bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization
Authors: Farnaes Lauge , Hildreth Amber , Sweeney Nathaly M. , Clark Michelle M. , Chowdhury Shimul , Nahas Shareef , Cakici Julie A. , Benson Wendy , Kaplan Robert H. , Kronick Richard , Bainbridge Matthew N. , Friedman Jennifer , Gold Jeffrey J. , Ding Yan , Veeraraghavan Narayanan , Dimmock David , Kingsmore Stephen F.
Published: March 2018

Genetic disorders are a leading cause of morbidity and mortality in infants. Rapid whole-genome sequencing (rWGS) can diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants. We report a retrospective cohort study of acutely ill inpatient infants in a regional children’s hospital from July 2016–March 2017. Forty-two families received rWGS for etiologic diagnosis of genetic disorders. Probands also received standard genetic testing as clinically indicated. Primary end-points were rate of diagnosis, clinical utility, and healthcare utilization. The latter was modelled in six infants by comparing actual utilization with matched historical controls and/or counterfactual utilization had rWGS been performed at different time points. The diagnostic sensitivity of rWGS was 43% (eighteen of 42 infants) and 10% (four of 42 infants) for standard genetic tests (P = .0005). The rate of clinical utility of rWGS (31%, thirteen of 42 infants) was significantly greater than for standard genetic tests (2%, one of 42; P = .0015). Eleven (26%) infants with diagnostic rWGS avoided morbidity, one had a 43% reduction in likelihood of mortality, and one started palliative care. In six of the eleven infants, the changes in management reduced inpatient cost by $800,000–$2,000,000. These findings replicate a prior study of the clinical utility of rWGS in acutely ill inpatient infants, and demonstrate improved outcomes and net healthcare savings. rWGS merits consideration as a first tier test in this setting.
Gene transfers can date the tree of life
Authors: Davín Adrián A. , Tannier Eric , Williams Tom A. , Boussau Bastien , Daubin Vincent , Szöllősi Gergely J.
Published: March 2018

Biodiversity has always been predominantly microbial, and the scarcity of fossils from bacteria, archaea and microbial eukaryotes has prevented a comprehensive dating of the tree of life. Here, we show that patterns of lateral gene transfer deduced from an analysis of modern genomes encode a novel and abundant source of information about the temporal coexistence of lineages throughout the history of life. We use state-of-the-art species tree-aware phylogenetic methods to reconstruct the history of thousands of gene families and demonstrate that dates implied by gene transfers are consistent with estimates from relaxed molecular clocks in Bacteria, Archaea and Eukarya. We present the order of speciations according to lateral gene transfer data calibrated to geological time for three datasets comprising 40 genomes for Cyanobacteria, 60 genomes for Archaea and 60 genomes for Fungi. An inspection of discrepancies between transfers and clocks and a comparison with mammalian fossils show that gene transfer in microbes is potentially as informative for dating the tree of life as the geological record in macroorganisms.
N2-rich fluid in the vein-type Yangjingou scheelite deposit, Yanbian, NE China
Authors: Wang Yicun , Wang Keyong , Konare Yassa
Published: March 2018

Nearly pure N2 fluid inclusions (Th (L) = −151~−168 °C; Th (V) = ~150.3 °C) were identified in W-mineralized quartz veins from the Yangjingou scheelite deposit, in the eastern Yanbian area, NE China. Other fluid inclusion populations include N2-CO2, NaCl-H2O ± N2 and CO2 ± N2-NaCl-H2O, but no hydrocarbons were detected. The host rocks are part of the Wudaogou Group metamorphic series, which mainly consist of Ca-rich mica schist. Subhedral sulfide minerals occur in early disseminated W-mineralized quartz veins, or have partially replaced early scheelite. ThN2 and ThN2-H2O indicate N2 fluid-trapping from 315 °C to 410 °C and from 80 MPa to 350 MPa. Oxygen and hydrogen isotopic data (δD = −74.9‰~−77‰, δ18O = 9.6‰~12‰, V-SMOW) suggest that the mineralizing fluids were composed of mixed magmatic and metamorphic water, N2-rich inclusions (δ15N = −0.5‰ to 1.4‰) indicate fluid-rock interaction with metamorphic rocks. The N2-rich fluid was closely associated with scheelite precipitation. During thermal decomposition under high oxygen fugacity conditions, which occurred synchronously with metamorphism and magmatic activity, large amounts of N2 were liberated from NH4+-micas, which then accumulated in the parent fluid of the quartz scheelite veins.
Solvent Composition Drives the Rebinding Kinetics of Nitric Oxide to Microperoxidase
Authors: Mondal Padmabati , Meuwly Markus
Published: March 2018

The rebinding kinetics of NO after photodissociation from microperoxidase (Mp-9) is studied in different solvent environments. In mixed glycerol/water (G/W) mixtures the dissociating ligand rebinds with a yield close to 1 due to the cavities formed by the solvent whereas in pure water the ligand can diffuse into the solvent after photodissociation. In the G/W mixture, only geminate rebinding on the sub-picosecond and 5 ps time scales was found and the rebinding fraction is unity which compares well with available experiments. Contrary to that, simulations in pure water find two time scales – ~10 ps and ~200 ps - indicating that both, geminate rebinding and rebinding after diffusion of NO in the surrounding water contribute. The rebinding fraction is around 0.63 within 1 ns which is in stark contrast with experiment. Including ions (Na and Cl) at 0.15 M concentration in water leads to rebinding kinetics tending to that in the glycerol/water mixture and yields agreement with experiments. The effect of temperature is also probed and found to be non-negligible. The present simulations suggest that NO rebinding in Mp is primarily driven by thermal fluctuations which is consistent with recent resonance Raman spectroscopy experiments and simulations on MbNO.
Altered Insulin/Insulin-Like Growth Factor Signaling in a Comorbid Rat model of Ischemia and β-Amyloid Toxicity
Authors: Amtul Zareen , Hill David J. , Arany Edith J. , Cechetto David F.
Published: March 2018

