bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulation‐Derived Radar Cross Sections of a New Meteor Head Plasma Distribution Model
Authors: Sugar G. , Marshall R. , Oppenheim M. M. , Dimant Y. S. , Close S. 
Published: June 2021

AbstractWe present results and analysis of finite‐difference time‐domain (FDTD) simulations of electromagnetic waves scattering off meteor head plasma using an analytical model and a simulation‐derived model of the head plasma distribution. The analytical model was developed by (Dimant & Oppenheim, 2017b, https://doi.org/10.1002/2017JA023963) and the simulation‐derived model is based on particle‐in‐cell (PIC) simulations presented in (Sugar et al., 2019, https://doi.org/10.1029/2018JA026434). Both of these head plasma distribution models show the meteor head plasma is significantly different than the spherically symmetric distributions used in previous studies of meteor head plasma. We use the FDTD simulation results to fit a power law model that relates the meteoroid ablation rate to the head echo radar cross section (RCS), and show that the RCS of plasma distributions derived from the Dimant‐Oppenheim analytical model and the PIC simulations agree to within 4 dBsm. The power law model yields more accurate meteoroid mass estimates than previous methods based on spherically symmetric plasma distributions.
The Biophysical Role of Water and Ice Within Permafrost Nearing Collapse: Insights From Novel Geophysical Observations
Authors: James S. R. , Minsley B. J. , McFarland J. W. , Euskirchen E. S. , Edgar C. W. , Waldrop M. P. 
Published: June 2021

AbstractThe impact of permafrost thaw on hydrologic, thermal, and biotic processes remains uncertain, in part due to limitations in subsurface measurement capabilities. To better understand subsurface processes in thermokarst environments, we collocated geophysical and biogeochemical instruments along a thaw gradient between forested permafrost and collapse‐scar bogs at the Alaska Peatland Experiment site near Fairbanks, Alaska. Ambient seismic noise monitoring provided continuous high‐temporal resolution measurements of water and ice saturation changes. Maps of seismic velocity change identified areas of large summertime velocity reductions nearest the youngest bog, indicating potential thaw and expansion at the bog margin. These results corresponded well with complementary borehole nuclear magnetic resonance measurements of unfrozen water content with depth, which showed permafrost soils nearest the bog edges contained the largest amount of unfrozen water along the study transect, up to 25% by volume. In situ measurements of methane within permafrost soils revealed high concentrations at these bog‐edge locations, up to 30% soil gas. Supra‐permafrost talik zones were observed at the bog margins, indicating talik formation and perennial liquid water may drive lateral bog expansion and enhanced permafrost carbon losses preceding thaw. Comparison of seismic monitoring with wintertime surface carbon dioxide fluxes revealed differential responses depending on time and proximity to the bogs, capturing the controlling influence of subsurface water and ice on microbial activity and surficial emissions. This study demonstrates a multidisciplinary approach for gaining new understanding of how subsurface physical properties influence greenhouse gas production, emissions, and thermokarst development.
Using induced pluripotent stem cells to investigate human neuronal phenotypes in 1q21.1 deletion and duplication syndrome
Authors: Chapman Gareth , Alsaqati Mouhamed , Lunn Sharna , Singh Tanya , Linden Stefanie C. , Linden David E. J. , van den Bree Marianne B. M. , Ziller Mike , Owen Michael J. , Hall Jeremy , Harwood Adrian J. , Syed Yasir Ahmed 
Published: June 2021

AbstractCopy Number Variation (CNV) at the 1q21.1 locus is associated with a range of neurodevelopmental and psychiatric disorders in humans, including abnormalities in head size and motor deficits. Yet, the functional consequences of these CNVs (both deletion and duplication) on neuronal development remain unknown. To determine the impact of CNV at the 1q21.1 locus on neuronal development, we generated induced pluripotent stem cells from individuals harbouring 1q21.1 deletion or duplication and differentiated them into functional cortical neurons. We show that neurons with 1q21.1 deletion or duplication display reciprocal phenotype with respect to proliferation, differentiation potential, neuronal maturation, synaptic density and functional activity. Deletion of the 1q21.1 locus was also associated with an increased expression of lower cortical layer markers. This difference was conserved in the mouse model of 1q21.1 deletion, which displayed altered corticogenesis. Importantly, we show that neurons with 1q21.1 deletion and duplication are associated with differential expression of calcium channels and demonstrate that physiological deficits in neurons with 1q21.1 deletion or duplication can be pharmacologically modulated by targeting Ca2+ channel activity. These findings provide biological insight into the neuropathological mechanism underlying 1q21.1 associated brain disorder and indicate a potential target for therapeutic interventions.
FKBP4 integrates FKBP4/Hsp90/IKK with FKBP4/Hsp70/RelA complex to promote lung adenocarcinoma progression via IKK/NF-κB signaling
Authors: Zong Shuai , Jiao Yulian , Liu Xin , Mu Wenli , Yuan Xiaotian , Qu Yunyun , Xia Yu , Liu Shuang , Sun Huanxin , Wang Laicheng , Cui Bin , Liu Xiaowen , Li Ping , Zhao Yueran 
Published: June 2021

