bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetically engineered biosynthetic pathways for nonnatural C60 carotenoids using C5-elongases and C50-cyclases in Escherichia coli
Authors: Li Ling , Furubayashi Maiko , Wang Shifei , Maoka Takashi , Kawai-Noma Shigeko , Saito Kyoichi , Umeno Daisuke
Published: February 2019

While the majority of the natural carotenoid pigments are based on 40-carbon (C40) skeleton, some carotenoids from bacteria have larger C50 skeleton, biosynthesized by attaching two isoprene units (C5) to both sides of the C40 carotenoid pigment lycopene. Subsequent cyclization reactions result in the production of C50 carotenoids with diverse and unique skeletal structures. To produce even larger nonnatural novel carotenoids with C50 + C5 + C5 = C60 skeletons, we systematically coexpressed natural C50 carotenoid biosynthetic enzymes (lycopene C5-elongases and C50-cyclases) from various bacterial sources together with the laboratory-engineered nonnatural C50-lycopene pathway in Escherichia coli. Among the tested enzymes, the elongases and cyclases from Micrococcus luteus exhibited significant activity toward C50-lycopene, and yielded the novel carotenoids C60-flavuxanthin and C60-sarcinaxanthin. Moreover, coexpression of M. luteus elongase with Corynebacterium cyclase resulted in the production of C60-sarcinaxanthin, C60-sarprenoxanthin, and C60-decaprenoxanthin.
Revisiting the dynamic and thermodynamic processes driving the record-breaking January 2014 precipitation in the southern UK
Authors: Oueslati Boutheina , Yiou Pascal , Jézéquel Aglaé
Published: February 2019

Many attribution studies of precipitation extreme events have attempted to estimate the thermodynamic contribution (linked to temperature changes) and the dynamic contribution (linked to the atmospheric circulation). Those studies are based on statistical decompositions of atmospheric fields, and essentially focus on the horizontal motion of the atmosphere. This paper proposes a framework that decomposes those terms from first physical principles, which include the vertical atmospheric motion that has often been overlooked. The goal is to take into account the driving processes of the extreme event. We revisit a recent example of extreme precipitation that was extensively investigated through its relation with the atmospheric circulation. We find that although the horizontal motion plays a minor (but important) role, the vertical motion yields a dominating contribution to the event that is larger than the thermodynamic contribution. This analysis quantifies the processes leading to high winter precipitation rates, and can be extended for further attribution studies.
The nested structural organization of the worldwide trade multi-layer network
Authors: Alves Luiz G. A. , Mangioni Giuseppe , Cingolani Isabella , Rodrigues Francisco Aparecido , Panzarasa Pietro , Moreno Yamir
Published: February 2019

Nestedness has traditionally been used to detect assembly patterns in meta-communities and networks of interacting species. Attempts have also been made to uncover nested structures in international trade, typically represented as bipartite networks in which connections can be established between countries (exporters or importers) and industries. A bipartite representation of trade, however, inevitably neglects transactions between industries. To fully capture the organization of the global value chain, we draw on the World Input-Output Database and construct a multi-layer network in which the nodes are the countries, the layers are the industries, and links can be established from sellers to buyers within and across industries. We define the buyers’ and sellers’ participation matrices in which the rows are the countries and the columns are all possible pairs of industries, and then compute nestedness based on buyers’ and sellers’ involvement in transactions between and within industries. Drawing on appropriate null models that preserve the countries’ or layers’ degree distributions in the original multi-layer network, we uncover variations of country- and transaction-based nestedness over time, and identify the countries and industries that most contributed to nestedness. We discuss the implications of our findings for the study of the international production network and other real-world systems.
Ortholog of the polymerase theta helicase domain modulates DNA replication in Trypanosoma cruzi
Authors: de Lima Loyze P. , Calderano Simone G. , da Silva Marcelo S. , de Araujo Christiane B. , Vasconcelos Elton J. R. , Iwai Leo K. , Pereira Claudio A. , Fragoso Stenio P. , Elias M. Carolina
Published: February 2019

DNA polymerase theta (Polθ), a member of the DNA polymerase family A, exhibits a polymerase C-terminal domain, a central domain, and an N-terminal helicase domain. Polθ plays important roles in DNA repair via its polymerase domain, regulating genome integrity. In addition, in mammals, Polθ modulates origin firing timing and MCM helicase recruitment to chromatin. In contrast, as a model eukaryote, Trypanosoma cruzi exhibits two individual putative orthologs of Polθ in different genomic loci; one ortholog is homologous to the Polθ C-terminal polymerase domain, and the other is homologous to the Polθ helicase domain, called Polθ-polymerase and Polθ-helicase, respectively. A pull-down assay using the T. cruzi component of the prereplication complex Orc1/Cdc6 as bait captured Polθ-helicase from the nuclear extract. Orc1/Cdc6 and Polθ-helicase directly interacted, and Polθ-helicase presented DNA unwinding and ATPase activities. A T. cruzi strain overexpressing the Polθ-helicase domain exhibited a significantly decreased amount of DNA-bound MCM7 and impaired replication origin firing. Taken together, these data suggest that Polθ-helicase modulates DNA replication by directly interacting with Orc1/Cdc6, which reduces the binding of MCM7 to DNA and thereby impairs the firing of replication origins.
Household socio-economic position and individual infectious disease risk in rural Kenya
Authors: de Glanville W. A. , Thomas L. F. , Cook E. A. J. , Bronsvoort B. M. de C. , Wamae N. C. , Kariuki S. , Fèvre E. M.
Published: February 2019

