bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin remodeling protein HELLS is critical for retinoblastoma tumor initiation and progression
Authors: Zocchi Loredana , Mehta Aditi , Wu Stephanie C. , Wu Jie , Gu Yijun , Wang Jingtian , Suh Susie , Spitale Robert C. , Benavente Claudia A. 
Published: February 2020

AbstractRetinoblastoma is an aggressive childhood cancer of the developing retina that initiates by biallelic RB1 gene inactivation. Tumor progression in retinoblastoma is driven by epigenetics, as retinoblastoma genomes are stable, but the mechanism(s) that drive these epigenetic changes remain unknown. Lymphoid-specific helicase (HELLS) protein is an epigenetic modifier directly regulated by the RB/E2F pathway. In this study, we used novel genetically engineered mouse models to investigate the role of HELLS during retinal development and tumorigenesis. Our results indicate that Hells-null retinal progenitor cells divide, undergo cell-fate specification, and give rise to fully laminated retinae with minor bipolar cells defects, but normal retinal function. Despite the apparent nonessential role of HELLS in retinal development, failure to transcriptionally repress Hells during retinal terminal differentiation due to retinoblastoma (RB) family loss significantly contributes to retinal tumorigenesis. Loss of HELLS drastically reduced ectopic division of differentiating cells in Rb1/p107-null retinae, significantly decreased the incidence of retinoblastoma, delayed tumor progression, and increased overall survival. Despite its role in heterochromatin formation, we found no evidence that Hells loss directly affected chromatin accessibility in the retina but functioned as transcriptional co-activator of E2F3, decreasing expression of cell cycle genes. We propose that HELLS is a critical downstream mediator of E2F-dependent ectopic proliferation in RB-null retinae. Together with the nontoxic effect of HELLS loss in the developing retina, our results suggest that HELLS and its downstream pathways could serve as potential therapeutic targets for retinoblastoma.
Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS/MAPK signaling pathway in vitro and in vivo
Authors: Fan Jiangjiang , Ren Dongmei , Wang Jinxia , Liu Xiaoqing , Zhang Huaran , Wu Mingsheng , Yang Guotao 
Published: February 2020

AbstractWorldwide, lung cancer remains a leading cause of cancer mortality. Bruceine D (BD) has been shown to induce pancreatic cancer cell death via several different mechanisms. In this study, we demonstrated that BD inhibited lung cancer cell proliferation. Apoptosis and autophagy were the most important mechanisms involved in BD-induced lung cancer cell death, and complete autophagic flux was observed in A549 and NCI-H292 cells. In addition, BD significantly improved intracellular reactive oxygen species (ROS) levels. BD-mediated cell apoptosis and autophagy were almost inhibited in cells pretreated with N-acetylcysteine (NAC), an ROS scavenger. Furthermore, MAPK signaling pathway activation contributed to BD-induced cell proliferation inhibition and NAC could eliminate p-ERK and p-JNK upregulation. Finally, an in vivo study indicated that BD inhibited the growth of lung cancer xenografts. Overall, BD is a promising candidate for the treatment of lung cancer owing to its multiple mechanisms and low toxicity.
A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy
Authors: Wu Qi-ying , Cheng Zhao , Zhou Yang-zhao , Zhao Yuan , Li Jian-ming , Zhou Xin-min , Peng Hong-ling , Zhang Guang-sheng , Liao Xiao-bo , Fu Xian-ming 
Published: February 2020

