eLife最新文献

{"title":"Identification of nonsense-mediated decay inhibitors that alter the tumor immune landscape.","authors":"Ashley L Cook, Surojit Sur, Laura Dobbyn, Evangeline Watson, Joshua D Cohen, Blair Ptak, Bum Seok Lee, Suman Paul, Emily Hsiue, Maria Popoli, Bert Vogelstein, Nickolas Papadopoulos, Chetan Bettegowda, Kathy Gabrielson, Shibin Zhou, Kenneth W Kinzler, Nicolas Wyhs","doi":"10.7554/eLife.95952","DOIUrl":"10.7554/eLife.95952","url":null,"abstract":"<p><p>Despite exciting developments in cancer immunotherapy, its broad application is limited by the paucity of targetable antigens on the tumor cell surface. As an intrinsic cellular pathway, nonsense-mediated decay (NMD) conceals neoantigens through the destruction of the RNA products from genes harboring truncating mutations. We developed and conducted a high-throughput screen, based on the ratiometric analysis of transcripts, to identify critical mediators of NMD in human cells. This screen implicated disruption of kinase SMG1's phosphorylation of UPF1 as a potential disruptor of NMD. This led us to design a novel SMG1 inhibitor, KVS0001, that elevates the expression of transcripts and proteins resulting from human and murine truncating mutations in vitro and murine cells in vivo. Most importantly, KVS0001 concomitantly increased the presentation of immune-targetable human leukocyte antigens (HLA) class I-associated peptides from NMD-downregulated proteins on the surface of human cancer cells. KVS0001 provides new opportunities for studying NMD and the diseases in which NMD plays a role, including cancer and inherited diseases.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protection afforded by post-infection SARS-CoV-2 vaccine doses: A cohort study in Shanghai.","authors":"Bo Zheng, Bronner P Gonçalves, Pengfei Deng, Weibing Wang, Jie Tian, Xueyao Liang, Ye Yao, Caoyi Xue","doi":"10.7554/eLife.94990","DOIUrl":"10.7554/eLife.94990","url":null,"abstract":"<p><strong>Background: </strong>In many settings, a large fraction of the population has both been vaccinated against and infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, quantifying the protection provided by post-infection vaccination has become critical for policy. We aimed to estimate the protective effect against SARS-CoV-2 reinfection of an additional vaccine dose after an initial Omicron variant infection.</p><p><strong>Methods: </strong>We report a retrospective, population-based cohort study performed in Shanghai, China, using electronic databases with information on SARS-CoV-2 infections and vaccination history. We compared reinfection incidence by post-infection vaccination status in individuals initially infected during the April-May 2022 Omicron variant surge in Shanghai and who had been vaccinated before that period. Cox models were fit to estimate adjusted hazard ratios (aHRs).</p><p><strong>Results: </strong>275,896 individuals were diagnosed with real-time polymerase chain reaction-confirmed SARS-CoV-2 infection in April-May 2022; 199,312/275,896 were included in analyses on the effect of a post-infection vaccine dose. Post-infection vaccination provided protection against reinfection (aHR 0.82; 95% confidence interval 0.79-0.85). For patients who had received one, two, or three vaccine doses before their first infection, hazard ratios for the post-infection vaccination effect were 0.84 (0.76-0.93), 0.87 (0.83-0.90), and 0.96 (0.74-1.23), respectively. Post-infection vaccination within 30 and 90 days before the second Omicron wave provided different degrees of protection (in aHR): 0.51 (0.44-0.58) and 0.67 (0.61-0.74), respectively. Moreover, for all vaccine types, but to different extents, a post-infection dose given to individuals who were fully vaccinated before first infection was protective.</p><p><strong>Conclusions: </strong>In previously vaccinated and infected individuals, an additional vaccine dose provided protection against Omicron variant reinfection. These observations will inform future policy decisions on COVID-19 vaccination in China and other countries.</p><p><strong>Funding: </strong>This study was funded the Key Discipline Program of Pudong New Area Health System (PWZxk2022-25), the Development and Application of Intelligent Epidemic Surveillance and AI Analysis System (21002411400), the Shanghai Public Health System Construction (GWVI-11.2-XD08), the Shanghai Health Commission Key Disciplines (GWVI-11.1-02), the Shanghai Health Commission Clinical Research Program (20214Y0020), the Shanghai Natural Science Foundation (22ZR1414600), and the Shanghai Young Health Talents Program (2022YQ076).