bluuebunny/crossref_metadata_2025 huggingface dataset:
Selbstregulation als Mediator für den Zusammenhang zwischen Erziehung und der Entwicklung von Verhaltensproblemen und sozial-emotionalen Kompetenzen bei Grundschulkindern
Authors: Rademacher Annika , Koglin Ute
Published: December 2019

Zusammenfassung. Der Einfluss elterlicher Erziehung auf die Entwicklung von externalisierenden Verhaltensproblemen und sozial-emotionalen Kompetenzen bei Kindern wurde in vielzähligen Studien hervorgehoben. Zu den erklärenden Mechanismen für diese Zusammenhänge liegen bisher nur wenige Erkenntnisse vor. Das Ziel dieser Studie ist es, die Rolle der kindlichen Selbstregulation als möglichen Mediator für den Einfluss von den Erziehungsstilen Liebe, Strenge und Selbstständigkeit auf die Entwicklung von sozial-emotionalen Kompetenzen und externalisierenden Problemverhaltensweisen zu untersuchen. Die vorliegenden Pfadanalysen basieren auf Fragebogendaten über N = 445 Kinder und ihre Familien. Die Ergebnisse dieser Studie zeigen indirekte Effekte für die Zusammenhänge zwischen dem Erziehungsstil und kindlichen Verhaltensproblemen und Kompetenzen auf. Die Fähigkeit zur Selbstregulation kann in dieser Beziehung als eine Art Weiche für die Entwicklung von Kindern verstanden werden.
Explaining Perceived Interactivity Effects on Attitudinal Responses
Authors: Rauwers Fabiënne , Voorveld Hilde A. M. , Neijens Peter C.
Published: December 2019

Abstract. In the context of digital magazines, this study investigates why higher levels of perceived interactivity improve consumers’ attitudinal responses, and which interactive features have the ability to elicit these stronger interactivity perceptions. To examine this, a field experiment was conducted in which participants ( n = 197) used a digital magazine with either (a) external communication features (facilitating social interactions on external platforms, like Facebook), (b) internal communication features (facilitating social interactions within the digital magazine itself), or (c) no communication features. Results revealed that both feature types increased consumers’ interactivity perceptions, but that the effects of the internal communication features were the strongest. Subsequently, mediation analyses revealed that the higher levels of perceived interactivity elicited stronger feelings of flow and enjoyment through which the positive findings of perceived interactivity on consumers’ attitudinal responses can be explained.
Sinking of Gelatinous Zooplankton Biomass Increases Deep Carbon Transfer Efficiency Globally
Authors: Lebrato Mario , Pahlow Markus , Frost Jessica R. , Küter Marie , de Jesus Mendes Pedro , Molinero Juan‐Carlos , Oschlies Andreas
Published: December 2019

Gelatinous zooplankton (Cnidaria, Ctenophora, and Urochordata, namely, Thaliacea) are ubiquitous members of plankton communities linking primary production to higher trophic levels and the deep ocean by serving as food and transferring “jelly‐carbon” (jelly‐C) upon bloom collapse. Global biomass within the upper 200 m reaches 0.038 Pg C, which, with a 2–12 months life span, serves as the lower limit for annual jelly‐C production. Using over 90,000 data points from 1934 to 2011 from the Jellyfish Database Initiative as an indication of global biomass (JeDI: http://jedi.nceas.ucsb.edu, http://www.bco‐dmo.org/dataset/526852), upper ocean jelly‐C biomass and production estimates, organism vertical migration, jelly‐C sinking rates, and water column temperature profiles from GLODAPv2, we quantitatively estimate jelly‐C transfer efficiency based on Longhurst Provinces. From the upper 200 m production estimate of 0.038 Pg C year−1, 59–72% reaches 500 m, 46–54% reaches 1,000 m, 43–48% reaches 2,000 m, 32–40% reaches 3,000 m, and 25–33% reaches 4,500 m. This translates into ~0.03, 0.02, 0.01, and 0.01 Pg C year−1, transferred down to 500, 1,000, 2,000, and 4,500 m, respectively. Jelly‐C fluxes and transfer efficiencies can occasionally exceed phytodetrital‐based sediment trap estimates in localized open ocean and continental shelves areas under large gelatinous blooms or jelly‐C mass deposition events, but this remains ephemeral and transient in nature. This transfer of fast and permanently exported carbon reaching the ocean interior via jelly‐C constitutes an important component of the global biological soft‐tissue pump, and should be addressed in ocean biogeochemical models, in particular, at the local and regional scale.
Future Projection of Extreme Heavy Snowfall Events With a 5‐km Large Ensemble Regional Climate Simulation
Authors: Sasai T. , Kawase H. , Kanno Y. , Yamaguchi J. , Sugimoto S. , Yamazaki T. , Sasaki H. , Fujita M. , Iwasaki T.
Published: December 2019

