bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soft fibrin matrix downregulates DAB2IP to promote Nanog-dependent growth of colon tumor-repopulating cells
Authors: Zhang Meng , Xu Cong , Wang Hai-zhou , Peng Ya-nan , Li Hai-ou , Zhou Yun-jiao , Liu Shi , Wang Fan , Liu Lan , Chang Ying , Zhao Qiu , Liu Jing 
Published: February 2019

AbstractColon cancer stem cells (CSCs) have been shown to be responsible for the recurrence and metastasis of colorectal cancer (CRC). As a crucial microenvironmental factor, extracellular matrix (ECM) stiffness is known to affect the stemness of CSCs. Recently, fibrin deposition in the stroma of CRC was demonstrated to be responsible for tumor development. In this study, we used salmon fibrin gel to provide a 3D ECM for colon cancer cells and investigated its effects on cell growth as well as the underlying mechanisms. Compared with stiff 420 Pascal (Pa) and 1 050 Pa gels, 90 Pa soft fibrin gel was most efficient at isolating and enriching tumor colonies. The size and number of colony formation negatively correlated with gel stiffness. Specifically, these tumor colonies exhibited efficient tumorigenicity, upregulated stem cell markers, and had anti-chemotherapeutic properties and were thus named tumor-repopulating cells (TRCs). More importantly, the self-renewal molecule Nanog was sharply induced in 3D-cultured colon TRCs; further, Nanog siRNA significantly inhibited colony formation, suggesting the indispensable role of Nanog in TRC growth. A subsequent mechanistic study illustrated that Nanog expression could be modulated through fibrin gel stiffness-induced DAB2IP/PI3K/FOXA1 signaling in colon TRCs.
Fhit–Fdxr interaction in the mitochondria: modulation of reactive oxygen species generation and apoptosis in cancer cells
Authors: Druck Teresa , Cheung Douglas G. , Park Dongju , Trapasso Francesco , Pichiorri Flavia , Gaspari Marco , Palumbo Tiziana , Aqeilan Rami I. , Gaudio Eugenio , Okumura Hiroshi , Iuliano Rodolfo , Raso Cinzia , Green Kari , Huebner Kay , Croce Carlo M. 
Published: February 2019

AbstractFhit protein is lost in cancers of most, perhaps all, cancer types; when restored, it can induce apoptosis and suppress tumorigenicity, as shown in vitro and in mouse tumor models in vivo. Following protein cross-linking and proteomics analyses, we characterized a Fhit protein complex involved in triggering Fhit-mediated apoptosis. The complex includes the heat-shock chaperonin pair, HSP60/10, which is likely involved in importing Fhit into the mitochondria, where it interacts with ferredoxin reductase, responsible for transferring electrons from NADPH to cytochrome P450 via ferredoxin, in electron transport chain complex III. Overexpression of Fhit protein in Fhit-deficient cancer cells modulates the production of intracellular reactive oxygen species, causing increased ROS, following peroxide treatment, with subsequent increased apoptosis of lung cancer cells under oxidative stress conditions; conversely, Fhit-negative cells escape ROS overproduction and ROS-induced apoptosis, likely carrying oxidative damage. Thus, characterization of Fhit-interacting proteins has identified direct effectors of a Fhit-mediated apoptotic signal pathway that is lost in many cancers. This is of translational interest considering the very recent emphasis in a number of high-profile publications, concerning the role of oxidative phosphorylation in the treatment of human cancers, and especially cancer stem cells that rely upon oxidative phosphorylation for survival. Additionally, we have shown that cells from a Fhit-deficient lung cancer cell line, are sensitive to killing by exposure to atovaquone, thought to act as a selective oxidative phosphorylation inhibitor by targeting the CoQ10 dependence of the mitochondrial complex III, while the Fhit-expressing sister clone is resistant to this treatment.
Gigaxonin E3 ligase governs ATG16L1 turnover to control autophagosome production
Authors: Scrivo Aurora , Codogno Patrice , Bomont Pascale 
Published: February 2019

