bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self‐Aggregation of Convective Clouds With Interactive Sea Surface Temperature
Authors: Shamekh S. , Muller C. , Duvel J.‐P. , D'Andrea F. 
Published: August 2020

AbstractThis study investigates the feedbacks between an interactive sea surface temperature (SST) and the self‐aggregation of deep convective clouds, using a cloud‐resolving model in nonrotating radiative‐convective equilibrium. The ocean is modeled as one layer slab with a temporally fixed mean but spatially varying temperature. We find that the interactive SST decelerates the aggregation and that the deceleration is larger with a shallower slab, consistent with earlier studies. The surface temperature anomaly in dry regions is positive at first, thus opposing the diverging shallow circulation known to favor self‐aggregation, consistent with the slower aggregation. But surprisingly, the driest columns then have a negative SST anomaly, thus strengthening the diverging shallow circulation and favoring aggregation. This diverging circulation out of dry regions is found to be well correlated with the aggregation speed. It can be linked to a positive surface pressure anomaly (PSFC), itself the consequence of SST anomalies and boundary layer radiative cooling. The latter cools and dries the boundary layer, thus increasing PSFC anomalies through virtual effects and hydrostasy. Sensitivity experiments confirm the key role played by boundary layer radiative cooling in determining PSFC anomalies in dry regions, and thus the shallow diverging circulation and the aggregation speed.
Inhibition of DNMT1 and ERRα crosstalk suppresses breast cancer via derepression of IRF4
Authors: Vernier Mathieu , McGuirk Shawn , Dufour Catherine R. , Wan Liangxinyi , Audet-Walsh Etienne , St-Pierre Julie , Giguère Vincent 
Published: August 2020

AbstractDNA methylation is implicated in the acquisition of malignant phenotypes, and the use of epigenetic modulating drugs is a promising anti-cancer therapeutic strategy. 5-aza-2’deoxycytidine (decitabine, 5-azadC) is an FDA-approved DNA methyltransferase (DNMT) inhibitor with proven effectiveness against hematological malignancies and more recently triple-negative breast cancer (BC). Herein, genetic or pharmacological studies uncovered a hitherto unknown feedforward molecular link between DNMT1 and the estrogen related receptor α (ERRα), a key transcriptional regulator of cellular metabolism. Mechanistically, DNMT1 promotes ERRα stability which in turn couples DNMT1 transcription with that of the methionine cycle and S-adenosylmethionine synthesis to drive DNA methylation. In vitro and in vivo investigation using a pre-clinical mouse model of BC demonstrated a clear therapeutic advantage for combined administration of the ERRα inhibitor C29 with 5-azadC. A large-scale bisulfite genomic sequencing analysis revealed specific methylation perturbations fostering the discovery that reversal of promoter hypermethylation and consequently derepression of the tumor suppressor gene, IRF4, is a factor underlying the observed BC suppressive effects. This work thus uncovers a critical role of ERRα in the crosstalk between transcriptional control of metabolism and epigenetics and illustrates the potential for targeting ERRα in combination with DNMT inhibitors for BC treatment and other epigenetics-driven malignancies.
1,25-dihydroxyvitamin-D3 but not the clinically applied marker 25-hydroxyvitamin-D3 predicts survival after stem cell transplantation
Authors: Peter Katrin , Siska Peter J. , Roider Tobias , Matos Carina , Bruns Heiko , Renner Kathrin , Singer Katrin , Weber Daniela , Güllstorf Martina , Kröger Nicolaus , Wolff Daniel , Herr Wolfgang , Ayuk Francis , Holler Ernst , Stark Klaus , Heid Iris M. , Kreutz Marina 
Published: August 2020

