Friday, August 4, 2017

Nature Medicine Contents: August 2017 Volume 23 Number 8 pp 899-1004

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August 2017 Volume 23, Issue 8

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Lessons from reservoirs   p899



The epigenome editors: How tools such as CRISPR offer new details about epigenetics   pp900 - 903
Cassandra Willyard

The missing pieces: Lack of Zika data from Africa complicates search for answers   pp904 - 906
Nicole Wetsman

Breaking through: How researchers are gaining entry into barricaded bacteria   pp907 - 910
Shraddha Chakradhar

News and Views


Calculated risk: a new single-nucleotide polymorphism linked to severe influenza disease   pp911 - 912
Amie J Eisfeld and Yoshihiro Kawaoka
Clear links between human genes and susceptibility to influenza disease are scarce. A recent study uncovers a gene variant coupled to severe influenza, and shows how it hampers the expression of an antiviral gene that is key to immune cell survival.

See also: Article by Allen et al.

A three-drug combination to treat BRAF-mutant cancers   pp913 - 914
Ari J Firestone and Jeff Settleman
A new study that uses a triple-drug combination to overcome a major mechanism of drug resistance in cancer provides insights into the evolutionary paths taken by tumors in the face of selective pressure.

See also: Article by Xue et al.

Resolving a chronic inflammation mystery   pp914 - 916
Ben Roediger and Wolfgang Weninger
Using interleukin (IL)-9-deficient mice, Rauber and colleagues unveil a crucial role for group 2 innate lymphoid cells (ILC2s) in the resolution phase of arthritic inflammation, opening up new therapeutic avenues for chronic inflammatory disease.

See also: Article by Rauber et al.

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Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic   pp917 - 928
Benjamin Blasco, Didier Leroy and David A Fidock
In this Review, David Fidock discusses malarial resistance to artemisinin-based combination therapies, among others, and presents strategies for designing new therapeutics and to overcome resistance.

Nature Index: Melbourne Interactive Map 2017 

The Nature Index Melbourne interactive map enables you to explore the scientific job opportunities, collaborations and partnerships at the centre of Australia's life science and healthcare epicentre. Use the interactive map to benchmark the global reach of the Melbourne's key institutions and to view key connections at the heart of Melbourne's success.

Access the free Interactive Map



An approach to suppress the evolution of resistance in BRAFV600E-mutant cancer   pp929 - 937
Yaohua Xue, Luciano Martelotto, Timour Baslan, Alberto Vides, Martha Solomon et al.
Resistance to ERK signaling inhibitors in BRAFV600E-mutant melanomas and lung cancers is achieved by parallel convergent mechanisms, including amplification of the mutant allele in extrachromosomal elements, that allow tumors to adapt while maintaining their intratumor heterogeneity. Intermittent treatment with a combination of RAF, MEK and ERK inhibitors imposes a higher selective pressure than sequential therapy and produces the strongest antitumor effects while minimizing toxicity. These findings warrant evaluating the effectiveness of this combinatorial regimen in patients, to improve treatment responses and delay the emergence of drug resistance.

See also: News and Views by Firestone & Settleman

Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells   pp938 - 944
Simon Rauber, Markus Luber, Stefanie Weber, Lisa Maul, Alina Soare et al.
Number of IL-9-expressing ILC2s are elevated in patients with inflammatory arthritis during remission, and these cells are critical in mice for the resolution of inflammatory arthritis via regulatory T cell induction. Delivery of DNA minicircles encoding IL-9 into inflamed joints ameliorates mouse experimental arthritis, suggesting possible therapeutic applications.

See also: News and Views by Roediger & Weninger

A tripartite complex of suPAR, APOL1 risk variants and αvβ3 integrin on podocytes mediates chronic kidney disease   pp945 - 953
Salim S Hayek, Kwi Hye Koh, Morgan E Grams, Changli Wei, Yi-An Ko et al.
A complex of suPAR and high-risk variants of APOL1 acting on integrin signaling in the kidney contributes to APOL1-associated chronic kidney disease.

Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids   pp954 - 963
Fotios Sampaziotis, Alexander W Justin, Olivia C Tysoe, Stephen Sawiak, Edmund M Godfrey et al.
Repair of defects in the common bile duct is hampered by a lack of healthy donor tissue. Developing human extrahepatic cholangiocyte organoids and testing them in mouse models may provide a way to overcome this limitation.

Plk1 regulates contraction of postmitotic smooth muscle cells and is required for vascular homeostasis   pp964 - 974
Guillermo de Carcer, Paulina Wachowicz, Sara Martinez-Martinez, Jorge Oller, Nerea Mendez-Barbero et al.
The kinase Plk1 has been studied primarily as a mitotic regulator in dividing cells, but de Carcer et al. find that Plk1 deficiency or inhibition in mice causes nonmitotic defects in the vasculature, including aortic aneurysm and rupture, as well as defective vascular smooth muscle contractility. These results recommend a note of caution in the clinical use of PLK1 inhibitors as anticancer agents.

SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans   pp975 - 983
E Kaitlynn Allen, Adrienne G Randolph, Tushar Bhangale, Pranay Dogra, Maikke Ohlson et al.
IFITM3 encodes an antiviral protein that blocks entry of influenza A virus into cells. Paul Thomas and colleagues report that SNP rs34481144 in the 5′ UTR of IFITM3 is an expression quantitative trait locus for this gene and that the risk allele is associated with lower IFITM3 expression and severe influenza disease.

See also: News and Views by Eisfeld & Kawaoka

Scientific rigour and reproducibility 

Science progresses by standing on the shoulders of giants, to paraphrase Newton. But what if those shoulders aren't steady? Read about how to assess and improve the reliability of biomedical research. 

Access this Collection of articles free online

Produced with support from: 
Gilson & sciNote



Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism   pp984 - 989
Dwi U Kemaladewi, Eleonora Maino, Elzbieta Hyatt, Huayun Hou, Maylynn Ding et al.
An HDR-independent therapeutic genome-editing approach corrected the splice-site mutation in Lama2 in a mouse model of congenital muscular dystrophy type 1A, and may be applied more broadly to correct splice-site mutations associated with other diseases.

Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice   pp990 - 996
Berengere Benoit, Emmanuelle Meugnier, Martina Castelli, Stephanie Chanon, Aurelie Vieille-Marchiset et al.
FGF19 acts directly on skeletal muscle to increase its mass, and treatment with the hormone ameliorates muscle atrophy in three mouse models.

Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus   pp997 - 1003
Jason K Karimy, Jinwei Zhang, David B Kurland, Brianna Carusillo Theriault, Daniel Duran et al.
In a rat model of hydrocephalus triggered by intraventricular hemorrhage, Kristopher Kahle and colleagues show that TLR4-NF-κB-dependent inflammatory signaling in the choroid plexus causes hypersecretion of cerebrospinal fluid that drives hydrocephalus. Targeting TLR4-NF-κB-mediated signaling or the NKCC1-SPAK complex ameliorates hydrocephalus.



Corrigendum: Analysis of self-antigen specificity of islet-infiltrating T cells from human donors with type 1 diabetes   p1004
Jenny Aurielle B Babon, Megan E DeNicola, David M Blodgett, Inne Crevecoeur, Thomas S Buttrick et al.

Corrigendum: Is autoimmunity the Achilles' heel of cancer immunotherapy?   p1004
Carl H June, Jeremy T Warshauer and Jeffrey A Bluestone



Erratum: Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients   p1004
Ahmet Zehir, Ryma Benayed, Ronak H Shah, Aijazuddin Syed, Sumit Middha et al.

Leukemia: Collection on Acute Myeloid Leukemia

AML is an area of focus for Leukemia and this collection brings together a number of recent key articles published in the journal. 

Access this collection free online for six months

Funded by a grant from Astex Pharmaceuticals, Inc.
(a member of the Otsuka group)
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