bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surface Flux Equilibrium Theory Explains an Empirical Estimate of Water‐Limited Daily Evapotranspiration
Authors: McColl Kaighin A. , Salvucci Guido D. , Gentine Pierre 
Published: June 2019

AbstractEvapotranspiration (ET) plays a central role in the water, energy, and carbon cycles but is difficult to model and estimate due to its dependence on the heterogeneous land surface. Recent studies suggest that standard weather station atmospheric observations alone may be sufficient to estimate ET. This is surprising since ET over land is often strongly constrained by the land surface, for instance, by water limitation. While these studies have been empirically successful, a physical explanation for why this is possible has been lacking. Here, we provide a physical explanation for why one of these approaches—the ET from Relative Humidity at Equilibrium (ETRHEQ) method—works, using a simple model of a steady‐state idealized atmospheric boundary layer. We show that, across a wide range of plausible parameter values, this model reproduces ETRHEQ, suggesting that it contains the essential physics that lead to ETRHEQ. We derive a closed‐form expression for ETRHEQ at steady state and use it to show that ETRHEQ can be explained in terms of the near‐surface relative humidity (RH) budget of the idealized model: in particular, it is equivalent to assuming a balance between surface moistening and heating terms in the RH budget. Negative feedbacks between surface fluxes (constrained by the surface energy budget) and atmospheric temperature and humidity mean that these terms typically balance, explaining the empirical success of ETRHEQ over a wide range of conditions. We define this state—in which the moistening and heating terms balance in the RH budget—as “surface flux equilibrium.”
Ets-1 deficiency alleviates nonalcoholic steatohepatitis via weakening TGF-β1 signaling-mediated hepatocyte apoptosis
Authors: Liu Dechen , Wang Kai , Li Kai , Xu Rufeng , Chang Xiaoai , Zhu Yunxia , Sun Peng , Han Xiao 
Published: June 2019

AbstractHepatocyte apoptosis is a hallmark of nonalcoholic steatohepatitis (NASH) and contributes to liver injury, fibrosis, and inflammation. However, the molecular mechanisms underlying excessive hepatocyte apoptosis in NASH remain largely unknown. This study aimed to explore whether and how the v-ets avian erythroblastosis virus E26 oncogene homolog 1 (Ets-1) is involved in diet-induced hepatocyte apoptosis in mice. The study found that the expression level of hepatic Ets-1 was elevated in a NASH mouse model as a result of the activation of transforming growth factor beta1 (TGF-β1) signaling. In the presence of TGF-β1, phosphorylated mothers against decapentaplegic homolog 2/3 (p-Smad2/3) translocated to the binding sites of the Ets-1 promoter to upregulate the expression of Ets-1 in primary hepatocytes. In addition, Ets-1 bound directly to phosphorylated Smad3 (p-Smad3), thereby preventing the ubiquitination and proteasomal degradation of p-Smad3 and enhancing the activity of TGF-β1/Smad3 signaling. Consequently, elevated Ets-1 stimulated TGF-β1-induced hepatocyte apoptosis. However, Ets-1 knockdown alleviated diet-induced hepatocyte apoptosis and NASH with reduced liver injury, inflammation, and fibrosis. Taken together, Ets-1 had an adverse impact on hepatocyte survival under TGF-β1 treatment and accelerated the development of NASH in mice.
ATR mediates cisplatin resistance in 3D-cultured breast cancer cells via translesion DNA synthesis modulation
Authors: Gomes Luciana Rodrigues , Rocha Clarissa Ribeiro Reily , Martins Davi Jardim , Fiore Ana Paula Zen Petisco , Kinker Gabriela Sarti , Bruni-Cardoso Alexandre , Menck Carlos Frederico Martins 
Published: June 2019

