bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caveolin-1 suppresses tumor formation through the inhibition of the unfolded protein response
Authors: Díaz María I. , Díaz Paula , Bennett Jimena Castillo , Urra Hery , Ortiz Rina , Orellana Pamela Contreras , Hetz Claudio , Quest Andrew F. G. 
Published: August 2020

AbstractCaveolin-1 (CAV1), is a broadly expressed, membrane-associated scaffolding protein that acts both, as a tumor suppressor and a promoter of metastasis, depending on the type of cancer and stage. CAV1 is downregulated in human tumors, tumor cell lines and oncogene-transformed cells. The tumor suppressor activity of CAV1 is generally associated with its presence at the plasma membrane, where it participates, together with cavins, in the formation of caveolae and also has been suggested to interact with and inhibit a wide variety of proteins through interactions mediated by the scaffolding domain. However, a pool of CAV1 is also located at the endoplasmic reticulum (ER), modulating the secretory pathway in a manner dependent on serine-80 (S80) phosphorylation. In melanoma cells, CAV1 expression suppresses tumor formation, but the protein is largely absent from the plasma membrane and does not form caveolae. Perturbations to the function of the ER are emerging as a central driver of cancer, highlighting the activation of the unfolded protein response (UPR), a central pathway involved in stress mitigation. Here we provide evidence indicating that the expression of CAV1 represses the activation of the UPR in vitro and in solid tumors, reflected in the attenuation of PERK and IRE1α signaling. These effects correlated with increased susceptibility of cells to ER stress and hypoxia. Interestingly, the tumor suppressor activity of CAV1 was abrogated by site-directed mutagenesis of S80, correlating with a reduced ability to repress the UPR. We conclude that the tumor suppression by CAV1 involves the attenuation of the UPR, and identified S80 as essential in this context. This suggests that intracellular CAV1 regulates cancer through alternative signaling outputs.
Cisplatin inhibits SIRT3-deacetylation MTHFD2 to disturb cellular redox balance in colorectal cancer cell
Authors: Wan Xingyou , Wang Chao , Huang Zhenyu , Zhou Dejian , Xiang Sheng , Qi Qian , Chen Xinyuan , Arbely Eyal , Liu Chen-Ying , Du Peng , Yu Wei 
Published: August 2020

AbstractThe folate-coupled metabolic enzyme MTHFD2 (the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase) confers redox homeostasis and drives cancer cell proliferation and migration. Here, we show that MTHFD2 is hyperacetylated and lysine 88 is the critical acetylated site. SIRT3, the major deacetylase in mitochondria, is responsible for MTHFD2 deacetylation. Interestingly, chemotherapeutic agent cisplatin inhibits expression of SIRT3 to induce acetylation of MTHFD2 in colorectal cancer cells. Cisplatin-induced acetylated K88 MTHFD2 is sufficient to inhibit its enzymatic activity and downregulate NADPH levels in colorectal cancer cells. Ac-K88-MTHFD2 is significantly decreased in human colorectal cancer samples and is inversely correlated with the upregulated expression of SIRT3. Our findings reveal an unknown regulation axis of cisplatin-SIRT3-MTHFD2 in redox homeostasis and suggest a potential therapeutic strategy for cancer treatments by targeting MTHFD2.
The rs7911488-T allele promotes the growth and metastasis of colorectal cancer through modulating miR-1307/PRRX1
Authors: Yang Man , Liu Xinchang , Meng Fanyi , Zhang Yawen , Wang Mengmeng , Chen Yinshuang , Guo Xuqin , Chen Weichang , Wang Weipeng 
Published: August 2020

