bluuebunny/crossref_metadata_2025 huggingface dataset:
Coherent control of quasi-degenerate stationary-like states via multiple resonances
Authors: Luo Yunrong , Hai Kuo , Zou Mingliang , Hai Wenhua
Published: February 2017

We use three bosons held in a depth-tilt combined-modulated double-well to study coherent control of quantum transitions between quasi-degenerate stationary-like states (QDSLSs) with the same quasienergy. Within the high-frequency approximation and for multiple-resonance conditions, we analytically obtain the different QDSLSs including the maximal bipartite entangled states, which enable us to manipulate the transitions between QDSLSs without the observable multiphoton absorption and to simulate a two-qubit system with the considered bosons. The analytical results are confirmed numerically and good agreement is shown. The quantum transitions between QDSLSs can be observed and controlled by adjusting the initial and the final atomic distributions in the currently proposed experimental setup, and possess potential applications in qubit control based on the bipartite entangled states and in engineering quantum dynamics for quantum information processing.
Long noncoding RNA expression signature to predict platinum-based chemotherapeutic sensitivity of ovarian cancer patients
Authors: Liu Rong , Zeng Ying , Zhou Cheng-Fang , Wang Ying , Li Xi , Liu Zhao-Qian , Chen Xiao-Ping , Zhang Wei , Zhou Hong-Hao
Published: February 2017

Dysregulated long noncoding RNAs (lncRNAs) are potential markers of several tumor prognoses. This study aimed to develop a lncRNA expression signature that can predict chemotherapeutic sensitivity for patients with advanced stage and high-grade serous ovarian cancer (HGS-OvCa) treated with platinum-based chemotherapy. The lncRNA expression profiles of 258 HGS-OvCa patients from The Cancer Genome Atlas were analyzed. Results revealed that an eight-lncRNA signature was significantly associated with chemosensitivity in the multivariate logistic regression model, which can accurately predict the chemosensitivity of patients [Area under curve (AUC) = 0.83]. The association of a chemosensitivity predictor with molecular subtypes indicated the excellent prognosis performance of this marker in differentiated, mesenchymal, and immunoreactive subtypes (AUC > 0.8). The significant correlation between ZFAS1 expression and chemosensitivity was confirmed in 233 HGS-OvCa patients from the Gene Expression Omnibus datasets (GSE9891, GSE63885, and GSE51373). In vitro experiments demonstrated that the ZFAS1 expression was upregulated by cisplatin in A2008, HeyA8, and HeyC2 cell lines. This finding suggested that ZFAS1 may participate in platinum resistance. Therefore, the evaluation of the eight-lncRNA signature may be clinically implicated in the selection of platinum-resistant HGS-OvCa patients. The role of ZFAS1 in platinum resistance should be further investigated.
“Deflecting elastic prism” and unidirectional localisation for waves in chiral elastic systems
Authors: Carta G. , Jones I. S. , Movchan N. V. , Movchan A. B. , Nieves M. J.
Published: February 2017

For the first time, a design of a “deflecting elastic prism” is proposed and implemented for waves in a chiral medium. A novel model of an elastic lattice connected to a non-uniform system of gyroscopic spinners is designed to create a unidirectional wave pattern, which can be diverted by modifying the arrangement of the spinners within the medium. This important feature of the gyro-system is exploited to send a wave from a point of the lattice to any other point in the lattice plane, in such a way that the wave amplitude is not significantly reduced along the path. We envisage that the proposed model could be very useful in physical and engineering applications related to directional control of elastic waves.
Inkjet printed circuits based on ambipolar and p-type carbon nanotube thin-film transistors
Authors: Kim Bongjun , Geier Michael L. , Hersam Mark C. , Dodabalapur Ananth
Published: February 2017

Ambipolar and p-type single-walled carbon nanotube (SWCNT) thin-film transistors (TFTs) are reliably integrated into various complementary-like circuits on the same substrate by inkjet printing. We describe the fabrication and characteristics of inverters, ring oscillators, and NAND gates based on complementary-like circuits fabricated with such TFTs as building blocks. We also show that complementary-like circuits have potential use as chemical sensors in ambient conditions since changes to the TFT characteristics of the p-channel TFTs in the circuit alter the overall operating characteristics of the circuit. The use of circuits rather than individual devices as sensors integrates sensing and signal processing functions, thereby simplifying overall system design.
The Calcium-Dependent Switch Helix of L-Plastin Regulates Actin Bundling
Authors: Ishida Hiroaki , Jensen Katharine V. , Woodman Andrew G. , Hyndman M. Eric , Vogel Hans J.
Published: February 2017

L-plastin is a calcium-regulated actin-bundling protein that is expressed in cells of hematopoietic origin and in most metastatic cancer cells. These cell types are mobile and require the constant remodeling of their actin cytoskeleton, where L-plastin bundles filamentous actin. The calcium-dependent regulation of the actin-bundling activity of L-plastin is not well understood. We have used NMR spectroscopy to determine the solution structure of the EF-hand calcium-sensor headpiece domain. Unexpectedly, this domain does not bind directly to the four CH-domains of L-plastin. A novel switch helix is present immediately after the calcium-binding region and it binds tightly to the EF-hand motifs in the presence of calcium. We demonstrate that this switch helix plays a major role during actin-bundling. Moreover a peptide that competitively inhibits the association between the EF-hand motifs and the switch helix was shown to deregulate the actin-bundling activity of L-plastin. Overall, these findings may help to develop new drugs that target the L-plastin headpiece and interfere in the metastatic activity of cancer cells.
Sublethal pesticide doses negatively affect survival and the cellular responses in American foulbrood-infected honeybee larvae
Authors: López Javier Hernández , Krainer Sophie , Engert Antonia , Schuehly Wolfgang , Riessberger-Gallé Ulrike , Crailsheim Karl
Published: February 2017

