bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conjunction of potential G-quadruplex and adjacent cis-elements in the 5′ UTR of hepatocyte nuclear factor 4-alpha strongly inhibit protein expression
Authors: Guo Shangdong , Lu Hong 
Published: December 2017

AbstractHepatocyte nuclear factor 4-alpha (HNF4α) is a well established master regulator of liver development and function. We identified the in vitro presence of a stable secondary structure, G-quadruplex (G4) in the 5′ UTR of P1-HNF4A, the predominant HNF4α isoform(s) in adult liver. Our data suggest that the cooperation of G4 and the adjacent putative protein-binding sites within the 5′ UTR was necessary and sufficient to mediate a strong translational repression. This was supported by analysis of deleted/mutated 5′UTRs and two native regulatory single-nucleotide polymorphisms in the 5′UTR. Additional results indicated that G4 motifs in the 5′ UTRs of other liver-enriched transcription factors also inhibited protein expression. Moreover, pyridostatin, a G4 ligand, specifically potentiated the translational suppressing effect of P1-HNF4A-5′ UTR. In summary, the present study provides the first evidence of the presence of G4 in human P1-HNF4A-5′ UTR in vitro, and establishes a novel working model of strong inhibition of protein translation via interactions of G4 with potential RNA-binding proteins (RBPs). The protein expression of the tumor suppressor HNF4α may be inhibited by interactions of RBPs with the G4 motif in the 5′ UTR to promote cell proliferation during liver development and carcinogenesis.
The Sam-Sam interaction between Ship2 and the EphA2 receptor: design and analysis of peptide inhibitors
Authors: Mercurio Flavia Anna , Di Natale Concetta , Pirone Luciano , Iannitti Roberta , Marasco Daniela , Pedone Emilia Maria , Palumbo Rosanna , Leone Marilisa 
Published: December 2017

AbstractThe lipid phosphatase Ship2 represents a drug discovery target for the treatment of different diseases, including cancer. Its C-terminal sterile alpha motif domain (Ship2-Sam) associates with the Sam domain from the EphA2 receptor (EphA2-Sam). This interaction is expected to mainly induce pro-oncogenic effects in cells therefore, inhibition of the Ship2-Sam/EphA2-Sam complex may represent an innovative route to discover anti-cancer therapeutics. In the present work, we designed and analyzed several peptide sequences encompassing the interaction interface of EphA2-Sam for Ship2-Sam. Peptide conformational analyses and interaction assays with Ship2-Sam conducted through diverse techniques (CD, NMR, SPR and MST), identified a positively charged penta-amino acid native motif in EphA2-Sam, that once repeated three times in tandem, binds Ship2-Sam. NMR experiments show that the peptide targets the negatively charged binding site of Ship2-Sam for EphA2-Sam. Preliminary in vitro cell-based assays indicate that -at 50 µM concentration- it induces necrosis of PC-3 prostate cancer cells with more cytotoxic effect on cancer cells than on normal dermal fibroblasts. This work represents a pioneering study that opens further opportunities for the development of inhibitors of the Ship2-Sam/EphA2-Sam complex for therapeutic applications.
Homeostatic plasticity and synaptic scaling in the adult mouse auditory cortex
Authors: Teichert Manuel , Liebmann Lutz , Hübner Christian A. , Bolz Jürgen 
Published: December 2017