AbstractWe previously discovered that rs7911488T>C in pre-miR-1307 was closely correlated to the risk of colorectal cancer (CRC). However, the roles of rs7911488 in CRC are still largely unknown. Here we explored the roles of rs7911488 in the growth and metastasis of CRC. We firstly generated cell lines SW480-T and SW480-C for stable expression of rs7911488 T-allelic and C-allelic pre-miR-1307, respectively. We subcutaneously grafted the cells into nude mice. We found that SW480-T tumors with high expression of miR-1307 obviously grew faster than the SW480-C tumors. Moreover, liver metastases (5/8) were observed in the mice bearing SW480-T tumors but not the SW480-C tumor-bearing mice. The results from colony formation assays, transwell assays, and wound healing assays demonstrated that the proliferative and metastatic abilities of SW480-T cells were evidently more potent than the SW480-C cells. Then we utilized gene array, real-time PCR, western blotting, and dual-luciferase reporter assays to figure out that miR-1307 directly inhibited PPRX1 expression by binding to its 3′-UTR. Thereafter, we confirmed that the proliferative and metastatic abilities of SW480 and HCT-116 cells were markedly enhanced by miR-1307, but were suppressed by PRRX1. Moreover, the regulatory roles of miR-1307 in the proliferation and metastasis of CRC cells were reversed by PRRX1. Notably, we also found that PRRX1 repressed CRC tumor growth in nude mice. In summary, our current study revealed that rs7911488-T allele led to over-expression of miR-1307, which inhibited PRRX1 and consequently promoted the proliferation and migration of CRC cells. This might offer a novel insight into the progression of CRC.
An exponential build-up in seismic energy suggests a months-long nucleation of slow slip in Cascadia
Authors: Hulbert Claudia , Rouet-Leduc Bertrand , Jolivet Romain , Johnson Paul A. 
Published: August 2020

AbstractSlow slip events result from the spontaneous weakening of the subduction megathrust and bear strong resemblance to earthquakes, only slower. This resemblance allows us to study fundamental aspects of nucleation that remain elusive for classic, fast earthquakes. We rely on machine learning algorithms to infer slow slip timing from statistics of seismic waveforms. We find that patterns in seismic power follow the 14-month slow slip cycle in Cascadia, arguing in favor of the predictability of slow slip rupture. Here, we show that seismic power exponentially increases as the slowly slipping portion of the subduction zone approaches failure, a behavior that shares a striking similarity with the increase in acoustic power observed prior to laboratory slow slip events. Our results suggest that the nucleation phase of Cascadia slow slip events may last from several weeks up to several months.
Structure and dynamics of the active Gs-coupled human secretin receptor
Authors: Dong Maoqing , Deganutti Giuseppe , Piper Sarah J. , Liang Yi-Lynn , Khoshouei Maryam , Belousoff Matthew J. , Harikumar Kaleeckal G. , Reynolds Christopher A. , Glukhova Alisa , Furness Sebastian G. B. , Christopoulos Arthur , Danev Radostin , Wootten Denise , Sexton Patrick M. , Miller Laurence J. 
Published: August 2020

AbstractThe class B secretin GPCR (SecR) has broad physiological effects, with target potential for treatment of metabolic and cardiovascular disease. Molecular understanding of SecR binding and activation is important for its therapeutic exploitation. We combined cryo-electron microscopy, molecular dynamics, and biochemical cross-linking to determine a 2.3 Å structure, and interrogate dynamics, of secretin bound to the SecR:Gs complex. SecR exhibited a unique organization of its extracellular domain (ECD) relative to its 7-transmembrane (TM) core, forming more extended interactions than other family members. Numerous polar interactions formed between secretin and the receptor extracellular loops (ECLs) and TM helices. Cysteine-cross-linking, cryo-electron microscopy multivariate analysis and molecular dynamics simulations revealed that interactions between peptide and receptor were dynamic, and suggested a model for initial peptide engagement where early interactions between the far N-terminus of the peptide and SecR ECL2 likely occur following initial binding of the peptide C-terminus to the ECD.
High concentrations of plastic hidden beneath the surface of the Atlantic Ocean
Authors: Pabortsava Katsiaryna , Lampitt Richard S. 
Published: August 2020

AbstractConcern over plastic pollution of the marine environment is severe. The mass-imbalance between the plastic litter supplied to and observed in the ocean currently suggests a missing sink. However, here we show that the ocean interior conceals high loads of small-sized plastic debris which can balance and even exceed the estimated plastic inputs into the ocean since 1950. The combined mass of just the three most-littered plastics (polyethylene, polypropylene, and polystyrene) of 32–651 µm size-class suspended in the top 200 m of the Atlantic Ocean is 11.6–21.1 Million Tonnes. Considering that plastics of other sizes and polymer types will be found in the deeper ocean and in the sediments, our results indicate that both inputs and stocks of ocean plastics are much higher than determined previously. It is thus critical to assess these terms across all size categories and polymer groups to determine the fate and danger of plastic contamination.
Data augmentation in microscopic images for material data mining
Authors: Ma Boyuan , Wei Xiaoyan , Liu Chuni , Ban Xiaojuan , Huang Haiyou , Wang Hao , Xue Weihua , Wu Stephen , Gao Mingfei , Shen Qing , Mukeshimana Michele , Abuassba Adnan Omer , Shen Haokai , Su Yanjing 
Published: August 2020

