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Nature Communications

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https://www.readbyqxmd.com/read/29777171/mll-fusion-driven-leukemia-requires-setd2-to-safeguard-genomic-integrity
#1
Anna Skucha, Jessica Ebner, Johannes Schmöllerl, Mareike Roth, Thomas Eder, Adrián César-Razquin, Alexey Stukalov, Sarah Vittori, Matthias Muhar, Bin Lu, Martin Aichinger, Julian Jude, André C Müller, Balázs Győrffy, Christopher R Vakoc, Peter Valent, Keiryn L Bennett, Johannes Zuber, Giulio Superti-Furga, Florian Grebien
MLL-fusions represent a large group of leukemia drivers, whose diversity originates from the vast molecular heterogeneity of C-terminal fusion partners of MLL. While studies of selected MLL-fusions have revealed critical molecular pathways, unifying mechanisms across all MLL-fusions remain poorly understood. We present the first comprehensive survey of protein-protein interactions of seven distantly related MLL-fusion proteins. Functional investigation of 128 conserved MLL-fusion-interactors identifies a specific role for the lysine methyltransferase SETD2 in MLL-leukemia...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777157/transient-metal-centered-states-mediate-isomerization-of-a-photochromic-ruthenium-sulfoxide-complex
#2
Amy A Cordones, Jae Hyuk Lee, Kiryong Hong, Hana Cho, Komal Garg, Martial Boggio-Pasqua, Jeffrey J Rack, Nils Huse, Robert W Schoenlein, Tae Kyu Kim
Ultrafast isomerization reactions underpin many processes in (bio)chemical systems and molecular materials. Understanding the coupled evolution of atomic and molecular structure during isomerization is paramount for control and rational design in molecular science. Here we report transient X-ray absorption studies of the photo-induced linkage isomerization of a Ru-based photochromic molecule. X-ray spectra reveal the spin and valence charge of the Ru atom and provide experimental evidence that metal-centered excited states mediate isomerization...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777137/enhanced-efficacy-of-combined-temozolomide-and-bromodomain-inhibitor-therapy-for-gliomas-using-targeted-nanoparticles
#3
Fred C Lam, Stephen W Morton, Jeffrey Wyckoff, Tu-Lan Vu Han, Mun Kyung Hwang, Amanda Maffa, Elena Balkanska-Sinclair, Michael B Yaffe, Scott R Floyd, Paula T Hammond
Effective treatment for glioblastoma (GBM) is limited by the presence of the blood-brain barrier (BBB) and rapid resistance to single agent therapies. To address these issues, we developed a transferrin-functionalized nanoparticle (Tf-NP) that can deliver dual combination therapies. Using intravital imaging, we show the ability of Tf-NPs to traverse intact BBB in mice as well as achieve direct tumor binding in two intracranial orthotopic models of GBM. Treatment of tumor-bearing mice with Tf-NPs loaded with temozolomide and the bromodomain inhibitor JQ1 leads to increased DNA damage and apoptosis that correlates with a 1...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777131/activity-of-acetyltransferase-toxins-involved-in-salmonella-persister-formation-during-macrophage-infection
#4
Julian A Rycroft, Bridget Gollan, Grzegorz J Grabe, Alexander Hall, Angela M Cheverton, Gerald Larrouy-Maumus, Stephen A Hare, Sophie Helaine
Non-typhoidal Salmonella strains are responsible for invasive infections associated with high mortality and recurrence in sub-Saharan Africa, and there is strong evidence for clonal relapse following antibiotic treatment. Persisters are non-growing bacteria that are thought to be responsible for the recalcitrance of many infections to antibiotics. Toxin-antitoxin systems are stress-responsive elements that are important for Salmonella persister formation, specifically during infection. Here, we report the analysis of persister formation of clinical invasive strains of Salmonella Typhimurium and Enteritidis in human primary macrophages...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777109/tak1-mediates-microenvironment-triggered-autocrine-signals-and-promotes-triple-negative-breast-cancer-lung-metastasis
