bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microenvironment inflammatory infiltrate drives growth speed and outcome of hepatocellular carcinoma: a prospective clinical study
Authors: Critelli Rosina , Milosa Fabiola , Faillaci Francesca , Condello Rosario , Turola Elena , Marzi Luca , Lei Barbara , Dituri Francesco , Andreani Silvia , Sighinolfi Pamela , Manni Paola , Maiorana Antonino , Caporali Cristian , di Benedetto Fabrizio , Del Buono Mariagrazia , De Maria Nicola , Schepis Filippo , Martinez-Chantar Maria-Luz , Giannelli Gianluigi , Villa Erica 
Published: August 2017

AbstractIn HCC, tumor microenvironment, heavily influenced by the underlying chronic liver disease, etiology and stage of the tissue damage, affects tumor progression and determines the high heterogeneity of the tumor. Aim of this study was to identify the circulating and tissue components of the microenvironment immune-mediated response affecting the aggressiveness and the ensuing clinical outcome. We analyzed the baseline paired HCC and the surrounding tissue biopsies from a prospective cohort of 132 patients at the first diagnosis of HCC for immunolocalization of PD-1/PD-L1, FoxP3, E-cadherin, CLEC2 and for a panel of 82 microRNA associated with regulation of angiogenesis, cell proliferation, cell signaling, immune control and autophagy. Original microarray data were also explored. Serum samples were analyzed for a panel of 19 cytokines. Data were associated with biochemical data, histopathology and survival. Patients with a more aggressive disease and shorter survival, who we named fast-growing accordingly to the tumor doubling time, at presentation had significantly higher AFP levels, TGF-β1 and Cyphra 21-1 levels. Transcriptomic analysis evidenced a significant downregulation of CLEC2 and upregulation of several metalloproteinases. A marked local upregulation of both PD-1 and PD-L1, a concomitant FoxP3-positive lymphocytic infiltrate, a loss of E-cadherin, gain of epithelial–mesenchymal transition (EMT) phenotype and extreme poor differentiation at histology were also present. Upregulated microRNA in fast-growing HCCs are associated with TGF-β signaling, angiogenesis and inflammation. Our data show that fast HCCs are characterized not only by redundant neo-angiogenesis but also by unique features of distinctively immunosuppressed microenvironment, prominent EMT, and clear-cut activation of TGFβ1 signaling in a general background of long-standing and permanent inflammatory state.
Doxorubicin upregulates CXCR4 via miR-200c/ZEB1-dependent mechanism in human cardiac mesenchymal progenitor cells
Authors: Beji Sara , Milano Giuseppina , Scopece Alessandro , Cicchillitti Lucia , Cencioni Chiara , Picozza Mario , D'Alessandra Yuri , Pizzolato Sarah , Bertolotti Matteo , Spaltro Gabriella , Raucci Angela , Piaggio Giulia , Pompilio Giulio , Capogrossi Maurizio C , Avitabile Daniele , Magenta Alessandra , Gambini Elisa 
Published: August 2017

