bluuebunny/crossref_metadata_2025_split huggingface dataset:
Augmentation of myocardial If dysregulates calcium homeostasis and causes adverse cardiac remodeling
Authors: Yampolsky Pessah , Koenen Michael , Mosqueira Matias , Geschwill Pascal , Nauck Sebastian , Witzenberger Monika , Seyler Claudia , Fink Thomas , Kruska Mathieu , Bruehl Claus , Schwoerer Alexander P. , Ehmke Heimo , Fink Rainer H. A. , Draguhn Andreas , Thomas Dierk , Katus Hugo A. , Schweizer Patrick A. 
Published: July 2019

AbstractHCN channels underlie the depolarizing funny current (If) that contributes importantly to cardiac pacemaking. If is upregulated in failing and infarcted hearts, but its implication in disease mechanisms remained unresolved. We generated transgenic mice (HCN4tg/wt) to assess functional consequences of HCN4 overexpression-mediated If increase in cardiomyocytes to levels observed in human heart failure. HCN4tg/wt animals exhibit a dilated cardiomyopathy phenotype with increased cellular arrhythmogenicity but unchanged heart rate and conduction parameters. If augmentation induces a diastolic Na+ influx shifting the Na+/Ca2+ exchanger equilibrium towards ‘reverse mode’ leading to increased [Ca2+]i. Changed Ca2+ homeostasis results in significantly higher systolic [Ca2+]i transients and stimulates apoptosis. Pharmacological inhibition of If prevents the rise of [Ca2+]i and protects from ventricular remodeling. Here we report that augmented myocardial If alters intracellular Ca2+ homeostasis leading to structural cardiac changes and increased arrhythmogenicity. Inhibition of myocardial Ifper se may constitute a therapeutic mechanism to prevent cardiomyopathy.
Liver-specific androgen receptor knockout attenuates early liver tumor development in zebrafish
Authors: Li Hankun , Li Yan , Lu Jeng-Wei , Huo Xiaojing , Gong Zhiyuan 
Published: July 2019

AbstractHepatocellular carcinoma (HCC) is one of the most severe cancer types and many genetic and environmental factors contribute to the development of HCC. Androgen receptor (AR) signaling is increasingly recognized as one of the important factors associated with HCC. Previously, we have developed an inducible HCC model in kras transgenic zebrafish. In the present study, to investigate the role of AR in liver tumor development, we specifically knocked out ar gene in the liver of zebrafish via the CRISPR/Cas9 system and the knockout zebrafish was named L-ARKO for liver-specific ar knockout. We observed that liver-specific knockout of ar attenuated liver tumor development in kras transgenic zebrafish at the early stage (one week of tumor induction). However, at the late stage (two weeks of tumor induction), essentially all kras transgenic fish continue to develop HCC irrespective of the absence or presence of ar gene, indicating an overwhelming role of the driver oncogene kras over ar knockout. Consistently, cell proliferation was reduced at the early stage, but not the late stage, of liver tumor induction in the kras/L-ARKO fish, indicating that the attenuant effect of ar knockout was at least in part via cell proliferation. Furthermore, androgen treatment showed acceleration of HCC progression in kras fish but not in kras/L-ARKO fish, further indicating the abolishment of ar signalling. Therefore, we have established a tissue-specific ar knockout zebrafish and it should be a valuable tool to investigate AR signalling in the liver in future.
Long-lasting effects of historical land use on the current distribution of mammals revealed by ecological and archaeological patterns
Authors: Fukasawa Keita , Akasaka Takumi 
Published: July 2019

AbstractPast land-use activity has massively altered the environment and vegetation over centuries, resulting in range contractions and expansions of species. When habitat recovery and species recolonization require a long time, the fingerprint of past land use can remain on the current distribution of species. To evaluate millennial-scale effects of land use in Japan, we explained the current ranges of 29 mammalian genera based on three types of archaeological land-use patterns (settlement, ironwork and kiln) considering potential confounding factors. The results indicate that archaeological human activity associated with ironwork and pottery production had severe negative effects on many genera of small and medium-sized mammals. Despite positive effects on some genera, the magnitudes were less than those of the negative effects. The relative importance of archaeological factors on small mammals was greater than those for medium- to-large mammals. The persistent imprint of past land-use patterns was non-negligible, explaining current mammalian diversity. Spatial ecological and archaeological information can provide meaningful insights into long-term socio-ecological processes, which are crucial for the development of sustainable societies in the Anthropocene.
Loss of Ku’s DNA end binding activity affects telomere length via destabilizing telomere-bound Est1 rather than altering TLC1 homeostasis
Authors: Lemon Laramie D. , Morris Danna K. , Bertuch Alison A. 
Published: July 2019

