bluuebunny/crossref_metadata_2025 huggingface dataset:
Excursions of Interhemispheric Field‐Aligned Currents in Africa
Authors: Owolabi O. P. , Bolaji O. S. , Adeniyi J. O. , Oyeyemi E. O. , Rabiu A. B. , Habarulema J. B.
Published: July 2018

The interhemispheric field‐aligned currents (IHFACs) are the most evident currents connecting the solar quiet (Sq) current systems in the Northern and Southern Hemispheres. Understanding these coupling currents has practical importance for space weather forecast of the magnetosphere‐ionosphere interactions and their potential impacts on low‐orbiting spacecraft. In this paper, we have examined digital magnetic records from September 2008 to August 2009 at nine Magnetic Data Acquisition System (MAGDAS) stations in order to uniquely determine the variability of IHFACs in terms of their excursions in the African sector. By excursions, we mean the direction in which the IHFACs are moving as a function of local time or latitude. Different from theoretical prediction, we found prominent positive IHFACs around dusk in February and March equinox. A novel feature of this study is the semidiurnal variation control of the coupling between the Northern and Southern Hemispheres. In addition, we found terdiurnal variation in September with their associated strong diurnal variations from October through December. Quite unexpectedly, in January, a significant latitudinal depletion in the intensities of IHFACs was observed from dawn to dusk, compared to any other months under investigation, accompanied with a marked reduction of the prominent diurnal variations at the magnetic equator (Addis Ababa, AAB). The fact that the excursions of IHFACs in January experience an unusual retardation with respect to their intensities points to a relation with the effects of sudden stratospheric warming.
Effects of Wind and Buoyancy on Carbon Dioxide Distribution and Air‐Water Flux of a Stratified Temperate Lake
Authors: Czikowsky Matthew J. , MacIntyre Sally , Tedford Edmund W. , Vidal Javier , Miller Scott D.
Published: July 2018

Improved calculations of emissions of greenhouse gases from stratified lakes require understanding the physical processes controlling transport of dissolved gases to the air‐water interface on diel, synoptic, and seasonal time scales. We address this issue during the transition from late summer to autumn cooling in a small temperate lake by combining micrometeorology, physical limnology, and carbon dioxide (CO2) measurements throughout the water column. Over the 26‐day campaign, the lake cooled and emitted CO2 with daily average loss of 23 mmol CO2 m−2 d−1. Over diel cycles, lake surface pCO2 decreased during daytime heating and increased during nighttime cooling, while daytime CO2 fluxes exceeded nighttime fluxes by 35% due to higher daytime wind speeds. We compared the effects of diel and synoptic weather patterns on the CO2 distribution within the lake and lake‐atmosphere CO2 flux. Increases in near‐surface pCO2 scaled with stratification and heat loss which moderated transport of dissolved gases into the mixed layer. When winds were above ~4 m s−1, lake‐scale circulations drove upwelling and downwelling that redistributed heat and carbon dioxide between the northeast and southwest basins. Short‐burst peak CO2 fluxes exceeded 50 mmol m−2 d−1 during windy periods associated with storms. However, the seasonal cooling‐induced transition to persistent deep mixing led to the highest CO2 concentrations in the mixed layer and at the surface and the highest sustained CO2 fluxes (approaching 100 mmol m−2 d−1).
Changes in Madden‐Julian Oscillation Precipitation and Wind Variance Under Global Warming
Authors: Bui Hien X. , Maloney Eric D.
Published: July 2018

The Madden‐Julian oscillation (MJO) is the leading mode of tropical intraseasonal variability, having profound impacts on many weather and climate phenomena across the tropics and extratropics. Previous studies using a limited number of models have suggested complex changes in MJO activity in a warmer climate. While most studies have argued that MJO precipitation amplitude will increase in a future warmer climate, others note that this is not necessarily the case for MJO wind variability. This distinction is important since MJO wind fluctuations are responsible for producing remote impacts on extreme weather through teleconnections. In this study, we examine projected changes of MJO precipitation and wind variance at the end of the 21st century in Representative Concentration Pathway 8.5 using the multimodel Coupled Model Intercomparison Project phase 5 data set. Under global warming, most models show an increase in MJO band precipitation variance, while wind variability decreases. The discrepancy between MJO precipitation and wind variance changes under global warming is shown to be due to increases in tropical static stability in a warmer climate. The multimodel mean shows a 20% increase in both the 500‐hPa vertical tropical dry static energy gradient and the ratio of intraseasonal precipitation to 500 hPa omega fluctuations, consistent with scaling by weak temperature gradient theory. These results imply that tropical static stability increases may weaken the MJO's ability to influence extreme events in future warmer climate by weakening wind teleconnections, even though MJO precipitation amplitude may increase.
Contributions of Internal Variability and External Forcing to the Recent Pacific Decadal Variations
Authors: Hua Wenjian , Dai Aiguo , Qin Minhua
Published: July 2018

