bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole metagenome sequencing reveals links between mosquito microbiota and insecticide resistance in malaria vectors
Authors: Dada Nsa , Sheth Mili , Liebman Kelly , Pinto Jesus , Lenhart Audrey
Published: January 2018

In light of the declining global malaria burden attained largely due to insecticides, a deeper understanding of the factors driving insecticide resistance is needed to mitigate its growing threat to malaria vector control programs. Following evidence of microbiota-mediated insecticide resistance in agricultural pests, we undertook a comparative study of the microbiota in mosquitoes of differing insecticide resistance status. The microbiota of wild-caughtAnopheles albimanus, an important Latin American malaria vector, that were resistant (FEN_Res) or susceptible (FEN_Sus) to the organophosphate (OP) insecticide fenitrothion were characterized and compared using whole metagenome sequencing. Results showed differing composition of the microbiota and its functions between FEN_Res and FEN_Sus, with significant enrichment of OP-degrading bacteria and enzymes in FEN_Res compared to FEN_Sus. Lower bacterial diversity was observed in FEN_Res compared to FEN_Sus, suggesting the enrichment of bacterial taxa with a competitive advantage in response to insecticide selection pressure. We report and characterize for the first time whole metagenomes ofAn. albimanus, revealing associations between the microbiota and phenotypic resistance to the insecticide fenitrothion. This study lays the groundwork for further investigation of the role of the mosquito microbiota in insecticide resistance.
The GS-nitroxide JP4-039 improves intestinal barrier and stem cell recovery in irradiated mice
Authors: Wei Liang , Leibowitz Brian J. , Epperly Michael , Bi Cheng , Li Allen , Steinman Justin , Wipf Peter , Li Song , Zhang Lin , Greenberger Joel , Yu Jian
Published: January 2018

Total body irradiation (TBI) leads to dose- and tissue-specific lethality. In the current study, we demonstrate that a mitochondrion-targeted nitroxide JP4-039 given once 24 hours after 9–10 Gy TBI significantly improves mouse survival, and the recovery of intestinal barrier, differentiation and stem cell functions. The GI-protective effects are associated with rapid and selective induction of tight junction proteins and cytokines including TGF-β, IL-10, IL-17a, IL-22 and Notch signaling long before bone marrow depletion. However, no change was observed in crypt death or the expression of prototypic pro-inflammatory cytokines such as TNF-α, IL-6 or IL-1β. Surprisingly, bone marrow transplantation (BMT) performed 24 hours after TBI improves intestinal barrier and stem cell recovery with induction of IL-10, IL-17a, IL-22, and Notch signaling. Further, BMT-rescued TBI survivors display increased intestinal permeability, impaired ISC function and proliferation, but not obvious intestinal inflammation or increased epithelial death. These findings identify intestinal epithelium as a novel target of radiation mitigation, and potential strategies to enhance ISC recovery and regeneration after accidental or medical exposures.
A practical solution for preserving single cells for RNA sequencing
Authors: Attar Moustafa , Sharma Eshita , Li Shuqiang , Bryer Claire , Cubitt Laura , Broxholme John , Lockstone Helen , Kinchen James , Simmons Alison , Piazza Paolo , Buck David , Livak Kenneth J. , Bowden Rory
Published: January 2018

The design and implementation of single-cell experiments is often limited by their requirement for fresh starting material. We have adapted a method for histological tissue fixation using dithio-bis(succinimidyl propionate) (DSP), or Lomant’s Reagent, to stabilise cell samples for single-cell transcriptomic applications. DSP is a reversible cross-linker of free amine groups that has previously been shown to preserve tissue integrity for histology while maintaining RNA integrity and yield in bulk RNA extractions. Although RNA-seq data from DSP-fixed single cells appears to be prone to characteristic artefacts, such as slightly reduced yield of cDNA and a detectable 3′ bias in comparison with fresh cells, cell preservation using DSP does not appear to substantially reduce RNA complexity at the gene level. In addition, there is evidence that instantaneous fixation of cells can reduce inter-cell technical variability. The ability of DSP-fixed cells to retain commonly used dyes, such as propidium iodide, enables the tracking of experimental sub-populations and the recording of cell viability at the point of fixation. Preserving cells using DSP will remove several barriers in the staging of single-cell experiments, including the transport of samples and the scheduling of shared equipment for downstream single-cell isolation and processing.
Visual impairment and risk of depression: A longitudinal follow-up study using a national sample cohort
Authors: Choi Hyo Geun , Lee Min Joung , Lee Sang-Mok
Published: January 2018

The association of visual impairment and depression has been investigated in several studies based on a cross-sectional design, which cannot delineate temporal relationships. In the present study, we evaluated the influence of visual impairment on depression in all age groups using a longitudinal database of a national sample cohort from 2002 to 2013 provided by the Korean National Health Insurance Service. Of a total of 1,025,340 subjects, 5,846 participants who were registered as visually impaired persons without a previous diagnosis of depression were enrolled at a 1:4 ratio with 23,384 control participants matched for age, sex, income, and region of residence. The crude and adjusted (age, sex, income, region of residence, hypertension, diabetes, and dyslipidemia) hazard ratios (HRs) for the development of depression between the visually impaired and control groups were analyzed using a Cox proportional hazards model. Visual impairment increased the risk of depression after adjusting for age, sex, income, region of residence, hypertension, diabetes, and dyslipidemia (adjusted HR = 1.19, P = 0.002). The risk of depression increased significantly in both the non-blindness visual impairment (adjusted HR = 1.15, P = 0.036) and blindness subgroups (adjusted HR = 1.31, P = 0.016), with a higher HR in the blindness subgroup.
Vasoactive intestinal peptide gene polymorphisms, associated with its serum levels, predict treatment requirements in early rheumatoid arthritis
Authors: Seoane Iria V. , Martínez Carmen , García-Vicuña Rosario , Ortiz Ana M. , Juarranz Yasmina , Talayero Vanessa C. , González-Álvaro Isidoro , Gomariz Rosa P. , Lamana Amalia
Published: January 2018