AbstractIt has been demonstrated that sensory deprivation results in homeostatic adjustments recovering neuronal activity of the deprived cortex. For example, deprived vision multiplicatively scales up mEPSC amplitudes in the primary visual cortex, commonly referred to as synaptic scaling. However, whether synaptic scaling also occurs in auditory cortex after auditory deprivation remains elusive. Using periodic intrinsic optical imaging in adult mice, we show that conductive hearing loss (CHL), initially led to a reduction of primary auditory cortex (A1) responsiveness to sounds. However, this was followed by a complete recovery of A1 activity evoked sounds above the threshold for bone conduction, 3 days after CHL. Over the same time course patch-clamp experiments in slices revealed that mEPSC amplitudes in A1 layers 2/3 pyramids scaled up multiplicatively in CHL mice. No recovery of sensory evoked A1 activation was evident in TNFα KO animals, which lack synaptic scaling. Additionally, we could show that the suppressive effect of sounds on visually evoked visual cortex activity completely recovered along with TNFα dependent A1 homeostasis in WT animals. This is the first demonstration of homeostatic multiplicative synaptic scaling in the adult A1. These findings suggest that mild hearing loss massively affects auditory processing in adult A1.
Identification of two novel genes SLC15A2 and SLCO1B3 associated with maintenance dose variability of warfarin in a Chinese population
Authors: Cai Liang-Liang , Huang Wen-Qing , Su Zhi-Ying , Ye Hui-Ming , Wang Lian-Sheng , Wu Yuan , Zhang Zhong-Ying , Zhang Wei , Tzeng Chi-Meng 
Published: December 2017

AbstractWarfarin is a commonly prescribed and effective oral anticoagulant. Genetic polymorphisms associated with warfarin metabolism and sensitivity have been implicated in the wide inter-individual dose variation that is observed. Several algorithms integrating patients’ clinical characteristics and genetic polymorphism information have been explored to predict warfarin dose. However, most of these algorithms could explain only over half of the variation in a warfarin maintenance dose, suggesting that additional genetic factors may exist and need to be identified. Here, a drug absorption, distribution, metabolism and excretion (ADME) Core Panel Kit-based pharmacogenetic study was performed to screen for warfarin dose-associated SNP sites in Han-Chinese population patients taking warfarin therapy, and the screen was followed by pyrosequencing-based validation. Finally, we confirmed that the common variant rs9923231 in VKORC1 and two novel genes, SLC15A2 (rs1143671 and rs1143672) and SLCO1B3 (rs4149117 and rs7311358), are associated with the warfarin maintenance dose. As has been shown for those carriers with the variant rs9923231 in VKORC1, it was suggested that those subjects with homozygous minor alleles in those four SNPs should take a lower warfarin dose than those carrying the wild type alleles. Together with the established predictor rs9923231 in VKORC1, those four novel variants on SLC15A2 and SLCO1B3 should be considered as useful biomarkers for warfarin dose adjustment in clinical practice in Han-Chinese populations.
Evaluation of promoting effect of a novel Cu-bearing metal stent on endothelialization process from in vitro and in vivo studies
Authors: Jin Shujing , Qi Xun , Zhang Bin , Sun Ziqing , Zhang Bingchun , Yang Hui , Wang Tongmin , Zheng Bo , Wang Xingang , Shi Qiuping , Chen Ming , Ren Ling , Yang Ke , Zhong Hongshan 
Published: December 2017

AbstractDrug eluting stents (DES) have been extensively applied nowadays and reduce the incidence of in-stent restenosis (ISR) greatly as compared with bare metal stents (BMS). However, the development of DES is hindered by the risk of late stent thrombosis (LST) due to delayed re-endothelialization, while endothelialization is an important process related to ISR and LST after implantation. 316L is a traditional stent material without bioactivity and have a high risk of ISR. Cu is recognized for angiogenesis stimulation in these years. Hence a copper bearing 316L stainless steel (316L-Cu) was prepared and evaluated about its effect on endothelialization in this paper. Compared with traditional 316L, it was proved that 316L-Cu increased the proliferation of co-cultured human umbilical vein endothelial cells (HUVECs) at first day. Moreover, HUVECs stretched better on the surface of 316L-Cu. It also improved the expression of angiogenesis related genes and tube formation ability in vitro. 316L-Cu-BMS, DES and 316L-BMS were implanted in swine to evaluate the re-endothelialization ability in vivo. And 316L-Cu-BMS showed the best effect on endothelialization with good biosafety. Consequently, 316L-Cu is a kind of promising BMS material for coronary field.
Comparison between dual-energy X-ray absorptiometry and skinfold thickness in assessing body fat in overweigh/obese adult patients with type-2 diabetes
Authors: Bacchi Elisabetta , Cavedon Valentina , Zancanaro Carlo , Moghetti Paolo , Milanese Chiara 
Published: December 2017

