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| Open AccessCyclic microchip assay for measurement of hundreds of functional proteins in single neurons
Current single-cell tools are limited by the number of proteins they can analyse. Here the authors report a single-cell cyclic multiplex in situ tagging (CycMIST) method for functional proteome profiling of single cells, allowing multiple rounds of multiplexing of the same single cells on a microchip.
- Liwei Yang
- , Avery Ball
- & Jun Wang
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Article
| Open AccessNeuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein in C. elegans
Mitochondrial deficiency causes rare incurable disorders. Here, the authors use C. elegans to study these diseases and find that the natural compound lutein prevents neurodevelopmental deficits, thus pointing to a possible therapeutic target for the human diseases.
- Silvia Maglioni
- , Alfonso Schiavi
- & Natascia Ventura
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Article
| Open AccessProtective effect of platinum nano-antioxidant and nitric oxide against hepatic ischemia-reperfusion injury
Pharmacological interventions against hepatic ischemia-reperfusion injury remain limited. Here, the authors provide a nanotherapeutics-based solution combining reactive oxygen species scavenging and nitric oxide modulation.
- Jing Mu
- , Chunxiao Li
- & Xiaoyuan Chen
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Article
| Open AccessMultidimensional chromatin profiling of zebrafish pancreas to uncover and investigate disease-relevant enhancers
Alterations in cis-regulatory elements (CREs) can contribute to pancreatic diseases. Here the authors combine chromatin profiling and interaction points with in vivo reporter assays in zebrafish to uncover functionally equivalent human CREs, helping to predict disease-relevant enhancers.
- Renata Bordeira-Carriço
- , Joana Teixeira
- & José Bessa
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Article
| Open AccessEngineered osteoclasts as living treatment materials for heterotopic ossification therapy
Heterotopic ossification (HO) is the formation of pathological mature bone within extraskeletal soft tissues, and there are currently no reliable methods for removing these calcified plaques. Here, the authors demonstrate that chemically engineered osteoclasts coated with tetracycline can improve their targeting capacity to ectopic calcifications, which extends their bone resorption functions for the treatment of HO.
- Wenjing Jin
- , Xianfeng Lin
- & Ruikang Tang
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Article
| Open AccessClub cell-specific role of programmed cell death 5 in pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is a fatal adult lung disease. Here the authors investigate the functional significance of PDCD5 in club cells as a mediator of lung fibrosis and potential therapeutic target for IPF.
- Soo-Yeon Park
- , Jung Yeon Hong
- & Ho-Geun Yoon
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Article
| Open AccessDeletion of CTCF sites in the SHH locus alters enhancer–promoter interactions and leads to acheiropodia
Acheiropodia is associated with homozygous deletions in the LMBR1 gene around ZRS, an enhancer regulating SHH during limb development, but how these deletions lead to this phenotype is unknown. Here the authors use whole-genome sequencing, ChIP-seq, 4C-seq and DNA FISH to show that alterations in CTCF motifs are responsible via altered enhancer–promoter interactions.
- Aki Ushiki
- , Yichi Zhang
- & Nadav Ahituv
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Article
| Open AccessAge-related and disease locus-specific mechanisms contribute to early remodelling of chromatin structure in Huntington’s disease mice
The dynamics of chromatin and transcriptional changes underlying Huntington’s disease remain poorly understood. Here the authors use a Huntington’s mouse model to profile the striatal chromatin landscape, finding that the Huntington’s mutation accelerates age-dependent epigenetic and transcriptional changes, and locally affects 3D chromatin organization.
- Rafael Alcalá-Vida
- , Jonathan Seguin
- & Karine Merienne
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Comment
| Open AccessEmerging preclinical evidence does not support broad use of hydroxychloroquine in COVID-19 patients
There is an urgent need for drugs, therapies and vaccines to be available to protect the human population against COVID-19. One of the first approaches taken in the COVID-19 global response was to consider repurposing licensed drugs. This commentary highlights an extraordinary international collaborative effort of independent researchers who have recently all come to the same conclusion—that chloroquine or hydroxchloroquine are unlikely to provide clinical benefit against COVID-19.
