bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage migration inhibitory factor has a permissive role in concanavalin A-induced cell death of human hepatoma cells through autophagy
Authors: Lai Y-C , Chuang Y-C , Chang C-P , Yeh T-M 
Published: December 2015

AbstractConcanavalin A (ConA) is a lectin and T-cell mitogen that can activate immune responses. In recent times, ConA-induced cell death of hepatoma cells through autophagy has been reported and its therapeutic effect was confirmed in a murinein situhepatoma model. However, the molecular mechanism of ConA-induced autophagy is still unclear. As macrophage migration inhibitory factor (MIF), which is a proinflammatory cytokine, can trigger autophagy in human hepatoma cells, the possible involvement of MIF in ConA-induced autophagy was investigated in this study. We demonstrated that cell death is followed by an increment in MIF expression and secretion in the ConA-stimulated human hepatoma cell lines, HuH-7 and Hep G2. In addition, ConA-induced autophagy and cell death of hepatoma cells were blocked in the presence of an MIF inhibitor. Knockdown of endogenous MIF by small hairpin RNA confirmed that MIF is required for both ConA-induced autophagy and death of hepatoma cells. Furthermore, signal pathway studies demonstrated that ConA induces signal transducer and activator of transcription 3 (STAT3) phosphorylation to trigger MIF upregulation, which in turn promotes Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)-dependent autophagy. By using a murinein situhepatoma model, we further demonstrated that MIF contributes to anti-hepatoma activity of ConA by regulating STAT3–MIF–BNIP3-dependent autophagy. In summary, our findings uncover a novel role of MIF in lectin-mediated anti-hepatoma activities by regulating autophagy.
Legius Syndrome: two novel mutations in the SPRED1 gene
Authors: Bianchi Marika , Saletti Veronica , Micheli Roberto , Esposito Silvia , Molinaro Anna , Gagliardi Stella , Orcesi Simona , Cereda Cristina 
Published: December 2015

AbstractThe SPRED1 gene encodes a protein involved in the Ras/MAPK (mitogen-activated protein kinase) signaling pathway. Mutations in SPRED1 have been reported to cause Legius Syndrome, a rare developmental disorder that shares some clinical features with Neurofibromatosis-1. Direct sequencing was used to define SPRED1 mutations. We present two previously undescribed mutations: a frameshift mutation causing a stop codon, which was identified in an Italian family (p.Ile60Tyrfs*18) and a missense variation, which was identified in one sporadic Italian case (p.Pro422Arg). Our results led us to hypothesize that these modifications may contribute to the Legius Syndrome phenotype. Further studies will be needed to determine the roles of these mutations in the mechanisms of Legius Syndrome.
Ultralight shape-recovering plate mechanical metamaterials
Authors: Davami Keivan , Zhao Lin , Lu Eric , Cortes John , Lin Chen , Lilley Drew E. , Purohit Prashant K. , Bargatin Igor 
Published: December 2015

AbstractUnusual mechanical properties of mechanical metamaterials are determined by their carefully designed and tightly controlled geometry at the macro- or nanoscale. We introduce a class of nanoscale mechanical metamaterials created by forming continuous corrugated plates out of ultrathin films. Using a periodic three-dimensional architecture characteristic of mechanical metamaterials, we fabricate free-standing plates up to 2 cm in size out of aluminium oxide films as thin as 25 nm. The plates are formed by atomic layer deposition of ultrathin alumina films on a lithographically patterned silicon wafer, followed by complete removal of the silicon substrate. Unlike unpatterned ultrathin films, which tend to warp or even roll up because of residual stress gradients, our plate metamaterials can be engineered to be extremely flat. They weigh as little as 0.1 g cm−2 and have the ability to ‘pop-back’ to their original shape without damage even after undergoing multiple sharp bends of more than 90°.
Structural insights into the DNA-binding specificity of E2F family transcription factors
Authors: Morgunova Ekaterina , Yin Yimeng , Jolma Arttu , Dave Kashyap , Schmierer Bernhard , Popov Alexander , Eremina Nadejda , Nilsson Lennart , Taipale Jussi 
Published: December 2015

