bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of industrial treatments to donor human milk: influence of pasteurization treatments, storage temperature, and time on human milk gangliosides
Authors: Salcedo Jaime , Karav Sercan , Le Parc Annabelle , Cohen Joshua L. , de Moura Bell Juliana M. L. N. , Sun Adam , Lange Matthew C. , Barile Daniela
Published: February 2018

Donor milk is the best option when mother’s own milk is unavailable. Heat treatments are applied to ensure donor milk safety. The effects of heat treatments on milk gangliosides—bioactive compounds with beneficial antibacterial, anti-inflammatory, and prebiotic roles—have not been studied. The most abundant gangliosides in non-homogenized human milk were characterized and quantified by liquid chromatography–mass spectrometry (LC–MS)/MS before and after pasteurization treatments mimicking industrial conditions (63 °C/30 min, 72 °C/15 s, 127 °C/5 s, and 140 °C/6 s). Ganglioside stability over a 3-month period was assessed following the storage at 4 and 23 °C. Independent of the heat treatment applied, gangliosides were stable after 3 months of storage at 4 or 23 °C, with only minor variations in individual ganglioside structures. These findings will help to define the ideal processing and storage conditions for donor milk to maximize the preservation of the structure of bioactive compounds to enhance the health of fragile newborns. Moreover, these results highlight the need for, and provide a basis for, a standardized language enabling biological and food companies, regulatory agencies, and other food stakeholders to both annotate and compute the ways in which production, processing, and storage conditions alter or maintain the nutritive, bioactive, and organoleptic properties of ingredients and foods, as well as the qualitative effects these foods and ingredients may have on conferring phenotype in the consuming organism.
Population-based mechanistic modeling allows for quantitative predictions of drug responses across cell types
Authors: Gong Jingqi Q. X. , Sobie Eric A.
Published: February 2018

Quantitative mismatches between human physiology and experimental models can be problematic for the development of effective therapeutics. When the effects of drugs on human adult cardiac electrophysiology are of interest, phenotypic differences with animal cells, and more recently stem cell-derived models, can present serious limitations. We addressed this issue through a combination of mechanistic mathematical modeling and statistical analyses. Physiological metrics were simulated in heterogeneous populations of models describing cardiac myocytes from adult ventricles and those derived from induced pluripotent stem cells (iPSC-CMs). These simulated measures were used to construct a cross-cell type regression model that predicts adult myocyte drug responses from iPSC-CM behaviors. We found that (1) quantitatively accurate predictions of responses to selective or non-selective ion channel blocking drugs could be generated based on iPSC-CM responses under multiple experimental conditions; (2) altering extracellular ion concentrations is an effective experimental perturbation for improving the model’s predictive strength; (3) the method can be extended to predict and contrast drug responses in diseased as well as healthy cells, indicating a broader application of the concept. This cross-cell type model can be of great value in drug development, and the approach, which can be applied to other fields, represents an important strategy for overcoming experimental model limitations.
Integration of genome-scale metabolic networks into whole-body PBPK models shows phenotype-specific cases of drug-induced metabolic perturbation
Authors: Cordes Henrik , Thiel Christoph , Baier Vanessa , Blank Lars M. , Kuepfer Lars
Published: February 2018

Drug-induced perturbations of the endogenous metabolic network are a potential root cause of cellular toxicity. A mechanistic understanding of such unwanted side effects during drug therapy is therefore vital for patient safety. The comprehensive assessment of such drug-induced injuries requires the simultaneous consideration of both drug exposure at the whole-body and resulting biochemical responses at the cellular level. We here present a computational multi-scale workflow that combines whole-body physiologically based pharmacokinetic (PBPK) models and organ-specific genome-scale metabolic network (GSMN) models through shared reactions of the xenobiotic metabolism. The applicability of the proposed workflow is illustrated for isoniazid, a first-line antibacterial agent against Mycobacterium tuberculosis, which is known to cause idiosyncratic drug-induced liver injuries (DILI). We combined GSMN models of a human liver with N-acetyl transferase 2 (NAT2)-phenotype-specific PBPK models of isoniazid. The combined PBPK-GSMN models quantitatively describe isoniazid pharmacokinetics, as well as intracellular responses, and changes in the exometabolome in a human liver following isoniazid administration. Notably, intracellular and extracellular responses identified with the PBPK-GSMN models are in line with experimental and clinical findings. Moreover, the drug-induced metabolic perturbations are distributed and attenuated in the metabolic network in a phenotype-dependent manner. Our simulation results show that a simultaneous consideration of both drug pharmacokinetics at the whole-body and metabolism at the cellular level is mandatory to explain drug-induced injuries at the patient level. The proposed workflow extends our mechanistic understanding of the biochemistry underlying adverse events and may be used to prevent drug-induced injuries in the future.
Prospects for strain-specific immunotherapy in Alzheimer’s disease and tauopathies
Authors: Bittar Alice , Sengupta Urmi , Kayed Rakez
Published: February 2018