AbstractDoxorubicin (DOXO) treatment is limited by its cardiotoxicity, since it causes cardiac-progenitor-cell depletion. Although the cardioprotective role of the stromal cell-derived factor-1/C-X-C chemokine receptor type 4 (SDF1/CXCR4) axis is well established, its involvement during DOXO-induced cardiotoxicity has never been investigated. We showed that in a mouse model of DOXO-induced cardiomyopathy, CXCR4+ cells were increased in response to DOXO, mainly in human cardiac mesenchymal progenitor cells (CmPC), a subpopulation with regenerative potential. Our in vitro results showed a CXCR4 induction after 24 h of DOXO exposure in CmPC. SDF1 administration protected from DOXO-induced cell death and promoted CmPC migration. CXCR4 promoter analysis revealed zinc finger E-box binding homeobox 1 (ZEB1) binding sites. Upon DOXO treatment, ZEB1 binding decreased and RNA-polymerase-II increased, suggesting a DOXO-mediated transcriptional increase in CXCR4. Indeed, DOXO induced the upregulation of miR-200c, that directly targets ZEB1. SDF1 administration in DOXO-treated mice partially reverted the adverse remodeling, decreasing left ventricular (LV) end diastolic volume, LV ejection fraction and LV anterior wall thickness in diastole, recovering LV end systolic pressure and reducing±dP/dt. Moreover, in vivo administration of SDF1 partially reverted DOXO-induced miR-200c and p53 protein upregulation in mouse hearts. In addition, downmodulation of ZEB1 mRNA and protein by DOXO was significantly increased by SDF1. In keeping, p21 mRNA, that is induced by p53 and inhibited by ZEB1, is induced by DOXO treatment and is decreased by SDF1 administration. This study showed new players of the DOXO-induced cardiotoxicity, that can be exploited to ameliorate DOXO-associated cardiomyopathy.
Apelin involved in progression of diabetic nephropathy by inhibiting autophagy in podocytes
Authors: Liu Yu , Zhang Jia , Wang Yangjia , Zeng Xiangjun 
Published: August 2017

AbstractPodocyte autophagy dysfunction has been reported to be responsible for the progression of diabetic nephropathy (DN), however, the factors contributed to autophagy dysfunction in type 2 diabetes are not fully understood. Among promoting factors in DN, an adipokine, apelin, had been showed to trigger podocyte dysfunction. Therefore, it is hypothesized that apelin, which is increased in plasma in type 2 diabetes, lead to podocyte apoptosis through inhibiting podocyte autophagy, which resulted in podocyte dysfunction followed by DN. KkAy mice (diabetic mice) and cultured podocytes (MPC5 cells and native podocytes) were treated with high glucose (HG) and apelin or its antagonist F13A. Renal function, podocyte autophagy, podocyte apoptosis and corresponding cell signaling pathways in podocytes were detected. The results showed that apelin aggravated the renal dysfunction and foot process injuries in kkAy mice, which is positively correlated to podocyte apoptosis and negatively correlated to podocyte autophagy. Apelin induced podocyte apoptosis and inhibited podocyte autophagy in both normal glucose and HG conditions while F13A reversed these effects. Investigations by western blot found that apelin inhibits podocyte autophagy through ERK-, Akt- and mTOR-dependent pathways. In conclusion, increased apelin concentration in plasma inhibited podocyte autophagy, which would lead to podocyte apoptosis and renal dysfunction in diabetes. These effects would contribute to the progression of DN.
Mycobacterium abscessus glycopeptidolipids inhibit macrophage apoptosis and bacterial spreading by targeting mitochondrial cyclophilin D
Authors: Whang Jake , Back Yong Woo , Lee Kang-In , Fujiwara Nagatoshi , Paik Seungwha , Choi Chul Hee , Park Jeong-Kyu , Kim Hwa-Jung 
Published: August 2017

AbstractMycobacterium abscessus (MAB) is a species of nontuberculous mycobacteria (NTM) and a major causative pathogen of pulmonary diseases especially in patients with cystic fibrosis. MAB infection is notoriously difficult to treat because of its intrinsic or inducible resistance to most antibiotics. The rough (R) morphotype of MAB, lacking cell surface glycopeptidolipids (GPLs), is associated with more severe and persistent infection than the smooth (S) type; however, the mechanisms underlying the R type’s virulence and the relation with GPLs remain unclear. In this study, we found that R-type MAB is much more proapoptotic than the S type, as a result of GPL-mediated inhibition of macrophage apoptosis. Polar GPLs inhibited an apoptotic response (induced by proapoptotic stimuli) by suppressing ROS production and the cytochrome c release and by preserving mitochondrial transmembrane potential. Furthermore, GPLs were found to be targeted to mitochondria and interacted with cyclophilin D; their acetylation was essential for this interaction. Finally, GPLs inhibited the intracellular growth and bacterial spreading of R-type MAB among macrophages via apoptosis inhibition. These findings suggest that GPLs limit MAB virulence by inhibiting apoptosis and the spread of bacteria and therefore provide a novel insight into the mechanism underlying virulence of MAB.
Hydrologic resilience and Amazon productivity
Authors: Ahlström Anders , Canadell Josep G. , Schurgers Guy , Wu Minchao , Berry Joseph A. , Guan Kaiyu , Jackson Robert B. 
Published: August 2017

