bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating and differentiating maternal feeding practices in a country ranked first in childhood obesity
Authors: Salinas Martínez Ana María , Cordero Franco Hid Felizardo , Estrada de León Daniela Berenice , Medina Franco Gloria Estefanía , Guzmán de la Garza Francisco Javier , Núñez Rocha Georgina Mayela
Published: November 2019

Objective:

Mexico ranks first in childhood obesity worldwide. However, little is known about the factors influencing maternal feeding practices. The present study aimed to estimate the prevalence of feeding practices and explore associations between weight concern, weight perception, sociodemographic characteristics and those feeding practices.

Design:

Cross-sectional.

Setting:

North-eastern Mexico.

Participants:

Mothers aged ≥18 years who were in charge of feeding a singleton child aged 2–6 years with no endocrine disease or visible genetic malformations (n 507). Information on six maternal feeding practices, concern and perception of the child’s weight and demographics were collected by interview. The mother’s and child’s height and weight were measured. The feeding practices questionnaire was subject to content, construct and convergent validity analysis. Then, mean feeding scores were obtained and prevalence and 95 % CI were determined for scores ≥3; multivariate logistic regression was performed.

Results:

Not modelling (63·5 %; 95 % CI 59·2, 67·8 %) and pressuring to eat (55·6 %; 95 % CI 51·2, 60·0 %) were the most frequent feeding practices, followed by easy access to unhealthy foods (45·4 %; 95 % CI 40·9, 49·8 %) and child control (43·2 %; 95 % CI 38·8, 47·6 %). They prevailed despite concern about the child’s excess weight or a perception of the child as overweight/obese. Education was associated with the highest number of practices (educated mothers used more pressuring to eat, less regulation and less easy access; or monitoring was less absent).

Conclusions:

The frequency of certain feeding practices needs to be improved. Emphasis on the child’s weight concern, obesity perception and maternal education is essential for optimizing intervention planning.
A New Correction for He Loss Applied to (U‐Th)/He Dating of Grains with Complex Shapes and Polymineralic Aggregates
Authors: Huber Christian , Guenthner William , Karani Hamid
Published: November 2019

Applying the (U‐Th)/He chronometer to small domains with complex shapes is challenging because of He recoil loss. The development of date correction factors proves challenging when considering either a single grain with complex geometry or polymineralic crystal aggregates composed of many small U‐Th‐bearing grains with additional impurities, such as iron‐oxide aggregates. We introduce a new geometrical metric for the recoil loss correction factor—the two‐point correlation distribution S2(r)—that is independent of dimensionality (i.e., two‐dimensional [2‐D] or three‐dimensional [3‐D] images), grain shape, and existence or absence of internal porosity. S2(r) measures the probability of finding two points within the target phase (U‐Th‐He host, such as Fe oxides here) separated by a distance r in the physical sample (single grain or aggregate). It provides a metric that is independent of grain or aggregate size. We use a combination of forward recoil loss simulations in 2‐D and 3‐D domains (both complex single grains and aggregates) to show a one‐to‐one correspondence between a recoil loss factor and S2(r = He stopping distance). We illustrate the workflow to retrieve the loss factors for different isotopes and correct date determination in a complex 3‐D jasperoid sample imaged by X‐ray computed microtomography. Our jasperoid sample contains appreciable amounts of iron oxide with quartz impurities and is representative of a sample for which completely monomineralic separates cannot be obtained. The computation of loss factors based on S2(r) is extremely efficient, and the codes, including a simple user interface, are made available at https://repository.library.brown.edu/studio/item/bdr:957056/.
The Possible Transition From Glacial Surge to Ice Stream on Vavilov Ice Cap
Authors: Zheng Whyjay , Pritchard Matthew E. , Willis Michael J. , Stearns Leigh A.
Published: November 2019

Surge‐type glaciers typically undergo cyclical flow instability due to mass accumulation; however, some recent glacier surges have caused irreversible ice loss in a short period. At Vavilov Ice Cap, Russia, surge‐like behavior initiated in 2013 and by spring 2019 the ice cap had lost 9.5 Gt of ice (11% mass of the entire basin). Using time series of surface elevation and glacier velocity derived from satellite optical and synthetic‐aperture radar imagery, we identify a shift of flow pattern starting in 2017 when shear margins formed within the grounded marine piedmont fan. Multiple summer speedups correlate with warmer summers during 2015–2019 and suggest that surface melt may access the subglacial environment. Force balance analysis and examination of the Péclet number show that glacier thinning propagated upstream in 2016–2017, and diffusion became a significant dynamic response to thinning perturbations. Our results suggest that the glacier has entered a new ice stream‐like regime.
Simulating Water Residence Time in the Coastal Ocean: A Global Perspective
Authors: Liu Xiao , Dunne John P. , Stock Charles A. , Harrison Matthew J. , Adcroft Alistair , Resplandy Laure
Published: November 2019

Exchanges between coastal and oceanic waters shape both coastal ecosystem processes and signatures that they impart on global biogeochemical cycles. The timescales of these exchanges, however, are poorly represented in current‐generation, coarse‐grid climate models. Here we provide a novel global perspective on coastal residence time (CRT) and its spatio‐temporal variability using a new age tracer implemented in global ocean models. Simulated CRTs range widely from several days in narrow boundary currents to multiple years on broader shelves and in semi‐enclosed seas, in agreement with available observations. Overall, CRT is better characterized in high‐resolution models (1/8° and 1/4°) than in the coarser (1° and 1/2°) versions. This is in large part because coastal and open ocean grid cells are more directly connected in coarse models, prone to erroneous coastal flushing and an underestimated CRT. Additionally, we find that geometric enclosure of a coastal system places an important constraint on CRT.
New Crystal Preferred Orientation of Amphibole Experimentally Found in Simple Shear
Authors: Kim Junha , Jung Haemyeong
Published: November 2019

