bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benefit from decline: the primary transcriptome of Alteromonas macleodii str. Te101 during Trichodesmium demise
Authors: Hou Shengwei , López-Pérez Mario , Pfreundt Ulrike , Belkin Natalia , Stüber Kurt , Huettel Bruno , Reinhardt Richard , Berman-Frank Ilana , Rodriguez-Valera Francisco , Hess Wolfgang R 
Published: January 2018

Abstract
Interactions between co-existing microorganisms deeply affect the physiology of the involved organisms and, ultimately, the function of the ecosystem as a whole. Copiotrophic Alteromonas are marine gammaproteobacteria that thrive during the late stages of phytoplankton blooms in the marine environment and in laboratory co-cultures with cyanobacteria such as Trichodesmium. The response of this heterotroph to the sometimes rapid and transient changes in nutrient supply when the phototroph crashes is not well understood. Here, we isolated and sequenced the strain Alteromonas macleodii str. Te101 from a laboratory culture of Trichodesmium erythraeum IMS101, yielding a chromosome of 4.63 Mb and a single plasmid of 237 kb. Increasing salinities to ≥43 ppt inhibited the growth of Trichodesmium but stimulated growth of the associated Alteromonas. We characterized the transcriptomic responses of both microorganisms and identified the complement of active transcriptional start sites in Alteromonas at single-nucleotide resolution. In replicate cultures, a similar set of genes became activated in Alteromonas when growth rates of Trichodesmium declined and mortality was high. The parallel activation of fliA, rpoS and of flagellar assembly and growth-related genes indicated that Alteromonas might have increased cell motility, growth, and multiple biosynthetic activities. Genes with the highest expression in the data set were three small RNAs (Aln1a-c) that were identified as analogs of the small RNAs CsrB-C in E. coli or RsmX-Z in pathogenic bacteria. Together with the carbon storage protein A (CsrA) homolog Te101_05290, these RNAs likely control the expression of numerous genes in responding to changes in the environment.
The expression of inhibitor of bruton’s tyrosine kinase gene is progressively up regulated in the clinical course of chronic lymphocytic leukaemia conferring resistance to apoptosis
Authors: Albano Francesco , Chiurazzi Federico , Mimmi Selena , Vecchio Eleonora , Pastore Arianna , Cimmino Clementina , Frieri Camilla , Iaccino Enrico , Pisano Antonio , Golino Gaetanina , Fiume Giuseppe , Mallardo Massimo , Scala Giuseppe , Quinto Ileana 
Published: January 2018

AbstractChronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy with a variable clinical outcome. Biomarkers of CLL progression are required for optimising prognosis and therapy. The Inhibitor of Bruton’s tyrosine kinase—isoform α (IBTKα) gene encodes a substrate receptor of Cullin 3-dependent E3 ubiquitin ligase, and promotes cell survival in response to the reticulum stress. Searching for novel markers of CLL progression, we analysed the expression ofIBTKα in the peripheral blood B-cells of CLL patients, before and after first line therapy causing remission. The expression ofIBTKα was significantly increased in disease progression, and decreased in remission after chemotherapy. Consistently with a pro-survival action, RNA interference ofIBTKα increased the spontaneous and Fludarabine-induced apoptosis of MEC-1 CLL cells, and impaired the cell cycle of DeFew B-lymphoma cells by promoting the arrest in G0/G1 phase and apoptosis. Consistently, RNA interference ofIBTKα up regulated the expression of pro-apoptotic genes, includingTNF,CRADD, CASP7, BNIP3 and BIRC3. Our results indicate thatIBTKα is a novel marker of CLL progression promoting cell growth and resistance to apoptosis. In this view,IBTKα may represent an attractive cancer drug target for counteracting the therapy-resistance of tumour cells.
Author Correction: Spiraling pathways of global deep waters to the surface of the Southern Ocean
Authors: Tamsitt Veronica , Drake Henri F. , Morrison Adele K. , Talley Lynne D. , Dufour Carolina O. , Gray Alison R. , Griffies Stephen M. , Mazloff Matthew R. , Sarmiento Jorge L. , Wang Jinbo , Weijer Wilbert 
Published: January 2018

