bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncovering the hidden diversity of litter-decomposition mechanisms in mushroom-forming fungi
Authors: Floudas Dimitrios , Bentzer Johan , Ahrén Dag , Johansson Tomas , Persson Per , Tunlid Anders 
Published: May 2020

Abstract
Litter decomposing Agaricales play key role in terrestrial carbon cycling, but little is known about their decomposition mechanisms. We assembled datasets of 42 gene families involved in plant-cell-wall decomposition from seven newly sequenced litter decomposers and 35 other Agaricomycotina members, mostly white-rot and brown-rot species. Using sequence similarity and phylogenetics, we split the families into phylogroups and compared their gene composition across nutritional strategies. Subsequently, we used Raman spectroscopy to examine the ability of litter decomposers, white-rot fungi, and brown-rot fungi to decompose crystalline cellulose. Both litter decomposers and white-rot fungi share the enzymatic cellulose decomposition, whereas brown-rot fungi possess a distinct mechanism that disrupts cellulose crystallinity. However, litter decomposers and white-rot fungi differ with respect to hemicellulose and lignin degradation phylogroups, suggesting adaptation of the former group to the litter environment. Litter decomposers show high phylogroup diversity, which is indicative of high functional versatility within the group, whereas a set of white-rot species shows adaptation to bulk-wood decomposition. In both groups, we detected species that have unique characteristics associated with hitherto unknown adaptations to diverse wood and litter substrates. Our results suggest that the terms white-rot fungi and litter decomposers mask a much larger functional diversity.
The untapped potential of ascites in ovarian cancer research and treatment
Authors: Ford Caroline Elizabeth , Werner Bonnita , Hacker Neville Frederick , Warton Kristina 
Published: May 2020

AbstractThe build-up of fluid in the peritoneal cavity—ascites—is a hallmark of ovarian cancer, the most lethal of all gynaecological malignancies. This remarkable fluid, which contains a variety of cellular and acellular components, is known to contribute to patient morbidity and mortality by facilitating metastasis and contributing to chemoresistance, but remains largely under-researched. In this review, we will critically analyse the evidence associating ascites with metastasis and chemoresistance in ovarian cancer and provide an update on research in the field. We will argue the case for ascites as a unique and accessible substrate for tracking tumour progression and for translational research that will enhance our understanding of this cancer and lead to improvements in patient outcomes.
Does multiparametric imaging with 18F-FDG-PET/MRI capture spatial variation in immunohistochemical cancer biomarkers in head and neck squamous cell carcinoma?
Authors: Rasmussen Jacob H. , Olin Anders , Lelkaitis Giedrius , Hansen Adam E. , Andersen Flemming L. , Johannesen Helle H. , Kjær Andreas , Vogelius Ivan R. , Specht Lena , Bentzen Søren M. , Wessel Irene , von Buchwald Christian , Fischer Barbara M. 
Published: May 2020

Abstract
Background
The purpose of this study is to test if functional multiparametric imaging with 18F-FDG-PET/MRI correlates spatially with immunohistochemical biomarker status within a lesion of head and neck squamous cell carcinoma (HNSCC), and also whether a biopsy with the highest FDG uptake was more likely to have the highest PD-L1 expression or the highest percentage of vital tumour cells (VTC) compared with a random biopsy.

Methods
Thirty-one patients with HNSCC were scanned on an integrated PET/MRI scanner with FDG prior to surgery in this prospective study. Imaging was quantified with SUV, ADC and Ktrans. A 3D-morphometric MRI scan of the specimen was used to co-register the patient and the specimen scans. All specimens were sectioned in consecutive slices, and slices from six different locations were selected randomly from each tumour. Core biopsies were performed to construct TMA blocks for IHC staining with the ten predefined biomarkers. The spatial correlation was assessed with a partial correlation analysis.

Results
Twenty-eight patients with a total of 33 lesions were eligible for further analysis. There were significant correlations between the three imaging biomarkers and some of the IHC biomarkers. Moreover, a biopsy taken from the most FDG-avid part of the tumour did not have a statistically significantly higher probability of higher PD-L1 expression or VTC, compared with a random biopsy.