The importance of household socio-economic position (SEP) in shaping individual infectious disease risk is increasingly recognised, particularly in low income settings. However, few studies have measured the extent to which this association is consistent for the range of pathogens that are typically endemic among the rural poor in the tropics. This cross-sectional study assessed the relationship between SEP and human infection within a single community in western Kenya using a set of pathogens with diverse transmission routes. The relationships between household SEP and individual infection with Plasmodium falciparum, hookworm (Ancylostoma duodenale and/or Necator americanus), Entamoeba histolytica/dispar, Mycobacterium tuberculosis, and HIV, and co-infections between hookworm, P. falciparum and E. histolytica/dispar, were assessed using multivariable logistic and multinomial regression. Individuals in households with the lowest SEP were at greatest risk of infection with P. falciparum, hookworm and E. histolytica/dispar, as well as co-infection with each pathogen. Infection with M. tuberculosis, by contrast, was most likely in individuals living in households with the highest SEP. There was no evidence of a relationship between individual HIV infection and household SEP. We demonstrate the existence of a household socio-economic gradient within a rural farming community in Kenya which impacts upon individual infectious disease risk. Structural adjustments that seek to reduce poverty, and therefore the socio-economic inequalities that exist in this community, would be expected to substantially reduce overall infectious disease burden. However, policy makers and researchers should be aware that heterogeneous relationships can exist between household SEP and infection risk for different pathogens in low income settings.
Proximal perimeter encoding in the rat rostral thalamus
Authors: Matulewicz Pawel , Ulrich Katharina , Islam Md. Nurul , Mathiasen Mathias L. , Aggleton John P. , O’Mara Shane M.
Published: February 2019

Perimeters are an important part of the environment, delimiting its geometry. Here, we investigated how perimeters (vertical walls; vertical drops) affect neuronal responses in the rostral thalamus (the anteromedial and parataenial nuclei in particular). We found neurons whose firing patterns reflected the presence of walls and drops, irrespective of arena shape. Their firing patterns were stable across multiple sleep-wake cycles and were independent of ambient lighting conditions. Thus, rostral thalamic nuclei may participate in spatial representation by encoding the perimeters of environments.
Computer-aided diagnosis of colorectal polyps using linked color imaging colonoscopy to predict histology
Authors: Min Min , Su Song , He Wenrui , Bi Yiliang , Ma Zhanyu , Liu Yan
Published: February 2019

We developed a computer-aided diagnosis (CAD) system based on linked color imaging (LCI) images to predict the histological results of polyps by analyzing the colors of the lesions. A total of 139 images of adenomatous polyps and 69 images of non-adenomatous polyps obtained from our hospital were collected and used to train the CAD system. A test set of LCI images, including both adenomatous and non-adenomatous polyps, was prospectively collected from patients who underwent colonoscopies between Oct and Dec 2017; this test set was used to assess the diagnostic abilities of the CAD system compared to those of human endoscopists (two experts and two novices). The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of this novel CAD system for the training set were 87.0%, 87.1%, 87.0%, 93.1%, and 76.9%, respectively. The test set included 115 adenomatous polyps and 66 non-adenomatous polyps that were prospectively collected. The CAD system identified adenomatous or non-adenomatous polyps in the test set with an accuracy of 78.4%, a sensitivity of 83.3%, a specificity of 70.1%, a PPV of 82.6%, and an NPV of 71.2%. The accuracy of the CAD system was comparable to that of the expert endoscopists (78.4% vs 79.6%; p = 0.517). In addition, the diagnostic accuracy of the novices was significantly lower to the performance of the experts (70.7% vs 79.6%; p = 0.018). A novel CAD system based on LCI could be a rapid and powerful decision-making tool for endoscopists.
Metabolites related to purine catabolism and risk of type 2 diabetes incidence; modifying effects of the TCF7L2-rs7903146 polymorphism
Authors: Papandreou Christopher , Li Jun , Liang Liming , Bulló Mònica , Zheng Yan , Ruiz-Canela Miguel , Yu Edward , Guasch-Ferré Marta , Razquin Cristina , Clish Clary , Corella Dolores , Estruch Ramon , Ros Emilio , Fitó Montserrat , Arós Fernando , Serra-Majem Lluís , Rosique Nuria , Martínez-González Miguel A. , Hu Frank B. , Salas-Salvadó Jordi
Published: February 2019

Studies examining associations between purine metabolites and type 2 diabetes (T2D) are limited. We prospectively examined associations between plasma levels of purine metabolites with T2D risk and the modifying effects of transcription factor-7-like-2 (TCF7L2) rs7903146 polymorphism on these associations. This is a case-cohort design study within the PREDIMED study, with 251 incident T2D cases and a random sample of 694 participants (641 non-cases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 years). Metabolites were semi-quantitatively profiled with LC-MS/MS. Cox regression analysis revealed that high plasma allantoin levels, including allantoin-to-uric acid ratio and high xanthine-to-hypoxanthine ratio were inversely and positively associated with T2D risk, respectively, independently of classical risk factors. Elevated plasma xanthine and inosine levels were associated with a higher T2D risk in homozygous carriers of theTCF7L2-rs7903146 T-allele. The potential mechanisms linking the aforementioned purine metabolites and T2D risk must be also further investigated.
Distinct isoforms of Nrf1 diversely regulate different subsets of its cognate target genes
Authors: Wang Meng , Qiu Lu , Ru Xufang , Song Yijiang , Zhang Yiguo
Published: February 2019