The crystal preferred orientation (CPO) of amphibole has a large effect on seismic anisotropy in the crust. Previous studies have reported four CPO types (I–IV) of amphibole, but the genesis of type IV CPO, which is characterized by [100] axes aligned in a girdle subnormal to the shear direction, is unknown. In this study, shear deformation experiments on amphibolite were conducted to find the genesis of type IV CPO at high pressure (0.5 GPa) and temperature (500–700 °C). The type IV CPO was found under high shear strain (γ > 3.0), and the sample exhibited grains in a range of sizes but generally smaller than the grain size of samples with lower shear strain. The seismic anisotropy of type IV CPO is lower than that of types I–III. The weak seismic anisotropy of highly deformed amphibole could explain weak seismic anisotropy observed in the middle crust.
Crossing of Plasma Structures by Spacecraft: A Path Calculator
Authors: Manuzzo R. , Belmont G. , Rezeau L. , Califano F. , Denton R. E.
Published: November 2019

When spacecraft (s/c) missions probe plasma structures (PSs) the relative location of the s/c with respect to the PS is unknown. This information is, however, needed to measure the geometrical features of the PS (orientation and thickness) and to understand the physical processes underlying the PS dynamics. Methods to determine the s/c location exist, but they need strong assumptions to be satisfied (stationarity and special spatial dependencies). The number of cases for which these assumptions are likely to be valid for the entire PS seems to be limited, and even weak departures from these hypotheses may affect the results. For a quasi‐1‐D geometry in particular, the determination of the velocity component along the two quasi‐invariant directions is very inaccurate and the assumption of strict stationarity may lead these quantities to diverge. In this paper we present new methods to compute the s/c trajectory through a PS, without a priori assumption on its spatial geometry, and able to work even in the presence of weak nonstationarities. The methods are tested both on artificial and real data, the latter provided by the Magnetospheric Multiscale mission probing the Earth's magnetopause. The 1‐D and 2‐D trajectories of the Magnetospheric Multiscale are found that can be used as an initial step for future reconstruction studies. Advanced minimization procedures to optimize the results are discussed.
Multispacecraft Study of the Interaction Between an Interplanetary Shock and a Solar Wind Flux Rope
Authors: Blanco‐Cano X. , Burgess D. , Sundberg T. , Kajdič P.
Published: November 2019

Interplanetary (IP) shocks are driven in the heliosphere by fast coronal ejecta, they can accelerate particles and are associated with solar energetic particle and energetic storm particle events. IP shocks can interact with structures in the solar wind and with magnetospheres. We show how the properties of an IP shock change when it interacts with a small‐scale flux rope‐like structure (FRLS). Data from Cluster, Wind, and ACE show that the spacecraft observed the shock‐FRLS interaction at different stages of evolution. Wind and ACE observed the FRLS at shock crossing; Cluster observed the FRLS downstream, after it had crossed the shock. The shock‐FRLS interaction changes shock geometry, affecting ion injection processes, energetic particles fluxes, and the upstream/downstream regions. While Wind and ACE observed a quasi‐perpendicular shock, Cluster crossed a quasi‐parallel shock and a foreshock with a variety of ion distributions. The FRLS modified the shock on scales of at least ∼ 10–20 RE. The complexity of the ion foreshock measured by Cluster is explained by the dynamics of the shock transitioning from quasi‐perpendicular to quasi‐parallel and the geometry of the magnetic field within the flux rope. Fluxes of particles with energy up to 125 keV are affected by the FRLS‐shock interaction, modulating the associated energetic storm particle event. The interaction of a FRLS with an IP shock has not been discussed before using multispacecraft observations. Interactions like this should occur often along the shock fronts; hence, they are important for a better understanding of shock structure, evolution, and particle acceleration.
Magnetic Field Effect on Antenna Signals Induced by Dust Particle Impacts
Authors: Nouzák L. , Sternovsky Z. , Horányi M. , Hsu S. , Pavlů J. , Shen M.‐H. , Ye S.‐Y.
Published: November 2019

The Radio and Plasma Wave Science instrument on Cassini has observed fewer than expected dust particle impacts during the mission's Grand Finale orbits. The relatively strong magnetic field in the close vicinity of the planet has been suggested to affect the intensity of the dust impact generated signals. A laboratory investigation is performed using dust particles accelerated to ≥20 km/s speed impacting onto a previously developed model of the spacecraft and the Radio and Plasma Wave Science antennas. The external magnetic field is generated by two sets of magnetic coils. The recorded antenna waveforms are decomposed into contributions from the electrons and ions of the dust impact generated plasma cloud. A good qualitative understanding of the waveforms is achieved by dividing the electron and ion population into two portions: one that is escaping from the spacecraft and another that is collected by the spacecraft. The experimental results show that the part of the signal corresponding to escaping electrons is affected by the magnetic field and that dust impact signals can be significantly reduced for spacecraft floating potentials close to zero.
Three‐Dimensional Modeling of Spontaneous and Triggered Slow‐Slip Events at the Hikurangi Subduction Zone, New Zealand
Authors: Shibazaki Bunichiro , Wallace Laura M. , Kaneko Yoshihiro , Hamling Ian , Ito Yoshihiro , Matsuzawa Takanori
Published: November 2019