We previously reported that early arthritis (EA) patients with low vasoactive intestinal peptide (VIP) serum levels demonstrate a worse clinical disease course. In this study, we analysed whether variants in the VIP gene correlated with its serum levels and clinical EA parameters. The VIP gene was sequenced in patients with extremely high/low VIP levels, measured by enzyme immunoassay. Sixteen single nucleotide polymorphisms (SNPs) were differentially distributed between both groups, which were subsequently genotyped in two patients’ sets. We observed that patients with rs688136 CC genotype showed higher VIP levels in both discovery (n = 91; p = 0.033) and validation populations (n = 131; p = 0.007). This effect was attenuated by the presence of minor alleles rs35643203 and rs12201140, which showed a clear trend towards low VIP level association (p = 0.118 and p = 0.049, respectively). Functional studies with miR-205-5p, which has a target site in the 3′ UTR close to rs688136, revealed a miRNA-mediated regulatory mechanism explaining the higher VIP gene expression in homozygous patients. Moreover, patients with an rs688136 CC genotype and no minor alleles of the other polymorphisms required less treatment (p = 0.009). We concluded that the identification of polymorphisms associated with VIP serum levels would complement the clinical assessment of the disease severity in rheumatoid arthritis patients.
Roles of different types of oxalate surface complexes in dissolution process of ferrihydrite aggregates
Authors: Li Fengyi , Koopal Luuk , Tan Wenfeng
Published: January 2018

The dissolution of ferrihydrite induced by low molar mass (LMM) organics is an important process that provides bioavailable iron for organisms. Here, ATR-FTIR analysis was combined with characterization of ferrihydrite nanoparticles and kinetic modeling to investigate the roles of different oxalate surface complex species in the dissolution of ferrihydrite aggregates. ATR-FTIR results revealed that at least four different species were present at or near the ferrihydrite surface in the process of ferrihydrite aggregate dissolution. At a relatively low addition of oxalate (oxalate/Fe < 0.1), oxalate was dominantly present as binuclear bidentate surface complexes and aqueous species. The binuclear bidentate complexes mainly caused electrostatic repulsion between particles, resulting in the disaggregation of large ferrihydrite aggregates into colloidal particles with hydrodynamic diameters of 116–174 nm. Kinetic modeling showed that these colloidal particles were stable at the oxalate/Fe ratio of 0.1. With increasing addition of oxalate (oxalate/Fe ≥ 0.1), mononuclear bidentate oxalate complexes and hydrogen-bonded surface complex replaced the binuclear bidentate complexes and aqueous species. The aggregates or larger colloidal particles were further disaggregated into smaller colloidal particles with hydrodynamic diameters of 35–64 nm. Additionally, the mononuclear bidentate oxalate complexes promoted the dissolution of ferrihydrite colloids into dissolved Fe.
Age-related changes in function and gene expression of the male and female mouse bladder
Authors: Kamei Jun , Ito Hiroki , Aizawa Naoki , Hotta Harumi , Kojima Toshio , Fujita Yasunori , Ito Masafumi , Homma Yukio , Igawa Yasuhiko
Published: January 2018

We investigated age-related changes in in vivo and in vitro functions and gene expression of the bladder of male and female mice. Mature and aged (12 and 27–30 month old) C57BL/6 mice of both sexes were used. Frequency volume, conscious free-moving cystometry and detrusor contractile and relaxant properties in in vitro organ bath were evaluated. mRNA expression level of muscarinic, purinergic, and β-adrenergic receptors and gene expression changes by cDNA microarray analysis of the bladder were determined. Cystometry demonstrated storage and voiding dysfunctions with ageing in both sexes. Detrusor strips from aged mice showed weaker contractile responses particularly in the cholinergic component and weaker relaxant responses to isoproterenol. These age-related impairments were generally severer in males. mRNA expression of bladder tissue was decreased for M3 muscarinic receptors in aged males and β2-adrenoceptors in aged females. cDNA microarray analysis results, albeit substantial sex difference, indicated “cell-to-cell signaling and interaction” as the most common feature of age-related gene expression. In summary, aged mice demonstrated voiding and storage dysfunctions resembling to detrusor hyperactivity with impaired contractility (DHIC), which were more pronounced in males. Genomic changes associated with aging may contribute to the age-related bladder functional deterioration in mice.
Aminergic Signaling Controls Ovarian Dormancy in Drosophila
Authors: Andreatta Gabriele , Kyriacou Charalambos P. , Flatt Thomas , Costa Rodolfo
Published: January 2018

