bluuebunny/crossref_metadata_2025 huggingface dataset:
Revised version of the Cenozoic Collision along the Zagros Orogen, Insights from Cr-spinel and Sandstone Modal Analyses
Authors: Gholami Zadeh Parisa , Adabi Mohammad Hossein , Hisada Ken-ichiro , Hosseini-Barzi Mahboubeh , Sadeghi Abbas , Ghassemi Mohammad Reza
Published: September 2017

Geoscientists have always considered the Neyriz region, located along the Zagros Suture Zone, an important area of interest because of the outcrops of Neotethys ophiolitic rocks. We carried out a modal analysis of the Cenozoic sandstones and geochemistry of the detrital Cr-spinels at Neyriz region in order to determine their provenance and tectonic evolution in the proximal part of Zagros Basin. Our data shows a clear change in provenance from the Late Cretaceous onwards. As from the Late Cretaceous to Eocene, lithic grains are mostly chert and serpentinite; and higher Cr# values of the detrital Cr-spinel compositions indicate that they originate from the fore-arc peridotites and deposited in an accretionary prism setting during this period. From the Late Oligocene to the Miocene periods, volcaniclastic and carbonate lithic grains show an increasing trend, and in the Miocene, metasedimentary lithic grains appear in the sediments. Ophiolite obduction caused a narrow trough sub-basin to be formed parallel to the general trend of the Zagros Orogeny between the Arabian and Iranian plates in Oligocene. From the Miocene onwards, the axial metamorphic complex belt was uplifted in the upper plate. Therefore, the collision along the Zagros Suture Zone must have occurred in the Late Oligocene.
T cells display mitochondria hyperpolarization in human type 1 diabetes
Authors: Chen Jing , Chernatynskaya Anna V. , Li Jian-Wei , Kimbrell Matthew R. , Cassidy Richard J. , Perry Daniel J. , Muir Andrew B. , Atkinson Mark A. , Brusko Todd M. , Mathews Clayton E.
Published: September 2017

T lymphocytes constitute a major effector cell population in autoimmune type 1 diabetes. Despite essential functions of mitochondria in regulating activation, proliferation, and apoptosis of T cells, little is known regarding T cell metabolism in the progression of human type 1 diabetes. In this study, we report, using two independent cohorts, that T cells from patients with type 1 diabetes exhibited mitochondrial inner-membrane hyperpolarization (MHP). Increased MHP was a general phenotype observed in T cell subsets irrespective of prior antigen exposure, and was not correlated with HbA1C levels, subject age, or duration of diabetes. Elevated T cell MHP was not detected in subjects with type 2 diabetes. T cell MHP was associated with increased activation-induced IFNγ production, and activation-induced IFNγ was linked to mitochondria-specific ROS production. T cells from subjects with type 1 diabetes also exhibited lower intracellular ATP levels. In conclusion, intrinsic mitochondrial dysfunction observed in type 1 diabetes alters mitochondrial ATP and IFNγ production; the latter is correlated with ROS generation. These changes impact T cell bioenergetics and function.
Automated video-mosaicking approach for confocal microscopic imaging in vivo: an approach to address challenges in imaging living tissue and extend field of view
Authors: Kose Kivanc , Gou Mengran , Yélamos Oriol , Cordova Miguel , Rossi Anthony M. , Nehal Kishwer S. , Flores Eileen S. , Camps Octavia , Dy Jennifer G. , Brooks Dana H. , Rajadhyaksha Milind
Published: September 2017

We describe a computer vision-based mosaicking method for in vivo videos of reflectance confocal microscopy (RCM). RCM is a microscopic imaging technique, which enables the users to rapidly examine tissue in vivo. Providing resolution at cellular-level morphology, RCM imaging combined with mosaicking has shown to be highly sensitive and specific for non-invasively guiding skin cancer diagnosis. However, current RCM mosaicking techniques with existing microscopes have been limited to two﻿-dimensional sequences of individual still images, acquired in a highly controlled manner, and along a specific predefined raster path, covering a limited area. The recent advent of smaller handheld microscopes is enabling acquisition of videos, acquired in a relatively uncontrolled manner and along an ad-hoc arbitrarily free-form, non-rastered path. Mosaicking of video-images (video-mosaicking) is necessary to display large areas of tissue. Our video-mosaicking methods addresses this need. The method can handle unique challenges encountered during video capture such as motion blur artifacts due to rapid motion of the microscope over the imaged area, warping in frames due to changes in contact angle and varying resolution with depth. We present test examples of video-mosaics of melanoma and non-melanoma skin cancers, to demonstrate potential clinical utility.
CG200745, an HDAC inhibitor, induces anti-tumour effects in cholangiocarcinoma cell lines via miRNAs targeting the Hippo pathway
Authors: Jung Dawoon E. , Park Soo Been , Kim Kahee , Kim Chanyang , Song Si Young
Published: September 2017