At the southern Hikurangi margin, New Zealand, long‐term (duration of >1 year), deep (>25 km) slow‐slip events (SSEs) occur at intervals of approximately 5 years. In contrast, along the northern and central Hikurangi margin, short‐term and shallow (<10 km) SSEs (2‐ to 3‐week duration) occur at 1‐ to 2‐year intervals. However, it is not clear what controls these differences in SSE behavior. In this study, we simulate SSEs along the entire Hikurangi subduction zone using a 3‐D model of the plate boundary incorporating a rate‐and‐state friction law with a cutoff velocity to the evolution effect. Overall, our models are able to replicate the along‐strike and depth‐dependent variations in SSE behavior at the Hikurangi margin. Our models also show that the slip velocities of the deep, long‐term SSEs increase when the slip velocities at the deeper extension of the seismogenic zone increase during the latter half of the interseismic period. By imposing static stress changes induced by the Kaikōura earthquake in the SSE regions, we also reproduce patterns of triggering of deep, long‐term SSEs that followed the earthquake. Our results further suggest that the propensity for SSE triggering via static stress transfer depends on the amplitude of perturbation and the timing with respect to the SSE cycle. Overall, both spontaneous and triggered SSEs require larger values of effective stress for deep, long‐term events (~5 MPa) compared to the shallow, short‐term events (~1 MPa). Such low effective stresses can be explained by the existence of high pore fluid pressure in these SSE source regions.
Efficacy of Climate Forcings in PDRMIP Models
Authors: Richardson T. B. , Forster P. M. , Smith C. J. , Maycock A. C. , Wood T. , Andrews T. , Boucher O. , Faluvegi G. , Fläschner D. , Hodnebrog Ø. , Kasoar M. , Kirkevåg A. , Lamarque J.‐F. , Mülmenstädt J. , Myhre G. , Olivié D. , Portmann R. W. , Samset B. H. , Shawki D. , Shindell D. , Stier P. , Takemura T. , Voulgarakis A. , Watson‐Parris D.
Published: November 2019

Quantifying the efficacy of different climate forcings is important for understanding the real‐world climate sensitivity. This study presents a systematic multimodel analysis of different climate driver efficacies using simulations from the Precipitation Driver and Response Model Intercomparison Project (PDRMIP). Efficacies calculated from instantaneous radiative forcing deviate considerably from unity across forcing agents and models. Effective radiative forcing (ERF) is a better predictor of global mean near‐surface air temperature (GSAT) change. Efficacies are closest to one when ERF is computed using fixed sea surface temperature experiments and adjusted for land surface temperature changes using radiative kernels. Multimodel mean efficacies based on ERF are close to one for global perturbations of methane, sulfate, black carbon, and insolation, but there is notable intermodel spread. We do not find robust evidence that the geographic location of sulfate aerosol affects its efficacy. GSAT is found to respond more slowly to aerosol forcing than CO2 in the early stages of simulations. Despite these differences, we find that there is no evidence for an efficacy effect on historical GSAT trend estimates based on simulations with an impulse response model, nor on the resulting estimates of climate sensitivity derived from the historical period. However, the considerable intermodel spread in the computed efficacies means that we cannot rule out an efficacy‐induced bias of ±0.4 K in equilibrium climate sensitivity to CO2 doubling when estimated using the historical GSAT trend.
Convective Aggregation and Indices Examined from CERES Cloud Object Data
Authors: Xu Kuan‐Man , Hu Yongxiang , Wong Takmeng
Published: November 2019

Convective aggregation is a self‐aggregation phenomenon appearing in idealized radiative‐convective equilibrium simulations under constant, uniform sea surface temperature (SST). To gain an understanding of observed convective aggregation or organization, three metrics, i.e., simple convective aggregation index (SCAI), modified SCAI (MCAI), and convective organization potential (COP), are evaluated with cloud object data from CERES. MCAI is related to object sizes through a modified inter‐object distance (IOD). It is found that large‐size object groups are less aggregated according to SCAI but more organized according to COP, compared to small‐size object groups. The opposite sensitivities to object‐group size can be explained by the dominant roles of the IOD in SCAI and the sum of object radii in COP as object‐group sizes increase. However, large‐size object groups are slightly more aggregated than small‐size ones according to MCAI. Both SCAI and MCAI increase with the number of cloud objects (N) in an object group but COP has a weak dependency on N. Further sorting by object‐group total area shows that sensitivity of MCAI to object‐group area agrees with that of SCAI for small‐area ranges but with that of COP for large‐area ranges, which is related to the weak sensitivity of the modified IOD to object‐group area, as compared to that of the original IOD. Finally, the three metrics show the similar contrasts between continental and oceanic convection and the same weak sensitivity to SST. The latter suggests that self‐aggregation is weaker at higher SSTs than at lower SSTs, in contrast to the findings of many simulations.
Germanium/perovskite heterostructure for high-performance and broadband photodetector from visible to infrared telecommunication band
Authors: Hu Wei , Cong Hui , Huang Wei , Huang Yu , Chen Lijuan , Pan Anlian , Xue Chunlai
Published: November 2019