AbstractTissue architecture and cell–extracellular matrix (cell–ECM) interaction determine the organ specificity; however, the influences of these factors on anticancer drugs preclinical studies are highly neglected. For considering such aspects, three-dimensional (3D) cell culture models are relevant tools for accurate analysis of cellular responses to chemotherapy. Here we compared the MCF-7 breast cancer cells responses to cisplatin in traditional two-dimensional (2D) and in 3D-reconstituted basement membrane (3D-rBM) cell culture models. The results showed a substantial increase of cisplatin resistance mediated by 3D microenvironment. This phenotype was independent of p53 status and autophagy activity and was also observed for other cellular models, including lung cancer cells. Such strong decrease on cellular sensitivity was not due to differences on drug-induced DNA damage, since similar levels of γ-H2AX and cisplatin–DNA adducts were detected under both conditions. However, the processing of these cisplatin-induced DNA lesions was very different in 2D and 3D cultures. Unlike cells in monolayer, cisplatin-induced DNA damage is persistent in 3D-cultured cells, which, consequently, led to high senescence induction. Moreover, only 3D-cultured cells were able to progress through S cell cycle phase, with unaffected replication fork progression, due to the upregulation of translesion (TLS) DNA polymerase expression and activation of the ATR-Chk1 pathway. Co-treatment with VE-821, a pharmacological inhibitor of ATR, blocked the 3D-mediated changes on cisplatin response, including low sensitivity and high TLS capacity. In addition, ATR inhibition also reverted induction of REV3L by cisplatin treatment. By using REV3L-deficient cells, we showed that this TLS DNA polymerase is essential for the cisplatin sensitization effect mediated by VE-821. Altogether, our results demonstrate that 3D-cell architecture-associated resistance to cisplatin is due to an efficient induction of REV3L and TLS, dependent of ATR. Thus co-treatment with ATR inhibitors might be a promising strategy for enhancement of cisplatin treatment efficiency in breast cancer patients.
YIPF2 is a novel Rab-GDF that enhances HCC malignant phenotypes by facilitating CD147 endocytic recycle
Authors: Qi Shanshan , Su Linjia , Li Jing , Zhao Pu , Zhang Qing , Niu Xiuran , Liu Jingyuan , Jia Guhe , Wei Xiaoxuan , Tavernier Jan , Jiang Jianli , Chen Zhinan , Zhang Sihe 
Published: June 2019

AbstractAn increased surface level of CIE (clathrin-independent endocytosis) proteins is a new feature of malignant neoplasms. CD147 is a CIE glycoprotein highly up-regulated in hepatocellular carcinoma (HCC). The ability to sort out the early endosome and directly target the recycling pathway confers on CD147 a prolonged surface half-life. However, current knowledge on CD147 trafficking to and from the cell-surface is limited. In this study, an MSP (membrane and secreted protein)-cDNA library was screened against EpoR/LR-F3/CD147EP-expressed cells by MAPPIT (mammalian protein–protein interaction trap). CD147 co-expressing with the new binder was investigated by GEPIA (gene expression profiling interactive analysis). The endocytosis, ER-Golgi trafficking and recycling of CD147 were measured by confocal imaging, flow cytometry, and biotin-labeled chase assays, respectively. Rab GTPase activation was checked by GST-RBD pull-down and MMP activity was measured by gelatin zymography. HCC malignant phenotypes were determined by cell adhesion, proliferation, migration, Transwell motility, and invasion assays. An ER-Golgi-resident transmembrane protein YIPF2 was identified as an intracellular binder to CD147. YIPF2 correlated and co-expressed with CD147, which is a survival predictor for HCC patients. YIPF2 is critical for CD147 glycosylation and trafficking functions in HCC cells. YIPF2 acts as a Rab-GDF (GDI-displacement factor) regulating three independent trafficking steps. First, YIPF2 recruits and activates Rab5 and Rab22a GTPases to the endomembrane structures. Second, YIPF2 modulates the endocytic recycling of CD147 through distinctive regulation on Rab5 and Rab22a. Third, YIPF2 mediates the mature processing of CD147 via the ER-Golgi trafficking route. Decreased YIPF2 expression induced a CD147 efficient delivery to the cell-surface, promoted MMP secretion, and enhanced the adhesion, motility, migration, and invasion behaviors of HCC cells. Thus, YIPF2 is a new trafficking determinant essential for CD147 glycosylation and transport. Our findings revealed a novel YIPF2-controlled ER-Golgi trafficking signature that promotes CD147-medated malignant phenotypes in HCC.
DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass
Authors: Favaro Giulia , Romanello Vanina , Varanita Tatiana , Andrea Desbats Maria , Morbidoni Valeria , Tezze Caterina , Albiero Mattia , Canato Marta , Gherardi Gaia , De Stefani Diego , Mammucari Cristina , Blaauw Bert , Boncompagni Simona , Protasi Feliciano , Reggiani Carlo , Scorrano Luca , Salviati Leonardo , Sandri Marco 
Published: June 2019

