana , Jarvis Deborah L. , Spector Tim D. , Evans David M. , Lehtimäki Terho , Vitart Veronique , Kähönen Mika , Gyllensten Ulf , Rudan Igor , Deary Ian J. , Karrasch Stefan , Probst-Hensch Nicole M. , Heinrich Joachim , Stubbe Beate , Wilson James F. , Wareham Nicholas J. , James Alan L. , Morris Andrew P. , Jarvelin Marjo-Riitta , Hayward Caroline , Sayers Ian , Strachan David P. , Hall Ian P. , Tobin Martin D.
Published: December 2015

Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10−8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.
Two Distinct Moral Mechanisms for Ascribing and Denying Intentionality
Authors: Ngo Lawrence , Kelly Meagan , Coutlee Christopher G. , Carter R. McKell , Sinnott-Armstrong Walter , Huettel Scott A.
Published: December 2015

Philosophers and legal scholars have long theorized about how intentionality serves as a critical input for morality and culpability, but the emerging field of experimental philosophy has revealed a puzzling asymmetry. People judge actions leading to negative consequences as being more intentional than those leading to positive ones. The implications of this asymmetry remain unclear because there is no consensus regarding the underlying mechanism. Based on converging behavioral and neural evidence, we demonstrate that there is no single underlying mechanism. Instead, two distinct mechanisms together generate the asymmetry. Emotion drives ascriptions of intentionality for negative consequences, while the consideration of statistical norms leads to the denial of intentionality for positive consequences. We employ this novel two-mechanism model to illustrate that morality can paradoxically shape judgments of intentionality. This is consequential formens reain legal practice and arguments in moral philosophy pertaining to terror bombing, abortion and euthanasia among others.
Crossover behavior of the thermal conductance and Kramers’ transition rate theory
Authors: Velizhanin Kirill A. , Sahu Subin , Chien Chih-Chun , Dubi Yonatan , Zwolak Michael
Published: December 2015

Kramers’ theory frames chemical reaction rates in solution as reactants overcoming a barrier in the presence of friction and noise. For weak coupling to the solution, the reaction rate is limited by the rate at which the solution can restore equilibrium after a subset of reactants have surmounted the barrier to become products. For strong coupling, there are always sufficiently energetic reactants. However, the solution returns many of the intermediate states back to the reactants before the product fully forms. Here, we demonstrate that the thermal conductance displays an analogous physical response to the friction and noise that drive the heat current through a material or structure. A crossover behavior emerges where the thermal reservoirs dominate the conductance at the extremes and only in the intermediate region are the intrinsic properties of the lattice manifest. Not only does this shed new light on Kramers’ classic turnover problem, this result is significant for the design of devices for thermal management and other applications, as well as the proper simulation of transport at the nanoscale.
Circulating Microparticles Alter Formation, Structure and Properties of Fibrin Clots
Authors: Zubairova Laily D. , Nabiullina Roza M. , Nagaswami Chandrasekaran , Zuev Yuriy F. , Mustafin Ilshat G. , Litvinov Rustem I. , Weisel John W.
Published: December 2015

Despite the importance of circulating microparticles in haemostasis and thrombosis, there is limited evidence for potential causative effects of naturally produced cell-derived microparticles on fibrin clot formation and its properties. We studied the significance of blood microparticles for fibrin formation, structure and susceptibility to fibrinolysis by removing them from platelet-free plasma using filtration. Clots made in platelet-free and microparticle-depleted plasma samples from the same healthy donors were analyzed in parallel. Microparticles accelerate fibrin polymerisation and support formation of more compact clots that resist internal and external fibrinolysis. These variations correlate with faster thrombin generation, suggesting thrombin-mediated kinetic effects of microparticles on fibrin formation, structure and properties. In addition, clots formed in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contain 0.1–0.5-μm size granular and CD61-positive material on fibres, suggesting that platelet-derived microparticles attach to fibrin. Therefore, the blood of healthy individuals contains functional microparticles at the levels that have a procoagulant potential. They affect the structure and stability of fibrin clots indirectly through acceleration of thrombin generation and through direct physical incorporation into the fibrin network. Both mechanisms underlie a potential role of microparticles in haemostasis and thrombosis as modulators of fibrin formation, structure and resistance to fibrinolysis.
The Comparative Studies of Binding Activity of Curcumin and Didemethylated Curcumin with Selenite: Hydrogen Bonding vs Acid-Base Interactions
Authors: Liao Jiahn-Haur , Wu Tzu-Hua , Chen Ming-Yi , Chen Wei-Ting , Lu Shou-Yun , Wang Yi-Hsuan , Wang Shao-Pin , Hsu Yen-Min , Huang Yi-Shiang , Huang Zih-You , Lin Yu-Ching , Chang Ching-Ming , Huang Fu-Yung , Wu Shih-Hsiung
Published: December 2015

