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| Open AccessEpigenetically reprogrammed methylation landscape drives the DNA self-assembly and serves as a universal cancer biomarker
DNA methylation is an epigenetic modification that control genetic programs. Here, the authors found that the methylation landscape influences the physicochemical properties of DNA and that it can serve as a universal cancer biomarker, and developed a one-step assay for the detection of cancer DNA.
- Abu Ali Ibn Sina
- , Laura G. Carrascosa
- & Matt Trau
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Article
| Open AccessHemocyanin facilitates lignocellulose digestion by wood-boring marine crustaceans
Marine woodborers can digest woody biomass without the help of gut microbiota but the mechanism has remained unclear. Here, the authors provide evidence that the woodborer’s respiratory protein hemocyanin plays a central role in wood digestion and may offer a route toward biorefining of woody plant biomass.
- Katrin Besser
- , Graham P. Malyon
- & Simon J. McQueen-Mason
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Article
| Open AccessBioreactor-based mass production of human iPSC-derived macrophages enables immunotherapies against bacterial airway infections
Pulmonary infections constitute a substantial health problem worldwide. Here the authors show that phagocytes similar to primitive macrophages can be generated from human induced pluripotent stem cells, by the use of industry-compatible, stirred-tank bioreactors, and applied as a cell-based therapy to treat acute bacterial infections in mice.
- Mania Ackermann
- , Henning Kempf
- & Nico Lachmann
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Article
| Open AccessBiocatalytic production of adiponitrile and related aliphatic linear α,ω-dinitriles
Typically, preparation of the polymer precursors α,ω-dinitriles requires hydrogen cyanide. Here, the authors use aldoxime hydratase to produce adiponitrile and related aliphatic linear dinitriles under ambient conditions starting from readily available substrates without needing hydrogen cyanide.
- Tobias Betke
- , Manuel Maier
- & Harald Gröger
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Article
| Open AccessEngineering Saccharomyces cerevisiae for co-utilization of d-galacturonic acid and d-glucose from citrus peel waste
Pectin-rich agricultural byproducts are ideal feedstocks for biobased chemicals production. Here, the authors engineer the yeast, S. cerevisiae, in several steps to co-utilize d-galacturonic acid and d-glucose and demonstrate the potential of producing meso-galactaric acid from industrial orange peel.
- Ryan J. Protzko
- , Luke N. Latimer
- & John E. Dueber
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Article
| Open AccessA synthetic microbial biosensor for high-throughput screening of lactam biocatalysts
Efficient biosynthesis of lactams is still undesirable due to lacking of suitable enzyme. Here, the authors develop a sensitive transcription factor-based biosensor for high-throughput screening of marine metagenome and find a cyclase that can cyclize ω-amino fatty acids to lactam.
- Soo-Jin Yeom
- , Moonjeong Kim
- & Seung-Goo Lee
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Article
| Open AccessA scalable peptide-GPCR language for engineering multicellular communication
A bottleneck to engineered multicellular systems is the lack of a scalable signalling language. Here the authors use fungal mating peptide and GPCR pairs to build functional cell-to-cell communication links.
- Sonja Billerbeck
- , James Brisbois
- & Virginia W. Cornish
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Article
| Open AccessA CRISPR–Cas9-triggered strand displacement amplification method for ultrasensitive DNA detection
Isothermal DNA amplification techniques are useful for diagnostic applications in place of traditional PCR. Here the authors describe CRISDA, which combines CRISPR–Cas9 with strand displacement amplification and exhibits attomolar sensitivity and single-nucleotide specificity in DNA detection.
- Wenhua Zhou
- , Li Hu
- & Xue-Feng Yu
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Article
| Open AccessLocally anchoring enzymes to tissues via extracellular glycan recognition
The use of enzymes as drugs requires that they persist within target tissues over therapeutically relevant time frames. Here the authors use a galectin-3 fusion to anchor enzymes at injection sites for up to 14 days.
- Shaheen A. Farhadi
- , Evelyn Bracho-Sanchez
- & Gregory A. Hudalla
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Article
| Open AccessEncryption and steganography of synthetic gene circuits
Artificial gene circuits represent intellectual property that under some circumstances may need to be obfuscated to prevent discovery by third parties. Here the authors use encryption by overlapping recombinase sites and steganography by the introduction of superfluous components, to obscure circuit topology.
