bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ovarian BDNF promotes survival, migration, and attachment of tumor precursors originated from p53 mutant fallopian tube epithelial cells
Authors: Kang Min , Chong Kay Yi , Hartwich Tobias M. P. , Bi Fangfang , Witham Allyson K. , Patrick David , Morrisson Madeline J. , Cady Sarah L. , Cerchia Alexandra P. , Kelk Dawn , Liu Yifei , Nucci Jonah , Madarikan Oluwagbemisola , Ueno Daiki , Shuch Brian M. , Yang-Hartwich Yang 
Published: May 2020

AbstractHigh-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecological malignancy. New evidence supports a hypothesis that HGSOC can originate from fallopian tube epithelium (FTE). It is unclear how genetic alterations and pathophysiological processes drive the progression of FTE tumor precursors into widespread HGSOCs. In this study, we uncovered that brain-derived neurotrophic factor (BDNF) in the follicular fluid stimulates the tropomyosin receptor kinase B (TrkB)-expressing FTE cells to promote their survival, migration, and attachment. Using in vitro and in vivo models, we further identified that the acquisition of common TP53 gain-of-function (GOF) mutations in FTE cells led to enhanced BDNF/TrkB signaling compared to that of FTE cells withTP53loss-of-function (LOF) mutations. Different mutant p53 proteins can either increase TrkB transcription or enhance TrkB endocytic recycling. Our findings have demonstrated possible interplays between genetic alterations in FTE tumor precursors (i.e., p53 GOF mutations) and pathophysiological processes (i.e., the release of follicular fluid upon ovulation) during the initiation of HGSOC from the fallopian tube. Our data revealed molecular events underlying the link between HGSOC tumorigenesis and ovulation, a physiological process that has been associated with risk factors of HGSOC.
Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2
Authors: Catanzaro Michele , Fagiani Francesca , Racchi Marco , Corsini Emanuela , Govoni Stefano , Lanni Cristina 
Published: May 2020

AbstractTo date, no vaccines or effective drugs have been approved to prevent or treat COVID-19 and the current standard care relies on supportive treatments. Therefore, based on the fast and global spread of the virus, urgent investigations are warranted in order to develop preventive and therapeutic drugs. In this regard, treatments addressing the immunopathology of SARS-CoV-2 infection have become a major focus. Notably, while a rapid and well-coordinated immune response represents the first line of defense against viral infection, excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic level. Several studies highlight relevant changes occurring both in innate and adaptive immune system in COVID-19 patients. In particular, the massive cytokine and chemokine release, the so-called “cytokine storm”, clearly reflects a widespread uncontrolled dysregulation of the host immune defense. Although the prospective of counteracting cytokine storm is compelling, a major limitation relies on the limited understanding of the immune signaling pathways triggered by SARS-CoV-2 infection. The identification of signaling pathways altered during viral infections may help to unravel the most relevant molecular cascades implicated in biological processes mediating viral infections and to unveil key molecular players that may be targeted. Thus, given the key role of the immune system in COVID-19, a deeper understanding of the mechanism behind the immune dysregulation might give us clues for the clinical management of the severe cases and for preventing the transition from mild to severe stages.
TGF-β1-mediated repression of SLC7A11 drives vulnerability to GPX4 inhibition in hepatocellular carcinoma cells
Authors: Kim Do Hyung , Kim Won Dong , Kim Sang Kyum , Moon Dae Hyuk , Lee Seung Jin 
Published: May 2020

