Friday, April 7, 2017

Nature Medicine Contents: April 2017 Volume 23 Number 4 pp 397-526

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April 2017 Volume 23, Issue 4

News and Views
Brief Communication
Nature Outlook: Multiple Sclerosis

Multiple Sclerosis induces the immune system to damage the central nervous system. Research on causes and treatments offers new hope.

Access the Outlook free online today!

This activity has been supported by a grant from F. Hoffmann-La Roche Ltd, which has had no control over the educational content of this activity.

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Nature Reviews Immunology and Nature Reviews Molecular Cell Biology: Poster on Bone marrow niches and HSC fates

This poster shows the signalling pathways between stromal and haematopoietic cells of the bone marrow niche that direct the fate of haematopoietic stem cells. 


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Focus on Disease models: reproducibility and translation 

Lab Animal, a Nature Research journal focusing on in vivo methods, research and technology with model organisms of human health & disease, presents a special Focus on reproducibility and translation of in vivo research with disease models. 

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Nature Protocols: Poster on the production of Chimeric Antigen Receptor T-cells

This poster overviews the production of (CAR) T-cells, discussing the significant and unique challenges of the production process 

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Science over speed   p397



Beyond the breath: Exploring sex differences in tuberculosis outside the lungs   pp398 - 401
Alla Katsnelson

A curious connection: Teasing apart the link between gut microbes and lung disease   pp402 - 404
Shraddha Chakradhar



Correction   p404



The Drug Repurposing Hub: a next-generation drug library and information resource   pp405 - 408
Steven M Corsello, Joshua A Bittker, Zihan Liu, Joshua Gould, Patrick McCarren et al.

News and Views


Autoimmune T cell recognition of alternative-reading-frame-encoded peptides   pp409 - 410
Jiajie Wei and Jonathan W Yewdell
A recent study shows that a self-peptide generated in pancreatic islet beta cells through the translation of a noncanonical alternative reading frame in human insulin mRNA is recognized by both CD4+ and CD8+ T cells in type 1 diabetes.

See also: Letter by Kracht et al.

A mouse recapitulating APOL1-associated kidney disease   pp411 - 412
Cheryl A Winkler and George W Nelson
In a recent study, researchers generated a mouse model expressing variant APOL1 that recapitulates human kidney disease. Variant APOL1 leads to caspase-1-dependent pyroptosis, which opens the door for the development of new druggable targets to treat APOL1-mediated kidney disease.

See also: Article by Beckerman et al.

Untangling the role of mutant histone H3 in diffuse intrinsic pontine glioma   pp413 - 414
Caretha L Creasy
New studies advance the mechanistic understanding of mutant histone H3 in diffuse intrinsic pontine glioma (DIPG) and demonstrate two epigenetic approaches, BET inhibition and EZH2 inhibition, as potential therapeutic strategies for DIPG.

See also: Article by Mohammad et al. | Letter by Piunti et al.

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Refining strategies to translate genome editing to the clinic   pp415 - 423
Tatjana I Cornu, Claudio Mussolino and Toni Cathomen
In this Review, Cathomen and colleagues present the latest advances, including improvements in nuclease specificity and delivery, that will expedite the clinical translation of genome editing.

Brief Communication


Glucocorticoid hormone-induced chromatin remodeling enhances human hematopoietic stem cell homing and engraftment   pp424 - 428
Bin Guo, Xinxin Huang, Scott Cooper and Hal E Broxmeyer
Glucocorticoid treatment of human cord blood hematopoietic stem cells increases expression of the receptor CXCR4 by chromatin remodeling, thereby enhancing hematopoietic stem cell homing and engraftment.

Poster on Molecular mechanisms of amyotrophic lateral sclerosis

This poster from Nature Reviews Neuroscience provides an overview of the molecular and cellular mechanisms that have been proposed to contribute to the pathogenesis of amyotrophic lateral sclerosis, which is the most common form of motor neuron disease. 

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Funded by a grant from MT Pharma America, Inc



Transgenic expression of human APOL1 risk variants in podocytes induces kidney disease in mice   pp429 - 438
Pazit Beckerman, Jing Bi-Karchin, Ae Seo Deok Park, Chengxiang Qiu, Patrick D Dummer et al.
Risk variants of APOL1 associated with human chronic kidney disease have been identified, but causality has been unclear. Transgenic expression in mice now shows that such alleles can indeed cause renal disease.