AbstractThe Amazon rainforest is disproportionately important for global carbon storage and biodiversity. The system couples the atmosphere and land, with moist forest that depends on convection to sustain gross primary productivity and growth. Earth system models that estimate future climate and vegetation show little agreement in Amazon simulations. Here we show that biases in internally generated climate, primarily precipitation, explain most of the uncertainty in Earth system model results; models, empirical data and theory converge when precipitation biases are accounted for. Gross primary productivity, above-ground biomass and tree cover align on a hydrological relationship with a breakpoint at ~2000 mm annual precipitation, where the system transitions between water and radiation limitation of evapotranspiration. The breakpoint appears to be fairly stable in the future, suggesting resilience of the Amazon to climate change. Changes in precipitation and land use are therefore more likely to govern biomass and vegetation structure in Amazonia.
Biosynthesis of ilamycins featuring unusual building blocks and engineered production of enhanced anti-tuberculosis agents
Authors: Ma Junying , Huang Hongbo , Xie Yunchang , Liu Zhiyong , Zhao Jin , Zhang Chunyan , Jia Yanxi , Zhang Yun , Zhang Hua , Zhang Tianyu , Ju Jianhua 
Published: August 2017

AbstractTuberculosis remains one of the world’s deadliest communicable diseases, novel anti-tuberculosis agents are urgently needed due to severe drug resistance and the co-epidemic of tuberculosis/human immunodeficiency virus. Here, we show the isolation of six anti-mycobacterial ilamycin congeners (1–6) bearing rare L-3-nitro-tyrosine and L-2-amino-4-hexenoic acid structural units from the deep sea-derived Streptomyces atratus SCSIO ZH16. The biosynthesis of the rare L-3-nitrotyrosine and L-2-amino-4-hexenoic acid units as well as three pre-tailoring and two post-tailoring steps are probed in the ilamycin biosynthetic machinery through a series of gene inactivation, precursor chemical complementation, isotope-labeled precursor feeding experiments, as well as structural elucidation of three intermediates (6–8) from the respective mutants. Most impressively, ilamycins E1/E2, which are produced in high titers by a genetically engineered mutant strain, show very potent anti-tuberculosis activity with an minimum inhibitory concentration value ≈9.8 nM to Mycobacterium tuberculosis H37Rv constituting extremely potent and exciting anti-tuberculosis drug leads.
High-quality monolayer superconductor NbSe2 grown by chemical vapour deposition
Authors: Wang Hong , Huang Xiangwei , Lin Junhao , Cui Jian , Chen Yu , Zhu Chao , Liu Fucai , Zeng Qingsheng , Zhou Jiadong , Yu Peng , Wang Xuewen , He Haiyong , Tsang Siu Hon , Gao Weibo , Suenaga Kazu , Ma Fengcai , Yang Changli , Lu Li , Yu Ting , Teo Edwin Hang Tong , Liu Guangtong , Liu Zheng 
Published: August 2017