With increasing age, as the incidence of Alzheimer’s disease is increasing, finding a therapeutic intervention is becoming critically important to either prevent or slow down the progression of the disease. Passive immunotherapy has been demonstrated as a successful way of reducing large aggregates and improving cognition in animal models of both tauopathies and Alzheimer’s disease. However, with all the continuous attempts and significant success of immunotherapy in preclinical studies, finding a successful clinical therapy has been a great challenge, possibly indicating a lack of accuracy in targeting the toxic species. Both active and passive immunotherapy approaches in transgenic animals have been demonstrated to have pros and cons. Passive immunotherapy has been favored and many mechanisms have been shown to clear toxic amyloid and tau aggregates and improve memory. These mechanisms may differ depending on the antibodie's' target and administration route. In this regard, deciding on affinity vs. specificity of the antibodies plays a significant role in terms of avoiding the clearance of the physiological forms of the targeted proteins and reducing adverse side effects. In addition, knowing that a single protein can exist in different conformational states, termed as strains, with varying degrees of neurotoxicity and seeding properties, presents an additional level of complexity. Therefore, immunotherapy targeting specifically the toxic strains will aid in developing potential strategies for intervention. Moreover, an approach of combinatorial immunotherapies against different amyloidogenic proteins, at distinct levels of the disease progression, might offer an effective therapy in many neurodegenerative diseases.
Preparation and Imaging Investigation of Dual-targeted C3F8-filled PLGA Nanobubbles as a Novel Ultrasound Contrast Agent for Breast Cancer
Authors: Du Jing , Li Xiao-Yu , Hu He , Xu Li , Yang Shi-Ping , Li Feng-Hua
Published: February 2018

Molecularly-targeted contrast enhanced ultrasound (US) imaging is a promising imaging strategy with large potential for improving diagnostic accuracy of conventional US imaging in breast cancer detection. Therefore, we constructed a novel dual-targeted nanosized US contrast agent (UCA) directed at both vascular endothelial growth factor receptor 2 (VEGFR2) and human epidermal growth factor receptor 2 (HER2) based on perfluoropropane (C3F8)-filled poly(lactic-co-glycolic acid) (PLGA) (NBs) for breast cancer detection. In vitro, single- or dual-targeted PLGA NBs showed high target specificities and better effects of target enhancement in VEGFR2 or HER2-positive cells. In vivo, US imaging signal in the murine breast cancer model was significantly higher (P < 0.01) for dual-targeted NBs than single-targeted and non-targeted NBs. Small animal fluorescence imaging further confirmed the special affinity of the dual-targeted nanosized contrast agent to both VEGFR2 and HER2. Immunofluorescence and immunohistochemistry staining confirmed the expressions of VEGFR2 and HER2 on tumor neovasculature and tumor cells of breast cancer. In conclusions, the feasibility of using dual-targeted PLGA NBs to enhance ultrasonic images is demonstrated in vitro and in vivo. This may be a promising approach to target biomarkers of breast cancer for two site-specific US molecular imaging.
Reducing group delay spread using uniform long-period gratings
Authors: Liu Huiyuan , Wen He , Huang Bin , Correa Rodrigo Amezcua , Sillard Pierre , Chen Haoshuo , Li Zhihong , Li Guifang
Published: February 2018

Despite the promise of an orders-of-magnitude increase in transmission capacity, practical implementation of mode-division multiplexing faces a number of challenges. The most important among them is the complexity of digital signal processing (DSP) for compensating mode crosstalk and modal dispersion. The most promising method proposed so far for reducing this DSP complexity is strong mode coupling. We propose and demonstrate, for the first time, a method of inducing strong mode coupling and reducing group delay spread using uniform long-period gratings (LPGs). Even though the LPGs have a fixed grating period, mode coupling is effective among all mode groups and over a broad wavelength range. Both insertion loss and mode-dependent loss can be significantly reduced by optimizing the index profile of and the number of modes supported by the fiber in which the LPG is applied.
The influence of a high fat diet on bone and soft tissue formation in Matrix Gla Protein knockout mice
Authors: Lanham S. A. , Cagampang F. R. , Oreffo R. O. C.
Published: February 2018

Studies suggest bone growth and development are influenced by maternal nutrition, during intrauterine and early postnatal life. This study assessed the role of MGP and a maternal high fat diet on vitamin K-dependent proteins’ gene expression and their impact on bone formation. Knockout (KO) offspring were smaller than wild type (WT) littermates, yet possessed the same volume of intrascapular brown adipose tissue. The total proportion of body fat was reduced, but only in animals on a control diet. Lung air volume was observed to be comparable in both KO and WT animals on the same diet. The degree of aortic calcification was reduced in KO animals maintained on a HF diet. KO females on the high fat diet showed reduced cortical bone volume and thickness in the femur and tibia. Gene expression levels of GGCX and VKOR were reduced in control fed KO animals suggesting a potential link between gene expression levels of MGP, GGCX, and VKOR and total volumes of bone, calcified soft tissue, and iBAT; with implications for modulation of body length and mass. Our results confirm the important role for vitamin K in bone and calcified soft tissue, but now extend this role to include iBAT.
Genetic loci simultaneously controlling lignin monomers and biomass digestibility of rice straw
Authors: Hu Zhen , Zhang Guifen , Muhammad Ali , Samad Rana Abdul , Wang Youmei , Walton Jonathan D. , He Yuqing , Peng Liangcai , Wang Lingqiang
Published: February 2018

