RSSMix.com Mix ID 13587

A checkup for the flu vaccine

Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 375 (2018). doi:10.1038/nm.4535

Influenza causes almost 650,000 deaths worldwide each year, yet a long-lasting, protective vaccine remains elusive. Global investment—both scientific and financial—in a universal flu vaccine is overdue.

A tale of two diseases: Aging HIV patients inspire a closer look at Alzheimer's disease

Shraddha Chakradhar — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 376 (2018). doi:10.1038/nm0418-376

Author: Shraddha Chakradhar

Experimenting with blockchain: Can one technology boost both data integrity and patients' pocketbooks?

Katharine Gammon — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 378 (2018). doi:10.1038/nm0418-378

Author: Katharine Gammon

A new site of attack for a malaria vaccine

Simon J Draper — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 382 (2018). doi:10.1038/nm.4533

Authors: Simon J Draper & Matthew K Higgins

A newly discovered antibody epitope on the liver-infective form of the parasite that causes malaria opens new doors for vaccine development.

Inflammation weakens HIV prevention

Thomas J Hope — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 384 (2018). doi:10.1038/nm.4534

Author: Thomas J Hope

The presence of multiple inflammatory cytokines predicts the failure of a topical 1% tenofovir microbicide gel to protect women against HIV infection.

Predicting leukemia relapse

José Ignacio Martín-Subero — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 385 (2018). doi:10.1038/nm.4529

Author: José Ignacio Martín-Subero

Mass cytometry of acute B cell lymphoblastic leukemias at diagnosis reveals intrapatient phenotypic heterogeneity and specific signatures that mimic cell developmental stage and predict future relapse.

Catalyzing the field of precision oncology, one basket at a time

William Pao — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 387 (2018). doi:10.1038/nm.4530

Authors: William Pao & Imola Fodor

A bedside strategy to overcome the limitations of testing in preclinical models and to determine the role of gene mutations and their targetability directly in patients is presented.

Transplanted neural progenitors bridge gaps to benefit cord–injured monkeys

Steven A Goldman — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 388 (2018). doi:10.1038/nm.4531

Author: Steven A Goldman

Human neural progenitor cells have been grafted successfully into rhesus monkeys with spinal cord hemisection, resulting in anatomic integration and improved neurological function.

Current understanding of the human microbiome

Jack A Gilbert — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 392 (2018). doi:10.1038/nm.4517

Authors: Jack A Gilbert, Martin J Blaser, J Gregory Caporaso, Janet K Jansson, Susan V Lynch & Rob Knight

Corrigendum: Classification and characterization of microsatellite instability across 18 cancer types

Ronald J Hause — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 525 (2018). doi:10.1038/nm0418-525a

Author: Ronald J Hause, Colin C Pritchard, Jay Shendure & Stephen J Salipante

Corrigendum: Suppression of luteinizing hormone enhances HSC recovery after hematopoietic injury

Enrico Velardi — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 525 (2018). doi:10.1038/nm0418-525b

Author: Enrico Velardi, Jennifer J Tsai, Stefan Radtke, Kirsten Cooper, Kimon V Argyropoulos, Shieh Jae-Hung, Lauren F Young, Amina Lazrak, Odette M Smith, Sophie Lieberman, Fabiana Kreines, Yusuke Shono, Tobias Wertheimer, Robert R Jenq, Alan M Hanash, Prema Narayan, Zhenmin Lei, Malcolm A Moore, Hans-Peter Kiem, Marcel R M van den Brink & Jarrod A Dudakov

Corrigendum: Positively selected enhancer elements endow osteosarcoma cells with metastatic competence

James J Morrow — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 525 (2018). doi:10.1038/nm0418-525c

Author: James J Morrow, Ian Bayles, Alister P W Funnell, Tyler E Miller, Alina Saiakhova, Michael M Lizardo, Cynthia F Bartels, Maaike Y Kapteijn, Stevephen Hung, Arnulfo Mendoza, Gursimran Dhillon, Daniel R Chee, Jay T Myers, Frederick Allen, Marco Gambarotti, Alberto Righi, Analisa DiFeo, Brian P Rubin, Alex Y Huang, Paul S Meltzer, Lee J Helman, Piero Picci, Henri H Versteeg, John A Stamatoyannopoulos, Chand Khanna & Peter C Scacheri

Corrigendum: Sex-specific transcriptional signatures in human depression

Benoit Labonté — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 525 (2018). doi:10.1038/nm0418-525d

Author: Benoit Labonté, Olivia Engmann, Immanuel Purushothaman, Caroline Menard, Junshi Wang, Chunfeng Tan, Joseph R Scarpa, Gregory Moy, Yong-Hwee E Loh, Michael Cahill, Zachary S Lorsch, Peter J Hamilton, Erin S Calipari, Georgia E Hodes, Orna Issler, Hope Kronman, Madeline Pfau, Aleksandar L J Obradovic, Yan Dong, Rachael L Neve, Scott Russo, Andrew Kasarskis, Carol Tamminga, Naguib Mechawar, Gustavo Turecki, Bin Zhang, Li Shen & Eric J Nestler

Corrigendum: Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness

Nicholas M Morton — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 525 (2018). doi:10.1038/nm0418-525e

Author: Nicholas M Morton, Jasmina Beltram, Roderick N Carter, Zoi Michailidou, Gregor Gorjanc, Clare McFadden, Martin E Barrios-Llerena, Sergio Rodriguez-Cuenca, Matthew T G Gibbins, Rhona E Aird, José Maria Moreno-Navarrete, Steven C Munger, Karen L Svenson, Annalisa Gastaldello, Lynne Ramage, Gregorio Naredo, Maximilian Zeyda, Zhao V Wang, Alexander F Howie, Aila Saari, Petra Sipilä, Thomas M Stulnig, Vilmundur Gudnason, Christopher J Kenyon, Jonathan R Seckl, Brian R Walker, Scott P Webster, Donald R Dunbar, Gary A Churchill, Antonio Vidal-Puig, José Manuel Fernandez-Real, Valur Emilsson & Simon Horvat

Corrigendum: Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing

Miguel Crespo — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 526 (2018). doi:10.1038/nm0418-526a

Author: Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin, Tara Srinivasan, Tuo Zhang, Nina H Pipalia, Huanhuan Joyce Chen, Mavee Witherspoon, Miriam Gordillo, Jenny Zhaoying Xiang, Frederick R Maxfield, Steven Lipkin, Todd Evans & Shuibing Chen

Erratum: The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions

Hamid Bolouri — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 526 (2018). doi:10.1038/nm0418-526b

Author: Hamid Bolouri, Jason E Farrar, Timothy Triche, Rhonda E Ries, Emilia L Lim, Todd A Alonzo, Yussanne Ma, Richard Moore, Andrew J Mungall, Marco A Marra, Jinghui Zhang, Xiaotu Ma, Yu Liu, Yanling Liu, Jaime M Guidry Auvil, Tanja M Davidsen, Patee Gesuwan, Leandro C Hermida, Bodour Salhia, Stephen Capone, Giridharan Ramsingh, Christian Michel Zwaan, Sanne Noort, Stephen R Piccolo, E Anders Kolb, Alan S Gamis, Malcolm A Smith, Daniela S Gerhard & Soheil Meshinchi

