bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine-resistant breast cancer
Authors: Achinger-Kawecka Joanna , Valdes-Mora Fatima , Luu Phuc-Loi , Giles Katherine A. , Caldon C. Elizabeth , Qu Wenjia , Nair Shalima , Soto Sebastian , Locke Warwick J. , Yeo-Teh Nicole S. , Gould Cathryn M. , Du Qian , Smith Grady C. , Ramos Irene R. , Fernandez Kristine F. , Hoon Dave S. , Gee Julia M. W. , Stirzaker Clare , Clark Susan J. 
Published: January 2020

AbstractEndocrine therapy resistance frequently develops in estrogen receptor positive (ER+) breast cancer, but the underlying molecular mechanisms are largely unknown. Here, we show that 3-dimensional (3D) chromatin interactions both within and between topologically associating domains (TADs) frequently change in ER+ endocrine-resistant breast cancer cells and that the differential interactions are enriched for resistance-associated genetic variants at CTCF-bound anchors. Ectopic chromatin interactions are preferentially enriched at active enhancers and promoters and ER binding sites, and are associated with altered expression of ER-regulated genes, consistent with dynamic remodelling of ER pathways accompanying the development of endocrine resistance. We observe that loss of 3D chromatin interactions often occurs coincidently with hypermethylation and loss of ER binding. Alterations in active A and inactive B chromosomal compartments are also associated with decreased ER binding and atypical interactions and gene expression. Together, our results suggest that 3D epigenome remodelling is a key mechanism underlying endocrine resistance in ER+ breast cancer.
Tunable light and drug induced depletion of target proteins
Authors: Deng Wen , Bates Jack A. , Wei Hai , Bartoschek Michael D. , Conradt Barbara , Leonhardt Heinrich 
Published: January 2020

AbstractBiological processes in development and disease are controlled by the abundance, localization and modification of cellular proteins. We have developed versatile tools based on recombinant E3 ubiquitin ligases that are controlled by light or drug induced heterodimerization for nanobody or DARPin targeted depletion of endogenous proteins in cells and organisms. We use this rapid, tunable and reversible protein depletion for functional studies of essential proteins like PCNA in DNA repair and to investigate the role of CED-3 in apoptosis during Caenorhabditis elegans development. These independent tools can be combined for spatial and temporal depletion of different sets of proteins, can help to distinguish immediate cellular responses from long-term adaptation effects and can facilitate the exploration of complex networks.
Surface-reaction induced structural oscillations in the subsurface
Authors: Sun Xianhu , Zhu Wenhui , Wu Dongxiang , Li Chaoran , Wang Jianyu , Zhu Yaguang , Chen Xiaobo , Boscoboinik Jorge Anibal , Sharma Renu , Zhou Guangwen 
Published: January 2020

AbstractSurface and subsurface are commonly considered as separate entities because of the difference in the bonding environment and are often investigated separately due to the experimental challenges in differentiating the surface and subsurface effects. Using in-situ atomic-scale transmission electron microscopy to resolve the surface and subsurface at the same time, we show that the hydrogen–CuO surface reaction results in structural oscillations in deeper atomic layers via the cycles of ordering and disordering of oxygen vacancies in the subsurface. Together with atomistic calculations, we show that the structural oscillations in the subsurface are induced by the hydrogen oxidation-induced cyclic loss of oxygen from the oxide surface. These results demonstrate the propagation of the surface reaction dynamics into the deeper layers in inducing nonstoichiometry in the subsurface and have significant implications in modulating various chemical processes involving surface–subsurface mass transport such as heterogeneous catalysis, oxidation, corrosion and carburization.
Towards full-colour tunability of inorganic electrochromic devices using ultracompact fabry-perot nanocavities
Authors: Wang Zhen , Wang Xiaoyu , Cong Shan , Chen Jian , Sun Hongzhao , Chen Zhigang , Song Ge , Geng Fengxia , Chen Qin , Zhao Zhigang 
Published: January 2020