There is substantial uncertainty in the relative contributions of internal variability and external forcing to the recent Pacific decadal variability, especially regarding their linkage with the Interdecadal Pacific Oscillation. By analyzing observations and large ensembles of coupled climate model simulations, here we show that observed Pacific decadal variations since 1920 resulted primarily from internal variability, although greenhouse gas (GHG) and other external forcing did modulate decadal variations in Pacific sea surface temperatures (SSTs) significantly, especially for the period since the early 1990s. Specifically, the GHG‐induced warming and the recovery from the volcanic cooling caused by the 1991 Pinatubo eruption led to large warming in the tropical Pacific during 1993–2012, while recent anthropogenic aerosols contributed to Pacific regional SST variations on multiyear to decadal scales, causing a La Niña‐like cooling pattern in the Pacific since 1998 in some of the models. Our results provide new evidence that both internal variability and external forcing have contributed to the recent decadal variations in Pacific SSTs since the early 1990s, although large uncertainties exist among the model‐simulated effects of anthropogenic aerosols.
Carriers and Sources of Magnetopause Current: MMS Case Study
Authors: Dong X.‐C. , Dunlop M. W. , Wang T.‐Y. , Cao J.‐B. , Trattner K. J. , Bamford R. , Russell C. T. , Bingham R. , Strangeway R. J. , Fear R. C. , Giles B. L. , Torbert R. B.
Published: July 2018

We investigate the current carriers and current sources of an ion scale tangential magnetopause current layer using the Magnetospheric Multiscale four spacecraft data. Within this magnetopause current layer, ions and electrons equally contribute to the perpendicular current, while electrons carry nearly all the parallel current. The energy range of all these current carriers is predominantly from middle to high (>100 eV), where particles with higher energies are more efficient in producing the current. By comparing each term, two‐fluid magnetohydrodynamic (MHD) theory is able to describe the current sources to a large degree because the sum of all the perpendicular currents from MHD theory could account for the currents observed. In addition, we find that the ion diamagnetic current is the main source of the total perpendicular current, while the curvature current can be neglected. Nevertheless, ions and electrons both carry comparable current due to the redistribution of the electric field and show features beyond the classic Chapman‐Ferraro model, particularly on the front side of the boundary layer where the electric field reversal is most intense. We also show a second, comparative event in which ions do not satisfy MHD theory, while the electrons do. The small‐scale, adiabatic parameter (square of curvature radius/gyroradius) supports our interpretation that this second event contains ion scale substructure. We suggest that comparing the predicted MHD current with plasma current can be a good method to judge whether the MHD theory is satisfied in each specific circumstance, especially for high‐precision Magnetospheric Multiscale data.
Statistical Results of Multiband Chorus by Using THEMIS Waveform Data
Authors: Gao Xinliang , Lu Quanming , Wang Shui
Published: July 2018

In this paper, we have studied thousands of multiband chorus events in the Earth's magnetosphere by utilizing seven‐year THEMIS waveform data. There are two types of multiband chorus events in the magnetosphere: electromagnetic multiband chorus (EM‐MBC) event, where two‐band structure is found in both magnetic and electric spectrograms, and quasi‐electrostatic multiband chorus (QE‐MBC) event, where two‐band structure is only detected in the electric spectrogram. EM‐MBC events preferentially occur at low L‐shells on the nightside but at high L‐shells on the dayside. In EM‐MBC events, lower‐band waves typically have relatively larger magnetic amplitudes (>100 pT) and finite wave normal angles (10°–30°). The magnetic amplitudes of upper‐band harmonic waves are found to be typically smaller than 30 pT and peak in the range of <5 pT. QE‐MBC events tend to be detected at low L‐shells on both dayside and nightside. They distribute mainly at relatively higher magnetic latitudes (6° to 15°) in the dawn sector. Lower‐band chorus in QE‐MBC events are typically highly oblique with very large wave normal angles (>60°), and their electric amplitudes peak in the range of 5–15 mV/m. For upper‐band harmonic waves, their electric amplitudes mainly concentrate in the range of 0.15–0.5 mV/m. MBC events occupy a large population in upper‐band chorus observed in the magnetosphere, which even contribute nearly half of upper‐band chorus within L < 10RE. Our study not only provides the first statistical results of MBC events but also reveals the significant role of the lower band cascade in generating upper‐band chorus waves in the magnetosphere.
Effects of Climate Change on CO2 Concentration and Efflux in a Humic Boreal Lake: A Modeling Study
Authors: Kiuru Petri , Ojala Anne , Mammarella Ivan , Heiskanen Jouni , Kämäräinen Matti , Vesala Timo , Huttula Timo
Published: July 2018

Climate change may have notable impacts on carbon cycling in freshwater ecosystems, especially in the boreal zone. Higher atmospheric temperature and changes in annual discharge patterns and carbon loading from the catchment affect the thermal and biogeochemical conditions in a lake. We developed an extension of a one‐dimensional process‐based lake model MyLake for simulating carbon dioxide (CO2) dynamics of a boreal lake. We calibrated the model for Lake Kuivajärvi, a small humic boreal lake, for the years 2013–2014, using the extensive data available on carbon inflow and concentrations of water column CO2 and dissolved organic carbon. The lake is a constant source of CO2 to the atmosphere in the present climate. We studied the potential effects of climate change‐induced warming on lake CO2 concentration and air‐water flux using downscaled air temperature data from three recent‐generation global climate models with two alternative representative concentration pathway forcing scenarios. Literature estimates were used for climate change impacts on the lake inflow. The scenario simulations showed a 20–35% increase in the CO2 flux from the lake to the atmosphere in the scenario period 2070–2099 compared to the control period 1980–2009. In addition, we estimated possible implications of different changes in terrestrial inorganic and organic carbon loadings to the lake. The scenarios with plausible increases of 10% and 20% in CO2 and dissolved organic carbon loadings, respectively, produced increases of 2.1–2.5% and 2.2–2.3% in the annual CO2 flux.
The Mechanistic Role of the Central American Seaway in a GFDL Earth System Model. Part 1: Impacts on Global Ocean Mean State and Circulation
Authors: Sentman Lori T. , Dunne John P. , Stouffer Ronald J. , Krasting John P. , Toggweiler J. R. , Broccoli Anthony J.
Published: July 2018