AbstractAutophagy is an essential self-digestion machinery for cell survival and homoeostasis. Membrane elongation is fundamental, as it drives the formation of the double-membrane vesicles that engulf cytosolic material. LC3-lipidation, the signature of autophagosome formation, results from a complex ubiquitin-conjugating cascade orchestrated by the ATG16L1 protein, whose regulation is unknown. Here, we identify the Gigaxonin-E3 ligase as the first regulator of ATG16L1 turn-over and autophagosome production. Gigaxonin interacts with the WD40 domain of ATG16L1 to drive its ubiquitination and subsequent degradation. Gigaxonin depletion induces the formation of ATG16L1 aggregates and impairs LC3 lipidation, hence altering lysosomal fusion and degradation of the main autophagy receptor p62. Altogether, we demonstrate that the Gigaxonin-E3 ligase controls the production of autophagosomes by a reversible, ubiquitin-dependent process selective for ATG16L1. Our findings unveil the fundamental mechanisms of the control of autophagosome formation, and provide a molecular switch to fine-tune the activation of autophagy.
A multi-substrate screening approach for the identification of a broadly applicable Diels–Alder catalyst
Authors: Kim Hyejin , Gerosa Gabriela , Aronow Jonas , Kasaplar Pinar , Ouyang Jie , Lingnau Julia B. , Guerry Paul , Farès Christophe , List Benjamin 
Published: February 2019

AbstractWhen developing a synthetic methodology, chemists generally optimize a single substrate and then explore the substrate scope of their method. This approach has led to innumerable and widely-used chemical reactions. However, it frequently provides methods that only work on model substrate-like compounds. Perhaps worse, reaction conditions that would enable the conversion of other substrates may be missed. We now show that a different approach, originally proposed by Kagan, in which a collection of structurally distinct substrates are evaluated in a single reaction vessel, can not only provide information on the substrate scope at a much earlier stage in methodology development, but even lead to a broadly applicable synthetic methodology. Using this multi-substrate screening approach, we have identified an efficient and stereoselective imidodiphosphorimidate organocatalyst for scalable Diels–Alder reactions of cyclopentadiene with different classes of α,β-unsaturated aldehydes.
Ripplocations provide a new mechanism for the deformation of phyllosilicates in the lithosphere
Authors: Aslin Joe , Mariani Elisabetta , Dawson Karl , Barsoum Michel W. 
Published: February 2019

AbstractDeformation in Earth’s lithosphere is localised in narrow, high-strain zones. Phyllosilicates, strongly anisotropic layered minerals, are abundant in these rocks, where they accommodate much of the strain and play a significant role in inhibiting or triggering earthquakes. Until now it was understood that phyllosilicates could deform only by dislocation glide along layers and could not accommodate large strains without cracking and dilation. Here we show that a new class of atomic-scale defects, known as ripplocations, explain the development of layer-normal strain without brittle damage. We use high-resolution transmission electron microscopy (TEM) to resolve nano-scale bending characteristic of ripplocations in the phyllosilicate mineral biotite. We demonstrate that conjugate delamination arrays are the result of elastic strain energy release due to the accumulation of layer-normal strain in ripplocations. This work provides the missing mechanism necessary to understand phyllosilicate deformation, with important rheological implications for phyllosilicate bearing seismogenic faults and subduction zones.
Extortion strategies resist disciplining when higher competitiveness is rewarded with extra gain
Authors: Becks Lutz , Milinski Manfred 
Published: February 2019

AbstractCooperative strategies are predicted for repeated social interactions. The recently described Zero Determinant (ZD) strategies enforce the partner’s cooperation because the ‘generous’ ZD players help their cooperative partners while ‘extortionate’ ZD players exploit their partners’ cooperation. Partners may accede to extortion because it pays them to do so, but the partner can sabotage his own and his extortioner’s score by defecting to discipline the extortioner. Thus, extortion is predicted to turn into generous and disappear. Here, we show with human volunteers that an additional monetary incentive (bonus) paid to the finally competitively superior player maintains extortion. Unexpectedly, extortioners refused to become disciplined, thus forcing partners to accede. Occasional opposition reduced the extortioners’ gain so that using extortion paid off only because of the bonus. With no bonus incentive, players used the generous ZD strategy. Our findings suggest that extortion strategies can prevail when higher competitiveness is rewarded with extra gain.
ASPP proteins discriminate between PP1 catalytic subunits through their SH3 domain and the PP1 C-tail
Authors: Bertran M. Teresa , Mouilleron Stéphane , Zhou Yanxiang , Bajaj Rakhi , Uliana Federico , Kumar Ganesan Senthil , van Drogen Audrey , Lee Rebecca , Banerjee Jennifer J. , Hauri Simon , O’Reilly Nicola , Gstaiger Matthias , Page Rebecca , Peti Wolfgang , Tapon Nicolas 
Published: February 2019