#5
Oihana Iriondo, Yarong Liu, Grace Lee, Mostafa Elhodaky, Christian Jimenez, Lin Li, Julie Lang, Pin Wang, Min Yu
Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer that has limited therapeutic options. Thus, developing novel treatments for metastatic TNBC is an urgent need. Here, we show that nanoparticle-mediated delivery of transforming growth factor-β1-activated kinase-1 (TAK1) inhibitor 5Z-7-Oxozeaenol can inhibit TNBC lung metastasis in most animals tested. P38 is a central signal downstream of TAK1 in TNBC cells in TAK1-mediated response to multiple cytokines. Following co-culturing with macrophages or fibroblasts, TNBC cells express interleukin-1 (IL1) or tumor necrosis factor-α (TNFα), respectively...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777108/factor-xiiia-expressing-inflammatory-monocytes-promote-lung-squamous-cancer-through-fibrin-cross-linking
#6
Alessandro Porrello, Patrick L Leslie, Emily B Harrison, Balachandra K Gorentla, Sravya Kattula, Subrata K Ghosh, Salma H Azam, Alisha Holtzhausen, Yvonne L Chao, Michele C Hayward, Trent A Waugh, Sanggyu Bae, Virginia Godfrey, Scott H Randell, Cecilia Oderup, Liza Makowski, Jared Weiss, Matthew D Wilkerson, D Neil Hayes, H Shelton Earp, Albert S Baldwin, Alisa S Wolberg, Chad V Pecot
Lung cancer is the leading cause of cancer-related deaths worldwide, and lung squamous carcinomas (LUSC) represent about 30% of cases. Molecular aberrations in lung adenocarcinomas have allowed for effective targeted treatments, but corresponding therapeutic advances in LUSC have not materialized. However, immune checkpoint inhibitors in sub-populations of LUSC patients have led to exciting responses. Using computational analyses of The Cancer Genome Atlas, we identified a subset of LUSC tumors characterized by dense infiltration of inflammatory monocytes (IMs) and poor survival...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777105/phenotypic-diversification-by-enhanced-genome-restructuring-after-induction-of-multiple-dna-double-strand-breaks
#7
Nobuhiko Muramoto, Arisa Oda, Hidenori Tanaka, Takahiro Nakamura, Kazuto Kugou, Kazuki Suda, Aki Kobayashi, Shiori Yoneda, Akinori Ikeuchi, Hiroki Sugimoto, Satoshi Kondo, Chikara Ohto, Takehiko Shibata, Norihiro Mitsukawa, Kunihiro Ohta
DNA double-strand break (DSB)-mediated genome rearrangements are assumed to provide diverse raw genetic materials enabling accelerated adaptive evolution; however, it remains unclear about the consequences of massive simultaneous DSB formation in cells and their resulting phenotypic impact. Here, we establish an artificial genome-restructuring technology by conditionally introducing multiple genomic DSBs in vivo using a temperature-dependent endonuclease TaqI. Application in yeast and Arabidopsis thaliana generates strains with phenotypes, including improved ethanol production from xylose at higher temperature and increased plant biomass, that are stably inherited to offspring after multiple passages...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777104/optical-wireless-link-between-a-nanoscale-antenna-and-a-transducing-rectenna
#8
Arindam Dasgupta, Marie-Maxime Mennemanteuil, Mickaël Buret, Nicolas Cazier, Gérard Colas-des-Francs, Alexandre Bouhelier