The single Nrf1 gene has capability to be differentially transcripted alongside with alternative mRNA-splicing and subsequent translation through different initiation signals so as to yield distinct lengths of polypeptide isoforms. Amongst them, three of the most representatives are Nrf1α, Nrf1β and Nrf1γ, but the putative specific contribution of each isoform to regulating ARE-driven target genes remains unknown. To address this, we have herein established three cell lines on the base of the Flp-In T-REx system, which are allowed for the tetracycline-inducibly stable expression of Nrf1α, Nrf1β and Nrf1γ. Consequently, the RNA-Sequencing results have demonstrated that a vast majority of differentially expressed genes (i.e. >90% DEGs detected) were dominantly up-regulated by Nrf1α and/or Nrf1β following induction by tetracycline. By contrast, the other DEGs regulated by Nrf1γ were far less than those regulated by Nrf1α/β (i.e. ~11% of Nrf1α and ~7% of Nrf1β). However, further transcriptomic analysis revealed that the tetracycline-induced expression of Nrf1γ significantly increased the percentage of down-regulated genes in total DEGs. These statistical data were further validated by quantitative real-time PCR. The experimental results indicate that distinct Nrf1 isoforms make diverse and even opposing contributions to regulating different subsets of target genes, such as those encoding 26S proteasomal subunits and others involved in various biological processes and functions. Collectively, Nrf1γ acts as a major dominant-negative inhibitor competitively against Nrf1α/β activity, such that a number of DEGs regulated by Nrf1α/β are counteracted by Nrf1γ.
RAE1 mediated ZEB1 expression promotes epithelial–mesenchymal transition in breast cancer
Authors: Oh Ji Hoon , Lee Ji-Yeon , Yu Sungsook , Cho Yejin , Hur Sumin , Nam Ki Taek , Kim Myoung Hee
Published: February 2019

Breast cancer metastasis accounts for most of the deaths from breast cancer. Since epithelial-mesenchymal transition (EMT) plays an important role in promoting metastasis of cancer, many mechanisms regarding EMT have been studied. We previously showed that Ribonucleic acid export 1 (RAE1) is dysregulated in breast cancer and its overexpression leads to aggressive breast cancer phenotypes by inducing EMT. Here, we evaluated the functional capacity of RAE1 in breast cancer metastasis by using a three-dimensional (3D) culture system and xenograft models. Furthermore, to investigate the mechanisms of RAE1-driven EMT, in vitro studies were carried out. The induction of EMT with RAE1-overexpression was confirmed under the 3D culture system and in vivo system. Importantly, RAE1 mediates upregulation of an EMT marker ZEB1, by binding to the promoter region of ZEB1. Knockdown of ZEB1 in RAE1-overexpressing cells suppressed invasive and migratory behaviors, accompanied by an increase in epithelial and a decrease in mesenchymal markers. Taken together, these data demonstrate that RAE1 contributes to breast cancer metastasis by regulating a key EMT-inducing factor ZEB1 expression, suggesting its potential as a therapeutic target.
Efficacy of chemical and biological slug control measures in response to watering and earthworms
Authors: Dörler Daniel , Scheucher Agnes , Zaller Johann G.
Published: February 2019

The Spanish Slug (Arion vulgaris, formerly known as Arion lusitanicus) is an invasive agricultural and horticultural pest species that causes great damages all over Europe. Numerous options to control this slug are on the market; among the most commonly used are slug pellets containing the active ingredients metaldehyde or iron-III-phosphate and the application of parasitic nematodes (Phasmarhabditis hermaphrodita). These control measures potentially also affect non-target organisms like earthworms (Lumbricidae), which themselves can directly and/or indirectly alter a plant’s susceptibility against slug herbivory. Also, the efficacy of slug control treatments is expected to be influenced by watering. In a greenhouse experiment we investigated the influence of daily watering vs. every third day watering on slug control efficacy and potential interactions with earthworms. We found significant interactions between watering and slug control efficacy. Slug herbivory and biomass decreased after application of slug pellets; metaldehyde was more effective under less frequent watering while iron-III-phosphate was unaffected by watering. Parasitic nematodes had no effect on slug herbivory and biomass production. Earthworm activity was reduced with less frequent watering but did not interact with slug control. We conclude that watering patterns should be considered when choosing slug control measures.
Electron spin relaxations of phosphorus donors in bulk silicon under large electric field
Authors: Park Daniel K. , Park Sejun , Jee Hyejung , Lee Soonchil
Published: February 2019

Modulation of donor electron wavefunction via electric fields is vital to quantum computing architectures based on donor spins in silicon. For practical and scalable applications, the donor-based qubits must retain sufficiently long coherence times in any realistic experimental conditions. Here, we present pulsed electron spin resonance studies on the longitudinal (T1) and transverse (T2) relaxation times of phosphorus donors in bulk silicon with various electric field strengths up to near avalanche breakdown in high magnetic fields of about 1.2 T and low temperatures of about 8 K. We find that the T1 relaxation time is significantly reduced under large electric fields due to electric current, and T2 is affected as the T1 process can dominate decoherence. Furthermore, we show that the magnetoresistance effect in silicon can be exploited as a means to combat the reduction in the coherence times. While qubit coherence times must be much longer than quantum gate times, electrically accelerated T1 can be found useful when qubit state initialization relies on thermal equilibration.
Quantitative assessment of regional variation in tissue clearing efficiency using optical coherence tomography (OCT) and magnetic resonance imaging (MRI): A feasibility study
Authors: Baek Kwangyeol , Jung Sunwoo , Lee Junwon , Min Eunjung , Jung Woonggyu , Cho Hyungjoon
Published: February 2019