- S. G. P. Funnell
- , W. E. Dowling
- & C. M. Coleman
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Article
| Open AccessBrain leptin reduces liver lipids by increasing hepatic triglyceride secretion and lowering lipogenesis
Obesity is associated with leptin resistance and rising blood leptin levels while central leptin exposure may be limited. Here, the authors show that brain leptin infusion reduces hepatic lipid content in rats by increasing hepatic VLDL secretion and lowering liver de novo lipogenesis via a vagal mechanism.
- Martina Theresa Hackl
- , Clemens Fürnsinn
- & Thomas Scherer
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Article
| Open AccessFactors other than hTau overexpression that contribute to tauopathy-like phenotype in rTg4510 mice
The rTg4510 mosue line has a tauopathy-like phenotype which is attributed to overexpression of human tau in the frontal cortex. Here the authors identify potential confounding genetic factors that could contribute to the phenotype.
- Julia Gamache
- , Kellie Benzow
- & Michael D. Koob
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Article
| Open AccessHIV-1 vaccination by needle-free oral injection induces strong mucosal immunity and protects against SHIV challenge
Oral vaccination is a potential option to elicit systemic and mucosal immunity against HIV. Here, Jones et al. show that oral vaccination with a modified needle-free injector induces protective immunity against SHIV in non-human primates and is superior to topical application of vaccines to oral tissues.
- Andrew T. Jones
- , Xiaoying Shen
- & Rama Rao Amara
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| Open AccessPrevention of SIVmac251 reservoir seeding in rhesus monkeys by early antiretroviral therapy
The latent HIV-1 reservoir is the key obstacle for curing HIV-1 infection, but the timepoint at which the HIV-1 reservoir is established is currently unclear. Here, Whitney et al. show in non-human primates that the SIV reservoir in CD4+ T cells is seeded within the first 2 days after infection.
- James B. Whitney
- , So-Yon Lim
- & Dan H. Barouch
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| Open AccessEvidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation
Allogeneic hematopoietic cell transplantation (allo-HCT) has led to the cure of HIV in one individual, but the underlying mechanisms are unclear. Here, the authors present a model of allo-HCT in SHIV-infected nonhuman primates and show that the SHIV reservoir persists in multiple tissues early after transplantation.
- Lucrezia Colonna
- , Christopher W. Peterson
- & Leslie S. Kean
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Article
| Open AccessChemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction
Excessive production of reactive oxygen species (ROS) is associated with cardiac dysfunction, but the causal role of ROS remains poorly understood. Here the authors use an in vivo chemogenetic approach to develop a heart failure model in which generation of hydrogen peroxide in the heart leads to systolic heart failure without fibrotic remodeling.
- Benjamin Steinhorn
- , Andrea Sorrentino
- & Thomas Michel
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| Open AccessIntraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease
Zika virus infection of pregnant women can cause congenital brain defects. Here, Coffey et al. establish a pregnant rhesus macaque model, using intravenous and intraamniotic route of infection, that reliably reproduces fetal neurologic defects of congenital Zika syndrome in humans.
- Lark L. Coffey
- , Rebekah I. Keesler
- & Koen K. A. Van Rompay
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| Open AccessEfficacy of a respiratory syncytial virus vaccine candidate in a maternal immunization model
RSV infection is a major cause of bronchiolitis in infants and maternal vaccination is a potential preventive option. Here, Blanco et al. show efficacy of a Newcastle disease virus-based virus-like particle vaccine candidate in naive and pre-exposed cotton rat dams and their offspring.
- Jorge C. G. Blanco
- , Lioubov M. Pletneva
- & Trudy G. Morrison
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| Open AccessBioluminescence imaging of G protein-coupled receptor activation in living mice
G protein-coupled receptors are involved in numerous physiological functions, thus, they represent potential pharmaceutical targets. Here Kono et al. describe a new mouse model to image GPCR activation in real-time by exploiting firefly split luciferase fragment complementation that can be detected by bioluminescence imaging.