</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statistical learning beyond words in human neonates.","authors":"Ana Fló, Lucas Benjamin, Marie Palu, Ghislaine Dehaene-Lambertz","doi":"10.7554/eLife.101802","DOIUrl":"10.7554/eLife.101802","url":null,"abstract":"<p><p>Interest in statistical learning in developmental studies stems from the observation that 8-month-olds were able to extract words from a monotone speech stream solely using the transition probabilities (TP) between syllables (Saffran et al., 1996). A simple mechanism was thus part of the human infant's toolbox for discovering regularities in language. Since this seminal study, observations on statistical learning capabilities have multiplied across domains and species, challenging the hypothesis of a dedicated mechanism for language acquisition. Here, we leverage the two dimensions conveyed by speech -speaker identity and phonemes- to examine (1) whether neonates can compute TPs on one dimension despite irrelevant variation on the other and (2) whether the linguistic dimension enjoys an advantage over the voice dimension. In two experiments, we exposed neonates to artificial speech streams constructed by concatenating syllables while recording EEG. The sequence had a statistical structure based either on the phonetic content, while the voices varied randomly (Experiment 1) or on voices with random phonetic content (Experiment 2). After familiarisation, neonates heard isolated duplets adhering, or not, to the structure they were familiarised with. In both experiments, we observed neural entrainment at the frequency of the regularity and distinct Event-Related Potentials (ERP) to correct and incorrect duplets, highlighting the universality of statistical learning mechanisms and suggesting it operates on virtually any dimension the input is factorised. However, only linguistic duplets elicited a specific ERP component, potentially an N400 precursor, suggesting a lexical stage triggered by phonetic regularities already at birth. These results show that, from birth, multiple input regularities can be processed in parallel and feed different higher-order networks.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioural pharmacology predicts disrupted signalling pathways and candidate therapeutics from zebrafish mutants of Alzheimer's disease risk genes.","authors":"François Kroll, Joshua Donnelly, Güliz Gürel Özcan, Eirinn Mackay, Jason Rihel","doi":"10.7554/eLife.96839","DOIUrl":"10.7554/eLife.96839","url":null,"abstract":"<p><p>By exposing genes associated with disease, genomic studies provide hundreds of starting points that should lead to druggable processes. However, our ability to systematically translate these genomic findings into biological pathways remains limited. Here, we combine rapid loss-of-function mutagenesis of Alzheimer's risk genes and behavioural pharmacology in zebrafish to predict disrupted processes and candidate therapeutics. FramebyFrame, our expanded package for the analysis of larval behaviours, revealed that decreased night-time sleep was common to F0 knockouts of all four late-onset Alzheimer's risk genes tested. We developed an online tool, ZOLTAR, which compares any behavioural fingerprint to a library of fingerprints from larvae treated with 3677 compounds. ZOLTAR successfully predicted that <i>sorl1</i> mutants have disrupted serotonin signalling and identified betamethasone as a drug which normalises the excessive day-time sleep of <i>presenilin-2</i> knockout larvae with minimal side effects. Predictive behavioural pharmacology offers a general framework to rapidly link disease-associated genes to druggable pathways.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T3SS translocon induces pyroptosis by direct interaction with NLRC4/NAIP inflammasome.","authors":"Yan Zhao, Hanshuo Zhu, Jinqian Li, Hang Xu, Li Sun","doi":"10.7554/eLife.100820","DOIUrl":"10.7554/eLife.100820","url":null,"abstract":"<p><p>Type III secretion system (T3SS) is a virulence apparatus existing in many bacterial pathogens. Structurally, T3SS consists of the base, needle, tip, and translocon. The NLRC4 inflammasome is the major receptor for T3SS needle and basal rod proteins. Whether other T3SS components are recognized by NLRC4 is unclear. In this study, using <i>Edwardsiella tarda</i> as a model intracellular pathogen, we examined T3SS-inflammasome interaction and its effect on cell death. <i>E. tarda</i> induced pyroptosis in a manner that required the bacterial translocon and the host inflammasome proteins of NLRC4, NLRP3, ASC, and caspase 1/4. The translocon protein EseB triggered NLRC4/NAIP-mediated pyroptosis by binding NAIP via its C-terminal region, particularly the terminal 6 residues (T6R). EseB homologs exist widely in T3SS-positive bacteria and share high identities in T6R. Like <i>E. tarda</i> EseB, all of the representatives of the EseB homologs exhibited T6R-dependent NLRC4 activation ability. Together these results revealed the function and molecular mechanism of EseB to induce host cell pyroptosis and suggested a highly conserved inflammasome-activation mechanism of T3SS translocon in bacterial pathogens.