Tissue clearing has gained attention as a pioneering research tool for imaging of large tissue samples. This technique improves light transmission by reducing light scattering within tissues, either by removing lipids or by replacing water with a high refractive index solution. Although various clearing techniques have been developed, quantitative assessments on clearing efficacy depending on tissue properties are rare. In this study, we developed the quantitative mapping of regional clearing efficacy using mean free path in optical coherence tomography (OCT) and proton density in magnetic resonance imaging (MRI), and demonstrated its feasibility in the brain sample with four representative clearing techniques (benzyl alcohol and benzyl benzoate [BABB], ClearT, Scale, and passive CLARITY technique [PACT]). BABB (solvent-based clearing), involving both refractive index matching and lipid removal, exhibited best optical clearing performance with the highest proton density reduction both in gray and white matter. Lipid-removing techniques such as Scale (aqueous hyperhydration) and PACT (hydrogel embedding) showed higher clearing efficiency in white matter than gray matter in accordance with larger proton density increase in white matter. For ClearT (aqueous-based simple immersion), we observed lowest clearing efficiency in the white matter as well as poor lipid removal reflected in low proton density reduction. Our results showed the feasibility of the regional mapping of clearing efficacy and correlating optical transparency and proton density changes using OCT and MRI from existing tissue clearing techniques. This novel quantitative mapping of clearing efficacy depending on tissue types and clearing methods may be helpful in the development of optimized clearing methods for different biological samples.
Protein SUMOylation regulates insulin secretion at multiple stages
Authors: Davey Jeffrey S. , Carmichael Ruth E. , Craig Tim J.
Published: February 2019

Type-II Diabetes Mellitus (T2DM) is one of the fastest growing public health issues of modern times, consuming 12% of worldwide health budgets and affecting an estimated 400 million people. A key pathological trait associated with this disease is the failure of normal glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells. Several lines of evidence suggest that vesicle trafficking events such as insulin secretion are regulated by the post-translational modification, SUMOylation, and indeed SUMOylation has been proposed to act as a ‘brake’ on insulin exocytosis. Here, we show that diabetic stimuli which inhibit GSIS are correlated with an increase in cellular protein SUMOylation, and that inhibition of deSUMOylation reduces GSIS. We demonstrate that manipulation of cellular protein SUMOylation levels, by overexpression of several different components of the SUMOylation pathway, have varied and complex effects on GSIS, indicating that SUMOylation regulates this process at multiple stages. We further demonstrate that inhibition of syntaxin1A SUMOylation, via a knockdown-rescue strategy, greatly enhances GSIS. Our data are therefore consistent with the model that SUMOylation acts as a brake on GSIS, and we have identified SUMOylation of syntaxin 1 A as a potential component of this brake. However, our data also demonstrate that the role of SUMOylation in GSIS is complex and may involve many substrates.
Superconducting Diamond on Silicon Nitride for Device Applications
Authors: Bland Henry A. , Thomas Evan L. H. , Klemencic Georgina M. , Mandal Soumen , Morgan David J. , Papageorgiou Andreas , Jones Tyrone G. , Williams Oliver A.
Published: February 2019

Chemical vapour deposition (CVD) grown nanocrystalline diamond is an attractive material for the fabrication of devices. For some device architectures, optimisation of its growth on silicon nitride is essential. Here, the effects of three pre-growth surface treatments, often employed as cleaning methods, were investigated. Such treatments provide control over the surface charge of the silicon nitride substrate through modification of the surface functionality, allowing for the optimisation of electrostatic diamond seeding densities. Zeta potential measurements and X-ray photoelectron spectroscopy (XPS) were used to analyse the silicon nitride surface following each treatment. Exposing silicon nitride to an oxygen plasma offered optimal surface conditions for the electrostatic self-assembly of a hydrogen-terminated diamond nanoparticle monolayer. The subsequent growth of boron-doped nanocrystalline diamond thin films on modified silicon nitride, under CVD conditions, produced coalesced films for oxygen plasma and solvent treatments, whilst pin-holing of the diamond film was observed following RCA-1 treatment. The sharpest superconducting transition was observed for diamond grown on oxygen plasma treated silicon nitride, demonstrating it to be of the least structural disorder. Modifications to the substrate surface optimise the seeding and growth processes for the fabrication of diamond on silicon nitride devices.
A ferroptosis–based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis
Authors: Devos David , Moreau Caroline , Kyheng Maeva , Garçon Guillaume , Rolland Anne Sophie , Blasco Hélène , Gelé Patrick , Timothée Lenglet T. , Veyrat-Durebex C. , Corcia Philippe , Dutheil Mary , Bede Peter , Jeromin Andreas , Oeckl Patrick , Otto Markus , Meininger Vincent , Danel-Brunaud Véronique , Devedjian Jean-christophe , Duce James A. , Pradat Pierre François
Published: February 2019