AbstractThe discovery of monolayer superconductors bears consequences for both fundamental physics and device applications. Currently, the growth of superconducting monolayers can only occur under ultrahigh vacuum and on specific lattice-matched or dangling bond-free substrates, to minimize environment- and substrate-induced disorders/defects. Such severe growth requirements limit the exploration of novel two-dimensional superconductivity and related nanodevices. Here we demonstrate the experimental realization of superconductivity in a chemical vapour deposition grown monolayer material—NbSe2. Atomic-resolution scanning transmission electron microscope imaging reveals the atomic structure of the intrinsic point defects and grain boundaries in monolayer NbSe2, and confirms the low defect concentration in our high-quality film, which is the key to two-dimensional superconductivity. By using monolayer chemical vapour deposited graphene as a protective capping layer, thickness-dependent superconducting properties are observed in as-grown NbSe2 with a transition temperature increasing from 1.0 K in monolayer to 4.56 K in 10-layer.
Correlated electronic states at domain walls of a Mott-charge-density-wave insulator 1T-TaS2
Authors: Cho Doohee , Gye Gyeongcheol , Lee Jinwon , Lee Sung-Hoon , Wang Lihai , Cheong Sang-Wook , Yeom Han Woong 
Published: August 2017

AbstractDomain walls in interacting electronic systems can have distinct localized states, which often govern physical properties and may lead to unprecedented functionalities and novel devices. However, electronic states within domain walls themselves have not been clearly identified and understood for strongly correlated electron systems. Here, we resolve the electronic states localized on domain walls in a Mott-charge-density-wave insulator 1T-TaS2 using scanning tunneling spectroscopy. We establish that the domain wall state decomposes into two nonconducting states located at the center of domain walls and edges of domains. Theoretical calculations reveal their atomistic origin as the local reconstruction of domain walls under the strong influence of electron correlation. Our results introduce a concept for the domain wall electronic property, the walls own internal degrees of freedom, which is potentially related to the controllability of domain wall electronic properties.
Chaperones rescue the energetic landscape of mutant CFTR at single molecule and in cell
Authors: Bagdany Miklos , Veit Guido , Fukuda Ryosuke , Avramescu Radu G. , Okiyoneda Tsukasa , Baaklini Imad , Singh Jay , Sovak Guy , Xu Haijin , Apaja Pirjo M. , Sattin Sara , Beitel Lenore K. , Roldan Ariel , Colombo Giorgio , Balch William , Young Jason C. , Lukacs Gergely L. 
Published: August 2017

AbstractMolecular chaperones are pivotal in folding and degradation of the cellular proteome but their impact on the conformational dynamics of near-native membrane proteins with disease relevance remains unknown. Here we report the effect of chaperone activity on the functional conformation of the temperature-sensitive mutant cystic fibrosis channel (∆F508-CFTR) at the plasma membrane and after reconstitution into phospholipid bilayer. Thermally induced unfolding at 37 °C and concomitant functional inactivation of ∆F508-CFTR are partially suppressed by constitutive activity of Hsc70 and Hsp90 chaperone/co-chaperone at the plasma membrane and post-endoplasmic reticulum compartments in vivo, and at single-molecule level in vitro, indicated by kinetic and thermodynamic remodeling of the mutant gating energetics toward its wild-type counterpart. Thus, molecular chaperones can contribute to functional maintenance of ∆F508-CFTR by reshaping the conformational energetics of its final fold, a mechanism with implication in the regulation of metastable ABC transporters and other plasma membrane proteins activity in health and diseases.
The onset of widespread marine red beds and the evolution of ferruginous oceans
Authors: Song Haijun , Jiang Ganqing , Poulton Simon W. , Wignall Paul B. , Tong Jinnan , Song Huyue , An Zhihui , Chu Daoliang , Tian Li , She Zhenbing , Wang Chengshan 
Published: August 2017