AbstractPercentage of body fat (%BF) is estimated in clinical practice using anthropometric equations, but little is known about their reliability in overweight/obese patients with type-2 diabetes. The aim of this study was to compare, in overweight/obese adults with type-2 diabetes, %BF estimated with several commonly used anthropometric equations and %BF measured with dual-energy X-ray absorptiometry (DXA, Hologic). The %BF was measured with DXA in 40 patients aged 40–68 years with type-2 diabetes (mean HbA1c, 7.3 ± 0.9%). Body density was estimated in the same patients by means of four anthropometric equations and converted to %BF using the Siri and Brozek equations. Paired-sample t-test and the mean signed difference procedure were used to compare anthropometric equation-derived %BF and DXA measurements. The coefficient of determination was computed. Bland-Altman analysis was used to test the agreement between methods. Among the four anthropometric equations, the Durnin-Womersley equation only showed close agreement with DXA in both female and male patients; the other equations significantly underestimated or overestimated %BF. Two new predictive equations were developed using DXA as the reference to predict total body and trunk %BF. Further comparative studies are required to confirm and refine the accuracy of practical, non-invasive methods for monitoring %BF in this population.
Cannabinoid type 2 receptors in dopamine neurons inhibits psychomotor behaviors, alters anxiety, depression and alcohol preference
Authors: Liu Qing-Rong , Canseco-Alba Ana , Zhang Hai-Ying , Tagliaferro Patricia , Chung Monika , Dennis Eugene , Sanabria Branden , Schanz Norman , Escosteguy-Neto Joao Carlos , Ishiguro Hiroki , Lin Zhicheng , Sgro Susan , Leonard Claire M. , Santos-Junior Jair Guilherme , Gardner Eliot L. , Egan Josephine M. , Lee Jeung Woon , Xi Zheng-Xiong , Onaivi Emmanuel S. 
Published: December 2017

AbstractCannabinoid CB2 receptors (CB2Rs) are expressed in mouse brain dopamine (DA) neurons and are involved in several DA-related disorders. However, the cell type-specific mechanisms are unclear since the CB2R gene knockout mice are constitutive gene knockout. Therefore, we generated Cnr2-floxed mice that were crossed with DAT-Cre mice, in which Cre- recombinase expression is under dopamine transporter gene (DAT) promoter control to ablate Cnr2 gene in midbrain DA neurons of DAT-Cnr2 conditional knockout (cKO) mice. Using a novel sensitive RNAscope in situ hybridization, we detected CB2R mRNA expression in VTA DA neurons in wildtype and DAT-Cnr2 cKO heterozygous but not in the homozygous DAT-Cnr2 cKO mice. Here we report that the deletion of CB2Rs in dopamine neurons enhances motor activities, modulates anxiety and depression-like behaviors and reduces the rewarding properties of alcohol. Our data reveals that CB2Rs are involved in the tetrad assay induced by cannabinoids which had been associated with CB1R agonism. GWAS studies indicates that the CNR2 gene is associated with Parkinson’s disease and substance use disorders. These results suggest that CB2Rs in dopaminergic neurons may play important roles in the modulation of psychomotor behaviors, anxiety, depression, and pain sensation and in the rewarding effects of alcohol and cocaine.
Planetary nebulae with UVIT: Far ultra-violet halo around the Bow Tie nebula (NGC 40)
Authors: Kameswara Rao N. , Sutaria F. , Murthy J. , Krishna S. , Mohan R. , Ray A. 
Published: December 2017

