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donderdag 7 december 2017

Nature Medicine Contents: December 2017 Volume 23 Number 12 pp 1385-1499

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Nature Medicine

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December 2017 Volume 23, Issue 12

News and Views
Technical Report


Better Visualize, Analyze, and Phenotype Immune Cells in situ in FFPE Tissue Sections and TMAs

Learn how Vectra Polaris™ quantitative pathology imaging system provides unparalleled speed and performance for extracting proteomic and morphometric information from tissue sections. 

Download Application Note

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Nature Index 2017 Science Inc. 

This supplement investigates the changing role of corporate institutions in the world of science and the costs and benefits to high-quality research of these evolving arrangements. 

Read the full supplement >>
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.

Access the Outlook free online to learn more >>

Produced with support from: Symbiomix Therapeutics, LLC

Poster on: The expanding CRISPR toolbox 

The CRISPR-Cas9 system can do a lot more than gene editing. This Poster, from Nature Methods, explores the newest possibilities of CRISPR. 

Available to download free online >> 

Produced with support from: 



Cutting out the liver fat   p1385
Better animal models of nonalcoholic steatohepatitis are needed to more fully understand the disease and to identify potential new therapeutic treatments for this increasingly common condition.



The Yearbook   p1386
Shraddha Chakradhar
From policy advisors who resigned in protest to an agency trying to settle a patent dispute, many of the newsmakers in our 2017 Yearbook made notable decisions.

Notable advances 2017   pp1387 - 1389
Tanya Bondar, Javier Carmona, Kate Gao, Brett Benedetti, Michael Basson et al.
This past year included numerous research studies that broke the mold and elucidated new biology and drug targets. Here are some of the exciting papers from 2017 that moved biomedicine forward.

Timeline of events   pp1390 - 1391
Shraddha Chakradhar
From a worldwide march in favor of science to an increased focus on diversity and gender equality in the workplace, 2017 was a year that was dominated by activism and social causes. Amidst these events, however, were concerns over unproven treatments and emergency funding.

Drugs that made headlines in 2017   pp1392 - 1393
Shraddha Chakradhar
In 2017, cancer drugs once again dominated the news, with many of these medications making headlines for being the first of their kind to gain approval. Beyond cancer, drugs for inflammatory diseases also received attention, for both their successes and their failures.



Correction   p1391



The small molecule CLP257 does not modify activity of the K+-Cl- co-transporter KCC2 but does potentiate GABAA receptor activity   pp1394 - 1396
Ross A Cardarelli, Karen Jones, Lucie I Pisella, Heike J Wobst, Lisa J McWilliams et al.

Reply to The small molecule CLP257 does not modify activity of the K+-Cl- co-transporter KCC2 but does potentiate GABAA receptor activity   pp1396 - 1398
Martin Gagnon, Marc J Bergeron, Jimena Perez-Sanchez, Isabel Plasencia-Fernandez, Louis-Etienne Lorenzo et al.

News and Views


Organoids lead the cancer attack   pp1399 - 1400
Amber R Smith and Calvin J Kuo
In an article published recently in Nature Medicine, the authors generate organoid models of liver neoplasia. In doing so, they highlight both the diversity of current organoid methodologies and their application to cancer modeling and therapeutics discovery.

See also: Article by Hosen et al.

Recognition of self-DNA drives cardiac inflammation: why broken hearts fail   pp1400 - 1401
Kory J Lavine and Douglas L Mann
Signals that govern immune cells in the heart remain poorly defined. A new report in mice shows that pathways involved in sensing viruses orchestrate monocyte and macrophage activation through recognition of DNA derived from dying cardiomyocytes following myocardial infarction.

See also: Letter by King et al.

Targeted cellular immunotherapy for T cell malignancies   pp1402 - 1403
Teresa Palomero and Adolfo Ferrando
In a recent study, Maciocia et al. develop a novel T cell receptor beta (TCRB) constant C1-chain-directed cellular immunotherapy for the treatment of T cell malignancies.

See also: Article by Maciocia et al.

Fattening the role of Ca2+ cycling in adaptive thermogenesis   pp1403 - 1404
Daniel Gamu and A Russell Tupling
A new study shows that deleting uncoupling protein 1 activates Ca2+ cycling thermogenesis within beige fat, protecting mice against cold-induced hypothermia and dysglycemia following diet-induced obesity.

See also: Article by Ikeda et al.

Nature Medicine
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ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis   pp1405 - 1415
David Lagares, Parisa Ghassemi-Kakroodi, Caroline Tremblay, Alba Santos, Clemens K Probst et al.
TGF-[beta] induces expression of ADAM10, which results in greater shedding of ephrin-B2. This shedding promotes the chemotaxis and activation of myofibroblasts and thus the progression of organ fibrosis.