- Oliver Purcell
- , Jerry Wang
- & Timothy K. Lu
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Article
| Open AccessMetabolic engineering of Escherichia coli for de novo biosynthesis of vitamin B12
Vitamin B12 is an essential nutrient with limited natural sources. Here the authors transfer 28 pathway synthesis genes from several bacteria including R. capsulatus to E. coli and, using metabolic engineering and optimised fermentation conditions, achieve high yields.
- Huan Fang
- , Dong Li
- & Dawei Zhang
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Article
| Open AccessOrthogonal Cas9–Cas9 chimeras provide a versatile platform for genome editing
Therapeutic genome engineering relies on the development of reliable, robust and versatile tools. Here the authors develop Cas9-Cas9 chimeras with high target site activity that generate predictable deletions.
- Mehmet Fatih Bolukbasi
- , Pengpeng Liu
- & Scot A. Wolfe
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Article
| Open AccessSynthetic RNA-based logic computation in mammalian cells
The construction of complex RNA-delivered genetic circuits in mammalian cells is challenging, though offers advantages over DNA circuits in clinical use. Here the authors construct a set of logic gates that respond to multiple miRNAs and demonstrate an apoptosis-regulatory AND gate.
- Satoshi Matsuura
- , Hiroki Ono
- & Hirohide Saito
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Article
| Open AccessOver 1000-fold enhancement of upconversion luminescence using water-dispersible metal-insulator-metal nanostructures
Upconversion nanoparticles are already used in bio-imaging but still suffer from low luminescence. Here, metal-insulator-metal nanostructures with 1-2 orders magnitude enhancement in upconversion are introduced enabling bioimaging at reduced particle or excitation power densities, respectively.
- Ananda Das
- , Chenchen Mao
- & Wounjhang Park
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Article
| Open AccessA tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity
Cancer therapy using systemically administrated 4-1BB-targeting antibodies is often associated with severe toxicity due to the nonspecific activation of autoreactive T cells. Here, the authors have developed a trimeric antibody targeting both 4-1BB and EGFR, which activates T cells effectively and shows negligible cytotoxicity.
- Marta Compte
- , Seandean Lykke Harwood
- & Luis Alvarez-Vallina
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Article
| Open AccessMR imaging tracking of inflammation-activatable engineered neutrophils for targeted therapy of surgically treated glioma
Imaging tracking of the migration of cell-based drug delivery systems are needed for expanding their clinical application for glioma. Here they report inflammation activatable engineered neutrophils containing doxorubicin-loaded magnetic mesoporous silica nanoparticles to image and actively target brain tumors after resection.
- Meiying Wu
- , Haixian Zhang
- & Hairong Zheng
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Article
| Open AccessMicrofluidic active loading of single cells enables analysis of complex clinical specimens
Single-cell detection methods are limited by the trade-off between flow rate and measurement precision. Here the authors introduce active loading, an optically triggered microfluidic system to concentrate diluted cell samples, which reduces clogging and decreases processing time in single-cell assays.
- Nicholas L. Calistri
- , Robert J. Kimmerling
- & Scott R. Manalis
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Article
| Open AccessDiscovery of rare cells from voluminous single cell expression data
Algorithms designed to find rare cells in single cell RNA-seq data sets cannot cope with data sets containing tens of thousands of cells. Here the authors present Finder of Rare Entities (FiRE), an algorithm that uses the Sketching technique to assign a rareness score to every expression profile in large RNA-seq data sets.
- Aashi Jindal
- , Prashant Gupta
- & Debarka Sengupta
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Article
| Open AccessA common genetic mechanism underlies morphological diversity in fruits and other plant organs
Remarkable organ shape morphological diversity exists in fruits, vegetables and seeds. Here, the authors establish a link between OVATE Family Proteins and TONNEAU1 Recruiting Motif family proteins in the development pathway that governs fruit shape of tomato, melon, and cucumber as well as potato tuber shape.
- Shan Wu
- , Biyao Zhang
- & Esther van der Knaap
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Article
| Open AccessBMI1 enables interspecies chimerism with human pluripotent stem cells
Conventional human pluripotent stem cells (hPSCs) fail to contribute to interspecies chimaeras when injected into mouse blastocysts. Here the authors show that forced expression of BMI1 overcomes apoptosis of hPSCs in blastocysts of mouse, rabbit and pig allowing them to contribute to chimaeras.
