bluuebunny/crossref_metadata_2025_split huggingface dataset:
Termite mounds contain soil-derived methanotroph communities kinetically adapted to elevated methane concentrations
Authors: Chiri Eleonora , Greening Chris , Lappan Rachael , Waite David W , Jirapanjawat Thanavit , Dong Xiyang , Arndt Stefan K , Nauer Philipp A 
Published: July 2020

Abstract
Termite mounds have recently been confirmed to mitigate approximately half of termite methane (CH4) emissions, but the aerobic CH4 oxidising bacteria (methanotrophs) responsible for this consumption have not been resolved. Here, we describe the abundance, composition and CH4 oxidation kinetics of the methanotroph communities in the mounds of three distinct termite species sampled from Northern Australia. Results from three independent methods employed show that methanotrophs are rare members of microbial communities in termite mounds, with a comparable abundance but distinct composition to those of adjoining soil samples. Across all mounds, the most abundant and prevalent methane monooxygenase sequences were affiliated with upland soil cluster α (USCα), with sequences homologous to Methylocystis and tropical upland soil cluster (TUSC) also detected. The reconstruction of a metagenome-assembled genome of a mound USCα representative highlighted the metabolic capabilities of this group of methanotrophs. The apparent Michaelis–Menten kinetics of CH4 oxidation in mounds were estimated from in situ reaction rates. Methane affinities of the communities were in the low micromolar range, which is one to two orders of magnitude higher than those of upland soils, but significantly lower than those measured in soils with a large CH4 source such as landfill cover soils. The rate constant of CH4 oxidation, as well as the porosity of the mound material, were significantly positively correlated with the abundance of methanotroph communities of termite mounds. We conclude that termite-derived CH4 emissions have selected for distinct methanotroph communities that are kinetically adapted to elevated CH4 concentrations. However, factors other than substrate concentration appear to limit methanotroph abundance and hence these bacteria only partially mitigate termite-derived CH4 emissions. Our results also highlight the predominant role of USCα in an environment with elevated CH4 concentrations and suggest a higher functional diversity within this group than previously recognised.
Exercise as a protective mechanism against the negative effects of oxidative stress in first-episode psychosis: a biomarker-led study
Authors: Fisher Emily , Wood Stephen J. , Elsworthy Richard J. , Upthegrove Rachel , Aldred Sarah 
Published: July 2020

AbstractFirst-episode psychosis (FEP) is a psychiatric disorder, characterised by positive and negative symptoms, usually emerging during adolescence and early adulthood. FEP represents an early intervention opportunity for intervention in psychosis. Redox disturbance and subsequent oxidative stress have been linked to the pathophysiology of FEP. Exercise training can perturb oxidative stress and rebalance the antioxidant system and thus represents an intervention with the potential to interact with a mechanism of disease. The aim of this study was to assess the effect of exercise on markers of redox status in FEP. Twenty-two young men were recruited from Birmingham Early Intervention services and randomised to either a 12-week exercise programme or treatment as usual (control). Measures of blood and brain glutathione (GSH), markers of oxidative damage, inflammation, neuronal health, symptomology and habitual physical activity were assessed. Exercise training was protective against changes related to continued psychosis. Symptomatically, those in the exercise group showed reductions in positive and general psychopathology, and stable negative symptoms (compared to increased negative symptoms in the control group). Peripheral GSH was increased by 5.6% in the exercise group, compared to a significant decrease (24.4%) (p = 0.04) in the control group. Exercise attenuated negative changes in markers of neuronal function (brain-derived neurotrophic factor), lipid damage (thiobarbituric acid-reactive substances) and total antioxidant capacity. C-reactive protein and tumour necrosis factor-α also decreased in the exercise group, although protein and DNA oxidation were unchanged. Moderate-intensity exercise training has the ability to elicit changes in markers of oxidative stress and antioxidant concentration, with subsequent improvements in symptoms of psychosis.
Anlotinib suppresses tumor progression via blocking the VEGFR2/PI3K/AKT cascade in intrahepatic cholangiocarcinoma
Authors: Song Fei , Hu Bo , Cheng Jian-Wen , Sun Yun-Fan , Zhou Kai-Qian , Wang Peng-Xiang , Guo Wei , Zhou Jian , Fan Jia , Chen Zhong , Yang Xin-Rong 
Published: July 2020

