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  1. Article ; Online: Origin and Evolution of Nitrogen Fixation in Prokaryotes.

    Pi, Hong-Wei / Lin, Jinn-Jy / Chen, Chi-An / Wang, Po-Hsiang / Chiang, Yin-Ru / Huang, Chieh-Chen / Young, Chiu-Chung / Li, Wen-Hsiung

    Molecular biology and evolution

    2022  Volume 39, Issue 9

    Abstract: The origin of nitrogen fixation is an important issue in evolutionary biology. While nitrogen is required by all living organisms, only a small fraction of bacteria and archaea can fix nitrogen. The prevailing view is that nitrogen fixation first evolved ...

    Abstract The origin of nitrogen fixation is an important issue in evolutionary biology. While nitrogen is required by all living organisms, only a small fraction of bacteria and archaea can fix nitrogen. The prevailing view is that nitrogen fixation first evolved in archaea and was later transferred to bacteria. However, nitrogen-fixing (Nif) bacteria are far larger in number and far more diverse in ecological niches than Nif archaea. We, therefore, propose the bacteria-first hypothesis, which postulates that nitrogen fixation first evolved in bacteria and was later transferred to archaea. As >30,000 prokaryotic genomes have been sequenced, we conduct an in-depth comparison of the two hypotheses. We first identify the six genes involved in nitrogen fixation in all sequenced prokaryotic genomes and then reconstruct phylogenetic trees using the six Nif proteins individually or in combination. In each of these trees, the earliest lineages are bacterial Nif protein sequences and in the oldest clade (group) the archaeal sequences are all nested inside bacterial sequences, suggesting that the Nif proteins first evolved in bacteria. The bacteria-first hypothesis is further supported by the observation that the majority of Nif archaea carry the major bacterial Mo (molybdenum) transporter (ModABC) rather than the archaeal Mo transporter (WtpABC). Moreover, in our phylogeny of all available ModA and WtpA protein sequences, the earliest lineages are bacterial sequences while archaeal sequences are nested inside bacterial sequences. Furthermore, the bacteria-first hypothesis is supported by available isotopic data. In conclusion, our study strongly supports the bacteria-first hypothesis.
    MeSH term(s) Archaea/genetics ; Archaea/metabolism ; Bacteria/metabolism ; Bacterial Proteins/genetics ; Nitrogen/metabolism ; Nitrogen Fixation/genetics ; Nitrogenase/genetics ; Nitrogenase/metabolism ; Phylogeny
    Chemical Substances Bacterial Proteins ; Nitrogenase (EC 1.18.6.1) ; Nitrogen (N762921K75)
    Language English
    Publishing date 2022-08-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 998579-7
    ISSN 1537-1719 ; 0737-4038
    ISSN (online) 1537-1719
    ISSN 0737-4038
    DOI 10.1093/molbev/msac181
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  2. Article ; Online: Conserved regulatory switches for the transition from natal down to juvenile feather in birds.

    Chen, Chih-Kuan / Chang, Yao-Ming / Jiang, Ting-Xin / Yue, ZhiCao / Liu, Tzu-Yu / Lu, Jiayi / Yu, Zhou / Lin, Jinn-Jy / Vu, Trieu-Duc / Huang, Tao-Yu / Harn, Hans I-Chen / Ng, Chen Siang / Wu, Ping / Chuong, Cheng-Ming / Li, Wen-Hsiung

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 4174

    Abstract: The transition from natal downs for heat conservation to juvenile feathers for simple flight is a remarkable environmental adaptation process in avian evolution. However, the underlying epigenetic mechanism for this primary feather transition is mostly ... ...

    Abstract The transition from natal downs for heat conservation to juvenile feathers for simple flight is a remarkable environmental adaptation process in avian evolution. However, the underlying epigenetic mechanism for this primary feather transition is mostly unknown. Here we conducted time-ordered gene co-expression network construction, epigenetic analysis, and functional perturbations in developing feather follicles to elucidate four downy-juvenile feather transition events. We report that extracellular matrix reorganization leads to peripheral pulp formation, which mediates epithelial-mesenchymal interactions for branching morphogenesis. α-SMA (ACTA2) compartmentalizes dermal papilla stem cells for feather renewal cycling. LEF1 works as a key hub of Wnt signaling to build rachis and converts radial downy to bilateral symmetry. Novel usage of scale keratins strengthens feather sheath with SOX14 as the epigenetic regulator. We show that this primary feather transition is largely conserved in chicken (precocial) and zebra finch (altricial) and discuss the possibility that this evolutionary adaptation process started in feathered dinosaurs.
    MeSH term(s) Animals ; Feathers/growth & development ; Feathers/metabolism ; Chickens/genetics ; Finches/genetics ; Gene Expression Regulation, Developmental ; Extracellular Matrix/metabolism ; Epigenesis, Genetic ; Gene Regulatory Networks ; Wnt Signaling Pathway ; Keratins/metabolism ; Keratins/genetics ; Biological Evolution ; Morphogenesis/genetics
    Language English
    Publishing date 2024-05-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-48303-3
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  3. Article ; Online: Positional distribution of transcription factor binding sites in Arabidopsis thaliana.