Ischemic stroke and diabetes are vascular risk factors for the development of impaired memory such as dementia and/or Alzheimer’s disease. Clinical studies have demonstrated that minor striatal ischemic lesions in combination with β-amyloid (Aβ) load are critical in generating cognitive deficits. These cognitive deficits are likely to be associated with impaired insulin signaling. In this study, we examined the histological presence of insulin-like growth factor-I (IGF-1) and insulin receptor substrate (IRS-1) in anatomically distinct brain circuits compared with morphological brain damage in a co-morbid rat model of striatal ischemia (ET1) and Aβ toxicity. The results demonstrated a rapid increase in the presence of IGF-1 and IRS-1 immunoreactive cells in Aβ + ET1 rats, mainly in the ipsilateral striatum and distant regions with synaptic links to the striatal lesion. These regions included subcortical white matter, motor cortex, thalamus, dentate gyrus, septohippocampal nucleus, periventricular region and horizontal diagonal band of Broca in the basal forebrain. The alteration in IGF-1 and IRS-1 presence induced by ET1 or Aβ rats alone was not severe enough to affect the entire brain circuit. Understanding the causal or etiologic interaction between insulin and IGF signaling and co-morbidity after ischemia and Aβ toxicity will help design more effective therapeutics.
Identification of p38 MAPK as a novel therapeutic target for Friedreich’s ataxia
Authors: Cotticelli M. Grazia , Xia Shujuan , Kaur Avinash , Lin Daniel , Wang Yongping , Ruff Eric , Tobias John W. , Wilson Robert B.
Published: March 2018

Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardio-degenerative disorder caused by decreased expression of frataxin, a protein that localizes to mitochondria and is critical for iron-sulfur-cluster (ISC) assembly. There are no proven effective treatments for FRDA. We previously screened a random shRNA library and identified a synthetic shRNA (gFA11) that reverses the growth defect of FRDA cells in culture. We now report that gFA11 decreases cytokine secretion in primary FRDA fibroblasts and reverts other changes associated with cell senescence. The gene-expression profile induced by gFA11 is remarkably similar to the gene-expression profile induced by the p38 MAPK inhibitor SB203580. We found that p38 phosphorylation, indicating activation of the p38 pathway, is higher in FRDA cells than in normal control cells, and that siRNA knockdown of frataxin in normal fibroblasts also increases p38 phosphorylation. Treatment of FRDA cells with p38 inhibitors recapitulates the reversal of the slow-growth phenotype induced by clone gFA11. These data highlight the involvement of the p38 MAPK pathway in the pathogenesis of FRDA and the potential use of p38 inhibitors as a treatment for FRDA.
Author Correction: A Flexible Electret Membrane with Persistent Electrostatic Effect and Resistance to Harsh Environment for Energy Harvesting
Authors: Huiming Xiao , Gangjin Chen , Xumin Chen , Zhi Chen
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Fast first-photon ghost imaging
Authors: Liu Xialin , Shi Jianhong , Wu Xiaoyan , Zeng Guihua
Published: March 2018

Conventional imaging at low light levels requires hundreds of detected photons per pixel to suppress the Poisson noise for accurate reflectivity inference. We propose a high-efficiency photon-limited imaging technique, called fast first-photon ghost imaging, which recovers the image by conditional averaging of the reference patterns selected by the first-photon detection signal. Our technique merges the physics of low-flux measurements with the framework of computational ghost imaging. Experimental results demonstrate that it can reconstruct an image from less than 0.1 detected photon per pixel, which is three orders of magnitude less than conventional imaging techniques. A signal-to-noise ratio model of the system is established for noise analysis. With less data manipulation and shorter time requirements, our technique has potential applications in many fields, ranging from biological microscopy to remote sensing.
Prevalence and serogroup changes of Neisseria meningitidis in South Korea, 2010–2016
Authors: Lee Hyukmin , Seo Younghee , Kim Kyung-Hyo , Lee Kyungwon , Choe Kang-Won
Published: March 2018

Determination of the major serogroups is an important step for establishing a vaccine programme and management strategy targetingNeisseria meningitidis. From April 2010 to November 2016, a total of 25 N. meningitidisisolates were collected in South Korea, in collaboration with the Korean Society of Clinical Microbiology. Among isolates, 19 isolates were recovered from blood and/or cerebrospinal fluid (CSF) in 46 patients who suffered from invasive meningococcal disease (IMD), and six isolates were found in sputum or the throat. The most common serogroup was serogroup B (overall, 36%, n = 9/25; IMD, 37%, n = 7/19), which was isolated in every year of the research period except for 2011. There were five serogroup W isolates recovered from patients in military service. W was no longer isolated after initiation of a vaccine programme for military trainees, but serogroup B caused meningitis in an army recruit training centre in 2015. In MLST analysis, 14 sequence types were found, and all isolates belonging to W showed the same molecular epidemiologic characteristics (W:P1.5-1, 2-2:F3-9:ST-8912). All isolates showed susceptibility to ceftriaxone, meropenem, ciprofloxacin, minocycline, and rifampin; however, the susceptibility rates to penicillin and ampicillin for isolates with W and C capsules were 22% and 30%, respectively.
Author Correction: Correlations between gut microbiota community structures of Tibetans and geography
Authors: Lan Daoliang , Ji Wenhui , Lin Baoshan , Chen Yabing , Huang Cai , Xiong Xianrong , Fu Mei , Mipam Tserang Donko , Ai Yi , Zeng Bo , Li Ying , Cai Zhixin , Zhu Jiangjiang , Zhang Dawei , Li Jian
Published: March 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Non-linear phonon Peltier effect in dissipative quantum dot systems
Authors: De Bitan , Muralidharan Bhaskaran
Published: March 2018