Cholangiocarcinoma is a devastating malignancy with fatal complications that exhibits low response and resistance to chemotherapy. Here, we evaluated the anticancer effects of CG200745, a novel histone deacetylase inhibitor, either alone or in combination with standard chemotherapy drugs in cholangiocarcinoma cells. CG200745 dose-dependently reduced the viability of cholangiocarcinoma cells in vitro and decreased tumour volume and weight in a xenograft model. Administering CG200745 along with other chemotherapeutic agents including gemcitabine, 5-fluorouracil (5-FU), cisplatin, oxaliplatin, or gemcitabine plus cisplatin further decreased cholangiocarcinoma cell viability, with a combination index < 1 that indicated synergistic action. CG200745 also enhanced the sensitivity of gemcitabine-resistant cells to gemcitabine and 5-FU, thereby decreasing cell viability and inducing apoptosis. This was accompanied by downregulation of YAP, TEAD4, TGF-β2, SMAD3, NOTCH3, HES5, Axl, and Gas6 and upregulation of the miRNAs miR-22-3p, miR-22-5p, miR-194-5p, miR-194-3p, miR-194-5p, miR-210-3p, and miR-509-3p. The Ingenuity Pathway Analysis revealed that CG200745 mainly targets the Hippo signalling pathway by inducing miR-509-3p expression. Thus, CG200745 inhibits cholangiocarcinoma growth in vitro and in vivo, and acts synergistically when administered in combination with standard chemotherapeutic agents, enabling dose reduction. CG200745 is therefore expected to improve the outcome of cholangiocarcinoma patients who exhibit resistance to conventional therapies.
Computational genome-wide survey of odorant receptors from two solitary bees Dufourea novaeangliae (Hymenoptera: Halictidae) and Habropoda laboriosa (Hymenoptera: Apidae)
Authors: Karpe Snehal D. , Dhingra Surbhi , Brockmann Axel , Sowdhamini R.
Published: September 2017

Olfactory/odorant receptors (ORs) probably govern eusocial behaviour in honey bees through detection of cuticular hydrocarbons (CHCs) and queen mandibular gland pheromones (QMP). CHCs are involved in nest-mate recognition whereas QMP acts as sex pheromone for drones and as retinue pheromone for female workers. Further studies on the effect of eusociality on the evolution of ORs are hindered by the non-availability of comprehensive OR sets of solitary species. We report complete OR repertoires from two solitary beesDufourea novaeangliae(112 ORs) andHabropoda laboriosa(151 ORs). We classify these ORs into 34 phylogenetic clades/subfamilies. Differences in the OR sets of solitary and eusocial bees are observed in individual subfamilies like subfamily 9-exon (putative CHC receptors) and L (contains putative QMP receptor group). A subfamily (H) including putative floral scent receptors is expanded in the generalist honey bees only, but not in the specialists. On the contrary, subfamily J is expanded in all bees irrespective of their degree of social complexity or food preferences. Finally, we show species-lineage specific and OR-subfamily specific differences in the putativecis-regulatory DNA motifs of the ORs from six hymenopteran species. Out of these, [A/G]CGCAAGCG[C/T] is a candidate master transcription factor binding site for multiple olfactory genes.
Associations between trunk muscle morphology, strength and function in older adults
Authors: Shahtahmassebi Behnaz , Hebert Jeffrey J. , Hecimovich Mark D. , Fairchild Timothy J.
Published: September 2017

Skeletal muscle plays an important role in performing activities of daily living. While the importance of limb musculature in performing these tasks is well established, less research has focused on the muscles of the trunk. The purpose of the current study therefore, was to examine the associations between functional ability and trunk musculature in sixty-four community living males and females aged 60 years and older. Univariate and multivariate analyses of the a priori hypotheses were performed and reported with correlation coefficients and unstandardized beta coefficients (β) respectively. The univariate analysis revealed significant correlations between trunk muscle size and functional ability (rectus abdominis: six-minute walk performance, chair stand test, sitting and rising test; lumbar multifidus: timed up and go) as well as trunk muscle strength and functional ability (trunk composite strength: six-minute walk performance, chair stand test, Berg balance performance, sitting and rising test). After controlling for covariates (age and BMI) in the multivariate analysis, higher composite trunk strength (β = 0.34) and rectus abdominis size (β = 0.33) were associated with better performance in the sitting and rising test. The importance of incorporating trunk muscle training into programs aimed at improving balance and mobility in older adults merits further exploration.
Target margin design for real-time lung tumor tracking stereotactic body radiation therapy using CyberKnife Xsight Lung Tracking System
Authors: Yang Zhi-Yong , Chang Yu , Liu Hong-Yuan , Liu Gang , Li Qin
Published: September 2017

The objective of this study is to quantify the clinical accuracy of the Cyberknife Xsight Lung Tracking System (XLTS) in our center and calculate the PTV margin of XLTS treated lung tumors. Data from the treatment log files of 22 lung cancer patients treated with the CyberKnife XLTS were analyzed and the PTV margin was calculated. Segmentation, deformation, correlation, prediction and targeting errors were calculated from the log files of XLTS treatments. Two different methods were used to calculate anisotropic treatment margin. The relationships between tumor motion ranges and the correlation and prediction errors were also analyzed. Based on our estimation of a 4 mm global margin, 95% coverage in the S-I direction and 100% coverage in the L-R and A-P directions were obtained. Strong correlations between tumor motion range and the standard deviation (SD) of correlation and prediction errors were also found. Tumor position motion caused by respiration can be compensated using the Xsight Lung Tracking System. We found total tracking errors to be less than 4 mm in all three directions. This result could provide a reference for the selection of PTV margin for treatment with the CyberKnife XLTS.
Reconciling the opposing effects of warming on phytoplankton biomass in 188 large lakes
Authors: Kraemer Benjamin M. , Mehner Thomas , Adrian Rita
Published: September 2017