AbstractIntercalation-based inorganic materials that change their colours upon ion insertion/extraction lay an important foundation for existing electrochromic technology. However, using only such inorganic electrochromic materials, it is very difficult to achieve the utmost goal of full-colour tunability for future electrochromic technology mainly due to the absence of structural flexibility. Herein, we demonstrate an ultracompact asymmetric Fabry-Perot (F-P) nanocavity-type electrochromic device formed by using partially reflective metal tungsten as the current collector and reflector layer simultaneously; this approach enables fairly close matching of the reflections at both interfaces of the WO3 thin layer in device form, inducing a strong interference. Such an interference-enhanced device that is optically manipulated at the nanoscale displays various structural colours before coloration and, further, can change to other colours including blue, red, and yellow by changing the optical indexes (n, k) of the tungsten oxide layer through ion insertion.
A spontaneous mitonuclear epistasis converging on Rieske Fe-S protein exacerbates complex III deficiency in mice
Authors: Purhonen Janne , Grigorjev Vladislav , Ekiert Robert , Aho Noora , Rajendran Jayasimman , Pietras Rafał , Truvé Katarina , Wikström Mårten , Sharma Vivek , Osyczka Artur , Fellman Vineta , Kallijärvi Jukka 
Published: January 2020

AbstractWe previously observed an unexpected fivefold (35 vs. 200 days) difference in the survival of respiratory chain complex III (CIII) deficient Bcs1lp.S78G mice between two congenic backgrounds. Here, we identify a spontaneous homoplasmic mtDNA variant (m.G14904A, mt-Cybp.D254N), affecting the CIII subunit cytochrome b (MT-CYB), in the background with short survival. We utilize maternal inheritance of mtDNA to confirm this as the causative variant and show that it further decreases the low CIII activity in Bcs1lp.S78G tissues to below survival threshold by 35 days of age. Molecular dynamics simulations predict D254N to restrict the flexibility of MT-CYB ef loop, potentially affecting RISP dynamics. In Rhodobacter cytochrome bc1 complex the equivalent substitution causes a kinetics defect with longer occupancy of RISP head domain towards the quinol oxidation site. These findings represent a unique case of spontaneous mitonuclear epistasis and highlight the role of mtDNA variation as modifier of mitochondrial disease phenotypes.
Boron arsenide heterostructures: lattice-matched heterointerfaces and strain effects on band alignments and mobility
Authors: Bushick Kyle , Chae Sieun , Deng Zihao , Heron John T. , Kioupakis Emmanouil 
Published: January 2020

AbstractBAs is a III–V semiconductor with ultra-high thermal conductivity, but many of its electronic properties are unknown. This work applies predictive atomistic calculations to investigate the properties of BAs heterostructures, such as strain effects on band alignments and carrier mobility, considering BAs as both a thin film and a substrate for lattice-matched materials. The results show that isotropic biaxial in-plane strain decreases the band gap independent of sign or direction. In addition, 1% biaxial tensile strain increases the in-plane electron and hole mobilities at 300 K by >60% compared to the unstrained values due to a reduction of the electron effective mass and of hole interband scattering. Moreover, BAs is shown to be nearly lattice-matched with InGaN and ZnSnN2, two important optoelectronic semiconductors with tunable band gaps by alloying and cation disorder, respectively. The results predict type-II band alignments and determine the absolute band offsets of these two materials with BAs. The combination of the ultra-high thermal conductivity and intrinsic p-type character of BAs, with its high electron and hole mobilities that can be further increased by tensile strain, as well as the lattice-match and the type-II band alignment with intrinsically n-type InGaN and ZnSnN2 demonstrate the potential of BAs heterostructures for electronic and optoelectronic devices.
Proneural and mesenchymal glioma stem cells display major differences in splicing and lncRNA profiles
Authors: Guardia Gabriela D. A. , Correa Bruna R. , Araujo Patricia Rosa , Qiao Mei , Burns Suzanne , Penalva Luiz O. F. , Galante Pedro A. F. 
Published: January 2020

AbstractTherapy resistance and recurrence in high-grade gliomas are driven by their populations of glioma stem cells (GSCs). Thus, detailed molecular characterization of GSCs is needed to develop more effective therapies. We conducted a study to identify differences in the splicing profile and expression of long non-coding RNAs in proneural and mesenchymal GSC cell lines. Genes related to cell cycle, DNA repair, cilium assembly, and splicing showed the most differences between GSC subgroups. We also identified genes distinctly associated with survival among patients of mesenchymal or proneural subgroups. We determined that multiple long non-coding RNAs with increased expression in mesenchymal GSCs are associated with poor survival of glioblastoma patients. In summary, our study established critical differences between proneural and mesenchymal GSCs in splicing profiles and expression of long non-coding RNA. These splicing isoforms and lncRNA signatures may contribute to the uniqueness of GSC subgroups, thus contributing to cancer phenotypes and explaining differences in therapeutic responses.
Combined proteomics/miRNomics of dendritic cell immunotherapy-treated glioblastoma patients as a screening for survival-associated factors
Authors: Erhart Friedrich , Hackl Matthias , Hahne Hannes , Buchroithner Johanna , Meng Chen , Klingenbrunner Simone , Reitermaier René , Fischhuber Katrin , Skalicky Susanna , Berger Walter , Spiegl-Kreinecker Sabine , Lötsch Daniela , Ricken Gerda , Kuster Bernhard , Wöhrer Adelheid , Widhalm Georg , Hainfellner Johannes , Felzmann Thomas , Dohnal Alexander M. , Marosi Christine , Visus Carmen 
Published: January 2020