We have recently experienced several heavy snowfall events, but still do not sufficiently understand how global warming will impact changes in local extreme snowfall events. The analysis relevant to the extreme events requires ensemble experiments with high‐resolution regional climate modeling. In this study, we use a large number of ensemble warming projections downscaled dynamically to 5‐km grids to examine the differences in distribution and mechanism in extreme snowfall events over Japan between present and future climates. Japan has two typical snowfall patterns, the winter monsoon and the south coast cyclone patterns. The domain‐averaged amount of extreme snowfall in the south coast cyclone pattern regions appear to decrease with the rise in temperatures. Meanwhile, the winter monsoon pattern regions showed little change as the increases in extreme snowfall in the mountainous areas are canceled out by the decrease in the coastal areas. Based on the existing mechanism of normal snowfall, the increase in mountain snow is caused by a temporary intensification of cold air outbreaks. The amount of the cold air blowing from Japan Sea clearly increases only during the days preceding the extreme snowfall event, and as the cold dry air obtains more latent heat over the ocean, the precipitable water vapor increases. The winter monsoon then transports this air over land where the intensification of precipitation results from orographic updraft. This sequence of processes beginning with cold air outbreaks may have a stronger control over extreme snowfall phenomena on the warmer field.
Meteorological Imagery for the Geostationary Lightning Mapper
Authors: Bruning Eric C. , Tillier Clemens E. , Edgington Samantha F. , Rudlosky Scott D. , Zajic Joe , Gravelle Chad , Foster Matt , Calhoun Kristin M. , Campbell P. Adrian , Stano Geoffrey T. , Schultz Christopher J. , Meyer Tiffany C.
Published: December 2019

The Geostationary Lightning Mapper (GLM) on the Geostationary Operational Environmental Satellite‐R series of weather satellites provides point geolocations of lightning flashes that are further comprised of a hierarchy of geolocated groups and events. This study describes an open‐source method for reconstruction of imagery from those point detections that retains the quantitative physical measurements made by GLM, restores the spatial footprint of the events, and connects that spatial footprint to the groups and flashes. Meteorological signals are demonstrated to be more apparent in the gridded imagery than in the point detections, leading to their adoption by the United States National Weather Service as the first GLM product available in their real‐time displays. Analysis of a mesoscale convective system over Argentina confirms that there is a class of propagating lightning observed by GLM (distinct from that in storm cores) that can be visualized and quantified using our imagery‐based approach.
Hydrogenation of the Martian Core by Hydrated Mantle Minerals With Implications for the Early Dynamo
Authors: O'Rourke J. G. , Shim S. ‐H.
Published: December 2019

Mars lacks an internally generated magnetic field today. Crustal remanent magnetism and meteorites indicate that a dynamo existed after accretion but died roughly four billion years ago. Standard models rely on core/mantle heat flow dropping below the adiabatic limit for thermal convection in the core. However, rapid core cooling after the Noachian is favored instead to produce long‐lived mantle plumes and magmatism at volcanic provinces such as Tharsis and Elysium. Hydrogenation of the core could resolve this apparent contradiction by impeding the dynamo while core/mantle heat flow is superadiabatic. Here we present parameterized models for the rate at which mantle convection delivers hydrogen into the core. Our models suggest that most of the water that the mantle initially contained was effectively lost to the core. We predict that the mantle became increasingly ironrich over time and a stratified layer awaits detection in the uppermost core—analogous to the E′ layer atop Earth's core but likely thicker than alternative sources of stratification in the Martian core such as iron snow. Entraining buoyant, hydrogen‐rich fluid downward in the core subtracts gravitational energy from the total dissipation budget for the dynamo. The calculated fluxes of hydrogen are high enough to potentially reduce the lifetime of the dynamo by several hundred million years or longer relative to conventional model predictions. Future work should address the complicated interactions between the stratified, hydrogen‐rich layer and convection in the underlying core.
Water Vapor Vertical Profiles on Mars in Dust Storms Observed by TGO/NOMAD
Authors: Aoki S. , Vandaele A. C. , Daerden F. , Villanueva G. L. , Liuzzi G. , Thomas I. R. , Erwin J. T. , Trompet L. , Robert S. , Neary L. , Viscardy S. , Clancy R. T. , Smith M. D. , Lopez‐Valverde M. A. , Hill B. , Ristic B. , Patel M. R. , Bellucci G. , Lopez‐Moreno J.‐J. ,   the NOMAD team
Published: December 2019

It has been suggested that dust storms efficiently transport water vapor from the near‐surface to the middle atmosphere on Mars. Knowledge of the water vapor vertical profile during dust storms is important to understand water escape. During Martian Year 34, two dust storms occurred on Mars: a global dust storm (June to mid‐September 2018) and a regional storm (January 2019). Here we present water vapor vertical profiles in the periods of the two dust storms (Ls = 162–260° and Ls = 298–345°) from the solar occultation measurements by Nadir and Occultation for Mars Discovery (NOMAD) onboard ExoMars Trace Gas Orbiter (TGO). We show a significant increase of water vapor abundance in the middle atmosphere (40–100 km) during the global dust storm. The water enhancement rapidly occurs following the onset of the storm (Ls~190°) and has a peak at the most active period (Ls~200°). Water vapor reaches very high altitudes (up to 100 km) with a volume mixing ratio of ~50 ppm. The water vapor abundance in the middle atmosphere shows high values consistently at 60°S‐60°N at the growth phase of the dust storm (Ls = 195°–220°), and peaks at latitudes greater than 60°S at the decay phase (Ls = 220°–260°). This is explained by the seasonal change of meridional circulation: from equinoctial Hadley circulation (two cells) to the solstitial one (a single pole‐to‐pole cell). We also find a conspicuous increase of water vapor density in the middle atmosphere at the period of the regional dust storm (Ls = 322–327°), in particular at latitudes greater than 60°S.
Do bedroom screens and the mealtime environment shape different trajectories of child overweight and obesity? Research using the Growing Up in Scotland study
Authors: Parkes Alison , Green Michael , Pearce Anna
Published: December 2019

Objective

To investigate how mealtime setting, mealtime interaction and bedroom screens are associated with different trajectories of child overweight and obesity, using a population sample.