Lake ecosystems are deeply integrated into local and regional economies through recreation, tourism, and as sources of food and drinking water. Shifts in lake phytoplankton biomass, which are mediated by climate warming will alter these benefits with potential cascading effects on human well-being. The metabolic theory of ecology suggests that warming reduces lake phytoplankton biomass as basal metabolic costs increase, but this hypothesis has not been tested at the global scale. We use satellite-based estimates of lake surface temperature (LST) and lake surface chlorophyll-a concentration (chl-a; as a proxy for phytoplankton biomass) in 188 of the world’s largest lakes from 2002-2016 to test for interannual associations between chl-a and LST. In contrast to predictions from metabolic ecology, we found that LST and chl-a were positively correlated in 46% of lakes (p < 0.05). The associations between LST and chl-a depended on lake trophic state; warming tended to increase chl-a in phytoplankton-rich lakes and decrease chl-a in phytoplankton-poor lakes. We attribute the opposing responses of chl-a to LST to the effects of temperature on trophic interactions, and the availability of resources to phytoplankton. These patterns provide insights into how climate warming alters lake ecosystems on which millions of people depend for their livelihoods.
Pokémon GO and psychological distress, physical complaints, and work performance among adult workers: a retrospective cohort study
Authors: Watanabe Kazuhiro , Kawakami Norito , Imamura Kotaro , Inoue Akiomi , Shimazu Akihito , Yoshikawa Toru , Hiro Hisanori , Asai Yumi , Odagiri Yuko , Yoshikawa Etsuko , Tsutsumi Akizumi
Published: September 2017

The effects of Pokémon GO, a new mobile game application which utilizes augmented reality, on risky behavior and health have already been discussed in anecdotal evidence. However, there have been no studies about its effects on mental health. This study investigated the relationships between Pokémon GO and psychological distress from an existing workers’ cohort in Japan. Online surveys were conducted to 3,915 full-time workers, at baseline (Nov 26, 2015–Feb 18, 2016) and at follow-up (Dec 1–4, 2016), using a self-report questionnaire. Pokémon GO players were defined as participants who had played Pokémon GO for one month or longer. Psychological distress was measured using validated scales. Of the completers, 246 (9.7%) had continued to play Pokémon GO. They were significantly younger than non-players. From the results of the general linear modeling, improvement in psychological distress was significantly greater among Pokémon GO players than among non-players (p = 0.025). Cohen’s d for the difference in psychological distress was −0.20 (95% CI, −0.33, −0.07). Pokémon GO may be effective for improving psychological distress among workers. Although its effect size is small, the game could have positive effects on the mental health of the adult working population.
Quantitative imaging of anti-phase domains by polarity sensitive orientation mapping using electron backscatter diffraction
Authors: Naresh-Kumar G. , Vilalta-Clemente A. , Jussila H. , Winkelmann A. , Nolze G. , Vespucci S. , Nagarajan S. , Wilkinson A. J. , Trager-Cowan C.
Published: September 2017

Advanced structural characterisation techniques which are rapid to use, non-destructive and structurally definitive on the nanoscale are in demand, especially for a detailed understanding of extended-defects and their influence on the properties of materials. We have applied the electron backscatter diffraction (EBSD) technique in a scanning electron microscope to non-destructively characterise and quantify antiphase domains (APDs) in GaP thin films grown on different (001) Si substrates with different offcuts. We were able to image and quantify APDs by relating the asymmetrical intensity distributions observed in the EBSD patterns acquired experimentally and comparing the same with the dynamical electron diffraction simulations. Additionally mean angular error maps were also plotted using automated cross-correlation based approaches to image APDs. Samples grown on substrates with a 4° offcut from the [110] do not show any APDs, whereas samples grown on the exactly oriented substrates contain APDs. The procedures described in our work can be adopted for characterising a wide range of other material systems possessing non-centrosymmetric point groups.
Effects of influent C/N ratios and treatment technologies on integral biogas upgrading and pollutants removal from synthetic domestic sewage
Authors: Xu Jie , Wang Xue , Sun Shiqing , Zhao Yongjun , Hu Changwei
Published: September 2017

Three different treatment technologies, namely mono-algae culture, algal-bacterial culture, and algal-fungal culture, were applied to remove pollutants form synthetic domestic sewage and to remove CO2from biogas in a photobioreactor. The effects of different initial influent C/N ratios on microalgal growth rates and pollutants removal efficiencies by the three microalgal cultures were investigated. The best biogas upgrading and synthetic domestic sewage pollutants removal effect was achieved in the algal-fungal system at the influent C/N ratio of 5:1. At the influent C/N ratio of 5:1, the algal-fungal system achieved the highest mean chemical oxygen demand (COD) removal efficiency of 81.92% and total phosphorus (TP) removal efficiency of 81.52%, respectively, while the algal-bacterial system demonstrated the highest mean total nitrogen (TN) removal efficiency of 82.28%. The average CH4concentration in upgraded biogas and the removal efficiencies of COD, TN, and TP were 93.25 ± 3.84% (v/v), 80.23 ± 3.92%, 75.85 ± 6.61%, and 78.41 ± 3.98%, respectively. These results will provide a reference for wastewater purification ad biogas upgrading with microalgae based technology.
Integrated Method to Attach DNA Handles and Functionally Select Proteins to Study Folding and Protein-Ligand Interactions with Optical Tweezers
Authors: Hao Yuxin , Canavan Clare , Taylor Susan S. , Maillard Rodrigo A.
Published: September 2017