AbstractSaccharomyces cerevisiae telomerase, which maintains telomere length, is comprised of an RNA component, TLC1, the reverse transcriptase, Est2, and regulatory subunits, including Est1. The Yku70/Yku80 (Ku) heterodimer, a DNA end binding (DEB) protein, also contributes to telomere length maintenance. Ku binds TLC1 and telomere ends in a mutually exclusive fashion, and is required to maintain levels and nuclear localization of TLC1. Ku also interacts with Sir4, which localizes to telomeres. Here we sought to determine the role of Ku’s DEB activity in telomere length maintenance by utilizing yku70-R456E mutant strains, in which Ku has reduced DEB and telomere association but proficiency in TLC1 and Sir4 binding, and TLC1 nuclear retention. Telomere lengths in a yku70-R456E strain were nearly as short as those in yku∆ strains and shorter than in strains lacking either Sir4, Ku:Sir4 interaction, or Ku:TLC1 interaction. TLC1 levels were decreased in the yku70-R456E mutant, yet overexpression of TLC1 failed to restore telomere length. Reduced DEB activity did not impact Est1’s ability to associate with telomerase but did result in decreased association of Est1 with the telomere. These findings suggest Ku’s DEB activity maintains telomere length homeostasis by preserving Est1’s interaction at the telomere rather than altering TLC1 levels.
Mucin-1 is required for Coxsackie Virus B3-induced inflammation in pancreatitis
Authors: Liu Xiang , Clemens Dahn L. , Grunkemeyer James A. , Price Jeffrey D. , O’Connell Kelly , Chapman Nora M. , Storz Peter , Wen Haitao , Cox Jesse L. , Reid Whitney L. , Hollingsworth Michael A. , Thayer Sarah 
Published: July 2019

AbstractThe Muc-1 oncoprotein is a tumor-associated mucin often overexpressed in pancreatic cancer. We report that knockout of Muc-1 reduced the degree of pancreatic inflammation that resulted from infection with Coxsackievirus B3 (CVB3) in a mouse model. CVB3-infected Muc-1-deficient (Muc-1KO) mice had significantly reduced infiltration of macrophages into the murine pancreas. We found that Muc-1 signaling through NF-κB increased expression of ICAM-1, a pro-inflammatory mediator that recruits macrophages. Further investigation revealed that bone marrow derived macrophages (BMDM) from the Muc-1KOmice exhibited defective migration properties, in part due to low expression of the C-C motif chemokine receptor (CCR2) and the integrin Very Late Antigen 4 (VLA-4). The results presented here provide novel insight into the role of Muc-1 in regulating the inflammatory response and the cellular microenvironment in pancreatitis.
The Potential of Wearable Limb Ballistocardiogram in Blood Pressure Monitoring via Pulse Transit Time
Authors: Yousefian Peyman , Shin Sungtae , Mousavi Azin , Kim Chang-Sei , Mukkamala Ramakrishna , Jang Dae-Geun , Ko Byung-Hoon , Lee Jongwook , Kwon Ui Kun , Kim Youn Ho , Hahn Jin-Oh 
Published: July 2019

AbstractThe goal of this study was to investigate the potential of wearable limb ballistocardiography (BCG) to enable cuff-less blood pressure (BP) monitoring, by investigating the association between wearable limb BCG-based pulse transit time (PTT) and BP. A wearable BCG-based PTT was calculated using the BCG and photoplethysmogram (PPG) signals acquired by a wristband as proximal and distal timing reference (called the wrist PTT). Its efficacy as surrogate of BP was examined in comparison with PTT calculated using the whole-body BCG acquired by a customized weighing scale (scale PTT) as well as pulse arrival time (PAT) using the experimental data collected from 22 young healthy participants under multiple BP-perturbing interventions. The wrist PTT exhibited close association with both diastolic (group average r = 0.79; mean absolute error (MAE) = 5.1 mmHg) and systolic (group average r = 0.81; MAE = 7.6 mmHg) BP. The efficacy of the wrist PTT was superior to scale PTT and PAT for both diastolic and systolic BP. The association was consistent and robust against diverse BP-perturbing interventions. The wrist PTT showed superior association with BP when calculated with green PPG rather than infrared PPG. In sum, wearable limb BCG has the potential to realize convenient cuff-less BP monitoring via PTT.
Image quality evaluation in a modern PET system: impact of new reconstructions methods and a radiomics approach
Authors: Reynés-Llompart Gabriel , Sabaté-Llobera Aida , Llinares-Tello Elena , Martí-Climent Josep M. , Gámez-Cenzano Cristina 
Published: July 2019