Methods

Growth mixture modelling used data from children in the Growing Up in Scotland Study born in 2004/5 (boys n = 2085, girls n = 1991) to identify trajectories of overweight or obesity across four time points, from 46 to 122 months. Using data from children present at all sweeps, and combining sexes (n = 2810), mutually adjusted associations between primary exposures (mealtime setting, mealtime interaction and bedroom screens) and trajectory class were explored in multinomial models; controlling for early life factors, household organisation and routines, and children’s diet patterns, overall screen use, physical activity and sleep.

Results

Five trajectories were identified in both sexes: Low Risk (68% of sample), Decreasing Overweight (9%), Increasing Overweight (12%), High/Stable Overweight (6%) and High/Increasing Obesity (5%). Compared with the Low Risk trajectory, High/Increasing Obesity and High/Stable Overweight trajectories were characterised by early increases in bedroom screen access (respective relative risk ratios (RRR) and 95% confidence intervals: 2.55 [1.30–5.00]; 1.62 [1.01–2.57]). An informal meal setting (involving mealtime screen use, not eating in a dining area and not sitting at a table) characterised the High/Increasing Obesity and Increasing Overweight trajectories (respective RRRs compared with Low Risk trajectory: 3.67 [1.99–6.77]; 1.75 [1.17–2.62]). Positive mealtime interaction was associated with membership of the Increasing Overweight trajectory (RRR 1.64 [1.13–2.36]).

Conclusion

Bedroom screen access and informal mealtime environments were associated with higher-risk overweight and obesity trajectories in a representative sample of Scottish children, after adjusting for a wide range of confounders. Findings may challenge the notion that positive mealtime interaction is protective. Promoting mealtimes in a screen-free dining area and removing screens from bedrooms may help combat childhood obesity.
Correction: Cardiomyocyte-specific disruption of Cathepsin K protects against doxorubicin-induced cardiotoxicity
Authors: Guo Rui , Hua Yinan , Ren Jun , Bornfeldt Karin E. , Nair Sreejayan
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Colloidal quantum dot molecules manifesting quantum coupling at room temperature
Authors: Cui Jiabin , Panfil Yossef E. , Koley Somnath , Shamalia Doaa , Waiskopf Nir , Remennik Sergei , Popov Inna , Oded Meirav , Banin Uri
Published: December 2019

Coupling of atoms is the basis of chemistry, yielding the beauty and richness of molecules. We utilize semiconductor nanocrystals as artificial atoms to form nanocrystal molecules that are structurally and electronically coupled. CdSe/CdS core/shell nanocrystals are linked to form dimers which are then fused via constrained oriented attachment. The possible nanocrystal facets in which such fusion takes place are analyzed with atomic resolution revealing the distribution of possible crystal fusion scenarios. Coherent coupling and wave-function hybridization are manifested by a redshift of the band gap, in agreement with quantum mechanical simulations. Single nanoparticle spectroscopy unravels the attributes of coupled nanocrystal dimers related to the unique combination of quantum mechanical tunneling and energy transfer mechanisms. This sets the stage for nanocrystal chemistry to yield a diverse selection of coupled nanocrystal molecules constructed from controlled core/shell nanocrystal building blocks. These are of direct relevance for numerous applications in displays, sensing, biological tagging and emerging quantum technologies.
Sexual dimorphism and the role of estrogen in the immune microenvironment of liver metastases
Authors: Milette Simon , Hashimoto Masakazu , Perrino Stephanie , Qi Shu , Chen Michely , Ham Boram , Wang Ni , Istomine Roman , Lowy Andrew M. , Piccirillo Ciriaco A. , Brodt Pnina
Published: December 2019

Liver metastases (LM) remain a major cause of cancer-associated death and a clinical challenge. Here we explore a sexual dimorphism observed in the regulation of the tumor immune microenvironment (TIME) of LM, wherein the accumulation of myeloid-derived suppressor cells (MDSC) and regulatory T cells in colon and lung carcinoma LM is TNFR2-dependent in female, but not in male mice. In ovariectomized mice, a marked reduction is observed in colorectal, lung and pancreatic carcinoma LM that is reversible by estradiol reconstitution. This is associated with reduced liver MDSC accumulation, increased interferon-gamma (IFN-γ) and granzyme B production in CD8+ T cells and reduced TNFR2, IDO2, TDO and Serpin B9 expression levels. Treatment with tamoxifen increases liver cytotoxic T cell accumulation and reduces colon cancer LM. The results identify estrogen as a regulator of a pro-metastatic immune microenvironment in the liver and a potential target in the management of liver metastatic disease.
A transposable element insertion is associated with an alternative life history strategy
Authors: Woronik Alyssa , Tunström Kalle , Perry Michael W. , Neethiraj Ramprasad , Stefanescu Constanti , Celorio-Mancera Maria de la Paz , Brattström Oskar , Hill Jason , Lehmann Philipp , Käkelä Reijo , Wheat Christopher W.
Published: December 2019