AbstractSystem xc− contributes to glutathione (GSH) synthesis and protects cells against ferroptosis by importing cystine and exchanging it with glutamate. Transforming growth factor β1 (TGF-β1) induces redox imbalance; however, its role in system xc− regulation remains poorly understood. The present study was the first to show that TGF-β1 repressed the protein and mRNA levels of xCT, a catalytic subunit of system xc−, in PLC/PRF/5, Huh7, Huh6, and HepG2 cells with an early TGF-β1 gene signature but not in SNU387, SNU449, SNU475, and SK-Hep1 cells with a late TGF-β1 gene signature. TGF-β1 treatment for 24 h reduced xCT expression in a dose-dependent manner but this TGF-β1-induced repression was blunted by pretreatment with a TGF-β1 receptor inhibitor. TGF-β1-mediated xCT repression was prevented by Smad3, but not Smad2 or Smad4, knockdown, whereas it was enhanced by Smad3 overexpression. TGF-β1 decreased GSH levels in control cells but not xCT-overexpressed cells. Furthermore, TGF-β1 increased reactive oxygen species (ROS) levels in PLC/PRF/5 cells and enhanced tert-butyl hydroperoxide-induced ROS levels in Huh7 cells; these changes were reversed by xCT overexpression. TGF-β1 treatment ultimately induced the ferrostatin-1- and deferoxamine-dependent lipid peroxidation after 2 days and 8 days in PLC/PRF/5 and Huh7 cells but not in SNU475 and SK-Hep1 cells. Pre-treatment of TGF-β1 for 2 days enhanced the reduction of cell viability induced by RSL3, a GSH peroxidase 4 (GPX4) inhibitor, in PLC/PRF/5 and Huh7 cells. In conclusion, TGF-β1 represses xCT expression via Smad3 activation and enhances lipid peroxidation in hepatocellular carcinoma cells with an early TGF-β1 signature, which would benefit from the targeting of GPX4.
Loss of Rictor in tubular cells exaggerates lipopolysaccharide induced renal inflammation and acute kidney injury via Yap/Taz-NF-κB axis
Authors: Gui Yuan , Hou Qing , Lu Qingmiao , Dai Chunsun , Li Jianzhong 
Published: May 2020

AbstractOur previous study demonstrated that the mammalian target of rapamycin complex 2 (mTORC2) signaling alleviates renal inflammation and protects against cisplatin-induced AKI. However, the underlying mechanisms for mTORC2 in regulating renal inflammation in AKI remain to be determined. In this study, we found that lipopolysaccharide (LPS) could activate mTORC2 signaling in NRK-52E cells, and blockage of mTORC2 signaling led to Yap/Taz degradation, which in turn activated NF-κB signaling and induced inflammatory cytokines secretion. Overexpression of constitutively active Taz (Taz-S89A) could attenuate the inflammation-amplified role of mTORC2 blockage. In mouse models, tubule-specific deletion of Rictor had higher blood urea nitrogen level, severe morphological injury as well as more inflammatory cells accumulation compared with those in their littermate controls. Overall, these results demonstrate that mTORC2 signaling protects against renal inflammation and dictates the outcome of AKI by modulating Yap/Taz degradation.
SIRT1 directly activates autophagy in human chondrocytes
Authors: Sacitharan Pradeep K. , Bou-Gharios George , Edwards James R. 
Published: May 2020

AbstractOsteoarthritis (OA) is the most common form of arthritis worldwide with no effective treatment. Ageing is the primary risk factor for OA. We sought to investigate if there is a distinct and functional convergence of ageing-related mechanisms SIRT1 and autophagy in chondrocytes. Our results show that, levels of SIRT1 are decreased in human normal aged and OA cartilage compared with young cartilage. Moreover, silencing SIRT1 in chondrocytes lead to decreased expression of chondrogenic markers but did not alter the expression of catabolic proteases. In contrast, activation of SIRT1 increased autophagy in chondrocytes by the deacetylation of lysine residues on crucial autophagy proteins (Beclin1, ATG5, ATG7, LC3). This activation was shown to be mTOR/ULK1 independent. Our results indicate that maintenance of autophagy in chondrocytes by SIRT1 is essential for preserving cartilage integrity throughout life and therefore is a target for drug intervention to protect against OA.
Evolution and structure of clinically relevant gene fusions in multiple myeloma
Authors: Foltz Steven M. , Gao Qingsong , Yoon Christopher J. , Sun Hua , Yao Lijun , Li Yize , Jayasinghe Reyka G. , Cao Song , King Justin , Kohnen Daniel R. , Fiala Mark A. , Ding Li , Vij Ravi 
Published: May 2020

