Volume 20 Issue 11, November 2014

Pluripotent stem cells can be differentiated in vitro to form immature human intestinal organoids. In this issue, Michael Helmrath and his colleagues report that these organoids engraft in vivo to form mature and functional small intestine. The cover image, courtesy of Carey Watson (Cincinnati Children's Hospital Medical Center), depicts pluripotent stem cellgenerated human small intestine engrafted under the mouse kidney capsule, with human intestinal DNA (pink), total DNA (blue), smooth muscle (green) and recipient's kidney (red).

Editorial

Course correction

The international response to the ongoing Ebola epidemic has in many respects been more reactive than proactive. But there are changes that, if made, may shift the balance toward future readiness.

Editorial 06 Nov 2014

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News

Tumor sequencing takes off, but insurance reimbursement lags

Shraddha Chakradhar
News 06 Nov 2014
Biomedical briefing

News 06 Nov 2014
FDA's post-approval studies continue to suffer delays and setbacks

Cassandra Willyard
News 06 Nov 2014
As funds to sync health records dwindle, research could suffer

Manasi Vaidya
News 06 Nov 2014

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Book Review

Eradicating infectious disease

William R Jacobs Jr
Book Review 06 Nov 2014

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Correspondence

Lrp5 regulation of bone mass and serotonin synthesis in the gut

Aruna Kode
Arnaud Obri
Gerard Karsenty
Correspondence 06 Nov 2014
Reply to Lrp5 regulation of bone mass and gut serotonin synthesis

Yajun Cui
Paul J Niziolek
Alexander G Robling
Correspondence 06 Nov 2014
Colorectal cancer classification based on gene expression is not associated with FOLFIRI response

Raquel Martinez-Garcia
Pedro P Lopez-Casas
Manuel Hidalgo
Correspondence 06 Nov 2014
Reply to Colorectal cancer classification based on gene expression is not associated with FOLFIRI response

Anguraj Sadanandam
Joe Gray
Douglas Hanahan
Correspondence 06 Nov 2014

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News & Views

Megakaryocytes in the hematopoietic stem cell niche

Mesenchymal stromal cells are key components of hematopoietic stem cell (HSC) niches in the bone marrow. Two studies now show that hematopoietic-derived megakaryocytes also contribute to the HSC niche, regulating HSC quiescence and function.

Ryan B. Day
Daniel C. Link
News & Views 06 Nov 2014
Fatty acid synthesis tips the T_H17-T_reg cell balance

A recent study reports that de novo fatty acid synthesis is important for differentiation of T helper 17 (T_H17) cells. Suppression of this pathway through inhibition of acetyl-CoA carboxylase (ACC) with soraphen A prevents T_H17 cell differentiation and consequently enforces a regulatory T cell phenotype.

David O'Sullivan
Erika L. Pearce
News & Views 06 Nov 2014
Asparagine endopeptidase cleaves tau and promotes neurodegeneration

Truncation of tau contributes to the formation of neurofibrillary tangles in Alzheimer's disease. A new study finds a direct role for a lysosomal cysteine protease, asparagine endopeptidase, in cleaving tau into neurotoxic fragments.

Hanna Rosenmann
News & Views 06 Nov 2014
Osteoclast progenitors promote bone vascularization and osteogenesis

Preosteoclasts give rise to bone-resorbing osteoclasts, which are crucial for skeletal homeostasis. A study now shows that preosteoclasts also contribute to bone formation by releasing platelet-derived growth factor-BB, which promotes bone vascularization and osteogenesis.

Anjali P. Kusumbe
Ralf H. Adams
News & Views 06 Nov 2014

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Research Highlights

T cell activation in hypertension

Michael Basson
Research Highlights 06 Nov 2014
Linking exercise and depression

Hannah Stower
Research Highlights 06 Nov 2014
Myeloid cells mapped out

Kevin Da Silva
Research Highlights 06 Nov 2014
Mixed and matched tumors

Victoria Aranda
Research Highlights 06 Nov 2014

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Review Article

Ubiquitination in disease pathogenesis and treatment

Doris Popovic
Domagoj Vucic
Ivan Dikic
Review Article 06 Nov 2014

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Article

Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer's disease

Tau cleavage and aggregation, key processes in many neurodegenerative diseases, can be reduced by blocking the activity of a protease called asparagine endopeptidase.