AbstractThe present work investigates the influence of different biological and physical parameters on image quality (IQ) perception of the abdominal area in a modern PET scanner, using new reconstruction algorithms and testing the utility of a radiomics approach. Scans of 112 patients were retrospectively included. Images were reconstructed using both OSEM + PSF and BSRM methods, and IQ of the abdominal region was subjectively evaluated. First, 22 IQ related parameters were obtained (including count rate and biological or mixed parameters) and compared to the subjective IQ scores by means of correlations and logistic regression. Second, an additional set of radiomics features was extracted, and a model was constructed by means of an elastic-net regression. For the OSEM + PSF and especially for the BSRM reconstructions, IQ parameters presented only at best moderated correlations with the subjective IQ. None of the studied parameters presented a good predictive power for IQ, while a simple radiomics model increased the performance of the IQ prediction. These results suggest the necessity of changing the standard parameters to evaluate IQ, particularly when a BSRM algorithm is involved. Furthermore, it seems that a simple radiomics model can outperform the use of any single parameter to assess IQ.
Wood properties of Carapa guianensis from floodplain and upland forests in Eastern Amazonia, Brazil
Authors: Firmino Anderson Vasconcelos , Vidaurre Graziela Baptista , Oliveira José Tarcísio da Silva , Guedes Marcelino , Almeida Maria Naruna Felix de , Silva João Gabriel Missia da , Latorraca João Vicente de Figueiredo , Zanuncio José Cola 
Published: July 2019

AbstractThe variable environmental conditions of the Amazon forest can affect the wood properties of the tree species distributed across its diverse phytophysiognomies.Carapa guianensis(Andiroba) occurs in upland and floodplain forests, and the wood and oil of its seeds have multiple uses. The aim of this study was to evaluate the wood properties ofC. guianensistrees in upland and estuarine floodplain forests of the Amazon River. Eight trees were selected, with four being from the upland and four from the floodplain forests. The fiber length, fiber wall thickness, vessel diameter and frequency, microfibril angle, specific gravity and wood shrinkage were evaluated. The juvenile and mature wood zones were determined according to these variables. The fiber length, fiber wall thickness and specific gravity increased, and microfibril angle decreased, in the pith to bark direction. Only the fiber length variable was efficient for delimiting juvenile, transition and mature wood. The fiber length, wall thickness and specific gravity of wood were higher in upland forest trees. However, the environment did not alter the beginning of the formation and proportion ofC. guianensismature wood. This information is important for the log fit in cutting diagrams, aiming toward improving the production, classification and processing of pieces with specific quality indexes in order to direct them to appropriate wood uses.
A prospective study of knee pain, low back pain, and risk of dementia: the JAGES project
Authors: Yamada Keiko , Kubota Yasuhiko , Tabuchi Takahiro , Shirai Kokoro , Iso Hiroyasu , Kondo Naoki , Kondo Katsunori 
Published: July 2019

AbstractThe aim of this prospective study was to investigate the associations of knee and low back pain with dementia development. Participants were 14,627 older people with no history of stroke, cancer, injuries, depression, Parkinson’s disease, or dementia who did not require support for daily living completed self-administered questionnaires with 3-years follow-up. A Cox regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia development. Stratified analyses by age and regular walking were conducted. Dementia risk was higher in participants aged 65–79 years with knee pain and without low back pain than in those without knee and low back pain [HR: 1.73 (95% CI: 1.11–2.68)]. Dementia risk was lower in participants ≥80 years with low back pain but no knee pain than in those without low back or knee pain [HR: 0.50 (95% CI: 0.31–0.80)]. Participants with knee pain who did not walk regularly had the highest dementia risk [HR: 1.71 (95% CI: 1.26–2.33)]. Knee pain may increase dementia risk among individuals aged 65–79 years, and may further increase risk in non-regular walkers. Low back pain may be a marker of maintained cognitive function despite age for individuals ≥80 years.
Modified tailoring the electronic phase and emergence of midstates in impurity-imbrued armchair graphene nanoribbons
Authors: Hien Nguyen D. , Mirabbaszadeh Kavoos , Davoudiniya Masoumeh , Hoi Bui D. , Phuong Le T. T. , Yarmohammadi Mohsen 
Published: July 2019