Erratum: Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells

Nimitha R Mathew — Tue, 10 Apr 2018 00:00:00 GMT

Nature Medicine 24, 526 (2018). doi:10.1038/nm0418-526c

Author: Nimitha R Mathew, Francis Baumgartner, Lukas Braun, David O'Sullivan, Simone Thomas, Miguel Waterhouse, Tony A Müller, Kathrin Hanke, Sanaz Taromi, Petya Apostolova, Anna L Illert, Wolfgang Melchinger, Sandra Duquesne, Annette Schmitt-Graeff, Lena Osswald, Kai-Li Yan, Arnim Weber, Sonia Tugues, Sabine Spath, Dietmar Pfeifer, Marie Follo, Rainer Claus, Michael Lübbert, Christoph Rummelt, Hartmut Bertz, Ralph Wäsch, Johanna Haag, Andrea Schmidts, Michael Schultheiss, Dominik Bettinger, Robert Thimme, Evelyn Ullrich, Yakup Tanriver, Giang Lam Vuong, Renate Arnold, Philipp Hemmati, Dominik Wolf, Markus Ditschkowski, Cordula Jilg, Konrad Wilhelm, Christian Leiber, Sabine Gerull, Jörg Halter, Claudia Lengerke, Thomas Pabst, Thomas Schroeder, Guido Kobbe, Wolf Rösler, Soroush Doostkam, Stephan Meckel, Kathleen Stabla, Stephan K Metzelder, Sebastian Halbach, Tilman Brummer, Zehan Hu, Joern Dengjel, Björn Hackanson, Christoph Schmid, Udo Holtick, Christof Scheid, Alexandros Spyridonidis, Friedrich Stölzel, Rainer Ordemann, Lutz P Müller, Flore Sicre-de-Fontbrune, Gabriele Ihorst, Jürgen Kuball, Jan E Ehlert, Daniel Feger, Eva-Maria Wagner, Jean-Yves Cahn, Jacqueline Schnell, Florian Kuchenbauer, Donald Bunjes, Ronjon Chakraverty, Simon Richardson, Saar Gill, Nicolaus Kröger, Francis Ayuk, Luca Vago, Fabio Ciceri, Antonia M Müller, Takeshi Kondo, Takanori Teshima, Susan Klaeger, Bernhard Kuster, Dennis (Dong Hwan) Kim, Daniel Weisdorf, Walter van der Velden, Daniela Dörfel, Wolfgang Bethge, Inken Hilgendorf, Andreas Hochhaus, Geoffroy Andrieux, Melanie Börries, Hauke Busch, John Magenau, Pavan Reddy, Myriam Labopin, Joseph H Antin, Andrea S Henden, Geoffrey R Hill, Glen A Kennedy, Merav Bar, Anita Sarma, Donal McLornan, Ghulam Mufti, Betul Oran, Katayoun Rezvani, Omid Shah, Robert S Negrin, Arnon Nagler, Marco Prinz, Andreas Burchert, Andreas Neubauer, Dietrich Beelen, Andreas Mackensen, Nikolas von Bubnoff, Wolfgang Herr, Burkhard Becher, Gerard Socié, Michael A Caligiuri, Eliana Ruggiero, Chiara Bonini, Georg Häcker, Justus Duyster, Jürgen Finke, Erika Pearce, Bruce R Blazar & Robert Zeiser

The long view on sequencing

Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 287 (2018). doi:10.1038/nbt.4125

Ultra-long read, single-molecule nanopore sequencers are beginning to find an expanding set of research applications in both human genomics and pathogenomics.

Roche pays $1.9 billion for Flatiron's army of electronic health record curators

Justin Petrone — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 289 (2018). doi:10.1038/nbt0418-289

Author: Justin Petrone

FDA approves stroke-detecting AI software

Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 290 (2018). doi:10.1038/nbt0418-290

New drug for multidrug-resistant HIV

Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 291 (2018). doi:10.1038/nbt0418-291b

Rollout of high-priced cell and gene therapies forces payer rethink

Melanie Senior — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 291 (2018). doi:10.1038/nbt0418-291a

Author: Melanie Senior

Low-molecular-weight albumin drug touted for severe osteoarthritis

Cormac Sheridan — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 293 (2018). doi:10.1038/nbt0418-293

Author: Cormac Sheridan

Critics say 'right to try' wrong for patients

Christopher Morrison — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 294 (2018). doi:10.1038/nbt0418-294

Author: Christopher Morrison

Around the world in a month

Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 296 (2018). doi:10.1038/nbt0418-296

Nature Biotechnology's academic spinouts of 2017

Malorye Allison Branca — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 297 (2018). doi:10.1038/nbt.4121

Authors: Malorye Allison Branca, Ken Garber & Laura DeFrancesco

Our annual survey highlights how immune-oncology and screens based on the application of cutting-edge omics technologies are providing a launchpad for a succession of startups interrogating biology across biomedicine.

Gender differences in obtaining and maintaining patent rights

Kyle Jensen — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 307 (2018). doi:10.1038/nbt.4120

Authors: Kyle Jensen, Balázs Kovács & Olav Sorenson

An examination of the prosecution and maintenance histories of approximately 2.7 million US patent applications indicates that women have less favorable outcomes than men.

Recent patents in tumor detection and treatment

Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 310 (2018). doi:10.1038/nbt.4123

Patching the retina with stem cells

Kapil Bharti — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 311 (2018). doi:10.1038/nbt.4118

Author: Kapil Bharti

An engineered patch of retinal pigment epithelium shows promise in two macular degeneration patients.

Portable gene expression guaranteed

Marios Tomazou — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 313 (2018). doi:10.1038/nbt.4119

Authors: Marios Tomazou & Guy-Bart Stan

Synthetic biology is made more reliable by borrowing ideas from systems and control theory.

Research Highlights

Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 314 (2018). doi:10.1038/nbt.4117

Epigenome editing to the rescue

Markus Elsner — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 315 (2018). doi:10.1038/nbt.4116

Author: Markus Elsner

Metabolomics activity screening for identifying metabolites that modulate phenotype

Carlos Guijas — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 316 (2018). doi:10.1038/nbt.4101

Authors: Carlos Guijas, J Rafael Montenegro-Burke, Benedikt Warth, Mary E Spilker & Gary Siuzdak

Erratum: Open-source, community-driven microfluidics with Metafluidics

David S Kong — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 368 (2018). doi:10.1038/nbt0418-368a

Authors: David S Kong, Todd A Thorsen, Jonathan Babb, Scott T Wick, Jeremy J Gam, Ron Weiss & Peter A Carr

Erratum: The illusion of control in germline engineering policy

Harald König — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 368 (2018). doi:10.1038/nbt0418-368b

Author: Harald König

Erratum: 1,003 reference genomes of bacterial and archaeal isolates expand coverage of the tree of life

Supratim Mukherjee — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 368 (2018). doi:10.1038/nbt0418-368c

Authors: Supratim Mukherjee, Rekha Seshadri, Neha J Varghese, Emiley A Eloe-Fadrosh, Jan P Meier-Kolthoff, Markus Göker, R Cameron Coates, Michalis Hadjithomas, Georgios A Pavlopoulos, David Paez-Espino, Yasuo Yoshikuni, Axel Visel, William B Whitman, George M Garrity, Jonathan A Eisen, Philip Hugenholtz, Amrita Pati, Natalia N Ivanova, Tanja Woyke, Hans-Peter Klenk & Nikos C Kyrpides

Erratum: Pearl millet genome sequence provides a resource to improve agronomic traits in arid environments

Rajeev K Varshney — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 368 (2018). doi:10.1038/nbt0418-368d

Authors: Rajeev K Varshney, Chengcheng Shi, Mahendar Thudi, Cedric Mariac, Jason Wallace, Peng Qi, He Zhang, Yusheng Zhao, Xiyin Wang, Abhishek Rathore, Rakesh K Srivastava, Annapurna Chitikineni, Guangyi Fan, Prasad Bajaj, Somashekhar Punnuri, S K Gupta, Hao Wang, Yong Jiang, Marie Couderc, Mohan A V S K Katta, Dev R Paudel, K D Mungra, Wenbin Chen, Karen R Harris-Shultz, Vanika Garg, Neetin Desai, Dadakhalandar Doddamani, Ndjido Ardo Kane, Joann A Conner, Arindam Ghatak, Palak Chaturvedi, Sabarinath Subramaniam, Om Parkash Yadav, Cécile Berthouly-Salazar, Falalou Hamidou, Jianping Wang, Xinming Liang, Jérémy Clotault, Hari D Upadhyaya, Philippe Cubry, Bénédicte Rhoné, Mame Codou Gueye, Ramanjulu Sunkar, Christian Dupuy, Francesca Sparvoli, Shifeng Cheng, R S Mahala, Bharat Singh, Rattan S Yadav, Eric Lyons, Swapan K Datta, C Tom Hash, Katrien M Devos, Edward Buckler, Jeffrey L Bennetzen, Andrew H Paterson, Peggy Ozias-Akins, Stefania Grando, Jun Wang, Trilochan Mohapatra, Wolfram Weckwerth, Jochen C Reif, Xin Liu, Yves Vigouroux & Xun Xu

Erratum: Visualizing detailed postdoctoral employment trends using a new career outcome taxonomy

Hong Xu — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 368 (2018). doi:10.1038/nbt0418-368e

Authors: Hong Xu, Richard S T Gilliam, Shyamal D Peddada, Gregory M Buchold & Tammy R L Collins

Involving undergraduates in genomics research to narrow the education–research gap

Serghei Mangul — Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 369 (2018). doi:10.1038/nbt.4113

Authors: Serghei Mangul, Lana S Martin & Eleazar Eskin

Engaging undergraduates in computational tasks can improve genomic research laboratory productivity, benefiting both students and senior laboratory members.