Disclosing interactions between pesticides and bee infections is of most interest to understand challenges that pollinators are facing and to which extent bee health is compromised. Here, we address the individual and combined effect that three different pesticides (dimethoate, clothianidin and fluvalinate) and an American foulbrood (AFB) infection have on mortality and the cellular immune response of honeybee larvae. We demonstrate for the first time a synergistic interaction when larvae are exposed to sublethal doses of dimethoate or clothianidin in combination with Paenibacillus larvae, the causative agent of AFB. A significantly higher mortality than the expected sum of the effects of each individual stressor was observed in co-exposed larvae, which was in parallel with a drastic reduction of the total and differential hemocyte counts. Our results underline that characterizing the cellular response of larvae to individual and combined stressors allows unmasking previously undetected sublethal effects of pesticides in colony health.
M48U1 and Tenofovir combination synergistically inhibits HIV infection in activated PBMCs and human cervicovaginal histocultures
Authors: Musumeci Giuseppina , Bon Isabella , Lembo David , Cagno Valeria , Re Maria Carla , Signoretto Caterina , Diani Erica , Lopalco Lucia , Pastori Claudia , Martin Loïc , Ponchel Gilles , Gibellini Davide , Bouchemal Kawthar
Published: February 2017

Microbicides are considered a promising strategy for preventing human immunodeficiency virus (HIV-1) transmission and disease. In this report, we first analyzed the antiviral activity of the miniCD4 M48U1 peptide formulated in hydroxyethylcellulose (HEC) hydrogel in activated peripheral blood mononuclear cells (PBMCs) infected with R5- and X4–tropic HIV-1 strains. The results demonstrate that M48U1 prevented infection by several HIV-1 strains including laboratory strains, and HIV-1 subtype B and C strains isolated from the activated PBMCs of patients. M48U1 also inhibited infection by two HIV-1 transmitted/founder infectious molecular clones (pREJO.c/2864 and pTHRO.c/2626). In addition, M48U1 was administered in association with tenofovir, and these two antiretroviral drugs synergistically inhibited HIV-1 infection. In the next series of experiments, we tested M48U1 alone or in combination with tenofovir in HEC hydrogel with an organ-like structure mimicking human cervicovaginal tissue. We demonstrated a strong antiviral effect in absence of significant tissue toxicity. Together, these results indicate that co-treatment with M48U1 plus tenofovir is an effective antiviral strategy that may be used as a new topical microbicide to prevent HIV-1 transmission.
Two strategies to engineer flexible loops for improved enzyme thermostability
Authors: Yu Haoran , Yan Yihan , Zhang Cheng , Dalby Paul A.
Published: February 2017

Flexible sites are potential targets for engineering the stability of enzymes. Nevertheless, the success rate of the rigidifying flexible sites (RFS) strategy is still low due to a limited understanding of how to determine the best mutation candidates. In this study, two parallel strategies were applied to identify mutation candidates within the flexible loops of Escherichia coli transketolase (TK). The first was a “back to consensus mutations” approach, and the second was computational design based on ΔΔG calculations in Rosetta. Forty-nine single variants were generated and characterised experimentally. From these, three single-variants I189H, A282P, D143K were found to be more thermostable than wild-type TK. The combination of A282P with H192P, a variant constructed previously, resulted in the best all-round variant with a 3-fold improved half-life at 60 °C, 5-fold increased specific activity at 65 °C, 1.3-fold improved kcat and a Tm increased by 5 °C above that of wild type. Based on a statistical analysis of the stability changes for all variants, the qualitative prediction accuracy of the Rosetta program reached 65.3%. Both of the two strategies investigated were useful in guiding mutation candidates to flexible loops, and had the potential to be used for other enzymes.
TDtest: easy detection of bacterial tolerance and persistence in clinical isolates by a modified disk-diffusion assay
Authors: Gefen Orit , Chekol Betty , Strahilevitz Jacob , Balaban Nathalie Q.
Published: February 2017

Antibiotic tolerance - the ability for prolonged survival under bactericidal treatments - is a potentially clinically significant phenomenon that is commonly overlooked in the clinical microbiology laboratory. Recent in vitro experiments show that high tolerance can evolve under intermittent antibiotic treatments in as little as eight exposures to high doses of antibiotics, suggesting that tolerance may evolve also in patients. However, tests for antibiotic susceptibilities, such as the disk-diffusion assay, evaluate only the concentration at which a bacterial strain stops growing, namely resistance level. High tolerance strains will not be detected using these tests. We present a simple modification of the standard disk-diffusion assay that allows the semi-quantitative evaluation of tolerance levels. This novel method, the “TDtest”, enabled the detection of tolerant and persistent bacteria by promoting the growth of the surviving bacteria in the inhibition zone, once the antibiotic has diffused away. Using the TDtest, we were able to detect different levels of antibiotic tolerance in clinical isolates of E. coli. The TDtest also identified antibiotics that effectively eliminate tolerant bacteria. The additional information on drug susceptibility provided by the TDtest should enable tailoring better treatment regimens for pathogenic bacteria.
ERAMOSA controls lateral branching in snapdragon
Authors: Mizzotti Chiara , Galliani Bianca M. , Dreni Ludovico , Sommer Hans , Bombarely Aureliano , Masiero Simona
Published: February 2017

