The EMBO JournalPub Date : 2025-05-12DOI: 10.1038/s44318-025-00444-x
Jennie Dinh,Danielle Yi,Frances Lin,Pengya Xue,Nicholas D Holloway,Ying Xie,Nnejiuwa U Ibe,Hai P Nguyen,Jose A Viscarra,Yuhui Wang,Hei Sook Sul
{"title":"The microprotein C16orf74/MICT1 promotes thermogenesis in brown adipose tissue.","authors":"Jennie Dinh,Danielle Yi,Frances Lin,Pengya Xue,Nicholas D Holloway,Ying Xie,Nnejiuwa U Ibe,Hai P Nguyen,Jose A Viscarra,Yuhui Wang,Hei Sook Sul","doi":"10.1038/s44318-025-00444-x","DOIUrl":"https://doi.org/10.1038/s44318-025-00444-x","url":null,"abstract":"Brown and beige adipose tissues are metabolically beneficial for increasing energy expenditure via thermogenesis, mainly through UCP1 (uncoupling protein 1). Here, we identify C16orf74, subsequently named MICT1 (microprotein for thermogenesis 1), as a microprotein that is specifically and highly expressed in brown adipose tissue (BAT) and is induced upon cold exposure. MICT1 interacts with protein phosphatase 2B (PP2B, calcineurin) through the docking motif PNIIIT, thereby interfering with dephosphorylation of the regulatory subunit of protein kinase A (PKA), RIIβ, and potentiating PKA activity in brown adipocytes. Overexpression of MICT1 in differentiated brown adipocytes promotes thermogenesis, showing increased oxygen consumption rate (OCR) with higher thermogenic gene expression during β3-adrenergic stimulation, while knockdown of MICT1 impairs thermogenic responses. Moreover, BAT-specific MICT1 ablation in mice suppresses thermogenic capacity to increase adiposity and insulin resistance. Conversely, MICT1 overexpression in BAT or treating mice with a chemical inhibitor that targets the PP2B docking motif of MICT1 enhances thermogenesis. This results in cold tolerance and increased energy expenditure, protection against diet-induced and genetic obesity and insulin resistance, thus suggesting a therapeutic potential of MICT1 targeting.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2025-05-12DOI: 10.1038/s44318-025-00449-6
Daniel Hayat,Ariel Ogran,Shaked Ashkenazi,Alexander Plotnikov,Roni Oren,Mirie Zerbib,Amir Ben-Shmuel,Rivka Dikstein
{"title":"Inhibitors of eIF1A-ribosome interaction unveil uORF-dependent regulation of translation initiation and antitumor and antiviral effects.","authors":"Daniel Hayat,Ariel Ogran,Shaked Ashkenazi,Alexander Plotnikov,Roni Oren,Mirie Zerbib,Amir Ben-Shmuel,Rivka Dikstein","doi":"10.1038/s44318-025-00449-6","DOIUrl":"https://doi.org/10.1038/s44318-025-00449-6","url":null,"abstract":"During translation initiation, eIF1A binds the ribosome through its N- and C-terminal tails, but the functional importance of this temporal interaction in mammalian cells is lacking. Using a high-throughput drug screen targeting eIF1A-RPS10 interaction, we identified inhibitors (1Ais) for eIF1A, RPS10, or both. Applying 1Ais in biochemical assays along specific and global translation experiments, we confirmed known functions of eIF1A and uncovered new roles for both eIF1A and RPS10. Specifically, the eIF1A N-terminal tail (NTT) binding inhibitors revealed the requirement of eIF1A for translation re-initiation. Moreover, a cytosine at position +5 relative to the start codon AUG, located near eIF1A-NTT in the 48S structure, enhances sensitivity to 1Ais, suggesting that the initiating ribosome recognizes a broader AUG context than the conventional Kozak. Additionally, eIF1A-specific 1Ais predominately affect cancer-related pathways. In xenograft models of ovarian cancer, these 1Ais reduced tumor growth without apparent toxicity. Furthermore, inhibition of RPS10, but not eIF1A, modulates a context-dependent regulatory translation initiation at CUG codon of SARS-CoV-2 and impedes infection. Our study underscores 1Ais as effective means to study the role of eIF1A and RPS10 in translation and suggests their targeted inhibition as potential therapies for cancer and viral infections.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2025-05-09DOI: 10.1038/s44318-025-00454-9
Furkan E Oflaz,Alexander I Bondarenko,Michael Trenker,Markus Waldeck-Weiermair,Benjamin Gottschalk,Eva Bernhart,Zhanat Koshenov,Snježana Radulović,Rene Rost,Martin Hirtl,Johannes Pilic,Aditya Karunanithi Nivedita,Adlet Sagintayev,Gerd Leitinger,Bent Brachvogel,Susanne Summerauer,Varda Shoshan-Barmatz,Roland Malli,Wolfgang F Graier