To explore the mechanisms involved in the global ocean circulation response to the shoaling and closure of the Central American Seaway (CAS), we performed a suite of sensitivity experiments using the Geophysical Fluid Dynamics Laboratory Earth System Model (ESM), GFDL‐ESM2G, varying only the seaway widths and sill depths. Changes in large‐scale transport, global ocean mean state, and deep ocean circulation in all simulations are driven by the direct impacts of the seaway on global mass, heat, and salt transports. Net mass transport through the seaway into the Caribbean is 20.5–23.1 Sv with a deep CAS but only 14.1 Sv for the wide, shallow CAS. Seaway transport originates from the Antarctic Circumpolar Current in the Pacific and rejoins it in the South Atlantic, reducing the Indonesian Throughflow and transporting heat and salt southward into the South Atlantic, in contrast to present‐day and previous CAS simulations. The increased southward salt transport increases the large‐scale upper ocean density, and the freshening and warming from the changing ocean transports decreases the intermediate and deep water density. The ocean circulation pathway with a CAS traps heat in the Southern Hemisphere oceans and reduces the northern extent of Antarctic Bottom Water penetration in the Atlantic, strengthening and deepening Atlantic meridional overturning, in contrast to previous studies. In all simulations, the seaway has a profound effect on the global ocean mean state and alters deep water mass properties and circulation in the Atlantic, Indian, and Pacific basins, with implications for changing deep water circulation as a possible driver for changes in long‐term climate.
Modulation of M1/M2 polarization by capsaicin contributes to the survival of dopaminergic neurons in the lipopolysaccharide-lesioned substantia nigra in vivo
Authors: Bok Eugene , Chung Young Cheul , Kim Ki-Suk , Baik Hyung Hwan , Shin Won-Ho , Jin Byung Kwan
Published: July 2018

The present study examined the neuroprotective effects of capsaicin (CAP) and explored their underlying mechanisms in a lipopolysaccharide (LPS)-lesioned inflammatory rat model of Parkinson’s dieases (PD). LPS was unilaterally injected into the substantia nigra (SN) in the absence or presence of CAP or capsazepine (CZP, a TRPV1 antagonist). The SN tissues were prepared for immunohistochemical staining, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, western blot analysis, blood–brain barrier (BBB) permeability evaluation, and reactive oxygen species (ROS) detection. We found that CAP prevented the degeneration of nigral dopamine neurons in a dose-dependent manner and inhibited the expression of proinflammatory mediators in the LPS-lesioned SN. CAP shifted the proinflammatory M1 microglia/macrophage population to an anti-inflammatory M2 state as demonstrated by decreased expression of M1 markers (i.e., inducible nitric oxide synthase; iNOS and interleukin-6) and elevated expression of M2 markers (i.e., arginase 1 and CD206) in the SN. RT-PCR, western blotting, and immunohistochemical analysis demonstrated decreased iNOS expression and increased arginase 1 expression in the CAP-treated LPS-lesioned SN. Peroxynitrate production, reactive oxygen species levels and oxidative damage were reduced in the CAP-treated LPS-lesioned SN. The beneficial effects of CAP were blocked by CZP, indicating TRPV1 involvement. The present data indicate that CAP regulated the M1 and M2 activation states of microglia/macrophage in the LPS-lesioned SN, which resulted in the survival of dopamine neurons. It is therefore likely that TRPV1 activation by CAP has therapeutic potential for treating neurodegenerative diseases, that are associated with neuroinflammation and oxidative stress, such as PD.
Therapeutic effect of dental pulp stem cell transplantation on a rat model of radioactivity-induced esophageal injury
Authors: Zhang Chunwei , Zhang Yichi , Feng Zhenning , Zhang Feifei , Liu Zishuai , Sun Xiaoli , Ruan Mengting , Liu Mingna , Jin Shizhu
Published: July 2018

Dental pulp stem cell (DPSC) transplantation has been demonstrated to promote the regeneration and repair of tissues and organs and is a potentially effective treatment for radioactive esophageal injury. In this study, to explore the therapeutic effects of DPSCs on acute radiation-induced esophageal injury, DPSCs were cultured and transplanted into rats with acute radioactive esophageal injuries induced by radioactive 125I seeds in vivo. In the injured esophagus, PKH26-labeled DPSCs co-localized with PCNA, CK14, CD71, and integrin α6, and the expression levels of these four makers of esophageal stem cells were significantly increased. After DPSC transplantation, the injured esophagus exhibited a greater thickness. In addition, the esophageal function and inflammation recovered faster. The results demonstrated that transplanted DPSCs, which trans-differentiated into esophageal stem cells in vivo, could repair the damaged esophageal tissue.
PIK3CA mutations confer resistance to first-line chemotherapy in colorectal cancer
Authors: Wang Qiang , Shi Yan-long , Zhou Kai , Wang Li-li , Yan Ze-xuan , Liu Yu-lin , Xu Li-li , Zhao Shi-wei , Chu Hui-li , Shi Ting-ting , Ma Qing-hua , Bi Jingwang
Published: July 2018