Context. NGC 40 is a planetary nebula with diffuse X-ray emission, suggesting an interaction of the high-speed wind from WC8 central star (CS) with the nebula. It shows strong C IV 1550 Å emission that cannot be explained by thermal processes alone. We present here the first map of this nebula in C IV emission using broad band filters on the Ultra-Violet Imaging Telescope (UVIT).
Aim. We aim to map the hot C IV-emitting gas and its correspondence with soft X-ray (0.3–8 keV) emitting regions in order to study the shock interaction between the nebula and the ISM. We also aim to illustrate the potential of UVIT for nebular studies.
Methods. We carry out a morphological study of images of the nebula obtained at an angular resolution of about 1.3″ in four UVIT filter bands that include C IV 1550 Å and [C II] 2326 Å lines as well as UV continuum. We also make comparisons with X-ray, optical, and IR images from the literature.
Results. The [C II] 2326 Å images show the core of the nebula with two lobes on either side of CS similar to [N II]. The C IV emission in the core shows similar morphology and extent to that of diffuse X-ray emission concentrated in nebular condensations. A surprising UVIT discovery is the presence of a large faint far UV (FUV) halo in an FUV filter with λeff of 1608 Å. The UV halo is not present in any other UV filter. The FUV halo is most likely due to UV fluorescence emission from the Lyman bands of H2 molecules. Unlike the optical and IR halo, the FUV halo trails predominantly towards the south-east side of the nebular core, opposite to the CS’s proper motion direction.
Conclusions. Morphological similarity of C IV 1550 Å and X-ray emission in the core suggests that it results mostly from the interaction of strong CS wind with the nebula. The FUV halo in NGC 40 highlights the extensive existence of H2 molecules in the regions even beyond the optical and IR halos. Thus UV studies are important to estimate the amount of H2, which is probably the most dominant molecule and significant for mass-loss studies.
Aufwand bei der Betreuung von COPD-Patienten unter Alltagsbedingungen in pneumologischen Praxen differenziert nach bekannten und neuen Patienten und nach Schweregraden der Erkrankung
Authors: Hellmann A. , Hering T. , Andres J. 
Published: December 2017

ZusammenfassungDer Aufwand einer pneumologischen Praxis ist für Ärzte bei der Kontaktfrequenz und zeitlichen Inanspruchnahme und für das Team durch Schulung und vermehrte diagnostische Leistungen bei Neupatienten höher als bei Altpatienten. Ein ähnlicher Zusammenhang besteht bei den verschiedenen Schwergraden der COPD nicht. Insgesamt ist der Aufwand von Neupatienten annähernd doppelt so groß wie bei den Altpatienten. Das heißt, eine pneumologische Praxis kann in der Zeit, die sie für die Versorgung von ca. 50 Neupatienten aufwendet, ca. 100 Altpatienten mit COPD betreuen. Da der Mehraufwand nicht in der Gebührenordnung abgebildet ist, verstärkt das die Tendenz zu Kontrolluntersuchungen und zur Risikoselektion. Anreize für die Behandlung von Neupatienten könnten dagegen eine wirksame Maßnahme zur Entspannung der Terminnot bei Fachärzten darstellen. Dies sollte durch eine entsprechende Umgestaltung der Gebührenordnung erreicht werden.
A novel lens cleaner to prevent water drop adhesions during colonoscopy and esophagogastroduodenoscopy
Authors: Yoshida Naohisa , Naito Yuji , Yasuda Ritsu , Murakami Takaaki , Ogiso Kiyoshi , Hirose Ryohei , Inada Yutaka , Dohi Osamu , Okayama Tetsuya , Kamada Kazuhiro , Uchiyama Kazuhiko , Ishikawa Takeshi , Handa Osamu , Konishi Hideyuki , Rani Rafiz , Itoh Yoshito 
Published: December 2017