In response to adverse environmental conditions many organisms from nematodes to mammals deploy a dormancy strategy, causing states of developmental or reproductive arrest that enhance somatic maintenance and survival ability at the expense of growth or reproduction. Dormancy regulation has been studied in C. elegans and in several insects, but how neurosensory mechanisms act to relay environmental cues to the endocrine system in order to induce dormancy remains unclear. Here we examine this fundamental question by genetically manipulating aminergic neurotransmitter signaling in Drosophila melanogaster. We find that both serotonin and dopamine enhance adult ovarian dormancy, while the downregulation of their respective signaling pathways in endocrine cells or tissues (insulin producing cells, fat body, corpus allatum) reduces dormancy. In contrast, octopamine signaling antagonizes dormancy. Our findings enhance our understanding of the ability of organisms to cope with unfavorable environments and illuminate some of the relevant signaling pathways.
Gene silencing in Tribolium castaneum as a tool for the targeted identification of candidate RNAi targets in crop pests
Authors: Knorr Eileen , Fishilevich Elane , Tenbusch Linda , Frey Meghan L. F. , Rangasamy Murugesan , Billion Andre , Worden Sarah E. , Gandra Premchand , Arora Kanika , Lo Wendy , Schulenberg Greg , Valverde-Garcia Pablo , Vilcinskas Andreas , Narva Kenneth E.
Published: January 2018

RNAi shows potential as an agricultural technology for insect control, yet, a relatively low number of robust lethal RNAi targets have been demonstrated to control insects of agricultural interest. In the current study, a selection of lethal RNAi target genes from the iBeetle (Tribolium castaneum) screen were used to demonstrate efficacy of orthologous targets in the economically important coleopteran pests Diabrotica virgifera virgifera and Meligethes aeneus. Transcript orthologs of 50 selected genes were analyzed in D. v. virgifera diet-based RNAi bioassays; 21 of these RNAi targets showed mortality and 36 showed growth inhibition. Low dose injection- and diet-based dsRNA assays in T. castaneum and D. v. virgifera, respectively, enabled the identification of the four highly potent RNAi target genes: Rop, dre4, ncm, and RpII140. Maize was genetically engineered to express dsRNA directed against these prioritized candidate target genes. T0 plants expressing Rop, dre4, or RpII140 RNA hairpins showed protection from D. v. virgifera larval feeding damage. dsRNA targeting Rop, dre4, ncm, and RpII140 in M. aeneus also caused high levels of mortality both by injection and feeding. In summary, high throughput systems for model organisms can be successfully used to identify potent RNA targets for difficult-to-work with agricultural insect pests.
The effects of pressure on the energy landscape of proteins
Authors: Librizzi Fabio , Carrotta Rita , Peters Judith , Cupane Antonio
Published: January 2018

Protein dynamics is characterized by fluctuations among different conformational substates, i.e. the different minima of their energy landscape. At temperatures above ~200 K, these fluctuations lead to a steep increase in the thermal dependence of all dynamical properties, phenomenon known as Protein Dynamical Transition. In spite of the intense studies, little is known about the effects of pressure on these processes, investigated mostly near room temperature. We studied by neutron scattering the dynamics of myoglobin in a wide temperature and pressure range. Our results show that high pressure reduces protein motions, but does not affect the onset temperature for the Protein Dynamical Transition, indicating that the energy differences and barriers among conformational substates do not change with pressure. Instead, high pressure values strongly reduce the average structural differences between the accessible conformational substates, thus increasing the roughness of the free energy landscape of the system.
Pattern recognition with machine learning on optical microscopy images of typical metallurgical microstructures
Authors: Bulgarevich Dmitry S. , Tsukamoto Susumu , Kasuya Tadashi , Demura Masahiko , Watanabe Makoto
Published: January 2018

For advanced materials characterization, a novel and extremely effective approach of pattern recognition in optical microscopic images of steels is demonstrated. It is based on fast Random Forest statistical algorithm of machine learning for reliable and automated segmentation of typical steel microstructures. Their percentage and location areas excellently agreed between machine learning and manual examination results. The accurate microstructure pattern recognition/segmentation technique in combination with other suitable mathematical methods of image processing and analysis can help to handle the large volumes of image data in a short time for quality control and for the quest of new steels with desirable properties.
The characterization, renoprotection and antioxidation of enzymatic and acidic exopolysaccharides from Hypsizigus marmoreus
Authors: Liu Min , Lan Yufei , Tian Chengye , Zhu Yongfa , Liu Hui , Wang Wenshuai , Liu Weiru , Zhang Jianjun , Jia Le
Published: January 2018

The present work was designed to investigate the characterization, as well as the antioxidation and renoprotection in streptozocin (STZ)-induced diabetic mice, of exopolysaccharides (EPS) and the enzymatic-EPS (EEPS) and acidic-EPS (AEPS) hydrolysates, which were separated from the fermentation liquor ofHypsizigus marmoreus. Animal results demonstrated that EPS, EEPS and AEPS had potential antioxidant and renoprotective effects, especially EEPS. Additionally, they were the most effective, reflecting increases in superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant capacity (T-AOC), and albumin (ALB) of 168.33%, 124.8%, 268.17% 179.49%, and 68.71%, respectively, and decreases in the contents of malondialdehyde (MDA), lipid peroxide (LPO) and levels of serum urea nitrogen (BUN) and creatinine (CRE) by 70.58%, 58.43%, 23.97% and 29.60%, respectively, at a dose of 800 mg/kg compared to those of model mice. Three polysaccharides ameliorated the histopathological alterations which were observed in the kidney of diabetic mice. Furthermore, the characterization of polysaccharides had been expressed. These findings indicated that the EEPS fromH.marmoreuspossesses more effective renoprotection and antioxidation effects and provided insight into its potential clinical values on preventing diabetes.
ATP12A promotes mucus dysfunction during Type 2 airway inflammation
Authors: Lennox Alison T. , Coburn Stefanie L. , Leech John A. , Heidrich Elisa M. , Kleyman Thomas R. , Wenzel Sally E. , Pilewski Joseph M. , Corcoran Timothy E. , Myerburg Mike M.
Published: January 2018