Chemotherapy represents an important treatment option for colorectal cancer (CRC), but only half of the patients benefit from these regimens. We explored the potential predicting value and mechanism of PIK3CA mutation in CRC chemotherapy. CRC specimens from 440 patients were retrospectively collected and examined with a fluorescence PCR-based method. The correlation of first-line chemotherapy response and PIK3CA mutation was evaluated according to follow-up and medical records. The underlying mechanism of PIK3CA mutation in chemotherapy resistance was assessed with CRC tumors and primary cells. The mutation frequency of the PIK3CA gene in CRC patients was 9.55%, which was correlated with late TNM staging and lower histological grade. The CRC patients with PIK3A mutation showed worse response to first-line chemotherapy than those without PIK3CA mutation. PIK3A mutation tumor cells showed poor sensitivity to first-line chemotherapy in vitro and in vivo. PIK3CA mutation induced PI3K/Akt signaling activation to increase LGR5+ CRC stem cells survival and proliferation, from which lead to chemotherapy resistance. Furthermore, PIK3CAmutation/LGR5+ expression was an independent detrimental factor for CRC patients. Our findings indicated that PIK3CA mutation induced PI3K/Akt activation contributed to CRC stem cells survival and proliferation, from which cells further resistance to chemotherapy. PIK3CA mutation/LGR5+ expression was a potential biomarker for monitoring chemotherapy resistance in CRC.
An antisense RNA capable of modulating the expression of the tumor suppressor microRNA-34a
Authors: Serviss Jason T. , Andrews Nathanael , Van den Eynden Jimmy , Richter Felix Clemens , Houtman Miranda , Vesterlund Mattias , Schwarzmueller Laura , Johnsson Per , Larsson Erik , Grandér † Dan , Pokrovskaja Tamm Katja
Published: July 2018

The microRNA-34a is a well-studied tumor suppressor microRNA (miRNA) and a direct downstream target of TP53 with roles in several pathways associated with oncogenesis, such as proliferation, cellular growth, and differentiation. Due to its broad tumor suppressive activity, it is not surprising that miR34a expression is altered in a wide variety of solid tumors and hematological malignancies. However, the mechanisms by which miR34a is regulated in these cancers is largely unknown. In this study, we find that a long noncoding RNA transcribed antisense to the miR34a host gene, is critical for miR34a expression and mediation of its cellular functions in multiple types of human cancer. We name this long noncoding RNA lncTAM34a, and characterize its ability to facilitate miR34a expression under different types of cellular stress in both TP53-deficient and wild-type settings.
Heterogeneity in tumor chromatin-doxorubicin binding revealed by in vivo fluorescence lifetime imaging confocal endomicroscopy
Authors: Sparks Hugh , Kondo Hiroshi , Hooper Steven , Munro Ian , Kennedy Gordon , Dunsby Christopher , French Paul , Sahai Erik
Published: July 2018

We present an approach to quantify drug–target engagement using in vivo fluorescence endomicroscopy, validated with in vitro measurements. Doxorubicin binding to chromatin changes the fluorescence lifetime of histone-GFP fusions that we measure in vivo at single-cell resolution using a confocal laparo/endomicroscope. We measure both intra- and inter-tumor heterogeneity in doxorubicin chromatin engagement in a model of peritoneal metastasis of ovarian cancer, revealing striking variation in the efficacy of doxorubicin–chromatin binding depending on intra-peritoneal or intravenous delivery. Further, we observe significant variations in doxorubicin–chromatin binding between different metastases in the same mouse and between different regions of the same metastasis. The quantitative nature of fluorescence lifetime imaging enables direct comparison of drug–target engagement for different drug delivery routes and between in vitro and in vivo experiments. This uncovers different rates of cell killing for the same level of doxorubicin binding in vitro and in vivo.
TCR signal strength controls thymic differentiation of iNKT cell subsets
Authors: Tuttle Kathryn D. , Krovi S. Harsha , Zhang Jingjing , Bedel Romain , Harmacek Laura , Peterson Lisa K. , Dragone Leonard L. , Lefferts Adam , Halluszczak Catherine , Riemondy Kent , Hesselberth Jay R. , Rao Anjana , O’Connor Brian P. , Marrack Philippa , Scott-Browne James , Gapin Laurent
Published: July 2018

During development in the thymus, invariant natural killer T (iNKT) cells commit to one of three major functionally different subsets, iNKT1, iNKT2, and iNKT17. Here, we show that T cell antigen receptor (TCR) signal strength governs the development of iNKT cell subsets, with strong signaling promoting iNKT2 and iNKT17 development. Altering TCR diversity or signaling diminishes iNKT2 and iNKT17 cell subset development in a cell-intrinsic manner. Decreased TCR signaling affects the persistence of Egr2 expression and the upregulation of PLZF. By genome-wide comparison of chromatin accessibility, we identify a subset of iNKT2-specific regulatory elements containing NFAT and Egr binding motifs that is less accessible in iNKT2 cells that develop from reduced TCR signaling. These data suggest that variable TCR signaling modulates regulatory element activity at NFAT and Egr binding sites exerting a determinative influence on the dynamics of gene enhancer accessibility and the developmental fate of iNKT cells.
Subclonal mutation selection in mouse lymphomagenesis identifies known cancer loci and suggests novel candidates
Authors: Webster Philip , Dawes Joanna C. , Dewchand Hamlata , Takacs Katalin , Iadarola Barbara , Bolt Bruce J. , Caceres Juan J. , Kaczor Jakub , Dharmalingam Gopuraja , Dore Marian , Game Laurence , Adejumo Thomas , Elliott James , Naresh Kikkeri , Karimi Mohammad , Rekopoulou Katerina , Tan Ge , Paccanaro Alberto , Uren Anthony G.
Published: July 2018