Accurate patient stratification into prognostic categories and targeting Amyotrophic Lateral Sclerosis (ALS)-associated pathways may pave the way for promising trials. We evaluated blood-based prognostic indicators using an array of pathological markers. Plasma samples were collected as part of a large, phase III clinical trial (Mitotarget/TRO19622) at months 1, 6, 12 and 18. The ALSFRS-r score was used as a proxy of disease progression to assess the predictive value of candidate biological indicators. First, established clinical predictors were evaluated in all 512 patients. Subsequently, pathologic markers, such as proxies of neuronal integrity (Neurofilament light chain and phosphorylated heavy chain), DNA oxidation (8-oxo-2′-desoxyguanosine), lipid peroxidation (4-hydroxy-2-nonenal, isoprostane), inflammation (interleukin-6) and iron status (ferritin, hepcidin, transferrin) were assessed in a subset of 109 patients that represented the whole cohort. Markers of neuronal integrity, DNA and lipid oxidation, as well as iron status at baseline are accurate predictors of disability at 18-month follow-up. The composite scores of these markers in association with established clinical predictors enable the accurate forecasting of functional decline. The identified four biomarkers are all closely associated with ‘ferroptosis’, a recently discovered form of programmed cell death with promising therapeutic targets. The predictive potential of these pathophysiology-based indicators may offer superior patient stratification for future trials, individualised patient care and resource allocation.
Wavelength-dependent Optical Instability Mechanisms and Decay Kinetics in Amorphous Oxide Thin-Film Devices
Authors: Bae Junyoung , Jeong Inkyung , Lee Sungsik
Published: February 2019

We present a study on decay kinetics for a recovery process depending on the light wavelength selected in optical instability measurements against amorphous In-Ga-Zn-O (a-IGZO) thin-film devices. To quantitatively analyze optically-induced instability behaviors, a stretched exponential function (SEF) and its inverse Laplace transform are employed for a time- and energy-dependent analysis, respectively. The analyzed results indicate that a shorter wavelength light activates electrons largely from the valence band while metastable states are deionized with the respective photon energy (hv). In contrast, a longer wavelength illumination is mainly activating trapped electrons at metastable states, e.g. oxygen defects. In particular, at 500 nm wavelength (hv ~ 2.5 eV), it shows an early persistency with a much higher activation energy. This also implies that the majority of metastable states remain ionized, thus the deionization energy >2.5 eV. However, the decay trend at 600 nm wavelength (hv ~ 2 eV) is found to be less persistent and lower current level compared to the case at 500 nm wavelength, suggesting the ionization energy of metastable states >2 eV. Finally, it is deduced that majority of oxygen defects before the illumination reside within the energy range between 2 eV and 2.5 eV from the conduction band edge.
Machine Learning Methods for Control of Fibre Lasers with Double Gain Nonlinear Loop Mirror
Authors: Kokhanovskiy Alexey , Ivanenko Aleksey , Kobtsev Sergey , Smirnov Sergey , Turitsyn Sergey
Published: February 2019

Many types of modern lasers feature nonlinear properties, which makes controlling their operation a challenging engineering problem. In particular, fibre lasers present both high-performance devices that are already used for diverse industrial applications, but also interesting and not yet fully understood nonlinear systems. Fibre laser systems operating at high power often have multiple equilibrium states, and this produces complications with the reproducibility and management of such devices. Self-tuning and feedback-enabled machine learning approaches might define a new era in laser science and technology. The present study is the first to demonstrate experimentally the application of machine learning algorithms for control of the pulsed regimes in an all-normal dispersion, figure-eight fibre laser with two independent amplifying fibre loops. The ability to control the laser operation state by electronically varying two drive currents makes this scheme particularly attractive for implementing machine learning approaches. The self-tuning adjustment of two independent gain levels in the laser cavity enables generation-on-demand pulses with different duration, energy, spectral characteristics and time coherence. We introduce and evaluate the application of several objective functions related to selection of the pulse duration, energy and degree of temporal coherence of the radiation. Our results open up the possibility for new designs of pulsed fibre lasers with robust electronics-managed control.
Dynamic heterogeneity in complex interfaces of soft interface-dominated materials
Authors: Sagis Leonard M. C. , Liu Bingxue , Li Yuan , Essers Jeffrey , Yang Jack , Moghimikheirabadi Ahmad , Hinderink Emma , Berton-Carabin Claire , Schroen Karin
Published: February 2019

Complex interfaces stabilized by proteins, polymers or nanoparticles, have a much richer dynamics than those stabilized by simple surfactants. By subjecting fluid-fluid interfaces to step extension-compression deformations, we show that in general these complex interfaces have dynamic heterogeneity in their relaxation response that is well described by a Kohlrausch-Williams-Watts function, with stretch exponent β between 0.4–0.6 for extension, and 0.6–1.0 for compression. The difference in β between expansion and compression points to an asymmetry in the dynamics. Using atomic force microscopy and simulations we prove that the dynamic heterogeneity is intimately related to interfacial structural heterogeneity and show that the dominant mode for stretched exponential relaxation is momentum transfer between bulk and interface, a mechanism which has so far largely been ignored in experimental surface rheology. We describe how its rate constant can be determined using molecular dynamics simulations. These interfaces clearly behave like disordered viscoelastic solids and need to be described substantially different from the 2d homogeneous viscoelastic fluids typically formed by simple surfactants.
Fibroblast origin shapes tissue homeostasis, epidermal differentiation, and drug uptake
Authors: Hausmann Christian , Zoschke Christian , Wolff Christopher , Darvin Maxim E. , Sochorová Michaela , Kováčik Andrej , Wanjiku Barbara , Schumacher Fabian , Tigges Julia , Kleuser Burkhard , Lademann Jürgen , Fritsche Ellen , Vávrová Kateřina , Ma Nan , Schäfer-Korting Monika
Published: February 2019