In this report, the in vitro relative capabilities of curcumin (CCM) and didemethylated curcumin (DCCM) in preventing the selenite-induced crystallin aggregation were investigated by turbidity tests and isothermal titration calorimetry (ITC). DCCM showed better activity than CCM. The conformers of CCM/SeO32− and DCCM/SeO32− complexes were optimized by molecular orbital calculations. Results reveal that the selenite anion surrounded by CCM through the H-bonding between CCM and selenite, which is also observed via IR and NMR studied. For DCCM, the primary driving force is the formation of an acid-base adduct with selenite showing that the phenolic OH group of DCCM was responsible for forming major conformer of DCCM. The formation mechanisms of selenite complexes with CCM or DCCM explain why DCCM has greater activity than CCM in extenuating the toxicity of selenite as to prevent selenite-induced lens protein aggregation.
Graphene Distributed Amplifiers: Generating Desirable Gain for Graphene Field-Effect Transistors
Authors: Lyu Hongming , Lu Qi , Huang Yilin , Ma Teng , Zhang Jinyu , Wu Xiaoming , Yu Zhiping , Ren Wencai , Cheng Hui-Ming , Wu Huaqiang , Qian He
Published: December 2015

Ever since its discovery, graphene bears great expectations in high frequency electronics due to its irreplaceably high carrier mobility. However, it has long been blamed for the weakness in generating gains, which seriously limits its pace of development. Distributed amplification, on the other hand, has successfully been used in conventional semiconductors to increase the amplifiers’ gain-bandwidth product. In this paper, distributed amplification is first applied to graphene. Transmission lines phase-synchronize paralleled graphene field-effect transistors (GFETs), combining the gain of each stage in an additive manner. Simulations were based on fabricated GFETs whose fT ranged from 8.5 GHz to 10.5 GHz and fmax from 12 GHz to 14 GHz. A simulated four-stage graphene distributed amplifier achieved up to 4 dB gain and 3.5 GHz bandwidth, which could be realized with future IC processes. A PCB level graphene distributed amplifier was fabricated as a proof of circuit concept.
The influence of input and output modality on following instructions in working memory
Authors: Yang Tian-xiao , Allen Richard J. , Yu Qi-jing , Chan Raymond C. K.
Published: December 2015

Following instructions is an important component of learning and has been shown to rely on working memory. This study examined the ability to follow instructions within working memory under varying input and output modalities. In Experiment 1, participants heard, read, or viewed demonstration of short sequences of instructions and recalled either by oral repetition or physical enactment. There was a significant main effect of encoding, showing superior recall performance when instructions were demonstrated relative to spoken or written presentation. Experiment 2 examined whether recall is further improved when instructions are presented both in spoken and demonstrated form, relative to single modality presentation. The advantage for demonstration over spoken instructions was replicated and dual input was superior to spoken instructions. However, dual input did not bring extra benefit compared to demonstration of instructions. We also observed a significant enacted-retrieval recall advantage. These findings suggest effects of both input and output modalities on the ability to remember and follow instructions in working memory. Outcomes substantially inform the underexplored but important new area of action-based working memory and its links to embodied cognition, with implications for pedagogic practice.
Content and activity of human liver microsomal protein and prediction of individual hepatic clearance in vivo
Authors: Zhang Haifeng , Gao Na , Tian Xin , Liu Tingting , Fang Yan , Zhou Jun , Wen Qiang , Xu Binbin , Qi Bing , Gao Jie , Li Hongmeng , Jia Linjing , Qiao Hailing
Published: December 2015

The lack of information concerning individual variation in content and activity of human liver microsomal protein is one of the most important obstacles for designing personalized medicines. We demonstrated that the mean value of microsomal protein per gram of liver (MPPGL) was 39.46 mg/g in 128 human livers and up to 19-fold individual variations existed. Meanwhile, the metabolic activities of 10 cytochrome P450 (CYPs) were detected in microsomes and liver tissues, respectively, which showed huge individual variations (200-fold). Compared with microsomes, the activities of liver tissues were much suitable to express the individual variations of CYP activities. Furthermore, individual variations in the in vivo clearance of tolbutamide were successfully predicted with the individual parameter values. In conclusion, we offer the values for MPPGL contents in normal liver tissues and build a new method to assess the in vitro CYP activities. In addition, large individual variations exist in predicted hepatic clearance of tolbutamide. These findings provide important physiological parameters for physiologically-based pharmacokinetics models and thus, establish a solid foundation for future development of personalized medicines.
Metabolomic profiles delineate mycolactone signature in Buruli ulcer disease
Authors: Niang Fatoumata , Sarfo Fred S. , Frimpong Michael , Guenin-Macé Laure , Wansbrough-Jones Mark , Stinear Timothy , Phillips Richard O. , Demangel Caroline
Published: December 2015