AbstractBanded iron formations were a prevalent feature of marine sedimentation ~3.8–1.8 billion years ago and they provide key evidence for ferruginous oceans. The disappearance of banded iron formations at ~1.8 billion years ago was traditionally taken as evidence for the demise of ferruginous oceans, but recent geochemical studies show that ferruginous conditions persisted throughout the later Precambrian, and were even a feature of Phanerozoic ocean anoxic events. Here, to reconcile these observations, we track the evolution of oceanic Fe-concentrations by considering the temporal record of banded iron formations and marine red beds. We find that marine red beds are a prominent feature of the sedimentary record since the middle Ediacaran (~580 million years ago). Geochemical analyses and thermodynamic modelling reveal that marine red beds formed when deep-ocean Fe-concentrations were > 4 nM. By contrast, banded iron formations formed when Fe-concentrations were much higher (> 50 μM). Thus, the first widespread development of marine red beds constrains the timing of deep-ocean oxygenation.
Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis
Authors: Liu Yongmei , Reynolds Lindsay M. , Ding Jingzhong , Hou Li , Lohman Kurt , Young Tracey , Cui Wei , Huang Zhiqing , Grenier Carole , Wan Ma , Stunnenberg Hendrik G. , Siscovick David , Hou Lifang , Psaty Bruce M. , Rich Stephen S. , Rotter Jerome I. , Kaufman Joel D. , Burke Gregory L. , Murphy Susan , Jacobs David R. , Post Wendy , Hoeschele Ina , Bell Douglas A. , Herrington David , Parks John S. , Tracy Russell P. , McCall Charles E. , Stein James H. 
Published: August 2017

AbstractLittle is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human atherosclerosis. The transcriptome signature includes transcription coactivator,ARID5B, which is known to form a chromatin derepressor complex with a histone H3K9Me2-specific demethylase and promote adipogenesis and smooth muscle development.ARID5BCpG (cg25953130) methylation is inversely associated with bothARID5Bexpression and atherosclerosis, consistent with this CpG residing in anARID5Benhancer region, based on chromatin capture and histone marks data. Mediation analysis supports assumptions thatARID5Bexpression mediates effects of cg25953130 methylation and several cardiovascular disease risk factors on atherosclerotic burden. In lipopolysaccharide-stimulated human THP1 monocytes,ARID5Bknockdown reduced expression of genes involved in atherosclerosis-related inflammatory and lipid metabolism pathways, and inhibited cell migration and phagocytosis. These data suggest thatARID5Bexpression, possibly regulated by an epigenetically controlled enhancer, promotes atherosclerosis by dysregulating immunometabolism towards a chronic inflammatory phenotype.
MHC matching improves engraftment of iPSC-derived neurons in non-human primates
Authors: Morizane Asuka , Kikuchi Tetsuhiro , Hayashi Takuya , Mizuma Hiroshi , Takara Sayuki , Doi Hisashi , Mawatari Aya , Glasser Matthew F. , Shiina Takashi , Ishigaki Hirohito , Itoh Yasushi , Okita Keisuke , Yamasaki Emi , Doi Daisuke , Onoe Hirotaka , Ogasawara Kazumasa , Yamanaka Shinya , Takahashi Jun 
Published: August 2017

AbstractThe banking of human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cells (iPSCs) is considered a future clinical strategy for HLA-matched cell transplantation to reduce immunological graft rejection. Here we show the efficacy of major histocompatibility complex (MHC)-matched allogeneic neural cell grafting in the brain, which is considered a less immune-responsive tissue, using iPSCs derived from an MHC homozygous cynomolgus macaque. Positron emission tomography imaging reveals neuroinflammation associated with an immune response against MHC-mismatched grafted cells. Immunohistological analyses reveal that MHC-matching reduces the immune response by suppressing the accumulation of microglia (Iba-1+) and lymphocytes (CD45+) into the grafts. Consequently, MHC-matching increases the survival of grafted dopamine neurons (tyrosine hydroxylase: TH+). The effect of an immunosuppressant, Tacrolimus, is also confirmed in the same experimental setting. Our results demonstrate the rationale for MHC-matching in neural cell grafting to the brain and its feasibility in a clinical setting.
Designing artificial 2D crystals with site and size controlled quantum dots
Authors: Xie Xuejun , Kang Jiahao , Cao Wei , Chu Jae Hwan , Gong Yongji , Ajayan Pulickel M. , Banerjee Kaustav 
Published: August 2017

