bluuebunny/crossref_metadata_2025_split huggingface dataset:
The histone demethylase LSD1 promotes renal inflammation by mediating TLR4 signaling in hepatitis B virus-associated glomerulonephritis
Authors: Yang Yi-Tong , Wang Xuan , Zhang Yue-Yue , Yuan Wei-Jie 
Published: March 2019

AbstractRenal inflammation significantly contributes to the progression of hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN), but the mechanisms that control its precise regulation remain largely unknown. In this study, we showed that the lysine-specific demethylase 1 (LSD1) was significantly upregulated in renal tissue of HBV-GN patients, and its expression was positively correlated with inflammation. Functionally, LSD1 could promote HBV-induced release of proinflammatory mediators in HK-2 cells, a human renal tubular epithelial (RTE) cell line. Mechanistic investigations suggested that LSD1 directly promoted the transcription of the inflammatory-related gene Tlr4 by eliminating the mono- or di-methylation of H3K9 near its promoter. Knockdown of Lsd1 further inhibited TLR4-NF-κB/JNK signaling cascades, and subsequently decreased HBV-induced production of proinflammatory mediators in HK-2 cells. Co-transfection with Tlr4-expressing plasmids counteracted these effects. Meanwhile, downregulation of abovementioned TLR4-related pathways using small-molecule inhibitors attenuated inflammation. Importantly, LSD1 inhibitor tranylcypromine (TCP) could inhibit TLR4-NF-κB/JNK signaling axis and alleviate renal inflammation in HBV transgenic mice. Taken together, our data identify LSD1 as a novel regulator of renal inflammation and as a potential therapeutic target in HBV-GN.
Synthetic control over orientational degeneracy of spacer cations enhances solar cell efficiency in two-dimensional perovskites
Authors: Hu Jun , Oswald Iain W. H. , Stuard Samuel J. , Nahid Masrur Morshed , Zhou Ninghao , Williams Olivia F. , Guo Zhenkun , Yan Liang , Hu Huamin , Chen Zheng , Xiao Xun , Lin Yun , Yang Zhibin , Huang Jinsong , Moran Andrew M. , Ade Harald , Neilson James R. , You Wei 
Published: March 2019

AbstractTwo-dimensional perovskites have emerged as more intrinsically stable materials for solar cells. Chemical tuning of spacer organic cations has attracted great interest due to their additional functionalities. However, how the chemical nature of the organic cations affects the properties of two-dimensional perovskites and devices is rarely reported. Here we demonstrate that the selection of spacer cations (i.e., selective fluorination of phenethylammonium) affects the film properties of two-dimensional perovskites, leading to different device performance of two-dimensional perovskite solar cells (average n = 4). Structural analysis reveals that different packing arrangements and orientational disorder of the spacer cations result in orientational degeneracy and different formation energies, largely explaining the difference in film properties. This work provides key missing information on how spacer cations exert influence on desirable electronic properties and device performance of two-dimensional perovskites via the weak and cooperative interactions of these cations in the crystal lattice.
Nonlinear magnetotransport shaped by Fermi surface topology and convexity
Authors: He Pan , Hsu Chuang-Han , Shi Shuyuan , Cai Kaiming , Wang Junyong , Wang Qisheng , Eda Goki , Lin Hsin , Pereira Vitor M. , Yang Hyunsoo 
Published: March 2019

AbstractThe nature of Fermi surface defines the physical properties of conductors and many physical phenomena can be traced to its shape. Although the recent discovery of a current-dependent nonlinear magnetoresistance in spin-polarized non-magnetic materials has attracted considerable attention in spintronics, correlations between this phenomenon and the underlying fermiology remain unexplored. Here, we report the observation of nonlinear magnetoresistance at room temperature in a semimetal WTe2, with an interesting temperature-driven inversion. Theoretical calculations reproduce the nonlinear transport measurements and allow us to attribute the inversion to temperature-induced changes in Fermi surface convexity. We also report a large anisotropy of nonlinear magnetoresistance in WTe2, due to its low symmetry of Fermi surfaces. The good agreement between experiments and theoretical modeling reveals the critical role of Fermi surface topology and convexity on the nonlinear magneto-response. These results lay a new path to explore ramifications of distinct fermiology for nonlinear transport in condensed-matter.
Deep-water circulation changes lead North Atlantic climate during deglaciation
Authors: Muschitiello Francesco , D’Andrea William J. , Schmittner Andreas , Heaton Timothy J. , Balascio Nicholas L. , deRoberts Nicole , Caffee Marc W. , Woodruff Thomas E. , Welten Kees C. , Skinner Luke C. , Simon Margit H. , Dokken Trond M. 
Published: March 2019