AbstractThe serum level of 25-hydroxyvitamin-D3 is accepted as marker for a person’s vitamin D status but its role for the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) is controversially discussed. The impact of 1,25-dihydroxyvitamin-D3 on HSCT outcome, however, has never been studied. In a discovery cohort of 143 HSCT patients we repeatedly (day −16 to 100) measured 1,25-dihydroxyvitamin-D3 and in comparison the well-established marker for serum vitamin D status 25-hydroxyvitamin-D3. Only lower 1,25-dihydroxyvitamin-D3 levels around HSCT (day −2 to 7, peritransplant) were significantly associated with higher 1-year treatment-related mortality (TRM) risk (Mann–Whitney U test, P = 0.001). This was confirmed by Cox-model regression without and with adjustment for baseline risk factors and severe acute Graft-versus-Host disease (aGvHD; unadjusted P = 0.001, adjusted P = 0.005). The optimal threshold for 1,25-dihydroxyvitamin-D3 to identify patients at high risk was 139.5 pM. Also in three replication cohorts consisting of altogether 365 patients 1,25-dihydroxyvitamin-D3 levels below 139.5 pM had a 3.3-fold increased risk of TRM independent of severe aGvHD compared to patients above 139.5 pM (Cox-model unadjusted P < 0.0005, adjusted P = 0.001). Our data highlight peritransplant 1,25-dihydroxyvitamin-D3 levels but not the commonly monitored 25-hydroxyvitamin-D3 levels as potent predictor of 1-year TRM and suggest to monitor both vitamin D metabolites in HSCT patients.
Y772 phosphorylation of EphA2 is responsible for EphA2-dependent NPC nasopharyngeal carcinoma growth by Shp2/Erk-1/2 signaling pathway
Authors: Xiang Yi-Ping , Xiao Ta , Li Qi-Guang , Lu Shan-Shan , Zhu Wei , Liu Yun-Ya , Qiu Jie-Ya , Song Zheng-Hui , Huang Wei , Yi Hong , Tang Yao-Yun , Xiao Zhi-Qiang 
Published: August 2020

AbstractEphA2 is an important oncogenic protein and emerging drug target, but the oncogenic role and mechanism of ligand-independent phosphorylation of EphA2 at tyrosine 772 (pY772-EphA2) is unclear. In this study, we established nasopharyngeal carcinoma (NPC) cell lines with stable expression of exogenous EphA2 and EphA2-Y772A (phosphorylation inactivation) using endogenous EphA2-knockdown cells, and observed that pY772A EphA2 was responsible for EphA2-promoting NPC cell proliferation and anchorage-independent and in vivo growth in mice. Mechanistically, EphA2-Y772A mediated EphA2-activating Shp2/Erk-1/2 signaling pathway in the NPC cells, and Gab1 (Grb2-associated binder 1) and Grb2 (growth factor receptor-bound protein 2) were involved in pY772-EphA2 activating this signaling pathway. Our results further showed that Shp2/Erk-1/2 signaling mediated pY772-EphA2-promoting NPC cell proliferation and anchorage-independent growth. Moreover, we observed that EphA2 tyrosine kinase inhibitor ALW-II-41-27 inhibited pY772-EphA2 and EphA2-Y772A decreased the inhibitory effect of ALW-II-41-27 on NPC cell proliferation. Collectively, our results demonstrate that pY772-EphA2 is responsible for EphA2-dependent NPC cell growth in vitro and in vivo by activating Shp2/Erk-1/2 signaling pathway, and is a pharmacologic target of ALW-II-41-27, suggesting that pY772-EphA2 can serve as a therapeutic target in NPC and perhaps in other cancers.
Identification of osteogenic progenitor cell-targeted peptides that augment bone formation
Authors: Jiang Min , Liu Ruiwu , Liu Lixian , Kot Alexander , Liu Xueping , Xiao Wenwu , Jia Junjing , Li Yuanpei , Lam Kit S. , Yao Wei 
Published: August 2020

AbstractActivation and migration of endogenous mesenchymal stromal cells (MSCs) are critical for bone regeneration. Here, we report a combinational peptide screening strategy for rapid discovery of ligands that not only bind strongly to osteogenic progenitor cells (OPCs) but also stimulate osteogenic cell Akt signaling in those OPCs. Two lead compounds are discovered, YLL3 and YLL8, both of which increase osteoprogenitor osteogenic differentiation in vitro. When given to normal or osteopenic mice, the compounds increase mineral apposition rate, bone formation, bone mass, and bone strength, as well as expedite fracture repair through stimulated endogenous osteogenesis. When covalently conjugated to alendronate, YLLs acquire an additional function resulting in a “tri-functional” compound that: (i) binds to OPCs, (ii) targets bone, and (iii) induces “pro-survival” signal. These bone-targeted, osteogenic peptides are well suited for current tissue-specific therapeutic paradigms to augment the endogenous osteogenic cells for bone regeneration and the treatment of bone loss.
Caveolin-1-mediated sphingolipid oncometabolism underlies a metabolic vulnerability of prostate cancer
Authors: Vykoukal Jody , Fahrmann Johannes F. , Gregg Justin R. , Tang Zhe , Basourakos Spyridon , Irajizad Ehsan , Park Sanghee , Yang Guang , Creighton Chad J. , Fleury Alia , Mayo Jeffrey , Paulucci-Holthauzen Adriana , Dennison Jennifer B. , Murage Eunice , Peterson Christine B. , Davis John W. , Kim Jeri , Hanash Samir , Thompson Timothy C. 
Published: August 2020