See also: News and Views by Winkler & Nelson

Targeting CASP8 and FADD-like apoptosis regulator ameliorates nonalcoholic steatohepatitis in mice and nonhuman primates   pp439 - 449
Pi-Xiao Wang, Yan-Xiao Ji, Xiao-Jing Zhang, Ling-Ping Zhao, Zhen-Zhen Yan et al.
Targeting CFLAR in mouse and non-human primates ameliorates non-alcoholic steatohepatitis by decreasing JNK signaling in hepatocytes.

Gpr124 is essential for blood-brain barrier integrity in central nervous system disease   pp450 - 460
Junlei Chang, Michael R Mancuso, Carolina Maier, Xibin Liang, Kanako Yuki et al.
The G-protein-coupled receptor GPR124, acting through the canonical Wnt pathway, is required for the maintenance of blood-brain barrier function in mouse models of stroke and glioblastoma.

A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress   pp461 - 471
Peter M Bruno, Yunpeng Liu, Ga Young Park, Junko Murai, Catherine E Koch et al.
Whereas cisplatin and carboplatin kill cancer cells by inducing DNA damage, another platinum derivative, oxaliplatin, induces cell death by triggering ribosome biogenesis stress.

Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia   pp472 - 482
Meenu Kesarwani, Zachary Kincaid, Ahmed Gomaa, Erika Huber, Sara Rohrabaugh et al.
The intrinsic resistance of BCR-ABL-expressing chronic myeloid leukemia stem cells to treatment with tyrosine-kinase inhibitors requires growth-factor signaling through the proteins c-Fos and DUSP1. Combined inhibition of BCR-ABL, c-Fos, and DUSP1 eradicated leukemia in vivo, pointing to a new therapeutic strategy for kinase-driven leukemias.

EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas   pp483 - 492
Faizaan Mohammad, Simon Weissmann, Benjamin Leblanc, Deo P Pandey, Jonas W Hojfeldt et al.
Although mutant H3K27M histones inhibit PRC2 in diffuse intrinsic pontine gliomas, these tumors exhibit significant amounts of PRC2 activity. The repression of several genes, including INK4A, by residual EZH2 activity is required for tumor growth, and EZH2 inhibitors therefore represent potential therapies for these patients.

See also: News and Views by Creasy | Letter by Piunti et al.



Therapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas   pp493 - 500
Andrea Piunti, Rintaro Hashizume, Marc A Morgan, Elizabeth T Bartom, Craig M Horbinski et al.
Nucleosomes containing mutant K27M histones in diffuse intrinsic pediatric gliomas (DIPG) exclude PRC2 binding and recruit BET bromodomain proteins; however, residual PRC2-dependent repression of specific loci, is required for DIPG oncogenesis. These results provide a rationale for targeting these epigenetic regulators in patients.

See also: News and Views by Creasy | Article by Mohammad et al.

Autoimmunity against a defective ribosomal insulin gene product in type 1 diabetes   pp501 - 507
Maria J L Kracht, Menno van Lummel, Tatjana Nikolic, Antoinette M Joosten, Sandra Laban et al.
Use of an alternative open reading frame, potentially as a result of cellular stress, drives production of an unconventional insulin epitope that is recognized by cytotoxic T cells from individuals with type 1 diabetes; these T cells kill beta cells in vitro.

See also: News and Views by Wei & Yewdell

Deficiency of the hepatokine selenoprotein P increases responsiveness to exercise in mice through upregulation of reactive oxygen species and AMP-activated protein kinase in muscle   pp508 - 516
Hirofumi Misu, Hiroaki Takayama, Yoshiro Saito, Yuichiro Mita, Akihiro Kikuchi et al.
Selenoprotein P is released from the liver and acts through LRP1 in the muscle to contribute to exercise resistance in mouse and man by inhibiting ROS levels via inhibition of AMPK and PGC-1α.



HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures   pp517 - 525
Helen Davies, Dominik Glodzik, Sandro Morganella, Lucy R Yates, Johan Staaf et al.
HRDetect represents a model integrating whole-genome sequencing mutation signatures associated with BRCA1 and BRCA2 deficiency. The implementation of this predictor across different tumor types identifies a larger proportion of patients displaying /`BRCAness/' than previously recognized; they might derive benefit from platinum and PARP-inhibitor therapies.



Corrigendum: Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure   p526
Stephanus T Malherbe, Shubhada Shenai, Katharina Ronacher, Andre G Loxton, Gregory Dolganov et al.



Erratum: Reply to “Neutrophils are not required for resolution of acute gouty arthritis in mice”   p526
Christiane Reinwald, Christine Schauer, Janka Zsofia Csepregi, Deborah Kienhofer, Daniela Weidner et al.

Erratum: PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer   p526
Fara Braso-Maristany, Simone Filosto, Steven Catchpole, Rebecca Marlow, Jelmar Quist et al.

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