    Yu, Chun-Ping / Lin, Jinn-Jy / Li, Wen-Hsiung

    Scientific reports

    2016  Volume 6, Page(s) 25164

    Abstract: Binding of a transcription factor (TF) to its DNA binding sites (TFBSs) is a critical step to initiate the transcription of its target genes. It is therefore interesting to know where the TFBSs of a gene are likely to locate in the promoter region. Here ... ...

    Abstract Binding of a transcription factor (TF) to its DNA binding sites (TFBSs) is a critical step to initiate the transcription of its target genes. It is therefore interesting to know where the TFBSs of a gene are likely to locate in the promoter region. Here we studied the positional distribution of TFBSs in Arabidopsis thaliana, for which many known TFBSs are now available. We developed a method to identify the locations of TFBSs in the promoter sequences of genes in A. thaliana. We found that the distribution is nearly bell-shaped with a peak at 50 base pairs (bp) upstream of the transcription start site (TSS) and 86% of the TFBSs are in the region from -1,000 bp to +200 bp with respect to the TSS. Our distribution was supported by chromatin immunoprecipitation sequencing and microarray data and DNase I hypersensitive site sequencing data. When TF families were considered separately, differences in positional preference were observed between TF families. Our study of the positional distribution of TFBSs seems to be the first in a plant.
    Language English
    Publishing date 2016--27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep25164
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  4. Article ; Online: Many human RNA viruses show extraordinarily stringent selective constraints on protein evolution.

    Lin, Jinn-Jy / Bhattacharjee, Maloyjo Joyraj / Yu, Chun-Ping / Tseng, Yan Yuan / Li, Wen-Hsiung

    Proceedings of the National Academy of Sciences of the United States of America

    2019  Volume 116, Issue 38, Page(s) 19009–19018

    Abstract: How negative selection, positive selection, and population size contribute to the large variation in nucleotide substitution rates among RNA viruses remains unclear. Here, we studied the ratios of nonsynonymous-to-synonymous substitution rates ( ...

    Abstract How negative selection, positive selection, and population size contribute to the large variation in nucleotide substitution rates among RNA viruses remains unclear. Here, we studied the ratios of nonsynonymous-to-synonymous substitution rates (
    MeSH term(s) Animals ; Evolution, Molecular ; Genome, Viral ; Humans ; Mammals ; Mutation Rate ; RNA Virus Infections/virology ; RNA Viruses/genetics ; Selection, Genetic ; Viral Proteins/genetics
    Chemical Substances Viral Proteins
    Keywords covid19
    Language English
    Publishing date 2019-09-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1907626116
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The rises and falls of opsin genes in 59 ray-finned fish genomes and their implications for environmental adaptation.

    Lin, Jinn-Jy / Wang, Feng-Yu / Li, Wen-Hsiung / Wang, Tzi-Yuan

    Scientific reports

    2017  Volume 7, Issue 1, Page(s) 15568

    Abstract: We studied the evolution of opsin genes in 59 ray-finned fish genomes. We identified the opsin genes and adjacent genes (syntenies) in each genome. Then we inferred the changes in gene copy number (N), syntenies, and tuning sites along each phylogenetic ... ...