AbstractPlasma and tumor caveolin-1 (Cav-1) are linked with disease progression in prostate cancer. Here we report that metabolomic profiling of longitudinal plasmas from a prospective cohort of 491 active surveillance (AS) participants indicates prominent elevations in plasma sphingolipids in AS progressors that, together with plasma Cav-1, yield a prognostic signature for disease progression. Mechanistic studies of the underlying tumor supportive onco-metabolism reveal coordinated activities through which Cav-1 enables rewiring of cancer cell lipid metabolism towards a program of 1) exogenous sphingolipid scavenging independent of cholesterol, 2) increased cancer cell catabolism of sphingomyelins to ceramide derivatives and 3) altered ceramide metabolism that results in increased glycosphingolipid synthesis and efflux of Cav-1-sphingolipid particles containing mitochondrial proteins and lipids. We also demonstrate, using a prostate cancer syngeneic RM-9 mouse model and established cell lines, that this Cav-1-sphingolipid program evidences a metabolic vulnerability that is targetable to induce lethal mitophagy as an anti-tumor therapy.
Tuning proton-coupled electron transfer by crystal orientation for efficient water oxidization on double perovskite oxides
Authors: Zhu Yunmin , He Zuyun , Choi YongMan , Chen Huijun , Li Xiaobao , Zhao Bote , Yu Yi , Zhang Hui , Stoerzinger Kelsey A. , Feng Zhenxing , Chen Yan , Liu Meilin 
Published: August 2020

AbstractDeveloping highly efficient and cost-effective oxygen evolution reaction (OER) electrocatalysts is critical for many energy devices. While regulating the proton-coupled electron transfer (PCET) process via introducing additive into the system has been reported effective in promoting OER activity, controlling the PCET process by tuning the intrinsic material properties remains a challenging task. In this work, we take double perovskite oxide PrBa0.5Sr0.5Co1.5Fe0.5O5+δ (PBSCF) as a model system to demonstrate enhancing OER activity through the promotion of PCET by tuning the crystal orientation and correlated proton diffusion. OER kinetics on PBSCF thin films with (100), (110), and (111) orientation, deposited on single crystal LaAlO3 substrates, were investigated using electrochemical measurements, density functional theory (DFT) calculations, and synchrotron-based near ambient X-ray photoelectron spectroscopy. The results clearly show that the OER activity and the ease of deprotonation depend on orientation and follow the order of (100) > (110) > (111). Correlated with OER activity, proton diffusion is found to be the fastest in the (100) film, followed by (110) and (111) films. Our results point out a way of boosting PCET and OER activity, which can also be successfully applied to a wide range of crucial applications in green energy and environment.
The dynamic landscape of transcription initiation in yeast mitochondria
Authors: Sohn Byeong-Kwon , Basu Urmimala , Lee Seung-Won , Cho Hayoon , Shen Jiayu , Deshpande Aishwarya , Johnson Laura C. , Das Kalyan , Patel Smita S. , Kim Hajin 
Published: August 2020

AbstractControlling efficiency and fidelity in the early stage of mitochondrial DNA transcription is crucial for regulating cellular energy metabolism. Conformational transitions of the transcription initiation complex must be central for such control, but how the conformational dynamics progress throughout transcription initiation remains unknown. Here, we use single-molecule fluorescence resonance energy transfer techniques to examine the conformational dynamics of the transcriptional system of yeast mitochondria with single-base resolution. We show that the yeast mitochondrial transcriptional complex dynamically transitions among closed, open, and scrunched states throughout the initiation stage. Then abruptly at position +8, the dynamic states of initiation make a sharp irreversible transition to an unbent conformation with associated promoter release. Remarkably, stalled initiation complexes remain in dynamic scrunching and unscrunching states without dissociating the RNA transcript, implying the existence of backtracking transitions with possible regulatory roles. The dynamic landscape of transcription initiation suggests a kinetically driven regulation of mitochondrial transcription.
TET1 is a beige adipocyte-selective epigenetic suppressor of thermogenesis
Authors: Damal Villivalam Sneha , You Dongjoo , Kim Jinse , Lim Hee Woong , Xiao Han , Zushin Pete-James H. , Oguri Yasuo , Amin Pouya , Kang Sona 
Published: August 2020

