Abstract:
:Despite recent advances in optogenetics, it remains challenging to manipulate gene expression in specific populations of neurons. We present a dual-protein switch system, Cal-Light, that translates neuronal-activity-mediated calcium signaling into gene expression in a light-dependent manner. In cultured neurons and brain slices, we show that Cal-Light drives expression of the reporter EGFP with high spatiotemporal resolution only in the presence of both blue light and calcium. Delivery of the Cal-Light components to the motor cortex of mice by viral vectors labels a subset of excitatory and inhibitory neurons related to learned lever-pressing behavior. By using Cal-Light to drive expression of the inhibitory receptor halorhodopsin (eNpHR), which responds to yellow light, we temporarily inhibit the lever-pressing behavior, confirming that the labeled neurons mediate the behavior. Thus, Cal-Light enables dissection of neural circuits underlying complex mammalian behaviors with high spatiotemporal precision.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Lee D,Hyun JH,Jung K,Hannan P,Kwon HBdoi
10.1038/nbt.3902subject
Has Abstractpub_date
2017-09-01 00:00:00pages
858-863issue
9eissn
1087-0156issn
1546-1696pii
nbt.3902journal_volume
35pub_type
杂志文章abstract::A major shortcoming to the use of adeno-associated virus (rAAV) vectors is their limited packaging size. To overcome this hurdle, we split an expression cassette and cloned it into two separate vectors. The vectors contained either a nuclear localizing Escherichia coli lacZ transgene (nlslacZ) with a splice acceptor, ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/75390
更新日期:2000-05-01 00:00:00
abstract::The unique bread-making characteristic of wheat flour is closely related to the elasticity and extensibility of the gluten proteins stored in the starchy endosperm, particularly the high-molecular-weight glutenin subunits (HMW-GS), which are important in determining gluten and dough elasticity. The quality of wheat cu...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0996-1155
更新日期:1996-09-01 00:00:00
abstract::Cellular function is critically regulated through degradation of substrates by the proteasome. To enable direct analysis of naturally cleaved proteasomal peptides under physiological conditions, we developed mass spectrometry analysis of proteolytic peptides (MAPP), a method for proteasomal footprinting that allows fo...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4279
更新日期:2018-10-22 00:00:00
abstract::Effective proteome-wide strategies that distinguish the N-termini of proteins from the N-termini of their protease cleavage products would accelerate identification of the substrates of proteases with broad or unknown specificity. Our approach, named terminal amine isotopic labeling of substrates (TAILS), addresses th...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.1611
更新日期:2010-03-01 00:00:00
abstract::Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strai...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2858
更新日期:2014-04-01 00:00:00
abstract::Transgenic crops are approved for release in some countries, while many more countries are wrestling with the issue of how to conduct risk assessments. Controls on field trials often include monitoring of horizontal gene transfer (HGT) from crops to surrounding soil microorganisms. Our analysis of antibiotic-resistant...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1009
更新日期:2004-09-01 00:00:00
abstract::Fewer than half of all tandem mass spectrometry (MS/MS) spectra acquired in shotgun proteomics experiments are typically matched to a peptide with high confidence. Here we determine the identity of unassigned peptides using an ultra-tolerant Sequest database search that allows peptide matching even with modifications ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3267
更新日期:2015-07-01 00:00:00
abstract::Protein phosphorylation is a key post-translational modification regulating protein function in almost all cellular processes. Although tens of thousands of phosphorylation sites have been identified in human cells, approaches to determine the functional importance of each phosphosite are lacking. Here, we manually cu...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-019-0344-3
更新日期:2020-03-01 00:00:00
abstract::The Human Proteome Organization (HUPO) recently completed the first large-scale collaborative study to characterize the human serum and plasma proteomes. The study was carried out in different locations and used diverse methods and instruments to compare and integrate tandem mass spectrometry (MS/MS) data on aliquots ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1183
更新日期:2006-03-01 00:00:00
abstract::Although mass spectrometry is well suited to identifying thousands of potential protein post-translational modifications (PTMs), it has historically been biased towards just a few. To measure the entire set of PTMs across diverse proteomes, software must overcome the dual challenges of covering enormous search spaces ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-019-0067-5
更新日期:2019-04-01 00:00:00
abstract::Pluripotent stem cell-derived cardiomyocyte grafts can remuscularize substantial amounts of infarcted myocardium and beat in synchrony with the heart, but in some settings cause ventricular arrhythmias. It is unknown whether human cardiomyocytes can restore cardiac function in a physiologically relevant large animal m...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4162
更新日期:2018-08-01 00:00:00
abstract::The discovery of large multiprotein complexes in cells has increased the demand for improved heterologous protein production techniques to study their molecular structure and function. Here we describe MultiBac, a simple and versatile system for generating recombinant baculovirus DNA to express protein complexes compr...