AbstractAbdominal Aortic aneurysm (AAA) is associated with chronic inflammation, cells apoptosis, and impairment of autophagy. BP-1-102, a novel potent STAT3 inhibitor, has been recently reported to significantly block inflammation-related signaling pathways of JAK2/STAT3 and NF-κB, as well as regulate autophagy. However, its role in vascular inflammation and AAA progression remains to be elucidated. In the present study, the effect and potential mechanisms of BP-1-102 on angiotensin II (AngII) induced AAA in ApoE−/− mice were investigated. AAA was induced in ApoE−/− mice with infusion of AngII for 28 days. BP-1-102 was administrated orally to mice every other day. Mice were sacrificed on day 7, day 14, and day 28 to evaluate the treatment effects. BP-1-102 markedly decreased AAA incidence and aortic diameter, maintained elastin structure and volume, reduced the expression of pro-inflammatory cytokines and MMPs, and inhibited inflammatory cells infiltration. Moreover, BP-1-102 dramatically reduced the expression of JAK2, p-STAT3, p-NF-κB, and Bcl-xL but maintained the expression of LC3B and Beclin in AAA tissues. In vitro, vascular smooth muscle cells (VSMCs) were treated with AngII and/or BP-1-102 at indicated time and concentration. BP-1-102 inhibited AngII-induced JAK2/STAT3 and NF-κB signaling activation and maintained autophagy-related proteins expression in VSMCs. Taken together, our findings suggest that BP-1-102 inhibits vascular inflammation and AAA progression through decreasing JAK2/STAT3 and NF-κB activation and maintaining autophagy.
Delivery of phosphatidylethanolamine blunts stress in hepatoma cells exposed to elevated palmitate by targeting the endoplasmic reticulum
Authors: Trentzsch Marcus , Nyamugenda Eugene , Miles Tiffany K. , Griffin Haven , Russell Susan , Koss Brian , Cooney Kimberly A. , Phelan Kevin D. , Tackett Alan J. , Iyer Srividhya , Boysen Gunnar , Baldini Giulia 
Published: February 2020

AbstractGenetic obesity increases in liver phosphatidylcholine (PC)/phosphatidylethanolamine (PE) ratio, inducing endoplasmic reticulum (ER) stress without concomitant increase of ER chaperones. Here, it is found that exposing mice to a palm oil-based high fat (HF) diet induced obesity, loss of liver PE, and loss of the ER chaperone Grp78/BiP in pericentral hepatocytes. In Hepa1–6 cells treated with elevated concentration of palmitate to model lipid stress, Grp78/BiP mRNA was increased, indicating onset of stress-induced Unfolded Protein Response (UPR), but Grp78/BiP protein abundance was nevertheless decreased. Exposure to elevated palmitate also induced in hepatoma cells decreased membrane glycosylation, nuclear translocation of pro-apoptotic C/EBP-homologous-protein-10 (CHOP), expansion of ER-derived quality control compartment (ERQC), loss of mitochondrial membrane potential (MMP), and decreased oxidative phosphorylation. When PE was delivered to Hepa1–6 cells exposed to elevated palmitate, effects by elevated palmitate to decrease Grp78/BiP protein abundance and suppress membrane glycosylation were blunted. Delivery of PE to Hepa1–6 cells treated with elevated palmitate also blunted expansion of ERQC, decreased nuclear translocation of CHOP and lowered abundance of reactive oxygen species (ROS). Instead, delivery of the chemical chaperone 4-phenyl-butyrate (PBA) to Hepa1–6 cells treated with elevated palmitate, while increasing abundance of Grp78/BiP protein and restoring membrane glycosylation, also increased ERQC, expression and nuclear translocation of CHOP, non-mitochondrial oxygen consumption, and generation of ROS. Data indicate that delivery of PE to hepatoma cells under lipid stress recovers cell function by targeting the secretory pathway and by blunting pro-apoptotic branches of the UPR.
Simulation-based reconstruction of global bird migration over the past 50,000 years
Authors: Somveille Marius , Wikelski Martin , Beyer Robert M. , Rodrigues Ana S. L. , Manica Andrea , Jetz Walter 
Published: February 2020

AbstractMigration is a widespread response of birds to seasonally varying climates. As seasonality is particularly pronounced during interglacial periods, this raises the question of the significance of bird migration during past periods with different patterns of seasonality. Here, we apply a mechanistic model to climate reconstructions to simulate the past 50,000 years of bird migration worldwide, a period encompassing the transition between the last glacial period and the current interglacial. Our results indicate that bird migration was also a prevalent phenomenon during the last ice age, almost as much as today, suggesting that it has been continually important throughout the glacial cycles of recent Earth history. We find however regional variations, with increasing migratory activity in the Americas, which is not mirrored in the Old World. These results highlight the strong flexibility of the global bird migration system and offer a baseline in the context of on-going anthropogenic climate change.
Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas
Authors: Aslan Katrin , Turco Verena , Blobner Jens , Sonner Jana K. , Liuzzi Anna Rita , Núñez Nicolás Gonzalo , De Feo Donatella , Kickingereder Philipp , Fischer Manuel , Green Ed , Sadik Ahmed , Friedrich Mirco , Sanghvi Khwab , Kilian Michael , Cichon Frederik , Wolf Lara , Jähne Kristine , von Landenberg Anna , Bunse Lukas , Sahm Felix , Schrimpf Daniel , Meyer Jochen , Alexander Allen , Brugnara Gianluca , Röth Ralph , Pfleiderer Kira , Niesler Beate , von Deimling Andreas , Opitz Christiane , Breckwoldt Michael O. , Heiland Sabine , Bendszus Martin , Wick Wolfgang , Becher Burkhard , Platten Michael 
Published: February 2020

AbstractIntrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, we investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental gliomas and show a clear dichotomy and acquired immune heterogeneity in ICB-responder and non-responder tumors. We made use of this dichotomy to establish a radiomic signature predicting tumor regression after pseudoprogression induced by ICB therapy based on serial magnetic resonance imaging. We provide evidence that macrophage-driven ICB resistance is established by CD4 T cell suppression and Treg expansion in the tumor microenvironment via the PD-L1/PD-1/CD80 axis. These findings uncover an unexpected heterogeneity of response to ICB in strictly syngeneic tumors and provide a rationale for targeting PD-L1-expressing tumor-associated macrophages to overcome resistance to ICB.
Light control of surface–bulk coupling by terahertz vibrational coherence in a topological insulator
Authors: Yang Xu , Luo Liang , Vaswani Chirag , Zhao Xin , Yao Yongxin , Cheng Di , Liu Zhaoyu , Kim Richard H. J. , Liu Xinyu , Dobrowolska-Furdyna Malgorzata , Furdyna Jacek K. , Perakis Ilias E. , Wang Caizhuang , Ho Kaiming , Wang Jigang 
Published: February 2020

AbstractThe demand for disorder-tolerant quantum logic and spin electronics can be met by generating and controlling dissipationless spin currents protected by topology. Dirac fermions with helical spin-locking surface transport offer a way of achieving such a goal. Yet, surface-bulk coupling can lead to strong Dirac electron scattering with bulk carriers and phonons as well as impurities, assisted by such dissipative channel, which results in “topological breakdown”. Here, we demonstrate that coherent lattice vibrations periodically driven by a single-cycle terahertz (THz) pulse can significantly suppress such dissipative channel in topological insulators. This is achieved by reducing the phase space in the bulk available for Dirac fermion scattering into during coherent lattice oscillations in Bi2Se3. This light-induced suppression manifests as a remarkable transition exclusively in surface transport, absent for bulk, above the THz electric fields for driving coherent phonons, which prolongs the surface transport lifetime. These results, together with simulations, identify the critical role of spin–orbit coupling for the “phase space contraction” mechanism that suppresses the surface-bulk coupling. Imposing vibrational quantum coherence into topological states of matter may become a universal light control principle for reinforcing the symmetry-protected helical transport.
Experiments Investigating the Competitive Growth Advantage of Two Different Genotypes of Human Metapneumovirus: Implications for the Alternation of Genotype Prevalence
Authors: Zhou Zhen , Zhang Pan , Cui Yuxia , Zhang Yongbo , Qin Xian , Li Rongpei , Liu Ping , Dou Ying , Wang Lijia , Zhao Yao 
Published: February 2020

AbstractHuman metapneumovirus (hMPV) is an important pathogen that causes upper and lower respiratory tract infections in children worldwide. hMPV has two major genotypes, hMPV-A and hMPV-B. Epidemiological studies have shown that the two hMPV genotypes alternate in predominance worldwide in recent years. Co-circulation of the two genotypes of hMPV was usually observed and there is no study about the interaction between them, such as competitive replication, which maybe the possible mechanisms for alternating prevalence of subtypes. Our present study have used two different genotypes of hMPV (genotype A: NL/1/00; B: NL/1/99) in different proportions in animal model (BALB/c mice) and cell model (Vero-E6) separately. The result showed that the competitive growth does exist in BALB/c mice, genotype B had a strong competitive advantage. However, genotype B did not cause more severe disease than non-predominant (genotype A) or mixed strains in the study, which were evaluated by the body weight, airway hyperresponsiveness and lung pathology of mouse. In cell model, competitive growth and the two genotypes alternately prevalence were observed. In summary, we confirmed that there was a competitive replication between hMPV genotype A and B, and no difference in disease severity caused by the two subtypes. This study shows a new insight to understand the alternation of hMPV genotype prevalence through genotype competition and provide experimental evidence for disease control and vaccine design.
Species-specific genetic variation in response to deep-sea environmental variation amongst Vulnerable Marine Ecosystem indicator taxa
Authors: Zeng Cong , Rowden Ashley A. , Clark Malcolm R. , Gardner Jonathan P. A. 
Published: February 2020