AbstractIntrahepatic cholangiocarcinoma (ICC) is a malignant tumor derived from bile duct epithelium. Its characteristics include an insidious onset and frequent recurrence or metastasis after surgery. Current chemotherapies and molecular target therapies provide only modest survival benefits to patients with ICC. Anlotinib is a novel multi-target tyrosine kinase inhibitor that has good antitumor effects in a variety of solid tumors. However, there are few studies of anlotinib-associated mechanisms and use as a treatment in ICC. In this study using in vitro experiments, we found that anlotinib had significant effects on proliferation inhibition, migration and invasion restraint, and cell-cycle arrestment. Anlotinib treatment affected induction of apoptosis and the mesenchymal–epithelial transition. Patient-derived xenograft models generated directly from patients with ICC revealed that anlotinib treatment dramatically hindered in vivo tumor growth. We also examined anlotinib’s mechanism of action using transcriptional profiling. We found that anlotinib treatment might mainly inhibit tumor cell proliferation and invasion and promote apoptosis via cell-cycle arrestment by inactivating the VEGF/PI3K/AKT signaling pathway, as evidenced by significantly decreased phosphorylation levels of these kinases. The activation of vascular endothelial growth factor receptor 2 (VEGFR2) can subsequently activate PI3K/AKT signaling. We identified VEGRF2 as the main target of anlotinib. High VEGFR2 expression might serve as a promising indicator when used to predict a favorable therapeutic response. Taken together, these results indicated that anlotinib had excellent antitumor activity in ICC, mainly via inhibiting the phosphorylation level of VEGFR2 and subsequent inactivation of PIK3/AKT signaling. This work provides evidence and a rationale for using anlotinib to treat patients with ICC in the future.
Crosstalk between noncoding RNAs and ferroptosis: new dawn for overcoming cancer progression
Authors: Zhang Xuefei , Wang Lingling , Li Haixia , Zhang Lei , Zheng Xiulan , Cheng Wen 
Published: July 2020

AbstractCancer progression including proliferation, metastasis, and chemoresistance has become a serious hindrance to cancer therapy. This phenomenon mainly derives from the innate insensitive or acquired resistance of cancer cells to apoptosis. Ferroptosis is a newly discovered mechanism of programmed cell death characterized by peroxidation of the lipid membrane induced by reactive oxygen species. Ferroptosis has been confirmed to eliminate cancer cells in an apoptosis-independent manner, however, the specific regulatory mechanism of ferroptosis is still unknown. The use of ferroptosis for overcoming cancer progression is limited. Noncoding RNAs have been found to play an important roles in cancer. They regulate gene expression to affect biological processes of cancer cells such as proliferation, cell cycle, and cell death. Thus far, the functions of ncRNAs in ferroptosis of cancer cells have been examined, and the specific mechanisms by which noncoding RNAs regulate ferroptosis have been partially discovered. However, there is no summary of ferroptosis associated noncoding RNAs and their functions in different cancer types. In this review, we discuss the roles of ferroptosis-associated noncoding RNAs in detail. Moreover, future work regarding the interaction between noncoding RNAs and ferroptosis is proposed, the possible obstacles are predicted and associated solutions are put forward. This review will deepen our understanding of the relationship between noncoding RNAs and ferroptosis, and provide new insights in targeting noncoding RNAs in ferroptosis associated therapeutic strategies.
Pyroptosis and ferroptosis induced by mixed lineage kinase 3 (MLK3) signaling in cardiomyocytes are essential for myocardial fibrosis in response to pressure overload
Authors: Wang Junyan , Deng Bo , Liu Qing , Huang Yusheng , Chen Weitao , Li Jing , Zhou Zheng , Zhang Lu , Liang Birong , He Jiaqi , Chen Zixin , Yan Cui , Yang Zhongqi , Xian Shaoxiang , Wang Lingjun 
Published: July 2020