Allergic airway disease is known to cause significant morbidity due to impaired mucociliary clearance, however the mechanism that leads to the mucus dysfunction is not entirely understood. Interleukin 13 (IL-13), a key mediator of Type 2 (T2) inflammation, profoundly alters the ion transport properties of airway epithelium. However, these electrophysiological changes cannot explain the thick, tenacious airway mucus that characterizes the clinical phenotype. Here we report that IL-13 dramatically increases the airway surface liquid (ASL) viscosity in cultured primary human bronchial epithelial cells and thereby inhibits mucus clearance. These detrimental rheological changes require ATP12A, a non-gastric H+/K+-ATPase that secretes protons into the ASL. ATP12A knockdown or inhibition prevented the IL-13 dependent increase in ASL viscosity but did not alter the ASL pH. We propose that ATP12A promotes airway mucus dysfunction in individuals with T2 inflammatory airway diseases and that ATP12A may be a novel therapeutic target to improve mucus clearance.
Development and performance of prototype serologic and molecular tests for hepatitis delta infection
Authors: Coller Kelly E. , Butler Emily K. , Luk Ka-Cheung , Rodgers Mary A. , Cassidy Michael , Gersch Jeffrey , McNamara Anne L. , Kuhns Mary C. , Dawson George J. , Kaptue Lazare , Bremer Birgit , Wedemeyer Heiner , Cloherty Gavin A.
Published: January 2018

Worldwide, an estimated 5% of hepatitis B virus (HBV) infected people are coinfected with hepatitis delta virus (HDV). HDV infection leads to increased mortality over HBV mono-infection, yet HDV diagnostics are not widely available. Prototype molecular (RNA) and serologic (IgG) assays were developed for high-throughput testing on the Abbott m2000 and ARCHITECT systems, respectively. RNA detection was achieved through amplification of a ribozyme region target, with a limit of detection of 5 IU/ml. The prototype serology assay (IgG) was developed using peptides derived from HDV large antigen (HDAg), and linear epitopes were further identified by peptide scan. Specificity of an HBV negative population was 100% for both assays. A panel of 145 HBsAg positive samples from Cameroon with unknown HDV status was tested using both assays: 16 (11.0%) had detectable HDV RNA, and 23 (15.7%) were sero-positive including the 16 HDV RNA positive samples. Additionally, an archival serial bleed panel from an HDV superinfected chimpanzee was tested with both prototypes; data was consistent with historic testing data using a commercial total anti-Delta test. Overall, the two prototype assays provide sensitive and specific methods for HDV detection using high throughput automated platforms, allowing opportunity for improved diagnosis of HDV infected patients.
Polyoxygenated cyathane diterpenoids from the mushroom Cyathus africanus, and their neurotrophic and anti-neuroinflammatory activities
Authors: Wei Jing , Guo Wan-Hui , Cao Chen-Yu , Kou Rong-Wei , Xu Yuan-Zhen , Górecki Marcin , Di Bari Lorenzo , Pescitelli Gennaro , Gao Jin-Ming
Published: January 2018

In a previous study, we reported ten new polyoxygenated cyathane diterpenoids, neocyathins A–J, and their anti-neuroinflammatory effects from the liquid culture of the medicinal BasidiomyceteCyathus africanus. In the present study, eight new highly polyoxygenated cyathane diterpenoids, named neocyathins K–R (1–8), were isolated from the solid culture ofC. africanuscultivated on cooked rice, together with three known congeners (9–11). The structures and the absolute configurations of the new compounds were elucidated through comprehensive NMR and HRESIMS spectroscopic data, electronic circular dichroism (ECD) data, and chemical conversion. Compounds1and2represent the first reported naturally occurring compounds with 4,9-seco-cyathane carbon skeleton incorporating an unprecedented medium-sized 9/7 fused ring system, while the 3,4-seco-cyathane derivative (3) was isolated fromCyathusspecies for the first time. All compounds were evaluated for their neurotrophic and anti-neuroinflammatory activity. All the isolates at 1–25 μM displayed differential nerve growth factor (NGF)-induced neurite outgrowth-promoting activity in PC-12 cells, while one of the compounds, allocyathin B2(11), inhibited NO production in lipopolysaccharide (LPS)-stimulated microglia BV-2 cells. In addition, molecular docking studies showed that compound11generated interactions with the inducible nitric oxide synthase (iNOS) protein.
Unravelling genetic variation underlying de novo-synthesis of bovine milk fatty acids
Authors: Knutsen Tim Martin , Olsen Hanne Gro , Tafintseva Valeria , Svendsen Morten , Kohler Achim , Kent Matthew Peter , Lien Sigbjørn
Published: January 2018