The original version of this Article contained errors in Fig. 6. In panel a, the grey highlights obscured the curves for CESM, CM2.6 and SOSE, and the labels indicating SWIR, KP, MR, PAR, and DP were inadvertently omitted. These have now been corrected in both the PDF and HTML versions of the Article.
Radical asymmetric intramolecular α-cyclopropanation of aldehydes towards bicyclo[3.1.0]hexanes containing vicinal all-carbon quaternary stereocenters
Authors: Ye Liu , Gu Qiang-Shuai , Tian Yu , Meng Xiang , Chen Guo-Cong , Liu Xin-Yuan 
Published: January 2018

AbstractThe development of a general catalytic method for the direct and stereoselective construction of cyclopropanes bearing highly congested vicinal all-carbon quaternary stereocenters remains a formidable challenge in chemical synthesis. Here, we report an intramolecular radical cyclopropanation of unactivated alkenes with simple α-methylene group of aldehydes as C1 source via a Cu(I)/secondary amine cooperative catalyst, which enables the single-step construction of bicyclo[3.1.0]hexane skeletons with excellent efficiency, broad substrate scope covering various terminal, internal alkenes as well as diverse (hetero)aromatic, alkenyl, alkyl-substituted geminal alkenes. Moreover, this reaction has been successfully realized to an asymmetric transformation, providing an attractive approach for the construction of enantioenriched bicyclo[3.1.0]hexanes bearing two crucial vicinal all-carbon quaternary stereocenters with good to excellent enantioselectivity. The utility of this method is illustrated by facile transformations of the products into various useful chiral synthetic intermediates. Preliminary mechanistic studies support a stepwise radical process for this formal [2 + 1] cycloaddition.
Causal associations between risk factors and common diseases inferred from GWAS summary data
Authors: Zhu Zhihong , Zheng Zhili , Zhang Futao , Wu Yang , Trzaskowski Maciej , Maier Robert , Robinson Matthew R. , McGrath John J. , Visscher Peter M. , Wray Naomi R. , Yang Jian 
Published: January 2018

AbstractHealth risk factors such as body mass index (BMI) and serum cholesterol are associated with many common diseases. It often remains unclear whether the risk factors are cause or consequence of disease, or whether the associations are the result of confounding. We develop and apply a method (called GSMR) that performs a multi-SNP Mendelian randomization analysis using summary-level data from genome-wide association studies to test the causal associations of BMI, waist-to-hip ratio, serum cholesterols, blood pressures, height, and years of schooling (EduYears) with common diseases (sample sizes of up to 405,072). We identify a number of causal associations including a protective effect of LDL-cholesterol against type-2 diabetes (T2D) that might explain the side effects of statins on T2D, a protective effect of EduYears against Alzheimer’s disease, and bidirectional associations with opposite effects (e.g., higher BMI increases the risk of T2D but the effect of T2D on BMI is negative).
Monitoring single-cell gene regulation under dynamically controllable conditions with integrated microfluidics and software
Authors: Kaiser Matthias , Jug Florian , Julou Thomas , Deshpande Siddharth , Pfohl Thomas , Silander Olin K. , Myers Gene , van Nimwegen Erik 
Published: January 2018

AbstractMuch is still not understood about how gene regulatory interactions control cell fate decisions in single cells, in part due to the difficulty of directly observing gene regulatory processes in vivo. We introduce here a novel integrated setup consisting of a microfluidic chip and accompanying analysis software that enable long-term quantitative tracking of growth and gene expression in single cells. The dual-input Mother Machine (DIMM) chip enables controlled and continuous variation of external conditions, allowing direct observation of gene regulatory responses to changing conditions in single cells. The Mother Machine Analyzer (MoMA) software achieves unprecedented accuracy in segmenting and tracking cells, and streamlines high-throughput curation with a novel leveraged editing procedure. We demonstrate the power of the method by uncovering several novel features of an iconic gene regulatory program: the induction of Escherichia coli’s lac operon in response to a switch from glucose to lactose.
Experimental quantum simulation of fermion-antifermion scattering via boson exchange in a trapped ion
Authors: Zhang Xiang , Zhang Kuan , Shen Yangchao , Zhang Shuaining , Zhang Jing-Ning , Yung Man-Hong , Casanova Jorge , Pedernales Julen S. , Lamata Lucas , Solano Enrique , Kim Kihwan 
Published: January 2018