A high-performance and broadband heterojunction photodetector has been successfully fabricated. The heterostructure device is based on a uniform and pinhole-free perovskite film constructed on top of a single-crystal germanium layer. The perovskite/germanium photodetector shows enhanced performance and a broad spectrum compared with the single-material-based device. The photon response properties are characterized in detail from the visible to near-infrared spectrum. At an optical fibre communication wavelength of 1550 nm, the heterojunction device exhibits the highest responsivity of 1.4 A/W. The performance is promoted because of an antireflection perovskite coating, the thickness of which is optimized to 150 nm at the telecommunication band. At a visible light wavelength of 680 nm, the device shows outstanding responsivity and detectivity of 228 A/W and 1.6 × 1010 Jones, respectively. These excellent properties arise from the photoconductive gain boost in the heterostructure device. The presented heterojunction photodetector provides a competitive approach for wide-spectrum photodetection from visible to optical communication areas. Based on the distinguished capacity of light detection and harvesting from the visible to near-infrared spectrum, the designed germanium/perovskite heterostructure configuration is believed to provide new building blocks for novel optoelectronic devices.
The DNA methylome in panic disorder: a case-control and longitudinal psychotherapy-epigenetic study
Authors: Ziegler Christiane , Grundner-Culemann Franziska , Schiele Miriam A. , Schlosser Pascal , Kollert Leonie , Mahr Marina , Gajewska Agnieszka , Lesch Klaus-Peter , Deckert Jürgen , Köttgen Anna , Domschke Katharina
Published: November 2019

In panic disorder (PD), epigenetic mechanisms such as DNA methylation of candidate genes have been suggested to play a key role at the intersection of genetic and environmental factors. On an epigenome-wide level, however, only two studies in PD patients have been published so far, while to date no study has intra-individually analyzed dynamic epigenetic correlates of treatment-response in PD on a DNA methylome level. Here, an epigenome-wide association study (EWAS) was performed in a sample of 57 PD patients and matched healthy controls using the Illumina MethylationEPIC BeadChip, along with a longitudinal approach assessing changes on the DNA methylome level corresponding to clinical effects of a manualized six-week cognitive-behavioral therapy (CBT) in PD. While no epigenome-wide significant hits could be discerned, top suggestive evidence was observed for decreased methylation in PD at cg19917903 in the Cilia and Flagella Associated Protein 46 (CFAP46) gene, and for an increase in methylation after CBT at cg06943668 in the Interleukin 1 Receptor Type 1 (IL1R1) gene in treatment responders to CBT. Additional exploratory analyses based on biological validity and a combined statistical/biological ranking point to further new potential PD risk genes such as the CCL4L1 or GMNN genes, and suggest dynamic methylation of, e.g., the ZFP622 and the SLC43A2 genes along with response to CBT. These EWAS and first longitudinal epigenome-wide pilot data in PD add to the emerging candidate gene-based body of evidence for epigenetic mechanisms to be involved in PD pathogenesis and to possibly constitute dynamic biological correlates of therapeutic interventions.
Tenascin-c mediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma
Authors: Cai Hai-ping , Wang Jing , Xi Shao-yan , Ni Xiang-rong , Chen Yin-sheng , Yu Yan-jiao , Cen Zi-wen , Yu Zhi-hui , Chen Fu-rong , Guo Cheng-cheng , Zhang Ji , Ke Chao , Wang Jian , Chen Zhong-ping
Published: November 2019

Vasculogenic mimicry (VM), the formation of vessel-like structures by highly invasive tumor cells, has been considered one of several mechanisms responsible for the failure of anti-angiogenesis therapy in glioma patients. Therefore, inhibiting VM formation might be an effective therapeutic method to antagonize the angiogenesis resistance. This study aimed to show that an extracellular protein called Tenascin-c (TNC) is involved in VM formation and that TNC knockdown inhibits VM in glioma. TNC was upregulated with an increase in glioma grade. TNC and VM formation are potential independent predictors of survival of glioma patients. TNC upregulation was correlated with VM formation, and exogenous TNC stimulated VM formation. Furthermore, TNC knockdown significantly suppressed VM formation and proliferation in glioma cells in vitro and in vivo, with a reduction in cellular invasiveness and migration. Mechanistically, TNC knockdown decreased Akt phosphorylation at Ser473 and Thr308 and subsequently downregulated matrix metalloproteinase 2 and 9, both of which are important proteins associated with VM formation and migration. Our results indicate that TNC plays an important role in VM formation in glioma, suggesting that TNC is a potential therapeutic target for anti-angiogenesis therapy for glioma.
RUNX1 contributes to the mesenchymal subtype of glioblastoma in a TGFβ pathway-dependent manner
Authors: Zhao Kai , Cui Xiaoteng , Wang Qixue , Fang Chuan , Tan Yanli , Wang Yunfei , Yi Kaikai , Yang Chao , You Hua , Shang Rui , Wang Jiachong , Kang Chunsheng
Published: November 2019