Tradeoffs affect resource allocation during development and result in fitness consequences that drive the evolution of life history strategies. Yet despite their importance, we know little about the mechanisms underlying life history tradeoffs. Many species of Colias butterflies exhibit an alternative life history strategy (ALHS) where females divert resources from wing pigment synthesis to reproductive and somatic development. Due to this reallocation, a wing color polymorphism is associated with the ALHS: either yellow/orange or white. Here we map the locus associated with this ALHS in Colias crocea to a transposable element insertion located downstream of the Colias homolog of BarH-1, a homeobox transcription factor. Using CRISPR/Cas9 gene editing, antibody staining, and electron microscopy we find white-specific expression of BarH-1 suppresses the formation of pigment granules in wing scales and gives rise to white wing color. Lipid and transcriptome analyses reveal physiological differences associated with the ALHS. Together, these findings characterize a mechanism for a female-limited ALHS.
SAM-VI riboswitch structure and signature for ligand discrimination
Authors: Sun Aiai , Gasser Catherina , Li Fudong , Chen Hao , Mair Stefan , Krasheninina Olga , Micura Ronald , Ren Aiming
Published: December 2019

Riboswitches are metabolite-sensing, conserved domains located in non-coding regions of mRNA that are central to regulation of gene expression. Here we report the first three-dimensional structure of the recently discovered S-adenosyl-L-methionine responsive SAM-VI riboswitch. SAM-VI adopts a unique fold and ligand pocket that are distinct from all other known SAM riboswitch classes. The ligand binds to the junctional region with its adenine tightly intercalated and Hoogsteen base-paired. Furthermore, we reveal the ligand discrimination mode of SAM-VI by additional X-ray structures of this riboswitch bound to S-adenosyl-L-homocysteine and a synthetic ligand mimic, in combination with isothermal titration calorimetry and fluorescence spectroscopy to explore binding thermodynamics and kinetics. The structure is further evaluated by analysis of ligand binding to SAM-VI mutants. It thus provides a thorough basis for developing synthetic SAM cofactors for applications in chemical and synthetic RNA biology.
Elimination of fukutin reveals cellular and molecular pathomechanisms in muscular dystrophy-associated heart failure
Authors: Ujihara Yoshihiro , Kanagawa Motoi , Mohri Satoshi , Takatsu Satomi , Kobayashi Kazuhiro , Toda Tatsushi , Naruse Keiji , Katanosaka Yuki
Published: December 2019

Heart failure is the major cause of death for muscular dystrophy patients, however, the molecular pathomechanism remains unknown. Here, we show the detailed molecular pathogenesis of muscular dystrophy-associated cardiomyopathy in mice lacking the fukutin gene (Fktn), the causative gene for Fukuyama muscular dystrophy. Although cardiac Fktn elimination markedly reduced α-dystroglycan glycosylation and dystrophin-glycoprotein complex proteins in sarcolemma at all developmental stages, cardiac dysfunction was observed only in later adulthood, suggesting that membrane fragility is not the sole etiology of cardiac dysfunction. During young adulthood, Fktn-deficient mice were vulnerable to pathological hypertrophic stress with downregulation of Akt and the MEF2-histone deacetylase axis. Acute Fktn elimination caused severe cardiac dysfunction and accelerated mortality with myocyte contractile dysfunction and disordered Golgi-microtubule networks, which were ameliorated with colchicine treatment. These data reveal fukutin is crucial for maintaining myocyte physiology to prevent heart failure, and thus, the results may lead to strategies for therapeutic intervention.
Impacts of Zika emergence in Latin America on endemic dengue transmission
Authors: Borchering Rebecca K. , Huang Angkana T. , Mier-y-Teran-Romero Luis , Rojas Diana P. , Rodriguez-Barraquer Isabel , Katzelnick Leah C. , Martinez Silvio D. , King Gregory D. , Cinkovich Stephanie C. , Lessler Justin , Cummings Derek A. T.
Published: December 2019

In 2015 and 2016, Zika virus (ZIKV) swept through dengue virus (DENV) endemic areas of Latin America. These viruses are of the same family, share a vector and may interact competitively or synergistically through human immune responses. We examine dengue incidence from Brazil and Colombia before, during, and after the Zika epidemic. We find evidence that dengue incidence was atypically low in 2017 in both countries. We investigate whether subnational Zika incidence is associated with changes in dengue incidence and find mixed results. Using simulations with multiple assumptions of interactions between DENV and ZIKV, we find cross-protection suppresses incidence of dengue following Zika outbreaks and low periods of dengue incidence are followed by resurgence. Our simulations suggest correlations in DENV and ZIKV reproduction numbers could complicate associations between ZIKV incidence and post-ZIKV DENV incidence and that periods of low dengue incidence are followed by large increases in dengue incidence.
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome
Authors: Sharma Deepti , De Falco Louis , Padavattan Sivaraman , Rao Chang , Geifman-Shochat Susana , Liu Chuan-Fa , Davey Curt A.
Published: December 2019

The poly(ADP-ribose) polymerase, PARP1, plays a key role in maintaining genomic integrity by detecting DNA damage and mediating repair. γH2A.X is the primary histone marker for DNA double-strand breaks and PARP1 localizes to H2A.X-enriched chromatin damage sites, but the basis for this association is not clear. We characterize the kinetics of PARP1 binding to a variety of nucleosomes harbouring DNA double-strand breaks, which reveal that PARP1 associates faster with (γ)H2A.X- versus H2A-nucleosomes, resulting in a higher affinity for the former, which is maximal for γH2A.X-nucleosome that is also the activator eliciting the greatest poly-ADP-ribosylation catalytic efficiency. The enhanced activities with γH2A.X-nucleosome coincide with increased accessibility of the DNA termini resulting from the H2A.X-Ser139 phosphorylation. Indeed, H2A- and (γ)H2A.X-nucleosomes have distinct stability characteristics, which are rationalized by mutational analysis and (γ)H2A.X-nucleosome core crystal structures. This suggests that the γH2A.X epigenetic marker directly facilitates DNA repair by stabilizing PARP1 association and promoting catalysis.
HDAC3 maintains oocyte meiosis arrest by repressing amphiregulin expression before the LH surge
Authors: Wang Huarong , Cai Han , Wang Xiao , Zhang Meiling , Liu Bingying , Chen Ziqi , Yang Tingting , Fang Junshun , Zhang Yanhao , Liu Wei , Han Jun , Guo Qirui , Zhang Hua , Wang Haibin , Xia Guoliang , Wang Chao
Published: December 2019