Targeting the T cell receptor [beta]-chain constant region for immunotherapy of T cell malignancies   pp1416 - 1423
Paul M Maciocia, Patrycja A Wawrzyniecka, Brian Philip, Ida Ricciardelli, Ayse U Akarca et al.
Pule and colleagues identify the TCR [beta]-chain constant region as a new target for chimeric antigen receptor (CAR) T cells in treatment of T cell cancers while potentially preserving a healthy T cell repertoire. They demonstrate that anti-TCRB1 CAR T cells eliminate cancerous TCRB1+ T cells while sparing nearly one-third of normal TCRB2+ T cells.

See also: News and Views by Palomero & Ferrando

Human primary liver cancer-derived organoid cultures for disease modeling and drug screening   pp1424 - 1435
Laura Broutier, Gianmarco Mastrogiovanni, Monique MA Verstegen, Hayley E Francies, Lena Morrill Gavarro et al.
Tumor organoids derived from the most common subtypes of primary liver cancer recapitulate the histologic and molecular features of the tissues of origin, even after long-term culture. These in vitro models, as well as those for colorectal cancer reported in Crespo et al. in a previous issue, are amenable for drug screening and allow the identification of therapeutic approaches with potential for cancer treatment.

The activated conformation of integrin [beta]7 is a novel multiple myeloma-specific target for CAR T cell therapy   pp1436 - 1443
Naoki Hosen, Yukiko Matsunaga, Kana Hasegawa, Hiroshi Matsuno, Yuki Nakamura et al.
Hosen et al. identify an active conformation of integrin beta-7 as a cancer-associated antigen in multiple myeloma, and engineer a CAR-T cell that shows efficacy against MM in a mouse model. These findings describe the first conformation-specific CAR-T cell and highlight the potential of conformational targets in cancer immunotherapy.

See also: News and Views by Smith & Kuo

Asprosin is a centrally acting orexigenic hormone   pp1444 - 1453
Clemens Duerrschmid, Yanlin He, Chunmei Wang, Chia Li, Juan C Bournat et al.
Asprosin, a recently identified secreted hormone from adipose tissue, acts centrally to promote food intake.

UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis   pp1454 - 1465
Kenji Ikeda, Qianqian Kang, Takeshi Yoneshiro, Joao Paulo Camporez, Hiroko Maki et al.
Calcium cycling induced by the SERCA2b-RyR2 pathway in beige fat cells allows for thermogenic activity independent of UCP1.

See also: News and Views by Gamu & Tupling

Nature Outlook: Amyotrophic lateral sclerosis 

ALS is mysterious and deadly, but new discoveries and treatments bring hope.

Access the Outlook here >>

Produced with support from: 

Funded by a grant from 
Mitsubishi Tanabe Pharma America, Inc. 



A microRNA screen reveals that elevated hepatic ectodysplasin A expression contributes to obesity-induced insulin resistance in skeletal muscle   pp1466 - 1473
Motoharu Awazawa, Paula Gabel, Eva Tsaousidou, Hendrik Nolte, Marcus Kruger et al.
Screening reveals that obesity induces the expression of liver ectodysplasin A, which acts on the muscle to induce insulin resistance.

Selective neuronal lapses precede human cognitive lapses following sleep deprivation   pp1474 - 1480
Yuval Nir, Thomas Andrillon, Amit Marmelshtein, Nanthia Suthana, Chiara Cirelli et al.
In humans, a full night of sleep deprivation causes attenuated and delayed neuronal responses that correlate with impaired cognitive performance.

IRF3 and type I interferons fuel a fatal response to myocardial infarction   pp1481 - 1487
Kevin R King, Aaron D Aguirre, Yu-Xiang Ye, Yuan Sun, Jason D Roh et al.
The massive cell death that occurs during myocardial infarction releases self-DNA and triggers an interferon response in infiltrating leukocytes via a cGAS-STING-IRF3 pathway. Interference with this response[mdash]either by genetic disruption of the pathway or antibody blockade of the type I interferon receptor[mdash]is beneficial in mice subjected to myocardial infarction.

See also: News and Views by Lavine & Mann

Technical Report


Enhancing the precision of genetic lineage tracing using dual recombinases   pp1488 - 1498
Lingjuan He, Yan Li, Yi Li, Wenjuan Pu, Xiuzhen Huang et al.
Genetic cell-lineage tracing studies in mice are crucial for delineating the contribution of stem and progenitor cells to different cell types, both in disease states and after regenerative therapy. He et al. have developed new genetic lineage-tracing systems that provide more definitive results than the commonly used Cre-based system and show that this new technology can resolve current controversies in the field, as demonstrated by lineage-tracing studies in the heart and liver.



Corrigendum: Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure   p1499
Stephanus T Malherbe, Shubhada Shenai, Katharina Ronacher, Andre G Loxton, Gregory Dolganov et al.

Corrigendum: ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis   p1499
David Lagares, Parisa Ghassemi-Kakroodi, Caroline Tremblay, Alba Santos, Clemens K Probst et al.

Nature Reviews Collection — The obesity epidemic: molecular and clinical considerations 

This collection of articles describes the latest efforts to understand the molecular mechanisms underlying obesity against a complex backdrop of factors that include socioeconomic status, environment and personal behaviour, as well as advances in treatment. 

View the collection
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