- Ke Huang
- , Yanling Zhu
- & Guangjin Pan
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Article
| Open AccessSelf-implantable double-layered micro-drug-reservoirs for efficient and controlled ocular drug delivery
Treatment for eye injuries and diseases is most efficient when delivered directly into the eye. Here, the authors developed a patient-friendly eye patch equipped with an array of detachable microneedles, through which drugs can be delivered through the cornea for an extended period of time.
- Aung Than
- , Chenghao Liu
- & Peng Chen
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Article
| Open AccessGenome sequences of two diploid wild relatives of cultivated sweetpotato reveal targets for genetic improvement
Sweetpotato is an important food security crop providing rich source of macro- and micronutrients including carbohydrates and vitamins. Here, the authors assemble of the two diploid relatives of cultivated sweetpotato and identify genes and alleles associated with carotenoid biosynthesis from breeding lines.
- Shan Wu
- , Kin H. Lau
- & Zhangjun Fei
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Article
| Open AccessVapor detection and discrimination with a panel of odorant receptors
Biomimetic “noses” have been proposed to replace trained animals for chemical detection. Here the authors select 31 mouse olfactory receptors (ORs), based on a large cell-based screen of >800 ORs against seven chemicals, to build an OR-based sensor able to discriminate structurally similar compounds.
- Hitoshi Kida
- , Yosuke Fukutani
- & Hiroaki Matsunami
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Article
| Open AccessShort-chain ketone production by engineered polyketide synthases in Streptomyces albus
Mutating natural enzymes is effective in broadening the substrate or product range, but generally leads to reduced titers. Here the authors engineer hybrid polyketide synthases for efficient production of short-chain ketones from plant biomass hydrolysates in Streptomyces, which can increase the octane of gasoline.
- Satoshi Yuzawa
- , Mona Mirsiaghi
- & Jay D. Keasling
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Article
| Open AccessCloaking nanoparticles with protein corona shield for targeted drug delivery
The efficacy of nanoparticles can be significantly inhibited by serum proteins binding to them. Here, the author developed a supramolecularly constructed protein corona on nanoparticles, which minimises interactions with serum proteins to prevent the clearance of these particles by macrophages.
- Jun Yong Oh
- , Han Sol Kim
- & Ja-Hyoung Ryu
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Article
| Open AccessA biomaterial with a channel-like pore architecture induces endochondral healing of bone defects
A bioengineering approach to enhance the regeneration of large bone defects is lacking. Here, the authors show that a biomaterial scaffold with a channel-like pore architecture enables organized endochondral ossification through directional cell recruitment and extracellular matrix alignment.
- A. Petersen
- , A. Princ
- & G. N. Duda
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Article
| Open AccessGene synthesis allows biologists to source genes from farther away in the tree of life
Gene synthesis has expanded the ability to modify and create DNA sequences, with implications for biosurveillance. The authors use machine learning and codon theory to identify synthetic genes in Addgene data, and show that synthesis accelerates human-directed gene transfer across the tree of life.
- Aditya M. Kunjapur
- , Philipp Pfingstag
- & Neil C. Thompson
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Article
| Open AccessMulti-hierarchical profiling the structure-activity relationships of engineered nanomaterials at nano-bio interfaces
Understanding nano-bio interactions is key to optimizing the biocompatible design of nanomaterials. Here, the authors combine proteomic and metabolomics studies to evaluate the effect of varying physicochemical properties of iron oxide nanoparticles in macrophage-like cells and mouse lungs.
- Xiaoming Cai
- , Jun Dong
- & Ruibin Li
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Article
| Open AccessA microfabricated nerve-on-a-chip platform for rapid assessment of neural conduction in explanted peripheral nerve fibers
Peripheral nerves have a complex physiology and it is therefore difficult to measure axonal activity in vitro. Here the authors make a nerve-on-a-chip platform to align peripheral nerves and permit measurement of conduction amplitude and velocity along several axons in a single experiment.
- Sandra Gribi
- , Sophie du Bois de Dunilac
- & Stéphanie P. Lacour
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Article
| Open AccessA RNA producing DNA hydrogel as a platform for a high performance RNA interference system
Interfering RNA have a range of therapeutic and research based applications, issues with delivery have made systems that make siRNA in situ of interest. Here, the author report on the creation of a DNA hydrogel with improved stability and transcription efficiency over plasmid DNA.
