Table of contents



News Features

Challenge accepted: Human challenge trials for dengue pp828 - 830

Wudan Yan


Going batty: Studying natural reservoirs to inform drug development pp831 - 833

Wudan Yan


News in Brief

Biomedical briefing pp834 - 835


Problem of persisters persists, but anti-cancer drugs hold hope pp836 - 837

Boer Deng


Lung mapping seeks to crack microbial code in cystic fibrosis pp837 - 838

Shraddha Chakradhar



News and Views

Germs and joints: the contribution of the human microbiome to rheumatoid arthritis pp839 - 841

Geraint B Rogers


Rheumatoid arthritis (RA) is a debilitating autoimmune disorder, the etiology of which is poorly understood. A new study reveals dysbiosis in gut and oral microbiomes of affected individuals, potentially providing a basis for patient stratification and clues to pathophysiological mechanisms of RA onset and progression.

See also: Article by Zhang et al.

Supporting itch: a new role for astrocytes in chronic itch pp841 - 842

Dustin Green & Xinzhong Dong


A new study shows that astrocytes are involved in the development of chronic itch in a mouse model. This is dependent on upregulation of lipocalin 2 (LCN2) by the transcription factor STAT-3 and astrogliosis.

See also: Letter by Shiratori-Hayashi et al.

Progenitor cell engraftment in the lung: at last? pp842 - 844

Hans-Willem Snoeck


Engraftment of progenitor cells to effect repair of injured lungs has been a major challenge. A new study combines a conditioning strategy adopted from bone marrow transplantation with a lung injury model to bring this potential therapeutic approach closer to reality.

See also: Article by Rosen et al.

Breaking bad blood: β2-microglobulin as a pro-aging factor in blood pp844 - 845

Anthony J Filiano & Jonathan Kipnis


Aging is a major risk factor for cognitive decline and neurodegenerative diseases. A new study identified β2-microglobulin as a blood-borne factor that detrimentally influences the brain during the aging process.

See also: Letter by Smith et al.



Toward understanding and exploiting tumor heterogeneity pp846 - 853

Ash A Alizadeh, Victoria Aranda, Alberto Bardelli, Cedric Blanpain, Christoph Bock, Christine Borowski, Carlos Caldas, Andrea Califano, Michael Doherty, Markus Elsner, Manel Esteller, Rebecca Fitzgerald, Jan O Korbel, Peter Lichter, Christopher E Mason, Nicholas Navin, Dana Pe'er, Kornelia Polyak, Charles W M Roberts, Lillian Siu, Alexandra Snyder, Hannah Stower, Charles Swanton, Roel G W Verhaak, Jean C Zenklusen, Johannes Zuber & Jessica Zucman-Rossi


In this Perspective, attendees of the Herrenhausen Tumour Heterogeneity meeting discuss the challenges in understanding tumour heterogeneity and propose ways forward for overcoming these hurdles.

The central role of muscle stem cells in regenerative failure with aging pp854 - 862

Helen M Blau, Benjamin D Cosgrove & Andrew T V Ho


In this Perspective, the authors discuss the importance of intrinsic and extrinsic factors in muscle regeneration, and they conclude that both are necessary for the action of muscle stem cells in the aging process.


Brief Communications

Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus pp863 - 865

Mark J W Hanssen, Joris Hoeks, Boudewijn Brans, Anouk A J J van der Lans, Gert Schaart, José J van den Driessche, Johanna A Jörgensen, Mark V Boekschoten, Matthijs K C Hesselink, Bas Havekes, Sander Kersten, Felix M Mottaghy, Wouter D van Marken Lichtenbelt & Patrick Schrauwen


A small clinical trial shows that short-term cold acclimation to moderately-cold temperature improves the glucose homeostasis of individuals with type 2 diabetes, without an appreciable activation of their brown adipose tissue.

c-kit+ cells adopt vascular endothelial but not epithelial cell fates during lung maintenance and repair pp866 - 868

Qiaozhen Liu, Xiuzhen Huang, Hui Zhang, Xueying Tian, Lingjuan He, Rui Yang, Yan Yan, Qing-Dong Wang, Astrid Gillich & Bin Zhou


Lineage tracing shows that, contrary to a recent report, c-kit+ cells take on a vascular endothelial cell fate, not an epithelial one, after lung injury or during normal homeostasis.