AbstractFKBP4 belongs to the family of immunophilins, which serve as a regulator for steroid receptor activity. Thus, FKBP4 has been recognized to play a critical role in several hormone-dependent cancers, including breast and prostate cancer. However, there is still no research to address the role of FKBP4 on lung adenocarcinoma (LUAD) progression. We found that FKBP4 expression was elevated in LUAD samples and predicted significantly shorter overall survival based on TCGA and our cohort of LUAD patients. Furthermore, FKBP4 robustly increased the proliferation, metastasis, and invasion of LUAD in vitro and vivo. Mechanistic studies revealed the interaction between FKBP4 and IKK kinase complex. We found that FKBP4 potentiated IKK kinase activity by interacting with Hsp90 and IKK subunits and promoting Hsp90/IKK association. Also, FKBP4 promotes the binding of IKKγ to IKKβ, which supported the facilitation role in IKK complex assembly. We further identified that FKBP4 TPR domains are essential for FKBP4/IKK interaction since its association with Hsp90 is required. In addition, FKBP4 PPIase domains are involved in FKBP4/IKKγ interaction. Interestingly, the association between FKBP4 and Hsp70/RelA favors the transport of RelA toward the nucleus. Collectively, FKBP4 integrates FKBP4/Hsp90/IKK with FKBP4/Hsp70/RelA complex to potentiate the transcriptional activity and nuclear translocation of NF-κB, thereby promoting LUAD progression. Our findings suggest that FKBP4 may function as a prognostic biomarker of LUAD and provide a newly mechanistic insight into modulating IKK/NF-κB signaling.
LncRNA CTD-2528L19.6 prevents the progression of IPF by alleviating fibroblast activation
Authors: Chen Tingting , Guo Yingying , Wang Jiayi , Ai Liqiang , Ma Lu , He Wenxin , Li Zhixin , Yu Xiaojiang , Li Jinrui , Fan Xingxing , Gu Yunyan , Liang Haihai 
Published: June 2021

AbstractLong non-coding RNAs (lncRNAs) have emerged as critical factors for regulating multiple biological processes during organ fibrosis. However, the mechanism of lncRNAs in idiopathic pulmonary fibrosis (IPF) remains incompletely understood. In the present study, two sets of lncRNAs were defined: IPF pathogenic lncRNAs and IPF progression lncRNAs. IPF pathogenic and progression lncRNAs-mRNAs co-expression networks were constructed to identify essential lncRNAs. Network analysis revealed a key lncRNA CTD-2528L19.6, which was up-regulated in early-stage IPF compared to normal lung tissue, and subsequently down-regulated during advanced-stage IPF. CTD-2528L19.6 was indicated to regulate fibroblast activation in IPF progression by mediating the expression of fibrosis related genes LRRC8C, DDIT4, THBS1, S100A8 and TLR7 et al. Further studies showed that silencing of CTD-2528L19.6 increases the expression of Fn1 and Collagen I both at mRNA and protein levels, promoted the transition of fibroblasts into myofibroblasts and accelerated the migration and proliferation of MRC-5 cells. In contrast, CTD-2528L19.6 overexpression alleviated fibroblast activation in MRC-5 cells induced by TGF-β1. LncRNA CTD-2528L19.6 inhibited fibroblast activation through regulating the expression of LRRC8C in vitro assays. Our results suggest that CTD-2528L19.6 may prevent the progression of IPF from early-stage and alleviate fibroblast activation during the advanced-stage of IPF. Thus, exploring the regulatory effect of lncRNA CTD-2528L19.6 may provide new sights for the prevention and treatment of IPF.
A meta-analysis of epigenome-wide association studies in Alzheimer’s disease highlights novel differentially methylated loci across cortex
Authors: Smith Rebecca G. , Pishva Ehsan , Shireby Gemma , Smith Adam R. , Roubroeks Janou A. Y. , Hannon Eilis , Wheildon Gregory , Mastroeni Diego , Gasparoni Gilles , Riemenschneider Matthias , Giese Armin , Sharp Andrew J. , Schalkwyk Leonard , Haroutunian Vahram , Viechtbauer Wolfgang , van den Hove Daniel L. A. , Weedon Michael , Brokaw Danielle , Francis Paul T. , Thomas Alan J. , Love Seth , Morgan Kevin , Walter Jörn , Coleman Paul D. , Bennett David A. , De Jager Philip L. , Mill Jonathan , Lunnon Katie 
Published: June 2021

