Tuesday, June 6, 2017

Nature Medicine Contents: June 2017 Volume 23 Number 6 pp 645-788

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June 2017 Volume 23, Issue 6

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Source code: Putting metagenomics to the test in the clinic   pp645 - 648
Carrie Arnold

Biased for benefit: Stimulating the world's most popular drug targets with more nuance   pp649 - 651
Dyani Lewis

Viral vanguard: Designing cancer-killing viruses to chase metastatic tumors   pp652 - 655
Shraddha Chakradhar

News and Views


Understanding cancer from the stem cells up   pp656 - 657
Christopher A Eide and Brian J Druker
A new study that uses an integrated single-cell transcriptomics approach to characterize cancer stem cell populations during treatment with molecularly targeted therapies offers insights into disease evolution and points to new therapeutic targets.

See also: Article by Giustacchini et al.

A role for neutrophils in asthma exacerbations   pp658 - 659
William W Busse
A recent study has found that rhinovirus-induced exacerbation of asthma is in part mediated by the release of neutrophil extracellular traps and double-stranded DNA by neutrophils in the airway.

See also: Article by Toussaint et al.

Patrolling monocytes sense peripheral infection and induce cytokine-mediated neuronal dysfunction   pp659 - 661
Josef Priller and Chotima Bottcher
A new study reveals that virus-associated activation of a subset of circulating monocytes results in the release of the proinflammatory cytokine tumor necrosis factor (TNF)-α, which induces increased turnover of synapses in the brain and learning deficits in mice.

See also: Article by Garre et al.

The cannabis paradox: when age matters   pp661 - 662
Andres Ozaita and Ester Aso
New evidence in mouse models reveals that exposure to Δ9-tetrahydrocannabinol (THC), the main psychoactive component in Cannabis sativa, might improve cognitive performance in aging animals.

See also: Letter by Bilkei-Gorzo et al.

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Biology and evolution of poorly differentiated neuroendocrine tumors   pp1 - 10
David S Rickman, Himisha Beltran, Francesca Demichelis and Mark A Rubin
Rubin and colleagues discuss the origin and evolution of poorly differentiated neuroendocrine tumors, and highlight potential new therapeutic strategies.

Brief Communications


Metformin ameliorates core deficits in a mouse model of fragile X syndrome   pp674 - 677
Ilse Gantois, Arkady Khoutorsky, Jelena Popic, Argel Aguilar-Valles, Erika Freemantle et al.
Metformin treatment for 10 d rescues several behavioral deficits related to fragile X syndrome in adult Fmr1-/y mice.

Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer's disease   pp678 - 680
Alice D Lam, Gina Deck, Alica Goldman, Emad N Eskandar, Jeffrey Noebels et al.
Using intracranial electrode recordings in two individuals with Alzheimer's disease, Lam et al. discover hippocampal seizure activity that could not be detected by traditional EEG monitoring.

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Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation   pp681 - 691
Marie Toussaint, David J Jackson, Dawid Swieboda, Anabel Guedan, Theodora-Dorita Tsourouktsoglou et al.
Targeting NETosis alleviates type-2 immunopathology induced by rhinovirus infection in a mouse model of airway hypersensitivity, and correlative data suggest that a similar mechanism may operate in human rhinovirus-exacerbated asthma.

See also: News and Views by Busse

Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia   pp692 - 702
Alice Giustacchini, Supat Thongjuea, Nikolaos Barkas, Petter S Woll, Benjamin J Povinelli et al.
Applying a new, more sensitive single-cell transcriptomics method to diagnosis, remission and progression samples from patients with chronic myeloid leukemia reveals insight into the heterogeneity of cells that resist treatment with targeted therapy, as well as into the dynamics of disease progression and its effects on nontransformed hematopoietic stem cells.

See also: News and Views by Eide & Druker

Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients   pp703 - 713
Ahmet Zehir, Ryma Benayed, Ronak H Shah, Aijazuddin Syed, Sumit Middha et al.
MSK-IMPACT is a clinical sequencing platform able to detect genomic mutations, copy number alterations and structural variants in a panel of cancer-related genes. This assay is implemented prospectively to inform patient enrollment in genomically matched clinical trials at Memorial Sloan Kettering Cancer Center (MSKCC). Sequencing results of tumor and matched normal tissue from a cohort of >10,000 patients with detailed clinical annotation provide an overview of the genomic landscape of advanced solid cancers and bring new insights into molecularly guided cancer therapy.

