bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tailoring manganese oxide with atomic precision to increase surface site availability for oxygen reduction catalysis
Authors: Eom C. John , Kuo Ding-Yuan , Adamo Carolina , Moon Eun Ju , May Steve J. , Crumlin Ethan J. , Schlom Darrell G. , Suntivich Jin 
Published: September 2018

AbstractControlling the structure of catalysts at the atomic level provides an opportunity to establish detailed understanding of the catalytic form-to-function and realize new, non-equilibrium catalytic structures. Here, advanced thin-film deposition is used to control the atomic structure of La2/3Sr1/3MnO3, a well-known catalyst for the oxygen reduction reaction. The surface and sub-surface is customized, whereas the overall composition and d-electron configuration of the oxide is kept constant. Although the addition of SrMnO3 benefits the oxygen reduction reaction via electronic structure and conductivity improvements, SrMnO3 can react with ambient air to reduce the surface site availability. Placing SrMnO3 in the sub-surface underneath a LaMnO3 overlayer allows the catalyst to maintain the surface site availability while benefiting from improved electronic effects. The results show the promise of advanced thin-film deposition for realizing atomically precise catalysts, in which the surface and sub-surface structure and stoichiometry are tailored for functionality, over controlling only bulk compositions.
Cdk1 inactivation induces post-anaphase-onset spindle migration and membrane protrusion required for extreme asymmetry in mouse oocytes
Authors: Wei Zhe , Greaney Jessica , Zhou Chenxi , A. Homer Hayden 
Published: September 2018

AbstractFemale meiotic divisions are extremely asymmetric, producing large oocytes and small polar bodies (PBs). In mouse oocytes, the spindle relocates to the cortex before anaphase of meiosis I (MI). It is presumed that by displacing the future midzone, pre-anaphase spindle repositioning alone ensures asymmetry. But how subsequent anaphase events might contribute to asymmetric PB extrusion (PBE) is unknown. Here, we find that inactivation of cyclin-dependent kinase 1 (Cdk1) induces anaphase and simultaneously triggers cytoplasmic formin-mediated F-actin polymerisation that propels the spindle into the cortex causing it to protrude while anaphase progresses. Significantly, if post-anaphase-onset spindle migration fails, protrusion and asymmetry are severely threatened even with intact pre-anaphase migration. Conversely, post-anaphase migration can completely compensate for failed pre-anaphase migration. These data identify a cell-cycle-triggered phase of spindle displacement occurring after anaphase-onset, which, by inducing protrusion, is necessary for extreme asymmetry in mouse oocytes and uncover a pathway for maximising unequal division.
‘Levodopa Phobia’: a review of a not uncommon and consequential phenomenon
Authors: Titova Nataliya , Levin Oleg , Katunina Elena , Ray Chaudhuri K. 
Published: September 2018

Abstract‘Levodopa Phobia’ is under-recognised in Parkinson’s disease but can cause profound detrimental clinical complications if left to continue. Several types can be encountered in clinical practice and can be driven by a misplaced fear of levodopa-induced dyskinesias, other gastrointestinal side effects and also the theoretical notion that levodopa may be toxic to dopaminergic neurons in the brain. The condition can be underpinned by a sense of strong influence from the physicians or carers who are unwilling to prescribe or consider levodopa, and also high levels of anxiety or even impulsive compulsive traits in patients who have been influenced by available literature or social media-based information. If unrecognised, the clinical issue may lead to motor deterioration and related muscle contractures leading to social isolation as well as a range of non-motor symptoms. In some, there may be emergence of intrusive impulse control disorders because of reliance on only dopamine agonists related to the fear of taking levodopa. Four cases illustrate the different patterns of ‘Levodopa Phobia’ in this study. Management of levodopa phobia is complex and includes recognition and skilled neuropsychological interventions to break the misperceptions about the complications of levodopa therapy.
Primary rat LSECs preserve their characteristic phenotype after cryopreservation
Authors: Mönkemöller Viola , Mao Hong , Hübner Wolfgang , Dumitriu Gianina , Heimann Peter , Levy Gahl , Huser Thomas , Kaltschmidt Barbara , Kaltschmidt Christian , Øie Cristina I. 
Published: September 2018