AbstractConstraining the response time of the climate system to changes in North Atlantic Deep Water (NADW) formation is fundamental to improving climate and Atlantic Meridional Overturning Circulation predictability. Here we report a new synchronization of terrestrial, marine, and ice-core records, which allows the first quantitative determination of the response time of North Atlantic climate to changes in high-latitude NADW formation rate during the last deglaciation. Using a continuous record of deep water ventilation from the Nordic Seas, we identify a ∼400-year lead of changes in high-latitude NADW formation ahead of abrupt climate changes recorded in Greenland ice cores at the onset and end of the Younger Dryas stadial, which likely occurred in response to gradual changes in temperature- and wind-driven freshwater transport. We suggest that variations in Nordic Seas deep-water circulation are precursors to abrupt climate changes and that future model studies should address this phasing.
A global analysis of coral bleaching over the past two decades
Authors: Sully S. , Burkepile D. E. , Donovan M. K. , Hodgson G. , van Woesik R. 
Published: March 2019

AbstractThermal-stress events associated with climate change cause coral bleaching and mortality that threatens coral reefs globally. Yet coral bleaching patterns vary spatially and temporally. Here we synthesize field observations of coral bleaching at 3351 sites in 81 countries from 1998 to 2017 and use a suite of environmental covariates and temperature metrics to analyze bleaching patterns. Coral bleaching was most common in localities experiencing high intensity and high frequency thermal-stress anomalies. However, coral bleaching was significantly less common in localities with a high variance in sea-surface temperature (SST) anomalies. Geographically, the highest probability of coral bleaching occurred at tropical mid-latitude sites (15–20 degrees north and south of the Equator), despite similar thermal stress levels at equatorial sites. In the last decade, the onset of coral bleaching has occurred at significantly higher SSTs (∼0.5 °C) than in the previous decade, suggesting that thermally susceptible genotypes may have declined and/or adapted such that the remaining coral populations now have a higher thermal threshold for bleaching.
Coming together to define membrane contact sites
Authors: Scorrano Luca , De Matteis Maria Antonietta , Emr Scott , Giordano Francesca , Hajnóczky György , Kornmann Benoît , Lackner Laura L. , Levine Tim P. , Pellegrini Luca , Reinisch Karin , Rizzuto Rosario , Simmen Thomas , Stenmark Harald , Ungermann Christian , Schuldiner Maya 
Published: March 2019

AbstractClose proximities between organelles have been described for decades. However, only recently a specific field dealing with organelle communication at membrane contact sites has gained wide acceptance, attracting scientists from multiple areas of cell biology. The diversity of approaches warrants a unified vocabulary for the field. Such definitions would facilitate laying the foundations of this field, streamlining communication and resolving semantic controversies. This opinion, written by a panel of experts in the field, aims to provide this burgeoning area with guidelines for the experimental definition and analysis of contact sites. It also includes suggestions on how to operationally and tractably measure and analyze them with the hope of ultimately facilitating knowledge production and dissemination within and outside the field of contact-site research.
ER stress-induced mediator C/EBP homologous protein thwarts effector T cell activity in tumors through T-bet repression
Authors: Cao Yu , Trillo-Tinoco Jimena , Sierra Rosa A. , Anadon Carmen , Dai Wenjie , Mohamed Eslam , Cen Ling , Costich Tara L. , Magliocco Anthony , Marchion Douglas , Klar Richard , Michel Sven , Jaschinski Frank , Reich Richard R. , Mehrotra Shikhar , Cubillos-Ruiz Juan R. , Munn David H. , Conejo-Garcia Jose R. , Rodriguez Paulo C. 
Published: March 2019