Conclusion
We found statistically significant correlations between functional imaging parameters and key molecular cancer markers.
SOX1 promotes differentiation of nasopharyngeal carcinoma cells by activating retinoid metabolic pathway
Authors: Lei Xin-Xing , Liu Yun , Wang Jin-Xing , Cai Qian , Yan Min , He Hui-Ping , Liu Quentin , Long Zi-Jie , Guan Zhong 
Published: May 2020

AbstractUndifferentiation is a key feature of nasopharyngeal carcinoma (NPC), which presents as a unique opportunity for intervention by differentiation therapy. In this study, we found that SOX1 inhibited proliferation, promoted differentiation, and induced senescence of NPC cells, which depended on its transcriptional function. RNA-Seq-profiling analysis showed that multiple undifferentiated markers of keratin family, including KRT5, KRT13, and KRT19, were reduced in SOX1 overexpressed NPC cells. Interestingly, gene ontology (GO) analysis revealed genes in SOX1 overexpressed cells were enriched in extracellular functions. The data of LC/MS untargeted metabolomics showed that the content of retinoids in SOX1 overexpressed cells and culture medium was both higher than that in the control group. Subsequently, we screened mRNA level of genes in retinoic acid (RA) signaling or metabolic pathway and found that the expression of UDP-glucuronosyltransferases was significantly decreased. Furtherly, UGT2B7 could rescue the differentiation induced by SOX1 overexpression. Inhibition of UGTs by demethylzeylasteral (T-96) could mimic SOX1 to promote the differentiation of NPC cells. Thus, we described a mechanism by which SOX1 regulated the differentiation of NPC cells by activating retinoid metabolic pathway, providing a potential target for differentiation therapy of NPC.
The USP10-HDAC6 axis confers cisplatin resistance in non-small cell lung cancer lacking wild-type p53
Authors: Hu Chen , Zhang Mu , Moses Niko , Hu Cong-li , Polin Lisa , Chen Wei , Jang Hyejeong , Heyza Joshua , Malysa Agnes , Caruso Joseph A. , Xiang Shengyan , Patrick Steve , Stemmer Paul , Lou Zhenkun , Bai Wenlong , Wang Chuangui , Bepler Gerold , Zhang Xiaohong Mary 
Published: May 2020

Abstract
Ubiquitin-specific peptidase 10 (USP10) stabilizes both tumor suppressors and oncogenes in a context-dependent manner. However, the nature of USP10’s role in non-small cell lung cancer (NSCLC) remains unclear. By analyzing The Cancer Genome Atlas (TCGA) database, we have shown that high levels of USP10 are associated with poor overall survival in NSCLC with mutant p53, but not with wild-type p53. Consistently, genetic depletion or pharmacological inhibition of USP10 dramatically reduces the growth of lung cancer xenografts lacking wild-type p53 and sensitizes them to cisplatin. Mechanistically, USP10 interacts with, deubiquitinates, and stabilizes oncogenic protein histone deacetylase 6 (HDAC6). Furthermore, reintroducing either USP10 or HDAC6 into a USP10-knockdown NSCLC H1299 cell line with null-p53 renders cisplatin resistance. This result suggests the existence of a “USP10-HDAC6-cisplatin resistance” axis. Clinically, we have found a positive correlation between USP10 and HDAC6 expression in a cohort of NSCLC patient samples. Moreover, we have shown that high levels of USP10 mRNA correlate with poor overall survival in a cohort of advanced NSCLC patients who received platinum-based chemotherapy. Overall, our studies suggest that USP10 could be a potential biomarker for predicting patient response to platinum, and that targeting USP10 could sensitize lung cancer patients lacking wild-type p53 to platinum-based therapy.
CRIF1 overexpression facilitates tumor growth and metastasis through inducing ROS/NFκB pathway in hepatocellular carcinoma
Authors: Chang Hulin , Li Juntang , Qu Kai , Wan Yong , Liu Sinan , Zheng Wei , Zhang Zhiyong , Liu Chang 
Published: May 2020

ABSTRACTCR6-interacting factor 1 (Crif1) is a mitochondrial protein which is required for the assembly of oxidative phosphorylation (OXPHOS) complexes. Our bioinformatics analysis based on Cancer Genome Atlas (TCGA) database revealed an aberrant overexpression of CRIF1 in hepatocellular carcinoma (HCC). However, the clinical significance and biological functions of CRIF1 are still unclear in this malignancy. Here, we report that CRIF1 is frequently overexpressed in HCC cells mainly due to the downregulation of miR-497-5p, which is associated with poor prognosis of patients with HCC. CRIF1-promoted HCC growth and metastasis by suppressing cell apoptosis and inducing cell cycle progression and epithelial to mesenchymal transition (EMT). Mechanistically, increased mitochondrial ROS production and consequently activation of the NFκB signaling pathway was found to be involved in the promotion of growth and metastasis by CRIF1 in HCC cells. In summary, CRIF1 plays an oncogenic role in HCC progression through activating ROS/NFKB pathway, implying CRIF1 as a potential prognostic factor and therapeutic target in HCC.
ZHX2 drives cell growth and migration via activating MEK/ERK signal and induces Sunitinib resistance by regulating the autophagy in clear cell Renal Cell Carcinoma
Authors: Zhu Liangsong , Ding Rong , Yan Hao , Zhang Jin , Lin Zongming 
Published: May 2020