AbstractOrdered arrays of quantum dots in two-dimensional (2D) materials would make promising optical materials, but their assembly could prove challenging. Here we demonstrate a scalable, site and size controlled fabrication of quantum dots in monolayer molybdenum disulfide (MoS2), and quantum dot arrays with nanometer-scale spatial density by focused electron beam irradiation induced local 2H to 1T phase change in MoS2. By designing the quantum dots in a 2D superlattice, we show that new energy bands form where the new band gap can be controlled by the size and pitch of the quantum dots in the superlattice. The band gap can be tuned from 1.81 eV to 1.42 eV without loss of its photoluminescence performance, which provides new directions for fabricating lasers with designed wavelengths. Our work constitutes a photoresist-free, top-down method to create large-area quantum dot arrays with nanometer-scale spatial density that allow the quantum dots to interfere with each other and create artificial crystals. This technique opens up new pathways for fabricating light emitting devices with 2D materials at desired wavelengths. This demonstration can also enable the assembly of large scale quantum information systems and open up new avenues for the design of artificial 2D materials.
Tylophorine Analogs Allosterically Regulates Heat Shock Cognate Protein 70 And Inhibits Hepatitis C Virus Replication
Authors: Wang Ying , Lee Sangwon , Ha Ya , Lam Wing , Chen Shao-Ru , Dutschman Ginger E. , Gullen Elizabeth A. , Grill Susan P. , Cheng Yao , Fürstner Alois , Francis Samson , Baker David C. , Yang Xiaoming , Lee Kuo-Hsiung , Cheng Yung-Chi 
Published: August 2017

AbstractTylophorine analogs have been shown to exhibit diverse activities against cancer, inflammation, arthritis, and lupus in vivo. In this study, we demonstrated that two tylophorine analogs, DCB-3503 and rac-cryptopleurine, exhibit potent inhibitory activity against hepatitis C virus (HCV) replication in genotype 1b Con 1 isolate. The inhibition of HCV replication is at least partially mediated through cellular heat shock cognate protein 70 (Hsc70). Hsc70 associates with the HCV replication complex by primarily binding to the poly U/UC motifs in HCV RNA. The interaction of DCB-3503 and rac-cryptopleurine with Hsc70 promotes the ATP hydrolysis activity of Hsc70 in the presence of the 3′ poly U/UC motif of HCV RNA. Regulating the ATPase activity of Hsc70 may be one of the mechanisms by which tylophorine analogs inhibit HCV replication. This study demonstrates the novel anti-HCV activity of tylophorine analogs. Our results also highlight the importance of Hsc70 in HCV replication.
Analysis of the first Taraxacum kok-saghyz transcriptome reveals potential rubber yield related SNPs
Authors: Luo Zinan , Iaffaldano Brian J. , Zhuang Xiaofeng , Fresnedo-Ramírez Jonathan , Cornish Katrina 
Published: August 2017

AbstractTaraxacum kok-saghyz (TK) is a potential alternative crop for natural rubber (NR) production, due to its high molecular weight rubber, short breeding cycle, and diverse environmental adaptation. However, improvements in rubber yield and agronomically relevant traits are still required before it can become a commercially-viable crop. An RNA-Seq based transcriptome was developed from a pool of roots from genotypes with high and low rubber yield. A total of 55,532 transcripts with lengths over 200 bp were de novo assembled. As many as 472 transcripts were significantly homologous to 49 out of 50 known plant putative rubber biosynthesis related genes. 158 transcripts were significantly differentially expressed between high rubber and low rubber genotypes. 21,036 SNPs were different in high and low rubber TK genotypes. Among these, 50 SNPs were found within 39 transcripts highly homologous to 49 publically-searched rubber biosynthesis related genes. 117 SNPs were located within 36 of the differentially expressed gene sequences. This comprehensive TK transcriptomic reference, and large set of SNPs including putative exonic markers associated with rubber related gene homologues and differentially expressed genes, provides a solid foundation for further genetic dissection of rubber related traits, comparative genomics and marker-assisted selection for the breeding of TK.