People

Thu, 05 Apr 2018 00:00:00 GMT

Nature Biotechnology 36, 372 (2018). doi:10.1038/nbt.4122

The Author File: Shai Shen-Orr

Vivien Marx — Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 231 (2018). doi:10.1038/nmeth.4659

Author: Vivien Marx

Comparing single-cell trajectories with a new tool and what happens when aversion turns into love.

Points of Significance: Statistics versus machine learning

Danilo Bzdok — Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 233 (2018). doi:10.1038/nmeth.4642

Authors: Danilo Bzdok, Naomi Altman & Martin Krzywinski

Statistics draws population inferences from a sample, and machine learning finds generalizable predictive patterns.

Imaging: Illuminating the brain's dark matter

Christian Schnell — Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 241 (2018). doi:10.1038/nmeth.4653

Author: Christian Schnell

SUSHI is a new method for imaging the extracellular space with high resolution in living brain tissue to reveal insights into the structure and dynamics of the extracellular space.

Neuroscience: Minimally invasive optogenetics

Nina Vogt — Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 242 (2018). doi:10.1038/nmeth.4654

Author: Nina Vogt

Upconversion nanoparticles can serve as intermediaries to illuminate optogenetic tools in the mouse brain.

Proteomics: Heating up cells to bring down complexes

Allison Doerr — Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 242 (2018). doi:10.1038/nmeth.4655

Author: Allison Doerr

A combination of heat denaturation and mass spectrometry is applied to monitor protein-complex dynamics in the cell.

Cell biology: Live-streaming the cytoplasm

Tal Nawy — Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 244 (2018). doi:10.1038/nmeth.4656

Author: Tal Nawy

A new approach uses beams of light to direct cytoplasmic flows.

Chemical biology: Detecting kiss-and-run interactions with LIPSTIC

Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 245 (2018). doi:10.1038/nmeth.4645

Genomics: Single-cell hat trick

Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 245 (2018). doi:10.1038/nmeth.4646

Neuroscience: A clear window into the brain

Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 245 (2018). doi:10.1038/nmeth.4647

Stem cells: From somatic cells to naive pluripotent cells

Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 245 (2018). doi:10.1038/nmeth.4648

Imaging: Peptide-tag-specific nanobody for dSTORM

Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 246 (2018). doi:10.1038/nmeth.4649

Genomics: Off-targets in epigenome editing

Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 246 (2018). doi:10.1038/nmeth.4650

Structural biology: Local resolution of cryo-EM maps with MonoRes

Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 246 (2018). doi:10.1038/nmeth.4651

Genomics: Genome editing with ease

Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 246 (2018). doi:10.1038/nmeth.4652

Genomics: Transcription triggers enhancer movement

Nicole Rusk — Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 247 (2018). doi:10.1038/nmeth.4657

Author: Nicole Rusk

CRISPR-based imaging of regulatory elements shows that their mobility increases as transcription is initiated.

How to pull the blanket off dormant cancer cells

Vivien Marx — Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 249 (2018). doi:10.1038/nmeth.4640

Author: Vivien Marx

When asleep, cancer cells can evade chemo. When they wake up, they can cause cancer recurrence. By deciphering dormancy cues, labs explore how to break this cycle.

A deep (learning) dive into a cell

Kristin Branson — Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, 253 (2018). doi:10.1038/nmeth.4658

Author: Kristin Branson

An interpretable, deep neural network produces mechanistic hypotheses on how genetic interactions contribute to whole-cell phenotypes.

Improving biosensor assay development by determining sample quality with Tycho NT.6

Dennis Breitsprecher — Tue, 03 Apr 2018 00:00:00 GMT

Nature Methods 15, (2018). doi:10.1038/nmeth.f.406

Authors: Dennis Breitsprecher, Peter A Fung & Nuska Tschammer

CRISPR off-targets: a reassessment

Fri, 30 Mar 2018 00:00:00 GMT

Nature Methods 15, 229 (2018). doi:10.1038/nmeth.4664

There was insufficient data to support the claim of unexpected off-target effects due to CRISPR in a paper published in Nature Methods. More work is needed to determine whether such events occur in vivo.

Response to “Unexpected mutations after CRISPR–Cas9 editing in vivo”

Lauryl M J Nutter — Fri, 30 Mar 2018 00:00:00 GMT

Nature Methods 15, 235 (2018). doi:10.1038/nmeth.4559

Authors: Lauryl M J Nutter, Jason D Heaney, K C Kent Lloyd, Stephen A Murray, John R Seavitt, William C Skarnes, Lydia Teboul, Steve D M Brown & Mark Moore

Response to “Unexpected mutations after CRISPR–Cas9 editing in vivo”

Christopher J Wilson — Fri, 30 Mar 2018 00:00:00 GMT

Nature Methods 15, 236 (2018). doi:10.1038/nmeth.4552

Authors: Christopher J Wilson, Tim Fennell, Anne Bothmer, Morgan L Maeder, Deepak Reyon, Cecilia Cotta-Ramusino, Cecilia A Fernandez, Eugenio Marco, Luis A Barrera, Hariharan Jayaram, Charles F Albright, Gerald F Cox, George M Church & Vic E Myer

Response to “Unexpected mutations after CRISPR–Cas9 editing in vivo”

Reynald M Lescarbeau — Fri, 30 Mar 2018 00:00:00 GMT

Nature Methods 15, 237 (2018). doi:10.1038/nmeth.4553

Authors: Reynald M Lescarbeau, Bradley Murray, Thomas M Barnes & Nessan Bermingham

Response to “Unexpected mutations after CRISPR–Cas9 editing in vivo”

Caleb A Lareau — Fri, 30 Mar 2018 00:00:00 GMT

Nature Methods 15, 238 (2018). doi:10.1038/nmeth.4541

Authors: Caleb A Lareau, Kendell Clement, Jonathan Y Hsu, Vikram Pattanayak, J Keith Joung, Martin J Aryee & Luca Pinello

Response to “Unexpected mutations after CRISPR–Cas9 editing in vivo”

Sang-Tae Kim — Fri, 30 Mar 2018 00:00:00 GMT

Nature Methods 15, 239 (2018). doi:10.1038/nmeth.4554

Authors: Sang-Tae Kim, Jeongbin Park, Daesik Kim, Kyoungmi Kim, Sangsu Bae, Matthias Schlesner & Jin-Soo Kim

Combinatorial inhibition of PTPN12-regulated receptors leads to a broadly effective therapeutic strategy in triple-negative breast cancer

Amritha Nair — Mon, 26 Mar 2018 00:00:00 GMT

Nature Medicine 24, 505 (2018). doi:10.1038/nm.4507

Authors: Amritha Nair, Hsiang-Ching Chung, Tingting Sun, Siddhartha Tyagi, Lacey E Dobrolecki, Rocio Dominguez-Vidana, Sarah J Kurley, Mayra Orellana, Alexander Renwick, David M Henke, Panagiotis Katsonis, Earlene Schmitt, Doug W Chan, Hui Li, Sufeng Mao, Ivana Petrovic, Chad J Creighton, Carolina Gutierrez, Julien Dubrulle, Fabio Stossi, Jeffrey W Tyner, Olivier Lichtarge, Charles Y Lin, Bing Zhang, Kenneth L Scott, Susan G Hilsenbeck, Jinpeng Sun, Xiao Yu, C Kent Osborne, Rachel Schiff, James G Christensen, David J Shields, Mothaffar F Rimawi, Matthew J Ellis, Chad A Shaw, Michael T Lewis & Thomas F Westbrook