Plant forms display a wide variety of architectures, depending on the number of lateral branches, internode elongation and phyllotaxy. These are in turn determined by the number, the position and the fate of the Axillary Meristems (AMs). Mutants that affect AM determination during the vegetative phase have been isolated in several model plants. Among these genes, the GRAS transcription factorLATERAL SUPPRESSOR (Ls) plays a pivotal role in AM determination during the vegetative phase. Hereby we characterize the phylogenetic orthologue of Ls in Antirrhinum, ERAMOSA (ERA). Our data supported ERA control of AM formation during both the vegetative and the reproductive phase in snapdragon. A phylogenetic analysis combined with an analysis of the synteny of Ls in several species strongly supported the hypothesis that ERA is a phylogenetic orthologue of Ls, although it plays a broader role. During the reproductive phase ERA promotes the establishment of the stem niche at the bract axis but, after the reproductive transition, it is antagonized by the MADS box transcription factor SQUAMOSA (SQUA). Surprisingly double mutantera squaplants display asquaphenotype developing axillary meristems, which can eventually turn into inflorescences or flowers.
Efficient electrochemical remediation of microcystin-LR in tap water using designer TiO2@carbon electrodes
Authors: Sanz Lobón Germán , Yepez Alfonso , Garcia Luane Ferreira , Morais Ruiter Lima , Vaz Boniek Gontijo , Carvalho Veronica Vale , de Oliveira Gisele Augusto Rodrigues , Luque Rafael , Gil Eric de Souza
Published: February 2017

Microcystin-leucine arginine (MC-LR) is the most abundant and toxic secondary metabolite produced by freshwater cyanobacteria. This toxin has a high potential hazard health due to potential interactions with liver, kidney and the nervous system. The aim of this work was the design of a simple and environmentally friendly electrochemical system based on highly efficient nanostructured electrodes for the removal of MC-LR in tap water. Titania nanoparticles were deposited on carbon (graphite) under a simple and efficient microwave assisted approach for the design of the electrode, further utilized in the electrochemical remediation assays. Parameters including the applied voltage, time of removal and pH (natural tap water or alkaline condition) were investigated in the process, with results pointing to a high removal efficiency for MC-LR (60% in tap water and 90% in alkaline media experiments, under optimized conditions).
Role of thermal physiology and bioenergetics on adaptation in tree shrew (Tupaia belangeri): the experiment test
Authors: Zhang Lin , Yang Fang , Wang Zheng-kun , Zhu Wan-long
Published: February 2017

Ambient conditions, as temperature and photoperiod, play a key role in animals’ physiology and behaviors. To test the hypothesis that the maximum thermal physiological and bioenergetics tolerances are induced by extreme environments in Tupaia belangeri. We integrated the acclimatized and acclimated data in several physiological, hormonal, and biochemical markers of thermogenic capacity and bioenergetics in T. belangeri. Results showed that T. belangeri increased body mass, thermogenesis capacity, protein contents and cytochrome c oxidase (COX) activity of liver and brown adipose tissue in winter-like environments, which indicated that temperature was the primary signal for T. belangeri to regulate several physiological capacities. The associated photoperiod signal also elevated the physiological capacities. The regulations of critical physiological traits play a primary role in meeting the survival challenges of winter-like condition in T. belangeri. Together, to cope with cold, leptin may play a potential role in thermogenesis and body mass regulation, as this hormonal signal is associated with other hormones. The strategies of thermal physiology and bioenergetics differs between typical Palearctic species and the local species. However, the maximum thermal physiology and bioenergetic tolerance maybe is an important strategy to cope with winter-like condition of T. belangeri.
Induction of Bex genes by curcumin is associated with apoptosis and activation of p53 in N2a neuroblastoma cells
Authors: Sidhar Himakshi , Giri Ranjit K.
Published: February 2017

Brain expressed X-linked (Bex) genes are newer group of pro-apoptotic genes. Role of any Bex gene in neuroblastoma and Bex4 and Bex6 in any cancer is completely unknown. Re-expression of all endogenous Bex genes by any nutraceutical is also unknown. Therefore, we investigated the induction of all endogenous Bex genes and associated mechanisms by curcumin using N2a, an aggressive neuroblastoma cell line. Curcumin induced all endogenous Bex genes prior to apoptosis in N2a cells in a dose- and time-dependent manner. Wortmannin (PI-3Kinases inhibitor), SP600125 (JNK inhibitor) and pifithrin-α (p53 inhibitor) abrogated curcumin-mediated induction of Bex genes. Inhibition of curcumin-mediated induction of Bex genes by pifithrin-α also inhibited N2a cells apoptosis suggesting, a direct role of Bex genes in N2a cells apoptosis and involvement of p53 in Bex genes induction. Curcumin treatment activated p53 through hyperphosphorylation at serine 15 before Bex genes induction indicating Bex genes are novel downstream targets of p53. Collectively, curcumin, a safe nutraceutical has the potential to induce all endogenous Bex genes to harness their anti-cancer properties in neuroblastoma cells. Re-expression of Bex genes by curcumin acts as tumor suppressors and may provide alternate strategy to treat neuroblastomas and other cancers with silenced Bex genes.
Hydrogen-enabled microstructure and fatigue strength engineering of titanium alloys
Authors: Paramore James D. , Fang Zhigang Zak , Dunstan Matthew , Sun Pei , Butler Brady G.
Published: February 2017

