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Patterned prevascularised tissue constructs by assembly of polyelectrolyte hydrogel fibres
Tissue engineering relies on the vascular compatibility of the synthesised constructs with target tissues. Here, the authors fabricate a prevascularised tissue construct of cell-laden hydrogel fibres as a framework that allows the formation of vascularised adipose and hepatic tissues.
- Meng Fatt Leong
- , Jerry K. C. Toh
- & Jackie Y. Ying
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Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells
Artificial heart tissue may find application in novel therapies of cardiac disease in the future. Here, Lu et al. take a step towards the creation of personalized heart tissue by repopulating decellularized mouse hearts with cells derived from human induced pluripotent stem cells.
- Tung-Ying Lu
- , Bo Lin
- & Lei Yang
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Immunologic and chemical targeting of the tight-junction protein Claudin-6 eliminates tumorigenic human pluripotent stem cells
The potential tumorigenicity of human pluripotent stem cells (hPSCs) limits their application in cell therapies. Ben-David et al.identify the tight-junction protein Claudin-6 as a cell-surface marker of hPSCs, and demonstrate three Claudin-6-based strategies to remove tumorigenic hPSCs from mixed cell cultures.
- Uri Ben-David
- , Neta Nudel
- & Nissim Benvenisty
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InVERT molding for scalable control of tissue microarchitecture
Artificially engineered tissues may be useful for regenerative therapies but their fabrication tends to be complicated. Stevens et al. present a technique for the precise organization of microstructurally complex tissues that works with a variety of cell types and does not require sophisticated equipment.
- K. R. Stevens
- , M. D. Ungrin
- & S. N. Bhatia
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G-quadruplex structures are stable and detectable in human genomic DNA
Guanine-rich DNA can form four-stranded structures called G-quadruplexes, which are thought to influence DNA replication, transcription and repair; their stability and prevalence in the genome is in need of further elucidation. Here the authors employ an antibody-based approach to sensitively map G-quadruplexes in the genome.
- Enid Yi Ni Lam
- , Dario Beraldi
- & Shankar Balasubramanian
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Identifying sources of tick blood meals using unidentified tandem mass spectral libraries
The identification of hosts of blood-sucking insects is important for studying ecological factors that affect pathogen distribution. Önder et al. report a proteomics-based methodology for the analysis of blood remnants in ticks that identifies the host species from which the tick has fed up to 6 months earlier.
- Özlem Önder
- , Wenguang Shao
- & Dustin Brisson
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| Open AccessArginine clustering on calix[4]arene macrocycles for improved cell penetration and DNA delivery
Arginine-rich peptides act as delivery systems for the internalization of cargoes in cells. Here, the clustering of arginine units in a parallel array on a macrocyclic scaffold produces a vector with high efficiency in DNA delivery and transfection.
- Valentina Bagnacani
- , Valentina Franceschi
- & Rocco Ungaro
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Three-dimensional shape transformations of hydrogel sheets induced by small-scale modulation of internal stresses
The complex shapes of biological tissues are often formed as a result of stress modulations. Wu et al.exploit such behaviour experimentally and theoretically to demonstrate a new mechanism of the formation of three-dimensional structures that is driven by engineered small-scale stresses within patterned hydrogel sheets.
- Zi Liang Wu
- , Michael Moshe
- & Eugenia Kumacheva
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Engineering the type III secretion system in non-replicating bacterial minicells for antigen delivery
Bacterial type III secretion systems (T3SS) improve the delivery of vaccine antigens and antigen-specific immune responses but require the use of live vaccines. Carleton et al. report the assembly of a functional T3SS in replication-incompetent bacterial minicells that can deliver vaccine antigens in vitro and in vivo.
- Heather A. Carleton
- , María Lara-Tejero
- & Jorge E. Galán
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Tet-mediated covalent labelling of 5-methylcytosine for its genome-wide detection and sequencing
A number of methylome sequencing technologies depend on affinity purification of methylated DNA. Zhang et al. demonstrate a click-chemistry-based protocol for covalently labelling 5-methylcytosine residues with biotin, providing enhanced sensitivity and specificity compared with antibody-based enrichment.