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specific presynaptic functions require distinct <i>Drosophila</i> Ca_v2 splice isoforms.","authors":"Christopher Bell, Lukas Kilo, Daniel Gottschalk, Jashar Arian, Lea Deneke, Hanna Kern, Christof Rickert, Oliver Kobler, Julia Strauß, Martin Heine, Carsten Duch, Stefanie Ryglewski","doi":"10.7554/eLife.100394","DOIUrl":"10.7554/eLife.100394","url":null,"abstract":"<p><p>At many vertebrate synapses, presynaptic functions are tuned by expression of different Ca_v2 channels. Most invertebrate genomes contain only one <i>Ca_v2</i> gene. The <i>Drosophila</i> Ca_v2 homolog, cacophony (cac), induces synaptic vesicle release at presynaptic active zones (AZs). We hypothesize that <i>Drosophila</i> cac functional diversity is enhanced by two mutually exclusive exon pairs that are not conserved in vertebrates, one in the voltage sensor and one in the loop binding Ca_β and G_βγ subunits. We find that alternative splicing in the voltage sensor affects channel activation voltage. Only the isoform with the higher activation voltage localizes to AZs at the glutamatergic <i>Drosophila</i> larval neuromuscular junction and is imperative for normal synapse function. By contrast, alternative splicing at the other alternative exon pair tunes multiple aspects of presynaptic function. While expression of one exon yields normal transmission, expression of the other reduces channel number in the AZ and thus release probability. This also abolishes presynaptic homeostatic plasticity. Moreover, reduced channel number affects short-term plasticity, which is rescued by increasing the external calcium concentration to match release probability to control. In sum, in <i>Drosophila</i> alternative splicing provides a mechanism to regulate different aspects of presynaptic functions with only one <i>Ca_v2</i> gene.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Late killing of <i>Plasmodium berghei</i> sporozoites in the liver by an anti-circumsporozoite protein antibody.","authors":"Manuela C Aguirre-Botero, Olga Pacios, Susanna Celli, Eduardo Aliprandini, Anisha Gladston, Jean-Michel Thiberge, Pauline Formaglio, Rogerio Amino","doi":"10.7554/eLife.105291","DOIUrl":"10.7554/eLife.105291","url":null,"abstract":"<p><p><i>Plasmodium</i> sporozoites are inoculated into the skin during the bite of an infected mosquito. This motile stage invades cutaneous blood vessels to reach the liver and infect hepatocytes. The circumsporozoite protein (CSP) on the sporozoite surface is an important antigen targeted by protective antibodies (Abs) in immunoprophylaxis or elicited by vaccination. Antibody-mediated protection mainly unfolds during parasite skin migration, but rare and potent protective Abs additionally neutralize sporozoite in the liver. Here, using a rodent malaria model, microscopy and bioluminescence imaging, we show a late-neutralizing effect of 3D11 anti-CSP monoclonal antibody (mAb) in the liver. The need for several hours to eliminate parasites in the liver was associated with an accumulation of 3D11 effects, starting with the inhibition of sporozoite motility, sinusoidal extravasation, cell invasion, and terminating with the parasite killing inside the invaded cell. This late-neutralizing activity could be helpful to identify more potent therapeutic mAbs with stronger activity in the liver.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep need driven oscillation of glutamate synaptic phenotype.","authors":"Kaspar E Vogt, Ashwinikumar Kulkarni, Richa Pandey, Mantre Dehnad, Genevieve Konopka, Robert W Greene","doi":"10.7554/eLife.98280","DOIUrl":"10.7554/eLife.98280","url":null,"abstract":"<p><p>Sleep loss increases AMPA-synaptic strength and number in the neocortex. However, this is only part of the synaptic sleep loss response. We report an increased AMPA/NMDA EPSC ratio in frontal-cortical pyramidal neurons of layers 2-3. Silent synapses are absent, decreasing the plastic potential to convert silent NMDA to active AMPA synapses. These sleep loss changes are recovered by sleep. Sleep genes are enriched for synaptic shaping cellular components controlling glutamate synapse phenotype, overlap with autism risk genes, and are primarily observed in excitatory pyramidal neurons projecting intra-telencephalically. These genes are enriched with genes controlled by the transcription factor, MEF2c, and its repressor, HDAC4. Sleep genes can thus provide a framework within which motor learning and training occur mediated by the sleep-dependent oscillation of glutamate-synaptic phenotypes.