Lignin content and composition are crucial factors affecting biomass digestibility. Exploring the genetic loci simultaneously affecting lignin-relevant traits and biomass digestibility is a precondition for lignin genetic manipulation towards energy crop breeding. In this study, a high-throughput platform was employed to assay the lignin content, lignin composition and biomass enzymatic digestibility of a rice recombinant inbred line population. Correlation analysis indicated that the absolute content of lignin monomers rather than lignin content had negative effects on biomass saccharification, whereas the relative content ofp-hydroxyphenyl unit and the molar ratio ofp-hydroxyphenyl unit to guaiacyl unit exhibited positive roles. Eight QTL clusters were identified and four of them affecting both lignin composition and biomass digestibility. The additive effects of clustered QTL revealed consistent relationships between lignin-relevant traits and biomass digestibility. Pyramiding rice lines containing the above four positive alleles for increasing biomass digestibility were selected and showed comparable lignin content, decreased syringyl or guaiacyl unit and increased molar percentage ofp-hydroxyphenyl unit, the molar ratio ofp-hydroxyphenyl unit to guaiacyl unit and sugar releases. More importantly, the lodging resistance and eating/cooking quality of pyramiding lines were not sacrificed, indicating the QTL information could be applied to select desirable energy rice lines.
Objective Test of Cochlear Dead Region: Electrophysiologic Approach using Acoustic Change Complex
Authors: Kang Soojin , Woo Jihwan , Park Heesung , Brown Carolyn J. , Hong Sung Hwa , Moon Il Joon
Published: February 2018

The goal of this study was to develop an objective and neurophysiologic method of identifying the presence of cochlear dead region (CDR) by combining acoustic change complex (ACC) responses with threshold-equalizing noise (TEN) test. The goal of the first study was to confirm whether ACC could be evoked with TEN stimuli and to also optimize the test conditions. The goal of the second study was to determine whether the TEN-ACC test is capable of detecting CDR(s). The ACC responses were successfully recorded from all study participants. Both behaviorally and electrophysiologically obtained masked thresholds (TEN threshold and TEN-ACC threshold) were similar and below 10 and 12 dB SNR in NH listeners, respectively. HI listeners were divided into HI (non-CDR) and CDR groups based on the behavioral TEN test. For the non-CDR group, TEN-ACC thresholds were below 12 dB which were similar to NH listeners. However, for the CDR group, TEN-ACC thresholds were significantly higher (≥12 dB SNR) than those in the NH and HI groups, indicating that CDR(s) can be objectively detected using the ACC. Results of this study demonstrate that it is possible to detect the presence of CDR using an electrophysiologic method.
The prevalence of underweight, overweight and obesity in children and adolescents from Ukraine
Authors: Dereń Katarzyna , Nyankovskyy Serhiy , Nyankovska Olena , Łuszczki Edyta , Wyszyńska Justyna , Sobolewski Marek , Mazur Artur
Published: February 2018

The aim of this study was to evaluate the prevalence of overweight, obesity and underweight in children from Ukraine. A cross-sectional study was performed on data collected from a representative sample of Ukraine children (13,739 children (boys 48%, girls 52%) aged 6.0–18.9 years). The measurement of body weight was performed with medical scales and height was measured using a stadiometer. Based on the results obtained, body mass index (BMI) was calculated. Three criteria were used to define childhood underweight, overweight and obesity: The International Obesity Task Force (IOTF) reference, World Health Organization (WHO) child growth standard and The US Center for Disease Control and Prevention (CDC). The combined prevalence of obesity and overweight among children aged 6–18 years old was 12.1%, 17.6%, and 12.6% based on the IOTF reference, WHO growth standard, and the CDC, respectively. Obesity was 2.1%, 4.2%, and 3.6% respectively. Significantly more girls were underweight than boys. Furthermore, a higher prevalence of overweight and obesity was diagnosed in younger that older Ukrainian population.
Charge-spin mutual entanglement: A case study by exact diagonalization of the one hole doped t-J loop
Authors: Zheng Wayne , Weng Zheng-Yu
Published: February 2018

We investigate the ground state and excitations of finite-size Heisenberg loops doped with one hole as the simplest example to illustrate the nature of strong correlations in a doped Mott insulator. We show that the doped hole form a peculiar long-range entanglement with the surrounding spins as revealed by inspecting the mutual correlations between the charge and spin using exact diagonalization (ED). In particular, the one-hole ground state acquires a series of non-trivial total momenta depending on the ratio J/t (J and t denote the superexchange coupling and hopping integral, respectively), which gives rise to distinct quantum phases separated by critical points (CPs). Interestingly the novel total momentum and correlations completely disappear once a singular sign structure is turned off in the t-J model, indicating the latter is the true original source for strong correlation via many-body quantum interference. We emphasize that the novelties discovered here are not restricted to the one-dimensional loop. We introduce a new charge-spin mutual entanglement that can well characterize these exotic properties, which can be then easily generalized to more realistic situations like two dimensions.
High-resolution 3D photopolymerization assisted by upconversion nanoparticles for rapid prototyping applications
Authors: Rocheva Vasilina V. , Koroleva Anastasia V. , Savelyev Alexander G. , Khaydukov Kirill V. , Generalova Alla N. , Nechaev Andrey V. , Guller Anna E. , Semchishen Vladimir A. , Chichkov Boris N. , Khaydukov Evgeny V.
Published: February 2018

Three-dimensional (3D) rapid prototyping technology based on near-infrared light-induced polymerization of photocurable compositions containing upconversion nanomaterials has been explored. For this aim, the rationally-designed core/shell upconversion nanoparticles NaYF4:Yb3+,Tm3+/NaYF4, with the distinct ultraviolet-emitting lines and unprecedentedly high near-infrared to ultraviolet conversion efficiency of $${\eta }_{{\bf{UC}}}^{({\bf{UV}})}=2{\boldsymbol{ \% }}$$