- Liang Zhang
- , Keith E. Szulwach
- & Chuan He
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Perceiving invisible light through a somatosensory cortical prosthesis
Primary sensory areas of newborn mammals typically display input-dependent plasticity. Thomson and colleagues use a sensory prosthetic device in rats to show that adult rats can discriminate different infrared light signals, when the signals are routed to somatosensory cortex by electrical microstimulation.
- Eric E. Thomson
- , Rafael Carra
- & Miguel A.L. Nicolelis
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Transferring a synthetic gene circuit from yeast to mammalian cells
Gene circuits created by synthetic biologists working in one system may not be functional when transferred to a different organism. Using computational modelling to identify factors underlying such differences, the authors successfully adapt a yeast ‘linearizer’ circuit so that it functions in mammalian cells.
- Dmitry Nevozhay
- , Tomasz Zal
- & Gábor Balázsi
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Synthetic RNA devices to expedite the evolution of metabolite-producing microbes
Genome-wide variation in the directed evolution of metabolite-overproducing microbes requires high-throughput screening platforms. Yang et al.show that synthetic RNA devices can sense target metabolites, enrich pathway optimisation, and expedite the evolution of metabolite-producing microbes.
- Jina Yang
- , Sang Woo Seo
- & Gyoo Yeol Jung
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Article
| Open AccessIn vitro fabrication of functional three-dimensional tissues with perfusable blood vessels
Artificially engineered tissues may have many therapeutic applications but complex tissues are hard to create in vitro. Here, Okano and colleagues report the production of functional cardiac tissue sheets with perfusable blood vessels, which increase the thickness and survival of transplanted tissue.
- Hidekazu Sekine
- , Tatsuya Shimizu
- & Teruo Okano
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A platform pathway for production of 3-hydroxyacids provides a biosynthetic route to 3-hydroxy-γ-butyrolactone
3-hydroxy-γ-butyrolactone (3HBL) is a building block for many valuable drugs and is synthesized via a costly industrial process. Martin et al. engineer a novel biosynthetic pathway for the inexpensive production of 3HBL and other 3-hydroxyacids in E. coli.
- Collin H. Martin
- , Himanshu Dhamankar
- & Kristala L.J. Prather
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Modular optimization of multi-gene pathways for fatty acids production in E. coli
Microbial fatty acid-derived fuels represent promising alternatives to the traditionally used fossil fuels. Koffas and colleagues report that E. colicentral metabolism can be modified to produce large quantities of fatty acids through a modular pathway engineering strategy.
- Peng Xu
- , Qin Gu
- & Mattheos A.G. Koffas
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Monitoring and robust induction of nephrogenic intermediate mesoderm from human pluripotent stem cells
Stem cells have raised hopes of developing regenerative therapies of renal disease. Here, Osafune et al.provide a protocol for the differentiation of induced human pluripotent stem cells into renal lineages with the capacity to form tubular renal structures in mice.
- Shin-Ichi Mae
- , Akemi Shono
- & Kenji Osafune
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| Open AccessA visible dominant marker for insect transgenesis
Genetic modification in insects mostly involves the use of fluorescent markers to identify successful transformation. Here Osanai-Futahashi et al.report a marker system based on changes in melanin pigmentation that allows the identification of genetically modified insects with the naked eye.
- Mizuko Osanai-Futahashi
- , Takahiro Ohde
- & Hideki Sezutsu
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Delivery of chemotherapeutic drugs in tumour cell-derived microparticles
Microparticles are small vesicular structures that are shed from cellular plasma membranes. Tang and colleagues show that cells treated with chemotherapeutic drugs produce drug-containing microparticles, which can be used as anticancer agents in mice.