Infection of human skin with Mycobacterium ulcerans, the causative agent of Buruli ulcer, is associated with the systemic diffusion of a bacterial macrolide named mycolactone. Patients with progressive disease show alterations in their serum proteome, likely reflecting the inhibition of secreted protein production by mycolactone at the cellular level. Here, we used semi-quantitative metabolomics to characterize metabolic perturbations in serum samples of infected individuals and human cells exposed to mycolactone. Among the 430 metabolites profiled across 20 patients and 20 healthy endemic controls, there were significant differences in the serum levels of hexoses, steroid hormones, acylcarnitines, purine, heme, bile acids, riboflavin and lysolipids. In parallel, analysis of 292 metabolites in human T cells treated or not with mycolactone showed alterations in hexoses, lysolipids and purine catabolites. Together, these data demonstrate that M. ulcerans infection causes systemic perturbations in the serum metabolome that can be ascribed to mycolactone. Of particular importance to Buruli ulcer pathogenesis is that changes in blood sugar homeostasis in infected patients are mirrored by alterations in hexose metabolism in mycolactone-exposed cells.
The Long Noncoding RNA IFNG-AS1 Promotes T Helper Type 1 Cells Response in Patients with Hashimoto’s Thyroiditis
Authors: Peng Huiyong , Liu Yingzhao , Tian Jie , Ma Jie , Tang Xinyi , Rui Ke , Tian Xinyu , Mao Chaoming , Lu Liwei , Xu Huaxi , Jiang Pengcheng , Wang Shengjun
Published: December 2015

The long noncoding (lnc) RNA-Ifng-AS1 plays an essential role in the transcription of the gene encoding IFN-γ by Th1 cells and its human ortholog, IFNG-AS1, is expressed in human Th1 cells. However, IFNG-AS1 contributing to Th1 cells’ response in Hashimoto’s thyroiditis (HT) patients has not been reported. Twenty-eight HT patients and 20 healthy controls were enrolled in the study. The proportion of circulating Th1 cells and the level of T-bet, IFNG mRNA were increased in HT patients, the expression of IFNG-AS1 was upregulated and positively correlated with the proportion of circulating Th1 cells or T-bet and IFNG expression, or serum level of anti-thyroglobulin antibody/thyroperoxidase antibody in HT patients. IFNG-AS1 regulated the expression of IFNG at both transcriptional and translational level in human CD4+ T cells. Furthermore, strong positive correlations between the increased transcript level of IFNG-AS1 and the increased transcript level of T-bet or IFNG were revealed in thyroid tissues from HT patients. Our results indicate that enhanced expression of lncRNA-IFNG-AS1 contributes to Th1 cell response in HT patients and may be involved in the pathogenesis of HT.
The brown and brite adipocyte marker Cox7a1 is not required for non-shivering thermogenesis in mice
Authors: Maurer Stefanie F. , Fromme Tobias , Grossman Lawrence I. , Hüttemann Maik , Klingenspor Martin
Published: December 2015

The cytochrome c oxidase subunit isoform Cox7a1 is highly abundant in skeletal muscle and heart and influences enzyme activity in these tissues characterised by high oxidative capacity. We identified Cox7a1, well-known as brown adipocyte marker gene, as a cold-responsive protein of brown adipose tissue. We hypothesised a mechanistic relationship between cytochrome c oxidase activity and Cox7a1 protein levels affecting the oxidative capacity of brown adipose tissue and thus non-shivering thermogenesis. We subjected wildtype and Cox7a1 knockout mice to different temperature regimens and tested characteristics of brown adipose tissue activation. Cytochrome c oxidase activity, uncoupling protein 1 expression and maximal norepinephrine-induced heat production were gradually increased during cold-acclimation, but unaffected by Cox7a1 knockout. Moreover, the abundance of uncoupling protein 1 competent brite cells in white adipose tissue was not influenced by presence or absence of Cox7a1. Skin temperature in the interscapular region of neonates was lower in uncoupling protein 1 knockout pups employed as a positive control, but not in Cox7a1 knockout pups. Body mass gain and glucose tolerance did not differ between wildtype and Cox7a1 knockout mice fed with high fat or control diet. We conclude that brown adipose tissue function in mice does not require the presence of Cox7a1.
The Assembling of Poly (3-Octyl-Thiophene) on CVD Grown Single Layer Graphene
Authors: Jiang Yanqiu , Yang Ling , Guo Zongxia , Lei Shengbin
Published: December 2015