AbstractGlioblastoma is the most prevalent and aggressive brain cancer. With a median overall survival of ~15–20 months under standard therapy, novel treatment approaches are desperately needed. A recent phase II clinical trial with a personalized immunotherapy based on tumor lysate-charged dendritic cell (DC) vaccination, however, failed to prolong survival. Here, we investigated tumor tissue from trial patients to explore glioblastoma survival-related factors. We followed an innovative approach of combining mass spectrometry-based quantitative proteomics (n = 36) with microRNA sequencing plus RT-qPCR (n = 38). Protein quantification identified, e.g., huntingtin interacting protein 1 (HIP1), retinol-binding protein 1 (RBP1), ferritin heavy chain (FTH1) and focal adhesion kinase 2 (FAK2) as factor candidates correlated with a dismal prognosis. MicroRNA analysis identified miR-216b, miR-216a, miR-708 and let-7i as molecules potentially associated with favorable tissue characteristics as they were enriched in patients with a comparably longer survival. To illustrate the utility of integrated miRNomics and proteomics findings, focal adhesion was studied further as one example for a pathway of potential general interest.Taken together, we here mapped possible drivers of glioblastoma outcome under immunotherapy in one of the largest DC vaccination tissue analysis cohorts so far—demonstrating usefulness and feasibility of combined proteomics/miRNomics approaches. Future research should investigate agents that sensitize glioblastoma to (immuno)therapy—potentially building on insights generated here.
High-performance ceramic/epoxy composite adhesives enabled by rational ceramic bandgaps
Authors: Hu J. B. 
Published: January 2020

AbstractHigh over-all properties, including low dielectric loss, high breakdown strength, high mechanical shock strength, high thermal conductivity and high weight stability, are very difficult to simultaneously achieve in electrical-insulation applicable cured potting-adhesive materials. To deal with this challenge, in this work, we have designed and fabricated a series of epoxy based composite potting-adhesives filled with low-cost and high-performance inorganic micro-particles including alpha-silica, alpha-alumina and alpha-SiC. Combination employment of high-molecular-weight and low-molecular-weight epoxy resins as matrices has been made. Heat-induced curing or crosslink of resin matrices has been carried out. Large band gap of silica filler has endowed the cured composite with high breakdown strength and ageing breakdown strength, and meanwhile relatively high deformation trait of silica has led to high shock strength of cured composite. Silica filler has been found to be superior to other two fillers, namely, optimal over-all properties such as dielectric, breakdown, mechanical and thermal features have been obtained in silica filled cured composite. High breakdown strength of ~48 MV m−1 and shock strength of ~9950 J m−2 have been achieved in silica loaded composite. This work might open up the way for large-scale fabrication of promising epoxy-based hybrid potting-adhesives.
Chronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery
Authors: Al-Waeli H. , Nicolau B. , Stone L. , Abu Nada L. , Gao Q. , Abdallah MN. , Abdulkader E. , Suzuki M. , Mansour A. , Al Subaie A. , Tamimi F. 
Published: January 2020

AbstractPostoperative pain relief is crucial for full recovery. With the ongoing opioid epidemic and the insufficient effect of acetaminophen on severe pain; non-steroidal anti-inflammatory drugs (NSAIDs) are heavily used to alleviate this pain. However, NSAIDs are known to inhibit postoperative healing of connective tissues by inhibiting prostaglandin signaling. Pain intensity, inflammatory mediators associated with wound healing and the pharmacological action of NSAIDs vary throughout the day due to the circadian rhythm regulated by the clock genes. According to this rhythm, most of wound healing mediators and connective tissue formation occurs during the resting phase, while pain, inflammation and tissue resorption occur during the active period of the day. Here we show, in a murine tibia fracture surgical model, that NSAIDs are most effective in managing postoperative pain, healing and recovery when drug administration is limited to the active phase of the circadian rhythm. Limiting NSAID treatment to the active phase of the circadian rhythm resulted in overexpression of circadian clock genes, such as Period 2 (Per2) at the healing callus, and increased serum levels of anti-inflammatory cytokines interleukin-13 (IL-13), interleukin-4 (IL-4) and vascular endothelial growth factor. By contrast, NSAID administration during the resting phase resulted in severe bone healing impairment.
Mesenchymal stem cells used as carrier cells of oncolytic adenovirus results in enhanced oncolytic virotherapy
Authors: Mahasa Khaphetsi Joseph , de Pillis Lisette , Ouifki Rachid , Eladdadi Amina , Maini Philip , Yoon A-Rum , Yun Chae-Ok 
Published: January 2020