Traditionally, titanium alloys with satisfactory mechanical properties can only be produced via energy-intensive and costly wrought processes, while titanium alloys produced using low-cost powder metallurgy methods consistently result in inferior mechanical properties, especially low fatigue strength. Herein, we demonstrate a new microstructural engineering approach for producing low-cost titanium alloys with exceptional fatigue strength via the hydrogen sintering and phase transformation (HSPT) process. The high fatigue strength presented in this work is achieved by creating wrought-like microstructures without resorting to wrought processing. This is accomplished by generating an ultrafine-grained as-sintered microstructure through hydrogen-enabled phase transformations, facilitating the subsequent creation of fatigue-resistant microstructures via simple heat treatments. The exceptional strength, ductility, and fatigue performance reported in this paper are a breakthrough in the field of low-cost titanium processing.
Targeted nanoparticles encapsulating (−)-epigallocatechin-3-gallate for prostate cancer prevention and therapy
Authors: Sanna Vanna , Singh Chandra K. , Jashari Rahime , Adhami Vaqar M. , Chamcheu Jean Christopher , Rady Islam , Sechi Mario , Mukhtar Hasan , Siddiqui Imtiaz A.
Published: February 2017

Earlier we introduced the concept of ‘nanochemoprevention’ i.e. the use of nanotechnology to improve the outcome of cancer chemoprevention. Here, we extended our work and developed polymeric EGCG-encapsulated nanoparticles (NPs) targeted with small molecular entities, able to bind to prostate specific membrane antigen (PSMA), a transmembrane protein that is overexpressed in prostate cancer (PCa), and evaluated their efficacy in preclinical studies. First, we performed a molecular recognition of DCL- and AG-PEGylation on ligand binding on PSMA active site. Next, the biocompatible polymers PLGA-PEG-A were synthesized and used as base to conjugate DCL or AG to obtain the respective copolymers, needed for the preparation of targeted NPs. The resulting EGCG encapsulating NPs led to an enhanced anti-proliferative activity in PCa cell lines compared to the free EGCG. The behavior of EGCG encapsulated in NPs in modulating apoptosis and cell-cycle, was also determined. Then, in vivo experiments, in mouse xenograft model of prostatic tumor, using EGCG-loaded NPs, with a model of targeted nanosystems, were conducted. The obtained data supported our hypothesis of target-specific enhanced bioavailability and limited unwanted toxicity, thus leading to a significant potential for probable clinical outcome.
Overcoming the dichotomy between open and isolated populations using genomic data from a large European dataset
Authors: Anagnostou Paolo , Dominici Valentina , Battaggia Cinzia , Pagani Luca , Vilar Miguel , Wells R. Spencer , Pettener Davide , Sarno Stefania , Boattini Alessio , Francalacci Paolo , Colonna Vincenza , Vona Giuseppe , Calò Carla , Destro Bisol Giovanni , Tofanelli Sergio
Published: February 2017

Human populations are often dichotomized into “isolated” and “open” categories using cultural and/or geographical barriers to gene flow as differential criteria. Although widespread, the use of these alternative categories could obscure further heterogeneity due to inter-population differences in effective size, growth rate, and timing or amount of gene flow. We compared intra and inter-population variation measures combining novel and literature data relative to 87,818 autosomal SNPs in 14 open populations and 10 geographic and/or linguistic European isolates. Patterns of intra-population diversity were found to vary considerably more among isolates, probably due to differential levels of drift and inbreeding. The relatively large effective size estimated for some population isolates challenges the generalized view that they originate from small founding groups. Principal component scores based on measures of intra-population variation of isolated and open populations were found to be distributed along a continuum, with an area of intersection between the two groups. Patterns of inter-population diversity were even closer, as we were able to detect some differences between population groups only for a few multidimensional scaling dimensions. Therefore, different lines of evidence suggest that dichotomizing human populations into open and isolated groups fails to capture the actual relations among their genomic features.
Muscle-specific overexpression of AdipoR1 or AdipoR2 gives rise to common and discrete local effects whilst AdipoR2 promotes additional systemic effects
Authors: Keshvari Sahar , Henstridge Darren C. , Ng Choaping , Febbraio Mark A. , Whitehead Jonathan P.
Published: February 2017

Hypoadiponectinemia and adiponectin resistance are implicated in the aetiology of obesity-related cardiometabolic disorders, hence represent a potential therapeutic axis. Here we characterised the effects of in vivo electrotransfer-mediated overexpression of the adiponectin receptors, AdipoR1 or AdipoR2, into tibialis anterior muscle (TAM) of lean or obese mice. In lean mice, TAM-specific overexpression of AdipoR1 (TAMR1) or AdipoR2 (TAMR2) increased phosphorylation of AMPK, AKT and ERK and expression of the insulin responsive glucose transporter glut4. In contrast, only TAMR2 increased pparα and a target gene acox1. These effects were decreased in obese mice despite no reduction in circulating adiponectin levels. TAMR2 also increased expression of adipoQ in TAM of lean and obese mice. Furthermore, in obese mice TAMR2 promoted systemic effects including; decreased weight gain; reduced epididymal fat mass and inflammation; increased epididymal adipoQ expression; increased circulating adiponectin. Collectively, these results demonstrate that AdipoR1 and AdipoR2 exhibit overlapping and distinct effects in skeletal muscle consistent with enhanced adiponectin sensitivity but these appear insufficient to ameliorate established obesity-induced adiponectin resistance. We also identify systemic effects upon TAMR2 in obese mice and postulate these are mediated by altered myokine production. Further studies are warranted to investigate this possibility which may reveal novel therapeutic approaches.
Membrane engineering of S. cerevisiae targeting sphingolipid metabolism
Authors: Lindahl Lina , Santos Aline X. S. , Olsson Helén , Olsson Lisbeth , Bettiga Maurizio
Published: February 2017

