bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of anti-correlation of hot and cold baryons in galaxy clusters
Authors: Farahi Arya , Mulroy Sarah L. , Evrard August E. , Smith Graham P. , Finoguenov Alexis , Bourdin Hervé , Carlstrom John E. , Haines Chris P. , Marrone Daniel P. , Martino Rossella , Mazzotta Pasquale , O’Donnell Christine , Okabe Nobuhiro 
Published: July 2019

AbstractThe largest clusters of galaxies in the Universe contain vast amounts of dark matter, plus baryonic matter in two principal phases, a majority hot gas component and a minority cold stellar phase comprising stars, compact objects, and low-temperature gas. Hydrodynamic simulations indicate that the highest-mass systems retain the cosmic fraction of baryons, a natural consequence of which is anti-correlation between the masses of hot gas and stars within dark matter halos of fixed total mass. We report observational detection of this anti-correlation based on 4 elements of a 9 × 9-element covariance matrix for nine cluster properties, measured from multi-wavelength observations of 41 clusters from the Local Cluster Substructure Survey. These clusters were selected using explicit and quantitative selection rules that were then encoded in our hierarchical Bayesian model. Our detection of anti-correlation is consistent with predictions from contemporary hydrodynamic cosmological simulations that were not tuned to reproduce this signal.
Multi-functional soft-bodied jellyfish-like swimming
Authors: Ren Ziyu , Hu Wenqi , Dong Xiaoguang , Sitti Metin 
Published: July 2019

AbstractThe functionalities of the untethered miniature swimming robots significantly decrease as the robot size becomes smaller, due to limitations of feasible miniaturized on-board components. Here we propose an untethered jellyfish-inspired soft millirobot that could realize multiple functionalities in moderate Reynolds number by producing diverse controlled fluidic flows around its body using its magnetic composite elastomer lappets, which are actuated by an external oscillating magnetic field. We particularly investigate the interaction between the robot’s soft body and incurred fluidic flows due to the robot’s body motion, and utilize such physical interaction to achieve different predation-inspired object manipulation tasks. The proposed lappet kinematics can inspire other existing jellyfish-like robots to achieve similar functionalities at the same length and time scale. Moreover, the robotic platform could be used to study the impacts of the morphology and kinematics changing in ephyra jellyfish.
Spatial suppression promotes rapid figure-ground segmentation of moving objects
Authors: Tadin Duje , Park Woon Ju , Dieter Kevin C. , Melnick Michael D. , Lappin Joseph S. , Blake Randolph 
Published: July 2019

AbstractSegregation of objects from their backgrounds is a fundamental visual function and one that is particularly effective when objects are in motion. Theoretically, suppressive center-surround mechanisms are well suited for accomplishing motion segregation. This longstanding hypothesis, however, has received limited empirical support. We report converging correlational and causal evidence that spatial suppression of background motion signals is critical for rapid segmentation of moving objects. Motion segregation ability is strongly predicted by both individual and stimulus-driven variations in spatial suppression strength. Moreover, aging-related superiority in perceiving background motion is associated with profound impairments in motion segregation. This segregation deficit is alleviated via perceptual learning, but only when motion segregation training also causes decreased sensitivity to background motion. We argue that perceptual insensitivity to large moving stimuli effectively implements background subtraction, which, in turn, enhances the visibility of moving objects and accounts for the observed link between spatial suppression and motion segregation.
The deubiquitylase OTUD3 stabilizes GRP78 and promotes lung tumorigenesis
Authors: Du Tongde , Li Hongchang , Fan Yongsheng , Yuan Lin , Guo Xiaodan , Zhu Qiong , Yao Yuying , Li Xin , Liu Chunlei , Yu Xinhe , Liu Zhaofei , Cui Chun-Ping , Han Chuanchun , Zhang Lingqiang 
Published: July 2019