AbstractUnderstanding the intrinsic mediators that render CD8+ T cells dysfunctional in the tumor microenvironment is a requirement to develop more effective cancer immunotherapies. Here, we report that C/EBP homologous protein (Chop), a downstream sensor of severe endoplasmic reticulum (ER) stress, is a major negative regulator of the effector function of tumor-reactive CD8+ T cells. Chop expression is increased in tumor-infiltrating CD8+ T cells, which correlates with poor clinical outcome in ovarian cancer patients. Deletion of Chop in T cells improves spontaneous antitumor CD8+ T cell immunity and boosts the efficacy of T cell-based immunotherapy. Mechanistically, Chop in CD8+ T cells is elevated primarily through the ER stress-associated kinase Perk and a subsequent induction of Atf4; and directly represses the expression of T-bet, a master regulator of effector T cell function. These findings demonstrate the primary role of Chop in tumor-induced CD8+ T cell dysfunction and the therapeutic potential of blocking Chop or ER stress to unleash T cell-mediated antitumor immunity.
Stronger influence of anthropogenic disturbance than climate change on century-scale compositional changes in northern forests
Authors: Danneyrolles Victor , Dupuis Sébastien , Fortin Gabriel , Leroyer Marie , de Römer André , Terrail Raphaële , Vellend Mark , Boucher Yan , Laflamme Jason , Bergeron Yves , Arseneault Dominique 
Published: March 2019

AbstractPredicting future ecosystem dynamics depends critically on an improved understanding of how disturbances and climate change have driven long-term ecological changes in the past. Here we assembled a dataset of >100,000 tree species lists from the 19th century across a broad region (>130,000km2) in temperate eastern Canada, as well as recent forest inventories, to test the effects of changes in anthropogenic disturbance, temperature and moisture on forest dynamics. We evaluate changes in forest composition using four indices quantifying the affinities of co-occurring tree species with temperature, drought, light and disturbance. Land-use driven shifts favouring more disturbance-adapted tree species are far stronger than any effects ascribable to climate change, although the responses of species to disturbance are correlated with their expected responses to climate change. As such, anthropogenic and natural disturbances are expected to have large direct effects on forests and also indirect effects via altered responses to future climate change.
Functional interplay between TFIIH and KAT2A regulates higher-order chromatin structure and class II gene expression
Authors: Sandoz Jérémy , Nagy Zita , Catez Philippe , Caliskan Gizem , Geny Sylvain , Renaud Jean-Baptiste , Concordet Jean-Paul , Poterszman Arnaud , Tora Laszlo , Egly Jean-Marc , Le May Nicolas , Coin Frédéric 
Published: March 2019

AbstractThe TFIIH subunit XPB is involved in combined Xeroderma Pigmentosum and Cockayne syndrome (XP-B/CS). Our analyses reveal that XPB interacts functionally with KAT2A, a histone acetyltransferase (HAT) that belongs to the hSAGA and hATAC complexes. XPB interacts with KAT2A-containing complexes on chromatin and an XP-B/CS mutation specifically elicits KAT2A-mediated large-scale chromatin decondensation. In XP-B/CS cells, the abnormal recruitment of TFIIH and KAT2A to chromatin causes inappropriate acetylation of histone H3K9, leading to aberrant formation of transcription initiation complexes on the promoters of several hundred genes and their subsequent overexpression. Significantly, this cascade of events is similarly sensitive to KAT2A HAT inhibition or to the rescue with wild-type XPB. In agreement, the XP-B/CS mutation increases KAT2A HAT activity in vitro. Our results unveil a tight connection between TFIIH and KAT2A that controls higher-order chromatin structure and gene expression and provide new insights into transcriptional misregulation in a cancer-prone DNA repair-deficient disorder.
Gfi1b regulates the level of Wnt/β-catenin signaling in hematopoietic stem cells and megakaryocytes
Authors: Shooshtarizadeh Peiman , Helness Anne , Vadnais Charles , Brouwer Nelleke , Beauchemin Hugues , Chen Riyan , Bagci Halil , Staal Frank J. T. , Coté Jean-François , Möröy Tarik 
Published: March 2019

AbstractGfi1b is a transcriptional repressor expressed in hematopoietic stem cells (HSCs) and megakaryocytes (MKs). Gfi1b deficiency leads to expansion of both cell types and abrogates the ability of MKs to respond to integrin. Here we show that Gfi1b forms complexes with β-catenin, its co-factors Pontin52, CHD8, TLE3 and CtBP1 and regulates Wnt/β-catenin-dependent gene expression. In reporter assays, Gfi1b can activate TCF-dependent transcription and Wnt3a treatment enhances this activation. This requires interaction between Gfi1b and LSD1 and suggests that a tripartite β-catenin/Gfi1b/LSD1 complex exists, which regulates Wnt/β-catenin target genes. Consistently, numerous canonical Wnt/β-catenin target genes, co-occupied by Gfi1b, β-catenin and LSD1, have their expression deregulated in Gfi1b-deficient cells. When Gfi1b-deficient cells are treated with Wnt3a, their normal cellularity is restored and Gfi1b-deficient MKs regained their ability to spread on integrin substrates. This indicates that Gfi1b controls both the cellularity and functional integrity of HSCs and MKs by regulating Wnt/β-catenin signaling pathway.
Mechanical behaviour of fluid-lubricated faults
Authors: Cornelio C. , Spagnuolo E. , Di Toro G. , Nielsen S. , Violay M. 
Published: March 2019