Preclinical studies frequently lack predictive value for human conditions. Human cell-based disease models that reflect patient heterogeneity may reduce the high failure rates of preclinical research. Herein, we investigated the impact of primary cell age and body region on skin homeostasis, epidermal differentiation, and drug uptake. Fibroblasts derived from the breast skin of female 20- to 30-year-olds or 60- to 70-year-olds and fibroblasts from juvenile foreskin (<10 years old) were compared in cell monolayers and in reconstructed human skin (RHS). RHS containing aged fibroblasts differed from its juvenile and adult counterparts, especially in terms of the dermal extracellular matrix composition and interleukin-6 levels. The site from which the fibroblasts were derived appeared to alter fibroblast-keratinocyte crosstalk by affecting, among other things, the levels of granulocyte-macrophage colony-stimulating factor. Consequently, the epidermal expression of filaggrin and e-cadherin was increased in RHS containing breast skin fibroblasts, as were lipid levels in the stratum corneum. In conclusion, the region of the body from which fibroblasts are derived appears to affect the epidermal differentiation of RHS, while the age of the fibroblast donors determines the expression of proteins involved in wound healing. Emulating patient heterogeneity in preclinical studies might improve the treatment of age-related skin conditions.
Quantification of hepatic steatosis in chronic liver disease using novel automated method of second harmonic generation and two-photon excited fluorescence
Authors: Goh George Boon-Bee , Leow Wei Qiang , Liang Shen , Wan Wei Keat , Lim Tony Kiat Hon , Tan Chee Kiat , Chang Pik Eu
Published: February 2019

The presence of hepatic steatosis (HS) is an important histological feature in a variety of liver disease. It is critical to assess HS accurately, particularly where it plays an integral part in defining the disease. Conventional methods of quantifying HS remain semi-quantitative, with potential limitations in precision, accuracy and subjectivity. Second Harmonic Generation (SHG) microscopy is a novel technology using multiphoton imaging techniques with applicability in histological tissue assessment. Using an automated algorithm based on signature SHG parameters, we explored the utility and application of SHG for the diagnosis and quantification of HS. SHG microscopy analysis using GENESIS (HistoIndex, Singapore) was applied on 86 archived liver biopsy samples. Reliability was correlated with 3 liver histopathologists. Data analysis was performed using SPSS. There was minimal inter-observer variability between the 3 liver histopathologists, with an intraclass correlation of 0.92 (95% CI 0.89–0.95; p < 0.001). Good correlation was observed between the histopathologists and automated SHG microscopy assessment of HS with Pearson correlation of 0.93: p < 0.001. SHG microscopy provides a valuable tool for objective, more precise measure of HS using an automated approach. Our study reflects proof of concept evidence for potential future refinement to current conventional histological assessment.
Antitumoral effect of maintained neutrophilia induced by rhG-CSF in a murine model of pancreatic cancer
Authors: Brú A. , Bosch R. , Céspedes M. V. , Carmona-Güedes S. , Pascual E. , Brú I. , Souto J. C.
Published: February 2019

Although the protumoral functions of polymorphonuclear neutrophils are well known, some now-forgotten studies report antitumoral roles for these cells. The present work examines the antitumoral effect of maintained neutrophilia induced via the injection of recombinant human granulocyte colony stimulating factor (rhG-CSF, 100 μg/kg/day) in a Panc-1 subcutaneous xenograft murine model of pancreatic cancer. This treatment was compared with gemcitabine administration (120 mg/kg every two days) and a saline control (n = 6–7 mice per group). Compared to the controls, both the rhG-CSF- and gemcitabine-treated mice showed significantly suppressed tumor growth by day 4 (p < 0.001 and p = 0.013 respectively). From a mean starting volume of 106.9 ± 3.1 mm3 for all treatment groups, the final mean tumor volumes reached were 282.0 ± 30.7 mm3 for the rhG-CSF-treated mice, 202.6 ± 18.1 mm3 for the gemcitabine-treated mice and 519.4 ± 62.9 mm3 for the control mice (p < 0.004 and p < 0.01, respectively, vs. control). The rhG-CSF-treated tumors showed higher percentage necrosis than those treated with gemcitabine (37.4 ± 4.6 vs. 7.5 ± 3.0; p < 0.001). This is the first report of a clear anti-tumoral effect of rhG-CSF when used in monotherapy against pancreatic cancer. Since rhG-CSF administration is known to be associated with very few adverse events, it may offer an attractive alternative in the clinical treatment of pancreatic cancer.
The impact of fasting on resting state brain networks in mice
Authors: Tsurugizawa Tomokazu , Djemai Boucif , Zalesky Andrew
Published: February 2019

Fasting is known to influence learning and memory in mice and alter the neural networks that subserve these cognitive functions. We used high-resolution functional MRI to study the impact of fasting on resting-state functional connectivity in mice following 12 h of fasting. The cortex and subcortex were parcellated into 52 subregions and functional connectivity was measured between each pair of subregions in groups of fasted and non-fasted mice. Functional connectivity was globally increased in the fasted group compared to the non-fasted group, with the most significant increases evident between the hippocampus (bilateral), retrosplenial cortex (left), visual cortex (left) and auditory cortex (left). Functional brain networks in the non-fasted group comprised five segregated modules of strongly interconnected subregions, whereas the fasted group comprised only three modules. The amplitude of low frequency fluctuations (ALFF) was decreased in the ventromedial hypothalamus in the fasted group. Correlation in gamma oscillations derived from local field potentials was increased between the left visual and retrosplenial cortices in the fasted group and the power of gamma oscillations was reduced in the ventromedial hypothalamus. These results indicate that fasting induces profound changes in functional connectivity, most likely resulting from altered coupling of neuronal gamma oscillations.
Random-Reaction-Seed Method for Automated Identification of Neurite Elongation and Branching
Authors: Li Alvason Zhenhua , Corey Lawrence , Zhu Jia
Published: February 2019

