bluuebunny/crossref_metadata_2025_split huggingface dataset:
Saturn's Northern Auroras and Their Modulation by Rotating Current Systems During Late Northern Spring in Early 2014
Authors: Kinrade J. , Badman S. V. , Provan G. , Cowley S. W. H. , Lamy L. , Bader A. 
Published: July 2018

AbstractThe Hubble Space Telescope imaged Saturn's northern ultraviolet auroras during February–June 2014, when Saturn's northern and southern magnetic perturbation fields were locked in antiphase and matched in rotation period (~10.69 hr). During this coalescence period, we test for evidence of rotational modulation of the auroras using the latest rotating current system model and kilometric radio phases derived from Cassini measurements. While we see modulation of auroral intensity in the rotating frames of the planetary period current systems, the pattern is opposite to that expected and is dominated by an asymmetric local time profile that peaks at dawn. Enhancement of the north emission by rotating upward field aligned currents (FACs) is expected to peak at magnetic longitudes of ~90°, whereas here the intensity increased at ~270°. This unexpected finding is attributed to the presence of nonplanetary period oscillation dynamics having affected the auroral morphology, together with insufficient sampling of the rotational system orientations provided during such Hubble Space Telescope campaigns. Rotational modulation is clearest at dawn regardless of the pattern's orientation, suggesting that the physical relationship between rotating FACs and auroral intensity is not direct, having a local time dependence that is not generally observed in the rotating FAC magnitudes. We also find no statistically significant planetary period oscillation of the auroral circle position, but the mean center was offset from the spin pole by ~3° latitude toward early morning local times. Mean auroral boundaries were located at equatorward and poleward colatitudes of 15.0 ± 2.8° and 12.4 ± 3.0°, respectively.
MENTAT: A New Wind Model for Earth's Thermosphere
Authors: Dandenault P. B. 
Published: July 2018

AbstractA global database of ionosonde hmF2 observations was used to develop a global database of equivalent neutral winds, which was then used to develop a new empirical horizontal neutral wind model called the Magnetic mEridional NeuTrAl Thermospheric model. In this paper, we (1) developed and optimized a technique for deriving magnetic meridional thermospheric neutral winds using the altitude of the peak ionosphere (hmF2) observations from bottomside ionospheric sounders, (2) validated these neutral winds with observations from Fabry‐Pérot interferometers (FPIs), (3) developed a new model of horizontal, magnetic meridional, equivalent neutral winds in the midlatitude regions from a global database of ionosonde observations spanning the years 1961 to 1990. Our new method for generating the winds compares well with FPI wind observations and illuminates nonphysical behavior in the horizontal thermospheric neutral wind model. Magnetic mEridional NeuTrAl Thermospheric neutral winds compare well with FPI wind observations over both short‐ and long‐time periods, and the model produces winds as a function of the year, day of year, universal time, solar flux, geographic latitude, and geographic longitude. Two major findings are (1) a distinct solar cycle wind variation that was not captured in other empirical models using other data sets and (2) global measurements of ionospheric hmF2, which provide constraints on the global wind field that is particularly valuable considering the persistent lack of space‐based F region winds and the inability of FPIs to operate during the day, when cloudy, or under moon‐up conditions.
The 6 September 2017 X‐Class Solar Flares and Their Impacts on the Ionosphere, GNSS, and HF Radio Wave Propagation
Authors: Yasyukevich Y. , Astafyeva E. , Padokhin A. , Ivanova V. , Syrovatskii S. , Podlesnyi A. 
Published: July 2018

AbstractOn 6 September 2017, the Sun emitted two significant solar flares (SFs). The first SF, classified X2.2, peaked at 09:10 UT. The second one, X9.3, which is the most intensive SF in the current solar cycle, peaked at 12:02 UT and was accompanied by solar radio emission. In this work, we study ionospheric response to the two X‐class SFs and their impact on the Global Navigation Satellite Systems and high‐frequency (HF) propagation. In the ionospheric absolute vertical total electron content (TEC), the X2.2 SF caused an overall increase of 2–4 TECU on the dayside. The X9.3 SF produced a sudden increase of ~8–10 TECU at midlatitudes and of ~15–16 TECU enhancement at low latitudes. These vertical TEC enhancements lasted longer than the duration of the EUV emission. In TEC variations within 2–20 min range, the two SFs provoked sudden increases of ~0.2 TECU and 1.3 TECU. Variations in TEC from geostationary and GPS/GLONASS satellites show similar results with TEC derivative of ~1.3–1.7 TECU/min for X9.3 and 0.18–0.24 TECU/min for X2.2 in the subsolar region. Further, analysis of the impact of the two SFs on the Global Navigation Satellite Systems‐based navigation showed that the SF did not cause losses‐of‐lock in the GPS, GLONASS, or Galileo systems, while the positioning error increased by ~3 times in GPS precise point positioning solution. The two X‐class SFs had an impact on HF radio wave propagation causing blackouts at <30 MHz in the subsolar region and <15 MHz in the postmidday sector.
The major depressive disorder GWAS-supported variant rs10514299 in TMEM161B-MEF2C predicts putamen activation during reward processing in alcohol dependence
Authors: Muench Christine , Schwandt Melanie , Jung Jeesun , Cortes Carlos R. , Momenan Reza , Lohoff Falk W. 
Published: July 2018