Determining whether recurrent but rare cancer mutations are bona fide driver mutations remains a bottleneck in cancer research. Here we present the most comprehensive analysis of murine leukemia virus-driven lymphomagenesis produced to date, sequencing 700,000 mutations from >500 malignancies collected at time points throughout tumor development. This scale of data allows novel statistical approaches for identifying selected mutations and yields a high-resolution, genome-wide map of the selective forces surrounding cancer gene loci. We also demonstrate negative selection of mutations that may be deleterious to tumor development indicating novel avenues for therapy. Screening of two BCL2 transgenic models confirmed known drivers of human non-Hodgkin lymphoma, and implicates novel candidates including modifiers of immunosurveillance and MHC loci. Correlating mutations with genotypic and phenotypic features independently of local variance in mutation density also provides support for weakly evidenced cancer genes. An online resourcehttp://mulvdb.orgallows customized queries of the entire dataset.
Priming of dendritic cells by DNA-containing extracellular vesicles from activated T cells through antigen-driven contacts
Authors: Torralba Daniel , Baixauli Francesc , Villarroya-Beltri Carolina , Fernández-Delgado Irene , Latorre-Pellicer Ana , Acín-Pérez Rebeca , Martín-Cófreces Noa B , Jaso-Tamame Ángel Luis , Iborra Salvador , Jorge Inmaculada , González-Aseguinolaza Gloria , Garaude Johan , Vicente-Manzanares Miguel , Enríquez José Antonio , Mittelbrunn María , Sánchez-Madrid Francisco
Published: July 2018

Interaction of T cell with antigen-bearing dendritic cells (DC) results in T cell activation, but whether this interaction has physiological consequences on DC function is largely unexplored. Here we show that when antigen-bearing DCs contact T cells, DCs initiate anti-pathogenic programs. Signals of this interaction are transmitted from the T cell to the DC, through extracellular vesicles (EV) that contain genomic and mitochondrial DNA, to induce antiviral responses via the cGAS/STING cytosolic DNA-sensing pathway and expression of IRF3-dependent interferon regulated genes. Moreover, EV-treated DCs are more resistant to subsequent viral infections. In summary, our results show that T cells prime DCs through the transfer of exosomal DNA, supporting a specific role for antigen-dependent contacts in conferring protection to DCs against pathogen infection. The reciprocal communication between innate and adaptive immune cells thus allow efficacious responses to unknown threats.
Targeting TRPV1 to relieve motion sickness symptoms in mice by electroacupuncture and gene deletion
Authors: Inprasit Chanya , Lin Yi-Wen , Huang Chun-Ping , Wu Shu-Yih , Hsieh Ching-Liang
Published: July 2018

Motion sickness (MS) is an acute disorder that occurs in healthy individuals worldwide regardless of gender, age, or ethnicity. Our study used a mouse model to rule out the effects of any psychological factors related to MS and EA. Subjects were randomly separated into four groups, namely the control group (Con), motion sickness inducing group (MS), mentioning sickness inducing with electroacupuncture treatment group (EA) and motion sickness inducing only in TRPV1 knockout mice group (TRPV1−/−). The consumption of kaolin, a non-nutrient substance, was measured as a behavior observed response of an emetic reflex in a murine model. This behavior is referred to as pica behavior. Our results showed that pica behavior was observed in the MS group. Moreover, kaolin consumption in the EA group decreased to the average baseline of the control group. A similar result was observed in TRPV1 null mice. We also observed an increase of TRPV1 and related molecules in the thalamus, hypothalamic and brain stem after MS stimulation and a significant decrease in the EA and TRPV1 null groups. This is the first study to demonstrate that TRPV1 pathways are possibly associated with mechanisms of MS, and can be attended through EA or TRPV1 genetic manipulation.
Thermally assisted self-healing behavior of anhydride modified polybenzoxazines based on transesterification
Authors: Fu Feiya , Huang Meiqi , Zhang Weilan , Zhao Yang , Liu Xiangdong
Published: July 2018

A self-healing polybenzoxazine is synthesized solely based on dynamic ester bonds. For this purpose, an anhydride (succinic anhydride) was added into bisphenol F derived benzoxazine monomer before thermocuring. Owing to the transesterification of newly formed ester bonds, the thermoset network behaves as a thermoplastic at 140 °C in the presence of Zn (Ac)2, and shows self-healing properties even after multiple damage-healing cycles. Furthermore, kinetics study indicates that the transesterification is a first-order reaction and the activation energy is about 135.4 kJ/mol. This study proposes a facile and economical way to prepare self-healing polybenzoxazine. It has promising applications in coating, adhesive, and other smart materials that rely on structurally dynamic polymers.
Detecting intermittent switching leadership in coupled dynamical systems
Authors: Mwaffo Violet , Keshavan Jishnu , L. Hedrick Tyson , Humbert Sean
Published: July 2018

