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dinsdag 6 maart 2018

Nature Medicine Contents: March 2018 Volume 24 Number 3 pp 247-374

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The Vilcek Foundation congratulates the recipients of the
2018 Vilcek Prizes in Biomedical Science.

Alexander Rudensky (Sloan Kettering Institute) receives $100,000 Vilcek Prize.
Polina Anikeeva (Massachusetts Institute of Technology),
Sergiu P. Pasca
(Stanford University),
and Feng Zhang (Broad Institute)
each win $50,000 Vilcek Prize for Creative Promise in Biomedical Science. 

Click here for more information.
TABLE OF CONTENTS

March 2018 Volume 24, Issue 3

Editorial
News
News and Views
Articles
Letters

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Nature Collection: Mitochondria and the heart

Nature Reviews Cardiology brings together a collection of articles from Nature Research journals highlighting the importance of mitochondria in the heart and the new opportunities for mitochondria-targeted therapies in cardiac diseases.
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Mitochondrial Medicine (9-11 May 2018) 

This conference aims to bridge the gap between our current understanding of the mechanisms and processes involved in mitochondrial disease and the novel approaches being developed to treat them.

Deadlines: Early bird: 27 Feb/ Bursaries: 13 Mar/ Abstracts: 27 Mar / Registration: 10 Apr
 

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Nature Outline: Non-union bone fracture 

Bone fractures that fail to heal with conventional treatment are known as non-union bone fractures. They cause prolonged pain and disability. Work is under way to improve the success rate of surgical repair and to accelerate the bone-healing process. 

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Editorial

Top

Stimulus package   p247
doi:10.1038/nm.4515
Therapies for Alzheimer's disease and other neurodegenerative diseases are desperately needed. Yet, a string of disappointments in the neurodegenerative therapy space has meant that several companies over the years have ended their investment in the field. Some companies have diversified their research and development (R&D) models to hedge their bets. Maintaining this diversity to bring down the silos between big pharma and smaller research teams may be necessary to jumpstart and sustain progress in combatting neurodegenerative conditions.

News

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News Features

Going live: How microRNAs might bring living vaccines back into the fold   pp248 - 250
Shraddha Chakradhar
doi:10.1038/nm0318-248

Gut checkpoint: A rising cancer treatment may get a boost from intestinal bacteria   pp251 - 253
Anna Azvolinsky
doi:10.1038/nm0318-251

News and Views

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The intestinal microbiome influences checkpoint blockade   pp254 - 255
Cynthia L Sears and Drew M Pardoll
doi:10.1038/nm.4511
Studies in metastatic melanoma, non-small-cell lung carcinoma and renal cell carcinoma indicate certain bacteria within the gut microbiota enhance clinical responses to checkpoint blockade.

A human cellular model of amyotrophic lateral sclerosis   pp256 - 257
Rebecca M Marton and Sergiu P Pasca
doi:10.1038/nm.4509
Stem cell-derived human motor neurons were used to investigate the cellular mechanisms underlying C9ORF72-related amyotrophic lateral sclerosis.

See also: Article by Shi et al.

A previously undetected pathology of Zika virus infection   pp258 - 259
Kimberly M Christian, Hongjun Song and Guo-li Ming
doi:10.1038/nm.4510
In a nonhuman primate model of Zika virus infection, structural and cellular pathology deficits that could have a long-lasting impact on neural development and neurocognitive function are detected in offspring of infected mothers.

See also: Letter by Adams Waldorf et al.

An immunosuppressive pathway for tumor progression   pp260 - 261
Antoine Marcais and Thierry Walzer
doi:10.1038/nm.4508
An active immunosuppressive pathway is identified in colon cancer that confers immune evasion by the cancer and can be targeted to synergize with immunotherapies.

See also: Article by Xiao et al.

Nature Medicine
JOBS of the week
Faculty Member ? Cryo-EM
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University of Geneva - Faculty of Medicine
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Naturejobs Career Guide China 2018 

China's scientific landscape is shifting fast. Where can you fit in?
Read the latest issue of our career guide to see what opportunities await you.

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Articles

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DKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activation   pp262 - 270
Qian Xiao, Jibo Wu, Wei-Jia Wang, Shiyang Chen, Yingxia Zheng et al.
doi:10.1038/nm.4496
A negative regulator of the Wnt pathway secreted by tumor cells promotes immune evasion by suppressing lymphocyte cytotoxicity.