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer diagnosed in more than 200,000 women each year and is recalcitrant to targeted therapies. Although TNBCs harbor multiple hyperactive receptor tyrosine kinases (RTKs), RTK inhibitors have been largely ineffective in TNBC patients thus far. We developed a broadly effective therapeutic strategy for TNBC that is based on combined inhibition of receptors that share the negative regulator PTPN12. Previously, we and others identified the tyrosine phosphatase PTPN12 as a tumor suppressor that is frequently inactivated in TNBC. PTPN12 restrains several RTKs, suggesting that PTPN12 deficiency leads to aberrant activation of multiple RTKs and a co-dependency on these receptors. This in turn leads to the therapeutic hypothesis that PTPN12-deficient TNBCs may be responsive to combined RTK inhibition. However, the repertoire of RTKs that are restrained by PTPN12 in human cells has not been systematically explored. By methodically identifying the suite of RTK substrates (MET, PDGFRβ, EGFR, and others) inhibited by PTPN12, we rationalized a combination RTK-inhibitor therapy that induced potent tumor regression across heterogeneous models of TNBC. Orthogonal approaches revealed that PTPN12 was recruited to and inhibited these receptors after ligand stimulation, thereby serving as a feedback mechanism to limit receptor signaling. Cancer-associated mutation of PTPN12 or reduced PTPN12 protein levels diminished this feedback mechanism, leading to aberrant activity of these receptors. Restoring PTPN12 protein levels restrained signaling from RTKs, including PDGFRβ and MET, and impaired TNBC survival. In contrast with single agents, combined inhibitors targeting the PDGFRβ and MET receptors induced the apoptosis in TNBC cells in vitro and in vivo. This therapeutic strategy resulted in tumor regressions in chemo-refractory patient-derived TNBC models. Notably, response correlated with PTPN12 deficiency, suggesting that impaired receptor feedback may establish a combined addiction to these proto-oncogenic receptors. Taken together, our data provide a rationale for combining RTK inhibitors in TNBC and other malignancies that lack receptor-activating mutations.

Targeting hepatic glutaminase activity to ameliorate hyperglycemia

Russell A Miller — Mon, 26 Mar 2018 00:00:00 GMT

Nature Medicine 24, 518 (2018). doi:10.1038/nm.4514

Authors: Russell A Miller, Yuji Shi, Wenyun Lu, David A Pirman, Aditi Jatkar, Matthew Blatnik, Hong Wu, César Cárdenas, Min Wan, J Kevin Foskett, Junyoung O Park, Yiyi Zhang, William L Holland, Joshua D Rabinowitz & Morris J Birnbaum

Glucagon levels increase under homeostatic, fasting conditions, promoting the release of glucose from the liver by accelerating the breakdown of glycogen (also known as glycogenolysis). Glucagon also enhances gluconeogenic flux, including from an increase in the hepatic consumption of amino acids. In type 2 diabetes, dysregulated glucagon signaling contributes to the elevated hepatic glucose output and fasting hyperglycemia that occur in this condition. Yet, the mechanism by which glucagon stimulates gluconeogenesis remains incompletely understood. Contrary to the prevailing belief that glucagon acts primarily on cytoplasmic and nuclear targets, we find glucagon-dependent stimulation of mitochondrial anaplerotic flux from glutamine that increases the contribution of this amino acid to the carbons of glucose generated during gluconeogenesis. This enhanced glucose production is dependent on protein kinase A (PKA) and is associated with glucagon-stimulated calcium release from the endoplasmic reticulum, activation of mitochondrial α-ketoglutarate dehydrogenase, and increased glutaminolysis. Mice with reduced levels of hepatic glutaminase 2 (GLS2), the enzyme that catalyzes the first step in glutamine metabolism, show lower glucagon-stimulated glutamine-to-glucose flux in vivo, and GLS2 knockout results in higher fasting plasma glucagon and glutamine levels with lower fasting blood glucose levels in insulin-resistant conditions. As found in genome-wide association studies (GWAS), human genetic variation in the region of GLS2 is associated with higher fasting plasma glucose; here we show in human cryopreserved primary hepatocytes in vitro that these natural gain-of-function missense mutations in GLS2 result in higher glutaminolysis and glucose production. These data emphasize the importance of gluconeogenesis from glutamine, particularly in pathological states of increased glucagon signaling, while suggesting a possible new therapeutic avenue to treat hyperglycemia.

Linear assembly of a human centromere on the Y chromosome

Miten Jain — Mon, 19 Mar 2018 00:00:00 GMT

Nature Biotechnology 36, 321 (2018). doi:10.1038/nbt.4109

Authors: Miten Jain, Hugh E Olsen, Daniel J Turner, David Stoddart, Kira V Bulazel, Benedict Paten, David Haussler, Huntington F Willard, Mark Akeson & Karen H Miga

Base editing with a Cpf1–cytidine deaminase fusion

Xiaosa Li — Mon, 19 Mar 2018 00:00:00 GMT

Nature Biotechnology 36, 324 (2018). doi:10.1038/nbt.4102

Authors: Xiaosa Li, Ying Wang, Yajing Liu, Bei Yang, Xiao Wang, Jia Wei, Zongyang Lu, Yuxi Zhang, Jing Wu, Xingxu Huang, Li Yang & Jia Chen

Phase 1 clinical study of an embryonic stem cell–derived retinal pigment epithelium patch in age-related macular degeneration

Lyndon da Cruz — Mon, 19 Mar 2018 00:00:00 GMT

Nature Biotechnology 36, 328 (2018). doi:10.1038/nbt.4114

Authors: Lyndon da Cruz, Kate Fynes, Odysseas Georgiadis, Julie Kerby, Yvonne H Luo, Ahmad Ahmado, Amanda Vernon, Julie T Daniels, Britta Nommiste, Shazeen M Hasan, Sakina B Gooljar, Amanda-Jayne F Carr, Anthony Vugler, Conor M Ramsden, Magda Bictash, Mike Fenster, Juliette Steer, Tricia Harbinson, Anna Wilbrey, Adnan Tufail, Gang Feng, Mark Whitlock, Anthony G Robson, Graham E Holder, Mandeep S Sagoo, Peter T Loudon, Paul Whiting & Peter J Coffey

Engineered promoters enable constant gene expression at any copy number in bacteria

Thomas H Segall-Shapiro — Mon, 19 Mar 2018 00:00:00 GMT

Nature Biotechnology 36, 352 (2018). doi:10.1038/nbt.4111

Authors: Thomas H Segall-Shapiro, Eduardo D Sontag & Christopher A Voigt

The internal environment of growing cells is variable and dynamic, making it difficult to introduce reliable parts, such as promoters, for genetic engineering. Here, we applied control-theoretic ideas to design promoters that maintained constant levels of expression at any copy number. Theory predicts that independence to copy number can be achieved by using an incoherent feedforward loop (iFFL) if the negative regulation is perfectly non-cooperative. We engineered iFFLs into Escherichia coli promoters using transcription-activator-like effectors (TALEs). These promoters had near-identical expression in different genome locations and plasmids, even when their copy number was perturbed by genomic mutations or changes in growth medium composition. We applied the stabilized promoters to show that a three-gene metabolic pathway to produce deoxychromoviridans could retain function without re-tuning when the stabilized-promoter-driven genes were moved from a plasmid into the genome.