{"title":"Annexin A5 controls VDAC1-dependent mitochondrial Ca2+ homeostasis and determines cellular susceptibility to apoptosis.","authors":"Furkan E Oflaz,Alexander I Bondarenko,Michael Trenker,Markus Waldeck-Weiermair,Benjamin Gottschalk,Eva Bernhart,Zhanat Koshenov,Snježana Radulović,Rene Rost,Martin Hirtl,Johannes Pilic,Aditya Karunanithi Nivedita,Adlet Sagintayev,Gerd Leitinger,Bent Brachvogel,Susanne Summerauer,Varda Shoshan-Barmatz,Roland Malli,Wolfgang F Graier","doi":"10.1038/s44318-025-00454-9","DOIUrl":"https://doi.org/10.1038/s44318-025-00454-9","url":null,"abstract":"Annexin A5 (AnxA5) is a Ca2+-dependent phospholipid-binding protein associated with the regulation of intracellular Ca2+ homeostasis. However, the precise role of AnxA5 in controlling mitochondrial Ca2+ signaling remains elusive. Here, we introduce a novel function of AnxA5 in regulating mitochondrial Ca2+ signaling. Our investigation revealed that AnxA5 localizes at and in the mitochondria and orchestrates intermembrane space Ca2+ signaling upon high Ca2+ elevations induced by ER Ca2+ release. Proximity ligation assays and co-immunoprecipitation revealed a close association but no direct contact of AnxA5 with the voltage-dependent anion channel (VDAC1) in the outer mitochondrial membrane (OMM). In single-cell mitochondrial Ca2+ measurements and electrophysiological recordings, AnxA5 was found to enhance Ca2+ flux through the OMM by promoting the Ca2+-permeable state of VDAC1. By modulating intermembrane space Ca2+ signaling, AnxA5 shapes mitochondrial ultrastructure and influences the dynamicity of the mitochondrial Ca2+ uniporter. Furthermore, by controlling VDAC1's oligomeric state, AnxA5 is protective against cisplatin and selenite-induced apoptotic cell death. Our study uncovers AnxA5 as an integral regulator of VDAC1 in physiological and pathological conditions.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2025-05-08DOI: 10.1038/s44318-025-00451-y
Rachel E Butler,Marion Schuller,Ritu Jaiswal,Jayanta Mukhopadhyay,Jim Barber,Suzie Hingley-Wilson,Emily Wasson,Alex Couto Alves,Ivan Ahel,Graham R Stewart
{"title":"Control of replication and gene expression by ADP-ribosylation of DNA in Mycobacterium tuberculosis.","authors":"Rachel E Butler,Marion Schuller,Ritu Jaiswal,Jayanta Mukhopadhyay,Jim Barber,Suzie Hingley-Wilson,Emily Wasson,Alex Couto Alves,Ivan Ahel,Graham R Stewart","doi":"10.1038/s44318-025-00451-y","DOIUrl":"https://doi.org/10.1038/s44318-025-00451-y","url":null,"abstract":"Mycobacterium tuberculosis maintains long-term infections characterised by the need to regulate growth and adapt to contrasting in vivo environments. Here we show that M. tuberculosis complex bacteria utilise reversible ADP-ribosylation of single-stranded DNA as a mechanism to coordinate stationary phase growth with transcriptional adaptation. The DNA modification is controlled by DarT, an ADP-ribosyltransferase, which adds ADP-ribose to thymidine, and DarG, which enzymatically removes this base modification. Using darG-knockdown M. bovis BCG, we map the first DNA ADP-ribosylome from any organism. We show that inhibition of replication by DarT is reversible and accompanied by extensive ADP-ribosylation at the origin of replication (OriC). In addition, we observe ADP-ribosylation across the genome and demonstrate that ADP-ribose-thymidine alters the transcriptional activity of M. tuberculosis RNA polymerase. Furthermore, we demonstrate that during stationary phase, DarT-dependent ADP-ribosylation of M. tuberculosis DNA is required to optimally induce expression of the Zur regulon, including the ESX-3 secretion system and multiple alternative ribosome proteins. Thus, ADP-ribosylation of DNA can provide a mechanistic link through every aspect of DNA biology from replication to transcription to translation.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"229 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2025-05-06DOI: 10.1038/s44318-025-00447-8
Mark Waterhouse,Kyren Lazarus,Maria Francesca Santolla,Sara Pensa,Eleanor Williams,Abigail J Q Siu,Hisham Mohammed,Irina Mohorianu,Marcello Maggiolini,Jason Carroll,Laura S Itzhaki,Taufiq Rahman,Walid T Khaled