The sustainable production of fuels and chemicals using microbial cell factories is now well established. However, many microbial production processes are still limited in scale due to inhibition from compounds that are present in the feedstock or are produced during fermentation. Some of these inhibitors interfere with cellular membranes and change the physicochemical properties of the membranes. Another group of molecules is dependent on their permeation rate through the membrane for their inhibition. We have investigated the use of membrane engineering to counteract the negative effects of inhibitors on the microorganism with focus on modulating the abundance of complex sphingolipids in the cell membrane ofSaccharomyces cerevisiae. Overexpression ofELO3, involved in fatty acid elongation, andAUR1, which catalyses the formation of complex sphingolipids, had no effect on the membrane lipid profile or on cellular physiology. Deletion of the genesORM1andORM2, encoding negative regulators of sphingolipid biosynthesis, decreased cell viability and considerably reduced phosphatidylinositol and complex sphingolipids. Additionally, combiningELO3andAUR1overexpression withorm1/2Δimproved cell viability and increased fatty acyl chain length compared with onlyorm1/2Δ. These findings can be used to further study the sphingolipid metabolism, as well as giving guidance in membrane engineering.
Zwitterionic amidinates as effective ligands for platinum nanoparticle hydrogenation catalysts
Authors: Martínez-Prieto L. M. , Cano I. , Márquez A. , Baquero E. A. , Tricard S. , Cusinato L. , del Rosal I. , Poteau R. , Coppel Y. , Philippot K. , Chaudret B. , Cámpora J. , van Leeuwen P. W. N. M.
Published: February 2017

Pt NPs covered with zwitterionic amidinates as ligands exhibit an exciting ligand effect in the hydrogenation of carbonyl groups when electron donor/acceptor groups are introduced in theN-substituents.
Compositional tailoring effect on electric field distribution for significantly enhanced breakdown strength and restrained conductive loss in sandwich-structured ceramic/polymer nanocomposites
Authors: Wang Yifei , Cui Jin , Wang Linxi , Yuan Qibin , Niu Yujuan , Chen Jie , Wang Qing , Wang Hong
Published: February 2017

A sandwich-structured ceramic/polymer dielectric nanocomposite with significantly enhanced breakdown strength and restrained conductive loss was obtained by tailoring filler contents.
N-Annulated perylene diimide dimers: acetylene linkers as a strategy for controlling structural conformation and the impact on physical, electronic, optical and photovoltaic properties
Authors: Cann Jonathan , Dayneko Sergey , Sun Jon-Paul , Hendsbee Arthur D. , Hill Ian G. , Welch Gregory C.
Published: February 2017

The geometry of organic π-conjugated small molecules can impact the morphology of blended-thin films and subsequent performance in opto-electronic devices.
The mutagenic mechanism of oxygenated alkylhydrazones occurs through alkyl radicals and alkyldiazonium ions
Authors: Inami Keiko , Takada Miki , Nagata Miho , Higashi Toshinori , Mochizuki Masataka
Published: February 2017

Hydrazone hydroperoxides were formed by autoxidation and their mutagenicity was derived from the alkyldiazonium ion and the radical species.
Surface-enhanced Raman scattering of uranyl in aqueous samples: implications for nuclear forensics and groundwater testing
Authors: Trujillo M. J. , Jenkins D. M. , Bradshaw J. A. , Camden J. P.
Published: February 2017

A surface-enhanced Raman scattering (SERS) method, based on functionalized silver colloids, is developed for the detection of uranyl ions that yields a limit of detection of 24 ppb.
Cupric oxide nanowires on three-dimensional copper foam for application in click reaction
Authors: Wang Chunxia , Yang Fan , Cao Yan , He Xing , Tang Yushu , Li Yongfeng
Published: February 2017

CuO nanowires can be synthesized by facile thermal oxidation of 3D Cu foam in air, which were found to be effective heterogeneous catalysts for the 1,3-dipolar cycloaddition reactions without using any additional support and bases.
Insights into the pathological mechanisms of p85α mutations using a yeast-based phosphatidylinositol 3-kinase model
Authors: Oliver María D. , Fernández-Acero Teresa , Luna Sandra , Rodríguez-Escudero Isabel , Molina María , Pulido Rafael , Cid Víctor J.
Published: February 2017