AbstractChronic heart failure (CHF) is the final outcome of many cardiovascular diseases, and is a severe health issue faced by the elderly population. Mixed lineage kinase 3 (MLK3), a member of MAP3K family, is associated with aging, inflammation, oxidative stress, and related diseases, such as CHF. MLK3 has also been reported to play an important role in protecting against cardiomyocyte injury; however, its function in myocardial fibrosis is unknown. To investigate the role of MLK3 in myocardial fibrosis, we inhibited the expression of MLK3, and examined cardiac function and remodeling in TAC mice. In addition, we assessed the expression of MLK3 protein in ventricular cells and its downstream associated protein. We found that MLK3 mainly regulates NF-κB/NLRP3 signaling pathway-mediated inflammation and that pyroptosis causes myocardial fibrosis in the early stages of CHF. Similarly, MLK3 mainly regulates the JNK/p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of CHF. We also found that promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC. These results suggest the pyroptosis and ferroptosis induced by MLK3 signaling in cardiomyocytes are essential for adverse myocardial fibrosis, in response to pressure overload. Furthermore, miR-351, which has a protective effect on ventricular remodeling in heart failure caused by pressure overload, may be a key target for the regulation of MLK3.
RETRACTED ARTICLE: Upregulation of OSBPL3 by HIF1A promotes colorectal cancer progression through activation of RAS signaling pathway
Authors: Jiao Hong-li , Weng Bin-shu , Yan Shan-shan , Lin Zi-mo , Wang Shu-yang , Chen Xiao-ping , Liang Guang-hua , Li Xiao-Qing , Zhao Wei-yi , Huang Jia-Yi , Zhang Dan , Zhang Ling-jie , Han Fang-yi , Li Sheng-nan , Chen Li-jie , Zhu Jiong-hua , He Wen-feng , Ding Yan-qing , Ye Ya-ping 
Published: July 2020

AbstractOxysterol-binding protein like protein 3 (OSBPL3) has been shown involving in the development of several human cancers. However, the relationship between OSBPL3 and colorectal cancer (CRC), particularly the role of OSBPL3 in the proliferation, invasion and metastasis of CRC remains unclear. In this study, we investigated the role of OSBPL3 in CRC and found that its expression was significantly higher in CRC tissues than that in normal tissues. In addition, high expression of OSBPL3 was closely related to poor differentiation, advanced TNM stage and poor prognosis of CRC. Further experiments showed that over-expression of OSBPL3 promoted the proliferation, invasion and metastasis of CRC in vitro and in vivo models. Moreover, we revealed that OSBPL3 promoted CRC progression through activation of RAS signaling pathway. Furthermore, we demonstrated that hypoxia induced factor 1 (HIF-1A) can regulate the expression of OSBPL3 via binding to the hypoxia response element (HRE) in the promoter of OSBPL3. In summary, Upregulation of OSBPL3 by HIF1A promotes colorectal cancer progression through activation of RAS signaling pathway. This novel mechanism provides a comprehensive understanding of both OSBPL3 and the RAS signaling pathway in the progression of CRC and indicates that the HIF1A–OSBPL3–RAS axis is a potential target for early therapeutic intervention in CRC progression.
Combining PARP with ATR inhibition overcomes PARP inhibitor and platinum resistance in ovarian cancer models
Authors: Kim Hyoung , Xu Haineng , George Erin , Hallberg Dorothy , Kumar Sushil , Jagannathan Veena , Medvedev Sergey , Kinose Yasuto , Devins Kyle , Verma Priyanka , Ly Kevin , Wang Yifan , Greenberg Roger A. , Schwartz Lauren , Johnson Neil , Scharpf Robert B. , Mills Gordon B. , Zhang Rugang , Velculescu Victor E. , Brown Eric J. , Simpkins Fiona 
Published: July 2020

AbstractOvarian cancer (OVCA) inevitably acquires resistance to platinum chemotherapy and PARP inhibitors (PARPi). We show that acquisition of PARPi-resistance is accompanied by increased ATR-CHK1 activity and sensitivity to ATR inhibition (ATRi). However, PARPi-resistant cells are remarkably more sensitive to ATRi when combined with PARPi (PARPi-ATRi). Sensitivity to PARPi-ATRi in diverse PARPi and platinum-resistant models, including BRCA1/2 reversion and CCNE1-amplified models, correlate with synergistic increases in replication fork stalling, double-strand breaks, and apoptosis. Surprisingly, BRCA reversion mutations and an ability to form RAD51 foci are frequently not observed in models of acquired PARPi-resistance, suggesting the existence of alternative resistance mechanisms. However, regardless of the mechanisms of resistance, complete and durable therapeutic responses to PARPi-ATRi that significantly increase survival are observed in clinically relevant platinum and acquired PARPi-resistant patient-derived xenografts (PDXs) models. These findings indicate that PARPi-ATRi is a highly promising strategy for OVCAs that acquire resistance to PARPi and platinum.
Phase-controllable growth of ultrathin 2D magnetic FeTe crystals
Authors: Kang Lixing , Ye Chen , Zhao Xiaoxu , Zhou Xieyu , Hu Junxiong , Li Qiao , Liu Dan , Das Chandreyee Manas , Yang Jiefu , Hu Dianyi , Chen Jieqiong , Cao Xun , Zhang Yong , Xu Manzhang , Di Jun , Tian Dan , Song Pin , Kutty Govindan , Zeng Qingsheng , Fu Qundong , Deng Ya , Zhou Jiadong , Ariando Ariando , Miao Feng , Hong Guo , Huang Yizhong , Pennycook Stephen J. , Yong Ken-Tye , Ji Wei , Renshaw Wang Xiao , Liu Zheng 
Published: July 2020