AbstractLiver disease is a leading cause of morbidity and mortality worldwide. Recently, the liver non-parenchymal cells have gained increasing attention for their potential role in the development of liver disease. Liver sinusoidal endothelial cells (LSECs), a specialized type of endothelial cells that have unique morphology and function, play a fundamental role in maintaining liver homeostasis. Current protocols for LSEC isolation and cultivation rely on freshly isolated cells which can only be maintained differentiated in culture for a few days. This creates a limitation in the use of LSECs for research and a need for a consistent and reliable source of these cells. To date, no LSEC cryopreservation protocols have been reported that enable LSECs to retain their functional and morphological characteristics upon thawing and culturing. Here, we report a protocol to cryopreserve rat LSECs that, upon thawing, maintain full LSEC-signature features: fenestrations, scavenger receptor expression and endocytic function on par with freshly isolated cells. We have confirmed these features by a combination of biochemical and functional techniques, and super-resolution microscopy. Our findings offer a means to standardize research using LSECs, opening the prospects for designing pharmacological strategies for various liver diseases, and considering LSECs as a therapeutic target.
The potential of eye-tracking as a sensitive measure of behavioural change in response to intervention
Authors: Fletcher-Watson Sue , Hampton Sarah 
Published: September 2018

AbstractOne challenge to the development of effective interventions to support learning and behavioural change in neurodevelopmental disorders is a lack of suitable outcome measures. Eye-tracking has been used widely to chart cognitive development and clinically-relevant group differences in many populations. This proof-of-concept study investigates whether it also has the potential to act as a marker of treatment effects, by testing its sensitivity to differential change over a short period of exposure to an iPad app in typically developing children. The app targets a key skill in early social communication development, by rewarding attention to people, operationalised via a finger-tap on screen. We measured attention to images taken from the app, and a selection of matched stimuli to test generalisation of effects, at baseline and two weeks later. Children were assigned to either an app-exposure or no-app condition in the intervening period. The app exposure group showed increases in fixation on people for images from the app, and for distant-generalisation photographs, at high levels of complexity. We conclude that, with careful selection of stimuli, eye-tracking has the potential to make a valuable contribution to the range of outcome measures available for psycho-behavioural interventions in neurodevelopmental disorders.
Supplementation with a selective amino acid formula ameliorates muscular dystrophy in mdx mice
Authors: Banfi Stefania , D’Antona Giuseppe , Ruocco Chiara , Meregalli Mirella , Belicchi Marzia , Bella Pamela , Erratico Silvia , Donato Elisa , Rossi Fabio , Bifari Francesco , Lonati Caterina , Campaner Stefano , Nisoli Enzo , Torrente Yvan 
Published: September 2018

AbstractDuchenne muscular dystrophy (DMD) is one of the most common and severe forms of muscular dystrophy. Oxidative myofibre content, muscle vasculature architecture and exercise tolerance are impaired in DMD. Several studies have demonstrated that nutrient supplements ameliorate dystrophic features, thereby enhancing muscle performance. Here, we report that dietary supplementation with a specific branched-chain amino acid-enriched mixture (BCAAem) increased the abundance of oxidative muscle fibres associated with increased muscle endurance in dystrophic mdx mice. Amelioration of the fatigue index in BCAAem-treated mdx mice was caused by a cascade of events in the muscle tissue, which were promoted by endothelial nitric oxide synthase (eNOS) activation and vascular endothelial growth factor (VEGF) expression. VEGF induction led to recruitment of bone marrow (BM)-derived endothelial progenitors (EPs), which increased the capillary density of dystrophic skeletal muscle. Functionally, BCAAem mitigated the dystrophic phenotype of mdx mice without inducing dystrophin protein expression or replacing the dystrophin-associated glycoprotein (DAG) complex in the membrane, which is typically lost in DMD. BCAAem supplementation could be an effective adjuvant strategy in DMD treatment.
Mesenchymal stem cells are attracted to latent HIV-1-infected cells and enable virus reactivation via a non-canonical PI3K-NFκB signaling pathway
Authors: Chandra Partha K. , Gerlach Samantha L. , Wu Chengxiang , Khurana Namrata , Swientoniewski Lauren T. , Abdel-Mageed Asim B. , Li Jian , Braun Stephen E. , Mondal Debasis 
Published: September 2018

