Featured
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| Open AccessTherapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma
Neural stem cells have a tropism for glioblastoma. Here the authors employ fibroblasts directly reprogrammed into induced neural stem cells and loaded with cytotoxic molecules to migrate to xenotransplanted brain tumours in mice, achieving tumour shrinkage and prolonged survival.
- Juli R. Bagó
- , Adolfo Alfonso-Pecchio
- & Shawn D. Hingtgen
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Article
| Open AccessOctanol-assisted liposome assembly on chip
A broad application of liposomes calls for high throughout techniques to produce them in a controlled and fast manner. Here, Deshpande et al. show a microfluidic approach using alcohol-based lipid-carrying material to generate monodisperse and unilamellar liposomes within a just few minutes.
- Siddharth Deshpande
- , Yaron Caspi
- & Cees Dekker
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Article
| Open AccessAutonomous beating rate adaptation in human stem cell-derived cardiomyocytes
The use of stem cell-derived cardiomyocytes for heart repair is hampered by their immature structural and contractile properties that may cause arrhythmia. Here, Eng et al.show that electrical conditioning of human cardiomyocytes in 3D culture can enhance connectivity and provide resistance to arrhythmia.
- George Eng
- , Benjamin W. Lee
- & Gordana Vunjak-Novakovic
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Article
| Open AccessCell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects
A challenge in regenerative medicine is the development of cell-free, non-immunogenic miRNA-delivering scaffolds. Here the authors design a cell-free scaffold capable of efficient and prolonged delivery of miRNA-26a to endogenous cells and show that it can regenerate a full-thickness calvarial bone defect in mice.
- Xiaojin Zhang
- , Yan Li
- & Peter X. Ma
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Article
| Open AccessTwo-dimensional honeycomb network through sequence-controlled self-assembly of oligopeptides
Peptide nanostructures are currently arousing interest thanks to their potential applications in medicine, electronics and coatings. Here, through experiment and theory, the authors demonstrate exquisite control over surface peptide assembly behaviour through manipulation of amino acid sequence.
- Sabine Abb
- , Ludger Harnau
- & Klaus Kern
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Article
| Open AccessMulti-reporter selection for the design of active and more specific zinc-finger nucleases for genome editing
Zinc finger nucleases have an established role in genome editing. Here, the authors report a strategy for identifying zinc finger nucleases that discriminate between desired targets and provide genome-wide specificity.
- Benjamin L. Oakes
- , Danny F. Xia
- & Marcus B. Noyes
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Article
| Open AccessA microfluidic platform enabling single-cell RNA-seq of multigenerational lineages
Existing single-cell RNA-seq methods provide the transcriptome of a cellular phenotype at a single time point. Here, Kimmerlinget al. present a microfluidic platform that enables off-chip single-cell RNA-seq after multigenerational lineage tracking under controlled culture conditions.
- Robert J. Kimmerling
- , Gregory Lee Szeto
- & Scott R. Manalis
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Article
| Open AccessLarge-scale inference of protein tissue origin in gram-positive sepsis plasma using quantitative targeted proteomics
Sepsis can lead to multiple organ failure that could potentially be reflected by change in plasma protein abundance. Here the authors describe a proteomics strategy that allows the determination of plasma proteins tissue origin in a quantitative manner for use as biomarkers—illustrated in a mouse model of sepsis.
- Erik Malmström
- , Ola Kilsgård
- & Johan Malmström
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Article
| Open AccessProteomic maps of breast cancer subtypes
Breast cancers have been extensively studied at the genomic and transcriptomic levels in the hope of tailoring therapeutic regimens. Here the authors generate deep coverage proteomes from several clinical breast cancer samples, and use machine learning techniques to uncover biological processes altered in specific cancer subtypes.
- Stefka Tyanova
- , Reidar Albrechtsen
- & Tamar Geiger
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Article
| Open AccessRational engineering of a mesohalophilic carbonic anhydrase to an extreme halotolerant biocatalyst
Halophilic organisms thrive in high salt conditions and express proteins that display desirable characteristics for industrial applications. Here, the authors use a rational design approach to transform wild-type carbonic anhydrase into a strongly halophilic enzyme.