- Ke Tang
- , Yi Zhang
- & Bo Huang
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| Open AccessA multi-omic map of the lipid-producing yeast Rhodosporidium toruloides
The ability of oleaginous fungi to produce lipids for biofuels remains untapped, in part due to a lack of genetic information required to engineer industrial strains. Zhuet al. present the genome of R. toruloides, and identify transcriptomic and proteomic changes associated with lipid production.
- Zhiwei Zhu
- , Sufang Zhang
- & Zongbao K. Zhao
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Production of α-L-iduronidase in maize for the potential treatment of a human lysosomal storage disease
The lysosomal storage disease mucopolysaccharidosis I is treated with recombinant α-L-iduronidase but production of the enzyme is expensive. In this study, α-L-iduronidase is compartmentalized within the endosperm of maize via a unique mRNA strategy yielding the active, correctly glycosylated protein.
- Xu He
- , Thomas Haselhorst
- & Allison R. Kermode
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Biocompatibility of a genetically encoded calcium indicator in a transgenic mouse model
Calcium-sensing fluorescent proteins such as TN-XXL are valuable tools for studying cellular function but, when expressed in mice, may affect animal physiology and behaviour. The authors of this paper create transgenic mice expressing TN-XXL and show that long-term expression of TN-XXL is tolerated well.
- Stephan Direnberger
- , Marsilius Mues
- & Oliver Griesbeck
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| Open AccessGenome sequence of the model medicinal mushroom Ganoderma lucidum
Ganoderma lucidumis a macrofungus in traditional Chinese medicine known to produce different bioactive compounds. In this study, the genome ofG. lucidumis sequenced, making this organism a potential model system for future studies of secondary metabolic pathways and their regulation in medicinal fungi.
- Shilin Chen
- , Jiang Xu
- & Chao Sun
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| Open AccessActivin induces cortical interneuron identity and differentiation in embryonic stem cell-derived telencephalic neural precursors
Signalling inputs to neural progenitors regulate the differentiation of the stem cell pool. By analysing the mechanisms occuring during neurogenesis, Cambrayet al. report that activin is the pivotal factor regulating the differentiation of telencephalic neural precursors towards a cortical interneuron fate.
- Serafí Cambray
- , Charles Arber
- & Tristan A. Rodríguez
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| Open AccessFully functional hair follicle regeneration through the rearrangement of stem cells and their niches
Bioengineered hair follicles can be produced from embryonic follicle germ cells, but whether these follicles can interact with the surrounding tissue and function normally is unknown. Here, bioengineered hair follicles transplanted into mouse dermis make connections with the surrounding tissue and show normal hair cycles.
- Koh-ei Toyoshima
- , Kyosuke Asakawa
- & Takashi Tsuji
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Graphene-based wireless bacteria detection on tooth enamel
Graphene is characterized by unique physical properties that offer substantial promise, most notably for electronic applications. Mannooret al. present a wireless graphene-based sensor for detecting bacteria on a range of biological tissues.
- Manu S. Mannoor
- , Hu Tao
- & Michael C. McAlpine
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Fast and ultrasensitive method for quantitating prion infectivity titre
Bioassays are the standard way to measure prion infectivity titres, but can be time-consuming. In this study, bioassays are compared with a modified version of the protein misfolding cyclic amplification technique with beads (PMCAb), demonstrating that PMCAb can be more precise and faster than bioassays.
- Natallia Makarava
- , Regina Savtchenko
- & Ilia V. Baskakov
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| Open AccessDraft genome sequence and genetic transformation of the oleaginous alga Nannochloropsis gaditana
Algae show much promise in the production of biofuels owing to their high photoautotrophic biomass and lipid production rates. In this study, the draft genome ofNannochloropsis gaditanaCCMP526 and a method for the transformation of this alga are reported, facilitating the investigation of lipid synthesis and biofuel production.