Initiated as a cable-replacement solution, short-range wireless power transfer has rapidly become ubiquitous in the development of modern high-data throughput networking in centimeter to meter accessibility range. Wireless technology is now penetrating a higher level of system integration for chip-to-chip and on-chip radiofrequency interconnects. However, standard CMOS integrated millimeter-wave antennas have typical size commensurable with the operating wavelength, and are thus an unrealistic solution for downsizing transmitters and receivers to the micrometer and nanometer scale...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777103/bacterial-encapsulins-as-orthogonal-compartments-for-mammalian-cell-engineering
#9
Felix Sigmund, Christoph Massner, Philipp Erdmann, Anja Stelzl, Hannes Rolbieski, Mitul Desai, Sarah Bricault, Tobias P Wörner, Joost Snijder, Arie Geerlof, Helmut Fuchs, Martin Hrabĕ de Angelis, Albert J R Heck, Alan Jasanoff, Vasilis Ntziachristos, Jürgen Plitzko, Gil G Westmeyer
We genetically controlled compartmentalization in eukaryotic cells by heterologous expression of bacterial encapsulin shell and cargo proteins to engineer enclosed enzymatic reactions and size-constrained metal biomineralization. The shell protein (EncA) from Myxococcus xanthus auto-assembles into nanocompartments inside mammalian cells to which sets of native (EncB,C,D) and engineered cargo proteins self-target enabling localized bimolecular fluorescence and enzyme complementation. Encapsulation of the enzyme tyrosinase leads to the confinement of toxic melanin production for robust detection via multispectral optoacoustic tomography (MSOT)...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777101/supramolecularly-directed-rotary-motion-in-a-photoresponsive-receptor
#10
Sander J Wezenberg, Ben L Feringa
Stimuli-controlled motion at the molecular level has fascinated chemists already for several decades. Taking inspiration from the myriad of dynamic and machine-like functions in nature, a number of strategies have been developed to control motion in purely synthetic systems. Unidirectional rotary motion, such as is observed in ATP synthase and other motor proteins, remains highly challenging to achieve. Current artificial molecular motor systems rely on intrinsic asymmetry or a specific sequence of chemical transformations...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777099/targeting-g-protein-coupled-receptor-signaling-at-the-g-protein-level-with-a-selective-nanobody-inhibitor
#11
Sahil Gulati, Hui Jin, Ikuo Masuho, Tivadar Orban, Yuan Cai, Els Pardon, Kirill A Martemyanov, Philip D Kiser, Phoebe L Stewart, Christopher P Ford, Jan Steyaert, Krzysztof Palczewski
G protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by mediating a GDP to GTP exchange in the Gα subunit. This leads to dissociation of the heterotrimer into Gα-GTP and Gβγ dimer. The Gα-GTP and Gβγ dimer each regulate a variety of downstream pathways to control various aspects of human physiology. Dysregulated Gβγ-signaling is a central element of various neurological and cancer-related anomalies. However, Gβγ also serves as a negative regulator of Gα that is essential for G protein inactivation, and thus has the potential for numerous side effects when targeted therapeutically...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777098/stepwise-control-of-host-guest-interaction-using-a-coordination-polymer-gel
#12
Rahul Dev Mukhopadhyay, Gourab Das, Ayyappanpillai Ajayaghosh
Precise control of host-guest interaction as seen in biological processes is difficult to achieve with artificial systems. Herein we have exploited the thermodynamic benefits of a system in equilibrium to achieve controlled stepwise release and capture of cyclodextrin (guest) using a coordination polymer (Mg-CP) as the host and temperature as the stimulus. Since temperature is not a precision stimulus for artificial host-guest interaction, the present system is a distinct prototype that manifests temperature-controlled natural host-guest interaction...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773874/mutations-in-six-nephrosis-genes-delineate-a-pathogenic-pathway-amenable-to-treatment