AbstractMesenchymal stem cells (MSCs) loaded with oncolytic viruses are presently being investigated as a new modality of advanced/metastatic tumors treatment and enhancement of virotherapy. MSCs can, however, either promote or suppress tumor growth. To address the critical question of how MSCs loaded with oncolytic viruses affect virotherapy outcomes and tumor growth patterns in a tumor microenvironment, we developed and analyzed an integrated mathematical-experimental model. We used the model to describe both the growth dynamics in our experiments of firefly luciferase-expressing Hep3B tumor xenografts and the effects of the immune response during the MSCs-based virotherapy. We further employed it to explore the conceptual clinical feasibility, particularly, in evaluating the relative significance of potential immune promotive/suppressive mechanisms induced by MSCs loaded with oncolytic viruses. We were able to delineate conditions which may significantly contribute to the success or failure of MSC-based virotherapy as well as generate new hypotheses. In fact, one of the most impactful outcomes shown by this investigation, not inferred from the experiments alone, was the initially counter-intuitive fact that using tumor-promoting MSCs as carriers is not only helpful but necessary in achieving tumor control. Considering the fact that it is still currently a controversial debate whether MSCs exert a pro- or anti-tumor action, mathematical models such as this one help to quantitatively predict the consequences of using MSCs for delivering virotherapeutic agents in vivo. Taken together, our results show that MSC-mediated systemic delivery of oncolytic viruses is a promising strategy for achieving synergistic anti-tumor efficacy with improved safety profiles.
Measurement of diallyl disulfide and allyl methyl sulfide emanating from human skin surface and influence of ingestion of grilled garlic
Authors: Sato Shodai , Sekine Yoshika , Kakumu Yuya , Hiramoto Tadahiro 
Published: January 2020

AbstractDiallyl disulfide (DADS) and allyl methyl sulfide (AMS) have been known as a metabolic product of sulfur-containing foods, typically garlic. The odour of such organosulfur compounds following garlic ingestion is often considered as an unpleasant element. Although previous studies have identified the DADS and AMS associated with garlic breath, no study has been reported on the determination of both compounds emanating from human skin surface. This study aimed to demonstrate the effect of garlic ingestion on the dermal emissions of DADS and AMS using a passive flux sampler coupled with gas chromatography-mass spectrometry. Firstly, baseline levels were investigated for 30 healthy volunteers in their daily life. The results of 1 h-sampling at the forearm showed the emission fluxes of both compounds followed the lognormal distribution with a geometric mean of 0.18 ng cm−2 h−1 for DADS and 0.22 ng cm−2 h−1 for AMS. Subsequently, the garlic ingestion tests were conducted for selected volunteers. The emission flux of DADS increased just after grilled garlic ingestion and decreased gradually thereafter. In contrast, the dermal emission flux of AMS reached a peak at 30 min after ingestion, and then gradually decreased. This peak shift suggests AMS is relatively latent in the skin organs.
Evolution and Determinants of Lung Function until Late Infancy among Infants Born Preterm
Authors: Lai Shen-Hao , Chiang Ming-Chou , Chu Shih-Ming , Hsu Jen-Fu , Yao Tsung-Chieh , Tsai Ming-Han , Hua Man-Chin , Chiu Chih-Yung , Yeh Kuo-Wei , Huang Jing-Long , Liao Sui-Ling 
Published: January 2020