AbstractTwo-dimensional (2D) magnets with intrinsic ferromagnetic/antiferromagnetic (FM/AFM) ordering are highly desirable for future spintronic devices. However, the direct growth of their crystals is in its infancy. Here we report a chemical vapor deposition approach to controllably grow layered tetragonal and non-layered hexagonal FeTe nanoplates with their thicknesses down to 3.6 and 2.8 nm, respectively. Moreover, transport measurements reveal these obtained FeTe nanoflakes show a thickness-dependent magnetic transition. Antiferromagnetic tetragonal FeTe with the Néel temperature (TN) gradually decreases from 70 to 45 K as the thickness declines from 32 to 5 nm. And ferromagnetic hexagonal FeTe is accompanied by a drop of the Curie temperature (TC) from 220 K (30 nm) to 170 K (4 nm). Theoretical calculations indicate that the ferromagnetic order in hexagonal FeTe is originated from its concomitant lattice distortion and Stoner instability. This study highlights its potential applications in future spintronic devices.
Accounting for diverse evolutionary forces reveals mosaic patterns of selection on human preterm birth loci
Authors: LaBella Abigail L. , Abraham Abin , Pichkar Yakov , Fong Sarah L. , Zhang Ge , Muglia Louis J. , Abbot Patrick , Rokas Antonis , Capra John A. 
Published: July 2020

AbstractCurrently, there is no comprehensive framework to evaluate the evolutionary forces acting on genomic regions associated with human complex traits and contextualize the relationship between evolution and molecular function. Here, we develop an approach to test for signatures of diverse evolutionary forces on trait-associated genomic regions. We apply our method to regions associated with spontaneous preterm birth (sPTB), a complex disorder of global health concern. We find that sPTB-associated regions harbor diverse evolutionary signatures including conservation, excess population differentiation, accelerated evolution, and balanced polymorphism. Furthermore, we integrate evolutionary context with molecular evidence to hypothesize how these regions contribute to sPTB risk. Finally, we observe enrichment in signatures of diverse evolutionary forces in sPTB-associated regions compared to genomic background. By quantifying multiple evolutionary forces acting on sPTB-associated regions, our approach improves understanding of both functional roles and the mosaic of evolutionary forces acting on loci. Our work provides a blueprint for investigating evolutionary pressures on complex traits.
Duplex DNA engagement and RPA oppositely regulate the DNA-unwinding rate of CMG helicase
Authors: Kose Hazal B. , Xie Sherry , Cameron George , Strycharska Melania S. , Yardimci Hasan 
Published: July 2020

AbstractA ring-shaped helicase unwinds DNA during chromosome replication in all organisms. Replicative helicases generally unwind duplex DNA an order of magnitude slower compared to their in vivo replication fork rates. However, the origin of slow DNA unwinding rates by replicative helicases and the mechanism by which other replication components increase helicase speed are unclear. Here, we demonstrate that engagement of the eukaryotic CMG helicase with template DNA at the replication fork impairs its helicase activity, which is alleviated by binding of the single-stranded DNA binding protein, RPA, to the excluded DNA strand. Intriguingly, we found that, when stalled due to interaction with the parental duplex, DNA rezipping-induced helicase backtracking reestablishes productive helicase-fork engagement, underscoring the significance of plasticity in helicase action. Our work provides a mechanistic basis for relatively slow duplex unwinding by replicative helicases and explains how replisome components that interact with the excluded DNA strand stimulate fork rates.
In vivo cell biological screening identifies an endocytic capture mechanism for T-tubule formation
Authors: Hall Thomas E. , Martel Nick , Ariotti Nicholas , Xiong Zherui , Lo Harriet P. , Ferguson Charles , Rae James , Lim Ye-Wheen , Parton Robert G. 
Published: July 2020