- Mari Kono
- , Elizabeth G. Conlon
- & Richard L. Proia
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| Open AccessThe comparative immunology of wild and laboratory mice, Mus musculus domesticus
Laboratory mice are the cornerstone of immunology but how well they represent wild mice is not clear. Here the authors compare and contrast various immune parameters between wild-caught mice and laboratory (C57BL/6) mice and identify a previously unknown myeloid cell population specific to wild mice.
- Stephen Abolins
- , Elizabeth C. King
- & Eleanor M. Riley
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Article
| Open AccessHyperactivation of Nrf2 in early tubular development induces nephrogenic diabetes insipidus
Nrf2 regulates oxidative and electrophilic stress responses by modulating the expression of enzymes involved in detoxification pathways. Here Suzukiet al. show that Nrf2 activation in early tubular development promotes nephrogenic diabetes insipidus by regulating aquaporin 2 expression and trafficking and water permeability.
- Takafumi Suzuki
- , Shiori Seki
- & Masayuki Yamamoto
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| Open AccessA rhesus macaque model of Asian-lineage Zika virus infection
Animal models of infection with Zika virus (ZIKV) are urgently needed for a better understanding of pathogenesis and for testing potential therapies. Here, the authors describe infection of rhesus macaques with an Asian-lineage ZIKV strain as a relevant animal model for studying ZIKV pathogenesis.
- Dawn M. Dudley
- , Matthew T. Aliota
- & David H. O’Connor
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Article
| Open AccessAntibody-based PET imaging of amyloid beta in mouse models of Alzheimer’s disease
Imaging tools for evaluating progression of Alzheimer’s disease have been lacking. Here the authors develop a blood brain barrier-permeable Aß probe based on a radiolabelled, anti-Aß antibody, and report age-dependent brain uptake visualized in vivo with PET in mouse models of the disease.
- Dag Sehlin
- , Xiaotian T. Fang
- & Stina Syvänen
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Article
| Open AccessENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy
Generalized arterial calcification of infancy (GACI) is a terminal disease caused by the ENPP1 enzyme deficiency. Here, Albrigh et al. show that ENPP1 enzyme replacement therapy prevents the ectopic calcifications and mortality in mice with GACI, suggesting a novel treatment for vascular calcification in humans.
- Ronald A. Albright
- , Paul Stabach
- & Demetrios T. Braddock
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Article
| Open AccessPlasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice
Mice engrafted with human cells are useful models for research on human malaria parasites. Here the authors show that the complete life cycle of Plasmodium falciparum and the liver stages of Plasmodium ovalecan be studied in mice doubly engrafted with human primary hepatocytes and red blood cells.
- Valérie Soulard
- , Henriette Bosson-Vanga
- & Dominique Mazier
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| Open AccessStereomicroscopic 3D-pattern profiling of murine and human intestinal inflammation reveals unique structural phenotypes
The gut epithelium is damaged in inflammatory bowel disease, but capturing such lesions by histology can be difficult. Here, the authors use stereomicroscopy to visualize different 3D inflammatory structures and associated microbes in humans and in 16 genetic mouse models relevant to intestinal inflammation.
- Alex Rodriguez-Palacios
- , Tomohiro Kodani
- & Fabio Cominelli
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| Open AccessImpaired protein translation in Drosophila models for Charcot–Marie–Tooth neuropathy caused by mutant tRNA synthetases
Charcot–Marie–Tooth (CMT) neuropathy is associated with dominant mutations in five tRNA synthetase genes. Niehues et al. use BONCAT and FUNCAT to monitor proteome dynamics in a DrosophilaCMT model, and reveal that these mutations result in translational slowdown.
- Sven Niehues
- , Julia Bussmann
- & Erik Storkebaum
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Housing temperature-induced stress drives therapeutic resistance in murine tumour models through β2-adrenergic receptor activation
Anticancer treatments are tested in mice housed below thermoneutrality which represents chronic cold-stress. Here Eng et al. show that these mice have activated stress responses leading to therapeutic resistance and that inhibiting adrenergic signaling increases efficacy of anticancer therapies.
- Jason W.-L. Eng
- , Chelsey B. Reed
- & Bonnie L. Hylander