It is known that granulosa cells (GCs) mediate gonadotropin-induced oocyte meiosis resumption by releasing EGF-like factors in mammals, however, the detailed molecular mechanisms remain unclear. Here, we demonstrate that luteinizing hormone (LH) surge-induced histone deacetylase 3 (HDAC3) downregulation in GCs is essential for oocyte maturation. Before the LH surge, HDAC3 is highly expressed in GCs. Transcription factors, such as FOXO1, mediate recruitment of HDAC3 to the amphiregulin (Areg) promoter, which suppresses AREG expression. With the LH surge, decreased HDAC3 in GCs enables histone H3K14 acetylation and binding of the SP1 transcription factor to the Areg promoter to initiate AREG transcription and oocyte maturation. Conditional knockout of Hdac3 in granulosa cells in vivo or inhibition of HDAC3 activity in vitro promotes the maturation of oocytes independent of LH. Taking together, HDAC3 in GCs within ovarian follicles acts as a negative regulator of EGF-like growth factor expression before the LH surge.
Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA
Authors: Caldas Paulo , López-Pelegrín Mar , Pearce Daniel J. G. , Budanur Nazmi Burak , Brugués Jan , Loose Martin
Published: December 2019

During bacterial cell division, the tubulin-homolog FtsZ forms a ring-like structure at the center of the cell. This Z-ring not only organizes the division machinery, but treadmilling of FtsZ filaments was also found to play a key role in distributing proteins at the division site. What regulates the architecture, dynamics and stability of the Z-ring is currently unknown, but FtsZ-associated proteins are known to play an important role. Here, using an in vitro reconstitution approach, we studied how the well-conserved protein ZapA affects FtsZ treadmilling and filament organization into large-scale patterns. Using high-resolution fluorescence microscopy and quantitative image analysis, we found that ZapA cooperatively increases the spatial order of the filament network, but binds only transiently to FtsZ filaments and has no effect on filament length and treadmilling velocity. Together, our data provides a model for how FtsZ-associated proteins can increase the precision and stability of the bacterial cell division machinery in a switch-like manner.
IL-17+ CD8+ T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis
Authors: Lückel Christina , Picard Felix , Raifer Hartmann , Campos Carrascosa Lucia , Guralnik Anna , Zhang Yajuan , Klein Matthias , Bittner Stefan , Steffen Falk , Moos Sonja , Marini Federico , Gloury Renee , Kurschus Florian C. , Chao Ying-Yin , Bertrams Wilhelm , Sexl Veronika , Schmeck Bernd , Bonetti Lynn , Grusdat Melanie , Lohoff Michael , Zielinski Christina E. , Zipp Frauke , Kallies Axel , Brenner Dirk , Berger Michael , Bopp Tobias , Tackenberg Björn , Huber Magdalena
Published: December 2019

IL-17-producing CD8+ (Tc17) cells are enriched in active lesions of patients with multiple sclerosis (MS), suggesting a role in the pathogenesis of autoimmunity. Here we show that amelioration of MS by dimethyl fumarate (DMF), a mechanistically elusive drug, associates with suppression of Tc17 cells. DMF treatment results in reduced frequency of Tc17, contrary to Th17 cells, and in a decreased ratio of the regulators RORC-to-TBX21, along with a shift towards cytotoxic T lymphocyte gene expression signature in CD8+ T cells from MS patients. Mechanistically, DMF potentiates the PI3K-AKT-FOXO1-T-BET pathway, thereby limiting IL-17 and RORγt expression as well as STAT5-signaling in a glutathione-dependent manner. This results in chromatin remodeling at the Il17 locus. Consequently, T-BET-deficiency in mice or inhibition of PI3K-AKT, STAT5 or reactive oxygen species prevents DMF-mediated Tc17 suppression. Overall, our data disclose a DMF-AKT-T-BET driven immune modulation and suggest putative therapy targets in MS and beyond.
Slow recombination of spontaneously dissociated organic fluorophore excitons
Authors: Yamanaka Takahiko , Nakanotani Hajime , Adachi Chihaya
Published: December 2019

The harvesting of excitons as luminescence by organic fluorophores forms the basis of light-emitting applications. Although high photoluminescence quantum yield is essential for efficient light emission, concentration-dependent quenching of the emissive exciton is generally observed. Here we demonstrate generation and accumulation of concentration-dependent “long-lived” (i.e., over 1 h) photo-generated carriers and the successive release of their energy as electroluminescence in a solid-state film containing a polar fluorophore. While fluorophore excitons are generally believed to be stable because of their high exciton binding energies, our observations show that some of the excitons undergo spontaneous exciton dissociation in a solid-state film by spontaneous orientation polarization even without an external electric field. These results lead to the reconsideration of the meaning of “luminescence quantum yield” for the solid films containing polar organic molecules because it can differ for optical and electrical excitation.
Guanidinocalix[5]arene for sensitive fluorescence detection and magnetic removal of perfluorinated pollutants
Authors: Zheng Zhe , Yu Huijuan , Geng Wen-Chao , Hu Xin-Yue , Wang Yu-Ying , Li Zhihao , Wang Yuefei , Guo Dong-Sheng
Published: December 2019