Runt-Related Transcription Factor 1 (RUNX1) is highly expressed in the Mesenchymal (Mes) subtype of glioblastoma (GBM). However, the specific molecular mechanism of RUNX1 in Mes GBM remains largely elusive. In this study, cell and tumor tissue typing were performed by RNA-sequencing. Co-immunoprecipitation (co-IP) and immunofluorescence (IF) were employed to identify members of the RUNX1 transcriptional protein complex. Bioinformatics analysis, chromatin immunoprecipitation (ChIP), and luciferase reporter experiments were utilized to verify target genes. Analyses of The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) verified the expression levels and prognoses associated with RUNX1/p-SMAD3/SUV39H1 target genes. In vivo patient-derived xenograft (PDX) studies and in vitro functional studies verified the impact of RUNX1 on the occurrence and development of GBM. The results showed that RUNX1 was upregulated in Mes GBM cell lines, tissues and patients and promoted proliferation and invasion in GBM in a TGFβ pathway-dependent manner in vivo and in vitro. We found and verified that BCL3 and MGP are transcriptionally activated by p-SMAD3 /RUNX1, while MXI1 is transcriptionally suppressed by the RUNX1/SUV39H1-H3K9me3 axis. This finding offers a theoretical rationale for using molecular markers and choosing therapeutic targets for the Mes type of GBM.
The differential statin effect on cytokine production of monocytes or macrophages is mediated by differential geranylgeranylation-dependent Rac1 activation
Authors: Fu Hang , Alabdullah Mohamad , Großmann Julia , Spieler Florian , Abdosh Reem , Lutz Veronika , Kalies Katrin , Knöpp Kai , Rieckmann Max , Koch Susanne , Noutsias Michel , Pilowski Claudia , Dutzmann Jochen , Sedding Daniel , Hüttelmaier Stefan , Umezawa Kazuo , Werdan Karl , Loppnow Harald
Published: November 2019

Monocytes and macrophages contribute to pathogenesis of various inflammatory diseases, including auto-inflammatory diseases, cancer, sepsis, or atherosclerosis. They do so by production of cytokines, the central regulators of inflammation. Isoprenylation of small G-proteins is involved in regulation of production of some cytokines. Statins possibly affect isoprenylation-dependent cytokine production of monocytes and macrophages differentially. Thus, we compared statin-dependent cytokine production of lipopolysaccharide (LPS)-stimulated freshly isolated human monocytes and macrophages derived from monocytes by overnight differentiation. Stimulated monocytes readily produced tumor necrosis factor-α, interleukin-6, and interleukin-1β. Statins did not alter cytokine production of LPS-stimulated monocytes. In contrast, monocyte-derived macrophages prepared in the absence of statin lost the capacity to produce cytokines, whereas macrophages prepared in the presence of statin still produced cytokines. The cells expressed indistinguishable nuclear factor-kB activity, suggesting involvement of separate, statin-dependent regulation pathways. The presence of statin was necessary during the differentiation phase of the macrophages, indicating that retainment-of-function rather than costimulation was involved. Reconstitution with mevalonic acid, farnesyl pyrophosphate, or geranylgeranyl pyrophosphate blocked the retainment effect, whereas reconstitution of cholesterol synthesis by squalene did not. Inhibition of geranylgeranylation by GGTI-298, but not inhibition of farnesylation or cholesterol synthesis, mimicked the retainment effect of the statin. Inhibition of Rac1 activation by the Rac1/TIAM1-inhibitor NSC23766 or by Rac1-siRNA (small interfering RNA) blocked the retainment effect. Consistent with this finding, macrophages differentiated in the presence of statin expressed enhanced Rac1-GTP-levels. In line with the above hypothesis that monocytes and macrophages are differentially regulated by statins, the CD14/CD16-, merTK-, CX3CR1-, or CD163-expression (M2-macrophage-related) correlated inversely to the cytokine production. Thus, monocytes and macrophages display differential Rac1-geranylgeranylation-dependent functional capacities, that is, statins sway monocytes and macrophages differentially.
BET and Aurora Kinase A inhibitors synergize against MYCN-positive human glioblastoma cells
Authors: Čančer Matko , Drews Lisa F. , Bengtsson Johan , Bolin Sara , Rosén Gabriela , Westermark Bengt , Nelander Sven , Forsberg-Nilsson Karin , Uhrbom Lene , Weishaupt Holger , Swartling Fredrik J.
Published: November 2019

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Patients usually undergo surgery followed by aggressive radio- and chemotherapy with the alkylating agent temozolomide (TMZ). Still, median survival is only 12–15 months after diagnosis. Many human cancers including GBMs demonstrate addiction to MYC transcription factor signaling and can become susceptible to inhibition of MYC downstream genes. JQ1 is an effective inhibitor of BET Bromodomains, a class of epigenetic readers regulating expression of downstream MYC targets. Here, we show that BET inhibition decreases viability of patient-derived GBM cell lines. We propose a distinct expression signature of MYCN-elevated GBM cells that correlates with significant sensitivity to BET inhibition. In tumors showing JQ1 sensitivity, we found enrichment of pathways regulating cell cycle, DNA damage response and repair. As DNA repair leads to acquired chemoresistance to TMZ, JQ1 treatment in combination with TMZ synergistically inhibited proliferation of MYCN-elevated cells. Bioinformatic analyses further showed that the expression of MYCN correlates with Aurora Kinase A levels and Aurora Kinase inhibitors indeed showed synergistic efficacy in combination with BET inhibition. Collectively, our data suggest that BET inhibitors could potentiate the efficacy of either TMZ or Aurora Kinase inhibitors in GBM treatment.
Neural computations underlying strategic social decision-making in groups
Authors: Park Seongmin A. , Sestito Mariateresa , Boorman Erie D. , Dreher Jean-Claude
Published: November 2019