AbstractThe mammalian cell cycle is controlled by the E2F family of transcription factors. Typical E2Fs bind to DNA as heterodimers with the related dimerization partner (DP) proteins, whereas the atypical E2Fs, E2F7 and E2F8 contain two DNA-binding domains (DBDs) and act as repressors. To understand the mechanism of repression, we have resolved the structure of E2F8 in complex with DNA at atomic resolution. We find that the first and second DBDs of E2F8 resemble the DBDs of typical E2F and DP proteins, respectively. Using molecular dynamics simulations, biochemical affinity measurements and chromatin immunoprecipitation, we further show that both atypical and typical E2Fs bind to similar DNA sequences in vitro and in vivo. Our results represent the first crystal structure of an E2F protein with two DBDs, and reveal the mechanism by which atypical E2Fs can repress canonical E2F target genes and exert their negative influence on cell cycle progression.
Gln40 deamidation blocks structural reconfiguration and activation of SCF ubiquitin ligase complex by Nedd8
Authors: Yu Clinton , Mao Haibin , Novitsky Eric J. , Tang Xiaobo , Rychnovsky Scott D. , Zheng Ning , Huang Lan 
Published: December 2015

AbstractThe full enzymatic activity of the cullin-RING ubiquitin ligases (CRLs) requires a ubiquitin-like protein (that is, Nedd8) modification. By deamidating Gln40 of Nedd8 to glutamate (Q40E), the bacterial cycle-inhibiting factor (Cif) family is able to inhibit CRL E3 activities, thereby interfering with cellular functions. Despite extensive structural studies on CRLs, the molecular mechanism by which Nedd8 Gln40 deamidation affects CRL functions remains unclear. We apply a new quantitative cross-linking mass spectrometry approach to characterize three different types of full-length human Cul1–Rbx1 complexes and uncover major Nedd8-induced structural rearrangements of the CRL1 catalytic core. More importantly, we find that those changes are not induced by Nedd8(Q40E) conjugation, indicating that the subtle change of a single Nedd8 amino acid is sufficient to revert the structure of the CRL catalytic core back to its unmodified form. Our results provide new insights into how neddylation regulates the conformation and activity of CRLs.
Nanoscale assembly processes revealed in the nacroprismatic transition zone of Pinna nobilis mollusc shells
Authors: Hovden Robert , Wolf Stephan E. , Holtz Megan E. , Marin Frédéric , Muller David A. , Estroff Lara A. 
Published: December 2015

AbstractIntricate biomineralization processes in molluscs engineer hierarchical structures with meso-, nano- and atomic architectures that give the final composite material exceptional mechanical strength and optical iridescence on the macroscale. This multiscale biological assembly inspires new synthetic routes to complex materials. Our investigation of the prism–nacre interface reveals nanoscale details governing the onset of nacre formation using high-resolution scanning transmission electron microscopy. A wedge-polishing technique provides unprecedented, large-area specimens required to span the entire interface. Within this region, we find a transition from nanofibrillar aggregation to irregular early-nacre layers, to well-ordered mature nacre suggesting the assembly process is driven by aggregation of nanoparticles (∼50–80 nm) within an organic matrix that arrange in fibre-like polycrystalline configurations. The particle number increases successively and, when critical packing is reached, they merge into early-nacre platelets. These results give new insights into nacre formation and particle-accretion mechanisms that may be common to many calcareous biominerals.
The RNA-binding proteomes from yeast to man harbour conserved enigmRBPs
Authors: Beckmann Benedikt M. , Horos Rastislav , Fischer Bernd , Castello Alfredo , Eichelbaum Katrin , Alleaume Anne-Marie , Schwarzl Thomas , Curk Tomaž , Foehr Sophia , Huber Wolfgang , Krijgsveld Jeroen , Hentze Matthias W. 
Published: December 2015

AbstractRNA-binding proteins (RBPs) exert a broad range of biological functions. To explore the scope of RBPs across eukaryotic evolution, we determined the in vivo RBP repertoire of the yeast Saccharomyces cerevisiae and identified 678 RBPs from yeast and additionally 729 RBPs from human hepatocytic HuH-7 cells. Combined analyses of these and recently published data sets define the core RBP repertoire conserved from yeast to man. Conserved RBPs harbour defined repetitive motifs within disordered regions, which display striking evolutionary expansion. Only 60% of yeast and 73% of the human RBPs have functions assigned to RNA biology or structural motifs known to convey RNA binding, and many intensively studied proteins surprisingly emerge as RBPs (termed ‘enigmRBPs’), including almost all glycolytic enzymes, pointing to emerging connections between gene regulation and metabolism. Analyses of the mitochondrial hydroxysteroid dehydrogenase (HSD17B10) uncover the RNA-binding specificity of an enigmRBP.
Optogenetic mutagenesis in Caenorhabditis elegans
Authors: Noma Kentaro , Jin Yishi 
Published: December 2015