AbstractRecent progress in material data mining has been driven by high-capacity models trained on large datasets. However, collecting experimental data (real data) has been extremely costly owing to the amount of human effort and expertise required. Here, we develop a novel transfer learning strategy to address problems of small or insufficient data. This strategy realizes the fusion of real and simulated data and the augmentation of training data in a data mining procedure. For a specific task of grain instance image segmentation, this strategy aims to generate synthetic data by fusing the images obtained from simulating the physical mechanism of grain formation and the “image style” information in real images. The results show that the model trained with the acquired synthetic data and only 35% of the real data can already achieve competitive segmentation performance of a model trained on all of the real data. Because the time required to perform grain simulation and to generate synthetic data are almost negligible as compared to the effort for obtaining real data, our proposed strategy is able to exploit the strong prediction power of deep learning without significantly increasing the experimental burden of training data preparation.
Pharmacogenomics of COVID-19 therapies
Authors: Takahashi Takuto , Luzum Jasmine A. , Nicol Melanie R. , Jacobson Pamala A. 
Published: August 2020

AbstractA new global pandemic of coronavirus disease 2019 (COVID-19) has resulted in high mortality and morbidity. Currently numerous drugs are under expedited investigations without well-established safety or efficacy data. Pharmacogenomics may allow individualization of these drugs thereby improving efficacy and safety. In this review, we summarized the pharmacogenomic literature available for COVID-19 drug therapies including hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir/ritonavir, darunavir/cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib, and corticosteroids. We searched PubMed, reviewed the Pharmacogenomics Knowledgebase (PharmGKB®) website, Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, the U.S. Food and Drug Administration (FDA) pharmacogenomics information in the product labeling, and the FDA pharmacogenomics association table. We found several drug-gene variant pairs that may alter the pharmacokinetics of hydroxychloroquine/chloroquine (CYP2C8, CYP2D6, SLCO1A2, and SLCO1B1); azithromycin (ABCB1); ribavirin (SLC29A1, SLC28A2, and SLC28A3); and lopinavir/ritonavir (SLCO1B1, ABCC2, CYP3A). We also identified other variants, that are associated with adverse effects, most notable in hydroxychloroquine/chloroquine (G6PD; hemolysis), ribavirin (ITPA; hemolysis), and interferon β -1b (IRF6; liver toxicity). We also describe the complexity of the risk for QT prolongation in this setting because of additive effects of combining more than one QT-prolonging drug (i.e., hydroxychloroquine/chloroquine and azithromycin), increased concentrations of the drugs due to genetic variants, along with the risk of also combining therapy with potent inhibitors. In conclusion, although direct evidence in COVID-19 patients is lacking, we identified potential actionable genetic markers in COVID-19 therapies. Clinical studies in COVID-19 patients are deemed warranted to assess potential roles of these markers.
Reduced levels of circulating adhesion molecules in adolescents with early-onset psychosis
Authors: Wedervang-Resell Kirsten , Ueland Thor , Aukrust Pål , Friis Svein , Holven Kirsten B. , H. Johannessen Cecilie , Lekva Tove , Lonning Vera , Smelror Runar E. , Szabo Attila , Andreassen Ole A. , Myhre Anne M. , Agartz Ingrid 
Published: August 2020

AbstractIt is suggested that neurodevelopmental abnormalities are involved in the disease mechanisms of psychotic disorders. Although cellular adhesion molecules (CAMs) participate in neurodevelopment, modulate blood–brain barrier permeability, and facilitate leukocyte migration, findings concerning their systemic levels in adults with psychosis are inconsistent. We examined plasma levels and mRNA expression in peripheral blood mononuclear cells (PBMCs) of selected CAMs in adolescents with early-onset psychosis (EOP) aged 12–18 years (n = 37) and age-matched healthy controls (HC) (n = 68). EOP patients exhibited significantly lower circulating levels of soluble platelet selectin (~−22%) and soluble vascular cell adhesion molecule-1 (~−14%) than HC. We found no significant associations with symptom severity. PSEL mRNA expression was increased in PBMCs of patients and significantly negatively correlated to duration of illness. These findings suggest a role for CAMs in the pathophysiology of psychotic disorders.
Deep-learning-based image quality enhancement of compressed sensing magnetic resonance imaging of vessel wall: comparison of self-supervised and unsupervised approaches
Authors: Eun Da-in , Jang Ryoungwoo , Ha Woo Seok , Lee Hyunna , Jung Seung Chai , Kim Namkug 
Published: August 2020

