bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma
Authors: Enfield Katey S. S. , Marshall Erin A. , Anderson Christine , Ng Kevin W. , Rahmati Sara , Xu Zhaolin , Fuller Megan , Milne Katy , Lu Daniel , Shi Rocky , Rowbotham David A. , Becker-Santos Daiana D. , Johnson Fraser D. , English John C. , MacAulay Calum E. , Lam Stephen , Lockwood William W. , Chari Raj , Karsan Aly , Jurisica Igor , Lam Wan L. 
Published: November 2019

AbstractGene function in cancer is often cell type-specific. The epithelial cell-specific transcription factor ELF3 is a documented tumor suppressor in many epithelial tumors yet displays oncogenic properties in others. Here, we show that ELF3 is an oncogene in the adenocarcinoma subtype of lung cancer (LUAD), providing genetic, functional, and clinical evidence of subtype specificity. We discover a region of focal amplification at chromosome 1q32.1 encompassing the ELF3 locus in LUAD which is absent in the squamous subtype. Gene dosage and promoter hypomethylation affect the locus in up to 80% of LUAD analyzed. ELF3 expression was required for tumor growth and a pan-cancer expression network analysis supports its subtype and tissue specificity. We further show that ELF3 displays strong prognostic value in LUAD but not LUSC. We conclude that, contrary to many other tumors of epithelial origin, ELF3 is an oncogene and putative therapeutic target in LUAD.
A general orientation distribution function for clay-rich media
Authors: Dabat Thomas , Hubert Fabien , Paineau Erwan , Launois Pascale , Laforest Claude , Grégoire Brian , Dazas Baptiste , Tertre Emmanuel , Delville Alfred , Ferrage Eric 
Published: November 2019

AbstractThe role of the preferential orientation of clay platelets on the properties of a wide range of natural and engineered clay-rich media is well established. However, a reference function for describing the orientation of clay platelets in these different materials is still lacking. Here, we conducted a systematic study on a large panel of laboratory-made samples, including different clay types or preparation methods. By analyzing the orientation distribution functions obtained by X-ray scattering, we identified a unique signature for the preferred orientation of clay platelets and determined an associated reference orientation function using the maximum-entropy method. This new orientation distribution function is validated for a large set of engineered clay materials and for representative natural clay-rich rocks. This reference function has many potential applications where consideration of preferred orientation is required, including better long-term prediction of water and solute transfer or improved designs for new generations of innovative materials.
Primary decidual zone formation requires Scribble for pregnancy success in mice
Authors: Yuan Jia , Aikawa Shizu , Deng Wenbo , Bartos Amanda , Walz Gerd , Grahammer Florian , Huber Tobias B. , Sun Xiaofei , Dey Sudhansu K. 
Published: November 2019

AbstractScribble (Scrib) is a scaffold protein with multifunctional roles in PCP, tight junction and Hippo signaling. This study shows that Scrib is expressed in stromal cells around the implantation chamber following implantation. Stromal cells transform into epithelial-like cells to form the avascular primary decidual zone (PDZ) around the implantation chamber (crypt). The PDZ creates a permeability barrier around the crypt restricting immune cells and harmful agents from maternal circulation to protect embryonic health. The mechanism underlying PDZ formation is not yet known. We found that uterine deletion of Scrib by a Pgr-Cre driver leads to defective PDZ formation and implantation chamber (crypt) formation, compromising pregnancy success. Interestingly, epithelial-specific Scrib deletion by a lactoferrin-Cre (Ltf-Cre) driver does not adversely affect PDZ formation and pregnancy success. These findings provide evidence for a previously unknown function of stromal Scrib in PDZ formation, potentially involving ZO-1 and Hippo signaling.
Electrochemical oxidation induced intermolecular aromatic C-H imidation
Authors: Hu Xia , Zhang Guoting , Nie Lei , Kong Taige , Lei Aiwen 
Published: November 2019