Optical tweezers has emerged as a powerful tool to study folding, ligand binding, and motor enzymes. The manipulation of proteins with optical tweezers requires attaching molecular handles to the protein of interest. Here, we describe a novel method that integrates the covalent attachment of DNA handles to target proteins with a selection step for functional and properly folded molecules. In addition, this method enables obtaining protein molecules in different liganded states and can be used with handles of different lengths. We apply this method to study the cAMP binding domain A (CBD-A) of Protein kinase A. We find that the functional selection step drastically improves the reproducibility and homogeneity of the single molecule data. In contrast, without a functional selection step, proteins often display misfolded conformations. cAMP binding stabilizes the CBD-A against a denaturing force, and increases the folded state lifetime. Data obtained with handles of 370 and 70 base pairs are indistinguishable, but at low forces short handles provide a higher spatial resolution. Altogether, this method is flexible, selects for properly folded molecules in different liganded states, and can be readily applicable to study protein folding or protein-ligand interactions with force spectroscopy that require molecular handles.
Structural basis for functional selectivity and ligand recognition revealed by crystal structures of human secreted phospholipase A2 group IIE
Authors: Hou Shulin , Xu Tingting , Xu Jinxin , Qu Linbing , Xu Yong , Chen Ling , Liu Jinsong
Published: September 2017

Secreted phospholipases A2s (sPLA2s) are involved in various pathological conditions such as rheumatoid arthritis and cardiovascular disease. Many inhibitors were developed and studied in clinical trials, but none have reached the market yet. This failure may be attributed to the lack of subtype selectivity for these inhibitors. Therefore, more structural information for subtype sPLA2 is needed to guide the selective inhibitor development. In this study, the crystal structure of human sPLA2 Group IIE (hGIIE), coupled with mutagenesis experiments, proved that the flexible second calcium binding site and residue Asn21 in hGIIE are essential to its enzymatic activity. Five inhibitor bound hGIIE complex structures revealed the key residues (Asn21 and Gly6) of hGIIE that are responsible for interacting with inhibitors, and illustrated the difference in the inhibitor binding pocket with other sPLA2s. This will facilitate the structure-based design of sPLA2’s selective inhibitors.
Extraction, separation and characterization of endotoxins in water samples using solid phase extraction and capillary electrophoresis-laser induced fluorescence
Authors: Fung Fun Man , Su Min , Feng Hua-tao , Li Sam Fong Yau
Published: September 2017

This study focuses on one of the key environmental threats, endotoxins, also known as lipopolysaccharides (LPS). A capillary electrophoresis method in combination with laser induced fluorescence (LIF) detection was developed for the analysis of endotoxins from 16 different bacterial strains. LPSs were derivatized with the amino-reactive fluorescent dye, fluorescein isothiocyanate (FITC), separated by capillary zone electrophoresis (CZE) under the optimized conditions with the use of 50 mM sodium tetraborate buffer (pH 9.30), and detected by LIF detector. To improve the sensitivity of CZE-LIF detection for the determination of trace amounts of endotoxins and to remove possible interference materials in environmental samples, a solid phase extraction (SPE) pre-concentration technique was applied successfully. The SPE targeted at polysaccharide moieties of LPSs and showed LPS enrichment effects too. CE migration time could also reveal the O-antigen chain lengths of LPSs. This CE method and SPE pretreatment showed linearity at 99.84%, and repeatabilities at 8.44% and 11.0% for endotoxins from E. Coli O55:B5 and E. Coli O26:B6. The limit of detection (LOD) could reach around 5 ng/mL at optimized condition. The method was applied successfully to the determination of LPS levels in tap water and wastewater, and demonstrated sensitive, reproducible and reliable results.
Software for improved field surveys of nesting marine turtles
Authors: Anastácio R. , Gonzalez J. M. , Slater K. , Pereira M. J.
Published: September 2017

Field data are still recorded on paper in many worldwide beach surveys of nesting marine turtles. The data must be subsequently transferred into an electronic database, and this can introduce errors in the dataset. To minimize such errors, the “Turtles” software was developed and piloted to record field data by one software user accompanying one Tortuguero in Akumal beaches, Quintana Roo, Mexico, from June 1st to July 31st during the night patrols. Comparisons were made between exported data from the software with the paper forms entered into a database (henceforth traditional). Preliminary assessment indicated that the software user tended to record a greater amount of metrics (i.e., an average of 18.3 fields ± 5.4 sd vs. 8.6 fields ± 2.1 sd recorded by the traditional method). The traditional method introduce three types of “errors” into a dataset: missing values in relevant fields (40.1%), different answers for the same value (9.8%), and inconsistent data (0.9%). Only 5.8% of these (missing values) were found with the software methodology. Although only tested by a single user, the software may suggest increased efficacy and warrants further examination to accurately assess the merit of replacing traditional methods of data recording for beach monitoring programmes.
Alpha subunit-dependent glycine receptor clustering and regulation of synaptic receptor numbers
Authors: Patrizio A. , Renner M. , Pizzarelli R. , Triller A. , Specht C. G.
Published: September 2017

Accumulation of glycine receptors at synapses requires the interaction between the beta subunit of the receptor and the scaffold protein gephyrin. Here, we questioned whether different alpha subunits could modulate the receptors’ diffusion and propensity to cluster at spinal cord synapses. Using quantitative photoactivated localisation microscopy we found that alpha-1 and alpha-3 containing glycine receptors display the same α3:β2 stoichiometry and gephyrin binding. Despite these similarities, alpha-3 containing receptors are less mobile and cluster at higher density compared to alpha-1, with 1500 versus 1100 complexes µm−2, respectively. Furthermore, we identified a subunit-specific regulation of glycine receptor copy numbers at synapses: when challenged with interleukin 1β, the synaptic occupancy of alpha-1 but not alpha-3 receptors was reduced. This mechanism may play a role in the cell-type dependent regulation of glycinergic currents in response to interleukin 1β and highlights the capacity of the alpha subunits to affect receptor-gephyrin binding at synapses.
A massive tsunami promoted gene flow and increased genetic diversity in a near threatened plant species
Authors: Ohbayashi Kako , Hodoki Yoshikuni , I. Kondo Natsuko , Kunii Hidenobu , Shimada Masakazu
Published: September 2017