Solid state thermoelectric cooling is based on the electronic Peltier effect, which cools via an electronic heat current in the absence of an applied temperature gradient. In this work, we demonstrate that equivalently, a phonon Peltier effect may arise in the non-linear thermoelectric transport regime of a dissipative quantum dot thermoelectric setup described via Anderson-Holstein model. This effect leads to an electron induced phonon heat current in the absence of a thermal gradient. Utilizing the modification of quasi-equilibrium phonon distribution via charge induced phonon accumulation, we show that in a special case the polarity of the phonon heat current can be reversed so that setup can dump heat into the hotter reservoirs. In further exploring possibilities that can arise from this effect, we propose a novel charge-induced phonon switching mechanism that may be incited via electrostatic gating.
The molecular mechanism for activating IgA production by Pediococcus acidilactici K15 and the clinical impact in a randomized trial
Authors: Kawashima Tadaomi , Ikari Naho , Kouchi Tomoko , Kowatari Yasuyuki , Kubota Yoshiro , Shimojo Naoki , Tsuji Noriko M.
Published: March 2018

IgA secretion at mucosal sites is important for host defence against pathogens as well as maintaining the symbiosis with microorganisms present in the small intestine that affect IgA production. In the present study, we tested the ability of 5 strains of lactic acid bacteria stimulating IgA production, being Pediococcus acidilactici K15 selected as the most effective on inducing this protective immunoglobulin. We found that this response was mainly induced via IL-10, as efficiently as IL-6, secreted by K15-stimulated dendritic cells. Furthermore, bacterial RNA was largely responsible for the induction of these cytokines; double-stranded RNA was a major causative molecule for IL-6 production whereas single-stranded RNA was critical factor for IL-10 production. In a randomized, double-blind, placebo-controlled clinical trial, ingestion of K15 significantly increased the secretory IgA (sIgA) concentration in saliva compared with the basal level observed before this intervention. These results indicate that functional lactic acid bacteria induce IL-6 and IL-10 production by dendritic cells, which contribute to upregulating the sIgA concentration at mucosal sites in humans.
Optical Detection of Degraded Therapeutic Proteins
Authors: Herrington William F. , Singh Gajendra P. , Wu Di , Barone Paul W. , Hancock William , Ram Rajeev J.
Published: March 2018

The quality of therapeutic proteins such as hormones, subunit and conjugate vaccines, and antibodies is critical to the safety and efficacy of modern medicine. Identifying malformed proteins at the point-of-care can prevent adverse immune reactions in patients; this is of special concern when there is an insecure supply chain resulting in the delivery of degraded, or even counterfeit, drug product. Identification of degraded protein, for example human growth hormone, is demonstrated by applying automated anomaly detection algorithms. Detection of the degraded protein differs from previous applications of machine-learning and classification to spectral analysis: only example spectra of genuine, high-quality drug products are used to construct the classifier. The algorithm is tested on Raman spectra acquired on protein dilutions typical of formulated drug product and at sample volumes of 25 µL, below the typical overfill (waste) volumes present in vials of injectable drug product. The algorithm is demonstrated to correctly classify anomalous recombinant human growth hormone (rhGH) with 92% sensitivity and 98% specificity even when the algorithm has only previously encountered high-quality drug product.
Mechanically Reconfigurable Single-Arm Spiral Antenna Array for Generation of Broadband Circularly Polarized Orbital Angular Momentum Vortex Waves
Authors: Li Long , Zhou Xiaoxiao
Published: March 2018

In this paper, a mechanically reconfigurable circular array with single-arm spiral antennas (SASAs) is designed, fabricated, and experimentally demonstrated to generate broadband circularly polarized orbital angular momentum (OAM) vortex waves in radio frequency domain. With the symmetrical and broadband properties of single-arm spiral antennas, the vortex waves with different OAM modes can be mechanically reconfigurable generated in a wide band from 3.4 GHz to 4.7 GHz. The prototype of the circular array is proposed, conducted, and fabricated to validate the theoretical analysis. The simulated and experimental results verify that different OAM modes can be effectively generated by rotating the spiral arms of single-arm spiral antennas with corresponding degrees, which greatly simplify the feeding network. The proposed method paves a reconfigurable way to generate multiple OAM vortex waves with spin angular momentum (SAM) in radio and microwave satellite communication applications.
Canagliflozin inhibits interleukin-1β-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms
Authors: Mancini Sarah J. , Boyd Daria , Katwan Omar J. , Strembitska Anastasiya , Almabrouk Tarek A. , Kennedy Simon , Palmer Timothy M. , Salt Ian P.
Published: March 2018