AbstractReactive oxygen species (ROS) can modify and damage DNA. Here we report an optogenetic mutagenesis approach that is free of toxic chemicals and easy to perform by taking advantage of a genetically encoded ROS generator. This method relies on the potency of ROS generation by His-mSOG, the mini singlet oxygen generator, miniSOG, fused to a histone. Caenorhabditis elegans expressing His-mSOG in the germline behave and reproduce normally, without photoinduction. Following exposure to blue light, the His-mSOG animals produce progeny with a wide range of heritable phenotypes. We show that optogenetic mutagenesis by His-mSOG induces a broad spectrum of mutations including single-nucleotide variants (SNVs), chromosomal deletions, as well as integration of extrachromosomal transgenes, which complements those derived from traditional chemical or radiation mutagenesis. The optogenetic mutagenesis expands the toolbox for forward genetic screening and also provides direct evidence that nuclear ROS can induce heritable and specific genetic mutations.
Exome sequencing of osteosarcoma reveals mutation signatures reminiscent of BRCA deficiency
Authors: Kovac Michal , Blattmann Claudia , Ribi Sebastian , Smida Jan , Mueller Nikola S. , Engert Florian , Castro-Giner Francesc , Weischenfeldt Joachim , Kovacova Monika , Krieg Andreas , Andreou Dimosthenis , Tunn Per-Ulf , Dürr Hans Roland , Rechl Hans , Schaser Klaus-Dieter , Melcher Ingo , Burdach Stefan , Kulozik Andreas , Specht Katja , Heinimann Karl , Fulda Simone , Bielack Stefan , Jundt Gernot , Tomlinson Ian , Korbel Jan O. , Nathrath Michaela , Baumhoer Daniel 
Published: December 2015

AbstractOsteosarcomas are aggressive bone tumours with a high degree of genetic heterogeneity, which has historically complicated driver gene discovery. Here we sequence exomes of 31 tumours and decipher their evolutionary landscape by inferring clonality of the individual mutation events. Exome findings are interpreted in the context of mutation and SNP array data from a replication set of 92 tumours. We identify 14 genes as the main drivers, of which some were formerly unknown in the context of osteosarcoma. None of the drivers is clearly responsible for the majority of tumours and even TP53 mutations are frequently mapped into subclones. However, >80% of osteosarcomas exhibit a specific combination of single-base substitutions, LOH, or large-scale genome instability signatures characteristic of BRCA1/2-deficient tumours. Our findings imply that multiple oncogenic pathways drive chromosomal instability during osteosarcoma evolution and result in the acquisition of BRCA-like traits, which could be therapeutically exploited.
CX3CR1 deficiency promotes muscle repair and regeneration by enhancing macrophage ApoE production
Authors: Arnold Ludovic , Perrin Hélène , de Chanville Camille Baudesson , Saclier Marielle , Hermand Patricia , Poupel Lucie , Guyon Elodie , Licata Fabrice , Carpentier Wassila , Vilar José , Mounier Rémi , Chazaud Bénédicte , Benhabiles Nora , Boissonnas Alexandre , Combadiere Béhazine , Combadiere Christophe 
Published: December 2015

AbstractMuscle injury triggers inflammation in which infiltrating mononuclear phagocytes are crucial for tissue regeneration. The interaction of the CCL2/CCR2 and CX3CL1/CX3CR1 chemokine axis that guides phagocyte infiltration is incompletely understood. Here, we show that CX3CR1 deficiency promotes muscle repair and rescues Ccl2−/− mice from impaired muscle regeneration as a result of altered macrophage function, not infiltration. Transcriptomic analysis of muscle mononuclear phagocytes reveals that Apolipoprotein E (ApoE) is upregulated in mice with efficient regeneration. ApoE treatment enhances phagocytosis by mononuclear phagocytes in vitro, and restores phagocytic activity and muscle regeneration in Ccl2−/− mice. Because CX3CR1 deficiency may compensate for defective CCL2-dependant monocyte recruitment by modulating ApoE-dependent macrophage phagocytic activity, targeting CX3CR1 expressed by macrophages might be a powerful therapeutic approach to improve muscle regeneration.
Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche
Authors: Lawson Michelle A. , McDonald Michelle M. , Kovacic Natasa , Hua Khoo Weng , Terry Rachael L. , Down Jenny , Kaplan Warren , Paton-Hough Julia , Fellows Clair , Pettitt Jessica A. , Neil Dear T. , Van Valckenborgh Els , Baldock Paul A. , Rogers Michael J. , Eaton Colby L. , Vanderkerken Karin , Pettit Allison R. , Quinn Julian M. W. , Zannettino Andrew C. W. , Phan Tri Giang , Croucher Peter I. 
Published: December 2015