The magnitude and frequency of disturbances affect species diversity and spatial distributions, but the direct effects of large-scale disturbances on genetic diversity are poorly understood. On March 11, 2011, the Great Tohoku Earthquake in Japan caused a massive tsunami that resulted in substantial alteration of community compositions. Populations of a near-threatened tidal marsh Carex rugulosa inhabiting brackish sandbars was also affected. We found four out of six remnant C. rugulosa populations along the Pacific Ocean had become completely extinct. Newly emergent post-tsunami populations, however, had higher allelic numbers than pre-tsunami populations, indicating higher genetic diversity after the tsunami. In addition, genetic differentiation (Fst) between post-tsunami populations was significantly lower than that of pre-tsunami populations. We therefore conclude that the tsunami enhanced gene flow. Seeds of many Carex species persist for long periods in soil, which suggests that seed banks are important genetic resources for post-disturbance recovery of genetic diversity. When its brackish sandbar habitat is no longer subject to disturbance and changes to the land, C. rugulosa is outcompeted by terrestrial plant competitors and eliminated. Disturbance is a driving force for the recovery and maintenance of populations of species such as C. rugulosa—even after near-complete eradication.
Magneto-actuated cell apoptosis by biaxial pulsed magnetic field
Authors: Wong De Wei , Gan Wei Liang , Liu Ning , Lew Wen Siang
Published: September 2017

We report on a highly efficient magneto-actuated cancer cell apoptosis method using a biaxial pulsed magnetic field configuration, which maximizes the induced magnetic torque. The light transmissivity dynamics show that the biaxial magnetic field configuration can actuate the magnetic nanoparticles with higher responsiveness over a wide range of frequencies as compared to uniaxial field configurations. Its efficacy was demonstrated in in vitro cell destruction experiments with a greater reduction in cell viability. Magnetic nanoparticles with high aspect ratios were also found to form a triple vortex magnetization at remanence which increases its low field susceptibility. This translates to a larger magneto-mechanical actuated force at low fields and 12% higher efficacy in cell death as compared to low aspect ratio nanoparticles.
Tissue alkalosis in cold-ischemia time
Authors: Denninghoff V. , Olivieri E. H. R. , Fresno C. , Uceda A. , Mota L. , Suenaga A. P. , Carraro D. M. , Martins V. R. , Avagnina A. , Soares F. A. , Campos A. H. J. Fróes Marques
Published: September 2017

The control of pre-analytical-factors in human biospecimens collected for health research is currently required. Only two previous reports using post-mortem brain samples have tried to address the impact of cold-ischemia on tissue pH. Here we report pH variations according to time (third-order polynomial model) in mice for liver, kidney and lung samples. Tissue alkalosis in cold-ischemia time may be an underlying mechanism of gene expression changes. Therefore, tissue-pH regulation after organ removal may minimize biological stress in human tissue samples.
The effect of a high frequency electromagnetic field in the microwave range on red blood cells
Authors: Nguyen The Hong Phong , Pham Vy T. H. , Baulin Vladimir , Croft Rodney J. , Crawford Russell J. , Ivanova Elena P.
Published: September 2017

The effect of red blood cells (RBC) exposed to an 18 GHz electromagnetic field (EMF) was studied. The results of this study demonstrated for the first time that exposure of RBCs to 18 GHz EMF has the capacity to induce nanospheres uptake in RBCs. The uptake of nanospheres (loading efficiency 96% and 46% for 23.5 and 46.3 nm nanospheres respectively), their presence and locality were confirmed using three independent techniques, namely scanning electron microscopy, confocal laser scanning microscopy and transmission electron microscopy. It appeared that 23.5 nm nanospheres were translocated through the membrane into the cytosol, while the 46.3 nm-nanospheres were mostly translocated through the phospholipid-cholesterol bilayer, with only some of these nanospheres passing the 2D cytoskeleton network. The nanospheres uptake increased by up to 12% with increasing temperature from 33 to 37 °C. The TEM analysis revealed that the nanospheres were engulfed by the cell membrane itself, and then translocated into the cytosol. It is believed that EMF-induced rotating water dipoles caused disturbance of the membrane, initiating its deformation and result in an enhanced degree of membrane trafficking via a quasi-exocytosis process.
Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes
Authors: Nakamura Jun , Shimomoto Takasumi , Collins Leonard B. , Holley Darcy W. , Zhang Zhenfa , Barbee Jenna M. , Sharma Vyom , Tian Xu , Kondo Tomohiro , Uchida Koji , Yi Xianwen , Perkins Diana O. , Willis Monte S. , Gold Avram , Bultman Scott J.
Published: September 2017