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have been used. The upconverted ultraviolet photons were capable to efficiently activate photoinitiators contained in light-sensitive resins under moderate intensities of NIR excitation below 10 W cm−2 and induce generation of radicals and photopolymerization in situ. Near infrared-activated polymerization process, both at the millimeter and sub-micron scales, was investigated. Polymeric macro- and microstructures were fabricated by means of near infrared laser scanning photolithography in the volume of liquid photocurable compositions with focused laser light at 975 nm wavelength. Examination of the polymerization process in the vicinity of the nanoparticles shows strong differences in the rate of polymer shell growth on flat and edge nanoparticle sides. This phenomenon mainly defines the resolution of the demonstrated near infrared - ultraviolet 3D printing technology at the micrometer scale level.
Fermentation and kinetics characteristics of a bioflocculant from potato starch wastewater and its application
Authors: Guo Junyuan , Liu Jianying , Yang Yijin , Zhou Yuling , Jiang Shilin , Chen Cheng
Published: February 2018

Potato starch wastewater was used as fermentation medium forRhodococcus erythropolisto produce bioflocculant. Kinetics of cell growth and bioflocculant production were firstly constructed. After fermentation for 60 h, 0.97 g of bioflocculant with polysaccharides nature was extracted from 1 L of fermentation liquor. Kinetics characteristics showed that cell growth and bioflocculant production could be simulated well with Logistic and Luedeking-Piret equations, respectively. WhenR. erythropoliswas in logarithm growth phase, COD, ammonium, and TP of the potato starch wastewater medium were rapidly down to 1736, 188, and 146 mg/L, respectively, from 7836, 975, and 712 mg/L, while the medium’s exactly pH value was almost not changed. Furthermore, bioflocculant flocculation can be used as an effective pretreatment way for potato starch wastewater, and it was feasible in actual treatment projects in Ronghua Starch Co., Ltd., Sichuan Province.
Abrogation of TGF-beta signalling in TAGLN expressing cells recapitulates Pentalogy of Cantrell in the mouse
Authors: Aldeiri Bashar , Roostalu Urmas , Albertini Alessandra , Behnsen Julia , Wong Jason , Morabito Antonino , Cossu Giulio
Published: February 2018

Pentalogy of Cantrell (PC) is a rare multi-organ congenital anomaly that impedes ventral body wall closure and results in diaphragmatic hernia, intra- and pericardial defects. The underlying cellular and molecular changes that lead to these severe developmental defects have remained unknown largely due to the lack of representative animal models. Here we provide in depth characterization of a mouse model with conditional ablation of TGFβRII in Transgelin (Tagln) expressing cells. We show that Tagln is transiently expressed in a variety of cells that participate in the embryonic development and patterning of ventral structures. Genetic ablation of TGFβRII in these cells leads to ventral midline closure defect, diaphragmatic hernia, dilated cardiac outflow tract and aberrant cardiac septation, providing a reliable model to study the morphological changes leading to PC. We show that myogenisis in the diaphragm is independent of TGFβ and the diaphragmatic hernia arises from fibroblast-specific migration defect. In the dorsal body wall Tagln expression is initiated after the closure process, revealing a remarkable difference between ventral and dorsal body walls development. Our study demonstrates the use of micro-CT scanning to obtain a 3-dimensional high-resolution overview of embryonic anomalies and provides the first mechanistic insight into the development of PC.
Novel 3D Liquid Cell Culture Method for Anchorage-independent Cell Growth, Cell Imaging and Automated Drug Screening
Authors: Abe-Fukasawa Natsuki , Otsuka Keiichiro , Aihara Ayako , Itasaki Nobue , Nishino Taito
Published: February 2018

Cells grown in three-dimensional (3D) cultures are more likely to have native cell-cell and cell-matrix interactions than in 2D cultures that impose mechanical constraints to cells. However, most 3D cultures utilise gel matrix which, while serving as a scaffold, limits application due to its solid and opaque nature and inconsistency in cell exposure to exogenous signals. In 3D culture without gel matrix, cells tend to adhere to each other and form clumps with necrotic zone at the centre, making them unsuitable for analyses. Here we report that addition of low-molecular-weight agar named LA717 to culture media allows cells to grow as dispersed clonal spheroids in 3D. LA717 maintains cells dispersed and settled to the bottom of the medium while keeping the medium clear with little additional viscosity, making it suitable for microscopic observation. Importantly, cancer spheroids formed in LA717-containing medium show higher sensitivity to anti-cancer drugs such as Trametinib and MK-2206 that are not as effective in 2D. Because of the small and consistent size of spheroids, cell viability and drug toxicity are readily detectable in automated imaging analysis. These results demonstrate that LA717 offers a novel 3D culture system with great in vivo reflection and practicality.
Superamphiphobic coatings based on liquid-core microcapsules with engineered capsule walls and functionality
Authors: Nordenström Malin , Riazanova Anastasia V. , Järn Mikael , Paulraj Thomas , Turner Charlotta , Ström Valter , Olsson Richard T. , Svagan Anna J.
Published: February 2018