The interface between organic semiconductor and graphene electrode, especially the structure of the first few molecular layers at the interface, is crucial for the device properties such as the charge transport in organic field effect transistors. In this work, we have used scanning tunneling microscopy to investigate the poly (3-octyl-thiophene) (P3OT)-graphene interface. Our results reveal the dynamic assembling of P3OT on single layer graphene. As on other substrates the epitaxial effect plays a role in determining the orientation of the P3OT assembling, however, the inter-thiophene distance along the backbone is consistent with that optimized in vaccum, no compression was observed. Adsorption of P3OT on ripples is weaker due to local curvature, which has been verified both by scanning tunneling microscopy and density functional theory simulation. Scanning tunneling microscopy also reveals that P3OT tends to form hairpin folds when meets a ripple.
Enzyme-guided DNA Sewing Architecture
Authors: Song In Hyun , Shin Seung Won , Park Kyung Soo , Lansac Yves , Jang Yun Hee , Um Soong Ho
Published: December 2015

With the advent of nanotechnology, a variety of nanoarchitectures with varied physicochemical properties have been designed. Owing to the unique characteristics, DNAs have been used as a functional building block for novel nanoarchitecture. In particular, a self-assembly of long DNA molecules via a piece DNA staple has been utilized to attain such constructs. However, it needs many talented prerequisites (e.g., complicated computer program) with fewer yields of products. In addition, it has many limitations to overcome: for instance, (i) thermal instability under moderate environments and (ii) restraint in size caused by the restricted length of scaffold strands. Alternatively, the enzymatic sewing linkage of short DNA blocks is simply designed into long DNA assemblies but it is more error-prone due to the undeveloped sequence data. Here, we present, for the first time, a comprehensive study for directly combining DNA structures into higher DNA sewing constructs through the 5′-end cohesive ligation of T4 enzyme. Inspired by these achievements, the synthesized DNA nanomaterials were also utilized for effective detection and real-time diagnosis of cancer-specific and cytosolic RNA markers. This generalized protocol for generic DNA sewing is expected to be useful in several DNA nanotechnology as well as any nucleic acid-related fields.
Tunable lasing in cholesteric liquid crystal elastomers with accurate measurements of strain
Authors: Varanytsia Andrii , Nagai Hama , Urayama Kenji , Palffy-Muhoray Peter
Published: December 2015

We report wide range and reversible tuning of the selective reflection band of a single crystal cholesteric liquid crystal elastomer (CLCE). The tuning is the result of mechanical shortening of the helical pitch achieved by imposing a uniform uniaxial strain along the helical axis. On doping the CLCE sample with a laser dye, we observe lasing from the CLCE in both glassy and rubbery states. By changing the cholesteric pitch, mechanical compression provides tuning of the laser emission from the dye doped CLCE over a significant part of the fluorescence band of the laser dye. In this work we demonstrate for the first time that both the CLCE pitch and the lasing wavelength are linearly dependent on the strain imposed on the CLCE film.
Aquaporin7 plays a crucial role in tolerance to hyperosmotic stress and in the survival of oocytes during cryopreservation
Authors: Tan Ya-Jing , Zhang Xue-Ying , Ding Guo-Lian , Li Rong , Wang Li , Jin Li , Lin Xian-Hua , Gao Ling , Sheng Jian-Zhong , Huang He-Feng
Published: December 2015