Endogenous formaldehyde is abundantly present in our bodies, at around 100 µM under normal conditions. While such high steady state levels of formaldehyde may be derived by enzymatic reactions including oxidative demethylation/deamination and myeloperoxidation, it is unclear whether endogenous formaldehyde can initiate and/or promote diseases in humans. Here, we show that fluorescent malondialdehyde-formaldehyde (M2FA)-lysine adducts are immunogenic without adjuvants in mice. Natural antibody titers against M2FA are elevated in atherosclerosis-prone mice. Staining with an antibody against M2FA demonstrated that M2FA is present in plaque found on the aortic valve of ApoE−/− mice. To mimic inflammation during atherogenesis, human myeloperoxidase was incubated with glycine, H2O2, malondialdehyde, and a lysine analog in PBS at a physiological temperature, which resulted in M2FA generation. These results strongly suggest that the 1,4-dihydropyridine-type of lysine adducts observed in atherosclerosis lesions are likely produced by endogenous formaldehyde and malondialdehyde with lysine. These highly fluorescent M2FA adducts may play important roles in human inflammatory and degenerative diseases.
Transcriptome profiling of genes involved in induced systemic salt tolerance conferred by Bacillus amyloliquefaciens FZB42 in Arabidopsis thaliana
Authors: Liu Shaofang , Hao Haiting , Lu Xiang , Zhao Xia , Wang Yun , Zhang Yubao , Xie Zhongkui , Wang Ruoyu
Published: September 2017

Plant growth-promoting Bacillus amyloliquefaciens FZB42 induces systemic salt tolerance in Arabidopsis and enhances the fresh and dry weight. However, the underlying molecular mechanism that allows plants to respond to FZB42 and exhibit salt tolerance is largely unknown. Therefore, we performed large-scale transcriptome sequencing of Arabidopsis shoot tissues grown under salt stress with or without FZB42 inoculation by using Illumina sequencing to identify the key genes and pathways with important roles during this interaction. In total, 1461 genes were differentially expressed (FZB42-inoculated versus non-inoculated samples) at 0 mM NaCl, of which 953 were upregulated and 508 downregulated, while 1288 genes were differentially expressed at 100 mM NaCl, of which 1024 were upregulated and 264 were downregulated. Transcripts associated with photosynthesis, auxin-related, SOS scavenging, Na+ translocation, and osmoprotectant synthesis, such as trehalose and proline, were differentially expressed by FZB42 inoculation, which reduced the susceptibility to salt and facilitated salt adaptation. Meanwhile, etr1-3, eto1, jar1-1, and abi4-102 hormone-related mutants demonstrated that FZB42 might induce plant salt tolerance via activating plants ET/JA signaling but not ABA-dependent pathway. The results here characterize the plant transcriptome under salt stress with plant growth-promoting bacteria inoculation, thereby providing insights into the molecular mechanisms responsible for induced salt tolerance.
Differential impact of lipopolysaccharide defects caused by loss of RfaH in Yersinia pseudotuberculosis and Yersinia pestis
Authors: Hoffman Jared M. , Sullivan Shea , Wu Erin , Wilson Eric , Erickson David L.
Published: September 2017

RfaH enhances transcription of a select group of operons controlling bacterial surface features such as lipopolysaccharide (LPS). Previous studies have suggested that rfaH may be required for Yersinia pseudotuberculosis resistance to antimicrobial chemokines and survival during mouse infections. In order to further investigate the role of RfaH in LPS synthesis, resistance to host defense peptides, and virulence of Yersinia, we constructed ΔrfaH mutants of Y. pseudotuberculosis IP32953 and Y. pestis KIM6+. Loss of rfaH affected LPS synthesis in both species, resulting in a shorter core oligosaccharide. Susceptibility to polymyxin and the antimicrobial chemokine CCL28 was increased by loss of rfaH in Y. pseudotuberculosis but not in Y. pestis. Transcription of genes in the ddhD-wzz O-antigen gene cluster, but not core oligosaccharide genes, was reduced in ΔrfaH mutants. In addition, mutants with disruptions in specific ddhD-wzz O-antigen cluster genes produced LPS that was indistinguishable from the ΔrfaH mutant. This suggests that both Y. pseudotuberculosis and Y. pestis produce an oligosaccharide core with a single O-antigen unit attached in an RfaH-dependent fashion. Despite enhanced sensitivity to host defense peptides, the Y. pseudotuberculosis ΔrfaH strain was not attenuated in mice, suggesting that rfaH is not required for acute infection.
Deamination-independent restriction of LINE-1 retrotransposition by APOBEC3H
Authors: Feng Yuqing , Goubran Mariam H. , Follack Tyson B. , Chelico Linda
Published: September 2017

The APOBEC3 family of cytosine deaminase enzymes are able to restrict replication of retroelements, such as LINE-1. However, each of the seven APOBEC3 enzymes have been reported to act differentially to prevent LINE-1 retrotransposition and the mechanisms of APOBEC3-mediated LINE-1 inhibition has not been well understood. The prevailing view for many years was that APOBEC3-mediated LINE-1 inhibition was deamination-independent and relied on APOBEC3s blocking the LINE-1 reverse transcriptase DNA polymerization or transport of the LINE-1 RNA into the nucleus. However, recently it was shown that APOBEC3A can deaminate cytosine, to form uracil, on transiently exposed single-stranded LINE-1 cDNA and this leads to LINE-1 cDNA degradation. In this study, we confirmed that APOBEC3A is a potent deamination-dependent inhibitor of LINE-1 retrotransposition, but show that in contrast, A3H haplotype II and haplotype V restrict LINE-1 activity using a deamination-independent mechanism. Our study supports the model that different APOBEC3 proteins have evolved to inhibit LINE-1 retrotransposition through distinct mechanisms.
Hysteretic Dynamics of Multi-Stable Early Afterdepolarisations with Repolarisation Reserve Attenuation: A Potential Dynamical Mechanism for Cardiac Arrhythmias
Authors: Tsumoto Kunichika , Kurata Yasutaka , Furutani Kazuharu , Kurachi Yoshihisa
Published: September 2017