AbstractWe theoretically address the electronic structure of mono- and simple bi-layer armchair graphene nanoribbons (AGNRs) when they are infected by extrinsic charged dilute impurity. This is done with the aid of the modified tight-binding method considering the edge effects and the Green’s function approach. Also, the interplay of host and guest electrons are studied within the full self-consistent Born approximation. Given that the main basic electronic features can be captured from the electronic density of states (DOS), we focus on the perturbed DOS of lattices corresponding to the different widths. The modified model says that there is no metallic phase due to the edge states. We found that the impurity effects lead to the emergence of midgap states in DOS of both systems so that a semiconductor-to-semimetal phase transition occurs at strong enough impurity concentrations and/or impurity scattering potentials. The intensity of semiconductor-to-semimetal phase transition in monolayer (bilayer) ultra-narrow (realistic) ribbons is sharper than bilayers (monolayers). In both lattices, electron-hole symmetry breaks down as a result of induced-impurity states. The findings of this research would provide a base for future experimental studies and improve the applications of AGNRs in logic semiconductor devices in industry.
HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules
Authors: Ackermann Christin , Smits Maike , Woost Robin , Eberhard Johanna M. , Peine Sven , Kummer Silke , Marget Matthias , Kuntzen Thomas , Kwok William W. , Lohse Ansgar W. , Jacobs Thomas , Boettler Tobias , Schulze zur Wiesch Julian 
Published: July 2019

AbstractThe combined regulation of a network of inhibitory and activating T cell receptors may be a critical step in the development of chronic HCV infection. Ex vivo HCV MHC class I + II tetramer staining and bead-enrichment was performed with baseline and longitudinal PBMC samples of a cohort of patients with acute, chronic and spontaneously resolved HCV infection to assess the expression pattern of the co-inhibitory molecule TIGIT together with PD-1, BTLA, Tim-3, as well as OX40 and CD226 (DNAM-1) of HCV-specific CD4+ T cells, and in a subset of patients of HCV-specific CD8+ T cells. As the main result, we found a higher expression level of TIGIT+ PD-1+ on HCV-specific CD4+ T cells during acute and chronic HCV infection compared to patients with spontaneously resolved HCV infection (p < 0,0001). Conversely, expression of the complementary co-stimulatory receptor of TIGIT, CD226 (DNAM-1) was significantly decreased on HCV-specific CD4+ T cells during chronic infection. The predominant phenotype of HCV-specific CD4+ T cells during acute and chronic infection was TIGIT+, PD-1+, BTLA+, Tim-3−. This comprehensive phenotypic study confirms TIGIT together with PD-1 as a discriminatory marker of dysfunctional HCV-specific CD4+ T cells.
A novel antibacterial resin-based root canal sealer modified by Dimethylaminododecyl Methacrylate
Authors: Liu Dan , Peng Xian , Wang Suping , Han Qi , Li Bolei , Zhou Xinxuan , Ren Biao , Xu Hockin H. K. , Weir Michael D. , Li Mingyun , Zhou Xuedong , Cheng Lei 
Published: July 2019