AbstractThe deubiquitylase OTUD3 plays a suppressive role in breast tumorigenesis through stabilizing PTEN protein, but its role in lung cancer remains unclear. Here, we demonstrate that in vivo deletion of OTUD3 indeed promotes breast cancer development in mice, but by contrast, it slows down KrasG12D-driven lung adenocarcinoma (ADC) initiation and progression and markedly increases survival in mice. Moreover, OTUD3 is highly expressed in human lung cancer tissues and its higher expression correlates with poorer survival of patients. Further mechanistic studies reveal that OTUD3 interacts with, deubiquitylates and stabilizes the glucose-regulated protein GRP78. Knockdown of OTUD3 results in a decrease in the level of GRP78 protein, suppression of cell growth and migration, and tumorigenesis in lung cancer. Collectively, our results reveal a previously unappreciated pro-oncogenic role of OTUD3 in lung cancer and indicate that deubiquitylases could elicit tumor-suppressing or tumor-promoting activities in a cell- and tissue-dependent context.
An anionic human protein mediates cationic liposome delivery of genome editing proteins into mammalian cells
Authors: Kim Y. Bill , Zhao Kevin T. , Thompson David B. , Liu David R. 
Published: July 2019

AbstractDelivery into mammalian cells remains a significant challenge for many applications of proteins as research tools and therapeutics. We recently reported that the fusion of cargo proteins to a supernegatively charged (–30)GFP enhances encapsulation by cationic lipids and delivery into mammalian cells. To discover polyanionic proteins with optimal delivery properties, we evaluate negatively charged natural human proteins for their ability to deliver proteins into cultured mammalian cells and human primary fibroblasts. Here we discover that ProTα, a small, widely expressed, intrinsically disordered human protein, enables up to ~10-fold more efficient cationic lipid-mediated protein delivery compared to (–30)GFP. ProTα enables efficient delivery at low- to mid-nM concentrations of two unrelated genome editing proteins, Cre recombinase and zinc-finger nucleases, under conditions in which (–30)GFP fusion or cationic lipid alone does not result in substantial activity. ProTα may enable mammalian cell protein delivery applications when delivery potency is limiting.
Mechanically strong MXene/Kevlar nanofiber composite membranes as high-performance nanofluidic osmotic power generators
Authors: Zhang Zhen , Yang Sheng , Zhang Panpan , Zhang Jian , Chen Guangbo , Feng Xinliang 
Published: July 2019

AbstractTwo-dimensional nanofluidic channels are emerging candidates for capturing osmotic energy from salinity gradients. However, present two-dimensional nanofluidic architectures are generally constructed by simple stacking of pristine nanosheets with insufficient charge densities, and exhibit low-efficiency transport dynamics, consequently resulting in undesirable power densities (<1 W m−2). Here we demonstrate MXene/Kevlar nanofiber composite membranes as high-performance nanofluidic osmotic power generators. By mixing river water and sea water, the power density can achieve a value of approximately 4.1 W m−2, outperforming the state-of-art membranes to the best of our knowledge. Experiments and theoretical calculations reveal that the correlation between surface charge of MXene and space charge brought by nanofibers plays a key role in modulating ion diffusion and can synergistically contribute to such a considerable energy conversion performance. This work highlights the promise in the coupling of surface charge and space charge in nanoconfinement for energy conversion driven by chemical potential gradients.
Fas signaling-mediated TH9 cell differentiation favors bowel inflammation and antitumor functions
Authors: Shen Yingying , Song Zhengbo , Lu Xinliang , Ma Zeyu , Lu Chaojie , Zhang Bei , Chen Yinghu , Duan Meng , Apetoh Lionel , Li Xu , Guo Jufeng , Miao Ying , Zhang Gensheng , Yang Diya , Cai Zhijian , Wang Jianli 
Published: July 2019

AbstractFas induces apoptosis in activated T cell to maintain immune homeostasis, but the effects of non-apoptotic Fas signaling on T cells remain unclear. Here we show that Fas promotes TH9 cell differentiation by activating NF-κB via Ca2+-dependent PKC-β activation. In addition, PKC-β also phosphorylates p38 to inactivate NFAT1 and reduce NFAT1-NF-κB synergy to promote the Fas-induced TH9 transcription program. Fas ligation exacerbates inflammatory bowel disease by increasing TH9 cell differentiation, and promotes antitumor activity in p38 inhibitor-treated TH9 cells. Furthermore, low-dose p38 inhibitor suppresses tumor growth without inducing systemic adverse effects. In patients with tumor, relatively high TH9 cell numbers are associated with good prognosis. Our study thus implicates Fas in CD4+ T cells as a target for inflammatory bowel disease therapy. Furthermore, simultaneous Fas ligation and low-dose p38 inhibition may be an effective approach for TH9 cell induction and cancer therapy.
Cell type-dependent differential activation of ERK by oncogenic KRAS in colon cancer and intestinal epithelium
Authors: Brandt Raphael , Sell Thomas , Lüthen Mareen , Uhlitz Florian , Klinger Bertram , Riemer Pamela , Giesecke-Thiel Claudia , Schulze Silvia , El-Shimy Ismail Amr , Kunkel Desiree , Fauler Beatrix , Mielke Thorsten , Mages Norbert , Herrmann Bernhard G. , Sers Christine , Blüthgen Nils , Morkel Markus 
Published: July 2019