- Andrew C. Warden
- , Michelle Williams
- & Victoria S. Haritos
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Article
| Open AccessAbasic pivot substitution harnesses target specificity of RNA interference
RNA interference inadvertently represses off-target transcripts. Here, Lee et al.report that substituting nucleotide in position 6 of the seed region of the small interfering RNAs with abasic spacers can significantly decrease miRNA-like off-target repression while preserving on-target activity.
- Hye-Sook Lee
- , Heeyoung Seok
- & Sung Wook Chi
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Article
| Open AccessEfficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase
Cyclotides are plant backbone-cyclised peptides with potential as pharmaceutical scaffolds. Here the authors report on the efficient backbone cyclization of cyclotides and unrelated peptides by a newly identified asparaginyl endopeptidase from Oldenlandia affinis.
- Karen S. Harris
- , Thomas Durek
- & Marilyn A. Anderson
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Article
| Open AccessSepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy
Sepsis patients often develop muscle atrophy that can last for years. Here the authors show in a mouse model that sepsis causes long-term impairment of the satellite cells, affecting mitochondrial function and energy metabolism, and that injection of mesenchymal stem cells restores satellite cell metabolism and muscle regeneration.
- P. Rocheteau
- , L. Chatre
- & F. Chrétien
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Article
| Open AccessHybrid integrated biological–solid-state system powered with adenosine triphosphate
There is enormous potential in combining the capabilities of the biological and the solid-state to create hybrid engineered systems. Here, the authors develop a technique to incorporate and activate ATPases in in vitromembranes to produce energy-harvestable currents to power an integrated circuit.
- Jared M. Roseman
- , Jianxun Lin
- & Kenneth L. Shepard
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Article
| Open AccessUltrahigh-throughput discovery of promiscuous enzymes by picodroplet functional metagenomics
Environmental DNA from unculturable microorganisms contains genes with useful functions that remain difficult to identify and isolate. Here Colin, Kintses et al.demonstrate the screening of millions of samples in pL volumes to directly identify new enzymatic activities and complements sequence-based approaches.
- Pierre-Yves Colin
- , Balint Kintses
- & Florian Hollfelder
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Article
| Open AccessA biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of theranostic agents
Nanoparticles have the potential for enhancing drug delivery; however, low drug encapsulation efficiency and drug loading content limit their application. Here, the authors engineer a complex nanostructure for drug delivery in cancer treatment and evaluate it in different conditions with encouraging results.
- Hai Wang
- , Pranay Agarwal
- & Xiaoming He
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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 AccessRescue of neonatal cardiac dysfunction in mice by administration of cardiac progenitor cells in utero
The protein Speg is expressed in the developing mouse heart, where its absence leads to neonatal cardiac disease. Here the authors trace the cardiomyopathy of Speg KO mice back to defects in cardiac progenitor cells (CPCs) and rescue it with injections of wild type CPCs into the foetal heart.
- Xiaoli Liu
- , Sean R. R. Hall
- & Mark A. Perrella
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Article
| Open AccessScalable amplification of strand subsets from chip-synthesized oligonucleotide libraries
Synthetic oligonucleotides are the main cost factor for studies in DNA nanotechnology. Here, the authors present a selective oligonucleotide amplification method, based on three rounds of rolling-circle amplification, that produces nanomole amounts of single-stranded oligonucleotides per millilitre reaction.
- Thorsten L. Schmidt
- , Brian J. Beliveau
- & William M. Shih
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| Open AccessPropagation of oestrogen receptor-positive and oestrogen-responsive normal human breast cells in culture
Culturing normal primary breast cells that express the oestrogen receptor is difficult. Here, the authors isolate oestrogen receptor positive normal breast cells using the cell surface markers CD166 and CD117, and show that the cultures can be repeatedly passaged and retain oestrogen receptor protein expression.
- Agla J. Fridriksdottir
- , Jiyoung Kim
- & Lone Rønnov-Jessen
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Article |
Targeted drug delivery using genetically engineered diatom biosilica
Transgenic diatom algae can incorporate proteins in their silica shells. Here the authors design diatoms that can be decorated with tumour-specific antibody of choice and use them as natural nanoparticles for targeted delivery of a chemotherapeutic drug, impeding mouse xenograft tumour growth.