Perfluorinated alkyl substances, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are toxic materials that are known to globally contaminate water, air, and soil resources. Strategies for the simultaneous detection and removal of these compounds are desired to address this emerging health and environmental issue. Herein, we develop a type of guanidinocalix[5]arene that can selectively and strongly bind to PFOS and PFOA, which we use to demonstrate the sensitive and quantitative detection of these compounds in contaminated water through a fluorescent indicator displacement assay. Moreover, by co-assembling iron oxide nanoparticle with the amphiphilic guanidinocalix[5]arene, we are able to use simple magnetic absorption and filtration to efficiently remove PFOS and PFOA from contaminated water. This supramolecular approach that uses both molecular recognition and self-assembly of macrocyclic amphiphiles is promising for the detection and remediation of water pollution.
Super-resolution provided by the arbitrarily strong superlinearity of the blackbody radiation
Authors: Graciani Guillaume , Amblard François
Published: December 2019

Blackbody radiation is a fundamental phenomenon in nature, and its explanation by Planck marks a cornerstone in the history of Physics. In this theoretical work, we show that the spectral radiance given by Planck’s law is strongly superlinear with temperature, with an arbitrarily large local exponent for decreasing wavelengths. From that scaling analysis, we propose a new concept of super-resolved detection and imaging: if a focused beam of energy is scanned over an object that absorbs and linearly converts that energy into heat, a highly nonlinear thermal radiation response is generated, and its point spread function can be made arbitrarily smaller than the excitation beam focus. Based on a few practical scenarios, we propose to extend the notion of super-resolution beyond its current niche in microscopy to various kinds of excitation beams, a wide range of spatial scales, and a broader diversity of target objects.
Genomes of early-diverging streptophyte algae shed light on plant terrestrialization
Authors: Wang Sibo , Li Linzhou , Li Haoyuan , Sahu Sunil Kumar , Wang Hongli , Xu Yan , Xian Wenfei , Song Bo , Liang Hongping , Cheng Shifeng , Chang Yue , Song Yue , Çebi Zehra , Wittek Sebastian , Reder Tanja , Peterson Morten , Yang Huanming , Wang Jian , Melkonian Barbara , Van de Peer Yves , Xu Xun , Wong Gane Ka-Shu , Melkonian Michael , Liu Huan , Liu Xin
Published: December 2019

Mounting evidence suggests that terrestrialization of plants started in streptophyte green algae, favoured by their dual existence in freshwater and subaerial/terrestrial environments. Here, we present the genomes of Mesostigma viride and Chlorokybus atmophyticus, two sister taxa in the earliest-diverging clade of streptophyte algae dwelling in freshwater and subaerial/terrestrial environments, respectively. We provide evidence that the common ancestor of M. viride and C. atmophyticus (and thus of streptophytes) had already developed traits associated with a subaerial/terrestrial environment, such as embryophyte-type photorespiration, canonical plant phytochrome, several phytohormones and transcription factors involved in responses to environmental stresses, and evolution of cellulose synthase and cellulose synthase-like genes characteristic of embryophytes. Both genomes differed markedly in genome size and structure, and in gene family composition, revealing their dynamic nature, presumably in response to adaptations to their contrasting environments. The ancestor of M. viride possibly lost several genomic traits associated with a subaerial/terrestrial environment following transition to a freshwater habitat.
Rapid MinION profiling of preterm microbiota and antimicrobial-resistant pathogens
Authors: Leggett Richard M. , Alcon-Giner Cristina , Heavens Darren , Caim Shabhonam , Brook Thomas C. , Kujawska Magdalena , Martin Samuel , Peel Ned , Acford-Palmer Holly , Hoyles Lesley , Clarke Paul , Hall Lindsay J. , Clark Matthew D.
Published: December 2019

The MinION sequencing platform offers near real-time analysis of DNA sequence; this makes the tool attractive for deployment in fieldwork or clinical settings. We used the MinION platform coupled to the NanoOK RT software package to perform shotgun metagenomic sequencing and profile mock communities and faecal samples from healthy and ill preterm infants. Using Nanopore data, we reliably classified a 20-species mock community and captured the diversity of the immature gut microbiota over time and in response to interventions such as probiotic supplementation, antibiotic treatment or episodes of suspected sepsis. We also performed rapid real-time runs to assess gut-associated microbial communities in critically ill and healthy infants, facilitated by NanoOK RT software package, which analysed sequences as they were generated. Our pipeline reliably identified pathogenic bacteria (that is,Klebsiella pneumoniaeandEnterobacter cloacae) and their corresponding antimicrobial resistance gene profiles within as little as 1 h of sequencing. Results were confirmed using pathogen isolation, whole-genome sequencing and antibiotic susceptibility testing, as well as mock communities and clinical samples with known antimicrobial resistance genes. Our results demonstrate that MinION (including cost-effective Flongle flow cells) with NanoOK RT can process metagenomic samples to a rich dataset in < 5 h, which creates a platform for future studies aimed at developing these tools and approaches in clinical settings with a focus on providing tailored patient antimicrobial treatment options.
Corticosterone-mediated physiological stress modulates hepatic lipid metabolism, metabolite profiles, and systemic responses in chickens
Authors: Zaytsoff Sarah J. M. , Brown Catherine L. J. , Montina Tony , Metz Gerlinde A. S. , Abbott D. Wade , Uwiera Richard R. E. , Inglis G. Douglas
Published: December 2019