Hyperosmotic stress may induce apoptosis of different cells. However, oocytes show tolerance to osmotic stress during cryopreservation by vitrification, which is an assisted reproductive technique. The underlying mechanism is still not understood. Here, we demonstrated that hyperosmosis produced by high concentrations of cryoprotectants, including DMSO, ethylene glycol and sucrose, significantly upregulated the protein levels of aquaporin (AQP) 7, but not AQP3 and AQP9, in mouse oocytes. Knockdown of AQP7 expression by siRNA-injection significantly reduced the survival of oocytes after vitrification. In oocytes, AQP7 was shown to bind with F-actin, a protein involved in almost all biological events. Moreover, we found that hyperosmosis could upregulate the phosphorylation levels of CPE-binding protein (CPEB) and Aurora A. Inhibition of the PI3K and PKC pathways blocked the hyperosmosis-induced upregulation of AQP7 and the phosphorylation of CPEB and Aurora A in oocytes. In conclusion, hyperosmosis could upregulate the expression of AQP7 via Aurora A/CPEB phosphorylation mediated by the PI3K and PKC pathways and upregulation of AQP7 plays an important role in improving of tolerance to hyperosmotic stress and survival of oocytes during cryopreservation by vitrification.
CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord
Authors: Paniagua-Torija Beatriz , Arevalo-Martin Angel , Ferrer Isidro , Molina-Holgado Eduardo , Garcia-Ovejero Daniel
Published: December 2015

Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1HIGH cell subpopulation described in rodents. Our results support the existence of ependymal CB1HIGH cells across species and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions.
Electrolithography- A New and Versatile Process for Nano Patterning
Authors: Talukder Santanu , Kumar Praveen , Pratap Rudra
Published: December 2015

We report a new lithography technique based on electromigration driven material transport for drawing patterns at nanometer scales in ambient conditions. We use a thin metal film as a masking layer and a polymer layer beneath it as a pattern transfer layer. The desired pattern is drawn in the metal layer by etching the metal with a conducting scanning probe assisted by liquid electromigration. The pattern drawn on the metal layer is transferred to the polymer layer by etching the polymer with an appropriate solvent. Subsequently, the pattern is transferred to the desired material layer using a film deposition technique followed by conventional lift-off process. Using this simple technique, we have achieved pattern resolutions of 9 nm on the polymer and 40 nm on transferring the pattern to another material. Based on the ease of use and process costs, this technique promises to be competitive to e-beam lithography that employs high energy and ultra-high vacuum, or the industrial standard ultra-violet light photolithography that employs extremely expensive implements to reach nano-scale resolutions. We also demonstrate direct mask writing using this technique and explain the fundamentals behind the workings of the developed method.
Surgical Ventricular Entry is a Key Risk Factor for Leptomeningeal Metastasis of High Grade Gliomas
Authors: Roelz Roland , Reinacher Peter , Jabbarli Ramazan , Kraeutle Rainer , Hippchen Beate , Egger Karl , Weyerbrock Astrid , Machein Marcia
Published: December 2015

Leptomeningeal metastasis (LM) of high grade gliomas (HGG) can lead to devastating disease courses. Understanding of risk factors for LM is important to identify patients at risk. We reviewed patient records and magnetic resonance imaging (MRI) of all patients with a first diagnosis of HGG who underwent surgery in our institution between 2008 and 2012. To assess the influence of potential risk factors for LM and the impact of LM on survival multivariate statistics were performed. 239 patients with a diagnosis of HGG and at least 6 months of MRI and clinical follow-up were included. LM occurred in 27 (11%) patients and was symptomatic in 17 (65%). A strong correlation of surgical entry to the ventricle and LM was found (HR: 8.1). Ventricular entry was documented in 137 patients (57%) and LM ensued in 25 (18%) of these. Only two (2%) of 102 patients without ventricular entry developed LM. Median overall survival of patients after diagnosis of LM (239 days) was significantly shorter compared to patients without LM (626 days). LM is a frequent complication in the course of disease of HGG and is associated with poor survival. Surgical entry to the ventricle is a key risk factor for LM.
Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets
Authors: Stroehlein Andreas J. , Young Neil D. , Jex Aaron R. , Sternberg Paul W. , Tan Patrick , Boag Peter R. , Hofmann Andreas , Gasser Robin B.
Published: December 2015

The blood fluke Schistosoma haematobium causes urogenital schistosomiasis, a neglected tropical disease (NTD) that affects more than 110 million people. Treating this disease by targeted or mass administration with a single chemical, praziquantel, carries the risk that drug resistance will develop in this pathogen. Therefore, there is an imperative to search for new drug targets in S. haematobium and other schistosomes. In this regard, protein kinases have potential, given their essential roles in biological processes and as targets for drugs already approved by the US Food and Drug Administration (FDA) for use in humans. In this context, we defined here the kinome of S. haematobium using a refined bioinformatic pipeline. We classified, curated and annotated predicted kinases and assessed the developmental transcription profiles of kinase genes. Then, we prioritised a panel of kinases as potential drug targets and inferred chemicals that bind to them using an integrated bioinformatic pipeline. Most kinases of S. haematobium are very similar to those of its congener, S. mansoni, offering the prospect of designing chemicals that kill both species. Overall, this study provides a global insight into the kinome of S. haematobium and should assist the repurposing or discovery of drugs against schistosomiasis.
Distant Influence of Kuroshio Eddies on North Pacific Weather Patterns?
Authors: Ma Xiaohui , Chang Ping , Saravanan R. , Montuoro Raffaele , Hsieh Jen-Shan , Wu Dexing , Lin Xiaopei , Wu Lixin , Jing Zhao
Published: December 2015