AbstractWhile high-resolution proton density-weighted magnetic resonance imaging (MRI) of intracranial vessel walls is significant for a precise diagnosis of intracranial artery disease, its long acquisition time is a clinical burden. Compressed sensing MRI is a prospective technology with acceleration factors that could potentially reduce the scan time. However, high acceleration factors result in degraded image quality. Although recent advances in deep-learning-based image restoration algorithms can alleviate this problem, clinical image pairs used in deep learning training typically do not align pixel-wise. Therefore, in this study, two different deep-learning-based denoising algorithms—self-supervised learning and unsupervised learning—are proposed; these algorithms are applicable to clinical datasets that are not aligned pixel-wise. The two approaches are compared quantitatively and qualitatively. Both methods produced promising results in terms of image denoising and visual grading. While the image noise and signal-to-noise ratio of self-supervised learning were superior to those of unsupervised learning, unsupervised learning was preferable over self-supervised learning in terms of radiomic feature reproducibility.
Innovative prolonged-release oral alkalising formulation allowing sustained urine pH increase with twice daily administration: randomised trial in healthy adults
Authors: Guittet C. , Roussel-Maupetit C. , Manso-Silván M. A. , Guillaumin F. , Vandenhende F. , Granier L. A. 
Published: August 2020

AbstractA multi-particulate fixed-dose combination product, consisting of a combination of two alkalising salts formulated as prolonged-release granules, ADV7103, was developed to obtain a sustained and prolonged alkalising effect. The specific release of both types of granules was shown in vitro through their dissolution profiles, which indicated that potassium citrate was released within the first 2–3 h and potassium bicarbonate up to 10–12 h after administration. The long-lasting coverage of ADV7103 was confirmed through a randomised, placebo-controlled, double-blind, two-period study, measuring its effect on urine pH in healthy adults (n = 16) at doses of alkalising agent ranging between 0.98 and 2.88 meq/kg/day. A significant increase of urine pH with a positive dose–response in healthy adult subjects was shown. Urine pH above 7 was maintained during 24 h with a dosing equivalent to 1.44 meq/kg twice a day, while urine pH was below 6 most of the time with placebo. The effect observed was non-saturating within the range of doses evaluated and the formulation presented a good safety profile. ADV7103 provided an effective prolonged release of alkalising salts to cover a 12-h effect with adequate tolerability and could afford a twice a day (morning and evening) dosing in patients requiring long-term treatment.
An interphase pool of KIF11 localizes at the basal bodies of primary cilia and a reduction in KIF11 expression alters cilia dynamics
Authors: Zalenski Abigail A. , Majumder Shubhra , De Kuntal , Venere Monica 
Published: August 2020

AbstractKIF11 is a homotetrameric kinesin that peaks in protein expression during mitosis. It is a known mitotic regulator, and it is well-described that KIF11 is necessary for the formation and maintenance of the bipolar spindle. However, there has been a growing appreciation for non-mitotic roles for KIF11. KIF11 has been shown to function in such processes as axon growth and microtubule polymerization. We previously demonstrated that there is an interphase pool of KIF11 present in glioblastoma cancer stem cells that drives tumor cell invasion. Here, we identified a previously unknown association between KIF11 and primary cilia. We confirmed that KIF11 localized to the basal bodies of primary cilia in multiple cell types, including neoplastic and non-neoplastic cells. Further, we determined that KIF11 has a role in regulating cilia dynamics. Upon the reduction of KIF11 expression, the number of ciliated cells in asynchronously growing populations was significantly increased. We rescued this effect by the addition of exogenous KIF11. Lastly, we found that depleting KIF11 resulted in an increase in cilium length and an attenuation in the kinetics of cilia disassembly. These findings establish a previously unknown link between KIF11 and the dynamics of primary cilia and further support non-mitotic functions for this kinesin.
Reversible control of magnetism in FeRh thin films
Authors: Merkel Dániel G. , Lengyel Attila , Nagy Dénes L. , Németh Attila , Horváth Zsolt E. , Bogdán Csilla , Gracheva Maria A. , Hegedűs Gergő , Sajti Szilárd , Radnóczi György Z. , Szilágyi Edit 
Published: August 2020