Recent clinical trials of the hypoglycaemic sodium-glucose co-transporter-2 (SGLT2) inhibitors, which inhibit renal glucose reabsorption, have reported beneficial cardiovascular outcomes. Whether SGLT2 inhibitors directly affect cardiovascular tissues, however, remains unclear. We have previously reported that the SGLT2 inhibitor canagliflozin activates AMP-activated protein kinase (AMPK) in immortalised cell lines and murine hepatocytes. As AMPK has anti-inflammatory actions in vascular cells, we examined whether SGLT2 inhibitors attenuated inflammatory signalling in cultured human endothelial cells. Incubation with clinically-relevant concentrations of canagliflozin, but not empagliflozin or dapagliflozin activated AMPK and inhibited IL-1β-stimulated adhesion of pro-monocytic U937 cells and secretion of IL-6 and monocyte chemoattractant protein-1 (MCP-1). Inhibition of MCP-1 secretion was attenuated by expression of dominant-negative AMPK and was mimicked by the direct AMPK activator, A769662. Stimulation of cells with either canagliflozin or A769662 had no effect on IL-1β-stimulated cell surface levels of adhesion molecules or nuclear factor-κB signalling. Despite these identical effects of canagliflozin and A769662, IL-1β-stimulated IL-6/MCP-1 mRNA was inhibited by canagliflozin, but not A769662, whereas IL-1β-stimulated c-jun N-terminal kinase phosphorylation was inhibited by A769662, but not canagliflozin. These data indicate that clinically-relevant canagliflozin concentrations directly inhibit endothelial pro-inflammatory chemokine/cytokine secretion by AMPK-dependent and -independent mechanisms without affecting early IL-1β signalling.
Diverse Assemblage of Ediacaran fossils from Central Iran
Authors: Vaziri Seyed Hamid , Majidifard Mahmoud Reza , Laflamme Marc
Published: March 2018

Reinvestigation of the Kushk and Chahmir areas (Bafq and Behabad regions) of central Iran has yielded a diverse assemblage of Ediacaran fossils, including several new species, just prior to the Cambrian explosion of complex animals. The Kushk series consists mainly of shallow marine carbonate deposits followed by deep-water calcareous marine shales. Ediacaran fossils occur commonly in the shale deposits and include biostratigraphically-important taxa Cloudina and Corumbella, which confirms a latest Ediacaran age for these deposits, the youngest examples of Kimberellomorphs (stem-group molluscs) that helps bridge the gap between their first occurrence in the middle-Ediacaran and the crown diversification in the Cambrian, and likely sponges, which are rare prior to the Cambrian.
The membrane-distal regions of integrin α cytoplasmic domains contribute differently to integrin inside-out activation
Authors: Thinn Aye Myat Myat , Wang Zhengli , Zhu Jieqing
Published: March 2018

Functioning as signal receivers and transmitters, the integrin α/β cytoplasmic tails (CT) are pivotal in integrin activation and signaling. 18 α integrin subunits share a conserved membrane-proximal region but have a highly diverse membrane-distal (MD) region at their CTs. Recent studies demonstrated that the presence of α CTMD region is essential for talin-induced integrin inside-out activation. However, it remains unknown whether the non-conserved α CTMD regions differently regulate the inside-out activation of integrin. Using αIIbβ3, αLβ2, and α5β1as model integrins and by replacing their α CTMD regions with those of α subunits that pair with β3, β2, and β1subunits, we analyzed the function of CTMD regions of 17 α subunits in talin-mediated integrin activation. We found that the α CTMD regions play two roles on integrin, which are activation-supportive and activation-regulatory. The regulatory but not the supportive function depends on the sequence identity of α CTMD region. A membrane-proximal tyrosine residue present in the CTMD regions of a subset of α integrins was identified to negatively regulate integrin inside-out activation. Our study provides a useful resource for investigating the function of α integrin CTMD regions.
Author Correction: Association of wall shear stress with intracranial aneurysm rupture: systematic review and meta-analysis
Authors: Zhou Geng , Zhu Yueqi , Yin Yanling , Su Ming , Li Minghua
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: Fast modal decomposition for optical fibers using digital holography
Authors: Lyu Meng , Lin Zhiquan , Li Guowei , Situ Guohai
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Information about peer choices shapes human risky decision-making
Authors: Tomova Livia , Pessoa Luiz
Published: March 2018

Humans frequently make choices that involve risk for health and well-being. At the same time, information about others’ choices is omnipresent due to new forms of social media and information technology. However, while past research has shown that peers can exert a strong influence on such risky choices, understanding howinformation about risky decisions of othersaffects one’s own risky decisions is still lacking. We therefore developed a behavioral task to measure how information about peer choices affects risky decision-making and call it the social Balloon Analogue Risk Task (sBART). We tested this novel paradigm in a sample of 52 college young adults. Here we show that risky decisions were influenced in the direction of the perceived choices of others – riskier choices of others led to riskier behavior whereas safer choices of others led to less risky behavior. These findings indicate thatinformationabout peer choices is sufficient to shape one’s own risky behavior.
Matrix Metalloproteinase Mediated Type I Collagen Degradation is an Independent Predictor of Increased Risk of Acute Myocardial Infarction in Postmenopausal Women
Authors: Bertelsen Ditte Marie , Neergaard Jesper Skov , Bager Cecilie Liv , Nielsen Signe Holm , Secher Niels Henry , Svendsen Jesper Hastrup , Bihlet Asger Reinstrup , Andersen Jeppe Ragnar , Karsdal Morten Asser , Christiansen Claus , Nielsen Henning Bay
Published: March 2018