High-resolution satellite measurements of surface winds and sea-surface temperature (SST) reveal strong coupling between meso-scale ocean eddies and near-surface atmospheric flow over eddy-rich oceanic regions, such as the Kuroshio and Gulf Stream, highlighting the importance of meso-scale oceanic features in forcing the atmospheric planetary boundary layer (PBL). Here, we present high-resolution regional climate modeling results, supported by observational analyses, demonstrating that meso-scale SST variability, largely confined in the Kuroshio-Oyashio confluence region (KOCR), can further exert a significant distant influence on winter rainfall variability along the U.S. Northern Pacific coast. The presence of meso-scale SST anomalies enhances the diabatic conversion of latent heat energy to transient eddy energy, intensifying winter cyclogenesis via moist baroclinic instability, which in turn leads to an equivalent barotropic downstream anticyclone anomaly with reduced rainfall. The finding points to the potential of improving forecasts of extratropical winter cyclones and storm systems and projections of their response to future climate change, which are known to have major social and economic impacts, by improving the representation of ocean eddy–atmosphere interaction in forecast and climate models.
Hepatic steatosis depresses alpha-1-antitrypsin levels in human and rat acute pancreatitis
Authors: Wang Qian , Du Jianjun , Yu Pengfei , Bai Bin , Zhao Zhanwei , Wang Shiqi , Zhu Junjie , Feng Quanxin , Gao Yun , Zhao Qingchuan , Liu Chaoxu
Published: December 2015

Hepatic steatosis (HS) can exacerbate acute pancreatitis (AP). This study aimed to investigate the relation between α1-antitrypsin (AAT) and acute pancreatitis when patients have HS. Using proteomic profiling, we identified 18 differently expressed proteins pots in the serum of rats with or without HS after surgical establishment of AP. AAT was found to be one of the significantly down-regulated proteins. AAT levels were significantly lower in hepatic steatosis acute pancreatitis (HSAP) than in non-HSAP (NHSAP) (P < 0.001). To explore the clinical significance of these observations, we measured the levels of AAT in the serum of 240 patients with HSAP, NHSAP, fatty liver disease (FLD), or no disease. Compared with healthy controls, serum AAT levels in patients with NHSAP were significantly higher (P < 0.01), while in patients with HSAP serum AAT levels were significantly lower (P < 0.01). Further studies showed that acute physiology and chronic health evaluation (APACHE-II) scores were negatively correlated with serum AAT levels (r = −0.85, P < 0.01). In conclusion, low serum levels of AAT in patients with HSAP are correlated with disease severity and AAT may represent a potential target for therapies aiming to improve pancreatitis.
Determination of sites of U50,488H-promoted phosphorylation of the mouse κ opioid receptor (KOPR): disconnect between KOPR phosphorylation and internalization
Authors: Chen Chongguang , Chiu Yi-Ting , Wu Wenman , Huang Peng , Mann Anika , Schulz Stefan , Liu-Chen Lee-Yuan
Published: December 2015