AbstractPersistence of latent HIV-1 in macrophages (MACs) and T-helper lymphocytes (THLs) remain a major therapeutic challenge. Currently available latency reversing agents (LRAs) are not very effective in vivo. Therefore, understanding of physiologic mechanisms that dictate HIV-1 latency/reactivation in reservoirs is clearly needed. Mesenchymal stromal/stem cells (MSCs) regulate the function of immune cells; however, their role in regulating virus production from latently-infected MACs & THLs is not known. We documented that exposure to MSCs or their conditioned media (MSC-CM) rapidly increased HIV-1 p24 production from the latently-infected U1 (MAC) & ACH2 (THL) cell lines. Exposure to MSCs also increased HIV-1 long terminal repeat (LTR) directed gene expression in the MAC and THL reporter lines, U937-VRX and J-Lat (9.2), respectively. MSCs exposed to CM from U1 cells (U1-CM) showed enhanced migratory ability towards latently-infected cells and retained their latency-reactivation potential. Molecular studies showed that MSC-mediated latency-reactivation was dependent upon both the phosphatidyl inositol-3-kinase (PI3K) and nuclear factor-κB (NFκB) signaling pathways. The pre-clinically tested inhibitors of PI3K (PX-866) and NFκB (CDDO-Me) suppressed MSC-mediated HIV-1 reactivation. Furthermore, coexposure to MSC-CM enhanced the latency-reactivation efficacy of the approved LRAs, vorinostat and panobinostat. Our findings on MSC-mediated latency-reactivation may provide novel strategies against persistent HIV-1 reservoirs.
Identification of target genes for RNAi-mediated control of the Twospotted Spider Mite
Authors: Yoon June-Sun , Sahoo Dipak K. , Maiti Indu B , Palli Subba R. 
Published: September 2018

AbstractRNA interference (RNAi) is being developed for the management of pests that destroy crops. The twospotted Spider Mite (TSSM), Tetranychus urticae is a worldwide pest due to its unique physiological and behavioral characteristics including extraordinary ability to detoxify a wide range of pesticides and feed on many host plants. In this study, we conducted experiments to identify target genes that could be used for the development of RNAi-based methods to control TSSM. Leaf disc feeding assays revealed that knockdown in the expression genes coding for proteins involved in the biosynthesis and action of juvenile hormone (JH) and action of ecdysteroids [Methoprene-tolerant (Met), retinoid X receptor β, farnesoic acid O-methyltransferase, and CREB-binding protein] caused 35–56% mortality. Transgenic tobacco plants expressing hairpin dsRNA targeting Met gene were generated and tested. About 48% mortality was observed in TSSM raised on transgenic tobacco plants expressing dsMet. These studies not only broaden our knowledge on understanding hormone action in TSSM but also identified target genes that could be used in RNAi-mediated control of TSSM.
Electromagnetic Fields Due to the Wake of a Moving Slender Body in a Finite-Depth Ocean with Density Stratification
Authors: Xu Zhi-Hua , Du Chang-Ping , Xia Ming-Yao 
Published: September 2018

AbstractWeak electric currents are induced in moving seawater by cutting the geomagnetic fields. These electric currents can produce measurable electromagnetic fields that may be used for some purposes such as monitoring of ocean internal waves. This article is aimed at presenting the procedure to calculate the electromagnetic fields owing to the wake raised by an undersea moving slender body. A pair of Havelock point sources are introduced to model the moving body, which generate the similar wake at places far from the body. The ocean is taken to be of finite-depth with density stratification due to thermocline. Three distinct forms of water-flow wake can be identified, the free-surface Kelvin wake, the internal interfacial wake, and the localized volume wake. The electric currents evoked by the motional wake may produce observable electromagnetic fields, which may be solved using rigorous electromagnetic field theory. At the sea level, the magnitudes of the induced electric field and magnetic field are on the order of a few microvolts per meter and one nano-Tesla, respectively, which are appreciable in terms of nowadays marine electric and magnetic sensors.
Dysregulation of the endothelin pathway in lymphangioleiomyomatosis with no direct effect on cell proliferation and migration
Authors: Chebib Nader , Archer Fabienne , Bobet-Erny Alexandra , Leroux Caroline , Cottin Vincent 
Published: September 2018