CX3CR1+ monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-α   pp714 - 722
Juan Mauricio Garre, Hernandez Moura Silva, Juan J Lafaille and Guang Yang
In a rodent model of viral infection, immune activation causes impairments in motor-learning-dependent cortical synaptic remodeling that are mediated by peripheral monocytes rather than by CNS-resident microglia.

See also: News and Views by Priller & Bottcher

MAFB prevents excess inflammation after ischemic stroke by accelerating clearance of damage signals through MSR1   pp723 - 732
Takashi Shichita, Minako Ito, Rimpei Morita, Kyoko Komai, Yoshiko Noguchi et al.
The scavenger receptor MSR1 contributes to the clearance of damage-associated molecular patterns (DAMPs) by infiltrating myeloid cells in the post-stroke rodent brain. Myeloid cell MSR1 deficiency impairs clearance and exacerbates stroke-induced impairments, whereas a pharmacological intervention to boost MSR1 expression improves pathological and functional outcomes.

Pericytes impair capillary blood flow and motor function after chronic spinal cord injury   pp733 - 741
Yaqing Li, Ana M Lucas-Osma, Sophie Black, Mischa V Bandet, Marilee J Stephens et al.
In rat models of spinal cord injury, the region of the spinal cord below the site of injury becomes hypoxic owing to inadequate blood flow. This effect on blood flow is due to increased production of neurotransmitters known as /`trace amines,/' which act on pericytes to constrict blood vessels. Alleviation of hypoxia by hyperoxic breathing or inhibition of trace amine synthesis or action improves locomotor function in the injured rats.

Tmbim1 is a multivesicular body regulator that protects against non-alcoholic fatty liver disease in mice and monkeys by targeting the lysosomal degradation of Tlr4   pp742 - 752
Guang-Nian Zhao, Peng Zhang, Jun Gong, Xiao-Jing Zhang, Pi-Xiao Wang et al.
Toll-like receptor (TLR) 4 is a key mediator of non-alcoholic fatty liver disease progression. Targeting TLR4 degradation via the lysosome pathway improves outcome in mouse and monkey models of this condition.

Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction   pp753 - 762
Weier Qi, Hillary A Keenan, Qian Li, Atsushi Ishikado, Aimo Kannt et al.
Studying patients with long-term diabetes who lack diabetic nephropathy reveals that targeting pyruvate kinase M2 protects against renal disease.

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A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models   pp763 - 767
Chao Shan, Antonio E Muruato, Bruno T D Nunes, Huanle Luo, Xuping Xie et al.
Pei-Yong Shi and colleagues report that a deletion mutant of Zika virus is safe and effective as a live-attenuated vaccine in mice and induces sterilizing immunity. Their results encourage further testing of the candidate vaccine for possible future use in humans.

Decreased alertness due to sleep loss increases pain sensitivity in mice   pp768 - 774
Chloe Alexandre, Alban Latremoliere, Ashley Ferreira, Giulia Miracca, Mihoko Yamamoto et al.
In mice, sleep loss increases sensitivity to painful stimuli. Restoration of normal sleep or acute treatment with wake-promoting agents can normalize pain sensitivities.

Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment   pp775 - 781
Ok Hee Jeon, Chaekyu Kim, Remi-Martin Laberge, Marco Demaria, Sona Rathod et al.
Pharmacological or genetic depletion of senescent cells in the joint ameliorates osteoarthritis in mice.

A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice   pp782 - 787
Andras Bilkei-Gorzo, Onder Albayram, Astrid Draffehn, Kerstin Michel, Anastasia Piyanova et al.
In mice aged 12-18 months, chronic administration of low-dose Δ9-tetrahydrocannabinol (THC) improves performance in behavioral learning and memory tasks, whereas a similar administration in younger mice (aged 2 months) impairs performance.

See also: News and Views by Ozaita & Aso



Corrigendum: SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia   p788
Constanze Schneider, Thomas Oellerich, Hanna-Mari Baldauf, Sarah-Marie Schwarz, Dominique Thomas et al.



Erratum: PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer   p788
Fara Braso-Maristany, Simone Filosto, Steven Catchpole, Rebecca Marlow, Jelmar Quist et al.

Erratum: Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents   p788
Nicole E Burma, Robert P Bonin, Heather Leduc-Pessah, Corey Baimel, Zoe F Cairncross et al.

Erratum: Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease   p788
Nathaniel R West, Ahmed N Hegazy, Benjamin M J Owens, Samuel J Bullers, Bryan Linggi et al.

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