Tuesday, March 7, 2017

Nature Medicine Contents: March 2017 Volume 23 Number 3 pp 265-395

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Nature Medicine

The Vilcek Foundation congratulates the recipients of the 2017 Vilcek Prizes in Biomedical Science.

Lily & Yuh-Nung Jan (University of California, San Francisco) receive $100,000 Vilcek Prize.
Michaela Gack (University of Chicago),
Michael Halassa (NYU School of Medicine),
and Ahmet Yildiz (University of California, Berkeley)
each win $50,000 Vilcek Prize for Creative Promise in Biomedical Science. 

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March 2017 Volume 23, Issue 3

News and Views
Brief Communication
Technical Report

Nature Milestones: Antibodies

Nature Milestones: Antibodies chronicles the history of antibodies from their earliest description in antisera, their structure, generation and function, right through to their recent application in cancer immunotherapy. It also includes a timeline and a collection of seminal papers reproduced from Springer Nature. 

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Circulating Tumour Cells: Liquid biopsy by high-throughput, high-resolution imaging flow cytometry

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Focus on Psychiatric Disorders

Compared to other areas, psychiatric research faces unique biological, technological, clinical, regulatory and ethical challenges.

In this focus Nature Neuroscience and Nature Medicine present a collection of Commentaries, Perspectives, and Reviews that address these challenges.

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Custom webcast on: Analyzing Ebola virus glycoprotein and its interactions with therapeutic antibodies using CG-MALS
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Take science off the stand   p265
The scientific process relies on people's willingness to publish data-driven findings. Turning to the legal system to adjudicate the merit of evidence-based assertions in the scientific literature leads us down a dangerous path.



A protein puzzle   pp266 - 269
Shraddha Chakradhar
Untangling the mysterious condition of amyloidosis

Womb zoom: What advances in fetal and newborn imaging have revealed   pp270 - 271
Wudan Yan



Correction   p269

News and Views


Opioids: keeping the good, eliminating the bad   pp272 - 273
Stephanie Puig and Howard B Gutstein
Two new studies show that mechanisms mediating the opioid side effects of tolerance, hyperalgesia and physical dependence are mediated spinally and can be dissociated from analgesia. These side effects can be selectively targeted by clinically available drugs without affecting their pain-relieving effects.

See also: Letter by Burma et al.

The shape of the microbiome in early life   pp274 - 275
Erika von Mutius
A recent study shows that microbial-community structure and function substantially expand and diversify in all body sites from birth to age 4-6 weeks. It then resembles microbiota from its corresponding maternal body site, independently of the infant's mode of delivery or other prenatal factors.

See also: Article by Chu et al.

Taking inventory of metastasis effectors   pp275 - 276
Laura Pisarsky, Jinxiang Dai and Cyrus M Ghajar
In a recent study in mice, researchers combined tumor barcoding with unbiased genomic analysis and identified Cd109 as a hub gene involved in metastatic progression. They show that pharmacological inhibition of its downstream effectors JAK1 and STAT3 curtails metastatic growth.

See also: Article by Chuang et al.

α5 nicotinic receptors link smoking to schizophrenia   pp277 - 278
Xin-an Liu and Paul J Kenny
A new study shows that nicotinic receptors activate a particular type of interneuron in the prefrontal cortex. Deficits in this relationship give rise to behavioral abnormalities similar to those associated with schizophrenia, which can be ameliorated by nicotine.

See also: Letter by Koukouli et al.



An emerging role for neutrophil extracellular traps in noninfectious disease   pp279 - 287
Selina K Jorch and Paul Kubes
Kubes and Fassl discuss the role of NETosis in sterile inflammation and disease, and propose windows of opportunity for therapeutic targeting of NETs.

Brief Communication


α-Lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria   pp288 - 290
Tiffany Zee, Neelanjan Bose, Jarcy Zee, Jennifer N Beck, See Yang et al.
Excess urinary cystine can lead to painful stone formation. There is no current effective treatment, but here Pankaj Kapahi, Marshall Stoller and colleagues have found that α-lipoic acid can prevent or even reverse formation of these stones in a mouse model.

Animation: Alzheimer's disease 

Nature Neuroscience presents this animation, which introduces the molecular, cellular and physiological mechanisms associated with Alzheimer's disease and highlights some of the most recent advances in our understanding of the onset and progression of this devastating neurological condition.

Watch the Animation free online >>



Molecular definition of a metastatic lung cancer state reveals a targetable CD109-Janus kinase-Stat axis   pp291 - 300
Chen-Hua Chuang, Peyton G Greenside, Zoe N Rogers, Jennifer J Brady, Dian Yang et al.
In vivo screening of pro-metastatic factors in a genetically engineered mouse model of lung cancer uncovered the CD109-JAK-STAT3 axis as a key contributor of metastatic dissemination of lung cancer cells. Activation of this pathway predicts poor outcome in patients with cancer, and its pharmacological inhibition dramatically reduces the metastatic ability of tumor cells, suggesting that it might be an effective intervention in patients.