#13
Shazia Ashraf, Hiroki Kudo, Jia Rao, Atsuo Kikuchi, Eugen Widmeier, Jennifer A Lawson, Weizhen Tan, Tobias Hermle, Jillian K Warejko, Shirlee Shril, Merlin Airik, Tilman Jobst-Schwan, Svjetlana Lovric, Daniela A Braun, Heon Yung Gee, David Schapiro, Amar J Majmundar, Carolin E Sadowski, Werner L Pabst, Ankana Daga, Amelie T van der Ven, Johanna M Schmidt, Boon Chuan Low, Anjali Bansal Gupta, Brajendra K Tripathi, Jenny Wong, Kirk Campbell, Kay Metcalfe, Denny Schanze, Tetsuya Niihori, Hiroshi Kaito, Kandai Nozu, Hiroyasu Tsukaguchi, Ryojiro Tanaka, Kiyoshi Hamahira, Yasuko Kobayashi, Takumi Takizawa, Ryo Funayama, Keiko Nakayama, Yoko Aoki, Naonori Kumagai, Kazumoto Iijima, Henry Fehrenbach, Jameela A Kari, Sherif El Desoky, Sawsan Jalalah, Radovan Bogdanovic, Nataša Stajić, Hildegard Zappel, Assel Rakhmetova, Sharon-Rose Wassmer, Therese Jungraithmayr, Juergen Strehlau, Aravind Selvin Kumar, Arvind Bagga, Neveen A Soliman, Shrikant M Mane, Lewis Kaufman, Douglas R Lowy, Mohamad A Jairajpuri, Richard P Lifton, York Pei, Martin Zenker, Shigeo Kure, Friedhelm Hildebrandt
No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773832/distinct-epigenetic-landscapes-underlie-the-pathobiology-of-pancreatic-cancer-subtypes
#14
Gwen Lomberk, Yuna Blum, Rémy Nicolle, Asha Nair, Krutika Satish Gaonkar, Laetitia Marisa, Angela Mathison, Zhifu Sun, Huihuang Yan, Nabila Elarouci, Lucile Armenoult, Mira Ayadi, Tamas Ordog, Jeong-Heon Lee, Gavin Oliver, Eric Klee, Vincent Moutardier, Odile Gayet, Benjamin Bian, Pauline Duconseil, Marine Gilabert, Martin Bigonnet, Stephane Garcia, Olivier Turrini, Jean-Robert Delpero, Marc Giovannini, Philippe Grandval, Mohamed Gasmi, Veronique Secq, Aurélien De Reyniès, Nelson Dusetti, Juan Iovanna, Raul Urrutia
Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitation-sequencing (ChIP-seq) on multiple histone modifications, RNA-sequencing (RNA-seq), and DNA methylation to define epigenomic landscapes for PDAC subtypes, which can predict their relative aggressiveness and survival...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773803/a-novel-small-molecule-chaperone-of-rod-opsin-and-its-potential-therapy-for-retinal-degeneration
#15
Yuanyuan Chen, Yu Chen, Beata Jastrzebska, Marcin Golczak, Sahil Gulati, Hong Tang, William Seibel, Xiaoyu Li, Hui Jin, Yong Han, Songqi Gao, Jianye Zhang, Xujie Liu, Hossein Heidari-Torkabadi, Phoebe L Stewart, William E Harte, Gregory P Tochtrop, Krzysztof Palczewski
Rhodopsin homeostasis is tightly coupled to rod photoreceptor cell survival and vision. Mutations resulting in the misfolding of rhodopsin can lead to autosomal dominant retinitis pigmentosa (adRP), a progressive retinal degeneration that currently is untreatable. Using a cell-based high-throughput screen (HTS) to identify small molecules that can stabilize the P23H-opsin mutant, which causes most cases of adRP, we identified a novel pharmacological chaperone of rod photoreceptor opsin, YC-001. As a non-retinoid molecule, YC-001 demonstrates micromolar potency and efficacy greater than 9-cis-retinal with lower cytotoxicity...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773802/cd4-t-cells-are-activated-in-regional-lymph-nodes-and-migrate-to-skin-to-initiate-lymphedema
#16
Gabriela D García Nores, Catherine L Ly, Daniel A Cuzzone, Raghu P Kataru, Geoffrey E Hespe, Jeremy S Torrisi, Jung Ju Huang, Jason C Gardenier, Ira L Savetsky, Matthew D Nitti, Jessie Z Yu, Sonia Rehal, Babak J Mehrara