In higher eukaryotes, cell proliferation is regulated by class I phosphatidylinositol 3-kinase (PI3K), which transduces stimuli received from neighboring receptors by local generation of PtdIns(3,4,5)P3 in cellular membranes. PI3K is a heterodimeric protein consisting of a regulatory and a catalytic subunit (p85 and p110 respectively). Heterologous expression of p110α in Saccharomyces cerevisiae leads to toxicity by conversion of essential PtdIns(4,5)P2 into futile PtdIns(3,4,5)P3, providing a humanized yeast model for functional studies on this pathway. Here, we report expression and functional characterization in yeast of all regulatory and catalytic human PI3K isoforms, and exploitation of the most suitable setting to functionally assay panels of tumor- and germ line-associated PI3K mutations, with indications to the limits of the system. The activity of p110α in yeast was not compromised by truncation of its N-terminal adaptor-binding domain (ABD) or inactivation of the Ras-binding domain (RBD). In contrast, a cluster of positively charged residues at the C2 domain was essential. Expression of a membrane-driven p65α oncogenic-truncated version of p85α, but not the full-length protein, led to enhanced activity of α, β, and δ p110 isoforms. Mutations impairing the inhibitory regulation exerted by the p85α iSH2 domain on the C2 domain of p110α yielded the latter non-responsive to negative regulation, thus reproducing this oncogenic mechanism in yeast. However, p85α germ line mutations associated with short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome did not increase PI3K activity in this model, supporting the idea that SHORT syndrome-associated p85α mutations operate through mechanisms different from the canonical disruption of inhibitory p85–p110 interactions typical of cancer.
Habitat effects on home range and schooling behaviour in a herbivorous fish (Kyphosus bigibbus) revealed by acoustic tracking
Authors: Pillans R. D. , Babcock R. C. , Thomson D. P. , Haywood M. D. E. , Downie R. A. , Vanderklift M. A. , Rochester W. A.
Published: February 2017

Large mobile herbivorous fish that specialise in browsing large brown algae are particularly important on coral reefs because their activities mediate algal–coral competition. Despite this important ecological role, we have a poor understanding of the movement patterns of such large herbivorous fish, including Kyphosus bigibbus. Nineteen K. bigibbus captured near adjacent but distinct patch reefs were tagged with internal acoustic tags and their movements monitored for up to 20 months by an array of 60 acoustic receivers. Home-range estimates showed that movements of individuals from each patch reef encompassed different spatial extents and resulted in differences in habitat used by the two groups of fish. The average 50 and 95% kernel utilisation distribution for long-term resident fish was 0.27±0.03 and 1.61±0.30km2 respectively, ranges that represent the largest values for a herbivorous coral reef fish recorded to date. There was a significantly higher degree of fidelity among fish from the same school, and to particular patch reefs, despite the proximity of the reefs and substantial overlap between schools of conspecifics. A coefficient of sociality was used on pairs of fish and showed that there was no evidence that individuals were consistently detected together when they were detected by receivers away from their home reef. The variability of movement patterns among individuals of K. bigibbus results in an increased niche footprint for this important browser, potentially increasing reef resilience.
Angptl4 does not control hyperglucagonemia or α-cell hyperplasia following glucagon receptor inhibition
Authors: Okamoto Haruka , Cavino Katie , Na Erqian , Krumm Elizabeth , Kim Steven , Stevis Panayiotis E. , Harp Joyce , Murphy Andrew J. , Yancopoulos George D. , Gromada Jesper
Published: February 2017

Significance

Glucagon supports glucose homeostasis by stimulating hepatic glucose output. Inhibition of glucagon signaling has drawn much attention because of potential implications for diabetes treatment. It is well established that inhibition of glucagon signaling effectively lowers blood glucose but results in compensatory glucagon hypersecretion and expansion of pancreatic α-cell mass. It was recently proposed that Angptl4, an inhibitor of lipoprotein lipase-mediated plasma triglyceride clearance, links glucagon receptor inhibition to α-cell proliferation. Here we confirm that Angptl4 is a powerful regulator of plasma triglycerides, but not of hyperglucagonemia or α-cell hyperplasia. We observed an increase in plasma amino acids in humans following administration of a glucagon receptor-blocking antibody, confirming preclinical findings indicate that amino acids mediate the compensatory α-cell response.
Trophic Interactions and Consumption Rates of Subyearling Chinook Salmon and Nonnative Juvenile American Shad in Columbia River Reservoirs
Authors: Haskell Craig A. , Beauchamp David A. , Bollens Stephen M.
Published: February 2017

We used a large lampara seine coupled with nonlethal gastric lavage to examine the diets and estimate consumption rates of subyearling Chinook Salmon Oncorhynchus tshawytscha during July and August 2013. During August we also examined the diet and consumption rates of juvenile American Shad Alosa sapidissima, a potential competitor of subyearling Chinook Salmon. Subyearling Chinook Salmon consumed Daphnia in July but switched to feeding on smaller juvenile American Shad in August. We captured no juvenile American Shad in July, but in August juvenile American Shad consumed cyclopoid and calanoid copepods. Stomach evacuation rates for subyearling Chinook Salmon were high during both sample periods (0.58 h−1 in July, 0.51 h−1 in August), and daily ration estimates were slightly higher than values reported in the literature for other subyearlings. By switching from planktivory to piscivory, subyearling Chinook Salmon gained greater growth opportunity. While past studies have shown that juvenile American Shad reduce zooplankton availability for Chinook Salmon subyearlings, our work indicates that they also become important prey after Daphnia abundance declines. The diet and consumption data here can be used in future bioenergetics modeling to estimate the growth of subyearling Chinook Salmon in lower Columbia River reservoirs.