AbstractOncogenic mutations in KRAS or BRAF are frequent in colorectal cancer and activate the ERK kinase. Here, we find graded ERK phosphorylation correlating with cell differentiation in patient-derived colorectal cancer organoids with and without KRAS mutations. Using reporters, single cell transcriptomics and mass cytometry, we observe cell type-specific phosphorylation of ERK in response to transgenic KRASG12Vin mouse intestinal organoids, while transgenic BRAFV600Eactivates ERK in all cells. Quantitative network modelling from perturbation data reveals that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identify dual-specificity phosphatases as candidate modulators of ERK in the intestine. Furthermore, we find that oncogenic KRAS, together with β-Catenin, favours expansion of crypt cells with high ERK activity. Our experiments highlight key differences between oncogenic BRAF and KRAS in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy.
Chemical logic of MraY inhibition by antibacterial nucleoside natural products
Authors: Mashalidis Ellene H. , Kaeser Benjamin , Terasawa Yuma , Katsuyama Akira , Kwon Do-Yeon , Lee Kiyoun , Hong Jiyong , Ichikawa Satoshi , Lee Seok-Yong 
Published: July 2019

AbstractNovel antibacterial agents are needed to address the emergence of global antibiotic resistance. MraY is a promising candidate for antibiotic development because it is the target of five classes of naturally occurring nucleoside inhibitors with potent antibacterial activity. Although these natural products share a common uridine moiety, their core structures vary substantially and they exhibit different activity profiles. An incomplete understanding of the structural and mechanistic basis of MraY inhibition has hindered the translation of these compounds to the clinic. Here we present crystal structures of MraY in complex with representative members of the liposidomycin/caprazamycin, capuramycin, and mureidomycin classes of nucleoside inhibitors. Our structures reveal cryptic druggable hot spots in the shallow inhibitor binding site of MraY that were not previously appreciated. Structural analyses of nucleoside inhibitor binding provide insights into the chemical logic of MraY inhibition, which can guide novel approaches to MraY-targeted antibiotic design.
Myc targeted CDK18 promotes ATR and homologous recombination to mediate PARP inhibitor resistance in glioblastoma
Authors: Ning Jian-Fang , Stanciu Monica , Humphrey Melissa R. , Gorham Joshua , Wakimoto Hiroko , Nishihara Reiko , Lees Jacqueline , Zou Lee , Martuza Robert L. , Wakimoto Hiroaki , Rabkin Samuel D. 
Published: July 2019

AbstractPARP inhibitors (PARPis) have clinical efficacy in BRCA-deficient cancers, but not BRCA-intact tumors, including glioblastoma (GBM). We show that MYC or MYCN amplification in patient-derived glioblastoma stem-like cells (GSCs) generates sensitivity to PARPi via Myc-mediated transcriptional repression of CDK18, while most tumors without amplification are not sensitive. In response to PARPi, CDK18 facilitates ATR activation by interacting with ATR and regulating ATR-Rad9/ATR-ETAA1 interactions; thereby promoting homologous recombination (HR) and PARPi resistance. CDK18 knockdown or ATR inhibition in GSCs suppressed HR and conferred PARPi sensitivity, with ATR inhibitors synergizing with PARPis or sensitizing GSCs. ATR inhibitor VE822 combined with PARPi extended survival of mice bearing GSC-derived orthotopic tumors, irrespective of PARPi-sensitivity. These studies identify a role of CDK18 in ATR-regulated HR. We propose that combined blockade of ATR and PARP is an effective strategy for GBM, even for low-Myc GSCs that do not respond to PARPi alone, and potentially other PARPi-refractory tumors.
Two-gap superconductivity in CaFe0.88Co0.12AsF revealed by temperature dependence of the lower critical field Hc1c (T)
Authors: Wang Teng , Ma Yonghui , Li Wei , Chu Jianan , Wang Lingling , Feng Jiaxin , Xiao Hong , Li Zhuojun , Hu Tao , Liu Xiaosong , Mu Gang 
Published: July 2019