Leader-follower relationships are commonly hypothesized as a fundamental mechanism underlying collective behaviour in many biological and physical systems. Understanding the emergence of such behaviour is relevant in science and engineering to control the dynamics of complex systems toward a desired state. In prior works, due in part to the limitations of existing methods for dissecting intermittent causal relationships, leadership is assumed to be consistent in time and space. This assumption has been contradicted by recent progress in the study of animal behaviour. In this work, we leverage information theory and time series analysis to propose a novel and simple method for dissecting changes in causal influence. Our approach computes the cumulative influence function of a given individual on the rest of the group in consecutive time intervals and identify change in the monotonicity of the function as a change in its leadership status. We demonstrate the effectiveness of our approach to dissect potential changes in leadership on self-propelled particles where the emergence of leader-follower relationship can be controlled and on tandem flights of birds recorded in their natural environment. Our method is expected to provide a novel methodological tool to further our understanding of collective behaviour.
Hidden hearing loss in patients with Charcot-Marie-Tooth disease type 1A
Authors: Choi Ji Eun , Seok Jin Myoung , Ahn Jungmin , Ji Yoon Sang , Lee Kyung Myun , Hong Sung Hwa , Choi Byung-Ok , Moon Il Joon
Published: July 2018

The aim of this study was to investigate hidden hearing loss in patients with Charcot-Marie-Tooth disease type 1 A (CMT1A), a common inherited demyelinating neuropathy. By using pure-tone audiometry, 43 patients with CMT1A and 60 healthy controls with normal sound detection abilities were enrolled. Speech perception in quiet and noisy backgrounds, spectral ripple discrimination (SRD), and temporal modulation detection (TMD) were measured. Although CMT1A patients and healthy controls had similar pure-tone thresholds and speech perception scores in a quiet background, CMT1A patients had significantly (p < 0.05) decreased speech perception ability in a noisy background compared to controls. CMT1A patients showed significantly decreased temporal and spectral resolution (both p < 0.05). Also, auditory temporal processing of CMT1A patients was correlated with speech perception in a noisy background (r = 0.447, p < 0.01) and median motor conduction velocity (r = 0.335, p < 0.05). Therefore, we assumed that demyelination of auditory nerve in CMT1A causes defective cochlear neurotransmission, which reduces temporal resolution and speech perception in a noisy background. Because the temporal resolution test was well correlated with the degree of demyelination in auditory and peripheral motor nerves, temporal resolution testing could be performed as an additional marker for CMT1A.
Hotspots within a global biodiversity hotspot - areas of endemism are associated with high mountain ranges
Authors: Noroozi Jalil , Talebi Amir , Doostmohammadi Moslem , Rumpf Sabine B. , Linder Hans Peter , Schneeweiss Gerald M.
Published: July 2018

Conservation biology aims at identifying areas of rich biodiversity. Currently recognized global biodiversity hotspots are spatially too coarse for conservation management and identification of hotspots at a finer scale is needed. This might be achieved by identification of areas of endemism. Here, we identify areas of endemism in Iran, a major component of the Irano-Anatolian biodiversity hotspot, and address their ecological correlates. Using the extremely diverse sunflower family (Asteraceae) as our model system, five consensus areas of endemism were identified using the approach of endemicity analysis. Both endemic richness and degree of endemicity were positively related to topographic complexity and elevational range. The proportion of endemic taxa at a certain elevation (percent endemism) was not congruent with the proportion of total surface area at this elevation, but was higher in mountain ranges. While the distribution of endemic richness (i.e., number of endemic taxa) along an elevational gradient was hump-shaped peaking at mid-elevations, the percentage of endemism gradually increased with elevation. Patterns of endemic richness as well as areas of endemism identify mountain ranges as main centres of endemism, which is likely due to high environmental heterogeneity and strong geographic isolation among and within mountain ranges. The herein identified areas can form the basis for defining areas with conservation priority in this global biodiversity hotspot.
Structural and functional characterization of suramin-bound MjTX-I from Bothrops moojeni suggests a particular myotoxic mechanism
Authors: Salvador Guilherme H. M. , Dreyer Thiago R. , Gomes Antoniel A. S. , Cavalcante Walter L. G. , dos Santos Juliana I. , Gandin César A. , de Oliveira Neto Mário , Gallacci Márcia , Fontes Marcos R. M.
Published: July 2018

Local myonecrosis is the main event resulting from snakebite envenomation by theBothropsgenus and, frequently, it is not efficiently neutralized by antivenom administration. Proteases, phospholipases A2(PLA2) and PLA2-like toxins are found in venom related to muscle damage. Functional sites responsible for PLA2-like toxins activity have been proposed recently; they consist of a membrane docking-site and a membrane rupture-site. Herein, a combination of functional, biophysical and crystallographic techniques was used to characterize the interaction between suramin and MjTX-I (a PLA2-like toxin fromBothrops moojenivenom). Functionalin vitroneuromuscular assays were performed to study the biological effects of the protein-ligand interaction, demonstrating that suramin neutralizes the myotoxic effect of MjTX-I. Calorimetric assays showed two different binding events:(i)inhibitor-protein interactions and(ii)toxin oligomerization processes. These hypotheses were also corroborated with dynamic light and small angle X-ray scattering assays. The crystal structure of the MjTX-I/suramin showed a totally different interaction mode compared to other PLA2-like/suramin complexes. Thus, we suggested a novel myotoxic mechanism for MjTX-I that may be inhibited by suramin. These results can further contribute to the search for inhibitors that will efficiently counteract local myonecrosis in order to be used as an adjuvant of conventional serum therapy.
Coordinated autophagy modulation overcomes glioblastoma chemoresistance through disruption of mitochondrial bioenergetics
Authors: Kriel Jurgen , Müller-Nedebock Kristian , Maarman Gerald , Mbizana Siyasanga , Ojuka Edward , Klumperman Bert , Loos Ben
Published: July 2018