AbstractEpigenome-wide association studies of Alzheimer’s disease have highlighted neuropathology-associated DNA methylation differences, although existing studies have been limited in sample size and utilized different brain regions. Here, we combine data from six DNA methylomic studies of Alzheimer’s disease (N = 1453 unique individuals) to identify differential methylation associated with Braak stage in different brain regions and across cortex. We identify 236 CpGs in the prefrontal cortex, 95 CpGs in the temporal gyrus and ten CpGs in the entorhinal cortex at Bonferroni significance, with none in the cerebellum. Our cross-cortex meta-analysis (N = 1408 donors) identifies 220 CpGs associated with neuropathology, annotated to 121 genes, of which 84 genes have not been previously reported at this significance threshold. We have replicated our findings using two further DNA methylomic datasets consisting of a further >600 unique donors. The meta-analysis summary statistics are available in our online data resource (www.epigenomicslab.com/ad-meta-analysis/).
Impairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis
Authors: Jungwirth Ute , van Weverwijk Antoinette , Evans Rachel J. , Jenkins Liam , Vicente David , Alexander John , Gao Qiong , Haider Syed , Iravani Marjan , Isacke Clare M. 
Published: June 2021

AbstractProfiling studies have revealed considerable phenotypic heterogeneity in cancer-associated fibroblasts (CAFs) present within the tumour microenvironment, however, functional characterisation of different CAF subsets is hampered by the lack of specific markers defining these populations. Here we show that genetic deletion of the Endo180 (MRC2) receptor, predominantly expressed by a population of matrix-remodelling CAFs, profoundly limits tumour growth and metastasis; effects that can be recapitulated in 3D co-culture assays. This impairment results from a CAF-intrinsic contractility defect and reduced CAF viability, which coupled with the lack of phenotype in the normal mouse, demonstrates that upregulated Endo180 expression by a specific, potentially targetable CAF subset is required to generate a supportive tumour microenvironment. Further, characterisation of a tumour subline selected via serial in vivo passage for its ability to overcome these stromal defects provides important insight into, how tumour cells adapt to a non-activated stroma in the early stages of metastatic colonisation.
TLR4 signalling via Piezo1 engages and enhances the macrophage mediated host response during bacterial infection
Authors: Geng Jing , Shi Yiran , Zhang Jinjia , Yang Bingying , Wang Ping , Yuan Weihong , Zhao Hao , Li Junhong , Qin Funiu , Hong Lixin , Xie Changchuan , Deng Xianming , Sun Yujie , Wu Congying , Chen Lanfen , Zhou Dawang 
Published: June 2021

AbstractTLR4 signaling plays key roles in the innate immune response to microbial infection. Innate immune cells encounter different mechanical cues in both health and disease to adapt their behaviors. However, the impact of mechanical sensing signals on TLR4 signal-mediated innate immune response remains unclear. Here we show that TLR4 signalling augments macrophage bactericidal activity through the mechanical sensor Piezo1. Bacterial infection or LPS stimulation triggers assembly of the complex of Piezo1 and TLR4 to remodel F-actin organization and augment phagocytosis, mitochondrion-phagosomal ROS production and bacterial clearance and genetic deficiency of Piezo1 results in abrogation of these responses. Mechanistically, LPS stimulates TLR4 to induce Piezo1-mediated calcium influx and consequently activates CaMKII-Mst1/2-Rac axis for pathogen ingestion and killing. Inhibition of CaMKII or knockout of either Mst1/2 or Rac1 results in reduced macrophage bactericidal activity, phenocopying the Piezo1 deficiency. Thus, we conclude that TLR4 drives the innate immune response via Piezo1 providing critical insight for understanding macrophage mechanophysiology and the host response.
Cell segmentation-free inference of cell types from in situ transcriptomics data
Authors: Park Jeongbin , Choi Wonyl , Tiesmeyer Sebastian , Long Brian , Borm Lars E. , Garren Emma , Nguyen Thuc Nghi , Tasic Bosiljka , Codeluppi Simone , Graf Tobias , Schlesner Matthias , Stegle Oliver , Eils Roland , Ishaque Naveed 
Published: June 2021

