解剖学和形态学
麻醉学
听力与言语-语言病理学
行为科学
心脏和心血管系统
细胞和组织工程学
临床神经病学
危重症监护医学
牙科,口腔外科和医学
皮肤病学
急诊医学
内分泌学和新陈代谢
肠胃学和肝脏学
老人病学和老年医学
卫生保健科学和服务
血液学
免疫学
传染病
综合和补充性医学
医学伦理学
医学信息学
医学实验室技术
医学,全科和内科
医学,法律
医学,研究和试验
神经系统科学
护理
营养学和饮食学
产科医学和妇科医学
肿瘤学
眼科学
整形外科学
耳鼻喉科学
病理学
儿科学
周围血管疾病
药理学和药剂学
生理学
基本医疗保健
精神病学
公共、环境和职业卫生
放射学,核医学和医学成像
康复学
生殖生物学
呼吸系统
风湿病学
运动科学
外科学
毒理学
热带医学
泌尿学和肾脏学
病毒学
老年医学
健康政策和服务
心理学,临床
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::Preeclampsia is a placentally induced hypertensive disorder of pregnancy that is associated with substantial morbidity and mortality to mothers and fetuses. Clinical manifestations of preterm preeclampsia result from excess circulating soluble vascular endothelial growth factor receptor FLT1 (sFLT1 or sVEGFR1) of plac...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4297
更新日期:2018-11-19 00:00:00
abstract::How intrinsic gene-regulatory networks interact with a cell's spatial environment to define its identity remains poorly understood. We developed an approach to distinguish between intrinsic and extrinsic effects on global gene expression by integrating analysis of sequencing-based and imaging-based single-cell transcr...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4260
更新日期:2018-10-29 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::Protein interaction networks and protein compartmentalization underlie all signaling and regulatory processes in cells. Enzyme-catalyzed proximity labeling (PL) has emerged as a new approach to study the spatial and interaction characteristics of proteins in living cells. However, current PL methods require over 18 h ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4201
更新日期:2018-10-01 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::We present two algorithms to predict the activity of AsCpf1 guide RNAs. Indel frequencies for 15,000 target sequences were used in a deep-learning framework based on a convolutional neural network to train Seq-deepCpf1. We then incorporated chromatin accessibility information to create the better-performing DeepCpf1 a...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4061
更新日期:2018-03-01 00:00:00
abstract::Therapeutic ex vivo T-cell expansion is limited by low rates and T-cell products of limited functionality. Here we describe a system that mimics natural antigen-presenting cells (APCs) and consists of a fluid lipid bilayer supported by mesoporous silica micro-rods. The lipid bilayer presents membrane-bound cues for T-...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4047
更新日期:2018-02-01 00:00:00
abstract::We present a technology to screen millions of B cells for natively paired human antibody repertoires. Libraries of natively paired, variable region heavy and light (VH:VL) amplicons are expressed in a yeast display platform that is optimized for human Fab surface expression. Using our method we identify HIV-1 broadly ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4052
更新日期:2018-02-01 00:00:00
abstract::Droplet single-cell RNA-sequencing (dscRNA-seq) has enabled rapid, massively parallel profiling of transcriptomes. However, assessing differential expression across multiple individuals has been hampered by inefficient sample processing and technical batch effects. Here we describe a computational tool, demuxlet, that...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4042
更新日期:2018-01-01 00:00:00
abstract::Many promising targets for T-cell-based cancer immunotherapies are self-antigens. During thymic selection, T cells bearing T cell receptors (TCRs) with high affinity for self-antigen are eliminated. The affinity of the remaining low-avidity TCRs can be improved to increase their antitumor efficacy, but conventional sa...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4004
更新日期:2017-12-01 00:00:00
abstract::Linear, medium-chain (C8-C12) hydrocarbons are important components of fuels as well as commodity and specialty chemicals. As industrial microbes do not contain pathways to produce medium-chain chemicals, approaches such as overexpression of endogenous enzymes or deletion of competing pathways are not available to the...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt.4022
更新日期:2017-12-01 00:00:00
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 br...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3902
更新日期:2017-09-01 00:00:00
abstract::Lipid production in the industrial microalga Nannochloropsis gaditana exceeds that of model algal species and can be maximized by nutrient starvation in batch culture. However, starvation halts growth, thereby decreasing productivity. Efforts to engineer N. gaditana strains that can accumulate biomass and overproduce ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3865