AbstractPersistent apical periodontitis, mainly caused by microorganisms infections, represents a critical challenge for endodontists. Dimethylaminododecyl methacrylate (DMADDM) is a well-studied and potent antibacterial agent used in various studies described in the literature. The aim of this study is to develop a novel antibacterial root canal sealer by incorporating DMADDM into EndoREZ and investigate the properties of the resulting material. Different mass fractions (0, 1.25%, 2.5%, and 5%) of DMADDM were incorporated into EndoREZ and the cytotoxicity, apical sealing ability and solubility of the resulting material were evaluated. Furthermore, a direct contact test, determination of colony-forming units, a crystal violet assay, scanning electronic microscopy and live/dead bacteria staining were performed to evaluate the antibacterial effect of the sealer to multispecies bacteria (Enterococcus faecalis, Streptococcus gordonii, Actinomyces naeslundii, and Lactobacillus acidophilus), in planktonic cells or biofilms. Fluorescence in situ hybridization and quantitative real-time polymerase chain reaction were carried out to assess the composition of the multispecies biofilms. No difference on the cytotoxicity, apical sealing ability and solubility between sealers containing DMADDM (1.25%, 2.5%) and EndoREZ (0%) could be determined. However, when the mass fraction of DMADDM increased to 5%, significantly different properties were found compared to the 0% (p < 0.05) group. Moreover, incorporating DMADDM into the sealer could greatly improve the antibacterial properties of EndoREZ. In addition, the composition ratio of E. faecalis could be decreased in multispecies microecology in sealers containing DMADDM. Therefore, a EndoREZ sealer material containing DMADDM could be considered useful in clinical applications for preventing and treating persistent apical periodontitis.
Genipin and EDC crosslinking of extracellular matrix hydrogel derived from human umbilical cord for neural tissue repair
Authors: Výborný Karel , Vallová Jana , Kočí Zuzana , Kekulová Kristýna , Jiráková Klára , Jendelová Pavla , Hodan Jiří , Kubinová Šárka 
Published: July 2019

AbstractExtracellular matrix (ECM) hydrogels, produced by tissue decellularization are natural injectable materials suitable for neural tissue repair. However, the rapid biodegradation of these materials may disrupt neural tissue reconstruction in vivo. The aim of this study was to improve the stability of the previously described ECM hydrogel derived from human umbilical cord using genipin and N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC), crosslinking at concentration of 0.5–10 mM. The hydrogels, crosslinked by genipin (ECM/G) or EDC (ECM/D), were evaluated in vitro in terms of their mechanical properties, degradation stability and biocompatibility. ECM/G, unlike ECM/D, crosslinked hydrogels revealed improved rheological properties when compared to uncrosslinked ECM. Both ECM/G and ECM/D slowed down the gelation time and increased the resistance against in vitro enzymatic degradation, while genipin crosslinking was more effective than EDC. Crosslinkers concentration of 1 mM enhanced the in vitro bio-stability of both ECM/G and ECM/D without affecting mesenchymal stem cell proliferation, axonal sprouting or neural stem cell growth and differentiation. Moreover, when injected into cortical photochemical lesion, genipin allowed in situ gelation and improved the retention of ECM for up to 2 weeks without any adverse tissue response or enhanced inflammatory reaction. In summary, we demonstrated that genipin, rather than EDC, improved the bio-stability of injectable ECM hydrogel in biocompatible concentration, and that ECM/G has potential as a scaffold for neural tissue application.
Quantitative Mass Spectrometry Imaging Reveals Mutation Status-independent Lack of Imatinib in Liver Metastases of Gastrointestinal Stromal Tumors
Authors: Abu Sammour Denis , Marsching Christian , Geisel Alexander , Erich Katrin , Schulz Sandra , Ramallo Guevara Carina , Rabe Jan-Hinrich , Marx Alexander , Findeisen Peter , Hohenberger Peter , Hopf Carsten 
Published: July 2019

AbstractMass spectrometry imaging (MSI) is an enabling technology for label-free drug disposition studies at high spatial resolution in life science- and pharmaceutical research. We present the first extensive clinical matrix-assisted laser desorption/ionization (MALDI) quantitative mass spectrometry imaging (qMSI) study of drug uptake and distribution in clinical specimen, analyzing 56 specimens of tumor and corresponding non-tumor tissues from 27 imatinib-treated patients with the biopsy-proven rare disease gastrointestinal stromal tumors (GIST). For validation, we compared MALDI-TOF-qMSI with conventional UPLC-ESI-QTOF-MS-based quantification from tissue extracts and with ultra-high resolution MALDI-FTICR-qMSI. We introduced a novel generalized nonlinear calibration model of drug quantities based on computational evaluation of drug-containing areas that enabled better data fitting and assessment of the inherent method nonlinearities. Imatinib tissue spatial maps revealed striking inefficiency in drug penetration into GIST liver metastases even though the corresponding healthy liver tissues in the vicinity showed abundant imatinib levels beyond the limit of quantification (LOQ), thus providing evidence for secondary drug resistance independent of mutation status. Taken together, these findings underscore the important application of MALDI-qMSI in studying the spatial distribution of molecularly targeted therapeutics in oncology, namely to serve as orthogonal post-surgical approach to evaluate the contribution of anticancer drug disposition to resistance against treatment.