AbstractFluids are pervasive in fault zones cutting the Earth's crust; however, the effect of fluid viscosity on fault mechanics is mainly conjectured by theoretical models. We present friction experiments performed on both dry and fluid-permeated silicate and carbonate bearing-rocks, at normal effective stresses up to 20 MPa, with a slip-rate ranging between 10 μm/s and 1 m/s. Four different fluid viscosities were tested. We show that both static and dynamic friction coefficients decrease with viscosity and that dynamic friction depends on the dimensionless Sommerfeld number (S) as predicted by the elastohydrodynamic-lubrication theory (EHD).Under favourable conditions (depending on the fluid viscosity (η), co-seismic slip-rate (V), fault geometry (L/H02) and earthquake nucleation depth (∝σeff)), EHD might be an effective weakening mechanism during natural and induced earthquakes. However, at seismic slip-rate, the slip weakening distance (Dc) increases markedly for a range of fluid viscosities expected in the Earth, potentially favouring slow-slip rather than rupture propagation for small to moderate earthquakes.
The conserved NxNNWHW motif in Aha-type co-chaperones modulates the kinetics of Hsp90 ATPase stimulation
Authors: Mercier Rebecca , Wolmarans Annemarie , Schubert Jonathan , Neuweiler Hannes , Johnson Jill L. , LaPointe Paul 
Published: March 2019

AbstractHsp90 is a dimeric molecular chaperone that is essential for the folding and activation of hundreds of client proteins. Co-chaperone proteins regulate the ATP-driven Hsp90 client activation cycle. Aha-type co-chaperones are the most potent stimulators of the Hsp90 ATPase activity but the relationship between ATPase regulation and in vivo activity is poorly understood. We report here that the most strongly conserved region of Aha-type co-chaperones, the N terminal NxNNWHW motif, modulates the apparent affinity of Hsp90 for nucleotide substrates. The ability of yeast Aha-type co-chaperones to act in vivo is ablated when the N terminal NxNNWHW motif is removed. This work suggests that nucleotide exchange during the Hsp90 functional cycle may be more important than rate of catalysis.
Sequence variation at ANAPC1 accounts for 24% of the variability in corneal endothelial cell density
Authors: Ivarsdottir Erna V. , Benonisdottir Stefania , Thorleifsson Gudmar , Sulem Patrick , Oddsson Asmundur , Styrkarsdottir Unnur , Kristmundsdottir Snaedis , Arnadottir Gudny A. , Thorgeirsson Gudmundur , Jonsdottir Ingileif , Zoega Gunnar M. , Thorsteinsdottir Unnur , Gudbjartsson Daniel F. , Jonasson Fridbert , Holm Hilma , Stefansson Kari 
Published: March 2019

AbstractThe corneal endothelium is vital for transparency and proper hydration of the cornea. Here, we conduct a genome-wide association study of corneal endothelial cell density (cells/mm2), coefficient of cell size variation (CV), percentage of hexagonal cells (HEX) and central corneal thickness (CCT) in 6,125 Icelanders and find associations at 10 loci, including 7 novel. We assess the effects of these variants on various ocular biomechanics such as corneal hysteresis (CH), as well as eye diseases such as glaucoma and corneal dystrophies. Most notably, an intergenic variant close to ANAPC1 (rs78658973[A], frequency = 28.3%) strongly associates with decreased cell density and accounts for 24% of the population variance in cell density (β = −0.77 SD, P = 1.8 × 10−314) and associates with increased CH (β = 0.19 SD, P = 2.6 × 10−19) without affecting risk of corneal diseases and glaucoma. Our findings indicate that despite correlations between cell density and eye diseases, low cell density does not increase the risk of disease.
Multiple ABCB1 transcriptional fusions in drug resistant high-grade serous ovarian and breast cancer
Authors: Christie Elizabeth L. , Pattnaik Swetansu , Beach Jessica , Copeland Anthony , Rashoo Nineveh , Fereday Sian , Hendley Joy , Alsop Kathryn , Brady Samuel L. , Lamb Greg , Pandey Ahwan , deFazio Anna , Thorne Heather , Bild Andrea , Bowtell David D. L. 
Published: March 2019