AbstractQuantum field theories describe a variety of fundamental phenomena in physics. However, their study often involves cumbersome numerical simulations. Quantum simulators, on the other hand, may outperform classical computational capacities due to their potential scalability. Here we report an experimental realization of a quantum simulation of fermion–antifermion scattering mediated by bosonic modes, using a multilevel trapped ion, which is a simplified model of fermion scattering in both perturbative and non-perturbative quantum electrodynamics. The simulated model exhibits prototypical features in quantum field theory including particle pair creation and annihilation, as well as self-energy interactions. These are experimentally observed by manipulating four internal levels of a 171Yb+ trapped ion, where we encode the fermionic modes, and two motional degrees of freedom that simulate the bosonic modes. Our experiment establishes an avenue towards the efficient implementation of field modes, which may prove useful in studies of quantum field theories including non-perturbative regimes.
High-resolution TADs reveal DNA sequences underlying genome organization in flies
Authors: Ramírez Fidel , Bhardwaj Vivek , Arrigoni Laura , Lam Kin Chung , Grüning Björn A. , Villaveces José , Habermann Bianca , Akhtar Asifa , Manke Thomas 
Published: January 2018

AbstractDespite an abundance of new studies about topologically associating domains (TADs), the role of genetic information in TAD formation is still not fully understood. Here we use our software, HiCExplorer (hicexplorer.readthedocs.io) to annotate >2800 high-resolution (570 bp) TAD boundaries in Drosophila melanogaster. We identify eight DNA motifs enriched at boundaries, including a motif bound by the M1BP protein, and two new boundary motifs. In contrast to mammals, the CTCF motif is only enriched on a small fraction of boundaries flanking inactive chromatin while most active boundaries contain the motifs bound by the M1BP or Beaf-32 proteins. We demonstrate that boundaries can be accurately predicted using only the motif sequences at open chromatin sites. We propose that DNA sequence guides the genome architecture by allocation of boundary proteins in the genome. Finally, we present an interactive online database to access and explore the spatial organization of fly, mouse and human genomes, available at http://chorogenome.ie-freiburg.mpg.de.
Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer
Authors: Fang Tian , Lv Hongwei , Lv Guishuai , Li Ting , Wang Changzheng , Han Qin , Yu Lexing , Su Bo , Guo Linna , Huang Shanna , Cao Dan , Tang Liang , Tang Shanhua , Wu Mengchao , Yang Wen , Wang Hongyang 
Published: January 2018

AbstractThe communication between tumor-derived elements and stroma in the metastatic niche has a critical role in facilitating cancer metastasis. Yet, the mechanisms tumor cells use to control metastatic niche formation are not fully understood. Here we report that in the lung metastatic niche, high-metastatic hepatocellular carcinoma (HCC) cells exhibit a greater capacity to convert normal fibroblasts to cancer-associated fibroblasts (CAFs) than low-metastatic HCC cells. We show high-metastatic HCC cells secrete exosomal miR-1247-3p that directly targets B4GALT3, leading to activation of β1-integrin–NF-κB signaling in fibroblasts. Activated CAFs further promote cancer progression by secreting pro-inflammatory cytokines, including IL-6 and IL-8. Clinical data show high serum exosomal miR-1247-3p levels correlate with lung metastasis in HCC patients. These results demonstrate intercellular crosstalk between tumor cells and fibroblasts is mediated by tumor-derived exosomes that control lung metastasis of HCC, providing potential targets for prevention and treatment of cancer metastasis.
Chronic alcohol exposure disrupts top-down control over basal ganglia action selection to produce habits
Authors: Renteria Rafael , Baltz Emily T. , Gremel Christina M. 
Published: January 2018