Received July 27, 2016; accepted November 22, 2016 Published online February 1, 2017
Citizens in appropriate numbers: evaluating five claims about justice and population size
Authors: Meijers Tim
Published: February 2017

While different worries about population size are present in public debates, political philosophers often take population size as given. This paper is an attempt to formulate a Rawlsian liberal egalitarian approach to population size: does it make sense to speak of ‘too few’ or ‘too many’ people from the point of view of justice? It argues that, drawing on key features of liberal egalitarian theory, several clear constraints on demographic developments – to the extent that they are under our control – can be formulated. Based on these claims, we can clarify both the grounds and content of our obligations to future generations.
Residual urinary extracellular vesicles in ultracentrifugation supernatants after hydrostatic filtration dialysis enrichment
Authors: Musante Luca , Tataruch‐Weinert Dorota , Kerjaschki Dontscho , Henry Michael , Meleady Paula , Holthofer Harry
Published: February 2017

Urinary extracellular vesicles (UEVs) appear an ideal source of biomarkers for kidney and urogenital diseases. The majority of protocols designed for their isolation are based on differential centrifugation steps. However, little is still known of the type and amount of vesicles left in the supernatant. Here we used an isolation protocol for UEVs which uses hydrostatic filtration dialysis as first pre‐enrichment step, followed by differential centrifugation. Transmission electron microscopy (TEM), mass spectrometry (MS), western blot, ELISA assays and tuneable resistive pulse sensing (TRPS) were used to characterise and quantify UEVs in the ultracentrifugation supernatant. TEM showed the presence of a variety of small size vesicles in the supernatant while protein identification by MS matched accurately with the protein list available in Vesiclepedia. Screening and relative quantification for specific vesicle markers showed that the supernatant was preferentially positive for CD9 and TSG101. ELISA tests for quantification of exosome revealed that 14%, was left in the supernatant with a particle diameter of 110 nm and concentration of 1.54 × 1010/ml. Here we show a comprehensive characterisation of exosomes and other small size urinary vesicles which the conventional differential centrifugation protocol may lose.
Ribonucleic artefacts: are some extracellular RNA discoveries driven by cell culture medium components?
Authors: Tosar Juan Pablo , Cayota Alfonso , Eitan Erez , Halushka Marc K. , Witwer Kenneth W.
Published: February 2017

In a recently published study, Anna Krichevsky and colleagues raise the important question of whether results of in vitro extracellular RNA (exRNA) studies, including extracellular vesicle (EV) investigations, are confounded by the presence of RNA in cell culture medium components such as foetal bovine serum (FBS). The answer, according to their data, is a resounding “yes”. Even after lengthy ultracentrifugation to remove bovine EVs from FBS, the majority of exRNA in FBS remained. Although technical factors may affect the degree of depletion, residual EVs and exRNA in FBS could influence the conclusions of in vitro studies: certainly, for secreted RNA, and possibly also for cell‐associated RNA. In this commentary, we critically examine some of the literature in this field, including a recent study from some of the authors of this piece, in light of the Wei et al. study and explore how cell culture‐derived RNAs may affect what we think we know about EV RNAs. These findings hold particular consequence as the field moves towards a deeper understanding of EV–RNA associations and potential functions.
TRAIL delivery by MSC‐derived extracellular vesicles is an effective anticancer therapy
Authors: Yuan ZhengQiang , Kolluri Krishna K. , Gowers Kate H. C. , Janes Sam M.
Published: February 2017

Extracellular vesicles (EVs) are lipid membrane‐enclosed nanoparticles released by cells. They mediate intercellular communication by transferring biological molecules and therefore have potential as innovative drug delivery vehicles. TNF‐related apoptosis‐inducing ligand (TRAIL) selectively induces apoptosis of cancer cells. Unfortunately, the clinical application of recombinant rTRAIL has been hampered by its low bioavailability and resistance of cancer cells. EV‐mediated TRAIL delivery may circumvent these problems. Mesenchymal stromal cells (MSCs) produce EVs and could be a good source for therapeutic EV production. We investigated if TRAIL could be expressed in MSC‐derived EVs and examined their cancer cell‐killing efficacy. EVs were isolated by ultracentrifugation and were membranous particles of 50–70 nm in diameter. Both MSC‐ and TRAIL‐expressing MSC (MSCT)‐derived EVs express CD63, CD9 and CD81, but only MSCT‐EVs express surface TRAIL. MSCT‐EVs induced apoptosis in 11 cancer cell lines in a dose‐dependent manner but showed no cytotoxicity in primary human bronchial epithelial cells. Caspase activity inhibition or TRAIL neutralisation blocked the cytotoxicity of TRAIL‐positive EVs. MSCT‐EVs induced pronounced apoptosis in TRAIL‐resistant cancer cells and this effect could be further enhanced using a CDK9 inhibitor. These data indicate that TRAIL delivery by MSC‐derived EVs is an effective anticancer therapy.
On Tonelli periodic orbits with low energy on surfaces
Authors: Asselle Luca , Mazzucchelli Marco
Published: February 2017

We prove that on a closed surface, a Lagrangian system defined by a Tonelli Lagrangian

L
L

possesses a periodic orbit that is a local minimizer of the free-period action functional on every energy level belonging to the low range of energies

(

e
0

(
L
)
,

c

u

(
L
)
)

(e_0(L),c_{\mathrm {u}}(L))

. We also prove that almost every energy level in

(

e
0

(
L
)
,

c

u

(
L
)
)

(e_0(L),c_{\mathrm {u}}(L))

possesses infinitely many periodic orbits. These statements extend two results, respectively due to Taimanov and Abbondandolo–Macarini–Mazzucchelli–Paternain, valid for the special case of electromagnetic Lagrangians.
The densest matroids in minor-closed classes with exponential growth rate
Authors: Geelen Jim , Nelson Peter
Published: February 2017

The growth rate function for a nonempty minor-closed class of matroids

M

\mathcal {M}

is the function

h

M

(
n
)

h_{\mathcal {M}}(n)

whose value at an integer

n
≥
0

n \ge 0

is defined to be the maximum number of elements in a simple matroid in

M

\mathcal {M}

of rank at most

n
n

. Geelen, Kabell, Kung and Whittle showed that, whenever

h

M

(
2
)

h_{\mathcal {M}}(2)

is finite, the function

h

M

h_{\mathcal {M}}

grows linearly, quadratically or exponentially in

n
n

(with base equal to a prime power

q
q

), up to a constant factor.