AbstractMitochondrial quality control is essential in highly structured cells such as neurons and muscles. In skeletal muscle the mitochondrial fission proteins are reduced in different physiopathological conditions including ageing sarcopenia, cancer cachexia and chemotherapy-induced muscle wasting. However, whether mitochondrial fission is essential for muscle homeostasis is still unclear. Here we show that muscle-specific loss of the pro-fission dynamin related protein (DRP) 1 induces muscle wasting and weakness. Constitutive Drp1 ablation in muscles reduces growth and causes animal death while inducible deletion results in atrophy and degeneration. Drp1 deficient mitochondria are morphologically bigger and functionally abnormal. The dysfunctional mitochondria signals to the nucleus to induce the ubiquitin-proteasome system and an Unfolded Protein Response while the change of mitochondrial volume results in an increase of mitochondrial Ca2+ uptake and myofiber death. Our findings reveal that morphology of mitochondrial network is critical for several biological processes that control nuclear programs and Ca2+ handling.
Hsp90 middle domain phosphorylation initiates a complex conformational program to recruit the ATPase-stimulating cochaperone Aha1
Authors: Xu Wanping , Beebe Kristin , Chavez Juan D. , Boysen Marta , Lu YinYing , Zuehlke Abbey D. , Keramisanou Dimitra , Trepel Jane B. , Prodromou Christosomos , Mayer Matthias P. , Bruce James E. , Gelis Ioannis , Neckers Len 
Published: June 2019

AbstractComplex conformational dynamics are essential for function of the dimeric molecular chaperone heat shock protein 90 (Hsp90), including transient, ATP-biased N-domain dimerization that is necessary to attain ATPase competence. The intrinsic, but weak, ATP hydrolyzing activity of human Hsp90 is markedly enhanced by the co-chaperone Aha1. However, the cellular concentration of Aha1 is substoichiometric relative to Hsp90. Here we report that initial recruitment of this cochaperone to Hsp90 is markedly enhanced by phosphorylation of a highly conserved tyrosine (Y313 in Hsp90α) in the Hsp90 middle domain. Importantly, phosphomimetic mutation of Y313 promotes formation of a transient complex in which both N- and C-domains of Aha1 bind to distinct surfaces of the middle domains of opposing Hsp90 protomers prior to ATP-directed N-domain dimerization. Thus, Y313 represents a phosphorylation-sensitive conformational switch, engaged early after client loading, that affects both local and long-range conformational dynamics to facilitate initial recruitment of Aha1 to Hsp90.
A pan-cancer analysis of synonymous mutations
Authors: Sharma Yogita , Miladi Milad , Dukare Sandeep , Boulay Karine , Caudron-Herger Maiwen , Groß Matthias , Backofen Rolf , Diederichs Sven 
Published: June 2019

AbstractSynonymous mutations have been viewed as silent mutations, since they only affect the DNA and mRNA, but not the amino acid sequence of the resulting protein. Nonetheless, recent studies suggest their significant impact on splicing, RNA stability, RNA folding, translation or co-translational protein folding. Hence, we compile 659194 synonymous mutations found in human cancer and characterize their properties. We provide the user-friendly, comprehensive resource for synonymous mutations in cancer, SynMICdb (http://SynMICdb.dkfz.de), which also contains orthogonal information about gene annotation, recurrence, mutation loads, cancer association, conservation, alternative events, impact on mRNA structure and a SynMICdb score. Notably, synonymous and missense mutations are depleted at the 5'-end of the coding sequence as well as at the ends of internal exons independent of mutational signatures. For patient-derived synonymous mutations in the oncogene KRAS, we indicate that single point mutations can have a relevant impact on expression as well as on mRNA secondary structure.
Non-coding cis-element of Period2 is essential for maintaining organismal circadian behaviour and body temperature rhythmicity
Authors: Doi Masao , Shimatani Hiroyuki , Atobe Yuta , Murai Iori , Hayashi Hida , Takahashi Yukari , Fustin Jean-Michel , Yamaguchi Yoshiaki , Kiyonari Hiroshi , Koike Nobuya , Yagita Kazuhiro , Lee Choogon , Abe Manabu , Sakimura Kenji , Okamura Hitoshi 
Published: June 2019

AbstractNon-coding cis-regulatory elements are essential determinants of development, but their exact impacts on behavior and physiology in adults remain elusive. Cis-element-based transcriptional regulation is believed to be crucial for generating circadian rhythms in behavior and physiology. However, genetic evidence supporting this model is based on mutations in the protein-coding sequences of clock genes. Here, we report generation of mutant mice carrying a mutation only at the E′-box cis-element in the promoter region of the core clock gene Per2. The Per2 E′-box mutation abolishes sustainable molecular clock oscillations and renders circadian locomotor activity and body temperature rhythms unstable. Without the E′-box, Per2 messenger RNA and protein expression remain at mid-to-high levels. Our work delineates the Per2 E′-box as a critical nodal element for keeping sustainable cell-autonomous circadian oscillation and reveals the extent of the impact of the non-coding cis-element in daily maintenance of animal locomotor activity and body temperature rhythmicity.
Critical spin liquid versus valence-bond glass in a triangular-lattice organic antiferromagnet
Authors: Riedl Kira , Valentí Roser , Winter Stephen M. 
Published: June 2019