T cell-mediated responses have been implicated in the development of fibrosis, impaired lymphangiogenesis, and lymphatic dysfunction in secondary lymphedema. Here we show that CD4+ T cells are necessary for lymphedema pathogenesis by utilizing adoptive transfer techniques in CD4 knockout mice that have undergone tail skin and lymphatic excision or popliteal lymph node dissection. We also demonstrate that T cell activation following lymphatic injury occurs in regional skin-draining lymph nodes after interaction with antigen-presenting cells such as dendritic cells...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773801/lrrc8-vrac-anion-channels-enhance-%C3%AE-cell-glucose-sensing-and-insulin-secretion
#17
Till Stuhlmann, Rosa Planells-Cases, Thomas J Jentsch
Glucose homeostasis depends critically on insulin that is secreted by pancreatic β-cells. Serum glucose, which is directly sensed by β-cells, stimulates depolarization- and Ca2+ -dependent exocytosis of insulin granules. Here we show that pancreatic islets prominently express LRRC8A and LRRC8D, subunits of volume-regulated VRAC anion channels. Hypotonicity- or glucose-induced β-cell swelling elicits canonical LRRC8A-dependent VRAC currents that depolarize β-cells to an extent that causes electrical excitation...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773800/x-ray-structure-of-a-carpet-like-antimicrobial-defensin-phospholipid-membrane-disruption-complex
#18
Michael Järvå, Fung T Lay, Thanh Kha Phan, Cassandra Humble, Ivan K H Poon, Mark R Bleackley, Marilyn A Anderson, Mark D Hulett, Marc Kvansakul
Defensins are cationic antimicrobial peptides expressed throughout the plant and animal kingdoms as a first line of defense against pathogens. Membrane targeting and disruption is a crucial function of many defensins, however the precise mechanism remains unclear. Certain plant defensins form dimers that specifically bind the membrane phospholipids phosphatidic acid (PA) and phosphatidylinositol 4,5-bisphosphate, thereby triggering the assembly of defensin-lipid oligomers that permeabilize cell membranes. To understand this permeabilization mechanism, here we determine the crystal structure of the plant defensin NaD1 bound to PA...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773799/elucidating-the-genetic-architecture-of-reproductive-ageing-in-the-japanese-population
#19
Momoko Horikoshi, Felix R Day, Masato Akiyama, Makoto Hirata, Yoichiro Kamatani, Koichi Matsuda, Kazuyoshi Ishigaki, Masahiro Kanai, Hollis Wright, Carlos A Toro, Sergio R Ojeda, Alejandro Lomniczi, Michiaki Kubo, Ken K Ong, John R B Perry
Population studies elucidating the genetic architecture of reproductive ageing have been largely limited to European ancestries, restricting the generalizability of the findings and overlooking possible key genes poorly captured by common European genetic variation. Here, we report 26 loci (all P < 5 × 10-8 ) for reproductive ageing, i.e. puberty timing or age at menopause, in a non-European population (up to 67,029 women of Japanese ancestry). Highlighted genes for menopause include GNRH1, which supports a primary, rather than passive, role for hypothalamic-pituitary GnRH signalling in the timing of menopause...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773798/probing-femtosecond-lattice-displacement-upon-photo-carrier-generation-in-lead-halide-perovskite
#20
Giovanni Batignani, Giuseppe Fumero, Ajay Ram Srimath Kandada, Giulio Cerullo, Marina Gandini, Carino Ferrante, Annamaria Petrozza, Tullio Scopigno
Electronic properties and lattice vibrations are expected to be strongly correlated in metal-halide perovskites, due to the soft fluctuating nature of their crystal lattice. Thus, unveiling electron-phonon coupling dynamics upon ultrafast photoexcitation is necessary for understanding the optoelectronic behavior of the semiconductor. Here, we use impulsive vibrational spectroscopy to reveal vibrational modes of methylammonium lead-bromide perovskite under electronically resonant and non-resonant conditions...
May 17, 2018: Nature Communications
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