Acute myocardial infarction (AMI) is often underdiagnosed in women. It is therefore of interest to identify biomarkers that indicate increased risk of AMI and thereby help clinicians to have additional focus on the difficult AMI diagnosis. Type I Collagen, a component of the cardiac extracellular matrix, is cleaved by matrix metalloproteinases (MMPs) generating the neo-epitope C1M. We investigated the association between serum-C1M and AMI and evaluated whether C1M is a prognostic marker for outcome following AMI. This study is based on The Prospective Epidemiological Risk Factor (PERF) Study including postmenopausal women. 316 out of 5,450 women developed AMI within the follow-up period (14 years, median). A multivariate Cox analysis assessed association between serum-C1M and AMI, and re-infaction or death subsequent to AMI. The risk of AMI increased by 18% (p = 0.03) when serum-C1M was doubled and women in the highest quartile had a 33% increased risk compared to those in the low quartiles (p = 0.025). Serum-C1M was, however not related to reinfarction or death subsequent to AMI. In this study C1M was be an independent risk factor for AMI. Measuring MMP degraded type I collagen could be useful for prediction of increased risk of AMI if replicated in other cohorts.
Influence of optic disc-fovea distance on macular thickness measurements with OCT in healthy myopic eyes
Authors: Qiu Kunliang , Wang Geng , Zhang Riping , Lu Xuehui , Zhang Mingzhi , Jansonius Nomdo M.
Published: March 2018

Assessment of macular thickness is important in the evaluation of various eye diseases. This study aimed to determine the influence of the optic disc-fovea distance (DFD) on macular thickness in myopic eyes. We determined the DFD and the macular thickness in 138 eyes from 138 healthy myopic subjects using the Cirrus HD-OCT. Correlation analysis and multiple linear regression were performed to determine the influence of DFD, axial length, disc area, and β-PPA on macular thickness. To further remove the confounding effect of ocular magnification on the DFD and OCT scan area, a subgroup analysis was performed in eyes with a limited axial length range (24–25 mm). DFD was significantly correlated with both regional (central, inner, and outer ETDRS subfields) and overall average macular thickness at a Bonferroni corrected P value of 0.004 (r ranging from −0.27 to −0.47), except for the temporal outer (r = −0.15, P = 0.089) and inferior outer (r = −0.22, P = 0.011) macular thickness. In the multivariable analysis, DFD was significantly associated with the average inner and outer macular thickness, the central subfield thickness, and the overall macular thickness (all P < 0.001), independent of ocular magnification and other covariates. Our findings indicate that eyes with a greater DFD have a lower macular thickness.
First detection of human hepegivirus-1 (HHpgV-1) in Iranian patients with hemophilia
Authors: Bijvand Yazdan , Aghasadeghi Mohammad Reza , Sakhaee Fatemeh , Pakzad Parviz , Vaziri Farzam , Saraji Alireza Azizi , Jamnani Fatemeh Rahimi , Siadat Seyed Davar , Fateh Abolfazl
Published: March 2018

A novel blood-borne virus called the human hepegivirus 1 (HHpgV-1) was recently discovered in hemophilia patients. The present study aimed to investigate the presence of HHpgV-1 in hemophilia patients. A total of 436 serum samples were investigated for the presence of hepatitis C virus (HCV), human pegivirus-1 (HPgV-1), torque teno virus (TTV), and HHpgV-1. Out of the 436 patients, 163 (37.4%), 19 (4.4%), 76 (17.4%), and four (0.9%) patients were positive for HCV, HPgV-1, TTV, and HHpgV-1, respectively. HHpgV-1 patients had a mean viral load of 4.9 ± 0.3 log RNA copies/mL and were co-infected with HCV-1a, HPgV-1, and TTV. Moreover, three HHpgV-1-positive patients exhibited stage F0 liver fibrosis. HCV viral load in HHpgV-1-positive patients was lower than those of HHpgV-1-negative patients. Results also revealed that co-infection of HHpgV-1 with HPgV-1 and HCV may play a protective role in patients with chronic HCV. In conclusion, we detected a low frequency of HHpgV-1 infection in hemophilia patients, and results suggested that HHpgV-1 infection was correlated with the presence of other blood-borne viruses and is likely to also correlate with low HCV viral load and reduced severity of liver disease. Additional studies are required to further investigate the clinical importance of HHpgV-1.
Sex Genotyping of Archival Fixed and Immunolabeled Guinea Pig Cochleas
Authors: Depreux Frédéric F. , Czech Lyubov , Whitlon Donna S.
Published: March 2018

For decades, outbred guinea pigs (GP) have been used as research models. Various past research studies using guinea pigs used measures that, unknown at the time, may be sex-dependent, but from which today, archival tissues may be all that remain. We aimed to provide a protocol for sex-typing archival guinea pig tissue, whereby past experiments could be re-evaluated for sex effects. No PCR sex-genotyping protocols existed for GP. We found that published sequence of the GP Sry gene differed from that in two separate GP stocks. We used sequences from other species to deduce PCR primers for Sry. After developing a genomic DNA extraction for archival, fixed, decalcified, immunolabeled, guinea pig cochlear half-turns, we used a multiplex assay (Y-specific Sry; X-specific Dystrophin) to assign sex to tissue as old as 3 years. This procedure should allow reevaluation of prior guinea pig studies in various research areas for the effects of sex on experimental outcomes.
Bile Acids Increase Doxorubicin Sensitivity in ABCC1-expressing Tumour Cells
Authors: Chewchuk Simon , Boorman Tyler , Edwardson Derek , Parissenti Amadeo M.
Published: March 2018