AbstractThe dehydrogenative aryl C-H/N-H cross-coupling is a powerful synthetic methodology to install nitrogen functionalities into aromatic compounds. Herein, we report an electrochemical oxidation induced intermolecular cross-coupling between aromatics and sulfonimides with high regioselectivity through N-radical addition pathway under external-oxidant-free and catalyst-free conditions. A wide variety of arenes, heteroarenes, alkenes and sulfonimides are applicable scaffolds in this transformation. In addition, aryl sulfonamides or amines (aniline derivatives) can be obtained through different deprotection process. The cyclic voltammetry mechanistic study indicates that the N-centered imidyl radicals are generated via proton-coupled electron transfer event jointly mediated by tetrabutylammonium acetate and anode oxidation process.
Effect of Parkinson’s disease and related medications on the composition of the fecal bacterial microbiota
Authors: Weis Severin , Schwiertz Andreas , Unger Marcus M. , Becker Anouck , Faßbender Klaus , Ratering Stefan , Kohl Matthias , Schnell Sylvia , Schäfer Karl-Herbert , Egert Markus 
Published: November 2019

AbstractParkinson’s disease (PD) is one of the most common neurodegenerative disorders. PD patients suffer from gastrointestinal dysfunctions and alterations of the autonomous nervous system, especially its part in the gut wall, i.e., the enteric nervous system (ENS). Such alterations and functional gastrointestinal deficits often occur years before the classical clinical symptoms of PD appear. Until now, only little is known about PD-associated changes in gut microbiota composition and their potential implication in PD development. In order to increase knowledge in this field, fecal samples of 34 PD patients and 25 healthy, age-matched control persons were investigated. Here, the V4 and V5 hypervariable region of bacterial 16S rRNA genes was PCR-amplified and sequenced using an Ion Torrent PGM platform. Within the PD group, we observed a relative decrease in bacterial taxa which are linked to health-promoting, anti-inflammatory, neuroprotective or other beneficial effects on the epithelial barrier, such as Faecalibacterium and Fusicatenibacter. Both taxa were lowered in PD patients with elevated levels of the fecal inflammation marker calprotectin. In addition, we observed an increase in shares of the Clostridiales family XI and their affiliated members in these samples. Finally, we found that the relative abundances of the bacterial genera Peptoniphilus, Finegoldia, Faecalibacterium Fusicatenibacter, Anaerococcus, Bifidobacterium, Enterococcus, and Ruminococcus were significantly influenced by medication with L-dopa and entacapone, respectively. Our data confirm previously reported effects of COMT inhibitors on the fecal microbiota of PD patients and suggest a possible effect of L-dopa medication on the relative abundance of several bacterial genera.
Isodeoxyelephantopin, a Sesquiterpene Lactone Induces ROS Generation, Suppresses NF-κB Activation, Modulates LncRNA Expression and Exhibit Activities Against Breast Cancer
Authors: Verma Sumit S. , Rai Vipin , Awasthee Nikee , Dhasmana Anupam , Rajalaksmi Dhanya S , Nair Mangalam S. , Gupta Subash C. 
Published: November 2019

AbstractThe sesquiterpene lactones, Isodeoxyelephantopin (IDET) and Deoxyelephantopin (DET) are known to exhibit activities against some cancer types. The activities of these lactones against breast cancer and the molecular bases is not known. We examined the efficacy of lactones in breast cancer preclinical model. Although both lactones exhibited drug like properties, IDET was relatively effective in comparison to DET. IDET suppressed the proliferation of both invasive and non-invasive breast cancer cell lines. IDET also suppressed the colony formation and migration of breast cancer cells. The assays for Acridine Orange (AO)/Propidium Iodide (PI) staining, cell cycle distribution, phosphatidylserine externalization and DNA laddering suggested the apoptosis inducing potential of IDET. The treatment with IDET also induced an accumulation of cells in the sub-G1 and G2/M phases. The exposure of breast cancer cells to the lactone was associated with a depolarization in mitochondrial membrane potential, and cleavage of caspase and PARP. The lactone induced reactive oxygen species (ROS) generation in breast cancer cells. Further, the use of N-acetyl cysteine (NAC) suppressed IDET induced ROS generation and apoptosis. The NF-κB-p65 nuclear translocation induced by okadaic acid (OA) was suppressed by the sesquiterpene. IDET also suppressed the expression of NF-κB regulated tumorigenic proteins, and induced the expression of proapoptotic gene (Bax) in cancer cells. While the expression of oncogenic lncRNAs was suppressed, the tumor suppressor lncRNAs were induced by the sesquiterpene. Collectively, the modulation of multiple cell signaling molecules by IDET may contribute to its activities in breast cancer cells.
Brazilian montane rainforest expansion induced by Heinrich Stadial 1 event
Authors: Pinaya Jorge L. D. , Cruz Francisco W. , Ceccantini Gregório C. T. , Corrêa Pedro L. P. , Pitman Nigel , Vemado Felipe , Lopez Maria del Carmen S. , Pereira Filho Augusto J. , Grohmann Carlos H. , Chiessi Cristiano M. , Stríkis Nicolás M. , Horák-Terra Ingrid , Pinaya Walter H. L. , de Medeiros Vanda B. , Santos Rudney de A. , Akabane Thomas K. , Silva Maicon A. , Cheddadi Rachid , Bush Mark , Henrot Alexandra-Jane , François Louis , Hambuckers Alain , Boyer Frédéric , Carré Matthieu , Coissac Eric , Ficetola Francesco , Huang Kangyou , Lézine Anne-Marie , Nourelbait Majda , Rhoujjati Ali , Taberlet Pierre , Sarmiento Fausto , Abel-Schaad Daniel , Alba-Sánchez Francisca , Zheng Zhuo , De Oliveira Paulo E. 
Published: November 2019