We prove that in the exponential case, there are nonnegative integers

k
k

and

d
≤

q

2
k

−
1

q
−
1

d \le \tfrac {q^{2k}-1} {q-1}

such that

h

M

(
n
)
=

q

n
+
k

−
1

q
−
1

−
q
d

h_{\mathcal {M}}(n) = \frac {q^{n+k}-1}{q-1} - qd

for all sufficiently large

n
n

, and we characterise which matroids attain the growth rate function for large

n
n

. We also show that if

M

\mathcal {M}

is specified in a certain ‘natural’ way (by intersections of classes of matroids representable over different finite fields and/or by excluding a finite set of minors), then the constants

k
k

and

d
d

, as well as the point that ‘sufficiently large’ begins to apply to

n
n

, can be determined by a finite computation.
Conservation aspects of natural populations and captive-bred stocks of turbot (Scophthalmus maximus) and Dover sole (Solea solea) using estimates of genetic diversity
Authors: Exadactylos Athanasios , Rigby Mark J. , Geffen Audrey J. , Thorpe John P.
Published: February 2017

Exadactylos, A., Rigby, M. J., Geffen, A. J., and Thorpe, J. P. 2007. Conservation aspects of natural populations and captive-bred stocks of turbot (Scophthalmus maximus) and Dover sole (Solea solea) using estimates of genetic diversity. – ICES Journal of marine Science, 64: 1173–1181. Population genetic analyses have been highly successful in predicting inter- and intraspecific evolutionary relationships, levels of gene flow, genetic divergence, and effective population sizes. Parameters estimated are evolutionary averages and are therefore relevant for addressing contemporary ecological or conservation issues. Changes in genetic variation within the range of a species may indicate patterns of population structure resulting from past ecological and demographic events that are otherwise difficult to infer, so may provide an insight into evolutionary development. Genetic data, drawn from 14 enzyme loci amplified from two populations of turbot (Scophthalmus maximus) and five populations of Dover sole (Solea solea) from the Irish Sea were used to examine population structure estimated from measures of genetic diversity. The aim was to provide an empirical assessment of whether artificial propagation poses a genetic threat to conservation of naturally spawning populations, and whether the fitness for natural spawning and rearing can be rapidly and substantially reduced or increased by artificial propagation. Because of prolonged overfishing, turbot and sole populations in the region are below natural levels, and survive in small local populations in fragmented habitats. Genetic data derived from allozymes have shown that populations are characterized by relatively low levels of genetic diversity. A hypothetical model supporting genetic population substructure, such as range expansion with founder-flush effects, and subsequent population decline with small effective population sizes was considered. Observations support our belief that conservation measures based on genetic diversity have to be developed to ensure the survival of this diverse gene pool.
Pharmacokinetics of anti-TB drugs in Malawian children: reconsidering the role of ethambutol
Authors: Mlotha R. , Waterhouse D. , Dzinjalamala F. , Ardrey A. , Molyneux E. , Davies G. R. , Ward S.
Published: February 2017

Background

Current guidelines for dosing of anti-TB drugs in children advocate higher doses for rifampicin and isoniazid despite limited availability of paediatric data on the pharmacokinetics of these drugs, especially from Africa, where the burden of childhood disease remains high.

Methods

Thirty children aged 6 months to 15 years underwent intensive pharmacokinetic sampling for first-line anti-TB drugs at Queen Elizabeth Central Hospital, Blantyre, Malawi. Rifampicin, isoniazid, pyrazinamide and ethambutol were dosed at 10, 5, 25 and 20 mg/kg, respectively. Plasma drug concentrations were determined using sensitive, validated bioanalytical methods and summary pharmacokinetic parameters were estimated using non-compartmental analysis.

Results

The median (IQR) Cmax was 2.90 (2.08–3.43), 3.37 (2.55–4.59), 34.60 (32.30–40.90) and 1.20 (0.85–1.68) mg/L while the median (IQR) AUC0–∞ was 16.92 (11.10–22.74), 11.48 (7.35–18.93), 333.50 (279.50–487.2) and 8.65 (5.96–11.47) mg·h/L for rifampicin, isoniazid, pyrazinamide and ethambutol, respectively. For all drugs, pharmacokinetic parameters relating to drug absorption and exposure were lower than those published for adults, though similar to existing paediatric data from sub-Saharan Africa. Weight and/or dose predicted at least one measure of exposure for all drugs. Age-related decreases in CL/F for rifampicin and pyrazinamide and a biphasic elimination pattern of isoniazid were observed. Predicted AUC0–∞ for rifampicin dosed at 15 mg/kg was comparable to that of adults while the dose required to achieve ethambutol exposure similar to that in adults was 55 mg/kg or higher.

Conclusions

These data support recently revised WHO recommendations for dosing of anti-TB drugs in children, but dosing of ethambutol in children also appears inadequate by comparison with adult pharmacokinetic data.