Tumour cells possess or acquire various mechanisms to circumvent the cytotoxic effects of chemotherapy drugs. One such mechanism involves the overexpression of ABC transporters that facilitate the extrusion of a variety of structurally distinct chemotherapy drugs from the cytoplasm into the extracellular space. While specific ABC transporter inhibitors have been developed, many affect other ABC transporters, particularly at elevated concentrations. It is also unclear whether they show clear efficacy for combatting drug resistance in cancer patients with minimal host toxicity. In this study, we demonstrate the ability of two bile acids [β-cholanic acid (urso-cholanic acid) and deoxycholic acid] to specifically inhibit ABCC1-mediated drug transport, augmenting doxorubicin accumulation in breast and lung tumour cells selected for doxorubicin resistance through overexpression of the ABCC1 (but not ABCB1) drug transporter. The bile acids could also restore uptake and sensitivity to doxorubicin in human endothelial kidney cells genetically engineered to overexpress the ABCC1 drug transporter. These observations suggest a previously unreported role for bile acids as ABCC1 inhibitors or regulators. Given its additional properties of minimal clinical toxicity in humans and its ability to inhibit aldo-keto reductases involved in anthracycline resistance and anthracycline-induced cardiotoxicity, β-cholanic acid merits further in vivo and clinical investigation.
Asymmetries in Distractibility: Left Distractors Improve Reaction Time Performance
Authors: Thomas Nicole A. , Nicholls Michael E. R.
Published: March 2018

Research using the irrelevant-distractor paradigm shows perceptual load influences distractibility, such that distractors are more likely to be processed and decrease reaction times during low perceptual load. In contrast, under high load, attentional resources are limited, and the likelihood of distractibility is decreased. We manipulated distractor placement to determine whether location differentially influenced distractibility. During low load, reaction times were increased equally for all distractor locations. Under high load, left distractors speeded reaction times significantly more than right distractors. We suggest two potential explanations: (1) the central focus of attention was sufficiently large to encapsulate both the distractor and the visual array during low perceptual load, leading to increased distraction—during high load, attention was split across the two visual stimuli, allowing the distractors and array to be processed independently; (2) superior executive control for stimuli in the left visual field allowed participants to ‘catch and release’ left distractors more efficiently, ultimately decreasing distraction and providing a performance benefit. Our findings represent an intriguing development in relation to visual asymmetries in distractibility.
Hybrid graphene/cadmium-free ZnSe/ZnS quantum dots phototransistors for UV detection
Authors: Sun Yi-Lin , Xie Dan , Sun Meng-Xing , Teng Chang-Jiu , Qian Liu , Chen Ruo-Song , Xiang Lan , Ren Tian-Ling
Published: March 2018

Graphene-based optoelectronic devices have attracted much attention due to their broadband photon responsivity and fast response time. However, the performance of such graphene-based photodetectors is greatly limited by weak light absorption and low responsivity induced by the gapless nature of graphene. Here, we achieved a high responsivity above 103 AW−1 for Ultraviolet (UV) light in a hybrid structure based phototransistor, which consists of CVD-grown monolayer graphene and ZnSe/ZnS core/shell quantum dots. The photodetectors exhibit a selective photo responsivity for the UV light with the wavelength of 405 nm, confirming the main light absorption from QDs. The photo-generated charges have been found to transfer from QDs to graphene channel, leading to a gate-tunable photo responsivity with the maximum value obtained at V
G
about 15V. A recirculate 100 times behavior with a good stability of 21 days is demonstrated for our devices and another flexible graphene/QDs based photoconductors have been found to be functional after 1000 bending cycles. Such UV photodetectors based on graphene decorated with cadmium-free ZnSe/ZnS quantum dots offer a new way to build environmental friendly optoelectronics.
Proteins involved in embryo-maternal interaction around the signalling of maternal recognition of pregnancy in the horse
Authors: Smits Katrien , Willems Sander , Van Steendam Katleen , Van De Velde Margot , De Lange Valérie , Ververs Cyrillus , Roels Kim , Govaere Jan , Van Nieuwerburgh Filip , Peelman Luc , Deforce Dieter , Van Soom Ann
Published: March 2018

During maternal recognition of pregnancy (MRP), a conceptus-derived signal leads to the persistence of the corpus luteum and the maintenance of gestation. In the horse, the nature of this signal remains to be elucidated. Several studies have focused on the changes in gene expression during MRP, but little information exists at the protein level. The aim of this study was to identify the proteins at the embryo-maternal interface around signalling of MRP in the horse (day 13) by means of mass spectrometry. A distinct influence of pregnancy was established, with 119 proteins differentially expressed in the uterine fluid of pregnant mares compared to cyclic mares and with upregulation of several inhibitors of the prostaglandin synthesis during pregnancy. By creating an overview of the proteins at the embryo-maternal interface in the horse, this study provides a solid foundation for further targeted studies of proteins potentially involved in embryo-maternal interactions, MRP and pregnancy loss in the horse.
Transcriptome-wide identification and screening of WRKY factors involved in the regulation of taxol biosynthesis in Taxus chinensis
Authors: Zhang Meng , Chen Ying , Nie Lin , Jin Xiaofei , Liao Weifang , Zhao Shengying , Fu Chunhua , Yu Longjiang
Published: March 2018