Microcapsules with specific functional properties, related to the capsule wall and core, are highly desired in a number of applications. In this study, hybrid cellulose microcapsules (1.2 ± 0.4 µm in diameter) were prepared by nanoengineering the outer walls of precursor capsules. Depending on the preparation route, capsules with different surface roughness (raspberry or broccoli-like), and thereby different wetting properties, could be obtained. The tunable surface roughness was achieved as a result of the chemical and structural properties of the outer wall of a precursor capsule, which combined with a new processing route allowed in-situ formation of silica nanoparticles (30–40 nm or 70 nm in diameter). By coating glass slides with “broccoli-like” microcapsules (30–40 nm silica nanoparticles), static contact angles above 150° and roll-off angles below 6° were obtained for both water and low surface-tension oil (hexadecane), rendering the substrate superamphiphobic. As a comparison, coatings from raspberry-like capsules were only strongly oleophobic and hydrophobic. The liquid-core of the capsules opens great opportunities to incorporate different functionalities and here hydrophobic superparamagnetic nanoparticles (SPIONs) were encapsulated. As a result, magnetic broccoli-like microcapsules formed an excellent superamphiphobic coating-layer on a curved geometry by simply applying an external magnetic field.
An automated method for the analysis of food intake behaviour in Caenorhabditis elegans
Authors: Rodríguez-Palero Mª Jesús , López-Díaz Ana , Marsac Roxane , Gomes José-Eduardo , Olmedo María , Artal-Sanz Marta
Published: February 2018

The study of mechanisms that govern feeding behaviour and its related disorders is a matter of global health interest. The roundworm Caenorhabditis elegans is becoming a model organism of choice to study these conserved pathways. C. elegans feeding depends on the contraction of the pharynx (pumping). Thanks to the worm transparency, pumping can be directly observed under a stereoscope. Therefore, C. elegans feeding has been historically investigated by counting pharyngeal pumping or by other indirect approaches. However, those methods are short-term, time-consuming and unsuitable for independent measurements of sizable numbers of individuals. Although some particular devices and long-term methods have been lately reported, they fail in the automated, scalable and/or continuous aspects. Here we present an automated bioluminescence-based method for the analysis and continuous monitoring of worm feeding in a multi-well format. We validate the method using genetic, environmental and pharmacological modulators of pharyngeal pumping. This flexible methodology allows studying food intake at specific time-points or during longer periods of time, in single worms or in populations at any developmental stage. Additionally, changes in feeding rates in response to differential metabolic status or external environmental cues can be monitored in real time, allowing accurate kinetic measurements.
Real-time energy/mass transfer mapping for online 4D dose reconstruction
Authors: Ziegenhein Peter , Kamerling Cornelis Ph. , Fast Martin F. , Oelfke Uwe
Published: February 2018

In this work we describe an ultra-fast, low-latency implementation of the energy/mass transfer (EMT) mapping method to accumulate dose on deforming geometries such as lung using the central processing unit (CPU). It enables the computation of the actually delivered dose for intensity-modulated radiation therapy on 4D image data in real-time at 25 Hz. In order to accumulate the delivered dose onto a reference phase a pre-calculated deformable vector field is used. The aim of this study is to present an online dose accumulation technique that can be carried out in less than 40 ms to accommodate the machine log update rate of our research linac. Three speed optimisation strategies for the CPU are discussed: single-core optimisation, parallelisation for multiple cores and vectorisation. The single-core implementation accumulates dose in about 1.1 s on a typical high resolution grid for a lung stereotactic body radiation therapy case. Adding parallelisation decreased the runtime to about 50 ms while adding vectorisation satisfied our real-time constraint by further reducing the dose accumulation time to 15 ms without compromising on resolution or accuracy. The presented method allows real-time dose accumulation on deforming patient geometries and has the potential to enable online dose evaluation and re-planning scenarios.
Age variation in the body coloration of the orb-weaver spider Alpaida tuonabo and its implications on foraging
Authors: Gálvez Dumas , Añino Yostin , De la O Jorge M.
Published: February 2018

Spiders show a repertoire of strategies to increase their foraging success. In particular, some orb-weaver spiders use attractive body colorations to lure prey. Interestingly, coloration varies with age in many species, which may result in ontogenetic variation of foraging success. By using field observations, laboratory experiments and spectrophotometric analysis, we investigated whether pale juveniles and bright adults of the orb-weaverAlpaida tuonabouse different foraging strategies due to ontogenetic variation in coloration. Field observations revealed that foraging success of juveniles and adults was influenced by web properties. However, foraging success increased with body size only in adults, supporting the idea that larger individuals produce a stronger visual signal for prey. The attractiveness of the adult coloration for prey was confirmed in the laboratory with frame-web-choice experiments, in which webs bearing a spider intercepted more bees than empty webs. Our spectrophotometric analysis suggests that the yellow coloration may produce the deceiving signal for prey. Moreover, we identified potential alternative foraging strategies: cryptic juveniles at higher heights and ‘attractive’ adults at lower heights. This study reveals how ontogenetic colour variation may favour the use of alternative foraging strategies in orb-weaver spiders and reduces intraspecific competition.
Co-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low-genotoxicity events, even after removal of insult
Authors: Martins Marta , Silva Ana , Costa Maria H. , Miguel Célia , Costa Pedro M.
Published: February 2018