    Abstract We studied the evolution of opsin genes in 59 ray-finned fish genomes. We identified the opsin genes and adjacent genes (syntenies) in each genome. Then we inferred the changes in gene copy number (N), syntenies, and tuning sites along each phylogenetic branch during evolution. The Exorh (rod opsin) gene has been retained in 56 genomes. Rh1, the intronless rod opsin gene, first emerged in ancestral Actinopterygii, and N increased to 2 by the teleost-specific whole genome duplication, but then decreased to 1 in the ancestor of Neoteleostei fishes. For cone opsin genes, the rhodopsin-like (Rh2) and long-wave-sensitive (LWS) genes showed great variation in N among species, ranging from 0 to 5 and from 0 to 4, respectively. The two short-wave-sensitive genes, SWS1 and SWS2, were lost in 23 and 6 species, respectively. The syntenies involving LWS, SWS2 and Rh2 underwent complex changes, while the evolution of the other opsin gene syntenies was much simpler. Evolutionary adaptation in tuning sites under different living environments was discussed. Our study provides a detailed view of opsin gene gains and losses, synteny changes and tuning site changes during ray-finned fish evolution.
    MeSH term(s) Animals ; Evolution, Molecular ; Fishes/genetics ; Genome/genetics ; Metagenomics ; Opsins/classification ; Opsins/genetics ; Phylogeny ; Rod Opsins/classification ; Rod Opsins/genetics ; Synteny/genetics
    Chemical Substances Opsins ; Rod Opsins
    Language English
    Publishing date 2017-11-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-017-15868-7
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  6. Article ; Online: Constructing a human complex type N-linked glycosylation pathway in Kluyveromyces marxianus.

    Lee, Ming-Hsuan / Hsu, Tsui-Ling / Lin, Jinn-Jy / Lin, Yu-Ju / Kao, Yi-Ying / Chang, Jui-Jen / Li, Wen-Hsiung

    PloS one

    2020  Volume 15, Issue 5, Page(s) e0233492

    Abstract: Glycosylation can affect various protein properties such as stability, biological activity, and immunogenicity. To produce human therapeutic proteins, a host that can produce glycoproteins with correct glycan structures is required. Microbial expression ... ...

    Abstract Glycosylation can affect various protein properties such as stability, biological activity, and immunogenicity. To produce human therapeutic proteins, a host that can produce glycoproteins with correct glycan structures is required. Microbial expression systems offer economical, rapid and serum-free production and are more amenable to genetic manipulation. In this study, we developed a protocol for CRISPR/Cas9 multiple gene knockouts and knockins in Kluyveromyces marxianus, a probiotic yeast with a rapid growth rate. As hyper-mannosylation is a common problem in yeast, we first knocked out the α-1,3-mannosyltransferase (ALG3) and α-1,6-mannosyltransferase (OCH1) genes to reduce mannosylation. We also knocked out the subunit of the telomeric Ku domain (KU70) to increase the homologous recombination efficiency of K. marxianus. In addition, we knocked in the MdsI (α-1,2-mannosidase) gene to reduce mannosylation and the GnTI (β-1,2-N-acetylglucosaminyltransferase I) and GnTII genes to produce human N-glycan structures. We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine. This study lays a cornerstone of glycosylation engineering in K. marxianus toward producing human glycoproteins.
    MeSH term(s) Biotechnology ; CRISPR-Cas Systems ; Gene Knock-In Techniques ; Gene Knockout Techniques ; Genes, Fungal ; Glycoproteins/biosynthesis ; Glycoproteins/chemistry ; Glycoproteins/genetics ; Glycosylation ; Humans ; Kluyveromyces/genetics ; Kluyveromyces/metabolism ; Mannosidases/genetics ; Mannosidases/metabolism ; Mannosyltransferases/antagonists & inhibitors ; Mannosyltransferases/genetics ; Mannosyltransferases/metabolism ; Metabolic Engineering/methods ; N-Acetylglucosaminyltransferases/genetics ; N-Acetylglucosaminyltransferases/metabolism ; Polysaccharides/biosynthesis ; Polysaccharides/chemistry ; Polysaccharides/genetics ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics
    Chemical Substances Glycoproteins ; Polysaccharides ; Recombinant Proteins ; Mannosyltransferases (EC 2.4.1.-) ; N-Acetylglucosaminyltransferases (EC 2.4.1.-) ; UDP-GlcNAc-Gb(5)Cer beta1-6N-acetylglucosaminyltransferase (EC 2.4.1.-) ; Mannosidases (EC 3.2.1.-) ; mannosyl-oligosaccharide 1,2-alpha-mannosidase (EC 3.2.1.113)
    Language English
    Publishing date 2020-05-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0233492
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  7. Article ; Online: Discovering unknown human and mouse transcription factor binding sites and their characteristics from ChIP-seq data.