WRKY, a plant-specific transcription factor family, plays important roles in pathogen defense, abiotic cues, phytohormone signaling, and regulation of plant secondary metabolism. However, little is known about the roles, functions, and mechanisms of WRKY in taxane biosynthesis in Taxus spp. In this study, 61 transcripts were identified from Taxus chinensis transcriptome datasets by using hidden Markov model search. All of these transcripts encoded proteins containing WRKY domains, which were designated as TcWRKY1–61. After phylogenetic analysis of the WRKY domains of TcWRKYs and AtWRKYs, 16, 8, 10, 14, 5, 7, and 1 TcWRKYs were cladded into Group I, IIa–IIe, and III, respectively. Then, six representative TcWRKYs were selected to classify their effects on taxol biosynthesis. After MeJA (methyl jasmonate acid) and SA (salicylic acid) treatments, all of the six TcWRKYs were upregulated by MeJA treatment. TcWRKY44 (IId) and TcWRKY47 (IIa) were upregulated, whereas TcWRKY8 (IIc), TcWRKY20 (III), TcWRKY26 (I), TcWRKY41 (IIe), and TcWRKY52 (IIb) were downregulated by SA treatment. Overexpression experiments showed that the six selected TcWRKYs exerted different effects on taxol biosynthesis. In specific, TcWRKY8 and TcWRKY47 significantly improved the expression levels of taxol-biosynthesis-related genes. Transcriptome-wide identification of WRKY factors in Taxus not only enhances our understanding of plant WRKY factors but also identifies candidate regulators of taxol biosynthesis.
Discovery of a highly selective JAK3 inhibitor for the treatment of rheumatoid arthritis
Authors: Pei Heying , He Linhong , Shao Mingfeng , Yang Zhuang , Ran Yan , Li Dan , Zhou Yuanyuan , Tang Minghai , Wang Taijin , Gong Yanqiu , Chen Xiaoxin , Yang Shengyong , Xiang Mingli , Chen Lijuan
Published: March 2018

Janus tyrosine kinase 3 (JAK3) is expressed in lymphoid cells and is involved in the signalling of T cell functions. The development of a selective JAK3 inhibitor has been shown to have a potential benefit in the treatment of autoimmune disorders. In this article, we developed the 4-aminopiperidine-based compound RB1, which was highly selective for JAK3 inhibition, with an IC50 of value of 40 nM, but did not inhibit JAK1, JAK2 or tyrosine kinase 2 (TYK2) at concentrations up to 5 µM. Furthermore, RB1 also exhibited favourable selectivity against a panel of representative kinases. In a battery of cytokine-stimulated cell-based assays, this potent inhibitor of JAK3 activity with good selectivity against other kinases could potently inhibit JAK3 activity over the activity of JAK1 or JAK2 (over at least 100-fold). A combination of liquid chromatography-mass spectrometry (LC-MS) experiments validated that RB1 covalently modified the unique cysteine 909 residue in JAK3. In vivo, RB1 exerted significantly improved pathology in the joints of a collagen-induced arthritis mouse model. The reasonable pharmacokinetics properties (F = 72.52%, T1/2 = 14.6 h) and favourable results of toxicology experiments (LD50 > 2 g/kg) suggest that RB1 has the potential to be an efficacious treatment for RA.
Maresin-1 suppresses imiquimod-induced skin inflammation by regulating IL-23 receptor expression
Authors: Saito-Sasaki Natsuko , Sawada Yu , Mashima Emi , Yamaguchi Takashi , Ohmori Shun , Yoshioka Haruna , Haruyama Sanehito , Okada Etsuko , Nakamura Motonobu
Published: March 2018

The anti-inflammatory effect of omega 3 polyunsaturated fatty acids has been confirmed in various inflammatory disease models. Maresin-1 (MaR1) is a lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid (DHA) that has displayed strong anti-inflammatory effects in various inflammatory disease models. However, the effect of topical MaR1 on cutaneous inflammation remains unclear. Therefore, we initially examined the anti-inflammatory effects of topical Maresin-1 using an imiquimod (IMQ)-induced psoriasis-like mouse model of inflammation. Topical MaR1 reduced the ear swelling response as seen in histological findings. RT-PCR and flow cytometry analyses revealed MaR1 had no inhibitory effect on IL-23, but MaR1 suppressed IL-17A production by γδTCRmid+ and CD4+ cells in the skin. These inhibitory effects were also observed in a subcutaneous IL-23-injected psoriasis model. MaR1 downmodulated IL-23 receptor (IL-23R) expression by suppressing retinoic acid-related orphan receptor γt (RORγt) expression and internalization in a clathrin-dependent manner in γδTCRmid+ and CD4+ cells. These results lead to assumptions that topical MaR1 may be a new therapeutic agent for psoriasis and other IL-17-mediated cutaneous inflammatory diseases.
Early clinical experience with Guidezilla for transradial interventions in China
Authors: Ma Min , Diao Kai-yue , Liu Xiao-jing , He Yong
Published: March 2018