- Jaejung Song
- , Minhyuk Lee
- & Nokyoung Park
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Article
| Open AccessMulti-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors
Combining decellularised scaffolds with patient-derived cells holds promise for bioengineering of functional tissues. Here the authors develop a two-stage approach to engineer an oesophageal graft that retains the structural organisation of native oesophagus.
- Luca Urbani
- , Carlotta Camilli
- & Paolo De Coppi
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Article
| Open AccessDNA engineered micromotors powered by metal nanoparticles for motion based cellphone diagnostics
Micromotors have a range of potential healthcare applications. Here, the authors describe the development of a metal nanoparticle DNA micromotor which can be used to detect human HIV-1 by a change in the motion of the micromotors, monitored by cell phone camera, triggered by binding of HIV-1 RNA.
- Mohamed Shehata Draz
- , Kamyar Mehrabi Kochehbyoki
- & Hadi Shafiee
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Article
| Open AccessLipopolysaccharide-affinity copolymer senses the rapid motility of swarmer bacteria to trigger antimicrobial drug release
Urinary tract infections are a common side effect of urethral catheters. Here, the authors report on the development of antibiotic loaded NPs with functional polymer coatings which attach too and are removed by motile bacteria to trigger the release of antibiotic.
- Shengtao Lu
- , Wuguo Bi
- & Edwin K. L. Yeow
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Article
| Open AccessAn engineered thermal-shift screen reveals specific lipid preferences of eukaryotic and prokaryotic membrane proteins
Membrane bilayers are made up of a myriad of different lipids that affect membrane proteins, but identifying those specific lipid requirements remains a challenge. Here authors present an engineered thermal-shift screen which reveals specific lipid preferences of eukaryotic and prokaryotic membrane proteins.
- Emmanuel Nji
- , Yurie Chatzikyriakidou
- & David Drew
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Article
| Open AccessPredicting CTCF-mediated chromatin interactions by integrating genomic and epigenomic features
CTCF mediates long-range chromatin interactions which are important for genome organization and function. Here, the authors demonstrate that CTCF-mediated interactome exhibits extensive plasticity and present Lollipop, a machine-learning framework which predicts CTCF-mediated long-range interactions using genomic and epigenomic features.
- Yan Kai
- , Jaclyn Andricovich
- & Weiqun Peng
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Article
| Open AccessGeneration of orthotopically functional salivary gland from embryonic stem cells
Functional salivary glands have not been generated from embryonic stem cells (mESCs) to date. Here the authors demonstrate directed in vitro differentiation of mESCs to oral ectoderm and salivary gland rudiments that form mature, functional salivary glands after orthotopic transplantation.
- Junichi Tanaka
- , Miho Ogawa
- & Kenji Mishima
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Article
| Open AccessEnhanced validation of antibodies for research applications
Five validation pillars have been proposed to verify the specificity of research antibodies. Here the authors screen 6,000 antibodies from the Human Protein Atlas with these methods to provide an antibody validation resource for providers and users.
- Fredrik Edfors
- , Andreas Hober
- & Mathias Uhlen
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Article
| Open AccessDeletions linked to PROG1 gene participate in plant architecture domestication in Asian and African rice
Plant architecture transition is one of the great consequences during rice domestication. Here, the authors find that chromosomal deletions linked to the previously known PROG1 gene also participate in plant architecture domestication in both Asian and African cultivated rice.
- Yongzhen Wu
- , Shuangshuang Zhao
- & Lubin Tan
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Article
| Open AccessHaplosaurus computes protein haplotypes for use in precision drug design
Proteoforms arise as protein isoforms or as protein haplotypes, which are the result of genetic variation. Here, the authors develop Haplosaurus, a database that computes protein haplotypes genome-wide from existing genotype data and analyse protein haplotype variability in the 1000 Genomes dataset.
- William Spooner
- , William McLaren
- & Catherine Chaillan Huntington
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Article
| Open AccessDirect electrical quantification of glucose and asparagine from bodily fluids using nanopores
Protein nanopores are emerging as sensors for a variety of biomolecules. Here the authors develop a nanopore based on the bacterial toxin ClyA, in conjunction with binding proteins for glucose and asparagine, to detect these biomolecules simultaneously from a variety of unprocessed, diluted body fluids.
