bluuebunny/crossref_metadata_2025_split 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

AbstractDonor 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

AbstractQuantitative 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

AbstractDrug-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

AbstractWith 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

AbstractMolecularly-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

AbstractDespite 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

AbstractStudies 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

AbstractLignin 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

AbstractThe 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

AbstractThe 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

AbstractWe 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

AbstractThree-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

AbstractPotato 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

AbstractPentalogy 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

AbstractCells 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.