- Bahman Delalat
- , Vonda C. Sheppard
- & Nicolas H. Voelcker
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Article
| Open AccessIdentification of DNA lesions using a third base pair for amplification and nanopore sequencing
Genomic DNA lesions exist in low levels and cannot be amplified by standard PCR. Here, Riedlet al. report a method to amplify damaged DNA sites by replacing them via DNA repair with unnatural base pairs, which are subsequently identified by Sanger sequencing or α-hemolysin nanopore sequencing.
- Jan Riedl
- , Yun Ding
- & Cynthia J. Burrows
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Article
| Open AccessEngineering intracellular biomineralization and biosensing by a magnetic protein
Magnetic manipulation of biological systems requires the development of improved molecular handles. Here the authors isolate ferritin mutants with enhanced biomineralization from a yeast genetic screen and show their application to cell separation, multiscale imaging, and construction of sensors.
- Yuri Matsumoto
- , Ritchie Chen
- & Alan Jasanoff
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Article
| Open AccessResident c-kit+ cells in the heart are not cardiac stem cells
The issue whether the cell surface protein c-kit identifies resident cardiac stem cells (CSC) is controversial. By using novel reporter mouse models, Sultana et al. show that c-kit+cells represent a subpopulation of endothelial cells in the developing and adult heart and do not exhibit CSC traits in health or disease.
- Nishat Sultana
- , Lu Zhang
- & Chen-Leng Cai
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Article
| Open AccessThe γ-tubulin-specific inhibitor gatastatin reveals temporal requirements of microtubule nucleation during the cell cycle
Current microtubule inhibitors target α/β-tubulin, but no specific inhibitor of γ-tubulin has been developed. Here the authors present gatastatin as a γ-tubulin inhibitor and use it to probe the role of γ-tubulin during the cell cycle.
- Takumi Chinen
- , Peng Liu
- & Elmar Schiebel
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Article
| Open AccessTumour-associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug
Drug-loaded nanoparticles allow controlled release and enhanced delivery, yet understanding in vivobehavior has been difficult. Here, the authors develop a platinum prodrug coupled to a polymer platform, and use intravital imaging to show that the nanoparticle accumulates in macrophages, from the which drug redistributes to neighboring tumour cells.
- Miles A. Miller
- , Yao-Rong Zheng
- & Ralph Weissleder
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Article
| Open AccessMulti-level engineering facilitates the production of phenylpropanoid compounds in tomato
Metabolic engineering offers an effective strategy for producing valuable bioactive compounds in plants. Here, the authors show that by harnessing transcriptional regulation of carbon flux, tomato fruit metabolism can be optimized for the production of phenylpropanoids.
- Yang Zhang
- , Eugenio Butelli
- & Cathie Martin
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Article
| Open AccessModelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids
Generating organized kidney tissues from human pluripotent stem cell is a major challenge. Here, Freedman et al. describe a differentiation system forming spheroids and tubular structures, characteristic of these kidney structures, and using CRISPR/Cas9, delete PKD1/2, to model polycystic kidney disease.
- Benjamin S. Freedman
- , Craig R. Brooks
- & Joseph V. Bonventre
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Article
| Open AccessRibozyme-enhanced single-stranded Ago2-processed interfering RNA triggers efficient gene silencing with fewer off-target effects
Short hairpin RNAs are widely used to produce small interfering RNAs (siRNAs) for gene silencing. Here, the authors show that an alternative siRNA precursor in the presence of a self-cleaving ribozyme has enhanced silencing activity and reduced off-target effects, providing a potential RNAi tool.
- Renfu Shang
- , Fengjuan Zhang
- & Ligang Wu
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Article
| Open AccessNano-guided cell networks as conveyors of molecular communication
Living cells have to interpret and react to changes in local environmental conditions. Here the authors exploit that by combining magnetic nanoparticles and bacterial quorum sensing to investigate and convey alterations in the molecular landscape.