See also: News and Views by Marcais & Walzer

Noncanonical hedgehog pathway activation through SRF-MKL1 promotes drug resistance in basal cell carcinomas   pp271 - 281
Ramon J Whitson, Alex Lee, Nicole M Urman, Amar Mirza, Catherine Y Yao et al.
doi:10.1038/nm.4476
A large proportion of basal cell carcinomas develop resistance independently of the canonical mutations in genes encoding hedgehog pathway components. An unbiased analysis investigating alternative pathways of resistance uncovers the role of cytoskeletal signaling in driving noncanonical activation of hedgehog signaling through nuclear translocation of SRF and MKL1. These results advance understanding of the mechanisms underlying drug resistance and provide new actionable insights for clinical translation.

Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells   pp282 - 291
Nimitha R Mathew, Francis Baumgartner, Lukas Braun, David O'Sullivan, Simone Thomas et al.
doi:10.1038/nm.4484
Combining the kinase inhibitor sorafenib with allogeneic stem cell transplantation boosts immune responses against a subtype of acute myelogenous leukemia, suggesting potential clinical benefit.

Brown adipose tissue thermogenic adaptation requires Nrf1-mediated proteasomal activity   pp292 - 303
Alexander Bartelt, Scott B Widenmaier, Christian Schlein, Kornelia Johann, Renata L S Goncalves et al.
doi:10.1038/nm.4481
Nrf1-mediated proteosome activity in brown fat is required for the normal thermogenic behavior of this tissue in mice.

Transcriptional regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA   pp304 - 312
Tamer Sallam, Marius Jones, Brandon J Thomas, Xiaohui Wu, Thomas Gilliland et al.
doi:10.1038/nm.4479
The conserved long noncoding RNA MeXis has anti-atherosclerotic effects in mice by acting with the nuclear hormone receptor LXR in macrophages to promote cholesterol efflux.

Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons   pp313 - 325
Yingxiao Shi, Shaoyu Lin, Kim A Staats, Yichen Li, Wen-Hsuan Chang et al.
doi:10.1038/nm.4490
Human ALS/FTD patient iPSC-derived neurons are used to uncover mechanisms by which C9ORF72 mutations cause neurodegeneration.

See also: News and Views by Marton & Pasca

Pericyte degeneration causes white matter dysfunction in the mouse central nervous system   pp326 - 337
Axel Montagne, Angeliki M Nikolakopoulou, Zhen Zhao, Abhay P Sagare, Gabriel Si et al.
doi:10.1038/nm.4482
Degeneration of pericytes causes toxic fibrin(ogen) accumulation, cell death and microcirculation dysfunction in CNS white-matter axon tracts.

A histone deacetylase 3-dependent pathway delimits peripheral myelin growth and functional regeneration   pp338 - 351
Xuelian He, Liguo Zhang, Luis F Queme, Xuezhao Liu, Andrew Lu et al.
doi:10.1038/nm.4483
Screening for small-molecule epigenetic modulators identifies HDAC3 inhibitors that promote peripheral myelin repair after nerve injury in rodents.

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Nature Outlook: Women's health

From common diseases that affect the sexes differently to conditions that affect only women - and from birth, through the menopause, to old age - there are many challenges in women's health.

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Letters

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A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects   pp352 - 359
Yuki Kagoya, Shinya Tanaka, Tingxi Guo, Mark Anczurowski, Chung-Hsi Wang et al.
doi:10.1038/nm.4478
Optimal T cell activation requires signaling through the T cell receptor (signal 1), a co-stimulatory receptor (signal 2) and a cytokine receptor (signal 3), yet most chimeric antigen receptors (CARs) lack a domain to transduce signal 3. Kagoya et al. now report their development of a new CAR that incorporates a JAK-STAT cytokine signaling domain and mediates potent antitumor effects.

Antagonism of PPAR-γ signaling expands human hematopoietic stem and progenitor cells by enhancing glycolysis   pp360 - 367
Bin Guo, Xinxin Huang, Man Ryul Lee, Sang A Lee and Hal E Broxmeyer
doi:10.1038/nm.4477
A small-molecule antagonist of PPAR-γ expands human cord blood HSPCs via downregulation of fructose 1,6-bisphosphatase expression, thereby enhancing glycolysis.

Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain   pp368 - 374
Kristina M Adams Waldorf, Branden R Nelson, Jennifer E Stencel-Baerenwald, Colin Studholme, Raj P Kapur et al.
doi:10.1038/nm.4485
Zika virus infection of pregnant nonhuman primates results in the loss of fetal neuronal progenitor cells, even in the absence of overt microcephaly.

See also: News and Views by Christian et al.

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Nature Collection: 2017 Nobel Prize in Physiology or Medicine

The 2017 Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash and Michael W. Young for their pioneering work in Drosophila that elucidated the molecular mechanisms controlling circadian rhythm. 

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