AbstractIt has been suggested that beige fat thermogenesis is tightly controlled by epigenetic regulators that sense environmental cues such as temperature. Here, we report that subcutaneous adipose expression of the DNA demethylase TET1 is suppressed by cold and other stimulators of beige adipocyte thermogenesis. TET1 acts as an autonomous repressor of key thermogenic genes, including Ucp1 and Ppargc1a, in beige adipocytes. Adipose-selective Tet1 knockout mice generated by using Fabp4-Cre improves cold tolerance and increases energy expenditure and protects against diet-induced obesity and insulin resistance. Moreover, the suppressive role of TET1 in the thermogenic gene regulation of beige adipocytes is largely DNA demethylase-independent. Rather, TET1 coordinates with HDAC1 to mediate the epigenetic changes to suppress thermogenic gene transcription. Taken together, TET1 is a potent beige-selective epigenetic breaker of the thermogenic gene program. Our findings may lead to a therapeutic strategy to increase energy expenditure in obesity and related metabolic disorders.
Circadian clock mechanism driving mammalian photoperiodism
Authors: Wood S. H. , Hindle M. M. , Mizoro Y. , Cheng Y. , Saer B. R. C. , Miedzinska K. , Christian H. C. , Begley N. , McNeilly J. , McNeilly A. S. , Meddle S. L. , Burt D. W. , Loudon A. S. I. 
Published: August 2020

AbstractThe annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-based coincidence timer for photoperiodic synchronization in plants. Formal studies support the universality of this so-called coincidence timer, but we lack understanding of the mechanisms involved. Here we show in mammals that long photoperiods induce the circadian transcription factorBMAL2, in thepars tuberalisof the pituitary, and triggers summer biology through the eyes absent/thyrotrophin (EYA3/TSH) pathway. Conversely, long-duration melatonin signals on short photoperiods induce circadian repressors includingDEC1, suppressing BMAL2 and the EYA3/TSH pathway, triggering winter biology. These actions are associated with progressive genome-wide changes in chromatin state, elaborating the effect of the circadian coincidence timer. Hence, circadian clock-pituitary epigenetic pathway interactions form the basis of the mammalian coincidence timer mechanism. Our results constitute a blueprint for circadian-based seasonal timekeeping in vertebrates.
Warsaw Breakage Syndrome associated DDX11 helicase resolves G-quadruplex structures to support sister chromatid cohesion
Authors: van Schie Janne J. M. , Faramarz Atiq , Balk Jesper A. , Stewart Grant S. , Cantelli Erika , Oostra Anneke B. , Rooimans Martin A. , Parish Joanna L. , de Almeida Estéves Cynthia , Dumic Katja , Barisic Ingeborg , Diderich Karin E. M. , van Slegtenhorst Marjon A. , Mahtab Mohammad , Pisani Francesca M. , te Riele Hein , Ameziane Najim , Wolthuis Rob M. F. , de Lange Job 
Published: August 2020

AbstractWarsaw Breakage Syndrome (WABS) is a rare disorder related to cohesinopathies and Fanconi anemia, caused by bi-allelic mutations in DDX11. Here, we report multiple compound heterozygous WABS cases, each displaying destabilized DDX11 protein and residual DDX11 function at the cellular level. Patient-derived cell lines exhibit sensitivity to topoisomerase and PARP inhibitors, defective sister chromatid cohesion and reduced DNA replication fork speed. Deleting DDX11 in RPE1-TERT cells inhibits proliferation and survival in a TP53-dependent manner and causes chromosome breaks and cohesion defects, independent of the expressed pseudogene DDX12p. Importantly, G-quadruplex (G4) stabilizing compounds induce chromosome breaks and cohesion defects which are strongly aggravated by inactivation of DDX11 but not FANCJ. The DNA helicase domain of DDX11 is essential for sister chromatid cohesion and resistance to G4 stabilizers. We propose that DDX11 is a DNA helicase protecting against G4 induced double-stranded breaks and concomitant loss of cohesion, possibly at DNA replication forks.
Lumenal Galectin-9-Lamp2 interaction regulates lysosome and autophagy to prevent pathogenesis in the intestine and pancreas
Authors: Sudhakar Janaki N. , Lu Hsueh-Han , Chiang Hung-Yu , Suen Ching-Shu , Hwang Ming-Jing , Wu Sung-Yu , Shen Chia-Ning , Chang Yao-Ming , Li Fu-An , Liu Fu-Tong , Shui Jr-Wen 
Published: August 2020