Zhentao Zhang
Mingke Song
Keqiang Ye
Article 19 Oct 2014
Niclosamide ethanolamine–induced mild mitochondrial uncoupling improves diabetic symptoms in mice

By acting as a mild mitochondrial uncoupler, a derivative of the approved drug niclosamide may offer a new approach to treat diabetes.

Hanlin Tao
Yong Zhang
Shengkan Jin
Article 05 Oct 2014
PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis

Preostoclasts secrete PDGF-BB to promote angiogenesis in the bone, promoting bone homeostasis and preventing bone loss in an osteoporosis model.

Hui Xie
Zhuang Cui
Xu Cao
Article 05 Oct 2014
Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures

A new study shows that Wnt16 inhibits osteoclast formation, suggesting it may be a possible therapeutic option for treating bone fractures in osteoporosis.

Sofia Movérare-Skrtic
Petra Henning
Claes Ohlsson
Article 12 Oct 2014
Pro-proliferative and inflammatory signaling converge on FoxO1 transcription factor in pulmonary hypertension

Activation of the transcription factor FoxO1 ameliorates vascular remodeling in pulmonary hypertension, pointing to a potential new therapeutic strategy for this disease.

Rajkumar Savai
Hamza M Al-Tamari
Soni Savai Pullamsetti
Article 26 Oct 2014
Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy

Anthracyclines can induce a type 1 interferon response in tumor cells that may predict clinical response to these drugs.

Antonella Sistigu
Takahiro Yamazaki
Laurence Zitvogel
Article 26 Oct 2014

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Letter

An in vivo model of human small intestine using pluripotent stem cells

An in vivo model of the human small intestine is established in mice using human pluripotent stem cells.

Carey L Watson
Maxime M Mahe
Michael A Helmrath
Letter 19 Oct 2014
Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion

Two papers in this issue, by Bruns et al. and Zhao et al., show that megakaryocytes constitute a niche for hematopoietic stem cells in the mouse bone marrow and produce factors that regulate hematopoietic stem cell quiescence and proliferation.

Ingmar Bruns
Daniel Lucas
Paul S Frenette
Letter 19 Oct 2014
Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells

Two papers in this issue, by Bruns et al. and Zhao et al., show that megakaryocytes constitute a niche for hematopoietic stem cells in the mouse bone marrow and produce factors that regulate hematopoietic stem cell quiescence and proliferation.

Meng Zhao
John M Perry
Linheng Li
Letter 19 Oct 2014
De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells

T_H17 and T_reg cell development are reciprocally regulated by de novo fatty acid synthesis, and inhibition of acetyl-CoA carboxylase 1 (ACC1) attenuates T_H17 cell–mediated autoimmune disease.

Luciana Berod
Christin Friedrich
Tim Sparwasser
Letter 05 Oct 2014
Regulatory B cells are induced by gut microbiota–driven interleukin-1β and interleukin-6 production

The gut microbiota promotes regulatory B cell development and function through interleukin-1β and interleukin-6.

Elizabeth C Rosser
Kristine Oleinika
Claudia Mauri
Letter 19 Oct 2014

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Technical Report

A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer

The next generation of genetically engineered mouse models of pancreatic cancer involving a new inducible dual-recombinase system that combines Flp-FRT and Cre-loxP.

Nina Schönhuber
Barbara Seidler
Dieter Saur
Technical Report 19 Oct 2014
Microscopic lymph node tumor burden quantified by macroscopic dual-tracer molecular imaging

Tichauer et al. describe a dual-tracer approach to quantify cancer cell receptor concentrations, in this case epidermal growth factor receptor, in lymph nodes, that can also correct for nonspecific uptake.

Kenneth M Tichauer
Kimberley S Samkoe
Brian W Pogue
Technical Report 26 Oct 2014

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Volume 20 Issue 11, November 2014

Editorial

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