The impact of physiological stress on lipid metabolism, the metabolome, and systemic responses was examined in chickens. To incite a stress response, birds were continuously administered corticosterone (CORT) in their drinking water at three doses (0 mg/L, 10 mg/L, and 30 mg/L), and they were sampled 1, 5, and 12 days after commencement of CORT administration. Corticosterone administration to birds differentially regulated lipogenesis genes (i.e. FAS, ACC, ME, and SREBF1), and histopathological examination indicated lipid deposition in hepatocytes. In addition, CORT affected water-soluble metabolite profiles in the liver, as well as in kidney tissue and breast muscle; thirteen unique metabolites were distinguished in CORT-treated birds and this was consistent with the dysregulation of lipid metabolism due to physiological stress. Acute phase responses (APRs) were also altered by CORT, and in particular, expression of SAA1 was decreased and expression of CP was increased. Furthermore, CORT administration caused lymphoid depletion in the bursa of Fabricius and elevated IL6 and TGFβ2 mRNA expression after 5 and 12 days of CORT administration. Collectively, incitement of physiological stress via administration of CORT in chickens modulated host metabolism and systemic responses, which indicated that energy potentials are diverted from muscle anabolism during periods of stress.
Mutation signature analysis identifies increased mutation caused by tobacco smoke associated DNA adducts in larynx squamous cell carcinoma compared with oral cavity and oropharynx
Authors: South Andrew P. , den Breems Nicoline Y. , Richa Tony , Nwagu Uche , Zhan Tingting , Poojan Shiv , Martinez-Outschoorn Ubaldo , Johnson Jennifer M. , Luginbuhl Adam J. , Curry Joseph M.
Published: December 2019

Squamous cell carcinomas of the head and neck (HNSCC) arise from mucosal keratinocytes of the upper aero-digestive tract. Despite a common cell of origin and similar driver-gene mutations which divert cell fate from differentiation to proliferation, HNSCC are considered a heterogeneous group of tumors categorized by site of origin within the aero-digestive mucosa, and the presence or absence of HPV infection. Tobacco use is a major driver of carcinogenesis in HNSCC and is a poor prognosticator that has previously been associated with poor immune cell infiltration and higher mutation numbers. Here, we study patterns of mutations in HNSCC that are derived from the specific nucleotide changes and their surrounding nucleotide context (also known as mutation signatures). We identify that mutations linked to DNA adducts associated with tobacco smoke exposure are predominantly found in the larynx. Presence of this class of mutation, termed COSMIC signature 4, is responsible for the increased burden of mutation in this anatomical sub-site. In addition, we show that another mutation pattern, COSMIC signature 5, is positively associated with age in HNSCC from non-smokers and that larynx SCC from non-smokers have a greater number of signature 5 mutations compared with other HNSCC sub-sites. Immunohistochemistry demonstrates a significantly lower Ki-67 proliferation index in size matched larynx SCC compared with oral cavity SCC and oropharynx SCC. Collectively, these observations support a model where larynx SCC are characterized by slower growth and increased susceptibility to mutations from tobacco carcinogen DNA adducts.
The DNA topoisomerase II inhibitor amsacrine as a novel candidate adjuvant in a model of glaucoma filtration surgery
Authors: Yamamoto Kotaro , Kokubun Taiki , Sato Kota , Akaishi Takahiro , Shimazaki Atsushi , Nakamura Masatsugu , Shiga Yukihiro , Tsuda Satoru , Omodaka Kazuko , Saya Hideyuki , Nakazawa Toru
Published: December 2019

Treatments for refractory glaucoma include trabeculectomy, in which a filtering bleb is created to reduce aqueous pressure. Mitomycin C (MMC) is often used as an adjuvant to reduce post-trabeculectomy bleb scarring and consequent failure. However, scarring sometimes still occurs. Thus, we searched for more effective trabeculectomy adjuvants with high-throughput screening (HTS) of a library of 1,165 off-patent drug compounds. This revealed that amsacrine (AMSA), a DNA topoisomerase II (TOP2) inhibitor, was the top candidate. Compared to MMC, rabbits that underwent trabeculectomy with 10% AMSA had lower IOP at 42, 56, and 70 days (P < 0.01 at all measurement points) and a higher bleb score at 28, 42, 56, and 70 days (P =  < 0.01, 0.04, 0.04, and < 0.01, respectively). Compared to saline, rabbits that received 1% AMSA also had lower IOP and better bleb score at all time points, without a sharp drop in IOP just after surgery (all P < 0.01). Both effects were milder than MMC at 7 days (P = 0.02 and <0.01, respectively). Thus, this study showed that HTS may help identify new, promising uses for off-patent drugs. Furthermore, trabeculectomy with AMSA at a suitable concentration may improve the prognosis after trabeculectomy compared to MMC.
How dietary patterns affect left ventricular structure, function and remodelling: evidence from the Kardiovize Brno 2030 study
Authors: Maugeri Andrea , Hruskova Jana , Jakubik Juraj , Hlinomaz Ota , Medina-Inojosa Jose R. , Barchitta Martina , Agodi Antonella , Vinciguerra Manlio
Published: December 2019