AbstractMultiple myeloma is a plasma cell blood cancer with frequent chromosomal translocations leading to gene fusions. To determine the clinical relevance of fusion events, we detect gene fusions from a cohort of 742 patients from the Multiple Myeloma Research Foundation CoMMpass Study. Patients with multiple clinic visits enable us to track tumor and fusion evolution, and cases with matching peripheral blood and bone marrow samples allow us to evaluate the concordance of fusion calls in patients with high tumor burden. We examine the joint upregulation ofWHSC1andFGFR3in samples with t(4;14)-related fusions, and we illustrate a method for detecting fusions from single cell RNA-seq. We report fusions atMYCand a neighboring gene,PVT1, which are related toMYCtranslocations and associated with divergent progression-free survival patterns. Finally, we find that 4% of patients may be eligible for targeted fusion therapies, including three with anNTRK1fusion.
The neuropeptide substance P regulates aldosterone secretion in human adrenals
Authors: Wils Julien , Duparc Céline , Cailleux Anne-Françoise , Lopez Antoine-Guy , Guiheneuf Caroline , Boutelet Isabelle , Boyer Hadrien-Gaël , Dubessy Christophe , Cherifi Saloua , Cauliez Bruno , Gobet Françoise , Defortescu Guillaume , Ménard Jean-François , Louiset Estelle , Lefebvre Hervé 
Published: May 2020

AbstractAldosterone, produced by the adrenals and under the control of plasma angiotensin and potassium levels, regulates hydromineral homeostasis and blood pressure. Here we report that the neuropeptide substance P (SP) released by intraadrenal nerve fibres, stimulates aldosterone secretion via binding to neurokinin type 1 receptors (NK1R) expressed by aldosterone-producing adrenocortical cells. The action of SP is mediated by the extracellular signal-regulated kinase pathway and involves upregulation of steroidogenic enzymes. We also conducted a prospective proof-of-concept, double blind, placebo-controlled clinical trial aimed to investigate the impact of the NK1R antagonist aprepitant on aldosterone secretion in healthy male volunteers (EudraCT: 2008-003367-40, ClinicalTrial.gov: NCT00977223). Participants received during two 7-day treatment periods aprepitant (125 mg on the 1st day and 80 mg during the following days) or placebo in a random order at a 2-week interval. The primary endpoint was plasma aldosterone levels during posture test. Secondary endpoints included basal aldosterone alterations, plasma aldosterone variation during metoclopramide and hypoglycaemia tests, and basal and stimulated alterations of renin, cortisol and ACTH during the three different stimulatory tests. The safety of the treatment was assessed on the basis of serum transaminase measurements on days 4 and 7. All pre-specified endpoints were achieved. Aprepitant decreases aldosterone production by around 30% but does not influence the aldosterone response to upright posture. These results indicate that the autonomic nervous system exerts a direct stimulatory tone on mineralocorticoid synthesis through SP, and thus plays a role in the maintenance of hydromineral homeostasis. This regulatory mechanism may be involved in aldosterone excess syndromes.
Efficient and stable tin perovskite solar cells enabled by amorphous-polycrystalline structure
Authors: Liu Xiao , Wang Yanbo , Wu Tianhao , He Xin , Meng Xiangyue , Barbaud Julien , Chen Han , Segawa Hiroshi , Yang Xudong , Han Liyuan 
Published: May 2020

AbstractTin perovskite solar cells (TPSCs) have triggered intensive research as a promising candidate for lead-free perovskite solar cells. However, it is still challenging to obtain efficient and stable TPSCs because of the low defects formation energy and the oxidation of bivalent tin; Here, we report a TPSC with a stable amorphous-polycrystalline structure, which is composed of a tin triple-halide amorphous layer and cesium-formamidinium tin iodide polycrystals. This structure effectively blocks the outside oxygen, moisture and also suppresses the ion diffusion inside the devices. In addition, its energy level benefits the charge extraction and transport in TPSCs. This design enabled us to obtain the certified quasi-steady-state efficiency over 10% for TPSCs from an accredited certification institute. The cell was stable, maintaining 95% of the initial PCE after operation at the maximum power point under AM 1.5 G simulated solar light (100 mWcm−2) for 1000 hours.
Detection of air and surface contamination by SARS-CoV-2 in hospital rooms of infected patients
Authors: Chia Po Ying , Coleman Kristen Kelli , Tan Yian Kim , Ong Sean Wei Xiang , Gum Marcus , Lau Sok Kiang , Lim Xiao Fang , Lim Ai Sim , Sutjipto Stephanie , Lee Pei Hua , Son Than The , Young Barnaby Edward , Milton Donald K. , Gray Gregory C. , Schuster Stephan , Barkham Timothy , De Partha Pratim , Vasoo Shawn , Chan Monica , Ang Brenda Sze Peng , Tan Boon Huan , Leo Yee-Sin , Ng Oon-Tek , Wong Michelle Su Yen , Marimuthu Kalisvar ,   for the Singapore 2019 Novel Coronavirus Outbreak Research Team, Lye David Chien , Lim Poh Lian , Lee Cheng Chuan , Ling Li Min , Lee Lawrence , Lee Tau Hong , Wong Chen Seong , Sadarangani Sapna , Lin Ray Junhao , Ng Deborah Hee Ling , Sadasiv Mucheli , Yeo Tsin Wen , Choy Chiaw Yee , Tan Glorijoy Shi En , Dimatatac Frederico , Santos Isais Florante , Go Chi Jong , Chan Yu Kit , Tay Jun Yang , Tan Jackie Yu-Ling , Pandit Nihar , Ho Benjamin Choon Heng , Mendis Shehara , Chen Yuan Yi Constance , Abdad Mohammad Yazid , Moses Daniela 
Published: May 2020

AbstractUnderstanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.01, χ2 test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 µm and 1–4 µm in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2.
Computational framework for a systematic investigation of anionic redox process in Li-rich compounds
Authors: Tygesen Alexander Sougaard , Chang Jin Hyun , Vegge Tejs , García-Lastra Juan Maria 
Published: May 2020

AbstractAnionic redox processes play a key role in determining the accessible capacity and cycle life of Li-rich cathode materials for batteries. We present a framework for investigating the anionic redox processes based on data readily available from standard DFT calculations. Our recipe includes a method of classifying different anionic species, counting the number of species present in the structure and a preconditioning scheme to promote anionic redox. The method is applied to a set of LixMnO3 (1 ≤ x ≤2) structures, with cationic disorder, to identify the evolution of anionic redox processes during cycling. Additionally, we investigate how different choices of exchange-correlation functionals affect the formation of anionic redox species. The preconditioning of the structures is shown to promote the formation of peroxo-like species. Furthermore, the choice of exchange-correlation functional has a large impact on the type of anionic redox species present, and thus care must be taken when considering localization in anionic species.
dbPSP 2.0, an updated database of protein phosphorylation sites in prokaryotes
Authors: Shi Ying , Zhang Ying , Lin Shaofeng , Wang Chenwei , Zhou Jiaqi , Peng Di , Xue Yu 
Published: May 2020

AbstractIn prokaryotes, protein phosphorylation plays a critical role in regulating a broad spectrum of biological processes and occurs mainly on various amino acids, including serine (S), threonine (T), tyrosine (Y), arginine (R), aspartic acid (D), histidine (H) and cysteine (C) residues of protein substrates. Through literature curation and public database integration, here we reported an updated database of phosphorylation sites (p-sites) in prokaryotes (dbPSP 2.0) that contains 19,296 experimentally identified p-sites in 8,586 proteins from 200 prokaryotic organisms, which belong to 12 phyla of two kingdoms, bacteria and archaea. To carefully annotate these phosphoproteins and p-sites, we integrated the knowledge from 88 publicly available resources that covers 9 aspects, namely, taxonomy annotation, genome annotation, function annotation, transcriptional regulation, sequence and structure information, family and domain annotation, interaction, orthologous information and biological pathway. In contrast to version 1.0 (~30 MB), dbPSP 2.0 contains ~9 GB of data, with a 300-fold increased volume. We anticipate that dbPSP 2.0 can serve as a useful data resource for further investigating phosphorylation events in prokaryotes. dbPSP 2.0 is free for all users to access at: http://dbpsp.biocuckoo.cn.
First-passage times and normal tissue complication probabilities in the limit of large populations
Authors: Hufton Peter G. , Buckingham-Jeffery Elizabeth , Galla Tobias 
Published: May 2020