{"title":"CHD8 interacts with BCL11A to induce oncogenic transcription in triple negative breast cancer.","authors":"Mark Waterhouse,Kyren Lazarus,Maria Francesca Santolla,Sara Pensa,Eleanor Williams,Abigail J Q Siu,Hisham Mohammed,Irina Mohorianu,Marcello Maggiolini,Jason Carroll,Laura S Itzhaki,Taufiq Rahman,Walid T Khaled","doi":"10.1038/s44318-025-00447-8","DOIUrl":"https://doi.org/10.1038/s44318-025-00447-8","url":null,"abstract":"The identification of tumour-specific protein-protein interactions remains a challenge for the development of targeted cancer therapies. In this study we describe our approach for the identification of triple negative breast cancer (TNBC)-specific protein-protein interactions focusing on the oncogene BCL11A. We used a proteomic approach to identify the BCL11A protein networks in TNBC and compared it to its network in B-cells, a cell type in which BCL11A plays crucial roles. This approach identified the chromatin remodeller CHD8 as a TNBC-specific interaction partner of BCL11A. We show that CHD8 also plays a key role in TNBC pathogenesis, with detailed multi-omics analysis revealing that BCL11A and CHD8 co-regulate several targets and synergise to drive tumour development and progression. Using a battery of biophysical assays, we confirm that the BCL11A-CHD8 interaction is direct and identify chemical fragments that disrupt this interaction and affect downstream targets, decreasing proliferation in 3D colony assays. Our study provides a proof-of-principle approach for investigating tumour-specific protein-protein interactions and identifies lead chemical compounds that could be developed into novel therapeutics for TNBC.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2025-04-29DOI: 10.1038/s44318-025-00443-y
Anna D Biela,Jakub S Nowak,Artur P Biela,Sunandan Mukherjee,Seyed Naeim Moafinejad,Satyabrata Maiti,Andrzej Chramiec-Głąbik,Rahul Mehta,Jakub Jeżowski,Dominika Dobosz,Priyanka Dahate,Veronique Arluison,Frank Wien,Paulina Indyka,Michal Rawski,Janusz M Bujnicki,Ting-Yu Lin,Sebastian Glatt
{"title":"Determining the effects of pseudouridine incorporation on human tRNAs.","authors":"Anna D Biela,Jakub S Nowak,Artur P Biela,Sunandan Mukherjee,Seyed Naeim Moafinejad,Satyabrata Maiti,Andrzej Chramiec-Głąbik,Rahul Mehta,Jakub Jeżowski,Dominika Dobosz,Priyanka Dahate,Veronique Arluison,Frank Wien,Paulina Indyka,Michal Rawski,Janusz M Bujnicki,Ting-Yu Lin,Sebastian Glatt","doi":"10.1038/s44318-025-00443-y","DOIUrl":"https://doi.org/10.1038/s44318-025-00443-y","url":null,"abstract":"Transfer RNAs (tRNAs) are ubiquitous non-coding RNA molecules required to translate mRNA-encoded sequence information into nascent polypeptide chains. Their relatively small size and heterogenous patterns of their RNA modifications have impeded the systematic structural characterization of individual tRNAs. Here, we use single-particle cryo-EM to determine the structures of four human tRNAs before and after incorporation of pseudouridines (Ψ). Following post-transcriptional modifications by distinct combinations of human pseudouridine synthases, we find that tRNAs become stabilized and undergo specific local structural changes. We establish interactions between the D- and T-arms as the key linchpin in the tertiary structure of tRNAs. Our structures of human tRNAs highlight the vast potential of cryo-EM combined with biophysical measurements and computational simulations for structure-function analyses of tRNAs and other small, folded RNA domains.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2025-04-28DOI: 10.1038/s44318-025-00445-w
Na Liu,Jia-Xin Li,Dan-Yang Yuan,Yin-Na Su,Pei Zhang,Qi Wang,Xiao-Min Su,Lin Li,Haitao Li,She Chen,Xin-Jian He
{"title":"Essential angiosperm-specific subunits of HDA19 histone deacetylase complexes in Arabidopsis.","authors":"Na Liu,Jia-Xin Li,Dan-Yang Yuan,Yin-Na Su,Pei Zhang,Qi Wang,Xiao-Min Su,Lin Li,Haitao Li,She Chen,Xin-Jian He","doi":"10.1038/s44318-025-00445-w","DOIUrl":"https://doi.org/10.1038/s44318-025-00445-w","url":null,"abstract":"Although the Arabidopsis thaliana RPD3-type histone deacetylase HDA19 and its close homolog HDA6 participate in SIN3-type histone deacetylase complexes, they display distinct biological roles, with the reason for these differences being poorly understood. This study identifies three angiosperm-specific HDA19-interacting homologous proteins, termed HDIP1, HDIP2, and HDIP3 (HDIP1/2/3). These proteins interact with HDA19 and other conserved histone deacetylase complex components, leading to the formation of HDA19-containing SIN3-type complexes, while they are not involved in the formation of HDA6-containing complexes. While mutants of conserved SIN3-type complex components show