AbstractThe origin of modern disjunct plant distributions in the Brazilian Highlands with strong floristic affinities to distant montane rainforests of isolated mountaintops in the northeast and northern Amazonia and the Guyana Shield remains unknown. We tested the hypothesis that these unexplained biogeographical patterns reflect former ecosystem rearrangements sustained by widespread plant migrations possibly due to climatic patterns that are very dissimilar from present-day conditions. To address this issue, we mapped the presence of the montane arboreal taxa Araucaria, Podocarpus, Drimys, Hedyosmum, Ilex, Myrsine, Symplocos, and Weinmannia, and cool-adapted plants in the families Myrtaceae, Ericaceae, and Arecaceae (palms) in 29 palynological records during Heinrich Stadial 1 Event, encompassing a latitudinal range of 30°S to 0°S. In addition, Principal Component Analysis and Species Distribution Modelling were used to represent past and modern habitat suitability for Podocarpus and Araucaria. The data reveals two long-distance patterns of plant migration connecting south/southeast to northeastern Brazil and Amazonia with a third short route extending from one of them. Their paleofloristic compositions suggest a climatic scenario of abundant rainfall and relative lower continental surface temperatures, possibly intensified by the effects of polar air incursions forming cold fronts into the Brazilian Highlands. Although these taxa are sensitive to changes in temperature, the combined pollen and speleothems proxy data indicate that this montane rainforest expansion during Heinrich Stadial 1 Event was triggered mainly by a less seasonal rainfall regime from the subtropics to the equatorial region.
Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release – a cohort study design combined with an experimental study
Authors: Eliasson Pernilla , Dietrich-Zagonel Franciele , Lundin Anna-Carin , Aspenberg Per , Wolk Alicja , Michaëlsson Karl 
Published: November 2019

AbstractRecent experimental evidence indicates potential adverse effects of statin treatment on tendons but previous clinical studies are few and inconclusive. The aims of our study were, first, to determine whether statin use in a cohort design is associated with tendinopathy disorders, and second, to experimentally understand the pathogenesis of statin induced tendinopathy. We studied association between statin use and different tendon injuries in two population-based Swedish cohorts by time-dependent Cox regression analysis. Additionally, we tested simvastatin in a 3D cell culture model with human tenocytes. Compared with never-users, current users of statins had a higher incidence of trigger finger with adjusted hazard ratios (aHRs) of 1.50 for men (95% confidence interval [CI] 1.21–1.85) and 1.21 (1.02–1.43) for women. We also found a higher incidence of shoulder tendinopathy in both men (aHR 1.43; 1.24–1.65) and women (aHR 1.41; 0.97–2.05). Former users did not confer a higher risk of tendinopathies. In vitro experiments revealed an increased release of matrix metalloproteinase (MMP)-1 and MMP-13 and a weaker, disrupted matrix after simvastatin exposure. Current statin use seems to increase the risk of trigger finger and shoulder tendinopathy, possibly through increased MMP release, and subsequently, a weakened tendon matrix which will be more prone to injuries.
Germline de novo variants in CSNK2B in Chinese patients with epilepsy
Authors: Li Jinliang , Gao Kai , Cai Shuying , Liu Yin , Wang Yuzhen , Huang Shaoping , Zha Jian , Hu Wenjing , Yu Shujie , Yang Zhixian , Xie Han , Yan Huifang , Wang Jingmin , Wu Ye , Jiang Yuwu 
Published: November 2019