Conventional deterministic algorithms (i.e., skeletonization and edge-detection) lack robustness and sensitivity to reliably detect the neurite elongation and branching of low signal-to-noise-ratio microscopy images. Neurite outgrowth experiments produce an enormous number of images that require automated measurement; however, the tracking of neurites is easily lost in the automated process due to the intrinsic variability of neurites (either axon or dendrite) under stimuli. We have developed a stochastic random-reaction-seed (RRS) method to identify neurite elongation and branching accurately and automatically. The random-seeding algorithm of RRS is based on the hidden-Markov-model (HMM) to offer a robust enough way for tracing arbitrary neurite structures, while the reaction-seeding algorithm of RRS secures the efficiency of random seeding. It is noteworthy that RRS is capable of tracing a whole neurite branch by only one initial seed, so that RRS is proficient at quantifying extensive amounts of neurite outgrowth images with noisy background in microfluidic devices of biomedical engineering fields. The method also showed notable performance for reconstructing of net-like structures, and thus is expected to be proficient for biomedical feature extractions in a wide range of applications, such as retinal vessel segmentation and cell membrane profiling in spurious-edge-tissues.
New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma
Authors: Verhoeven Jeroen , Hulpia Fabian , Kersemans Ken , Bolcaen Julie , De Lombaerde Stef , Goeman Jan , Descamps Benedicte , Hallaert Giorgio , Van den Broecke Caroline , Deblaere Karel , Vanhove Christian , Van der Eycken Johan , Van Calenbergh Serge , Goethals Ingeborg , De Vos Filip
Published: February 2019

The use of O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) as a positron emission tomography (PET) tracer for brain tumor imaging might have some limitations because of the relatively low affinity for the L-type amino acid transporter 1 (LAT1). To assess the stereospecificity and evaluate the influence of aromatic ring modification of phenylalanine LAT1 targeting tracers, six different fluoroalkylated phenylalanine analogues were synthesized. After in vitro Ki determination, the most promising compound, 2-[18F]-2-fluoroethyl-l-phenylalanine (2-[18F]FELP), was selected for further evaluation and in vitro comparison with [18F]FET. Subsequently, 2-[18F]FELP was assessed in vivo and compared with [18F]FET and [18F]FDG in a F98 glioblastoma rat model. 2-[18F]FELP showed improved in vitro characteristics over [18F]FET, especially when the affinity and specificity for system L is concerned. Based on our results, 2-[18F]FELP is a promising new PET tracer for brain tumor imaging.
On the emerging relationship between the stratospheric Quasi-Biennial oscillation and the Madden-Julian oscillation
Authors: Klotzbach P. , Abhik S. , Hendon H. H. , Bell M. , Lucas C. , G. Marshall A. , Oliver E. C. J.
Published: February 2019

A strong relationship between the quasi-biennial oscillation (QBO) of equatorial stratospheric winds and the amplitude of the Madden-Julian oscillation (MJO) during the boreal winter has recently been uncovered using observational data from the mid-1970s to the present. When the QBO is in its easterly phase in the lower stratosphere, it favors stronger MJO activity during boreal winter, while the MJO tends to be weaker during the westerly phase of the QBO. Here we show using reconstructed indices of the MJO and QBO back to 1905 that the relationship between enhanced boreal winter MJO activity and the easterly phase of the QBO has only emerged since the early 1980s. The emergence of this relationship coincides with the recent cooling trend in the equatorial lower stratosphere and the warming trend in the equatorial upper troposphere, which appears to have sensitized MJO convective activity to QBO-induced changes in static stability near the tropopause. Climate change is thus suggested to have played a role in promoting coupling between the MJO and the QBO.
Quantum walk hydrodynamics
Authors: Hatifi Mohamed , Di Molfetta Giuseppe , Debbasch Fabrice , Brachet Marc
Published: February 2019

A simple Discrete-Time Quantum Walk (DTQW) on the line is revisited and given an hydrodynamic interpretation through a novel relativistic generalization of the Madelung transform. Numerical results show that suitable initial conditions indeed produce hydrodynamical shocks and that the coherence achieved in current experiments is robust enough to simulate quantum hydrodynamical phenomena through DTQWs. An analytical computation of the asymptotic quantum shock structure is presented. The non-relativistic limit is explored in the Supplementary Material (SM).
Rapid progression and future of environmental DNA research
Authors: Seymour Mathew
Published: February 2019

Environmental DNA based research is a new field within molecular ecology that is seeing an amazing increase in research activity. In our Communications Biology article, we studied the degradation of eDNA in variable systems. Presented here is a short overview of eDNA science and current research activities underway in North Wales.
GE11-PDA-Pt@USPIOs nano-formulation for relief of tumor hypoxia and MRI/PAI-guided tumor radio-chemotherapy
Authors: Yang Chengcheng , Mi Xuan , Su Huilan , Yang Jingxing , Gu Yiyun , Zhang Lu , Sun Wenshe , Liang Xiaowen , Zhang Chunfu
Published: February 2019

GE11-PDA-Pt@USPIOs can relieve tumor hypoxic conditions efficiently and are highly effective for radio-chemotherapy of EGFR-positive tumors.
Aurophilicity in action: stepwise formation of dinuclear Au(i) macrocycles with rigid 1,8-dialkynylanthracenes
Authors: Niermeier Philipp , Wickemeyer Lucas , Neumann Beate , Stammler Hans-Georg , Goett-Zink Lukas , Kottke Tilman , Mitzel Norbert W.
Published: February 2019