Anatomic variations, calcified, tortuous, angulated lesions, and lack of support to increase the complexity of transradial intervention (TRI). Guidezilla is a mother-and-child catheter enabling increased support during complex interventions. As there are few published reports of its use, we describe our experience using this device to assist TRI in Chinese patients. The aim of this study was to investigate the efficacy and safety of the Guidezilla guide extension catheter in complex coronary interventions. Thirty-two patients’ clinical characteristics, angiographic details, and in-hospital outcome retrospectively collected between June 2015 and August 2017. Patients were 59.44 ± 10.48 years of age and 26 (81%) were men. The most frequent target vessels were the RCA (34%) and LAD (31%), patients had complex type C (53%) or B (47%) lesions, severely tortuous (41%) and angulated (22%).With the use of Guidezilla, technique success was 100%, and procedural success was 94%. The mean diameter of the deployed stents was 2.97 ± 0.37 mm, and the length was 27.19 ± 8.14 mm. The estimated mean distance of Guidezilla intubation into the target vessel was 7.66 ± 2.29 cm.The Guidezilla catheter extension safely facilitated successful completion of TRI in complex coronary artery lesions. This device can help interventionalists successfully perform difficult procedures.
Elucidation of the bacterial communities associated with the harmful microalgae
Alexandrium tamarense
and
Cochlodinium polykrikoides
using nanopore sequencing
Authors: Shin HyeonSeok , Lee Eunju , Shin Jongoh , Ko So-Ra , Oh Hyung-Seok , Ahn Chi-Yong , Oh Hee-Mock , Cho Byung-Kwan , Cho Suhyung
Published: March 2018

Interactions between microalgae and bacteria are often obligatory for harmful algal blooms (HABs). Here, we investigated the specific bacterial communities associated with Alexandrium tamarense and Cochlodinium polykrikoides, which cause ecological and economic damage during their blooms. To this end, the bacterial metagenome was selectively isolated from the two dinoflagellates and subsequently used for 16S rRNA analysis via the Nanopore MinION and Illumina sequencing platforms. Although the full-length 16S rRNA reads from the MinION platform showed high correlation in higher taxonomic ranks to the partial-length 16S rRNA reads from the Illumina platform, there was less correlation at the genus and species levels. MinION reads that are similar in the V3-V4 hypervariable regions with Illumina reads are classified to different taxonomies due to the extra information encoded in the full-length 16S rRNA reads. This indicates that bias arising from the short length Illumina reads can be supplemented by MinION reads. Furthermore, integrated analysis of the Illumina and MinION data showed that A. tamarense was predominantly enriched in the Roseobacter clade and C. polykrikoides was enriched in Gammaproteobacteria and Alphaproteobacteria. These results suggest that the association of different bacterial communities with A. tamarense and C. polykrikoides may be required for HABs.
Topological estimation of signal flow in complex signaling networks
Authors: Lee Daewon , Cho Kwang-Hyun
Published: March 2018

In a cell, any information about extra- or intra-cellular changes is transferred and processed through a signaling network and dysregulation of signal flow often leads to disease such as cancer. So, understanding of signal flow in the signaling network is critical to identify drug targets. Owing to the development of high-throughput measurement technologies, the structure of a signaling network is becoming more available, but detailed kinetic parameter information about molecular interactions is still very limited. A question then arises as to whether we can estimate the signal flow based only on the structure information of a signaling network. To answer this question, we develop a novel algorithm that can estimate the signal flow using only the topological information and apply it to predict the direction of activity change in various signaling networks. Interestingly, we find that the average accuracy of the estimation algorithm is about 60–80% even though we only use the topological information. We also find that this predictive power gets collapsed if we randomly alter the network topology, showing the importance of network topology. Our study provides a basis for utilizing the topological information of signaling networks in precision medicine or drug target discovery.
Polarized electron beams elastically scattered by atoms as a tool for testing fundamental predictions of quantum mechanics
Authors: Dapor Maurizio
Published: March 2018

Quantum information theory deals with quantum noise in order to protect physical quantum bits (qubits) from its effects. A single electron is an emblematic example of a qubit, and today it is possible to experimentally produce polarized ensembles of electrons. In this paper, the theory of the polarization of electron beams elastically scattered by atoms is briefly summarized. Then the POLARe program suite, a set of computer programs aimed at the calculation of the spin-polarization parameters of electron beams elastically interacting with atomic targets, is described. Selected results of the program concerning Ar, Kr, and Xe atoms are presented together with the comparison with experimental data about the Sherman function for low kinetic energy of the incident electrons (1.5eV–350eV). It is demonstrated that the quantum-relativistic theory of the polarization of electron beams elastically scattered by atoms is in good agreement with experimental data down to energies smaller than a few eV.
Sex-based differences in phagocyte metabolic profile in rats with monosodium glutamate-induced obesity
Authors: Rudyk Mariia P. , Pozur Valentyna V. , Voieikova Daryna O. , Hurmach Yevheniia V. , Khranovska Nataliia M. , Skachkova Oksana V. , Svyatetska Vitalina M. , Fedorchuk Olexander G. , Skivka Larysa M. , Berehova Tetiana V. , Ostapchenko Liudmyla I.
Published: March 2018

The important component of obesity pathogenesis is inflammatory activation of innate immune cells within adipose tissue and in other body locations. Both the course of obesity and innate immune reactivity are characterized by sex-associated differences. The aim of the work was a comparative investigation of metabolic profiles of phagocytes from different locations in male and female rats with MSG-induced obesity. The administration of monosodium glutamate (MSG) caused obesity, with sex-associated differences, that was more severe in male rats. Obesity was associated with pro-inflammatory activation of CD14+ phagocytes from adipose tissue in female, but not in male rats, which was demonstrated by decreased phagocytosis activity along with increased ROS generation. Phagocytes from the peritoneal cavity and peripheral blood of obese female rats exhibited neutral metabolic profile, whereas those cells from obese male rats displayed a pro-inflammatory metabolic profile. Thus, the manifestation of obesity-induced inflammation was characterized by different patterns of metabolic profile of phagocytes in male and female rats. Identified immune cell characteristics expand our knowledge of obesity immunobiology and may help to develop more effective preventive and therapeutic interventions for obese patients of different sexes.