AbstractThe multilayer of approximate structure MgO(100)/[nFe51Rh49(63 Å)/57Fe51Rh49(46 Å)]10 deposited at 200 °C is primarily of paramagnetic A1 phase and is fully converted to the magnetic B2 phase by annealing at 300 °C for 60 min. Subsequent irradiation by 120 keV Ne+ ions turns the thin film completely to the paramagnetic A1 phase. Repeated annealing at 300 °C for 60 min results in 100% magnetic B2 phase, i.e. a process that appears to be reversible at least twice. The A1 → B2 transformation takes place without any plane-perpendicular diffusion while Ne+ irradiation results in significant interlayer mixing.
Tissue-targeted R-spondin mimetics for liver regeneration
Authors: Zhang Zhengjian , Broderick Caroline , Nishimoto Marni , Yamaguchi Teppei , Lee Sung-Jin , Zhang Haili , Chen Hui , Patel Mehaben , Ye Jay , Ponce Alberto , Brady Jennifer , Baribault Hélène , Li Yang , Yeh Wen-Chen 
Published: August 2020

AbstractR-spondin (RSPO) proteins amplify Wnt signaling and stimulate regeneration in a variety of tissues. To repair tissue in a tissue-specific manner, tissue-targeted RSPO mimetic molecules are desired. Here, we mutated RSPO (RSPO2 F105R/F109A) to eliminate LGR binding while preserving ZNRF3/RNF43 binding and targeted the mutated RSPO to a liver specific receptor, ASGR1. The resulting bi-specific molecule (αASGR1-RSPO2-RA) enhanced Wnt signaling effectively in vitro, and its activity was limited to ASGR1 expressing cells. Systemic administration of αASGR1-RSPO2-RA in mice specifically upregulated Wnt target genes and stimulated cell proliferation in liver but not intestine (which is more responsive to non-targeted RSPO2) in healthy mice, and improved liver function in diseased mice. These results not only suggest that a tissue-specific RSPO mimetic protein can stimulate regeneration in a cell-specific manner, but also provide a blueprint of how a tissue-specific molecule might be constructed for applications in a broader context.
The effects of contextual diversity on incidental vocabulary learning in the native and a foreign language
Authors: Frances Candice , Martin Clara D. , Duñabeitia Jon Andoni 
Published: August 2020

AbstractVocabulary learning occurs throughout the lifespan, often implicitly. For foreign language learners, this is particularly challenging as they must acquire a large number of new words with little exposure. In the present study, we explore the effects of contextual diversity—namely, the number of texts a word appears in—on native and foreign language word learning. Participants read several texts that had novel pseudowords replacing high-frequency words. The total number of encounters with the novel words was held constant, but they appeared in 1, 2, 4, or 8 texts. In addition, some participants read the texts in Spanish (their native language) and others in English (their foreign language). We found that increasing contextual diversity improved recall and recognition of the word, as well as the ability to match the word with its meaning while keeping comprehension unimpaired. Using a foreign language only affected performance in the matching task, where participants had to quickly identify the meaning of the word. Results are discussed in the greater context of the word learning and foreign language literature as well as their importance as a teaching tool.
Experimental demonstration of dynamic thermal regulation using vanadium dioxide thin films
Authors: Morsy Ahmed M. , Barako Michael T. , Jankovic Vladan , Wheeler Virginia D. , Knight Mark W. , Papadakis Georgia T. , Sweatlock Luke A. , Hon Philip W. C. , Povinelli Michelle L. 
Published: August 2020

AbstractWe present an experimental demonstration of passive, dynamic thermal regulation in a solid-state system with temperature-dependent thermal emissivity switching. We achieve this effect using a multilayered device, comprised of a vanadium dioxide (VO2) thin film on a silicon substrate with a gold back reflector. We experimentally characterize the optical properties of the VO2 film and use the results to optimize device design. Using a calibrated, transient calorimetry experiment we directly measure the temperature fluctuations arising from a time-varying heat load. Under laboratory conditions, we find that the device regulates temperature better than a constant emissivity sample. We use the experimental results to validate our thermal model, which can be used to predict device performance under the conditions of outer space. In this limit, thermal fluctuations are halved with reference to a constant-emissivity sample.