- Randor Radakovits
- , Robert E. Jinkerson
- & Matthew C. Posewitz
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Inhibition of specific gene expressions by protein-mediated mRNA interference
RNA can be silenced in a sequence-specific manner but whether proteins can silence RNA in this way is unknown. Now, Yamaguchi and colleagues show that an enzyme isolated fromHaloquadra walsbyi cleaves 7-base-pair sequences in Escherichia coli, and this high sequence specificity permits the silencing of targeted genes.
- Yoshihiro Yamaguchi
- , Hirofumi Nariya
- & Masayori Inouye
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| Open AccessMuscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model
The function of adult stem cells is diminished with age but the role this dysfunction plays in the aging process is unknown. Here, the injection of muscle-derived stem/progenitor cells from young mice rescues symptoms in progeroid mice and is shown to regenerate tissues independent of engraftment.
- Mitra Lavasani
- , Andria R. Robinson
- & Johnny Huard
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A role for T-bet-mediated tumour immune surveillance in anti-IL-17A treatment of lung cancer
The tumour microenvironment is often found to be immunosuppressive. Reppert and colleagues show that human and murine lung tumours harbour IL-17A-producing T cells, and that blocking IL-17A increases survival in mice, suggesting that anti-IL-17A therapy may be useful in treating lung cancer.
- S. Reppert
- , I. Boross
- & S. Finotto
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| Open AccessCompetition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential
The half-life of IgG is regulated by binding to the neonatal Fc receptor and, in the case of IgG3, is reduced compared to other IgG proteins. In this study, a mutation in IgG3 is shown to reduce binding to the neonatal Fc receptor, which can be competitively blocked by IgG1.
- Nigel M. Stapleton
- , Jan Terje Andersen
- & Gestur Vidarsson
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Low-concentration mechanical biosensor based on a photonic crystal nanowire array
Nanomechanical resonators are attractive as ultra-low concentration sensors of biomolecules, as their small scale allows for sensitive mass detection. Here, using a nanowire array as part of a photonic crystal, such a device is presented for light trapping, absorption and low-concentration sensing.
- Yuerui Lu
- , Songming Peng
- & Amit Lal
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Functionalized arrays of Raman-enhancing nanoparticles for capture and culture-free analysis of bacteria in human blood
Detecting bacteria in clinical samples usually requires culture processes that are time consuming and impede rapid diagnoses. Now, a surface-enhanced Raman spectroscopic method is reported that allows the label- and culture-free detection and analysis of bacteria.
- Ting-Yu Liu
- , Kun-Tong Tsai
- & Yuh-Lin Wang
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| Open AccessEngineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology
Biological digital sensors require the fabrication of modular genetic logic gates. Using thePseudomonas syringae hrpsystem, Wang and colleagues generate AND, NOT and NAND gates, demonstrating the ability to engineer a modular system from biological elements.
- Baojun Wang
- , Richard I Kitney
- & Martin Buck
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| Open AccessIdentification and microbial production of a terpene-based advanced biofuel
Advanced biofuels with comparable properties to petroleum-based fuels could be microbially produced from lignocellulosic biomass. In this study,Escherichia coliis engineered to produce bisabolene, the immediate precursor of bisabolane, a biosynthetic alternative to D2 diesel.
- Pamela P. Peralta-Yahya
- , Mario Ouellet
- & Taek Soon Lee
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Plasmonic substrates for multiplexed protein microarrays with femtomolar sensitivity and broad dynamic range
Protein microarrays are useful both in basic research and also in disease monitoring and diagnosis, but their dynamic range is limited. By using plasmonic gold substrates with near-infrared fluorescent enhancement, Tabakman et al. demonstrate a multiplexed protein array with improved detection limits and dynamic range.
- Scott M. Tabakman
- , Lana Lau
- & Hongjie Dai
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| Open AccessA bacterial platform for fermentative production of plant alkaloids
Secondary metabolites are widely used in human health and nutrition, but extraction yields from plants are often low. Nakagawaet al. have engineered the metabolism of Escherichia colito develop a fermentation system that produces plant alkaloids from simple carbon sources.