Cultivation and sequencing of rumen microbiome members from the Hungate1000 Collection

Rekha Seshadri — Mon, 19 Mar 2018 00:00:00 GMT

Nature Biotechnology 36, 359 (2018). doi:10.1038/nbt.4110

Authors: Rekha Seshadri, Sinead C Leahy, Graeme T Attwood, Koon Hoong Teh, Suzanne C Lambie, Adrian L Cookson, Emiley A Eloe-Fadrosh, Georgios A Pavlopoulos, Michalis Hadjithomas, Neha J Varghese, David Paez-Espino, Nikola Palevich, Peter H Janssen, Ron S Ronimus, Samantha Noel, Priya Soni, Kerri Reilly, Todd Atherly, Cherie Ziemer, Andre-Denis Wright, Suzanne Ishaq, Michael Cotta, Stephanie Thompson, Katie Crosley, Nest McKain, R John Wallace, Harry J Flint, Jennifer C Martin, Robert J Forster, Robert J Gruninger, Tim McAllister, Rosalind Gilbert, Diane Ouwerkerk, Athol Klieve, Rafat Al Jassim, Stuart Denman, Chris McSweeney, Carly Rosewarne, Satoshi Koike, Yasuo Kobayashi, Makoto Mitsumori, Takumi Shinkai, Silvio Cravero, María Cerón Cucchi, Rechelle Perry, Gemma Henderson, Christopher J Creevey, Nicolas Terrapon, Pascal Lapebie, Elodie Drula, Vincent Lombard, Edward Rubin, Nikos C Kyrpides, Bernard Henrissat, Tanja Woyke, Natalia N Ivanova & William J Kelly

A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein

Joshua Tan — Mon, 19 Mar 2018 00:00:00 GMT

Nature Medicine 24, 401 (2018). doi:10.1038/nm.4513

Authors: Joshua Tan, Brandon K Sack, David Oyen, Isabelle Zenklusen, Luca Piccoli, Sonia Barbieri, Mathilde Foglierini, Chiara Silacci Fregni, Jessica Marcandalli, Said Jongo, Salim Abdulla, Laurent Perez, Giampietro Corradin, Luca Varani, Federica Sallusto, Betty Kim Lee Sim, Stephen L Hoffman, Stefan H I Kappe, Claudia Daubenberger, Ian A Wilson & Antonio Lanzavecchia

A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite

Neville K Kisalu — Mon, 19 Mar 2018 00:00:00 GMT

Nature Medicine 24, 408 (2018). doi:10.1038/nm.4512

Authors: Neville K Kisalu, Azza H Idris, Connor Weidle, Yevel Flores-Garcia, Barbara J Flynn, Brandon K Sack, Sean Murphy, Arne Schön, Ernesto Freire, Joseph R Francica, Alex B Miller, Jason Gregory, Sandra March, Hua-Xin Liao, Barton F Haynes, Kevin Wiehe, Ashley M Trama, Kevin O Saunders, Morgan A Gladden, Anthony Monroe, Mattia Bonsignori, Masaru Kanekiyo, Adam K Wheatley, Adrian B McDermott, S Katie Farney, Gwo-Yu Chuang, Baoshan Zhang, Natasha Kc, Sumana Chakravarty, Peter D Kwong, Photini Sinnis, Sangeeta N Bhatia, Stefan H I Kappe, B Kim Lee Sim, Stephen L Hoffman, Fidel Zavala, Marie Pancera & Robert A Seder

Dentate granule cell recruitment of feedforward inhibition governs engram maintenance and remote memory generalization

Nannan Guo — Mon, 12 Mar 2018 00:00:00 GMT

Nature Medicine 24, 438 (2018). doi:10.1038/nm.4491

Authors: Nannan Guo, Marta E Soden, Charlotte Herber, Michael TaeWoo Kim, Antoine Besnard, Paoyan Lin, Xiang Ma, Constance L Cepko, Larry S Zweifel & Amar Sahay

Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling

Pernilla Roswall — Mon, 12 Mar 2018 00:00:00 GMT

Nature Medicine 24, 463 (2018). doi:10.1038/nm.4494

Authors: Pernilla Roswall, Matteo Bocci, Michael Bartoschek, Hong Li, Glen Kristiansen, Sara Jansson, Sophie Lehn, Jonas Sjölund, Steven Reid, Christer Larsson, Pontus Eriksson, Charlotte Anderberg, Eliane Cortez, Lao H Saal, Christina Orsmark-Pietras, Eugenia Cordero, Bengt Kristian Haller, Jari Häkkinen, Ingrid J G Burvenich, Elgene Lim, Akira Orimo, Mattias Höglund, Lisa Rydén, Holger Moch, Andrew M Scott, Ulf Eriksson & Kristian Pietras

Alignment of single-cell trajectories to compare cellular expression dynamics

Ayelet Alpert — Mon, 12 Mar 2018 00:00:00 GMT

Nature Methods 15, 267 (2018). doi:10.1038/nmeth.4628

Authors: Ayelet Alpert, Lindsay S Moore, Tania Dubovik & Shai S Shen-Orr

Single-cell RNA sequencing and high-dimensional cytometry can be used to generate detailed trajectories of dynamic biological processes such as differentiation or development. Here we present cellAlign, a quantitative framework for comparing expression dynamics within and between single-cell trajectories. By applying cellAlign to mouse and human embryonic developmental trajectories, we systematically delineate differences in the temporal regulation of gene expression programs that would otherwise be masked.

IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor

Keishi Adachi — Mon, 05 Mar 2018 00:00:00 GMT

Nature Biotechnology 36, 346 (2018). doi:10.1038/nbt.4086

Authors: Keishi Adachi, Yosuke Kano, Tomohiko Nagai, Namiko Okuyama, Yukimi Sakoda & Koji Tamada

Infiltration, accumulation, and survival of chimeric antigen receptor T (CAR-T) cells in solid tumors is crucial for tumor clearance. We engineered CAR-T cells to express interleukin (IL)-7 and CCL19 (7 × 19 CAR-T cells), as these factors are essential for the maintenance of T-cell zones in lymphoid organs. In mice, 7 × 19 CAR-T cells achieved complete regression of pre-established solid tumors and prolonged mouse survival, with superior anti-tumor activity compared to conventional CAR-T cells. Histopathological analyses showed increased infiltration of dendritic cells (DC) and T cells into tumor tissues following 7 × 19 CAR-T cell therapy. Depletion of recipient T cells before 7 × 19 CAR-T cell administration dampened the therapeutic effects of 7 × 19 CAR-T cell treatment, suggesting that CAR-T cells and recipient immune cells collaborated to exert anti-tumor activity. Following treatment of mice with 7 × 19 CAR-T cells, both recipient conventional T cells and administered CAR-T cells generated memory responses against tumors.

Nociceptor sensory neurons suppress neutrophil and γδ T cell responses in bacterial lung infections and lethal pneumonia

Pankaj Baral — Mon, 05 Mar 2018 00:00:00 GMT

Nature Medicine 24, 417 (2018). doi:10.1038/nm.4501

Authors: Pankaj Baral, Benjamin D Umans, Lu Li, Antonia Wallrapp, Meghna Bist, Talia Kirschbaum, Yibing Wei, Yan Zhou, Vijay K Kuchroo, Patrick R Burkett, Bryan G Yipp, Stephen D Liberles & Isaac M Chiu

Selective modulation of the androgen receptor AF2 domain rescues degeneration in spinal bulbar muscular atrophy

Nisha M Badders — Mon, 05 Mar 2018 00:00:00 GMT

Nature Medicine 24, 427 (2018). doi:10.1038/nm.4500

Authors: Nisha M Badders, Ane Korff, Helen C Miranda, Pradeep K Vuppala, Rebecca B Smith, Brett J Winborn, Emmanuelle R Quemin, Bryce L Sopher, Jennifer Dearman, James Messing, Nam Chul Kim, Jennifer Moore, Brian D Freibaum, Anderson P Kanagaraj, Baochang Fan, Heather Tillman, Ping-Chung Chen, Yingzhe Wang, Burgess B Freeman III, Yimei Li, Hong Joo Kim, Albert R La Spada & J Paul Taylor

Bone marrow niche trafficking of miR-126 controls the self-renewal of leukemia stem cells in chronic myelogenous leukemia