AbstractGap symmetry and structure are crucial issues in understanding the superconducting mechanism of unconventional superconductors. Here, we report an in-depth investigation on the out-of-plane lower critical field $$H_{c1}^c$$

H

c
1

c

of fluorine-based 1111 system superconductor CaFe0.88Co0.12AsF with Tc = 21 K. A pronounced two-gap feature is revealed by the kink in the temperature-dependent $$H_{c1}^c(T)$$

H

c
1

c

(

T

)

curve. The magnitudes of the two gaps are determined to be Δ1 = 0.86 meV and Δ2 = 4.48 meV, which account for 74% and 26% of the total superfluid density, respectively. Our results suggest that the local antiferromagnetic exchange pairing picture is favored compared to the Fermi surface nesting scenario.
Sex differences in respiratory and circulatory cost during hypoxic walking: potential impact on oxygen saturation
Authors: Horiuchi Masahiro , Kirihara Yoko , Fukuoka Yoshiyuki , Pontzer Herman 
Published: July 2019

AbstractEnergy expenditure (EE) during treadmill walking under normal conditions (normobaric normoxia, 21% O2) and moderate hypoxia (13% O2) was measured. Ten healthy young men and ten healthy young women walked on a level (0°) gradient a range of speeds (0.67–1.67 m s−1). During walking, there were no significant differences in reductions in arterial oxygen saturation (SpO2) between the sexes. The hypoxia-induced increase in EE, heart rate (HR [bpm]) and ventilation ($${\dot{{\rm{V}}}}_{{\rm{E}}}$$

V
̇

E

[L min−1]) were calculated. Using a multivariate model that combined EE, $${\dot{{\rm{V}}}}_{{\rm{E}}}$$

V
̇

E

, and HR to predict ΔSpO2 (hypoxia-induced reduction), a very strong fit model both for men (r2 = 0.900, P < 0.001) and for women was obtained (r2 = 0.957, P < 0.001). The contributions of EE, VE, and HR to ΔSpO2 were markedly different between men and women. $${\dot{{\rm{V}}}}_{{\rm{E}}}$$

V
̇

E

and EE had a stronger effect on ΔSpO2 in women ($${\dot{{\rm{V}}}}_{{\rm{E}}}$$

V
̇

E

: 4.1% in women vs. 1.7% in men; EE: 28.1% in women vs. 15.8% in men), while HR had a greater effect in men (82.5% in men and 67.9% in women). These findings suggested that high-altitude adaptation in response to hypoxemia has different underlying mechanisms between men and women. These results can help to explain how to adapt high-altitude for men and women, respectively.
Making stratigraphy in the Anthropocene: climate change impacts and economic conditions controlling the supply of sediment to Lake Geneva
Authors: Lane S. N. , Bakker M. , Costa A. , Girardclos S. , Loizeau J.-L. , Molnar P. , Silva T. , Stutenbecker L. , Schlunegger F. 
Published: July 2019

AbstractThe Anthropocene has been proposed as a profound, globally synchronous rupture in the history of the Earth System with its current state fundamentally different to that of the Holocene and driven by the geological force of human activity. Here, we show how stratigraphy is being made in a lake that is heavily impacted upon by climate change and human activities. For one of the largest inner-Alpine catchments in the European Alps, we draw attention to how sedimentation rates are a product of non-stationary, reflexive, human actions. In Lake Geneva, we identify both a human-induced climate change (HCC) signature and the effects of a recent economic shock on sediment extraction upon sediment loading to and sedimentation rates in the lake. The HCC signature thus reflects the nature of climate change impacts in this basin, where sediment accumulation rates evolve with climate, but where economic conditions contribute to shifts in the supply of sediment to the lake. Following social theory, we call this glocalization because of the combined importance and inseparability of human impacts across different spatial scales. The nature of human impacts on sediment delivery to the lake mean that the influence of humans is unlikely to be captured in the long-term depositional record.
Tomato plants rather than fertilizers drive microbial community structure in horticultural growing media
Authors: Grunert Oliver , Robles-Aguilar Ana A. , Hernandez-Sanabria Emma , Schrey Silvia D. , Reheul Dirk , Van Labeke Marie-Christine , Vlaeminck Siegfried E. , Vandekerckhove Tom G. L. , Mysara Mohamed , Monsieurs Pieter , Temperton Vicky M. , Boon Nico , Jablonowski Nicolai D. 
Published: July 2019