AbstractIntracellular galectins are carbohydrate-binding proteins capable of sensing and repairing damaged lysosomes. As in the physiological conditions glycosylated moieties are mostly in the lysosomal lumen but not cytosol, it is unclear whether galectins reside in lysosomes, bind to glycosylated proteins, and regulate lysosome functions. Here, we show in gut epithelial cells, galectin-9 is enriched in lysosomes and predominantly binds to lysosome-associated membrane protein 2 (Lamp2) in a Asn(N)-glycan dependent manner. At the steady state, galectin-9 binding to glycosylated Asn175 of Lamp2 is essential for functionality of lysosomes and autophagy. Loss of N-glycan-binding capability of galectin-9 causes its complete depletion from lysosomes and defective autophagy, leading to increased endoplasmic reticulum (ER) stress preferentially in autophagy-active Paneth cells and acinar cells. Unresolved ER stress consequently causes cell degeneration or apoptosis that associates with colitis and pancreatic disorders in mice. Therefore, lysosomal galectins maintain homeostatic function of lysosomes to prevent organ pathogenesis.
Diffusion of flue gas desulfurization reveals barriers and opportunities for carbon capture and storage
Authors: van Ewijk Stijn , McDowall Will 
Published: August 2020

AbstractAddressing climate change may require rapid global diffusion of Carbon Capture and Storage (CCS). To understand its potential diffusion, we analysed a historical analogy: Flue Gas Desulfurization (FGD) in the global coal power market. Our findings challenge common patterns: diffusion of FGD is not described by a single S-curve but by multiple steps and does not slow down after materiality. The regulation-driven diffusion of FGD can be fast, especially for retrofit since it does not require new power plants. Owing to the mature size of coal power plants, the diffusion of FGD is driven by unit numbers instead of unit capacity growth. We find that the diffusion of CCS in climate change mitigation pathways, when normalised for economic growth, rarely exceeds the historical maximum diffusion rate of FGD. Our findings suggest that end-of-pipe abatement technology can diffuse fast and to a great extent provided deep, consistent long-term regulatory commitment.
Clinically applicable histopathological diagnosis system for gastric cancer detection using deep learning
Authors: Song Zhigang , Zou Shuangmei , Zhou Weixun , Huang Yong , Shao Liwei , Yuan Jing , Gou Xiangnan , Jin Wei , Wang Zhanbo , Chen Xin , Ding Xiaohui , Liu Jinhong , Yu Chunkai , Ku Calvin , Liu Cancheng , Sun Zhuo , Xu Gang , Wang Yuefeng , Zhang Xiaoqing , Wang Dandan , Wang Shuhao , Xu Wei , Davis Richard C. , Shi Huaiyin 
Published: August 2020

AbstractThe early detection and accurate histopathological diagnosis of gastric cancer increase the chances of successful treatment. The worldwide shortage of pathologists offers a unique opportunity for the use of artificial intelligence assistance systems to alleviate the workload and increase diagnostic accuracy. Here, we report a clinically applicable system developed at the Chinese PLA General Hospital, China, using a deep convolutional neural network trained with 2,123 pixel-level annotated H&E-stained whole slide images. The model achieves a sensitivity near 100% and an average specificity of 80.6% on a real-world test dataset with 3,212 whole slide images digitalized by three scanners. We show that the system could aid pathologists in improving diagnostic accuracy and preventing misdiagnoses. Moreover, we demonstrate that our system performs robustly with 1,582 whole slide images from two other medical centres. Our study suggests the feasibility and benefits of using histopathological artificial intelligence assistance systems in routine practice scenarios.
Thermodynamic feasibility of the four-stage chloride-induced depassivation mechanism of iron
Authors: Pang Qin , DorMohammadi Hossein , Isgor O. Burkan , Árnadóttir Líney 
Published: August 2020

AbstractThe atomistic mechanism of chloride-induced depassivation of iron is still debated. A recent study suggests a four-stage depassivation mechanism, in general agreement with the point defect model. The proposed four-stage mechanism is based on reactive force field molecular dynamics simulations and is rather complex but here we use density functional theory to confirm the thermodynamic feasibility of the proposed mechanism. We find that the four surface species, formed in the four stages, have decreasing surface stability, which is consistent with the order of species formed in the depassivation process proposed in the reactive force field molecular dynamics study. The Fe vacancy formation energy, that is the energy needed to form a surface Fe vacancy by removing different surface species, indicates that surface species with more chlorides dissolve more easily from the surface, suggesting that chloride acts as catalyst in the iron dissolution process. The results are consistent with the suggested four-stage reaction mechanism and the point defect model.