The relative abundance of specific fatty acids in milk can be important for consumer health and manufacturing properties of dairy products. Understanding of genes controlling milk fat synthesis may contribute to the development of dairy products with high quality and nutritional value. This study aims to identify key genes and genetic variants affecting de novo synthesis of the short- and medium-chained fatty acids C4:0 to C14:0. A genome-wide association study using 609,361 SNP markers and 1,811 animals was performed to detect genomic regions affecting fatty acid levels. These regions were further refined using sequencing data to impute millions of additional genetic variants. Results suggest associations of PAEP with the content of C4:0, AACS with the content of fatty acids C4:0-C6:0, NCOA6 or ACSS2 with the longer chain fatty acids C6:0-C14:0, and FASN mainly associated with content of C14:0. None of the top-ranking markers caused amino acid shifts but were mostly situated in putatively regulating regions and suggested a regulatory role of the QTLs. Sequencing mRNA from bovine milk confirmed the expression of all candidate genes which, combined with knowledge of their roles in fat biosynthesis, supports their potential role in de novo synthesis of bovine milk fatty acids.
Deep vein thrombosis in mice is regulated by platelet HMGB1 through release of neutrophil-extracellular traps and DNA
Authors: Dyer Mitchell R. , Chen Qiwei , Haldeman Shannon , Yazdani Hamza , Hoffman Rosemary , Loughran Patricia , Tsung Allan , Zuckerbraun Brian S. , Simmons Richard L. , Neal Matthew D.
Published: January 2018

Venous thromboembolic (VTE) disease, consisting of deep venous thrombosis (DVT) and pulmonary embolism (PE) is a leading cause of morbidity and mortality. Current prophylactic measures are insufficient to prevent all occurrence in part due to an incomplete understanding of the underlying pathophysiology. Mounting evidence describes interplay between activation of the innate immune system and thrombus development. Recent work has demonstrated that platelet release of HMGB1 leads to increased microvascular complications following injury. Additionally, platelet HMGB1 was found to enhance DVT and increase the formation of neutrophil extracellular traps (NETs), although the role of HMGB1 induced NET release in thrombosis remains unexplored. Utilizing a transgenic mouse lacking HMGB1 specifically from platelets and megakaryocytes we now demonstrate the specific role of platelet-derived HMGB1 in acute and subacute/chronic venous thrombosis. Platelets account for the majority of circulating HMGB1 and HMGB1 deposition within the developing clot. The pro-thrombotic effect of platelet-derived HMGB1 is mediated through enhanced neutrophil recruitment, NET formation and specifically release of extracellular DNA during NET formation. Taken together, these data suggest that platelet HMGB1 mediated NET release is a primary regulator of DVT formation in mice.
Kaempferol mitigates Endoplasmic Reticulum Stress Induced Cell Death by targeting caspase 3/7
Authors: Abdullah Ahmad , Ravanan Palaniyandi
Published: January 2018

The Endoplasmic Reticulum (ER) plays a fundamental role in executing multiple cellular processes required for normal cellular function. Accumulation of misfolded/unfolded proteins in the ER triggers ER stress which contributes to progression of multiple diseases including neurodegenerative disorders. Recent reports have shown that ER stress inhibition could provide positive response against neuronal injury, ischemia and obesity inin vivomodels. Our search towards finding an ER stress inhibitor has led to the functional discovery of kaempferol, a phytoestrogen possessing ER stress inhibitory activity in cultured mammalian cells. We have shown that kaempferol pre-incubation significantly inhibits the expression ofGRP78(a chaperone) andCHOP(ER stress associated pro-apoptotic transcription factor) under stressed condition. Also, our investigation in the inhibitory specificity of kaempferol has revealed that it inhibits cell death induced by diverse stimuli. Further study on exploring the molecular mechanism implied that kaempferol renders protection by targeting caspases. Both thein silicodocking andin vitroassay using recombinant caspase-3 enzyme confirmed the binding of kaempferol to caspases, through an allosteric mode of competitive inhibition. Altogether, we have demonstrated the ability of kaempferol to alleviate ER stress inin vitromodel.
Duplicated RGS (Regulator of G-protein signaling) proteins exhibit conserved biochemical but differential transcriptional regulation of heterotrimeric G-protein signaling in Brassica species
Authors: Kumar Roshan , Bisht Naveen C.
Published: January 2018

G-alpha (Gα) and ‘Regulator of G-protein Signaling (RGS)’ proteins are the two key components primarily involved in regulation of heterotrimeric G-proteins signaling across phyla. Unlike Arabidopsis thaliana, our knowledge about G-protein regulation in polyploid Brassica species is sparse. In this study, we identified one Gα and two RGS genes each from three species of Brassica ‘U’ triangle and assessed the effects of whole genome triplication on the divergence of gene sequence and structure, protein-protein interaction, biochemical activities, and gene expression. Sequence and phylogenetic analysis revealed that the deduced Gα and RGS proteins are evolutionarily conserved across Brassica species. The duplicated RGS proteins of each Brassica species interacted with their cognate Gα but displayed varying levels of interaction strength. The Gα and the duplicated RGS proteins of Brassica species exhibited highly conserved G-protein activities when tested under in-vitro conditions. Expression analysis of the B. rapa RGS genes revealed a high degree of transcriptional differentiation across the tested tissue types and in response to various elicitors, particularly under D-glucose, salt and phytohormone treatments. Taken together, our results suggest that the RGS-mediated regulation of G-protein signaling in Brassica species is predominantly governed by stage and condition-specific expression differentiation of the duplicated RGS genes.
COMSOL-Based Modeling and Simulation of SnO2/rGO Gas Sensor for Detection of NO2
Authors: Yaghouti Niyat Farshad , Shahrokh Abadi M. H.
Published: January 2018