    Yu, Chun-Ping / Kuo, Chen-Hao / Nelson, Chase W / Chen, Chi-An / Soh, Zhi Thong / Lin, Jinn-Jy / Hsiao, Ru-Xiu / Chang, Chih-Yao / Li, Wen-Hsiung

    Proceedings of the National Academy of Sciences of the United States of America

    2021  Volume 118, Issue 20

    Abstract: Transcription factor binding sites (TFBSs) are essential for gene regulation, but the number of known TFBSs remains limited. We aimed to discover and characterize unknown TFBSs by developing a computational pipeline for analyzing ChIP-seq (chromatin ... ...

    Abstract Transcription factor binding sites (TFBSs) are essential for gene regulation, but the number of known TFBSs remains limited. We aimed to discover and characterize unknown TFBSs by developing a computational pipeline for analyzing ChIP-seq (chromatin immunoprecipitation followed by sequencing) data. Applying it to the latest ENCODE ChIP-seq data for human and mouse, we found that using the irreproducible discovery rate as a quality-control criterion resulted in many experiments being unnecessarily discarded. By contrast, the number of motif occurrences in ChIP-seq peak regions provides a highly effective criterion, which is reliable even if supported by only one experimental replicate. In total, we obtained 2,058 motifs from 1,089 experiments for 354 human TFs and 163 motifs from 101 experiments for 34 mouse TFs. Among these motifs, 487 have not previously been reported. Mapping the canonical motifs to the human genome reveals a high TFBS density ±2 kb around transcription start sites (TSSs) with a peak at -50 bp. On average, a promoter contains 5.7 TFBSs. However, 70% of TFBSs are in introns (41%) and intergenic regions (29%), whereas only 12% are in promoters (-1 kb to +100 bp from TSSs). Notably, some TFs (e.g., CTCF, JUN, JUNB, and NFE2) have motifs enriched in intergenic regions, including enhancers. We inferred 142 cobinding TF pairs and 186 (including 115 completely) tethered binding TF pairs, indicating frequent interactions between TFs and a higher frequency of tethered binding than cobinding. This study provides a large number of previously undocumented motifs and insights into the biological and genomic features of TFBSs.
    MeSH term(s) Animals ; Binding Sites ; Chromatin Immunoprecipitation Sequencing/methods ; Humans ; Mice ; Nucleotide Motifs ; Promoter Regions, Genetic ; Transcription Factors/metabolism
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2021-05-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2026754118
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  8. Article ; Online: Genome-wide prediction of CRISPR/Cas9 targets in Kluyveromyces marxianus and its application to obtain a stable haploid strain.

    Lee, Ming-Hsuan / Lin, Jinn-Jy / Lin, Yu-Ju / Chang, Jui-Jen / Ke, Huei-Mien / Fan, Wen-Lang / Wang, Tzi-Yuan / Li, Wen-Hsiung

    Scientific reports

    2018  Volume 8, Issue 1, Page(s) 7305

    Abstract: Kluyveromyces marxianus, a probiotic yeast, is important in industrial applications because it has a broad substrate spectrum, a rapid growth rate and high thermotolerance. To date, however, there has been little effort in its genetic engineering by the ... ...

    Abstract Kluyveromyces marxianus, a probiotic yeast, is important in industrial applications because it has a broad substrate spectrum, a rapid growth rate and high thermotolerance. To date, however, there has been little effort in its genetic engineering by the CRISPR/Cas9 system. Therefore, we aimed at establishing the CRISPR/Cas9 system in K. marxianus and creating stable haploid strains, which will make genome engineering simpler. First, we predicted the genome-wide target sites of CRISPR/Cas9 that have been conserved among the eight sequenced genomes of K. marxianus strains. Second, we established the CRISPR/Cas9 system in the K. marxianus 4G5 strain, which was selected for its high thermotolerance, rapid growth, a pH range of pH3-9, utilization of xylose, cellobiose and glycerol, and toxin tolerance, and we knocked out its MATα3 to prevent mating-type switching. Finally, we used K. marxianus MATα3 knockout diploid strains to obtain stable haploid strains with a growth rate comparable to that of the diploid 4G5 strain. In summary, we present the workflow from identifying conserved CRISPR/Cas9 targets in the genome to knock out the MATα3 genes in K. marxianus to obtain a stable haploid strain, which can facilitate genome engineering applications.
    MeSH term(s) CRISPR-Cas Systems/genetics ; Conserved Sequence ; Gene Knockout Techniques ; Genomics ; Haploidy ; Kluyveromyces/genetics ; Kluyveromyces/physiology ; Spores, Fungal/physiology ; Transformation, Genetic
    Language English
    Publishing date 2018-05-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-018-25366-z
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  9. Article ; Online: The Cone Opsin Repertoire of Osteoglossomorph Fishes: Gene Loss in Mormyrid Electric Fish and a Long Wavelength-Sensitive Cone Opsin That Survived 3R.