- Jessica L. Terrell
- , Hsuan-Chen Wu
- & William E. Bentley
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Article
| Open AccessDevelopment of potent in vivo mutagenesis plasmids with broad mutational spectra
Random DNA mutagenesis provides genetic diversity both in nature and the laboratory. Here, Badran and Liu present a potent, inducible, broad-spectrum and vector-based mutagenesis system in E. coli that surpasses the mutational efficiency and spectra of the most widely used in vivo and in vitromutagenesis methods.
- Ahmed H. Badran
- & David R. Liu
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Article
| Open AccessExpanding the biotechnology potential of lactobacilli through comparative genomics of 213 strains and associated genera
Lactobacillus is a lactic acid bacteria and has a wide range of application from use in probiotic food production to biotherapeutics. Here, the authors sequence and compare the genomes of 213 different Lactobacillusstrains and related genera, and provide new insight into phylogenomic organization and adaptive immunity elements in this bacteria family.
- Zhihong Sun
- , Hugh M. B. Harris
- & Paul W. O’Toole
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Article
| Open AccessRedox-switch regulatory mechanism of thiolase from Clostridium acetobutylicum
n-Butanol is a valuable biofuel that can be produced industrially by bacterial fermentation. Here the authors uncover a redox-switch within Clostridium acetobutylicum’s thiolase—a key enzyme involved in n-butanol biosynthesis—that controls the rate of fermentative butanol production.
- Sangwoo Kim
- , Yu-Sin Jang
- & Kyung-Jin Kim
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Article
| Open AccessDe novo assembly and next-generation sequencing to analyse full-length gene variants from codon-barcoded libraries
This paper described a new and efficient method for de novoassembly of multiple DNA sequence information from mutagenized clone libraries. Using codon-barcoded libraries and calling the method JigsawSeq, the authors overcome limitations of short-read sequencing assembly from next-generation sequencing.
- Namjin Cho
- , Byungjin Hwang
- & Duhee Bang
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Article
| Open AccessThe Lingula genome provides insights into brachiopod evolution and the origin of phosphate biomineralization
Lingulid brachiopods possess calcium phosphate shells. Here, the authors sequence the genome of Lingula anatine to show that Lingula is evolutionary close to molluscs, but distant from annelids, and identify the genomic background of Lingula’sunique biomineralization mechanism.
- Yi-Jyun Luo
- , Takeshi Takeuchi
- & Noriyuki Satoh
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Article
| Open AccessdNP2 is a blood–brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis
Most of the cell penetrating peptides can transport therapeutic agents across plasma membranes but barely across the blood-brain barrier. Here the authors develop a peptide that can enter the brain, and show that its fusion to immunomodulatory protein ctCTLA-4 is effective in a mouse model of multiple sclerosis.
- Sangho Lim
- , Won-Ju Kim
- & Je-Min Choi
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Article
| Open AccessSonogenetics is a non-invasive approach to activating neurons in Caenorhabditis elegans
Common optogenetic approaches require surgical procedures to deliver light of specific wavelengths to the target cells. Here the authors demonstrate the use of low-pressure ultrasound as a non-invasive trigger to activate specific neurons in Caenorhabditis elegansand find that the mechanotransduction channel TRP-4 sensitizes cells to the ultrasound stimulus.
- Stuart Ibsen
- , Ada Tong
- & Sreekanth H. Chalasani
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Article
| Open AccessNano-socketed nickel particles with enhanced coking resistance grown in situ by redox exsolution
Metal particles supported on oxide surfaces are widely used catalysts, and the composites are generally formed by deposition or exsolution methods. Here, the authors show that nickel particles exsolved from the parent perovskite exhibit enhanced stability due to a stronger metal–oxide interface.
- Dragos Neagu
- , Tae-Sik Oh
- & John T.S. Irvine
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Article
| Open AccessA synthetic hydrogel for the high-throughput study of cell–ECM interactions
Multiple extracellular matrix parameters influence cellular behaviour, but it is difficult to dissect their cooperative contributions. Here the authors describe a hydrogel system in which ligand density and substrate stiffness can be tuned orthogonally to study the contribution of combinations of these parameters simultaneously.
- Andrew D. Rape
- , Mikhail Zibinsky
- & Sanjay Kumar
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Article
| Open AccessThe interactions between a small molecule and G-quadruplexes are visualized by fluorescence lifetime imaging microscopy
Guanine-rich oligonucleotides can fold into secondary structures known as G-quadruplexes that are proposed to have various biological roles. Here, Shivalingam et al. develop a cell-permeable, low-toxicity probe that can be used to probe interactions between G-quadruplexes and small molecules in vivo.