Despite SIESTA and COMSOL being increasingly used for the simulation of the sensing mechanism in the gas sensors, there are no modeling and simulation reports in literature for detection of NO2 based rGO/SnO2 sensors. In the present study, we model, simulate, and characterize an NO2 based rGO/SnO2 gas sensor using COMSOL by solving the Poisson’s equations under associated boundary conditions of mass, heat and electrical transitions. To perform the simulation, we use an exposure model for presenting the required NO2, a heat transfer model to obtain a reaction temperature, and an electrical model to characterize the sensor’s response in the presence of the gas. We characterize the sensor’s response in the presence of different concentrations of NO2 at different working temperatures and compare the results with the experimental data, reported by Zhang et al. The results from the simulated sensor show a good agreement with the real sensor with some inconsistencies due to differences between the practical conditions in the real chamber and applied conditions to the analytical equations. The results also show that the method can be used to define and predict the behavior of the rGO-based gas sensors before undergoing the fabrication process.
5-HT1A receptor-dependent modulation of emotional and neurogenic deficits elicited by prolonged consumption of alcohol
Authors: Belmer Arnauld , Patkar Omkar L. , Lanoue Vanessa , Bartlett Selena E.
Published: January 2018

Repeated episodes of binge-like alcohol consumption produce anxiety, depression and various deleterious effects including alterations in neurogenesis. While the involvement of the serotonin receptor 1 A (5-HT1A) in the regulation of anxiety-like behavior and neurogenesis is well documented, its contribution to alcohol withdrawal-induced anxiety and alcohol-induced deficits in neurogenesis is less documented. Using the Drinking-In-the-Dark (DID) paradigm to model chronic long-term (12 weeks) binge-like voluntary alcohol consumption in mice, we show that the selective partial activation of 5-HT1A receptors by tandospirone (3 mg/kg) prevents alcohol withdrawal-induced anxiety in a battery of behavioral tests (marble burying, elevated-plus-maze, open-field), which is accompanied by a robust decrease in binge-like ethanol intake (1 and 3 mg/kg). Furthermore, using triple immunolabelling of proliferation and neuronal differentiation markers, we show that long-term DID elicits profound deficits in neurogenesis and neuronal fate specification in the dorsal hippocampus that are entirely reversed by a 2-week chronic treatment with the 5-HT1A partial agonist tandospirone (3 mg/kg/day). Together, our results confirm previous observations that 5-HT1A receptors play a pivotal role in alcohol drinking behavior and the associated emotional and neurogenic impairments, and suggest that 5-HT1A partial agonists represent a promising treatment strategy for alcohol abuse.
High Energy electron and proton acceleration by circularly polarized laser pulse from near critical density hydrogen gas target
Authors: Sharma Ashutosh
Published: January 2018

Relativistic electron rings hold the possibility of very high accelerating rates, and hopefully a relatively cheap and compact accelerator/collimator for ultrahigh energy proton source. In this work, we investigate the generation of helical shaped quasi-monoenergetic relativistic electron beam and high-energy proton beam from near critical density plasmas driven by petawatt-circularly polarized-short laser pulses. We numerically observe the efficient proton acceleration from magnetic vortex acceleration mechanism by using the three dimensional particle-in-cell simulations; proton beam with peak energy 350 MeV, charge ~10nC and conversion efficiency more than 6% (which implies 2.4 J proton beam out of the 40 J incident laser energy) is reported. We detailed the microphysics involved in the ion acceleration mechanism, which requires investigating the role of self-generated plasma electric and magnetic fields. The concept of efficient generation of quasi-monoenergetic electron and proton beam from near critical density gas targets may be verified experimentally at advanced high power – high repetition rate laser facilities e.g. ELI-ALPS. Such study should be an important step towards the development of high quality electron and proton beam.
Cholesterol-like effects of a fluorotelomer alcohol incorporated in phospholipid membranes
Authors: Jbeily Mark , Bärenwald Ruth , Kressler Jörg , Saalwächter Kay , Ferreira Tiago Mendes
Published: January 2018

Fluorocarbon amphiphiles are anthropogenic substances widely used in diverse applications such as food packaging, clothing or cookware. Due to their widespread use and non-biodegradability, these chemicals are now ubiquitous in the natural world with high propensity to bioaccumulate in biological membranes, wherein they may affect microscopic properties. Here, we test the hypothesis that a typical fluorocarbon amphiphile can affect lipid membranes similarly to cholesterol by investigating the effect of 1H,1H,2H,2H-perfluoro-1-decanol (8:2 FTOH) on 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) membranes. Using solid-state nuclear magnetic resonance spectroscopy, differential scanning calorimetry and confocal microscopy, we present a consistent set of independent experimental evidences supporting this hypothesis, namely that upon incorporation of 8:2 FTOH, (i) a condensing effect on the acyl chains occurs in the fluid phase, (ii) coexistence of two membrane phases is observed below melting, and (iii) the melting temperature of DPPC varies no more than approximately ±1 °C up to a concentration of 40 mol% of 8:2 FTOH. The condensing effect is quantified by means of advanced dipolar recoupling solid-state NMR experiments and is found to be of approximately half the magnitude of the cholesterol effect at the same concentration.
Improvement in bladder dysfunction after bladder transplantation of amniotic fluid stem cells in diabetic rats
Authors: Liang Ching-Chung , Shaw Sheng-Wen Steven , Huang Yung-Hsin , Lin Yi-Hao , Lee Tsong-Hai
Published: January 2018