phenotypes divergent from the hda19 mutant, the hdip1/2/3 mutant closely phenocopies the hda19 mutant with respect to development, abscisic acid response, and drought stress tolerance. Genomic and transcriptomic analyses indicate that HDIP1/2/3 and HDA19 co-occupy chromatin and jointly repress gene transcription, especially for stress-related genes. An α-helix motif within HDIP1 has the capacity to bind to nucleosomes and architectural DNA, and is required for its function in Arabidopsis plants. These findings suggest that the angiosperm SIN3-type complexes have evolved to include additional subunits for the precise regulation of histone deacetylation and gene transcription.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rbm24a dictates mRNA recruitment for germ granule assembly in zebrafish.","authors":"Yizhuang Zhang,Jiasheng Wang,Hailing Fang,Shuqi Hu,Boya Yang,Jiayi Zhou,Raphaëlle Grifone,Panfeng Li,Tong Lu,Zhengyang Wang,Chong Zhang,Yubin Huang,Dalei Wu,Qianqian Gong,De-Li Shi,Ang Li,Ming Shao","doi":"10.1038/s44318-025-00442-z","DOIUrl":"https://doi.org/10.1038/s44318-025-00442-z","url":null,"abstract":"The germ granules are ribonucleoprotein (RNP) biomolecular condensates that determine the fate of primordial germ cells (PGCs) and serve as a model for studying RNP granule assembly. Here, we show that the maternal RNA-binding protein Rbm24a is a key factor governing the specific sorting of mRNAs into germ granules. Mechanistically, Rbm24a interacts with the germ plasm component Buc to dictate the specific recruitment of germ plasm mRNAs into phase-separated condensates. Germ plasm particles lacking Rbm24a and mRNAs fail to undergo kinesin-dependent transport toward cleavage furrows where small granules fuse into large aggregates. Therefore, the loss of maternal Rbm24a causes a complete degradation of the germ plasm and the disappearance of PGCs. These findings demonstrate that the Rbm24a/Buc complex functions as a nucleating organizer of germ granules, highlighting an emerging mechanism for RNA-binding proteins in reading and recruiting RNA components into a phase-separated protein scaffold.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2025-04-25DOI: 10.1038/s44318-025-00417-0
Robert A Bone,Molly P Lowndes,Silvia Raineri,Alba R Riveiro,Sarah L Lundregan,Morten Dall,Karolina Sulek,Jose A H Romero,Luna Malzard,Sandra Koigi,Indra J Heckenbach,Victor Solis-Mezarino,Moritz Völker-Albert,Catherine G Vasilopoulou,Florian Meier,Ala Trusina,Matthias Mann,Michael L Nielsen,Jonas T Treebak,Joshua M Brickman
{"title":"Altering metabolism programs cell identity via NAD+-dependent deacetylation.","authors":"Robert A Bone,Molly P Lowndes,Silvia Raineri,Alba R Riveiro,Sarah L Lundregan,Morten Dall,Karolina Sulek,Jose A H Romero,Luna Malzard,Sandra Koigi,Indra J Heckenbach,Victor Solis-Mezarino,Moritz Völker-Albert,Catherine G Vasilopoulou,Florian Meier,Ala Trusina,Matthias Mann,Michael L Nielsen,Jonas T Treebak,Joshua M Brickman","doi":"10.1038/s44318-025-00417-0","DOIUrl":"https://doi.org/10.1038/s44318-025-00417-0","url":null,"abstract":"Cells change their metabolic profiles in response to underlying gene regulatory networks, but how can alterations in metabolism encode specific transcriptional instructions? Here, we show that forcing a metabolic change in embryonic stem cells (ESCs) promotes a developmental identity that better approximates the inner cell mass (ICM) of the early mammalian blastocyst in cultures. This shift in cellular identity depends on the inhibition of glycolysis and stimulation of oxidative phosphorylation (OXPHOS) triggered by the replacement of D-glucose by D-galactose in ESC media. Enhanced OXPHOS in turn activates NAD + -dependent deacetylases of the Sirtuin family, resulting in the deacetylation of histones and key transcription factors to focus enhancer activity while reducing transcriptional noise, which results in a robustly enhanced ESC phenotype. This exploitation of a NAD + /NADH coenzyme coupled to OXPHOS as a means of programming lineage-specific transcription suggests new paradigms for how cells respond to alterations in their environment, and implies cellular rejuvenation exploits enzymatic activities for simultaneous activation of a discrete enhancer set alongside silencing genome-wide transcriptional noise.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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