Preconditioning allows engraftment of mouse and human embryonic lung cells, enabling lung repair in mice pp869 - 879

Chava Rosen, Elias Shezen, Anna Aronovich, Yael Zlotnikov Klionsky, Yasmin Yaakov, Miri Assayag, Inbal Eti Biton, Orna Tal, Guy Shakhar, Herzel Ben-Hur, David Shneider, Zvi Vaknin, Oscar Sadan, Shmuel Evron, Enrique Freud, David Shoseyov, Michael Wilschanski, Neville Berkman, Willem E Fibbe, David Hagin, Carmit Hillel-Karniel, Irit Milman Krentsis, Esther Bachar-Lustig & Yair Reisner


Preconditioning the niche after lung injury allows better engraftment by fetal lung tissue and repair.

See also: News and Views by Green & Dong

Neutrophils promote Alzheimer's disease–like pathology and cognitive decline via LFA-1 integrin pp880 - 886

Elena Zenaro, Enrica Pietronigro, Vittorina Della Bianca, Gennj Piacentino, Laura Marongiu, Simona Budui, Ermanna Turano, Barbara Rossi, Stefano Angiari, Silvia Dusi, Alessio Montresor, Tommaso Carlucci, Sara Nanì, Gabriele Tosadori, Lucia Calciano, Daniele Catalucci, Giorgio Berton, Bruno Bonetti & Gabriela Constantin


Neutrophils infiltrate the CNS and promote Alzheimer's disease–like pathology and memory loss.

Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization pp887 - 894

Shangyu Hong, Jose M Moreno-Navarrete, Xiaojing Wei, Yusuke Kikukawa, Iphigenia Tzameli, Deepthi Prasad, Yoonjin Lee, John M Asara, Jose Manuel Fernandez-Real, Eleftheria Maratos-Flier & Pavlos Pissios


Nicotinamide N-methyltransferase acts through its product, N1-methylnicotinamide, to stabilize Sirt1 and thus regulate hepatic glucose and lipid metabolism.

The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment pp895 - 905

Xuan Zhang, Dongya Zhang, Huijue Jia, Qiang Feng, Donghui Wang, Di Liang, Xiangni Wu, Junhua Li, Longqing Tang, Yin Li, Zhou Lan, Bing Chen, Yanli Li, Huanzi Zhong, Hailiang Xie, Zhuye Jie, Weineng Chen, Shanmei Tang, Xiaoqiang Xu, Xiaokai Wang, Xianghang Cai, Sheng Liu, Yan Xia, Jiyang Li, Xingye Qiao, Jumana Yousuf Al-Aama, Hua Chen, Li Wang, Qing-jun Wu, Fengchun Zhang, Wenjie Zheng, Yongzhe Li, Mingrong Zhang, Guangwen Luo, Wenbin Xue, Liang Xiao, Jun Li, Wanting Chen, Xun Xu, Ye Yin, Huanming Yang, Jian Wang, Karsten Kristiansen, Liang Liu, Ting Li, Qingchun Huang, Yingrui Li & Jun Wang


The gut and oral microbiomes are altered in individuals with rheumatoid arthritis, and these changes can be used to stratify individuals for diagnostic and prognostic purposes.

See also: News and Views by Rogers

Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt pp906 - 913

Justin E Wilson, Alex S Petrucelli, Liang Chen, A Alicia Koblansky, Agnieszka D Truax, Yoshitaka Oyama, Arlin B Rogers, W June Brickey, Yuli Wang, Monika Schneider, Marcus Mühlbauer, Wei-Chun Chou, Brianne R Barker, Christian Jobin, Nancy L Allbritton, Dale A Ramsden, Beckley K Davis & Jenny P Y Ting


AIM2 suppresses colon tumorigenesis, independently of the inflammasome and IL-1β, by interacting with DNA-PK and inhibiting Akt activation.

NY-ESO-1–specific TCR–engineered T cells mediate sustained antigen-specific antitumor effects in myeloma pp914 - 921

Aaron P Rapoport, Edward A Stadtmauer, Gwendolyn K Binder-Scholl, Olga Goloubeva, Dan T Vogl, Simon F Lacey, Ashraf Z Badros, Alfred Garfall, Brendan Weiss, Jeffrey Finklestein, Irina Kulikovskaya, Sanjoy K Sinha, Shari Kronsberg, Minnal Gupta, Sarah Bond, Luca Melchiori, Joanna E Brewer, Alan D Bennett, Andrew B Gerry, Nicholas J Pumphrey, Daniel Williams, Helen K Tayton- Martin, Lilliam Ribeiro, Tom Holdich, Saul Yanovich, Nancy Hardy, Jean Yared, Naseem Kerr, Sunita Philip, Sandra Westphal, Don L Siegel, Bruce L Levine, Bent K Jakobsen, Michael Kalos & Carl H June


Carl June and colleagues report the results of a phase I/II trial of adoptively transferred engineered T cells in patients with advanced multiple myeloma.



Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma pp922 - 926

Wyndham H Wilson, Ryan M Young, Roland Schmitz, Yandan Yang, Stefania Pittaluga, George Wright, Chih-Jian Lih, P Mickey Williams, Arthur L Shaffer, John Gerecitano, Sven de Vos, Andre Goy, Vaishalee P Kenkre, Paul M Barr, Kristie A Blum, Andrei Shustov, Ranjana Advani, Nathan H Fowler, Julie M Vose, Rebecca L Elstrom, Thomas M Habermann, Jacqueline C Barrientos, Jesse McGreivy, Maria Fardis, Betty Y Chang, Fong Clow, Brian Munneke, Davina Moussa, Darrin M Beaupre & Louis M Staudt


Clinical testing of BCR inhibition on DLBCL reveals determinants of response.

STAT3-dependent reactive astrogliosis in the spinal dorsal horn underlies chronic itch pp927 - 931

Miho Shiratori-Hayashi, Keisuke Koga, Hidetoshi Tozaki-Saitoh, Yuta Kohro, Honami Toyonaga, Chiharu Yamaguchi, Ayumi Hasegawa, Takeshi Nakahara, Junichi Hachisuka, Shizuo Akira, Hideyuki Okano, Masutaka Furue, Kazuhide Inoue & Makoto Tsuda


In response to signals from afferent TRPV1+ C-fibers, STAT3-dependent upregulation of LCN2 in reactive astrocytes of the spinal dorsal horn amplifies itch signaling in multiple rodent models of atopic and contact dermatitis.

See also: News and Views by Green & Dong

β2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis pp932 - 937

Lucas K Smith, Yingbo He, Jeong-Soo Park, Gregor Bieri, Cedric E Snethlage, Karin Lin, Geraldine Gontier, Rafael Wabl, Kristopher E Plambeck, Joe Udeochu, Elizabeth G Wheatley, Jill Bouchard, Alexander Eggel, Ramya Narasimha, Jacqueline L Grant, Jian Luo, Tony Wyss-Coray & Saul A Villeda


Circulating β2-microglobulin, a component of MHC I, increases with age, promoting age-related cognitive decline and decreased neurogenesis.

See also: News and Views by Snoeck



The prognostic landscape of genes and infiltrating immune cells across human cancers pp938 - 945

Andrew J Gentles, Aaron M Newman, Chih Long Liu, Scott V Bratman, Weiguo Feng, Dongkyoon Kim, Viswam S Nair, Yue Xu, Amanda Khuong, Chuong D Hoang, Maximilian Diehn, Robert B West, Sylvia K Plevritis & Ash A Alizadeh


A searchable pan-cancer resource generated using data from nearly 18,000 human tumors reveals links between tumor infiltration by particular leukocyte subsets, tumor expression of particular gene signatures, and patient prognosis.

Genomic landscape of carcinogen-induced and genetically induced mouse skin squamous cell carcinoma pp946 - 954

Dany Nassar, Mathilde Latil, Bram Boeckx, Diether Lambrechts & Cédric Blanpain


Genomic profiling of carcinogen-induced skin tumors in mice provides a comprehensive characterization of their mutational landscape.


Technical Report

Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met pp955 - 961

Jacobus Burggraaf, Ingrid M C Kamerling, Paul B Gordon, Lenneke Schrier, Marieke L de Kam, Andrea J Kales, Ragnar Bendiksen, Bård Indrevoll, Roger M Bjerke, Siver A Moestue, Siavash Yazdanfar, Alexandra M J Langers, Marit Swaerd-Nordmo, Geir Torheim, Madhuri V Warren, Hans Morreau, Philip W Voorneveld, Tessa Buckle, Fijs W B van Leeuwen, Liv-Ingrid Ødegårdstuen, Grethe T Dalsgaard, Andrew Healey & James C H Hardwick


Intravenous administration of a fluorescently labeled c-Met–binding peptide enables visualization of polyps not detected using white light.