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>fmo-4</i> promotes longevity and stress resistance via ER to mitochondria calcium regulation in <i>C. elegans</i>.","authors":"Angela M Tuckowski, Safa Beydoun, Elizabeth S Kitto, Ajay Bhat, Marshall B Howington, Aditya Sridhar, Mira Bhandari, Kelly Chambers, Scott F Leiser","doi":"10.7554/eLife.99971","DOIUrl":"10.7554/eLife.99971","url":null,"abstract":"<p><p>Flavin-containing monooxygenases (FMOs) are a conserved family of xenobiotic enzymes upregulated in multiple longevity interventions, including nematode and mouse models. Previous work supports that <i>C. elegans fmo-2</i> promotes longevity, stress resistance, and healthspan by rewiring endogenous metabolism. However, there are five <i>C. elegans</i> FMOs and five mammalian FMOs, and it is not known whether promoting longevity and health benefits is a conserved role of this gene family. Here, we report that expression of <i>C. elegans fmo-4</i> promotes lifespan extension and paraquat stress resistance downstream of both dietary restriction and inhibition of mTOR. We find that overexpression of <i>fmo-4</i> in just the hypodermis is sufficient for these benefits, and that this expression significantly modifies the transcriptome. By analyzing changes in gene expression, we find that genes related to calcium signaling are significantly altered downstream of <i>fmo-4</i> expression. Highlighting the importance of calcium homeostasis in this pathway, <i>fmo-4</i> overexpressing animals are sensitive to thapsigargin, an ER stressor that inhibits calcium flux from the cytosol to the ER lumen. This calcium/<i>fmo-4</i> interaction is solidified by data showing that modulating intracellular calcium with either small molecules or genetics can change expression of <i>fmo-4</i> and/or interact with <i>fmo-4</i> to affect lifespan and stress resistance. Further analysis supports a pathway where <i>fmo-4</i> modulates calcium homeostasis downstream of activating transcription factor-6 (<i>atf-6</i>), whose knockdown induces and requires <i>fmo-4</i> expression. Together, our data identify <i>fmo-4</i> as a longevity-promoting gene whose actions interact with known longevity pathways and calcium homeostasis.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A within-host infection model to explore tolerance and resistance.","authors":"David Duneau, Pierre D M Lafont, Christine Lauzeral, Nathalie Parthuisot, Christian Faucher, Xuerong Jin, Nicolas Buchon, Jean-Baptiste Ferdy","doi":"10.7554/eLife.104052","DOIUrl":"https://doi.org/10.7554/eLife.104052","url":null,"abstract":"<p><p>How are some individuals surviving infections while others die? The answer lies in how infected individuals invest into controlling pathogen proliferation and mitigating damage, two strategies respectively called resistance and disease tolerance. Pathogen within-host dynamics (WHD), influenced by resistance, and its connection to host survival, determined by tolerance, decide the infection outcome. To grasp these intricate effects of resistance and tolerance, we used a deterministic theoretical model where pathogens interact with the immune system of a host. The model describes the positive and negative regulation of the immune response, consider the way damage accumulate during the infection and predicts WHD. When chronic, infections stabilize at a Set-Point Pathogen Load (SPPL). Our model predicts that this situation can be transient, the SPPL being then a predictor of life span which depends on initial condition (e.g. inoculum). When stable, the SPPL is rather diagnostic of non lethal chronic infections. In lethal infections, hosts die at a Pathogen Load Upon Death (PLUD) which is almost independent from the initial conditions. As the SPPL, the PLUD is affected by both resistance and tolerance but we demonstrate that it can be used in conjunction with mortality measurement to distinguish the effect of disease tolerance from that of resistance. We validate empirically this new approach, using Drosophila melanogaster and the pathogen Providencia rettgeri. We found that, as predicted by the model, hosts that were wounded or deficient of key antimicrobial peptides had a higher PLUD, while Catalase mutant hosts, likely to have a default in disease tolerance, had a lower PLUD.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}