Little is still known about the effect of dietary patterns on left ventricular hypertrophy (LVH). Here, we derived dietary patterns by principal component analysis (PCA) and evaluated their association with LV structure, function, and remodelling. Our cross-sectional study included 438 members (aged 25–65 years; 59.1% women) of the Kardiovize Brno 2030 with no history of cardiovascular disease. Two dietary patterns were derived using PCA, namely prudent and western. Primary outcomes were echocardiographic parameters and LV geometric patterns, such as concentric LV remodelling (cLVR), concentric LVH (cLVH), and eccentric LVH (eLVH). Interestingly, participants with high adherence to the prudent dietary pattern had decreased odds of cLVH after adjustment for socio-demographic, clinical and behavioral covariates (OR = 0.24, 95% CI = 0.08–0.88; p = 0.031). By contrast, several echocardiographic parameters increased with increasing adherence to the western dietary pattern, which resulted in higher odds of cLVH among participants with high adherence (OR = 5.38, 95% CI = 1.17–23.58; p = 0.035). Although our findings may have an immediate relevance for public-health strategies, further large-size prospective studies should be encouraged to better understand the observed association and their causality.
Prediction and final temporal errors are used for trial-to-trial motor corrections
Authors: López-Moliner Joan , Vullings Cécile , Madelain Laurent , van Beers Robert J.
Published: December 2019

Many daily life situations (e.g. dodging an approaching object or hitting a moving target) require people to correct planning of future movements based on previous temporal errors. However, the actual temporal error can be difficult to perceive: imagine a baseball batter that swings and misses a fastball. Here we show that in such situations people can use an internal error signal to make corrections in the next trial. This signal is based on the discrepancy between the actual and the planned action onset time: the prediction error. In this study, we used three interception tasks: reaching movements, saccadic eye movements and a button press that released a cursor moving ballistically for a fixed time. We found that action onset depended on the previous temporal error in the arm movement experiment only and not in the saccadic and button press experiments. However, this dependency was modulated by the movement time: faster arm movements depended less on the previous actual temporal error. An analysis using a Kalman filter confirmed that people used the prediction error rather than the previous temporal error for trial-by-trial corrections in fast arm movements, saccades and button press.
Characterization of multi-channel intraneural stimulation in transradial amputees
Authors: Strauss I. , Valle G. , Artoni F. , D’Anna E. , Granata G. , Di Iorio R. , Guiraud D. , Stieglitz T. , Rossini P. M. , Raspopovic S. , Petrini F. M. , Micera S.
Published: December 2019

Although peripheral nerve stimulation using intraneural electrodes has been shown to be an effective and reliable solution to restore sensory feedback after hand loss, there have been no reports on the characterization of multi-channel stimulation. A deeper understanding of how the simultaneous stimulation of multiple electrode channels affects the evoked sensations should help in improving the definition of encoding strategies for bidirectional prostheses. We characterized the sensations evoked by simultaneous stimulation of median and ulnar nerves (multi-channel configuration) in four transradial amputees who had been implanted with four TIMEs (Transverse Intrafascicular Multichannel Electrodes). The results were compared with the characterization of single-channel stimulation. The sensations were characterized in terms of location, extent, type, and intensity. Combining two or more single-channel configurations caused a linear combination of the sensation locations and types perceived with such single-channel stimulations. Interestingly, this was also true when two active sites from the same nerve were stimulated. When stimulating in multi-channel configuration, the charge needed from each electrode channel to evoke a sensation was significantly lower than the one needed in single-channel configuration (sensory facilitation). This result was also supported by electroencephalography (EEG) recordings during nerve stimulation. Somatosensory potentials evoked by multi-channel stimulation confirmed that sensations in the amputated hand were perceived by the subjects and that a perceptual sensory facilitation occurred. Our results should help the future development of more efficient bidirectional prostheses by providing guidelines for the development of more complex stimulation approaches to effectively restore multiple sensations at the same time.
Excitatory and inhibitory lateral interactions effects on contrast detection are modulated by tRNS
Authors: Battaglini L. , Contemori G. , Fertonani A. , Miniussi C. , Coccaro A. , Casco C.
Published: December 2019

Contrast sensitivity for a Gabor signal is affected by collinear high-contrast Gabor flankers. The flankers reduce (inhibitory effect) or increase (facilitatory effect) sensitivity, at short (2λ) and intermediate (6λ) target-to-flanker separation respectively. We investigated whether these inhibitory/facilitatory sensitivity effects are modulated by transcranial random noise stimulation (tRNS) applied to the occipital and frontal cortex of human observers during task performance. Signal detection theory was used to measure sensitivity (d’) and the Criterion (C) in a contrast detection task, performed with sham or tRNS applied over the occipital or the frontal cortex. After occipital stimulation results show a tRNS-dependent increased sensitivity for the single Gabor signal of low but not high contrast. Moreover, results suggest a dissociation of the tRNS effect when the Gabor signal is presented with the flankers, consisting in a general increased sensitivity at 2λ where the flankers had an inhibitory effect (reduction of inhibition) and a decreased sensitivity at 6λ where the flankers had a facilitatory effect on the Gabor signal (reduction of facilitation). After a frontal stimulation, no specific effect of the tRNS was found. We account for these complex interactions between tRNS and flankers by assuming that tRNS not only enhances feedforward input from the Gabor signal to the cortex, but also enhances the excitatory or inhibitory lateral intracortical input from the flankers. The boosted lateral input depends on the excitation-inhibition (E/I) ratio, namely when the lateral input is weak, it is boosted by tRNS with consequent modification of the contrast-dependent E/I ratio.