AbstractAlcohol dependence (AD) frequently co-occurs with major depressive disorder (MDD). While this comorbidity is associated with an increase in disease burden, worse treatment outcomes, and greater economic costs, the underlying neurobiology remains poorly understood. A recent large-scale GWAS of MDD has identified a locus in theTMEM161B-MEF2Cregion (rs10514299) as a novel risk variant; however, the biological relevance of this variant has not yet been studied. Given previous reports of disrupted reward processing in both AD and MDD, we hypothesized that rs10514299 would be associated with differences in striatal BOLD responses during reward/loss anticipation in AD. DNA samples from 45 recently detoxified patients with AD and 45 healthy controls (HC) were genotyped for rs10514299. Participants performed the Monetary Incentive Delay task in a 3-Tesla MRI scanner. Effects of rs10514299 on striatal activation during anticipation of high/low reward/loss were investigated. Furthermore, we examined associations between rs10514299 and lifetime AD diagnosis in two independent clinical samples [NIAAA:n = 1858 (1123 cases, 735 controls); SAGE:n = 3838 (1848 cases, 1990 controls)], as well as its association with depression severity in a subsample of individuals with a lifetime AD diagnosis(n = 953). Patients carrying the T allele showed significantly greater putamen activation during anticipation of high reward (p = 0.014), low reward (at trend-level;p = 0.081), high loss (p = 0.024), and low loss (p = 0.046) compared to HCs. Association analyses in the NIAAA sample showed a trend-level relationship between rs10514299 and a lifetime AD diagnosis in the European American subgroup (odds ratio = 0.82,p = 0.09). This finding was not replicated in the SAGE sample. In the NIAAA sample, the T allele was significantly associated with greater depression symptom severity in individuals with a lifetime AD diagnosis (β = 1.25,p = 0.02); this association was driven by the African American ancestry subgroup (β = 2.11,p = 0.008). We show for the first time that the previously identified MDD risk variant rs10514299 inTMEM161B-MEF2Cpredicts neuronal correlates of reward processing in an AD phenotype, possibly explaining part of the shared pathophysiology and comorbidity between the disorders.
A broad-spectrum antibiotic, DCAP, reduces uropathogenic Escherichia coli infection and enhances vorinostat anticancer activity by modulating autophagy
Authors: Allavena Giulia , Debellis Doriana , Marotta Roberto , Joshi Chetanchandra S. , Mysorekar Indira U. , Grimaldi Benedetto 
Published: July 2018

AbstractThe cellular recycling pathway of autophagy plays a fundamental role in adaptive responses to nutrient deprivation and other forms of stress under physiological and pathological conditions. However, autophagy can also be a double-edge sword during certain bacterial infections (such as urinary tract infections) and in cancer, where it can be hijacked by the pathogens and cancer cells, respectively, to promote their own survival. Thus, autophagy modulation can potentially have multiple effects in multiple contexts and this property can be leveraged to improve outcomes. In this report, we identify that a broad-spectrum antibiotic, 2-((3-(3, 6-dichloro-9H-carbazol-9-yl)-2-hydroxypropyl) amino)-2-(hydroxymethyl) propane-1, 3-diol (DCAP) modulates autophagy. We employed combined biochemical, fluorescence microscopy and correlative light electron microscopy approaches to demonstrate that DCAP treatment blocks autophagy at the late stages by preventing autophagolysosome maturation and interrupting the autophagic flux. We further show that, DCAP significantly reduces UPEC infection in urinary tract epithelial cells via inhibition of autophagy. Finally, we reveal that DCAP enhances the anticancer activity of the histone acetyltransferase (HDAC) inhibitor, vorinostat, which has been reported to increase susceptibility to bacterial infections as a common adverse effect. Collectively, our data support the concept that DCAP represents a valuable chemical scaffold for the development of an innovative class of bactericidal autophagy inhibitors for treatment of urinary tract infections and/or for adjuvant therapy in cancer treatment.
PRMT5-mediated regulation of developmental myelination
Authors: Scaglione Antonella , Patzig Julia , Liang Jialiang , Frawley Rebecca , Bok Jabez , Mela Angeliki , Yattah Camila , Zhang Jingxian , Teo Shun Xie , Zhou Ting , Chen Shuibing , Bernstein Emily , Canoll Peter , Guccione Ernesto , Casaccia Patrizia 
Published: July 2018