AbstractUnderstanding the ecological processes that shape spatial genetic patterns of population structure is critical for understanding evolutionary dynamics and defining significant evolutionary and management units in the deep sea. Here, the role of environmental factors (topographic, physico-chemical and biological) in shaping the population genetic structure of four deep-sea habitat-forming species (one sponge - Poecillastra laminaris, three corals - Goniocorella dumosa, Madrepora oculata, Solenosmilia variabilis) was investigated using seascape genetics. Genetic data (nuclear and mitochondrial sequences and microsatellite multilocus genotypes) and environmental variables were employed to build individual-based and population-level models. The results indicated that environmental factors affected genetic variation differently amongst the species, as well as at different geographic scales. For individual-based analyses, different environmental variables explained genetic variation in P. laminaris (dissolved oxygen), G. dumosa (dynamic topography), M. oculata (sea surface temperature and surface water primary productivity), and S. variabilis (tidal current speed). At the population level, factors related to current and food source explained the regional genetic structure in all four species, whilst at the geomorphic features level, factors related to food source and topography were most important. Environmental variation in these parameters may be acting as barriers to gene flow at different scales. This study highlights the utility of seascape genetic studies to better understand the processes shaping the genetic structure of organisms, and to identify environmental factors that can be used to locate sites for the protection of deep-sea Vulnerable Marine Ecosystems.
MiR-4435 is an UQCRB-related circulating miRNA in human colorectal cancer
Authors: Hong Ji Won , Kim Jung Min , Kim Jeong Eun , Cho Hee , Kim Dasol , Kim Wankyu , Oh Jong-Won , Kwon Ho Jeong 
Published: February 2020

AbstractUbiquinol-cytochrome c reductase (UQCRB), a subunit of the mitochondrial complex III, is highly expressed in tissues from colorectal cancer patients. Since UQCRB is highly expressed in colorectal cancer, we investigated miRNAs from mutant UQCRB-expressing cell lines to identify new miRNA biomarkers. After sequencing miRNAs in the mutant UQCRB-expressing cell lines, miR-4435 was selected as a potential biomarker candidate from the six up-regulated miRNAs. The expression level of miR-4435 in the mutant UQCRB-expressing cell lines and colon cancer was increased. Notably, the expression level of miR-4435 was increased in exosomes isolated from cell culture medium, suggesting that miR-4435 is closely related to colon cancer and that large amounts of miR-4435 may be secreted outside of the cells through exosomes. Additionally, exosomes extracted from the serum samples of colorectal cancer patients showed increased miR-4435 levels depending on the cancer progression stage. Moreover, analyses of a miRNA database and mRNA-sequencing data of the mutant UQCRB-expressing cell lines revealed that TIMP3, a tumor suppressor, could be a target of miR-4435. Additionally, the expression of miR-4435 was suppressed by UQCRB inhibitor treatment whereas TIMP3 was up-regulated. Upregulation of TIMP3 decreased proliferation of the mutant UQCRB-expressing cell lines and a colorectal cancer cell line. TIMP3 was also upregulated in response to miR-4435 inhibitor and UQCRB inhibitor treatments. Furthermore, these findings suggest that miR-4435 is related to an oncogenic function in UQCRB related disease, CRC, and that effects migration and invasion on mutant UQCRB-expressing cell lines and colorectal cancer cell. In conclusion, our results identified miR-4435 as a potential circulating miRNA biomarker of colorectal cancer associated with UQCRB.
Exploring Natural Clusters of Chronic Migraine Phenotypes: A Cross-Sectional Clinical Study
Authors: Woldeamanuel Yohannes W. , Sanjanwala Bharati M. , Peretz Addie M. , Cowan Robert P. 
Published: February 2020