更新日期:2017-07-01 00:00:00
abstract::The application of single-cell genome sequencing to large cell populations has been hindered by technical challenges in isolating single cells during genome preparation. Here we present single-cell genomic sequencing (SiC-seq), which uses droplet microfluidics to isolate, fragment, and barcode the genomes of single ce...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3880
更新日期:2017-07-01 00:00:00
abstract::We present 1,003 reference genomes that were sequenced as part of the Genomic Encyclopedia of Bacteria and Archaea (GEBA) initiative, selected to maximize sequence coverage of phylogenetic space. These genomes double the number of existing type strains and expand their overall phylogenetic diversity by 25%. Comparativ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3886
更新日期:2017-07-01 00:00:00
abstract::Colorectal cancer (CRC) is a leading cause of death in the developed world, yet facile preclinical models that mimic the natural stages of CRC progression are lacking. Through the orthotopic engraftment of colon organoids we describe a broadly usable immunocompetent CRC model that recapitulates the entire adenoma-aden...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3837
更新日期:2017-06-01 00:00:00
abstract::After nearly 40 years of development, oligonucleotide therapeutics are nearing meaningful clinical productivity. One of the key advantages of oligonucleotide drugs is that their delivery and potency are derived primarily from the chemical structure of the oligonucleotide whereas their target is defined by the base seq...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt.3765
更新日期:2017-03-01 00:00:00
abstract::Methods to rapidly assess cell growth would be useful for many applications, including drug susceptibility testing, but current technologies have limited sensitivity or throughput. Here we present an approach to precisely and rapidly measure growth rates of many individual cells simultaneously. We flow cells in suspen...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3666
更新日期:2016-10-01 00:00:00
abstract::Identification of the peptides recognized by individual T cells is important for understanding and treating immune-related diseases. Current cytometry-based approaches are limited to the simultaneous screening of 10-100 distinct T-cell specificities in one sample. Here we use peptide-major histocompatibility complex (...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3662
更新日期:2016-10-01 00:00:00
abstract::The biology of multicellular organisms is coordinated across multiple size scales, from the subnanoscale of molecules to the macroscale, tissue-wide interconnectivity of cell populations. Here we introduce a method for super-resolution imaging of the multiscale organization of intact tissues. The method, called magnif...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3641
更新日期:2016-09-01 00:00:00
abstract::Dietary omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), docosahexaenoic acid (DHA, C22:6) and eicosapentaenoic acid (EPA, C20:5) are usually derived from marine fish. Although production of both EPA and DHA has been engineered into land plants, including Arabidopsis, Camelina sativa and Brassica juncea, nei...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3585
更新日期:2016-08-01 00:00:00
abstract::High-throughput genetic screens have become essential tools for studying a wide variety of biological processes. Here we experimentally compare systems based on clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) or its transcriptionally repressive variant, CRISPR-inter...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3536
更新日期:2016-06-01 00:00:00
abstract::Genetic studies of human disease have traditionally focused on the detection of disease-causing mutations in afflicted individuals. Here we describe a complementary approach that seeks to identify healthy individuals resilient to highly penetrant forms of genetic childhood disorders. A comprehensive screen of 874 gene...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3514
更新日期:2016-05-01 00:00:00
abstract::CRISPR-Cas9-based genetic screens are a powerful new tool in biology. By simply altering the sequence of the single-guide RNA (sgRNA), one can reprogram Cas9 to target different sites in the genome with relative ease, but the on-target activity and off-target effects of individual sgRNAs can vary widely. Here, we use ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3437
更新日期:2016-02-01 00:00:00