AbstractCSNK2B, which encodes the beta subunit of casein kinase II (CK2), plays an important role in neuron morphology and synaptic transmission. Variants in CSNK2B associated with epilepsy and/or intellectual disability (ID)/developmental delay (DD) have been reported in five cases only. Among the 816 probands suspected hereditary epilepsy whose initial report of trio-based whole exome sequencing (WES) were negative, 10 de novo pathogenic or likely pathogenic variants of CSNK2B in nine probands were identified after reanalysis of their raw Trio-WES data. Six of the nine epileptic patients had ID/DD. The age of seizure onset of these nine patients with CSNK2B variants ranged from 2–12 months. Eight patients had age of seizure onset of less than 6 months. The epilepsy of most probands (8/9) was generalized tonic-clonic seizure and clustered (6/9). Most patients had normal electroencephalogram (5/9) and brain magnetic resonance image (7/9) results. Most patients (7/9) had easy-to-control seizures. Levetiracetam was the most commonly used drug in seizure-free patients (5/7). The variants detected in five patients (5/9, 55.6%) were located in the zinc-binding domain. In summary, our research provided evidence that variants in CSNK2B are associated with epilepsy with or without ID/DD. CSNK2B-related epilepsy is relatively easy to be controlled. The zinc-binding domain appears to be the hotspot region for mutation.
Marine fish traits follow fast-slow continuum across oceans
Authors: Beukhof Esther , Frelat Romain , Pecuchet Laurene , Maureaud Aurore , Dencker Tim Spaanheden , Sólmundsson Jón , Punzón Antonio , Primicerio Raul , Hidalgo Manuel , Möllmann Christian , Lindegren Martin 
Published: November 2019

AbstractA fundamental challenge in ecology is to understand why species are found where they are and predict where they are likely to occur in the future. Trait-based approaches may provide such understanding, because it is the traits and adaptations of species that determine which environments they can inhabit. It is therefore important to identify key traits that determine species distributions and investigate how these traits relate to the environment. Based on scientific bottom-trawl surveys of marine fish abundances and traits of >1,200 species, we investigate trait-environment relationships and project the trait composition of marine fish communities across the continental shelf seas of the Northern hemisphere. We show that traits related to growth, maturation and lifespan respond most strongly to the environment. This is reflected by a pronounced “fast-slow continuum” of fish life-histories, revealing that traits vary with temperature at large spatial scales, but also with depth and seasonality at more local scales. Our findings provide insight into the structure of marine fish communities and suggest that global warming will favour an expansion of fast-living species. Knowledge of the global and local drivers of trait distributions can thus be used to predict future responses of fish communities to environmental change.
A SUMO-dependent pathway controls elongating RNA Polymerase II upon UV-induced damage
Authors: Heckmann Irina , Kern Maximilian J. , Pfander Boris , Jentsch Stefan 
Published: November 2019

AbstractRNA polymerase II (RNAPII) is the workhorse of eukaryotic transcription and produces messenger RNAs and small nuclear RNAs. Stalling of RNAPII caused by transcription obstacles such as DNA damage threatens functional gene expression and is linked to transcription-coupled DNA repair. To restore transcription, persistently stalled RNAPII can be disassembled and removed from chromatin. This process involves several ubiquitin ligases that have been implicated in RNAPII ubiquitylation and proteasomal degradation. Transcription by RNAPII is heavily controlled by phosphorylation of the C-terminal domain of its largest subunit Rpb1. Here, we show that the elongating form of Rpb1, marked by S2 phosphorylation, is specifically controlled upon UV-induced DNA damage. Regulation of S2-phosphorylated Rpb1 is mediated by SUMOylation, the SUMO-targeted ubiquitin ligase Slx5-Slx8, the Cdc48 segregase as well as the proteasome. Our data suggest an RNAPII control pathway with striking parallels to known disassembly mechanisms acting on defective RNA polymerase III.
Exacerbation of ozone-induced pulmonary and systemic effects by β2-adrenergic and/or glucocorticoid receptor agonist/s
Authors: Henriquez Andres R. , Snow Samantha J. , Schladweiler Mette C. , Miller Colette N. , Dye Janice A. , Ledbetter Allen D. , Hargrove Marie M. , Richards Judy E. , Kodavanti Urmila P. 
Published: November 2019