AbstractSerine/threonine phosphatases such as PP1 lack substrate specificity and associate with a large array of targeting subunits to achieve the requisite selectivity. The tumour suppressor ASPP (apoptosis-stimulating protein of p53) proteins associate with PP1 catalytic subunits and are implicated in multiple functions from transcriptional regulation to cell junction remodelling. Here we show that Drosophila ASPP is part of a multiprotein PP1 complex and that PP1 association is necessary for several in vivo functions of Drosophila ASPP. We solve the crystal structure of the human ASPP2/PP1 complex and show that ASPP2 recruits PP1 using both its canonical RVxF motif, which binds the PP1 catalytic domain, and its SH3 domain, which engages the PP1 C-terminal tail. The ASPP2 SH3 domain can discriminate between PP1 isoforms using an acidic specificity pocket in the n-Src domain, providing an exquisite mechanism where multiple motifs are used combinatorially to tune binding affinity to PP1.
Divalent EuRh2Si2 as a reference for the Luttinger theorem and antiferromagnetism in trivalent heavy-fermion YbRh2Si2
Authors: Güttler M. , Generalov A. , Fujimori S. I. , Kummer K. , Chikina A. , Seiro S. , Danzenbächer S. , Koroteev Yu. M. , Chulkov E. V. , Radovic M. , Shi M. , Plumb N. C. , Laubschat C. , Allen J. W. , Krellner C. , Geibel C. , Vyalikh D. V. 
Published: February 2019

AbstractApplication of the Luttinger theorem to the Kondo lattice YbRh2Si2 suggests that its large 4f-derived Fermi surface (FS) in the paramagnetic (PM) regime should be similar in shape and volume to that of the divalent local-moment antiferromagnet (AFM) EuRh2Si2 in its PM regime. Here we show by angle-resolved photoemission spectroscopy that paramagnetic EuRh2Si2 has a large FS essentially similar to the one seen in YbRh2Si2 down to 1 K. In EuRh2Si2 the onset of AFM order below 24.5 K induces an extensive fragmentation of the FS due to Brillouin zone folding, intersection and resulting hybridization of the Fermi-surface sheets. Our results on EuRh2Si2 indicate that the formation of the AFM state in YbRh2Si2 is very likely also connected with similar changes in the FS, which have to be taken into account in the controversial analysis and discussion of anomalies observed at the quantum critical point in this system.
The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes
Authors: Luu Maik , Pautz Sabine , Kohl Vanessa , Singh Rajeev , Romero Rossana , Lucas Sébastien , Hofmann Jörg , Raifer Hartmann , Vachharajani Niyati , Carrascosa Lucia Campos , Lamp Boris , Nist Andrea , Stiewe Thorsten , Shaul Yoav , Adhikary Till , Zaiss Mario M. , Lauth Matthias , Steinhoff Ulrich , Visekruna Alexander 
Published: February 2019

AbstractShort-chain fatty acids (SCFAs) have immunomodulatory effects, but the underlying mechanisms are not well understood. Here we show that pentanoate, a physiologically abundant SCFA, is a potent regulator of immunometabolism. Pentanoate induces IL-10 production in lymphocytes by reprogramming their metabolic activity towards elevated glucose oxidation. Mechanistically, this reprogramming is mediated by supplying additional pentanoate-originated acetyl-CoA for histone acetyltransferases, and by pentanoate-triggered enhancement of mTOR activity. In experimental mouse models of colitis and multiple sclerosis, pentanoate-induced regulatory B cells mediate protection from autoimmune pathology. Additionally, pentanoate shows a potent histone deacetylase-inhibitory activity in CD4+ T cells, thereby reducing their IL-17A production. In germ-free mice mono-colonized with segmented filamentous bacteria (SFB), pentanoate inhibits the generation of small-intestinal Th17 cells and ameliorates SFB-promoted inflammation in the central nervous system. Taken together, by enhancing IL-10 production and suppressing Th17 cells, the SCFA pentanoate might be of therapeutic relevance for inflammatory and autoimmune diseases.
1D versus 2D cocrystals growth via microspacing in-air sublimation
Authors: Ye Xin , Liu Yang , Guo Qing , Han Quanxiang , Ge Chao , Cui Shuangyue , Zhang Leilei , Tao Xutang 
Published: February 2019