AbstractABCB1 encodes Multidrug Resistance protein (MDR1), an ATP-binding cassette member involved in the cellular efflux of chemotherapeutic drugs. Here we report that ovarian and breast samples from chemotherapy treated patients are positive for multiple transcriptional fusions involving ABCB1, placing it under the control of a strong promoter while leaving its open reading frame intact. We identified 15 different transcriptional fusion partners involving ABCB1, as well as patients with multiple distinct fusion events. The partner gene selected depended on its structure, promoter strength, and chromosomal proximity to ABCB1. Fusion positivity was strongly associated with the number of lines of MDR1-substrate chemotherapy given. MDR1 inhibition in a fusion positive ovarian cancer cell line increased sensitivity to paclitaxel more than 50-fold. Convergent evolution of ABCB1 fusion is therefore frequent in chemotherapy resistant recurrent ovarian cancer. As most currently approved PARP inhibitors (PARPi) are MDR1 substrates, prior chemotherapy may precondition resistance to PARPi.
Metabolic phenotypes and the gut microbiota in response to dietary resistant starch type 2 in normal-weight subjects: a randomized crossover trial
Authors: Zhang Lei , Ouyang Yang , Li Huating , Shen Li , Ni Yueqiong , Fang Qichen , Wu Guangyu , Qian Lingling , Xiao Yunfeng , Zhang Jing , Yin Peiyuan , Panagiotou Gianni , Xu Guowang , Ye Jianping , Jia Weiping 
Published: March 2019

AbstractResistant starch (RS) has been reported to reduce body fat in obese mice. However, this effect has not been demonstrated in humans. In this study, we tested the effects of RS in 19 volunteers with normal body weights. A randomized, double-blinded and crossover design clinical trial was conducted. The study subjects were given either 40 g high amylose RS2 or energy-matched control starch with three identical diets per day throughout the study. The effect of RS was evaluated by monitoring body fat, glucose metabolism, gut hormones, gut microbiota, short-chain fatty acids (SCFAs) and metabolites. The visceral and subcutaneous fat areas were significantly reduced following RS intake. Acetate and early-phase insulin, C-peptide and glucagon-like peptide-1 (GLP-1) secretion were increased, and the low-density lipoprotein cholesterol (LDL-C) and blood urea nitrogen (BUN) levels were decreased after the RS intervention. Based on 16S rRNA sequencing, certain gut microbes were significantly decreased after RS supplementation, whereas the genus Ruminococcaceae_UCG-005 showed an increase in abundance. Other potential signatures of the RS intervention included Akkermansia, Ruminococcus_2, Victivallis, and Comamonas. Moreover, the baseline abundance of the genera Streptococcus, Ruminococcus_torques_group, Eubacterium_hallii_group, and Eubacterium_eligens_group was significantly associated with the hormonal and metabolic effects of RS. These observations suggest that a daily intake of 40 g of RS is effective in modulating body fat, SCFAs, early-phase insulin and GLP-1 secretion and the gut microbiota in normal-weight subjects.
Analytical model of surface second-harmonic generation
Authors: Javůrek Dalibor , Peřina Jan 
Published: March 2019

AbstractThe process of second-harmonic generation (SHG) in a finite one-dimensional nonlinear medium is analyzed in parallel by the Green-function technique and the Fourier-transform method. Considering the fundamental pump field propagating along a given direction and eliminating back-reflections at the boundaries the terms giving the surface second-harmonic fields in the particular solution of the wave equation are uniquely identified. Using these terms the flow of energy corresponding to the surface second-harmonic fields is analyzed in the vicinity of the boundaries. The formula giving the depth of the nonlinear medium contributing to the surface SHG is obtained. Both approaches for describing the SHG are compared considering complexity and quantization of the interacting fields. In addition, a theoretical model of surface SHG in centrosymmetric media is proposed. The model is built upon assumption that the second-order nonlinearity decays exponentially with distance from the boundary. As an important example, the generation of surface SHG from a thin dielectric nonlinear layer placed on a silicon substrate is analyzed by the proposed model.