AbstractThe time of a stochastic process first passing through a boundary is important to many diverse applications. However, we can rarely compute the analytical distribution of these first-passage times. We develop an approximation to the first and second moments of a general first-passage time problem in the limit of large, but finite, populations using Kramers–Moyal expansion techniques. We demonstrate these results by application to a stochastic birth-death model for a population of cells in order to develop several approximations to the normal tissue complication probability (NTCP): a problem arising in the radiation treatment of cancers. We specifically allow for interaction between cells, via a nonlinear logistic growth model, and our approximations capture the effects of intrinsic noise on NTCP. We consider examples of NTCP in both a simple model of normal cells and in a model of normal and damaged cells. Our analytical approximation of NTCP could help optimise radiotherapy planning, for example by estimating the probability of complication-free tumour under different treatment protocols.
Upconversion photoluminescence of Ho3+-Yb3+ doped barium titanate nanocrystallites: Optical tools for structural phase detection and temperature probing
Authors: Mahata Manoj Kumar , Koppe Tristan , Kumar Kaushal , Hofsäss Hans , Vetter Ulrich 
Published: May 2020

AbstractAuthors have explored the photo-physical properties of Ho3+-Yb3+ doped BaTiO3 nanocrystals and proposed an intuitive method to probe temperature and crystal phase structure of the matrix. Structural phase change of doped crystals was analyzed in terms of their X-ray diffraction, and it was confirmed through second harmonic generation. We give insights on upconversion of energy of light-emission in Ho3+-Yb3+: BaTiO3 nanocrystals upon a 980 nm laser-light excitation and subsequently, the excited state dynamics were studied with the help of dependence of upconversion luminescence on excitation power and measuring-temperature. To understand the nature of occupancies of the Ho3+ ions at the Ti- and Ba-sites, we performed site-selective, time-resolved spectroscopic measurements at various crystal phases. Based on the lifetime analysis, it is inferred that the Ho3+ ions are present at two types of sites in barium titanate lattice. One of those is the 6-coordinated Ti-site of low symmetry, while the other one is the 12-coordinated Ba-site of higher symmetry. The upconversion emission of the nanocrystals are found to be temperature-sensitive (12 to 300 K), indicating possible use as a self-referenced temperature probe. An analysis of the temperature dependent emissions from 5F4 and 5S2 levels of Ho3+ ions, gives a maximum value of temperature sensitivity ~ 0.0095 K−1 at 12 K. Furthermore, we observe a sharp change in the luminescence intensity at ~180 K due to a ferroelectric phase change of the sample. The correlation of upconversion luminescence with the results of X-ray diffraction and second harmonic generation at different crystal phases implies that the frequency upconversion may be used as a probe of structural change of the lattice.
The Effects of Tetracycline Residues on the Microbial Community Structure of Tobacco Soil in Pot Experiment
Authors: Zheng Jiayu , Zhang Jixu , Gao Lin , Kong Fanyu , Shen Guoming , Wang Rui , Gao Jiaming , Zhang Jiguang 
Published: May 2020

AbstractTo evaluate the micro-ecological effects of tetracycline residues on tobacco soil, high-throughput sequencing technology was used to study the effects of the addition of different concentrations (0, 5, 50, and 500 mg·kg−1) of tetracycline on the abundance, diversity, and structure of bacterial and fungal communities in the rhizosphere and non-rhizosphere soil of flue-cured tobacco in China. Results showed that the presence of tetracycline had an important but varying effect on soil bacterial and fungal community richness, diversity, and structure. Changes in the diversity indices (Chao index and Shannon index) of soil bacterial and fungal communities showed a similar pattern after the addition of tetracycline; however, a few differences were found in the effects of tetracycline in the rhizosphere and non-rhizosphere soil, suggesting an evident rhizosphere-specific effect. The bacterial community at the phylum level in the rhizosphere closely clustered into one group, which might be the result of tobacco root secretions and rhizodeposition. Tetracycline showed a concentration-dependent effect on the soil bacterial community structure. The soil bacterial community structures observed after treatments with higher concentrations of tetracycline (50 and 500 mg·kg−1) were found to be closely related. Moreover, the effects of the treatments with higher concentrations of tetracycline, on the soil bacterial community at the phylum level, were different from those with lower concentrations of tetracycline (5 mg·kg−1), and CK treatments. This might have resulted from the induction of increasing selective pressure with increasing antibiotic concentration. Tetracycline continued to affect the soil bacterial community throughout the experiment. Tetracycline was found to have a varying impact on the community structure of soil fungi compared to that of soil bacteria, and the addition of an intermediate concentration of tetracycline (50 mg·kg−1) significantly increased the soil fungal diversity in the non-rhizosphere soil. The biological effects of tetracycline on the soil fungal community and the fungal-bacterial interactions, therefore, require further elucidation, warranting further research.