AbstractLAM is a rare low-grade metastasizing lung neoplasm. Inhibitors of mTOR improve clinical outcome of LAM patients by preventing loss of lung function. Nevertheless, other cell targets may be of interest for drug development. Therefore, we explored the potential role of EDN1 (endothelin) in LAM. We report an increased endothelin blood level in LAM patients as well as EDN1 overexpression and EDN1 receptor downregulation in LAM-derived primary cells and in TSC2NEG cells mutated in TSC2. We evidenced EDN pathway dysregulation based on EDN1, EDNRA, EDNRB and ARRB1 mRNA expression in LAM-derived primary cells. We showed overexpression of EDN1 and ARRB1 mRNAs in TSC2NEG cells; these cells lost their ability to respond to stimulation by endothelin. We analyzed the effects of endothelin receptor antagonists alone or in combination with rapamycin, an mTOR inhibitor, on proliferation and migration of LAM cells. Rapamycin treatment of TSC2NEG cells significantly reduced cell proliferation or migration, while none of the tested inhibitors of EDN receptors impaired these functions. We showed that TSC2NEG cells have acquired a transformed phenotype as showed by their ability to grow as spheroids in semi-solid medium and that unlike endothelin receptors antagonists, rapamycin reduced anchorage-independent cell growth and prevented expansion of TSC2NEG spheroids.
A Non-Targeted LC-MS Profiling Reveals Elevated Levels of Carnitine Precursors and Trimethylated Compounds in the Cord Plasma of Pre-Eclamptic Infants
Authors: Jääskeläinen Tiina , Kärkkäinen Olli , Jokkala Jenna , Litonius Kaisa , Heinonen Seppo , Auriola Seppo , Lehtonen Marko , Hanhineva Kati , Laivuori Hannele ,   FINNPEC, Kajantie Eero , Kere Juha , Kivinen Katja , Pouta Anneli 
Published: September 2018

AbstractPreeclampsia (PE) is a complex pregnancy disorder. It is not extensively known how the metabolic alterations of PE women contribute to the metabolism of newborn. We applied liquid chromatography-mass spectrometry (LC-MS) based non-targeted metabolomics to determine whether the metabolic profile of plasma from umbilical cord differs between infants born to PE and non-PE pregnancies in the FINNPEC study. Cord plasma was available from 42 newborns born from PE and 53 from non-PE pregnancies. 133 molecular features differed between PE and non-PE newborns after correction for multiple testing. Decreased levels of 4-pyridoxic acid were observed in the cord plasma samples of PE newborns when compared to non-PE newborns. Compounds representing following areas of metabolism were increased in the cord plasma of PE newborns: urea and creatine metabolism; carnitine biosynthesis and acylcarnitines; putrescine metabolites; tryptophan metabolism and phosphatidylcholines. To our knowledge, this study is the first one to apply LC-MS based metabolomics in cord plasma of PE newborns. We demonstrate that this strategy provides a global picture of the widespread metabolic alterations associated with PE and particularly the elevated levels of carnitine precursors and trimethylated compounds appear to be associated with PE at birth.
Allosteric Role of Substrate Occupancy Toward the Alignment of P-glycoprotein Nucleotide Binding Domains
Authors: Pan Lurong , Aller Stephen G. 
Published: September 2018

AbstractP-glycoprotein (Pgp) is an ATP-binding cassette transporter that eliminates toxins from the cell but causes multidrug resistance in chemotherapies. The crystal structures of Pgp revealed drug-like compounds bound to an inward-facing conformation in which the energy-harnessing nucleotide binding domains (NBDs) were widely separated with no interfacial interaction. Following drug binding, inward-facing Pgp must transition to an NBD dimer conformation to achieve ATP binding and hydrolysis at canonical sites defined by both halves of the interface. However, given the high degree of flexibility shown for this transporter, it is difficult to envision how NBDs overcome entropic considerations for achieving proper alignment in order to form the canonical ATP binding site. We explored the hypothesis that substrate occupancy of the polyspecific drug-binding cavity plays a role in the proper alignment of NBDs using computational approaches. We conducted twelve atomistic molecular dynamics (MD) simulations (100–300 ns) on inward-facing Pgp in a lipid bilayer with and without small molecule substrates to ascertain effects of drug occupancy on NBD dimerization. Both apo- and drug-occupied simulations showed NBDs approaching each other compared to the crystal structures. Apo-Pgp reached a pseudo-dimerization in which NBD signature motifs for ATP binding exhibited a significant misalignment during closure. In contrast, occupancy of three established substrates positioned by molecular docking achieved NBD alignment that was much more compatible with a canonical NBD dimerization trajectory. Additionally, aromatic amino acids, known to confer the polyspecific drug-binding characteristic of the internal pocket, may also govern polyspecific drug access to the cavity. The enrichment of aromatics comprising the TM4-TM6 portal suggested a preferential pathway over the aromatic-poor TM10-TM12 for lateral drug entry from the lipid bilayer. Our study also suggested that drug polyspecificity is enhanced due to a synergism between multiple drug-domain interactions involving 36 residues identified in TM1, 5, 6, 7, 11 and 12.
Discordant multi-decadal trend in the intensity of the Kuroshio along its path during 1993–2013
Authors: Wang You-Lin , Wu Chau-Ron 
Published: September 2018