Bin Zhang — Mon, 05 Mar 2018 00:00:00 GMT

Nature Medicine 24, 450 (2018). doi:10.1038/nm.4499

Authors: Bin Zhang, Le Xuan Truong Nguyen, Ling Li, Dandan Zhao, Bijender Kumar, Herman Wu, Allen Lin, Francesca Pellicano, Lisa Hopcroft, Yu-Lin Su, Mhairi Copland, Tessa L Holyoake, Calvin J Kuo, Ravi Bhatia, David S Snyder, Haris Ali, Anthony S Stein, Casey Brewer, Huafeng Wang, Tinisha McDonald, Piotr Swiderski, Estelle Troadec, Ching-Cheng Chen, Adrienne Dorrance, Vinod Pullarkat, Yate-Ching Yuan, Danilo Perrotti, Nadia Carlesso, Stephen J Forman, Marcin Kortylewski, Ya-Huei Kuo & Guido Marcucci

Single-cell developmental classification of B cell precursor acute lymphoblastic leukemia at diagnosis reveals predictors of relapse

Zinaida Good — Mon, 05 Mar 2018 00:00:00 GMT

Nature Medicine 24, 474 (2018). doi:10.1038/nm.4505

Authors: Zinaida Good, Jolanda Sarno, Astraea Jager, Nikolay Samusik, Nima Aghaeepour, Erin F Simonds, Leah White, Norman J Lacayo, Wendy J Fantl, Grazia Fazio, Giuseppe Gaipa, Andrea Biondi, Robert Tibshirani, Sean C Bendall, Garry P Nolan & Kara L Davis

SHP2 inhibition restores sensitivity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors

Leila Dardaei — Mon, 05 Mar 2018 00:00:00 GMT

Nature Medicine 24, 512 (2018). doi:10.1038/nm.4497

Authors: Leila Dardaei, Hui Qin Wang, Manrose Singh, Paul Fordjour, Katherine X Shaw, Satoshi Yoda, Grainne Kerr, Kristine Yu, Jinsheng Liang, Yichen Cao, Yan Chen, Michael S Lawrence, Adam Langenbucher, Justin F Gainor, Luc Friboulet, Ibiayi Dagogo-Jack, David T Myers, Emma Labrot, David Ruddy, Melissa Parks, Dana Lee, Richard H DiCecca, Susan Moody, Huaixiang Hao, Morvarid Mohseni, Matthew LaMarche, Juliet Williams, Keith Hoffmaster, Giordano Caponigro, Alice T Shaw, Aaron N Hata, Cyril H Benes, Fang Li & Jeffrey A Engelman

Most anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung tumors initially respond to small-molecule ALK inhibitors, but drug resistance often develops. Of tumors that develop resistance to highly potent second-generation ALK inhibitors, approximately half harbor resistance mutations in ALK, while the other half have other mechanisms underlying resistance. Members of the latter group often have activation of at least one of several different tyrosine kinases driving resistance. Such tumors are not expected to respond to lorlatinib—a third-generation inhibitor targeting ALK that is able to overcome all clinically identified resistant mutations in ALK—and further therapeutic options are limited. Herein, we deployed a shRNA screen of 1,000 genes in multiple ALK-inhibitor-resistant patient-derived cells (PDCs) to discover those that confer sensitivity to ALK inhibition. This approach identified SHP2, a nonreceptor protein tyrosine phosphatase, as a common targetable resistance node in multiple PDCs. SHP2 provides a parallel survival input downstream of multiple tyrosine kinases that promote resistance to ALK inhibitors. Treatment with SHP099, the recently discovered small-molecule inhibitor of SHP2, in combination with the ALK tyrosine kinase inhibitor (TKI) ceritinib halted the growth of resistant PDCs through preventing compensatory RAS and ERK1 and ERK2 (ERK1/2) reactivation. These findings suggest that combined ALK and SHP2 inhibition may be a promising therapeutic strategy for resistant cancers driven by several different ALK-independent mechanisms underlying resistance.

Using deep learning to model the hierarchical structure and function of a cell

Jianzhu Ma — Mon, 05 Mar 2018 00:00:00 GMT

Nature Methods 15, 290 (2018). doi:10.1038/nmeth.4627

Authors: Jianzhu Ma, Michael Ku Yu, Samson Fong, Keiichiro Ono, Eric Sage, Barry Demchak, Roded Sharan & Trey Ideker

Restorative effects of human neural stem cell grafts on the primate spinal cord

Ephron S Rosenzweig — Mon, 26 Feb 2018 00:00:00 GMT

Nature Medicine 24, 484 (2018). doi:10.1038/nm.4502

Authors: Ephron S Rosenzweig, John H Brock, Paul Lu, Hiromi Kumamaru, Ernesto A Salegio, Ken Kadoya, Janet L Weber, Justine J Liang, Rod Moseanko, Stephanie Hawbecker, J Russell Huie, Leif A Havton, Yvette S Nout-Lomas, Adam R Ferguson, Michael S Beattie, Jacqueline C Bresnahan & Mark H Tuszynski

Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women

Lyle R McKinnon — Mon, 26 Feb 2018 00:00:00 GMT

Nature Medicine 24, 491 (2018). doi:10.1038/nm.4506

Authors: Lyle R McKinnon, Lenine J Liebenberg, Nonhlanhla Yende-Zuma, Derseree Archary, Sinaye Ngcapu, Aida Sivro, Nico Nagelkerke, Jose Gerardo Garcia Lerma, Angela D Kashuba, Lindi Masson, Leila E Mansoor, Quarraisha Abdool Karim, Salim S Abdool Karim & Jo-Ann S Passmore

Bias, robustness and scalability in single-cell differential expression analysis

Charlotte Soneson — Mon, 26 Feb 2018 00:00:00 GMT

Nature Methods 15, 255 (2018). doi:10.1038/nmeth.4612

Authors: Charlotte Soneson & Mark D Robinson

A hybridization-chain-reaction-based method for amplifying immunosignals

Rui Lin — Mon, 26 Feb 2018 00:00:00 GMT

Nature Methods 15, 275 (2018). doi:10.1038/nmeth.4611

Authors: Rui Lin, Qiru Feng, Peng Li, Ping Zhou, Ruiyu Wang, Zhe Liu, Zhiqiang Wang, Xiangbing Qi, Nan Tang, Feng Shao & Minmin Luo

Immunosignal hybridization chain reaction (isHCR) combines antibody–antigen interactions with hybridization chain reaction (HCR) technology, which results in amplification of immunofluorescence signals by up to two to three orders of magnitude with low background. isHCR's highly modular and easily adaptable design enables the technique to be applied broadly, and we further optimized its use in multiplexed imaging and in state-of-the-art tissue expansion and clearing techniques.

Cell-type specific sequencing of microRNAs from complex animal tissues

Chiara Alberti — Mon, 26 Feb 2018 00:00:00 GMT

Nature Methods 15, 283 (2018). doi:10.1038/nmeth.4610

Authors: Chiara Alberti, Raphael A Manzenreither, Ivica Sowemimo, Thomas R Burkard, Jingkui Wang, Katharina Mahofsky, Stefan L Ameres & Luisa Cochella

H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers

Michael Seiler — Mon, 19 Feb 2018 00:00:00 GMT

Nature Medicine 24, 497 (2018). doi:10.1038/nm.4493

Authors: Michael Seiler, Akihide Yoshimi, Rachel Darman, Betty Chan, Gregg Keaney, Michael Thomas, Anant A Agrawal, Benjamin Caleb, Alfredo Csibi, Eckley Sean, Peter Fekkes, Craig Karr, Virginia Klimek, George Lai, Linda Lee, Pavan Kumar, Stanley Chun-Wei Lee, Xiang Liu, Crystal Mackenzie, Carol Meeske, Yoshiharu Mizui, Eric Padron, Eunice Park, Ermira Pazolli, Shouyong Peng, Sudeep Prajapati, Justin Taylor, Teng Teng, John Wang, Markus Warmuth, Huilan Yao, Lihua Yu, Ping Zhu, Omar Abdel-Wahab, Peter G Smith & Silvia Buonamici

Genomic analyses of cancer have identified recurrent point mutations in the RNA splicing factor–encoding genes SF3B1, U2AF1, and SRSF2 that confer an alteration of function. Cancer cells bearing these mutations are preferentially dependent on wild-type (WT) spliceosome function, but clinically relevant means to therapeutically target the spliceosome do not currently exist. Here we describe an orally available modulator of the SF3b complex, H3B-8800, which potently and preferentially kills spliceosome-mutant epithelial and hematologic tumor cells. These killing effects of H3B-8800 are due to its direct interaction with the SF3b complex, as evidenced by loss of H3B-8800 activity in drug-resistant cells bearing mutations in genes encoding SF3b components. Although H3B-8800 modulates WT and mutant spliceosome activity, the preferential killing of spliceosome-mutant cells is due to retention of short, GC-rich introns, which are enriched for genes encoding spliceosome components. These data demonstrate the therapeutic potential of splicing modulation in spliceosome-mutant cancers.