AbstractSynthetic fertilizer production is associated with a high environmental footprint, as compounds typically dissolve rapidly leaching emissions to the atmosphere or surface waters. We tested two recovered nutrients with slower release patterns, as promising alternatives for synthetic fertilizers: struvite and a commercially available organic fertilizer. Using these fertilizers as nitrogen source, we conducted a rhizotron experiment to test their effect on plant performance and nutrient recovery in juvenile tomato plants. Plant performance was significantly improved when organic fertilizer was provided, promoting higher shoot biomass. Since the microbial community influences plant nitrogen availability, we characterized the root-associated microbial community structure and functionality. Analyses revealed distinct root microbial community structure when different fertilizers were supplied. However, plant presence significantly increased the similarity of the microbial community over time, regardless of fertilization. Additionally, the presence of the plant significantly reduced the potential ammonia oxidation rates, implying a possible role of the rhizosheath microbiome or nitrification inhibition by the plant. Our results indicate that nitrifying community members are impacted by the type of fertilizer used, while tomato plants influenced the potential ammonia-oxidizing activity of nitrogen-related rhizospheric microbial communities. These novel insights on interactions between recovered fertilizers, plant and associated microbes can contribute to develop sustainable crop production systems.
Extracellular matrix stiffness regulates human airway smooth muscle contraction by altering the cell-cell coupling
Authors: Polio Samuel R. , Stasiak Suzanne E. , Jamieson Ryan R. , Balestrini Jenna L. , Krishnan Ramaswamy , Parameswaran Harikrishnan 
Published: July 2019

AbstractFor an airway or a blood vessel to narrow, there must be a connected path that links the smooth muscle (SM) cells with each other, and transmits forces around the organ, causing it to constrict. Currently, we know very little about the mechanisms that regulate force transmission pathways in a multicellular SM ensemble. Here, we used extracellular matrix (ECM) micropatterning to study force transmission in a two-cell ensemble of SM cells. Using the two-SM cell ensemble, we demonstrate (a) that ECM stiffness acts as a switch that regulates whether SM force is transmitted through the ECM or through cell-cell connections. (b) Fluorescent imaging for adherens junctions and focal adhesions show the progressive loss of cell-cell borders and the appearance of focal adhesions with the increase in ECM stiffness (confirming our mechanical measurements). (c) At the same ECM stiffness, we show that the presence of a cell-cell border substantially decreases the overall contractility of the SM cell ensemble. Our results demonstrate that connectivity among SM cells is a critical factor to consider in the development of diseases such as asthma and hypertension.
The Epstein-Barr Virus Oncoprotein, LMP1, Regulates the Function of SENP2, a SUMO-protease
Authors: Selby Thomas L. , Biel Natalie , Varn Matthew , Patel Sheetal , Patel Akash , Hilding Leslie , Ray Ashley , Ross Tabithia , Cramblet Wyatt T. , Moss C. Randall , Lowrey Angela J. , Bentz Gretchen L. 
Published: July 2019

AbstractEpstein-Barr virus (EBV) latent membrane protein-1 (LMP1) activates numerous signal transduction pathways using its C-terminal activating regions. We reported that LMP1 increased global levels of sumoylated proteins, which aided the oncogenic nature of LMP1. Because increased protein sumoylation is detected in numerous cancers, we wanted to elucidate additional mechanisms by which LMP1 modulates the sumoylation machinery. Results indicated that SUMO-protease activity decreased in a LMP1-dependent manner, so we hypothesized that LMP1 inhibits SUMO-protease activity, resulting in reduced de-sumoylation of cellular proteins, which contributes to the detected accumulation of sumoylated proteins in EBV-positive lymphomas. Focusing on SENP2, findings revealed that LMP1 expression corresponded with increased sumoylation of SENP2 at K48 and K447 in a CTAR-dependent manner. Interestingly, independent of LMP1-induced sumoylation of SENP2, LMP1 also decreased SENP2 activity, decreased SENP2 turnover, and altered the localization of SENP2, which led us to investigate if LMP1 regulated the biology of SENP2 by a different post-translational modification, specifically ubiquitination. Data showed that expression of LMP1 inhibited the ubiquitination of SENP2, and inhibition of ubiquitination was sufficient to mimic LMP1-induced changes in SENP2 activity and trafficking. Together, these findings suggest that LMP1 modulates different post-translational modifications of SENP2 in order to modulate its biology and identify a third member of the sumoylation machinery that is manipulated by LMP1 during latent EBV infections, which can affect oncogenesis.