AbstractThe Kuroshio transports warm water in the Pacific poleward from the tropics and plays a crucial role in modulating surrounding climate. Based on independent data sets, we demonstrated that the Kuroshio weakened downstream east of Taiwan, but intensified upstream east of Luzon Island during 1993–2013. The surface velocity (volume transport) of the Kuroshio has decreased 12.5% (4~5%) off east Taiwan but increased 18% (8~18%) off east Luzon. The discordant upstream–downstream trend was attributable to changes in oceanic eddies and basin surface winds: greater (lesser) cyclonic eddies, lesser (greater) anticyclonic eddies, and positive (negative) tendency in the Pacific Basin wind curl contributed to a weakened (intensified) downstream (upstream) Kuroshio. The difference in water mass between the upstream and downstream Kuroshio was balanced by an anomalous eastward flow, the southern branch of the Subtropical Counter Current which was enhanced and evacuated the redundant water eastward into the Pacific.
The mapping of cancer incidence and mortality trends in the UK from 1980–2013 reveals a potential for overdiagnosis
Authors: Oke Jason L. , O’Sullivan Jack W. , Perera Rafael , Nicholson Brian D. 
Published: September 2018

AbstractThe incidence of cancer in the United Kingdom has increased significantly over the last four decades. The aim of this study was to examine trends in UK cancer incidence and mortality by cancer site and assess the potential for overdiagnosis. Using Cancer Research UK incidence and mortality data for the period (1971–2014) we estimated percentage change in incidence and mortality rates and the incidence-mortality ratio (IMR) for cancers in which incidence had increased >50%. Incidence and mortality trend plots were used to assess the potential for overdiagnosis. Incidence rates increased from 67% (uterine) to 375% (melanoma). Change in mortality rates ranged from −69% (cervical) to +239% (liver). The greatest divergences occurred in uterine (IMR = 132), prostate (IMR = 9.6), oral (IMR = 9.8) and thyroid cancer (IMR = 5.3). Only in liver cancer did mortality track incidence (IMR = 1.1). For four cancer sites; uterine, prostate, oral and thyroid, incidence and mortality trends are suggestive of overdiagnosis. Trends in melanoma and kidney cancer suggest potential overdiagnosis and an underlying increase in true risk, whereas for cervical and breast cancer, trends may also reflect improvements in treatments or earlier diagnosis. A more detailed analysis is required to fully understand these patterns.
A systems-approach reveals human nestin is an endothelial-enriched, angiogenesis-independent intermediate filament protein
Authors: Dusart Philip , Fagerberg Linn , Perisic Ljubica , Civelek Mete , Struck Eike , Hedin Ulf , Uhlén Mathias , Trégouët David-Alexandre , Renné Thomas , Odeberg Jacob , Butler Lynn M. 
Published: September 2018

AbstractThe intermediate filament protein nestin is expressed during embryonic development, but considered largely restricted to areas of regeneration in the adult. Here, we perform a body-wide transcriptome and protein-profiling analysis to reveal that nestin is constitutively, and highly-selectively, expressed in adult human endothelial cells (EC), independent of proliferative status. Correspondingly, we demonstrate that it is not a marker for tumour EC in multiple malignancy types. Imaging of EC from different vascular beds reveals nestin subcellular distribution is shear-modulated. siRNA inhibition of nestin increases EC proliferation, and nestin expression is reduced in atherosclerotic plaque neovessels. eQTL analysis reveals an association between SNPs linked to cardiovascular disease and reduced aortic EC nestin mRNA expression. Our study challenges the dogma that nestin is a marker of proliferation, and provides insight into its regulation and function in EC. Furthermore, our systems-based approach can be applied to investigate body-wide expression profiles of any candidate protein.