Phosphorylation sites of KOPR (κ opioid receptor) following treatment with the selective agonist U50,488H {(−)(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidiny)cyclo-hexyl]benzeneacetamide} were identified after affinity purification, SDS/PAGE, in-gel digestion with Glu-C and HPLC–MS/MS. Single- and double-phosphorylated peptides were identified containing phosphorylated Ser356, Thr357, Thr363 and Ser369 in the C-terminal domain. Antibodies were generated against three phosphopeptides containing pSer356/pThr357, pThr363 and pSer369 respectively, and affinity-purified antibodies were found to be highly specific for phospho-KOPR. U50,488H markedly enhanced staining of the KOPR by pThr363-, pSer369- and pSer356/pThr357-specific antibodies in immunoblotting, which was blocked by the selective KOPR antagonist norbinaltorphimine. Ser369 phosphorylation affected Thr363 phosphorylation and vice versa, and Thr363 or Ser369 phosphorylation was important for Ser356/Thr357 phosphorylation, revealing a phosphorylation hierarchy. U50,488H, but not etorphine, promoted robust KOPR internalization, although both were full agonists. U50,488H induced higher degrees of phosphorylation than etorphine at Ser356/Thr357, Thr363 and Ser369 as determined by immunoblotting. Using SILAC (stable isotope labelling by amino acids in cell culture) and HPLC–MS/MS, we found that, compared with control (C), U50,488H (U) and etorphine (E) KOPR promoted single phosphorylation primarily at Thr363 and Ser369 with U/E ratios of 2.5 and 2 respectively. Both induced double phosphorylation at Thr363+Ser369 and Thr357+Ser369 with U/E ratios of 3.3 and 3.4 respectively. Only U50,488H induced triple phosphorylation at Ser356+Thr357+Ser369. An unphosphorylated KOPR-(354–372) fragment containing all of the phosphorylation sites was detected with a C/E/U ratio of 1/0.7/0.4, indicating that ∼60% and ∼30% of the mouse KOPR are phosphorylated following U50,488H and etorphine respectively. Thus KOPR internalization requires receptor phosphorylation above a certain threshold, and higher-order KOPR phosphorylation may be disproportionally important.
Protein kinase Cζ exhibits constitutive phosphorylation and phosphatidylinositol-3,4,5-triphosphate-independent regulation
Authors: Tobias Irene S. , Kaulich Manuel , Kim Peter K. , Simon Nitya , Jacinto Estela , Dowdy Steven F. , King Charles C. , Newton Alexandra C.
Published: December 2015

Atypical protein kinase C (aPKC) isoenzymes are key modulators of insulin signalling, and their dysfunction correlates with insulin-resistant states in both mice and humans. Despite the engaged interest in the importance of aPKCs to type 2 diabetes, much less is known about the molecular mechanisms that govern their cellular functions than for the conventional and novel PKC isoenzymes and the functionally-related protein kinase B (Akt) family of kinases. Here we show that aPKC is constitutively phosphorylated and, using a genetically-encoded reporter for PKC activity, basally active in cells. Specifically, we show that phosphorylation at two key regulatory sites, the activation loop and turn motif, of the aPKC PKCζ in multiple cultured cell types is constitutive and independently regulated by separate kinases: ribosome-associated mammalian target of rapamycin complex 2 (mTORC2) mediates co-translational phosphorylation of the turn motif, followed by phosphorylation at the activation loop by phosphoinositide-dependent kinase-1 (PDK1). Live cell imaging reveals that global aPKC activity is constitutive and insulin unresponsive, in marked contrast to the insulin-dependent activation of Akt monitored by an Akt-specific reporter. Nor does forced recruitment to phosphoinositides by fusing the pleckstrin homology (PH) domain of Akt to the kinase domain of PKCζ alter either the phosphorylation or activity of PKCζ. Thus, insulin stimulation does not activate PKCζ through the canonical phosphatidylinositol-3,4,5-triphosphate-mediated pathway that activates Akt, contrasting with previous literature on PKCζ activation. These studies support a model wherein an alternative mechanism regulates PKCζ-mediated insulin signalling that does not utilize conventional activation via agonist-evoked phosphorylation at the activation loop. Rather, we propose that scaffolding near substrates drives the function of PKCζ.
Effect of SLC26 anion transporter disease-causing mutations on the stability of the homologous STAS domain of E. coli DauA (YchM)
Authors: Bai Xiaoyun , Moraes Trevor F. , Reithmeier Reinhart A.F.
Published: December 2015

The human solute carrier 26 (SLC26) family of anion transporters consists of ten members that are found in various organs in the body including the stomach, intestine, kidney, thyroid and ear where they transport anions including bicarbonate, chloride and sulfate, typically in an exchange mode. Mutations in these genes cause a plethora of diseases such as diastrophic dysplasia affecting sulfate uptake into chondrocytes (SLC26A2), congenital chloride-losing diarrhoea (SLC26A3) affecting chloride secretion in the intestine and Pendred's syndrome (SLC26A4) resulting in hearing loss. To understand how these mutations affect the structures of the SLC26 membrane proteins and their ability to function properly, 12 human disease-causing mutants from SLC26A2, SLC26A3 and SLC26A4 were introduced into the equivalent sites of the sulfate transporter anti-sigma factor antagonist (STAS) domain of a bacterial homologue SLC26 protein DauA (YchM). Biophysical analyses including size-exclusion chromatography, circular dichroism (CD), differential scanning fluorimetry (DSF) and tryptophan fluorescence revealed that most mutations caused protein instability and aggregation. The mutation A463K, equivalent to N558K in human SLC26A4, which is located within α-helix 1 of the DauA STAS domain, stabilized the protein. CD measurements showed that most disease-related mutants had a mildly reduced helix content, but were more sensitive to thermal denaturation. Fluorescence spectroscopy showed that the mutants had more open structures and were more readily denatured by urea, whereas DSF indicated more labile folds. Overall, we conclude that the disease-associated mutations destabilized the STAS domain resulting in an increased propensity to misfold and aggregate.
Circulating FGF21 proteolytic processing mediated by fibroblast activation protein
Authors: Zhen Eugene Y. , Jin Zhaoyan , Ackermann Bradley L. , Thomas Melissa K. , Gutierrez Jesus A.
Published: December 2015