AbstractHeterogeneity in chronic migraine (CM) presents significant challenge for diagnosis, management, and clinical trials. To explore naturally occurring clusters of CM, we utilized data reduction methods on migraine-related clinical dataset. Hierarchical agglomerative clustering and principal component analyses (PCA) were conducted to identify natural clusters in 100 CM patients using 14 migraine-related clinical variables. Three major clusters were identified. Cluster I (29 patients) – the severely impacted patient featured highest levels of depression and migraine-related disability. Cluster II (28 patients) – the minimally impacted patient exhibited highest levels of self-efficacy and exercise. Cluster III (43 patients) – the moderately impacted patient showed features ranging between Cluster I and II. The first 5 principal components (PC) of the PCA explained 65% of variability. The first PC (eigenvalue 4.2) showed one major pattern of clinical features positively loaded by migraine-related disability, depression, poor sleep quality, somatic symptoms, post-traumatic stress disorder, being overweight and negatively loaded by pain self-efficacy and exercise levels. CM patients can be classified into three naturally-occurring clusters. Patients with high self-efficacy and exercise levels had lower migraine-related disability, depression, sleep quality, and somatic symptoms. These results may ultimately inform different management strategies.
Organic bases catalyze the synthesis of urea from ammonium salts derived from recovered environmental ammonia
Authors: Manaka Yuichi , Nagatsuka Yuki , Motokura Ken 
Published: February 2020

AbstractAmmonia from sewage and livestock manure is a major environmental pollutant. To consume environmental ammonia, we investigated the organic base-catalyzed synthesis of urea. 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) catalyzes the conversion of ammonium carbamate to urea in 35% yield at 100 °C. Moreover, DBU also converts other ammonium salts into urea. A mechanism that involves nucleophilic attack of ammonia following ion exchange is proposed.
Genomic scan of selective sweeps in Djallonké (West African Dwarf) sheep shed light on adaptation to harsh environments
Authors: Álvarez Isabel , Fernández Iván , Traoré Amadou , Pérez-Pardal Lucía , Menéndez-Arias Nuria A. , Goyache Félix 
Published: February 2020

AbstractThe Djallonké (West African Dwarf) sheep is a small-sized haired sheep resulting from a costly evolutionary process of natural adaptation to the harsh environment of West Africa including trypanosome challenge. However, genomic studies carried out in this sheep are scant. In this research, genomic data of 184 Djallonké sheep (and 12 Burkina-Sahel sheep as an outgroup) generated using medium-density SNP Chips were analyzed. Three different statistics (iHS, XP-EHH and nSL) were applied to identify candidate selection sweep regions spanning genes putatively associated with adaptation of sheep to the West African environment. A total of 207 candidate selection sweep regions were defined. Gene-annotation enrichment and functional annotation analyses allowed to identify three statistically significant functional clusters involving 12 candidate genes. Genes included in Functional Clusters associated to selection signatures were mainly related to metabolic response to stress, including regulation of oxidative and metabolic stress and thermotolerance. The bovine chromosomal areas carrying QTLs for cattle trypanotolerance were compared with the regions on which the orthologous functional candidate cattle genes were located. The importance of cattle BTA4 for trypanotolerant response might have been conserved between species. The current research provides new insights on the genomic basis for adaptation and highlights the importance of obtaining information from non-cosmopolite livestock populations managed in harsh environments.
A comparative study on the mechanical, physical and morphological properties of cement-micro/nanoFe3O4 composite
Authors: Ghazanlou Siamak Imanian , Jalaly Maisam , Sadeghzadeh Sadegh , Korayem Asghar Habibnejad 
Published: February 2020

AbstractIn this study, fabrication of a composite containing the ordinary Portland cement (OPC) and magnetite (Fe3O4) micro/nanoparticles is reported. In the first stage, the cement paste samples with a fixed 0.2 wt.% Fe3O4additive in four different particle sizes (20–40 nm, 80–100 nm, 250–300 nm, and 1–2 µm) were prepared to check the effect of magnetite size. Magnetite was found to play an effective role in reinforcing cement matrix. The results showed that the cement paste reinforced by magnetite nanoparticles of 20–40 nm size range had the highest compressive, flexural, and tensile strengths compared to those of the other samples reinforced by larger particles. In the second stage, various amounts of the Fe3O4nanoparticles of 20–40 nm size range were added to the cement to evaluate the influence of magnetite amount and find the optimized reinforcement amount. It was revealed that adding 0.25 wt.% Fe3O4nanoparticles of 20–40 nm size range, as the optimal specimen, increased the compressive strength, flexural strength and tensile splitting strength by 23–32, 17–25, and 15–19%, respectively, and decreased the electrical resistance by 19–31%.