Some cardiovascular and non-cardiovascular drugs frequently cause excessive prolongation of the cardiac action potential (AP) and lead to the development of early afterdepolarisations (EADs), which trigger lethal ventricular arrhythmias. Combining computer simulations in APs with numerical calculations based on dynamical system theory, we investigated stability changes of APs observed in a paced human ventricular myocyte model by decreasing and/or increasing the rapid (IKr) and slow (IKs) components of delayed rectifying K+ current. Upon reducing IKr, the APs without EADs (no-EAD response) showed gradual prolongation of AP duration (APD), and were annihilated without AP configuration changes due to the occurrence of saddle-node bifurcations. This annihilation caused a transition to an AP with EADs as a new stable steady state. Furthermore, reducing repolarisation currents (repolarisation reserve attenuation) evoked multi-stable states consisting of APs with different APDs, and caused multiple hysteretic dynamics. Depending on initial ion circumstances within ventricular myocytes, these multi-stable AP states might increase the local/global heterogeneity of AP repolarisations in the ventricle. Thus, the EAD-induced arrhythmias with repolarisation reserve attenuation might be attributed to the APD variability caused by multi-stability in cardiac AP dynamics.
MITF and BRN2 contribute to metastatic growth after dissemination of melanoma
Authors: Simmons Jacinta L. , Pierce Carly J. , Al-Ejeh Fares , Boyle Glen M.
Published: September 2017

Melanoma tumors are highly heterogeneous, comprising of different cell types that vary in their potential for growth and invasion. Heterogeneous expression of the Microphthalmia-associated Transcription Factor (MITF) and the POU domain transcription factor BRN2 (POU3F2) has been found in malignant melanoma. Changing expression of these transcription factors as the disease progresses has been linked to the metastatic mechanism of phenotype switching. We therefore investigated the effects of MITF and BRN2 expression in melanoma growth and metastasis. Depletion of MITF resulted in a cell population that had a slowed cell cycle progression, was less invasive in vitro and had hindered tumor and metastasis forming ability in mouse xenograft studies. BRN2 depletion left a cell population with intact proliferation and invasion in vitro; however metastatic growth was significantly reduced in the mouse xenograft model. These results suggest that the proliferative population within melanoma tumors express MITF, and both MITF and BRN2 are important for metastatic growth in vivo. This finding highlights the importance of BRN2 and MITF expression in development of melanoma metastasis.
β-catenin, Twist and Snail: Transcriptional regulation of EMT in smokers and COPD, and relation to airflow obstruction
Authors: Mahmood Malik Quasir , Walters Eugene Haydn , Shukla Shakti D. , Weston Steve , Muller Hans Konrad , Ward Chris , Sohal Sukhwinder Singh
Published: September 2017

COPD is characterised by poorly reversible airflow obstruction usually due to cigarette smoking. The transcription factor clusters of β-catenin/Snail1/Twist has been implicated in the process of epithelial mesenchymal transition (EMT), an intermediate between smoking and airway fibrosis, and indeed lung cancer. We have investigated expression of these transcription factors and their “cellular localization” in bronchoscopic airway biopsies from patients with COPD, and in smoking and non-smoking controls. An immune-histochemical study compared cellular protein expression of β-catenin, Snail1 and Twist, in these subject groups in 3 large airways compartment: epithelium (basal region), reticular basement membrane (Rbm) and underlying lamina propria (LP). β-catenin and Snail1 expression was generally high in all subjects throughout the airway wall with marked cytoplasmic to nuclear shift in COPD (P < 0.01). Twist expression was generalised in the epithelium in normal but become more basal and nuclear with smoking (P < 0.05). In addition, β-catenin and Snail1 expression, and to lesser extent of Twist, was related to airflow obstruction and to expression of a canonical EMT biomarker (S100A4). The β-catenin-Snail1-Twist transcription factor cluster is up-regulated and nuclear translocated in smokers and COPD, and their expression is closely related to both EMT activity and airway obstruction.
Quantifying the efficacy of first aid treatments for burn injuries using mathematical modelling and in vivo porcine experiments
Authors: Simpson Matthew J. , McInerney Sean , Carr Elliot J. , Cuttle Leila
Published: September 2017

First aid treatment of burns reduces scarring and improves healing. We quantify the efficacy of first aid treatments using a mathematical model to describe data from a series of in vivo porcine experiments. We study burn injuries that are subject to various first aid treatments. The treatments vary in the temperature and duration. Calibrating the mathematical model to the experimental data provides estimates of the thermal diffusivity, the rate at which thermal energy is lost to the blood, and the heat transfer coefficient controlling the loss of thermal energy at the interface of the fat and muscle. A limitation of working with in vivo experiments is the difficulty of measuring variations in temperature across the tissue layers. This limitation motivates us to use a simple, single layer mathematical model. Using the solution of the calibrated mathematical model we visualise the temperature distribution across the thickness of the tissue. With this information we propose a novel measure of the potential for tissue damage. This measure quantifies two important factors: (i) the volume of tissue that rises above the threshold temperature associated with the accumulation of tissue damage; and (ii) the duration of time that the tissue remains above this threshold temperature.
Magnetic states of nanostructures containing Ni2+ ions at the surface of SiO2 nanospheres
Authors: Barrera Gabriele , Alberto Gabriele , Tiberto Paola , Martra Gianmario , Allia Paolo
Published: September 2017