Abstract
Background and study aims Water drop adhesions (WDA) impair endoscopic view during gastrointestinal endoscopy. We developed a novel lens cleaner designed using two types of harmLess surfactants and it is reported to be useful for preventing lens cloudiness during colorectal ESD. In the current study, we examined the ability of it for preventing and removing WDA.
Patients and methods During laboratory experiments, the cleaner (Cleash; Fujifilm Co., Tokyo, Japan and Nagase Medicals Co., Hyogo, Japan) was applied to the endoscopic lens and an air/water device (AWD) (water 200 mL, dimethicone 1 mL, Cleash 1 mL). The endoscope was submerged in water 100 times for 5 cycles. Rates of WDA were calculated for various groups (lens and AWD with or without Cleash) and compared to a normal cleaner (SL cleaner). During clinical research, 30 colonoscopies and 30 esophagogastroduodenoscopies were analyzed. For the Cleash group, the cleaner was applied to both lens and AWD. The numbers of WDA and WDA with non-rapid removal were calculated, compared to those of the SL cleaner group.
Results The mean WDA rate for the Cleash setting (lens: Cleash; AWD: Cleash) was 11.0 %, which was significantly lower than other settings (lens: SL cleaner; AWD: water, 31.0 %; P < 0.001) (lens: Cleash; AWD: water, 19.0 %; P < 0.001). Clinical research of colonoscopies indicated that the numbers of WDA (number/15 sec) and WDA with non-rapid removal were 0.38 and 0.17 for the Cleash group and 0.91 and 0.46 for the SL cleaner groups (P < 0.001, P < 0.001). For esophagogastroduodenoscopies, the results were 0.47 and 0.24 for the Cleash group and 0.54 and 0.42 for the SL cleaner group (P = 0.72, P = 0.018).
Conclusion A clear and beautiful image without WDA is useful not only for routine endoscopy but also, more importantly, for magnifying endoscopy and other endoscopic treatments. The use of Cleash to lens and AWD showed positive results for preventing and removing WDA during laboratory experiments and clinical research involving CS. Additionally, it also showed positive results for the removal of WDA during EGD.
Invitation letters increase participation in colorectal cancer screening – results from an observational study
Authors: Zhan Tianzuo , Hielscher Thomas , Bilge Asmé , Giese Thomas , Schäfer Christoph , Riemann Jürgen , Ebert Matthias , Belle Sebastian 
Published: December 2017

Abstract
Background and Aim Participation rates in the German colorectal cancer screening program are low. Starting in 2013, a large health insurance plan in Bavaria, Germany, is sending an additional invitation letter to insured individuals when they turn 50 or 55 years and become eligible for participation in the program. The letter provides detailed information on colorectal cancer screening. We assessed the impact of the invitation letter on utilization rates.
Methods Insurance claims data of a total of 48 343 individuals who had turned 50 or 55 years between 2012 to 2014 were reviewed for utilization rates of screening colonoscopy and fecal blood tests. Utilization rates 1 year prior (2012) and 2 years after introduction of the invitation letter (2013 and 2014) were compared. Furthermore, providers of colorectal cancer screening were determined.
Results Within 6 months after turning 50 or 55 years, 8.8 – 10.2 % of all insured individuals participated in colorectal cancer screening, with the majority being females. After the introduction of the invitation letter, a moderate increase in participation rates could be observed (increase to 109 % [RR 101.7 – 117.3 %, p = 0.02] in 2014). The uptake rate of screening colonoscopy was significantly higher in recipients of the letter (increase to 138.4 % [RR 110.4 – 173.8 %, p = 0.0043] in 2013 and to 149 % [RR 119.5 – 186.3 %, p = 0.0003] in 2014). Furthermore, a significantly higher proportion of general practitioners and gastroenterologists provided colorectal cancer screening in individuals receiving the invitation letter.
Conclusions Introduction of an invitation letter can improve participation rates for colorectal cancer screening.
Sekundärprävention des ischämischen Schlaganfalls bei Vorhofflimmern oder Karotisstenose
Authors: Häusler Karl , Ringleb Peter 
Published: December 2017