AbstractMultiplexed fluorescence in situ hybridization techniques have enabled cell-type identification, linking transcriptional heterogeneity with spatial heterogeneity of cells. However, inaccurate cell segmentation reduces the efficacy of cell-type identification and tissue characterization. Here, we present a method called Spot-based Spatial cell-type Analysis by Multidimensional mRNA density estimation (SSAM), a robust cell segmentation-free computational framework for identifying cell-types and tissue domains in 2D and 3D. SSAM is applicable to a variety of in situ transcriptomics techniques and capable of integrating prior knowledge of cell types. We apply SSAM to three mouse brain tissue images: the somatosensory cortex imaged by osmFISH, the hypothalamic preoptic region by MERFISH, and the visual cortex by multiplexed smFISH. Here, we show that SSAM detects regions occupied by known cell types that were previously missed and discovers new cell types.
Deciphering an AgRP-serotoninergic neural circuit in distinct control of energy metabolism from feeding
Authors: Han Yong , Xia Guobin , Srisai Dollada , Meng Fantao , He Yanlin , Ran Yali , He Yang , Farias Monica , Hoang Giang , Tóth István , Dietrich Marcelo O. , Chen Miao-Hsueh , Xu Yong , Wu Qi 
Published: June 2021

AbstractContrasting to the established role of the hypothalamic agouti-related protein (AgRP) neurons in feeding regulation, the neural circuit and signaling mechanisms by which they control energy expenditure remains unclear. Here, we report that energy expenditure is regulated by a subgroup of AgRP neurons that send non-collateral projections to neurons within the dorsal lateral part of dorsal raphe nucleus (dlDRN) expressing the melanocortin 4 receptor (MC4R), which in turn innervate nearby serotonergic (5-HT) neurons. Genetic manipulations reveal a bi-directional control of energy expenditure by this circuit without affecting food intake. Fiber photometry and electrophysiological results indicate that the thermo-sensing MC4RdlDRN neurons integrate pre-synaptic AgRP signaling, thereby modulating the post-synaptic serotonergic pathway. Specifically, the MC4RdlDRN signaling elicits profound, bi-directional, regulation of body weight mainly through sympathetic outflow that reprograms mitochondrial bioenergetics within brown and beige fat while feeding remains intact. Together, we suggest that this AgRP neural circuit plays a unique role in persistent control of energy expenditure and body weight, hinting next-generation therapeutic approaches for obesity and metabolic disorders.
Projected losses of ecosystem services in the US disproportionately affect non-white and lower-income populations
Authors: Gourevitch Jesse D. , Alonso-Rodríguez Aura M. , Aristizábal Natalia , de Wit Luz A. , Kinnebrew Eva , Littlefield Caitlin E. , Moore Maya , Nicholson Charles C. , Schwartz Aaron J. , Ricketts Taylor H. 
Published: June 2021

AbstractAddressing how ecosystem services (ES) are distributed among groups of people is critical for making conservation and environmental policy-making more equitable. Here, we evaluate the distribution and equity of changes in ES benefits across demographic and socioeconomic groups in the United States (US) between 2020 and 2100. Specifically, we use land cover and population projections to model potential shifts in the supply, demand, and benefits of the following ES: provision of clean air, protection against a vector-borne disease (West Nile virus), and crop pollination. Across the US, changes in ES benefits are unevenly distributed among socioeconomic and demographic groups and among rural and urban communities, but are relatively uniform across geographic regions. In general, non-white, lower-income, and urban populations disproportionately bear the burden of declines in ES benefits. This is largely driven by the conversion of forests and wetlands to cropland and urban land cover in counties where these populations are expected to grow. In these locations, targeted land use policy interventions are required to avoid exacerbating inequalities already present in the US.
Ventral tegmental area GABA neurons mediate stress-induced blunted reward-seeking in mice
Authors: Lowes Daniel C. , Chamberlin Linda A. , Kretsge Lisa N. , Holt Emma S. , Abbas Atheir I. , Park Alan J. , Yusufova Lyubov , Bretton Zachary H. , Firdous Ayesha , Enikolopov Armen G. , Gordon Joshua A. , Harris Alexander Z. 
Published: June 2021