AbstractOrganic cocrystals possess valuable properties owing to the synergistic effect of the individual components. However, the growth of molecular cocrystals is still in its primary stage. Here we develop a microspacing in-air sublimation method to grow organic cocrystals, and furthermore to realize morphology control on them, which is essential for structure–property relations. A series of polycyclic aromatic hydrocarbon (PAH)‒1,2,4,5-tetracyanobenzene (TCNB) complexes cocrystals are grown directly on the substrate, with the morphology tunable from 1D needle-like to 2D plate-like on demand. Spatially resolved photoluminescence spectra analyses on different cocrystals display morphology dependent and anisotropic optical waveguiding properties. In situ observation and energy calculations of the crystallization processes reveal the formation mechanism being from a competition between growth kinetics-defined crystal habit and the thermodynamics driving force. This growth technique may serve the future demand for tunable morphology organic cocrystals in different functional applications.
Stress-induced inactivation of the Staphylococcus aureus purine biosynthesis repressor leads to hypervirulence
Authors: Goncheva Mariya I. , Flannagan Ronald S. , Sterling Brigid E. , Laakso Holly A. , Friedrich Nancy C. , Kaiser Julienne C. , Watson David W. , Wilson Christy H. , Sheldon Jessica R. , McGavin Martin J. , Kiser Patti K. , Heinrichs David E. 
Published: February 2019

AbstractStaphylococcus aureus is a significant cause of human infection. Here, we demonstrate that mutations in the transcriptional repressor of purine biosynthesis, purR, enhance the pathogenic potential of S. aureus. Indeed, systemic infection with purR mutants causes accelerated mortality in mice, which is due to aberrant up-regulation of fibronectin binding proteins (FnBPs). Remarkably, purR mutations can arise upon exposure of S. aureus to stress, such as an intact immune system. In humans, naturally occurring anti-FnBP antibodies exist that, while not protective against recurrent S. aureus infection, ostensibly protect against hypervirulent S. aureus infections. Vaccination studies support this notion, where anti-Fnb antibodies in mice protect against purR hypervirulence. These findings provide a novel link between purine metabolism and virulence in S. aureus.
Phenazine production promotes antibiotic tolerance and metabolic heterogeneity in Pseudomonas aeruginosa biofilms
Authors: Schiessl Konstanze T. , Hu Fanghao , Jo Jeanyoung , Nazia Sakila Z. , Wang Bryan , Price-Whelan Alexa , Min Wei , Dietrich Lars E. P. 
Published: February 2019

AbstractAntibiotic efficacy can be antagonized by bioactive metabolites and other drugs present at infection sites. Pseudomonas aeruginosa, a common cause of biofilm-based infections, releases metabolites called phenazines that accept electrons to support cellular redox balancing. Here, we find that phenazines promote tolerance to clinically relevant antibiotics, such as ciprofloxacin, in P. aeruginosa biofilms and that this effect depends on the carbon source provided for growth. We couple stable isotope labeling with stimulated Raman scattering microscopy to visualize biofilm metabolic activity in situ. This approach shows that phenazines promote metabolism in microaerobic biofilm regions and influence metabolic responses to ciprofloxacin treatment. Consistent with roles of specific respiratory complexes in supporting phenazine utilization in biofilms, phenazine-dependent survival on ciprofloxacin is diminished in mutants lacking these enzymes. Our work introduces a technique for the chemical imaging of biosynthetic activity in biofilms and highlights complex interactions between bacterial products, their effects on biofilm metabolism, and the antibiotics we use to treat infections.
Capturing the inherent structural dynamics of the HIV-1 envelope glycoprotein fusion peptide
Authors: Kumar Sonu , Sarkar Anita , Pugach Pavel , Sanders Rogier W. , Moore John P. , Ward Andrew B. , Wilson Ian A. 
Published: February 2019

AbstractThe N-terminal fusion peptide (FP) of the human immunodeficiency virus (HIV)-1 envelope glycoprotein (Env) gp41 subunit plays a critical role in cell entry. However, capturing the structural flexibility in the unbound FP is challenging in the native Env trimer. Here, FP conformational isomerism is observed in two crystal structures of a soluble clade B transmitted/founder virus B41 SOSIP.664 Env with broadly neutralizing antibodies (bNAbs) PGT124 and 35O22 to aid in crystallization and that are not specific for binding to the FP. Large rearrangements in the FP and fusion peptide proximal region occur around M530, which remains anchored in the tryptophan clasp (gp41 W623, W628, W631) in the B41 Env prefusion state. Further, we redesigned the FP at position 518 to reinstate the bNAb VRC34.01 epitope. These findings provide further structural evidence for the dynamic nature of the FP and how a bNAb epitope can be restored during vaccine design.
On the degradation mechanisms of quantum-dot light-emitting diodes
Authors: Chen Song , Cao Weiran , Liu Taili , Tsang Sai-Wing , Yang Yixing , Yan Xiaolin , Qian Lei 
Published: February 2019