AbstractTo investigate the evolution of lung function in preterm infants with and without bronchopulmonary dysplasia (BPD) and to determine the perinatal characteristics associated with indexes of lung function in later infancy. Longitudinal lung function assessments were performed at approximately 6, 12, 18, and 24 months of corrected age in preterm infants. Perinatal characteristics were further analyzed to ascertain the determinants of lung function indexes. Although all preterm infants (n = 121; 61 without BPD and 60 with BPD) exhibited decreased lung function in early infancy (6 months of age), after body length was adjusted for, only infants with BPD exhibited poor performance. Furthermore, the lung function of infants with mild to moderate BPD caught up gradually, but the generally poor lung function performance of infants with severe BPD, especially in forced expiratory flow, persisted until later age (24 months). Regarding perinatal characteristics, the z-score of body length at the time of examination and total number of days on positive-pressure ventilation are the major determinants of lung function in later infancy.
Risk factors for carpal tunnel syndrome or trigger finger following distal radius fracture: a nationwide study
Authors: Yeh Kuang-Ting , Lee Ru-Ping , Yu Tzai-Chiu , Wang Jen-Hung , Liu Kuan-Lin , Peng Cheng-Huan , Chen Hao-Wen , Chen Ing-Ho , Hsu Chung-Yi , Lin Cheng-Li , Wu Wen-Tien 
Published: January 2020

AbstractNew-onset carpal tunnel syndrome (CTS) and trigger finger after distal radius fractures (DRFs) with or without open reduction and internal fixation (ORIF) have been reported inconsistently across different studies. This study assessed the incidence of CTS and trigger finger after DRFs using Taiwan National Health Insurance Research Database. In total, 1454 patients in the case (ORIF) cohort and 1454 patients in the control (non-ORIF) cohort were included in this retrospective study. The mean age was approximately 55 years old, and the female to male ratio was approximately 3/2. Nine patients underwent carpal tunnel release (CTR) surgery after diagnosis of CTS in the case group, and no patients did in the control group; whereas 19 cases of CTS were diagnosed without CTR in the case group, and 4 such cases were observed in the control group. Five cases of trigger finger were diagnosed in the case group, and 3 cases were diagnosed in the control group. CTS were significantly associated with ORIF for DRFs within 9 months after the fracture, whereas trigger finger was not significantly different between groups. Diabetes mellitus was a significant risk factor for CTS and trigger finger within 9 months after the incidence of DRFs.
The Difference in the Changes of Indoxyl Sulfate after Catheter Ablation among Atrial Fibrillation Patients with and without Kidney Dysfunction
Authors: Koike Hideki , Morita Toshisuke , Tatebe Junko , Watanabe Ippei , Shinohara Masaya , Kinoshita Toshio , Yuzawa Hitomi , Suzuki Takeya , Fujino Tadashi , Ikeda Takanori 
Published: January 2020

AbstractIndoxyl sulfate (IS), a protein-bound uremic toxin, induces chronic kidney disease (CKD) and atrial fibrillation (AF). Catheter ablation (CA) of AF improves the renal function. However, the transition of uremic toxins is unclear. This study aimed to investigate the transition of the serum IS level in AF patients with and without CKD after CA. A total of 138 consecutive AF patients who underwent CA and maintained sinus rhythm were prospectively enrolled (paroxysmal AF 67.4%). The patients were divided into 4 groups (non-CKD/low-IS:68, non-CKD/high-IS:28, CKD/low-IS:13, and CKD/high-IS:29). The plasma IS levels and estimated glomerular filtration rate (eGFR) were determined before and 1-year after CA. CKD was defined as CKD stage III and a high-IS according to the mean IS (IS ≥ 1.1 μg/ml). CA significantly improved the eGFR in CKD patients (p < 0.001). The serum IS level in the non-CKD/high-IS group was significantly decreased (from 1.7 ± 0.7 to 1.1 ± 0.6 μg/ml, p < 0.001). However, the serum IS level in the CKD/high-IS group did not improve (from 1.9 ± 0.9 to 1.7 ± 0.7 μg/ml, p = 0.22). The change in the IS in the CKD patients significantly differed from that in those without CKD. In the CKD patients, CA did not significantly decrease the IS, a risk factor of CKD, regardless of an improved eGFR.
Positron Annihilation Spectroscopy Study of Carbon-Vacancy Interaction in Low-Temperature Bainite
Authors: Rementeria Rosalia , Domínguez-Reyes Ricardo , Capdevila Carlos , Garcia-Mateo Carlos , Caballero Francisca G. 
Published: January 2020

AbstractNano-scale investigations of bainitic structures formed at temperatures below 350 °C have shown that the bainitic ferrite lattice is super-saturated in carbon. A high density of intrinsic defects would be playing a part in the carbon-supersaturation levels detected. In this work, the role of C−vacancy complexes on carbon-supersaturation in low temperature bainite is investigated by means of Positron Annihilation Spectroscopy. Results reveal the presence of a significant amount of monovacancies in the structures that plays an important role on the formation of carbon clusters in the ferrite lattice of nano-scale bainitic structures.