AbstractDecreased pleasure-seeking (anhedonia) forms a core symptom of depression. Stressful experiences precipitate depression and disrupt reward-seeking, but it remains unclear how stress causes anhedonia. We recorded simultaneous neural activity across limbic brain areas as mice underwent stress and discovered a stress-induced 4 Hz oscillation in the nucleus accumbens (NAc) that predicts the degree of subsequent blunted reward-seeking. Surprisingly, while previous studies on blunted reward-seeking focused on dopamine (DA) transmission from the ventral tegmental area (VTA) to the NAc, we found that VTA GABA, but not DA, neurons mediate stress-induced blunted reward-seeking. Inhibiting VTA GABA neurons disrupts stress-induced NAc oscillations and rescues reward-seeking. By contrast, mimicking this signature of stress by stimulating NAc-projecting VTA GABA neurons at 4 Hz reproduces both oscillations and blunted reward-seeking. Finally, we find that stress disrupts VTA GABA, but not DA, neural encoding of reward anticipation. Thus, stress elicits VTA-NAc GABAergic activity that induces VTA GABA mediated blunted reward-seeking.
IrW nanochannel support enabling ultrastable electrocatalytic oxygen evolution at 2 A cm−2 in acidic media
Authors: Li Rui , Wang Haiyun , Hu Fei , Chan K. C. , Liu Xiongjun , Lu Zhaoping , Wang Jing , Li Zhibin , Zeng Longjiao , Li Yuanyuan , Wu Xiaojun , Xiong Yujie 
Published: June 2021

AbstractA grand challenge for proton exchange membrane electrolyzers is the rational design of oxygen evolution reaction electrocatalysts to balance activity and stability. Here, we report a support-stabilized catalyst, the activated ~200 nm-depth IrW nanochannel that achieves the current density of 2 A cm−2 at an overpotential of only ~497 mV and maintains ultrastable gas evolution at 100 mA cm−2 at least 800 h with a negligible degradation rate of ~4 μV h−1. Structure analyses combined with theoretical calculations indicate that the IrW support alters the charge distribution of surface (IrO2)n clusters and effectively confines the cluster size within 4 (n≤4). Such support-stabilizing effect prevents the surface Ir from agglomeration and retains a thin layer of electrocatalytically active IrO2 clusters on surface, realizing a win-win strategy for ultrahigh OER activity and stability. This work would open up an opportunity for engineering suitable catalysts for robust proton exchange membrane-based electrolyzers.
Automated scoring of pre-REM sleep in mice with deep learning
Authors: Grieger Niklas , Schwabedal Justus T. C. , Wendel Stefanie , Ritze Yvonne , Bialonski Stephan 
Published: June 2021

AbstractReliable automation of the labor-intensive manual task of scoring animal sleep can facilitate the analysis of long-term sleep studies. In recent years, deep-learning-based systems, which learn optimal features from the data, increased scoring accuracies for the classical sleep stages of Wake, REM, and Non-REM. Meanwhile, it has been recognized that the statistics of transitional stages such as pre-REM, found between Non-REM and REM, may hold additional insight into the physiology of sleep and are now under vivid investigation. We propose a classification system based on a simple neural network architecture that scores the classical stages as well as pre-REM sleep in mice. When restricted to the classical stages, the optimized network showed state-of-the-art classification performance with an out-of-sample F1 score of 0.95 in male C57BL/6J mice. When unrestricted, the network showed lower F1 scores on pre-REM (0.5) compared to the classical stages. The result is comparable to previous attempts to score transitional stages in other species such as transition sleep in rats or N1 sleep in humans. Nevertheless, we observed that the sequence of predictions including pre-REM typically transitioned from Non-REM to REM reflecting sleep dynamics observed by human scorers. Our findings provide further evidence for the difficulty of scoring transitional sleep stages, likely because such stages of sleep are under-represented in typical data sets or show large inter-scorer variability. We further provide our source code and an online platform to run predictions with our trained network.
Extraversion level predicts perceived benefits from social resources and tool use
Authors: Murday Vincent , Campos-Moinier Kévin , Osiurak François , Brunel Lionel 
Published: June 2021

AbstractSocial baseline theory states that there are differences in how humans integrate social resources into their economy of action when they face environmental demands. However, although several authors suggested that extraversion may be an indicator of the social baseline, no study has demonstrated it. The present study aims to test this hypothesis and, in particular, examines whether extraversion is a specific indicator of the social baseline. In two experiments, participants were asked to move rolls either alone (with their hands), or with the help of a social resource (Experiment 1), or a tool (Experiment 2). Results showed that extraversion predicted the choice to use both types of resource. Specifically, the more participants were extraverted, the more they tended to consider the use of the social resource or the tool as beneficial. We argue that these results indicate that extraversion is not specifically an indicator of the social baseline, but rather an indicator of how individuals integrate technical and social resources into their economy of action. In addition, this study encourages future research endeavors to define what constitutes a resource and how it could fit into the Social Baseline Theory.