- Arun Shivalingam
- , M. Angeles Izquierdo
- & Ramon Vilar
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Article
| Open AccessA flexible codon in genomically recoded Escherichia coli permits programmable protein phosphorylation
The effects of protein phosphorylation, a common post-translational modification, are difficult to study using recombinant proteins. Here the authors use genomically engineered E. colito enhance translation systems that express phosphor-serine containing proteins, and use these systems to produce phosphorylated MEK1 kinase.
- Natasha L. Pirman
- , Karl W. Barber
- & Jesse Rinehart
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Article
| Open AccessSliding tethered ligands add topological interactions to the toolbox of ligand–receptor design
Biological adhesion is mediated by specific lock and key interactions between ligand receptor pairs. Here Bauer et al.engineer tethered ligands for which spacers can slide at the anchoring point to produce versatile bio-adhesive substrates.
- Martin Bauer
- , Patrick Kékicheff
- & Carlos M. Marques
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Article
| Open AccessModular pathway rewiring of Saccharomyces cerevisiae enables high-level production of L-ornithine
The complexity of yeast amino acid metabolism has limited carbon channelling to produce valuable chemical metabolites. Here, the authors implement a yeast customized pathway optimization strategy and demonstrate its use for overproduction of L-ornithine, an intermediate of L-arginine biosynthesis.
- Jiufu Qin
- , Yongjin J. Zhou
- & Jens Nielsen
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Article |
In vivo capture and label-free detection of early metastatic cells
Tumour metastasis is a significant source of mortality, often because it is detected at an advanced stage. In this study, in an effort to identify metastasis at an early stage, Azarin et. al. capture and image metastasizing cells in mice in vivousing a biomaterial scaffold.
- Samira M. Azarin
- , Ji Yi
- & Lonnie D Shea
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Article
| Open AccessA highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism
Respiratory syncytial virus (RSV) is a highly contagious childhood pathogen of the respiratory tract for which no vaccine is currently available. Here the authors present a strategy to stabilize the RSV F protein in a prefusion conformation that can elicit a strong protective immune response in animal models.
- Anders Krarup
- , Daphné Truan
- & Johannes P. M. Langedijk
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Article
| Open AccessCas9-Assisted Targeting of CHromosome segments CATCH enables one-step targeted cloning of large gene clusters
Genomic engineering often requires the cloning of long DNA segments that contain large gene clusters. Here, the authors describe an RNA-guided Cas9 nuclease assistedin vitrotechnique that allows the targeted cloning of near-arbitrary, long bacterial genomic sequences of up to 100 kb in a single step.
- Wenjun Jiang
- , Xuejin Zhao
- & Ting F. Zhu
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Article
| Open AccessDirecting cell therapy to anatomic target sites in vivo with magnetic resonance targeting
Cell therapy requires the targeting of cells to specific sites in the body. Here Muthana et al.use a standard MRI scanner to direct oncolytic macrophages, labelled with magnetic nanoparticles, to primary and metastatic tumour sites in mice, and demonstrate that this leads to reduced tumour growth.
- Munitta Muthana
- , Aneurin J. Kennerley
- & Claire Lewis
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Article |
Injectable cryogel-based whole-cell cancer vaccines
Immune responses are induced in the organized, cytokine-rich environment of lymph nodes, which can be mimicked by biomaterials. Here the authors show that injectable sponge-like gels decorated with immunostimulatory factors attract dendritic cells and boost antitumour immune responses in mice.
- Sidi A. Bencherif
- , R. Warren Sands
- & David J. Mooney
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Article
| Open AccessResolving bundled microtubules using anti-tubulin nanobodies
Super-resolution imaging of microtubules requires labels that increase their apparent diameter, making it difficult to resolve individual microtubules within a bundle. Here, the authors develop single-chain antibody fragments against tubulin that enable closely spaced individual microtubules to be distinguished in cells.
- Marina Mikhaylova
- , Bas M. C. Cloin
- & Lukas C Kapitein
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