AbstractThe skeletal muscle T-tubule is a specialized membrane domain essential for coordinated muscle contraction. However, in the absence of genetically tractable systems the mechanisms involved in T-tubule formation are unknown. Here, we use the optically transparent and genetically tractable zebrafish system to probe T-tubule development in vivo. By combining live imaging of transgenic markers with three-dimensional electron microscopy, we derive a four-dimensional quantitative model for T-tubule formation. To elucidate the mechanisms involved in T-tubule formation in vivo, we develop a quantitative screen for proteins that associate with and modulate early T-tubule formation, including an overexpression screen of the entire zebrafish Rab protein family. We propose an endocytic capture model involving firstly, formation of dynamic endocytic tubules at transient nucleation sites on the sarcolemma, secondly, stabilization by myofibrils/sarcoplasmic reticulum and finally, delivery of membrane from the recycling endosome and Golgi complex.
A non-invasive far-red light-induced split-Cre recombinase system for controllable genome engineering in mice
Authors: Wu Jiali , Wang Meiyan , Yang Xueping , Yi Chengwei , Jiang Jian , Yu Yuanhuan , Ye Haifeng 
Published: July 2020

AbstractThe Cre-loxP recombination system is a powerful tool for genetic manipulation. However, there are widely recognized limitations with chemically inducible Cre-loxP systems, and the UV and blue-light induced systems have phototoxicity and minimal capacity for deep tissue penetration. Here, we develop a far-red light-induced split Cre-loxP system (FISC system) based on a bacteriophytochrome optogenetic system and split-Cre recombinase, enabling optogenetical regulation of genome engineering in vivo solely by utilizing a far-red light (FRL). The FISC system exhibits low background and no detectable photocytotoxicity, while offering efficient FRL-induced DNA recombination. Our in vivo studies showcase the strong organ-penetration capacity of FISC system, markedly outperforming two blue-light-based Cre systems for recombination induction in the liver. Demonstrating its strong clinical relevance, we successfully deploy a FISC system using adeno-associated virus (AAV) delivery. Thus, the FISC system expands the optogenetic toolbox for DNA recombination to achieve spatiotemporally controlled, non-invasive genome engineering in living systems.
Highly compressible and anisotropic lamellar ceramic sponges with superior thermal insulation and acoustic absorption performances
Authors: Jia Chao , Li Lei , Liu Ying , Fang Ben , Ding He , Song Jianan , Liu Yibo , Xiang Kejia , Lin Sen , Li Ziwei , Si Wenjie , Li Bo , Sheng Xing , Wang Dongze , Wei Xiaoding , Wu Hui 
Published: July 2020

AbstractAdvanced ceramic sponge materials with temperature-invariant high compressibility are urgently needed as thermal insulators, energy absorbers, catalyst carriers, and high temperature air filters. However, the application of ceramic sponge materials is severely limited due to their complex preparation process. Here, we present a facile method for large-scale fabrication of highly compressible, temperature resistant SiO2-Al2O3 composite ceramic sponges by blow spinning and subsequent calcination. We successfully produce anisotropic lamellar ceramic sponges with numerous stacked microfiber layers and density as low as 10 mg cm−3. The anisotropic lamellar ceramic sponges exhibit high compression fatigue resistance, strain-independent zero Poisson’s ratio, robust fire resistance, temperature-invariant compression resilience from −196 to 1000 °C, and excellent thermal insulation with a thermal conductivity as low as 0.034 W m−1 K−1. In addition, the lamellar structure also endows the ceramic sponges with excellent sound absorption properties, representing a promising alternative to existing thermal insulation and acoustic absorption materials.
Differential expression of tissue-restricted antigens among mTEC is associated with distinct autoreactive T cell fates
Authors: Lebel Marie-Ève , Coutelier Marie , Galipeau Maria , Kleinman Claudia L. , Moon James J. , Melichar Heather J. 
Published: July 2020

AbstractMedullary thymic epithelial cells (mTEC) contribute to the development of T cell tolerance by expressing and presenting tissue-restricted antigens (TRA), so that developing T cells can assess the self-reactivity of their antigen receptors prior to leaving the thymus. mTEC are a heterogeneous population of cells that differentially express TRA. Whether mTEC subsets induce distinct autoreactive T cell fates remains unclear. Here, we establish bacterial artificial chromosome (BAC)-transgenic mouse lines with biased mTEClo or mTEChi expression of model antigens. The transgenic lines support negative selection of antigen-specific thymocytes depending on antigen dose. However, model antigen expression predominantly by mTEClo supports TCRαβ+ CD8αα intraepithelial lymphocyte development; meanwhile, mTEChi-restricted expression preferentially induces Treg differentiation of antigen-specific cells in these models to impact control of infectious agents and tumor growth. In summary, our data suggest that mTEC subsets may have a function in directing distinct mechanisms of T cell tolerance.