abstract::Recombinant adeno-associated viruses (rAAVs) are commonly used vehicles for in vivo gene transfer. However, the tropism repertoire of naturally occurring AAVs is limited, prompting a search for novel AAV capsids with desired characteristics. Here we describe a capsid selection method, called Cre recombination-based AA...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3440
更新日期:2016-02-01 00:00:00
abstract::Programmable DNA cleavage using CRISPR-Cas9 enables efficient, site-specific genome engineering in single cells and whole organisms. In the research arena, versatile CRISPR-enabled genome editing has been used in various ways, such as controlling transcription, modifying epigenomes, conducting genome-wide screens and ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3659
更新日期:2016-01-01 00:00:00
abstract::Genome editing with targeted nucleases and DNA donor templates homologous to the break site has proven challenging in human hematopoietic stem and progenitor cells (HSPCs), and particularly in the most primitive, long-term repopulating cell population. Here we report that combining electroporation of zinc finger nucle...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3408
更新日期:2015-12-01 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::We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laboratories and fed either a ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3353
更新日期:2015-10-01 00:00:00
abstract::Industrial strain development requires system-wide engineering and optimization of cellular metabolism while considering industrially relevant fermentation and recovery processes. It can be conceptualized as several strategies, which may be implemented in an iterative fashion and in different orders. The key challenge...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt.3365
更新日期:2015-10-01 00:00:00
abstract::Calcium (Ca(2+)) signals that are precisely modulated in space and time mediate a myriad of cellular processes, including contraction, excitation, growth, differentiation and apoptosis. However, study of Ca(2+) responses has been hampered by technological limitations of existing Ca(2+)-modulating tools. Here we presen...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3350
更新日期:2015-10-01 00:00:00
abstract::Although bile duct disorders are well-recognized causes of liver disease, the molecular and cellular events leading to biliary dysfunction are poorly understood. To enable modeling and drug discovery for biliary disease, we describe a protocol that achieves efficient differentiation of biliary epithelial cells (cholan...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3294
更新日期:2015-08-01 00:00:00
abstract::A central hurdle in developing small interfering RNAs (siRNAs) as therapeutics is the inefficiency of their delivery across the plasma and endosomal membranes to the cytosol, where they interact with the RNA interference machinery. With the aim of improving endosomal release, a poorly understood and inefficient proces...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3298
更新日期:2015-08-01 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::Brief expression of pluripotency-associated factors such as Oct4, Klf4, Sox2 and c-Myc (OKSM), in combination with differentiation-inducing signals, has been reported to trigger transdifferentiation of fibroblasts into other cell types. Here we show that OKSM expression in mouse fibroblasts gives rise to both induced ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3247
更新日期:2015-07-01 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::Gossypium hirsutum has proven difficult to sequence owing to its complex allotetraploid (AtDt) genome. Here we produce a draft genome using 181-fold paired-end sequences assisted by fivefold BAC-to-BAC sequences and a high-resolution genetic map. In our assembly 88.5% of the 2,173-Mb scaffolds, which cover 89.6%∼96.7%...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3208
更新日期:2015-05-01 00:00:00
abstract::Methods used to sequence the transcriptome often produce more than 200 million short sequences. We introduce StringTie, a computational method that applies a network flow algorithm originally developed in optimization theory, together with optional de novo assembly, to assemble these complex data sets into transcripts...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3122
更新日期:2015-03-01 00:00:00
abstract::Recent therapeutic successes have renewed interest in drug combinations, but experimental screening approaches are costly and often identify only small numbers of synergistic combinations. The DREAM consortium launched an open challenge to foster the development of in silico methods to computationally rank 91 compound...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3052
更新日期:2014-12-01 00:00:00