Fibroblast growth factor 21 (FGF21), a hormone implicated in the regulation of glucose homoeostasis, insulin sensitivity, lipid metabolism and body weight, is considered to be a promising therapeutic target for the treatment of metabolic disorders. Despite observations that FGF21 is rapidly proteolysed in circulation rending it potentially inactive, little is known regarding mechanisms by which FGF21 protein levels are regulated. We systematically investigated human FGF21 protein processing using mass spectrometry. In agreement with previous reports, circulating human FGF21 was found to be cleaved primarily after three proline residues at positions 2, 4 and 171. The extent of FGF21 processing was quantified in a small cohort of healthy human volunteers. Relative abundance of FGF21 proteins cleaved after Pro-2, Pro-4 and Pro-171 ranged from 16 to 30%, 10 to 25% and 10 to 34%, respectively. Dipeptidyl peptidase IV (DPP-IV) was found to be the primary protease responsible for N-terminal cleavages after residues Pro-2 and Pro-4. Importantly, fibroblast activation protein (FAP) was implicated as the protease responsible for C-terminal cleavage after Pro-171, rendering the protein inactive. The requirement of FAP for FGF21 proteolysis at the C-terminus was independently demonstrated by in vitro digestion, immunodepletion of FAP in human plasma, administration of an FAP-specific inhibitor and by human FGF21 protein processing patterns in FAP knockout mouse plasma. The discovery that FAP is responsible for FGF21 inactivation extends the FGF21 signalling pathway and may enable novel approaches to augment FGF21 actions for therapeutic applications.
The STAS domain of mammalian SLC26A5 prestin harbours an anion-binding site
Authors: Lolli Graziano , Pasqualetto Elisa , Costanzi Elisa , Bonetto Greta , Battistutta Roberto
Published: December 2015

Prestin is a unique ATP- and Ca2+-independent molecular motor with piezoelectric characteristics responsible for the electromotile properties of mammalian cochlear outer hair cells, i.e. the capacity of these cells to modify their length in response to electric stimuli. This ‘electromotility’ is at the basis of the exceptional sensitivity and frequency selectivity distinctive of mammals. Prestin belongs to the SLC26 (solute carrier 26) family of anion transporters and needs anions to function properly, particularly Cl−. In the present study, using X-ray crystallography we reveal that the STAS (sulfate transporter and anti-sigma factor antagonist) domain of mammalian prestin, considered an ‘incomplete’ transporter, harbours an unanticipated anion-binding site. In parallel, we present the first crystal structure of a prestin STAS domain from a non-mammalian vertebrate prestin (chicken) that behaves as a ‘full’ transporter. Notably, in chicken STAS, the anion-binding site is lacking because of a local structural rearrangement, indicating that the presence of the STAS anion-binding site is exclusive to mammalian prestin.
Five‐level inverter for solar system and its self‐adaptive pulse‐width modulation strategy
Authors: Wang Fei , Wang Yong , Hang Lijun , Wang Chengmin
Published: December 2015

Five‐level inverters have been used in solar systems because of their smaller harmonic, smaller filter inductance, and less power network pollution than those of the three‐level inverters. This study compares the advantages and disadvantages of I‐type five‐level inverters and T‐type five‐level inverters, involving the conduction loss, commutation path in reactive power, and switching loss, especially at high frequency. On the basis of the drawbacks of I‐type and T‐type five‐level inverters, this study proposes a novel five‐level inverter for solar systems and its relevant self‐adaptive pulse‐width modulation strategy, aiming at reducing both the conduction loss and switching loss at high frequency, and solving their common issue of unbalanced devices dissipation. A prototype has been built to verify the operation and performance of the proposed inverter.