1,8-Bis(gold(i)-ethynyl)anthracene units find stabilisation by maximising aurophilic contacts under formation of macrocyclic anions linked to cationic gold(i) fragments.
Metallophore profiling of nitrogen-fixing Frankia spp. to understand metal management in the rhizosphere of actinorhizal plants
Authors: Deicke Michael , Mohr Jan Frieder , Roy Sébastien , Herzsprung Peter , Bellenger Jean-Philippe , Wichard Thomas
Published: February 2019

Frankia spp. are widespread nitrogen-fixing soil bacteria, which often live in symbiosis with a broad range of hosts. Metal homeostasis plays a crucial role in the success of the symbiosis regarding the acquisition of essential trace metals and detoxification of potentially toxic elements. We have hypothesised that Frankia releases many organic ligands with a broad spectrum of affinity for essential and toxic metals. We coined the term ‘ligandosphere’ to describe the entirety of excreted metal complexing agents and ligands derived from the dissolved organic matter. Using metal isotope-coded profiling (MICP); metallophores of physiological important and toxic trace metals were identified by the addition of stable metal isotope pairs such as 54Fe/58Fe, 63Cu/65Cu, 66Zn/68Zn or 95Mo/98Mo. Liquid chromatography coupled to a mass spectrometer revealed strong variations of the metallophore profile in between the 14 test-strains. In total, about 83 organic ligands were identified as binding to one of the tested metals. The predicted sum formula of the major Fe binding ligands and MS/MS experiments suggested that several metallophore candidates have a similar molecular backbone. Growth experiments with a hyper-producer of metallophores revealed a positive relationship between metallophore production and the concentration of Cu in the growth medium. The present study provides the first comprehensive overview of the complexity of Frankia’s ligandosphere. It opens a path to a deeper understanding of mechanisms that regulate metal homeostasis in frankiae. Deciphering these mechanisms is important since the fitness of actinorhizal plants and their potential in ecological restoration relies heavily on their symbiosis with frankiae.
Nanosensors for diagnosis with optical, electric and mechanical transducers
Authors: Munawar Anam , Ong Yori , Schirhagl Romana , Tahir Muhammad Ali , Khan Waheed S. , Bajwa Sadia Z.
Published: February 2019

Nanosensors with high sensitivity utilize electrical, optical, and acoustic properties to improve the detection limits of analytes.
A cationic polymethacrylate-copolymer acts as an agonist for β-amyloid and an antagonist for amylin fibrillation
Authors: Sahoo Bikash R. , Genjo Takuya , Nakayama Takahiro W. , Stoddard Andrea K. , Ando Toshio , Yasuhara Kazuma , Fierke Carol A. , Ramamoorthy Ayyalusamy
Published: February 2019

This study demonstrates the modulation of amyloid aggregation of two human proteins, amyloid-beta and amylin, by a cationic polymer (PMAQA).
Constructing metallic zinc–cobalt sulfide hierarchical core–shell nanosheet arrays derived from 2D metal–organic-frameworks for flexible asymmetric supercapacitors with ultrahigh specific capacitance and performance
Authors: Sun Wei , Du Yuchuan , Wu Guangming , Gao Guohua , Zhu Han , Shen Jun , Zhang Kun , Cao Guozhong
Published: February 2019

Electrode materials of flexible asymmetric supercapacitors are usually suffers from low capacitance and sluggish kinetics.
Anodic formation and biomedical properties of hafnium-oxide nanofilms
Authors: Fohlerova Zdenka , Mozalev Alexander
Published: February 2019

Nanostructured anodic hafnium-oxide coatings reveal good cytocompatibility, antibacterial activity, excellent affinity to proteins, and promote attachment and proliferation of osteoblast-like cells.
Lead-free double halide perovskite Cs3BiBr6 with well-defined crystal structure and high thermal stability for optoelectronics
Authors: Tang Yingying , Liang Mingli , Chang Bingdong , Sun Hongyu , Zheng Kaibo , Pullerits Tönu , Chi Qijin
Published: February 2019

A lead-free double-halide perovskite with a well-defined structure was synthesized, likely providing a new candidate material for eco-friendly optoelectronic devices.
Bioactivity of a radical scavenger bis(pyrazolium p-toluenesulphonate) on ctDNA and certain microbes: a combined experimental and theoretical analysis
Authors: Balachandar S. , Sethuram M. , Muthuraja P. , Dhandapani M.
Published: February 2019

Free radical scavenging capability of BPPTS was proved by biological experiments, docking analysis and theoretical calculations.
Alkylammoniotrifluoroborate functionalized polystyrenes: polymeric pre-catalysts for the metal-free borylation of heteroarenes
Authors: Bouchard Nicolas , Fontaine Frédéric-Georges
Published: February 2019

The synthesis and activity of the first polymeric frustrated Lewis pairs for the borylation of heteroarenes is reported.
Characterization and molecular docking of new Δ17 fatty acid desaturase genes from Rhizophagus irregularis and Octopus bimaculoides
Authors: Rong Chunchi , Chen Haiqin , Tang Xin , Gu Zhennan , Zhao Jianxin , Zhang Hao , Chen Wei , Chen Yong Q.
Published: February 2019

Fatty acid desaturases are key enzymes in the biosynthesis of n-3 polyunsaturated fatty acids (PUFAs) via conversion of n-6 polyunsaturates to their n-3 counterparts.