AbstractOligodendrocytes (OLs) are the myelin-forming cells of the central nervous system. They are derived from differentiation of oligodendrocyte progenitors through a process requiring cell cycle exit and histone modifications. Here we identify the histone arginine methyl-transferase PRMT5, a molecule catalyzing symmetric methylation of histone H4R3, as critical for developmental myelination. PRMT5 pharmacological inhibition, CRISPR/cas9 targeting, or genetic ablation decrease p53-dependent survival and impair differentiation without affecting proliferation. Conditional ablation of Prmt5 in progenitors results in hypomyelination, reduced survival and differentiation. Decreased histone H4R3 symmetric methylation is followed by increased nuclear acetylation of H4K5, and is rescued by pharmacological inhibition of histone acetyltransferases. Data obtained using purified histones further validate the results obtained in mice and in cultured oligodendrocyte progenitors. Together, these results identify PRMT5 as critical for oligodendrocyte differentiation and developmental myelination by modulating the cross-talk between histone arginine methylation and lysine acetylation.
Abrupt events and population synchrony in the dynamics of Bovine Tuberculosis
Authors: Moustakas Aristides , Evans Matthew R. , Daliakopoulos Ioannis N. , Markonis Yannis 
Published: July 2018

AbstractDisease control strategies can have both intended and unintended effects on the dynamics of infectious diseases. Routine testing for the harmful pathogen Bovine Tuberculosis (bTB) was suspended briefly during the foot and mouth disease epidemic of 2001 in Great Britain. Here we utilize bTB incidence data and mathematical models to demonstrate how a lapse in management can alter epidemiological parameters, including the rate of new infections and duration of infection cycles. Testing interruption shifted the dynamics from annual to 4-year cycles, and created long-lasting shifts in the spatial synchrony of new infections among regions of Great Britain. After annual testing was introduced in some GB regions, new infections have become more de-synchronised, a result also confirmed by a stochastic model. These results demonstrate that abrupt events can synchronise disease dynamics and that changes in the epidemiological parameters can lead to chaotic patterns, which are hard to be quantified, predicted, and controlled.
The potassium channel KCNJ13 is essential for smooth muscle cytoskeletal organization during mouse tracheal tubulogenesis
Authors: Yin Wenguang , Kim Hyun-Taek , Wang ShengPeng , Gunawan Felix , Wang Lei , Kishimoto Keishi , Zhong Hua , Roman Dany , Preussner Jens , Guenther Stefan , Graef Viola , Buettner Carmen , Grohmann Beate , Looso Mario , Morimoto Mitsuru , Mardon Graeme , Offermanns Stefan , Stainier Didier Y. R. 
Published: July 2018

AbstractTubulogenesis is essential for the formation and function of internal organs. One such organ is the trachea, which allows gas exchange between the external environment and the lungs. However, the cellular and molecular mechanisms underlying tracheal tube development remain poorly understood. Here, we show that the potassium channel KCNJ13 is a critical modulator of tracheal tubulogenesis. We identify Kcnj13 in an ethylnitrosourea forward genetic screen for regulators of mouse respiratory organ development. Kcnj13 mutants exhibit a shorter trachea as well as defective smooth muscle (SM) cell alignment and polarity. KCNJ13 is essential to maintain ion homeostasis in tracheal SM cells, which is required for actin polymerization. This process appears to be mediated, at least in part, through activation of the actin regulator AKT, as pharmacological increase of AKT phosphorylation ameliorates the Kcnj13-mutant trachea phenotypes. These results provide insight into the role of ion homeostasis in cytoskeletal organization during tubulogenesis.
Designing a norepinephrine optical tracer for imaging individual noradrenergic synapses and their activity in vivo
Authors: Dunn Matthew , Henke Adam , Clark Samuel , Kovalyova Yekaterina , Kempadoo Kimberly A. , Karpowicz Richard J. , Kandel Eric R. , Sulzer David , Sames Dalibor 
Published: July 2018