Addressing the risk of mixed carcinogensin vivounder environmentally-realistic scenarios is still a challenge. Searching for adequate biomarkers of exposure requires understanding molecular pathways and their connection with neoplasia-related benchmark pathologies. Subjecting the zebrafish model to realistic concentrations of two genotoxicants and carcinogens, cadmium and benzo[a]pyrene, isolated and combined, yielded low levels of DNA damage. Altogether, the organisms’ mechanisms of DNA repair, oxidative stress and phases I and II were not overwhelmed after two weeks of treatment. Still, transcriptional responses related to detoxification (epoxide hydrolase and UDP-glucuronosyltransferase) were higher in animals subjected to the combination treatment, inclusively following depuration. Nonetheless, inflammation and formation of hyperplasic foci in fish epithelia were more severe in animals exposed to the combined substances, showing slower recovery during depuration. Additionally, the combination treatment yielded unexpected increased expression of aras-family oncogene homologue after depuration, with evidence for increased tp53 counter-response in the same period. The findings indicate that oncogene expression, cell proliferation and inflammation, may not require noticeable DNA damage to occur. Furthermore, albeit absent proof for neoplasic growth, the removal of chemical insult may promote tissue recovery but does not entirely clear molecular and histopathological endpoints that are commonly associated to neoplasia.
The competing effects of microbially derived polymeric and low molecular-weight substances on the dispersibility of CeO2 nanoparticles
Authors: Nakano Yuriko , Ochiai Asumi , Kawamoto Keisuke , Takeda Ayaka , Ichiyoshi Kenta , Ohnuki Toshihiko , Hochella Michael F. , Utsunomiya Satoshi
Published: February 2018

To understand the competing effects of the components in extracellular substances (ES), polymeric substances (PS) and low-molecular-weight small substances (SS) <1 kDa derived from microorganisms, on the colloidal stability of cerium dioxide nanoparticles (CeNPs), we investigated their adsorption to sparingly soluble CeNPs at room temperature at pH 6.0. The ES was extracted from the fungus S. cerevisiae. The polypeptides and phosphates in all components preferentially adsorbed onto the CeNPs. The zeta potentials of ES + CeNPs, PS + CeNPs, and SS + CeNPs overlapped on the plot of PS itself, indicating the surface charge of the polymeric substances controls the zeta potentials. The sizes of the CeNP aggregates, 100–1300 nm, were constrained by the zeta potentials. The steric barrier derived from the polymers, even in SS, enhanced the CeNP dispersibility at pH 1.5–10. Consequently, the PS and SS had similar effects on modifying the CeNP surfaces. The adsorption of ES, which contains PS + SS, can suppress the aggregation of CeNPs over a wider pH range than that for PS only. The present study addresses the non-negligible effects of small-sized molecules derived from microbial activity on the migration of CeNP in aquatic environments, especially where bacterial consortia prevail.
Intragenic DNA methylation in buccal epithelial cells and intellectual functioning in a paediatric cohort of males with fragile X
Authors: Arpone Marta , Baker Emma K. , Bretherton Lesley , Bui Minh , Li Xin , Whitaker Simon , Dissanayake Cheryl , Cohen Jonathan , Hickerton Chriselle , Rogers Carolyn , Field Mike , Elliott Justine , Aliaga Solange M. , Ling Ling , Francis David , Hearps Stephen J. C. , Hunter Matthew F. , Amor David J. , Godler David E.
Published: February 2018

Increased intragenic DNA methylation of the Fragile X Related Epigenetic Element 2 (FREE2) in blood has been correlated with lower intellectual functioning in females with fragile X syndrome (FXS). This study explored these relationships in a paediatric cohort of males with FXS using Buccal Epithelial Cells (BEC). BEC were collected from 25 males with FXS, aged 3 to 17 years and 19 age-matched male controls without FXS. Methylation of 9 CpG sites within the FREE2 region was examined using the EpiTYPER approach. Full Scale IQ (FSIQ) scores of males with FXS were corrected for floor effect using the Whitaker and Gordon (WG) extrapolation method. Compared to controls, children with FXS had significant higher methylation levels for all CpG sites examined (p < 3.3 × 10−7), and within the FXS group, lower FSIQ (WG corrected) was associated with higher levels of DNA methylation, with the strongest relationship found for CpG sites withinFMR1intron 1 (p < 5.6 × 10−5). Applying the WG method to the FXS cohort unmasked significant epi-genotype-phenotype relationships. These results extend previous evidence in blood to BEC and demonstrate FREE2 DNA methylation to be a sensitive epigenetic biomarker significantly associated with the variability in intellectual functioning in FXS.
High-performance Platinum-free oxygen reduction reaction and hydrogen oxidation reaction catalyst in polymer electrolyte membrane fuel cell
Authors: Chandran Priji , Ghosh Arpita , Ramaprabhu Sundara
Published: February 2018

The integration of polymer electrolyte membrane fuel cell (PEMFC) stack into vehicles necessitates the replacement of high-priced platinum (Pt)-based electrocatalyst, which contributes to about 45% of the cost of the stack. The implementation of high-performance and durable Pt metal-free catalyst for both oxygen reduction reaction (ORR) and hydrogen oxidation reaction (HOR) could significantly enable large-scale commercialization of fuel cell–powered vehicles. Towards this goal, a simple, scalable, single-step synthesis method was adopted to develop palladium-cobalt alloy supported on nitrogen-doped reduced graphene oxide (Pd3Co/NG) nanocomposite. Rotating ring-disk electrode (RRDE) studies for the electrochemical activity towards ORR indicates that ORR proceeds via nearly four-electron mechanism. Besides, the mass activity of Pd3Co/NG shows an enhancement of 1.6 times compared to that of Pd/NG. The full fuel cell measurements were carried out using Pd3Co/NG at the anode, cathode in conjunction with Pt/C and simultaneously at both anode and cathode. A maximum power density of 68 mW/cm2is accomplished from the simultaneous use of Pd3Co/NG as both anode and cathode electrocatalyst with individual loading of 0.5 mg/cm2at 60 °C without any backpressure. To the best of our knowledge, the present study is the first of its kind of a fully non-Pt based PEM full cell.
RETRACTED ARTICLE: Antibiotic growth promoters virginiamycin and bacitracin methylene disalicylate alter the chicken intestinal metabolome
Authors: Gadde Ujvala Deepthi , Oh Sungtaek , Lillehoj Hyun S. , Lillehoj Erik. P.
Published: February 2018