AbstractMultiple myeloma is largely incurable, despite development of therapies that target myeloma cell-intrinsic pathways. Disease relapse is thought to originate from dormant myeloma cells, localized in specialized niches, which resist therapy and repopulate the tumour. However, little is known about the niche, and how it exerts cell-extrinsic control over myeloma cell dormancy and reactivation. In this study, we track individual myeloma cells by intravital imaging as they colonize the endosteal niche, enter a dormant state and subsequently become activated to form colonies. We demonstrate that dormancy is a reversible state that is switched ‘on’ by engagement with bone-lining cells or osteoblasts, and switched ‘off’ by osteoclasts remodelling the endosteal niche. Dormant myeloma cells are resistant to chemotherapy that targets dividing cells. The demonstration that the endosteal niche is pivotal in controlling myeloma cell dormancy highlights the potential for targeting cell-extrinsic mechanisms to overcome cell-intrinsic drug resistance and prevent disease relapse.
Superbunching and Nonclassicality as new Hallmarks of Superradiance
Authors: Bhatti Daniel , von Zanthier Joachim , Agarwal Girish S. 
Published: December 2015

AbstractSuperradiance, i.e., spontaneous emission of coherent radiation by an ensemble of two-level atoms in collective states introduced by Dicke in 1954, is one of the enigmatic problems of quantum optics. The startling gist is that even though the atoms have no dipole moment they radiate with increased intensity in particular directions. Following the advances in our understanding of superradiant emission by atoms in entangled W-states we examine the quantum statistical properties of superradiance. Such investigations require the system to have at least two excitations in order to explore the photon-photon correlations of the radiation emitted by such states. We present specifically results for the spatially resolved photon-photon correlations of systems prepared in doubly excited W-states and give conditions when the atomic system emits nonclassial light. Equally, we derive the conditions for the occurrence of bunching and even of superbunching, a rare phenomenon otherwise known only from nonclassical states of light like the squeezed vacuum. We finally investigate the photon-photon cross correlations of the spontaneously scattered light and highlight the nonclassicalty of such correlations. The theoretical findings can be implemented with current technology, e.g., using ions in a linear rf-trap, atoms in an optical lattice or quantum dots in a cavity.
Miniaturized Swimming Soft Robot with Complex Movement Actuated and Controlled by Remote Light Signals
Authors: Huang Chaolei , Lv Jiu-an , Tian Xiaojun , Wang Yuechao , Yu Yanlei , Liu Jie 
Published: December 2015

AbstractPowering and communication with micro robots to enable complex functions is a long-standing challenge as the size of robots continues to shrink. Physical connection of wires or components needed for wireless communication are complex and limited by the size of electronic and energy storage devices, making miniaturization of robots difficult. To explore an alternative solution, we designed and fabricated a micro soft swimming robot with both powering and controlling functions provided by remote light, which does not carry any electronic devices and batteries. In this approach, a polymer film containing azobenzene chromophore which is sensitive to ultra-violet (UV) light works as “motor” and the UV light and visible light work as “power and signal lines”. Periodically flashing UV light and white light drives the robot flagellum periodically to swing to eventually push forward the robot in the glass tube filled with liquid. The gripper on robot head can be opened or closed by lights to grab and carry the load. This kind of remotely light-driven approach realizes complex driving and controlling of micro robotic structures, making it possible to design and fabricate even smaller robots. It will have great potential among applications in the micro machine and robot fields.
MicroRNA-195 inhibits proliferation, invasion and metastasis in breast cancer cells by targeting FASN, HMGCR, ACACA and CYP27B1
Authors: Singh Richa , Yadav Vikas , kumar Sachin , Saini Neeru 
Published: December 2015