AbstractIn the quest for materials with unconventional quantum phases, the organic triangular-lattice antiferromagnet κ-(ET)2Cu2(CN)3 has been extensively discussed as a quantum spin liquid (QSL) candidate. The description of its low temperature properties has become, however, a particularly challenging task. Recently, an intriguing quantum critical behaviour was suggested from low-temperature magnetic torque experiments. Here we highlight significant deviations of the experimental observations from a quantum critical scenario by performing a microscopic analysis of all anisotropic contributions, including Dzyaloshinskii–Moriya and multi-spin scalar chiral interactions. Instead, we show that disorder-induced spin defects provide a comprehensive explanation of the low-temperature properties. These spins are attributed to valence bond defects that emerge spontaneously as the QSL enters a valence-bond glass phase at low temperature. This theoretical treatment is applicable to a general class of frustrated magnetic systems and has important implications for the interpretation of magnetic torque, nuclear magnetic resonance, thermal transport and thermodynamic experiments.
Artificial creation and separation of a single vortex–antivortex pair in a ferroelectric flatland
Authors: Kim Jeongyong , You Mujin , Kim Kwang-Eun , Chu Kanghyun , Yang Chan-Ho 
Published: June 2019

AbstractTopological defects have received much attention due to their stability against perturbations and potential applications in nonvolatile high-density memory. Topologically non-trivial textures can be compelled by constraints on boundary condition, geometrical structure, and curved space. Ferroelectric vortices have been realized in various finite-sized nanostructures that allow such constraints to be produced. However, manipulation of topological excitations in otherwise topologically trivial flat ferroelectrics remains a tantalizing challenge. Here we show that a vortex–antivortex pair can be produced by a momentary electric pulse using a tip in a usual Kittel’s stripe domain of a BiFeO3 thin film. Moreover, we demonstrate that the distance between the paired vortex and antivortex can be controlled by dragging the biased tip. The spatial distribution of the local piezoresponse vectors is directly mapped using angle-resolved piezoresponse force microscopy and analyzed by local winding number calculation. Our findings offer a useful concept for the control of topological defects in ferroelectrics.
Evolution of nitrogen cycling in regrowing Amazonian rainforest
Authors: Figueiredo Viviane , Enrich-Prast Alex , Rütting Tobias 
Published: June 2019

AbstractExtensive regions of tropical forests are subjected to high rates of deforestation and forest regrowth and both are strongly affect soil nutrient cycling. Nitrogen (N) dynamics changes during forest regrowth and the recovery of forests and functioning similar to pristine conditions depends on sufficient N availability. We show that, in a chronosequence of Amazonian forests, gross nitrification and, as a result, nitrate-to-ammonium (NO3−: NH4+) ratio were lower in all stages of regrowing forests (10 to 40 years) compared to pristine forest. This indicates the evolution of a more conservative and closed N cycle with reduced risk for N leaking out of the ecosystem in regrowing forests. Furthermore, our results indicate that mineralization and nitrification are decoupled in young regrowing forests (10 years), such as that high gross mineralization is accompanied by low gross nitrification, demonstrating a closed N cycle that at the same time maintains N supply for forest regrowth. We conclude that the status of gross nitrification in disturbed soil is a key process to understand the mechanisms of and time needed for tropical forest recovery.
Exploiting dispersion of higher-order-modes using M-type fiber for application in mid-infrared supercontinuum generation
Authors: Jain D. , Markos C. , Benson T. M. , Seddon A. B. , Bang O. 
Published: June 2019

AbstractM-type fibers have the exceptional property that the higher-order LP0n modes are core-confined and easily excited, while the LP01 and other modes are confined to a high-index ring surrounding the core, so they are not easily excited. This has profound consequences for mid-infrared supercontinuum sources, where the high zero-dispersion wavelength of chalcogenide and ZBLAN fibers means that exotic pump sources have so far been necessary. We show here that in chalcogenide and ZBLAN M-type fibers the lower ZDW of the core-confined higher-order LP02 mode can be in the range of 2 to 3 µm (around 1.55 µm), while the fiber still has a large core diameter and thus supports high average power. This will allow established pump laser technology to be used in future high-power mid-infrared supercontinuum sources.
Interdisziplinäre Fallkonferenzen als Chance für Myositis-Patienten?
Authors: Rademacher Jan-Gerd , Seitz Cornelia S. , Zschüntzsch Jana , Mößner Rotraut , Zeisberg Michael , Olgemöller Ulrike , Buck Cordula , Zechel Sabrina , Müller Gerhard A , Vasko Radovan , Schmidt Jens , Korsten Peter 
Published: June 2019