AbstractAddiction involves a predominance of habitual control mediated through action selection processes in dorsal striatum. Research has largely focused on neural mechanisms mediating a proposed progression from ventral to dorsal lateral striatal control in addiction. However, over reliance on habit striatal processes may also arise from reduced cortical input to striatum, thereby disrupting executive control over action selection. Here, we identify novel mechanisms through which chronic intermittent ethanol exposure and withdrawal (CIE) disrupts top-down control over goal-directed action selection processes to produce habits. We find CIE results in decreased excitability of orbital frontal cortex (OFC) excitatory circuits supporting goal-directed control, and, strikingly, selectively reduces OFC output to the direct output pathway in dorsal medial striatum. Increasing the activity of OFC circuits restores goal-directed control in CIE-exposed mice. Our findings show habitual control in alcohol dependence can arise through disrupted communication between top-down, goal-directed processes onto basal ganglia pathways controlling action selection.
Intelligent image-based in situ single-cell isolation
Authors: Brasko Csilla , Smith Kevin , Molnar Csaba , Farago Nora , Hegedus Lili , Balind Arpad , Balassa Tamas , Szkalisity Abel , Sukosd Farkas , Kocsis Katalin , Balint Balazs , Paavolainen Lassi , Enyedi Marton Z. , Nagy Istvan , Puskas Laszlo G. , Haracska Lajos , Tamas Gabor , Horvath Peter 
Published: January 2018

AbstractQuantifying heterogeneities within cell populations is important for many fields including cancer research and neurobiology; however, techniques to isolate individual cells are limited. Here, we describe a high-throughput, non-disruptive, and cost-effective isolation method that is capable of capturing individually targeted cells using widely available techniques. Using high-resolution microscopy, laser microcapture microscopy, image analysis, and machine learning, our technology enables scalable molecular genetic analysis of single cells, targetable by morphology or location within the sample.
Reconfiguring crystal and electronic structures of MoS2 by substitutional doping
Authors: Suh Joonki , Tan Teck Leong , Zhao Weijie , Park Joonsuk , Lin Der-Yuh , Park Tae-Eon , Kim Jonghwan , Jin Chenhao , Saigal Nihit , Ghosh Sandip , Wong Zicong Marvin , Chen Yabin , Wang Feng , Walukiewicz Wladyslaw , Eda Goki , Wu Junqiao 
Published: January 2018

AbstractDoping of traditional semiconductors has enabled technological applications in modern electronics by tailoring their chemical, optical and electronic properties. However, substitutional doping in two-dimensional semiconductors is at a comparatively early stage, and the resultant effects are less explored. In this work, we report unusual effects of degenerate doping with Nb on structural, electronic and optical characteristics of MoS2 crystals. The doping readily induces a structural transformation from naturally occurring 2H stacking to 3R stacking. Electronically, a strong interaction of the Nb impurity states with the host valence bands drastically and nonlinearly modifies the electronic band structure with the valence band maximum of multilayer MoS2 at the Γ point pushed upward by hybridization with the Nb states. When thinned down to monolayers, in stark contrast, such significant nonlinear effect vanishes, instead resulting in strong and broadband photoluminescence via the formation of exciton complexes tightly bound to neutral acceptors.
USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark from H2A
Authors: Uckelmann Michael , Densham Ruth M. , Baas Roy , Winterwerp Herrie H. K. , Fish Alexander , Sixma Titia K. , Morris Joanna R. 
Published: January 2018

AbstractBRCA1-BARD1-catalyzed ubiquitination of histone H2A is an important regulator of the DNA damage response, priming chromatin for repair by homologous recombination. However, no specific deubiquitinating enzymes (DUBs) are known to antagonize this function. Here we identify ubiquitin specific protease-48 (USP48) as a H2A DUB, specific for the C-terminal BRCA1 ubiquitination site. Detailed biochemical analysis shows that an auxiliary ubiquitin, an additional ubiquitin that itself does not get cleaved, modulates USP48 activity, which has possible implications for its regulation in vivo. In cells we reveal that USP48 antagonizes BRCA1 E3 ligase function and in BRCA1-proficient cells loss of USP48 results in positioning 53BP1 further from the break site and in extended resection lengths. USP48 repression confers a survival benefit to cells treated with camptothecin and its activity acts to restrain gene conversion and mutagenic single-strand annealing. We propose that USP48 promotes genome stability by antagonizing BRCA1 E3 ligase function.
Copper sulfide nanoparticles as a photothermal switch for TRPV1 signaling to attenuate atherosclerosis
Authors: Gao Wen , Sun Yuhui , Cai Michelle , Zhao Yujie , Cao Wenhua , Liu Zhenhua , Cui Guanwei , Tang Bo 
Published: January 2018