AbstractNorepinephrine is a monoamine neurotransmitter with a wide repertoire of physiological roles in the peripheral and central nervous systems. There are, however, no experimental means to study functional properties of individual noradrenergic synapses in the brain. Development of new approaches for imaging synaptic neurotransmission is of fundamental importance to study specific synaptic changes that occur during learning, behavior, and pathological processes. Here, we introduce fluorescent false neurotransmitter 270 (FFN270), a fluorescent tracer of norepinephrine. As a fluorescent substrate of the norepinephrine and vesicular monoamine transporters, FFN270 labels noradrenergic neurons and their synaptic vesicles, and enables imaging synaptic vesicle content release from specific axonal sites in living rodents. Combining FFN270 imaging and optogenetic stimulation, we find heterogeneous release properties of noradrenergic synapses in the somatosensory cortex, including low and high releasing populations. Through systemic amphetamine administration, we observe rapid release of cortical noradrenergic vesicular content, providing insight into the drug’s effect.
Microglia permit climbing fiber elimination by promoting GABAergic inhibition in the developing cerebellum
Authors: Nakayama Hisako , Abe Manabu , Morimoto Chie , Iida Tadatsune , Okabe Shigeo , Sakimura Kenji , Hashimoto Kouichi 
Published: July 2018

AbstractCircuit refinement during postnatal development is finely regulated by neuron–neuron interactions. Recent studies suggest participation of microglia in this process but it is unclear how microglia cooperatively act with neuronal mechanisms. To examine roles of microglia, we ablate microglia by microglia-selective deletion of colony-stimulating factor 1 receptor (Csf1r) by crossing floxed-Csf1r and Iba1-iCre mice (Csf1r-cKO). In Csf1r-cKO mice, refinement of climbing fiber (CF) to Purkinje cell (PC) innervation after postnatal day 10 (P10)–P12 is severely impaired. However, there is no clear morphological evidence suggesting massive engulfment of CFs by microglia. In Csf1r-cKO mice, inhibitory synaptic transmission is impaired and CF elimination is restored by diazepam, which suggests that impairment of CF elimination is caused by a defect of GABAergic inhibition on PCs, a prerequisite for CF elimination. These results indicate that microglia primarily promote GABAergic inhibition and secondarily facilitate the mechanism for CF elimination inherent in PCs.
CTC1-STN1 terminates telomerase while STN1-TEN1 enables C-strand synthesis during telomere replication in colon cancer cells
Authors: Feng Xuyang , Hsu Shih-Jui , Bhattacharjee Anukana , Wang Yongyao , Diao Jiajie , Price Carolyn M. 
Published: July 2018

AbstractTelomerase elongates the telomeric G-strand to prevent telomere shortening through conventional DNA replication. However, synthesis of the complementary C-strand by DNA polymerase α is also required to maintain telomere length. Polymerase α cannot perform this role without the ssDNA binding complex CST (CTC1-STN1-TEN1). Here we describe the roles of individual CST subunits in telomerase regulation and G-overhang maturation in human colon cancer cells. We show that CTC1-STN1 limits telomerase action to prevent G-overhang overextension. CTC1−/− cells exhibit telomeric DNA damage and growth arrest due to overhang elongation whereas TEN1−/− cells do not. However, TEN1 is essential for C-strand synthesis and TEN1−/− cells exhibit progressive telomere shortening. DNA binding analysis indicates that CTC1-STN1 retains affinity for ssDNA but TEN1 stabilizes binding. We propose CTC1-STN1 binding is sufficient to terminate telomerase action but altered DNA binding dynamics renders CTC1-STN1 unable to properly engage polymerase α on the overhang for C-strand synthesis.
Non-covalent control of spin-state in metal-organic complex by positioning on N-doped graphene
Authors: de la Torre Bruno , Švec Martin , Hapala Prokop , Redondo Jesus , Krejčí Ondřej , Lo Rabindranath , Manna Debashree , Sarmah Amrit , Nachtigallová Dana , Tuček Jiří , Błoński Piotr , Otyepka Michal , Zbořil Radek , Hobza Pavel , Jelínek Pavel 
Published: July 2018