Although dietary antibiotic growth promoters have long been used to increase growth performance in commercial food animal production, the biochemical details associated with these effects remain poorly defined. A metabolomics approach was used to characterize and identify the biochemical compounds present in the intestine of broiler chickens fed a standard, unsupplemented diet or a diet supplemented with the antibiotic growth promoters, virginiamycin or bacitracin methylene disalicylate. Compared with unsupplemented controls, the levels of 218 biochemicals were altered (156 increased, 62 decreased) in chickens given the virginiamycin-supplemented diet, while 119 were altered (96 increased, 23 decreased) with the bacitracin-supplemented diet. When compared between antibiotic-supplemented groups, 79 chemicals were altered (43 increased, 36 decreased) in virginiamycin- vs. bacitracin-supplemented chickens. The changes in the levels of intestinal biochemicals provided a distinctive biochemical signature unique to each antibiotic-supplemented group. These biochemical signatures were characterized by increases in the levels of metabolites of amino acids (e.g. 5-hydroxylysine, 2-aminoadipate, 5-hydroxyindoleaceate, 7-hydroxyindole sulfate), fatty acids (e.g. oleate/vaccenate, eicosapentaenoate, 16-hydroxypalmitate, stearate), nucleosides (e.g. inosine, N6-methyladenosine), and vitamins (e.g. nicotinamide). These results provide the framework for future studies to identify natural chemical compounds to improve poultry growth performance without the use of in-feed antibiotics.
Soil organic carbon and total nitrogen pools in permafrost zones of the Qinghai-Tibetan Plateau
Authors: Zhao Lin , Wu Xiaodong , Wang Zhiwei , Sheng Yu , Fang Hongbing , Zhao Yonghua , Hu Guojie , Li Wangping , Pang Qiangqiang , Shi Jianzong , Mo Bentian , Wang Qian , Ruan Xirui , Li Xiaodong , Ding Yongjian
Published: February 2018

There are several publications related to the soil organic carbon (SOC) on the Qinghai-Tibetan Plateau (QTP). However, most of these reports were from different parts of the plateau with various sampling depth. Here, we present the results from a systematic sampling and analysis of 200 soil pits. Most of the pits were deeper than 2 m from an east-west transect across the plateau. The SOC and total nitrogen (TN) pools of the 148 × 104 km2, the area of the permafrost zone, for the upper 2 m soils calculated from the vegetation map were estimated to be 17.07 Pg (interquartile range: 11.34–25.33 Pg) and 1.72 Pg (interquartile range: 1.08–2.06 Pg), respectively. We also predicted the distribution of land cover types in 2050 and 2070 using decision tree rules and climate scenarios, and then predicted SOC and TN pools of this region. The results suggested that the SOC and TN pools will decrease in the future. The results not only contribute to the carbon and nitrogen storage and stocks in the permafrost regions as a whole but most importantly, to our knowledge of the possible changes of C and N storage on the QTP in the future.
Functional Brain States Measure Mentor-Trainee Trust during Robot-Assisted Surgery
Authors: Shafiei Somayeh B. , Hussein Ahmed Aly , Muldoon Sarah Feldt , Guru Khurshid A.
Published: February 2018

Mutual trust is important in surgical teams, especially in robot-assisted surgery (RAS) where interaction with robot-assisted interface increases the complexity of relationships within the surgical team. However, evaluation of trust between surgeons is challenging and generally based on subjective measures. Mentor-Trainee trust was defined as assessment of mentor on trainee’s performance quality and approving trainee’s ability to continue performing the surgery. Here, we proposed a novel method of objectively assessing mentor-trainee trust during RAS based on patterns of brain activity of surgical mentor observing trainees. We monitored the EEG activity of a mentor surgeon while he observed procedures performed by surgical trainees and quantified the mentor’s brain activity using functional and cognitive brain state features. We used methods from machine learning classification to identity key features that distinguish trustworthiness from concerning performances. Results showed that during simple surgical task, functional brain features are sufficient to classify trust. While, during more complex tasks, the addition of cognitive features could provide additional accuracy, but functional brain state features drive classification performance. These results indicate that functional brain network interactions hold information that may help objective trainee specific mentorship and aid in laying the foundation of automation in the human-robot shared control environment during RAS.
The effectiveness, reproducibility, and durability of tailored mobile coaching on diabetes management in policyholders: A randomized, controlled, open-label study
Authors: Lee Da Young , Park Jeongwoon , Choi Dooah , Ahn Hong-Yup , Park Sung-Woo , Park Cheol-Young
Published: February 2018