Ultra-small magnetic particles containing Ni2+ions were grown at the surface of SiO2spheroidal nanoparticles (typical diameter: 50 nm) starting from NiCl2solutions. Depending on preparation details, two samples characterized by magnetic sub-nanostructures or lamellar sub-nanoparticles at the SiO2nanosphere surface were obtained. The decorated SiO2nanospheres were submitted to physico-chemical and magnetic characterization. In both samples, a magnetically blocked phase is observed at low temperature. Below 5 K, discontinuities in isothermal magnetization loops and magnetic relaxation effects suggest the onset of coherent quantum tunneling of nanoparticle magnetization (QTM). Relaxation effects give are described by a field- and temperature-dependent magnetic viscosity SV(H,T); the total spin number of magnetic units is estimated by fitting the isothermal SV(H) curve to a model for an assembly of particles with random anisotropy axes. The mean number of aligned spins involved in the low-temperature relaxation is 32 and 15 in the two considered samples. Phonon-assisted QTM plays an increasingly important role with raising temperature and the quantum regime gradually merges with the classical behavior. Above the blocking temperature the magnetic units behave as classical superparamagnetic particles. When the intra-particle ferromagnetic order disappears the Ni2+ions respond individually to the magnetic field.
Antibody production by in vivo RNA transfection
Authors: Romani Bizhan , Kavyanifard Amirarsalan , Allahbakhshi Elham
Published: September 2017

Monoclonal antibodies have a variety of applications in research and medicine. Here, we report development of a new method for production of monoclonal antibodies. Our method relies on in vivo RNA transfection rather than peptide vaccination. We took advantage of RNA transcripts complexed with DOTMA and DOPE lipids to transfect mice. Intravenous administration of our RNA vaccine to mice resulted in expression of the antigenic peptides by splenic dendritic cells and detection of the antigens in the serum. The RNA vaccine stimulated production of specific antibodies against the RNA-encoded peptides. We produced monoclonal antibodies against viral, bacterial, and human antigens. In addition, we showed that our RNA vaccine stimulated humoral immunity and rescued mice infected with influenza A virus. Our method could be used as an efficient tool to generate monoclonal antibodies and to stimulate humoral immunity for research and medical purposes.
Information seeking about tool properties in great apes
Authors: Bohn Manuel , Allritz Matthias , Call Josep , Völter Christoph J.
Published: September 2017

Evidence suggests that great apes engage in metacognitive information seeking for food items. To support the claim that a domain-general cognitive process underlies ape metacognition one needs to show that selective information seeking extends to non-food items. In this study, chimpanzees (Pan troglodytes) and orangutans (Pongo abelii) either had to determine the location of a desired food item or a property of a non-food item (length of a tool). We manipulated whether subjects received prior information about the item’s location or property. During the test, subjects had the opportunity to seek the respective information. Results show that apes engaged in more information seeking when they had no prior knowledge. Importantly, this selective pattern of information seeking applied to food as well as to tools.
Circulating miR-122 and miR-200a as biomarkers for fatal liver disease in ART-treated, HIV-1-infected individuals
Authors: Murray Daniel D. , Suzuki Kazuo , Law Matthew , Trebicka Jonel , Neuhaus Nordwall Jacquie , Johnson Margaret , Vjecha Michael J. , Kelleher Anthony D. , Emery Sean
Published: September 2017

Liver disease is one of the main contributors to the increased levels of morbidity and mortality seen in the HIV-1-infected, ART-treated population. Circulating miRNAs, particularly those located inside extracellular vesicles, are seen as promising biomarkers for a number of human disease conditions, including liver-related diseases. Here, we show that serum levels of miR-122 and miR-200a are greater in HIV/HCV co-infected individuals compared to HIV-1 mono-infected individuals. We also show that miR-122 and miR-200a are elevated in ART-treated, HIV-1-infected individuals prior to the development of fatal liver disease, suggesting that these miRNA may have some potential clinical utility as biomarkers. While this study is hypothesis generating, it shows clearly that both miR-122 and miR-200a are promising novel biomarkers for liver disease in the ART-treated, HIV-1-infected population.
Release and Degradation of Microencapsulated Spinosad and Emamectin Benzoate
Authors: Huang Bin Bin , Zhang Shao Fei , Chen Peng Hao , Wu Gang
Published: September 2017

The dynamics of release and degradation of the microencapsulation formulation containing spinosad (SP) and emamectin benzoate (EM) were evaluated in the present study. SP and EM were microencapsulated using biodegradable poly-lactic acid (PLA) as the wall material. Their release from and degradation within the prepared SP and EM microspheres (SP-EM-microspheres) were studied. It was found that the encapsulation significantly prolonged the insecticide release. The release could be further extended if the external aqueous phase was pre-saturated with the insecticides and the microspheres were additionally coated with gelatin. On the other hand, increasing the water content of the emulsion or the hydrophilic polycaprolactone (PCL) content in the PLA/PCL mixture accelerated the release. Due to the photolysis and hydrolysis of SP and EM by sunlight, the toxicity of the non-encapsulated insecticides in water declined continuously from 0 through the 9thday (d), and dissipated in 13 d. In contrast, an aqueous suspension containing 5% SP-EM-microspheres maintained a mostly constant toxicity toPlutella xylostellafor 17 d. The biodegradable SP-EM-microspheres showed significantly higher long-term toxicity toP. xylostelladue to lower release, reduced photolysis and hydrolysis of the encapsulated insecticides, which were affected by the varied preparation conditions.