When making decisions in groups, the outcome of one’s decision often depends on the decisions of others, and there is a tradeoff between short-term incentives for an individual and long-term incentives for the groups. Yet, little is known about the neurocomputational mechanisms at play when weighing different utilities during repeated social interactions. Here, using model-based fMRI and Public-good-games, we find that the ventromedial prefrontal cortex encodes immediate expected rewards as individual utility while the lateral frontopolar cortex encodes group utility (i.e., pending rewards of alternative strategies beneficial for the group). When it is required to change one’s strategy, these brain regions exhibited changes in functional interactions with brain regions engaged in switching strategies. Moreover, the anterior cingulate cortex and the temporoparietal junction updated beliefs about the decision of others during interactions. Together, our findings provide a neurocomputational account of how the brain dynamically computes effective strategies to make adaptive collective decisions.
In situ formation of mononuclear complexes by reaction-induced atomic dispersion of supported noble metal nanoparticles
Authors: Feng Siquan , Song Xiangen , Liu Yang , Lin Xiangsong , Yan Li , Liu Siyue , Dong Wenrui , Yang Xueming , Jiang Zheng , Ding Yunjie
Published: November 2019

Supported noble metal nanoclusters and single-metal-site catalysts are inclined to aggregate into particles, driven by the high surface-to-volume ratio. Herein, we report a general method to atomically disperse noble metal nanoparticles. The activated carbon supported nanoparticles of Ru, Rh, Pd, Ag, Ir and Pt metals with loading up to 5 wt. % are completely dispersed by reacting with CH3I and CO mixture. The dispersive process of the Rh nanoparticle is investigated in depth as an example. The in-situ detected I• radicals and CO molecules are identified to promote the breakage of Rh-Rh bonds and the formation of mononuclear complexes. The isolated Rh mononuclear complexes are immobilized by the oxygen-containing functional groups based on the effective atomic number rule. The method also provides a general strategy for the development of single-metal-site catalysts for other applications.
An efficient and stable photoelectrochemical system with 9% solar-to-hydrogen conversion efficiency via InGaP/GaAs double junction
Authors: Varadhan Purushothaman , Fu Hui-Chun , Kao Yu-Cheng , Horng Ray-Hua , He Jr-Hau
Published: November 2019

Despite III-V semiconductors demonstrating extraordinary solar-to-hydrogen (STH) conversion efficiencies, high cost and poor stability greatly impede their practical implementation in photoelectrochemical (PEC) water splitting applications. Here, we present a simple and efficient strategy for III-V-based photoelectrodes that functionally and spatially decouples the light harvesting component of the device from the electrolysis part that eliminates parasitic light absorption, reduces the cost, and enhances the stability without any compromise in efficiency. The monolithically integrated PEC cell was fabricated by an epitaxial lift-off and transfer of inversely grown InGaP/GaAs to a robust Ni-substrate and the resultant photoanode exhibits an STH efficiency of ~9% with stability ~150 h. Moreover, with the ability to access both sides of the device, we constructed a fully-integrated, unassisted-wireless “artificial leaf” system with an STH efficiency of ~6%. The excellent efficiency and stability achieved herein are attributed to the light harvesting/catalysis decoupling scheme, which concurrently improves the optical, electrical, and electrocatalytic characteristics.
Triplet–triplet upconversion enhanced by spin–orbit coupling in organic light-emitting diodes
Authors: Ieuji Ryota , Goushi Kenichi , Adachi Chihaya
Published: November 2019

Triplet–triplet upconversion, in which two triplet excitons are converted to one singlet exciton, is a well-known approach to exceed the limit of electroluminescence quantum efficiency in conventional fluorescence-based organic light-emitting diodes. Considering the spin multiplicity of triplet pairs, upconversion efficiency is usually limited to 20%. Although this limit can be exceeded when the energy of a triplet pair is lower than that of a second triplet excited state, such as for rubrene, it is generally difficult to engineer the energy levels of higher triplet excited states. Here, we investigate the upconversion efficiency of a series of new anthracene derivatives with different substituents. Some of these derivatives show upconversion efficiencies close to 50% even though the calculated energy levels of the second triplet excited states are lower than twice the lowest triplet energy. A possible upconversion mechanism is proposed based on the molecular structures and quantum chemical calculations.
Author Correction: Puma genomes from North and South America provide insights into the genomic consequences of inbreeding
Authors: Saremi Nedda F. , Supple Megan A. , Byrne Ashley , Cahill James A. , Coutinho Luiz Lehmann , Dalén Love , Figueiró Henrique V. , Johnson Warren E. , Milne Heather J. , O’Brien Stephen J. , O’Connell Brendan , Onorato David P. , Riley Seth P. D. , Sikich Jeff A. , Stahler Daniel R. , Villela Priscilla Marqui Schmidt , Vollmers Christopher , Wayne Robert K. , Eizirik Eduardo , Corbett-Detig Russell B. , Green Richard E. , Wilmers Christopher C. , Shapiro Beth
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Brain activity regulates loose coupling between mitochondrial and cytosolic Ca2+ transients
Authors: Lin Yuan , Li Lin-Lin , Nie Wei , Liu Xiaolei , Adler Avital , Xiao Chi , Lu Fujian , Wang Liping , Han Hua , Wang Xianhua , Gan Wen-Biao , Cheng Heping
Published: November 2019