AbstractZinc fingers and homeoboxes 2 (ZHX2) was found as a novel VHL substrate target, and acted as an oncogenic driver in ccRCC. However, the detailed mechanism of ZHX2 in ccRCC development remains elusive, and no research has focused on studying ZHX2 in drug resistance yet. A tissue microarray with 358 ccRCC samples was used to determine the expression of ZHX2 in ccRCC patients. VHL-deficient cell line 786-O and VHL-normal cell line CAKI-1 was used for lineage reprogramming by transfecting with lentivirus. The in vitro and in vivo experiments were performed with these new cell lines to determine the mechanism of ZHX2 in ccRCC development and drug resistance. Immunohistochemistry analysis showed that ZHX2 was not highly expressed in ccRCC tumor tissues, only 33.2% (119/358) patients have high ZHX2 expression. However, high ZHX2 was significantly associated with advanced Fuhrman grade (p = 0.004), and proved to be an independent prognosis factor for progression-free survival (p = 0.0003), while there is no significant correlation with overall survival. We further discovered that ZHX2 overexpression could increase VEGF secretion and transcriptional activate the MEK/ERK1/2 and promote its downstream targets. We also found ZHX2 overexpression induce Sunitinib resistance though activating autophagy and the combination treatment of Sunitinib and Chloroquine could significantly rescue the phenomenon. In summary, these results indicate that ZHX2 drivers cell growth, migration though increase VEGF expression, and transcriptional activate MEK/ERK1/2 signaling pathway, and could induce Sunitinib resistance by regulating self-protective autophagy, these may provide new insight in advanced ccRCC treatment.
Differential effectiveness of tyrosine kinase inhibitors in 2D/3D culture according to cell differentiation, p53 status and mitochondrial respiration in liver cancer cells
Authors: Rodríguez-Hernández María A. , Chapresto-Garzón Raquel , Cadenas Miryam , Navarro-Villarán Elena , Negrete María , Gómez-Bravo Miguel A. , Victor Victor M. , Padillo Francisco J. , Muntané Jordi 
Published: May 2020

AbstractSorafenib and Regorafenib are the recommended first- and second-line therapies in patients with advanced hepatocellular carcinoma (HCC). Lenvatinib and Cabozantinib have shown non-inferior antitumoral activities compared with the corresponding recommended therapies. The clinical trials have established recommended doses for each treatment that lead different blood concentrations in patients for Sorafenib (10 µM), Regorafenib (1 µM), Lenvatinib (0.1 µM), and Cabozantinib (1 µM). However, very low response rates are observed in patients attributed to intrinsic resistances or upregulation of survival signaling. The aim of the study was the comparative dose–response analysis of the drugs (0–100 µM) in well-differentiated (HepG2, Hep3B, and Huh7), moderately (SNU423), and poorly (SNU449) differentiated liver cancer cells in 2D/3D cultures. Cells harbors wild-type p53 (HepG2), non-sense p53 mutation (Hep3B), inframe p53 gene deletion (SNU423), and p53 point mutation (Huh7 and SNU449). The administration of regular used in vitro dose (10 µM) in 3D and 2D cultures, as well as the dose–response analysis in 2D cultures showed Sorafenib and Regorafenib were increasingly effective in reducing cell proliferation, and inducing apoptosis in well-differentiated and expressing wild-type p53 in HCC cells. Lenvatinib and Cabozantinib were particularly effective in moderately to poorly differentiated cells with mutated or lacking p53 that have lower basal oxygen consumption rate (OCR), ATP, and maximal respiration capacity than observed in differentiated HCC cells. Sorafenib and Regorafenib downregulated, and Lenvatinib and Cabozantinib upregulated epidermal growth factor receptor (EGFR) and mesenchymal–epithelial transition factor receptor (c-Met) in HepG2 cells. Conclusions: Sorafenib and Regorafenib were especially active in well-differentiated cells, with wild-type p53 and increased mitochondrial respiration. By contrast, Lenvatinib and Cabozantinib appeared more effective in moderately to poorly differentiated cells with mutated p53 and low mitochondrial respiration. The development of strategies that allow us to deliver increased doses in tumors might potentially enhance the effectiveness of the treatments.
Electron tunneling of hierarchically structured silver nanosatellite particles for highly conductive healable nanocomposites
Authors: Suh Daewoo , Faseela K. P. , Kim Wonjoon , Park Chanyong , Lim Jang Gyun , Seo Sungwon , Kim Moon Ki , Moon Hyungpil , Baik Seunghyun 
Published: May 2020