AbstractDe novo lipogenesis, a hallmark for cancers is required for cellular transformation. Further it is believed that resistance to apoptosis and epithelial-to-mesenchymal-transition(EMT) facilitates metastasis via over-expression of anti-apoptotic Bcl-2. Previously we demonstrated that hsa-miR-195 targets BCL2, induces apoptosis and augmented the effect of etoposide in breast cancer cells. However, the mechanism behind its function remains elusive. Herein gene expression profiling was done in presence/absence of hsa-miR-195 in Breast cancer cells. IPA revealed mitochondrial dysfunction, fatty acid metabolism and xenobiotic metabolism signalling among the top processes being affected. For the first time we herein identified ACACA, FASN (the key enzymes of de novo fatty acid synthesis), HMGCR (the key enzyme of de novo cholesterol synthesis) and CYP27B1 as direct targets of hsa-miR-195. We further showed that ectopic expression of hsa-miR-195 in MCF-7 and MDA-MB-231 cells not only altered cellular cholesterol and triglyceride levels significantly but also resulted in reduced proliferation, invasion and migration. We further demonstrated that over expression of hsa-miR-195 decreased the Mesenchymal markers expression and enhanced Epithelial markers. In conclusion we say that hsa-miR-195 targets the genes of de novo lipogenesis, inhibits cell proliferation, migration and invasion which potentially opens new avenues for the treatment of breast cancer.
Acetaminophen cytotoxicity is ameliorated in a human liver organotypic co-culture model
Authors: Nelson Leonard J. , Navarro Maria , Treskes Philipp , Samuel Kay , Tura-Ceide Olga , Morley Steven D. , Hayes Peter C. , Plevris John N. 
Published: December 2015

AbstractOrganotypic liver culture models for hepatotoxicity studies that mimic in vivo hepatic functionality could help facilitate improved strategies for early safety risk assessment during drug development. Interspecies differences in drug sensitivity and mechanistic profiles, low predictive capacity and limitations of conventional monocultures of human hepatocytes, with high attrition rates remain major challenges. Herein, we show stable, cell-type specific phenotype/cellular polarity with differentiated functionality in human hepatocyte-like C3A cells (enhanced CYP3A4 activity/albumin synthesis) when in co-culture with human vascular endothelial cells (HUVECs), thus demonstrating biocompatibility and relevance for evaluating drug metabolism and toxicity. In agreement with in vivo studies, acetaminophen (APAP) toxicity was most profound in HUVEC mono-cultures; whilst in C3A:HUVEC co-culture, cells were less susceptible to the toxic effects of APAP, including parameters of oxidative stress and ATP depletion, altered redox homeostasis and impaired respiration. This resistance to APAP is also observed in a primary human hepatocyte (PHH) based co-culture model, suggesting bidirectional communication/stabilization between different cell types. This simple and easy-to-implement human co-culture model may represent a sustainable and physiologically-relevant alternative cell system to PHHs, complementary to animal testing, for initial hepatotoxicity screening or mechanistic studies of candidate compounds differentially targeting hepatocytes and endothelial cells.
Identification of novel PKD1 and PKD2 mutations in a Chinese population with autosomal dominant polycystic kidney disease
Authors: Liu Bei , Chen Song-Chang , Yang Yan-Mei , Yan Kai , Qian Ye-Qing , Zhang Jun-Yu , Hu Yu-Ting , Dong Min-Yue , Jin Fan , Huang He-Feng , Xu Chen-Ming 
Published: December 2015

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is one of the most frequently inherited renal diseases caused by mutations in PKD1 and PKD2. We performed mutational analyses of PKD genes in 49 unrelated patients using direct PCR-sequencing and multiplex ligation-dependent probe amplification (MLPA) for PKD1 and PKD2. RT-PCR analysis was also performed in a family with a novel PKD2 splicing mutation. Disease-causing mutations were identified in 44 (89.8%) of the patients: 42 (95.5%) of the patients showed mutations in PKD1 and 2 (4.5%) showed mutations in PKD2. Ten nonsense, 17 frameshift, 4 splicing and one in-frame mutation were found in 32 of the patients. Large rearrangements were found in 3 patients and missense mutations were found in 9 patients. Approximately 61.4% (27/44) of the mutations are first reported with a known mutation rate of 38.6%. RNA analysis of a novel PKD2 mutation (c.595_595 + 14delGGTAAGAGCGCGCGA) suggested monoallelic expression of the wild-type allele. Furthermore, patients with PKD1-truncating mutations reached end-stage renal disease (ESRD) earlier than patients with non-truncating mutations (47 ± 3.522 years vs. 59 ± 11.687 years, P = 0.016). The mutation screening of PKD genes in Chinese ADPKD patients will enrich our mutation database and significantly contribute to improve genetic counselling for ADPKD patients.