Mitochondrial calcium ([Ca2+]mito) dynamics plays vital roles in regulating fundamental cellular and organellar functions including bioenergetics. However, neuronal [Ca2+]mito dynamics in vivo and its regulation by brain activity are largely unknown. By performing two-photon Ca2+ imaging in the primary motor (M1) and visual cortexes (V1) of awake behaving mice, we find that discrete [Ca2+]mito transients occur synchronously over somatic and dendritic mitochondrial network, and couple with cytosolic calcium ([Ca2+]cyto) transients in a probabilistic, rather than deterministic manner. The amplitude, duration, and frequency of [Ca2+]cyto transients constitute important determinants of the coupling, and the coupling fidelity is greatly increased during treadmill running (in M1 neurons) and visual stimulation (in V1 neurons). Moreover, Ca2+/calmodulin kinase II is mechanistically involved in modulating the dynamic coupling process. Thus, activity-dependent dynamic [Ca2+]mito-to-[Ca2+]cyto coupling affords an important mechanism whereby [Ca2+]mito decodes brain activity for the regulation of mitochondrial bioenergetics to meet fluctuating neuronal energy demands as well as for neuronal information processing.
Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention
Authors: Obermayer Joshua , Luchicchi Antonio , Heistek Tim S. , de Kloet Sybren F. , Terra Huub , Bruinsma Bastiaan , Mnie-Filali Ouissame , Kortleven Christian , Galakhova Anna A. , Khalil Ayoub J. , Kroon Tim , Jonker Allert J. , de Haan Roel , van de Berg Wilma D. J. , Goriounova Natalia A. , de Kock Christiaan P. J. , Pattij Tommy , Mansvelder Huibert D.
Published: November 2019

Neocortical choline acetyltransferase (ChAT)-expressing interneurons are a subclass of vasoactive intestinal peptide (ChAT-VIP) neurons of which circuit and behavioural function are unknown. Here, we show that ChAT-VIP neurons directly excite neighbouring neurons in several layers through fast synaptic transmission of acetylcholine (ACh) in rodent medial prefrontal cortex (mPFC). Both interneurons in layers (L)1–3 as well as pyramidal neurons in L2/3 and L6 receive direct inputs from ChAT-VIP neurons mediated by fast cholinergic transmission. A fraction (10–20%) of postsynaptic neurons that received cholinergic input from ChAT-VIP interneurons also received GABAergic input from these neurons. In contrast to regular VIP interneurons, ChAT-VIP neurons did not disinhibit pyramidal neurons. Finally, we show that activity of these neurons is relevant for behaviour and they control attention behaviour distinctly from basal forebrain ACh inputs. Thus, ChAT-VIP neurons are a local source of cortical ACh that directly excite neurons throughout cortical layers and contribute to attention.
Light programmable micro/nanomotors with optically tunable in-phase electric polarization
Authors: Liang Zexi , Teal Daniel , Fan Donglei
Published: November 2019

To develop active nanomaterials that can instantly respond to external stimuli with designed mechanical motions is an important step towards the realization of nanorobots. Herein, we present our finding of a versatile working mechanism that allows instantaneous change of alignment direction and speed of semiconductor nanowires in an external electric field with simple visible-light exposure. The light induced alignment switch can be cycled over hundreds of times and programmed to express words in Morse code. With theoretical analysis and simulation, the working principle can be attributed to the optically tuned real-part (in-phase) electrical polarization of a semiconductor nanowire in aqueous suspension. The manipulation principle is exploited to create a new type of microscale stepper motor that can readily switch between in-phase and out-phase modes, and agilely operate independent of neighboring motors with patterned light. This work could inspire the development of new types of micro/nanomachines with individual and reconfigurable maneuverability for many applications.
Femtosecond X-ray induced changes of the electronic and magnetic response of solids from electron redistribution
Authors: Higley Daniel J. , Reid Alex H. , Chen Zhao , Guyader Loïc Le , Hellwig Olav , Lutman Alberto A. , Liu Tianmin , Shafer Padraic , Chase Tyler , Dakovski Georgi L. , Mitra Ankush , Yuan Edwin , Schlappa Justine , Dürr Hermann A. , Schlotter William F. , Stöhr Joachim
Published: November 2019

Resonant X-ray absorption, where an X-ray photon excites a core electron into an unoccupied valence state, is an essential process in many standard X-ray spectroscopies. With increasing X-ray intensity, the X-ray absorption strength is expected to become nonlinear. Here, we report the onset of such a nonlinearity in the resonant X-ray absorption of magnetic Co/Pd multilayers near the Co L$${}_{3}$$

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edge. The nonlinearity is directly observed through the change of the absorption spectrum, which is modified in less than 40 fs within 2 eV of its threshold. This is interpreted as a redistribution of valence electrons near the Fermi level. For our magnetic sample this also involves mixing of majority and minority spins, due to sample demagnetization. Our findings reveal that nonlinear X-ray responses of materials may already occur at relatively low intensities, where the macroscopic sample is not destroyed, providing insight into ultrafast charge and spin dynamics.
The role of cyclone activity in snow accumulation on Arctic sea ice
Authors: Webster M. A. , Parker C. , Boisvert L. , Kwok R.
Published: November 2019