AbstractAgonists of β2adrenergic receptors (β2AR) and glucocorticoid receptors (GR) are prescribed to treat pulmonary diseases. Since ozone effects are mediated through the activation of AR and GR, we hypothesized that the treatment of rats with relevant therapeutic doses of long acting β2AR agonist (LABA; clenbuterol; CLEN) and/or GR agonist (dexamethasone; DEX) would exacerbate ozone-induced pulmonary and systemic changes. In the first study, male 12-week-old Wistar-Kyoto rats were injected intraperitoneally with vehicle (saline), CLEN (0.004 or 0.02 mg/kg), or DEX (0.02 or 0.1 mg/kg). Since dual therapy is commonly used, in the second study, rats received either saline or combined CLEN + DEX (each at 0.005 or 0.02 mg/kg) one day prior to and on both days of exposure (air or 0.8ppm ozone, 4 hr/day x 2-days). In air-exposed rats CLEN, DEX or CLEN + DEX did not induce lung injury or inflammation, however DEX and CLEN + DEX decreased circulating lymphocytes, spleen and thymus weights, increased free fatty acids (FFA) and produced hyperglycemia and glucose intolerance. Ozone exposure of vehicle-treated rats increased bronchoalveolar lavage fluid protein, albumin, neutrophils, IL-6 and TNF-α. Ozone decreased circulating lymphocytes, increased FFA, and induced hypeerglycemia and glucose intolerance. Drug treatment did not reverse ozone-induced ventillatory changes, however, lung effects (protein and albumin leakage, inflammation, and IL-6 increase) were exacerbated by CLEN and CLEN + DEX pre-treatment in a dose-dependent manner (CLEN > CLEN + DEX). Systemic effects induced by DEX and CLEN + DEX but not CLEN in air-exposed rats were analogous to and more pronounced than those induced by ozone. These data suggest that adverse air pollution effects might be exacerbated in people receiving LABA or LABA plus glucocorticoids.
Information Content of Prefrontal Cortex Activity Quantifies the Difficulty of Narrated Stories
Authors: Keshmiri Soheil , Sumioka Hidenobu , Yamazaki Ryuji , Shiomi Masahiro , Ishiguro Hiroshi 
Published: November 2019

AbstractThe ability to realize the individuals’ impressions during the verbal communication allows social robots to significantly facilitate their social interactions in such areas as child education and elderly care. However, such impressions are highly subjective and internalized and therefore cannot be easily comprehended through behavioural observations. Although brain-machine interface suggests the utility of the brain information in human-robot interaction, previous studies did not consider its potential for estimating the internal impressions during verbal communication. In this article, we introduce a novel approach to estimation of the individuals’ perceived difficulty of stories using the quantified information content of their prefrontal cortex activity. We demonstrate the robustness of our approach by showing its comparable performance in face-to-face, humanoid, speaker, and video-chat settings. Our results contribute to the field of socially assistive robotics by taking a step toward enabling robots determine their human companions’ perceived difficulty of conversations, thereby enabling these media to sustain their communication with humans by adapting to individuals’ pace and interest in response to conversational nuances and complexity.
Overweight and obesity are associated with cardiac adverse structure remodeling in Chinese elderly with hypertension
Authors: Liu Cheng , Li Gang , Laukkanen Jari A. , Hao Lan , Zhao Qianping , Zhang Jing , Zhang Xu 
Published: November 2019

AbstractThere is limited information on the association of overweight and obesity with cardiac remodeling in elderly population. Therefore, we investigated whether overweight and obesity are associated with cardiac geometric structures and function in Chinese elderly. A total of 1183 hospitalized patients (aged 65–99 years) with primary hypertension were collected retrospectively in a cross-sectional study, and divided into underweight, normal weight, overweight and obesity patient groups according to their body mass index (BMI). Cardiac echocardiographic parameters were compared between the groups. BMI was 17.2 ± 1.2, 21.4 ± 1.2, 25.1 ± 1.2, 30.2 ± 2.6 kg/m2 in underweight, normal weight, overweight and obesity groups respectively. Aortic and left atrial diameter, interventricular septal and left ventricular (LV) posterior wall thickness, LV end-diastolic and end-systolic diameter, and indexed LV mass, and prevalence of E/A reversal were higher, while LV ejection fraction and fractional shortening were lower in elderly with overweight or obesity, as compared with whose with underweight or normal weight separately (All P < 0.05). However, multivariable regression analysis showed that overweight and obesity are independently related to increased LV wall thickness, end-diastolic diameter and mass (All P < 0.05). In conclusions, this study demonstrates that overweight and obesity are associated with increased LV wall thickness, end-diastolic diameter and mass in Asian elderly.