- Akira Nakagawa
- , Hiromichi Minami
- & Hidehiko Kumagai
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| Open AccessComparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis
The conservation of embryonic development across species is of great interest in evolutionary biology. Here, using transcriptome analysis, the authors show that the pharyngula stage of development—in mid-embryogenesis—is conserved between mice, chickens, frogs and zebrafish.
- Naoki Irie
- & Shigeru Kuratani
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An optimized small molecule inhibitor cocktail supports long-term maintenance of human embryonic stem cells
Stem cell-mediated regenerative medicine requires the development of defined culture systems for the maintenance of human embryonic stem cells. Here, feedback system control is used to identify a combination of three small molecule inhibitors that enables long-term human embryonic stem cell maintenance.
- Hideaki Tsutsui
- , Bahram Valamehr
- & Hong Wu
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| Open AccessSynthetic human cell fate regulation by protein-driven RNA switches
The control of cell fate and apoptosis is a continuing challenge in synthetic biology. In this study, systems are developed in which an intracellularly expressed genome-encoded protein simultaneously achieves up- and downregulation of two distinct apoptosis pathways.
- Hirohide Saito
- , Yoshihiko Fujita
- & Tan Inoue
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Integrated multilaboratory systems biology reveals differences in protein metabolism between two reference yeast strains
The integration of microarray and metabolite data is important for understanding the physiology of model organisms. This study demonstrates how the integration of these kinds of data can provide novel insights into the growth and protein metabolism of two different yeast strains.
- André B. Canelas
- , Nicola Harrison
- & Jens Nielsen
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High rates of photobiological H2 production by a cyanobacterium under aerobic conditions
Hydrogen production using photosynthetic bacteria is an appealing energy source, but typically the bacteria require anaerobic conditions. Here, the authors report a wild-type cyanobacterium strain that shows very high rates of hydrogen production under aerobic environmental conditions.
- Anindita Bandyopadhyay
- , Jana Stöckel
- & Himadri B. Pakrasi
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A plasmid-based multigene expression system for mammalian cells
Fluorescent proteins are widely used in molecular biology to visualize protein expression and localization. Here, Krizet al. describe an efficient and flexible modular plasmid-based eukaryotic expression cloning strategy for the homogeneous expression of several fluorescent proteins in one cell.
- Andrijana Kriz
- , Katharina Schmid
- & Philipp Berger
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Protein-binding assays in biological liquids using microscale thermophoresis
Protein interactions in biological environments are expected to differ from the situationin vitro. In this study, a thermophoresis-based technique is described that allows the analysis of protein and small-molecule interactions in biological liquids; the work may allow more efficient drug development.
- Christoph J. Wienken
- , Philipp Baaske
- & Stefan Duhr
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Non-muscle myosin II regulates survival threshold of pluripotent stem cells
When cultured as single cells, embryonic stem cells have low viability. Here, blebbistatin, a non-muscle myosin II inhibitor, is shown to enhance the cloning efficiency, viability and adhesion of both human embryonic stem cells and human induced pluripotent stem cellsin vitro.
- Andrea Walker
- , Hua Su
- & Noboru Sato
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Motion-based DNA detection using catalytic nanomotors
Synthetic nanomotors convert chemical energy into motion. Here, they have been implemented in a motion-based assay that allows specific DNA and ribosomal RNA detection. The technique is fast, simple and sensitive, and the concentration-dependant distance signals of the magnetically aligned nanomotors are detected by optical microscopy.
- Jie Wu
- , Shankar Balasubramanian
- & Joseph Wang
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Viscoelastic solids explain spider web stickiness
Spider silk adhesion is reliant on sticky droplets composed of glycoproteins surrounded by an aqueous coat. Sahni and co-workers show that these droplets behave as viscoelastic solids that enable large, rate-dependent adhesive forces capable of trapping fast- and slow-moving prey.
- Vasav Sahni
- , Todd A. Blackledge
- & Ali Dhinojwala
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