ZUSAMMENFASSUNG
Gegenstand und Ziel Myositis-Patienten bedürfen einer interdisziplinären Diagnostik und Therapie. Über Konsile erfolgt die Besprechung unsystematisch und zum Teil therapeutisch divergent. Interdisziplinäre Fallkonferenzen bieten potenzielle Vorteile bei Myositiden und anderen Systemerkrankungen.
Material und Methoden Narrative Beschreibung des „Göttinger Modells“ und retrospektive Analyse der immunologischen Fallkonferenzen von September 2018 bis Februar 2019.
Ergebnisse 30 Patienten wurden vorgestellt, 15 im Rahmen einer Myositis. Weitere Diagnosen umfassten Sarkoidose, Sklerodermie und andere Entitäten. 20 Patienten wiesen positive antinukleäre Antikörper (AK) auf; weitere AK waren Ro52, Antisynthetase, Mi2-β, TIF1-γ, MDA5 und CENP-B/Fibrillarin. Eine CK-Erhöhung lag in 5 Fällen vor. 23 Patienten wurde eine weitere Diagnostik empfohlen. Therapieänderungen erfolgten bei 11 Patienten.
Schlussfolgerungen Interdisziplinäre Fallkonferenzen ermöglichen eine systematische diagnostische und therapeutische Strategie. In einer prospektiven Studie sollte untersucht werden, inwieweit sich Fallkonferenzen auf krankheitsassoziierte sowie patientenseitige Outcomes auswirken.
Klinische Relevanz Das „Göttinger Modell“ ist gut umsetzbar und führt überwiegend zu diagnostischen und therapeutischen Konsequenzen.
Diagnostischer Stellenwert der Muskelbiopsie bei Myositis
Authors: Stadelmann Christine , Zechel Sabrina 
Published: June 2019

ZUSAMMENFASSUNG
Gegenstand und Ziel Myositiden stellen eine der häufigsten Indikationen für eine Muskelbiopsie dar, die als wichtigstes morphologisches Untersuchungsverfahren zur Diagnosestellung gilt. Ihr Stellenwert im diagnostischen Prozess ist aber nur unzureichend untersucht.
Material und Methoden In der vorliegenden Arbeit wurden retrospektiv histopathologische Befunde von Muskelbiopsien mit klinischem Verdacht auf Myositis am neuromuskulärem Zentrum Göttingen von 2007 bis 2018 ausgewertet.
Ergebnisse In 27 % aller eingesandten Muskelbiopsien wurde der klinische Verdacht auf eine Myositis geäußert, der sich in ca. einem Drittel der Fälle histologisch bestätigte. Auch wenn eine Myositis histologisch nicht nachgewiesen werden konnte, ergaben sich durch die Muskelbiopsie in 84 % der Fälle weitere diagnostische Hinweise.
Schlussfolgerung Die Muskelbiopsie ist neben der Klinik und dem Antikörperprofil als integraler Bestandteil der Diagnose sowie zur Klassifikation einer Myositis unverzichtbar.
Klinische Relevanz Zur definitiven Diagnosestellung einer Myositis bedarf es der engen interdisziplinären Zusammenarbeit zwischen Klinik, Bildgebung und Neuropathologie.
Successful endoscopic closure of a refractory postoperative rectovaginal fistula
Authors: Matano Yutaka , Zianne Megumi , Omura Hitoshi , Hayashi Noriaki , Miwa Kazuhiro 
Published: June 2019

Abstract
Background and study aims A 71-year old female who received low anterior resection for rectal cancer visited Komatsu Municipal Hospital with complaints of passing feces from the vagina. Endoscopic examination revealed a postsurgical rectovaginal fistula. Medical approaches, including nonoperative management, initial endoscopic closure, transvaginal and endorectal surgery, and fecal diversion, were unsuccessful. Therefore, the patient underwent endoscopy with a pre-procedural endoscopic creation of mucosal pin holes around the fistula opening and clip insertion into the rectal wall in combination with electrocautery and clip closure. This novel approach was effective in achieving permanent closure of the fistula in a single procedure. Most rectovaginal fistulas are surgically managed, however, surgery may be more difficult, invasive, and unsatisfactory for refractory fistulas. Although endoscopic treatment with over-the-scope clips has been increasingly used as a less invasive approach for gastrointestinal fistulas with favorable results, it is not as effective for refractory rectovaginal fistulas. As a minimally invasive surgical procedure, this approach might be effective in small rectovaginal fistulas, particularly refractory ones.