Glioblastoma Multiforme (GBM) is known to be one of the most malignant and aggressive forms of brain cancer due to its resistance to chemotherapy. Recently, GBM was found to not only utilise both oxidative phosphorylation (OXPHOS) and aerobic glycolysis, but also depend on the bulk protein degradation system known as macroautophagy to uphold proliferation. Although autophagy modulators hold great potential as adjuvants to chemotherapy, the degree of upregulation or inhibition necessary to achieve cell death sensitisation remains unknown. Therefore, this study aimed to determine the degree of autophagy modulation necessary to impair mitochondrial bioenergetics to the extent of promoting cell death onset. It was shown that coordinated upregulation of autophagy followed by its inhibition prior to chemotherapy decreased electron transfer system (ETS) and oxidative phosphorylation (OXPHOS) capacity, impaired mitochondrial fission and fusion dynamics and enhanced apoptotic cell death onset in terms of cleaved caspase 3 and cleaved PARP expression. Therefore, coordinated autophagy modulation may present a favourable avenue for improved chemotherapeutic intervention in the future.
Author Correction: Investigation on the interface between Li10GeP2S12 electrolyte and carbon conductive agents in all-solid-state lithium battery
Authors: Yoon Kyungho , Kim Jung-Joon , Seong Won Mo , Lee Myeong Hwan , Kang Kisuk
Published: July 2018

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The inducible chemical-genetic fluorescent marker FAST outperforms classical fluorescent proteins in the quantitative reporting of bacterial biofilm dynamics
Authors: Monmeyran Amaury , Thomen Philippe , Jonquière Hugo , Sureau Franck , Li Chenge , Plamont Marie-Aude , Douarche Carine , Casella Jean-François , Gautier Arnaud , Henry Nelly
Published: July 2018

To increase our understanding of bacterial biofilm complexity, real- time quantitative analyses of the living community functions are required. To reach this goal, accurate fluorescent reporters are needed. In this paper, we used the classical fluorescent genetic reporters of the GFP family and demonstrated their limits in the context of a living biofilm. We showed that fluorescence signal saturated after only a few hours of growth and related this saturation to the reduction of oxygen concentration induced by bacterial consumption. This behaviour prevents the use of GFP-like fluorescent proteins for quantitative measurement in living biofilms. To overcome this limitation, we propose the use of a recently introduced small protein tag, FAST, which is fluorescent in the presence of an exogenously applied fluorogenic dye, enabling to avoid the oxygen sensitivity issue. We compared the ability of FAST to report on biofilm growth with that of GFP and mCherry, and demonstrated the superiority of the FAST:fluorogen probes for investigating dynamics in the complex environment of a living biofilm.
Unique Lipid Signatures of Extracellular Vesicles from the Airways of Asthmatics
Authors: Hough Kenneth P. , Wilson Landon S. , Trevor Jennifer L. , Strenkowski John G. , Maina Njeri , Kim Young-Il , Spell Marion L. , Wang Yong , Chanda Diptiman , Dager Jose Rodriguez , Sharma Nirmal S. , Curtiss Miranda , Antony Veena B. , Dransfield Mark T. , Chaplin David D. , Steele Chad , Barnes Stephen , Duncan Steven R. , Prasain Jeevan K. , Thannickal Victor J. , Deshane Jessy S.
Published: July 2018

Asthma is a chronic inflammatory disease process involving the conductive airways of the human lung. The dysregulated inflammatory response in this disease process may involve multiple cell-cell interactions mediated by signaling molecules, including lipid mediators. Extracellular vesicles (EVs) are lipid membrane particles that are now recognized as critical mediators of cell-cell communication. Here, we compared the lipid composition and presence of specific lipid mediators in airway EVs purified from the bronchoalveolar lavage (BAL) fluid of healthy controls and asthmatic subjects with and without second-hand smoke (SHS) exposure. Airway exosome concentrations were increased in asthmatics, and correlated with blood eosinophilia and serum IgE levels. Frequencies of HLA-DR+and CD54+exosomes were also significantly higher in asthmatics. Lipidomics analysis revealed that phosphatidylglycerol, ceramide-phosphates, and ceramides were significantly reduced in exosomes from asthmatics compared to the non-exposed control groups. Sphingomyelin 34:1 was more abundant in exosomes of SHS-exposed asthmatics compared to healthy controls. Our results suggest that chronic airway inflammation may be driven by alterations in the composition of lipid mediators within airway EVs of human subjects with asthma.
The active site residues Gln55 and Arg73 play a key role in DNA damage bypass by S. cerevisiae Pol η
Authors: Boldinova Elizaveta O. , Ignatov Artem , Kulbachinskiy Andrey , Makarova Alena V.
Published: July 2018