    Liu, Da-Wei / Wang, Feng-Yu / Lin, Jinn-Jy / Thompson, Ammon / Lu, Ying / Vo, Derek / Yan, Hong Young / Zakon, Harold

    Molecular biology and evolution

    2018  Volume 36, Issue 3, Page(s) 447–457

    Abstract: Vertebrates have four classes of cone opsin genes derived from two rounds of genome duplication. These are short wavelength sensitive 1(SWS1), short wavelength sensitive 2(SWS2), medium wavelength sensitive (RH2), and long wavelength sensitive (LWS). ... ...

    Abstract Vertebrates have four classes of cone opsin genes derived from two rounds of genome duplication. These are short wavelength sensitive 1(SWS1), short wavelength sensitive 2(SWS2), medium wavelength sensitive (RH2), and long wavelength sensitive (LWS). Teleosts had another genome duplication at their origin and it is believed that only one of each cone opsin survived the ancestral teleost duplication event. We tested this by examining the retinal cones of a basal teleost group, the osteoglossomorphs. Surprisingly, this lineage has lost the typical vertebrate green-sensitive RH2 opsin gene and, instead, has a duplicate of the LWS opsin that is green sensitive. This parallels the situation in mammalian evolution in which the RH2 opsin gene was lost in basal mammals and a green-sensitive opsin re-evolved in Old World, and independently in some New World, primates from an LWS opsin gene. Another group of fish, the characins, possess green-sensitive LWS cones. Phylogenetic analysis shows that the evolution of green-sensitive LWS opsins in these two teleost groups derives from a common ancestral LWS opsin that acquired green sensitivity. Additionally, the nocturnally active African weakly electric fish (Mormyroideae), which are osteoglossomorphs, show a loss of the SWS1 opsin gene. In comparison with the independently evolved nocturnally active South American weakly electric fish (Gymnotiformes) with a functionally monochromatic LWS opsin cone retina, the presence of SWS2, LWS, and LWS2 cone opsins in mormyrids suggests the possibility of color vision.
    MeSH term(s) Amino Acid Sequence ; Animals ; Cone Opsins/chemistry ; Cone Opsins/genetics ; Electric Fish/genetics ; Photoreceptor Cells, Vertebrate/chemistry ; Phylogeny ; Synteny
    Chemical Substances Cone Opsins
    Language English
    Publishing date 2018-12-24
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 998579-7
    ISSN 1537-1719 ; 0737-4038
    ISSN (online) 1537-1719
    ISSN 0737-4038
    DOI 10.1093/molbev/msy241
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  10. Article ; Online: Maize ANT1 modulates vascular development, chloroplast development, photosynthesis, and plant growth.

    Liu, Wen-Yu / Lin, Hsin-Hung / Yu, Chun-Ping / Chang, Chao-Kang / Chen, Hsiang-June / Lin, Jinn-Jy / Lu, Mei-Yeh Jade / Tu, Shih-Long / Shiu, Shin-Han / Wu, Shu-Hsing / Ku, Maurice S B / Li, Wen-Hsiung

    Proceedings of the National Academy of Sciences of the United States of America

    2020  Volume 117, Issue 35, Page(s) 21747–21756

    Abstract: ... ...

    Abstract Arabidopsis
    MeSH term(s) Adenine Nucleotide Translocator 1/metabolism ; Adenine Nucleotide Translocator 1/physiology ; Amino Acid Transport Systems, Neutral/genetics ; Amino Acid Transport Systems, Neutral/metabolism ; Chloroplasts/metabolism ; Flowers/genetics ; Flowers/growth & development ; Gene Expression Profiling ; Gene Expression Regulation, Plant/genetics ; Millets/genetics ; Millets/metabolism ; Organogenesis, Plant/genetics ; Photosynthesis/genetics ; Photosynthesis/physiology ; Plant Development/genetics ; Plant Leaves/metabolism ; Plant Proteins/genetics ; Transcription Factors/metabolism ; Transcriptome ; Zea mays/genetics ; Zea mays/growth & development
    Chemical Substances Adenine Nucleotide Translocator 1 ; Amino Acid Transport Systems, Neutral ; Plant Proteins ; Transcription Factors
    Language English
    Publishing date 2020-08-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2012245117
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