ZusammenfassungDer ischämische Schlaganfall zählt zu den häufigsten Todesursachen in Deutschland und ist die führende Ursache für erworbene Behinderungen. Etwa 10 – 15% aller ischämischen Schlaganfälle werden mutmaßlich durch eine durch Vorhofflimmern bedingte zerebrale Embolie hervorgerufen. In einer durchaus vergleichbaren Häufigkeit sind arteriosklerotische Stenosen der A. carotis als Ursache einer zerebralen Ischämie anzunehmen. Dieser Übersichtsartikel fasst den aktuellen Wissensstand zur (medikamentösen) Sekundärprävention für Schlaganfallpatienten mit bekanntem Vorhofflimmern bzw. für Schlaganfallpatienten mit einer Karotisstenose zusammen und soll den ambulant behandelnden Ärzten eine Handhabe für die Praxis sein.
Kardiomyopathien bei Muskeldystrophien
Authors: Blaszczyk Edyta , Perrot Andreas , Schmacht Luisa , Lim Carolin , Spuler Simone , Schulz-Menger Jeanette 
Published: December 2017

ZusammenfassungDie Muskeldystrophien stellen eine diagnostische und therapeutische Herausforderung in der klinischen Medizin dar. Eine enge Zusammenarbeit zwischen Neurologen und Kardiologen im Sinne einer „Neurokardiologie“ erweitert nicht nur das Verständnis für diese Patientengruppe, sondern stellt eine Chance dar, relevante Herzrhythmusstörungen adäquat zu behandeln und Kardiomyopathieformen frühzeitig zuzuordnen. Wenn auch das Verständnis für die Häufigkeit einer kardialen Beteiligung erst langsam wächst, sind die Muskeldystrophien doch bereits in den entsprechenden Leitlinien von ESC und DGK nicht nur allgemein unter die Kardiomyopathien subsumiert, sondern mit Empfehlungen für eine frühzeitige Device-Therapie gegen Herzrhythmusstörungen verankert. Es erscheint wichtig, dass wir als Kardiologen uns dieser Erkrankungsgruppe mehr zuwenden, da sie erstens bereits sehr junge Patienten betrifft und zweitens durch eine zielgerichtete Intervention deutliche symptomatische Verbesserungen erzielt werden können. Bei den meisten Patienten mit Muskeldystrophie liegt eine Erhöhung der Kreatinkinase und/oder des Troponins vor. Durch die Anwendung der kardialen Magnetresonanztomografie ist es gelungen, myokardiale Schäden wie fokale Fibrosierungen bereits bei erhaltener oder nur leicht eingeschränkter Pumpfunktion zu detektieren. Damit ist zu erwarten, dass in Zukunft zumindest grenzwertige elektrokardiografische und echokardiografische Befunde besser eingeordnet werden können.
Allyl isothiocyanate increases carbohydrate oxidation through enhancing insulin secretion by TRPV1
Authors: Mori Noriyuki , Kurata Manami , Yamazaki Hanae , Matsumura Shigenobu , Hashimoto Takashi , Kanazawa Kazuki , Nadamoto Tomonori , Inoue Kazuo , Fushiki Tohru 
Published: December 2017

Abstract
The transient receptor potential (TRP) V1 is a cation channel belonging to the TRP channel family and it has been reported to be involved in energy metabolism, especially glucose metabolism. While, we have previously shown that intragastric administration of allyl isothiocyanate (AITC) enhanced glucose metabolism via TRPV1, the underlying mechanism has not been elucidated. In this study, we examined the relationship between insulin secretion and the increase in carbohydrate oxidation due to AITC. Intragastric administration of AITC elevated blood insulin levels in mice and AITC directly enhanced insulin secretion from isolated islets. These observations were not reproduced in TRPV1 knockout mice. Furthermore, AITC did not increase carbohydrate oxidation in streptozotocin-treated mice. These results suggest that intragastric administration of AITC could induce insulin secretion from islets via TRPV1 and that enhancement of insulin secretion was related to the increased carbohydrate oxidation due to AITC.