Quantitative mapping and minimization of super-resolution optical imaging artifacts

Siân Culley — Mon, 19 Feb 2018 00:00:00 GMT

Nature Methods 15, 263 (2018). doi:10.1038/nmeth.4605

Authors: Siân Culley, David Albrecht, Caron Jacobs, Pedro Matos Pereira, Christophe Leterrier, Jason Mercer & Ricardo Henriques

Super-resolution microscopy depends on steps that can contribute to the formation of image artifacts, leading to misinterpretation of biological information. We present NanoJ-SQUIRREL, an ImageJ-based analytical approach that provides quantitative assessment of super-resolution image quality. By comparing diffraction-limited images and super-resolution equivalents of the same acquisition volume, this approach generates a quantitative map of super-resolution defects and can guide researchers in optimizing imaging parameters.

On the design of CRISPR-based single-cell molecular screens

Andrew J Hill — Mon, 19 Feb 2018 00:00:00 GMT

Nature Methods 15, 271 (2018). doi:10.1038/nmeth.4604

Authors: Andrew J Hill, José L McFaline-Figueroa, Lea M Starita, Molly J Gasperini, Kenneth A Matreyek, Jonathan Packer, Dana Jackson, Jay Shendure & Cole Trapnell

Several groups recently coupled CRISPR perturbations and single-cell RNA-seq for pooled genetic screens. We demonstrate that vector designs of these studies are susceptible to ∼50% swapping of guide RNA–barcode associations because of lentiviral template switching. We optimized a published alternative, CROP-seq, in which the guide RNA also serves as the barcode, and here confirm that this strategy performs robustly and doubled the rate at which guides are assigned to cells to 94%.

Identifying the favored mutation in a positive selective sweep

Ali Akbari — Mon, 19 Feb 2018 00:00:00 GMT

Nature Methods 15, 279 (2018). doi:10.1038/nmeth.4606

Authors: Ali Akbari, Joseph J Vitti, Arya Iranmehr, Mehrdad Bakhtiari, Pardis C Sabeti, Siavash Mirarab & Vineet Bafna

Most approaches that capture signatures of selective sweeps in population genomics data do not identify the specific mutation favored by selection. We present iSAFE (for “integrated selection of allele favored by evolution”), a method that enables researchers to accurately pinpoint the favored mutation in a large region (∼5 Mbp) by using a statistic derived solely from population genetics signals. iSAFE does not require knowledge of demography, the phenotype under selection, or functional annotations of mutations.

Altering form for function

Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 187 (2018). doi:10.1038/nchembio.2582

Elucidating the mechanisms by which biomolecules are chemically modified and how these alterations regulate biological pathways represents a leading frontier in chemical biology.

The ABCs of PTMs

Karl W Barber — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 188 (2018). doi:10.1038/nchembio.2572

Authors: Karl W Barber & Jesse Rinehart

Post-translational modifications (PTMs) are ubiquitous in all forms of life and often modulate critical protein functions. Recent chemical and biological advances have finally enabled scientists to precisely modify proteins at physiologically relevant positions, ushering in a new era of protein studies.

Covalent modifications of polysaccharides in mycobacteria

Shiva k Angala — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 193 (2018). doi:10.1038/nchembio.2571

Authors: Shiva k Angala, Zuzana Palčeková, Juan M Belardinelli & Mary Jackson

Mycobacteria produce carbohydrates of exceptional structures that are covalently modified by unique substituents, whose functional characterization could expand our understanding of how mycobacteria adapt to their environment.

Lipids: Picturing palmitoylation

Caitlin Deane — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 199 (2018). doi:10.1038/nchembio.2577

Author: Caitlin Deane

Viruses: Capsids under pressure

Mirella Bucci — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 199 (2018). doi:10.1038/nchembio.2578

Author: Mirella Bucci

Glycosylation: Gluing on glycans

Karin Kuehnel — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 199 (2018). doi:10.1038/nchembio.2579

Author: Karin Kuehnel

Ubiquitination: Trashing the CIA

Grant Miura — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 199 (2018). doi:10.1038/nchembio.2580

Author: Grant Miura

RNA structure: A LASER-focused view into cells

Philip C Bevilacqua — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 200 (2018). doi:10.1038/nchembio.2570

Authors: Philip C Bevilacqua & Sarah M Assmann

RNA structure is irrevocably linked to function. A new method, termed 'LASER', utilizes a light-activated chemical probe to query RNA tertiary structure and illuminate RNA–protein interactions in the living cell.

GPCR: Lock and key become flexible

Marc Baldus — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 201 (2018). doi:10.1038/nchembio.2567

Author: Marc Baldus

G-protein-coupled receptors (GPCRs) are critically involved in signal transduction. Structural views of several GPCRs have recently been obtained, but the structural principles determining subtype selectivity are still mostly elusive. Now, a combined solid-state NMR and molecular-modeling approach reveals how bradykinin GPCRs distinguish between closely related peptide ligands.

Protein evolution: Hacking an enzyme

Kristoffer E Johansson — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 202 (2018). doi:10.1038/nchembio.2574

Authors: Kristoffer E Johansson & Jakob R Winther

Early stages of protein evolution are inherently difficult to study. Genetic selection in Escherichia coli has now identified a life-sustaining de novo enzyme arising from a simple scaffold that is completely different from the native enzyme.

Synthetic biology: Reframing cell therapy for cancer

Taylor B Dolberg — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 204 (2018). doi:10.1038/nchembio.2573

Authors: Taylor B Dolberg, Patrick S Donahue & Joshua N Leonard

Technologies for engineering immune cells to recognize features on cancer cells are transforming oncology. Synthetic biologists now expand this approach by conferring therapeutic functions to nonimmune cells and by programming cells to sense and respond to a new class of physiological cues.

How many human proteoforms are there?

Ruedi Aebersold — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 206 (2018). doi:10.1038/nchembio.2576

Authors: Ruedi Aebersold, Jeffrey N Agar, I Jonathan Amster, Mark S Baker, Carolyn R Bertozzi, Emily S Boja, Catherine E Costello, Benjamin F Cravatt, Catherine Fenselau, Benjamin A Garcia, Ying Ge, Jeremy Gunawardena, Ronald C Hendrickson, Paul J Hergenrother, Christian G Huber, Alexander R Ivanov, Ole N Jensen, Michael C Jewett, Neil L Kelleher, Laura L Kiessling, Nevan J Krogan, Martin R Larsen, Joseph A Loo, Rachel R Ogorzalek Loo, Emma Lundberg, Michael J MacCoss, Parag Mallick, Vamsi K Mootha, Milan Mrksich, Tom W Muir, Steven M Patrie, James J Pesavento, Sharon J Pitteri, Henry Rodriguez, Alan Saghatelian, Wendy Sandoval, Hartmut Schlüter, Salvatore Sechi, Sarah A Slavoff, Lloyd M Smith, Michael P Snyder, Paul M Thomas, Mathias Uhlén, Jennifer E Van Eyk, Marc Vidal, David R Walt, Forest M White, Evan R Williams, Therese Wohlschlager, Vicki H Wysocki, Nathan A Yates, Nicolas L Young & Bing Zhang

Distinguishing RNA modifications from noise in epitranscriptome maps

Anya V Grozhik — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 215 (2018). doi:10.1038/nchembio.2546

Authors: Anya V Grozhik & Samie R Jaffrey

Structural and evolutionary insights into ribosomal RNA methylation

Petr V Sergiev — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 226 (2018). doi:10.1038/nchembio.2569

Authors: Petr V Sergiev, Nikolay A Aleksashin, Anastasia A Chugunova, Yury S Polikanov & Olga A Dontsova