This randomized, controlled, open-label study conducted in Kangbuk Samsung Hospital evaluated the effectiveness, reproducibility, and durability of tailored mobile coaching (TMC) on diabetes management. The participants included 148 Korean adult policyholders with type 2 diabetes divided into the Intervention-Maintenance (I-M) group (n = 74) and Control-Intervention (C-I) group (n = 74). Intervention was the addition of TMC to typical diabetes care. In the 6-month phase 1, the I-M group received TMC, and the C-I group received their usual diabetes care. During the second 6-month phase 2, the C-I group received TMC, and the I-M group received only regular information messages. After the 6-month phase 1, a significant decrease (0.6%) in HbA1c levels compared with baseline values was observed in only the I-M group (from 8.1 ± 1.4% to 7.5 ± 1.1%, P < 0.001 based on a paired t-test). At the end of phase 2, HbA1c levels in the C-I group decreased by 0.6% compared with the value at 6 months (from 7.9 ± 1.5 to 7.3 ± 1.0, P < 0.001 based on a paired t-test). In the I-M group, no changes were observed. Both groups showed significant improvements in frequency of blood-glucose testing and exercise. In conclusion, addition of TMC to conventional treatment for diabetes improved glycemic control, and this effect was maintained without individualized message feedback.
Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC)
Authors: Pathare Ganesh , Anderegg Manuel , Albano Giuseppe , Lang Florian , Fuster Daniel G.
Published: February 2018

Fibroblast growth factor 23 (FGF23) participates in the orchestration of mineral metabolism by inducing phosphaturia and decreasing the production of 1,25(OH)2D3. It is known that FGF23 release is stimulated by aldosterone and extracellular volume depletion. To characterize this effect further in a model of mild hypovolemia, we studied mice lacking the thiazide sensitive NaCl cotransporter (NCC). Our data indicate that NCC knockout mice (KO) have significantly higher FGF23, PTH and aldosterone concentrations than corresponding wild type (WT) mice. However, 1,25(OH)2D3, fractional phosphate excretion and renal brush border expression of the sodium/phosphate co-transporter 2a were not different between the two genotypes. In addition, renal expression of FGF23 receptor FGFR1 and the co-receptor Klotho were unaltered in NCC KO mice. FGF23 transcript was increased in the bone of NCC KO mice compared to WT mice, but treatment of primary murine osteoblasts with the NCC inhibitor hydrochlorothiazide did not elicit an increase of FGF23 transcription. In contrast, the mineralocorticoid receptor blocker eplerenone reversed excess FGF23 levels in KO mice but not in WT mice, indicating that FGF23 upregulation in NCC KO mice is primarily aldosterone-mediated. Together, our data reveal that lack of renal NCC causes an aldosterone-mediated upregulation of circulating FGF23.
Vasopressin-secreting neurons derived from human embryonic stem cells through specific induction of dorsal hypothalamic progenitors
Authors: Ogawa Koichiro , Suga Hidetaka , Ozone Chikafumi , Sakakibara Mayu , Yamada Tomiko , Kano Mayuko , Mitsumoto Kazuki , Kasai Takatoshi , Kodani Yu , Nagasaki Hiroshi , Yamamoto Naoki , Hagiwara Daisuke , Goto Motomitsu , Banno Ryoichi , Sugimura Yoshihisa , Arima Hiroshi
Published: February 2018

Arginine-vasopressin (AVP) neurons exist in the hypothalamus, a major region of the diencephalon, and play an essential role in water balance. Here, we established the differentiation method for AVP-secreting neurons from human embryonic stem cells (hESCs) by recapitulating in vitro the in vivo embryonic developmental processes of AVP neurons. At first, the differentiation efficiency was improved. That was achieved through the optimization of the culture condition for obtaining dorsal hypothalamic progenitors. Secondly, the induced AVP neurons were identified by immunohistochemistry and these neurons secreted AVP after potassium chloride stimulation. Additionally, other hypothalamic neuropeptides were also detected, such as oxytocin, corticotropin-releasing hormone, thyrotropin-releasing hormone, pro-opiomelanocortin, agouti-related peptide, orexin, and melanin-concentrating hormone. This is the first report describing the generation of secretory AVP neurons derived from hESCs. This method will be applicable to research using disease models and, potentially, for regenerative medicine of the hypothalamus.
Dysregulation of RNF213 promotes cerebral hypoperfusion
Authors: Morimoto Takaaki , Enmi Jun-ichiro , Hattori Yorito , Iguchi Satoshi , Saito Satoshi , Harada Kouji H. , Okuda Hiroko , Mineharu Yohei , Takagi Yasushi , Youssefian Shohab , Iida Hidehiro , Miyamoto Susumu , Ihara Masafumi , Kobayashi Hatasu , Koizumi Akio
Published: February 2018

RNF213is a susceptibility gene for moyamoya disease, yet its exact functions remain unclear. To evaluate the role ofRNF213in adaptation of cerebral blood flow (CBF) under cerebral hypoperfusion, we performed bilateral common carotid artery stenosis surgery using external microcoils onRnf213knockout (KO) and vascular endothelial cell-specificRnf213mutant (human p.R4810K orthologue) transgenic (EC-Tg) mice. Temporal CBF changes were measured by arterial spin-labelling magnetic resonance imaging. In the cortical area, no significant difference in CBF was found before surgery between the genotypes. Three of eight (37.5%) KO mice died after surgery but all wild-type and EC-Tg mice survived hypoperfusion. KO mice had a significantly more severe reduction in CBF on day 7 than wild-type mice (KO, 29.7% of baseline level; wild-type, 49.3%;p = 0.038), while CBF restoration on day 28 was significantly impaired in both KO (50.0%) and EC-Tg (56.1%) mice compared with wild-type mice (69.5%;p = 0.031 and 0.037, respectively). Changes in the subcortical area also showed the same tendency as the cortical area. Additionally, histological analysis demonstrated that angiogenesis was impaired in both EC-Tg and KO mice. These results are indicative of the essential role ofRNF213in the maintenance of CBF.