journal_title:Nature biotechnology
pub_type: 信件
doi:10.1038/nbt1036
更新日期:2004-12-01 00:00:00
abstract::We show that transplantation of adult bone marrow-derived cells expressing c-kit reduces hyperglycemia in mice with streptozotocin-induced pancreatic damage. Although quantitative analysis of the pancreas revealed a low frequency of donor insulin-positive cells, these cells were not present at the onset of blood gluco...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt841
更新日期:2003-07-01 00:00:00
abstract::Through sequential generations of random mutagenesis and screening, we have directed the evolution of an esterase for deprotection of an antibiotic p-nitrobenzyl ester in aqueous-organic solvents. Because rapid screening directly on the desired antibiotic (loracarbef) nucleus p-nitrobenzyl ester was not feasible, the ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0496-458
更新日期:1996-04-01 00:00:00
abstract::Transplantation of pancreatic progenitors or insulin-secreting cells derived from human embryonic stem cells (hESCs) has been proposed as a therapy for diabetes. We describe a seven-stage protocol that efficiently converts hESCs into insulin-producing cells. Stage (S) 7 cells expressed key markers of mature pancreatic...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3033
更新日期:2014-11-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature biotechnology
pub_type: 已发布勘误
doi:10.1038/s41587-020-0658-1
更新日期:2020-09-01 00:00:00
abstract::Technologies that enable targeted manipulation of epigenetic marks could be used to precisely control cell phenotype or interrogate the relationship between the epigenome and transcriptional control. Here we describe a programmable, CRISPR-Cas9-based acetyltransferase consisting of the nuclease-null dCas9 protein fuse...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3199
更新日期:2015-05-01 00:00:00
abstract::The reactive thiol in cysteine is used for coupling maleimide linkers in the generation of antibody conjugates. To assess the impact of the conjugation site, we engineered cysteines into a therapeutic HER2/neu antibody at three sites differing in solvent accessibility and local charge. The highly solvent-accessible si...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2108
更新日期:2012-01-22 00:00:00
abstract::The human genome encodes approximately 100,000 different genes, and at least partial sequence information for nearly all will be available soon. Sequence information alone, however, is insufficient for a full understanding of gene function, expression, regulation, and splice-site variation. Because cellular processes ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1296-1675
更新日期:1996-12-01 00:00:00
abstract::To select for bacterial strains with enhanced phenotypes, random fragments of a whole genome, or a defined region of the genome, are cloned in a nonreplicating vector. The resulting plasmids are integrated by recombination into the homologous DNA region of the original strain. Integration gives rise to a nontandem dir...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0697-564
更新日期:1997-06-01 00:00:00
abstract::Microbially catalyzed reactions, which occur in the natural sulfur cycle, have been integrated in a microbiological process to remove toxic metals from contaminated soils. Bioleaching using sulfuric acid produced by sulfur-oxidizing bacteria was followed by precipitation of the leachate metals as insoluble sulfides by...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0698-572
更新日期:1998-06-01 00:00:00
abstract::L-Ascorbic acid (vitamin C) in fruits and vegetables is an essential component of human nutrition. Surprisingly, only limited information is available about the pathway(s) leading to its biosynthesis in plants. Here, we report the isolation and characterization of GalUR, a gene from strawberry that encodes an NADPH-de...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt777
更新日期:2003-02-01 00:00:00
abstract::A problem in analyzing microarray-based gene expression data is the separation of genes causally involved in a disease from innocent bystander genes, whose expression levels have been secondarily altered by primary changes elsewhere. To investigate this issue systematically in the context of a class of complex human d...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt965
更新日期:2004-05-01 00:00:00
abstract::RNA-guided gene drives capable of spreading genomic alterations made in laboratory organisms through wild populations could be used to address environmental and public health problems. However, the possibility of unintended genome editing occurring through the escape of strains from laboratories, coupled with the pros...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3412
更新日期:2015-12-01 00:00:00
abstract::In the human malaria vector Anopheles gambiae, the gene doublesex (Agdsx) encodes two alternatively spliced transcripts, dsx-female (AgdsxF) and dsx-male (AgdsxM), that control differentiation of the two sexes. The female transcript, unlike the male, contains an exon (exon 5) whose sequence is highly conserved in all ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4245
更新日期:2018-12-01 00:00:00
abstract::Monitoring the T cell receptor (TCR) repertoire in health and disease can provide key insights into adaptive immune responses, but the accuracy of current TCR sequencing (TCRseq) methods is unclear. In this study, we systematically compared the results of nine commercial and academic TCRseq methods, including six rapi...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-020-0656-3
更新日期:2020-09-07 00:00:00
abstract::Analyzing patent data from 1995-2005 show the increasing importance of patenting by small and medium-sized biotech companies. ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0606-643
更新日期:2006-06-01 00:00:00
abstract::A bacteriophage lambda surface expression system, lambda foo, was used for epitope mapping of human galectin-3. We constructed random epitope and peptide libraries and compared their efficiencies in the mapping. The galectin-3 cDNA was randomly digested by DNase 1 to make random epitope libraries. The libraries were s...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0197-74
更新日期:1997-01-01 00:00:00
abstract::Enzymatic removal of blood group ABO antigens to develop universal red blood cells (RBCs) was a pioneering vision originally proposed more than 25 years ago. Although the feasibility of this approach was demonstrated in clinical trials for group B RBCs, a major obstacle in translating this technology to clinical pract...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1298
更新日期:2007-04-01 00:00:00
abstract::The side chain of the antifungal antibiotic ansatrienin A from Streptomyces collinus contains a cyclohexanecarboxylic acid (CHC)-derived moiety. This moiety is also observed in trace amounts of omega-cyclohexyl fatty acids (typically less than 1% of total fatty acids) produced by S. collinus. Coenzyme A-activated CHC ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/79479
更新日期:2000-09-01 00:00:00