Identifying the mechanisms controlling the timing and magnitude of snow accumulation on sea ice is crucial for understanding snow’s net effect on the surface energy budget and sea-ice mass balance. Here, we analyze the role of cyclone activity on the seasonal buildup of snow on Arctic sea ice using model, satellite, and in situ data over 1979–2016. On average, 44% of the variability in monthly snow accumulation was controlled by cyclone snowfall and 29% by sea-ice freeze-up. However, there were strong spatio-temporal differences. Cyclone snowfall comprised ~50% of total snowfall in the Pacific compared to 83% in the Atlantic. While cyclones are stronger in the Atlantic, Pacific snow accumulation is more sensitive to cyclone strength. These findings highlight the heterogeneity in atmosphere-snow-ice interactions across the Arctic, and emphasize the need to scrutinize mechanisms governing cyclone activity to better understand their effects on the Arctic snow-ice system with anthropogenic warming.
GPCR-induced calcium transients trigger nuclear actin assembly for chromatin dynamics
Authors: Wang Ying , Sherrard Alice , Zhao Bing , Melak Michael , Trautwein Jonathan , Kleinschnitz Eva-Maria , Tsopoulidis Nikolaos , Fackler Oliver T. , Schwan Carsten , Grosse Robert
Published: November 2019

Although the properties of the actin cytoskeleton in the cytoplasm are well characterized, the regulation and function of nuclear actin filaments are only recently emerging. We previously demonstrated serum-induced, transient assembly of filamentous actin within somatic cell nuclei. However, the extracellular cues, cell surface receptors as well as underlying signaling mechanisms have been unclear. Here we demonstrate that physiological ligands for G protein-coupled receptors (GPCRs) promote nuclear F-actin assembly via heterotrimeric Gαq proteins. Signal-induced nuclear actin responses require calcium release from the endoplasmic reticulum (ER) targeting the ER-associated formin INF2 at the inner nuclear membrane (INM). Notably, calcium signaling promotes the polymerization of linear actin filaments emanating from the INM towards the nuclear interior. We show that GPCR and calcium elevations trigger nuclear actin-dependent alterations in chromatin organization, uncovering a general cellular mechanism by which physiological ligands and calcium promote nuclear F-actin assembly for rapid responses towards chromatin dynamics.
Asian monsoon rainfall variation during the Pliocene forced by global temperature change
Authors: Wang Hanlin , Lu Huayu , Zhao Lin , Zhang Hongyan , Lei Fang , Wang Yichao
Published: November 2019

The Asian monsoon variations under global temperature changes during the Pliocene are still debated. Here we use a sedimentary record of phytoliths (plant silica) from the Weihe Basin, central China, to explore the history of C4 grasses and quantitatively reconstruct the Asian monsoon climate since the late Miocene. Our results show that C4 grasses have been a dominant grassland component since ~11.0 Ma. A subsequent marked decrease in warm- and humid-adapted C4 grasses and an increase in cool- and dry-adapted C3 grasses occurred in the Pliocene, ~4.0 Ma; the phytolith-based quantitative reconstruction of mean annual precipitation marked a decrease from 800~1673 mm to 443~900 mm, indicating a reduction in Asian monsoon rainfall in the Pliocene. Our newly obtained records conflict with the hypothesis that the growth of the Tibetan Plateau strengthened the Asian monsoon rainfall. Nevertheless, they emphasize the importance of global temperature as a determinant of Pliocene Asian monsoon variations.
Personalised analytics for rare disease diagnostics
Authors: Anderson Denise , Baynam Gareth , Blackwell Jenefer M. , Lassmann Timo
Published: November 2019

Whole genome and exome sequencing is a standard tool for the diagnosis of patients suffering from rare and other genetic disorders. The interpretation of the tens of thousands of variants returned from such tests remains a major challenge. Here we focus on the problem of prioritising variants with respect to the observed disease phenotype. We hypothesise that linking patterns of gene expression across multiple tissues to the phenotypes will aid in discovering disease causing variants. To test this, we construct classifiers that learn associations between tissue-specific gene expression and disease phenotypes. We find that using Genotype-Tissue Expression project (GTEx) expression data in conjunction with disease agnostic variant prioritisation methods (CADD or MetaSVM) results in consistent improvements in classification accuracy. Our method represents a previously overlooked avenue of utilising existing expression data for clinical diagnostics, and also opens the door to use of other functional genomic data sets in the same manner.
Atomistic simulations shed new light on the activation mechanisms of RORγ and classify it as Type III nuclear hormone receptor regarding ligand-binding paths
Authors: Saen-Oon Suwipa , Lozoya Estrella , Segarra Victor , Guallar Victor , Soliva Robert
Published: November 2019

The molecular recognition of the RORγ nuclear hormone receptor (NHR) ligand-binding domain (LBD) has been extensively studied with numerous X-ray crystal structures. However, the picture afforded by these complexes is static and does not fully explain the functional behavior of the LBD. In particular, the apo structure of the LBD seems to be in a fully active state, with no obvious differences to the agonist-bound structure. Further, several atypical in vivo inverse agonists have surprisingly been found to co-crystallize with the LBD in agonist mode (with co-activator), leading to a disconnection between molecular recognition and functional activity. Moreover, the experimental structures give no clues on how RORγ LBD binders access the interior of the LBD. To address all these points, we probe here, with a variety of simulation techniques, the fine structural balance of the RORγ LBD in its apo vs. holo form, the differences in flexibility and stability of the LBD in complex with agonists vs. inverse agonists and how binders diffuse in and out of the LBD in unbiased simulations. Our data conclusively point to the stability afforded by the so-called “agonist lock” between H479 and Y502 and the precise location of Helix 12 (H12) for the competence of the LBD to bind co-activator proteins. We observe the “water trapping” mechanism suggested previously for the atypical inverse agonists and discover a different behavior for the latter when co-activator is present or absent, which might help explain their conflicting data. Additionally, we unveil the same entry/exit path for agonists and inverse agonist into and out of the LBD for RORγ, suggesting it belongs to the type III NHR sub-family.