Eukaryotic DNA polymerase eta (Pol η) plays a key role in the efficient and accurate DNA translesion synthesis (TLS) opposite UV-induced thymine dimers. Pol η is also involved in bypass of many other DNA lesions but possesses low fidelity on undamaged DNA templates. To better understand the mechanism of DNA synthesis by Pol η we investigated substitutions of evolutionary conserved active site residues Gln55 and Arg73 in Saccharomyces cerevisiae Pol η. We analyzed the efficiency and fidelity of DNA synthesis by the mutant Pol η variants opposite thymine dimers, abasic site, thymine glycol, 8-oxoguanine and on undamaged DNA. Substitutions Q55A and R73A decreased the catalytic activity and significantly affected DNA damage bypass by Pol η. In particular, the Q55A substitution reduced the efficiency of thymine dimers bypass, R73A had a stronger effect on the TLS-activity opposite abasic site, while both substitutions impaired replication opposite thymine glycol. Importantly, the R73A substitution also increased the fidelity of Pol η. Altogether, these results reveal a key role of residues Gln55 and Arg73 in DNA synthesis opposite various types of DNA lesions and highlight the evolutionary importance of the Pol η TLS function at the cost of DNA replication accuracy.
Shifts of Faecal Microbiota During Sporadic Colorectal Carcinogenesis
Authors: Mori Giorgia , Rampelli Simone , Orena Beatrice Silvia , Rengucci Claudia , De Maio Giulia , Barbieri Giulia , Passardi Alessandro , Casadei Gardini Andrea , Frassineti Giovanni Luca , Gaiarsa Stefano , Albertini Alessandra M. , Ranzani Guglielmina Nadia , Calistri Daniele , Pasca Maria Rosalia
Published: July 2018

Gut microbiota has been implicated in the etiopathogenesis of colorectal cancer. The development of colorectal cancer is a multistep process by which healthy epithelium slowly develops into preneoplastic lesions, which in turn progress into malignant carcinomas over time. In particular, sporadic colorectal cancers can arise from adenomas (about 85% of cases) or serrated polyps through the “adenoma-carcinoma” or the “serrated polyp-carcinoma” sequences, respectively. In this study, we performed 16 S rRNA gene sequencing of bacterial DNA extracted from faecal samples to compare the microbiota of healthy subjects and patients with different preneoplastic and neoplastic lesions. We identified putative microbial biomarkers associated with stage-specific progression of colorectal cancer. In particular, bacteria belonging to the Firmicutes and Actinobacteria phyla, as well as members of the Lachnospiraceae family, proved to be specific of the faecal microbiota of patients with preneoplastic lesions, including adenomas and hyperplastic polyps. On the other hand, two families of the Proteobacteria phylum, Alcaligeneaceae and Enterobacteriaceae, with Sutterella and Escherichia/Shigella being the most representative genera, appeared to be associated with malignancy. These findings, once confirmed on larger cohorts of patients, can represent an important step towards the development of more effective diagnostic strategies.
Dynamic behavior of DNA topoisomerase IIβ in response to DNA double-strand breaks
Authors: Morotomi-Yano Keiko , Saito Shinta , Adachi Noritaka , Yano Ken-ichi
Published: July 2018

DNA topoisomerase II (Topo II) is crucial for resolving topological problems of DNA and plays important roles in various cellular processes, such as replication, transcription, and chromosome segregation. Although DNA topology problems may also occur during DNA repair, the possible involvement of Topo II in this process remains to be fully investigated. Here, we show the dynamic behavior of human Topo IIβ in response to DNA double-strand breaks (DSBs), which is the most harmful form of DNA damage. Live cell imaging coupled with site-directed DSB induction by laser microirradiation demonstrated rapid recruitment of EGFP-tagged Topo IIβ to the DSB site. Detergent extraction followed by immunofluorescence showed the tight association of endogenous Topo IIβ with DSB sites. Photobleaching analysis revealed that Topo IIβ is highly mobile in the nucleus. The Topo II catalytic inhibitors ICRF-187 and ICRF-193 reduced the Topo IIβ mobility and thereby prevented Topo IIβ recruitment to DSBs. Furthermore, Topo IIβ knockout cells exhibited increased sensitivity to bleomycin and decreased DSB repair mediated by homologous recombination (HR), implicating the role of Topo IIβ in HR-mediated DSB repair. Taken together, these results highlight a novel aspect of Topo IIβ functions in the cellular response to DSBs.
Thyroid cancer cells in space during the TEXUS-53 sounding rocket mission – The THYROID Project
Authors: Kopp Sascha , Krüger Marcus , Feldmann Stefan , Oltmann Hergen , Schütte Andreas , Schmitz Burkhard , Bauer Johann , Schulz Herbert , Saar Kathrin , Huebner Norbert , Wehland Markus , Nassef Mohamed Zakaria , Melnik Daniela , Meltendorf Stefan , Infanger Manfred , Grimm Daniela
Published: July 2018

Human follicular thyroid cancer cells (FTC-133) were sent to space via a sounding rocket during the TEXUS-53 mission to determine the impact of short-term microgravity on these cells. To enable cell culture and fixation in real microgravity, an automated experiment container (EC) was constructed. In order to ensure safe cell culture, cell-chambers consisting of polycarbonate (PC) material were used. They were highly biocompatible as proved by measuring cell survival using Annexin V flow cytometry. In the follow-up experiment, FTC-133 cells were sent to space via a sounding rocket and were fixed before and after the microgravity (µg) phase with RNAlater. In addition, cells were tested for reactions on hypergravity (hyper-g) as much as 18 g to determine whether worst case acceleration during launch can have an influence on the cells. We investigated genes belonging to biological processes such as cytoskeleton, cell adhesion, tumor growth, angiogenesis and apoptosis. Pathway analyses revealed central functions of VEGFA and EGF. EGF upregulates aspartate beta-hydroxylase (ASPH) which is influencing CASP3. Hyper-g induced a significant up-regulation of TUBB1, VIM, RDX, CAV1, VEGFA and BCL2. FTC-133 cells grown in an automated EC exposed to µg revealed moderate gene expression changes indicating their survival in orbit.