- Nicole Stéphanie Galenkamp
- , Misha Soskine
- & Giovanni Maglia
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Article
| Open AccessAntigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration
Immunogenicity of AAV vectors renders repeated AAV dosing ineffective. Here the authors show that coadministration of nanoparticle-encapsulated rapamycin overcomes AAV immunogenicity through Treg induction, enabling efficient AAV redosing in mice and nonhuman primates.
- Amine Meliani
- , Florence Boisgerault
- & Federico Mingozzi
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Article
| Open AccessTargeting of NLRP3 inflammasome with gene editing for the amelioration of inflammatory diseases
Activation of the NLRP3 inflammasome triggers the production of inflammatory cytokines. Here, the authors inactivate NLRP3 in macrophages using CRISPR/Cas9 encapsulated in nanoparticles, and show that administration in mice is effective in preventing septic shock and peritonitis, and in improving diabetes-associated inflammation and insulin resistance.
- Congfei Xu
- , Zidong Lu
- & Jun Wang
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Article
| Open AccessHigh-performance nanomaterials formed by rigid yet extensible cyclic β-peptide polymers
Synthetic materials tend to excel in either stiffness or extensibility, whereas a combination of the two is necessary to exceed the performance of natural biomaterials. Here the authors present a bioinspired polymer consisting of cyclic β-peptide rings that is capable of transitioning between rigid and unfolded conformations on demand.
- Kenan P. Fears
- , Manoj K. Kolel-Veetil
- & Thomas D. Clark
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Article
| Open AccessGenome mining of cyclodipeptide synthases unravels unusual tRNA-dependent diketopiperazine-terpene biosynthetic machinery
Diketopiperazine derivatives are bioactive molecules with scaffold formed by the condensation of two amino acids. Here, Yao et al. mine the genomes of Streptomyces strains and identify new biosynthetic machinery for drimentines biosynthesis, which includes cyclodipeptide synthase, prenyltransferase, and terpene cyclase.
- Tingting Yao
- , Jing Liu
- & Wenli Li
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Article
| Open AccessImprovement and extension of anti-EGFR targeting in breast cancer therapy by integration with the Avidin-Nucleic-Acid-Nano-Assemblies
The nature of the linker is known to affect the efficacy of antibody–drug conjugate (ADC). Here the authors show cetuximab-guided Avidin-Nucleic-Acid-Nanoassemblies to be superior to cetuximab-doxorubicin conjugate, and show its efficacy in KRAS mutant breast cancer, allowing for therapeutic expansion of anti-EGFR therapy.
- Francesco Roncato
- , Fatlum Rruga
- & Margherita Morpurgo
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Article
| Open AccessHigh-throughput in vivo mapping of RNA accessible interfaces to identify functional sRNA binding sites
Mapping RNA accessibility is valuable for identifying functional/regulatory RNA regions. Here the authors introduce INTERFACE, an intracellular method that quantifies antisense hybridization efficacy of any number of RNA regions simultaneously via a transcriptional elongation output, measurable via RNA-seq
- Mia K. Mihailovic
- , Jorge Vazquez-Anderson
- & Lydia M. Contreras
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Article
| Open AccessIn vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies
Current anti-venoms against black mamba (Dendroaspis polylepis) bites are animal-derived and associated with several limitations. Here, Laustsen and colleagues develop an experimental recombinant anti-venom based on oligoclonal human IgG antibodies and establish its potential protective value in neutralizing dendrotoxin-mediated neurotoxicity using venom challenge in vivo models.
- Andreas H. Laustsen
- , Aneesh Karatt-Vellatt
- & John McCafferty
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Article
| Open AccessA modified serine cycle in Escherichia coli coverts methanol and CO2 to two-carbon compounds
Assimilating the abundant one-carbon compounds by an industrially-relevant microorganism can broaden the substrate range and achieve reactions that are difficult for chemical process. Here the authors show a modified serine cycle can convert methanol and CO2 to two-carbon compounds in an engineered E. coli strain.
- Hong Yu
- & James C. Liao
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Article
| Open AccessMapping protein selectivity landscapes using multi-target selective screening and next-generation sequencing of combinatorial libraries
Characterizing the binding selectivity landscape of interacting proteins is crucial in protein engineering. Here the authors use multi-target selective library screening and in silico next-generation sequencing to map the binding landscape of proteins and produce improved proteases inhibitors.
- Si Naftaly
- , Itay Cohen
- & Niv Papo
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