AbstractThe operating lifetime of blue quantum-dot light-emitting diodes (QLED) is currently a short slab for this emerging display technology. To pinpoint the origin of device degradation, here we apply multiple techniques to monitor the electric-field distribution and space-charge accumulation across the multilayered structure before and after lifetime tests. Evident by charge-modulated electro-absorption and capacitance-voltage characteristics, the excited electrons in blue quantum dots (QD) are prone to cross the type II junction between the QD emission layer and the electron-transporting layer (ETL) due to the offset of conduction band minimum, leading to space-charge accumulation and operating-voltage rise in the ETL. Therefore, unlike those very stable red devices, of which the lifetime is primarily limited by the slow degradation of hole-transporting layer, the poor lifetime of blue QLED originates from the fast degradation at the QD-ETL junction. Materials engineering for efficient electron injection is prerequisite for the boost of operating lifetime.
Author Correction: FGL2 promotes tumor progression in the CNS by suppressing CD103+ dendritic cell differentiation
Authors: Yan Jun , Zhao Qingnan , Gabrusiewicz Konrad , Kong Ling-Yuan , Xia Xueqing , Wang Jian , Ott Martina , Xu Jingda , Davis R. Eric , Huo Longfei , Rao Ganesh , Sun Shao-Cong , Watowich Stephanie S. , Heimberger Amy B. , Li Shulin 
Published: February 2019

The original version of this Article contained errors in the author affiliations. Qingnan Zhao, Xueqing Xia, Longfei Huo and Shulin Li were incorrectly associated with Beijing Institute for Brain Disorders, 100069, Beijing, China.This has now been corrected in both the PDF and HTML versions of the Article.
An EDS1 heterodimer signalling surface enforces timely reprogramming of immunity genes in Arabidopsis
Authors: Bhandari Deepak D. , Lapin Dmitry , Kracher Barbara , von Born Patrick , Bautor Jaqueline , Niefind Karsten , Parker Jane E. 
Published: February 2019

AbstractPlant intracellular NLR receptors recognise pathogen interference to trigger immunity but how NLRs signal is not known. Enhanced disease susceptibility1 (EDS1) heterodimers are recruited by Toll-interleukin1-receptor domain NLRs (TNLs) to transcriptionally mobilise resistance pathways. By interrogating the Arabidopsis EDS1 ɑ-helical EP-domain we identify positively charged residues lining a cavity that are essential for TNL immunity signalling, beyond heterodimer formation. Mutating a single, conserved surface arginine (R493) disables TNL immunity to an oomycete pathogen and to bacteria producing the virulence factor, coronatine. Plants expressing a weakly active EDS1R493A variant have delayed transcriptional reprogramming, with severe consequences for resistance and countering bacterial coronatine repression of early immunity genes. The same EP-domain surface is utilised by a non-TNL receptor RPS2 for bacterial immunity, indicating that the EDS1 EP-domain signals in resistance conferred by different NLR receptor types. These data provide a unique structural insight to early downstream signalling in NLR receptor immunity.
Regulation of miRNAs by Snail during epithelial-to-mesenchymal transition in HT29 colon cancer cells
Authors: Przygodzka Patrycja , Papiewska-Pająk Izabela , Bogusz-Koziarska Helena , Sochacka Ewelina , Boncela Joanna , Kowalska M. Anna 
Published: February 2019

AbstractEpithelial-to-mesenchymal transition (EMT) in cancer cells, represents early stages of metastasis and is a promising target in colorectal cancer (CRC) therapy. There have been many attempts to identify markers and key pathways induced throughout EMT but the process is complex and depends on the cancer type and tumour microenvironment. Here we used the colon cancer cell line HT29, which stably overexpressed Snail, the key transcription factor in early EMT, as a model for colorectal adenocarcinoma cells with a pro-metastatic phenotype. We investigated miRNA expression regulation during that phenotypic switching. We found that overexpression of Snail in HT29 cells triggered significant changes in individual miRNA levels but did not change the global efficiency of miRNA processing. Snail abundance repressed the expression of miR-192 and miR-194 and increased miR-205, let-7i and SNORD13 levels. These identified changes correlated with the reported transcriptomic alterations in Snail-overexpressing HT29 cells. We also investigated how Snail affected the miRNA content of extracellular vesicles (EVs) released from HT29 cells. Our data suggest that the presence of Snail significantly alters the complex mRNA/miRNA interactions in the early steps of metastasis and also has an impact on the content of EVs released from HT29 cells.