To examine the effects of human amniotic fluid stem cells (hAFSCs) transplantation on bladder function and molecular changes in diabetic rats, 60 female Sprague-Dawley rats were used for study. Three groups were assigned including sham control rats, streptozotocin (STZ, 60 mg/kg)-induced diabetic rats and STZ-induced diabetic rats plus bladder hAFSCs transplantation. Compared to controls, diabetic rats had decreased body weight but increased bladder weight. Cystometries showed non-voiding contraction, residual volume, voided volume and intercontraction interval increased significantly in diabetic rats at week 4 and 12 after DM induction, but improved after hAFSCs transplantation. The immunoreactivities and mRNAs of nerve growth factor (NGF) decreased significantly in diabetic bladder at week 4 and 12 after DM induction, but recovered after hAFSCs transplantation. The immunoreactivities and mRNAs of M2 and M3 muscarinic receptor increased significantly in diabetic bladder at week 4 after DM induction but recovered after hAFSCs transplantation. The immunoreactivity of 8-hydroxy-20-deoxyguanosine increased significantly in diabetic bladder at week 4 and 12 after DM induction but reduced after hAFSCs transplantation. The present study showed bladder dysfunction in STZ-induced diabetic rats could be improved by hAFSCs transplantation into bladder, which may be related to the recovery of bladder NGF and muscarinic receptors.
Erythropoietin Signaling Increases Choroidal Macrophages and Cytokine Expression, and Exacerbates Choroidal Neovascularization
Authors: Bretz Colin A. , Divoky Vladimir , Prchal Josef , Kunz Eric , Simmons Aaron B. , Wang Haibo , Hartnett Mary Elizabeth
Published: January 2018

Erythropoietin (EPO) is recognized for neuroprotective and angiogenic effects and has been associated with aging and neovascular age-related macular degeneration (AMD). We hypothesized that systemic EPO facilitates the development of choroidal neovascularization (CNV). Wild type mice expressed murine EPOR (mWtEPOR) in RPE/choroids at baseline and had significantly increased serum EPO after laser treatment. To test the role of EPO signaling, we used human EPOR knock-in mice with the mWtEPOR gene replaced by either the human EPOR gene (hWtEPOR) or a mutated human EPOR gene (hMtEPOR) in a laser-induced choroidal neovascularization (LCNV) model. Loss-of-function hWtEPOR mice have reduced downstream activation, whereas gain-of-function hMtEPOR mice have increased EPOR signaling. Compared to littermate controls (mWtEPOR), hMtEPOR with increased EPOR signaling developed larger CNV lesions. At baseline, hMtEPOR mice had increased numbers of macrophages, greater expression of macrophage markers F4/80 and CD206, and following laser injury, had greater expression of cytokines CCL2, CXCL10, CCL22, IL-6, and IL-10 than mWtEPOR controls. These data support a hypothesis that injury from age- and AMD-related changes in the RPE/choroid leads to choroidal neovascularization through EPOR-mediated cytokine production.
Pharmaceutical compounding of aflibercept in prefilled syringes does not affect structural integrity, stability or VEGF and Fc binding properties
Authors: Sivertsen Magne Sand , Jørstad Øystein Kalsnes , Grevys Algirdas , Foss Stian , Moe Morten Carstens , Andersen Jan Terje
Published: January 2018

Macular edema due to neovascular age-related macular degeneration, diabetes or retinal vein occlusion can cause central vision loss. Intravitreal treatment with antibody-based biopharmaceutical compounds designed to neutralize vascular endothelial growth factor (VEGF) has proven to be an efficient strategy to ameliorate macular edema and restore visual acuity. At the same time, the use of anti-VEGF drugs places an economic burden on the health care system; the drugs are expensive, and repeated injections are usually required to maintain the therapeutic effect. Thus, there is an unmet need for more cost-effective procedures. We here describe how the most recently approved anti-VEGF drug, aflibercept, can be compounded into prefilled sterile syringes and stored for up to 4 weeks without compromising its quality, stability or functional properties, including VEGF and neonatal Fc receptor (FcRn) binding. The novel compounding method for repackaging of aflibercept in sterile plastic syringes can greatly reduce both cost and time spent per patient in the injection room.
Effects of blood glucose level on 18F fluorodeoxyglucose (18F-FDG) uptake for PET/CT in normal organs: an analysis on 5623 patients
Authors: Sprinz Clarice , Zanon Matheus , Altmayer Stephan , Watte Guilherme , Irion Klaus , Marchiori Edson , Hochhegger Bruno
Published: January 2018

Our purpose was to evaluate the effect of glycemia on 18F-FDG uptake in normal organs of interest. The influences of other confounding factors, such as body mass index (BMI), diabetes, age, and sex, on the relationships between glycemia and organ-specific standardized uptake values (SUVs) were also investigated. We retrospectively identified 5623 consecutive patients who had undergone clinical PET/CT for oncological indications. Patients were stratified into groups based on glucose levels, measured immediately before 18F-FDG injection. Differences in mean SUVmax values among glycemic ranges were clinically significant only when >10% variation was observed. The brain was the only organ that presented a significant inverse relationship between SUVmax and glycemia (p < 0.001), even after controlling for diabetic status. No such difference was observed for the liver or lung. After adjustment for sex, age, and BMI, the association of glycemia with SUVmax was significant for the brain and liver, but not for the lung. In conclusion, the brain was the only organ analyzed showing a clinically significant relationship to glycemia after adjustment for potentially confounding variables. The lung was least affected by the variables in our model, and may serve as an alternative background tissue to the liver.
Multi-slice ptychographic tomography
Authors: Li Peng , Maiden Andrew
Published: January 2018