AbstractNitrogen doping of graphene significantly affects its chemical properties, which is particularly important in molecular sensing and electrocatalysis applications. However, detailed insight into interaction between N-dopant and molecules at the atomic scale is currently lacking. Here we demonstrate control over the spin state of a single iron(II) phthalocyanine molecule by its positioning on N-doped graphene. The spin transition was driven by weak intermixing between orbitals with z-component of N-dopant (pz of N-dopant) and molecule (dxz, dyz, dz2) with subsequent reordering of the Fe d-orbitals. The transition was accompanied by an electron density redistribution within the molecule, sensed by atomic force microscopy with CO-functionalized tip. This demonstrates the unique capability of the high-resolution imaging technique to discriminate between different spin states of single molecules. Moreover, we present a method for triggering spin state transitions and tuning the electronic properties of molecules through weak non-covalent interaction with suitably functionalized graphene.
SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix
Authors: Fukuda Masatoshi , Yoshizawa Tatsuya , Karim Md. Fazlul , Sobuz Shihab U. , Korogi Wataru , Kobayasi Daiki , Okanishi Hiroki , Tasaki Masayoshi , Ono Katsuhiko , Sawa Tomohiro , Sato Yoshifumi , Chirifu Mami , Masuda Takeshi , Nakamura Teruya , Tanoue Hironori , Nakashima Kazuhisa , Kobashigawa Yoshihiro , Morioka Hiroshi , Bober Eva , Ohtsuki Sumio , Yamagata Yuriko , Ando Yukio , Oike Yuichi , Araki Norie , Takeda Shu , Mizuta Hiroshi , Yamagata Kazuya 
Published: July 2018

AbstractSP7/Osterix (OSX) is a master regulatory transcription factor that activates a variety of genes during differentiation of osteoblasts. However, the influence of post-translational modifications on the regulation of its transactivation activity is largely unknown. Here, we report that sirtuins, which are NAD(+)-dependent deacylases, regulate lysine deacylation-mediated transactivation of OSX. Germline Sirt7 knockout mice develop severe osteopenia characterized by decreased bone formation and an increase of osteoclasts. Similarly, osteoblast-specific Sirt7 knockout mice showed attenuated bone formation. Interaction of SIRT7 with OSX leads to the activation of transactivation by OSX without altering its protein expression. Deacylation of lysine (K) 368 in the C-terminal region of OSX by SIRT7 promote its N-terminal transactivation activity. In addition, SIRT7-mediated deacylation of K368 also facilitates depropionylation of OSX by SIRT1, thereby increasing OSX transactivation activity. In conclusion, our findings suggest that SIRT7 has a critical role in bone formation by regulating acylation of OSX.
Iridium-catalyzed reductive Ugi-type reactions of tertiary amides
Authors: Xie Lan-Gui , Dixon Darren J. 
Published: July 2018

AbstractAmides are ubiquitous in the fine chemical, agrochemical and pharmaceutical industries, but are rarely exploited as substrates for homologous amine synthesis. By virtue of their high chemical stability, they are essentially inert to all but the harshest of chemical reagents and to the majority of chemical transformations routinely used in organic synthesis. Accordingly, the development of chemoselective carbon−carbon bond-forming methodologies arising from the functionalization of the amide functionality should find widespread use across academia and industry. We herein present our findings on a series of Ugi-type reactions of tertiary amides enabled by an initial chemoselective iridium-catalyzed partial reduction, followed by reaction with isocyanide and (thio)acetic acid or trimethylsilyl azide, thus providing a multicomponent synthesis of α-amino (thio)amide or α-amino tetrazole derivatives. The reductive Ugi-type reactions are amenable to a broad range of amides and isocyanides, and are applicable to late-stage functionalization of various bioactive molecules and pharmaceutical compounds.
Enzymatic one-step ring contraction for quinolone biosynthesis
Authors: Kishimoto Shinji , Hara Kodai , Hashimoto Hiroshi , Hirayama Yuichiro , Champagne Pier Alexandre , Houk Kendall N. , Tang Yi , Watanabe Kenji 
Published: July 2018

AbstractThe 6,6-quinolone scaffolds on which viridicatin-type fungal alkaloids are built are frequently found in metabolites that display useful biological activities. Here we report in vitro and computational analyses leading to the discovery of a hemocyanin-like protein AsqI from the Aspergillus nidulans aspoquinolone biosynthetic pathway that forms viridicatins via a conversion of the cyclopenin-type 6,7-bicyclic system into the viridicatin-type 6,6-bicyclic core through elimination of carbon dioxide and methylamine through methyl isocyanate.