AbstractAtherosclerosis is characterized by the accumulation of lipids within the arterial wall. Although activation of TRPV1 cation channels by capsaicin may reduce lipid storage and the formation of atherosclerotic lesions, a clinical use for capsaicin has been limited by its chronic toxicity. Here we show that coupling of copper sulfide (CuS) nanoparticles to antibodies targeting TRPV1 act as a photothermal switch for TRPV1 signaling in vascular smooth muscle cells (VSMCs) using near-infrared light. Upon irradiation, local increases of temperature open thermo-sensitive TRPV1 channels and cause Ca2+ influx. The increase in intracellular Ca2+ activates autophagy and impedes foam cell formation in VSMCs treated with oxidized low-density lipoprotein. In vivo, CuS-TRPV1 allows photoacoustic imaging of the cardiac vasculature and reduces lipid storage and plaque formation in ApoE−/− mice fed a high-fat diet, with no obvious long-term toxicity. Together, this suggests CuS-TRPV1 may represent a therapeutic tool to locally and temporally attenuate atherosclerosis.
Escape from thymic deletion and anti-leukemic effects of T cells specific for hematopoietic cell-restricted antigen
Authors: Ju Ji-Min , Jung Min Ho , Nam Giri , Kim Woojin , Oh Sehwa , Kim Hyun Duk , Kim Joo Young , Chang Jun , Lee Sung Hak , Park Gyeong Sin , Min Chang-Ki , Lee Dong-Sup , Kim Moon Gyo , Choi Kyungho , Choi Eun Young 
Published: January 2018

AbstractWhether hematopoietic cell-restricted distribution of antigens affects the degree of thymic negative selection has not been investigated in detail. Here, we show that T cells specific for hematopoietic cell-restricted antigens (HRA) are not completely deleted in the thymus, using the mouse minor histocompatibility antigen H60, the expression of which is restricted to hematopoietic cells. As a result, low avidity T cells escape from thymic deletion. This incomplete thymic deletion occurs to the T cells developing de novo in the thymus of H60-positive recipients in H60-mismatched bone marrow transplantation (BMT). H60-specific thymic deletion escapee CD8+T cells exhibit effector differentiation potentials in the periphery and contribute to graft-versus-leukemia effects in the recipients of H60-mismatched BMT, regressing H60+hematological tumors. These results provide information essential for understanding thymic negative selection and developing a strategy to treat hematological tumors.
Quantum non-Gaussian multiphoton light
Authors: Straka Ivo , Lachman Lukáš , Hloušek Josef , Miková Martina , Mičuda Michal , Ježek Miroslav , Filip Radim 
Published: January 2018

AbstractWe propose an experimental method of recognizing quantum non-Gaussian multiphoton states. This is a native quantum property of Fock states, the fundamental quantum states with a constant number of particles. Our method allows experimental development and characterization of higher Fock states of light, reaching even beyond the current technical limits of their generation. We experimentally demonstrate that it is capable of distinguishing realistic quantum non-Gaussian light with the mean number of photons up to five despite detection efficiency of 50%. We also provide evidence that our method can help to distinguish the number of single-photon emitters based only on their collective emission.
Electron beam melting in the fabrication of three-dimensional mesh titanium mandibular prosthesis scaffold
Authors: Yan Rongzeng , Luo Danmei , Huang Haitao , Li Runxin , Yu Niu , Liu Changkui , Hu Min , Rong Qiguo 
Published: January 2018

AbstractThe study was designed to fulfill effective work-flow to fabricate three-dimensional mesh titanium scaffold for mandibular reconstruction. The 3D titanium mesh scaffold was designed based on a volunteer with whole mandible defect. (1) acquisition of the CT data; (2) design with computer aided design (CAD) and finite element analysis (FEA). The pore size and intervals with the best mechanic strength was also calculated using FEA. (3) fabrication of the scaffold using electron beam melting (EBM); (4) implantation surgery. The case recovered well, without loosening and rejection. Additionally, 12 mandibular defect model beagles were used to verify the results. The model was established via tooth extraction and mandibular resection surgeries, and the scaffold was designed individually based on CT data obtained at 2 weeks after extraction operation. Then scaffolds were fabricated using 3D EBM, and the implantation surgery was performed at 2 months after extraction operation. All the animals healed well after implantation, and the grafted mandibular recovered well with time. The relevant parameters of the grafted mandibular were nearly to the native mandibular at postoperative 12 months. It is feasible to fabricate mesh titanium scaffold for repairing mandibular defects individually using reverse engineering, CAD and EBM techniques.