AbstractHealable conductive materials have received considerable attention. However, their practical applications are impeded by low electrical conductivity and irreversible degradation after breaking/healing cycles. Here we report a highly conductive completely reversible electron tunneling-assisted percolation network of silver nanosatellite particles for putty-like moldable and healable nanocomposites. The densely and uniformly distributed silver nanosatellite particles with a bimodal size distribution are generated by the radical and reactive oxygen species-mediated vigorous etching and reduction reaction of silver flakes using tetrahydrofuran peroxide in a silicone rubber matrix. The close work function match between silicone and silver enables electron tunneling between nanosatellite particles, increasing electrical conductivity by ~5 orders of magnitude (1.02×103 Scm−1) without coalescence of fillers. This results in ~100% electrical healing efficiency after 1000 breaking/healing cycles and stability under water immersion and 6-month exposure to ambient air. The highly conductive moldable nanocomposite may find applications in improvising and healing electrical parts.
Analysis of cardiac magnetic resonance imaging in 36,000 individuals yields genetic insights into dilated cardiomyopathy
Authors: Pirruccello James P. , Bick Alexander , Wang Minxian , Chaffin Mark , Friedman Samuel , Yao Jie , Guo Xiuqing , Venkatesh Bharath Ambale , Taylor Kent D. , Post Wendy S. , Rich Stephen , Lima Joao A. C. , Rotter Jerome I. , Philippakis Anthony , Lubitz Steven A. , Ellinor Patrick T. , Khera Amit V. , Kathiresan Sekar , Aragam Krishna G. 
Published: May 2020

AbstractDilated cardiomyopathy (DCM) is an important cause of heart failure and the leading indication for heart transplantation. Many rare genetic variants have been associated with DCM, but common variant studies of the disease have yielded few associated loci. As structural changes in the heart are a defining feature of DCM, we report a genome-wide association study of cardiac magnetic resonance imaging (MRI)-derived left ventricular measurements in 36,041 UK Biobank participants, with replication in 2184 participants from the Multi-Ethnic Study of Atherosclerosis. We identify 45 previously unreported loci associated with cardiac structure and function, many near well-established genes for Mendelian cardiomyopathies. A polygenic score of MRI-derived left ventricular end systolic volume strongly associates with incident DCM in the general population. Even among carriers of TTN truncating mutations, this polygenic score influences the size and function of the human heart. These results further implicate common genetic polymorphisms in the pathogenesis of DCM.
Structural basis for Ca2+-dependent activation of a plant metacaspase
Authors: Zhu Ping , Yu Xiao-Hong , Wang Cheng , Zhang Qingfang , Liu Wu , McSweeney Sean , Shanklin John , Lam Eric , Liu Qun 
Published: May 2020

AbstractPlant metacaspases mediate programmed cell death in development, biotic and abiotic stresses, damage-induced immune response, and resistance to pathogen attack. Most metacaspases require Ca2+ for their activation and substrate processing. However, the Ca2+-dependent activation mechanism remains elusive. Here we report the crystal structures of Metacaspase 4 from Arabidopsis thaliana (AtMC4) that modulates Ca2+-dependent, damage-induced plant immune defense. The AtMC4 structure exhibits an inhibitory conformation in which a large linker domain blocks activation and substrate access. In addition, the side chain of Lys225 in the linker domain blocks the active site by sitting directly between two catalytic residues. We show that the activation of AtMC4 and cleavage of its physiological substrate involve multiple cleavages in the linker domain upon activation by Ca2+. Our analysis provides insight into the Ca2+-dependent activation of AtMC4 and lays the basis for tuning its activity in response to stresses for engineering of more sustainable crops for food and biofuels.
Drought and climate change impacts on cooling water shortages and electricity prices in Great Britain
Authors: Byers Edward A. , Coxon Gemma , Freer Jim , Hall Jim W. 
Published: May 2020