Insights into the biogenesis, function, and regulation of ADP-ribosylation

Michael S Cohen — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 236 (2018). doi:10.1038/nchembio.2568

Authors: Michael S Cohen & Paul Chang

Features and regulation of non-enzymatic post-translational modifications

Robert Harmel — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 244 (2018). doi:10.1038/nchembio.2575

Authors: Robert Harmel & Dorothea Fiedler

Light-activated chemical probing of nucleobase solvent accessibility inside cells

Chao Feng — Wed, 14 Feb 2018 00:00:00 GMT

Nature Chemical Biology 14, 325 (2018). doi:10.1038/nchembio0318-325

Author: Chao Feng, Dalen Chan, Jojo Joseph, Mikko Muuronen, William H Coldren, Nan Dai, Ivan R Corrêa, Filipp Furche, Christopher M Hadad & Robert C Spitale

Nanopore sequencing and assembly of a human genome with ultra-long reads

Miten Jain — Mon, 29 Jan 2018 00:00:00 GMT

Nature Biotechnology 36, 338 (2018). doi:10.1038/nbt.4060

Authors: Miten Jain, Sergey Koren, Karen H Miga, Josh Quick, Arthur C Rand, Thomas A Sasani, John R Tyson, Andrew D Beggs, Alexander T Dilthey, Ian T Fiddes, Sunir Malla, Hannah Marriott, Tom Nieto, Justin O'Grady, Hugh E Olsen, Brent S Pedersen, Arang Rhie, Hollian Richardson, Aaron R Quinlan, Terrance P Snutch, Louise Tee, Benedict Paten, Adam M Phillippy, Jared T Simpson, Nicholas J Loman & Matthew Loose

Lytic xylan oxidases from wood-decay fungi unlock biomass degradation

Marie Couturier — Mon, 29 Jan 2018 00:00:00 GMT

Nature Chemical Biology 14, 306 (2018). doi:10.1038/nchembio.2558

Authors: Marie Couturier, Simon Ladevèze, Gerlind Sulzenbacher, Luisa Ciano, Mathieu Fanuel, Céline Moreau, Ana Villares, Bernard Cathala, Florence Chaspoul, Kristian E Frandsen, Aurore Labourel, Isabelle Herpoël-Gimbert, Sacha Grisel, Mireille Haon, Nicolas Lenfant, Hélène Rogniaux, David Ropartz, Gideon J Davies, Marie-Noëlle Rosso, Paul H Walton, Bernard Henrissat & Jean-Guy Berrin

Partial DNA-guided Cas9 enables genome editing with reduced off-target activity

Hao Yin — Mon, 29 Jan 2018 00:00:00 GMT

Nature Chemical Biology 14, 311 (2018). doi:10.1038/nchembio.2559

Authors: Hao Yin, Chun-Qing Song, Sneha Suresh, Suet-Yan Kwan, Qiongqiong Wu, Stephen Walsh, Junmei Ding, Roman L Bogorad, Lihua Julie Zhu, Scot A Wolfe, Victor Koteliansky, Wen Xue, Robert Langer & Daniel G Anderson

Rewiring T-cell responses to soluble factors with chimeric antigen receptors

ZeNan L Chang — Mon, 29 Jan 2018 00:00:00 GMT

Nature Chemical Biology 14, 317 (2018). doi:10.1038/nchembio.2565

Authors: ZeNan L Chang, Michael H Lorenzini, Ximin Chen, Uyen Tran, Nathanael J Bangayan & Yvonne Y Chen

A whole-animal platform to advance a clinical kinase inhibitor into new disease space

Masahiro Sonoshita — Mon, 22 Jan 2018 00:00:00 GMT

Nature Chemical Biology 14, 291 (2018). doi:10.1038/nchembio.2556

Authors: Masahiro Sonoshita, Alex P Scopton, Peter M U Ung, Matthew A Murray, Lisa Silber, Andres Y Maldonado, Alexander Real, Avner Schlessinger, Ross L Cagan & Arvin C Dar

Chemical hijacking of auxin signaling with an engineered auxin–TIR1 pair

Naoyuki Uchida — Mon, 22 Jan 2018 00:00:00 GMT

Nature Chemical Biology 14, 299 (2018). doi:10.1038/nchembio.2555

Authors: Naoyuki Uchida, Koji Takahashi, Rie Iwasaki, Ryotaro Yamada, Masahiko Yoshimura, Takaho A Endo, Seisuke Kimura, Hua Zhang, Mika Nomoto, Yasuomi Tada, Toshinori Kinoshita, Kenichiro Itami, Shinya Hagihara & Keiko U Torii

A de novo enzyme catalyzes a life-sustaining reaction in Escherichia coli

Ann E Donnelly — Mon, 15 Jan 2018 00:00:00 GMT

Nature Chemical Biology 14, 253 (2018). doi:10.1038/nchembio.2550

Authors: Ann E Donnelly, Grant S Murphy, Katherine M Digianantonio & Michael H Hecht

Producing novel enzymes that are catalytically active in vitro and biologically functional in vivo is a key goal of synthetic biology. Here we describe Syn-F4, the first de novo protein that meets both criteria. Purified Syn-F4 hydrolyzes the siderophore ferric enterobactin, and expression of Syn-F4 allows an inviable strain of Escherichia coli to grow in iron-limited medium. These findings demonstrate that entirely new sequences can provide life-sustaining enzymatic functions in living organisms.

Light-activated chemical probing of nucleobase solvent accessibility inside cells

Chao Feng — Mon, 15 Jan 2018 00:00:00 GMT

Nature Chemical Biology 14, 276 (2018). doi:10.1038/nchembio.2548

Authors: Chao Feng, Dalen Chan, Jojo Joseph, Mikko Muuronen, William H Coldren, Nan Dai, Ivan R Corrêa, Filipp Furche, Christopher M Hadad & Robert C Spitale

The molecular basis of subtype selectivity of human kinin G-protein-coupled receptors

Lisa Joedicke — Mon, 15 Jan 2018 00:00:00 GMT

Nature Chemical Biology 14, 284 (2018). doi:10.1038/nchembio.2551

Authors: Lisa Joedicke, Jiafei Mao, Georg Kuenze, Christoph Reinhart, Tejaswi Kalavacherla, Hendrik R A Jonker, Christian Richter, Harald Schwalbe, Jens Meiler, Julia Preu, Hartmut Michel & Clemens Glaubitz

Employing a biochemical protecting group for a sustainable indigo dyeing strategy

Tammy M Hsu — Mon, 08 Jan 2018 00:00:00 GMT

Nature Chemical Biology 14, 256 (2018). doi:10.1038/nchembio.2552

Authors: Tammy M Hsu, Ditte H Welner, Zachary N Russ, Bernardo Cervantes, Ramya L Prathuri, Paul D Adams & John E Dueber

Na+-mimicking ligands stabilize the inactive state of leukotriene B4 receptor BLT1

Tetsuya Hori — Mon, 08 Jan 2018 00:00:00 GMT

Nature Chemical Biology 14, 262 (2018). doi:10.1038/nchembio.2547

Authors: Tetsuya Hori, Toshiaki Okuno, Kunio Hirata, Keitaro Yamashita, Yoshiaki Kawano, Masaki Yamamoto, Masakatsu Hato, Motonao Nakamura, Takao Shimizu, Takehiko Yokomizo, Masashi Miyano & Shigeyuki Yokoyama

Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases

Matthew Jenner — Mon, 08 Jan 2018 00:00:00 GMT

Nature Chemical Biology 14, 270 (2018). doi:10.1038/nchembio.2549

Authors: Matthew Jenner, Simone Kosol, Daniel Griffiths, Panward Prasongpholchai, Lucio Manzi, Andrew S Barrow, John E Moses, Neil J Oldham, Józef R Lewandowski & Gregory L Challis

A molecular mechanism governing memory precision

Josue Haubrich

Nature Medicine 24, 390 (2018). doi:10.1038/nm.4532

Authors: Josue Haubrich & Karim Nader

A key molecular mechanism has been identified that dictates whether memory will maintain or lose its details over time and that is relevant in post-traumatic stress disorder and dementia.