Ptychography is a form of Coherent Diffractive Imaging, where diffraction patterns are processed by iterative algorithms to recover an image of a specimen. Although mostly applied in two dimensions, ptychography can be extended to produce three dimensional images in two ways: via multi-slice ptychography or ptychographic tomography. Ptychographic tomography relies on 2D ptychography to supply projections to conventional tomographic algorithms, whilst multi-slice ptychography uses the redundancy in ptychographic data to split the reconstruction into a series of axial slices. Whilst multi-slice ptychography can handle multiple-scattering thick specimens and has a much smaller data requirement than ptychographic tomography, its depth resolution is relatively poor. Here we propose an imaging modality that combines the benefits of the two approaches, enabling isotropic 3D resolution imaging of thick specimens with a small number of angular measurements. Optical experiments validate our proposed method.
Determination of Ochratoxin A contamination in grapes, processed grape products and animal-derived products using ultra-performance liquid chromatography-tandem mass spectroscopy system
Authors: Wei Dongmei , Wu Xiaohu , Xu Jun , Dong Fengshou , Liu Xingang , Zheng Yongquan , Ji Mingshan
Published: January 2018

We developed a sensitive and rapid analytical method to determine the level of Ochratoxin A contamination in grapes, processed grape products and in foods of animal origin (a total of 11 different food matrices). A pretreatment that followed a “quick, easy, cheap, effective, rugged, and safe” protocol was optimized to extract Ochratoxin A from the matrices, and the extracted Ochratoxin A was then detected with the use of a highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry system. Good linearities of Ochratoxin A were obtained in the range of 0.1–500 µg L−1 (correlation coefficient (R2) > 0.9994 in each case). Mean recovery from the 11 matrices ranged from 70.3 to 114.7%, with a relative standard deviation ≤19.2%. The method is easy to use and yields reliable results for routine determination of Ochratoxin A in food products of grape and animal origin. In store-purchased foods and foods obtained from the field and wholesale suppliers, the Ochratoxin A concentration ranged from undetectable to 10.14 µg kg−1, with the more contaminated samples being mainly those of processed grape products. Our results indicate that the necessity for regulation of and supervision during the processing of grape products.
Dietary glucoraphanin prevents the onset of psychosis in the adult offspring after maternal immune activation
Authors: Matsuura Akiko , Ishima Tamaki , Fujita Yuko , Iwayama Yoshimi , Hasegawa Shunsuke , Kawahara-Miki Ryouka , Maekawa Motoko , Toyoshima Manabu , Ushida Yusuke , Suganuma Hiroyuki , Kida Satoshi , Yoshikawa Takeo , Iyo Masaomi , Hashimoto Kenji
Published: January 2018

Maternal immune activation (MIA) contributes to behavioral abnormalities relevant to schizophrenia in adult offspring, although the molecular mechanisms underlying MIA-induced behavioral changes remain unclear. Here we demonstrated that dietary intake of glucoraphanin (GF), the precursor of a natural antioxidant sulforaphane, during juvenile and adolescent stages prevented cognitive deficits and loss of parvalbumin (PV) immunoreactivity in the medial prefrontal cortex (mPFC) of adult offspring after MIA. Gene set enrichment analysis by RNA sequencing showed that MIA caused abnormal expression of centrosome-related genes in the PFC and hippocampus of adult offspring, and that dietary intake of GF improved these abnormal gene expressions. Particularly, MIA increased the expression of suppressor of fermentation-induced loss of stress resistance protein 1 (Sfi1) mRNA in the PFC and hippocampus of adult offspring, and dietary intake of GF prevented the expression of Sfi1 mRNA in these regions. Interestingly, we found altered expression of SFI1 in the postmortem brains and SFI1 mRNA in hair follicle cells from patients with schizophrenia compared with controls. Overall, these data suggest that centrosome-related genes may play a role in the onset of psychosis in offspring after MIA. Therefore, dietary intake of GF-rich vegetables in high-risk psychosis subjects may prevent the transition to psychosis in young adulthood.
Asymmetric dimethylarginine (ADMA) is identified as a potential biomarker of insulin resistance in skeletal muscle
Authors: Lee Woojung , Lee Hyo Jung , Jang Han Byul , Kim Hyo-Jin , Ban Hyo-Jeong , Kim Kwang Youl , Nam Moon Suk , Choi Joo Sun , Lee Kyung-Tae , Cho Seong Beom , Park Sang Ick , Lee Hye-Ja
Published: January 2018

To unravel metabolic determinats of insulin resistance, we performed a targeted metabolomics analysis in Korean Children-Adolescent Cohort Study (KoCAS, n = 430). Sixty-seven metabolites were associated with insulin resistance in adolescents and the association also found in an adult population (KoGES, n = 2,485). Functional interactions of metabolites with gene/proteins using biological pathway with insulin resistance were not identified biological significance and regulatory effects of asymmetric dimethylarginine (ADMA). However, ADMA showed a higher association with adolescent obesity (P < 0.001) and adult diabetes (P = 0.007) and decreased after obesity intervention program. Functional studies in cellular and mouse models demonstrated that an accumulation of ADMA is associated with the regulation of obesity-induced insulin resistance in skeletal muscle. ADMA treatment inhibited dimethylarginine-dimethylaminohydrolase (DDAH) activity and mRNA expression in insulin resistance muscle cell. Moreover, the treatment led to decrease of phosphorylation of insulin receptor (IR), AKT, and GLUT4 but increase of protein-tyrosine phosphatase 1B (PTP1B). Accordingly, increased ADMA significantly inhibited glucose uptake in myotube cell. We suggest that accumulation of ADMA is associated with modulation of insulin signaling and insulin resistance. ADMA might expand the possibilities of new therapeutic target for functional and clinical implications in the control of energy and metabolic homeostasis in humans.