AbstractThe risks of cooling water shortages to thermo-electric power plants are increasingly studied as an important climate risk to the energy sector. Whilst electricity transmission networks reduce the risks during disruptions, more costly plants must provide alternative supplies. Here, we investigate the electricity price impacts of cooling water shortages on Britain’s power supplies using a probabilistic spatial risk model of regional climate, hydrological droughts and cooling water shortages, coupled with an economic model of electricity supply, demand and prices. We find that on extreme days (p99), almost 50% (7GWe) of freshwater thermal capacity is unavailable. Annualized cumulative costs on electricity prices range from £29–66m.yr-1 GBP2018, whilst in 20% of cases from £66-95m.yr-1. With climate change, the median annualized impact exceeds £100m.yr-1. The single year impacts of a 1-in-25 year event exceed >£200m, indicating the additional investments justifiable to mitigate the 1st-order economic risks of cooling water shortage during droughts.
Iron-mediated organic matter decomposition in humid soils can counteract protection
Authors: Chen Chunmei , Hall Steven J. , Coward Elizabeth , Thompson Aaron 
Published: May 2020

AbstractSoil organic matter (SOM) is correlated with reactive iron (Fe) in humid soils, but Fe also promotes SOM decomposition when oxygen (O2) becomes limited. Here we quantify Fe-mediated OM protection vs. decomposition by adding 13C dissolved organic matter (DOM) and 57FeII to soil slurries incubated under static or fluctuating O2. We find Fe uniformly protects OM only under static oxic conditions, and only when Fe and DOM are added together: de novo reactive FeIII phases suppress DOM and SOM mineralization by 35 and 47%, respectively. Conversely, adding 57FeII alone increases SOM mineralization by 8% following oxidation to 57FeIII. Under O2 limitation, de novo reactive 57FeIII phases are preferentially reduced, increasing anaerobic mineralization of DOM and SOM by 74% and 32‒41%, respectively. Periodic O2 limitation is common in humid soils, so Fe does not intrinsically protect OM; rather reactive Fe phases require their own physiochemical protection to contribute to OM persistence.
Somatic mTOR mutation in clonally expanded T lymphocytes associated with chronic graft versus host disease
Authors: Kim Daehong , Park Giljun , Huuhtanen Jani , Lundgren Sofie , Khajuria Rajiv K. , Hurtado Ana M. , Muñoz-Calleja Cecilia , Cardeñoso Laura , Gómez-García de Soria Valle , Chen-Liang Tzu Hua , Eldfors Samuli , Ellonen Pekka , Hannula Sari , Kankainen Matti , Bruck Oscar , Kreutzman Anna , Salmenniemi Urpu , Lönnberg Tapio , Jerez Andrés , Itälä-Remes Maija , Myllymäki Mikko , Keränen Mikko A. I. , Mustjoki Satu 
Published: May 2020

AbstractGraft versus host disease (GvHD) is the main complication of allogeneic hematopoietic stem cell transplantation (HSCT). Here we report studies of a patient with chronic GvHD (cGvHD) carrying persistent CD4+ T cell clonal expansion harboring somatic mTOR, NFKB2, and TLR2 mutations. In the screening cohort (n = 134), we detect the mTOR P2229R kinase domain mutation in two additional cGvHD patients, but not in healthy or HSCT patients without cGvHD. Functional analyses of the mTOR mutation indicate a gain-of-function alteration and activation of both mTORC1 and mTORC2 signaling pathways, leading to increased cell proliferation and decreased apoptosis. Single-cell RNA sequencing and real-time impedance measurements support increased cytotoxicity of mutated CD4+ T cells. High throughput drug-sensitivity testing suggests that mutations induce resistance to mTOR inhibitors, but increase sensitivity for HSP90 inhibitors. Our findings imply that somatic mutations may contribute to aberrant T cell proliferations and persistent immune activation in cGvHD, thereby paving the way for targeted therapies.
Fundamental electronic structure and multiatomic bonding in 13 biocompatible high-entropy alloys
Authors: Ching Wai-Yim , San Saro , Brechtl Jamieson , Sakidja Ridwan , Zhang Miqin , Liaw Peter K. 
Published: May 2020

AbstractHigh-entropy alloys (HEAs) have attracted great attention due to their many unique properties and potential applications. The nature of interatomic interactions in this unique class of complex multicomponent alloys is not fully developed or understood. We report a theoretical modeling technique to enable in-depth analysis of their electronic structures and interatomic bonding, and predict HEA properties based on the use of the quantum mechanical metrics, the total bond order density (TBOD) and the partial bond order density (PBOD). Application to 13 biocompatible multicomponent HEAs yields many new and insightful results, including the inadequacy of using the valence electron count, quantification of large lattice distortion, validation of mechanical properties with experiment data, modeling porosity to reduce Young’s modulus. This work outlines a road map for the rational design of HEAs for biomedical applications.