See also: News and Views by Pisarsky et al.

The creatine kinase pathway is a metabolic vulnerability in EVI1-positive acute myeloid leukemia   pp301 - 313
Nina Fenouille, Christopher F Bassil, Issam Ben-Sahra, Lina Benajiba, Gabriela Alexe et al.
Transcriptomic and metabolic profiling reveals that the creatine kinase pathway is essential for growth of acute myeloid leukemias expressing the transcription factor EVI1.

Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery   pp314 - 326
Derrick M Chu, Jun Ma, Amanda L Prince, Kathleen M Antony, Maxim D Seferovic et al.
Whole-genome shotgun sequencing and sequencing of the gene encoding the 16S rRNA in samples from a variety of body sites in a large cohort of mothers and their infants reveals that, during the 6 weeks after birth, changes in the composition and function of the microbiome are driven by body site but not by the mode of delivery.

See also: News and Views by von Mutius

Targeting mitochondrial dysfunction can restore antiviral activity of exhausted HBV-specific CD8 T cells in chronic hepatitis B   pp327 - 336
Paola Fisicaro, Valeria Barili, Barbara Montanini, Greta Acerbi, Manuela Ferracin et al.
Carlo Ferrari and colleagues reveal that hepatitis B virus (HBV) specific CD8 T cells from individuals with chronic HBV infections have extensive mitochondrial dysfunction that contributes to impaired antiviral activity but can be targeted with antioxidants.

JNK1 negatively controls antifungal innate immunity by suppressing CD23 expression   pp337 - 346
Xueqiang Zhao, Yahui Guo, Changying Jiang, Qing Chang, Shilei Zhang et al.
Xin Lin and colleagues report that JNK1 negatively regulates immune responses against Candida albicans infection by inhibiting CD23 expression and subsequent nitric oxide production, which mediate antifungal resistance in JNK1-deficient mice.



Nicotine reverses hypofrontality in animal models of addiction and schizophrenia   pp347 - 354
Fani Koukouli, Marie Rooy, Dimitrios Tziotis, Kurt A Sailor, Heidi C O'Neill et al.
In transgenic mouse models of neuropsychiatric disease, loss of nicotinic cholinergic signaling in cortical inhibitory interneurons causes neurocognitive behavioral deficits and reduced neuronal activity in prefrontal circuits. Chronic administration of nicotine can restore this cortical hypofrontality phenotype.

See also: News and Views by Liu & Kenny

Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents   pp355 - 360
Nicole E Burma, Robert P Bonin, Heather Leduc-Pessah, Corey Baimel, Zoe F Cairncross et al.
The release of ATP from spinal microglia via pannexin-1 channels is required for withdrawal symptoms after termination of chronic opioid treatment in rodents, and pharmacological blockade of pannexin-1 channels reduces the severity of withdrawal without affecting opiate analgesia.

See also: News and Views by Puig & Gutstein

Sirtuin 1 regulates cardiac electrical activity by deacetylating the cardiac sodium channel   pp361 - 367
Ajit Vikram, Christopher M Lewarchik, Jin-Young Yoon, Asma Naqvi, Santosh Kumar et al.
Intracellular trafficking of the voltage-gated cardiac Na+ channel Nav1.5 is regulated by lysine deacetylation mediated by Sirt1, thereby affecting sodium current and cardiac electrical activity.

A distinct innate lymphoid cell population regulates tumor-associated T cells   pp368 - 375
Sarah Q Crome, Linh T Nguyen, Sandra Lopez-Verges, S Y Cindy Yang, Bernard Martin et al.
A previously uncharacterized population of innate lymphoid cells (ILCs) in the tumor microenvironment limits T cell expansion and cytokine production, and associates with early recurrence in patients with cancer. Depletion of this regulatory immunosuppressive cell population overcomes this effect, suggesting important implications for cancer immunotherapy.

Technical Report


Whole-genome single-cell copy number profiling from formalin-fixed paraffin-embedded samples   pp376 - 385
Luciano G Martelotto, Timour Baslan, Jude Kendall, Felipe C Geyer, Kathleen A Burke et al.
A method enabling copy-number analysis of single cells from formalin-fixed paraffin-embedded samples is described, validated and applied to analyze samples of synchronous ductal carcinoma in situ and invasive breast carcinoma.



DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma   pp386 - 395
Nathan C Sheffield, Gaelle Pierron, Johanna Klughammer, Paul Datlinger, Andreas Schonegger et al.
DNA methylation sequencing and bioinformatic analyses uncover an epigenetic disease spectrum in Ewing sarcoma. These characteristic epigenome patterns correlate with state of differentiation and disease aggressiveness, and pave the way for the development of biomarkers.

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